Yes kammy just adding Micelles to my searches had helped a lot ans sky shh too. The lysosomal storage disease this is an outcome of these micelles storing up , stacking up without exiting, I believe well here ABCB6 transporter is in the golgi apparatus, the lysosomal storage diseases, makes sense. vhttp://en.wikipedia.org/wiki/Golgi_apparatus
and this cut from another article shows so many tie ins, ABC transporters represent one of the largest families of membrane proteins that are found in all three phyla of life. Mitochondria comprise up to four ABC systems, ABCB7/ATM1, ABCB10/MDL1, ABCB8 and ABCB6. These half-transporters, which assemble into homodimeric complexes, are involved in a number of key cellular processes, e.g. biogenesis of cytosolic iron–sulfur clusters, heme biosynthesis, iron homeostasis, multidrug resistance, and protection against oxidative stress. Here, we summarize recent advances and emerging themes in our understanding of how these ABC systems in the inner and outer mitochondrial membrane fulfill their functions in important (patho) physiological processes, including neurodegenerative and hematological disorders.
Last Edit: Dec 11, 2010 20:31:03 GMT -5 by lilsissy
Still trying to figure this out on a basic level so one of us can present this to the people, one of us needs to go to the other sites and present this important information soon. Some of it can be cut and pasted straight from here... whoever wants to initiate it? I think it might help if we start putting our Questions at the bottom of our posts, like I just started doing, so we can see what other areas need to be looked at - or where we're needing to look further, etc. Maybe then someone else knows something about it and can post back... we've got to speed up our research and work together as a team.
But, first - still trying to get a good handle on this which I don't feel I have. Once we figure out what's happening then you gals can add your other research and have a very good photograph. What I'm trying to do is to give the people something practical that they can take to a doctor, a specific doctor or lab and have them look in that direction. We're all needing medicine - the correct medicines (or herbs, if you choose to go that route).
Ok, our culprit physically looks like a DMSO/DMS molecule. I've never heard of anyone being tested for DMSO in their system, have you? I haven't looked yet, and then I can look at its chemical composition and see what group it's close to - so we can ask to be tested for something legitimate if DMSO isn't an option.
What I'm thinking is that these particles are carbon based, humans are carbon based, they are like a 'god atom' that is a beginning place for life, like the CERN atoms that they are crashing together. Or, another example - when God breathed life into Adam - he breathed in these micelles and God's 'air' contained salty water which they must have to come to life.
You've got to imagine that you're a mad scientist and you're looking for what the god energy is inside of us that causes life to 'be'. They have discovered the closest thing to it - micelles - and figured out how to manipulate them into carrying life in many forms. From these carbon atoms - anything can pop out - a fungus, bacteria, virus, parasite, or a mite-like, gnat larvae or crab-like life form - most anything. Also, they have figured out how to make the micelle form most any known particle and it's reverse. (Thinking: if a micelle is programmed to create a fiber, is its 'reverse micelle' version programmed to create a micelle from a fiber? Need to look at reverse micelles.) They keep tinkering and testing... that's probably why some of us have one thing and others have another, we might represent the progressive stages of their discoveries?
"Good line to follow Kammy but remember the shhh signal that we are working on too, How do the two relate?"
I will have to look again... I'm glad the micelle formation is helping in your other areas, though...
"Biological membranes are composed of lipid, protein and carbohydrate that exist in a fluid state."
Question - What if they now exist in other states - fibers, particles, crystals... made up of wayward micelles?
"The lysosomal storage disease this is an outcome of these micelles storing up , stacking up without exiting, I believe well here"
Very good, Jen, I knew you gals will know where to look in the body... I'm just the pointer. We need something definite that the people can easily look, hopefully with a simple blood test...
lysosomal storage disease - what diseases are those, symptoms, where/how are they manifested, how and what to test for?
More than 40 lysosomal storage diseases are described. These include the mucopolysaccharidoses, which represent a group of lysosomal storage diseases with a prevalence of approximately 1 in 25,000 people.
Glycogen storage disease type II (GSDII): The 2 most well-described variants are (1) infantile acid maltase disease, or Pompe disease, and (2) slowly progressive acid maltase disease. (See the Glycogen Storage Disease Type II section below for detailed information.)
Mucopolysaccharidoses (See the Mucopolysaccharidoses section below for detailed information.)
MPS type IH, Hurler syndrome (alpha-L-iduronidase)
MPS type I H/S, Hurler-Scheie syndrome
MPS type IS, Scheie syndrome
MPS type II A, Hunter syndrome, severe (iduronate sulfatase)
MPS type II B, Hunter syndrome, mild (iduronate sulfatase)
MPS type III A-D, Sanfilippo syndrome (heparan N -sulfatase)
MPS type IV A, Morquio syndrome, classic (galactose 6-sulfatase)
MPS type VI, Maroteaux-Lamy syndrome (arylsulfatase B)
MPS type VII, Sly syndrome (beta-glucuronidase)
Mucolipidosis II (I-cell disease) and mucolipidosis III (phosphotransferase) (See the I-Cell Disease and Pseudo-Hurler Polydystrophy section below for detailed information.)
Schindler disease/Kanzaki disease (alpha-N -acetylgalactosaminidase) (See the Schindler Disease section below for more details.)
In a 1995 report, Kanzaki noted that Schindler disease and Kanzaki disease are caused by a deficient lysosomal enzyme, alpha-N -acetylgalactosaminidase (EC 220.127.116.11).8
Two German children were first described in 1987, and 2 Dutch children were described in 1993. These children were similar clinically, and their conditions were characterized by marked neuroaxonal dystrophy of an infantile onset. In these children, type 1 was named Schindler disease.
An adult patient with profuse angiokeratoma corporis diffusum but minimum involvement in the nervous system was reported in 1987 from Japan. This disease (type 2) was named Kanzaki disease (OMIM 104170).
Glycoprotein degradation Alpha-mannosidosis and beta-mannosidosis (See the Alpha-mannosidosis and Beta-mannosidosis section below for detailed information.)
Fucosidosis Fucosidosis is a rare autosomal recessive lysosomal storage disease.
Its main clinical findings are progressive neuromotor deterioration, seizures, coarse facial features, dysostosis multiplex, angiokeratoma corporis diffusum, visceromegaly, recurrent respiratory infections, and growth retardation. Fucosidosis type I rapidly evolves toward a progressive neurologic deterioration and death.
Sialidosis In 2003, Rodriguez Criado noted that sialidosis (OMIM 256550) is an autosomal recessive disorder resulting from mutations in the NEU gene, located in 6p21.3.9
This condition leads to deficiency of alpha-N -acetyl neuraminidase (sialidase) activity, causing an accumulation of its substrates, oligosaccharides, in the lysosomes of various organs and tissues and an increased presence in urine and other organic fluids.
Sialidosis is associated with progressively impaired vision, macular cherry-red spots, and myoclonus (sialidosis type I) or with skeletal dysplasia, Hurlerlike phenotype, dysostosis multiplex, mental retardation, and hepatosplenomegaly (sialidosis type II).10
Aspartylglucosaminuria (AGU) A deficiency of functional aspartylglucosaminidase (AGA) causes AGU, which is a lysosomal storage disease. In 1999, Aronson noted that AGU (OMIM 208400) is an autosomal recessive lysosomal storage disease caused by defective degradation of aspartate (Asn)-linked glycoproteins.11 AGU mutations occur in the gene (AGA) for glycosylasparaginase, the enzyme necessary for hydrolysis of the protein oligosaccharide linkage in Asn-linked glycoprotein substrates undergoing metabolic turnover.
Loss of glycosylasparaginase activity leads to accumulation of the linkage unit Asn-GlcNAc in tissue lysosomes. Storage of this fragment affects the pathophysiology of neuronal cells most severely.
Patients notably experience decreased cognitive abilities, skeletal abnormalities, and facial grotesqueness. The progress of the disease is slower than in many other lysosomal storage diseases. Patients appear healthy during infancy and generally live from 25-45 years.
Carbohydrate-deficient glycoprotein syndrome Patients with carbohydrate-deficient glycoprotein syndrome can present with dysmorphic features, hypotonia, ataxia, a convergent squint, nystagmus, myopia, progressive retinal degeneration, developmental delay, pericardial effusion, esotropia, retinitis pigmentosa, and strabismus. Carbohydrate-deficient glycoprotein syndrome can be confirmed by serum levels of carbohydrate-deficient transferrin. MRI can show atrophy of the cerebellum and brain stem and hypointensity in the pallidum on diffusion-weighted images, suggesting deposits of metal substances.
In the cerebellum, proton magnetic resonance spectroscopy can show decreased concentrations of N -acetylaspartate and a complex of glutamine and glutamate (Glx), while the concentration of myo-inositol is increased, indicating neuronal impairment and gliosis.
In the parietal lobe, concentration of Glx can be increased, possibly reflecting dysfunction caused by liver injury. Wolman and cholesterol ester storage disease (acid lipase) (See the Wolman Disease and Cholesteryl Ester Storage Disease section below for detailed information.)
Farber disease, disseminated lipogranulomatosis (ceramidase) Farber disease is a rare lysosomal storage disease characterized by the accumulation of ceramide in tissues because of acid ceramidase deficiency. The detection of low levels of acid ceramidase is diagnostic of the condition.
Histopathology shows foam cells and granulomatous infiltration. Ultramicroscopically, curvilinear tubular bodies are present as comma-shaped tubular structures consisting of 2 single membranes separated by a clear space in dermal fibroblasts. Banana bodies, variably membrane-bound structures that have a spindle and usually a curved shape, are found predominantly in Schwann cells of peripheral nerves.
Radiography can show diffuse osteopenia, underdevelopment of the terminal phalanges, and reduced long bone diameters. Farber disease starts to manifest in patients aged 4 months as a hoarse cry or swollen tender joints followed by subcutaneous nodules, flesh-colored papules, and periarticular tumors or nodules.
Reports exist of coarse facial features and xanthoma, such as papules on the face and hands.
This disease is fatal in the first years of life.
Niemann-Pick disease (See the Niemann-Pick Disease section below for detailed information.) Niemann-Pick disease type A (sphingomyelinase) Niemann-Pick disease type B (sphingomyelinase) Niemann-Pick disease C1 (NPC1) Niemann-Pick disease C2 Gaucher disease types I, II, and III (beta-glucosidase) Gaucher disease, a common lysosomal storage disease, is associated with mutations at the acid beta-glucosidase (GCase) locus.
Great phenotypic variety exists in the nonneuronopathic form (type I), ranging from clinically asymptomatic to massive hepatomegaly, hypersplenism, growth retardation in children, and extensive involvement of bone and lungs. Acute (type II) or subacute (type III) forms with neurologic manifestations exist.
Enzyme replacement therapy has become available and has resulted in a reduction in liver and spleen volume and consequently improved anemia and thrombocytopenia in most patients. OGT-918 (N -butyldeoxynojirimycin) is showing promise in patients with Gaucher disease. Krabbe disease, infantile globoid-cell leukodystrophy (galactosylceramidase)
Krabbe disease manifests in infants with central nervous system manifestations of spasticity, irritability, motor regression, and seizures associated with a positive family history. A form of late-onset Krabbe disease can manifest with asymmetrical peripheral neuropathy associated with pyramidal signs and with electrophysiologic examination showing slowing of nerve conduction velocities.
Fabry disease (alpha-galactosidase A) In 2003, Mohrenschlager performed an extensive survey of this condition.12 Fabry disease is also referred to as angiokeratoma corporis diffusum universale because it manifests with generalized angiokeratomas.
This disease is uncommon and inherited as an X chromosome–linked lysosomal storage disease. The deficient enzyme, alpha-galactosidase A (alpha-gal A), causes the accumulation of neutral glycosphingolipids within vascular endothelial lysosomes.
Fabry disease can involve the skin, kidneys, heart, and brain. The disease manifests primarily in affected hemizygous men and, to some extent, heterozygous women (carriers).
Clinical manifestations include angiokeratomas, irregularities in sweating, edema, scant body hair, painful sensations, and manifestations of cardiovascular, gastrointestinal, renal, ophthalmologic, phlebologic, and respiratory involvement. A deficiency of alpha-gal A in serum, leukocytes, tears, tissue specimens, or cultured skin fibroblasts can define the diagnosis in men.
Multiple sulfatase deficiency (sulfatases) Multiple sulfatase deficiency is caused by mutations in the gene encoding the human C (alpha)-formylglycine–generating enzyme. Multiple sulfatase deficiency is an inborn error of metabolism that combines the clinical features of late infantile metachromatic leukodystrophy and MPS. Multiple sulfatase deficiency (OMIM 272200) is an autosomal recessive leukodystrophy associated with the deficiency of 7 sulfatases. Clinical manifestations include ichthyosis, broad thumbs and index fingers, progression of the neurologic symptoms, and hepatosplenomegaly.
GM1 gangliosidosis and Morquio B disease (beta-galactosidase) In 2000, Gosele noted that the Morquio syndrome is a rare autosomal recessive MPS.13
Morquio syndrome is characterized by a reduced activity of N -acetylgalactosamine-6-sulfate-sulfatase (type A), or beta-galactosidase (type B). This deficiency leads to a lysosomal storage disease with accumulation of keratan sulfate and chondroitin-6-sulfate in connective tissue, bones, and teeth. Pathology of the skeletal system, aortic valvular disease, and dental abnormalities occur. In the eyes, diffuse corneal opacification and alterations of the trabecular meshwork occur, occasionally leading to glaucoma.
Galactosialidosis (protective protein) Galactosialidosis is an autosomal recessive lysosomal storage disease caused by a combined deficiency of lysosomal beta-galactosidase and neuraminidase as a result of a primary defect in the protective protein/cathepsin A (PPCA). This disease can manifest with gargoylism, macular cherry-red spots, angiokeratoma, vertebral deformities, epilepsy, action myoclonus, and ataxia. Its onset is variable. GM2 gangliosidosis, Tay-Sachs and Sandhoff diseases (hexosaminidase)
Tay-Sachs disease (TSD), Sandhoff disease (SD), and variants are caused by deficient activity of the lysosomal enzymes hexosaminidase A (HA) and total hexosaminidase (TH), ie, hexosaminidase A plus B, respectively. These diseases manifest with early and fatal neurologic disease. Cystinosis (cysteine transporter)
In 2003, Kalatzis reviewed cystinosis.14 Cystinosis is a lysosomal transport disorder characterized by an intralysosomal accumulation of cystine, the disulfide of the amino acid cysteine. It is the most common inherited cause of the renal Fanconi syndrome.
Various clinical forms exist, infantile, juvenile, and ocular, based on age of onset and severity of symptoms. The causative gene is CTNS. CTNS encodes cystinosin, a novel 7 transmembrane domain (TM) protein.
Cystinosin is a lysosomal membrane protein that requires 2 lysosomal targeting signals: a classic GYDQL motif in its C-terminal tail and a novel conformational motif, the core of which is YFPQA, situated in the fifth inter-TM loop. Cystinosin is the lysosomal cystine transporter, and its activity is H+ driven. Sialic acid storage disease (sialic acid transporter) In 2003, Kleta reviewed this disease.15
Sialic acid storage disease results in developmental delays and growth retardation. It is part of the group of allelic lysosomal sialic acid storage disorders, Salla disease, and infantile free sialic acid storage disease (ISSD).
Because of defective free sialic acid transport out of lysosomes, these diseases are derived from mutations in the SLC17A5 gene coding for the protein sialin. Pyknodysostosis (cathepsin K) Pyknodysostosis is a rare sclerosing bone disorder that has an autosomal trait.
It is characterized by short stature, brachycephaly, short and stubby fingers, open cranial sutures and fontanelle, and diffuse osteosclerosis, where multiple fractures of long bones and osteomyelitis of the jaw are frequent complications. Metachromatic leukodystrophy (galactose-3-sulfatase) Metachromatic leukodystrophy is characterized by dysmyelination caused by a deficiency of arylsulfatase A. Metachromatic leukodystrophy is both a dysmyelinating and a demyelinating disease. The main clinical forms are infantile or juvenile, but some forms appear at adulthood. Galactosialidosis (neuraminidase, beta-galactosidase, protective protein) Neuronal ceroid lipofuscinosis, infantile (palmityl protein thioesterase)
Neuronal ceroid lipofuscinosis is also known as Batten-Bielschowsky disease.
This condition is a group of neurodegenerative disorders associated with various progressive symptoms including seizures, dementia, visual loss, and cerebral atrophy. Neuronal ceroid lipofuscinosis, late infantile (carboxypeptidase) Cobalamin deficiency type F (cobalamin transporter)
A common finding in MPS is pathologic states of the eye, which can include corneal opacification, retinopathy, optic nerve swelling and atrophy, ocular hypertension, and glaucoma.
Glycogen Storage Disease Type II Glycogen storage disease type II, or acid alpha-glucosidase (acid maltase) deficiency, is an inherited disorder of glycogen metabolism resulting from defective activity of the lysosomal enzyme alpha-glucosidase in tissues of affected individuals. In turn, this defect results in intralysosomal accumulation of glycogen of normal structure in numerous tissues.
Two major presentations are (1) infantile acid maltase disease, or Pompe disease, and (2) slowly progressive acid maltase disease.
Infantile acid maltase disease, or Pompe disease, is rapidly progressive and usually has an onset in the first 6 months of life. This manifestation is also characterized by macroglossia; progressive cardiomegaly; and rapidly progressive motor weakness with hypotonia, as indicated by feeding and respiratory difficulties. Death prior to age 2 years may be due to cardiorespiratory failure.
Slowly progressive acid maltase disease is characterized by an onset of symptoms in childhood or adult life. Affected individuals may have progressive proximal weakness with manifestations limited to the skeletal muscles. Respiratory dysfunction with early ventilatory insufficiency may be out of proportion to the degree of limb weakness.
The mode of inheritance is autosomal recessive, and the gene encoding for acid alpha-glucosidase has been localized to chromosome arm 17q23.
The disorder is genetically heterogeneous with missense, nonsense, and frameshift mutation, as well as splice-site and partial deletions.
Phenotypic expression is variable, and the severity is probably correlated with residual acid alpha-glucosidase activity.
Laboratory and imaging findings
Laboratory tests may show increased serum creatine kinase (CK) levels.
Electromyographic (EMG) studies may show myopathic features associated with fibrillation potentials, positive waves, bizarre high-frequency discharge, and myotonic discharges. In adult patients, EMG abnormalities are more evident in the paraspinal muscles than elsewhere.
Electrocardiographic findings of short P-R interval, giant QRS complexes, and left ventricular or biventricular hypertrophy
In infantile forms, massive cardiomegaly is shown on chest radiography.
Results of pulmonary function tests show markedly decreased vital capacity, maximal breathing capacity, maximal expiratory, and inspiratory static pressure, as well as early diaphragmatic fatigue.
Diagnosis and differential diagnosis
The clinical diagnosis of glycogen storage disease type II is confirmed by absent or reduced activity in the slowly progressive form of acid glucosidase in muscle biopsy samples and cultured fibroblasts. Prenatal diagnosis is made by measuring alpha-glucosidase activity in cultures of amniotic cells and samples of chorionic villus.
The differential diagnosis includes Duchenne muscular dystrophy, dystrophy of the limb girdle dystrophy, and polymyositis
Conventional treatment for cardiorespiratory problems is indicated.
Definitive therapy is not currently available.
Enzyme therapy, gene replacement, or both are theoretically feasible, and research in these treatments is in progress. Recombinant human enzyme alpha-glucosidase (rhGAA) has recently been designated an orphan drug by the FDA. It has shown improved infant survival without requiring invasive ventilatory support compared with historical controls without treatment.
In 2005, Marsden et al compiled a report of physician narratives from an epidemiologic study regarding infantile-onset Pompe disease. In this report, the most common presenting symptom was hypotonia (75%), and muscle weakness was a presenting symptom in 59% of patients. Additionally, the sign most commonly noted during the physical examination was hypotonia (82%); respiratory distress, cardiomegaly, weakness, and cardiac failure were frequently reported but percentages were not specified. Progression of the disease was accompanied by increased respiratory distress (72%), hypotonia (66%), and cardiac failure (58%). The most frequent supportive treatments were cardiac medications (52%) and oxygen supplementation (35%).17
Mucopolysaccharides are sulfated polymers composed of a central protein moiety attached to repeating disaccharide branches normally degraded into inorganic sulfated monosaccharides in lysosomes.
Dermatan sulfate consists of alternating units of L-iduronic acid and N -acetylgalactosamine, usually found in the matrix of many different connective tissues.
Heparan sulfate is formed by the joining of a uronic acid (D-glucuronic acid or L-iduronic acid) alternating with N -acetylglucosamine and is associated with the cell plasma membrane of almost all cells.
Keratan sulfate is made of D-galactose residues alternating with N -acetylglucosamine and is found largely in cartilage, nucleus pulposus, and cornea.
Chondroitin sulfate is composed of D-glucuronic acid and N -acetylgalactosamine and is largely found in cartilage and cornea.
MPSs result from abnormal degradation of glycosaminoglycans such as dermatan sulfate, keratan sulfate, heparan sulfate, and chondroitin sulfate resulting in organ accumulation and eventual dysfunction. Glycosaminoglycans or mucopolysaccharides are normally a component of the cornea, cartilage, bone, connective tissue, and the reticuloendothelial system and are therefore target organs for excessive storage. The catabolic enzymes involved in the breakdown of glycosaminoglycans or mucopolysaccharides are deficient. Ten known enzyme deficiencies give rise to 6 distinct MPSs.
The stepwise degradation of the glycosaminoglycans requires 4 glycosidases, 5 sulfatases, and 1 nonhydrolytic transferase. The MPSs share similar clinical features of a chronic and progressive course, multisystem involvement, organomegaly, dysostosis multiplex, and abnormal facies. Mode of transmission is autosomal recessive except for MPS II, which is X-linked. A variety of mutations are described, and correlation of genotype with disease severity is beginning to emerge from mutation analysis.
In general, MPSs are progressive disorders, characterized by involvement of multiple organs, including brain, liver, spleen, heart and blood vessels and many are associated with coarse facial features, clouding of the cornea and mental retardation. Diagnosis can often be made by examination of urine, which reveals increased concentration of glycosaminoglycan fragments.
MPS type I includes Hurler, Hurler-Scheie, and Scheie syndromes. Alpha-L-iduronidase, which cleaves terminal L-iduronic acid residues from both dermatan and heparan sulfate, is deficient.
MPS type I H (Hurler syndrome) Excretion of dermatan sulfate and heparan sulfate in the urine is increased in a ratio of 2 to 1. A chromosomal abnormality occurs in chromosome arm 4p16.3. This is a progressive disorder with multiple organ and tissue involvement leading to death by age 10 years. Affected newborns appear healthy. At age 6-24 months, hepatosplenomegaly, skeletal deformities, coarse facial features, enlarged tongue, prominent forehead, and joint stiffness develop. Patients may be large in infancy, but a deceleration of growth occurs at age 6-18 months. Developmental delay is present by age 12-24 months, with a maximum functional age obtainable at 2-4 years, followed by progressive deterioration. Patients develop only limited language skills because of the developmental delay, chronic hearing loss, and enlarged tongue. Most children with Hurler syndrome have recurring upper respiratory tract and ear infections, noisy breathing, and persistent copious nasal discharge. Ophthalmologic manifestations include corneal clouding and glaucoma. Blindness may develop. Neurologic manifestations include communicating hydrocephalus with increased intracranial pressure due to decreased resorption of cerebrospinal fluid (CSF). Life expectancy is markedly reduced with average age of death at 5 years and nearly all succumb by 10 years. MPS type I H/S This form is intermediate between the Hurler syndrome and Scheie syndrome. It is characterized by progressive somatic involvement, with little or no intellectual deterioration. Corneal clouding, joint stiffness, deafness, valvular heart disease (occurring in the early to middle teenaged years), and micrognathism occur. Neurologic manifestations include pachymeningitis cervicalis, compression of the cervical cord due to mucopolysaccharide accumulation in the dura, but communicating hydrocephalus appears to be uncommon in patients with normal intelligence. Onset of symptoms is observed at age 3-8 years, and survival to adulthood is common. Cardiac involvement and upper airway obstruction lead to mortality. MPS type I S Biochemical findings are identical to type I Hurler syndrome, but the clinical features are less severe because of different mutations within the same gene coding for alpha-L-iduronidase on chromosome 4. Mildly coarsened facies occurs. Joints are stiffened, and the skeletal abnormalities are most pronounced in the hands, with claw hand deformity. Patients can have a stiff painful foot, pes cavus, and genu valgum. Patients achieve normal stature and have normal intelligence. Neurologic manifestations include pachymeningitis cervicalis and deafness. Entrapment neuropathy such as carpal tunnel syndrome is common. Ocular findings include glaucoma, corneal clouding, and retinal degeneration. Respiratory symptoms of obstructive airway disease cause sleep apnea. Cardiac symptoms of aortic valvular disease with stenosis and regurgitation occur due to buildup of mucopolysaccharides on valves and chordae tendinea. Life expectancy is longer than in Hurler syndrome and is dependent on degree of cardiac involvement. Onset of symptoms is usually after 5 years, with the diagnosis commonly made in patients aged 10-20 years. MPS type II (Hunter syndrome) Purified human recombinant idursulfase has been shown to alter disease manifestations in individuals with Hunter syndrome. Idursulfase has now been approved in the United States, Europe, Canada, and Japan for the treatment of Hunter syndrome.18 Iduronate-2 sulfatase (known as the Hunter corrective factor), which specifically removes the sulfate group from the 2 position of L-iduronic acid in dermatan sulfate and in heparan sulfate, is deficient. Transmission is X-linked recessive, with the abnormality mapped to Xq27/28. The distinctive feature of MPS II is the occurrence of a pebbly ivory-colored skin lesion over the back, upper arms, and lateral aspects of the thigh, but its presence or absence does not correlate with the severity of the disease. The phenotype is variable, ranging from a severe form similar to Hurler syndrome to a mild form analogous to MPS I S. In the severe form, the somatic features include coarse facial features, short stature, skeletal deformities, and joint stiffness. The onset of the disease usually occurs in patients aged 2-4 years, with progressive neurologic involvement and somatic involvement. Eye findings include severe retinal degeneration, but the cornea remains clear with 1 recorded exception. The neurologic symptoms include hearing impairment and compression neuropathy. Neurologic involvement may include mental retardation and moderate-to-severe communicating hydrocephalus with increased intracranial pressure after age 7-10 years. Extensive neurologic involvement similar to late stages of Sanfilippo syndrome precedes death, which usually occurs at age 10-15 years. Cardiac manifestations include severe diffuse coronary artery disease. Skeletal abnormalities are described as dysostosis multiplex with a large skull with thickened calvaria, premature closure of the lambdoidal and sagittal sutures, shallow orbits, enlarged J-shaped sella, abnormal spacing of teeth with dentigerous cysts, and anterior hypoplasia of lumbar vertebra with kyphosis. The diaphyses of the long bones are enlarged with irregular appearances of the metaphyses. Epiphyseal centers are not well developed. The pelvis is usually poorly formed with small femoral heads and coxa valga. The clavicles are short, thickened, and irregular. The ribs have been described as oar-shaped, narrowed at their vertebral ends and flat and broad at their sternal ends. Phalanges are shortened and trapezoidal in shape with widening of the diaphysis. In the mild form, intelligence is preserved and patients survive into late adulthood but with obvious somatic involvement. The somatic features may be similar to those of Hunter syndrome but with greatly reduced rate of progression. The eye findings include corneal opacities detected only by slit-lamp examination, retinal dysfunction, and chronic papilledema. Patients may survive into the fifth or sixth decades of life, with the longest known survival to age 87 years. Mortality results from cardiorespiratory dysfunction (ie, obstructive airway disease, cardiac failure due to valvular dysfunction, myocardial thickening, pulmonary hypertension, coronary artery narrowing, myocardial disease). MPS type III (Sanfilippo syndrome) This is a biochemically diverse but clinically similar group of 4 types (A, B, C, and D). Deficiencies in heparan N -sulfatase (type A), alpha N -acetylglucosaminidase (type B), acetyl CoA:alpha-glucosaminide acetyltransferase (type C), and N -acetylglucosamine 6-sulfatase (type D) can occur. All 4 enzymes are required for the degradation of heparan sulfate. All 4 forms have autosomal recessive inheritance. Alpha-N -acetylglucosaminidase is required for removal of the N -acetylglucosamine residues that exist in heparan sulfate or are generated during lysosomal degradation of this polymer by the action of acetyl CoA transferase. Heparan N -sulfatase (deficiency occurs in MPS III A) is specific for sulfate groups linked to the amino group of glucosamine. The enzyme deficient in the very rare MPS III D is localized to chromosome arm 12q14 by in situ hybridization. MPS III C is not characterized by a deficient hydrolase, but rather, a deficient catalyst for the acetylation of the glucosamine amino groups that have become exposed by the action of heparan-N -sulfatase. The distinguishing feature is severe central nervous system degeneration but only mild somatic disease. The onset of clinical features usually occurs at age 2-6 years in a previously normal child. Presenting features can include hyperactivity with aggressive behavior, delayed development, coarse hair, hirsutism, sleep disorders, and mild hepatosplenomegaly. Incidence of false-negative results is usually high in the urinary screening test for MPS. Gastrointestinal symptoms include recurrent and severe diarrhea. Neurologic manifestations include delayed speech development, severe hearing loss, and seizures. Deterioration is severe by age 6-10 years and is accompanied by severe rapid deterioration in social and adaptive skills. Progressive dementia occurs, with cortical atrophy visible on CT scanning. Sleep disturbances and insomnia are common. Severe behavioral problems occur, with poor attention span, uncontrollable hyperactivity, temper tantrums, destructive behavior, and physical aggression. Although any of the 4 types may be difficult to distinguish clinically, type A is the most severe, with earlier onset, more rapid progression of symptoms, and shorter survival. Type B may be heterogeneous, with severe and mild forms reported even within the same family. Type C appears to be intermediate between type A and milder type B forms. Type D appears heterogeneous also. MPS type IV (Morquio syndrome) MPS IV results from defective degradation of keratan sulfate. Two enzyme deficiencies are recognized: N -acetylgalactosamine-6-sulfatase (also known as galactose-6-sulfatase) in type IV A, and beta-galactosidase in type IV B. MPS IV A is localized to chromosome arm 16q24. The somatic manifestations include short trunk dwarfism and a skeletal dysplasia (spondyloepiphyseal) distinct from that of the other MPSs, with joint laxity, genu valgus, kyphosis, growth retardation with short trunk and neck, and a waddling gait and a tendency to fall. Typical skeletal anomalies include dwarfism with short trunk, platyspondyly, odontoid hypoplasia, kyphosis, hyperlordosis, scoliosis, ovoid deformities of the vertebrae, genu valgum, ulnar deviation of the wrist, valgus deformity of the elbow, inclination of the distal ends of the radius and ulna toward each other, deformities of the metacarpals and short phalanges and epiphyses, deformities of the tubular bones, widened metaphyses, and osteoporosis. Joints tend to be hypermobile secondary to ligamentous laxity, but decreased joint mobility can occur in the large joints, especially hips, knees, and elbows. Odontoid hypoplasia occurs with instability resulting in atlantoaxial subluxation as well as cervical myelopathy; this is also reported in MPS I and VII. Extraskeletal manifestation may include mild corneal clouding, hepatomegaly, cardiac valvular lesion, and small teeth with abnormally thin enamel and frequent caries formation. Unusual facial features (eg, coarsening of facies, prognathism, broad mouth) are commonly found. Cardiac signs of aortic regurgitation or congenital heart defects may be present. Birth is normal, with onset of symptoms at age 1-3.5 years, although the diagnosis is usually established in patients aged 3-15 years. MPS type VI (Maroteaux-Lamy syndrome) A deficiency in arylsulfatase B (ie, N -acetylgalactosamine 4-sulfatase) occurs. It hydrolyses the sulfate group in the 4 position of N -acetylgalactosamine residues of dermatan sulfate. The chromosome abnormality is localized to 5q13-q14. The phenotype similar to Hurler syndrome involves preservation of intelligence and excretion of predominantly dermatan sulfate in urine. Corneal clouding and hepatosplenomegaly also occur. The gene abnormality is located in chromosome arm 5q13.3. Severe skeletal anomalies occur, with limitation of joint movement and stunted linear growth in early childhood. Cardiac involvement is related to aortic and mitral valvular dysfunction from thickened calcified stenotic valves. Neurologic complications include hydrocephalus secondary to pachymeningitis, nerve entrapment syndrome, and myelopathy from dural thickening or vertebral body abnormalities or both. Death typically occurs from heart failure. MPS type VII (Sly syndrome) MPS VII is caused by a deficiency in beta-glucuronidase, which removes the glucuronic acid residues present in dermatan sulfate, heparan sulfate, and chondroitin sulfates. The abnormality is localized to chromosome arm 7q21.1-q22. Excessive urinary excretion of dermatan and heparan sulfate occurs. An abnormal gene location on chromosome arm 7q21.1-q22 produces a milder form of later onset. Features include dysmorphic facies, protruding sternum, hepatosplenomegaly, umbilical hernia, thoracolumbar gibbus, marked vertebral deformities, find corneal opacities, moderate mental deficiency, and radiologic changes of moderately severe dysostosis multiplex. The distinguishing features are excess glycosaminoglycan excretion and granulocytes showing striking coarse metachromatic granules.
Thanks Aqt for helping. That's a bit much for me - I'm going to leave the medical part to you gals that have more knowledge there. I think I saw somewhere the symptom list for Morgellons, we might want to look at that? And, especially the case study blood numbers compare those to other diseases that we're trying to pinpoint? Whichever direction you all want to look in... fine.
This last sentence above caused me to look it up to see what is that?:
"The distinguishing features are excess glycosaminoglycan excretion and granulocytes showing striking coarse metachromatic granules."
AMPHOTERIC SURFACTANTS CONTAINS BOTH AN ACIDIC & A BASIC HYDROPHILIC MOIETY IN THEIR SURFACE e.g.,
1. N -COCO 3-AMINOPROPIONIC ACID/ SODIUM SALT 2. N-TALLOW 3 -IMINODIPROPIONATE, DISODIUM SALT 3. N-CARBOXYMETHYL N DIMETHYL N-9 OCTADECENYL AMMONIUM HYDROXIDE. 4.N-COCOAMIDETHYL N HYDROXYETHYLGLYCINE, SODIUM SALT
"Dimethyl sulfoxide (DMSO) is the organosulfur compound with the formula (CH3)2SO. This colorless liquid is an important polar aprotic solvent that dissolves both polar and nonpolar compounds and is miscible in a wide range of organic solvents as well as water. It penetrates the skin very readily, giving it the unusual property of being secreted onto the surface of the tongue after contact with the skin and causing a garlic-like taste in the mouth."
Other names: Methylsulfinylmethane Methyl sulfoxide
DMSO is a polar aprotic solvent and is less toxic than other members of this class, such as dimethylformamide, dimethylacetamide, N-methyl-2-pyrrolidone, and HMPA. DMSO is frequently used as a solvent for chemical reactions involving salts, most notably Finkelstein reactions and other nucleophilic substitutions. It is also extensively used as an extractant in biochemistry and cell biology.
DMSO is finding increased use in manufacturing processes to produce microelectronic devices.
DMSO is a common ligand in coordination chemistry. The complex dichlorotetrakis(dimethyl sulfoxide)ruthenium(II), RuCl2(dmso)4, features DMSO bonded to ruthenium through sulfur and through oxygen.
Because DMSO easily penetrates the skin, substances dissolved in DMSO may be quickly absorbed. For instance, a solution of sodium cyanide in DMSO can cause cyanide poisoning through skin contact. DMSO by itself has low toxicity. Dimethyl sulfoxide can produce an explosive reaction when exposed to acid chlorides; at a low temperature, this reaction produces the oxidant for Swern oxidation.
Recently, DMSO disposed into sewers caused odor problems in cities: waste water bacteria transform DMSO under hypoxic (anoxic) conditions into dimethyl sulfide (DMS) that has a strong disagreeable odor, similar to rotten cabbage.
Varying oxidation of sulfur Dimethyl sulfide (DMS), the corresponding sulfide, also produced by marine phytoplankton and emitted to the oceanic atmosphere where it is oxidized to DMSO, SO2 and sulfate
Methylsulfonylmethane (MSM), a related chemical often marketed as a dietary supplement, although its benefits are disputed.
Related isomeric forms with methyl on oxygen
Dimethyl sulfite, the corresponding sulfite
Dimethyl sulfate (also DMS), the corresponding sulfate: a mutagenic alkylating compound"
"Organosulfur compounds are organic compounds that contain sulfur. Nature abounds with organosulfur compounds—sulfur is essential for life. Two of the 20 common amino acids are organosulfur compounds. Fossil fuels, coal, petroleum, and natural gas, which are derived from ancient organisms, necessarily contain organosulfur compounds, the removal of which is a major focus of oil refineries."
"To understand MSM, some background information is necessary. MSM is a "naturally-occurring nutrient found in normal human diets" (1). It gets into the diet through the sulfur cycle. Ocean plankton release sulfur compounds which rise into the ozone where ultra-violet light makes MSM and DMSO. DMSO, dimethyl sulfoxide, is a precursor to MSM. MSM and DMSO return to the surface of the earth in rain (1). Plants concentrate MSM and return it to the earth and the sea. Evaporation into the air results in their return to the earth (1).
MSM has a unique action on body tissues. It decreases the pressure inside the cell. In removing fluids and toxins, sulfur affects the cell membrane. MSM is an organic form of sulfur, whereas sulfites in foodstuffs are inorganic. Sue Williams states "sulfur is present in all cells" and is in the form of "organic compounds throughout the body’ (2). However, sulfur can be found in the body in sulfate forms. It forms sulfate compounds with sodium, potassium, magnesium, and selenium. MSM has a significance, because sulfur compounds are found everywhere throughout the body and in nature.
Sulfur has an indirect importance, because sulfur compounds play a role in many body organs and systems. Sulfur is in the hair, skin, and nails. Many amino acids, the building blocks of protein, have sulfur as a component. Taurine is a sulfur-containing amino acid formed from methionine (2). Taurine stabilizes cell membranes (2). Methionine contains sulfur, detoxifies cells, and is involved in pain relief (2). Carnitine comes from methionine and transports long chain fatty acids preventing accumulations of lipoproteins (2). Many B-complex vitamins interact with or contain sulfur. Sulfur is needed for insulin production.
For those who do not want to take MSM as a supplement, food sources of sulfur are as follows: sunflower seeds, garlic, lentils, soybeans, and yogurt. Persons with kidney problems or recurrent kidney stones may not want to take MSM. Certain renal tubular defects can make a person susceptible to recurrent kidney stones (2). Other kidney defects include errors of metabolism in which processing of sulfur amino acids is altered (2). Such persons may wish to avoid MSM.
MSM is not a medicine, a drug, or a food additive. It is a food. MSM is an organic form of sulfur that can be easily absorbed and utilized by the body. Although DMSO and MSM are chemically similar, each is unique. MSM is a pure, stable, white crystalline powder without the unpleasant smell or taste of DMSO.
There is a positive synergistic effect on building healthier cells when MSM is taken in combination with vitamin C.
When skin cells are soft and permeable, many toxins can be eliminated through the sweat glands, which takes some of the load off the liver and kidneys. While MSM is not a cure for allergies, supplementation may reduce symptoms by allowing allergens to be removed from the body more quickly."
Questions: Hair of the dog, good or bad? I think good because it helps remove 'allergens' quickly from the body.
Not all organosulfur compounds are foul-smelling pollutants. Compounds like allicin and ajoene are responsible for the odor of garlic, and lenthionine contributes to the flavor of shiitake mushrooms. Many of these natural products also have important medicinal properties such as preventing platelet aggregation or fighting cancer."
More hair of the dog - garlic & shiitake mushrooms?
"Abstract Methane and ethane are more soluble in dimethyl sulfoxide and acetone than in water at room temperature. This datum is rationalized by showing that the work of cavity creation is smaller in dimethyl sulfoxide and acetone than in water. The difference between dimethyl sulfoxide and water is not large, but is in line with the proposed direct proportionality between the work of cavity creation and (a) the surface tension, (b) the inverse of the isothermal compressibility, and (c) the cohesive energy density of the liquid."
"In the 1930s, a popular remedy for diabetes promoted by the Kaadt Diabetic Institute turned out to be a worthless mixture of vinegar and salt pepper. But that didn’t stop people from buying the concoction that earned an estimated $6 million for its promoters, Drs. Charles and Peter Kaadt.
The Kaadt brothers told patients they could forget their diet, eat anything they want including ice cream, cake, and other sweets, and not waste time monitoring their blood sugar levels. This led to the death of several patients.
DMSO or dimethyl sulfoxide has been used since the 1940s as an industrial solvent. Its therapeutic use started in the 1960s when it was prescribed for a variety of diseases, including diabetes. Diabetics were told they could reduce insulin requirements by as much as 50 percent and they could consume sugar regularly if they took DMSO. This chemical can be taken orally, rectally, rubbed into the skin, or injected.
Despite its appeal, there is no evidence that DMSO can cure diabetes or other diseases. After reviewing thousands of articles on DMSO, the FDA and the National Academy of Sciences concluded that DMSO has very limited uses but plenty of potential hazards when taken in large doses.
With topical applications of DMSO, the patient could experience burning, itching, local and general dermatitis, and bad breath. Possible kidney and eye damage may follow the use of large amounts while using DMSO as an enema could be fatal.
“The FDA has approved DMSO only for the treatment of interstitial cystitis, an uncommon bladder disease. DMSO has not been shown to alter the course of any other disease. For some diabetics, (using DMSO) could produce acidosis, possibly progressing to coma,” warned Dr. Stephen Barrett and the editors of Consumer Reports Books in Health Schemes, Scams and Frauds."
"I have also found it has a profound beneficial effect in the treatment of Crohn's Disease. It is the purpose of this Health Note to present my new insight/views into that needed description of the primary biochemical function of DMSO in combination with its spontaneously created oxidized form, MSM.
The primary mechanism discussed here is how I believe DMSO, in combination with its spontaneously generated oxidized form, MSM, act as an antioxidant pair, in the same sense as I discuss other antioxidants in the previous Health Note, in other words the biochemistry of how DMSO and MSM act together to enhance metabolism.
Oxidation States of DMSO
In the body, DMSO can and does take three different oxidation states. It is useful to think of them as being in equilibrium, with the distribution between them at any point being determined by the localized conditions that exist within the cells. The first oxidation state is DMSO itself which has one oxygen atom attached to the sulfur atom. The other two are 1) dimethyl sulfone, also known as methlysulfonylmethane (MSM), which is DMSO with an additional oxygen atom attached to the sulfur atom, forming a molecule with a total of two attached oxygen atoms, and 2) dimethyl sulfide which is DMSO with the oxygen atom removed, forming a molecule with no oxygen's attached. Both DMSO and MSM have the property of being quite soluble in both oil and water based liquids. However, dimethyl sulfide is hydrophobic and tends to be insoluble in water and soluble in oil-based liquids.
DMSO and MSM
It should be mentioned here that dimethyl sulfone, the oxidized form of DMSO, is just the more commonly used chemical name for methlysulfonylmethane (MSM) which is now readily available in health foods stores, and which many claim to greatly enhance energy. According to my theory presented here, DMSO and MSM, which form each other in the body, should be essentially indistinguishable in their biochemical effects. They reach a equilibrium distribution between them that is dependent on the local body chemistry, and is independent of which one you start with.
The Metabolic Enhancement (Antioxidant) Mechanism of the DMSO-MSM Pair
The metabolic enhancement mechanism of DMSO (or MSM) is that of an exceptionally effective oxygen transport system. This transport system involves only two of the three oxidation forms, DMSO and dimethyl sulphone (also known as MSM). If we consider both DMSO and MSM coexisting in equilibrium within the body, (as they always would no matter which you started with) and recognizing that different parts of the body have different oxidation potentials. Then, as the combination is exposed to a zone of high oxidation potential, DMSO is oxidized to MSM resulting in a new distribution of DMSO and MSM, which is higher in MSM. Then as the combination moves to a zone of lower oxidation potential, the MSM releases its oxygen, delivering it to the metabolic processes, resulting in a new distribution that is higher in DMSO again. The cycle then repeats itself and in doing so, serves as an exceptionally effective oxygen transport system. This system could be operative on a macro scale, enhancing the transport of oxygen from the lungs to the blood, from the blood to the cells, and on a micro scale within the cells transporting high oxidation potential to the lower oxidation potential of the mitochondria where it is used in metabolism. We have a continuously decreasing oxidation potential starting highest at the entry point, the lungs, lower in the blood, lower yet as it enters the cells, continuously lowered in the sequences of the metabolic reactions, and finally lowest of all as it is excreted as carbon dioxide and water, the products of metabolism. The DMSO-MSM system of transport will operate only at the front end, delivering oxygen to the mitochondria. It is unlikely that it will play a significant role after the oxygen has been delivered to the mitochondria and the complex metabolic reaction sequences start.
This system is made particularly effective by the feature that both DMSO and MSM are highly soluble in both oil and water. They are also small molecules that will diffuse rapidly. Thus, they both easily and rapidly diffuse through the hydrophilic cell cytoplasm as well as the hydrophobic cell membranes. They have no barriers. To my knowledge, we have no other molecules naturally occurring in our bodies quite like this. Oxygen transport is handled by passing it between different molecules that are hydrophilic in the cytoplasm and hydrophobic in the cell membranes. (Actually, this is handled in part by the transport of free electrons, which can be the equivalent of oxidation potential.)
Since we obtain DMSO from a plant source, do plants use it this way? More importantly, is it an important, but unrecognized component we obtain from eating plants that greatly assists our metabolism? It may be no accident that the body develops a garlic smell when one uses DMSO. Could the breakdown of known active components in garlic be a potent plant source of DMSO, which would explain some of the greatly touted health benefits of garlic? These are unanswered but reasonable questions.
The "Garlic" Body & Breath Odor from Dimethyl Sulfide Derived from DMSO
The elimination of DMSO and MSM happens not only by excretion in the urine and feces but also by elimination through the lungs and skin in the form of dimethyl sulfide. When DMSO gives up its oxygen atom it forms dimethyl sulfide, which is hydrophobic. Because of its hydrophobic property, it will concentrate not only in the cell membranes but also in the interior regions of the hemoglobin molecule. The exterior of the hemoglobin molecule is hydrophilic and thus can "dissolve" in a aqueous media and be carried in the blood. However, the interior is hydrophobic. Any dimethyl sulfide that is formed will eventually migrate to the interior of the hemoglobin molecule and as such be transported everywhere in the blood. However, it has a high vapor pressure so anywhere the blood vessels come in close contact with air, such as in the lungs and skin, there will be a tendency for the dimethyl sulfide to evaporate off and be released. In this way we get both the "garlic" breath and the "garlic" body odor.
In theory, there is another option for the dimethyl sulfide. When it is transported to the lungs where you have the highest oxidation potential, it could be oxidized back to DMSO, go back into solution, and not be released as dimethyl sulfide to the breath. Does this also happen? I believe it does. However, the conversion is not complete and can vary from one individual to the next and from one time to the next for a particular individual.
A First-Line Treatment for A Multitude of Medical Diseases/Disorders
Once it is understood that DMSO (& MSM) acts as a profoundly effective oxygen transport system, this opens up the opportunity to use this information to treat a multitude of medical disorders, immediate and long term that are caused by a deficiency of oxygen transport. As one example, it has been reported that DMSO is greatly helpful in minimizing the damage from a traumatic brain injury due to a blow to the head or a stroke."
Ok, this is exactly what I described earlier that I suspected was happening without even knowing this information! This DMSO/MSM process is at the center of our disease or a very important aspect... whatever is happening here in the body. Is ours malfunctioning...? or how can we help this system to operate better?
I suspect we aren't going to find a lot written around this subject for many reasons, I hope I'm wrong - just have to look at the different terminologies to find related material. He is describing in theory what happens... It is:
"However, it has a high vapor pressure so anywhere the blood vessels come in close contact with air, such as in the lungs and skin, there will be a tendency for the dimethyl sulfide to evaporate off and be released."
"In theory, there is another option for the dimethyl sulfide. When it is transported to the lungs where you have the highest oxidation potential, it could be oxidized back to DMSO, go back into solution, and not be released as dimethyl sulfide to the breath. Does this also happen? I believe it does. However, the conversion is not complete and can vary from one individual to the next and from one time to the next for a particular individual."
"go back into solution, and not be released as dimethyl sulfide to the breath."
I believe something like this second option is happening with us - we are not allowed to release the ever-changing, ever more toxic particles - as time goes by and the state of the atmosphere gets worse daily. Need to look at air quality indexes and oxygen levels in the air over time.
Goes back into what kind of 'solution'? Particles, crystals, micelles... into fibers?
Why is he having to write in theoretical form? His credentials are: "I have a formal education in chemistry and chemical engineering and am now retired after spending more than 30 years performing research at a national laboratory."
Morgellons is a deficiency of the oxygen transport system, that operates individually in people, where the dimethyl sulfide is not being released to the breath. ?
This site has lots of different topics to click on that might relate? I just saw in his Chronic Fatigue page where he talks about having a low body temperature, which we all do as per our case study... and what that means in this regard. I'm still studying his pages:
"Proposed Biochemical Mechanisms for DMSO Mitigating Crohn's Disease
The Proposed Biochemical Cause of Crohn's Disease
I propose that the cause of Crohn's Disease is oxidative attack on the intestine, and not an autoimmune attack. Specifically, the attack follows the Haber-Weiss reaction where ferrous ions catalyze the dissociation of biochemically-produced hydrogen peroxide into highly reactive hydroxyl radicals. The excessively high production rate of hydroxyl radicals then produces cellular damage in the intestine. The reaction goes as follows:
H2O2 + Fe(+2) = Fe(+3) + OH- + HO
hydrogen peroxide + ferrous ions react to produce ferric ions + hydroxyl ions + hydroxyl free radicals
This reaction is always taking place in normal cells and can play a constructive metabolic role by helping with the initial oxidation of fats in the peroxisomes. However, for people with Crohn's Disease, it takes place to excess."
How close is the Fenton's Reaction to the Haber-Weiss reaction, sounds very similar?
The single primary source of oxidants in the body is the oxygen in the air you breathe. This provides the initial source of oxygen that gets converted into a variety of oxidation species, some beneficial and some damaging. The single final reducing agent and thus the single final antioxidant is the food you eat. The food reacts with and thus reduces the oxygen and thus oxidative species producing carbon dioxide and water and the energy necessary for life in the process. This process is called aerobic metabolism. All the so-called antioxidants are simply ingredients that facilitate this process. The more it is facilitated the more rapidly oxidative species (that may be damaging) are reduced and converted into carbon dioxide and water. Thus, antioxidants are molecules that stimulate aerobic metabolism.
Aerobic metabolism takes place in the mitochondria in the cells. For discussion, I like to divide aerobic metabolism into three basic segments, 1) Oxygen transport to the mitochondria, 2) The Citric acid (Krebs) Cycle, and 3) Respiratory Chain. Each of these steps has sub-steps. They all act in sequence and thus they must all be operating for aerobic metabolism to take place. Thus, they must all be operating for a powerful antioxidant formulation to be maximally effective.
The Alpha Lipoic Acid Example:
Alpha lipoic acid (ALA) is well known for its antioxidant properties. It is thoroughly discussed in the book "The Antioxidant Miracle" by Packer & Coleman. However, this book points out that it is most effective when used in a complex comprising of ALA, vitamin C, vitamin E and Coenzyme Q10 (CoQ10). This combination has been found particularly effective as discussed in the book. I will present my explanation as to why in the context of stimulating aerobic metabolism (not explained in the book). The ALA stimulates the production of glutathione (described in the book). Both have the property of having stable oxidized and reduced states and can penetrate cell walls. They can be oxidized by oxidative species and then reduced again by a reduced species. Once oxidized they can be reduced by vitamin C which also has a stable oxidized and reduced state. This regenerates the reduced ALA. The vitamin C is soluble in the aqueous phase of the cell, the cytoplasm, and diffuses freely there. It diffuses to the cell wall. Vitamin E is soluble in the cell wall and also has a stable oxidized and reduced state. The oxidized vitamin C oxidizes the vitamin E in the cell wall, regenerating the reduced vitamin C. The oxidized vitamin E can then pass this on to vitamin C on the other side of the cell wall. Eventually, the oxidized vitamin C reaches the inner membrane of the mitochondria where it delivers its oxidation potential to CoQ10 dissolved in that membrane. This is where the final stage of aerobic metabolism takes place and the CoQ10 us reduced by a process that produces useful biochemical energy in the Respiratory Chain stage of aerobic metabolism. Without this sequence, the oxidized ALA would not be regenerated and it would be ineffective as an antioxidant. However, it should be noted that this complex only the oxygen transport stage of aerobic metabolism. Apparently it was sufficient to cure mushroom poisoning adding only ALA and employing the individual's reserve of the other components.
As applied to anthrax. The reduced ALA will hopefully penetrate the membranes of the infected macrophages, become oxidized, and the oxidized version transported out to be regenerated by vitamin C which triggers the rest of the regeneration sequence. As the cycle is repeated many times the oxidation species in the infected macrophages are eliminated or held to a concentration where the oxidative burst does not take place. Thus, anthrax toxicity is arrested.
The DMSO Example:
In one of my web pages (www.krysalis.net/dmso.htm) I describe how DMSO forms equilibrium with MSM, its oxidized state and the two together form a powerful oxygen transport system. Basically, DMSO has one oxygen atom and MSM has two. As the solution (in the blood) circulates to the lungs, which have a high oxidation potential, the equilibrium shifts to a higher concentration of MSM. As the oxidized equilibrium circulates to the cells where metabolism takes place, oxygen from some of the MSM is delivered to the inner membrane of the mitochondria and used for aerobic metabolism. This shifts the equilibrium back to more DMSO, the reduced state. The solution (in the blood) circulates back to the lungs and the process is repeated. We thus have created an oxygen transport system that can actually exceed the oxygen transport capacity of hemoglobin. (I should mention the recognized expert for both DMSO and MSM, Stanley Jacob, upon discovering this web page was kind enough to call me and congratulate me on the new significant insight as to the mechanism of DMSO and MSM.) This works not just on the macro scale transporting oxygen to cells from the lungs, but can also work on the micro scale transporting oxygen potential in and out of any individual cell. One of the particularly attractive features of this approach is that DMSO is well known for its ability to pass through any membrane, and diffuse rapidly because of its small size. The infected macrophages could not prevent its entry or MSM's exit. DMSO (the DMSO-MSM equilibrium) thus can serve as an "oxidation potential buffer" holding the oxidation potential of the macrophages down, close to that of their surroundings. This would then limit the ability of the macrophages to produce highly oxidative species and thus inhibit its ability to go through an oxidative burst, thus stopping the progression of the disease at that stage. If this is effective, and it should be, it should arrest the lethal progression of anthrax. Can enough be use safely to achieve this? In Dr. Jacob's book "The Miracle of MSM" he discusses both DMSO and MSM. One of the points he makes is the very low toxicity of both. The only thing lower appears to be water. Thus, very high doses of DMSO could be considered an emergency treatment for anthrax. I would use DMSO instead of MSM because even if either will produce the other, you want to start with the reduced species."
"As the cycle is repeated many times the oxidation species in the infected macrophages are eliminated or held to a concentration where the oxidative burst does not take place."
This 'explosion' that I referred to and as seen in Baraka's video - is this an 'oxidative burst'? I'm thinking - most likely.
This oxidative burst is the catalyst that causes the micelles to start forming the filaments or hyphae of our 'fungus'. To keep the micelles from getting to this state would be most beneficial for us.
"They can be oxidized by oxidative species and then reduced again by a reduced species." What's are these species?
Macrophages - what are they in relation to what I've been describing?
More about Alpha lipoic acid (ALA) and/or glutathione as supplements?
In a protocol - ALA, vitamin C, vitamin E and Coenzyme Q10?
Luminol-enhanced chemiluminescence (LECL) was used to determine the effect of soluble CD14 (sCD14) on the endotoxin inducible generation of reactive oxygen species in human monocytes. LPS is unable to activate monocytes under serum free conditions, but LECL responses were measured after pretreatment of LPS stock solution with serum, according to Wright et al., who described a LPS-binding protein (LBP), necessary for mediating LPS binding to the receptor CD14 on monocyte surfaces. In normal human serum a soluble form of CD14 (sCD14) exists, from which nothing is known about its possible function. sCD14 reduces the endotoxin inducible monocyte activation in our in vitro model in a dose dependent manner (5-30 micrograms/ml) suggesting an immunomodulatory function. Therefore it seems to be a new candidate for a therapeutic concept in endotoxic shock prevention."
"Cluster of differentiation 14 also known as CD14 is a human gene.
The protein encoded by this gene is a component of the innate immune system. CD14 exists in two forms. Either it is anchored into the membrane by a glycosylphosphatidylinositol tail (mCD14) or it appears in a soluble form (sCD14). Soluble CD14 either appears after shedding of mCD14 (48 KDa) or is directly secreted from intracellular vesicles (56 KDa).
CD14 is expressed mainly by macrophages and (at 10 times lesser extent) by neutrophil granulocytes. It is also expressed by dendritic cells. A soluble form sCD14 is secreted by the liver and monocytes and is sufficient in low concentrations to confer LPS-responsiveness to cells that otherwise do not express CD14. sCD14 is also present in human milk, where it is believed to regulate microbial growth in the infant gut.
CD14+ cells are monocytes that can differentiate into a host of different cells. (A '+' sign refers to the presence of the CD14 protein on a cell. )
One type of cell is the dendritic cell, where differentiation is encouraged by cytokines. Examples of cytokines that will cause dendritic cell differentiation includes GM-CSF and IL-4."
Strong binding of the acute phase protein serum amyloid-A (SAA) to human neutrophils was found using flow cytometry. This binding was shown to be functionally relevant with respect to the oxidative burst reaction assayed on N-formyl peptide-stimulated neutrophils by the intracellular oxidation of non-fluorescent dihydrorhodamine to fluorescent rhodamine 123. The results show reduction of the oxidative burst response by isolated SAA (and recombinant SAA2). Inhibition was also demonstrated by acute phase as compared to normal human serum. This inhibitory effect was abolished by the purified monoclonal anti-amyloid A antibody mc29, strongly suggesting that SAA counteracts neutrophil responses to cytokines or bacterial products. This newly recognized function of SAA may help to prevent oxidative tissue destruction."
"Serum amyloid A (SAA) proteins are a family of apolipoproteins associated with high-density lipoprotein (HDL) in plasma. Different isoforms of SAA are expressed constitutively (constitutive SAAs) at different levels or in response to inflammatory stimuli (acute phase SAAs). These proteins are produced predominantly by the liver. The conservation of these proteins throughout invertebrates and vertebrates suggests that SAAs play a highly essential role in all animals.
These proteins have several roles, including the transport of cholesterol to the liver for secretion into the bile, the recruitment of immune cells to inflammatory sites, and the induction of enzymes that degrade extracellular matrix. A-SAAs are implicated in several chronic inflammatory diseases, such as amyloidosis, atherosclerosis, and rheumatoid arthritis.
Three A-SAA genes have also been identified in humans, although the third gene, SAA3, is believed to represent a pseudogene that does not generate messenger RNA or protein."
"Respiratory burst is an abrupt release of chemically reactive oxygen molecules from cells within the body. This biological phenomenon plays a role in the immune system and can also be seen during the process of fertilizing an egg. The behavior has been observed in many different types of cells and is a topic of interest for researchers interested in developing new ways to support immune health. In addition, it is a subject for study in research involving damage to neighboring cells sometimes associated with a respiratory burst.
This process can be seen in action when a phagocyte destroys foreign material in the body. Phagocytes are specialized white blood cells designed to identify and engulf materials like bacteria, viruses, and fungi. As soon as the phagocyte has swallowed the invader, it can use a respiratory burst to blast it, causing it to degrade and break apart. This neutralizes the foreign material and prevents it from spreading elsewhere in the body.
Also known as an oxidative burst, respiratory burst can be used to attack a wide variety of unwanted organisms in the body. In the process of being attacked with reactive oxygen molecules, the targeted material undergoes oxidation, which degrades its genetic material and kills it. The highly effective cellular degradation accomplished with a respiratory burst can also work against the body, however, when neighboring healthy cells are exposed. The oxygen molecules cannot distinguish between friend and foe and will oxidize any cells they come into contact with.
The respiratory burst is also studied by researchers interested in learning how cells inside the body become damaged by reactive molecules of oxygen. Oxidative stress, as it is known, can contribute to a number of disease processes. Understanding how such molecules form and under what circumstances can help researchers address and prevent oxidative stress."
Pycnogenol (procyanidins extracted from Pinus maritima) has been reputed as a potent free-radical scavenger and an antioxidant phytochemical. We previously reported that pycnogenol prevents vascular endothelial cells from injury induced by an organic oxidant t-butyl hydroperoxide. In this study, we determined the effects of pycnogenol on (a) oxidative burst of macrophages, (b) oxidation of plasma low density lipoprotein (LDL), and (c) hydroxyl radical-induced breakage of plasmid DNA. Pycnogenol was incubated with J774 murine macrophages at 37°C and 5% CO2 and oxidative burst was triggered by zymosan. The intensity of fluorescence was measured. Pycnogenol exhibited a concentration-dependent inhibition of oxidative burst. CuSO4 was used to oxidize human plasma LDL and the formation of thiobarbituric acid reactive substances (TBARS) was determined. Co-incubation with pycnogenol resulted in a concentration-dependent inhibition of LDL oxidation. Exposure ofpBR322 plasmid DNA to iron/ascorbic acid system resulted in cleavage/damage of DNA by hydroxyl radical, measured by agarose gel electrophoresis. Pycnogenol significantly minimized this cleavage. The results indicate that pycnogenol exhibits an extensive antioxidant effect in all three in vitro systems."
"Bolivia's left-wing government was alone in objecting to the Cancun accord. It had demanded far deeper cuts in greenhouse gases by rich nations and accused them of "genocidal" policies causing 300,000 deaths a year.
Under the U.N.-led negotiations, all agreements are supposed to have consensus support, but Bolivia was sidelined with the accord simply noting its concerns."
Ok, I started having lesions break out on my skin and seem to get a new one everyday. The doctor looked at them visually and said they are psoriasis. My new Insurance does not cover extensive blood tests or biopsies right off the bat, so he gave me a cream that is petroleum based, the main ingredient is Salicylic Acid. Which I just saw yesterday is another agent that stops the oxidative burst process.
Salicylic Acid Mediated by the Oxidative Burst Is a Key Molecule in Local and Systemic Responses of Cotton Challenged by an Avirulent Race of Xanthomonas campestris pv malvacearum
"We analyzed the production of reactive oxygen species, the accumulation of salicylic acid (SA), and peroxidase activity during the incompatible interaction between cotyledons of the cotton (Gossypium hirsutum) cv Reba B50/Xanthomonas campestris pv malvacearum (Xcm) race 18."
I'm saying that my lesions are Morgellons related. And... the same thing that is happening in my body lesions is happening in one of my ears, my right ear. My first Morgellons symptoms showed up approximately 10 years ago - a small scaly path inside my right ear - my ear was visually diagnosed as eczema then. It was always there over the years but was a very small area and it would flair up and subside and didn't cause a lot of discomfort, I would put the prescribed cream on it and it would go away for a while. Today is is a very large area from just inside the ear to all of the opening and moving down toward the lobe and up toward the pinna. This ear lesion matches exactly what my arms, legs, other lesions are doing, they go through a cycle of being very red, a plastic-like, scaly scab forms, it comes off, the area gets larger and starts all over.
I haven't looked at psoriasis and eczema closely yet but I know that with both of them - they don't know what causes it necessarily, they say stress, etc. and when you put the creams on the skin, they help but as soon as you stop - your skin condition comes back. There is no cure, etc. Doctors are told to look visually and hand out creams - they don't preform skin scrapings, etc. My doctor said that the word of the doctor's opinion is used from looking visually as the diagnosis method, from what he said, it implied that the Insurance companies dictate the protocol by what they will and will not pay for.
So, from this I can assume that psoriasis and eczema are related and they are possibly related to Morgellons somehow with the DMSO/MSM intercellular vesicle exchange being out of balance or in oxidative burst situations, I haven't looked yet, just thinking out loud.
I have DMSO clear ointment here which I will add to the Salicylic Acid ointment as soon as I test the Salicylic Acid to make sure my skin doesn't have any adverse reactions. I will dedicate some lesions to just the Salicylic Acid and others to a mixture of the two.
There might be some over-the-counter salves available that contain Salicylic Acid that might help with lesions? This might be something to ask your doctor for? Or, medicines for psoriasis and eczema might help with our lesions because I suspect that the same thing that is happening with these diseases are happening with Morgellons. (I will conduct this experiment and let you know.)
And, what the heck is going on with the cotton? (Cotton Challenged by an Avirulent Race of Xanthomonas campestris pv malvacearum) ;D
I'm trying to give us some practical things we can do today to help us cope with disease and to feel better. I know those smokers out there don't want to hear this but... I did quit for a period of a few days and my lesions got better and I felt better. I suspect cigarette smoking impairs the DMSO/MSM exchange... and... I just looked and it does cause oxidative burst, and I am saying that the DMSO/MSM exchange are the micelles/vesicles involved in oxidative burst. (You just saw how I got there from the research, how can I see this and the scientists can't?) It says quitting for a period of 20 days, you can bring the exchange/burst ratios back to levels of non-smokers and this article also gives us some other terminologies to look at that are possibly involved.
Effect of smoking and abstention on oxidative burst and reactivity of neutrophils and monocytes
"Smoking is associated with surgical wound infections, impaired wound healing, and tissue-destructive disorders. The mechanisms are largely unknown, but changes in the function and activity of inflammatory cells may be involved.
After 20 days of abstinence, neutrophil oxidative burst increased to the level of never smokers (P < .05); monocyte oxidative burst increased by 50% (P < .05). Chemotaxis was only marginally affected. The changes induced by abstinence were less pronounced in the transdermal nicotine patch group compared to the placebo group.
Smoking attenuates the oxidative burst of inflammatory cells and increases chemotaxis. Three weeks of abstinence normalize the oxidative burst, but affect chemotaxis only marginally."
Abstract Sanguinarine (SA), a member of the benzo[c]phenanthridine isoquinoline alkaloids, has been shown to possess antimicrobial, anti-inﬂammatory, and antioxidant properties. We examined the effects of SA on oxidative burst in DMSO-differentiated HL-60 cells, an excellent model for studying oxidative burst. SA inhibited both N-formyl-Met–Leu–Phe (fMLP) and phorbol 12-myristate 13-acetate (PMA)-induced oxidative burst with half-maximal concentration for inhibition (IC50) of 1.5 and 1.8 M, respectively.
We conclude the SA inhibition of oxidative burst is not caused by SA redox activity but most likely is a result of SA affecting the activity of NADPH oxidase directly and in part by preventing the formation of NADPH oxidase protein complex."
"Sanguinarine is a quaternary ammonium salt from the group of benzylisoquinoline alkaloids. It is extracted from some plants, including bloodroot (Sanguinaria canadensis), Mexican prickly poppy Argemone mexicana, Chelidonium majus and Macleaya cordata. It is also found in the root, stem and leaves of the opium poppy but not in the capsule.
If applied to the skin, sanguinarine kills cells and may destroy tissue. In turn, the bleeding wound may produce a massive scab, called an Eschar. For this reason, sanguinarine is termed an escharotic.
Berberine; a plant based compound with similar chemical classification as sanguinarine"
"Berberine is a quaternary ammonium salt from the group of isoquinoline alkaloids. It is found in such plants as Berberis, goldenseal (Hydrastis canadensis), and Coptis chinensis, usually in the roots, rhizomes, stems, and bark. As a natural dye berberin has a Colour Index (CI) of 75160.
As a traditional medicine or dietary supplement, berberine has shown some activity against fungal infections, Candida albicans, yeast, parasites, and bacterial/viral infections. Berberine seems to exert synergistic effects with fluconazole even in drug-resistant Candida albicans infections. Some research has been undertaken into possible use against MRSA infection. Berberine is considered an ineffective antibiotic. However, when applied in vitro and in combination with methoxyhydnocarpin, an inhibitor of multidrug resistance pumps, berberine inhibits growth of Staphylococcus aureus.
Berberine is a component of some eye drop formulations. There is some evidence that it is useful in the treatment of trachoma, and it has been a standard treatment for leishmaniasis. Berberine prevents and suppresses proinflammatory cytokines, E-selectin, and genes, and increases adiponectin expression which partly explains its versatile health effects. Berberine is a nucleic acid-binding isoquinolone alkaloid with wide potential therapeutic properties.
This one-drug-multiple-target characteristic might be suitable for the treatment of metabolic syndrome. Berberine has been tested and used successfully in experimental and human diabetes mellitus. Berberine has been shown to lower elevated blood glucose as effectively as metformin."
"Respiratory burst (sometimes called oxidative burst) is the rapid release of reactive oxygen species (superoxide radical and hydrogen peroxide) from different types of cells.
Usually it denotes the release of these chemicals from immune cells, e.g., neutrophils and monocytes, as they come into contact with different bacteria or fungi. They are also released from the ovum of higher animals after the ovum has been fertilized. These substances can also be released from plant cells. Respiratory burst plays an important role in the immune system. It is a crucial reaction that occurs in phagocytes to degrade internalized particles and bacteria.
NADPH oxidase, an enzyme family in the vasculature (in particular, in vascular disease), produces superoxide, which spontaneously recombines with other molecules to produce reactive free radicals. The superoxide reacts with NO, resulting in the formation of peroxynitrite, reducing the bioactive NO needed to dilate terminal arterioles, feed arteries and resistance arteries. Superoxide anion, peroxynitrite, and other reactive oxygen species also lead to pathology via peroxidation of proteins and lipids, and via activation of redox sensitive signaling cascades and protein nitrosylation. NADPH oxidase activation has been suggested to depend on prior PKC activation. Myeloperoxidase uses one of these free radicals, hydrogen peroxide, to produce hypochlorous acid. Many vascular stimuli, including all those known to lead to insulin resistance, activate NADPH oxidase via both increased gene expression and complex activation mechanisms.
To combat infections, immune cells use NADPH oxidase to reduce O2 to oxygen free radical and then H2O2. Neutrophils and monocytes utilize myeloperoxidase to further combine H2O2 with Cl- to produce hypochlorite, which plays a role in destroying bacteria. Absence of NADPH oxidase will prevent the formation of reactive oxygen species and will result in chronic granulomatous disease."
"Absence of NADPH oxidase will prevent the formation of reactive oxygen species and will result in chronic granulomatous disease."
Abstract Chronic granulomatous disease (CGD), a genetic disorder characterized by the absence of a functional phagocyte NADPH oxidase, is a severe immune deficiency. However, non-infectious hyperinflammation is a second hallmark of the disease. In CGD mouse models, sterile hyperinflammation can be induced by A. fumigatus cell wall preparations. In this study, we used subcutaneous injection of microbial cell walls and cell wall components to identify causes of CGD hyperinflammation and to characterize its histological features. Sterile cell wall preparations from fungi (A. fumigatus, C. albicans, S. cerevisiae), but not from bacteria (S. aureus, P. aeruginosa, E. coli), caused prolonged and severe skin inflammation in CGD mice."
A. Certain fungi...
What is - non-infectious hyperinflammation?
"Chronic granulomatous disease (CGD), a genetic disorder..." What is the genetic disorder?
"There are two types of CGD transmission that make up autosomal forms, with mutations in NCF1, NCF2, and CYBA genes encoding p47phox, p67phox, or p22phox proteins, respectively, and the most common X-linked CGD type (60% of CGD cases), with defects in CYBB encoding gp91phox. CGD is a very heterogeneous genetic disease, caused by a large variety of mutations such as deletions, splice site mutations, and missense or nonsense mutations located in the four genes encoding NADPH oxidase components, with no "hot-spot" location except for the NCF1 gene [Stasia et al. (2008), Stasia and Li (2008)].
All ethnic groups are equally affected. The X-linked recessive transmission type of CGD (XCGD), characterized by mutations in the CYBB gene encoding NOX2, is the most frequent form of CGD (approximately 60% of cases). Beside this X linked common form. Most of the time, mutations in the CYBB gene lead to a lack of NOX2 expression, because of the instability of the corresponding mRNA or protein (X910CGD). In these patients, NADPH oxidase activity is always totally abolished. This phenotype, called X910 CGD, is the most frequent. It is usually caused by nonsense, missense, and splice mutations, small deletions, and insertions, sometimes associated with frameshift and early termination of protein synthesis [Stasia et al. (2005)].
X91- CGD mutants
Only 27 cases with “variant” forms of the disease, called X91..."
tash: Hi skizit, I have watched all your videos on youtube and cant thank you enough for all you have educated me on. I cry for you alot and a bit for me. I was wanting to send you photos of what is raining down everyday here in Australia in hope you can tell me
Dec 11, 2019 23:28:22 GMT -5
tash: not sure where to send them as hush mail and rocket mail bounced back
Dec 11, 2019 23:30:03 GMT -5