Schizophrenia and Hypoxia

Posted by gdnf on July 12, 2010
Posted in: CO2 Reactivity, Schizophrenia. Tagged: , , , , , , , , , , , .

Obstetric complications are probably one of the most oldest known complications suspected to be involved in the preconditioning of Schizophrenia. They seems to be more common in schizophrenia than in the general population (Cannon et al.) and it seems to be an higher risk to predisposed individuals that and obstetric events should occur (Schulze et al.) and that those patients who have suffered obstetric events often seems to have decreased volume of the hippocampus volume (Stefanis et al.). Such early environmental factors may impact on the development of the dopamine system. For example, hippocampal lesions made in neonatal rats result in increased striatal dopamine levels in post-pubertal rats. (Alquicer et al.)  Animal studies indicate that perinatal damage leads to a labile dopaminergic system vulnerable to sensitization. (Moore et al) suggested that developmental disruption of the hippocampus cortex can result in dysregulation of the dopaminergic inputs to the striatum, increasing the response to novelty, mild stress,or psychotomimetics.
When Schmidt and Kastner did a systematic review of the functional enviromics they suggested that more than 50% of genes potentially associated with schizophrenia, particularly AKT1, BDNF, CAPON, CCKAR, CHRNA7, CNR1, COMT, DNTBP1, GAD1, GRM3, IL10, MLC1, NOTCH4, NRG1, NR4A2/NURR1, PRODH, RELN, RGS4, RTN4/NOGO and TNF, are subject to regulation by hypoxia and/or are expressed in the vasculature.

Finally there presence of Carbon Disulfide (CS2) in the exhaled breath from persons with schizophrenia is also a sign in itself since CS2 inhibits the carbonic anhydrase catalysis (CAC) which could make the slow reaction to hypoxia slower. Part 1 in the Hypo-Thesis of Schizophrenia is about CS2.


References

Cannon M, Jones PB, Murray RM (2002). Obstetric complications and schizophrenia: historical and meta-analytic review. American Journal of Psychiatry, 159, 1080–1092.

Nicodemus KK, Marenco S, Batten AJ, Vakkalanka R, Egan MF, Straub RE, Weinberger DR. (2008). Serious obstetric complications interact with hypoxia-regulated/vascular-expression genes to influence schizophrenia risk. Mol Psychiatry 13:873–7.

Schmidt-Kastner R, van Os J, Steinbusch HWMS, Schmitz C. (2006). Gene regulation by hypoxia and the neurodevelopmental origin of schizophrenia. Schizophr Res 84:253–71.

Schulze K, McDonald C, Frangou S, Sham P, Grech A, Toulopoulou T, Walshe M, Sharma T, Sigmundsson T, Taylor M, Murray RM (2003). Hippocampal volume in familial and non-familial schizophrenic probands and their unaffected relatives. Biological Psychiatry, 53(7), 562–570.

Stefanis N, Frangou S, Yakeley J, Sharma T, O’connell P, Morgan K, Sigmundsson T, Taylor M, Murray RM (1999). Hippocampal volume reduction in schizophrenia: effects of genetic risk and pregnancy and birth complications. Biological Psychiatry, 46, 697–702.

 

Schizophrenia: The smoking hazards and nicotine benefits?

Posted by gdnf on June 28, 2010
Posted in: Addiction, Neuroscience, Schizophrenia, Science. Tagged: , , , , , , , , .

Many persons with Schizophrenia smokes and many of them have become heavy user’s long time before getting sick. There is obviously something with smoking, first of all it is very hard to start smoking and you really have to be strong to start smoking because the instincts tell almost everyone to puke when they inhale the first times.

But it is also hard to stop smoking. And it will be almost impossible to predict al the actions of 10 thousand different substances in the pyrolysis cocktail. But something we do know.
* The rate of smoking in people with schizophrenia is at least two to three times that in the general population
* Patients who smoke, smoke at heavier rates than in the general population
* Most patients start smoking in their teens, before the illness begins

A possible explanation for the association between schizophrenia and smoking is that smoking acts as an etiological risk factor for schizophrenia. It may be that repeated activation by nicotine of the mesolimbic system over a long time precipitates the onset of schizophrenia in vulnerable individuals. Researchers found that the earlier the age of starting smoking, the earlier was the onset of psychotic illness in women (Kelly & McCreadie, 1999). Interestingly, nicotine acts like other drugs of addiction such as cocaine and amphetamine, activating the mesolimbic dopamine system (Pontieri et al, 1996) and this is probably an effect of the M.A.O inhibiting effects of tobacco.

On the other hand genetic and/or environmental factors might predispose individuals to develop both schizophrenia and nicotine addiction. Much work in the genetics of both schizophrenia but very little has been done to clarify the positive effects of nicotine on the immune-response in Schizophrenia. CD25 and CD69 increased the expression when exposed to plasma from persons with Schizophrenia, suggesting that enchanted Il-2 processing….

“These results suggest that cigarette smoking has selective effects on serum components that, in turn, lead to altered immune function in schizophrenia patients relative to healthy subjects. Further studies aimed at characterizing these components could result in a better understanding of the onset and aetiology of schizophrenia and potentially lead to novel therapeutic strategies”

The changes does not correlate with changes in nicotine or cotinine levels

The most intriguing finding of the current study was the observed increase in T-cell proliferation after exposure to serum from schizophrenic smokers.  We have demonstrated that this effect was not due to differences in nicotine metabolism as cotinine levels were not significantly different in the sera of schizophrenic and control smokers. We also excluded the possibility that the effect was due to alterations in the inflammatory response by showing that the concentrations of IL-10 and IFN-g in serum from schizophrenic and HC smokers were comparable.

References:

Differential effects on T-cell function following exposure to serum from schizophrenia smokers
M Herberth, DN Krzyszton. 2008

Cigarette smoking and schizophrenia
Advances in Psychiatric Treatment (2000) 6: 327-331, the Royal College of Psychiatrists
Ciara Kelly and Robin McCreadie

Schizophrenia, Monoamine Oxidase Activity, and Cigarette Smoking
Neuropsychopharmacology (1999) 20 392-394.10.1038.George M Simpson MD, Jean C Shih Ph.D, Kevin Chen MD, Calvin Flowers MD, Takachi Kumazawa. MD and Bruce Spring1 MD

The Epidemiology of Schizophrenia – some facts

Posted by gdnf on June 27, 2010
Posted in: CO2 Reactivity, Neuroscience, Schizophrenia. Tagged: , , , .

Some facts about the incidence of Schizophrenia and it’s variability

-There seems to be a higher incidence associated with urbanity, living the first 2 years in urban areas seems  have an effect on incidence

-There seems to be a higher incidence associated with migration

-Greater lifetime risk in males and earlier onset in males

-Higher prevalence among lower socio-economic classes

-Schizophrenia is highly heritable and genetic factors seems to

-Schizophrenia is highly heritable and genetic factors contribute to approximately 80% of the liability for the illness.

-Several environmental factors of small effect, winter/spring birth, prenatal infection- (especially cytomegalovirus infection) and famine, obstetric and perinatal complications, social stress, older paternal age, etc.) are associated with an increased risk of developing schizophrenia

The global distribution of Schizophrenia according to WHO 2002

Pictures from wikipedia.

The Etiology of Schizophrenia – The Hypo-Thesis of Cognition – (Pdf) part 1 about Endogenous Carbon Disulfide CS2 and its Consequences.

After the next step of the CAC-Hålet theory dealing with the metabolites: H2S and COS, we will see if it is possible to integrate the epidemiological findings above into a more global picture of the prevalence, but maybe that is to big Utopia. Anyway the inhibition of Carbonic Anhydrase Catalysis – CAC by the metabolites show an interesting picture: how the Co2 reactivity gets slower.

Schizophrenia H2S and Carbonic Anhydrase

Posted by gdnf on June 22, 2010
Posted in: Neuroscience, Schizophrenia. Tagged: , , , , , , , , , , .

After the updates of the new page: The Etiology of Schizophrenia – CS2. The work now continues by following the metabolism from CS2 to H2S in what could be and the reactive core in the etiology of Schizophrenia. Up next are the effects of H2S.

But first of all let us see that the CAC-hålet theory shows that the reactive substance CS2 which in itself can cause some of the symptoms in Schizophrenia and is metabolized to Hydrogen Sulfide – H2S in the body, by a new route.  CS2 is also detected in the exhaled air from persons with Schizophrenia.

Aspiration and Respiration

The core function in aspiration is gas exchange with the biosphere and to regulate the breathing to the needs of the cellular respiration. In schizophrenia the Carbonic Anhydrase Catalysis – CAC is slower than normally resulting in a prolonged hypoxia in the mitochondria after increases in the O2 consumption, part of these fundamentals are later shown in the BOLD fMRI where the blood oxygenation levels curve are steeper in persons with schizophrenia.

CS2 and the metabolites dithiocarbamates and H2S are potent inhibitors of CAC, this will result in a further decrease in the function of Carbonic Anhydrase and the CO2 reactivity will get even slower. Or the other way around, H2S is the mother-substance to the reaction.

—

Refrenences
Carbonic anhydrase inhibitors. Inhibition of cytosolic isoforms I, II, III, VII and XIII with less investigated inorganic anions
Alessio Innocentia, Andrea Scozzafavaa and Claudiu T. SupuranCorresponding Author Contact Information, a, E-mail The Corresponding Author
Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino, Firenze, Italy
2009.

Chengelis, C. P. and Neal, R. A., Studies of carbonyl sulfide toxicity: metabolism by carbonic anhydrase,
Towicol. Appl. Pharmacol., 55, 198, 1980

Baird, T.T., A. Waheed, T. Okuyama, W.S. Sly, & C.A. Fierke (1997) Catalysis and Inhibition
of Human Carbonic Anhydrase IV, Biochemistry, 36: 2669 – 2678.

The possible role of CO2 in producing a post-stimulus CBF
and BOLD undershoot
Meryem A. Yücel1,2, Anna Devor2,3, Ata Akın1 and David A. Boas2*
1 Institute of Biomedical Engineering, Bogˇ aziçi University, Istanbul, Turkey

CS2 Protease inhibitors and Schizophrenia

Posted by gdnf on May 26, 2010
Posted in: Schizophrenia. Tagged: , , , , , , , , , , .

Disassociative states like Schizophrenia or psychosis seems to have a plethora of dysregulated organic pathways. Today we take a look at the Ubiquitin proteasome system. The Ubiquitin proteasome system is tagging unwanted or abnormal proteins. Dysfunction of these systems results in a buildup of malfunctioning proteins and is emerging as an important factor in neurodegenerative diseases.

New research show that the ubiquitin proteasome pathway was listed in the top ten canonical pathways for Bipolar Disorder and psychosis diagnostic groups across both samples with a considerably low likelihood of a chance occurrence
Preliminary evidence of ubiquitin proteasome system dysregulation in schizophrenia and bipolar disorder: convergent pathway analysis findings from two independent samples.

Why the interest in Ubiquitin protease?
Well the reactive agent in CAC-Hålet theory results in protease inhibitors, CS2 is known to metabolize to dithiocarbamate complexes and they tend to be strong protease inhibitors. This could in fact be an explanation to why the ubiquitin protease system is disturbed in Schizophrenia since the group already is known to have CS2 in their systems.

This pathway can possibly also explain why persons with Schizophrenia tends to have a lower rate of cancer when  the risk factors are calculated, since protease inhibitors is probably the mothers of anticancer therapies.
Disulfiram’s anticancer effects are getting interesting and its main
metabolite is CS2 – The same agent that the CAC-Hålet theory hypothesizes as a possible reactive factor in the etiology of Schizophrenia.

Targeting of Nuclear Factor-kB andproteasome by Dithiocarbamate.

The Etiology of Schizophrenia CAC-hålet Theory

Posted by gdnf on May 25, 2010
Posted in: CO2 Reactivity, Schizophrenia. Tagged: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , .

Manuscript Draft part 1,  part 2

Just like a dream, you entering this world and take your first breath

The Hypo-Thesis of cognition – A Central command in emergency light

In this hypothesis I will show a possible reactive agent in the etiology of Schizophrenia  This first step is showing a map of what CS2 are capable of. The next step will look into earlier steps in the etiological map of the etiology of Schizophrenia, the preconditioning.

Corresponding Author: POW Pär-Olof Wassén,
Corresponding Author’s Institution: CAC-Hålet Theory
First Author: Pär-Olof Wassén

CAC-Hålet theory The reactive agent
-Showing what hypotetically could be a reactive factor in the etiology of Schizophrenia

The thermodynamics of Homo Sapiens largely rely on old CODH/ACS constructions for TCA, carbon to carbon transfer, glucose and lipid metabolism. It is shown in bacterial CODH/ACS that CS2 can alter the thermodynamics of the process by tunnel gating in centre A. (9) Themechanisms in Homo Sapiens enzymology still remains to be elucidated.

CS2 exposure can give symptoms of Schizophrenia. (1) People with Schizophrenia have CS2 in their breath (2) other persons usually don’t. Persons with Schizophrenia appears to react differently and have different partial arterial pressure on CO2 than others (3), (4). The very ground-level carbon to carbon transfer used in CO2 fixation is done by constructions relying on the CODH/ ACS. The distribution of cerebral blood flow is highly sensitive to changes in the arterial CO2. (5) The CO2 regulations during sleep might be more vulnerable. (6) When the CS2 reactivity where measured between groups exposed to CS2 and not exposed to CS2, a remarkable difference was noted in the reactivity to CO2. (7) It has been shown in rats that low PaCO2 inhibits NMDA receptors. (8) The Thermodynamic backbone of human Neural transmittance is dependent on lipid and glucose metabolism, both is altered by the gating in the CODH/ACS tunnel A. One study suggests that the effect of CS2 on learning and memory ability in rats is related to the activity of NOS and the expression of nNOS in the hippocampus. (10)

B-vitamin metabolism disturbance
Exposure to carbon bisulfide results in an increased turnover of the B-vitamin complex (16, 17, 18, 19, 20) CS2 induced elevated serum lipid levels and decreased cholesterol synthesis ( on rat, 176 ppm, inh) are reportedly blocked by feeding nicotinic acid at a dose of 40 mg/kg/da (20) Nicotinic acid has protective effects against CS2 poisoning. CS2 reduces the levels of Nicotinic Acid. (21 22 23 24 25)


Chelating effects on various essential trace metals
Carbon disulfide reacts with the amino groups of amino acids and proteins to form thiocarbamate in blood and tissues (36) thiocarbamates, possessing sulfhydryl groups, may chelate polyvalent inorganic ions. CS2 reacts with endogenous amines to form dithiocarbamates.(26) which could be metabolized back to CS2. An implication is the formation of acid labile CS2 (AL CS2) that will continue to increase, even at steady-state concentrations of CS2, as long as free CS2 is available to the tissue and adequate amine substrates are available. (26) An additional important finding was the slow elimination of AL CS2, suggesting that AL CS2 may accumulate in the body after repeated exposure to CS2. (26) Dithiocarbamates are capable of chelating several polyvalent inorganic ions such as copper and zinc, and
thus may inactivate numerous enzymes in which these ions are essential for activity. (27) The hypothesis of a chelating effect has been supported by the results of some studies (28), Reports of increase in zinc and copper excretion in exposed rats, but also increased copper levels in peripheral nervous tissue of exposed rats (28) (29). Copper and zinc ions are essential for the prosthetic groups of many enzymes. The neurotoxic action of carbon disulfide and its interference with the activity of many enzymes could partly be explained by chelating effects. Zinc is required for the activity of enzymes such as lactic acid dehydrogenase a, carbonic anhydrase, glutamate dehydrogenase, and alcohol dehydrogenase. Copper, represents a cofactor of pyridoxol, a form of vitamin B6. Copper is required for the proper functioning of enzymes such as cytochrome c oxidase, the coenzyme A dehydrogenase system, eg. dopamine ß hydroxylase. The loss of copper from the spinal cord is accompanied by cellular damage, producing tissue degeneration. Disturbances of the central and peripheral nervous systems,
resulting from carbon disulfide exposure, could be connected with the loss of copper due to chelation and consequent inhibitory effects on enzyme systems (30) like Tyrosinase and the very core carbon to carbon transfer.

LOX, Lysyl oxidase is copperdependent. The LOX activity are essential for the mechanical stability of the fibers and other supramolecular assemblies formed by these proteins and the elasticity of elastin. Because collagens and elastin are important components of the extracellular matrix, abnormalities in their modification can be expected to affect many tissues, as seen in lathyrism, a connective tissue disorder caused by the administration of ß-aminopropionitrile, an irreversible inhibitor of lysyl oxidases. (31)
Extracellular copper enzymes initiate the formation of the lysine and hydroxylysine derived crosslinks in collagens and lysine-derived crosslinks in elastin. (32) CS2-mediated protein cross-linking occurs in vivo through the generation of Lys-Lys thiourea and that diethyldithiocarbamate can, through in vivo release of CS2, produce the same cross-linking structure. This observation supports the utility of cross-linking of peripheral proteins as a specific dosimeter of internal exposure for CS2 and provides a biomechanistic explanation to account for the high-molecular-weight neurofilament protein species isolated from rats exposed to CS2 or N, N-diethyldithiocarbamate. (33) High levels of homocysteine will irreversibly inhibit LOX. (34) One study suggest that LDL downregulation of LOX could contribute to the endothelial dysfunction caused by hypercholesterolemia, thus contributing to atherosclerotic plaque formation. (35) It has been reported that the glucose and lipid metabolism is disturbed by carbon disulfide both in experimental animals and in exposed workers, but not to conclusive. There is a large body of indirect information associating abnormal energy metabolism in peripheral neuropathies caused by CS2.


The energy depletion

The pathomorphology of CS2 neuropathy resembles much like other samples originating from an impaired energy metabolism. (37) A study in rats shows the oxidative effects of CS2 exposure, a marked increase in cerebral cortex hippocampus, spinal cord and serum. Reactive oxygen species, Malondialdehyd. Ca2+ and Calmodulin levels increased in in Cerebral Cortex, hippocampus and spinal cord. (38) Carbon disulfide is used in viscose rayon plants as a solvent in the spinning process. It is known to have central and peripheral neurotoxic effects, and among the pleiotrophic conditions it causes are atherosclerotic change, diabetes mellitus, and coronary heart disease (39-42). In previous studies, the radiologic findings of carbon disulfide poisoning were diffuse or focal brain atrophy, infarcts in the

basal ganglia, subcortial white matter and gray matter, and central demyelination (43-47). A few case reports have described the computed tomographic (CT) (43-47) or magnetic resonance imaging (MRI) findings (46, 47) Finding of decrease in the GSH contents and GSH-Px, CAT activities in cerebral cortex, hippocampus, spinal cord and serum. The activities of T-AOC also decreased in all three nerve tissues and serum, as time went on and symptom developed. Furthermore, significant correlations between LPO and gait abnormality were observed as symptom developed. Oxidation stress also resulted in increased Ca (2+) concentrations and calmodulin (CaM) levels increases in cerebral cortex, hippocampus and spinal cord. (48) Carbon disulfide intoxication results in alternations of microtubule and microfilament expression, and the alternations might be related to its neurotoxicity. fast changes in beta-tubulin and beta-actin in rats
exposed to CS2 could indicate a rapid change in the cytoskeleton metabolism: The beta-tubulin mRNA increased 207% and beta-actin 94% which might give insights in the metabokinetic prosperities of CS2 on a cytoskeletal level. (49) Many electrophiles toxicants cause synaptic dysfunction by unknown mechanisms. It is recognized that synaptic activity is regulated by the redox state of certain cysteine sulfhydryl groups on proteins. Research indicates that thiolates are receptors for the endogenous nitric oxide (NO) pathway and that subsequent reversible S-nitrosylation finely regulates a broad spectrum of synaptic activities. Electrophilic neurotoxicants like CS2 might, according to a hypothesized mechanism (16) produce synaptic toxicity by modifying these thiols. SNAP-25, NMDA, GAP-43, Methionine adenosyl transferases, v-ATPase are thiol-regulated proteins and protein complexes targeted by NO which further might explains the action of CS2 toxicity. One study suggests that the effect of CS2 on learning and memory ability in rats is related to the activity of NOS and the expression of nNOS in the hippocampus. (17)

Cancer and p53
The p53 gene has been proposed as tumour suppressor and a candidate susceptibility gene in schizophrenia. (52) results of one study indicate that occupational exposure results in a significant increase in P53 CGT>CTT transversions. (53) identified occupational exposure in combination with smoking as a significant risk factor for the mutation. It was concluded that AS-PCR of the P53 273rd codon transversions is a suitable technique for studying the effects of occupational exposure to CS2. (53), (57).

The CAC-Hålet Swedish site ADHD och ADD.

The Etiology of Schizophrenia CAC-Hålet Theory

Posted by gdnf on May 25, 2010
Posted in: CO2 Reactivity, Schizophrenia. Tagged: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , .

From Part 1

part II the CAC-hålet theory

The etiology of Schizophrenia could be linked to endogenous Carbon disulfide CS2 production. The manufacture and exposure to endogenous CS2, could probably act in months after months before showing some of the symptoms of high CS2 exposure (Hallucinations, Psychosis and personality changes)

Suggestions

To ensure a proper analysis of earlier undetectable biomarkers one might consider gas-analysis from skin and breath as an biomarker and emission source, since the CS2 otherwise could leave undetected through the biggest organ –  the skin. I propose analysis of total air content in a closed chamber with subjects naked to avoid contamination with techniques for gas detection (59), (60) to reveal the biometrics of human endogenous CS2 production. Which has not been done to my knowledge.

By practising these suggestions it might be easier to understand and prevent the disease by detecting the prodromal and active  systems conditions besides the genetic vulnerability and map out what role CS2 play in the etiology of Schizophrenia.

References:

(1)
Wien Klin Wochenschr. 1958 Jun 13;70(24):445-6.
[Schizophreniform reactions in chronic carbon disulfide poisoning.]
[Article in German]
Petran V
(2)
Clin Pathol 1993;46:861-864
Increased pentane and carbon disulfide in the
breath of patients with schizophrenia
M Phillips, M Sabas, J Greenberg
(3)
Respiration. 1987;52(1):34-41.Links
Respiratory sensitivity to carbon dioxide in schizophrenia.
Verma R, Dewan M, Ashutosh K.
(4)
Acta Psychiatr Scand. 1990 Jun;81(6):497-506.
Cerebral blood flow responses to inhaled carbon dioxide in schizophrenia.
Mathew RJ, Wilson WH.
Department of Psychiatry, Duke University Medical Center, Durham, North Carolina 27710.
(5)
Am J Physiol Regul Integr Comp Physiol. 2009 May;296(5):R1473-95.
Integration of cerebrovascular CO2 reactivity and chemoreflex control of breathing: mechanisms of regulation, measurement, and interpretation.
(6)
Adv Exp Med Biol. 2006;588:65-73
Control of cerebral blood flow during sleep and the effects of hypoxia.
Corfield DR, Meadows GE
(7)
J Korean Med Sci. 1998 Dec;13(6):645-51. Cerebral vasoreactivity by transcranial Doppler in carbon disulfide poisoning cases in Korea. Lee E, Kim MH.
(8)
Br J Anaesth. 2008 Nov;101(5):673-9. Epub 2008 Sep 12.
Carbon dioxide negatively modulates N-methyl-D-aspartate receptors.
Brosnan RJ, Pham TL.
(9)
1994: Kumar M; Lu W P; Ragsdale S W
Binding of carbon disulfide to the site of acetyl-CoA synthesis by the nickel-iron-sulfur protein, carbon monoxide dehydrogenase, from Clostridium thermoaceticum.
Biochemistry 1994;33(32):9769-77.
(10)
Chin Med J (Engl). 2008 Dec 20;121(24):2553-6.
Effects of carbon disulfide on the expression and activity of nitric oxide synthase in rat hippocampus.
Guo XM, Tang RH, Qin XY,Yang J, Chen GY.
(11)
Yang KS, Choi HR, Kim JJ, et al. Study of carbon disulfide intoxication.
Seoul: Korean Ministry of Labor Press, 1999
(12)
Lee E, Kim MH. Cerebral vasoreactivity by transcranial Doppler in carbon disulfide poisoning cases in Korea. J Korean
Med Sci 1998;13:645-651
(13)
J Korean Med Sci. 1998 Dec;13(6):645-51. Cerebral vasoreactivity by transcranial Doppler in carbon disulfide poisoning cases in Korea. Lee E, Kim MH.
(14)
Biochem. J. (1980) 188, 107-1 12 107
The Effects of Carbon Disulphide on Rat Liver Microsomal Mixed-Function
Oxidases, in vivo and in vitro
Maria J. OBREBSKA,* Peter KENTISH and Dennis V. PARKE
(15)
Journal of Ncurochcmistru. 1971, Vol. 18, pp. 177 to 182. Pergamon Press.
Oxidation and phosphorylation processes in brain mithochondria of rats exposed to carbon disulfide.
S. Tarkowski Hanna Sobczak
(16)
Lefaux, R. 1968. Carbon disulphide. Pp. 117-119 in Practical Toxicology of Plastics. Cleveland, OH: Chemical Rubber Company
(17)
Gorny, R., Carbon disulfide-induced vitamin 96 deficiency in rats fed diets with different vitamin B6 contents, Bromarol. Chem. Toksykol., 13(3), 299, 1980.
(18)
Washuettl, J., Winker, N., and Steiner, I.,The effects of carbon disulfide on the vitamin BI content in the serum of exposed workers, Munch. Med. Wochenschr., 121(24), 819, 1979.
(19)
165. Miyagawa, K., Carbon disulfide poisoning – Effects of L-methionine and L-methionine
combined with vitamin B12 on carbon disulfide poisoning, Shikoku Acra Med., 6(3), I, 1955.
(20)
Wronska-Nofer,. T., Nofer, J., and Stanislaw, T., Disorders in excretion of niacin metabolites in carbon disulfide-poisoned animals, Med. Pr., 16, 77, 1965.
(21)
Wronska-Nofer, T., The influence of low doses of nicotinic acid upon the development
of lipid disturbances in rats chronically exposed to carbon disulphide, hi. Arch. Arbeitsmed., 29(4), 285, 1972.
(22)
Knobloch, K., Effect of nicotinamide on excitability of the vestibular nerve and some motor nerves in chronic carbon disulfide poisoning in guinea pigs, Med. Pr., 12, 355, 1961.
(23)
Kuljak, S. and Stern, P., Protective effect of glutathione and xanthinol nicotinate against carbon disulfide poisoning in the mouse, Arh. Hig. Rada Toksikol., 22(2), 137, 1971
(24)
Paine, A. J., Williams, L., and Legg, R. F., Apparent maintenance of cytochrome P450 by
nicotinamides in primary cultures of rat hepatocytes, Life Sci., 24, 2185, 1979.
(25)
Silvestroni, A. and Rimiani, R., Microcirculation in chronic experimental intoxication with carbon disulfide. Effects of nicotinic acid, Folia Med., 53, 1, 1970.
(26)
McKenna, M. J. and DiStefano, V., Carbon disulfide. I. The metabolism of inhaled carbon disulfide in the rat, J. Pharmacol. Exp. Ther., 202(2), 245, 1977
Reaction of carbon disulfide with blood in vitro, Prac. Lek., 6, 11, 1954.
(27)
Brieger, H., Carbon disulfide in the living organism-retention, biotransformation and
pathophysiologic effects, in Toxicology of Carbon Disulfide, Brieger, H., Ed., Excerpta Medica Foundation,
Amsterdam, 27, 1967.
(28)
Gadaskina, I. D. and Andreeva, N. B., Biochemical shifts occurring in the organism
following carbon disulfide poisoning (free SH groups and blood ceruloplasmin; copper and zinc metabolism), Gig. Tr. Prof. Zabol.. 13, 28, 1969.
(29)
Kotas, P., Obrusnik, I., Lukas, E., and Krivanek, M., Determination of zinc and copper in the
periphera nerves of rats with carbon disulfide-induced neuropathy, J. Radioanal. Chem., 19(2), 263, 1974.

(30)
(Scheel, 1967). ISBN 92 4 154070 2, World Health Organization 1979
COHEN AE, SCHEEL LD, KOPP JF, STOCKELL FR, Jr, KEENAN RG, MOUNTAIN JT, PAULUS HJ.
Biochemical mechanisms in chronic carbon disulfide poisoning. Am Ind Hyg Assoc J. 1959
Aug;20(4):303–323.
(31)
Wilmarth KR, Froines JR (November 1992). “In vitro and in vivo inhibition of lysyl oxidase by aminopropionitriles”. J Toxicol Environ Health 37 (3): 411–23. PMID 1359158
(32)
Csiszar K. Lysyl oxidases: a novel multifunctional amine oxidase family. Prog Nucleic Acid Res Mol Biol.
2001; 70: 1–32.
(33)
Chem Res Toxicol. 1998 May;(5):544-9.
Carbon disulfide and N,N-diethyldithiocarbamate generate thiourea cross-links on erythrocyte spectrin in vivo.
Erve JC, Amarnath V, Graham DG, Sills RC, Morgan AL, Valentine WM.
(34)
Volume 272, Number 51, Issue of December 19, 1997 pp. 32370-32377
Irreversible Inhibition of Lysyl Oxidase by Homocysteine Thiolactone and Its Selenium and Oxygen Analogues Implications for Homocystinuria
(35)
Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:1409-1414
Low Density Lipoproteins Downregulate Lysyl Oxidase in Vascular Endothelial Cells and the Arterial Wall Cristina Rodríguez ; Berta Raposo ; José Martínez-González ; Laura Casaní ; and Lina Badimon
(36)
Madlo, Z. and Soucek, B., Absorption, metabolism, and action of carbon disulfide in the organism. VII. Inhibition of serum cholinesterase by carbon disulfide, Prac. Lek., 6, 312, 1953
Soucek, B. and Madlo, Z., Absorption metabolism, and action of carbon disulfide in the organism. VIII.
(37)
Acta Neuropathol. 1984;63(3):255-63.Links
Ultrastructure of carbon disulphie neuropathy.
Jirmanová I, Lukás E.
(38)
Ca2+ Calmodulin levels was increased in cerebral cortex, hippocampus and spinal cord. Volume 179, Issues 2-3, 15 May 2009, Pages 110-117 Changes of lipid peroxidation in carbon disulfide-treated rat nerve tissues and serum Da-Qing Suna, b Ai-Wu Lic, , Ju Lid, Dian-Guo Lib, Yi-Xin Lib, Hao-Fengb and
Ming-Zhi Gongb, Chemico-Biological Interactions.
(39).
Davidson M, Feinleib M. Carbon disulfide poisoning: A review.
Am Heart J 1972;83:100-114
(40).
Lee KB, Byoun HJ, Choi TS, Kim SS, Cho WY, Kim HK.
Clinical manifestation of chronic carbon disulfide intoxication.
Korean J Int Med 1990;39:245-251
(41).
Choi JW, Jang SH. A review of the carbon disulfide poisoning
experience in Korea. Korean J Occup Med 1991;3:11-20
(42).
Yang KS, Choi HR, Kim JJ, et al. Study of carbon disulfide intoxication.
Seoul: Korean Ministry of Labor Press, 1999
(43)
Aaserud O, Gierstad L, Nakstad P, et al. Neurological examination,
computerized tomography, cerebral blood flow and neurophysiological
examination in workers with long-term exposure
to carbon disulfide. Toxicology 1988;49:277-28
(44)
Aaserud O, Hommeren OJ, Tvedt B, et al. Carbon disulfide exposure
and neurotoxic sequelae among viscose rayon workers.
Am J Ind Med 1990;18:23-37
(45)
Sugimura K, Kabashima K, Tatetsu S. Computerized tomography
in chronic carbon disulfide poisoning. No to Shinkei 1979;
31:1245-1253
(46)
Huang CC, Chu CC, Chen RS, et al. Chronic carbon disulfide
encephalopathy. Eur Neurol 1996;36:364-368
(47)
Peters HA, Levine RL, Matthews CGM et al. Extrapyramidal
and other neurologic manifestations associated with carbon
disulfide fumigant exposure. Arch Neurol 1988;45:537-540
(48)
Ca2+ Calmodulin levels was increased in cerebral cortex, hippocampus and spinal cord. Volume 179, Issues 2-3, 15 May 2009, Pages 110-117 Changes of lipid peroxidation in carbon disulfide-treated rat nerve tissues and serum Da-Qing Suna, b Ai-Wu Lic, , Ju Lid, Dian-Guo Lib, Yi-Xin Lib, Hao-Fengb and
Ming-Zhi Gongb, Chemico-Biological Interactions.
(49)
Alterations of microtubule and microfilament expression in spinal cord of carbon disulfide intoxicated rats. Chinese journal of industrial hygiene and occupational diseases. Original title: Zhonghua lao dong wei sheng zhi ye bing za zhi Zhonghua laodong weisheng zhiyebing zazhi. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2007 Mar;25(3):148-51 Pan GB, Song FY, Zhao XL, Yu LH, Zhou GZ, Xie KQ.
(50)
Toxicological Sciences 94(2), 240–255. Richard M. LoPachin. David S. Barber
doi:10.1093/toxsci/k?066 Advance Access publication July 31, 2006
(51)
Chin Med J (Engl). 2008 Dec 20;121(24):2553-6.
Effects of carbon disulfide on the expression and activity of nitric oxide synthase in rat hippocampus.
Guo XM, Tang RH, Qin XY, Yang J, Chen GY.
(52)
Schizophr Res. 2000 Feb 14;41(3):405-15
Apoptosis and schizophrenia: is the tumour suppressor gene, p53, a candidate susceptibility gene?
Catts VS, Catts SV.
Schizophrenia Research Unit, South Western Sydney Area Health Service, Liverpool Hospital, Liverpool, NSW, Australia.
(53)
Int J Hyg Environ Health. 2007 Jan;210(1):69-77. Epub 2006 Sep 1.
Use of genotypic selection to detect P53 codon 273 CGT>CTT transversion: application to an
occupationally exposed population.
Carton T, Tan XD, Hartemann P, Joyeux M.
(54)
Forensic Sci Int. 2005 Oct 29;153(2-3):147-55. Epub 2004 Nov 25.
A study of volatile organic compounds evolved from the decaying human body.
Statheropoulos M, Spiliopoulou C, Agapiou A.
School of Chemical Engineering, National Technical University of Athens (NTUA)
(55)
(Purdon et al., 2002; Purdon and Rapoport, 2007).
(56)
Bartonicek V. The distribution of carbon disulfide in whole blood, the brain and the suprarenal gland over a given period in parenteral administration in white mice. Prac Lek 1957; 9:28-30.
(57)
The modification of genetic expression after CS2 exposure have been shown in humans with p53. Chem Biol Interact. 2009 May 15;179(2-3):110-7. Epub 2008 Nov 25.
Changes of lipid peroxidation in carbon disulfide-treated rat nerve tissues and serum.
Sun DQ, Li AW, Li J, Li DG, Li YX, Hao-Feng, Gong MZ.
Shandong University, Jinan, Shandong, China.
(58)
Schizophrenia Research Volume 62, Issue 3, 1 August 2003.
The niacin skin flush test in schizophrenia- a combined a quantitative dose–response study
(59)
MCCANN Patrick, NAMJOU Khosrow, ROLLER Chad, MCMILLEN Gina, KAMAT Pratyuma. IV-VI Semiconductor Lasers for Gas Phase Biomarker Detection
Proceedings of SPIE, the International Society for Optical Engineering ISSN 0277-786X
(60)
Mater. Res. Soc. Symp. Proc. Vol. 891 © 2006 Materials Research Society
Patrick J. McCann1 and Yurii Selivanov2 1 School of Electrical and Computer Engineering, University of Oklahoma, Norman, OK 73019 2 P. N. Lebedev Physical Institute, Russian Academy of Sciences, Leninskii Pr. 53, 119991, Moscow, Russia
(61)
Br J Anaesth. 2008 Nov;101(5):673-9. Epub 2008 Sep 12.
Carbon dioxide negatively modulates N-methyl-D-aspartate receptors. Brosnan RJ, Pham TL.
(62)
Am J Physiol Regul Integr Comp Physiol. 2009 May;296(5):R1473-95.
Integration of cerebrovascular CO2 reactivity and chemoreflex control of breathing: mechanisms of regulation, measurement, and interpretation.
(63)
Adv Exp Med Biol. 2006;588:65-73
Control of cerebral blood flow during sleep and the effects of hypoxia.
Corfield DR, Meadows GE
(64)
Activity of glutamate decarboxylase in the brain of rats exposed to carbon disulfide
International Archives of Occupational and Environmental Health Volume 33, Number 1 / March, 1974
Stanislstrokaw Tarkowski
(65)
Tarkowski S, Cremer JE. 1972. Metabolism of glucose and free amino acids in brain, studied with C-labelled glucose and butyrate in rats intoxicated with carbon disulfide. J Neurochem
19:2631-2640.
(66)
The Journal of Neuroscience, 1999, 19:RC16:1-9
RAPID COMMUNICATION Novel Injury Mechanism in Anoxia and Trauma of Spinal Cord White Matter: Glutamate Release via Reverse Na+-dependent Glutamate Transport Shuxin Li1, Geoff A. R. Mealing2, Paul Morley2, and Peter K. Stys1

The etiology of Schizophrenia

Posted by gdnf on May 19, 2010
Posted in: Schizophrenia. Tagged: , , , , , , , .

PCP, LSD, Ketamine and ….  have been used as models for the state of schizophrenia, the problem with that models is very simplified, that the person with schizophrenia usually don’t have them in their blood.

However there is a substance that can cause some of the phenomenological effects of Schizophrenia – personality changes, paranoia, mania and alternations in the transient receptor potential – TRPV secondary to environmental exposure. This effect has been known since the late 1800.  To make a complex story very short, we present the CAC-Hålet theory about-

The etiology of Schizophrenia in 3 very easy steps

1/ There is a substance known to cause some of the symptoms in Schizophrenia

2/The group of persons with Schizophrenia does have it, other usually don’t

3/ There might be a connection with, the reactive phase of Schizophrenia etiology and the substance.

The Substance is: Carbon Disulfide or CS2

Since  Carbon disulfide is a known neurotoxin one might think that we just have to remove the external source of CS2 exposure in order to eliminate the problem. But the source is not external it is internal. And this endogenous production of Carbon Disulfide is continuously taken it’s toll on the system. I conclude that Carbon Disulfide could be a reactive factor that trigger but don’t predispose for the etiology of Schizophrenia.

Ref:

Clin Pathol 1993;46:861-864
Increased pentane and carbon disulfide in the
breath of patients with schizophrenia

A part of the CAC-hålet theory is now moving to GDNF – BDNF from The Etiology of Schizophrenia @ Co2reactivity.

Penis envy and pussy addiction I

Posted by gdnf on May 14, 2010
Posted in: Addiction. Tagged: , , , , , , , , , .

Superman’s kryptonite

A person who see himself as strong don’t like to have any addiction of any kind, he likes to see  himself as totally independent, helps the weak with his strong dick, which actually also is his weak spot, since the iconography’s of strengths in any picture comes from the dots making it. The connector of  dots  will see the meaning and this will pinpoint the point.

The semantics of meaning have no need to hide in a interpolar shell, so the one realizing it’s construction picks up the meaning, which usually gives the point.

The shell fish and the mother of pearls

The Penis Envy is to probably a very large degree a lie or an interpolar shell, and what else can it be? Many men like to own and conquer the pussy, simply because they need it. To rule the pussy and thereby the world, that’s an interesting feeling, what does it really tell?

-He have to conquer the ruler in order to rule?

The nucleus is seldom known

But as said earlier the strong part can’t be addicted or the addiction have to be dealt with, so the pussy-addiction is hidden in an opposite cross-lie or interpolar shell, and see how handy the rubber comes into the glue, yahoo here we have the penis envy. An amazing fuckoff-invention by a Cocaine consuming man who wished to hide his own cocaine enslavement and his helpless pussy-addiction.

To hide his own head like he has hidden it before, he had to bring out the his mother’s pussy to figure the puzzle, but did not see the fig leaf of his own, cause it was brown and he could not see, cause he was up late at night making up histories about interpreting dreams, and not dreaming as he should.

But on the other hand he discovered the Pschycosexual roots of elementary fuckups and his own sneezing hickup’s lubricating for his viral thoughts. Ooh my dear what an fuck.

Lamb’s in the goat cheese?

Speaking in tongues with the point of arrival in life, well why not – but hey man what are you doing? you tear us a part – uterus a part. when getting closer to the point of entry you lose your language and then you die. Ooh and then you die.

Women’s pussy addiction

But there is more to come since even women are addicted to what they have, like every hearth they tend to use it and thereby confirming the status quo values of the state, by ruling under the name of lower, getting the tower, and at the same time have little mercy for the other rulers of the state, the sisters in this law – beat it baby. But women don’t likes to talk about what make them the ruler and man don’t like to be addicted so: What a Fuck!

—

–

 

Penis envy and pussy addiction II

Posted by gdnf on May 13, 2010
Posted in: Addiction. Tagged: , , , , , , , , , .

From :

Penis envy and pussy addiction I

The most obvious..

So the other roots of the penis envy is in man and often expressed as envy on other mans penis size or how much pussy they have fucked. So there is after al some true This is so obvious but never mentioned facts about the penis envy, The incitements’ for the both sexes not to speak about it, tells the story by itself cause both want to hide the truths about the fuckin fuck and really how fucked up it is.

The fuckups with this order – the disorder

Since the pussy is the ruler of the word there is a lot of pimping with truth here and there. Everyone like to be loved and satisfied so everyone in the game sell themselves on this market, the man pimping his proclaimed intentions and selling his dignity in order to get what he wants, because a strong man can’t suffer from addiction especially not to anything as weak as a women. The women love to have strong men’s attention and desire. This will result in that the children will grow up in a climate of intense broadcasting of fundamental lies.

But on the other hand, who da fuck cares about the children?

Since it is going on there is by itself an robust proof that the personal satisfaction is more worth than anything else, so there is plenty of logical reasons to say that this culture suffer from severe pussy-addiction or  to tell the truth the denial of it, and hence the self-inlocked blockbuster.

FMOOMP-ITFDPD

Fuck Meters of other mans penis in the fucking pussy. And the total admirations of his penis by the united universe emrirates dot com? could that be something?

Conclusion

The truth about the penis envy is hidden pussy addiction from a part that are not strong enough to confess it, and the other roots is probably to much cocaine in the mind of the inventor Dr. Sigmund Freud.

Dr Freud did not kiss his frog and it was still in his mind. Maybe he still see his mother in the frog, we are not really sure.