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Post by Max on Jun 12, 2005 7:52:22 GMT -5
Several factors link Accutane exposed subjects to factors causative for dementia and similiar degenerative diseases.A significantly elevated plasma homocysteine level has by independent research been observed in human acne subjects exposed to (Ro)accutane, as well as been reported by Hoffman la Roche itself [0, 5 and more]. It is suggested that the elevated Hcy levels in patients after 45 days on Iso therapy could be due either to the 'inhibition' of cystathionine-beta-synthase by the drug and/or their liver dysfunction [1]. Increased concentration of plasmatic homocysteine (tHcy) and decreased vitamin B 12 (B12) and folate (FOL) are associated with Alzheimer's (AD) and vascular (VaD) dementias [2]. Retinoic acid is of importance for myelination in the adult CNS [9 and more], and a vitamin A deficiency is suggested to have negative short and long term consequences. (Ro)accutane induced significant inhibition of angiogenesis, the formation of new blood vessels, may also play a substantial role in degenerative pathologies. Inhibition of IP(3) receptors in various areas of the brain found in subjects exposed to (Ro)accutane most likely due to decreased Sp1 binding affinity to GC boxes and reduced Sp1 formation In rats IP(3) receptors have been found to be promoted via Sp1 proteins that bind to GC-boxes. The promoter had no TATA-box but was highly GC-rich and contained two putative Sp1-binding sites. There was no sequence similarity between promoter regions of IP(3)R3 and IP(3)R2, another ubiquitous gene, except for GC-boxes [4]. In rats, mRNA levels of the type 1 IP(3) receptors were decreased significantly in cerebellum and hypothalamus, but not in the brain stem of rats exposed to 13-cis-retinoic acid, (Ro)accutane, compared to untreated littermates. The mRNA levels of the type 2 IP(3) receptor were significantly decreased in all tested tissues, cerebellum, hypothalamus, and also in brain stem after the treatment with retinoic acid. These results show that gene expression of both type 1 and 2 IP(3) receptors is regulated by retinoic acid, although the effect of retinoic acid on mRNA levels of the type 1 IP(3) receptors is dependent on brain area [3].  Picture 1. Bremner JD et al. Functional brain imaging alterations in acne patients treated with isotretinoin. (2005) Am J Psychiatry. May;162(5):983-91. Retinoic acid dependent neurogenesis: Inhibition of neurogenesis - the proliferation and development of stem-cells to functioning cells - a significant suppression during exposure suggested due to growth arrest and apoptosis, and also an inhibition of replacement post exposure due to vitamin A-deficiency is suggestedNeurogenesis persists throughout life in the rodent subventricular zone (SVZ)-olfactory bulb pathway. The molecular regulation of this neurogenic circuit is poorly understood. Components for retinoid signaling are present in this pathway. The influence of retinoic acid (RA) on postnatal SVZ-olfactory bulb neurogenesis was studied. Using both SVZ neurosphere stem cell and parasagittal brain slice cultures derived from postnatal mouse, a modest RA exposure increased neurogenesis by enhancing the proliferation and neuronal differentiation of forebrain SVZ neuroblasts. The RA precursor retinol had a similar effect, which was reversed by treating cultures with the RA synthesis inhibitor disulfiram. Electroporation of dominant-negative retinoid receptors into the SVZ of slice cultures also blocked neuroblast migration to the olfactory bulb and altered the morphology of the progenitors. Moreover, the administration of disulfiram to neonatal mice decreased in vivo cell proliferation in the striatal SVZ. These results indicate that RA is a potent mitogen for SVZ neuroblasts and is required for their migration to the olfactory bulb. The regulation of multiple steps in the SVZ-olfactory bulb neurogenic pathway by RA suggests that manipulation of retinoid signaling is a potential therapeutic strategy to augment neurogenesis after brain injury [7]. Roaccutane induced demyelination, block of myelination through multiple pathways in CNS and peripheral nervous systemIn small doses retinoic acid has shown to be positive for myelination through effects on the myelin basic protein (MBP) promoter [8]. However, it is here suggested that a toxic dose induces demyelination both during and post exposure. Also the myelination of the the peripheral nervous system is suggested to be significantly disrupted. Lipid binding activities of the P2 protein in peripheral nerve myelin were examined using retinoic acid, retinol and oleic acid as ligands. The P2 protein also showed the specific binding affinity to both of retinoic acid and retinol. The binding site of these ligands was suggested to be similar [11]. Also the Egr family is of importance for myelination. In the peripheral nervous system Egr proteins are critical modulators of transcription in myelinating Schwann cells. The Egr-family is found to be inhibited by retinoic acid in various human cell lines [16 and more]. Thyroid hormone and myelination Thyroid hormone plays an important role in brain development, in part by regulating myelination. Previous studies have shown that the myelin basic protein (MBP) promoter is activated by thyroid hormone (T3) via a T3-response element (T3RE) at position -186 [8]. Other factors of importance for myelination G21.3, a monoclonal antibody previously shown to block central nervous system (CNS) myelination is also found tp be upregulated by retinoic acid. The antigen is present on the surface of neurons but not oligodendrocytes and is highly abundant in the white matter of the adult rat brain; however, it is not found in isolated myelin [9]. The myelin basic protein (MBP) gene produces two families of proteins, the classic MBPs, important for myelination of the CNS, and the golli proteins, whose biological role in oligodendrocytes (OLs) is still unknown. Golli expression is regulated during OL development and can be modulated by growth factors such as basic fibroblast growth factor, neurotrophin-3, and retinoic acid [10].
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Post by Max on Jun 12, 2005 7:52:55 GMT -5
(Ro)accutane induced disruption of recycling of synaptic vesicles in nerve terminals through disruption and desphosphyraltion of AP-2 (clathrin adaptor mediated endocytosis)
Clathrin-mediated endocytosis plays a key role in the recycling of synaptic vesicles in nerve terminals, and several components of the molecular machinery involved in this process have been identified. These include, in addition to clathrin and the clathrin adaptors, the guanosine triphosphatase dynamin 1, the amphiphysin dimer, and synaptojanin 1. Dynamin 1 oligomerizes into collar structures at the neck of deeply ingirl thingyted clathrin-coated pits, and its conformational change is thought to be an essential step leading to vesicle fission. Synaptojanin 1 is a presynaptic inositol 5-phosphatase enriched on endocytic intermediates (3). The amphiphysin dimer (4-6) binds to both dynamin 1 and synaptojanin 1 through the COOH-terminal SH3 domains of its two subunits. Disruption of SH3-mediated interactions of amphiphysin blocks clathrin-mediated endocytosis at the step of ingirl thingyted coated pits. The amphiphysin dimer also binds to clathrin and to the -adaptin subunit of the plasma membrane clathrin adaptor AP-2 and thus may mediate recruitment of dynamin 1 and synaptojanin 1 to the site of clathrin-mediated endocytosis [6].
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Post by Max on Jun 12, 2005 7:53:24 GMT -5
Disrupted angiogenesis in the adult brain, a possible role in degenerative diseases such as Alzheimers diseaseRetinoic acid is found to significantly inhibit angiogenesis in several types of cancer tissue [13 and more]. However, the neurovascular effects of a (Ro)accutane exposure in human subjects is not clarified. Angiogenesis is a term for the continous formation of new blood vessels and currently targeted in anti-cancer therapy of various types of cancer [12 and more], because an inhibition of angiogenesis deprives the tumour-cells of oxygen and energy. Recent Alzheimers theory is beginning to include the possiblility that alterations in angiogenesis is involved in the pathology of AD [14 and more]. BEC-mediated formation of capillaries is greatly reduced in the Tg2576 mouse model of AD, and high concentrations of AƒÀ that is rich in ƒÀ-sheets is anti-angiogenic. In AD, reduced length of brain capillaries in the CA1 hippocampal region correlates well with increased clinical dementia rating scores. BEC-mediated capillary formation in AD is regulated by the Gax homebox gene, which controls differentiation of the vascular system and vascular remodeling in AD (Z. Wu et al., unpublished). Given a recent recognition that some molecular pathways mediating vasculogenesis might also regulate neurogenesis during brain development, insufficient angiogenesis and vascular regression in the AD brain could represent an important, yet to be fully defined, new pathogenic mechanism involved in the disease progression affecting repair of both vasculature and neurons [14].  Picture 2. Slokovich et al. (2005) Trends Neurosci. Apr;28(4):202-8.Neurovascular mechanisms of Alzheimer's neurodegeneration.
Neurovascular model of Alzheimer's disease. Multiple pathogenic cascades originating from altered cerebral arteries (green) or altered brain capillaries (red) can initiate disintegration of the neurovascular unit, including aberrant angiogenesis, cerebral amyloid angiopathy (CAA), senescence and faulty clearance of Aβ across the BBB, resulting in increased Aβ levels. Both sets of cascades can initiate neurovascular uncoupling and hypoperfusion, although only aberrant angiogenesis and accumulation of amyloid result in vessel regression and inflammation. This leads to the BBB compromise and reduced control of the chemical composition of brain interstitial fluid, which can result in, or amplify, synaptic and/or neuronal and oligodendroglial dysfunction, neuronal injury and loss.
In HNSCC tumour cells, owing to a decrease in the secretion of MCP-1 and transforming growth factor-beta 1 (TGF-beta 1), tumor cells treated with RA were unable to induce peripheral blood monocyte (PBM) chemotaxis. Also, as a result of the decrease in TGF-beta 1 secretion, RA-treated tumor cells were unable to activate macrophages for secretion of vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8). In addition to its affects on tumor cells, RA also directly altered the ability of monocytes to participate in the tumor angiogenesis process. PBM exposed to RA were unable to migrate toward inducers of PBM such as MCP-1 and TGF-beta 1. Finally, RA decreased the ability of tumor-activated macrophages to secrete IL-8 and VEGF [13].
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Post by Max on Jun 12, 2005 7:53:46 GMT -5
References:[0] No author Roche official complete US Accutane Product information www.rocheusa.com/products/accutane/pi.pdf [1] Schulpis KH, Karikas GA, Georgala S, Michas T, Tsakiris S. Elevated plasma homocysteine levels in patients on isotretinoin therapy for cystic acne.
(2001) Int J Dermatol. Jan;40(1):33-6. [2] Dominguez RO, Marschoff ER, Guareschi EM, Famulari AL, Pagano MA, Serra JA Homocysteine, vitamin B 12 and folate in Alzheimer's and vascular dementias: The paradoxical effect of the superimposed type II diabetes mellitus condition. (2005) Clin Chim Acta. [3] Stefanik P, Macejova D, Mravec B, Brtko J, Krizanova O. Distinct modulation of a gene expression of the type 1 and 2 IP(3) receptors by retinoic acid in brain areas. (2005) Neurochem Int. Jun;46(7):559-64. [4] Tamura T, Hashimoto M, Aruga J, Konishi Y, Nakagawa M, Ohbayashi T, Shimada M, Mikoshiba K. Promoter structure and gene expression of the mouse inositol 1,4,5-trisphosphate receptor type 3 gene. (2001) Gene. Sep 5;275(1):169-76. [5] [6] Slepnev VI, Ochoa GC, Butler MH, Grabs D, De Camilli P. Role of phosphorylation in regulation of the assembly of endocytic coat complexes.
(1998) Science. Aug 7;281(5378):821-4. [7] Wang TW, Zhang H, Parent JM. Retinoic acid regulates postnatal neurogenesis in the murine subventricular zone-olfactory bulb pathway. (2005) Development. Jun;132(12):2721-32. May 18. [8] Pombo PM, Barettino D, Ibarrola N, Vega S, Rodriguez-Pena A. Stimulation of the myelin basic protein gene expression by 9-cis-retinoic acid and thyroid hormone: activation in the context of its native promoter. (1999) Brain Res Mol Brain Res. Jan 22;64(1):92-100. [9] Notterpek LM, Rome LH. A protein involved in central nervous system myelination: localization in the extracellular matrix and induction in neuroblastoma cells. (1994) Dev Neurosci. 16(5-6):267-78. [10] Givogri MI, Bongarzone ER, Schonmann V, Campagnoni AT. Expression and regulation of golli products of myelin basic protein gene during in vitro development of oligodendrocytes. (2001) J Neurosci Res. Nov 15;66(4):679-90. [11] Uyemura K, Yoshimura K, Suzuki M, Kitamura K. Lipid binding activities of the P2 protein in peripheral nerve myelin. (1984) Neurochem Res. Oct;9(10):1509-14. [12] McKinnon C. Prostate cancer, biological therapy, signal transduction inhibitors and anti-angiogenesis agents. (1999) IDrugs. Jul;2(7):624-8. [13] Liss C, Fekete MJ, Hasina R, Lingen MW.
Retinoic acid modulates the ability of macrophages to participate in the induction of the angiogenic phenotype in head and neck squamous cell carcinoma. (2002) Int J Cancer. Jul 20;100(3):283-9. [14] Zlokovic BV. Neurovascular mechanisms of Alzheimer's neurodegeneration. (2005) Trends Neurosci. Apr;28(4):202-8. [15] Le N, Nagarajan R, Wang JY, Svaren J, LaPash C, Araki T, Schmidt RE, Milbrandt J. Nab proteins are essential for peripheral nervous system myelination.
(2005) Nat Neurosci. Jul;8(7):932-40. [16] Horie M, Sakamoto KM, Broxmeyer HE.
Regulation of egr-1 gene expression by retinoic acid in a human growth factor-dependent cell line.
(1996) Int J Hematol. Jun;63(4):303-9.
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Post by Max on Jul 17, 2005 6:19:18 GMT -5
Cancer Res. 1989 Feb 15;49(4):1014-9. Related Articles, Links
Modulation of growth and epidermal growth factor receptor activity by retinoic acid in human glioma cells.
Yung WK, Lotan R, Lee P, Lotan D, Steck PA.
Department of Neuro-Oncology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
The growth-inhibitory activity of beta-all-trans-retinoic acid (RA) was examined on seven cultured human gliomas and cells derived from one normal brain. Response in monolayer cultures was heterogenous: three cell lines were completely resistant whereas five cell lines were growth inhibited with 50% inhibitory dose ranging from greater than 10(-5) to 1 x 10(-8) M. Two glioma cell lines capable of forming colonies in soft agar exhibited dose-dependent sensitivity to RA-induced growth inhibition, whereas another cell line was not affected by RA under either growth condition. Cell cycle analysis of the glial-derived cells has shown that the RA-sensitive cells accumulated in the G0-G1 phase. The cell surface expression of epidermal growth factor (EGF) receptors displayed by the various cells was either slightly increased or not affected by RA. In addition, the affinity of binding was slightly decreased in some sensitive cells. The activity of EGF receptor as assessed by immunocomplex-kinase assays revealed a dose-dependent decrease in autophosphorylation activity that appeared to correlate with the growth inhibition. The decrease in phosphokinase activity represented a dose-dependent inhibition of phosphorylation on tyrosine residues on EGF receptor as well as several other substrates. Furthermore, the autophosphorylation of either RA-treated or untreated EGF receptors occurred on similar amino acid residues. These results demonstrate that RA exhibits a heterogeneous growth-inhibitory activity against human glioma cells and suggest that the effects of RA may be mediated, at least in part, by modulation of EGF receptor phosphotyrosine kinase activity.
PMID: 2912547 [PubMed - indexed for MEDLINE]
J Neurochem. 2002 Oct;83(1):67-79. Related Articles, Links
Analysis on the promoter region of exon IV brain-derived neurotrophic factor in NG108-15 cells.
Takeuchi Y, Miyamoto E, Fukunaga K.
Department of Pharmacology, Kumamoto University School of Medicine, 2-2-1 Honjo, Kumamoto 860-0811, Japan. yusuket@gpo.kumamoto-u.ac.jp
We have reported that the nuclear isoforms of Ca2+/calmodulin-dependent protein kinase II (CaM KII) are involved in the expression of the exon IV-containing brain-derived neurotrophic factor (BDNF) mRNA. We document here the cis-elements and transcription factors responsive to CaM KII in the activation of the promoter upstream of the exon IV (exon IV-BDNF promoter). Effects of constitutively active mutants of CaM KIV, MAPK kinase kinase (MEKK) and protein kinase A (PKA) on the exon IV-BDNF promoter activity were also evaluated by transfection and luciferase assay. The exon IV-BDNF promoter activity was increased by transfection with CaM KII, MEKK and PKA, but not by CaM KIV. Deletion and mutational analysis of the promoter revealed that the region between nucleotides -56 and -27 was responsive to CaM KII, which contained a CCAAT-box in the region between nucleotides -56 and -43. Expression of C/EBPbeta increased the promoter activity and potentiated the effects of CaM KII. The region between nucleotides -79 and -56 was responsive to MEKK, in which both a GA-rich sequence and a GC-box were included. Expression of Sp1 increased the promoter activity, which was further enhanced by transfection with MEKK. The region between nucleotides -43 and -27 was responsive to both PKA and CaM KII, but the transcription factors involved in the region remained unclear. These results suggest that the promoter of the exon IV-BDNF is at least regulated by CaM KII, MEKK and PKA, and that C/EBP/beta and Sp1 are potential transcription factors activated by CaM KII and MEKK, respectively.
PMID: 12358730 [PubMed - indexed for MEDLINE]
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Post by Max on Aug 30, 2005 7:23:21 GMT -5
Stroke. 2005 Jul;36(7):1533-7. Epub 2005 Jun 9. Related Articles, Links
Angiopoietin-2 facilitates vascular endothelial growth factor-induced angiogenesis in the mature mouse brain.
Zhu Y, Lee C, Shen F, Du R, Young WL, Yang GY.
Center for Cerebrovascular Research, Department of Anesthesia, University of California, San Francisco, CA, USA.
BACKGROUND AND PURPOSE: A better understanding of angiogenic factors and their effects on cerebral angiogenesis is necessary for the development of effective therapeutic strategies for ischemic brain injury. Vascular endothelial growth factor (VEGF) has been shown to induce angiogenesis in the adult mouse brain. However, the function of angiopoietin-2 (Ang-2) in cerebral angiogenesis has not been clarified. The goal of this study was to identify the combined effects of VEGF and Ang-2 on cerebral angiogenesis and the blood-brain barrier (BBB). METHODS: Six groups of 6 adult male CD-1 mice underwent AdlacZ (viral vector control), AdVEGF, AdAng2, VEGF protein, VEGF protein plus AdAng2, or saline (negative control) injection. Microvessels were counted using lectin staining on tissue sections after 2 weeks of treatment. Matrix metalloproteinase-9 (MMP-9) activity was determined by zymography. The presence of zonula occludens-1 (ZO-1) protein was determined by Western blot and immunohistochemistry. RESULTS: Mice treated with VEGF protein infusion plus AdAng-2 significantly increased microvessel counts relative to all other groups (P<0.05). The changes in MMP-9 activity paralleled the reduced ZO-1 expression in the VEGF plus Ang-2-treated group compared with the other 5 groups (P<0.05). Double-labeled immunostaining demonstrated that ZO-1-positive staining was significantly decreased on the microvessel wall in the VEGF plus Ang-2-treated group. CONCLUSIONS: Our study demonstrates that the combination of VEGF and Ang-2 promotes more angiogenesis compared with VEGF alone. Furthermore, the combination of VEGF and Ang-2 may lead to BBB disruption because it increases MMP-9 activity and inhibits ZO-1 expression.
PMID: 15947259 [PubMed - in process]
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Post by Max on Aug 30, 2005 9:05:00 GMT -5
Dement Geriatr Cogn Disord. 2005;19(1):1-10. Epub 2004 Sep 21. Related Articles, Links
Decreased release of the angiogenic peptide vascular endothelial growth factor in Alzheimer's disease: recovering effect with insulin and DHEA sulfate.
Solerte SB, Ferrari E, Cuzzoni G, Locatelli E, Giustina A, Zamboni M, Schifino N, Rondanelli M, Gazzaruso C, Fioravanti M.
Department of Internal Medicine and Geriatrics, University of Pavia, Pavia, Piazza Borromeo 2, IT-27100, Italy. brunos@unipv.it
Changes of vascular endothelial growth factor (VEGF) secretion have recently been demonstrated in patients with Alzheimer's disease (AD). Since VEGF has been involved in brain angiogenesis, neuroprotection and cerebromicrovascular exchange of substrates and nutrients, the study of VEGF could have important relapses into the pathogenesis and treatment of AD. Within this context, 35 healthy subjects (16 of young and 19 of old age), 18 patients with dementia of the vascular type (VAD) and 22 with dementia of the Alzheimer's type (AD) were included in the study. VEGF levels were determined in the supernates of circulating natural killer (NK) immune cells isolated by immunomagnetic separation (pure CD16 + CD56 + NK cells at a final density of 7.75 x 10(6) cells/ml). VEGF was measured in spontaneous conditions (without modulation) and after exposure of NK cells with IL-2, lipopolysaccharide (LPS), dehydroepiandrosterone sulfate (DHEAS), LPS + insulin, amyloid-beta (Abeta) fragment 1-42, the inactive sequence Abeta(40-1) and Abeta(1-42) + insulin. A significant decrease in VEGF released by NK cells was demonstrated in AD subjects compared to the other groups. No differences of VEGF levels were found between healthy subjects of old age and the VAD group. The incubation with LPS and DHEAS significantly increased, in a dose-dependent manner, VEGF levels in AD as well as in healthy subjects of young and old age and in VAD patients. The incubation of NK cells with Abeta(1-42) completely suppressed VEGF generation in AD subjects, also reducing VEGF release in the other groups. The co-incubation of NK with LPS + insulin, at different molar concentrations, significantly restored (4- and 6-fold increase from LPS alone) VEGF in AD, also enhancing VEGF secretion in healthy subjects and the VAD group, while the co-incubation of NK with Abeta(1-42) + insulin promptly abolished the negative effects of Abeta(1-42) on VEGF release. These data might suggest that the decreased VEGF secretion by peripheral immune cells of AD subjects could have a negative role for brain angiogenesis, neuroprotection and for brain microvascular permeability to nutrients, increasing brain frailty towards hypoxic injuries. On the contrary, insulin and DHEAS could have beneficial effects in AD, as well as in VAD and in physiological aging, by increasing, in a dose-dependent fashion, VEGF availability by peripheral and resident immune and endothelial cells, so contributing to increase its circulating pool. Copyright 2005 S. Karger AG, Basel.
PMID: 15383738 [PubMed - indexed for MEDLINE]
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Post by Max on Aug 30, 2005 9:06:20 GMT -5
Physiol Res. 2005 Aug 5; [Epub ahead of print] Related Articles, Links
Inhibition of vascular endothelial growth factor-induced retinal neovascularization by retinoic acid in experimental retinopathy of prematurity.
Ozkan H, Duman N, Kumral A, Kasap B, Ozer EA, Lebe B, Yaman A, Berk T, Yilmaz O, Ozer E.
Department of Pediatrics, Dokuz Eylul University, School of Medicine, 35340 Izmir, Turkey. hasan.ozkan@deu.edu.tr.
Vascular endothelial growth factor (VEGF) has an important role in the pathogenesis of retinopathy of prematurity (ROP) and inhibition of VEGF expression at the neovascular phase might prevent destructive neovascularization in ROP. It is suggested that retinoids have highly potent antiangiogenic activity by inhibiting VEGF expression. The aim of this study was to demonstrate the preventive effect of retinoic acid (RA) on the VEGF-induced retinal neovascularization in a rat model of ROP.Wistar albino rats were placed into incubators at birth and exposed to an atmosphere alternating between 50 % and 10 % O(2) every 24 hours. After 14 days, the animals were removed to room air and received either intraperitoneal injection of RA (5 mg/kg/day) (n=9) or saline (n=4) daily for six days, and sacrificed at 21 days. Additional rats (n=4) were raised in room air and served as age-matched controls. The globe of each eye was cut through the cornea and embedded in paraffin. Serial sections were stained with hematoxylin-eosin for quantification of neovascular nuclei. The avidin-biotin peroxidase method was performed for evaluation of VEGF expression. The average number of neovascular nuclei was significantly lower in the control group compared to that in the ROP groups. In addition, it significantly decreased in the RA-treated ROP group compared to that in the saline-administrated ROP group. VEGF immunostaining was overall negative in room air-exposed rats. VEGF immunostaining score significantly decreased in RA-treated ROP group compared to that in the saline-administrated ROP group. RA treatment might be beneficial in preventing neovascularization resulting from oxygen-induced retinopathy by downregulation of VEGF expression.
PMID: 16083310 [PubMed - as supplied by publisher]
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Post by KBH on Apr 8, 2008 12:24:17 GMT -5
According to the paper Functional Brain Imaging Alterations
in Acne Patients Treated With Isotretinoin, J. Douglas Bremner, M.D., Am J Psychiatry 2005; 162:983–991, the first paper adressing this issue, i would like for you to pay attention the following statement;
Isotretinoin is chemically similar to the retinoid vitamin A, a fat-soluble
vitamin stored in high concentrations in the liver. Vitamin
A is converted after oxidation to retinoic acid, when it has
biological effects. Arctic explorers who fed on polar bear
liver developed symptoms of confusion and psychosis.
Large doses of vitamin A can have a number of other neurological
and mental effects, including fatigue, decreased
interest, headache, and diplopia (double vision) (16, 17).
Published case reports of vitamin A toxicity include symptoms
of aggression, personality changes, depression, poor
concentration, tearfulness, psychotic symptoms, and
guilty rumination (17–19) that resolved with discontinuation
of vitamin A.
To my knowledge, the experiement did not look at the individuals post treatment, but during treatment. A study six month after the last pill taken, would be more relevant. Basicly, there is nothing in the paper stating that you get permanent damage, but that you will have decrease in metabolism in the orbitofrontal cortex following isotretinoin administration during treatment.
One patient suffered from headache, was noted by her family and clinician
to have disturbed behavior, and dropped out of school. She did not, however, have a clinically significant increase in depression as measured by the Hamilton depression scale.
I would strongly suggest that you all go easy on the hype, and read the studies carefully, the placebo effect on making accutane the answer to other post treatment problems, WILL cause more trouble than adressing the problem in much less dramatic way.
Best Regards, patient in Norway, 3rd month, with a lot of side effects mentally. still keeping things clear in regards to information about accutane.
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Post by adfa on May 4, 2010 11:14:20 GMT -5
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Post by adfa on May 4, 2010 11:15:50 GMT -5
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Post by abc on May 5, 2010 9:17:42 GMT -5
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Post by bnngnxgfnx on Jul 15, 2018 9:16:57 GMT -5
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Post by jfgjhfj on Sept 7, 2018 19:15:27 GMT -5
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