Since 2004, the anatomical distribution of vitamins in the monkey brain, studied using immunohistochemical techniques and new tools (specific antisera that discriminate different vitamins reasonably ...well), has been an ongoing research field. The visualization of immunoreactive structures containing vitamins (folic acid, riboflavin, thiamine, pyridoxal, and vitamin C) has recently been reported in the monkey brain (Macaca fascicularis), all these vitamins showing a restricted or very restricted distribution. Folic acid, thiamine, and riboflavin have only been observed in immunoreactive fibers, vitamin C has only been found in cell bodies (located in the primary somatosensory cortex), and pyridoxal has been found in both fibers and cell bodies. Perikarya containing pyridoxal have been observed in the paraventricular hypothalamic nucleus, the periventricular hypothalamic region, and in the supraoptic nucleus. The fibers containing vitamins are thick, smooth (without varicosities), and are of medium length or long, whereas immunoreactive cell bodies containing vitamins are round or triangular. At present, there are insufficient data to elucidate the roles played by vitamins in the brain, but the anatomical distribution of these compounds in the monkey brain provides a general idea (although imprecise and requiring much more study) about the possible functional implications of these molecules. In this sense, here the possible functional roles played by vitamins are discussed.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Currently, several drugs are accessible for the treatment of many chronic diseases (multiple sclerosis, amyotrophic lateral sclerosis, rheumatoid arthritis, etc.), but most of them have a large list ...of side effects. Here, we propose a new therapeutic approach called Endotherapia for the treatment of chronic diseases. This approach combines a biomedical evaluation of circulating immunoglobulins directed against specific self-antigens and self-antigens modified by free radicals. The therapy proposed here is a "tailor-made" combination of small molecules (e.g., fatty acids and vitamins) linked to a non-immunogenic chain of poly-L.Lysine (PLL). Each individual linkage or PLL derivative offers great advantages, such as an increase in the half-life of the active small molecules. Endotherapia also involves clinical aspects, allowing an exact diagnosis of the disease and the identification of specific circulating antibodies in the serum of patients in several clinical trials (e.g., multiple sclerosis). Endotherapia has been shown to be very safe. In summary, Endotherapia is the result of an immunopathological strategy addressing chronic incurable diseases with a multifactorial etiology. In light of the results obtained, it seems that Endotherapia is a promising therapy for chronic diseases, with no side effects, which is evidently mandatory in the management of long-term pathologies.
Aim
We aimed to delineate the effects of immunoglobulin (Ig)M‐mediated autoimmune responses directed against malondialdehyde (MDA) and nitroso (SNO) adducts on nitro‐oxidative stress and depressive ...and physiosomatic symptoms (DPSS) at the end of term.
Methods
IgM responses to MDA, NO (nitroso) adducts formed by nitrosylation, and NO2 tyrosine formed by nitration were measured as well as hydroperoxides (ferrous oxidation xylenol orange), advanced protein oxidation products (AOPP), and NO metabolite (NOx) levels in women at the end of term pregnancy and in normal controls.
Results
IgM responses to MDA were significantly and inversely associated with AOPP, ferrous oxidation xylenol orange, and NOx and DPSS. IgM responses to NO adducts were significantly and inversely associated with DPSS and positively with NOx levels. There were significant associations between IgM responses to MDA, NO adducts, and NO2 tyrosine. The DPSS score was predicted by AOPP and a lifetime history of premenstrual syndrome (both positively) and IgM responses to NO adducts (inversely). Furthermore, 71.8% of the variance in the index of nitro‐oxidative stress was explained by lowered IgM responses to MDA, antioxidant levels (zinc, total radical trapping parameter), and inflammatory mediators.
Conclusion
Lowered levels of IgM responses to MDA during pregnancy are accompanied by a reduced regulation of nitro‐oxidative processes thereby explaining increased oxidative and nitrosative stress biomarkers in association with DPSS. IgM responses to NO adducts, which reflect nitrosylation as a consequence of increased NO production, regulate DPSS symptoms at the end of term and are a trait marker of major depression. IgM responses to MDA are a key part of the compensatory anti‐inflammatory responses system.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
GEMSP is a mixture of functional polypeptides: fatty acids linked to poly-L-Lysine (PL), antioxidants linked to PL, free radical scavengers linked to PL, and amino acids linked to PL (patent numbers ...6114388 (USA) and 792167 (EU)). In this review, we update the data on this new drug reported in the literature. There is evidence suggesting that GEMSP is a good candidate for the treatment of multiple sclerosis (MS), an inflammatory and neurodegenerative disease of the central nervous system characterized by focal leukocyte inflammation, demyelization and axonal degeneration, resulting in nerve cell dysfunction. Experimental autoimmune encephalomyelitis (EAE) is the main animal model used in the study of MS, a T cell-mediated autoimmune disease of the central nervous system. EAE has many clinical and histopathological similarities to MS. In this model, preclinical studies on GEMSP have demonstrated that the drug strongly inhibits brain leukocyte infiltration and completely abolishes EAE episodes and clinical scores, and it also appears that GEMSP preserves myelin integrity. In general, treatment with the free constituents of GEMSP (not linked to the inert carrier protein) is poorly active against brain leukocyte infiltration in EAE-immunized animals. This means that free molecules (not linked to PL) exert a very poor action on such infiltration and that these molecules are either rapidly incorporated into the metabolism or are degraded. Moreover, with immunocytochemical techniques, it has been demonstrated that one component of GEMSP, the methionine compound, is stored inside the motoneurons of the ventral horn of the spinal cord. However, this component of GEMSP has not been found in the brain. The new candidate for MS therapy has shown no toxicity either in experimental animals or in humans. An open clinical trial in humans has demonstrated that GEMSP is completely safe. In addition, the approved drugs for the treatment of MS exert marked side effects, but no side effects have been reported following the administration of GEMSP. The results obtained at six months of treatment with low doses of GEMSP (0.75 mg/day) in that open clinical trial in humans were as follows: 55% of the patients maintained a stable expanded disability status scale (EDSS) value and 18% of the patients had a decreased EDSS value instead of a normal progression of 0.25 point on the mean EDSS scale. We focus our review on the following topics: 1) EAE models and clinical evaluation; 2) the synthesis of GEMSP; 3) the effects of GEMSP dosage on EAE; 4) the effects of GEMSP on brain leukocyte infiltration; 5) GEMSP inside motoneurons; 6) the role of the components of GEMSP; and 7) GEMSP in MS patients, GEMSP toxicity, and side effects. In conclusion, all the data reported indicate that GEMSP is a new potential drug candidate for the treatment of MS.
There is some evidence that lowered tryptophan and an activated tryptophan catabolite (TRYCAT) pathway play a role in depression, somatoform disorder, and postpartum blues. The aim of this study is ...to delineate the associations between the TRYCAT pathway and premenstrual syndrome (PMS) and perinatal depressive and physio-somatic symptoms. We examine the associations between end of term serum IgM and IgA responses to tryptophan and 9 TRYCATs in relation to zinc, C-reactive protein (CRP), and haptoglobin and prenatal physio-somatic (previously known as psychosomatic) symptoms (fatigue, back pain, muscle pain, dyspepsia, obstipation) and prenatal and postnatal depression and anxiety symptoms as measured using the Edinburgh Postnatal Depression Scale (EPDS), Hamilton Depression Rating Scale (HAMD), and Spielberger’s State Anxiety Inventory (STAI). We included pregnant females with (
n
= 24) and without depression (
n
= 25) and 24 non-pregnant females. There were no significant associations between the IgA/IgM responses to tryptophan and TRYCATs and prenatal and postnatal depression/anxiety symptoms, except for lowered IgA responses to anthranilic acid in prenatal depression. A large part of the variance in IgA responses to most TRYCATs was explained by PMS and haptoglobin (positively) and CRP (inversely) levels. The IgA responses to TRYCATs were significantly increased in PMS, in particular picolinic, anthranilic, xanthurenic and kynurenic acid, and 3OH-kynurenine. Variance (62.5%) in physio-somatic symptoms at the end of term was explained by PMS, previous depressions, zinc (inversely), CRP and haptoglobin (both positively), and the IgM responses to quinolinic acid (positively), anthranilic acid, and tryptophan (both negatively). The results suggest that mucosa-derived TRYCAT pathway activation is significantly associated with PMS, but not with perinatal depression/anxiety symptoms. Physio-somatic symptoms in pregnancy have an immune-inflammatory pathophysiology. Induction of the TRYCAT pathway appears to be more related to physio-somatic than to depression symptoms.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
To examine oxidative & nitrosative stress (O&NS) biomarkers at the end of term in relation to perinatal affective symptoms, neuro-immune biomarkers and pregnancy-related outcome variables.
We ...measured plasma advanced oxidation protein products (AOPP), nitric oxide metabolites (NOx), total radical trapping antioxidant parameter (TRAP), -sulfhydryl (-SH), peroxides (LOOH) and paraoxonase (PON)1 activity in pregnant women with and without prenatal depression and non-pregnant controls.
Pregnancy is accompanied by significantly increased AOPP and NOx, and lowered TRAP, -SH and LOOH. Increased O&NS and lowered LOOH and -SH levels are associated with prenatal depressive and physio-somatic symptoms (fatigue, pain, dyspepsia, gastro-intestinal symptoms). Increased AOPP and NOx are significantly associated with lowered –SH, TRAP and zinc, and with increased haptoglobin and C-reactive protein levels. Increased O&NS and lowered TRAP and PON 1 activity, at the end of term predict mother (e.g. hyperpigmentation, labor duration, caesarian section, cord length, breast milk flow) and baby (e.g. sleep and feeding problems) outcome characteristics.
Pregnancy is accompanied by interrelated signs of O&NS, lowered antioxidant defenses and activated neuro-immune pathways. Increased O&NS at the end of term is associated with perinatal depressive and physio-somatic symptoms and may predict obstetric and behavioral complications in mother and baby.
•Pregnancy is accompanied by activated nitro-oxidative pathways.•Prenatal inflammation is accompanied by activated nitro-oxidative pathways.•Nitro-oxidative stress is accompanied by prenatal depression symptoms.•Nitro-oxidative stress is associated with physio-somatic symptoms at the end of term.•Prenatal nitro-oxidative stress predict mother and baby outcome characteristics.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Objectives: The aim of the present study is to delineate the associations between body image dissatisfaction in pregnant women and immune-inflammatory biomarkers, i.e., C-reactive protein (CRP), zinc ...and IgA/IgM responses to tryptophan and tryptophan catabolites (TRYCATs).
Methods: We assessed 49 pregnant and 24 non-pregnant females and assessed Body Image Satisfaction (BIS) scores at the end of term (T1), and 2-4 days (T2) and 4-6 weeks (T3) after delivery. Subjects were divided in those with a lowered BIS score (≤ 3) versus those with a higher score.
Results: Logistic regression analysis showed that a lowered T1 BIS score was predicted by CRP levels and IgA responses to tryptophan (negative) and TRYCATs (positive), perinatal depression, body mass index (BMI) and age. The sum of quinolinic acid, kynurenine, 3-OH-kynurenine and 3-OH-anthranilic acid (reflecting brain quinolinic acid contents) was the single best predictor. In addition, a large part of the variance in the T1, T2 and T3 BIS scores was explained by IgA responses to tryptophan and TRYCATs, especially quinolinic acid.
Conclusions: Body image dissatisfaction is strongly associated with inflammation and mucosa-derived IDO activation independently from depression, pregnancy, BMI and age. IgA responses to peripheral TRYCATs, which determine brain quinolinic acid concentrations, also predict body image dissatisfaction.
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IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Immunoglubulin (Ig)M responses directed to oxidative specific epitopes (OSEs) and nitric oxide (NO)-adducts are significantly associated with major depression and physio-somatic symptoms. End of term ...serum IgM responses to OSEs and NO-adducts were assayed in pregnant women with (
n
= 24) and without prenatal depression (
n
= 25) as well as in 24 non-pregnant women. Associations of IgM/IgA responses to Gram-negative gut commensal bacteria (leaky gut index) and IgA/IgM responses to tryptophan catabolites (TRYCATs) were analyzed. IgM responses to OSEs, but not NO-adducts, were significantly reduced at the end of term. There were no significant associations between IgM responses to OSEs and perinatal depression, whilst IgM responses to NO-adducts, especially NO-cysteinyl, were significantly associated with a lifetime major depression. IgM responses to OSEs and NO-cysteinyl were significantly associated with IgA/IgM responses to Gram-negative bacteria, especially
Morganella morganii
,
Klebsiella pneumoniae
and
Citrobacter koseri
. IgM responses to NO-adducts and OSEs, especially malondialdehyde and myristic acid, and C-reactive protein (CRP) were inversely associated with TRYCAT pathway activity, whilst a lifetime depression and
Pseudomonas putida
were positively associated. The attenuation of natural IgM-mediated responses to OSEs at the end of term may indicate lowered activity of this part of the compensatory (anti-)inflammatory reflex system and may be partly explained by lowered bacterial translocation. Increased IgM responses to NO-cysteinyl is a biomarker of lifetime depression and may be induced by bacterial translocation. Natural IgM-mediated autoimmune responses, increased nitrosylation and higher CRP levels may have negative regulatory effects on the TRYCAT pathway.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
There is some evidence from epidemiological studies of an association between occupational exposure to electromagnetic fields and Amyotrophic Lateral Sclerosis (ALS). Our aim was to perform, for the ...first time, an animal study in a controlled magnetic environment. We used the SOD-1 mouse model to assess the possible effect of ELF magnetic fields on development of the disease. Seven mice per group were exposed to 50 Hz magnetic fields at two intensities (100 and 1000 µTrms) before the onset of the clinical signs of ALS. Exposure lasted 7 weeks, and body weight, motor performance and life span were monitored. Our results did not reveal any evidence of a link between ELF exposure and ALS in this transgenic animal model.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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