Methyl Vitamin Research Articles

The Effect of High-Dose Methyl Vitamin B12 Therapy on Epileptogenesis in Rats: An In Vivo Study.

Introduction Epileptogenesis has been considered one of the most prevalent diseases affecting significant numbers of individuals worldwide. Since vitamin B12 has been reported to possess antiepileptic effects, this supports that vitamin B12 deficiency is correlated to seizure occurrence. Hence, this study aimed to evaluate the neuroprotective effects of vitamin B12 injection on pentylenetetrazole (PTZ)-induced rats. Methods The study was performed using 40 adult female Sprague-Dawley rats (~250 g). A 45 mg/kg PTZ was intraperitoneally injected into rat models to induce seizure effects. Different groups of rat models received methyl vitamin B12 therapy at different dosages, a low dosage of 45 µg/kg and a high dosage of 85 µg/kg, at different pre-treatment periods, one day and two weeks prior to PTZ injection. A control group, which received only PTZ injection, served as a reference. The seizure latency, seizure intensity, and differences in the quality of seizures and their characteristics, from simple twitches to complete seizures, were observed after 30 minutes of PTZ injection. Results In general, the latency to convulsion significantly increased when vitamin B12 pre-treatment was employed. The longest latency time (LT) of 520.63±73.83 seconds was observed when a high dosage of vitamin B12 at 85 µg/kg was injected one day prior to PTZ inoculation, which was significantly higher than that of the control group at 176.88±62.67 seconds (P<0.001). Moreover, the duration of convulsion significantly decreased in which the lowest duration time (DT) of 7.00±4.68 seconds was observed when a high dosage of vitamin B12 at 85 µg/kg was injected two weeks prior to PTZ inoculation, which was significantly lower than that of the control group at 257.75±41.93 seconds (P<0.001). Lastly, the percentage of the population with PTZ-induced convulsion generally decreased after vitamin B12 pre-treatment in which majority showed more of simple less aggressive twitches rather than tonic-clonic seizures. Conclusion The results showed that vitamin B12 pre-treatment alleviates the seizure occurrence among PTZ-kindled rat models. These findings then suggest that vitamin B12 is a potential strategy and treatment for epilepsy and other related epileptogenesis activities.

Methyl B12 protects PC12 cells against cytotoxicity induced by Aβ25-35.

Alzheimer's disease (AD) is the most common aging-associated dementia. The population of AD patients is increasing as the world age grows. Currently, there is no cure for AD. Given that methyl vitamin B12 (methylcobalamin) deficiency is related to AD and Aβ-induced oxidative damage and that methylcobalamin can scavenge reactive oxygen species (ROS) by direct or indirect ways, we studied the effect of methylcobalamin on the cytotoxicity of Aβ. PC12 cells were chronically exposed (24 hours) to Aβ25-35 (25 μM) to establish an AD cell model. The cells were pretreated with or without methylcobalamin (1-100 μM) to investigate the role of methylcobalamin. Cell viability and apoptosis were tested, followed by testing of mitochondrial damage, oxidative stress, and mitochondrial calcium concentration. We observed that methylcobalamin improved the cell viability by decreasing the ratio of apoptosis cells in this AD cell model. Further experiments suggested that methylcobalamin functioned as an antioxidant to scavenge ROS, reducing the endoplasmic reticulum-mitochondria calcium flux through IP3R, preventing mitochondria dysfunction, ultimately protecting cells against apoptosis and cell death. Taken together, our results presented, for the first time, that methyl vitamin B12 can protect cells from Aβ-induced cytotoxicity and the mechanism was mainly relevant to the antioxidative function of methyl B12.

Research advances in the association between maternal intake of methyl donor nutrients during pregnancy and DNA methylation in offspring

Maternal nutrition during pregnancy plays a vital role in the health of the offspring. Methyl donor nutrients, including folate, vitamin B12, choline, betaine, and methionine, directly affect DNA methylation and are closely associated with the health of the offspring. As an important part of epigenetics, DNA methylation plays an important role in the maintenance of normal cellular function, gene expression regulation, and embryonic development. Recent studies have shown that maternal nutrition may have a long-lasting effect on the health of the offspring via the changes in genomic DNA and/or methylation level in the promoter region in specific genes. Therefore, this review article focuses on the effect of maternal intake of methyl donor nutrients during pregnancy on DNA methylation, in order to explore the effect of the changed methylation status on the health of the offspring at the molecular level.

Effects of Postoperative Methycobal Administration on Digital Replantation Based on Stellate Ganglion Stimulation

To study the impact of stellate ganglion block (SGB) on digital replantation and analyze its mechanism. Digital arterial diameter was enlarged after SGB, and the difference in the survival rate of severed finger after replantation was not statistically significant between the two groups (P>0.05). Through the treatment with Methycobal, the recovery of 2-point discrimination (2-pd) of the experimental groups (A, B) was significantly better than that of the negative control group, between which the difference was statistically significant (P<0.01 between Groups A and C, P<0.05 between Groups B and C), indicating that the methyl vitamin B 12 can significantly promote the regeneration of peripheral nerves. Methycobal is of great significance to the postoperative treatment of digital replantation, which is worthy of being widely applied in clinic practice.

Management of severe measles related pneumonia, acute respiratory distress syndrome and pleural effusion with intravenous methyl prednisolone, immunoglobulin and oral vitamin A

Introduction Measles still remains as one of the major causes of childhood morbidity and mortality in developing countries. In 2013, it was responsible for 2% of total deaths in children under five years of age. Measles related pneumonia (MRP) is the commonest cause of death in children with measles It may be associated with acute respiratory distress syndrome (ARDS) and pleural effusion (PE). We describe a case of severe measles related pneumonia with bilateral pleural effusion and ARDS in a 10 month old girl, successfully treated with high dose of methyl prednisolone, vitamin A and intravenous (IV) immunoglobulin during the outbreak in 2013.

Abstract 899: Cancer protection associated with dietary methyl donor deficiency is characterized by persistent changes to epithelial proliferation and metabolism

Abstract The role of folate one-carbon metabolism in colorectal cancer development is incompletely understood, and nutritional intervention studies have produced conflicting results. We previously demonstrated that a diet deficient in the methyl donors folic acid, methionine, choline and vitamin B12, and supplemented with homocysteine, reduces intestinal tumor incidence by greater than 95% in ApcMin/+ mice. Here we extend these findings to a second mouse tumor model, ApcÄ14, and further show that the cancer protection afforded by even short-term dietary methyl donor deficiency (MDD) is long-lasting. Eleven weeks of MDD followed by methyl donor repletion was sufficient to maintain tumor suppression for at least 7 additional weeks (22.2 ± 3.5 vs 70.2 ± 4.6 intestinal tumors; p &amp;lt; 0.001). Sustained tumor protection was associated with altered intestinal crypt homeostasis. MDD increased the proportion of intestinal epithelial cells undergoing apoptosis in normal crypts and in tumors (4.9- and 3.2-fold, respectively), while reducing cell proliferation (Ki-67) and mitosis (PHH3). In addition, metabolomic profiling and metabolite set enrichment analysis (MSEA) revealed that tumor protection is associated with persistent alterations to metabolic pathways related to cellular proliferation, including glutamine metabolism, biogenic amine synthesis, nucleotide salvage and glutathione synthesis. Taken together, these results indicate that even a temporary dietary methyl donor restriction in cancer-prone mice can induce persistent changes to the intestinal epithelium that provide long-lasting protection in adult mice. Citation Format: Matthew P. Hanley, Daniel W. Rosenberg. Cancer protection associated with dietary methyl donor deficiency is characterized by persistent changes to epithelial proliferation and metabolism. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 899.

Methyl vitamins contribute to obesogenic effects of a high multivitamin gestational diet and epigenetic alterations in hypothalamic feeding pathways in Wistar rat offspring.

High multivitamin (HV, tenfold AIN-93G) gestational diets fed to Wistar rats increase food intake, obesity, and characteristics of metabolic syndrome in the offspring. We hypothesized that methyl vitamins, and specifically folate, in the HV gestational diet contribute to the obesogenic phenotypes consistent with their epigenetic effects on hypothalamic food intake regulatory mechanisms. Male offspring of dams fed the AIN-93G diet with high methyl vitamins (HMethyl; tenfold folate, vitamins B12, and B6) (Study 1) and HV with recommended folate (HVRF) (Study 2) were compared with those from HV and recommended vitamin (RV) fed dams. All offspring were weaned to a high fat diet for 8 wks. HMethyl diet, similar to HV, and compared to RV, resulted in higher food intake, body weight, and metabolic disturbances. Removing folate additions to the HV diet in HVRF offspring normalized the obesogenic phenotype. Methyl vitamins, and folate in HV diets, altered hypothalamic gene expression toward increased food intake concurrent with DNA methylation and leptin and insulin receptor signaling dysfunction. Methyl vitamins in HV gestational diets contribute to obesogenic phenotypes and epigenetic alterations in the hypothalamic feeding pathways in the offspring. Folate alone accounts for many of these effects.

A high multivitamin diet fed to Wistar rat dams during pregnancy increases maternal weight gain later in life and alters homeostatic, hedonic and peripheral regulatory systems of energy balance

High multivitamin (10-fold, HV) and high folic acid (Fol) diets fed to pregnant Wistar rats increase body weight and characteristics of the metabolic syndrome in their offspring. Our objective was to determine the effects of a HV maternal diet on dams and whether methyl vitamins contribute to these effects. Pregnant Wistar rats were fed AIN-93G diets containing either (1) recommended multivitamins (RV, control), (2) HV, (3) HV with recommended Fol (HVRF; 1-fold Fol), or (4) RV with high methyl group vitamins (HMethyl; 10-fold Fol, vitamin B12 and B6). All groups were fed a RV diet during lactation until weaning and a RV high fat (HF; 60% fat) diet for 16 weeks post-weaning. The HV, HVRF and HMethyl diet fed dams gained 45% more weight from 2 to 15 weeks post-weaning and their weight gain (WG) was positively associated with cumulative post-weaning food intake (FI). However, only HV dams had a reduced preference for a sucrose solution, lower mesolimbic dopamine (DA) turnover in the nucleus accumbens (NAc), and higher expression of several genes involved in FI regulation in the arcuate nucleus of the hypothalamus (ARC). Energy conserving peroxisome proliferator-activated receptor (Ppar)-γ in adipose and -α in liver was also greater in these dams consistent with their WG. In conclusion, HV, HVRF and HMethyl maternal diets exacerbate maternal WG when dams are exposed to a HF diet post-weaning. However, the diets differed in their effects on central and peripheral regulatory systems of energy balance.

Role of methyl group vitamins in hypothalamic development of food intake regulation in Wistar rats

High multivitamin diets (HV; 10-fold AIN-93G) fed during pregnancy to Wistar rats produce offspring with increased food intake, obesity, and characteristics of metabolic syndrome. The hypothesis that methyl group vitamins in HV gestational and pup diets modify expression of the obesogenic phenotypes in the offspring through their effects on hypothalamic feeding pathways was tested by 4 studies. In studies 1 and 2, dams were fed the AIN-93G diet with recommended vitamin (RV), HV, high methyl vitamins (10-fold folate, vitamin B12 and vitamin B6) (HMethyl), or HV with normal folate (HVNF) and male offspring were weaned to a high-fat diet for 8 weeks. In studies 3 and 4, dams were fed RV, HV, or high 10-fold folate (HFol), and male offspring were weaned to RV, HV, or HFol diets for 29 weeks. The results were as follows: (i) HV and HMethyl diets increased obesogenic phenotypes and altered hypothalamic regulation of food intake and metabolism concurrent with epigenetic effects on gene expression. (ii) Removing folate additions to the HV diet showed that folate contributes to the obesogenic phenotype in the offspring and epigenetic alterations in the hypothalamus that favour increased food intake. (iii) Matching pup diet vitamin content with that of the HV and HFol diet-fed dams prevented their increased food intake, body weight, and insulin resistance when weaned to the RV diet. (iv) Both HFol gestational and pup diets altered hypothalamic feeding pathways through DNA methylation, showing that epigenetic effects of these vitamins occur not only in utero but also postnatally. In conclusion, methyl group vitamins in HV gestational and pup diets modify expression of the obesogenic phenotypes and hypothalamic food intake regulatory systems in the Wistar rat offspring.

Abstract LB-182: Effects of methyl donor status on intestinal tumorigenesis in ApcMin/+ mice

Abstract The goal of the present study is to determine the effects of folate deficiency on intestinal tumorigenesis in ApcMin/+ mice, a widely used animal model for human familial adenomatous polyposis (FAP). Since folate plays an important role in maintaining methyl donor status, dietary folate levels were reduced in combination with a panel of methyl donors, including choline, methionine and vitamin B12. Although the impact of folate on colorectal cancer (CRC) has been studied extensively, its role in cancer chemoprevention remains controversial. For example, folate supplementation has been widely discussed as a strategy for lowering cancer incidence. However, excess folate has also been associated with increased cancer risk. The following studies were designed to evaluate the effects of folate deficiency on intestinal tumorigenesis in ApcMin/+ mice. In Study 1, methyl donor sufficient diet (MDS) and methyl donor deficient diet (MDD) were fed to mice, beginning at either 5 or 10 weeks of age. Intestinal tumors were evaluated at 16 weeks of age. MDD diet suppressed intestinal tumor formation in ApcMin/+ mice by ∼80% when started at 5 weeks of age. Importantly, the protective effect was lost when the MDD diet was started at 10 weeks of age, indicating an important time-dependency on cancer suppression. Gene expression profiling of normal colonic mucosa after 11 weeks on MDD diet identified the most significantly down-regulated genes related to immune response and inflammation, data that are consistent with a recently published human colon expression profiling study (Protiva et al., 2011). The cancer suppression, however, was associated with reduced food intake and lowered body weight gain (up to 40%) throughout the experimental period. To control for this effect, Study 2 was performed in which ApcMin/+ mice were pair-fed with either methyl donor sufficient (MDS) or methyl donor deficient (MDD) diet, beginning at 5 weeks of age for a total of 11 weeks. A third group received MDS ad libitum. At 16 weeks of age, intestinal tumor formation was significantly reduced (54%, p&amp;lt;0.001) in the caloric-restricted MDS group. In the MDD group, however, tumor suppression was almost complete (∼96%, p&amp;lt;0.001). Associated with tumor protection were increased numbers of apoptotic cells within the villous epithelium of the small intestine, with a concomitant reduction in cell proliferation assessed by Ki-67 and Phospho-histone H3 (pHH3). While cancer protection by methyl donor deficiency is partially dependent on reduced caloric intake, additional mechanisms dependent on altered cell turnover must be invoked to explain these results. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-182. doi:1538-7445.AM2012-LB-182

Methyl Vitamin B12 but not methylfolate rescues a motor neuron-like cell line from homocysteine-mediated cell death

Homocysteine is an excitatory amino acid implicated in multiple diseases including amyotrophic lateral sclerosis (ALS). Information on the toxicity of homocysteine in motor neurons is limited and few studies have examined how this toxicity can be modulated. In NSC-34D cells (a hybrid cell line derived from motor neuron–neuroblastoma), homocysteine induces apoptotic cell death in the millimolar range with a TC 50 (toxic concentration at which 50% of maximal cell death is achieved) of 2.2 mM, confirmed by activation of caspase 3/7. Induction of apoptosis was independent of short-term reactive oxygen species (ROS) generation. Methyl Vitamin B12 (MeCbl) and methyl tetrahydrofolate (MTHF), used clinically to treat elevated homocysteine levels, were tested for their ability to reverse homocysteine-mediated motor neuron cell death. MeCbl in the micromolar range was able to provide neuroprotection (2 h pretreatment prior to homocysteine) and neurorescue (simultaneous exposure with homocysteine) against millimolar homocysteine with an IC 50 (concentration at which 50% of maximal cell death is inhibited) of 0.6 μM and 0.4 μM, respectively. In contrast, MTHF (up to 10 μM) had no effect on homocysteine-mediated cell death. MeCbl inhibited caspase 3/7 activation by homocysteine in a time- and dose-dependent manner, whereas MTHF had no effect. We conclude that MeCbl is effective against homocysteine-induced cell death in motor neurons in a ROS-independent manner, via a reduction in caspase activation and apoptosis. MeCbl decreases Hcy induced motor neuron death in vitro in a hybrid cell line derived from motor neuron–neuroblastoma and may play a role in the treatment of late stage ALS where HCy levels are increased in animal models of ALS.

Methyl transfer from a hydrophobic vitamin B 12 derivative to arsenic trioxide

The methylation reaction of arsenic trioxide conducted at 37 °C and pH 7.0 for 24 h using hydrophobic methylated vitamin B 12, (methyl) (aquo) heptamethylcobyrinate perchlorate, CH 3B 12 ester, as a methyl donor in the presence of reduced glutathione (GSH) yielded monomethylarsonous acid (MMA), dimethylarsinic acid (DMA), and trimethylarsine oxide (TMAO) as products with a methylation rate over 95%. In contrast, when methylcobalamin (CH 3B 12) was used as the methyl donor, only MMA and DMA were produced and the methylation rate dropped to around 20%. Reductive demethylation of a methyl-corrinoid coordination complex mediated by GSH is suggested as a mechanism of methyl transfer to arsenic trioxide. The differences observed for different corrinoid coordination complexes with respect to the reactivity of methyl transfer to arsenic is ascribable to differences inherent in the base-on (CH 3B 12) and base-off (CH 3B 12 ester) natures of the compounds.

Preparation of Targeting Vehicles for The Delivery of N-Bisphosphonates

Bisphosphonates (BP) are drugs currently administered orally to treat diseases characterised by an excessive bone resorption. Alternative and more efficient delivery routes and more potent compounds are being investigated. Three implantable delivery systems, which allow the controlled release of therapeutic agents from the device core, are examined in this paper. (4- (aminomethyl) benzene) bisphosphonic acid (ABBP) was incorporated on Ca8.8Na0.8(PO4)4.8(CO3)1.2(OH)0.4F1.6 particles by refluxing the powder in a 60 mmol suspension in acetone at 60°C for 5 hours. 4-aminophenyl acetic bisphosphonate monosodium salt (APBP) and 1- H-indole-3-acetic bisphosphonate monosodium (IBP) were loaded on Ca10(PO4)6(OH)1F1 ceramic bodies by stirring the ceramic bodies in 0.04M BP solutions. Injectable acrylic cements based on self-curing formulations of methyl methacrylate (MMA) and vitamin E were loaded with APBP and IBP. The incorporation of ABBP was confirmed by MAS-NMR spectroscopy. Modified powder shows two different phosphorous environments, the first one at 2.91 ppm can be assigned to the apatite base and the second one at 18.0 ppm has to be attributed to the phosphonic group of the ABBP. The IBP addition on ceramic surfaces did not decrease the number of osteoclast colonies and appeared to improve the performance of the HA as a surface for osteoblast culture. A therapeutic dosage of APBP and IBP can be achieved from acrylic cements that showed lack of toxicity and an increased cellular activity and proliferation.

The Role of Vitamin B12 in Fasting Hyperhomocysteinemia and Its Interaction with the Homozygous C677T Mutation of the Methylenetetrahydrofolate Reductase (MTHFR) Gene

Total fasting plasma homocysteine (tHcy), homozygosity for the C677T mutation of the methylenetetrahydrofolate reductase (MTHFR) gene and for the A2756G mutation of the methionine synthase (MS) gene, vitamin B12 and folate plasma levels were evaluated in 170 consecutive patients (89 M, 81 F; mean age 41 +/- 12 yrs) with documented early-onset thrombosis (89 venous, 69 arterial, 12 both; mean age at first episode 36 +/- 11 yrs), and in 182 age- and sex-matched healthy control subjects. Moderate hyperhomocysteinemia (HHcy, tHcy >19.5 microM in men and >15 microM in women) was detected in 45 patients (26.5%) and in 18 controls (9.9%, Mantel-Haenszel OR and 95% C.I. after stratification for arterial or venous thrombosis: 3.25, 1.78-5.91). The 677TT MTHFR genotype was not significantly more prevalent in patients (27.6%) than in controls (21.4%, RR = 1.42: 0.84-2.41), and markedly contributed to HHcy (Mantel-Haenszel RR after stratification for case/control status: 8.29, 4.61-14.9). The 2756GG MS genotype, observed in 4 patients (2.4%) and 8 controls (4.4%), was not associated to HHcy. tHcy was negatively correlated to folate and vitamin B12 levels, with better correlation found in subjects with the 677TT mutation (r = -0.42 and -0.25) than with the 677CC or CT MTHFR genotype (r = 0).37 and -0.11). However, folate was similar in patients and controls and vitamin B12 was higher in patients (460 +/- 206 vs. 408 +/-185 pg/ml, p = 0.011). In a generalized linear model, 44% of the variation in tHcy levels was explained by folate and vitamin B12 levels, the MTHFR genotype, gender, and by the interaction of the MTHFR genotype with folate (p < or =0.028); the interactions of vitamin B12 with the MTHFR genotype, gender and patient/control status also significantly contributed to the variation in tHcy levels (p < or =0.028). A 4-week administration of 5-methyltetrahydrofolate (15 mg/day) markedly lowered plasma tHcy in 24 patients with MTHFR 677TT genotype, but the response to treatment correlated with vitamin B,2 levels (p = 0.023). Subjects carrying the MTHFR 677TT genotype have higher folate and vitamin B12 requirements irrespective of the A2756G polymorphism of the MS gene. Yet unidentified abnormalities of MS or of any of the enzymes participating in the synthesis of methylated vitamin B12 may play an important role in the phenotypic expression of moderate hyperhomocysteinemia.

Synthesis and redox potentials of methylated vitamin K derivatives

We report the synthesis of derivatives of vitamin K3 as well as of vitamins K1 and K2 containing a different number of methyl groups in various positions in order to reduce their redox potentials and to change systematically their steric features. The long aliphatic chain of vitamins K1 and K2 is simulated by an undecyl chain or a methyl group, respectively. The redox potentials of the first reduction step were measured by cyclic voltammetry in DMF. These compounds are relevant for studies of the structure–function relationship of vitamin K dependent enzymes and the investigation of electron transfer reactions in photosynthetic reaction centers.

Enhancement of adhesive property of epithelial cell line Mm2T by culture in the presence of methylated vitamin B12.

A thymic epithelial cell line Mm2T was cultured in a medium containing a high concentration (100 micrograms/ml) of methylated vitamin B12 (CH3-B12). After 19 days, cells were found to have a flat phenotype, to have lost the floating cells which were observed in the control cells at the confluent stage, and to have acquired a resistance to trypsin. However, treatment of the CH3-B12-treated cells with EDTA resulted in a dissociation of cell-to-cell contact and reaggregation was achieved by addition of Ca2+, indicating the involvement of Ca2+ ion in cell-to-cell contact. Electron microscopic analyses revealed that the CH3-B12-treated cells were nearly square in their vertical section, which was in contrast to the dome-shaped feature of the control cells, and their cell-to-cell contact area was significantly widespread, as compared to those of the control, indicating that Mm2T cells acquires an adhesive property by treatment with CH3-B12. Biochemical analyses of both cells indicated that the concentration of glucosylceramide in the CH3-B12-treated cells was higher than that of the control. Free glucose characteristically inhibited the reattachment of cells dissociated with EDTA, suggesting the involvement of glucose in the cell-to-cell adhesion of CH3-B12-treated cells. In addition, WGA-binding glycoconjugates were intensely observed in the boundary region of CH3-B12-treated cells by immunohistochemical staining, but not in that of the control cells. It is suggested that CH3-B12 may affect the morphological alteration of Mm2T by enhancing cell adhesion through elevated expression of the C-type lectin.

The effect of prostaglandin E 1·αCD on vibratory threshold determined with the SMV-5 vibrometer in patients with diabetic neuropathy

We studied the effect of prostaglandin E 1·αCD (PGE 1) on diabetic peripheral neuropathy by evaluating subjective symptoms and vibration sensation using a new vibrometer (SMV-5). Patients with diabetic neuropathy ( n = 38) were divided into three groups; group A received no drugs (control), group B was treated with 1500 μg/day of oral methyl vitamin B 12 (VB 12) for four weeks, and group C received 1.2 μg/kg/day PGE 1 intravenously for four weeks. There was a close relationship between symptom scores and vibratory threshold (VT). The effect of PGE 1 on subjective symptoms and VT were compared with those in groups A and B. Patients who received PGE 1 showed a significant improvement rate in pain and hypesthesia compared to patients in groups A and B, and in numbness compared to group A. During the study period, there was no significant change in VT in groups A and B, whereas VT was significantly improved at styloid process ( P < 0.05) and at medial malleolus ( P < 0.001) in group C. Our results confirmed that PGE 1 significantly improved both subjective symptoms and VT, indicating that PGE 1 therapy may be useful in diabetic neuropathy.

Vitamin B 12 accelerates re-entrainment of activity rhythms in rats

The effects of methyl vitamin B 12 (5–6 mg/kg, p.o.) on the entrainment of circadian running wheel activity rhythm to a new lighting schedule were measured in rats. After the light-dark (LD) cycle was abruptly reversed, rats given vitamin B 12 took less time to entrain their circadian locomotor activity rhythm to the new cycle than did controls. This result indicates that vitamin B 12 accelerates the reentrainment of the mammalian circadian activity rhythm following an abrupt change in the environmental LD cycle.

Effects of methyl vitamin B12 on sperm quality.

Effects of methyl vitamin B12 on sperm quality.

A review of the biogeochemistry of germanium in natural waters

Three germanium species, inorganic germanium (Ge i), monomethylgermanium (MMGe) and dimethylgermanium (DMGe) have been identified in natural waters. Ge i in solution varies as a coherent pair with silicon, reflecting uptake into the release from the tests of siliceous organisms. MMGe and DMGe display conservative (non-reactive) behavior in estuaries and oceans, varying only with salinity. This conservative behavior implies that methylgermanium species are not incorporated into the silicon biogeochemical cycle. The residence time of methyl-Ge in the ocean is estimated to be on the order of a few million years. We have observed production of MMGe, DMGe and trimethylgermanium (TMGe) in an anaerobic sewage digester, suggesting that methyl-Ge in the environment may be produced by microbial biomethylation of Ge i during methanogenesis. Algal cultures grown in Ge i-enriched media were not observed to produce methylgermanium, nor was Ge i methylated by reaction with methylcobalamin, a methylated vitamin B 12 derivative.