The Management of Nausea and Vomiting in Pregnancy and Hyperemesis Gravidarum (Green-top Guideline No. 69).

An objective and validated index of nausea and vomiting such as the Pregnancy-Unique Quantification of Emesis (PUQE) and HyperEmesis Level Prediction (HELP) tools can be used to classify the severity of NVP and HG. [Grade C] Ketonuria is not an indicator of dehydration and should not be used to assess severity. [Grade A] There are safety and efficacy data for first line antiemetics such as anti (H1) histamines, phenothiazines and doxylamine/pyridoxine (Xonvea®) and they should be prescribed initially when required for NVP and HG (Appendix III). [Grade A] There is evidence that ondansetron is safe and effective. Its use as a second line antiemetic should not be discouraged if first line antiemetics are ineffective. Women can be reassured regarding a very small increase in the absolute risk of orofacial clefting with ondansetron use in the first trimester, which should be balanced with the risks of poorly managed HG. [Grade B] Metoclopramide is safe and effective and can be used alone or in combination with other antiemetics. [Grade B] Because of the risk of extrapyramidal effects metoclopramide should be used as second-line therapy. Intravenous doses should be administered by slow bolus injection over at least 3 minutes to help minimise these. [Grade C] Women should be asked about previous adverse reactions to antiemetic therapies. If adverse reactions occur, there should be prompt cessation of the medications. [GPP] Normal saline (0.9% NaCl) with additional potassium chloride in each bag, with administration guided by daily monitoring of electrolytes, is the most appropriate intravenous hydration. [Grade C] Combinations of different drugs should be used in women who do not respond to a single antiemetic. Suggested antiemetics for UK use are given in Appendix III. [GPP] Thiamine supplementation (either oral 100 mg tds or intravenous as part of vitamin B complex (Pabrinex®)) should be given to all women admitted with vomiting, or severely reduced dietary intake, especially before administration of dextrose or parenteral nutrition. [Grade D] All therapeutic measures should have been tried before considering termination of pregnancy. [Grade C].

B Vitamins Supplementation Can Improve Cognitive Functions and May Relate to the Enhancement of Transketolase Activity in A Rat Model of Cognitive Impairment Associated with High-fat Diets.

OBJECTIVE: To determine whether B vitamin treatment was sufficient to reduce cognitive impairment associated with high-fat diets in rats and to modulate transketolase (TK) expression and activity. METHODS: To test this, we separated 50 rats into five groups that were either fed a standard chow diet (controls) or a high-fat diet (experimental groups H0, H1, H2, and H3). H0 group animals received no additional dietary supplementation, while H1 group animals were administered 100 mg/kg body weight (BW) thiamine, 100 mg/kg BW riboflavin, and 250 mg/kg BW niacin each day, and group H2 animals received daily doses of 100 mg/kg BW pyridoxine, 100 mg/kg BW cobalamin, and 5 mg/kg BW folate. Animals in the H3 group received the B vitamin regimens administered to both H1 and H2 each day. RESULTS: Over time, group H0 exhibited greater increases in BW and fat mass relative to other groups. When spatial and memory capabilities in these animals were evaluated via conditioned taste aversion (CTA) and Morris Water Maze (MWM), we found B vitamin treatment was associated with significant improvements relative to untreated H0 controls. Similarly, B vitamin supplementation was associated with elevated TK expression in erythrocytes and hypothalamus of treated animals relative to those in H0 (P<0.05). CONCLUSION: Together, these findings suggest B vitamin can modulate hypothalamic TK activity to reduce the severity of cognitive deficits in a rat model of obesity. As such, B vitamin supplementation may be a beneficial method for reducing cognitive dysfunction in clinical settings associated with high-fat diets.

Isolated Pyridoxine Deficiency Presenting as Muscle Spasms in a Patient With Type 2 Diabetes: A Case Report and Literature Review.

Pyridoxine is an important co-factor for many biochemical reactions in cellular metabolism related to the synthesis and catabolism of amino acids, fatty acids, neurotransmitters. Deficiency of pyridoxine results in impaired transcellular signaling between neurons and presents with muscular convulsions, hyperirritability, and peripheral neuropathy. Deficiency of pyridoxine is usually found in association with other vitamin B deficiencies such as folate (vitamin B9) and cobalamin (vitamin B12). Isolated pyridoxine deficiency is extremely rare. We present the case of a 59-year old female with type 2 diabetes who complained of painful muscle spasms. Her muscle spasms involved in both feet, which have spread proximally to her legs. She also experienced intermittent muscle spasms in her left arm, which is not alleviated by baclofen, cyclobenzaprine. Her plasma pyridoxal 5-phosphate confirmed pyridoxine deficiency. Vitamins B1, B3, B12, and folate were within normal limits. The patient received standard-dose intramuscular pyridoxine injections for three weeks followed by oral supplements for 3 months and her symptoms resolved. This case illustrates the rare instance of isolated pyridoxine deficiency in type 2 diabetes patient manifesting as myoclonic muscle spasms involving the legs and arms in the absence of objective polyneuropathy. Pyridoxine level should, therefore, be assessed in patients with type 2 diabetes, including newly diagnosed patients.

High-dose pyridoxine treatment for inherited glycosylphosphatidylinositol deficiency.

OBJECTIVE: We aimed to assess the efficacy and safety of high-dose pyridoxine treatment for seizures and its effects on development in patients with inherited glycosylphosphatidylinositol deficiencies (IGDs). METHODS: In this prospective open-label multicenter pilot study, we enrolled patients diagnosed with IGDs using flow cytometry and/or genetic tests. The patients received oral pyridoxine (20-30 mg/kg/day) for 1 year, in addition to previous treatment. RESULTS: All nine enrolled patients (mean age: 66.3 ± 44.3 months) exhibited marked decreases in levels of CD16, a glycosylphosphatidylinositol-anchored protein, on blood granulocytes. The underlying genetic causes of IGDs were PIGO, PIGL, and unknown gene mutations in two, two, and five patients, respectively. Six patients experienced seizures, while all patients presented with developmental delay (mean developmental age: 11.1 ± 8.1 months). Seizure frequencies were markedly (>50%) and drastically (>90%) reduced in three and one patients who experienced seizures, respectively. None of the patients presented with seizure exacerbation. Eight of nine patients exhibited modest improvements in development (P = 0.14). No adverse events were observed except for mild transient diarrhea in one patient. CONCLUSION: One year of daily high-dose pyridoxine treatment was effective in the treatment of seizures in more than half of our patients with IGDs and modestly improved development in the majority of them. Moreover, such treatment was reasonably safe. These findings indicate that high-dose pyridoxine treatment may be effective against seizures in patients with IGDs, although further studies are required to confirm our findings. (University Hospital Medical Information Network Clinical Trials Registry [UMIN-CTR] number: UMIN000024185.).

Amelioration of Levetiracetam-Induced Behavioral Side Effects by Pyridoxine. A Randomized Double Blind Controlled Study.

BACKGROUND: Levetiracetam is a relatively new-generation antiseizure drug approved for the treatment of focal and generalized seizures. Despite its favorable side effect profile and minimal drug-drug interactions, neuropsychiatric side effects are reported in up to 13% of children. A few case series have suggested that supplementation of pyridoxine may mitigate these side effects, but controlled trials are lacking. To address this issue, a randomized interventional study was carried out in a pediatric tertiary hospital to qualify and quantify the potential beneficial effect of pyridoxine in attenuating the neuropsychiatric side effects of levetiracetam in children. METHODS: A total of 105 children with epilepsy who were taking levetiracetam (as a monotherapy or an adjunct) who showed behavioral symptoms coinciding with the start of levetiracetam, were included. Patients randomly and blindly received either a therapeutic (pyridoxine group, 46 of 105, 44%) or a homeopathic dose of pyridoxine (placebo, 59 of 105, 56%). A 30-item behavioral checklist was used to qualify and quantify the behavioral side effects at baseline and at different time points following initiation of treatment. RESULTS: Both placebo and pyridoxine groups experienced a statistical reduction in behavioral scores when compared with baseline. Our study indicated that although there was a placebo effect, the improvement in neuropsychiatric symptoms was more prominent in children who received therapeutic doses of pyridoxine. CONCLUSIONS: These data provide clinicians with pertinent evidence-based information that suggests that a trial of pyridoxine in patients who experience behavioral side effects due to the use of levetiracetam may avoid unnecessary change of antiseizure medications.

Clinical and biochemical outcome of a patient with pyridoxine-dependent epilepsy treated by triple therapy (pyridoxine supplementation, lysine-restricted diet, and arginine supplementation).

Pyridoxine-dependent epilepsy (PDE) is a recessive genetic disease characterized by epileptic encephalopathy with therapeutic response to pharmacological doses of pyridoxine and resistance to anti-epileptic treatments. The recent discovery in 2006 of the genetic defect antiquitin (ALDH7A1, OMIM #266100) has helped to understand the underlying mechanism, which is the accumulation of neurotoxic intermediates in the lysine catabolic pathway. The goal of the new therapeutic approach, termed triple therapy (TT) (pyridoxine, lysine-restricted diet and arginine supplementation), is to improve epilepsy control and neurocognitive development in patients with PDE. We present the 3-year treatment outcome for a child with PDE on pyridoxine treatment (started at age 5 months), lysine-restricted diet (started at age 17 months) and arginine supplementation therapy (started at age 19 months). The TT was well-tolerated with good compliance. No adverse events were reported. We observed a neurodevelopmental improvement, significantly fewer seizures, and a reduction of pipecolic acid (PA) as a biomarker of the illness. Our results show an improving clinical evolution, supporting and extending previous studies reporting efficacy of TT.

Neonatal pyridoxine administration long lastingly accelerates cortical spreading depression in male rats, without affecting anxiety-like behavior.

Objectives: Pyridoxine plays a key role in the development of the human nervous system. Several reports suggest that administration of high doses of pyridoxine can be helpful in improving disturbances such as anxiety and pyridoxine-dependent epilepsy, although it has also been associated with a proconvulsive action. In this study, we investigated in developing rats the effects of repeated administration of various doses of pyridoxine on anxiety-like behavior and the brain excitability-related phenomenon known as cortical spreading depression (CSD).Methods: From postnatal day (P) 7 to P27, Wistar rat pups received per gavage pyridoxine hydrochloride (1 mg/kg/day, or 5 mg/kg/day, or 10 mg/kg/day). On P60-70, the animals were tested in the elevated plus maze (EPM) to evaluate anxiety-like behavior. On P71-80, we recorded the CSD (4-hour recording session).Results: Compared with naïve (gavage-free) and saline-treated controls, pyridoxine-treated groups displayed a significant (p < 0.001) increase in CSD propagation velocity and amplitude of the CSD negative direct-current (DC)-shift, and a decrease in the CSD DC-shift duration. These effects were long-lasting and dose-dependent. In the EPM, no significant pyridoxine-associated effect was observed.Discussion: Our data demonstrate a novel action of pyridoxine on an electrical activity-related phenomenon (CSD) in the developing brain, confirming the hypothesis that the chronic treatment with pyridoxine early in life modulates CSD. Data on CSD propagation suggest that pyridoxine at a high dose might act as a prooxidant agent in the developing brain, a hypothesis that deserves further testing.

A pilot randomized double-blind, placebo-controlled study on the effects of the topical application of pyridoxine on palmar-plantar erythrodysesthesia (PPE) induced by capecitabine or pegylated liposomal doxorubicin (PLD).

PURPOSE: Palmar-Plantar Erythrodysesthesia (PPE) is a dose-limiting adverse event that commonly occurs with capecitabine and Pegylated Liposomal Doxorubicin-PLD treatment. The study aimed to test the effectiveness of a Pyridoxine (B6) treatment protocol in the management of PPE in patients receiving treatment with capecitabine or pegylated liposomal doxorubicin. METHODS: This was a pilot randomized double-blind, placebo-controlled study. Patients receiving capecitabine or pegylated liposomal doxorubicin with PPE grade 1 or above were randomly allocated to receive pyridoxine or placebo. The PPE grade, Quality of Life-QoL, Pain and patients' activities of daily living were assessed. RESULTS: Thirty patients were assigned in the Control and 24 in the Intervention group. No statistically significant difference was found in the PPE grade between baseline and week 6 in the 2 groups (p = 0.263). The control group exhibited worst PPE-associated QoL and higher PAIN levels between baseline and week 6. Respectively, the intervention group showed improved PPE-associated QoL and lower PAIN levels. At week 6, the ECOG status in the Intervention group was improved compared to the control (p = 0.018). Patients in the Intervention group experienced better Global Health Status (p = 0.012), Physical (p = 0.003), Emotional (p = 0.008), and Social function (p < 0.001), lower Fatigue (p = 0.001) and Pain (p = 0.006) compared to Control. CONCLUSION: Topical pyridoxine was not shown to have an effect on the treatment of PPE. However, results demonstrated its effectiveness on health related QoL, QoL-associated with PPE and pain levels. Due to the high attrition rate further validation of these results in a larger population is warranted. CLINICALTRIALS. GOV IDENTIFIER: NCT02625415.

Pyridoxine and Magnesium Administration-Induced Hyperactivity in Two Children With Autism Spectrum Disorder: Case Reports From a Clinical Trial.

PURPOSE: Pyridoxine hydrochloride and magnesium sulfate (pyridoxine-Mg) have been used for the management of autism spectrum disorder (ASD). We present a case report of 2 children with ASD who were administered pyridoxine-Mg for 2 months. METHODS: The Childhood Autism Rating Scale, Second Edition, was used to confirm the adverse reaction. The Naranjo Adverse Drug Reaction Probability Scale was used to assess causality. RESULTS: Children were reported by their parents as being hyperactive. Evaluation by the psychologist using the Childhood Autism Rating Scale, Second Edition, also confirmed the reaction. According to the Naranjo scale, hyperactivity had a possible and probable association with pyridoxine-Mg for child 1 and 2, respectively. IMPLICATIONS: A probable to possible association exists between hyperactivity and pyridoxine-Mg. Clinical Trial Registry-India identifier: CTRI/2019/07/020102.

Nutritional Optic Neuropathies: State of the Art and Emerging Evidences.

Nutritional optic neuropathy is a cause of bilateral, symmetrical, and progressive visual impairment with loss of central visual acuity and contrast sensitivity, dyschromatopsia, and a central or centrocecal scotoma. The clinical features are not pathognomonic, since hereditary and toxic forms share similar signs and symptoms. It is becoming increasingly common due to the widespread of bariatric surgery and strict vegetarian or vegan diets, so even the scientific interest has recently increased. In particular, recent studies have focused on possible pathogenetic mechanisms, and on novel diagnostic and therapeutic strategies in order to prevent the onset, make a prompt diagnosis and an accurate nutritional supplementation, and to avoid irreversible optic nerve atrophy. Nowadays, there is clear evidence of the role of cobalamin, folic acid, thiamine, and copper, whereas further studies are needed to define the role of niacin, riboflavin, and pyridoxine. This review aims to summarize the etiology, diagnosis, and treatment of nutritional optic neuropathy, and it is addressed not only to ophthalmologists, but to all physicians who could come in contact with a patient with a possible nutritional optic neuropathy, being a fundamental multidisciplinary approach.

A cautionary tale of pyridoxine toxicity in cystathionine beta-synthase deficiency detected by two-tier newborn screening highlights the need for clear pyridoxine dosing guidelines.

Classic homocystinuria is due to deficiency of cystathionine beta-synthase (CBS), a pyridoxine-dependent enzyme that, depending on the molecular variants, may be co-factor responsive. Elevated methionine is often used as the primary analyte to detect CBS deficiency (CBSD) on newborn screening (NBS), but is limited by increased detection of other biochemical disorders with less clear clinical significance such as methionine aminotransferase (MAT) I/III heterozygotes. Our state has implemented a two-tier NBS algorithm for CBSD that successfully reduced the number of MATI/III heterozygotes, yet effectively detected a mild, co-factor responsive form of CBSD. After initial diagnosis, newborns with CBSD often undergo a pyridoxine challenge with high-dose pyridoxine to determine responsiveness. Here we describe our NBS-identified patient with a mild form of pyridoxine responsive CBSD who developed respiratory failure and rhabdomyolysis consistent with pyridoxine toxicity during a pyridoxine challenge. This case highlights the need for weight-based dosing and duration recommendations for pyridoxine challenge in neonates.

The regulatory effects of pyridoxine deficiency on the grass carp (Ctenopharyngodon idella) gill barriers immunity, apoptosis, antioxidant, and tight junction challenged with Flavobacterium columnar.

The effects of dietary pyridoxine (PN) on the gill immunity, apoptosis, antioxidant and tight junction of grass cap (Ctenopharyngodon idella) were investigated in this study. Fish were fed semi-purified diets containing graded levels of PN for 10 weeks, and then challenged with Flavobacterium columnare by bath immersion exposure for 3 days. The results indicated that compared with the optimal PN level, PN deficiency resulted in a decline in the antimicrobial compound production of gill. In addition, PN deficiency up-regulated the pro-inflammatory cytokines and down-regulated the anti-inflammatory cytokines gene expression, which might be associated with the enhanced nuclear factor κB p65 and the inhibited target of rapamycin signalling pathways, respectively, suggesting that PN deficiency could impair gill immune barrier function. Furthermore, PN deficiency (1) induced cell apoptosis, which may be partly associated with the (apoptotic protease activating factor-1, Bcl-2 associated X protein)/caspase-9 and c-Rel/tumor necrosis factor α (rather than FasL)/caspase-8 mediated apoptosis pathway. (2) Inhibited Kelch-like ECH-associating protein 1a/NF-E2-related factor 2 mRNA expression, decreased the mRNA expression and activities of antioxidant enzymes, increased the levels of reactive oxygen species, protein carbonyl and malondialdehyde. (3) Increased the mRNA expression level of myosin light chain kinase, which may be result in the down-regulation of tight junction complexes such as zonula occludens 1, occludin and claudins (expect claudin-12 and claudin-15). These results suggest that PN deficiency could impair gill physical barrier function. In summary, dietary PN deficiency could cause the impairment of gill barrier function associated with immunity, apoptosis, antioxidant and tight junction, which may result in the increased the susceptibility of fish to pathogenic bacteria. Moreover, based on the gill rot morbidity, LZ activity and MDA content, the dietary PN requirements for grass cap were estimated to be 4.85, 4.78 and 4.77 mg kg-1 diet, respectively.

The effect of TJ-28 (Eppikajutsuto) on the prevention of hand-foot syndrome using Capecitabine for colorectal cancer: The Yokohama Clinical Oncology Group Study (YCOG1102).

BACKGROUND: Eppikajututo (TJ-28, a Kampo medicine) is effective against rheumatoid arthritis and eczema. We conducted a randomized comparative trial to assess the efficacy of TJ-28 for preventing hand-foot syndrome (HFS) as a complication of adjuvant chemotherapy using capecitabine. METHODS: The present study was a multi-institutional randomized-controlled trial (UMIN000005899). Colorectal cancer patients scheduled to receive capecitabine chemotherapy as adjuvant therapy were randomly assigned to receive TJ-28 (7500 mg/day) or oral pyridoxine (60 mg/day). Patients were monitored for the development of grade ≥ 2 HFS according to the National Cancer Institute Common Toxicity Criteria until chemotherapy completion. RESULTS: Twenty-two patients were enrolled in this study. The relative dose intensity of capecitabine was 76.2% in the TJ-28 group and 68.2% in the pyridoxine group. Grade ≥ 2 HFS developed in 6 (50.0%) of 12 TJ-28 patients and in 4 (40.0%) of 10 pyridoxine patients. Chemotherapy treatment failure was observed in seven patients, mainly due to HFS, liver dysfunction, diarrhea, and neutropenia. Chemotherapy treatment failure due to HFS occurred in none of the TJ-28 group and 2 patients (20.0%) in the pyridoxine group (p = 0.114). CONCLUSION: Capecitabine-associated HFS was not markedly prevented by TJ-28 compared with pyridoxine. However, TJ-28 might support the continuation of chemotherapy with capecitabine. Further studies are warranted to clarify the benefits of TJ-28.

Pyridoxine, folate and cobalamin for migraine: A systematic review.

There is a possible relationship between migraine and hypercoagulability inducing factors, such as hyperhomocysteinemia. In this context, homocysteine (Hcy)-lowering vitamins (B6-folate-B12) may prove beneficial in the management-prophylaxis of migraine. We performed a systematic literature search in order to retrieve studies assessing the supplementation of B6, folate and B12 (alone or as adjunctive therapies) to migraine patients, as well as patients suffering from other primary headache disorders. MEDLINE, EMBASE, CENTRAL, Google Scholar, trial registries and OpenGrey were searched. Twelve relevant articles were retrieved. The management of acute migraine attacks with Hcy-lowering vitamins has not provided promising results (one randomized controlled trial-RCT-and one prospective uncontrolled trial). On the contrary, significant benefits were registered for the use of B6 alone, in combination with folate and in combination with folate and B12 in the prophylaxis of migraine with aura (MA) in adults compared to placebo (five RCTs, only one did not obtain significant results). Folate supplementation alone was not more efficacious than placebo (one RCT). Limited data for the prophylaxis of migraine without aura (MO) in children (two prospective uncontrolled trials) and adults (two prospective uncontrolled trials involving both MA and MO participants) impede the extraction of safe conclusions. An overall attractive safety profile was exhibited with gastrointestinal adverse events being the most common. Overall, a potential beneficial effect regarding the administration of B6, folate and/or B12 in the prophylaxis of MA in adults was indicated. Additional high-quality RCTs that will investigate MO in adults as well as MO and MA in children are warranted.

O uso do cloridrato de piridoxina para induzir estro em cadelas / The use of pyridoxine chloridrate to induce estrus in female dogs

Os agonistas dopaminérgicos são utilizados para induzir estro em cadelas, pois atuam na síntese e liberação de prolactina. Objetivou-se avaliar o efeito da piridoxina como indutor de estro em cadelas por agir na neurotransmissão dopaminérgica. Foram selecionadas 40 cadelas em anestro, divididas em quatro grupos experimentais, tratadas com 10mg/kg/dia (G1) e 50mg/kg/dia (G2) de cloridrato de piridoxina, 5µg/kg/dia (G3) de cabergolina e grupo controle/placebo (G4) por até 20 dias. Foram realizadas citologias vaginais a cada 24h para acompanhamento do ciclo estral e análises hormonais (FSH, LH e PRL) no dia zero e 120h do início do tratamento. As cadelas do G3 (100%) manifestaram proestro após 12 dias de tratamento aproximadamente, tempo inferior aos demais grupos (P<0,05). Apenas uma cadela do G1 e uma do G2 ficaram gestantes contra oito fêmeas do G3 e nenhuma do G4 (P<0,05). As concentrações plasmáticas de prolactina foram reduzidas nas fêmeas do G2 e G3 (P<0,05). As demais avaliações hormonais não sofreram influência do tratamento (P>0,05). O cloridrato de piridoxina foi ineficiente para induzir estro em cadelas, mas foi capaz de suprimir a prolactina, de forma semelhante à cabergolina, quando utilizado na dose de 50mg/kg/dia.(AU)

Dopaminergic agonists are used to induce estrus in female dogs as they act in the synthesis and release of prolactin. The objective of this study was to evaluate the effect of pyridoxine as an inducer of estrus by acting on dopaminergic neurotransmission. A total of 40 female dogs in anestrous were divided into four experimental groups treated with 10mg/kg/day (G1) and 50mg/kg/day (G2) of pyridoxine hydrochloride, 5µg/kg/day (G3) of cabergoline and control group/placebo (G4) for up to 20 days. Vaginal cytologies were performed every 24h for follow-up of the estrous cycle and hormonal analyzes (FSH, LH and PRL) on day zero and 120 hours after the start of treatment. The female dogs from G3 (100%) showed proestrus after 12 days of treatment, less time than the other groups (P< 0.05). Only one female from G1 and one from G2 were pregnant against eight from G3 and none from G4 (P< 0.05). Plasma concentrations of prolactin were reduced by treatment in females from G2 and G3 (P< 0.05). The other hormonal evaluations were not influenced by the treatment (P> 0.05). Pyridoxine chloridrate was inefficient to induce estrus in female dogs but was able to suppress prolactin when used at a dose of 50mg/kg/day.(AU)

Pyridoxine induces glutathione synthesis via PKM2-mediated Nrf2 transactivation and confers neuroprotection.

Oxidative stress is a major pathogenic mechanism in Parkinson's disease (PD). As an important cellular antioxidant, glutathione (GSH) balances the production and incorporation of free radicals to protect neurons from oxidative damage. GSH level is decreased in the brains of PD patients. Hence, clarifying the molecular mechanism of GSH deficiency may help deepen our knowledge of PD pathogenesis. Here we report that the astrocytic dopamine D2 receptor (DRD2) regulates GSH synthesis via PKM2-mediated Nrf2 transactivation. In addition we find that pyridoxine can dimerize PKM2 to promote GSH biosynthesis. Further experiments show that pyridoxine supplementation increases the resistance of nigral dopaminergic neurons to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in wild-type mice as well as in astrocytic Drd2 conditional knockout mice. We conclude that dimerizing PKM2 may be a potential target for PD treatment.

Pyridoxine supplementation for levetiracetam-related neuropsychiatric adverse events: A systematic review.

OBJECTIVE: Among people with epilepsy, levetiracetam (LEV) can cause neuropsychiatric adverse events (NPAEs) that impact negatively on quality of life. It has been suggested that pyridoxine can ameliorate LEV-related NPAEs. We conducted a systematic review of studies on the use of pyridoxine supplementation to relieve NPAEs associated with LEV therapy. METHODS: The review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Medline, EMBASE, Scholar, Cochrane-CENTRAL (2000-2019), and EThOS platform were searched for studies on the use of pyridoxine in patients with LEV-related NPAEs. Proportions of patients reported to benefit from pyridoxine supplementation were tabulated, and a random-effect model meta-analysis was conducted. RESULTS: Eleven retrospective studies/case reports and one randomized prospective study, mostly including pediatric populations, were identified. Retrospective studies, which were rated as low quality due to failure to control for bias, reported an overall improvement of NPAEs after pyridoxine supplementation in 72.5% (108/149) of patients. The proportion of patients showing improvement in a pooled analysis of the four largest retrospective studies (n = 134) was 72.1% (95% confidence interval (CI) 47.1-88.3), although there was high heterogeneity across studies (I2 = 82%, pheterogeneity < 0.01). In the only prospective trial, patients randomized to pyridoxine supplementation were more likely to show relief from NPAEs than patients not receiving supplementation (p < 0.01), but outcomes might have been affected by assessment bias. CONCLUSION: This systematic review suggests that pyridoxine might be of benefit in relieving LEV-related NPAEs. However, the quality of the evidence is poor, and better-designed prospective studies that include quantitative as well as qualitative data are needed to define the role of pyridoxine in the management of LEV-related NPAEs.

Prophylaxis for Tuberculosis in Pregnant Women.

As more women at increased risk for tuberculosis (TB) reactivation immigrate to the United States, perinatal screening and chemoprophylaxis are increasingly important. Interferon-gamma release assays and the tuberculin skin test are acceptable screening tests with the latter supported by more data in pregnancy. Women screening positive should have active TB excluded, and if negative, latent TB is likely. Prophylaxis should be deferred until 3 months postpartum except in those severely immunosuppressed, human immunodeficiency virus positive, or recently exposed. Isoniazid with pyridoxine for 9 months is preferred with reasonable safety in pregnancy and breastfeeding. Monitoring for maternal hepatotoxicity is recommended.

Gene ontology analysis of expanded porcine blastocysts from gilts fed organic or inorganic selenium combined with pyridoxine.

BACKGROUND: Gene ontology analysis using the microarray database generated in a previous study by this laboratory was used to further evaluate how maternal dietary supplementation with pyridoxine combined with different sources of selenium (Se) affected global gene expression of expanded porcine blastocysts. Data were generated from 18 gilts randomly assigned to one of three experimental diets (n = 6 per treatment): i) basal diet without supplemental Se or pyridoxine (CONT); ii) CONT + 0.3 mg/kg of Na-selenite and 10 mg/kg of HCl-pyridoxine (MSeB610); and iii) CONT + 0.3 mg/kg of Se-enriched yeast and 10 mg/kg of HCl-pyridoxine (OSeB610). All gilts were inseminated at their fifth post-pubertal estrus and euthanized 5 days later for embryo harvesting. Differential gene expression between MSeB610 vs CONT, OSeB610 vs CONT and OSeB610 vs MSeB610 was performed using a porcine embryo-specific microarray. RESULTS: There were 559, 2458, and 1547 differentially expressed genes for MSeB610 vs CONT, OSeB610 vs CONT and OSeB610 vs MSeB610, respectively. MSeB610 vs CONT stimulated 13 biological processes with a strict effect on RNA binding and translation initiation. OSeB610 vs CONT and OSeB610 vs MSeB610 impacted 188 and 66 biological processes, respectively, with very similar effects on genome stability, ceramide biosynthesis, protein trafficking and epigenetic events. The stimulation of genes related with these processes was confirmed by quantitative real-time RT-PCR. CONCLUSIONS: Gene expression of embryos from OSeB610 supplemented gilts was more impacted than those from MSeB610 supplemented gilts. Whereas maternal OSeB610 supplementation influenced crucial aspects of embryo development, maternal MSeB610 supplementation was restricted to binding activity.

Chemical cross-linking: A feasible approach to prolong doxylamine/pyridoxine release from spray-dried chitosan microspheres.

Spray-dried chitosan microparticles have been widely exploited as vehicles for mucosal drug delivery. Despite their advantages as pharmaceutical formulations, one of the major challenges is achieving sustained drug release, which would diminish toxicity and dosage frequency. The aim of this study was to formulate mucoadhesive glutaraldehyde cross-linked chitosan microparticles loaded with doxylamine succinate and pyridoxine hydrochloride as potential nasal drug delivery systems with sustained release. Microparticle models were formulated via spray-drying technique, using glutaraldehyde in different concentrations (0.1-1.0 mg/mL) as a cross-linking agent for chitosan. The obtained particles were with spherical shape, smooth surface and median diameter of 4 µm. The drug entrapment efficiency was high (80.47%-94.25%), indicating a tendency to decrease at higher glutaraldehyde concentrations. FTIR data demonstrated that there were no chemical interactions between glutaraldehyde and the drugs. The in vitro studies showed that the cross-linking process substantially limited particles swelling. The cross-linked particles exhibited sustained drug release characteristics at pH 6.8 over a period of 5 h with an initial burst-effect in the first 30 min. Drug release followed Korsmeyer-Peppas kinetics. Although a decrease of the particles mucoadhesive properties was observed after modification, all cross-linked formulations demonstrated high in vitro adsorption of mucin. The proposed models of mucoadhesive microsphere with sustained drug release are a perspective ground for further development of a novel delivery system for nasal administration of doxylamine and pyridoxine.