Long-term abuse of caffeine sodium benzoate induces endothelial cells injury and leads to coagulation dysfunction.

Our hospital admitted a patient who had difficulty in coagulation even after blood replacement, and the patient had abused caffeine sodium benzoate (CSB) for more than 20 years. Hence, we aimed to explore whether CSB may cause dysfunction in vascular endothelial cells and its possible mechanism. Low, medium, and high concentrations of serum of long-term CSB intake patients were used to treat HUVECs, with LPS as the positive control. MTT and CCK8 were performed to verify CSB's damaging effect on HUVECs. The expression of ET-1, ICAM-1, VCAM-1, and E-selectin were measured by ELISA. TUNEL assay and Matrigel tube formation assay were carried out to detect apoptosis and angiogenesis of HUVECs. Flow cytometry was applied to analyze cell cycles and expression of CD11b, PDGF, and ICAM-1. Expression of PDGF-BB and PCNA were examined by western blot. The activation of MAPK signaling pathway was detected by qRT-PCR and western blot. Intracellular Ca2+ density was detected by fluorescent probes. CCK8 assay showed high concentration of CSB inhibited cell viability. Cell proliferation and angiogenesis were inhibited by CSB. ET-1, ICAM-1, VCAM-1, and E-selectin upregulated in CSB groups. CSB enhanced apoptosis of HUVECs. CD11b, ICAM-1 increased and PDGF reduced in CSB groups. The expression level and phosphorylation level of MEK, ERK, JUN, and p38 in MAPK pathway elevated in CSB groups. The expression of PCNA and PDGF-BB was suppressed by CSB. Intracellular Ca2+ intensity was increased by CSB. Abuse of CSB injured HUVECs and caused coagulation disorders.

Molecular docking study of frequently used food additives for selected targets depending on the chromosomal abnormalities they cause.

Food additives (FAs) (flavor enhancers, sweeteners, etc.) protect foods during storage and transportation, making them attractive to consumers. Today, while the desire to access natural foods is increasing, the chemicals added to foods have started to be questioned. In this respect, genotoxicity tests have gained importance. Studies show that some food additives may have genotoxic risks. Previous studies carried out in our laboratory also revealed genotoxic effects of Monopotassium glutamate (MPG), Monosodium glutamate (MSG), Magnesium diglutamate (MDG) as flavor enhancers; Potassium benzoate (PB), Potassium sorbate (PS), Sodium benzoate (SB), Sodium sorbate (SS) as preservatives; Acesulfame potassium (ACE-K), Xylitol (XYL) as sweeteners. In this study, we determined the interactions of these food additives with ATM and p53 proteins, which are activated in the cell due to genotoxic effects, and with DNA by employing the molecular docking method for the first time. Among the food additives, SB (-4.307) for ATM, XYL (-4.629) for p53, and XYL (-4.927) for DNA showed the highest affinity. Therefore, flexible docking (IFD) scores were determined for SB, XYL, and MDG from flavor enhancers. The potential binding modes of the food additives to target molecules' possible inhibition mechanisms were determined by molecular docking. Thus, new information was obtained to show how these additives cause chromosomal abnormalities.

Treatment and management for children with urea cycle disorder in chronic stage. / å°¿ç´ å¾ªçŽ¯éšœç¢æ‚£å„¿æ ¢æ€§æœŸæ²»ç–—å’Œç®¡ç†.

Urea cycle disorder (UCD) is a group of inherited metabolic diseases with high disability or fatality rate, which need long-term drug treatment and diet management. Except those with Citrin deficiency or liver transplantation, all pediatric patients require lifelong low protein diet with safe levels of protein intake and adequate energy and lipids supply for their corresponding age; supplementing essential amino acids and protein-free milk are also needed if necessary. The drugs for long-term use include nitrogen scavengers (sodium benzoate, sodium phenylbutyrate, glycerol phenylbutyrate), urea cycle activation/substrate supplementation agents (N-carbamylglutamate, arginine, citrulline), etc. Liver transplantation is recommended for pediatric patients not responding to standard diet and drug treatment, and those with severe progressive liver disease and/or recurrent metabolic decompensations. Gene therapy, stem cell therapy, enzyme therapy and other novel technologies may offer options for treatment in UCD patients. The regular biochemical assessments like blood ammonia, liver function and plasma amino acid profile are needed, and physical growth, intellectual development, nutritional intake should be also evaluated for adjusting treatment in time.

Elucidating the Mechanisms of Sodium Benzoate in Alzheimer Disease: Insights from Quantitative Proteomics Analysis of Serum Samples.

BACKGROUND: N-methyl-D-aspartate receptors (NMDARs) are crucial components of brain function involved in memory and neurotransmission. Sodium benzoate is a promising NMDAR enhancer and has been proven to be a novel, safe, and efficient therapy for patients with Alzheimer disease (AD). However, in addition to the role of sodium benzoate as an NMDA enhancer, other mechanisms of sodium benzoate in treating AD are still unclear. To elucidate the potential mechanisms of sodium benzoate in Alzheimer disease, this study employed label-free quantitative proteomics to analyze serum samples from AD cohorts with and without sodium benzoate treatment. METHODS: The serum proteins from each patient were separated into 24 fractions using an immobilized pH gradient, digested with trypsin, and then subjected to nanoLC‒MS/MS to analyze the proteome of all patients. The nanoLC‒MS/MS data were obtained with a label-free quantitative proteomic approach. Proteins with fold changes were analyzed with STRING and Cytoscape to find key protein networks/processes and hub proteins. RESULTS: Our analysis identified 861 and 927 protein groups in the benzoate treatment cohort and the placebo cohort, respectively. The results demonstrated that sodium benzoate had the most significant effect on the complement and coagulation cascade pathways, amyloidosis disease, immune responses, and lipid metabolic processes. Moreover, Transthyretin, Fibrinogen alpha chain, Haptoglobin, Apolipoprotein B-100, Fibrinogen beta chain, Apolipoprotein E, and Alpha-1-acid glycoprotein 1 were identified as hub proteins in the protein‒protein interaction networks. CONCLUSIONS: These findings suggest that sodium benzoate may exert its influence on important pathways associated with AD, thus contributing to the improvement in the pathogenesis of the disease.

Treatment and outcomes of symptomatic hyperammonemia following asparaginase therapy in children with acute lymphoblastic leukemia.

Hyperammonemia has been reported following asparaginase administration, consistent with the mechanisms of asparaginase, which catabolizes asparagine to aspartic acid and ammonia, and secondarily converts glutamine to glutamate and ammonia. However, there are only a few reports on the treatment of these patients, which varies widely from watchful waiting to treatment with lactulose, protein restriction, sodium benzoate, and phenylbutyrate to dialysis. While many patients with reported asparaginase-induced hyperammonemia (AIH) are asymptomatic, some have severe complications and even fatal outcomes despite medical intervention. Here, we present a cohort of five pediatric patients with symptomatic AIH, which occurred after switching patients from polyethylene glycolated (PEG)- asparaginase to recombinant Crisantaspase Pseudomonas fluorescens (4 patients) or Erwinia (1 patient) asparaginase, and discuss their subsequent management, metabolic workup, and genetic testing. We developed an institutional management plan, which gradually evolved based on our local experience and previous treatment modalities. Because of the significant reduction in glutamine levels after asparaginase administration, sodium benzoate should be used as a first-line ammonia scavenger for symptomatic AIH instead of sodium phenylacetate or phenylbutyrate. This approach facilitated continuation of asparaginase doses, which is known to improve cancer outcomes. We also discuss the potential contribution of genetic modifiers to AIH. Our data highlights the need for increased awareness of symptomatic AIH, especially when an asparaginase with higher glutaminase activity is used, and its prompt management. The utility and efficacy of this management approach should be systematically investigated in a larger cohort of patients.

Sodium benzoate attenuates 2,8-dihydroxyadenine nephropathy by inhibiting monocyte/macrophage TNF-α expression.

Sodium benzoate (SB), a known D-amino acid oxidase (DAO) enzyme inhibitor, has an anti-inflammatory effect, although its role in renal damage has not been explored. 2,8-dihydroxyadenine crystal induced chronic kidney disease, in which TNF-α is involved in the pathogenesis, was established by oral adenine administration in C57BL/6JJcl mice (AdCKD) with or without SB to investigate its renal protective effects. SB significantly attenuated AdCKD by decreasing serum creatinine and urea nitrogen levels, and kidney interstitial fibrosis and tubular atrophy scores. The survival of AdCKD mice improved 2.6-fold by SB administration. SB significantly decreased the number of infiltrating macrophages observed in the positive F4/80 immunohistochemistry area and reduced the expression of macrophage markers and inflammatory genes, including TNF-α, in the kidneys of AdCKD. Human THP-1 cells stimulated with either lipopolysaccharide or TNF-α showed increased expression of inflammatory genes, although this was significantly reduced by SB, confirming the anti-inflammatory effects of SB. SB exhibited renal protective effects in AdCKD in DAO enzyme deficient mice, suggesting that anti-inflammatory effect of SB was independent of DAO enzyme activity. Moreover, binding to motif DNA sequence, protein level, and mRNA level of NF-κB RelB were significantly inhibited by SB in AdCKD kidneys and lipopolysaccharide treated THP-1 cells, respectively. We report that anti-inflammatory property of SB is independent of DAO enzymatic activity and is associated with down regulated NF-κB RelB as well as its downstream inflammatory genes such as TNF-α in AdCKD.

Determination of D-serine and D-alanine Tissue Levels in the Prefrontal Cortex and Hippocampus of Rats After a Single Dose of Sodium Benzoate, a D-Amino Acid Oxidase Inhibitor, with Potential Antipsychotic and Antidepressant Properties.

The effects of the N-methyl-D-aspartate receptor activators D-serine, D-alanine, and sarcosine against schizophrenia and depression are promising. Nevertheless, high doses of D-serine and sarcosine are associated with undesirable nephrotoxicity or worsened prostatic cancer. Thus, alternatives are needed. DAAO inhibition can increase D-serine as well as D-alanine and protect against D-serine-induced nephrotoxicity. Although several DAAO inhibitors improve the symptoms of schizophrenia and depression, they can increase the plasma levels but not brain levels of D-serine. The mechanism of action of DAAO inhibitors remains unclear. We investigated the effects of the DAAO inhibitor sodium benzoate on the prefrontal cortex and hippocampal level of D-alanine as known another substrate with antipsychotic and antidepressant properties and other NMDAR-related amino acids, such as, L-alanine, D-serine, L-serine, D-glutamate, L-glutamate, and glycine levels. Our results indicate that sodium benzoate exerts antipsychotic and antidepressant-like effects without changing the D-serine levels in the brain prefrontal cortex (PFC) and hippocampus. Moreover, D-alanine levels in the PFC and hippocampus did not change. Despite these negative findings regarding the effects of D-amino acids in the PFC and hippocampus, sodium benzoate exhibited antipsychotic and antidepressant-like effects. Thus, the therapeutic effects of sodium benzoate are independent of D-serine or D-alanine levels. In conclusion, sodium benzoate may be effective among patients with schizophrenia or depression; however, the mechanisms of actions remain to be elucidated.

Metabolomic analysis of the sera of patients with the long-term inhalation of caffeine-sodium benzoate using LC-MS.

The present study aimed to systematically assess the potential biomarkers in the serum samples of patients with long-term inhalation of caffeine-sodium benzoate (CSB). LC-MS was applied to analyze the metabolic profiles of serum samples of patients with the long-term intake of CSB (n = 35) and other volunteers with no intake of CSB treated as the control group (n = 35). The raw data of metabolic profiles were analyzed via principal component analysis, partial least squares analysis, and orthogonal partial least squares analysis. MBRole 2.0 online tools were used to analyze the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of different metabolites. The serum metabolic profiles showed several metabolites with large variations, including 2-propyl-2,4-pentadienoic acid, 24-hydroxycholesterol, 3-O-sulfogalactosylceramide (d18:1/24:1(15Z)), 3-O-sulfogalactosylceramide (d18:1/12:0), 3-O-sulfogalactosylceramide (d18:1/14:0), 3a,7a-dihydroxy-5b-cholestan-26-al, 3a,7a-dihydroxy-5b-cholestane, 7a,25-dihydroxycholesterol, bilirubin, and dehydroepiandrosterone sulfate. The Kyoto Encyclopedia of Genes and Genomes pathways involved in metabolism included 'choline metabolism in cancer' and 'glycerophospholipid metabolism'. In conclusion, the present study provides a basis with which to explore the molecular-specific mechanisms concerning the effects of the long-term inhalation of CSB on human physical and mental health.

Endogenous antioxidants predicted outcome and increased after treatment: A benzoate dose-finding, randomized, double-blind, placebo-controlled trial for Alzheimer's disease.

AIM: Previous pilot studies suggest that sodium benzoate may be a potential cognitive enhancer for patients with Alzheimer's disease (AD), schizophrenia, or late-life depression. Especially for AD treatment, a confirmatory trial with predictive biomarkers is urgently needed. This study aimed to confirm benzoate as a novel treatment for AD and to discover its optimal dose and biomarkers. METHODS: A 24-week, dose-finding, randomized, double-blind, placebo-controlled trial, with clinical measurements at weeks 0, 8, 16, and 24, was conducted in three major medical centers in Taiwan. Among 154 patients screened for AD, 149 were eligible and randomized to one of the four treatments: (i) benzoate 500 group (fixed 500 mg/day); (ii) benzoate 750 (500 mg/day for the first 4 weeks, 750 mg/day from the 5th week); (iii) benzoate 1000 (500 mg/day for the first 4 weeks, 1000 mg/day from the 5th week); and (iv) placebo. The primary outcome measure was AD assessment scale-cognitive subscale (ADAS-cog). RESULTS: The benzoate 1000 group performed best in improving ADAS-cog (P = 0.026 at week 24), with female advantage. Higher plasma catalase at baseline predicted better outcome. Benzoate receivers tended to have higher catalase and glutathione than placebo recipients after treatment. The four intervention groups showed similar safety profiles. CONCLUSIONS: By enhancing two vital endogenous antioxidants, catalase and glutathione, sodium benzoate therapy improved cognition of patients with AD, with higher baseline catalase predicting better response. Supporting the oxidative stress theory, the results show promise for benzoate as a novel treatment for AD.

Zinc supplement reverses short-term memory deficit in sodium benzoate-induced neurotoxicity in male Wistar rats by enhancing anti-oxidative capacity via Nrf 2 up-regulation.

Sodium benzoate (SB) is a commonly-used food preservative, with a controversial report to its neurological benefit and toxicity. Zinc (Zn) is a trace element that plays a crucial role in memory, inflammation and oxidative stress. This study was to investigate the effect of SB on rat cognition and memory and the possible modulatory effect of Zn supplement. Twenty four male Wistar rats were divided into four groups of six animals each. Animals in groups 1-4 were treated with normal saline 1 ml/kg, SB 200 mg/kg, zinc sulphate 10 ml/kg and SB 200 mg/kg + zinc sulphate 10 ml/kg/day daily respectively for three weeks. After treatment, the animals were subjected to different behavioural tests, and then sacrificed. Their blood samples were collected for catalase(CAT), superoxide dismutase(SOD) and interleukin-1B(IL-1B) assay. Brain samples were also collected for nuclear factor-erythroid-related factor 2(Nrf2), and acetylcholinesterase (AchE) mRNA gene expression. The serum levels of CAT and SOD were (p < 0.0001; p < 0.0001) reduced in the SB only-treated group compared to the other groups. Nrf2 gene expression was totally shut down in the SB only-treated group but, up-regulated in the Zn-treated groups (p < 0.0001). The serum level of IL-1B was higher in the SB only-treated group compared to the other groups. SB-treated group spent longer time in the close arm (p = <0.0001), shorter time in the open arm (p = <0.0001) and had higher anxiety index (p = 0.0045) than the Zn-treated groups. Conclusively, Zinc improves memory deficit, has anxiolytic, anti-oxidant and anti-inflammatory properties.

Toxicological and Teratogenic Effect of Various Food Additives: An Updated Review.

Scientific evidence is mounting that synthetic chemicals used as food additives may have harmful impacts on health. Food additives are chemicals that are added to food to keep it from spoiling, as well as to improve its colour and taste. Some are linked to negative health impacts, while others are healthy and can be ingested with little danger. According to several studies, health issues such as asthma, attention deficit hyperactivity disorder (ADHD), heart difficulties, cancer, obesity, and others are caused by harmful additives and preservatives. Some food additives may interfere with hormones and influences growth and development. It is one of the reasons why so many children are overweight. Children are more likely than adults to be exposed to these types of dietary intakes. Several food additives are used by women during pregnancy and breast feeding that are not fully safe. We must take specific precaution to avoid consuming dangerous compounds before they begin to wreak havoc on our health. This study is intended to understand how the preservatives induce different health problem in the body once it is consumed. This review focuses on some specific food additives such as sodium benzoate, aspartame, tartrazine, carrageenan, and potassium benzoate, as well as vitamin A. Long-term use of food treated with the above-mentioned food preservatives resulted in teratogenicity and other allergens, according to the study. Other health issues can be avoided in the future by using natural food additives derived from plants and other natural sources.

Headspace control and antimicrobials: Inhibition strategies to prevent the growth of Alicyclobacillus acidoterrestris in orange juice.

Alicyclobacillus acidoterrestris can cause spoilage in orange juice that leads to consumer rejection. Six different orange juices were physiochemically characterized (pH, total soluble solids, titratable acidity, total polyphenols and vitamin C). A bottle for each sampling point per juice was filled (headspace: 40% volume) and inoculated with 102 -103 CFU per ml of A. acidoterrestris ATCC® 49025™ (heat shocked before inoculation: 75°C, 20 min). Samples were stored for 21 days at 45 ± 1°C and plate counted periodically on acidified YSG agar (pH 3·7) incubated at 45 ± 1°C for 3 days. The effect of headspace (6% versus 40% volume) on A. acidoterrestris growth was also evaluated. The effect of nisin (0·006, 0·003, 0·0015, and 0·00075%), sodium benzoate (0·1%), potassium sorbate (0·1%) and a mix of benzoate and sorbate (0·05% each) on A. acidoterrestris was additionally addressed. Alicyclobacillus acidoterrestris reached up to 107 CFU per ml in five of the six juices in less than 1 week. Headspace significantly impacted (P < 0·05) A. acidoterrestris maximum population, which reached the critical value of 5 log CFU per ml at 40% headspace. All preservatives, regardless of concentration, showed a bacteriostatic effect during 22 days of storage with no significant differences amongst treatments (P > 0·05).

Sodium benzoate induces neurobehavioral deficits and brain oxido-inflammatory stress in male Wistar rats: Ameliorative role of ascorbic acid.

BACKGROUND: Sodium benzoate (SB) is a widely used food preservative. However, excessive intake of a high dose of SB poses a risk of neurotoxicity. Ascorbic acid (AA) is a naturally occurring antioxidant found in fruits with reported neuroprotective properties. The present study investigated the neurobehavioral and biochemical alterations in SB-treated rats and the ameliorative effect of AA in rats. METHODS: Forty-two male Wistar rats were divided into six groups (n = 7). Group 1 (vehicle, 10 ml/kg), Groups 2-4 rats SB (150, 300, and 600 mg/kg), Group 5 AA (100 mg/kg) and Group 6 (SB 600 mg/kg + AA 100 mg/kg). Treatment was daily administered for 28 days by oral route. Anxiogenic behavior, locomotor, and exploratory activities were evaluated in the open field monitored with a camera, and memory performance in Y-maze. Brain oxidative stress, inflammatory, apoptosis, and cholinergic markers were determined. The cortico-hippocampal tissues were examined histologically. RESULTS: SB-treated rats showed significant anxiogenic-like behavior and impairment in locomotor, exploratory, and memory performance. This was reversed in SB (600 mg/kg)-treated rats coadministered with AA. SB-treated rats showed a decrease in antioxidant enzyme activities, increase malondialdehyde (MDA), nitrite, tumor necrosis factor-alpha, caspase-3, and acetylcholinesterase activity in the striatum, hippocampus, frontal cortex, and cerebellum. These biochemical changes were reversed in AA-treated rats. Reduced cortico-hippocampal neuronal cell count and the pyknotic index were found in SB-treated rats, which was also reversed in AA-treated rats. CONCLUSION: Conclusively, sodium-benzoate-induced neurobehavioral deficits and brain biochemical changes were ameliorated by ascorbic acid probably via antioxidant, anti-inflammatory, and apoptotic mechanisms.

Toxicological impact of sodium benzoate on inflammatory cytokines, oxidative stress and biochemical markers in male Wistar rats.

Sodium benzoate is a widely used food and pharmaceutical preservative due to its antibacterial and antifungal activity. In the present study effect of different concentrations of sodium benzoate on hepatic antioxidants, inflammatory cytokines (TNF-α, IFN-γ, IL-1ß and IL-6), biochemical markers and histopathology of liver was evaluated. Twenty five adult rats (aged 1-2 months) with 5 rats per group were randomly distributed into 5 groups. Group 1 rats were used as control and all groups (1-5) were provided with water and fed ad libitum. In addition to usual water and food, rats of group 2, 3, 4 and 5 were treated with 70, 200, 400 and 700 mg/kg b.wt of sodium benzoate once a day via oral gavage for 30 days. Our results showed that activity of glutathione peroxidase (GPx), catalase (CAT), glutathione-s-transferase (GST), glutathione reductase (GR) and superoxide dismutase (SOD) in rats decreased significantly when treated with 200, 400 and 700 mg/kg b.wt of sodium benzoate. Increase in the concentration of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, serum total protein, albumin, globulin, urea and creatinine was found to be dose dependent. Severe histopathological damage was observed in the hepatic tissue at higher concentrations of sodium benzoate. It was noticed that high concentrations of sodium benzoate (200, 400 and 700 mg/kg b.wt) produce significant increase in inflammatory cytokine markers (TNF-α, IFN-γ, IL-1ß and IL-6) in comparison to control. Sodium benzoate at concentration of 70 mg/kg b.wt did not produce any significant changes in any of the above studied parameters.

Neuroprotective Effects of Virgin Coconut Oil Supplemented Diet against Sodium Benzoate-induced Acetylcholinesterase Dysfunction and Cognitive Impairment: Role of Nrf2/NfKb Signaling Pathway.

The effect of virgin coconut oil (VCO) supplemented diet on sodium benzoate (SB) - induced neurotoxicity in male Wistar rats was investigated. Twenty (20) male Wistar rats weighing 160-180g were divided into four (4) groups: Control which received 1ml of normal saline, SB-treated; received 200 mg/kg b.w, SB + Low Dose VCO-treated (SB + 5% VCO mixed with 95g of rat chow), and SB + High Dose VCO-treated (SB+ 15% VCO mixed with 85g of rat chow). The brain was processed for NRF-2, NF-kB, and acetylcholine esterase (AchE) gene expression levels. Also, the blood sample was processed for assessment of superoxide dismutase (SOD), catalase (CAT), and IL1B levels. One-way ANOVA and Tukey post hoc tests were used to analyze data. SB-treated rats with no intervention showed anxiety-like behavior and impaired memory as depicted by a significant (p<0.0001) increase in anxiety index, increase in brain NF-KB, increase in serum IL1B and increase in AchE gene expression level, reduction in the recognition ratio, decreased spontaneous alternation performance, decreased CAT and SOD levels and decreased NRF-2 expression level when compared to other groups (especially control and SB + 5% VCO). VCO supplemented diet (both 5% and 15%) significantly (p<0.0001) increased the CAT and SOD levels, increased the NRF-2 gene expression level, and significantly (p <0.0001) decreased the IL1-B level. Moreover, 5% VCO significantly (p<0.0001) decreased the anxiety index, decreased AchE and NFkB gene expression levels, increased spontaneous alternation performance, and increased recognition ratio compared to 15% VCO. VCO shows a neuroprotective effect in attenuating cognitive impairment and anxiety-like behavior in SB-induced model by modulating oxidative stress and inflammatory pathways, and also enhancing cholinergic neurotransmission. Keywords: Virgin coconut oil; sodium benzoate; acetylcholinesterase; catalase; superoxide dismutase; oxidative stress.

Association of long-term inhalation of caffeine-sodium benzoate with coronary heart disease in men.

OBJECTIVE: A possible correlation between caffeine and coronary heart disease (CHD) is controversial. The objective of this study was to explore the effect of long-term inhalation of caffeine-sodium benzoate (CSB) on the development of CHD in men, the severity of coronary artery lesions and the possible contributing effects of smoking. MATERIALS: A retrospective analysis was performed on 2,001 consecutive men who underwent selective coronary angiography. These men were assigned to a CSB inhalation group (CSB; 1 - 6 times/d, 274 - 1,644 mg/d, > 10 years; n = 326) or a non-inhalation group (non-CSB; n = 1,675). METHODS: The two groups were compared for the prevalence, onset age, and risk factors of CHD. The men were also stratified as CSB-only, smoking-only, combined CSB+ smoking, and the control (non-CSB+non-smoking). The prevalence, onset age, risk factors of CHD, and severity of coronary artery lesions and major adverse cardiovascular events (MACE) were compared among these groups. RESULTS: The prevalence of CHD in the CSB group was higher compared with the non-CSB group (91.72 vs. 86.09%, p < 0.01). In the CSB+smoking group, the percentages of men with CHD (93.11%) or > 70% stenosis of the coronary artery lesion (64.92%) were significantly higher than that of the smoking-only group (88.19 and 54.29%, respectively) or control (83.20 and 52.90%), while the percentage with stenosis involving the anterior descending branch was lower (62.30 vs. 72.29% and 74.17%, p < 0.01). CONCLUSION: Men who inhaled CSB long-term had a higher rate of CHD compared with those who did not take CSB. The combination of CSB inhalation and smoking appears to increase synergistically the risk and severity of CHD.

Cancer proteome and metabolite changes linked to SHMT2.

Serine hydroxymethyltransferase 2 (SHMT2) converts serine plus tetrahydrofolate (THF) into glycine plus methylene-THF and is upregulated at the protein level in lung and other cancers. In order to better understand the role of SHMT2 in cancer a model system of HeLa cells engineered for inducible over-expression or knock-down of SHMT2 was characterized for cell proliferation and changes in metabolites and proteome as a function of SHMT2. Ectopic over-expression of SHMT2 increased cell proliferation in vitro and tumor growth in vivo. Knockdown of SHMT2 expression in vitro caused a state of glycine auxotrophy and accumulation of phosphoribosylaminoimidazolecarboxamide (AICAR), an intermediate of folate/1-carbon-pathway-dependent de novo purine nucleotide synthesis. Decreased glycine in the HeLa cell-based xenograft tumors with knocked down SHMT2 was potentiated by administration of the anti-hyperglycinemia agent benzoate. However, tumor growth was not affected by SHMT2 knockdown with or without benzoate treatment. Benzoate inhibited cell proliferation in vitro, but this was independent of SHMT2 modulation. The abundance of proteins of mitochondrial respiration complexes 1 and 3 was inversely correlated with SHMT2 levels. Proximity biotinylation in vivo (BioID) identified 48 mostly mitochondrial proteins associated with SHMT2 including the mitochondrial enzymes Acyl-CoA thioesterase (ACOT2) and glutamate dehydrogenase (GLUD1) along with more than 20 proteins from mitochondrial respiration complexes 1 and 3. These data provide insights into possible mechanisms through which elevated SHMT2 in cancers may be linked to changes in metabolism and mitochondrial function.

Survival and Neurologic Recovery After Prompt Diagnosis and Aggressive Management of Severe Idiopathic Hyperammonemic Encephalopathy in a Patient with Acute Myeloid Leukemia.

A case of a 19-year-old female with low-risk acute myeloid leukemia is presented who was diagnosed with idiopathic hyperammonemic encephalopathy following the development of abrupt neurologic decline, respiratory alkalosis, and elevated plasma ammonia levels of unknown etiology. Delayed symptom recognition of this exceedingly rare condition contributes to the often fatal outcomes of idiopathic hyperammonemic encephalopathy. As illustrated by this case, prompt diagnosis and utilization of a variety of ammonia-modulating treatment modalities can result in remarkable clinical recovery. This case provides guidance to clinicians in counseling families about the possibility of neurologic recovery in similar clinical scenarios.

Exploring the therapeutic potential of sodium benzoate in acetic acid-induced ulcerative colitis in rats.

Background Ulcerative colitis is a chronic mucosal inflammation of the large intestine mainly affecting the colon and rectum. The lack of effective and safe therapeutic agents led to the identification of new therapeutic agents to effectively manage the symptoms and complications of ulcerative colitis. The present study aimed to evaluate the protective effect of sodium benzoate in acetic acid-induced ulcerative colitis in rats. Methods Infusion of 3% acetic acid in the colon through the rectum was done to construct a rat model of ulcerative colitis. After 5 days of infusion, macroscopic, biochemical, and histopathological examinations and disease activity scoring of the colon were done to assess colonic damage. Results Acetic acid infusion resulted in severe inflammation in the colon assessed macroscopically and histopathologically. Moreover, it also led to increase in myeloperoxidase (MPO) and reduction in glutathione (GSH) levels. In the present study, repeated administration of sodium benzoate (400 and 800 mg/kg i.p.) and sulfasalazine (500 mg/kg orally) for 7 days, i.e. 2 days before and continued for 5 days after acetic acid infusion, significantly attenuated macroscopic damage and disease activity score as compared to disease control. Further, it also significantly reduced the levels of MPO and enhanced colonic levels of reduced GSH. However, the lower dose of sodium benzoate (200 mg/kg) did not show sufficient protective effect in acetic acid-induced ulcerative colitis. Further, sodium benzoate per se did not show any effect in normal rats. Conclusions The observed protective effect of sodium benzoate may be due to its antioxidant and anti-inflammatory activities in an ulcerative colitis model.

Prevalence of ethanol and other potentially harmful excipients in pediatric oral medicines: survey of community pharmacies in a Nigerian City.

OBJECTIVE: Excipients are needed in the formulation of oral liquid medicines intended for children; they have however been reported to trigger safety issues. This study evaluated the concentrations and prevalence of ethanol and other potentially harmful excipients in pediatric formulations marketed in South Eastern Nigeria in line with international labeling guidelines and allowable daily limits (ADL). The study sampled oral pediatric formulations offered for sale in registered pharmacies. Those with accessible information leaflets were assessed for the presence and quantity of previously flagged excipients with potential to harm the pediatric population. RESULT: Of the 380 oral pediatric medicines, 140 provided access to list/quantity of ingredients. 47.9% (67) of the formulations contain at least one of the flagged excipients while the remaining only listed the active ingredients. Ethanol had the highest occurrence (62.7%) and was more in cough/cold medicines. A homeopathic cough and cold remedy had concentration of 90% v/v. Ethanol and sucrose in some formulations exhibited concentrations with a potential of crossing their approved daily intake (ADI) (1-90% v/v and 1.7 g-3.7 g/5 ml respectively). Ethanol use in studied pediatric formulations was quite high, with ethanol-containing formulations being prescribed for children 0-6 years and older. Only 26 (38.8%) completely satisfied the labelling requirements for ethanol containing formulations.