Serum Glutamate Research Articles

Detection of Some Heavy Metals (Mercury and Lead) Pollutants and their Association with Type 2 Diabetes Mellitus (T2DM) in Baghdad, Iraq

Due to the increased use of products carrying heavy metals caused by human factors in the streets of the city of Baghdad and their direct impact on the air, water quality and soil pollution, heavy metals pollution is one of the important environmental problems. As heavy metals cannot be degraded, they accumulate biologically, and, therefore, can directly threaten higher organisms including humans. The current study focused on detecting heavy metals (mercury and lead) to determine the adverse effects and risk of developing type 2 diabetes mellitus (T2DM) in humans. One hundred total blood samples were collected from healthy people and the patients of both sexes who were suffering from T2DM, with mean age of 31 to 75 years, after 8 to 12 hours of fasting. The first group - G1 the control group consisted of 20 health people (6 males and 14 females). The second group - G2 included 40 patients (20 males and 20 females) who had T2DM and were not exposed to any pollutants. The third group - G3 included 40 males with T2DM and also who were exposed to smoke from local electricity generators, as these samples were collected from workers or living near generators and were exposed to air pollution for a long time. Blood samples were collected from each individual by drawing blood from a vein to evaluate each of the biochemical tests, as well as detecting of some heavy metals such as mercury and lead. The results showed that there was a highly significant increase (p≤0.01) when both fasting blood sugar (FBS) and HbA1c were analysed. As for the results of the analysis of the types of lipid profile, there is no significant difference in cholesterol, while there was a significant increase (p≤0.05) in both low-density lipoprotein (LDL) cholestrol and very low density lipoprotein (VLDL) cholestrol and a highly significant increase (p≤0.01) for both triglyceride and high density lipoporotein cholesterol (HDL) cholestrol. The results of the liver function analysis showed that there was no significant difference in the results of the enzyme serum glutamic oxaloacetic transaminase (SGOT) as well as total bilirubin, while there was a significant increase (p≤0.05) in serum glutamate pyruvate transaminase (SGPT). Significant increase (p≤0.01) was detected in the alkaline phosphatase (ALP) enzyme for each of the studied groups. The results of the detection of the presence of heavy metals using the atomic absorption spectrophotometer showed that there was a significant increase (p≤0.01) in lead, and as for mercury, no significant difference was noticed.

Hepatoprotective Effect of Padina gymnospora in Albino Wistar Rat; A Biochemical and Histopathological Studies

The methanolic extract of brown algae, Padina gymnospora (PG) was tested for hepatoprotective properties against paracetamol (acetaminophen, APAP)-induced liver damage in male albino Wistar rat through in-vitro model. Liver is damaged by the variation of serum enzymatic and biochemical markers, such as serum glutamate oxaloacetate transaminase (SGOT or AST), serum glutamate pyruvate transaminase (SGPT or ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT), bilirubin, albumin, and lipid peroxidation and antioxidant status were measured by SOD and SDH. The study found that PG caused dose-dependent histopathological changes in the liver and kidney of the rats. While low doses caused minimal alterations, higher doses resulted in significant tissue damage. This suggests that, despite its therapeutic potential, careful consideration is needed regarding dosage to ensure safety. Acute toxicity studies revealed that the LD50 value exceeded 3 g/kg body weight. These results indicate that the methanolic extract of PG contains active compounds with antioxidant, anti-inflammatory, detoxification support, liver regeneration, cholesterol regulation, prevention of liver fibrosis and hepatoprotective effects against high doses of paracetamol-induced hepatotoxicity [Fig. 1].

Serum Glutamate dehydrogenase activity enables sensitive and specific diagnosis of hepatocellular injury in humans.

Serum activities of alanine- and aspartate- aminotransferases (ALT and AST) are considered the "gold standard" biomarkers of hepatocyte injury in clinical practice and drug development. However, due to expression of ALT and AST in myocytes, the diagnosis of hepatocellular injury in patients with underlying muscle diseases, including drug-induced muscle injury, is severely limited. Thus, we proposed glutamate dehydrogenase (GLDH) as a liver-specific alternative to serum ALT and AST. In fact, our exploratory studies showed that GLDH has comparable performance to ALT for detecting hepatocyte injury without interference from concomitant muscle injury. Here, we report the results of studies confirming the reference intervals in a healthy human population and sensitivity and specificity of GLDH for detection of hepatocyte injury in human subjects. In human subjects, we could not perform liver biopsies due to ethical reasons, we also confirmed the relationship of GLDH and histopathologic lesions using 32 model toxicants in rats. Furthermore, we have shown that injury to tissues that are known to express appreciable levels of GLDH does not affect serum GLDH measurements, indicating excellent liver specificity of serum GLDH. Finally, we observed faster elimination of GLDH than ALT in humans, indicating that decreasing GLDH values could be considered an early sign of recovery. This study provides comprehensive evidence of excellent sensitivity and liver specificity of GLDH for diagnosis of hepatocellular injury, including evaluation of reference intervals that is essential for interpretation of serum GLDH in human subjects.

Study on the Mechanism of Dictyophora duplicata Polysaccharide in Reducing Depression-like Behavior in Mice.

Depression is a prevalent worldwide mental health disorder that inflicts significant harm to individuals and society. Dictyophora duplicata is an edible fungus that contains a variety of nutrients, including polysaccharides. This study aims to investigate the monosaccharide composition and molecular weight of the Dictyophora duplicata polysaccharide (DDP-B1), followed by an exploration of its antidepressant effects in chronic unpredictable mild stress (CUMS) mice. Dictyophora duplicata was purified using a DEAE-52 column and an S-400 column to obtain DDP-B1. The monosaccharide composition and molecular weight of DDP-B1 were investigated via high-performance gel permeation chromatograph. Six-week-old C57BL/6 male mice were utilized for the CUMS modeling to evaluate the antidepressant efficacy of DDP-B1. Fluoxetine served as the positive control group. The depressive-like behaviors and brain pathology of mice were evaluated. Immunofluorescence (IF) staining, metabolomics analysis, and western blot were employed to further investigate the underlying mechanisms. DDP-B1 significantly alleviated the depression-like behavior of CUMS mice and increased the expression of SYN and PSD-95 in the mice's brains, which was further validated by western blot. Metabolomics analysis indicated a reduction in serum glutamate in CUMS mice following DDP-B1 treatment. Moreover, DDP-B1 treatment led to an increase in levels of GABAAR, BDNF, p-TrkB and p-p70S6K. DDP-B1 regulated abnormalities in the glutamatergic system, subsequently activated the BDNF-TrkB-mTOR pathway and mitigated the pathological manifestations of CUMS mice. This study validated the potential of DDP-B1 as an antidepressant medication and established a theoretical foundation for the development of fungi with similar properties.

Elevated peripheral glutamate and upregulated expression of NMDA receptor NR1 subunit in insomnia disorder.

The present study explored the serum glutamate (Glu), glutamine (Gln), glutamic acid dehydrogenase (GAD) concentrations and the mRNA expression levels of the N-methyl-D-aspartate receptor (NMDAR) NR1 subunit in the peripheral blood of patients with insomnia disorder (ID). To our knowledge, this is the first study showing an increase in the mRNA expression levels of the NMDAR NR1 subunit in patients with ID. This study included 30 ID patients and 30 matched healthy controls. We investigated the demographic and illness information and assessed subjective sleep quality using the Pittsburgh Sleep Quality Index. The Hamilton Depression Scale-17 and Hamilton Anxiety Scale were used to evaluate the patients' symptoms of depression and anxiety, respectively. The quantifications of Glu, Gln and GAD concentrations were performed by Enzyme-linked immunosorbent assay (ELISA). Real-time PCR was used to detect the mRNA expression levels of the NMDAR NR1 subunit in peripheral blood. Compared with the healthy control group, the serum Glu concentrations and the mRNA expression levels of the NMDAR NR1 subunit in the ID group were significantly higher. However, there was no significant difference in Gln and GAD between the two groups. The receiver operating characteristic (ROC) analysis showed that the mRNA expression levels of the NMDAR NR1 subunit could distinguish ID patients from healthy individuals (area under the curve: 0.758; sensitivity: 73.3%; specificity: 76.7%). A negative correlation was found between the mRNA expression levels of the NMDAR NR1 subunit for age, total duration of illness, and age of first onset in the ID group, whereas a positive correlation was detected for daytime dysfunction. Glutamatergic neurotransmission was abnormal in ID patients. Additionally, the mRNA expression levels of the NMDAR NR1 subunit appeared to have potential as a clinical biomarker for ID. However, the sample size of our study was limited, and future studies with larger sample sizes are needed to further validate and explore the mechanisms involved and to assess the reliability of the biomarker.

Profil Kadar Enzim Serum Glutamat Piruvat Transaminase (SGPT) dan Serum Glutamat Oksaloasetat Transaminase (SGOT) Mencit Model Diabetes Melitus Pasca Pemberian Ekstrak Kulit Batang Cinnamomum burmanii

Diabetes mellitus is a chronic metabolic disease characterized by hyperglycemia. Prolonged hyperglycemia leads to oxidative stress, which plays a crucial role in causing further complications, including liver damage characterized by increased levels of Serum Glutamate Pyruvate Transaminase (SGPT) and Serum Glutamate Oxaloacetate Transaminase (SGOT). This study aimed to examine the effects of Cinnamomum burmanii bark extract on SGPT and SGOT levels in a mouse model of diabetes mellitus. The research employed an experimental design using a completely randomized design. It consisted of five treatment groups: K- (normal mice), K+ (diabetic mice), P1, P2, and P3 (diabetic mice treated with Cinnamomum burmanii bark extract at doses of 125, 250, and 500 mg/kg BW). Streptozotocin was injected into groups K+, P1, P2, and P3 at a dose of 0.1 ml per mouse for 14 days. If blood glucose levels increased, extracts were administered to groups P1, P2, and P3 according to the predetermined doses for 14 days. On day 28, surgery was performed to collect blood serum for SGPT and SGOT analysis.. The results of the study indicated that Cinnamomum burmanii bark extract could reduce SGPT and SGOT levels in the diabetic mouse model. This demonstrates the potential of Cinnamomum burmanii as a therapeutic agent that may help reduce liver damage often observed in diabetes mellitus

The Effect of Cinnamomum Burmanii Ethanol Extract on Isoniazid-induced Serum Levels of Serum Glutamate Piruvate Transaminase (SGPT) Wistar Strain Male Rats

Hepatotoxicity can be caused by excessive drug use, triggered by increased oxidative stress which is considered as the initial mechanism of Drug Induced Liver Injury (DILI). One of the causes of DILI is Isoniazid. One of the plants acting as a hepatoprotector in protecting liver cells is cinnamon (Cinamommum burmanii). This study aims to determine the effect of 96% ethanolic cinnamon extract as a hepatoprotector against an increase in Alanine Transaminase (ALT) levels induced by isoniazid. The parameters used to assess liver damage were rat plasma ALT. The sample used in this study was rat plasma, which was taken through the retro orbital sinus. This research is an experimental study with a sample of 25 experimental animals divided into five groups, namely negative control (K1), positive control l (K2), and experimental group with cinnamon ethanolic extract at a dose of 100 mg/kgbw (K3), 200 mg/kgbw(K4), and 400 mg/kgbw(K5). The research used a post-test-only control group design. The results were analyzed using the One-way ANOVA test followed by the post hoc Tukey test. The results proved that cinnamon ethanolic extract at doses of 100 mg/kgbw (P = 0.029), 200 mg/kgbw (P = 0.001), and 400 mg/kgbw (P = 0.000) was effective in reducing plasma SGPT levels in isoniazid-induced rats when compared with the positive control group (K2). The most effective dose was at 200 mg/kgbw (K4). Thus, this proves that all of the doses in experimental groups have a hepatoprotective effect against isoniazid-induced liver damage. Keywords: Alanine Transaminase (ALT), cinnamon ethanol extract, Drug Induced Liver Injury (DILI), isoniazid

Evaluation of the Hypoglycemic and Hypolipidemic Potential of Extract Fraction of Quercus baloot Griff Seeds in Alloxan-induced Diabetic Mice.

The discovery and development of new phytomedicines can be greatly aided by plants because of their tremendous therapeutic benefits, efficiency, cost-effectiveness, lack of side effects, and cheaper therapies. In this regard, Quercus baloot, generally known as oak, is used in folkloric medicine for treating and preventing various human disorders, including diabetes. For this purpose, the present study aimed to evaluate crude methanolic extract and various fractions of Quercus baloot for antihyperlipidemic and antihyperglycemic potential followed by the analysis of active compounds. The hypoglycemic and hypolipidemic activity was evaluated in Swiss male Albino mice by administering an oral dose of 150-300 mg/kg of Q. baloot extracts in alloxan induced diabetic mice for 14 days. The results revealed that crude methanolic extract at a dose of 300 mg/kg exhibited a significant reduction in the blood glucose level (198.50 ± 1.99 mg/dl) at day 14 and the same treatment significantly increased the body weight (31.26 ± 0.27 g) at day 14 in comparison to the control group. Moreover, the biochemical parameters were investigated which presented an increase in high-density lipids (HDL) (30.33 ± 0.33 mg/dl), whereas low-density lipids (LDL) showed a significant decrease (105.66 ± 0.26 mg/dl). Additionally, triglyceride levels 104.83 ± 0.70 mg/dl, and total cholesterol 185.50 ± 0.76 mg/dl are significantly decreased. In serum biochemical analysis creatinine and hepatic enzyme markers, like serum glutamate pyruvate transaminase (32.00 ± 0.36 U/mg), serum glutamate oxaloacetate transaminase (34.33 ± 0.61 U/mg), and alkaline phosphatase (157.00 ± 0.73 U/mg), were significantly reduced by the crude methanolic extract at a dose of 300 mg/kg as compared to the control group. The antioxidant enzymes like Superoxide dismutase (4.57 ± 0.011), peroxidases dismutase (6.53 ± 0.014, and catalase (8.38 ± 0.014) at a dosage of 300 mg/kg of methanolic extract exhibited a significant increase. The histopathological study of the diabetic heart, liver, and pancreas showed substantial restoration of damaged tissues in the methanolic extract 150 and 300 mg/kg treated group, which supports the effectiveness of Q. baloot seeds. The gas chromatography-mass spectrometry analysis of methanolic extract identified 10 antidiabetic active compounds in the Q. baloot seeds, validating the antihyperglycemic activity. Thus, methanolic crude extract at the doses 150 and 300 mg/kg of Q. baloot showed significant antihyperlipidemic and antihyperglycemic activities, which validate the folkloric utilization of Q. baloot as a remedy in diabetes. In conclusion, the 300 mg/kg methanolic extract of Q. baloot has notable hypoglycemic and hypolipidemic potential, supporting the plant's traditional medicinal usage in the treatment of diabetes and its complications. Further studies are needed for the purification, characterization, and structural clarification of bioactive compounds.

EFFECTS OF HUMAN CYTOMEGALOVIRUS ON SOME HEMATOLOGICAL PARAMETERS AND LIVER FUNCTION IN PREGNANT WOMEN, YEMEN

Human Cytomegalovirus (HCMV) infection is a common congenital infection that affects approximately 0.7%–1% of all live births worldwide. Approximately 11% of newborns who are infected show symptoms at birth, and of these, between 30% and 40% are at a risk of experiencing long-term neurological complications. This study aimed to evaluate the effect of HCMV on hematological parameters and liver function in pregnant women in Hajjah governorate, Yemen. This study is a cross-section study that conducted in the Hajjah governorate of Yemen during a period of March to June 2023. A total of 108 blood specimens were collected from participants; 78 from patients group and 30 health group. Hematological parameters, such as total red blood cell count (RBC), hemoglobin (HB), platelet count (PLT), and white blood cells (WBC), as well as liver function tests, such as total protein, albumin, alkaline phosphatase (ALP), serum glutamic oxaloacetic transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), total bilirubin, and direct bilirubin, were measured. Majority of participant patients aged between 16–21 years 27 (34.7%), studied at secondary schools (46.2%), in their second trimester 51 (65.4%), those with multigravida 54 (69.2%), and those with no history of congenital diseases 60 (76.9%). Compared with the control group, the mean WBC levels were significantly lower in HCMV patients (P < 0.05), whereas PLT levels were higher among HCMV patients (P < 0.05). Additionally, the mean levels of total bilirubin, direct bilirubin, SGOT, ALP, and albumin were significantly lower in patients with HCMV than in HC (P < 0.05). Furthermore, there were no significant differences between the patient and healthy groups in terms of HB, RBC counts, SGPT, and total protein (P > 0.05). It can be concluded that HCMV infection had a statistically significant effect on WBC, PLT, total bilirubin, direct bilirubin, SGOT, ALP, and albumin levels in pregnant women. Consequently, further studies are needed to define the role of HCMV in liver disorders.

Evaluating the Effects of Ketamine on Serum Glutamate Dehydrogenase, Glutamine Synthetase and Asparagine Synthetase Levels in Patients with Major Depressive Disorder Before and After Ketamine Treatment

Introduction: It has been revealed that major depressive disorder (MDD)is a common and debilitating psychiatric disorder. Dysfunctional enzymes involved in neurotransmission glutamate dehydrogenase (GDH), Glutamine synthetase (GS) and Asparagine synthetase (ASNS) may underlie the pathophysiology of MDD. The present project aimed to explore the effects of Ketamine on GDH, GS and ASNS in MDD patients. This study provides evidence of interactions between ketamine and GDH, ASNS and GS levels in patients with MDD. Materials and Methods: Patients with MDD are referred to the psychiatric ward of Shaheed Yahyanejad Hospital for regular follow-up. Patients diagnosed with MDD were based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), structured clinical interviews, as well as the severity of depression based on clinical criteria determined by a specialist physician. Serum samples from MDD patients before and after ketamine administration were taken to examine the changes in GDH, ASNS and GS levels. In this project, 29 patients with MDD therapy were evaluated with ketamine (0.75 mg/kg). Results: Our study showed that after administrating ketamine, the level of ASNS and Glutamate dehydrogenase GDH in patients with MDD was reduced compared to pre-treatment. However, the level of GS was increased compared to before treatment. The results show that ketamine occurs at the metabolism level in MDD patients. Also, our results demonstrated that GDH, ASNS, and GS levels can be measured to evaluate the effect of Ketamine on MDD patients. Conclusions: Patient success has improved depression after two months of administrating ketamine. Marginally, more than 80% of patients diagnosed with MDD treated with ketamine showed complete remission. Current results may be helpful in understanding the mechanisms responsible for ketamine’s clinical efficacy.

Predicting diabetes in adults: identifying important features in unbalanced data over a 5-year cohort study using machine learning algorithm

BackgroundImbalanced datasets pose significant challenges in predictive modeling, leading to biased outcomes and reduced model reliability. This study addresses data imbalance in diabetes prediction using machine learning techniques. Utilizing data from the Fasa Adult Cohort Study (FACS) with a 5-year follow-up of 10,000 participants, we developed predictive models for Type 2 diabetes.MethodsWe employed various data-level and algorithm-level interventions, including SMOTE, ADASYN, SMOTEENN, Random Over Sampling and KMeansSMOTE, paired with Random Forest, Gradient Boosting, Decision Tree and Multi-Layer Perceptron (MLP) classifier. We evaluated model performance using F1 score, AUC, and G-means—metrics chosen to provide a comprehensive assessment of model accuracy, discrimination ability, and overall balance in performance, particularly in the context of imbalanced datasets.Resultsour study uncovered key factors influencing diabetes risk and evaluated the performance of various machine learning models. Feature importance analysis revealed that the most influential predictors of diabetes differ between males and females. For females, the most important factors are triglyceride (TG), basal metabolic rate (BMR), and total cholesterol (CHOL), whereas for males, the key predictors are body Mass Index (BMI), serum glutamate Oxaloacetate Transaminase (SGOT), and Gamma-Glutamyl (GGT). Across the entire dataset, BMI remains the most important variable, followed by SGOT, BMR, and energy intake. These insights suggest that gender-specific risk profiles should be considered in diabetes prevention and management strategies. In terms of model performance, our results show that ADASYN with MLP classifier achieved an F1 score of 82.17 ± 3.38, AUC of 89.61 ± 2.09, and G-means of 89.15 ± 2.31. SMOTE with MLP followed closely with an F1 score of 79.85 ± 3.91, AUC of 89.7 ± 2.54, and G-means of 89.31 ± 2.78. The SMOTEENN with Random Forest combination achieved an F1 score of 78.27 ± 1.54, AUC of 87.18 ± 1.12, and G-means of 86.47 ± 1.28.ConclusionThese combinations effectively address class imbalance, improving the accuracy and reliability of diabetes predictions. The findings highlight the importance of using appropriate data-balancing techniques in medical data analysis.

Baseline serum glutamate: Implications for diagnosis and prediction in mild cognitive impairment and Alzheimer’s disease of the Alzheimer’s Disease Neuroimaging Initiative

PurposeNumerous studies have highlighted a close link between metabolic imbalances and Alzheimer’s Disease (AD). The advancement of metabolomics has recently enabled the exploration of characteristic metabolic changes associated with AD. Studies indicate that serum glutamate (Glu) levels may correlate with mild cognitive impairment (MCI) and AD. This study aims to further elucidate the characteristics of baseline serum Glu levels in MCI and AD. MethodsThis study included 783 participants from the Alzheimer’s Disease Neuroimaging Initiative-1 (ADNI-1) cohort, categorized into cognitively normal (CN, n = 224), stable MCI (sMCI, n = 181), progressive MCI (pMCI, n = 193), and AD (n = 185). The study aimed to analyze the diagnostic value of baseline serum Glu, to explore its predictive capability for the progression from CN to MCI or AD, and from MCI to AD, and to analyze the relationship between serum Glu and cerebrospinal fluid (CSF) biomarkers and cognitive functions in different diagnostic groups. ResultsCompared to the CN and sMCI groups, the pMCI group showed significantly lower levels of serum Glu, and the AD group also had lower Glu levels compared to the sMCI group. However, serum Glu did not show significant diagnostic value for MCI and AD. Lower levels of serum Glu could predict the progression from MCI to AD. ConclusionSerum Glu levels can predict the progression from MCI to AD, suggesting that it could provide new insights into the pathophysiological mechanisms of AD. However, serum Glu may not be an ideal peripheral biomarker for AD.

Effects of integrative therapy with Du Meridian moxibustion, ear acupuncture, and alprazolam on cardiac function and neurotransmitter levels in patients with coronary heart disease and insomnia: An observational study.

To explore the effects of Du Meridian moxibustion combined with ear acupuncture on clinical symptoms and serum neurotransmitters in patients with coronary heart disease and insomnia. This study is a retrospective study. From June 2021 to May 2023, 116 patients with coronary heart disease and insomnia treated at our hospital were selected as subjects. They were divided into 2 groups according to the treatment. The control group received treatment with alprazolam, while the experimental group received Du Meridian moxibustion combined with ear acupuncture in addition to alprazolam treatment. The efficacy of the 2 groups was compared, and the levels of cardiac function indicators, serum melatonin, leptin, and neurotransmitters were measured. The total effectiveness rate in the experimental group was 93.10% (with a cure rate of 36.21%, a significant improvement rate of 41.38%, and an effective rate of 15.52%), which was significantly higher than the 79.31% in the control group (with a cure rate of 24.14%, a significant improvement rate of 32.76%, and an effective rate of 22.41%) (P < .05). Both groups exhibited an increase in left ventricular ejection fraction, stroke volume, and cardiac output after treatment compared to before treatment. Additionally, left ventricular end-systolic diameter decreased after treatment compared to before treatment, but the cardiac function was compared between the 2 groups after treatment (P > .05). In both groups, serum melatonin and serotonin (5-HT) levels increased after treatment compared to before treatment, while serum leptin, dopamine, and glutamate levels decreased after treatment compared to before treatment. Furthermore, the experimental group had higher serum melatonin, 5-HT, and gamma-aminobutyric acid levels compared to the control group, and lower serum leptin, dopamine, and glutamate levels compared to the control group (P < .05). The serum traditional Chinese medicine syndrome score and Pittsburgh sleep quality index score of the 2 groups decreased after treatment, and the experimental group was lower than the conventional group (P < .05). The combination of Du Meridian acupuncture with ear acupuncture in the treatment of insomnia in coronary heart disease can regulate the expression of serum melatonin, leptin, and neurotransmitters, alleviate symptoms, and improve therapeutic efficacy.

Ameliorative Efficacy of &lt;i&gt;Moringa oleifera&lt;/i&gt; Lam. against the Sodium Fluoride Induced Nephrotoxicity in Wistar Rat

A study was conducted to evaluate the protective efficacy of a methanolic leaf extract of Moringa oleifera L. (MO) for the remediation of nephrotoxicity induced by exposure to a significant groundwater pollutant, fluoride. Wistar albino male rats weighing 150–200 g were divided into five groups, each containing five animals. The control group received normal drinking water, and Group I received sodium fluoride in drinking water (20 mg/l daily) for 90 days. Group II received M. oleifera extract (250 mg/l) for 90 days. Group III received sodium fluoride 20 mg/l along with a low dose of M. oleifera extract (250 mg/l) for 90 days, and Group IV received sodium fluoride 20 mg/l along with a high dose of M. oleifera extract (500 mg/l) for 90 days. After 90 days, the kidneys and blood samples were obtained to evaluate their histological characteristics and assess the levels of oxidative stress and various enzyme parameters. The current investigation showed that sodium fluoride has a notable impact on renal function by elevating levels of creatinine, Blood Urea Nitrogen (BUN), urea, as well as Serum Glutamic Oxaloacetic Transaminase (SGOT), Serum Glutamate Pyruvate Transaminase (SGPT), and Alkaline Phosphatase (ALP) indicators. Further exposure resulted in a decrease in Superoxide Dismutase (SOD) and Catalase (CAT) levels, whereas Lipid Peroxidation (LPO) activity increased in kidney tissue. The histopathological examination of the kidney revealed glomerular enlargement, degenerative changes in Bowman’s capsule, and alterations in the tubular portion of the glomerulus. The study’s findings indicate that the administration of M. oleifera extract had a notable impact on the renal function and antioxidant status of rats subjected to sodium fluoride treatment. The administration of M. oleifera extract demonstrated a significant ability to mitigate the nephrotoxic effects induced by sodium fluoride in rats, mainly when both substances were concurrently administered. M. oleifera extract may also provide hepatoprotective effects by modifying membrane permeability and blocking enzymes from entering the serum.

Sigma metrics – a good quality control guide to assess analytical performance of a clinical chemistry laboratory

Background: Clinical laboratories function to deliver accurate, reliable, and timely reported results which are used in decision-making, diagnosis, and monitoring. Sigma metrics help to assess analytic methodologies and provide benchmarks for laboratories to design protocols for internal quality control (IQC), address poor assay performance, and assess the efficiency of existing laboratory processes. Thus, this study was undertaken to estimate the coefficient of variation (CV%), bias%, and total allowable error (TEa) of quality control (QC) samples using EM 200, to compare the TEa using Clinical Laboratories Improvement Act (CLIA) guidelines, and to analyze the sigma metrics of level 1 QC samples. Aims and Objectives: The aims and objectives of the study are to estimate the CV%, Bias%, TEa of QC samples using EM 200, to compare the TEa using CLIA guidelines, and to analyze the sigma metrics of level 1 QC samples. Materials and Methods: A cross-sectional study was carried out in the Central Biochemistry Lab, Karwar Institute of Medical Sciences, Karwar. IQC data level 1 of 15 analytes was analyzed using EM200 for 3 months. CV% is calculated from internal quality data, whereas bias% is obtained from an external quality assurance program. Sigma metrics were calculated using bias% and CV%. TEa was calculated and compared with CLIA guidelines. Results: We have &lt; 3 sigma values (unstable, unacceptable) for urea, creatinine, BID, serum glutamic oxaloacetic transaminase, serum glutamate pyruvate transaminase (SGPT), protein, cholesterol, calcium, 3–6 (ideal) for glucose, uric acid, total bilirubin, alkaline phosphatase, albumin, high-density lipoprotein, and &gt;6 (excellent) for triglycerides. TEa observed less than or close to CLIA suggests quality requirement met, and TEa observed more than CLIA (urea, creatinine, BID, SGPT, protein, and calcium) suggests methodologies need evaluation. Conclusion: Sigma metrics help to assess analytical methodologies and augment laboratory performance. Each and every laboratory can use sigma metrics as a guideline for QC strategy and a self-assessment tool for proper functioning.

Metabolic Dysfunction in New-Onset Idiopathic Intracranial Hypertension: Identification of Novel Biomarkers.

Idiopathic intracranial hypertension (IIH) is a neurometabolic disease with an increasing incidence. The pathophysiology is unknown, but improvement of diagnosis and management requires discovery of novel biomarkers. Our objective was to identify such candidate biomarkers in IIH, and secondarily, test for associations between identified metabolites and disease severity. This is a prospective case-control study with collection of cerebrospinal fluid (CSF), serum, and clinical data from new-onset, treatment-naïve patients with IIH (n = 60). Patients were included consecutively from 2 tertiary headache centers in Denmark, and age, sex, and body mass index (BMI) -matched healthy controls (n = 35) were recruited. Clinical data were retrieved at ocular remission (n = 55). Samples were analyzed using non-targeted mass spectrometry. Serum sphingosine 1-phosphate (S1P), adenosine, and glutamate were 0.46-fold (q < 0.0001), 0.25-fold (q = 0.0048), and 0.44-fold (q < 0.0001) lower, respectively, in IIH. CSF stearoyl-lysophosphatidylcholine (LysoPC-18) and 2-palmitoyl-lysophosphatidylcholine (LysoPC-16) were 0.42 (q = 0.0025) and 0.37 (q < 0.001) -fold lower. LysoPC-18 was higher in patients with moderate-severe versus mild papilledema (p = 0.022). LysoPC-18 correlated positively with retinal nerve fiber layer thickness (p = 0.0012, r = 0.42) and inversely with mean deviation on automated perimetry (p = 0.01, r = -0.35). Higher baseline serum S1P (p = 0.018) and lower CSF LysoPC-16 (p = 0.003) were associated with optic nerve atrophy at ocular remission. Pathway analysis suggests dysregulated lipid metabolism and redox disturbances in new-onset IIH. We identify perturbed metabolism in new-onset IIH. S1P and LysoPC-16 demonstrate potential prognostic value due to association with subsequent optic nerve atrophy. This association between specific, differential metabolites and outcome provides substantial evidence for novel biomarkers of clinical significance that should be the focus of further targeted studies. ANN NEUROL 2024;96:595-607.

Olsalazine pretreatment augments chemosensitivity of gemcitabine in hepatocellular carcinoma.

Recently, olsalazine a DNA hypomethylating agent was found to inhibit the growth of breast cancer cells. The present study was carried out to evaluate the effects of olsalazine pretreatment in the potentiation of chemosensitivity of gemcitabine for the treatment of hepatocellular carcinoma (HCC).In silico molecular docking was performed to analyze the interaction of olsalazine and gemcitabine with DNMT1 and DNA, respectively, using the AutoDock tools 1.5.6. Cytotoxicity of olsalazine, gemcitabine, and combination were measured on human HePG2 cells using MTT assay. Antiproliferative effects were assessed using animal model of N-nitrosodiethylamine and carbon tetrachloride-induced HCC. Treatment was initiated from 8th week of induction to 11th week and change in body weight, liver weight, and survival rate were measured. Following treatment, blood samples were collected for estimation serum biochemistry. Blood serum was used for the estimation of inflammatory cytokines tumor necrosis factor-α(TNF-α) and interleukin-6 (IL-6), C-reactive protein[CRP],lactate dehydrogenase (LDH), and P53 levels. Oxidative stress markers were measured in liver tissue homogenates. Histopathology and immunohistochemistry (IHC) were performed on liver sections to detect the morphological changes and P53 expression. Docking analysis revealed the interactions between olsalazine and DNMT1 with a binding energy score of -5.34 and gemcitabine and DNA with a binding energy score of -5.93. Olsalazine pretreatment potentiated the antiproliferative effect of gemcitabine in cell line study. In the group receiving olsalazine pretreatment showed significant reductions in relative liver weight and improved survival rate of gemcitabine treatment group. Serum biochemical markers:serum glutamate pyruvate transaminase,serum glutamic oxaloacetic transaminase, alkaline phosphatase, and bilirubin revealed improved liver functions. Olsalazine pretreatment also reduced the levels of inflammatory markers like CRP, LDH, TNF-α, and IL-6 and oxidative stress markers dose dependently. Histopathology and IHC showed improved liver morphology with potentiated the induction of P53 upon olsalazine pretreatment in combination with gemcitabine. In conclusion, sequential combination of olsalazine and gemcitabine improvedthe treatment outcomes during the progression of HCC.

Diabetes Warriors from Heart Wood: Unveiling Dalbergin and Isoliquiritigenin from Dalbergia latifolia as Potential Antidiabetic Agents in-vitro and in-vivo.

Diabetes mellitus is a serious and complex metabolic disorder characterized by hyperglycemia. In recent years natural products has gained much more interest by researchers as alternative sources for diabetes treatment. Though many potential agents are identified so far but their clinical utility is limited because of their adverse effects. Therefore, there is a keen interest in discovering natural compounds to treat diabetes efficiently with less side effects. Dalbergia latifolia is well explored because of its diverse pharmacological activities including diabetes. Therefore, the present research work aimed to identify and isolate the potential antidiabetic agents from the heart wood of Dalbergia latifolia. We successfully extracted DGN and ISG from the heartwood and evaluated their antidiabetic potential both in-vivo and in-vitro. Alpha amylase activity inhibition of ISG and DGN was found to be 99.05 ± 8.54% (IC50 = 0.6025 µg/mL) and 84.68 ± 5.2% (IC50 = 0.0216 µg/mL) respectively. Glucose uptake assay revealed DGN (158%) promoted maximum uptake than ISG (77%) over control. In vivo anti diabetic activity was evaluated by inducing diabetes in SD rats with the help of HFD and STZ (35 mg/kg body weight). After the continuous administration of DGN (5 mg/kg, 10 mg/kg) and ISG (5 mg/kg, 10 mg/kg) for 14 days, we observed the reduction in the blood glucose levels, body weight, total cholesterol, low density lipoprotein, very low-density lipoprotein, blood urea, serum creatinine, serum glutamate oxaloacetic transaminase, serum glutamate pyruvate transaminase and alkaline phosphatase levels than vehicle group indicates the potency of ISG and DGN against diabetes.

Study of Haemolysis in Patients of Leprosy Being Administered Multi-Drug Therapy at a Tertiary Care Hospital in Western Maharashtra: A Prospective Study.

Dapsone forms the backbone of multi-drug therapy (MDT) in leprosy and many other dermatological disorders. Haemolysis is its common side effect which often necessitates drug stoppage. Currently, wide variation in data of haemolysis with dapsone exists in literature ranging from 24.7% to 83% and none of the studies point towards the timing of onset of haemolysis/timing of maximal haemolysis which is important in therapeutic decision making regarding continuing or stopping the drug. This study aimed to answer such unanswered questions. Primary: To estimate the fall in haemoglobin (Hb) levels after administering MDT for 3 months in patients with leprosy. Secondary: To determine factors associated with Hb change - age, glucose-6-phosphate dehydrogenase (G6PD) status, pole of leprosy and duration of MDT taken (if any). All freshly diagnosed cases of Hansen's disease were studied for 3 months. At baseline, demographic data (age, sex), skin biopsy, slit skin smear and G6PD were taken. Haemoglobin (Hb), serum glutamate oxaloacetate transferase (SGOT), serum glutamate pyruvate transferase (SGPT), serum bilirubin, lactate dehydrogenase (LDH), reticulocyte count, peripheral blood smear (PBS) along with clinical photography was done at baseline, 1, 2 and 3 months. Out of the 48 patients who completed the study: Mean Hb (g/dL) decreased from 13.37 at baseline to a minimum of 12.08 at 2 months, and then increased to 12.34 at 3 months. Of 42 patients (87.5%) with a fall in Hb, 13 (27.1%) had severe (fall >20%), 17 (35.4%) had moderate (fall 10-20%), 12 (25%) had mild fall (fall <10%) and in 6 (12.5%), there was no haemolysis. Reticulocyte count, LDH, SGOT and SGPT were significantly associated with haemolysis. Severe haemolysis occurred more frequently in the lepromatous spectrum. Dapsone causes maximal fall of hemoglobin by 1.29 g/dl at two months following which it increases. The fall of hemoglobin is reversible and hemoglobin starts to increase by 3 months of therapy making cessation of the drug unnecessary in most of the patients.

Comparison of fatty liver index with fibroscan in non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is an escalating global health issue. Early detection and precise diagnosis are imperative for effective management. To evaluate the sociodemographic and clinical attributes of study participants concerning their ultrasound grading with FibroScan and FLI values. A cross-sectional study was carried out among patients visiting gastroenterology clinics at a tertiary care hospital situated in Karachi, Pakistan. We included participants after written informed consent underwent an extensive array of laboratory assessments, encompassing liver function tests, lipid profile, fasting blood sugar analysis, hepatitis B and C screening, and abdominal ultrasound, while those with positive hepatitis B or C markers, documented alcohol use, or those who declined to offer informed consent were excluded from the study. Data were analyzed using SPSS version 26. Around 225 patients were studied with a median age of 42 years (IQR = 34-50 years). Metabolic syndrome (MetS) was present in 61.8%. Steatosis was not found among 4.9% of patients, whereas severe steatosis was seen among 51.1% of patients. Significant variations in BMI, WC, GGT, and TG levels were identified when comparing FLI scores. The same was observed for the frequency of MetS as FLI scores increased. The agreement between FLI and ultrasound observations was found to be slight (k = 0.077, P = 0.027). On the multivariable regression model, having diabetes, elevated serum glutamate pyruvate transaminase levels and mild disease on ultrasound were associated with increased odds of severe steatosis. FLI is a good predictor of frequency of MetS and NAFLD and correlates well with increasing steatosis score (CAP) on FibroScan which can be utilized for early detection of NAFLD in primary care.