Significant Increase In Cholesterol Research Articles

Evaluation of Lipid Profile and Oxidative Stress of Workers in Fast Food Restaurants and The Risk of Atherosclerosis

Cooking fumes and biomass smoke pose significant threats to air degradation and human health, especially to people who work in this field on a daily basis, due to the large amounts of hazardous pollutants released from grilling activities. Chronic exposure to these fumes is associated with a risk of inflammation and oxidative stress, which can increase the risk of atherosclerosis. In this study, the lipid profile Glutathion (GSH) and Malondialdehyde (MDA) of workers in fast food restaurants and patients with atherosclerosis were evaluated. The study included 40 Atherosclerosis patients, 40 fast food workers, and 40 healthy individuals as a control group, the ages ranges of (20-40) years. The obtained results indicated a significant increase in cholesterol, triglycerides, LDL, and VLDL and a decrease in HDL (p < 0.01) in patients and fast-food workers compared to control group. The results also indicated a significant increase in the level of MDA, and a significant decrease in the level of GSH for patients and fast-food workers compared to the control. In conclusion, it appears that fast food workers experience oxidative stress and disruption in lipid metabolism that may increase the risk of atherosclerosis. Therefore, safety and quality control measures must be strengthened to reduce the occupational risks of fast-food restaurant workers.

Impact des antiviraux à action directe sur l'athérosclérose subclinique chez les patients atteints d’une hépatite C chronique

The impact of direct antiviral drugs (DAAs) on extrahepatic manifestations in chronic hepatitis C (CHC) has been poorly studied. To assess the prevalence of subclinical atherosclerosis in patients with CHC and the impact of DAAs on atherosclerotic lesions. Methods A 5-year prospective evaluative study, including patients followed for CHC at hepato-gastroenterology department. The subclinical atherosclerosis was assessed by ultrasound measurement of carotid intima-media thickness (IMTc) and the highest IMTc measurements from the left and right side defined the IMTc maximum (IMTc max). IMTc>75th percentile (IMTc75) define subclinical atherosclerosis with high cardiovascular risk. Patients were evaluated before (T0) and one year after DAAs therapy achievement (T1). At time T0, forty patients (median age: 55 y.; sex ratio M / F = 0.48), were included. Average value of IMTc max was 0.68 ± 0.16 mm. Subclinical atherosclerosis was noted in 82.5 %. At time T1, 28 patients were evaluated, all of whom completed sustained virological response (SVR). Compared to time T0, there was a significant increase in cholesterol (p = 0.001) and triglyceride (p = 0.009) levels. IMTc max was significantly higher at time T1 compared to T0 (0.75 Vs 0.67 mm, p = 0.04). Prevalence of IMTc75 was 82.1% at time T0 and 75% at time T1 (p=0.5). SVR, in CHC patients treated with DAA, was associated with worsening of carotid atherosclerotic lesions.

P783 Exploring the impact of JAK Inhibitors on cholesterol levels in Patients with Inflammatory Bowel Disease: A Real-World Data Analysis

Abstract Background Janus Kinase (JAK) inhibitors represent a significant therapeutic advancement for individuals with inflammatory bowel disease (IBD). Previous research indicates an increase in total cholesterol (total-c) upon the initiation of JAK therapy.1The precise mechanisms remain unclear, but studies suggest that inflammation can lower lipid levels. Therefore, by addressing inflammation through JAK therapy, there may be a subsequent elevation in lipid levels. This study seeks to evaluate the impact of initiating JAK inhibitors on total cholesterol levels in patients with IBD, utilising real-world data for analysis. Methods A multi-site retrospective analysis was conducted on a cohort of patients with ulcerative colitis and Crohn’s disease who had been initiated on either filgotinib, tofacitinib or upadacitinib. Statistical analysis was applied to examine alterations in total cholesterol levels (total-c) before and after the initiation of JAK inhibitor therapy. Results A cohort of 49 patients was identified, with pre and post total-c levels available for 33 individuals included in the analysis. Utilising paired data and the Student's t-test, we examined whether initiating a JAK inhibitor led to increased total cholesterol levels. Patients commenced on tofacitinib and upadacitinib exhibited statistically significant increases in cholesterol (p=0.016, p=0.0001). Patients in the filgotinib group, although demonstrating rises in total-c in most cases, did not reach statistical significance (p=0.21). Graph 1 demonstrates the range and spread of the results. Upadacitinib increased cholesterol levels by the most on average (0.82), compared to tofacitinib (0.64) or filgotinib (0.3). Elevated cholesterol persisted beyond 12 weeks in some patients, but long-term data for all patients was not available. Notably, only one patient initiated a statin, resulting in lipid normalisation at the next assessment. No cardiac events were identified in this cohort. Conclusion This analysis of real-world data underscores a potential influence of JAK inhibitors on the cholesterol profiles of individuals with inflammatory bowel disease (IBD). Gaining insights into the interplay between JAK inhibitors and lipid metabolism within the realm of IBD treatment is essential for enhancing patient care and proactively addressing potential cardiovascular risks linked to these therapeutic interventions. 1.Herrera-deGuise C, Serra-Ruiz X, Lastiri E and Borruel N (2023) JAK inhibitors: A new dawn for oral therapies in inflammatory bowel diseases. Front. Med. 10:1089099. doi: 10.3389/fmed.2023.1089099

The bioprotective role of irradiated hibiscus against harmful effects of using repeatedly frying edible oil.

Repeatedly frying process of dietary edible oil has a potential role in the generation of free radicals. Therefore, questions have always been raised as to whether, there is an efficient and economical method to reduce the harmful effects of repeated use of frying edible oil. Since hibiscus has been stated to have a wide variety of therapeutic effects, it was important to investigate its properties against harmful effects of free radicals. The current study aspires to find out whether irradiated powder of hibiscus has a protective role against adverse effects of repeated use of frying edible oil. Thirty-five adult male albino rats were equally assigned into five groups. First group"G1" was fed with normal diet as control group, meanwhile, group"G2" the diet mixed with fresh oil, "G3" diet mixed with repeatedly frying oil only, "G4" diet mixed with frying oil treated with hibiscus and "G5" diet mixed with frying oil treated with irradiated hibiscus. Feeding duration was six weeks. Fatty acid analyses of oil as well as peroxide values were determined. Blood and liver samples were collected for biochemical analyses as well as histological study. Repeatedly heated cooked oil has significant increases in peroxide value, acid value, free fatty acid and both conjugated diene and triene compared with repeatedly frying oil treated with hibiscus. Also there are significant increases in cholesterol and triglyceride and impaired in liver functions in "G3"compared with others. In addition, relative to the hibiscus groups, there is a substantial reduction in oxygen consumption in "G3". Both hibiscus as well as irradiated hibiscus attract attention in order to play a vital and economical role against harmful effects of frequent use of frying edible oil on some biological functions but, irradiated hibiscus was more effective.

Effect of 90 Days Sub-chronic Administration of Omeprazole (A Proton Pump Inhibitor) on Haematological, Biochemical, Antioxidant, Reproductive and Histopathological Parameters in Male and Female Rats

Abstract Despite the widespread use of omeprazole (OME), there are still concerns about its long-term safety and tolerability, especially with long-term or indiscriminate use. This study was designed to evaluate the effect of 90 days sub-chronic administration of OME on haematological, biochemical, antioxidant, reproductive and histopathological parameters in male and female rats. Forty-eight (48) Wistar rats of both sexes were divided into 4 groups of 6 male and 6 female animals each. Group I received 10 mL/kg normal saline, while Groups II – IV received 0.12 mg/kg, 0.57 mg/kg, 2.85 mg/kg of OME respectively for 90 days. At the end of 90 days, 5 mL blood sample was collected, and vital organs were harvested for relevant analyses. In this study, OME did not elicit any significant (P>0.05) change in the body weight or weight of vital organs, but elicited a significant (P<0.05) reduction in sperm count at the supratherapeutic dose (2.85 mg/kg). The supratherapeutic dose of OME produced significant increase in cholesterol (P<0.0001) and LDL (P<0.0001) in female rats. OME did not generally produce a significant change in haematological parameters. OME elicited a significant decrease in CAT (P<0.05) in female and combined animals. Additionally, histopathological presentations of vital organs were generally non-abnormal. From this study, it can be concluded that long term administration of OME is generally safe and tolerable, especially at lower doses. Findings from this study suggest that OME may potentially induce changes in sperm characteristics (in relation to male rats), hepatoxicity, hypercholesteremia, hyperlipidemia and thrombocytosis over a long duration, at higher doses and especially in female animals.

Evaluation of Hemotoxic, Hepatotoxic and Nephrotoxic Potential of Profenofos-based Insecticide in Freshwater Labeo rohita Fish at Low Concentrations

Profenofos, an organophosphate, is a major pollutant that pollutes freshwater bodies, causing significant impacts on fish health. Objective: Present study was performed to assess the toxicological impacts of pesticide profenofos on hematological, biochemical and histological alterations in different organs of Labeo rohita. Methods: Fish were divided in three groups. Group one was treated as control while second and third groups were exposed to 0.6 mg/L and 1.2 mg/L profenofos respectively for 28 days. Results: Results revealed that MCV, MCHC, MCH, RDW-SD, PCT, PDW, HGB, RBC and HCT levels were significantly reduced. WBC, RDW, PLT, MPV, neutrophils, lymphocytes, monocytes and eosinophils were increased as compared to pesticide free group. Biochemical results showed significant increase in cholesterol, triglycerides, AST, albumin, A/G ratio, HDL T3, T4, blood glucose, creatinine and urea levels were documented while levels of LDL, VLDL, ALT, total proteins, globulin, TSH and blood urea nitrogen (BUN) decreased significantly in exposed fish. Furthermore, histological changes in kidney, gills and liver of fish showed degenerative effects after exposure to profenofos in both concentrations. Conclusions: The present study concluded that profenofos resulted in widespread toxic effects on aquatic organisms specially fish.

Adapalene Gel Therapy in Patients with Moderate to Severe Acne Vulgaris

Acne is a chronic inflammatory disease of pilosebaceous units. Topical Adapalene is the most effective despite the availability of various treatments. Abnormalities in plasma lipids are recognized side effects of Adapalene therapy. Minimal reports compare the lipid changes in intermittent and continuous Adapalene treatment. To evaluate the alteration in lipid profile before, during, and after constant/ intermittent topical Adapalene therapy. One hundred patients with moderate to severe acne were randomly assigned to two treatment regimens. Serum levels of lipids were measured at baseline, 4wk, 8wk, 12wk, 16wk, and at the end of the treatment. A significant increase in cholesterol, triglyceride, and LDL concentration and a decrease in HDL levels in a continuous regimen beyond the normal range but not requiring any treatment interruption compared to intermittent therapy. In intermittent therapy, the cholesterol, triglyceride, and LDL concentration increase was within the normal range. Intermittent Adapalene therapy was clinically equally effective, with lesser effects on serum lipid levels and cost than continuous Adapalene therapy.

Preventive Effect of Molecular Iodine in Pancreatic Disorders from Hypothyroid Rabbits.

Pancreatic alterations such as inflammation and insulin resistance accompany hypothyroidism. Molecular iodine (I2) exerts antioxidant and differentiation actions in several tissues, and the pancreas is an iodine-uptake tissue. We analyzed the effect of two oral I2 doses on pancreatic disorders in a model of hypothyroidism for 30 days. Adult female rabbits were divided into the following groups: control, moderate oral dose of I2 (0.2 mg/kg, M-I2), high oral dose of I2 (2.0 mg/kg, H-I2), oral dose of methimazole (MMI; 10 mg/kg), MMI + M-I2,, and MMI + H-I2. Moderate or high I2 supplementation did not modify circulating metabolites or pancreatic morphology. The MMI group showed reductions of circulating thyroxine (T4) and triiodothyronine (T3), moderate glucose increments, and significant increases in cholesterol and low-density lipoproteins. Acinar fibrosis, high insulin content, lipoperoxidation, and overexpression of GLUT4 were observed in the pancreas of this group. M-I2 supplementation normalized the T4 and cholesterol, but T3 remained low. Pancreatic alterations were prevented, and nuclear factor erythroid-2-related factor-2 (Nrf2), antioxidant enzymes, and peroxisome proliferator-activated receptor gamma (PPARG) maintained their basal values. In MMI + H-I2, hypothyroidism was avoided, but pancreatic alterations and low PPARG expression remained. In conclusion, M-I2 supplementation reestablishes thyronine synthesis and diminishes pancreatic alterations, possibly related to Nrf2 and PPARG activation.

Evaluating the in-vivo effects of olive oil, soya bean oil, and vitamins against oxidized ghee toxicity.

The aim of this study was to examine the protective role of various lipids (olive and soya oil) and vitamin (E and C) against the toxicity of thermally oxidized ghee in rabbits. Vanaspati ghee was thermally oxidized on a hot plate at 100°C for ten consecutive hours, and the oxidized ghee was stored in a refrigerator at -20°C until administration. Thirty male rabbits were purchased as experimental animals at a local market and were divided into ten corresponding groups of three based on their body weight. The blood samples of 5 ml were collected on day 0, 7, and 14 of the experiment for the analysis of hematological and biochemical serum parameters. We observed that oxidized ghee significantly elevated ALT level by affecting liver hepatocytes. Furthermore, vitamin E rapidly decreased the ALT levels compared to vitamin C and other oils. The oxidized ghee caused a significant increase in cholesterol compared to the other groups. Vitamin E and C showed the best antioxidant activity and decreased cholesterol levels to normal. Histopathological examinations of the normal rabbits' liver sections revealed no significant histological abnormality. The liver of the rabbits fed with oxidized ghee had an intact lobular architecture but the portal tracts showed inflammation and mild fibrosis, the bile ducts showed proliferation, and the hepatocytes showed feathery degeneration. In the liver sections from the groups fed with oxidized ghee and different doses of olive oil inflammation in portal tracts and large vacuoles in the hepatocytes were observed. The group fed with oxidized ghee and vitamin E had intact lobular architecture with no significant histological abnormality in portal tracts but fatty changes were present in the hepatocytes. These findings support the antioxidant activity of vitamins C and E as they reduced liver infection caused by oxidized ghee. It was concluded that oxidized ghee was highly toxic and not safe for consumption. The present study indicated that soya bean oil and vitamin E were more effective in protecting against the toxicity of thermally oxidized ghee than olive oil and vitamin C.

The impact of diabetes mellitus type 2 on the steroidogenesis of male Zucker Diabetic Fatty rats.

The aim of this study was to evaluate the impact of diabetes mellitus type 2 (DM2) on the male endocrine system of Zucker Diabetic Fatty (ZDF) rats. Sexually mature ZDF rats were divided to a lean (control) and obese group, and had diabetes confirmed by blood tests. For the in vivo experiment, fasting blood was collected to obtain blood plasma. In case of the in vitro experiments, testicular fragments were cultured for 24 h, and the culture medium was collected. The concentrations of testosterone (T), androstenedione (A4), dehydroepiandrosterone (DHEA-S), estradiol (E2), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were quantified in the blood plasma and the medium by the ELISA method, while cholesterol (CHOL) was assessed spectrophotometrically. A significant decline of T (36.31 %), A4 (25.11 %) and FSH (26.99 %) as well as a significant increase of CHOL and E2 (36.17 %) was observed in the blood plasma of obese ZDF rats in comparison to the control. Under in vitro conditions, a significant decrease of FSH (23.35 %) accompanied by an increase of E2 was observed in the obese group compared to the control. In the case of CHOL, LH, T, DHEA and A4 no significant differences were observed. Our results suggest that except for FSH and E2 all steroid biomolecules were synthetized normally by the testicular tissue, however a dramatic endocrine disturbance was observed at the system level. We may conclude that DM2 has negative effects on systemic hormone secretion and these alterations are more pronounced in combination with obesity.

Evaluation of metabolic and oxidative profile in ovine pregnancy toxemia and to determine their association with diagnosis and prognosis of disease.

This study was conducted on ewes with pregnancy toxemia (PT) with an attempt to evaluate metabolic and oxidative profile in subclinical and clinical ovine pregnancy toxemia and to determine their association with diagnosis and prognosis of the disease. A total of 20 ewes having beta-hydroxy butyric acid (β-HBA) > 2.5mmol/L and proven clinical sings of PT, categorized as clinical PT (CPT); 12 ewes having β-HBA 0.8-2.5mmol/L and no clinical signs of PT, categorized at subclinical PT (SPT); and 10 ewes having β-HBA ≤ 0.8mmol/L, categorized as healthy control (CON) were enrolled. Among 20 CPT ewes, 11 had negative outcomes (non-survivors), six ewes had positive outcomes (survivors), and three were lost during follow-up. A significant increase in non-esterified fatty acid, β-HBA, triglycerides, gamma-glutamyl transferase, lactate dehydrogenase, and malondialdehyde levels and a significant decrease in fructosamine were observed in CPT and SPT compared to CON. A significant increase in cholesterol, aspartate amino transferase, and creatinine kinase and a significant decrease in albumin, potassium, calcium, superoxide dismutase, and catalase were observed in CPT only. Glucose was significantly decreased in SPT only. The highest area under the curve (AUC) was observed for fructosamine (89.7% and 87.5% for CPT and SPT, respectively) with the optimum cutoff point calculated on the basis of maximum sensitivity (SE) and specificity (SP) being 0.607mmol/L (SE: 89.3% and SP: 72.2%) and 1.005mmol/L (SE: 90.0% and SP: 75.3%) for CPT and SPT, respectively. At the cutoff limit of 0.607mmol/L and 1.005mmol/L, the odds ratio was 10.8 and 8.0 for CPT and SPT, respectively. A significant decrease in fructosamine and potassium and a significant increase in creatinine, lactate dehydrogenase, and malondialdehyde were observed in non-survivors compared to survivors. It was thus concluded that fructosamine was the best diagnostic indicator of both CPT and SPT followed by non-esterified fatty acid. Fructosamine, creatinine, potassium, lactate dehydrogenase, and malondialdehyde were the best prognostic indicators of PT.

Involvement of cell shape and lipid metabolism in glioblastoma resistance to temozolomide.

Temozolomide (TMZ) has been used as standard-of-care for glioblastoma multiforme (GBM), but the resistance to TMZ develops quickly and frequently. Thus, more studies are needed to elucidate the resistance mechanisms. In the current study, we investigated the relationship among the three important phenotypes, namely TMZ-resistance, cell shape and lipid metabolism, in GBM cells. We first observed the distinct difference in cell shapes between TMZ-sensitive (U87) and resistant (U87R) GBM cells. We then conducted NMR-based lipid metabolomics, which revealed a significant increase in cholesterol and fatty acid synthesis as well as lower lipid unsaturation in U87R cells. Consistent with the lipid changes, U87R cells exhibited significantly lower membrane fluidity. The transcriptomic analysis demonstrated that lipid synthesis pathways through SREBP were upregulated in U87R cells, which was confirmed at the protein level. Fatostatin, an SREBP inhibitor, and other lipid pathway inhibitors (C75, TOFA) exhibited similar or more potent inhibition on U87R cells compared to sensitive U87 cells. The lower lipid unsaturation ratio, membrane fluidity and higher fatostatin sensitivity were all recapitulated in patient-derived TMZ-resistant primary cells. The observed ternary relationship among cell shape, lipid composition, and TMZ-resistance may be applicable to other drug-resistance cases. SREBP and fatostatin are suggested as a promising target-therapeutic agent pair for drug-resistant glioblastoma.

The utility of laboratory testing for pediatric patients undergoing isotretinoin treatment.

Isotretinoin, the most effective treatment for severe cystic acne, involves laboratory monitoring. In this retrospective case series of 130 pediatric patients taking isotretinoin, there were significant increases in cholesterol (143.9mg/dl to 155.3mg/dl), triglycerides (81.8mg/dl to 115.2mg/dl), and low-density lipoprotein (82.0mg/dl to 98.1mg/dl), and a decrease in high-density lipoprotein (50.0mg/dl to 44.7mg/dl) from baseline to follow-up (p < .05); there were no significant changes in liver enzymes. None of the patients had clinical sequelae (triglyceride-induced pancreatitis, retinoid-induced hepatotoxicity) related to their abnormal lab values. These findings question the utility of laboratory monitoring for prevention of severe clinical sequelae in pediatric patients, and suggest testing based on individualized risk factors may be more appropriate.

Zebrafish model of in utero glucose exposure alters developmental programming that leads to life‐long metabolic consequences

Background and AimOne in ten pregnancies in the US, suffers from Gestational Diabetes Mellitus (GDM). Offspring born to mothers who have GDM have a higher risk of developing Obesity, Type 2 diabetes and Non‐alcoholic fatty liver disease later in life. Although in utero glucose exposure provides evidence for developmental programming leading to metabolic disorders in adults, the molecular mechanisms are still unclear. We aim to understand the mechanisms implicated in developmental programming and their associated adult outcomes in a well‐established zebrafish model of fetal hyperglycemia that mimics the metabolic disorders in human GDM.MethodsWe developed a zebrafish model of fetal hyperglycemia by exposing embryos to high glucose (4.5% w/v) during the last day of embryogenesis from 96 to 120 hours post fertilization. Glucose level was detected in embryos and larvae homogenates and in adult serum by glucometer. Body composition was determined in adults by EchoMRI, gene expression of glycolytic, lipogenic (Acetyl‐CoA Carboxylase (acca) and mitochondria biogenesis (Peroxisome proliferator‐activated receptor‐gamma coactivator [PGC‐1α/β) markers were quantified by RT‐qPCR and acca by western blot. Lipid accumulation was detected by Oil‐Red‐O staining (ORO) and quantified by spectrophotometry. Triglyceride and cholesterol levels (ELISA), adiposity (Nile red staining) and mitochondrion number (mitotracker staining) were also evaluated. We also assessed if co‐administration of metformin or ND646 (known inhibitors of acca) with glucose can attenuate fetal hyperglycemia‐mediated metabolic outcomes.ResultsZebrafish embryos exposed to high glucose for 24 hrs are transiently hyperglycemic while normoglycemia is restored after glucose exposure. Larvae and adults with embryonic glucose exposure are normoglycemic. Embryos showed an upregulation of hexokinase and pyruvate Kinase expression when assessed at 120 hpf, but no change in expression was detected in larvae. Embryos exposed to glucose showed increased lipid accumulation by ORO staining (0.22 ±0.01 Vs 0.17±0.01) while larvae showed a 5‐fold increase in adiposity. Adult fish develop obesity characterized by increased BMI (0.83±26.34 Vs. 0.60± 33.89) kg/m2 and fat mass (12.07± 2.92 Vs 3.4± 0.4) g. Embryos showed increase in both acca mRNA expression (3‐folds) and activation (decreased phosphorylation). Interestingly, acca expression remained increased in larvae while glycemia was normal. Moreover, there was a significant increase in cholesterol (57.92± 0.7 Vs 34.8±1.01 µM) and triglyceride levels in glucose exposed embryos compared to controls (4.1± 0.75 Vs 0.98±0.27 µM). Our data in embryos revealed an increase in mitochondria number validated by an increase in the expression of PGC‐1α/β. Finally, ORO staining showed that embryonic lipid accumulation was decreased to normal levels, by metformin or ND646 exposure when co‐administered with glucose.Conclusion and significanceTogether our results show that embryonic glucose exposure alters developmental programming, including lipid homeostasis dysregulation that is persistent in larvae and adult. However, it can be rescued by pharmacological approaches.

Віддалені результати корекції метаболічних порушень при синдромі полікістозних яєчників після лікування метформіном

Актуальність. Синдром полікістозних яєчників (СПКЯ) — поліморфне захворювання з надзвичайно варіабельною клінічною картиною та різними фенотипами, що відзначається у 5–10 % жінок репродуктивного віку. Протягом життя у жінок із СПКЯ в 10 разів підвищується ризик розвитку цукрового діабету (ЦД) 2-го типу, в 7 разів — артеріальної гіпертензії та ішемічної хвороби серця, в тому числі інфаркту міокарда, більш ніж удвічі — онкологічних захворювань яєчників, ендометрію, молочної залози. Мета дослідження — проведення аналізу динаміки показників інсулінорезистентності, дисліпідемії, порушеної толерантності до глюкози після лікування метформіном у пацієнток із СПКЯ з використанням показників індексів Caro та НОМА-IR. Матеріали та методи. Проаналізовані 26 історій хвороби пацієнток із СПКЯ, яким за період з 2012 по 2018 р. проводили терапію метформіном протягом шести місяців з моменту постановки діагнозу. Всім пацієнткам в 2018 р. було проведене дослідження ліпідного спектра крові, стандартний глюкозотолерантний тест і дослідження вмісту імунореактивного інсуліну в плазмі венозної крові. Оцінку стану вуглеводного обміну проводили за допомогою розрахункових показників індексів Caro та НОМА-IR. Результати. Результатом застосування метформіну у 26 жінок із СПКЯ й інсулінорезистентністю стало вірогідне зниження рівня імунореактивного інсуліну натще (з 21,4 ± 2,3 до 6,9 ± 0,8 мкОД/мл; р = 0,005) через 6 місяців, в той час як значущих змін рівня глікемії натще не спостерігалося. Відповідно, показник НОМА-IR знизився з 4,38 ± 1,26 до 1,17 ± 0,18 (р = 0,01), а індекс Caro підвищився з 0,24 ± 0,05 до 0,58 ± 0,14 (р = 0,02). Оцінка показників ліпідного обміну через 6 місяців після початку лікування метформіном підтвердила вірогідне зниження рівня холестерину з 5,4 ± 0,3 до 3,6 ± 0,5 ммоль/л (р = 0,01) і рівня тригліцеридів з 1,7 ± 0,2 до 0,8 ± 0,2 ммоль/л (р = 0,03). Обстеження, проведене у 2018 р. в цих же пацієнток, засвідчило збільшення маси тіла не тільки порівняно з показниками через 6 місяців після лікування метформіном, але і з початковими. Спостерігалося вірогідне підвищення рівня холестерину при обстеженні в 2018 р. до 6,7 ± 0,4 ммоль/л (р = 0,01 порівняно з показником після лікування метформіном). Висновки. Жінки із СПКЯ та інсулінорезистентністю, дисліпідемією мають найбільший ризик розвитку ЦД і серцево-судинної патології. Застосування метформіну розглядається як потенційно ефективний метод для подолання інсулінорезистентності, поліпшення гормональних, біохімічних параметрів і можливого зниження кардіоваскулярного ризику при СПКЯ.

High cholesterol-supplemented diet during gestation and lactation alters liver glycosaminoglycans and associated lipoprotein receptors and results in fat accumulation in adulthood

In utero insults to growing fetus impact its health in adulthood. Glycosaminoglycans (GAGs) are involved in lipoprotein metabolism in the liver and vary both quantitively and qualitatively on feeding adult rats a diet rich in cholesterol. However, no reports are available to show the modulation of GAGs when the offspring are subjected to a high cholesterol diet in gestation and lactation stages. Hypercholesterolemia in pregnant rats was induced by feeding an AIN-93 diet supplemented with 0.5% cholesterol. The pups born to mothers fed with high cholesterol diet showed a significant increase in cholesterol and triglycerides accumulation in the liver. Quantitative changes in sulfated glycosaminoglycans (sGAGs), in particular of heparan sulfate, were observed across the developmental stages. Other players involved in lipoprotein metabolism, namely low-density lipoprotein receptor-related protein 1, apolipoprotein E, and low-density lipoprotein receptor expression levels, also showed differential changes across developmental stages. Interestingly, when pups from hypercholesterolemic mothers were fed a normal diet after weaning until adulthood, a considerable amount of fat accumulation in the liver was observed, implicating fetal exposure to early high cholesterol exposure on long term health.

In vivo toxicities of the hospital effluent in Mahdia Tunisia.

Hospital effluent (HE) is one of the most important sources of pharmaceuticals released into the environment. This kind of pollution is a recognized problem for both human health and aquatic life. Consequently, in the present study, we assessed the effects of untreated hospital effluent on mice via biochemical and histopathological determinations. Female mice were given free access to water bottles containing untreated HE at different dilutions for 21 days. Then clinical biochemistry and histopathology evaluation were conducted. Serum biochemistry analysis showed the presence of significant increase in cholesterol, triglycerides, glycaemia and total bilirubin. However, phosphatase alkaline and urea activities have been significantly decreased compared to the control group. No significant variation was observed for the rest of the studied parameters (high-density lipoproteins; low-density lipoproteins and uric acid). Additionally, multiple alterations, including cellular necrosis, leucocyte infiltration and congestion, were observed in different tissues of mice exposed to the tested HE.

Appraisal of amiodarone-loaded PLGA nanoparticles for prospective safety and toxicity in a rat model

AimsAmiodarone (AM) is a highly efficient drug for arrhythmias treatment, but its extra-cardiac adverse effects offset its therapeutic efficacy. Nanoparticles (NPs)-based delivery system could provide a strategy to allow sustained delivery of AM to the myocardium and reduction of adverse effects. The primary purpose was to develop AM-loaded NPs and explore their ameliorative effects versus off-target toxicities. Materials and methodsPolymeric NPs were prepared using poly lactic-co-glycolic acid and their physicochemical properties were characterized. Animal studies were conducted using a rat model to compare exposure to AM versus that of the AM-loaded NPs. Biochemical evaluation of liver enzymes, lipid profile, and thyroid hormones was achieved. Besides, histopathological changes in liver and lung were studied. Key findingsUnder optimal experimental conditions, the AM-loaded NPs had a size of 186.90 nm and a negative zeta potential (−14.67 mV). Biochemical evaluation of AM-treated animal group showed a significant increase in cholesterol, TG, LDL, T4, and TSH levels (ρ < 0.05). Remarkably, the AM-treated group exhibited a significant increase of liver enzymes (ρ < 0.05) coupled with an obvious change in liver architecture. The AM-loaded NPs displayed a reduction of liver damage and enzyme levels. Lung sections of the AM-treated group demonstrated thickening of interalveolar septa, mononuclear cellular infiltration with congested blood vessels, and heavy collagenous fibers deposition. Conversely, less cellular infiltration and septal thickening were observed in the animal lungs treated with the AM-loaded NPs-treated. SignificanceOur findings demonstrate the competence of the AM-loaded NPs to open several exciting avenues for evading the AM-induced off-target toxicities.

Farming and pastoral systems shape the physiological and immunological indices of the dromedary she-camels

Background: Camel (Camelus dromedarius) is a vital animal to the daily life of the desert as a source of food and transportation, its milk is used as medicine for diverse ailments. Aim: This study was planned to evaluate the effect of two different feeding systems (farming and pastoral systems) on physiological and immunological indices of one-humped dromedary she-camels during different physiological stages. Material and methods: Forty female camels under farm and grazing systems were used from the Camel Experimental Flock in Matrouh (farming system) and Bedouin flock in a grazing unit in the same area (pastoral system). Blood samples were collected during different physiological stages to determine the desired parameters. Results: It was revealed that lymphocytes significantly increased in grazing camels as compared to farm ones. Leukocytes significantly increased in post-partum and lactation than other camels. The number of RBCs increased significantly in pregnant and lactating than other camels. Albumin increased significantly in pregnant and lactating camels and decreased in dry and post-partum. Results showed a significant increase in blood lipids including total lipids, phospholipids, triglycerides, total cholesterol, and low-density lipoproteins in farm camels compared to grazing ones. Lactating and pregnant camels showed a significant increase in cholesterol compared to dry and post-partum. In lactating camels, insulin significantly increased compared to other groups. But, cortisol significantly increased in post-partum camels. Conclusion: Farm camels show better physiological and immunological profiles than grazing ones reflect the importance of supplementary feeding especially during pregnancy and lactation.

Correction of lipid metabolism disorders with atorvastatin in combination with UDCA in NAFLD

Objective: to evaluate the therapeutic efficacy of the combined use of ursodeoxycholic acid and atorvastatin in non-alcoholic fatty liver disease (NAFLD) with concomitant atherogenic dyslipidemia.Materials and methods.123 patients with NAFLD at the stage of steatosis were examined, among them 66 women and 57 men aged 30 to 70 years. In verification of NAFLD, an ultrasound examination (ultrasound) of the hepatobiliary system was used using the SONIX OP apparatus (Canada). To exclude fibrosis in the liver parenchyma, sonoelastographywas performed on an AIXPLORER apparatus (France) and the FibroTest and FibroMax tests developed by BioPredictiv (Paris, France) were used. The lipid profile was determined on an analyzer FP-901 (M) from Labsystems (Finland) (Spain, Barcelona). The method of multifractional (5-phase) duodenal sounding (MFDZ) was used, which makes it possible to evaluate bile indices (cholesterol and bile acids).Results. Ultrasound of the liver and SteatoTest revealed steatosis in all patients with NAFLD. The examined identified signs of atherogenic dyslipidemia. There was a significant increase in cholesterol in portions “B” and “C” of bile (by 79.9% (p = 0.001) and 76.89% (p = 0.001), respectively), a decrease in the amount of bile acids in portions “B” and “ C ”bile (by 46.74% (p = 0.001) and 30.56% (p = 0.1), respectively). A sharp decrease in the cholecholesterol coefficient (by 90.55% (p = 0.001) and 86.03% (p = 0.01), respectively) confirms the high lithogenic properties of bile. The combined use of ursodeoxycholic acid (UDCA), simultaneously with atorvastatin, manifested a more pronounced both lipid-lowering effect and correction of the lithogenic properties of bile, in comparison with UDCA monotherapy.Conclusion. The effectiveness of the course application of UDCA in combination with atorvastatin in the correction of hyper- and dyslipidemia and biochemical parameters of bile in patients with NAFLD at an early stage of steatosis was determined.