Insulin Resistance and Hypertension: Mechanisms Involved and Modifying Factors for Effective Glucose Control.

Factors such as aging, an unhealthy lifestyle with decreased physical activity, snacking, a standard Western diet, and smoking contribute to raising blood pressure to a dangerous level, increasing the risk of coronary artery disease and heart failure. Atherosclerosis, or aging of the blood vessels, is a physiological process that has accelerated in the last decades by the overconsumption of carbohydrates as the primary sources of caloric intake, resulting in increased triglycerides and VLDL-cholesterol and insulin spikes. Classically, medications ranging from beta blockers to angiotensin II blockers and even calcium channel blockers were used alone or in combination with lifestyle modifications as management tools in modern medicine to control arterial blood pressure. However, it is not easy to control blood pressure or the associated complications. A low-carbohydrate, high-fat (LCHF) diet can reduce glucose and insulin spikes, improve insulin sensitivity, and lessen atherosclerosis risk factors. We reviewed articles describing the etiology of insulin resistance (IR) and its impact on arterial blood pressure from databases including PubMed, PubMed Central, and Google Scholar. We discuss how the LCHF diet is beneficial to maintaining arterial blood pressure at normal levels, slowing down the progression of atherosclerosis, and reducing the use of antihypertensive medications. The mechanisms involved in IR associated with hypertension are also highlighted.

Discrimination Power of Short Essay Questions Versus Multiple Choice Questions as an Assessment Tool in Clinical Biochemistry.

Assessment is fundamental to the educational process. Multiple choice questions (MCQs) and short essay questions (SEQs) are the most widely used assessment method in medical school. The current study evaluated the discriminating value of SEQs compared to MCQs as assessment tools in clinical biochemistry and correlated undergraduate students' SEQ scores with their overall scores during the academic years 2021-2022 and 2022-2023. This is a descriptive-analytical study in which MCQ and SEQ papers of clinical biochemistry were analyzed. The mean score for SEQs in males was 66.7 ± 1.2 and for females it was 64.0 ± 1.1 SEM, with a p-value of 0.09; for MCQs, the mean score for males was 68.5 ± 0.9 SEM and for females it was 72.6 ± 0.8. When analyzing the difficulty index (DI) and discrimination factor (DF) of the questions, MCQs have a mean DI of 0.70 ± 0.01,and DF of 0.05 to 0.6. SEQs have a mean DI of 0.73 ± 0.03 and DF of 0.68 ± 0.01; there was a significant difference between the DF of MCQs and SEQs (p < 0.0001). Furthermore, there was a significant difference between SEQs and MCQs when categorizing students based on their scores, except for A-scored students. According to the current study, SEQs have a higher discriminating ability than MCQs and help differentiate high-achieving students from low-achieving students.

Low-Carbohydrate Ketogenic Diet for Improvement of Glycemic Control: Mechanism of Action of Ketosis and Beneficial Effects.

The incidence of metabolic syndrome and diabetes mellitus is increasing globally. A diet rich in carbohydrates increases the hyperglycemic state. While considering the lifestyle changes to combat life-threatening diseases, there is an effort to decrease the daily intake of carbohydrates. A low-carbohydrate diet also makes the body rely more on fat for energy, so there is less fat accumulation. A diet is considered to be low-carbohydrate ketogenic if the intake is ≤ 50 g per day. The 'low -carbohydrate ketogenic diet' (LCKD) produces ketosis. LCKD contains high-fat, moderateprotein, and low-carbohydrate components. The main objectives of the present review are to discuss insulin resistance in different viscera of the body, describe the role of adipokines in insulin resistance, understand the mechanism of ketogenesis, and determine the impact of LCKD in overcoming insulin resistance in the body. In the present review, we also highlight the beneficial effects of LCKD in metabolic, neurodegenerative, cardiovascular, and lipid disorders and discuss the effect on longevity and aging. LCKD may help in combating the morbidity and mortality arising from the above-mentioned diseases and also help in leading a better quality of life.

Endoplasmic reticulum stress and mitochondrial injury are critical molecular drivers of AlCl3-induced testicular and epididymal distortion and dysfunction: protective role of taurine.

Aluminum, the third most plentiful metal in the Earth's crust, has potential for human exposure and harm. Oxidative stress plays an essential role in producing male infertility by inducing defects in sperm functions. We aimed to investigate the role of endoplasmic reticulum (ER) stress and mitochondrial injury in the pathogenesis of aluminum chloride (AlCl3)-induced testicular and epididymal damage at the histological, biochemical, and molecular levels, and to assess the potential protective role of taurine. Forty-eight adult male albino rats were separated into four groups (12 in each): negative control, positive control, AlCl3, and AlCl3 plus taurine groups. Testes and epididymis were dissected. Histological and immunohistochemical (Bax and vimentin) studies were carried out. Gene expression of vimentin, PCNA, CHOP, Bcl-2, Bax, and XBP1 were investigated via quantitative real-time polymerase chain reaction (qRT-PCR), besides estimation of malondialdehyde (MDA) and total antioxidant capacity (TAC). Light and electron microscopic examinations of the testes and epididymis revealed pathological changes emphasizing both mitochondrial injury and ER stress in the AlCl3 group. Taurine-treated rats showed a noticeable improvement in the testicular and epididymal ultrastructure. Moreover, they exhibited increased gene expression of vimentin, Bcl-2, and PNCA accompanied by decreased CHOP, Bax, and XBP1 gene expression. In conclusion, male reproductive impairment is a significant hazard associated with AlCl3 exposure. Both ER stress and mitochondrial impairment are critical mechanisms of the deterioration in the testes and epididymis induced by AlCl3, but taurine can amend this.

Integrative global co-expression analysis identifies key microRNA-target gene networks as key blood biomarkers for obesity.

BACKGROUND: Obesity is associated with the quantitative changes in miRNAs and their target genes. However, the molecular basis of their dysregulation and expression status correlations is incompletely understood. Therefore, this study aims to examine the shared differentially expressed miRNAs and their target genes between blood and adipose tissues of obese individuals to identify potential blood-based biomarkers. METHODS: In this study, 3 gene expression datasets (two mRNA and one miRNA), generated from blood and adipose tissues of 68 obese and 39 lean individuals, were analyzed by a series of robust computational concepts, like protein interactome mapping, functional enrichment of biological pathways and construction of miRNA-mRNA and transcription factor gene networks. RESULTS: The comparison of blood versus tissue datasets has revealed the shared differential expression of 210 genes (59.5% upregulated) involved in lipid metabolism and inflammatory reactions. The blood miRNA (GSE25470) analysis has identified 79 differentially expressed miRNAs (71% downregulated). The miRNA-target gene scan identified regulation of 30 shared genes by 22miRNAs. The gene network analysis has identified the inverse expression correlation between 8 target genes (TP53, DYSF, GAB2, GFRA2, NACC2, FAM53C, JNK and GAB2) and 3 key miRNAs (hsa-mir-940, hsa-mir-765, hsa-mir-612), which are further regulated by 24 key transcription factors. CONCLUSIONS: This study identifies potential obesity related blood biomarkers from large-scale gene expression data by computational miRNA-target gene interactome and transcription factor network construction methods.

An Overview of the Perspective of Cellular Autophagy: Mechanism, Regulation, and the Role of Autophagy Dysregulation in the Pathogenesis of Diseases.

Autophagy is a cellular process that eliminates unnecessary cytoplasmic materials, such as long-age proteins, destroyed organelles, and foreign microorganisms. Macroautophagy (MaA), chaperone-mediated autophagy, and microautophagy are the three main types of autophagy. It is regulated by the integration of signaling from the AMPK and mTOR-ULK1 pathways. Autophagy plays a physiological role in health, and its dysregulation could be a pathophysiologic mechanism in different disease conditions. In the current study, we reviewed papers of Google Scholar database, PubMed, PubMed Central, Cochrane Database of Systematic Reviews, MEDLINE, and MedlinePlus with no time limitation and a recent World Health Organization report. In the current review, it could be concluded that autophagy plays many physiological functions, including immune system modulation, and regulates different cellular processes such as metabolism, protein synthesis, and cellular transportation. Dysregulation of autophagy is implicated in tumorigenesis, aging, age-related neurodegeneration, and endothelial dysfunctions. Autophagy dysregulation is also implicated in the newly discovered CoV-COVID-19 pathogenesis.

Methylation degree of metalloproteinase inhibitor RECK gene: Links to RECK protein level and hepatocellular carcinoma in chronic HCV infection patients.

The RECK gene, a tumor suppressor gene, inhibits angiogenesis, invasion, and tumor metastasis. Epigenetic regulation of the RECK gene constitutes a potent approach to the molecular basis of liver malignancy. This study aims to evaluate the promoter methylation status of the RECK gene and its serum level in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) and the potential association of RECK gene methylation with clinical criteria of HCC. One hundred and fifty-five subjects were included (healthy control [55], chronic HCV patients [55], HCV-related HCC patients [45]). The methylation status of the RECK gene promoter and serum RECK level were investigated by methylation-specific PCR and enzyme-linked immunosorbent assay techniques, respectively. RECK gene promoter hypermethylation was recorded in 46.7% of HCC patients, and 10.9% of HCV patients, but not in control subjects (0%). It was related to RECK protein level, varices, edema, ascites, lymph node metastasis, vascular invasion, and the largest diameter of focal lesions. Meanwhile, it was not associated with focal lesion number nor distant metastasis of HCC. In conclusion, RECK gene promoter hypermethylation is linked to HCV genotype-4-related HCC. Moreover, different degrees of RECK gene promoter methylation are associated with serum RECK level, lymph node metastasis, and vascular invasion, which could prove its pathogenic role in hepatocarcinogenesis in chronic HCV-infected patients.

MTHFR C677T Polymorphism and Serum Homocysteine Level as Risk Factors of Coronary Heart Disease in Patients with Androgenetic Alopecia: A Case Control Study.

BACKGROUND: Androgenetic alopecia (AGA) is associated with a risk of coronary heart disease (CHD), although the causes underlying this association are not clear. Serum homocysteine (SH) is a known risk factor for CHD, and methylene tetrahydrofolate reductase enzyme (MTHFR) plays a crucial role in the remethylation of homocysteine to methionine. The polymorphism C677T that affects the catalytic domain of the MTHFR protein leads to a high levels of SH. Our hypothesis was that this polymorphism and SH level are risk factors for CHD in patients with AGA. MATERIALS AND METHODS: A total of 106 patients with AGA and 100 well-matched healthy controls were enrolled in the study. SH levels were estimated. DNA was extracted and polymerase chain reaction amplification, followed by restriction enzyme digestion for MTHFR (C677T) gene, was conducted. RESULTS: SH levels were significantly higher in the patient group and highest in those with the TT genotype. The mutant T allele was associated with hyperhomocysteinemia and an increased risk of CHD in patients with AGA. CONCLUSIONS: AGA is associated with a higher risk of developing CHD due to the associated higher level of SH that, in turn, depends on and is correlated with mutant MTHFR genotypes. Cardiac evaluation and follow-up of patients with AGA is recommended for early detection and treatment of CHD to avoid an overall detrimental course.

Cellular Senescence and Vitamin D Deficiency Play a Role in the Pathogenesis of Obesity-Associated Subclinical Atherosclerosis: Study of the Potential Protective Role of Vitamin D Supplementation.

The exact link between obesity, vitamin D deficiency, and their relation to cellular senescence in the pathogenesis of subclinical atherosclerosis is still under debate. Therefore, the current study aims to verify the possible role of vitamin D deficiency and cellular senescence in the pathogenesis of obesity-related subclinical atherosclerosis. Moreover, it aims to investigate the possible protective role of vitamin D supplementation. Fifty-seven male albino rats were enrolled in the study and classified into four groups: negative (10) and positive control groups (10), an obese model group (24), and a vitamin-D-supplemented obese group (13). Aortic tissue samples and fasting blood samples were collected. The following biochemical investigations were performed: serum cholesterol, triglycerides, HDL-C, LDL-C, ALT, AST, CPK, CK-MB, and hs-cTnt. HOMA-IR was calculated. Moreover, serum SMP-30, 25 (OH)Vitamin D3, and eNOS were determined by the ELISA technique. Aortic gene expression of eNOS, SMP-30, and P53 was estimated by real-time qRT-PCR. Serum 25(OH) D3 and SMP-30 were lower in the obese group. In addition, the obese group showed higher serum lipid profile, HOMA-IR, eNOS, ALT, AST, CPK, CK-MB, and hs-cTnt than the control groups, while decreased levels were found in the vitamin-D-treated obese group. Gene expression of eNOS and SMP-30 were in accordance with their serum levels. A positive correlation was found between vitamin D level and SMP-30. In conclusion, obesity is associated with vitamin D deficiency and enhanced cellular senescence. They could play a role in the pathogenesis of obesity-associated subclinical atherosclerosis and endothelial dysfunction. Vitamin D supplements could play a protective role against such obesity-related comorbidity.

Study of Cellular Senescence and Vitamin D Deficiency in Nonalcoholic Fatty Liver Disease and The Potential Protective Effect of Vitamin D Supplementation.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a pathological process characterized by excessive hepatic fatty deposition with possible involvement of vitamin D deficiency and cellular senescence. The aim of this study is to investigate the pathophysiologic role of vitamin D deficiency and cellular senescence in NAFLD development. Moreover, it aims to investigate the potential protective role of vitamin D supplementation. METHODS: This is an experimental Case/Control study. Forty-five male albino rats were enrolled in this study. Animals were divided into four groups: negative and positive control groups (10 for each group), a model of NAFLD (11) and vitamin D-treated NAFLD groups (14). At the end of the experiment, all rats were subjected to the following investigation; biochemical estimation of serum 25 hydroxycholecalciferol, senescence marker protein-30 (SMP-30), lipid profile and calculation of homeostatic model of insulin resistance (HOMA-IR). RESULTS: NAFLD group shows a significant increase in glucose, insulin levels, and HOMA- IR compared with both normal controls. This finding indicates the intimate association between insulin resistance and NAFLD pathogenesis. Moreover, it was found that NAFLD group shows a significant decrease in SMP-30 level compared with normal controls. While vitamin D-treated NAFLD group shows significant increased SMP-30 and decrease in HOMA-IR in comparison with nontreated NAFLD group. CONCLUSION: Vitamin D deficiency and increased cellular senescence are key features of NAFLD. Vitamin D supplementation could play a protective role, which needs further investigation including clinical human study.

Clinicopathological Impact of Gene Polymorphism of Nephrin and Glucocorticoid Receptor Genes in Egyptian Children with Nonfamilial Nephrotic Syndrome.

Idiopathic nephrotic syndrome (NS) is one of the most common primary glomerular diseases in children. In this study, we investigate the association of single-nucleotide polymorphisms of nephrin gene and glucocorticoid receptor gene (NR3C1) and susceptibility to develop NS and the response to steroid therapy in 100 Egyptian children with NS using polymerase chain reaction-restriction fragment length polymorphism. We also analyzed the correlation between the genotypes and clinicopathologic features of the patients. Thirty-four patients (34%) were initial steroid nonresponders, renal biopsy findings of those patients were available, of which 22 (64.7%) showed minimal change NS and 12 (35.3%) had focal segmental glomerulosclerosis. The distribution of the genotypes was comparable between the patient and control groups, allele frequencies showed no significant difference between the patient's group and the control group. The genotypes showed no correlation with the age of onset of NS, initial steroid responsiveness, renal pathologic findings, estimated glomerular filtration rate (eGFR), and serum albumin. However, 24-h protein in urine showed a significant association with the NR3C1 gene. These data suggested that the nephrin gene and NR3C1 gene SNPs do not affect the development of NS, initial steroid responsiveness, renal pathological lesion, eGFR, and serum albumin. However, 24-h protein in urine showed a significant association with the NR3C1 gene in Egyptian children with NS.

Prognostic value of vascular endothelial growth factor in both conventional and drug eluting beads transarterial chemoembolization for treatment of unresectable hepatocellular carcinoma in HCV patients.

OBJECTIVES: This work aimed to measure serum vascular endothelial growth factor (VEGF) levels before and after Conventional transarterial chemoembolization (cTACE) versus drug-eluting beads (DEB)-TACE and evaluate its efficacy in predicting response to therapy and tumor recurrence. METHODS: 114 patients with unresectable hepatocellular carcinoma complicating hepatitis C virus-related cirrhosis were included. They underwent cTACE (58) or DEB-TACE (56). VEGF serum levels were measured before and on days 1 and 30 after TACE. Patients with complete response (CR) after TACE were followed-up for one year. Statistical analysis was done. RESULTS: VEGF level was higher than baseline after cTACE (P < 0.001), and DEB-TACE (P = 0.004). It was also significantly higher in patients with progressive disease (P < 0.001). VEGF level at cut off values of 97.3, 149.8, and 104.1 pg/ml could discriminate disease progression from treatment success with area under ROC curves of 0.806, 0.775, and 0.771, respectively. The sensitivity was 88.9%, 88.9%, and 77.8% and specificity was 62.5%, 64.6 and 66.7%, respectively. However, no relation to tumor recurrence in CR group could be detected after one year. CONCLUSION: VEGF serum levels may predict response to therapy in patients treated by DEB-TACE or cTACE but it has no relation to tumor recurrence.

The Protective Role of Prenatal Alpha Lipoic Acid Supplementation against Pancreatic Oxidative Damage in Offspring of Valproic Acid-Treated Rats: Histological and Molecular Study.

BACKGROUND: Sodium valproate (VPA) is an antiepileptic drug (AED) licensed for epilepsy and used during pregnancy in various indications. Alpha-lipoic acid (ALA) is a natural compound inducing endogenous antioxidant production. Our study aimed to investigate the effect of prenatal administration of VPA on the pancreas of rat offspring and assess the potential protective role of ALA co-administration during pregnancy. METHODS: Twenty-eight pregnant female albino rats were divided into four groups: group I (negative control), group II (positive control, ALA treated), group III (VPA-treated), and group IV (VPA-ALA-treated). The pancreases of the rat offspring were removed at the fourth week postpartum and prepared for histological, immune-histochemical, morphometric, molecular, and oxidative stress marker studies. RESULTS: In group III, there were pyknotic nuclei, vacuolated cytoplasm with ballooning of acinar, α, and ß cells of the pancreas. Ultrastructural degeneration of cytoplasmic organelles was detected. Additionally, there was a significant increase in oxidative stress, a decrease in insulin-positive cell percentage, and an increase in glucagon positive cells in comparison to control groups. Moreover, VPA increased the gene expression of an apoptotic marker, caspase-3, with a decrease in anti-apoptotic Bcl2 and nuclear factor erythroid 2-related factor 2 (Nrf2) transcriptional factor. Conversely, ALA improved oxidative stress and apoptosis in group VI, and a consequent improvement of the histological and ultrastructure picture was detected. CONCLUSION: ALA co-administration with VPA significantly improved the oxidative stress condition, histological and morphometric picture of the pancreas, and restored normal expression of related genes, including Nrf2, caspase-3, and Bcl-2. Administration of α-lipoic acid has a protective effect against VPA-induced pancreatic oxidative damage via its cytoprotective antioxidant effect.

Development of a novel glycated protein-based fibrosis prediction score for determination of significant liver fibrosis in HCV-infected patients, a preliminary study.

The current study aimed to investigate the diagnostic value of glycated albumin (GA), glycated hemoglobin (HbA1c), and a number of routine biomarkers as noninvasive indicators of liver fibrosis in patients with chronic hepatitis C (CHC). One hundred patients with CHC were subjected to full medical history and examination, in addition to ultrasound-guided liver biopsy and histopathological examination for assessment of liver fibrosis stage. GA and HbA1c values, GA/HbA1c ratio, liver function tests, complete blood count, and alpha fetoprotein (AFP) were determined. A novel noninvasive index, dubbed Fibrosis Prediction Score (FPS), was selected for predicting significant liver fibrosis based on total bilirubin, glycated albumin, platelet count, age, and AFP. A validation study for FPS was applied on archival data which include 66 diabetics' patients. The FPS had area under the curve (AUC) of 0.92 for classification of patients with significant fibrosis with 81% sensitivity and 95% specificity. The AUCs of FPS in predicting advanced fibrosis and cirrhosis were 0.86 and 0.82, respectively. Comparison of AST-to-platelet ratio index (APRI) and FIB-4 with FPS indicated increased sensitivity and specificity of FPS over APRI and FIB4 in both significant and advanced fibrosis. FPS has a good sensitivity and specificity for prediction of significant and advanced liver fibrosis in patients with CHC.

Molecular and ultrastructure study of endoplasmic reticulum stress in hepatic steatosis: role of hepatocyte nuclear factor 4α and inflammatory mediators.

Endoplasmic reticulum (ER) stress could participate in high-fat diet (HFD)-induced hepatic steatosis. The current study aims to investigate the role of ER stress as well as inflammation as possible pathophysiologic mechanisms of HFD-induced hepatic steatosis at ultrastructure and molecular levels. Fifteen control rats on ordinary diet and 30 HFD-fed rats were enrolled in the study. Histological and EM examinations of rats' liver were carried out. Molecular study of TNF-α, CRP, and HNF4α by RT qPCR as well as biochemical investigation of liver function and lipids profile were done. Hepatic steatosis was induced with lipid droplets accumulation at histological level and mega-mitochondria with reduced ER-mitochondrial distance at EM level. Increased gene expression of TNF-α and CRP was significantly correlated with the reduced HNF4α expression and with other ER stress markers. In conclusion, endoplasmic reticulum stress, confirmed at ultrastructure level, plays an important role in pathogenesis of HFD-induced hepatic steatosis. HNF4α downregulation as well as increased expression of hs-CRP and TNF-α enforce the concept of interplay between ER stress, hepatic subclinical inflammation, and disturbed gene expression regulation in the pathogenesis of HFD-induced hepatic steatosis.

The Association of XRCC1 Gene Polymorphisms and Chronic Hepatitis C Induced Insulin Resistance in Egyptian Patients.

Chronic hepatitis C is implicated in insulin resistance (IR) susceptibility. An X-ray repair cross-complementing group 1 gene (XRCC1) is proposed to be a candidate gene for a study of IR susceptibility. So, this study aims to investigate the possible association of the XRCC1 gene polymorphisms with the risk of IR related to chronic hepatitis C virus (HCV) infection in Egyptian patients. In a case-control study, a total of 210 subjects, including 140 chronic HCV patients (87 patients with IR and 53 without IR) and 70 healthy controls, were included. Two genetic polymorphisms (c.1254C > T and c.1517G > C) of the XRCC1 gene were genotyped via the PCR-restriction fragment length polymorphism (PCR-RFLP) technique. The result of the current study revealed that these two single nucleotide polymorphisms (SNPs) have statistically significant influences on susceptibility to IR in chronic HCV infected Egyptian patients. It could be concluded that c.1254C > T, the TT genotype, CT/CC carriers as well as c.1517G > C, the CC genotype and GC/GG carriers might be associated with increased IR susceptibility. Moreover, T-allele of c.1254C > T and the C-allele of c.1517G > C genetic variants might influence the susceptibility.

High Plasma Sphingosine 1-phosphate Levels Predict Osteoporotic Fractures in Postmenopausal Women: The Center of Excellence for Osteoporosis Research Study.

BACKGROUND: Higher sphingosine 1-phosphate (S1P) plasma levels are associated with decreased bone mineral density (BMD), and increased risk of prevalent vertebral fracture. So, we hypothesized that postmenopausal women with increased baseline plasma S1P levels have a greater risk for future incident fracture (osteoporosis-related fractures [ORFs]). METHODS: This study was conducted in a prospective longitudinal cohort of 707 women recruited in 2004 and followed up annually for a mean period of 5.2±1.3 years. They were postmenopausal (aged ≥50 years). The primary outcome measure was the time to the first confirmed ORF event using radiographs and/or a surgical report. RESULTS: The plasma S1P levels (µmol/L) were significantly higher in the women with incident fracture (7.23±0.79) than in those without ORFs (5.02±0.51; P<0.001). High S1P levels were strongly associated with increased fracture risk. After adjustment for age and other confounders, the hazard ratio (HR) was 6.12 (95% confidence interval [CI], 4.92-7.66) for each 1-standard deviation increase in plasma S1P levels. The women in the highest quartile of S1P levels had a significant increase in fracture risk (HR, 9.89; 95% CI, 2.83-34.44). Results were similar when we compared plasma S1P levels at the 1-year visit. CONCLUSIONS: The associations between plasma S1P levels and fracture risk were independent of BMD and other confounders. These findings demonstrate that high plasma S1P level at baseline and at years 1 to 5 is a strong and independent risk factor for future [ORFs] among postmenopausal women and could be a useful biomarker for fracture risk assessment in this population.

Spermatozoal Fractalkine Signaling Pathway Is Upregulated in Subclinical Varicocele Patients with Normal Seminogram and Low-Level Leucospermia.

BACKGROUND: Fractalkine is produced in seminal plasma in small amounts and correlates with sperm motility. PURPOSE: To investigate the possible effect of low-level leucospermia on spermatozoa oxidative stress and sDNA fragmentation in patients with subclinical varicocele and apparently normal seminogram, and also to study the role of spermatozoal fractalkine and its receptor (CX3CR1) gene expression as a marker of spermatozoa inflammatory response. METHODS: This study included 80 patients with subclinical varicocele (45 fertile and 35 infertile) and 45 age-matched fertile volunteers. In semen samples, fractalkine and CX3CR1 gene expression were investigated by qRT-PCR. Moreover, seminal plasma malondialdehyde (MDA) and total antioxidant capacity (TAC) were measured. RESULTS: There are significant decrease in semen quality and significant increase in seminal leucocytes count in subclinical varicocele. Our results show a significant increase in MDA and TAC levels, DNA fragmentation, and expression levels of fractalkine and its receptor (CX3CR1) in subclinical varicocele groups. CONCLUSION: Subclinical varicocele induces seminal and spermatozoal subclinical inflammatory response in the form of low-level leucospermia and increased mRNA expression of the fractalkine signaling pathway, leading to increased spermatozoal ROS production, oxidative stress, and DNA fragmentation. These could cooperate in the pathogenesis of delayed fertility in males with subclinical varicocele.

Spermatozoal cell death-inducing DNA fragmentation factor-α-like effector A (CIDEA) gene expression and DNA fragmentation in infertile men with metabolic syndrome and normal seminogram.

BACKGROUND: This is the first study to investigate spermatozoal cell death-inducing DNA fragmentation factor-α-like effector A (CIDEA) gene expression and DNA fragmentations in the spermatozoa of men diagnosed with metabolic syndrome (MS) who have normal seminograms with unexplained infertility, and to correlate these parameters with seminal glucose concentration. METHODS: This study included 120 participants: 75 male subjects with MS (38 fertile and 37 infertile), and a control group of 45 fertile males without MS. HOMA-IR, semen analysis, and biochemical measurement of seminal plasma insulin and glucose levels were carried out. Spermatozoal insulin gene and CIDEA gene expressions were performed by the RT-PCR method. The percentage of spermatozoal DNA fragmentation was also estimated. RESULTS: The spermatozoal insulin and CIDEA gene expression, as well as the DNA fragmentation, were significantly higher in the infertile MS group than in the fertile MS group, and significantly higher in both the MS groups than in the control group. Seminal glucose concentration showed significant positive correlations with seminal insulin level, spermatozoa insulin, CIDEA gene expression, and DNA fragmentation. Moreover, there was a positive correlation between spermatozoa CIDEA gene expression and DNA fragmentation. CONCLUSIONS: It can be concluded that MS may affect male fertility at the molecular level, through its possible inducing effect of spermatozoa CIDEA and insulin gene expression, DNA fragmentation, and increased seminal glucose.

Diagnostic non-invasive model of large risky esophageal varices in cirrhotic hepatitis C virus patients.

AIM: To build a diagnostic non-invasive model for screening of large varices in cirrhotic hepatitis C virus (HCV) patients. METHODS: This study was conducted on 124 post-HCV cirrhotic patients presenting to the clinics of the Endemic Medicine Department at Mansoura University Hospital for evaluation before HCV antiviral therapy: 78 were Child A and 46 were Child B (score ≤ 8). Inclusion criteria for patients enrolled in this study was presence of cirrhotic HCV (diagnosed by either biopsy or fulfillment of clinical basis). Exclusion criteria consisted of patients with other etiologies of liver cirrhosis, e.g., hepatitis B virus and patients with high MELD score on transplant list. All patients were subjected to full medical record, full basic investigations, endoscopy, and computed tomography (CT), and then divided into groups with no varices, small varices, or large risky varices. In addition, values of Fibrosis-4 score (FIB-4), aminotransferase-to-platelet ratio index (APRI), and platelet count/splenic diameter ratio (PC/SD) were also calculated. RESULTS: Detection of large varies is a multi-factorial process, affected by many variables. Choosing binary logistic regression, dependent factors were either large or small varices while independent factors included CT variables such coronary vein diameter, portal vein (PV) diameter, lieno-renal shunt and other laboratory non-invasive variables namely FIB-4, APRI, and platelet count/splenic diameter. Receiver operating characteristic (ROC) curve was plotted to determine the accuracy of non-invasive parameters for predicting the presence of large esophageal varices and the area under the ROC curve for each one of these parameters was obtained. A model was established and the best model for prediction of large risky esophageal varices used both PC/SD and PV diameter (75% accuracy), while the logistic model equation was shown to be (PV diameter × -0.256) plus (PC/SD × -0.006) plus (8.155). Values nearing 2 or more denote large varices. CONCLUSION: This model equation has 86.9% sensitivity and 57.1% specificity, and would be of clinical applicability with 75% accuracy.