Evaluating serum level of thymidylate synthase in post burn keloid patients before and after intralesional injection of 5-fluorouracil

Background Keloids are fibrous lesions formed at the site of trauma due to types I and III collagen irregular production. The presence of thymidylate synthase (TS) is a must for DNA synthesis and repairs causing cell death. 5-fluorouracil (5-FU) is a fluorinated pyrimidine analogue acting as an anti-metabolic agent that inhibits thymidylate synthase and interferes with ribo-nucleic acid (RNA) synthesis. Objectives we aimed to evaluate the level of thymidylate synthase in post burn keloid patients before and after intralesional injection of 5-fluorouracil. Methods The study included 20 keloid patients and 20 healthy subjects as a control. Serum TS was estimated using commercially available enzyme-linked immunosorbent assay (ELISA) kits before and after treatment with 5-fluorouracil. Results There was a statistically significant difference in TS levels before and after 5-FU treatment (p < 0.05). Also, results have shown that 5-FU injection has good satisfactory results in treatment of keloid causing reduction in scar volume and symptoms improvement (90% of the patients improved). On the other hand, there was no statistically significant difference in TS levels and the outcomes of the treatment. Conclusion Our findings suggest that intralesional 5-FU injection in keloid has very satisfactory results. However, thymidylate synthase enzyme has a minimal role in evaluating the treatment of keloid, so further studies are required to elaborate the relation between this enzyme and keloid scars.

Evaluation of Liver Enzymes and calculation of AST to ALT ratio in patients with acute viral hepatitis

Background: Acute viral hepatitis is a common liver-associated abnormality encountered in clinical practice. The number of biochemical parameters is estimated to detect a hepatic abnormality, which can measure the severity and types of damage to hepatocytes, among which liver enzymes and bilirubin levels are assessed routinely which are raised in acute viral hepatitis.Objective: This study aims to assess the liver enzymes, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, and calculation of AST to ALT ratio in acute viral hepatitis and to compare these parameters with the control group.Methodology: This study included a total of 81 subjects diagnosed with acute viral hepatitis as cases and age and sex-matched, the same number of healthy subjects as control. Serum levels of AST and ALT, alkaline phosphatase (ALP), and bilirubin were analyzed using standard methods. Serum AST to ALT ratio was calculated. Data analysis was done using SPSS Version 17.0 and the results were expressed as mean ±standard deviation (SD).Results: A mean serum activities of aminotransferases were statistically significantly raised in viral hepatitis compared to that in control.AST (514.85±350.66 VS 25.65±5.29; p<0.001) and ALT (781.65±525.69 VS 27.94±6.50; p<0.001). Similarly, serum levels of(ALP)were significantly increased in acute viral hepatitis compared to that in control (202.17±75.46 VS 98.83±27.99; p<0.001. However, a ratio of AST to ALT was decreased significantly (0.66±0.15 VS 0.94±0.21; p= 0.001) in acute viral hepatitis compared to that in control.Conclusion: Both the aminotransferases and bilirubin levels are raised significantly, where, a rise in ALT is greater than a rise in AST, hence, the ratio of AST to ALT is decreased significantly in acute viral hepatitis than that in control. Thus, this decreased pattern of AST to ALT can diagnose acute viral hepatitis at an early stage and can help appropriate care and treatment to the patients.

Neonatal and maternal factors associated with hepatic dysfunction after birth asphyxia

Background: Liver cell injury commonly occurs after perinatal asphyxia. This study aimed to identify the neonatal and maternal factors related to hepatic dysfunction associated with birth asphyxia. Methods: A case control study was carried out in Basra comprising 43 asphyxiated newborns, and 57 healthy full terms enrolled as control. Serum levels of liver enzymes [alanine transferase (ALT), aspartate transferase (AST), alkaline phosphatase (ALP)] were measured and compared between the study and control groups. Levels beyond +2SD above the mean of control considered high. Statistical analysis was done using SPSS program version 20. Chi-Square test and ANOVA were used where appropriate, P-value <0.05 was considered as significant. Elevated levels of enzymes were studied in relation to selected neonatal and maternal variables. Results: Higher levels of liver enzymes were found related to gestational age > 40 weeks, newborn’s body weight > 4 Kg, mother’s age>35 years, parity > 4 children and maternal medical disease. The results were statistically significant (P<0.05). However, no statistical differences were detected regarding newborn’s gender and growth status, maternal education and mode of delivery. Conclusion: The study highlights the relationship between maternal and neonatal risk factors and perinatal asphyxia associated with hepatic dysfunction.

Serum Lysyl Oxidase Levels and Lysyl Oxidase Gene Polymorphism in Ovarian Cancer Patients of Eastern Indian Population

(1) Background: Lysyl oxidase (LOX) plays a dual role in carcinogenesis and studies show a higher risk of cancer in LOX G473A variants. The present study evaluated the pattern of LOX G473A polymorphism (rs1800449) and serum LOX levels in ovarian cancer patients. (2) Methods: Serum LOX levels were estimated by enzyme linked immunosorbent assay (ELISA). A polymorphism of rs1800449 of LOX gene was detected by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Selected samples were sequenced for external validation. (3) Results: A majority of study participants were from low socio-economic status. Serum LOX level was significantly higher in ovarian cancer patients as compared to control. Serum LOX level in early-stage ovarian cancer was significantly lower as compared to advanced stage (FIGO stage III & IV). Wild type GG genotype was used as reference. Genotypes AA were associated with a significant risk of epithelial ovarian cancer (OR 3.208; p value- 0.033). A allele of rs1800449 polymorphism of LOX gene, the odds ratio was 1.866 (95% Confidence Interval 1.112–3.16) p value = 0.017 (4) Conclusions: A allele of rs1800449 polymorphism of LOX gene presents an increased risk of ovarian cancer in East Indian population. Serum LOX levels could be a potential biomarker for the diagnosis and prognosis of ovarian cancer.

Elevated IL-6 in Pre-Eclampsia Increases Neurite Growth and Mitochondrial Respiration in an in vitro Model of Neuronal Development

Pre-eclampsia (PE) is a common and serious hypertensive disorder of pregnancy, which affects 3-5% of first-time pregnancies and is a leading cause of maternal and neonatal morbidity and mortality. Prenatal exposure to PE is associated with an increased risk of neurodevelopmental disorders in affected offspring, although the cellular and molecular basis of this are largely unknown. In this study we examined the effects of exposure to maternal serum from women with PE or a healthy uncomplicated pregnancy on the survival, neurite growth and mitochondrial function of SH-SY5Y cells. We report that cells exposed to PE serum exhibited increased neurite growth and mitochondrial respiration, two important neurodevelopmental parameters, compared to those treated with control serum. Levels of the pleiotropic cytokine IL-6 were significantly elevated in the PE sera, and cells exposed to PE serum displayed increased phospho-STAT3 levels which is a key intracellular mediator of IL-6 signalling. Finally, we show that treating these cells with IL-6 alone is sufficient to induce a similar neurite growth and respiratory phenotype to PE serum-exposed cells. This suggests that elevated IL-6 seen in maternal serum in PE may be responsible at least in part for its inducing increased neurite growth and mitochondrial respiration in SH-SY5Y cells. Overall, this study demonstrates that there are circulating factors in the serum of women with pre-eclampsia that affect neuronal development and oxygen consumption differently to that of a healthy uncomplicated pregnancy, and that immune dysregulation via elevated IL-6 may be important in mediating these effects.

Bovine Serum as an Alternative to Control Serum for Total Protein Levels

Total protein describes the liver's ability to synthesize proteins and metabolize substances in the blood. Bovine serum can be used as a control material because the total protein analyte in bovine blood serum is almost identical to the analyte in human serum. The researchers intend to determine the homogeneity and stability of bovine serum with the addition of 7,5% ethylene glycol preservative after being stored for 12 weeks at -20°C as an alternative to control serum for total protein levels. This research used survey analytics using a one-group pretest-posttest research design. Data analysis used ISO 13528 2005 calculations. From the examination of the total protein level in the serum, the value of Xr – Yr = 0.23817, which is where the value meets the test criteria according to | Xr - Yr | <0.36, that is 0.23817 <0.91585. The total protein content of bovine serum was homogeneous and stable with the addition of 7.5% ethylene glycol stored at -20oC for 12 weeks.

How Much Obesity and Diabetes Do Impair Male Fertility?

BackgroundSubfertility in obese and diabetic men during the reproductive age is evident, but the mechanisms by which obesity and diabetes mellitus cause male infertility are not entirely understood. The current study aimed to evaluate the effects and potential mechanisms of obesity and diabetes on male fertilityMethodsWe enrolled control=40, obese=40, Lean-DM=35, and Obese-DM=35 individuals. The obesity-associated markers, diabetic markers, hormonal and lipid profile, inflammatory indices, and semen analysis were assessed in four experimental groups.ResultsOur finding showed that diabetic markers were significantly increased in two diabetic groups, while obesity indices were markedly increased in two obese groups. Conventional sperm parameters were significantly lower in three groups compared with the control. Serum levels of total testosterone and sex hormone-binding globulin were significantly lower in men with obesity and DM compared with the control. There was a significant difference in the concentration of high-sensitivity C-reactive protein among four experimental groups. Moreover, serum leptin was significantly increased in obese DM, lean DM, and obese groups. Serum insulin levels had a positive correlation with metabolic-associated indices and high-sensitivity C-reactive protein levels, whereas it had a negative correlation with count, motility, and morphology. ConclusionsOur findings showed the metabolic changes, hormonal dysfunction and inflammatory disturbance might be suspected mechanisms of subfertility in obese and diabetic subfertile men.

Biochemical profile of human infant cerebrospinal fluid in intraventricular hemorrhage and post-hemorrhagic hydrocephalus of prematurity

Background Intraventricular hemorrhage (IVH) and post-hemorrhagic hydrocephalus (PHH) have a complex pathophysiology involving inflammatory response, ventricular zone and cell–cell junction disruption, and choroid-plexus (ChP) hypersecretion. Increased cerebrospinal fluid (CSF) cytokines, extracellular matrix proteins, and blood metabolites have been noted in IVH/PHH, but osmolality and electrolyte disturbances have not been evaluated in human infants with these conditions. We hypothesized that CSF total protein, osmolality, electrolytes, and immune cells increase in PHH. Methods CSF samples were obtained from lumbar punctures of control infants and infants with IVH prior to the development of PHH and any neurosurgical intervention. Osmolality, total protein, and electrolytes were measured in 52 infants (18 controls, 10 low grade (LG) IVH, 13 high grade (HG) IVH, and 11 PHH). Serum electrolyte concentrations, and CSF and serum cell counts within 1-day of clinical sampling were obtained from clinical charts. Frontal occipital horn ratio (FOR) was measured for estimating the degree of ventriculomegaly. Dunn or Tukey’s post-test ANOVA analysis were used for pair-wise comparisons. Results CSF osmolality, sodium, potassium, and chloride were elevated in PHH compared to control (p = 0.012 − < 0.0001), LGIVH (p = 0.023 − < 0.0001), and HGIVH (p = 0.015 − 0.0003), while magnesium and calcium levels were higher compared to control (p = 0.031) and LGIVH (p = 0.041). CSF total protein was higher in both HGIVH and PHH compared to control (p = 0.0009 and 0.0006 respectively) and LGIVH (p = 0.034 and 0.028 respectively). These differences were not reflected in serum electrolyte concentrations nor calculated osmolality across the groups. However, quantitatively, CSF sodium and chloride contributed 86% of CSF osmolality change between control and PHH; and CSF osmolality positively correlated with CSF sodium (r, p = 0.55,0.0015), potassium (r, p = 0.51,0.0041), chloride (r, p = 0.60,0.0004), but not total protein across the entire patient cohort. CSF total cells (p = 0.012), total nucleated cells (p = 0.0005), and percent monocyte (p = 0.016) were elevated in PHH compared to control. Serum white blood cell count increased in PHH compared to control (p = 0.042) but there were no differences in serum cell differential across groups. CSF total nucleated cells also positively correlated with CSF osmolality, sodium, potassium, and total protein (p = 0.025 − 0.0008) in the whole cohort. Conclusions CSF osmolality increased in PHH, largely driven by electrolyte changes rather than protein levels. However, serum electrolytes levels were unchanged across groups. CSF osmolality and electrolyte changes were correlated with CSF total nucleated cells which were also increased in PHH, further suggesting PHH is a neuro-inflammatory condition.

Pathological manifestation of human endogenous retrovirus K in frontotemporal dementia

Background Behavioral variant frontotemporal dementia (bvFTD) is a common form of younger-onset dementia with a proportion of cases overlapping pathologically and genetically with amyotrophic lateral sclerosis (ALS). Previous studies have identified that the human endogenous retrovirus K (HERV-K) is elevated in ALS serum and is associated with ALS TDP-43 pathology. In contrast, little is known about HERV-K changes in bvFTD. Here, we investigated the possible role of HERV-K in bvFTD. Methods We measured the HERV-K env gene in sporadic bvFTD (N = 63), sporadic ALS (N = 89), and control (N = 21) serum by ddPCR. We also analyzed HERV-K env, by qPCR, and the HERV-K reverse transcriptase protein, by confocal immunofluorescence microscopy, in the disease-affected superior frontal cortex of bvFTD with TDP-43 pathology. Results Here, we show that HERV-K env levels are significantly elevated (P = 3.5 × 10−6) in bvFTD compared to control serum, differentiating cases with an AUC value of 0.867. HERV-K env levels are also specifically elevated in the superior frontal cortex of bvFTD with TDP-43 pathology, with the HERV-K reverse transcriptase protein and TDP-43 deposit localized to the neuronal cytoplasm. Furthermore, in a neuronal cell line overexpression of TDP-43 induces HERV-K env transcription. Conclusions These results suggest that manifestation of HERV-K is associated with bvFTD TDP-43 pathology. Analysis of HERV-K in bvFTD may provide insight into an unrecognized but targetable perturbed pathology.

Intraperitoneal exposure of iron oxide nanoparticles causes dose-dependent toxicity in Wistar rats

Nanoparticles of iron oxide, with diameters beteween 1 to 100 nm, have notable implications for human health and well being. In the current study, we have investigated the effects of iron oxide nanoparticles (IONP) exposure on general physiology and health of adult Wistar rats. IONP used in the study had spherical shape and average size in the range of 15–20 nm. A total of eight groups of rats were repeatedly injected with 0 (control), 20, 40, and 80 mg IONP per kg body weight intraperitoneally under two different exposure schemes (sub-acute and sub-chronic). IONP exposure caused significant changes in lungs, liver, and kidney indices in both exposure schemes. Sub-acute exposure did not affect body weight gain in treated rats, but longer duration exposure was responsible for significant reduction in body weight. Mesenteries, visceral fatty tissues, and visceral peritoneal membranes demonstrated apparent accumulations of IONP in a dose and time-dependent manner. Hematological analysis showed that total RBC count, hemoglobin content, hematocrit, mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and mean platelet volume (MPV) were not affected by IONP exposure. Total lymphocyte count, however, was elevated in low- and mid-dose treated rats, but not in high-dose group. Serum lactate dehydrogenase (LDH) increased significantly in rats treated with mid and high doses as compared to control. Serum creatinine and blood urea nitrogen levels were also significantly altered in treated rats. Histological study found significant hepatic damage and mild spleen toxicity. Our report suggests that IONP exhibit significant toxicity in rats.