Association of Vitamin D Receptor Gene Polymorphism with Metabolic Syndrome and Type 2 Diabetes Mellitus in a Sample of Egyptian Patients: Submitted: Sep 28, 2018 Accepted: Dec 29, 2018 Published online: 18 Sept, 2019

Background. There are insufficient data on the association of vitamin D receptor (VDR) genes polymorphism and type 2 diabetes mellitus (type 2 DM), and various components of metabolic syndrome among Egyptian patients. The aim of the present study was to study the association of different SNPs of VDR genes  BsmI, ApaI, TaqI and FokI and components of metabolic syndrome and type 2 DM among cohort of Egyptian patients. Methods. The study is a case-control study. Patients included in the study were divided into three groups. Group 1 included 78 patients with type 2 DM; group 2 included 72 patients with metabolic syndrome and one hundred age-matched healthy subjects were served as control group. Full biochemical study and serum 25 hydroxy vitamin D (25(OH)D) were done. Purified DNA was subjected to study with polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) for genotyping of SNPs of VDR gene. Data were presented as mean and standard deviation, and were analysed as appropriate by using the one-way ANOVA or paired t-test. Pearson correlation coefficient was used to correlate between variables. Results. Study of VDR genetic polymorphism had shown significant increase in the prevalence of Ff genotypes among diabetic patients and patients with manifestations of metabolic syndrome. There was significant negative correlation between 25(OH)D and total cholesterol, triglyceride, fasting and post-prandial blood glucose levels, waist circumference and diastolic blood pressure. Conclusion. The genetic polymorphism of VDR might play a role in the pathophysiology of type 2 DM and metabolic syndrome., however, more longitudinal studies are still required to support these finding

Numerical investigation of a hybrid double layer microchannel heat sink with jet impingement

This study investigates numerically, with experimental verification, the performance of a hybrid multilayer microchannel heat sink with jet impingement. The three-dimensional fluid flow and heat transfer processes were solved using the finite volume method using Fluent CFD Solver. The surface temperature distribution and pressure drop across the system were monitored under a range of designs and operating conditions including different flow rates, channel aspect ratios, jet spacings, and distribution of the flow rate between the jets and the channels. Our results show that increasing the number of jets minimizes the pressure drop, yet, results in higher surface temperatures. Increasing channel height decreased the pressure drop and enhanced the temperature uniformity. Using a double-layer heat sink instead of a single-layer one resulted in a decrease of 7.5% in surface temperature with a considerable reduction in pressure drop. Nevertheless, adding copper fins/posts in the lower channel layer is essential to help conduct the heat to the top layer and improve the heat removal rate. We also studied dividing the total flow rate between the jets and the main cooling channel and found that it can reduce the average temperature on the hot surface even though it did not improve the temperature uniformity. We verified our simulation results with experimental measurement for a single-layer hybrid heat sink with jet impingement and results matched with a temperature difference below 5 °C. Based on our simulations, the DL-hybrid module can remove high heat fluxes while maintaining an acceptable pressure drop

Femoral Head and Neck Ostectomy (FHO) for Treatment of Different Hip Joint Disorders in Dogs

In this research, surgical treatment of hip dysplasia, hip luxation, femoral neck fracture, and degenerative hip joint disease were performed using femoral head and neck ostectomy (FHO). Twelve different breeds of male dogs weighing 14-52 kg suffering from different hip joint disorders were admitted to the Vet. Surgery clinic, Faculty of Vet. Med. Zagazig University and from some different private pet animal clinics. The admitted cases were diagnosed by clinical signs (visual pain assessment and lameness scoring), clinical crepitus exam, and plain radiography. The FHO technique applied in the affected cases revealed successful results with the absence of painful lameness noticed after 3 weeks postoperatively but nonpainful lameness was observed then decreased gradually till disappearance when muscles become stronger to compensate for the absence of the head of the femur with minimal complications. FHO is a very good salvage economic satisfactory technique with minimal complications. Using an oscillating saw and sharp osteotome is better than using of Gigli saw

HPLC/UV approach method for the first simultaneous estimation of molnupiravir and ertapenem as a binary mixture in human plasma and dosage form as a regimen for COVID-19 treatments

Abstract COVID-19 is a serious virus that can have a lot of effects, one of which is a secondary bacterial infection that can be more life-threatening and even lethal than the initial viral infection. Hence a fast and sensitive HPLC/UV method was developed and validated for the first estimation of a binary mixture of molnupiravir (MOL) and ertapenem (ERT) as a co-administrated medicine for the management of COVID-19 in pharmaceutical dosage forms, and human plasma samples. The drug combination was separated within 5 min via RP-ODS column using isocratic elution with a mobile phase of 0.05 M phosphate buffer (pH 3.5): acetonitrile with a 76: 24% ratio v/v. The presented method provided a linear response ranging from 0.03 to 17.0 and 0.05–20 µg mL−1 with LOD values of 0.009 and 0.008 µg mL−1 for MOL and ERT respectively. The good separation and high sensitivity of the HPLC method provide the determination of the cited drugs in human plasma without matrix interference with a percent of recovery ranging from 94.97 ± 2.05 to 98.44 ± 1.92. Based on the results, this method could be utilized to monitor cited drugs in quality control and therapeutic laboratories

DNA Ploidy and Liver Cell Dysplasia in Liver Biopsies from Patients with Liver Cirrhosis

There is controversy among pathologists when assessing the presence or absence of liver cell dysplasia in liver biopsies taken from cirrhotic patients. The objective of the present study was to determine the DNA ploidy pattern of hepatocytes of patients with liver cirrhosis and its relationship to liver cell dysplasia. A total of 48 male patients diagnosed with liver cirrhosis based on clinical, laboratory and histopathological criteria were included in the study. A liver biopsy was taken from each patient; one part of the biopsy was subjected to histopathology, and the other to flow cytometry. The histopathological examination revealed liver cell dysplasia in 60% of patients with liver cirrhosis (62% of them had large cell dysplasia [LCD] and 38% had small cell dysplasia [SCD]). Abnormal DNA content (aneuploidy) was found in 81.5% of positive liver cell dysplasia specimens and found only in 11.1% of negative liver cell dysplasia specimens, with a statistically significant difference (P0.05) in comparison with SCD. In conclusion, SCD (similar to LCD) is also associated with aneuploidy and elevated DNA index, and may carry the same risk for progression to hepatocellular carcinoma

Value of preoperative biliary drainage on postoperative outcome after pancreaticoduodenectomy: A case–control study

Background/Objective: The potential benefit of preoperative biliary drainage (PBD) on postoperative outcomes remains controversial. The aim of this study was to elucidate surgical outcomes of pancreaticoduodenectomy (PD) in patients with PBD and to show the impact of bilirubin level. Methods: We retrospectively studied all patients who underwent PD in our center between January 2003 and June 2015. Patients were divided into: Group A (PBD) and Group B (no PBD). The primary outcome was the rate of postoperative complication. Results: A total of 588 cases underwent PD. Group A included 314 (53.4%) patients while Group B included 274 (46.6%) patients. The overall incidence of complications and its severity were higher in Group A (p = 0.03 and p = 0.02). There was significant difference in the incidence of postoperative pancreatic fistula (p = 0.002), delayed gastric emptying (p = 0.005), biliary leakage (p = 0.04), abdominal collection (p = 0.04), and wound infection (p = 0.04) in Group A. The mean length of hospital stay was significantly longer in Group A than in Group B (12.86 ± 7.65 days vs. 11.05 ± 7.98 days, p = 0.01). No significant impact of preoperative bilirubin level on surgical outcome was detected. Conclusion: PBD before PD was associated with major postoperative complications and stent-related complications

Dapagliflozin, Liraglutide, and Their Combination Attenuate Diabetes Mellitus-Associated Hepato-Renal Injury—Insight into Oxidative Injury/Inflammation/Apoptosis Modulation

In this study, we aim to explore the beneficial therapeutic impacts of dapagliflozin (Dapa), a highly potent, reversible, and selective sodium–glucose cotransporter-2 inhibitor, and liraglutide (Lira), a glucagon-like peptide-1 (GLP-1) receptor agonist, as hypoglycaemic agents for the management of diabetes mellitus (DM), as well as their combination against DM-induced complications, including hepato-renal injury. Indeed, the progression of DM was found to be associated with significant hepatic and renal injury, as confirmed by the elevated biochemical indices of hepatic and renal functions, as well as histopathological examination. Dapa, Lira, and their combination effectively attenuated DM-induced hepatic and renal injury, as confirmed by the recovery of hepatic and renal functional biomarkers. The administration of both drugs significantly reduced the tissue contents of MDA and restored the contents of GSH and catalase activity. Moreover, NF-κB and TNF-α expression at the protein and gene levels was significantly reduced in the liver and the kidney. This was in parallel with the significant reduction in the caspase-3 content in the liver and the kidney, as well as suppressed cleaved caspase-3 expression in the hepatic and renal specimens, as confirmed by immune–histochemical analysis. Notably, the combined Dapa/Lira treatment demonstrated an additive superior hepato-renal protective impact compared with the use of either drug alone. Thus, it appears that Dapa and Lira, through the coordinated modulation of oxidative, inflammatory, and apoptotic signalling, confer a significant hepato-renal protective impact against DM-induced complications and tissue injury

Application of the Box–Behnken design for the production of soluble curcumin: Skimmed milk powder inclusion complex for improving the treatment of colorectal cancer

The main objective of this study was to develop a soluble product of the practically insoluble curcumin (CMN) to treat colorectal cancer more effectively than with pure CMN. To improve the solubility of CMN, various hydrophilic carriers of skimmed milk powder (SMP), polyvinylpyrrolidone (PVP), and mannitol (MNT) were utilized to prepare solid dispersion (SD) binary complexes. The prepared complexes were characterized in terms of their aqueous solubility and in vitro drug release and analyzed by Fourier transform infrared spectrophotometry, powder X-ray diffractometry, scanning electron microscopy, dynamic light scattering, and the novel dyeing test. Based on this characterization, the best SD complex was optimized using the Box–Behnken design (RSM-BBD). These results showed that the solubility of CMN was greatly improved in combination with SMP. The SD of CMN with SMP produced significantly improved solubility (0.646 ± 0.024 mg/ml) and dissolution (54.94 ± 3.21% at 5 min). Further, solid-state characterization revealed that the complex exhibited intermolecular inclusion of the drug and carrier. Also, the complex did not undergo any chemical modification owing to its amorphous form, and the novel dye test showed better coloring impact, indicating the solubility of CMN. The in vitro cytotoxicity of the complex showed that 50% inhibition (IC50) of SW480 and Caco-2 cells was achieved at a considerably lower concentration than that of pure CMN. Flow cytometry analysis confirmed that the cell cycle arrest was at G2/M phase (43.26% and 65.14%), and DNA fragmentation analysis investigation confirmed that the complex induced more DNA damage during apoptosis

Nano-Structured Lipid Carrier-Based Oral Glutathione Formulation Mediates Renoprotection against Cyclophosphamide-Induced Nephrotoxicity, and Improves Oral Bioavailability of Glutathione Confirmed through RP-HPLC Micellar Liquid Chromatography

The study aimed to develop a new glutathione (GSH) oral formulation to enhance the delivery of GSH and counter the nephrotoxicity of the anticancer drug, cyclophosphamide (CP). A nanostructured lipid carrier glutathione formulation (GSH-NLCs) composed of glutathione (500 mg), stearic and oleic acid (300 mg, each), and Tween® 80 (2%, w/v) was prepared through the emulsification-solvent-evaporation technique, which exhibited a 452.4 ± 33.19 nm spheroidal-sized particulate material with narrow particle size distributions, −38.5 ± 1.4 mV zeta potential, and an entrapment efficiency of 79.8 ± 1.9%. The GSH formulation was orally delivered, and biologically tested to ameliorate the CP-induced renal toxicity in a rat model. Detailed renal morphology, before and after the GSH-NLCs administration, including the histopathological examinations, confirmed the ameliorating effects of the prepared glutathione formulation together with its safe oral delivery. CP-induced oxidative stress, superoxide dismutase depletion, elevation of malondialdehyde levels, depletion of Bcl-2 concentration levels, and upregulated NF-KB levels were observed and were controlled within the recommended and near normal/control levels. Additionally, the inflammatory mediator marker, IL-1β, serum levels were marginally normalized by delivery of the GHS-NLCs formulation. Oral administration of the pure glutathione did not exhibit any ameliorating effects on the renal tissues, which suggested that the pure glutathione is reactive and is chemically transformed during the oral delivery, which affected its pharmacological action at the renal site. The protective effects of the GSH-NLCs formulation through its antioxidant and anti-inflammatory effects suggested its prominent role in containing CP-induced renal toxicity and renal tissue damage, together with the possibility of administrating higher doses of the anticancer drug, cyclophosphamide, to achieve higher and effective anticancer action in combination with the GSH-NLCs formulation

Antitumor Activity of Nitazoxanide against Colon Cancers: Molecular Docking and Experimental Studies Based on Wnt/β-Catenin Signaling Inhibition

In colon cancer, wingless (Wnt)/β-catenin signaling is frequently upregulated; however, the creation of a molecular therapeutic agent targeting this pathway is still under investigation. This research aimed to study how nitazoxanide can affect Wnt/β-catenin signaling in colon cancer cells (HCT-116) and a mouse colon cancer model. Our study included 2 experiments; the first was to test the cytotoxic activity of nitazoxanide in an in vitro study on a colon cancer cell line (HCT-116) versus normal colon cells (FHC) and to highlight the proapoptotic effect by MTT assay, flow cytometry and real-time polymerase chain reaction (RT-PCR). The second experiment tested the in vivo cytotoxic effect of nitazoxanide against 1,2-dimethylhydrazine (DMH) prompted cancer in mice. Mice were grouped as saline, DMH control and DMH + nitazoxanide [100 or 200 mg per kg]. Colon levels of Wnt and β-catenin proteins were assessed by Western blotting while proliferation was measured via immunostaining for proliferating cell nuclear antigen (PCNA). Treating HCT-116 cells with nitazoxanide (inhibitory concentration 50 (IC50) = 11.07 µM) revealed that it has a more cytotoxic effect when compared to 5-flurouracil (IC50 = 11.36 µM). Moreover, it showed relatively high IC50 value (non-cytotoxic) against the normal colon cells. Nitazoxanide induced apoptosis by 15.86-fold compared to control and arrested the cell cycle. Furthermore, nitazoxanide upregulated proapoptotic proteins (P53 and BAX) and caspases but downregulated BCL-2. Nitazoxanide downregulated Wnt/β-catenin/glycogen synthase kinase-3β (GSK-3β) signaling and PCNA staining in the current mouse model. Hence, our findings highlighted the cytotoxic effect of nitazoxanide and pointed out the effect on Wnt/β-catenin/GSK-3β signaling