Serum selenium status in Egyptians patients who had Graves' disease with and without ophthalmopathy.

Selenium is efficient in reducing the progression of active Graves' orbitopathy and improving life quality. The impact of mending relative deficiency of selenium on improving Graves' orbitopathy is not known, due to the lack of previous measurement of baseline levels of selenium. The study object was to determine whether serum selenium levels are lower in patients with Graves' ophthalmopathy (GO) disease in comparison with those without ophthalmopathy. This prospective case control study was conducted between 2019 and 2021 at the endocrine and ophthalmology clinics, Ain Shams University, Cairo. The study included a total of 75 subjects, 50 patients with Graves' disease (GD) and 25 subjects as a control group. Of the GD patients, 25 had Graves' orbitopathy. Serum selenium concentrations were measured in each group. The mean level of serum selenium was significantly lower in patients with Graves' orbitopathy (16.6 ± 7.5 ng/ml) than in patients with Graves' disease (42.9 ± 8.2 ng/ml) (p < 0.001). Mean selenium levels were reduced with increasing severity of GO, as selenium level was 30-55 ng/ml in GD, 21-28 ng/ml in mild GO, 18-22 ng/ml in moderate GO and 5-16 ng/ml in severe GO (p < 0.001). In conclusion, serum selenium levels were lower in GO patients compared with GD patients in an Egyptian population. Low selenium levels may be a risk factor for ophthalmopathy in Graves' disease patients.

The problem of pulmonary arterial hypertension in end-stage renal disease: can peritoneal dialysis be the solution.

BACKGROUND: Pulmonary arterial hypertension (PAH) in the setting of end-stage renal disease (ESRD) has important prognostic and therapeutic consequences. We estimated the prevalence of PAH among patients with ESRD treated with automated peritoneal dialysis (APD), investigated the effect of different variables and compared pulmonary artery pressure and cardiac function at the beginning and end of the study. METHODS: This is a 5-year study in which 31 ESRD patients on APD were recruited after fulfilling inclusion criteria. Blood samples were collected from all patients for the biochemical and hematological data at the beginning of the study and every month and at the study termination. Total body water (TBW) and extracellular water (ECW) were calculated using Watson's and Bird's calculation methods. All patients were followed-up at 3-month interval for cardiac evaluation. Logistic regression analysis was used to assess the relation between different variables and PAH. RESULTS: The mean age of the study population (n = 31) was 51.23 ± 15.24 years. PAH was found in 24.2% of the patients. Mean systolic pulmonary artery pressure (sPAP) and mean pulmonary artery pressure (mPAP) were significantly higher in the APD patients at study initiation than at the end of the study (40.75 + 10.61 vs 23.55 + 9.20 and 29.66 + 11.35 vs 18.24 + 6.75 mmHg respectively, p = 0.001). The median ejection fraction was significantly lower in patients with PAH at zero point than at study termination [31% (27-34) vs 50% (46-52), p = 0.002]. Hypervolemia decreased significantly at the end of study (p <  0.001) and correlated positively with the PAP (r = 0.371 and r = 0.369), p = 0.002). sPAP correlated with left ventricular mass index, hemoglobin level, and duration on APD. CONCLUSIONS: Long term APD (> 1 years) seemed to decrease pulmonary arterial pressure, right atrial pressure and improve left ventricular ejection fraction (LVEF). Risk factors for PAH in ESRD were hypervolemia, abnormal ECHO findings and low hemoglobin levels. Clinical and echocardiographic abnormalities and complications are not uncommon among ESRD patients with PAH. Identification of those patients on transthoracic echocardiography may warrant further attention to treatment with APD.

Microwave-Assisted Synthesis, Biological Activity Evaluation, Molecular Docking, and ADMET Studies of Some Novel Pyrrolo [2,3-b] Pyrrole Derivatives.

Novel pyrrolo [2,3-b] pyrrole derivatives were synthesized and their hypolipidemic activity was assessed in hyperlipidemic rats. The chemical structures of the new derivatives were confirmed through spectral analysis. Compounds 5 and 6 were revealed to be the most effective hypolipidemic agents, with considerable hypocholesterolemic and hypotriglyceridemic effects. They appear to be promising candidates for creating new powerful derivatives with anti-atherosclerotic and hypolipidemic properties. As for antimicrobial activity, some of the tested compounds showed moderate activity against Pseudomonas aeruginosa: compound 2 revealed an MIC value of 50 µg/mL, compared to 25 µg/mL for ciprofloxacin. Compound 3 showed good antimicrobial activity against Staphylococcus aureus, comparable to ciprofloxacin, and roughly half the activity of ampicillin, according to MIC values. Compound 2 has an MIC approximately 25% of that of clotrimazole against Candida albicans. Compound 2 also showed the highest antioxidant activity with 59% inhibition of radical scavenging activity. Additionally, the cytotoxic activity of these new derivatives 1-7 was investigated and most of them showed good anticancer activity against the three tested cell lines.

New cell cycle checkpoint pathways regulators with 2-Oxo-indoline scaffold as potential anticancer agents: Design, synthesis, biological activities and in silico studies.

3-Arylidene-2-oxo-indoline derivatives are at the heart of a wide range of clinically, medicinally and biologically important compounds among the 2-oxo-indolines. A number of 3-arylidene-2-oxo-indolines have been approved for clinical application. Accordingly, the current work describes the structural based design of 3-arylidene-2-oxindole derivatives through docking of their structures in the active site of CDK2 as one of the dominant enzyme checkpoints. Based on the docking studies a range of 3-arylidene-2-oxindole derivatives, 5(a-n) and 6(a-x), with variable substituents at positions 1 and 5 of the 2-oxindole as well as 3 and 4 of the aryl moieties were synthesized. These molecules exist in either E or Z diastereomer about the exocyclic double bond at position 3 of oxindole nucleus. Their structures were confirmed by spectral and elemental methods of analyses and the E/Z-configuration of the diastereomers was confirmed by 2D NOE analysis. In vitro cytotoxicity of these molecules was tested against four cancerous cell lines, namely, breast cancer cell line (MCF7), liver carcinoma cell line (HepG2), cervix carcinoma cell line (HeLa), colon cancer cell line (HCT116) in addition to the diploid human normal non-cancerous cell line (F180) using SRB and MTT assays. The tested molecules showed variable cytotoxic effects on the four cancer cell lines with pronounced selectivity compared to the normal one (F180) with no significant difference between E and Z diastereomers. Compounds 5a, 5b, 5e1, 5m, 6f and 6j were tested for the effect on the expression on CDK2, p53, caspase-3 and caspase-9 proteins, and revealed variable activities compared to the positive controls Sunitinib and Staurosporine. These molecules seem to have multiple cellular targets as they induced expression of p53 and caspases while inhibited that of CDK2. Apoptotic effect of compound 6j was further investigated using annexin V-FITC/PI dual staining assay and showed that cells treated with 6j have nearly 15 folds greater apoptotic effect than that of the control cells. Furthermore, inhibitory activity of compounds 5a, 5b, 5e1, 5m, 6f and 6j on CDK2 enzyme were tested and revealed that compound 6f, with the N-4-flourobenzyl- 2-oxindole and 3-p-chlorobenzylidene moieties, has a comparable inhibitory activity to the reference drug sunitinib.

Inversion kinetics of some E/Z 3-(benzylidene)-2-oxo-indoline derivatives and their in silico CDK2 docking studies.

The structure-based design of some CDK2 inhibitors with a 3-(benzylidene)indolin-2-one scaffold as potential anticancer agents was realized. Target compounds were obtained as E/Z mixtures and were resolved to corresponding E- and Z-diastereomers. In silico studies using MOE 2019.01 software revealed better docking on the targeted enzyme for the Z-diastereomer compared to the E-one. A time-dependent kinetic isomerization study was carried out for the inversion of E/Z diastereomers in DMSO-d6 at room temperature, and were found to obey the first order kinetic reactions. Furthermore, a determination of the kinetic inter-conversion rate order by graphical analysis method and calculation of the rate constant and half-life of this kinetic process were carried out. For the prediction of the stability of the diastereomer(s), a good multiple regression equation was generated between the reaction rates of isomerization and some QM parameters with significant p value.

Tidal peritoneal dialysis versus ultrafiltration in type 1 cardiorenal syndrome: A prospective randomized study.

BACKGROUND: Ultrafiltration is an alternative strategy to diuretic therapy for the treatment of patients with acute decompensated heart failure. Little is known about the efficacy and safety of peritoneal dialysis in patients with acute decompensated heart failure complicated by acute cardiorenal syndrome. METHODS: We randomly assigned a total of 88 patients with type 1 acute cardiorenal syndrome to a strategy of ultrafiltration therapy (44 patients) or tidal peritoneal dialysis (44 patients). The primary endpoint was the change from baseline in the serum creatinine level and left ventricular function represented as ejection fraction, as assessed 72 and 120 h after random assignment. Patients were followed for 90 days after discharge from the hospital. RESULTS: Ultrafiltration therapy was inferior to tidal peritoneal dialysis therapy with respect to the primary endpoint of the change in the serum creatinine levels at 72 and 120 h (p = 0.041) and ejection fraction at 72 and 120 h after enrollment (p = 0.044 and p = 0.032), owing to both an increase in the creatinine level in the ultrafiltration therapy group and a decrease in its level in the tidal peritoneal dialysis group. At 120 h, the mean change in the creatinine level was 1.4 ± 0.5 mg/dL in the ultrafiltration therapy group, as compared with 2.4 ± 1.3 mg/dL in the tidal peritoneal dialysis group (p = 0.023). At 72 and 120 h, there was a significant difference in weight loss between patients in the ultrafiltration therapy group and those in the tidal peritoneal dialysis group (p = 0.025). Net fluid loss was also greater in tidal peritoneal dialysis patients (p = 0.018). Adverse events were more observed in the ultrafiltration therapy group (p = 0.007). At 90 days post-discharge, tidal peritoneal dialysis patients had fewer rehospitalization for heart failure (14.3% vs 32.5%, p = 0.022). CONCLUSION: Tidal peritoneal dialysis is a safe and effective means for removing toxins and large quantities of excess fluid from patients with intractable heart failure. In patients with cardiorenal syndrome type 1, the use of tidal peritoneal dialysis was superior to ultrafiltration therapy for the preservation of renal function, improvement of cardiac function, and net fluid loss. Ultrafiltration therapy was associated with a higher rate of adverse events.

Effect of Metformin Therapy on Serum Fetuin Levels in Insulin Resistant Type 1 Diabetics.

INTRODUCTION: Insulin resistance may develop with Type 1 diabetes. Insulin resistance is currently recognized by the estimated glucose disposal rate. Serum fetuin has been accused as a risk factor for metabolic syndrome. AIM: To determine the relationship between the serum fetuin and insulin resistance in Type 1 diabetes subjects and the effect of short-term Metformin therapy on this relationship. METHODS: 40 T1DM male ≥ 18 years of age were screened for insulin resistance (defined using estimated glucose disposal rate). 20 subjects (Group I) were insulin resistant with a mean estimated glucose disposal rate of (7.15±0.37 mg/kg/min) while 20 subjects (Group II) were non-insulin resistant with a mean estimated glucose disposal rate of (9.08±0.42 mg/kg/min). Fasting blood sugar, 2 hours-post prandial blood sugar, HbA1c%, C-peptide, lipid profile, highly sensitive-C reactive protein, and serum fetuin were assessed. Group I were given 1gm Metformin twice daily for 3 months as an add-on to their insulin regimen. All anthropometric and laboratory parameters were reassessed at the end of the 3 months. RESULTS: Group I had a higher age, BMI and waist/hip ratio, FBS, PPBS, HbA1c%, TC, LDL-C, TG, Hs-CRP and serum fetuin (ρ ≤ 0.001), and a lower C-peptide (ρ=0.001). Fetuin showed a positive correlation with age, FBS, HbA1c%, and Hs-CRP. After Metformin therapy, FBS, PPB and HbA1c%, Hs- CRP and fetuin decreased (ρ≤0.001) while eGDR and insulin dose in units/kg increased (ρ <0.001). Correlation after Metformin therapy within Group I showed that eGDR was inversely related with FBS and PPBS and fetuin showed a positive correlation with Hs-CRP. CONCLUSION: Serum fetuin was elevated in insulin resistant T1DM, yet this was not associated with eGDR. Levels of fetuin-A and HsCRP decreased after Metformin therapy.

Successful Cost-Effective Prevention of Cytomegalovirus Disease in Kidney Transplant Recipients Using Low-Dose Valganciclovir.

OBJECTIVES: Low-dose valganciclovir prophylaxis is still under investigation in renal transplant procedures. Our aim was to assess the cost effectiveness of 450 mg versus 900 mg valganciclovir prophylaxis in kidney transplant recipients. MATERIALS AND METHODS: In this prospective trial, 201 kidney transplant patients were randomized (1:1) to receive 450 mg/d (group 1, n = 100) or 900 mg/d (group 2, n = 101) valganciclovir prophylaxis for the first 6 months after transplant. Patients were studied for incidence of cytomegalovirus disease, leucopenia episodes, rejection episodes, and graft outcomes along with associated costs over 1 year. Costs (in US dollars) of treatment of rejection were also analyzed. RESULTS: Demographic features of the studied groups were comparable. We found that the cost of cytomegalovirus care in group 1 patients was significantly lower (by 50% at 6 months; P < .001), with less leukopenia episodes (P = .04), lower doses of granulocyte colony-stimulating factor (by 30% at 6 months; P = .03), higher doses of mycophenolate mofetil (P = .04), and less rejection episodes (P = .01) compared with group 2. In group 2, there were more episodes of cytomegalovirus infection (P = .052) and BK virus nephropathy (P = .04). Graft and patient outcomes were satisfactory in both groups. CONCLUSIONS: Low-dose valganciclovir for cytomegalovirus prophylaxis after renal transplant is safer, effective and without breakthrough infection, and less costly than using the usual dose.

Recurrent Urinary Tract Infection Among Renal Transplant Recipients: Risk Factors and Long-Term Outcome.

OBJECTIVES: Urinary tract infection is the most common type of bacterial infection in kidney transplant procedures, with adverse effects on graft and patient survival. We aimed to evaluate the risk factors of recurrent urinary tract infection in renal transplant recipients and its impact on patient and graft survival. MATERIALS AND METHODS: In a cohort of 1019 patients who were transplanted between 2000 and 2010 at Hamed Al-Essa Organ Transplant Center in Kuwait, 86% developed at least 1 episode of urinary tract infection, with only 6.2% of patients having recurrent infections. We compared patients with recurrent urinary tract infections (group 1) with those who had no recurrence (group 2) regarding their risk factors. RESULTS: Patients in group 1 were significantly younger than those in group 2 (34.9 ± 23 vs 42.8 ± 16 y; P < .001), with female preponderance (P < .001). The percentage of patients with thymoglobulin induction (21.5%) was significantly higher in group 1. Patients with pretransplant urologic problems experienced significantly more recurrent urinary tract infections (P < .001). Hepatitis C infections were significantly more prevalent among group 1 (10.8% vs 3.8%; P = .008). Long-term graft outcome (functioning and failed) were 78.5% and 21.5% in group 1 versus 85.1% and 13.9% in group 2 (P = .18). Patient outcomes (living and deceased donors) were 98.4% and 1.6% in group 1 versus 95.7% and 4.3% in group 2 (P = .187). CONCLUSIONS: Adult females, thymoglobulin induction, pretransplant urologic problems, and hepatitis C infection were the risk factors of recurrent urinary tract infection among our renal transplant patients. However, recurrence did not adversely affect graft or patient survival.

Leveraging elevated temperature and particle size reduction to extract API from various tablet formulations.

Several sample preparation techniques were evaluated for extracting active pharmaceutical ingredient (API) from immediate release (IR) and controlled release (CR) tablet formulations. These techniques utilized either elevated temperature [e.g., accelerated solvent extraction (ASE) and microwave assisted extraction (MAE)] or particle size reduction [e.g., ball mill and homogenizer/Tablet Processing Workstation II (TPWII)]. Results were compared for equivalence to those obtained with the existing standard method for each formulation. For the CR formulations, sample preparation times were significantly reduced when using these techniques compared to the standard method. Advantages and limitations associated with each technique are discussed.

Development and validation of a dissolution test for a once-a-day combination tablet of immediate-release cetirizine dihydrochloride and extended-release pseudoephedrine hydrochloride.

A dissolution test for a once daily combination tablet containing 10 mg of cetirizine dihydrochloride (cetirizine HCl) for immediate release and 240 mg of pseudoephedrine hydrochloride (pseudoephedrine HCl) for extended release was developed and validated according to current ICH and FDA guidelines. The cetirizine HCl is contained within an outer layer of the tablet while a semipermeable membrane of cellulose acetate and polyethylene glycol controls the rate at which pseudoephedrine HCl is released from the tablet core. The dissolution method, which uses USP apparatus 2 with paddles rotating at 50 rpm, 1000 ml of deaerated water as the dissolution medium, and reversed-phased HPLC for quantitation, was demonstrated to be robust, discriminating, and transferable. These test conditions were selected after it was demonstrated that the cetirizine HCl portion of the tablet rapidly dissolved in aqueous media over the physiologically relevant pH range of 1.1-7.5, and that the extended-release profile of pseudoephedrine HCl was independent of dissolution conditions (i.e., apparatus, pH, and agitation).