Hanan Hassan Fouad

SAP97 is a member of the MAGUK family of proteins, but unlike other MAGUK proteins that are selectively expressed in the CNS, SAP97 is also expressed in peripheral organs, like the heart and kidneys. SAP97 has several protein binding cassettes, and this review will describe their involvement in creating SAP97-anchored multiprotein networks. SAP97-anchored networks localized at the inner leaflet of the cell membrane play a major role in trafficking and targeting of membrane G protein-coupled receptors (GPCR), channels, and structural proteins. SAP97 plays a major role in compartmentalizing voltage gated sodium and potassium channels to specific cellular compartments of heart cells. SAP97 undergoes extensive alternative splicing. These splice variants give rise to different SAP97 isoforms that alter its cellular localization, networking, signaling and trafficking effects. Regarding GPCR, SAP97 binds to the β-adrenergic receptor and recruits AKAP5/PKA and PDE4D8 to create a multiprotein complex that regulates trafficking and signaling of cardiac β-AR. In the kidneys, SAP97 anchored networks played a role in trafficking of aquaporin-2 water channels. Cardiac specific ablation of SAP97 (SAP97-cKO) resulted in cardiac hypertrophy and failure in aging mice. Similarly, instituting transverse aortic constriction (TAC) in young SAP97 c-KO mice exacerbated TAC-induced cardiac remodeling and dysfunction. These findings highlight a critical role for SAP97 in the pathophysiology of a number of cardiac and renal diseases, suggesting that SAP97 is a relevant target for drug discovery.

Daclatasvir dihydrochloride (DAC) is a drug used to treat hepatitis C virus (HCV) infection. In this study, an ionophore-based nanosphere emulsion was made of tricresyl phosphate (TCP) as the oil phase that is dispersed in water using Pluronic F-127 as an emulsifying agent. The nanospheres, consisting of the oil phase TCP, were doped with sodium tetraphenyl borate (Na-TPB) as a cation-exchanger and dibenzo-18-Crown-6 (DB18C6) as an ionophore (chelating agent) for DAC. The nanosphere emulsion was employed as a titrant in the complexometric titration of DAC (the analyte), and the DAC-selective electrode (ISE) was used as an indicator electrode to detect the endpoint. In the sample solution, DAC2+ ions diffused into the emulsified nanospheres, replaced Na+ from the ion exchanger (Na-TPB), and bonded to the ionophore (DB18C6). The DAC-selective nanospheres were successfully utilized to determine DAC in various samples, including standard solutions, commercial tablets (Daclavirocyrl®), serum, and urine. The method exhibited a linear dynamic range of 81.18 µg/mL to 81.18 pg/mL (10−4 to 10−10 M), achieved high recovery values ranging from 99.4% to 106.5%, and displayed excellent selectivity over similar interfering species (sofosbuvir and ledipasvir). The proposed method offers a new approach to determine the drug species (neutral, anionic, and cationic) without the requirement of water-soluble ligands or pH control.

BACKGROUND: Total knee arthroplasty (TKA) is the standard treatment for terminal knee osteoarthritis. Simultaneous bilateral total knee arthroplasty (STKA) can be a cost-effective and practical option for patients with degenerative joint disease affecting both knees. The purpose of this study was to assess complication rates and functional outcomes following simultaneous versus staged bilateral total knee replacement.

MATERIAL AND METHODS: Approximately 60 individuals who experienced debilitating knee osteoarthritis were enrolled in a prospective study with a randomized comparative design. Out of these, 30 patients underwent simultaneous total knee arthroplasty (STKA), while the remaining 30 individuals underwent two separate surgeries with a gap of 3-6 months between each procedure for both knees. After excluding 7 patients from both groups, a total of 53 patients were included in the study and followed up for at least 12 months.

RESULTS: Pre-operative demographic parameters were equated between both groups. The overall number of systemic complications was higher in the simultaneous group compared with the stagedone. Systemic complications were correlated with the elderly and high-risk populations. However, simultaneous procedures were safe in a low-risk group with shorter hospitalization and operative times.

CONCLUSIONS: 1. Simultaneous bilateral total knee arthroplasty (TKA) is considered safe and feasible mainly for younger individuals with ASA 1 or 2 health status. 2. Patients undergoing simultaneous bilateral TKA experience significantly reduced hospital stays. 3. The procedure may not be advisable for elderly patients at a higher risk of systemic complications.

BACKGROUND: Patients with diabetic kidney disease (DKD) are at increased risk to develop post-contrast acute kidney injury (AKI). Diabetic patients under dipeptidyl peptidase 4 inhibitors (DPP4Is) experience a lower propensity to develop AKI. We speculated that linagliptin as a single agent or in combination with allopurinol may reduce the incidence of post-contrast AKI in stage 3-5 chronic kidney disease (CKD) patients with underlying DKD.

METHODS: Out of 951 DKD patients eligible for this study, 800 accepted to sign informed consent. They were randomly allocated to 4 equal groups that received their prophylaxis for 2 days before and after radiocontrast. The first control group received N-acetyl cysteine and saline, the 2 received allopurinol, the 3 group received linagliptin, and the 4 received both allopurinol and linagliptin. Post-procedure follow-up for kidney functions was conducted for 2 weeks in all patients.

RESULTS: 20, 19, 14, and 8 patients developed post-contrast AKI in groups 1 through 4, respectively. Neither linagliptin nor allopurinol was superior to N-acetyl cysteine and saline alone. However, the combination of the two agents provided statistically significant renal protection: post-contrast AKI in group 4 was significantly lower than in groups 1 and 2 ( < 0.02 and <0.03, respectively). None of the post-contrast AKI cases required dialysis.

CONCLUSION: Linagliptin and allopurinol in combination may offer protection against post-contrast AKI in DKD exposed to radiocontrast. Further studies are needed to support this view.

TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT03470454.

High frequency of infection and the unknown mode of transmission prompted us to investigate -wild housefly relationship. causes chronic gastritis, peptic ulcers, and stomach cancer. persists in the gut of the experimentally infected houseflies. The existence of strains isolated from wild houseflies, on the other hand, has never been documented. In this study, 902 wild houseflies from different sites were identified as , then 60 flies were screened by traditional microbiological techniques and -specific gene. The antibiotic resistance (ART) was investigated phenotypically. Wild housefly gut bacterial isolates were further evaluated genotypically to have gene mutation related to clarithromycin resistance. To find efficient therapeutic alternatives, the potency of three plant extracts (garlic, ginger, and lemon) and the wasp, venom was evaluated against . The cytotoxic effect of the crude wasp venom, the most potent extract, against Vero and Colon cancer (Caco2) cell lines was investigated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. All isolates from houseflies were positive. The isolated bacteria have variable resistance to frequently used antibiotics in all isolates. Minimum inhibitory concentration values of 15.625 mg/mL for both ginger and lemon extracts, 7.8125 mg/mL for garlic extract, and 0.0313 mg/mL for wasp venom were recorded. Wasp venom has the most potent antibacterial activity compared with the four antibiotics that are currently used in therapies against . We conclude that wild houseflies can play a role in disseminating The housefly gut may be a suitable environment for the horizontal transfer of ART genes among its associated microbiome and Wasp venom proved its potential activity as a new and effective anti- drug for both therapeutic and preventative usage.