Effect of treatment of chronic hepatitis c virus patients with direct-acting anti-retroviral drugs on semen and hormonal parameters.

Objective: Hepatitis C virus (HCV) infection is known to influence the seminal and hormonal parameters of infected men. This study was performed to assess the effects of HCV clearance using direct-acting antiviral (DAA) agents on semen and hormonal parameters. Methods: A total of 50 patients with chronic HCV were enrolled, and conventional semen analysis was performed according to World Health Organization guidelines. Basal levels of total testosterone, free testosterone (FT), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), prolactin, and sex hormone-binding globulin (SHBG) were assessed before and 3 months after treatment with DAAs. Results: Following DAA treatment, statistically significant increases were observed in sperm motility and the proportion of grade A sperm. Additionally, the percentage of abnormal forms was significantly decreased after treatment (p=0.000). However, no significant differences were observed in semen volume, concentration, or total sperm count. Sex hormone analysis of patients after DAA treatment revealed significant increases in FT, LH, and FSH levels, along with significant decreases in SHBG, prolactin, and E2 levels. Conclusion: Following HCV clearance, we noted an improvement in sperm motility and an increase in the percentage of sperm with normal morphology. Treatment with DAAs was also associated with increased levels of FT and LH, along with decreased levels of SHBG, prolactin, and E2.

Remdesivir ameliorates ulcerative colitis-propelled cell inflammation and pyroptosis in acetic acid rats by restoring SIRT6/FoxC1 pathway.

INTRODUCTION: Ulcerative colitis (UC) is a primary culprit of inflammatory bowel disease that entails prompt and effective clinical intervention. Remdesivir (RDV), a broad-spectrum antiviral nucleotide, has been found to exert anti-inflammatory effects in experimental animals. AIM: This study investigates the prospective anti-inflammatory merit of RDV on an experimental model of UC. The role of SIRT6/FoxC1 in regulating colonic cell inflammation and pyroptosis is delineated. METHOD: Rats were challenged with a single intrarectal dose of acetic acid (AA) solution (2 ml; 4 % v/v) to induce colitis. RDV (20 mg/kg, ip) and sulfasalazine (100 mg/kg, po) were administered to rats 14 days before the injection of AA. RESULTS: Administration of RDV ameliorated colonic cell injury and loss as manifested by improvement of severe colon histopathological mutilation and macroscopic damage and disease activity index scores together with restoration of normal colon weight/length ratio. In addition, RDV alleviated colonic inflammatory reactions, thereby curtailing NF-κB activation and the inflammatory cytokines, TNF-α, IL-18, and IL-1ß. Mitigation of colonic oxidative stress and apoptotic reactions were also evident in the setting of RDV treatment. Mechanistically, RDV enhanced the anti-inflammatory cascade, SIRT6/FoxC1, together with curbing the pyroptotic signal, NLRP3/cleaved caspase-1/Gasdermin D-elicited colonic inflammatory cell death. CONCLUSION: This study reveals, for the first time, the anti-inflammatory effect of RDV against experimental UC. Augmenting SIRT6/FoxC1-mediated repression of colonic inflammation and pyroptosis might advocate the colo-protective potential of RDV.

Optimized scleroglucan production by Athelia rolfsii and in vitro Sclg-5-fluorouracil release investigations.

Scleroglucan is a notable member of the ß-glucan microbial polysaccharides with a long tradition of industrial and therapeutic use. The local strain, previously identified as Athelia rolfsii TEMG MH 236106 produced an appreciable amount of scleroglucan using glucose as a carbon source and yeast extract as a nitrogen source. Plackett-Burman design was employed to effectively screen critical medium composition, culture, and fermentation conditions. Athelia rolfsii TEMG MH 236106 produced the maximum amount of scleroglucan (18.12 g/L) with a 45.3 % glucose conversion. Out of the eleven variables, the most effective factors showing a high level of significance are as follows: glucose, yeast extract, citric acid, inoculum disc numbers, culture volume and incubation time. An update to maximize scleroglucan production in the central composite design for four parameters (glucose and yeast extract concentrations, disc number, medium volume and incubation time) with 31 runs was applied and the production of scleroglucan reached its maximum at 31.56 g/L with 78.9 % glucose conversion. Three models of Sclg-5-fluorouracil complexes have been employed to study in vitro drug release investigations. Hence, the Sclg-5-FU (5 and 10 mg/mL) models appeared to be the most suitable for drug administration due to their concentration and distribution within capsules.

Efficacy and safety of etrolizumab in treatment of moderate to severe ulcerative colitis: A systematic review and meta-analysis.

Background: Etrolizumab is a promising drug for treating moderate to severe ulcerative colitis. Aim: The aim of this study was to assess the efficacy and safety of etrolizumab for induction and maintenance of remission in moderate to severe ulcerative colitis. Methods: We searched the following databases: PUBMED, Web of Science, OVID, and SCOPUS from inception to January 15. Inclusion criteria were any phase 2 and 3 clinical trials that compared etrolizumab with a placebo in treating moderate to severe ulcerative colitis, excluding case reports, animal studies, phase 1 trials, and conference abstracts due to duplication. We used RevMan software (5.4) for the meta-analysis. Results: Five clinical trials were included in our meta-analysis. The total number of patients included in the study is 1248 patients, 860 patients in the etrolizumab group and 388 patients in the placebo group. In the induction phase, the pooled analyses showed a statistically significant association between etrolizumab and increased clinical remission, and endoscopic remission compared with placebo (risk ratio [RR] = 2.66, 95% confidence interval [CI] = 1.69-4.19, p < 0.0001), and (RR = 2.35, 95% CI = 1.52-3.65, p = 0.0001), respectively. In the maintenance phase, the pooled analyses showed a statistically significant association between etrolizumab and increased histologic remission and endoscopic remission (RR = 2.04, 95% CI = 1.40-2.98, p = 0.0002) and (RR = 1.92, 95% CI = 1.29-2.85, p = 0.001), respectively. No statistically significant difference was observed in adverse events between etrolizumab and placebo in the induction and maintenance phases. Conclusion: Our results show that etrolizumab is an effective and safe drug for the induction and maintenance of clinical remission in moderate to severe ulcerative colitis patients, as proved by histologic and endoscopic findings. Future randomized trials are still needed to compare etrolizumab to the other agents and further establish its value for the practice.

Exploring the Heart Failure Connection in Long COVID Patients: A Narrative Review.

In this narrative review, we explore the relationship between long COVID patients and their risk of developing heart failure (HF). Patients with long COVID face a heightened risk of HF, a critical cardiovascular complication linked to the prolonged effects of COVID-19. Clinical manifestations of long COVID-associated HF present diagnostic challenges, complicating patient management. Multidisciplinary care is essential to address these complexities effectively. We found that long COVID can result in various cardiovascular issues including HF. The current view is long COVID leads to HF by activating systemic inflammation by causing endothelial dysfunction, which leads to activation of the complement pathways, tissue factor pathways, and Von Willebrand factor; activation of all these factors leads to venous and arterial thrombosis, which could lead to clogging of blood vessel of the heart leading to cardiovascular complications. The association between long COVID and HF can be challenging despite being recognized as comorbidity because biomarkers are not dependable in determining whether a patient had HF before or after contracting COVID-19. Emerging therapeutic modalities offer hope for improving outcomes, but further research is needed to refine management strategies and mitigate long-term cardiovascular consequences of COVID-19.

A Rare Case of Congenital Left Ventricular Diverticulum With Apical Thrombus: Diagnostic Challenges and Management Insights.

A myocardial diverticulum is a rare congenital anomaly characterized by pouch-like protrusions within the myocardial wall, which can potentially lead to various cardiac complications. This case report describes a unique presentation of a left ventricular diverticulum (LVD) with an associated apical thrombus, highlighting the diagnostic and management challenges posed by this condition. A 58-year-old man presented to the emergency department with left arm weakness, wrist drop, and chest pain, initially raising concerns for a stroke. Diagnostic evaluations, including echocardiography and magnetic resonance imaging (MRI), revealed a small focal outpouching at the left ventricular apex, consistent with a congenital LVD containing a thrombus. This diagnosis was supported by the patient's historical imaging dating back to 2007, which had similarly identified this outpouching. The patient was managed with anticoagulation therapy, transitioning from heparin to warfarin, alongside standard cardiac care. This case underscores the importance of considering myocardial diverticulum in the differential diagnosis of patients presenting with cardiac symptoms that might initially suggest more common conditions, such as stroke. It also highlights the essential role of echocardiography and MRI in diagnosing and managing myocardial diverticula.

Quantification of the aromatase inhibitor letrozole and its carbinol metabolite in mouse plasma by UHPLC-MS/MS.

A liquid chromatography - electrospray ionization-mass spectrometry (LC-ESI-MS) method was developed for the quantification of letrozole, a third-generation aromatase inhibitor, and its main carbinol metabolite (CM) in support of murine pharmacokinetic studies. Using polarity switching, simultaneous ESI-MS measurement of letrozole and CM was achieved in positive and negative mode, respectively. The assay procedure involved a one-step protein precipitation and extraction of all analytes from mouse plasma requiring only 5 µL of sample. Separation was optimized on an Accucore aQ column with gradient elution at a flow rate of 0.4 mL/min in 5 min. Two calibration curves per day over four consecutive measurement days showed satisfactory linear responses (r2 > 0.99) over concentration ranges of 5-1000 ng/mL and 20-2000 ng/mL for letrozole and CM, respectively. No matrix effect was found, and the mean extraction recoveries were 103-108 % for letrozole and 99.8-107 % for CM. Precision and accuracy within a single run and over four consecutive measurement days were verified to be within acceptable limits. Application of the developed method to preclinical pharmacokinetic studies in mice receiving oral letrozole at a dose 1 or 10 mg/kg revealed that the systemic exposure to letrozole was dose-, formulation-, and strain-dependent. These findings may inform the future design of preclinical studies aimed at refining the pharmacological profile of this clinically important drug.

Spontaneous Coronary Artery Dissection: An Updated Comprehensive Review.

Spontaneous coronary artery dissection (SCAD) is defined as a non-iatrogenic, non-traumatic separation of the coronary artery wall, which has gained considerable recognition as an important cause of acute coronary syndrome. Despite the emerging evidence, it is still frequently missed and requires a high index of suspicion, as failure to accurately identify SCAD promptly could prove fatal. SCAD is most prevalent among middle-aged women, although it can also be found in men and postmenopausal women. Risk factors of SCAD include exogenous hormone use, physical and emotional stressors, pregnancy, and several inflammatory and connective tissue disorders. COVID-19 also contributes to the prevalence of SCAD. SCAD is classified into four main types based on the angiographic findings - type 1, type 2, type 3, and type 4. The gold standard for diagnosis is coronary angiography; however, intracardiac imaging is useful if diagnostic doubts persist. Despite the increasing recognition of this disease, there is a paucity in the guidelines on the management of SCAD. Management may be conservative, medical, or interventional. Cardiac rehabilitation is also necessary in the management of patients with SCAD. In light of the gaps in evidence, the authors aim to provide a comprehensive review of the existing literature, outlining the pathophysiology, classification, and, most importantly, the evidence and pitfalls circulating diagnosis, acute, and long-term management of SCAD.

The impacts of dietary inclusion of soybean oil and linseed oil on growth performance, carcass yield, and health status of growing Japanese quail.

Polyunsaturated fatty acids (PUFA), including n-6 and n-3 fatty acids, are essential for enhancing the performance and health of poultry. Avian species lack desaturase enzymes for endogenous synthesis of n-6 and n-3 fatty acids. This work aimed to determine the impacts of including soybean oil (SO) and linseed oil (LO) in quail diets on growth, lipid profile, hepatic and renal functions, immunity, and antioxidant status. A total of 350 Japanese quail chicks (1-wk-old) were randomly arranged into 7 dietary treatment groups. Seven isocaloric and isonitrogenous experimental basal diets were formed based on the nutritional requirements of growing Japanese quail. Group 1, the control, received a basal with no oils, while groups 2 to 7 received a basal diet containing either 1% SO, 1.5% SO, 2% SO, 1% LO, 1.5% LO, or 2% LO, respectively. Quail groups that consumed diets containing LO at all levels showed significantly greater live body weight (LBW) at 5th wk of age than other experimental groups. The dietary incorporation of 1.5 or 2% SO or LO at all levels yielded significant improvements in body weight gain (BWG) and feed conversion ratio (FCR) through 3 to 5 and 1 to 5 wk of age. Different dietary oil sources and levels have no significant impacts on feed intake (FI) and carcass yield parameters. Lipid profile parameters were improved by adding SO and LO in quail diets, with LO having a higher effect than SO. The hepatic and renal functionality were improved by adding SO and LO in quail diets. The lowest uric acid (UA) bloodstream concentrations were recorded in the quail group fed a diet with 2% LO. Values of Gamma globulins (G-GLO) and immunoglobulins (G, M, and A) were increased by adding SO or LO to quail diets. Blood levels of MDA and TAC were improved significantly by including LO in quail diets. The activity of the superoxide dismutase (SOD) enzyme was significantly increased by adding SO or LO to quail diets. Generally, adding SO or LO to growing quail diets up to 2% could yield favorable effects on growth performance, blood lipids, hepatic and renal functions, immunity, and antioxidant status; however, LO seems to have better effects than SO.

Composition and antimicrobial activity of Rosmarinus officinalis L. and Artemisia monosperma L. leaf essential oils and methanolic extracts from plants grown in normal and saline habitats in Egypt.

The present work aimed to investigate the effect of salinity in natural habitats in Egypt on the main secondary metabolites of Rosmarinus officinalis L. and Artemisia monosperma L. plants compared to plants grown at normal conditions. Plants grown under salinity were collected from Egyptian Western Coastal region habitats irrigated with underground water. Results showed that salinity increased the essential oil percentage of R. officinalis L. by 52.7% and A. monosperma L by 0.29% in addition to the total phenolics and flavonoids content in dry leaves compared to control plants. GC/MS analysis of rosemary essential oils revealed that salinity decreased the amount of some major oil monoterpenes component as verbenone, with a slight effect on 1,8 cineole and increased Camphor, endo- Boreneol, and linalool in addition to the appearance of new specific components such as Chrysanthenone monoterpene ketone and Caryophyllene sesquiterpene, while, in the case of Artemisia, the GC/MS showed that Artemisia ketone, Camphor, ß -phellandrene monoterpenes andα-Bisabolol sesquiterpenewere the major oil components; salinity decreased Camphor and ß -phellandrene content and increased artemisia ketone and α-Bisabolol oil content. About 11 new oil constituents were detected such as ( +)-2-Bornanone and Sesquisabinene hydrate. Mineral ions (N, K+, Ca+2, P, and Mg+2) uptake by R. officinalis and A. monosperma decreased in plants grown under salinity, while Na content increased compared to corresponding controls. Results demonstrated that both plants could tolerate the high salinity level in natural Western Coastal region soil which promoted more production of valuable secondary metabolites. The antimicrobial effect of R. officinalis L. and A. monosperma L. leaf methanolic extracts, results showed that R. officinalis extracts had an inhibitory response against all tested gram-positive and negative bacteria, in addition to the yeast (Candida albicans), whereas there was no any inhibitory effect concerning A. monosperma L extract on the tested species.

Hexavalent chromium ion removal from wastewater using novel nanocomposite based on the impregnation of zero-valent iron nanoparticles into polyurethane foam.

In this study, we developed a novel nanocomposite, polyurethane foam impregnated with zero-valent iron nanoparticles (PU@nZVI), for the effective removal of chromium(VI) from various water sources. The characterization of nanocomposite (PU@nZVI) was performed by XRD, SEM-EDS, TEM and FT-IR techniques. Using the response surface methodology, we optimized the removal conditions, achieving an optimal pH of 2 and a dose of 0.5 g/L. The PU@nZVI demonstrated an excellent maximum adsorption capacity of 600.0 mg/g for Cr6+. The adsorption kinetics and isotherms were best described by the pseudo-second-order model and the Freundlich isotherm, respectively. Significantly, the nanocomposite removed 99.98% of Cr6+ from tap water, 96.81% from industrial effluent, and 94.57% from treated sewage wastewater. Furthermore, the PU@nZVI maintained its efficiency over five adsorption-desorption cycles, highlighting its reusability. These results suggest that the PU@nZVI nanocomposite is a highly efficient and sustainable option for chromium(VI) removal in water treatment applications.

Ramsay Hunt Syndrome Associated with Varicella-Zoster Virus Encephalitis in a Child.

Ramsay Hunt syndrome (RHS) is a triad of peri-auricular pain, ipsilateral facial nerve palsy and vesicular rash around the ear pinna. It is caused by reactivation of varicella-zoster virus (VZV) that lies dormant in the geniculate ganglia. It can be complicated by VZV encephalitis rarely. We report the case of an 8-year-old previously healthy boy who presented to a tertiary care hospital in Muscat, Oman in 2021 with fever, progressive left ear pain, vesicular rash around his ear pinna and left-sided facial nerve palsy. His course was complicated by VZV encephalitis where he was managed with intravenous (IV) acyclovir and IV corticosteroids. He improved significantly and was asymptomatic with a normal neurology examination at the 6-months follow-up.

Retrospective review of non-ST segment elevation acute coronary syndrome presenting to the emergency department of a major tertiary center in Saudi Arabia.

BACKGROUND: Acute coronary syndrome (ACS) comprises a spectrum of diseases ranging from unstable angina (UA), non-ST elevation myocardial infarction (non-STEMI) and ST elevation myocardial infarction (STEMI). Treatment of ACS without STEMI (NSTEMI-ACS) can vary, depending on the severity of presentation and multiple other factors. OBJECTIVE: Analyze the NSTEMI-ACS patients in our institution. DESIGN: Retrospective observational. SETTING: A tertiary care institution with accredited chest pain center. PATIENTS AND METHODS: The travel time from ED booking to the final disposition for patients presenting with chest pain was retrieved over a period of 6 months. The duration of each phase of management was measured with a view to identify the factors that influence their management and time from the ED to their final destination. The data was analyzed using descriptive statistics. MAIN OUTCOME MEASURES: Travel time from ED to final destination. SAMPLE SIZE: 300 patients. RESULTS: The majority of patients were males (64%) between 61 and 80 years of age (45%). The median disposition time (from ED booking to admission order by the cardiology team) was 5 hours and 19 minutes. Cardiology admissions took 10 hours and 20 minutes from ED booking to the inpatient bed. UA was diagnosed in 153 (51%) patients and non-STEMI in 52 (17%). Coronary catheterization was required in 79 (26%) patients, 24 (8%) had coronary artery bypass grafting (CABG) and 8 (3%) had both catheterization and CABG. CONCLUSION: The time from ED booking to final destination for NSTEMI-ACS patients is delayed due to multiple factors, which caused significant delays in overall management. Additional interventional steps can help improve the travel times, diagnosis, management and disposition of these patients. LIMITATIONS: Single center study done in a tertiary care center so the results from this study may not be extrapolated to other centers.

Synthesis, X-ray crystallography, computational investigation on quinoxaline derivatives as potent against adenosine receptor A2AAR.

Quinoxaline represents one of the most important classes of heterocyclic compounds, which have exhibited a wide range of biological activities and industrial importance in many different fields. In this regard, we have synthetized two new quinoxaline derivatives. Their structures were confirmed by single-crystal X-ray analysis. The compounds show potent activity against adenosine receptors A2AAR based on structural activity relationship studies. Further molecular docking, molecular dynamics, ADMET analysis, and DFT (density functional theory) calculations were performed to understand the titled compound's future drug candidacy. DFT computations confirmed the good stability of the synthesized compounds, as evidenced by the optimized molecular geometry, HOMO-LUMO energy gap, and intermolecular interactions. NBO analysis confirmed intermolecular interactions mediated by lone pair, bonding, and anti-bonding orbitals. All DFT findings were consistent with experimental results, indicating that the synthesized molecules are highly stable. These findings suggest that the synthesized compounds are promising candidates for further development as drugs for the treatment of A2AAR-related diseases.Communicated by Ramaswamy H. Sarma.

Impact of serum IL 10 on prediction of early allograft rejection in liver transplantation.

Tissue transplantation is the preferred treatment for end organ failure such as heart, lung, kidney, and liver. The immune system recognizes the transplant as non self if the donor and recipient are not genetically identical. Multiple cytokines are involved in this process; however, little is known about their predictive role in rejection. Interleukin 10 (IL-10) which exhibits anti-inflammatory activity could be used as early predictor of acute rejection. The current study intended to determine any potential relationship between acute allograft rejection and blood IL-10 levels in liver transplant (LT) recipients. This study included 45 patients with cirrhotic liver diseases planned for transplantation. Patients were followed up for 2 months and then divided into two groups: patients who developed early acute rejection and those who did not develop rejection (as controls). Of the study patients, 38 (84.4%) patients did not develop rejection and 7 (15.6%) patients developed rejection. The levels of IL-10 did not change during rejection of the LT. In conclusion, the findings of the current study indicated no relation of IL-10 levels during LT rejection.

Impact of Chlorella vulgaris, Nannochloropsis salina, and Arthrospira platensis as bio-stimulants on common bean plant growth, yield and antioxidant capacity.

The use of bio-stimulants in agriculture has emerged as a promising strategy to improve crop growth and yield. One type of bio-stimulant that has gained attention is microalgae extracts, which are known for their high metabolic activity, bioactive compounds, and ability to enhance plant growth and development. To investigate their effectiveness, a pot experiment was conducted at the Experimental Farm of Helwan University in Egypt during the 2022 season. The experiment aimed to evaluate the efficacy of Chlorella vulgaris, Nannochloropsis salina, and Arthrospira platensis (Spirulina platensis) extracts as bio-stimulants, applied through foliar spray at concentrations ranging from 0.25 to 2.0%, on common bean plants. Analysis of algal extract showed that . N. salina had the highest content of promotive growth hormones gibberellins (GA3) (74.85 ± 2.7mg100 g-1 d.wt). and auxins (IAA) (34.57 ± 2.7µg 100 g-1 d.wt.) compared to Chlorella and Arthrospira..The results revealed that the application of C. vulgaris, N. salina, and A. platensis extracts at concentrations up to 1.0% significantly improved various growth parameters, such as root, and shoot length, number of leaves and flowers per plant, leaf area, and total fresh and dry weight per plant. These extracts also positively affected yield attributes, including the number and fresh weight of pods per plant, seed index, seed yield per plant, and per feddan [a unit of land area]. Furthermore, the application of these extracts increased the chlorophyll content index with the maximum values of CCI (17.95. and 17.81%) was obtained at 0.50% N. salina, followed by 0.50% C.vulgaris. In addition to increase in the capacity of both non-enzymatic antioxidants [such as total antioxidant capacity, phenolics, and flavonoids] and enzymatic antioxidants [including catalase and ascorbic oxidase]. The most promising results were observed with the application of N. salina, and C. vulgaris extracts at a concentration of 0.5%. Additionally, the extracts significantly reduced the content of oxidative stress markers, such as malondialdehyde, percentage of electrolyte leakage, and hydrogen peroxide, in common bean plants compared to the control group. Contrarily, the measured parameters were reduced, while the levels of oxidative stress markers and some antioxidants including peroxidase, ascorbic peroxidase, superoxide dismutase, glutathione peroxidase, and glutathione transferase were increased by three algal extracts at a concentration of 2.0%, compared to control plants. Additionally, the application of these microalgae extracts improved the quality parameters, proximate composition, seed energy, and mineral contents of the harvested seeds, with the most significant positive impact was observed at 0.5% concentration of algal extract. These findings demonstrate the successful and safe utilization of extracts from C. vulgaris, N. salina, and A. platensis at concentrations up to 1.0% as bio-stimulants to enhance common bean yields and improve the nutritional quality of dried beans for consumers.

Synthesis and biological evaluation of new nicotinic acid derivatives as potential anti-inflammatory agents with enhanced gastric safety profile.

Two innovative series derived from nicotinic acid scaffold were synthesized and evaluated for their anti-inflammatory activity. Ibuprofen, celecoxib and indomethacin were used as standard drugs. All the newly synthesized compounds were in vitro screened for their anti-inflammatory activity adopting 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide dye (MTT), as well as Griess assays. The results showed that all compounds exhibited significant anti-inflammatory activity without affecting the viability of the macrophages compared to ibuprofen. In addition, compounds 4d, 4f, 4g, 4h and 5b exhibited the most potent nitrite inhibition activity and consequently superior anti-inflammatory activity with MTT results ranging between values 86.109 ± 0.51 to 119.084 ± 0.09. The most active compounds were subjected to evaluation of TNF-α, IL-6, iNOS and COX-2 levels in LPS/INF γ-stimulated RAW 264.7 macrophage cells in comparison to ibuprofen as a reference compound. The five compounds showed comparable inhibition potency of these inflammatory cytokines compared to ibuprofen. Same compounds were further in vivo evaluated for their anti-inflammatory activity via carrageenan induced arthritis in rats. Regarding the ulcerogenic profile, compound 4h showed mild infiltration of gastric mucosa superb to compound 5b displayed severe gastritis. Molecular docking of 4h and 5b in the COX-2 active site was performed to evaluate their preferential COX-2 inhibitory potency. The docking results were in accordance with the biological findings.

Vincristine Disposition and Neurotoxicity Are Unchanged in Humanized CYP3A5 Mice.

Previous studies have suggested that the incidence of vincristine-induced peripheral neuropathy (VIPN) is potentially linked with cytochrome P450 (CYP)3A5, a polymorphic enzyme that metabolizes vincristine in vitro, and with concurrent use of azole antifungals such as ketoconazole. The assumed mechanism for these interactions is through modulation of CYP3A-mediated metabolism, leading to decreased vincristine clearance and increased susceptibility to VIPN. Given the controversy surrounding the contribution of these mechanisms, we directly tested these hypotheses in genetically engineered mouse models with a deficiency of the entire murine Cyp3a locus [Cyp3a(-/-) mice] and in humanized transgenic animals with hepatic expression of functional and nonfunctional human CYP3A5 variants. Compared with wild-type mice, the systemic exposure to vincristine was increased by only 1.15-fold (95% confidence interval, 0.84-1.58) in Cyp3a(-/-) mice, suggesting that the clearance of vincristine in mice is largely independent of hepatic Cyp3a function. In line with these observations, we found that Cyp3a deficiency or pretreatment with the CYP3A inhibitors ketoconazole or nilotinib did not influence the severity and time course of VIPN and that exposure to vincristine was not substantially altered in humanized CYP3A5*3 mice or humanized CYP3A5*1 mice compared with Cyp3a(-/-) mice. Our study suggests that the contribution of CYP3A5-mediated metabolism to vincristine elimination and the associated drug-drug interaction potential is limited and that plasma levels of vincristine are unlikely to be strongly predictive of VIPN. SIGNIFICANCE STATEMENT: The current study suggests that CYP3A5 genotype status does not substantially influence vincristine disposition and neurotoxicity in translationally relevant murine models. These findings raise concerns about the causality of previously reported relationships between variant CYP3A5 genotypes or concomitant azole use with the incidence of vincristine neurotoxicity.

The possible role of nuclear factor erythroid-2-related factor 2 activators in the management of Covid-19.

COVID-19 is caused by a novel SARS-CoV-2 leading to pulmonary and extra-pulmonary manifestations due to oxidative stress (OS) development and hyperinflammation. COVID-19 is primarily asymptomatic though it may cause acute lung injury (ALI), acute respiratory distress syndrome (ARDS), systemic inflammation, and thrombotic events in severe cases. SARS-CoV-2-induced OS triggers the activation of different signaling pathways, which counterbalances this complication. One of these pathways is nuclear factor erythroid 2-related factor 2 (Nrf2), which induces a series of cellular interactions to mitigate SARS-CoV-2-mediated viral toxicity and OS-induced cellular injury. Nrf2 pathway inhibits the expression of pro-inflammatory cytokines and the development of cytokine storm in COVID-19. Therefore, Nrf2 activators may play an essential role in reducing SARS-CoV-2 infection-induced inflammation by suppressing NLRP3 inflammasome in COVID-19. Furthermore, Nrf2 activators can attenuate endothelial dysfunction (ED), renin-angiotensin system (RAS) dysregulation, immune thrombosis, and coagulopathy. Thus this mini-review tries to clarify the possible role of the Nrf2 activators in the management of COVID-19. Nrf2 activators could be an effective therapeutic strategy in the management of Covid-19. Preclinical and clinical studies are recommended in this regard.

Masson's Tumor as an Uncommon Cause of Neck Mass: A Case Presentation.

BACKGROUND: Masson's tumor, commonly referred to as intravascular papillary endothelial hyperplasia (IPEH), is an uncommon growth of endothelial cells within a vessel wall that is frequently assumed to indicate an abnormal resolution of thrombosis. IPEH is most typically found in the extremities however it is rare for IPEH to appear as a neck tumor. The issue with IPEH is that it could clinically, radiologically, and pathologically imitate some malignant neoplasms such as angiosarcomas creating a diagnostic challenge. CASE REPORT: We describe a 21-year-old male patient who presented with right anterolateral neck swelling for 12 months. Ultrasound revealed a 9.0 × 8.0 cm well-defined echogenic hyper-vascular lesion. The contrast computed tomography (CT) scan of the neck revealed an oval, well-defined subcutaneous mass, measuring 9 × 4.5 cm, situated over and separable from the right sternocleidomastoid muscle with no significant enhancement in the post-contract study. T1-weighted and T2-weighted MRI revealed a 10 × 9 × 7 cm well-defined subcutaneous lobulated lesion superficial to the sternocleidomastoid expanding upward to the Rt. side of the cheek and below to the suprasternal region, eliciting an intermediate signal in T1 and a heterogenous bright signal (mostly fluid) in T2 with low signal foci within the mass. The decision had been reached to entirely excise the lesion surgically with safety margins for histological evaluation. Histological examination indicated thrombosed variable-sized ectatic vascular spaces with papillary formations related to the thrombus, covered with a single layer of flat endothelium, and no features suggestive of malignancy. There was no recurrence at 18 months follow-up post-surgery. CONCLUSION: Masson's tumor is a benign intravascular disease with an unclear origin and no confirmed inheritance pattern. Presentation of Masson's tumor as a neck mass is incredibly uncommon. Masson's tumor lacks a distinct or distinguishing clinical and radiological appearance. Histopathologic examination is the sole definitive way for diagnosing the disease and the only tool for distinguishing it from angiosarcoma. Surgical excision is the best treatment for IPEH. Recurrence is extremely rare.