Effectiveness of early pharmaceutical interventions in symptomatic COVID-19 patients: A randomized clinical trial.

Objective: We assessed the effectiveness of oral Hydroxychloroquine (HC), Azithromycin (AZ) and Oseltamivir (OS), alone or combined, among patients hospitalized with mildly symptomatic coronavirus infectious disease (COVID-19). Methods: Following the approval of the National Bioethics Committee and prospective registration (clinicaltrials.gov NCT04338698), a multicenter randomized clinical trial of adaptive design was conducted at 10 multispecialty hospitals in Pakistan. Patients were randomized into seven treatment groups. Starting April 15, 2020, consenting, eligible, otherwise healthy adult patients or those with co-morbidities under control, were recruited if they presented with mildly symptomatic COVID-19 (scored 3 on a 7-point ordinal scale anchored between 1 = not hospitalized, able to undertake normal activities, to 7 = death) confirmed by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Two primary outcomes were assessed by day seven: Turning qRT-PCR negative; and clinical improvement of two points from the baseline. Outcome rates were compared using a chi-square test. Multiple imputations were applied to handle missing data. An interim data analysis was carried out on July 19, 2020, following which the study continued without treatment group changes. Data Safety and Monitoring Board advised to stop recruitment due to its futility on January 18, 2021. Results: Of 471 patients randomized, a total of 426 (90.4%) completed the follow-up for primary outcomes. Based on imputed data analyses at day seven: Total qRT-PCR negative cases were 137/471 (29%, 95% CI 25.0 - 33.4). By day seven, a total of 111/471 (23.5%, 95% CI 19.8 - 27.6) showed clinical improvement. No serious or non-serious adverse event was reported. Conclusions: Among patients with mild COVID-19, there was no statistically significant difference in the effectiveness of oral antimalarial, antiviral, or antibiotic treatments.Clinicaltrials.gov ID: NCT04338698.

Immunomodulatory effect of glabridin in ovalbumin induced allergic asthma and its comparison with methylprednisolone in a preclinical rodent model.

Glabridin, a polyphenolic flavonoid derived from Glycyrrhiza glabra (licorice) roots, has shown anti-inflammatory and antioxidant properties. The current study sought to investigate glabridin's immunomodulatory effect in ovalbumin induced allergic asthma. Healthy male Wistar rats were divided into five groups. Group I served as a control group. Asthma was induced in groups II- IV. Groups III and IV were treated with glabridin (40 mg/kg) and methylprednisolone (15 mg/kg), respectively. Inflammatory cells counts were determined in blood and bronchoalveolar lavage fluid (BALF). Serum IgE levels and levels of catalase, superoxide dismutase and glutathione peroxidase in lung homogenate were measured. The levels of mRNA expression of pro-inflammatory, anti-inflammatory and oxidative stress markers were analysed. Delayed type hypersensitivity (DTH) and acute toxicity of glabridin were also checked. Glabridin significantly decreased inflammatory cells in the blood and BALF. It increased the concentration of antioxidant enzymes catalase, superoxide dismutase and glutathione peroxidase. Glabridin markedly decreased serum IgE levels and DTH when compared to asthmatic rats. It significantly alleviated the expression of TNF-α, IL-4, IL-5, CXCL1, iNOS, and NF-κB. Administering 10 times the therapeutic dose of glabridin did not show any signs of acute toxicity. Findings suggest that glabridin has the potential to ameliorate allergic asthma and its effects are comparable to those of methylprednisolone. The immunomodulatory effect of glabridin might be contributed by the suppression of pro-inflammatory cytokines, oxidative stress markers, IgE antibodies, and elevation of antioxidant enzymes, suggesting future study and clinical trials to propose it as a candidate to treat allergic asthma.

Human immunodeficiency virus: The potential of medicinal plants as antiretroviral therapy.

Human immunodeficiency virus (HIV) infection is fast becoming widespread in the world with 37.7 million people living with HIV in 2020. Antiretroviral therapy involving chemical drugs has declined acquired immunodeficiency syndrome (AIDS)-related mortality and improved the life quality of AIDS/HIV sufferers. However, the emergence of drug resistance and side effects are the main obstacles for the long-term use of these chemicals as antiretroviral therapy. Recently, a lot of emphasis is being put on finding naturally occurring drug candidates that show activity against HIV and can be potentially used as antiretroviral therapy. In this study, different medicinal plants, Pistacia khinjuk, Teucrium stocksianum, Uncaria tomentosa, Pistacia integerrima, Trigonella gharuensis, and Artocarpus lakoocha, were explored for their anti-HIV potential. Syncytium and p24 assays were performed to determine antiviral activity, while the MTT assay was used to determine cytotoxicity. Results showed that extracts from all six plants inhibited HIV replication in vitro. Also, extracts from Pistacia khinjuk, Teucrium stocksianum, Uncaria tomentosa, and Pistacia integerrima showed low cytotoxicity with a 50% cytotoxicity concentration value of >200 µM. Results of this study indicate that there is potential in these natural extracts to become candidate drugs to be used as complementary and alternative medicine for HIV infection.

Investigations of Silymarine Effects on Prognosis of Patients With Severe and Moderate Traumatic Brain Injury.

OBJECTIVE: The purpose of this study was to evaluate Silymarine effects on prognosis of patients with severe and moderate traumatic brain injury. STUDY DESIGN: This double blind, placebo-controlled clinical trial. SETTING: Valiasr hospital hospital in Arak, Iran. SUBJECTS AND METHODS: Research was performed among patients between 15 and 65 years of age with severe moderate (Glasgow Coma Scale score 9 to 12) and moderate (GCS 3 to 8) traumatic brain injury (TBI). Patients were divided into two groups (Each group: 40 patients). Patients assigned to the control groupwere receiving all standard treatments. Patients in case groups were administered 140 mg of silymarin every 8 hours for 7 days. We Checked the Glasgow Outcome Scale (GOS), GCS, age, gender, location, mechanism of trauma, site of accident and the incidence time of accident to arrival at emergency unite. Statistical analysis was conducted using SPSS (SPSS version 18; Chicago, IL). RESULTS: Our findings suggested that there was no a significant difference between intervention group and control in terms of parameters as GOS, GCS, age, gender, location, mechanism of trauma, and site of accident and the incidence time of accident to arrival at emergency unite (P > .05). Brain CT in two groups showed a significant difference (P = .002), where in the silymarin group there were more normal cases when comparing with control group. CONCLUSIONS: Silymarin did not reveal a significant effect for improving prognosis of patients with moderate and severe TBI.

Investigation of Three Morchella Species for Anticancer Activity Against Colon Cancer Cell Lines by UPLC-MS-Based Chemical Analysis.

In search of new anticancer agents, natural products including fungal compounds had been used as potential anticancer agents. The aim of this study was to investigate the anticancer activity of Morchella extracts against colon cancer cell line and UPLC-DAD-MS/MS analysis for the identification of compounds. The cytotoxic activity of the three Morchella species was examined for their anti-carcinogenic properties against the colon cancer cell lines. Phytochemical analyses were performed to screen Morchella for the presence of anti-cancerous compounds. All the fungal extracts inhibited the viability of colon cancer cells in a dose-dependent manner. Major compounds identified in Morchella included amino acid, fatty acid, sterol, flavonoid, peptide, glutamic acid, alkaloid, terpenoid, cyclopyrrolones, and coumarin. Several new compounds were detected among all the three Morchella extracts. In conclusion, all the fungal extracts showed potential inhibition of colon cancer cells and actively arrested the cell viability. It was concluded that the identified bioactive compounds might be the main constituents contributing to the anticancer activity of Morchella against human colon cancer cell lines. Thus, Morchella extracts are a potential source of bioactive compounds with cytotoxicity and could potentially be used as functional food supplements. Due to the nature of impressive findings, this investigation should be undertaken further to allow the studies to explore and develop a potential cytotoxic agents against colon cancer.

Visual Perceptions Skills and its Association with Written Mathematical Communication Skills among Learning Disabilities Students in Jordan.

Aim: The present research sought at investigating the association between visual perception skills and written mathematical communication skills among a sample of students with learning disabilities in mathematics in Jordan. Method: This was a cross-sectional correlational study that included a sample of 90 primary-stage students who were diagnosed as having learning disabilities in mathematics. To collect data, the researchers developed two data collection tools; the visual perception skills test (50 items) and the written mathematical communication skills test (6 items). The tests were validated and ensured for reliability before implementation on the original study sample. The data gathered in this study was analyzed using the Statistical Package of Social Sciences (SPSS). Results: The results showed that there was a significant statistical association between visual discrimination and Written mathematical communication skills test (r=0.218), visual closing test and Written mathematical communication skills test (r=0.411), shape relationship perception test and Written mathematical communication skills test (r=0.438), Visual Integration and Spatial Relationship Perception Test and Written mathematical communication skills test (r=0.614), Visual information recall test and Written mathematical communication skills test (r=0.154). The results showed that there was a significant positive association between visual perception skills and written mathematical communication skills (r=0.509). Conclusion: The study ended up with that there is a significant positive association between visual perception skills and written mathematical communication skills among students with learning disabilities in mathematics. The study recommends developing mathematical educational material based on the visual approach and improving these skills among students with learning disabilities to develop their written mathematical communication skills.

Revolutionalizing the age old conventional treatment of psoriasis: An animal based comparative study between methylprednisolone and different doses of a novel anti-oxidant humanin analogue (HNG).

BACKGROUND AND OBJECTIVE: Psoriasis is a chronic skin disease with 2-4% of prevalence worldwide conferring a major burden on health systems. It is assumed that the prevalence might increase due to climatic change and deterioration of protective ozone barrier. With the chances of increasing prevalence, newer and specific treatment options need to be explored. Skin is a constant target of oxidative stress owing to continuous exposure to ultraviolet radiations. Oxidative stress is considered to have a central role in dermatological diseases, including psoriasis. This study was designed to explore the role of Humanin analogue (S14-G HNG) as an important anti oxidant for psoriasis like condition in BALB/c mice as till date the commomly used drugs for this disease are corticosteroids which have a dissatisfactory adverse effect profile in terms of chronic use. METHODOLOGY: Imiquimod 5% was used to induce Psoriasis like condition in mice, and the role of HNG was assessed through the histological examination, protein expressions and markers of oxidative stress. Two doses (low and high) of HNG were used and results were compared with an established drug methylprednisolone. KEY RESULT: Significant improvement was seen on histology, PASI scoring, protein expression and oxidative stress by the use of intraperitoneal injections of S14-G HNG and the results were comparable to those obtained through peritoneal injections of methylprednisolone. CONCLUSION: S14G-HNG can be considered as a suitable option for treatment of Psoriasis after clinical trials and it might prove to have lesser side effects as compared to other drugs employed for the treatment of psoriasis being an innate anti oxidant and anti apoptotic compound.

Adsorptive stripping voltammetric determination of copper(II) ion using phenyl pyridyl ketoneoxime (PPKO).

A sensitive and selective procedure is presented for the voltammetric determination of copper(II) ion. The procedure involves an adsorptive accumulation of Cu2+-PPKO on a hanging mercury drop electrode, followed by a stripping voltammetric measurement of reduction current of adsorbed complex at about -0.30 V (vs. SCE). The optimum conditions for the analysis of copper(II) ion include pH (5.8-7.0), 60 microgM PPKO and an accumulation potential of -0.5 V (vs. SCE). The peak current is proportional to the concentration of copper over the range 0.3-76 ng mL(-1) with a detection limit of 0.01ng mL(-1) with an accumulation time of 60 s. The speciation of different forms of complex between copper(II) ion and PPKO, using the Best (Martell program), followed pH measurement were examined. The method was applied to the determination of copper(II) ion content in real samples successfully.

Monitoring iron status in end-stage renal disease patients on hemodialysis.

Body iron stores should be assessed regularly and accurately during erythropoietin (r-HuEPO) replacement therapy. To evaluate the accuracy of the current tests, transferrin saturation (TSAT) and serum ferritin levels, in assessing and monitoring body iron stores, we studied 24 regular hemodialysis patients (19 males, mean age 47+/-18 years, and mean duration on hemodialysis 15+/-13 months) on regular erythropoietin therapy over a 12 month period. Patients were classified as having normal, deficient, indeterminate, or overload status depending on the values of TSAT and serum ferritin. Using TSAT and serum ferritin, iron status could be determined in 16 (67%) patients only; 12 (50%) had adequate (or normal) iron status, 3 (12.5%) had iron deficiency, and one (4.2%) had iron overload. In the remaining 8 patients, iron status was indeterminate; six patients had high serum ferritin with low TSAT (functional iron deficiency), and two patients had high TSAT values and low serum ferritin. Serum ferritin alone had very low specificity in diagnosing iron overload. In conclusion, when used together, TSAT and serum ferritin have a low sensitivity for diagnosing the iron status of CKD patients on HD. When TSAT and serum ferritin values diverge, they become unreliable in guiding iron therapy, and this set of findings generally indicates functional iron deficiency. There is a clear need to use the newer indices, like reticulocyte hemoglobin concentration and percentage of hypochromic red cells, which are more sensitive. This is likely to make the diagnosis of iron status more accurate and may reduce the requirements and frequency of iron and r-HuEPO administration.

Post-transplant erythrocytosis: a disease with multifactorial etiology.

Post-transplant erythrocytosis (PTE) is defined as an increase in hematocrit greater than 51%. This phenomenon affects 5 to 17% of renal transplant patients within two years of transplantation. Its etiology is not clearly known, but several factors have been implicated in its pathogenesis. We report on a 50-year-old male, known to have autosomal dominant polycystic kidney disease, diabetes mellitus and hypertension for 20 years, who underwent a living unrelated donor transplantation. Three years following renal transplan-tation, he was noted to have high hemogloblin and hematocrit (18.3 gm%, 53.8%). This erythrocytosis persisted for nine months during which period he underwent multiple phlebotomies before undergoing spontaneous remission. He did not develop any compli-cations of erythrocytosis. Our patient had multiple factors to account for occurrence of PTE: diabetes mellitus, hypertension, mild allograft dysfunction, polycystic kidney disease and cyclosporin therapy. Our case suggests that multiple factors may be operative in a given patient leading to the development of PTE.

End-stage renal failure as a complication of acute tubulo-interstitial nephritis.

Acute tubulo-interstitial nephritis (ATIN) is an important cause of acute renal failure, where renal impairment tends to be variable but recovery is the rule. End-stage renal failure (ESRF) has been rarely reported as a complication of ATIN. We report here a case of idiopathic ATIN that resulted in severe acute renal failure. The patient developed ESRF, which required permanent renal replacement therapy.

Post-transplant erythrocytosis: a review of 47 renal transplant recipients.

Post-transplant erythrocytosis (PTE) is a well known phenomenon occurring in 5-17% of renal transplant recipients (RTR). In this retrospective study, we studied 47 RTR which included 39 males and eight females. They were divided into two groups according to the presence or absence of PTE, which was defined as a hematocrit of more than 51%. Nine of the 47 patients (19%) developed PTE all of whom were males. The mean age of patients with PTE was 44 +/- 9 years versus 40 +/-11 years for patients without PTE. The mean follow-up period was 113 +/- 26 months and 93 +/- 58 months for the PTE and non-PTE groups respectively. The mean period after transplant when PTE developed was 9.8 +/- 9 months and it lasted for 37 +/- 3 months. Thromboembolic complications in the form of lower limb deep vein thrombosis occurred in one patient. Most patients were treated with phlebotomies, and one received an angiotensin converting enzyme inhibitor. There were no apparent predisposing factors in any but one patient, who had autosomal dominant polycystic kidney disease and developed hydronephrosis of the transplanted kidney. This might have caused excessive production of erythropoietin resulting in PTE. The serum creatinine values were higher, although statistically insignificant in patients with PTE. Chronic rejection was more commonly seen in patients with PTE (44%) than those without PTE (11%). Our findings suggest that PTE is a benign condition affecting males more than females. It may have an association with chronic rejection. Most cases can be controlled using phlebotomy.

Hyperuricemia and gout in renal transplant recipients.

Hyperuricemia, unlike clinical gout, is extremely common in renal transplant patients. The high prevalence of hyperuricemia is related to prolonged exposure to cyclosporine rather than to its dose or serum concentration. Serum creatinine levels do not show significant correlation with hyperuricemia, behaving more like a surrogate marker for cyclosporine dose and trough level. The low incidence of gout in renal transplant patients, despite the hyperuricemia, may be related to the prolonged immunosuppression effect.