A review study of Antibiotics with Antiviral and Anti-inflammatory Potential against Covid-19

In Covid-19 cases, elderly patients in long-term care facilities, children younger than five years with moderate symptoms, and patients admitted to ICU or with comorbidities are at a high risk of coinfection due to evidence. Thus, in these patients, antibiotic therapy based on empirical evidence is necessary. Finding appropriate antimicrobial agents, especially with antiviral and anti-inflammatory properties, is a promising approach to target the virus and its complications, hyper-inflammation, and microorganisms resulting co-infection. Moreover, indiscriminate use of antibiotics can be accompanied by Clostridioides difficile colitis, the emergence of resistant microorganisms, and adverse drug reactions, particularly kidney damage and QT prolongation. Therefore, rational administration of efficient antibiotics is an important issue. The main objective of the present review is to provide a summary of antibiotics with possible antiviral activity against SARS-CoV-2 and anti-immunomodulatory effects to guide scientists for further research. Besides, the findings can help health professionals in the rational prescription of antibiotics in Covid-19 patients with a high risk of coinfection.

Effect of Vitamin C supplements on respiratory tract infections: A systematic review and meta-analysis

Background: Respiratory tract infections are a primary cause of illness and mortality over the world. Objective: This study was aimed to investigate the effectiveness of vitamin C supplementation in preventing and treating respiratory tract infections. Methods: We used the Cochrane, PubMed, and MEDLINE Ovid databases to conduct our search. The inclusion criteria were placebo-controlled trials. Random effects meta-analyses were performed to measure the pooled effects of vitamin C supplementation on the incidence, severity, and duration of respiratory illness. Results: found ten studies that met our inclusion criteria out of a total of 2758.The pooled risk ratio (RR) of developing respiratory illness when taking vitamin C regularly across the study period was 0⸳94 (with a 95% confidence interval of 0⸳87 to 1⸳01) which found that supplementing with vitamin C lowers the occurrence of illness. This effect, however, was statistically insignificant (P= 0⸳09). This study showed that vitamin C supplementation had no consistent effect on the severity of respiratory illness (SMD 0⸳14, 95% CI -0⸳02 to 0⸳30: I2 = 22%, P=0⸳09). However, our study revealed that vitamin C group had a considerably shorter duration of respiratory infection (SMD -0⸳36, 95% CI -0⸳62 to -0⸳09, P = 0⸳01). Conclusion: Benefits of normal vitamin C supplementation for reducing the duration of respiratory tract illness were supported by our meta-analysis findings. Since few trials have examined the effects of therapeutic supplementation, further research is needed in this area.

Review of Clinical Equipoise: Examples from Oncology Trials

Background: The current standards that govern clinical research have been shaped over the years through many historical, social, and political events. The third principle of the Belmont report, Justice, guides the scientific community toward equal distribution of benefits and risks in research involving human subjects. Clinical equipoise is the status of genuine uncertainty by the investigator about the superiority of one treatment arm over the other. The term clinical equipoise was proposed to provide an ethical ground to conduct randomized controlled clinical trials. Objective: The objective of this review is to provide the reader with an overview about the emergence of the term equipoise and its utilization in randomized controlled trials. Methods: In the current review article, the major oncology clinical trials and relevant patents were reviewed for the application/utilization of clinical equipoise. Results: The concept of clinical equipoise has been challenged and different alternatives were proposed. Yet, these alternatives received numerous critiques and failed to fully replace equipoise. In addition, several patents related to anticancer agents tested in the described studies were examined. No specific reference was made as part of the patent to the status of clinical equipoise. Alternatively, a description of the study arms was provided. Conclusion: There is a need for revisiting the concept of equipoise and its suggested alternatives, for its ethical essence while addressing related challenges.

Perspective on the role of four beta-blockers in heart failure

Background: The current recommendations of the American College of Cardiology/American Heart Association and a previous Bayesian analysis clearly show a mortality benefit with the use of β- blockers in chronic HF, especially for bisoprolol, carvedilol, and sustained-release metoprolol succinate. Objective: The main objective was to report the evidence on the use of the afore-mentioned β-blockers in subjects with heart failure and to characterize the stages of heart failure in response to the four different β-blockers. Furthermore, it shed light on the patient’s satisfaction and improved quality of life using the afore-mentioned β-blockers in subjects with heart failure. Method: The current perspective presented the clinical outcomes, including hospitalization, morbidity, mortality, patient’s satisfaction, and quality of life, of four beta (β)-blockers, namely bisoprolol, carvedilol, metoprolol succinate, and nebivolol in different stages of heart failure. Results : The use of these three agents should be recommended for all stable subjects with current or previous symptoms of heart failure and heart failure with reduced ejection fraction unless there is any contraindication. The fore-mentioned β-blockers (bisoprolol, carvedilol, and metoprolol succinate) can be initiated early, even in stable and symptom-free (at rest) subjects with heart failure. β-blockers in heart failure should be commenced at small doses and then titrated upward as tolerated to achieve the desired clinical effects on heart rate and symptom control. Conclusion: Cardiologists should weigh the benefit-risk in subjects with heart failure and other co-existing cardiovascular problems such as atrial fibrillation and diabetes.

Drug Sensitivity Testing for Cancer Therapy, Technique Analysis and Trend

: The techniques and qualities of drug sensitivity testing (DST) for anticancer treatment grew rapidly in the past two decades worldwide. Much of DST progress came from advanced systems of technical versatility (faster, high-throughput, high-sensitive and smaller in tumor quantity). As the earliest drug selective system, biomedical knowledge and technical advances for DST are mutually supported. More importantly, many pharmacological controversies are resolved by these technical advances. With this technical stride, clinical landscape of DST was entering into a new phase (>500 samples per testing and extremely low quantity of tumor cells). As a forerunner of drug selection system, DST awaits new version that can adapt to complicated therapeutic situations and diverse tumor categories in the clinic. By upholding this goal of pathogenic and therapeutic diversity, DST could eventually cure more cancer patients by establishing high-quality drug selection systems. To smooth DST develop, it needs to increasingly understanding of cancer biology, pathology and pharmacology (cancer heterogeneity, plasticity, metastasis and drug resistance) with well-informative parameters before chemotherapy. In this Article, medicinal and technical insights into DST are especially highlighted.

Investigating Neuroprotective Potential of Berberine, Levetiracetam and Their Combination in The Management of Alzheimer’s Disease Utilizing Drug Repurposing Strategy.

Background: Alzheimer's disease (AD) is a neurodegenerative disease characterized by impairment of memory, disturbances in reasoning, planning, language and perception. Currently, there are only four drugs approved by US-FDA for AD; therefore, there is an extensive need for new drug development. The drug repositioning approach refers to the development of new uses for existing or abandoned pharmaceuticals. Several studies support the neuroprotective abilities of anti-oxidants resulting in neuronal protection against neurotoxins, suppression of oxidative stress and promotion of memory, learning and cognitive functions. Many natural polyphenols are being investigated as a potential therapeutic option for AD. Levetiracetam (LEV), a second-generation antiepileptic drug, is a new molecule that is clearly differentiated from conventional antiepileptic drugs by its pharmacologic properties. LEV also has been previously demonstrated to protect against oxidative stress-induced neurotoxicity in several models of seizures. Berberine (BBR) is an anti-inflammatory and anti-oxidant phytoconstituent. Objective: To study the therapeutic effect of berberine, levetiracetam and their physical mixture in lead acetate-induced neurotoxicity in Swiss albino mice for probable application in the management of Alzheimer's disease Methods: Neurotoxicity was induced in Swiss albino mice by lead acetate. Behavioural parameters, such as transfer latency time and percentage alternation, were studied using Morris water maze (MWM), Elevated plus-maze test (EPM) and Y- maze for the assessment of improvement in learning and memory. Concentrations of acetylcholinesterase, MDA and GSH in the brain were also estimated. Brain samples were subjected to histopathological studies. Results: Results revealed that the combination of BBR and LEV exhibited a significant neuroprotective effect by decreasing escape latency time and increasing time spent in the target quadrant in MWM. The combination also decreases transfer latency time in EPM and acetylcholinesterase levels in the brain as compared to standard donepezil. Reduced neuronal damage was also confirmed by the histopathological report. Conclusion: Leveteracitam, berberin and their combination resulted in the significant conservation of various behavioural, biochemical, enzymatic and anti-oxidant parameters that were evaluated. The neuroprotective effect of plain leveteracitam and berberin was significantly better than their combination. However, the anticipated synergism or additive effect was not observed with a combination of leveteracitam and berberin in lead acetate–induced neurotoxicity.

Direct-acting antivirals inducing HCV-RNA sustained suppression improve Xerophthalmia in HCV-infected patients

Background: Hepatitis C virus (HCV) infection represents a global problem, and it is related to both hepatic and extra-hepatic manifestations (e.g., xerophthalmia). New direct-acting antivirals (DAAs), IFN-free treatments, are commonly used to manage HCV infection. However, the impact of new DAAs on dry eyes (xerophthalmia) is lacking. In this study, we evaluated its incidence in HCV patients and the effect of DAAs on this manifestation. Methods: We performed an observational open-label non-randomized study in HCV patients from 01 April 2018 to 01 June 2020. Results : Patients who satisfied the inclusion criteria underwent clinical and laboratory evaluation, Schirmer's test, and Break-up time test. Enrolled patients were divided in two groups: Group 1: HCV patients with xerophthalmia: 24 patients (16 male and 8 female), HCV-RNA 2,685,813 ± 1,145,698; Group 2: HCV patients without xerophthalmia: 35 patients (19 male and 16 female), HCV-RNA 2,614,757 ± 2,820,433. The follow-ups (3 and 6 months after the enrollment) documented an improvement in both eyes’ manifestations and HCV-infection (HCV-RNA undetected). Conclusion: In conclusion, in this study, we reported that xerophthalmia could appear in HCV patients, and DAAs treatment reduces this manifestation without the development of adverse drug reactions.