Proposal of International Council for Harmonization (ICH) Guideline for the Approval of Biosimilars.

Objectives: Since the initial release of biosimilars 18 years ago, regulations for their licensing have changed considerably; however, there is no global consensus on these regulations. Establishing harmonized regulatory guidelines for the approval of biosimilars with support from the ICH, an independent, non-profit association under Swiss law, will significantly enhance the affordability of biological drugs. Methods: Regulatory guidelines from the Food and Drug Administration (FDA), European Medicines Agency (EMA), Medicines and Healthcare products Regulatory Agency (MHRA), and World Health Organization (WHO) were analyzed for historical changes and elements critical to the safety and efficacy of biosimilars. Results: Analysis of all EMA and FDA filings show that none of the animal testing and clinical efficacy testing failed because animals do not have the required receptors to initiate pharmacologic responses, and efficacy studies cannot be statistically powered to conclude any results. New analytical technologies will enable good biosimilarity determination, avoiding both tests. Conclusion: Scientifically based ICH guidelines that remove redundant studies will reduce development costs, improve safety, and allow global drug distribution based on single compliance. These guidelines are particularly necessary for emerging countries lacking the expertise and resources to evaluate biosimilar filings.

The myocardial and neuronal infectivity of SARS-CoV-2 and detrimental outcomes.

The epidemiological outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), alias COVID-19, began in Wuhan, Hubei, China, in late December and eventually turned into a pandemic that has led to over 3.71 million deaths and over 173 million infected cases worldwide. In addition to respiratory manifestations, COVID-19 patients with neurological and myocardial dysfunctions exhibit a higher risk of in-hospital mortality. The immune function tends to be affected by cardiovascular risk factors and is thus indirectly related to the prognosis of COVID-19 patients. Many neurological symptoms and manifestations have been reported in COVID-19 patients; however, detailed descriptions on the prevalence and characteristic features of these symptoms are restricted due to insufficient data. It is thus advisable for clinicians to be vigilant for both cardiovascular and neurological manifestations to detect them at an early stage to avoid inappropriate management of COVID-19 and to address the manifestations adequately. Patients with severe COVID-19 are notably more susceptible to developing cardiovascular and neurological complications than non-severe COVID-19 patients. This review focuses on the consequential outcomes of COVID-19 on cardiovascular and neuronal functions, including other influencing factors.

Interaction of procarbazine with calf thymus DNA-a biophysical and molecular docking study.

Interaction of procarbazine (PCZ) with calf thymus DNA was studied using biophysical and molecular docking studies. Procarbazine was to interact with DNA with a binding constant of 6.52 × 103  M-1 as calculated using ultraviolet-visible spectroscopy. To find out the binding mode, molecular docking was performed that predicted PCZ to interact with DNA through groove binding mode with binding affinity of -6.7 kcal/mole. To confirm the groove binding nature, different experiments were performed. Dye displacement assays confirmed the non-intercalative binding mode. Procarbazine displaced Hoechst dye from the minor groove of DNA while it was unable to displace intercalating dyes. There was no increase in the viscosity of DNA solution in presence of PCZ. Also, negligible change in the secondary structure of DNA was observed in presence of PCZ as evident by circular dichroism spectra. Procarbazine caused decrease in the melting temperature of DNA possibly because of decrease in the stability of DNA caused by groove binding interaction of PCZ with DNA.

Leishmaniasis in the middle East: incidence and epidemiology.

Leishmaniasis is a major health problem worldwide, with several countries reporting cases of leishmaniasis resulting in loss of human life or a lifelong stigma because of bodily scars. The Middle East is endemic for cutaneous leishmaniasis, with countries like Syria reporting very high incidence of the disease. Despite several countries establishing national control programs for containing the sandfly vector and treatment of infection, the disease continues to spread. In addition to the endemicity of the region for leishmaniasis, the Middle East has seen a great deal of human migration either for earning of livelihood or due to political upheaval in the region. These factors contribute to the spread and proliferation of the causative species Leishmania and its sandfly host. This review discusses the current epidemiological scenario in Iraq, Syria, Saudi Arabia, and Jordan, emphasizing the number of cases reported, vector species, Leishmania species, and treatment available. The data is primarily from WHO reports for each country and current and old literature.