Evaluation of immune response and haematological parameters in infected male albino rats by giardiasis.

The present work aimed to study the effects of Giardia lamblia infection on immunological and haematological studies and to evaluate immunoglobulins and some cytokines. Fifty male albino rats were divided into six groups. The control group includes 20 rats and the infected group includes 30 rats. All the estimations were checked all over five checkpoints (CP) (7, 14, 21, 28 and 35 days post-infection). Serum levels of IgA, IgG, IgM and IgE. Cytokines INF-γ, TNF-alpha, IL-4, IL-10 and haematological parameters were determined. Cyst and trophozoite were counted. A considerable increase in the level of immunoglobulins and cytokines in all infected groups compared with the control group was documented. Furthermore, a significant decrease in red blood corpuscles, haemoglobin and mean corpuscular haemoglobin concentration levels was observed, whereas substantial increases in mean corpuscular volume, mean corpuscular haemoglobin and platelets were observed. Moreover, infected rats had a substantial rise in WBCs, lymphocytes and eosinophil counts compared with the control group, whereas neutrophils and monocytes had a significant decrease. The number of trophozoites and cysts was significantly increased in infected groups before diminishing after day 28. The current results showed that Th1 and Th2 immune responses, which are characterized by the production of TNF-α, IFN-γ, IL-4 and IL-10, are important for protection against Giardia infections and also verified the balance between these cytokines and the timing of their production was crucial in G. lamblia immune response.

Discovery, Development, and Patent Trends on Molnupiravir: A Prospective Oral Treatment for COVID-19.

The COVID-19 pandemic needs no introduction at present. Only a few treatments are available for this disease, including remdesivir and favipiravir. Accordingly, the pharmaceutical industry is striving to develop new treatments for COVID-19. Molnupiravir, an orally active RdRp inhibitor, is in a phase 3 clinical trial against COVID-19. The objective of this review article is to enlighten the researchers working on COVID-19 about the discovery, recent developments, and patents related to molnupiravir. Molnupiravir was originally developed for the treatment of influenza at Emory University, USA. However, this drug has also demonstrated activity against a variety of viruses, including SARS-CoV-2. Now it is being jointly developed by Emory University, Ridgeback Biotherapeutics, and Merck to treat COVID-19. The published clinical data indicate a good safety profile, tolerability, and oral bioavailability of molnupiravir in humans. The patient-compliant oral dosage form of molnupiravir may hit the market in the first or second quarter of 2022. The patent data of molnupiravir revealed its granted compound patent and process-related patent applications. We also anticipate patent filing related to oral dosage forms, inhalers, and a combination of molnupiravir with marketed drugs like remdesivir, favipiravir, and baricitinib. The current pandemic demands a patient compliant, safe, tolerable, and orally effective COVID-19 treatment. The authors believe that molnupiravir meets these requirements and is a breakthrough COVID-19 treatment.

A homozygous missense variant in CHRM3 associated with familial urinary bladder disease.

CHRM3 codes for the M3 muscarinic acetylcholine receptor that is located on the surface of smooth muscle cells of the detrusor, the muscle that effects urinary voiding. Previously, we reported brothers in a family affected by a congenital prune belly-like syndrome with mydriasis due to homozygous CHRM3 frameshift variants. In this study, we describe two sisters with bladders that failed to empty completely and pupils that failed to constrict fully in response to light, who are homozygous for the missense CHRM3 variant c.352G > A; p.(Gly118Arg). Samples were not available for genotyping from their brother, who had a history of multiple urinary tract infections and underwent surgical bladder draining in the first year of life. He died at the age of 6 years. This is the first independent report of biallelic variants in CHRM3 in a family with a rare serious bladder disorder associated with mydriasis and provides important evidence of this association.

Small molecules as kinetoplastid specific proteasome inhibitors for leishmaniasis: a patent review from 1998 to 2021.

INTRODUCTION: Leishmaniasis is a neglected tropical infectious disease. The available limited therapeutic options for leishmaniasis are inadequate due to their poor pharmacokinetic profile, resistance, toxicity, high cost, and compliance problems. This warrants identification of new targets for the development of safer and effective anti-Leishmania therapy. The kinetoplastid specific proteasome (KSP) is a novel validated target to develop drugs against leishmaniasis. AREA COVERED: This review focuses on all the published patent applications and granted patents related to the studied small molecules as KSP inhibitors (KSPIs) against Leishmania from 1998 to 31 December 2021. EXPERT OPINION: A little amount of work has been done on KSPIs, but the study results are quite encouraging. LXE408 and GSK3494245 are two KSPIs in different phases of clinical trials. Some other small molecules have also shown KSP inhibitory potential, but they are not in clinical trials. The KSPIs are promising next-generation orally active patient compliant drugs against kinetoplastid diseases, including leishmaniasis. However, the main challenge to discover the KSPIs will be the resistance development and their selectivity against the proteasome of eukaryotic cells.

Anticancer Drug-Induced Cardiotoxicity: Insights and Pharmacogenetics.

The advancement in therapy has provided a dramatic improvement in the rate of recovery among cancer patients. However, this improved survival is also associated with enhanced risks for cardiovascular manifestations, including hypertension, arrhythmias, and heart failure. The cardiotoxicity induced by chemotherapy is a life-threatening consequence that restricts the use of several chemotherapy drugs in clinical practice. This article addresses the prevalence of cardiotoxicity mediated by commonly used chemotherapeutic and immunotherapeutic agents. The role of susceptible genes and radiation therapy in the occurrence of cardiotoxicity is also reviewed. This review also emphasizes the protective role of antioxidants and future perspectives in anticancer drug-induced cardiotoxicities.

Bilateral Central Retinal Vein Occlusion in a 40-Year-Old Man with Severe Coronavirus Disease 2019 (COVID-19) Pneumonia.

BACKGROUND COVID-19 is the disease caused by the novel virus, severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). The spectrum of disease seen in patients with COVID-19 infection ranges from asymptomatic or mild symptoms to severe pneumonia and even acute respiratory distress syndrome, which often requires invasive ventilation and intensive care. COVID-19-associated infection can be catastrophic, leading to both arterial and venous occlusion, microinfarcts, and multiorgan failure, although retinal vein occlusion has not yet been reported. CASE REPORT We present the case of a 40-year-old man who presented with a 3-day history of shortness of breath, cough, and fever. He also reported right calf pain and blurring of vision in both eyes. His medical history included hypertension and morbid obesity. The patient was found to have severe COVID-19 pneumonia on high-resolution computed tomography of the chest, right leg deep venous thrombosis on Doppler ultrasonography, and bilateral central retinal vein occlusion (RVO) on fundal examination. He was started on full-dose anticoagulation and discharged on rivaroxaban for 3 months. After 2 weeks of therapy, he had fully recovered from his COVID-19 symptoms and had near-normal vision. CONCLUSIONS COVID-19 infection can cause RVO. Early full-dose anticoagulation should be considered in high-risk patients with severe COVID-19 infection. Ophthalmologists and other clinicians should have a high index of suspicion for RVO in patients with COVID-19 infection who presenting with blurred vision and severe pneumonia.

Knowledge, awareness and perceptions of diabetes mellitus among the Saudi population.

Background: High prevalence of undiagnosed cases of diabetes mellitus (DM) has increased over the last two decades, most patients with DM only become aware of their condition once they develop a complication. Limited data are available regarding the knowledge and awareness about DM and the associated risk factors, complications and management in Saudi society. Aim: This study aimed to assess knowledge of DM in general Saudi society and among Saudi healthcare workers. Results: Only 37.3% of the participants were aware of the current DM prevalence. Obesity was the most frequently identified risk factor for DM. Most comparisons indicated better awareness among health workers. Conclusion: A significant lack of knowledge about DM in Saudi society was identified. Social media and educational curriculum can improve knowledge and awareness of DM.