Secondary bacterial infections and free radical injury have been known to play an important role in the pathogenesis and clinical outcome of acute pancreatitis. Despite the therapy models developed in recent years, the mortality rate is still reported to be higher than expected. The objective of this study therefore was to investigate the effectiveness of ciprofloxacin and metronidazole combination and curcumin together in the treatment of acute pancreatitis. Acute pancreatitis was induced in rats by sodium taurocholate (n = 60). Starting 6 h after the induction of acute pancreatitis, groups I and II were injected 200 mg/kg ciprofloxacin and 500 mg/kg metronidazole intraperitoneally every 12 h for 6 days. Groups II and III received 100 mg/kg curcumin since day 20 prior to the initiation of acute pancreatitis. On day 6, animals of all groups were killed. Blood and tissue samples were taken for biochemical, pathologic and bacteriologic examination. No statistical difference in the treatment groups versus the non-treatment group has been detected in the pancreatic tissue on the basis of histopathological scoring results. Prevalences of bacterial translocation were significantly lower in the treatment groups (groups I-III) than in the non-treatment group (group IV) (p < 0.001, p < 0.001, p < 0.05, respectively). Serum amylase, lipase, malon dialdehyde and nitric oxide (except for nitric oxide level in group I), levels of groups I, II and III were significantly lower than those of group IV (p < 0.05). The administration of ciprofloxacin and metronidazole in combination and curcumin in acute pancreatitis failed to provide a preventive effect on the occurrence of tissue injury, whereas free radical injury and prevalence of bacterial translocation were reduced significantly.
A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in the sprawling capital of Central China’s Hubei province Wuhan in 2019. Since late 2019, SARS-CoV-2 has been responsible for a global pandemic that has resulted in 405,961,201 confirmed cases of infection and 5,789,567 deaths as of February 11, 2022, according to the World Health Organization (WHO). Here we report the development of an inactivated SARS-CoV-2 vaccine candidate and show that its efficacy and safety in preclinical studies warrant further clinical evaluation. Efficiency and possible side effects of vaccine candidate on different doses were evaluated using histopathology, K18 hACE2 transgenic mice challenge, T-cell response, and serum neutralization test in Balb/c mice. All pilot production and propagation experiments of SARS-CoV-2 were performed in the Level 3 Negative Pressure Biosafety Facility (BSL3/ABSL-3) according to COVID-19 interim guidance of WHO. All analytical studies have shown that the quality control parameters of the vaccine candidate meet the requirements for inactivated viral vaccines according to European Pharmacopeia. The vaccine candidate (KOCAK-19) has been authorized by the Turkish Medicines and Medical Devices Agency and has now entered phase 2 clinical development (NCT04838080). Abbreviations: SARS-CoV-2: Severe Acute Respiratory Syndrome Coronavirus 2.; MERS-CoV: Middle East Respiratory Syndrome Coronavirus.; qRT-PCR: Quantitative Real-Time Polymerase Chain Reaction.; TEM: Transmissible Electron Microscopy.; SEC: Size Exclusion.; AEX: Anion exchange.; BPL: -Propiolactone.; CPE: Cytopathic Effect.; TCID50: 50% Tissue Culture Infectious Dose.; hACE-2: Human Angiotensin-Converting Enzyme 2.; mRNA: Messenger RNA.; RBD: Receptor binding domain.; Nab: Neutralizing antibody.; MOI: Multiply of Infection.