Anti-diabetic effect of cotreatment with resveratrol and pioglitazone in diabetic rats.

OBJECTIVE: Limitations and side effects associated with current anti-diabetic treatments have necessitated the search for new therapeutic alternatives. This study aimed to explore the combined use of resveratrol (RVT) and established anti-diabetic drug pioglitazone (PGZ) against streptozotocin (STZ)-induced diabetes mellitus (DM). MATERIALS AND METHODS: STZ was supplemented daily to Sprague-Dawley rats to induce DM. The synergistic effect of the RVT (20 mg/kg) and PGZ (0.65 mg/kg) on DM complications was evaluated after 8 weeks of treatment. Biochemical analyses were performed to evaluate the effectiveness of our treatment on glucose level, insulin sensitivity, lipid disturbances, oxidative mediators and inflammatory markers. RESULTS: STZ induced DM onset that is accompanied with elevated diabetic markers, lipid disturbances, remarkable oxidative damage and hyper-inflammation. The PGZ+RVT combination has the best effect as illustrated by significant (p < 0.05) decreases in fasting blood glucose, insulin, HbA1c and HOMA-IR levels. This combination attenuated (p < 0.05) lipid disturbances and their associated elevated atherogenic biomarkers. At the same time, treatments with PGZ+RVT exhibited an anti-inflammatory effect as it attenuated the increase in inflammatory parameters (CRP, TNF-α, IL-6). Also, it restored total antioxidant capacity and peroxisome proliferator-activated receptor (PPARg) levels that decreased by STZ-DM induction. CONCLUSIONS: This study provides PGZ+RVT as promising DM therapeutic alternative. This synergistic combination alleviates most of DM-related complications and insulin resistance.

Insulin potentiates the anticonvulsive activity of phenytoin against maximal electroshock-induced seizures in mice.

INTRODUCTION: The limitations imposed by the blood-brain barrier (BBB) on the sufficient accumulation of antiepileptic drugs (AEDs) in the epileptogenic focus is considered the major cause of the high percentage of morbidity and mortality cases among epilepsy patients. This study aimed at examining the potential effect of insulin on the anticonvulsant action of phenytoin (PHT) in the mouse maximal electroshock-induced seizure model. SUBJECTS AND METHODS: PHT was administered orally in single doses either alone or in combination with insulin given as single intraperitoneal injections. To assess the anticonvulsant activity of PHT, the ED50 values were calculated. The current strength (CS50) threshold for insulin was also estimated. The animals were sacrificed, and the brains were removed to measure their PHT concentrations in the brain. RESULTS: It has been demonstrated that insulin (in all used doses) has no effect on the CS50 but can cause a significant increase in concentrations of PHT in the brain and potentiate the antiepileptic efficiency of this drug in electroshock-induced models of epilepsy in mice. CONCLUSIONS: The combination of insulin with PHT may be of great importance for developing new treatment possibilities following further investigations with other animal models of epilepsy and preclinical studies. Further research is also needed to explore the concentrations of PHT in the brain and the anticonvulsant activity of this drug against maximal electroshock seizures in diabetic mice.

Apigenin inhibits infectious bronchitis virus replication in ovo.

OBJECTIVE: Infectious bronchitis virus (IBV), for which no effective drugs are available, is among the most important causes of economic loss within the poultry industry. Apigenin is a flavonoid that can be isolated from plants. Apigenin has low toxicity with anti-viral activity. However, the effects of apigenin against IBV remain unclear. MATERIALS AND METHODS: Thus, here we investigate the anti-viral effect of apigenin on IBV using 10 day-old embryonated eggs by determining the virus titer by embryo infective doses50 (EID50/mL) and determining IBV genomes copy number (per µL) of allantoic fluid. RESULTS: We found that apigenin protected embryonated eggs from IBV. Additionally, apigenin reduced the log titer of the IBV with a significant correlation of up to 9.4 times at 2 µg/egg. Also, apigenin appears to significantly reduce IBV genomes copy number (per µL) in the allantoic fluid. CONCLUSIONS: Apigenin may be a promising approach for the treatment of IBV, since it protects embryonated eggs from IBV in ovo and suppresses viral replication.

Assessment of anxiety level and sleep quality of medical staff treating patients with COVID-19.

OBJECTIVE: Worldwide transmission of the novel coronavirus (COVID-19) and related morbidity and mortality has presented a global challenge for several reasons. One such underrecognized and unaddressed aspect is the emotional health problems that medical staff have developed during this pandemic. The purpose of this one-month study was to examine anxiety levels and sleep quality of 100 medical staff members who worked in medical clinics treating COVID-19 patients in Saudi hospitals and to investigate the association of both anxiety levels and sleep quality with age, sex, and distinctive demographics. MATERIALS AND METHODS: We investigated anxiety levels and sleep quality of 100 medical staff members (age range 20-60 years) who worked in medical clinics treating COVID-19 patients in Saudi hospitals and the association of both anxiety levels and sleep quality with age, sex, and distinctive demographics. Anxiety levels and sleep quality were measured using the Self-Rating Anxiety Scale and the Pittsburgh Sleep Quality Index (SAS and PSQI, respectively). RESULTS: A significant increment in anxiety and poor sleep quality was found in medical staff caring for COVID-19 patients. Anxiety levels in females were higher than males; however, poor sleep quality was somewhat higher in males vs. females but did not vary between age groups. Age was significantly negatively correlated with anxiety symptoms; individuals < 40 years old vs. ≥ 40 had more significant anxiety levels. We observed that medical staff with top-level salaries demonstrated a significant correlation (p = 0.028) between poor sleep quality and ill effects vs. those who had lower pay rates. A correlation between income and anxiety was not found. CONCLUSIONS: The higher the probability and intensity of exposure to coronavirus patients, the more noteworthy the danger that medical staff will experience the ill effects of mental issues.

Effect of silver nanoparticles on the antibacterial activity of Levofloxacin against methicillin-resistant Staphylococcus aureus.

OBJECTIVE: The paper presents the antibacterial activity of silver nanoparticles (AgNPs) when conjugated with Levofloxacin. The AgNPs used in this study were synthesized from silver nitrate using sodium borohydride as a reducing agent. MATERIALS AND METHODS: Levofloxacin activity was determined by minimum inhibitory concentrations (MICs) and also the erythrocyte hemolytic assay determined the capability of conjugation to cause hemolysis in human erythrocyte. RESULTS: The synthesis of levofloxacin-AgNP conjugates was confirmed by ultraviolet/visible (UV/vis) spectroscopy. A peak absorption value between 400-450 nm for the extract and the color change to dark brown were corresponding to the plasmon absorbance of AgNPs. On the other hand, levofloxacin-AgNPs could be effective against methicillin-resistant Staphylococcus aureus (MRSA). The MICs of levofloxacin and levofloxacin-AgNPs were 12 and 10 µM, respectively. CONCLUSIONS: These findings indicated that levofloxacin-AgNPs had an effective bactericidal activity against the bacterial MRSAs. This conjugation appeared to inhibit bacterial adaptive capabilities, which leads to inhibition of bacterial resistance.

Punicalagin and zinc (II) ions inhibit the activity of SARS-CoV-2 3CL-protease in vitro.

OBJECTIVE: Coronavirus 2019 (COVID-19) has now been declared as a worldwide pandemic. Currently, no drugs have been endorsed for its treatment; in this manner, a pressing need has been developed for any antiviral drugs that will treat COVID-19. Coronaviruses require the SARS-CoV-2 3CL-Protease (3CL-protease) for cleavage of its polyprotein to yield a single useful protein and assume a basic role in the disease progression. In this study, we demonstrated that punicalagin, the fundamental active element of pomegranate in addition to the combination of punicalagin with zinc (Zn) II, appear to show powerful inhibitory activity against SARS-CoV-2. MATERIALS AND METHODS: The 3CL protease assay kit was used to quantify 3CL protease action. The tetrazolium dye, MTS, was used to evaluate cytotoxicity. RESULTS: Punicalagin showed inhibitory action against the 3CL-protease in a dose-dependent manner, and IC50 was found to be 6.192 µg/ml for punicalagin. Punicalagin (10 µg/mL) demonstrated a significant inhibitory activity toward 3CL-protease activity (p < 0.001), yet when punicalagin is combined with zinc sulfate monohydrate (punicalagin/Zn-II) extremely strong 3CL-protease activity (p < 0.001) was obtained. The action of 3CL-protease with punicalagin/Zn-II was decreased by approximately 4.4-fold in contrast to only punicalagin (10 µg/mL). Likewise, we did not notice any significant cytotoxicity caused by punicalagin, Zn-II, or punicalagin/Zn-II. CONCLUSIONS: We suggest that these compounds could be used as potential antiviral drugs against COVID-19.

Inhibitory effects of epigallocatechin gallate (EGCG) combined with zinc sulfate and silver nanoparticles on avian influenza A virus subtype H5N1.

OBJECTIVE: Even though antiviral drugs against H5N1 flu infection are accessible, they are still limited by antiviral drug resistance and unfavorable side effects. Thus, this work tested the action of epigallocatechin gallate (EGCG) co-administered with both zinc (II) ions and silver nanoparticles (AgNPs). MATERIALS AND METHODS: EGCG was used with both zinc sulfate (zinc II) and silver nanoparticles to test their antiviral activities against avian flu subtype H5N1 in embryonated SPF eggs. The MTS test was used to determine the cytotoxicity. RESULTS: Zinc sulfate (1.5 mg/mL) and silver nanoparticles showed comparable potentiated antiviral action with EGCG (50 µM) against the H5N1 avian flu virus. They decreased the log titer infection by up to 5.7 and 5.6 fold separately with critical antiviral activity (p<0.01). In most cases, an illustrative relationship was seen when H5N1 was tested with EGCG and various concentrations of zinc sulfate. The EGCG-AgNPs with zinc sulfate were observed to have very strong antiviral activity (p<0.001) against the H5N1 avian influenza virus with a reduction in the log titer of the virus by up to 7.6 times. No cytotoxicity was recognized. CONCLUSIONS: The potentiated antiviral activity of EGCG by co-administering it with zinc II and AgNPs indicates potential as a multi-activity novel topical therapeutic agent against H5N1 flue. This mix makes the adaptation of the virus difficult, which helps to reduce infection resistance.