Biomedical Research and Therapy

SARS-CoV-2 epidemic: causes and current situation, historical lessons, and strategical therapeutic interventions

2020-05-29T13:45:57+00:00

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused an initial outbreak in China, now has 40 strains with infections in more than 200 countries worldwide, according to scientists. To date, 4,121,777 people have become infected and 280,868 people died as a result of corona virus disease of 2019 (COVID-19), with many patients still under critical condition. The SARS-CoV-2 is phylogenetically similar to SARS-like bat viruses and, thus, bats can be a key host for SARS-CoV-2. Many viruses have been transmitted to humans due to the consumption of wild birds and animals as a food source. The lack of vaccine, improper containment, and diagnostic strategies by various countries have converted COVID-19 into a global pandemic. The lockdown conditions in developing countries may produce economic crises. COVID-19 patients can suffer from mental distress, partly resulting from quarantine restrictions, and therefore, there is dire need for mental counseling. The combination of previously used broad-spectrum antibiotics, antiviral and anti-parasite agents, and interferon have reduced viral infection at higher and frequent doses. Many patients have been discharged after clinical recovery, though COVID-19 can still leave severe adverse effects on patients. The use of traditional Chinese medicines (TCMs) has led to recovery of 90% of COVID-19 patients in China. The current review article highlights the current situation, the major causes which have led to the COVID-19 pandemic, as well as strategical interventions to control the pandemic and cure infected patients.

The predictive value of vascular endothelial growth factor-A gene polymorphism for clinical outcomes among acute ST-segment elevation myocardial infarction patients: A single center prospective study

2020-05-29T13:36:30+00:00

Background: Vascular endothelial growth factor (VEGF) is an angiopoetic factor; its variability in circulating levels is mediated by expression of specific VEGF-A gene variants. The aim of this study was to investigate the predictive role of VEGF-A gene polymorphism in clinical outcomes of STelevation myocardial infarction (STEMI) patients.

Methods: For the study, 135 patients with acute STEMI and 30 healthy volunteers were enrolled. The G634C polymorphism in VEGF-A gene was performed by real-time polymerase chain reaction at baseline. The 6-month combined clinical endpoint was then determined. Design: The study was an open prospective single-center cohort study.

Results: The entire patient population was distributed into two groups based on the G634G-genotype (n = 70) and combination of G634C and C634C-genotypes (n = 65). Unadjusted multivariate regressive logistic analysis showed peak troponin I levels at admission, Killip class of heart failure > 2, GC/CC polymorphisms in VEGF-A gene, and dynamic increase of NT-pro brain natriuretic peptide (BNP) and VEGF-A levels for 6 months, which were independent predictors for the combined clinical endpoint. After adjustment for dynamic changes of NT-proBNP and VEGF-A levels, we found that GC/CC polymorphisms in the VEGF-A gene was an independent predictor of clinical outcome. Kaplan-Meier curves demonstrated that STEMI patients with GG VEGF-A genotype had a lower frequency of clinical combined endpoint accumulation when compared to those who had GC/CC VEGF-A genotypes (Log-rank p = 0.02).

Conclusion: The G634C polymorphism in the VEGF-A gene was found to be an independent predictor for 6-month clinical combined endpoint in STEMI patients.

Analgesic, anti-inflammatory and hypouricemic effects of GT1 film-coated tablets on experimental animals

2020-05-29T13:36:34+00:00

Aim: To evaluate pain relief, anti-inflammatory and hypouricemic effects of GT1 tablets on experimental animals.

Method: GT1 at the doses of 22.32 g/kg/day and 66.96 g/kg/day were evaluated for its analgesic effect in three models (hot plate, pain threshold, and acetic acid-induced writhing), its chronic anti-inflammatory effect in the granulomatous reaction model, and its hypouricemic effect in potassium oxonate-induced hyperuricemic mice. Acute anti-inflammatory effects of GT1 at the doses of 11.16 g/kg/day and 33.48 g/kg/day were evaluated in rats with two models: carrageenin-induced paw edema and peritonitis.

Results: GT1 prolonged the temperature reaction time on the hot plate (22.73 s and 20.37 s at both doses of 22.32 g/kg and 66.96 g/kg, respectively, compared to 16.96 s in control group), reduced the number of acid acetic-induced writhing effects, decreased the weight of granulomas, and decreased the level of acid uric in blood and urine (p < 0.05). GT1 caused a significant reduction in paw edema after subplantar injection of carrageenan in rats (p < 0.05). Moreover, there was a substantial decline of GT1 at the dose of 11.16 g/kg/day in terms of the volume and the quantity of protein in the inflammation fluid of the peritonitis model (p < 0.05).

Conclusion: GT1 at both doses of 11.16 g/kg/day and 33.48 g/kg/day posed acute anti-inflammatory effects on rats. GT1 at both doses of 22.32 g/kg/day and 66.96 g/kg/day exerted analgesic, chronic anti-inflammatory and hypouricemic effects on mice.

Prophylactic treatment of ischemic stroke with Coffea arabica in rats: A preliminary study

2020-05-29T13:36:29+00:00

Introduction: Ischemic stroke is the third leading cause of death worldwide. The purpose of the current study was to assess the preliminary effects of Coffea arabica (CA) in experimentally-induced stroke in an animal model in the context of neuroprotection. The study was also designed to document the prophylactic use of CA in patients experiencing stroke symptoms.

Methods: A total of 25 male albino rats, 12 months of age, were purchased from the local market. They were acclimatized for seven days and divided into 5 groups. Each group consists of 5 subjects. Each subject was trained on a specific test for behavioral assessment. Behavioral modulation of each rat was performed using four tests, namely cylinder test, staircase test, forelimb flexion test, and pasta test. All the tests were performed as per standard criteria at the 4^th, 8^th, 12^th, and 14^th day of drug administration. The subjects were administered with caffeine (2.4 mg/kg) and CA (100 mg/kg and 200 mg/kg extract) doses for 14 days to assess the prophylactic use of CA. After 14 days of treatment, rats were subject to ischemic stroke induction using the middle cerebral artery ligation method. All four tests used for behavior modulation were applied at 24, 48, and 72 hours intervals of postsurgery. The subjects were further sacrificed for histopathological investigations. Statistical analysis was performed with SPSS (V. 22) software using one-way ANOVA.

Results: Our findings suggest that treatment with CA, 100 mg/kg and 200 mg/kg orally, decreases the infarct volume. However, there are not many considerable differences that were found in both doses. Histopathological investigations revealed characteristic structural changes occurring in both gray and white brain regions, depending on the severity, location, and duration of the ischemic stroke.

Conclusion: CA is a harmless and active mediator in the dissolution of blood clots and the recovery of stroke in rats. It is an agent that has been found to be efficient for brain activity with few side effects and behavioral modifications.

Acalypha wilkesiana ‘inferno’ hydroethanolic leaf extract has protective effect on carbon tetrachloride-induced subacute toxicity in animals

2020-05-29T13:36:33+00:00

Introduction: Liver fibrosis is one of the most common clinical manifestations of hepatic diseases. However, though many synthetic drugs exist for the treatment and prevention of liver diseases, liver injuries still persist. The present study, therefore, sought to investigate the subacute protective effects of Acalphya wilkesiana against carbon tetrachloride (CCl₄)-induced toxicity in animals.

Methodology: Liver injury was induced in experimental animals by administering CCl₄ (1:1 v/v in olive oil, intraperitoneally (i.p.), twice weekly for 8 weeks) after pre-treatment with extract of A. wilkesiana (AWE). AWE (250 mg/kg) and Silymarin (120 mg/kg) were administered orally (daily for 8 weeks). The hepatoprotective effect was studied by assaying the activity of liver enzymes, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and alpha-fetoprotein. The effect of the treatments on liver prooxidants (e.g. malondialdehyde [MDA]) and antioxidants (e.g. superoxide dismutase [SOD], reduced glutathione [GSH], glutathione peroxidase [GPx], and glutathione transferase [GST]), as well as inflammatory cytokines (e.g. interleukin [IL]-17, IL-23, nuclear factor kappa beta [NF-kB], and cycloxygenase-1 [COX-1]) and the histology of the liver were also examined.

Results: The activity of liver function biomarkers changed significantly upon CCl₄ administration; increases in ALT, total and direct bilirubin, and some fibrosis indices (e.g. alpha-fetoprotein and APRI [p<0.05-0.001, compared with normal]) were observed. Co-administration of AWE with CCl₄ restored these to normal levels. The intensity of structural alterations revealed that the AWE treatment has protective potential against subacute liver injury. AWE treatment also reduced the expression of IL-17, 1L-23, NF-kB and COX-1, underscoring its antiinflammatory properties.

Conclusion: The results of the current study generally suggest that hydroethanolic leaf extracts of A. wilkesiana inferno possess some subacute protective activity by improving liver function and inhibition of inflammation, and could be developed as a potent antifibrotic agent.

The effects of monocusp valve implantation and transannular patch angioplasty on pulmonary regurgitation and right ventricular failure after total correction of tetralogy of fallot

2020-05-29T13:36:28+00:00

Background: Pulmonary regurgitation (PR) is often known as an acquired condition after surgical correction of tetralogy of Fallot (TOF). Therefore, the present study aimed to compare the use of monocusp valve (MV) implantation and transannular patch (TAP) angioplasty on PR and right ventricular (RV) failure following surgery to repair TOF.

Methods: This prospective randomized clinical trial (RCT) was performed on a total number of 60 patients undergoing reconstructive surgery on TOF. For this purpose, TAPs without and with monocusp reconstruction were used in Group I (n = 30 patients) and Group II (n = 30 patients), respectively. Then, echocardiographic parameters, mortality rates, and clinical data from pediatric intensive care unit (PICU) were evaluated during a follow-up period for both groups.

Results: Out of the 60 patients undergoing surgery and evaluated, 39 individuals were male (65%) and the rest were female (n = 21 patients, 35%). No significant difference was observed in terms of age, body weight, body surface area (BSA), mortality rate, and ejection fraction (EF) between the two study groups. The findings revealed that the number of patients with severe PR was higher in the group receiving TAP angioplasty. Furthermore, the difference between the two groups with regards to severity of PR was significant (p = 0.012).

Conclusion: It was concluded that MV reconstruction of TOF is effective in reducing pulmonary artery (PA) and pulmonary valve (PV) insufficiency.

Association of a point mutation (m.9176T>G) of the MT-ATP6 gene with Leigh syndrome: A case report

2020-05-29T13:36:35+00:00

Leigh Syndrome (LS) is an uncommon progressive neurodegenerative mitochondrial disorder. The condition is characterized by progressive mental and developmental disabilities (psychomotor regression) and commonly brings about death within a few years of diagnosis, more often due to respiratory failure. In a small number of patients the disorder does not manifest until adulthood. The principal indications of Leigh syndrome found in early stages typically are diarrhea, vomiting, and difficulty swallowing (dysphagia), which disturbs eating. These problems usually result in powerlessness to develop and put on weight under the normal rate (failure to thrive). Serious movement and muscle problems are basic in Leigh syndrome. In this case report, we introduce the molecular and clinical features of a 19-year-old female as proband, and also, we study other members of the family consequently. The m.9176T>G heteroplasmic mutation in the MT-ATP6 gene was detected by high-resolution melt (HRM) and DNA sequencing techniques. Similarly, the m.9176T>G was heteroplasmic in the mother. In conclusion, this report in compliance with previous studies underlines the necessity of further research on prenatal distinguishing proof of the responsible mutations and avoidance of the disease in families with known cases.

Comparison between preoperative and post-operative administration of paracetamol, ibuprofen and mefenamic acid for post-extraction pain control

2020-05-29T13:36:32+00:00

Pain is a common aftereffect following a dental treatment, especially extractions. Hence, the main aim of the study was to compare the effect of pre-operative and post-operative analgesic usage on post-operative pain management following dental treatment. Moreover, the efficacies of three types of painkillers (Paracetamol, Ibuprofen and Mefenamic Acid) in pain relief were also evaluated. Volunteers (n = 120) who were undergoing extraction participated in this study and were randomly divided into two groups. One group consisting of 60 participants were given pre- and post-operative analgesics while another group (n = 60) received post-operative analgesics only. A visual scale was used to record pain from zero to 56 hours post-operatively at 8-hour intervals. The results showed that patients who were taking analgesics pre-operatively experienced significantly (p = 0.0045) less pain compared to those who had taken post-operative analgesics only However, a lower cumulative number of moderate and severe experiences of post-extraction pain was recorded for the pre- and post-operative analgesic treatment groups as compared to the postoperative only analgesic treatment group; no significant differences were observed. Moreover, no significant differences were observed among the analgesics used in this study as well. On the basis of these results, we conclude that preoperative analgesic usage has a positive impact on postextraction acute pain management.