Volume 32, Issue 3

Coronavirus COVID-19 pandemic invades the world. Public health evaluates the incidence of infections and death, which should be reduced and need desperately quarantines for infected individuals. This article review refers to the roles of Ginkgo Biloba to reduce the risk of infection in the respiratory tract, the details on the epidemiology of corona COVID-19 and influenza, and it highlights how the Ginko Biloba could have been used as a novel treatment. Ginkgo Biloba can reduce the risk of infection by several mechanisms; these mechanisms involve Ginkgo Biloba contains quercetin and other constituents, which have anti-inflammatory and immune modulator effects by reducing pro-inflammatory cytokines concentrations. Cytokines cause inflammation which have been induced the injuries in lung lining. Some observational studies confirmed that Ginkgo Biloba reduced the risk of asthma, sepsis and another respiratory disease as well as it reduced the risk of cigarette smoking on respiratory symptoms. While other evidences suggested the characters of Ginkgo Biloba as an antivirus agent through several mechanisms. Ginkgolic acid (GA) can inhibit the fusion and synthesis of viral proteins, thus, it inhibit the Herpes Simplex Virus type1 (HSV-1), genome replication in Human Cytomegalovirus (HCMV) and the infections of the Zika Virus (ZIKV). Also, it inhibits the wide spectrum of fusion by inhibiting the three types of proteins that have been induced fusion as (Influenza A Virus [IAV], Epstein Barr Virus [EBV], HIV and Ebola Virus [EBOV]). The secondary mechanism of GA targeting inhibition of the DNA and protein synthesis in virus, greatly have been related to its strong effects, even afterward the beginning of the infection, therefore, it potentially treats the acute viral contaminations like (Measles and Coronavirus COVID-19). Additionally, it has been used topically as an effective agent on vigorous lesions including (varicella-zoster virus [VZV], HSV-1 and HSV-2). Ginkgo Biloba may be useful for treating the infected people with coronavirus COVID-19 through its beneficial effect. To assess those recommendations should be conducted with random control trials and extensive population studies.

Objectives Heart rate variability (HRV) is often measured during clinical and experimental cardiovascular reflex tests (CRT), as a reflection of cardiac autonomic modulation, despite limited characterization of the rapid responses that occur. Therefore, we evaluated the responsiveness of HRV indices in 20 healthy young adults (age, 27 ± 6 y; mass, 76.9 ± 16.8 kg; height, 1.79 ± 0.12 m) during four separate established CRT. Methods These included the [I] orthostatic challenge, [II] isometric handgrip, [III] cold pressor and [IV] cold diving reflex tests. Electrocardiogram was recorded throughout, with HRV derived from RR intervals at rest and from each CRT. On a separate day, a subgroup of participants (n=9) completed the same protocol for a second time. Results The maximal slope of heart rate change (dTdt) was significantly different between all CRT, with the orthostatic challenge producing the fastest increase (2.56 ± 0.48) and the cold pressor the fastest reduction (−1.93 ± 0.68) in heart rate. Overall HRV, reflected by Poincaré plot ratio (SD1:SD2), was significantly reduced during all CRT ([I], −0.41 ± 0.12; [II], −0.19 ± 0.05; [III], −0.36 ± 0.12; [IV], −0.44 ± 0.11; p<0.05) relative to baseline and this was reproducible in time-series. However, when HRV indices were correlated to mean-RR an exponential growth-like relationship was evident (R 2 ranging from: 0.52–0.62). Conclusions These unique outcomes demonstrate that short-term alterations in HRV are evident during CRT, while indicating the importance of adjusting for, or at least reporting, underlying heart rate when interpreting such measures.

Objectives Cardiovascular disease (CVD) complication is common among chronic kidney disease (CKD) patients. Thus, knowledge about CVD and ECG abnormalities in CKD are essential due to progressive nature of the disease and increased risk of sudden cardiac death. This study aims to scrutinize the ECG abnormalities among nondialysis late-stage CKD patients. Methods A descriptive observational study was conducted at Dr. Soetomo General Hospital, Surabaya, Indonesia. Subjects were hospitalized patients with late-stage CKD between 1 January and 31 December 2019, who were consulted at the department of cardiology and vascular medicine during their initial admission at emergency room. ECG interpretation for this study was done by qualified cardiologist. Results There were 191 patients included in this study. Mean ages were 52.2 ± 11.8 years old and 51% were males. Total 143 (74.9%) patients had anemia, 111 (58.1%) had hypertension and 75 (39.3%) had type 2 diabetes mellitus. Mean serum creatinine was 10.5 ± 8.0 mg/dL. There were 176 (92.1%) patients with at least one form of ECG abnormalities. Prolonged QTc interval (36.6%), fragmented QRS complex (29.8%), poor R wave progression (24.6%), peaked T wave (22.0%) and left ventricular hypertrophy (16.7%) were the most common abnormalities. Conclusions ECG abnormalities are common among nondialysis late-stage CKD patients. Given the fact that long-term CKD influences the pathogenesis cardiovascular diseases and substantial cardiovascular mortality, there is a need to screen Indonesian CKD patients who are at risks of getting earlier complications.

Objectives Diabetes mellitus (DM) is associated with autonomic neuropathy and metabolic abnormalities. These predispose the patients to prolongation of QTc and risk of arrhythmias and sudden cardiac death. Vitamin D may also cause QTc prolongation. We hypothesized that concomitant Vitamin D deficiency and Type 2 DM may act in synergy to prolong QTc interval. Methods Newly diagnosed Type 2 DM patients were recruited from Department of Endocrinology. Lead II ECG was acquired for 5 min during supine rest using a digital data acquisition system. QTc interval extraction was performed using software. 25-hydroxy Vitamin D estimation was done using Chemiluminescence method. Patients were divided into two groups- Vitamin D deficient and insufficient (VDD/I) and optimal (VDO) as per standard criteria. QTc intervals were compared between the two groups. Results Sixty-five patients participated in the study. Age was comparable between the groups (p=0.67, Unpaired t-test). There was no significant difference amongst QTc intervals between the groups (p=0.19, Mann Whitney test). Also, there was no significant correlation between Vitamin D levels and QTc intervals assessed using Spearman’s correlation coefficient. Conclusions While it seems plausible, coexisting Vitamin D deficiency and Type 2 DM probably do not act in synergy to prolong QTc interval. These findings merit future research on larger cohorts to investigate the relationship between Vitamin D status and newly diagnosed Type 2 DM on QTc intervals.

Objectives This study aimed to explore the protective mechanism of caffeic acid (CAA) and chlorogenic acid (CHA) on cyclosporine (CSA) induced hypertensive rats. Methods Effect of CAA and CHA on diastolic blood pressure (DBP), mean arterial pressure (MAP), angiotensin-converting enzyme (ACE), e-nucleotide triphosphate dephosphorylase (e-NTPDase), 5′ nucleotidase and adenosine deaminase (ADA) activity in CSA-induced hypertensive rats were determined. Results CAA and CHA administration stabilized hypertensive effect caused by CSA administration. Also, altered activity of ACE (lung), e-NTPDase, 5′ nucleotidase, ADA as well as elevated malondiadehyde (MDA) level was restored in all the treated hypertensive rats in comparison with the untreated hypertensive rats. Conclusion Hence, these observed results could underlie some of the mechanisms through which CAA and CHA could offer antihypertensive effect.

Objectives Autonomic dysfunction (AD) and dynamic hyperinflation (DH) have been implicated as pathophysiological mechanisms of heart failure with preserved ejection fraction (HFpEF) in chronic obstructive pulmonary disease ( COPD) patients. Their association, however, remains elusive: The aims of the study were: (1) to determine the prevalence of AD and DH in non-severe COPD patients, with exertional dyspnea, without clinically overt cardio-vascular (CV) comorbidities; (2) to analyze the correlation and clinical significance between DH, AD, and maksed HFpEF. Methods We applied CPET in 68 subjects. Echocardiography was performed before CPET and 1–2 min after peak exercise. IC manoeuvres were applied. Patients were divided into two groups: patients with and without masked HFpEF. Wilkoff method calculated the meatabolic – chronotropic relationship (MCR). Chronotropic incompetence (CI) and abnormal HR recovery (HRR) were determined. Results The prevalence of CI was 77 vs. 52% in patients with/without masked HFpEF; of abnormal HRR – 98 vs. 62% respectively; of DH – 53 vs. 29%. ICdyn was associated with AD. Univariate regression showed association between masked HFpEF, ICdyn, HRR, oxygenuptake (’VO 2 ), ’VO 2 at anaerobic threshold, oxygen (O 2 ) pulse and ’VE/’VCO 2 slope. None of these parameters is an independent predictor for masked HFpEF. Conclusions DH, AD, and masked HFpEF are prevalent in non-severe COPD patients, who complain of exertional dyspnea and are free of clinically overt CV comorbidities. DH is independently associated with AD. Neither AD, nor DH and CPET are independent predictors for masked HFpEF.

Objectives Hypothyroidism adversely affects pulmonary function, which may improve by thyroxine therapy. Limited studies about the effect of hypothyroidism on spirometric parameters in adult patients were conducted in Basra, south of Iraq. Moreover, the effect of thyroxine therapy on spirometric parameters was not covered by these studies. In this study, pulmonary function in adult’s hypothyroid patients was evaluated by spirometry to detect any impairment, type of impairment, and to evaluate the effect of thyroxine therapy. Methods A comparative study was conducted in Al-Faiha Specialized Diabetes, Endocrine, and Metabolism Center (FDEMC) in Al-Faiha teaching hospital, Basrah, Iraq. Subjects are divided into four groups: uncontrolled hypothyroid group (n=72), controlled hypothyroid group (n=60), newly diagnosed hypothyroid group (n=52), and control group (n=110). Spirometry was done to all subjects in sitting position, it’s repeated at least three times and the best result was recorded. Results A significantly (p<0.05) less spirometric parameters and more abnormal pulmonary function test (PFT) were noticed in hypothyroid groups, the reduction were more pronounced in the uncontrolled hypothyroid group. The abnormality in PFT was mostly of restrictive type. A significantly (p<0.05) negative correlation has been found between thyroid-stimulating hormone (TSH) and spirometric parameters, while the correlation of fT4 is significantly (p<0.05) positive with FVC% and FEV%. Conclusion In hypothyroidism, high TSH and low fT4 are recognized causes of a reduction in spirometric parameters. Therefore, spirometry can be used to detect pulmonary function changes in hypothyroidism.

Objectives Presently, the pandemic of COVID-19 has worsened the situation worldwide and received global attention. The United States of America have the highest numbers of a patient infected by this disease followed by Brazil, Russia, India and many other countries. Moreover, lots of research is going on to find out effective vaccines or medicine, but still, no potent vaccine or drug is discovered to cure COVID-19. As a consequence, many types of research have designated that computer-based studies, such as protein–ligand interactions, structural dynamics, and chembio modeling are the finest choice due to its low cost and time-saving features. Here, oxindole derivatives have been chosen for docking because of their immense pharmacological applications like antiviral, antidiabetic, anti-inflammatory, and so on. Molecular docking of 30 oxindole derivatives done on the crystallized structure of the protein (COVID-19 Mpro). Methods The process of docking, interaction, and binding the structure of ligand with protein has executed using Molegro Virtual Docker v.7.0.0 (MVD) and visualized the usage by Molegro Molecular Viewer v.7.0.0 (MMV). Results Among the 30 derivatives, the outcomes depicted better steric interaction and hydrogen bonding amongst OD-22 ligand, OD-16 ligand, OD-4 ligand, and OD-9 ligand (oxindole derivatives) with COVID-19. In addition to this, the comparative study of these four compounds with existing drugs that are under clinical trials shows comparatively good results in terms of its MolDock scores, H-bonding and steric interactions. Conclusions Hence, It is proposed that these four oxindole derivatives have good potential as a new drug against coronavirus as possible therapeutic agents.

Objectives The effect of oestrogen in hormonal dysfunction is not clear, especially in the coronary vascular bed. This study aimed at estradiol action (E2) in the coronary vascular bed from sham-operated and gonadectomized female and male spontaneously hypertensive rats (SHRs). Methods Male and female SHRs had their mean arterial pressure (MAP) and baseline coronary perfusion pressure (CPP) determined. The effects of E2 (10 μM) were evaluated in isolated hearts by in bolus infusion before and after endothelium denudation (0.25 μM sodium deoxycholate) or perfusion with 100 μM N G -nitro- l -arginine methyl ester (L-NAME), 2.8 μM indomethacin, 0.75 μM clotrimazole, L-NAME after endothelium denudation, L-NAME plus indomethacin, or 4 mM tetraethylammonium (TEA). Results MAP was higher in males than in females, with gonadectomy increasing in females and reducing in males. CPP was higher in female group, remaining unaltered after gonadectomy. E2-induced vasorelaxation was observed in all groups, with no differences having been found between sexes even after gonadectomy. Perfusion with TEA, L-NAME, L-NAME plus indomethacin, and L-NAME after endothelium removal attenuated the relaxing response in all groups. Clotrimazole inhibited vasorelaxation only in female groups, and indomethacin did so only in gonadectomized groups. Endothelium participation was confirmed in female groups and in the gonadectomized male group. Conclusions Our results indicated that the vasodilator effect of E2 was mediated by an indirect mechanism – via endothelium – as well as by direct action – via vascular smooth muscle – in both groups. The characterization of these mechanisms in coronary arteries might shed light on the functional basis of hormonal dysfunction symptoms in hypertension.

Objectives Acute kidney injury (AKI) is a malady with a sudden onset resulting in buildup of waste matters in the body, but a specific cure hasn’t been found as a lasting solution to AKI. In this study, ramipril was evaluated for its potential therapy in glycerol-induced AKI in rats. Methods Twenty animals were divided into four groups of five animals each. Group I was the control while group II was given glycerol on day 8 only, groups III and IV were administered with pioglitazone (reference drug) and ramipril for seven days respectively and on day 8 received glycerol. On the ninth day, blood and tissue samples were taken to assay for serum indicators of oxidative damage, enzymatic and nonenzymatic antioxidants, and creatinine and blood urea nitrogen. Animals were sacrificed thereafter; kidney was harvested for histological and immunohistochemical analysis. Expressions of caspase 3, renin receptor, NK-KB, and KIM-1 were carried out. Results Ramipril significantly inhibited indicators of oxidative damage while also significantly increasing levels of enzymatic and nonenzymatic antioxidant markers. These drugs also significantly lowered the levels of creatinine and blood urea nitrogen. Histology also indicated that while there were massive infiltration of leucocytes and congestion of the kidney in toxicant group, the ramipril-treated group showed a milder condition. In immunohistochemistry, the two drugs significantly inhibited the expressions of the four proteins, which were highly expressed in the toxicant group. Conclusions The study showed that ramipril and pioglitazone have nephroprotective effect and thus have the ability to blunt AKI through their anti-inflammatory, antiapoptosis, antirenin, and antioxidant properties.

Objectives Cardiovascular diseases are major causes of non-infectious diseases globally. The use of pesticides has been linked with the high global burden of non-communicable diseases. Despite the indiscriminate exposure to dichlorvos (DDVP) by inhalation, no report exists on its possible cardiotoxic effect. This study investigated the cardiotoxicity of DDVP exposure by inhalation and the possible role of  Moringa oleifera  seed oil. Methods Twenty-one male rats were randomly assigned into 3 groups. Group A (control) received only standard rat diet and water ad’ libitum, group B (DDVP) was exposed to DDVP via inhalation for 15 min daily in addition to rat diet and water, and group C (DDVP +  M . oleifera seed oil) received treatment as group B as well as 300 mg/kg of M . oleifera seed oil p.o for 28 days. Results Significant reductions in body weight gain and cardiac weight were observed in DDVP-exposed animals (p<0.05). Similarly, 28 days of exposure to DDVP led to a significant increase in lactate dehydrogenase, creatinine kinase and troponin (p<0.05). DDVP-exposed rats also showed a significant increase in malondialdehyde, and a significant decline in superoxide dismutase and glutathione peroxidase (p<0.05). However, catalase was comparable in DDVP-exposed and control rats. Histopathological observations of the cardiac tissue revealed that DDVP caused marked fat degeneration and necrosis of the myocardial layer. The changes in DDVP-exposed rats were significantly, though not completely, restored by M. oleifera seed oil administration. Conclusions This study provides novel mechanistic information on the cardiotoxicity of DDVP inhalation, and the antioxidant potential of M. oleifera seed oil.

Objectives The novel corona virus disease, which was initially reported in China in late 2019, has become a global pandemic affecting 330 million cases. COVID-19 affects predominantly the respiratory system, in addition to other organ systems, mainly the cardiovascular system. One of the hypotheses is that virus entering the target cells by binding to angiotensin converting enzyme 2 affecting hypothalamic pituitary axis could lead to dysautonomia which is measured by heart rate variability (HRV). HRV is a non-invasive measure of autonomic function that facilitates identification of COVID-19 patients at the risk of developing cardiovascular complications. So, we aimed to assess HRV in COVID patients and compare between COVID patients and normal controls. Methods In a case control design, we compared 63 COVID-19 infected patients with 43 healthy controls matched for age and gender. Along with clinical characterization, heart rate variability was evaluated using ambulatory 5 min ECG in lead II and expressed in frequency and time domain measures. Statistical analysis was performed using SPSS 17.0. Results Mean age of the study population was 49.1 ± 14.2 years and 71 (66.9%) were males. Frequency domain measures high (HF) and low (LF) frequency powers were significantly decreased in COVID-19 patients compared to controls. HF/LF and LF/HF ratios were not different between groups. Time domain measures rMSSD (root mean square of successive RR interval differences) and SDNN (standard deviation of NN intervals) were significantly increased among COVID-19 subjects. COVID-19 infection was associated with increased parasympathetic activity as defined by rMSSD>40 {adjusted odds ratio 7.609 (95% CI 1.61–35.94); p=0.01} and SDNN>60 {adjusted odds ratio 2.620 (95% CI 1.070–6.44); p=0.035} after adjusting for age, gender and comorbidities. Conclusions Our study results showed increased parasympathetic tone in COVID patients. Early diagnosis of autonomic imbalance in COVID patients is needed to plan management and limit progression of disease.

Objectives Broad spectrum antimalarial drugs without deleterious effects on mitochondria are scarce. It is in this regard that we investigated the potency of methanol extract and solvent fractions of Phyllanthus amarus on chloroquine-susceptible and resistant strains of Plasmodium berghei , toxicity and its consequential effects on mitochondrial permeability transition (mPT) pore opening. Methods Malaria was induced in male Swiss mice with susceptible (NK 65) strain, divided into groups (n=5) and treated with 100, 200 and 400 mg/kg of methanol extract, n -hexane, dichloromethane, ethylacetate and methanol fractions daily for seven days. Percentage parasitemia and parasite clearance were determined microscopically. The two most potent fractions were tested on resistant (ANKA) strains. Heme and hemozoin contents were determined spectrophotometrically. The mPT, mitochondrial ATPase (mATPase) and lipid peroxidation (mLPO) were determined spectrophotometrically. Similar groups of animals were used for toxicity studies. Results Dichloromethane fraction (400 mg/kg) had the highest antimalarial curative effect via least parasitemia (0.49) and high clearance (96.63) compared with the negative control (10.08, 0.00, respectively), had the highest heme and least hemozoin contents (16.23; 0.03) compared with the negative control (8.2, 0.126, respectively). Malaria infection opened the mPT, caused significant increase in mLPO and enhanced mATPase; while dichloromethane fraction reversed these conditions. Serum ALT, AST, ALP, GGT, urea and creatinine of dichloromethane fraction-treated mice decreased relative to control. No significant lesion was noticed in liver and kidney tissue sections. Conclusions Dichloromethane fraction of Phyllanthus amarus had the highest antimalarial activity with the highest mito-protective effect and it was well tolerated without toxic effects.

Objectives With the emergence of Novel corona virus, hunt for finding a preventive and therapeutic treatment options has already begun at a rapid pace with faster clinical development programs. The present study was carried out to give an insight of therapeutic interventional trials registered under clinical trial registry of India (CTRI) for COVID-19 pandemic. Methods All trials registered under CTRI were evaluated using keyword “COVID” from its inception till 9th June 2020. Out of which, therapeutic interventional studies were chosen for further analysis. Following information was collected for each trial: type of therapeutic intervention (preventive/therapeutic), treatment given, no. of centers (single center/multicentric), type of institution (government/private), study design (randomized/single-blinded/double-blinded) and sponsors (Government/private). Microsoft Office Excel 2007 was used for tabulation and analysis. Results The search yielded total of 205 trials, out of which, 127 (62%) trials were interventional trials. Out of these, 71 (56%) were AYUSH interventions, 36 (28.3%) tested drugs, 9 (7%) tested a nondrug intervention, rest were nutraceuticals and vaccines. About 66 (56%) were therapeutic trials. Majority were single-centered trials, i.e. 87 (73.7%). Trials were government funded in 57 (48.3%) studies. Majority were randomized controlled trials, i.e. 67 (56.8%). AYUSH preparations included AYUSH-64, Arsenic Album, SamshamaniVati etc. Conclusions The number of therapeutic interventional clinical trials was fair in India. A clear-cut need exists for an increase in both quantity and quality of clinical trials for COVID-19. Drug repurposing approach in all systems of medicine can facilitate prompt clinical decisions at lower costs than de novo drug development.

Objectives Dibenzyl trisulfide (DTS) has been reported to have cytotoxic and anti-inflammatory effects. It also affects erythrocyte deformability. We investigated the effects of DTS on the p50 of the oxygen haemoglobin dissociation curve. Methods Blood samples from 10 healthy male volunteers with normal haemoglobin AA were exposed to 50, 100, 200 and 400 ng/mL, respectively, of DTS. A hemox-analyzer was used to obtain the p50 values. Results The mean p50 value for the control samples was 25.89 ± 2.18 mm Hg. The values for the samples exposed to 50, 100, 200 and 400 ng/mL were 23.53 ± 1.81 mm Hg, 22.62 ± 1.61 mm Hg, 21.88 ± 1.67 mm Hg and 21.68 ± 1.88 mm Hg, respectively. Conclusions DTS caused a significant (p<0.001) reduction in p50 values indicating a shift of the oxygen- haemoglobin dissociation curve to the left in all the samples compared with control, suggesting that the administration of DTS could result in decrease in oxygen supply to tissues.