Pentoxifylline: A Drug with Antiviral and Anti-Inflammatory Effects to Be Considered in the Treatment of Coronavirus Disease 2019

In December 2019, a new coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged from China, causing pneumonia outbreaks first in the Wuhan region and has now spread worldwide. There are no specific drugs for the disease caused by this virus, coronavirus disease 2019 (COVID-19). Considering that new synthesized drugs cannot be applied immediately to patients, conventional drug in new use is a feasible solution. Chloroquine, remdesivir, favipiravir, lopinavir, ribavirin, and ritonavir have shown efficacy to inhibit coronavirus in vitro. Pentoxifylline, a drug with anti-inflammatory, immunomodulatory, and bronchodilatory effects, has previously been shown to inhibit several viral infections. Immunological studies have shown that most patients with severe COVID-19 exhibit substantially elevated serum levels of pro-inflammatory cytokines. Pentoxifylline is a phosphodiesterase inhibitor that increases the levels of cyclic adenosine monophosphate, which in turn activates protein kinase, leading to a reduction in the synthesis of pro-inflammatory cytokines and immune cell migration. Here, we propose pentoxifylline, a drug with low cost and toxicity, as a possible treatment for COVID-19 based on its interesting properties.     

AIDS and heart disease: is cardiac surgery justified?

A compromised immune system, limited survival and increased risk to the anaesthetic and surgical team of acquiring HIV infection have been the major concerns in offering cardiac surgery to patients with AIDS. The current report presents a patient with AIDS who underwent successful, uncomplicated coronary artery surgery. He remains free of ischaemic and any infectioe symptoms 12 months postoperatively.     

Isfahan Healthy Heart Programme: a comprehensive integrated community-based programme for cardiovascular disease prevention and control. Design,methods and initial experience

The Isfahan Healthy Heart Programme (IHHP) is a five to six year comprehensive integrated community-based programme for cardiovascular diseases (CVD) prevention and control via reducing CVD risk factors and improvement of cardiovascular healthy behaviour in a target population. IHHP started late in 1999 and will be finished in 2005-2006. A primary survey was done to collect baseline data from interventional (Isfahan and Najaf-Abad) and reference (Arak) communities. In a two-stage sampling method, we randomly selected 5 to 10 percent of households from randomly selected clusters. Then individuals aged > or = 19 years were selected for the survey. This way, data from 12,600 individuals (6300 in interventional counties and 6300 in the reference county) was collected and stratified according to living area (urban vs. rural) and different age and sex groups. The samples underwent a 30-minute interview to complete validated questionnaires containing questions on demography, socioeconomic status, smoking behaviour, physical activity, nutritional habits and other behaviour regarding CVD. Blood pressure and body mass index (BMI) measurements were done and fasting blood samples were taken for two hours post load plasma glucose (2 hpp), serum (total, HDL and LDL) cholesterol and triglyceride levels. A twelve-lead electrocardiogram was recorded in all persons above 35 years of age. Community-wide surveillance of deaths, hospital discharges, myocardial infarction and stroke registry was carried out in the intervention and control areas. Four to five years of interventions based on different categories such as mass media, community partnerships, health system involvement and policy and legislation have started in the intervention area while Arak will be followed without intervention. Considering the results of the baseline surveys, (assessments needed, the objectives, existing resources and the possibility of national implementation) the interventions were planned. They were set based on specific target groups like school children, women, work-site, health personnel, high-risk persons, and community leaders were actively engaged as decision makers. A series of teams was arranged for planning and implementation of the intervention strategies. Monitoring will be done on small samples to assess the effect of different interventions in the intervention area. While four periodic surveys will be conducted on independent samples to assess health behaviours related to CVD risk factors in the intervention and reference areas, the original pre-intervention subjects aged more than 35 years will be followed in both areas to assess the individual effect of interventions and outcomes like sudden death, fatal and nonfatal MI and stroke. The whole baseline survey will be repeated on the original and an independent sample in both communities at the end of the study.     

Fingolimod, a sphingosine-1 phosphate receptor modulator, increases BDNF levels and improves symptoms of a mouse model of Rett syndrome

The functional relevance of brain-derived neurotrophic factor (BDNF) is beginning to be well appreciated not only in mice, but also in humans. Because reduced levels typically correlate with impaired neuronal function, increasing BDNF levels with well-tolerated drugs diffusing into the central nervous system may help in ameliorating functional deficits. With this objective in mind, we used the sphingosine-1 phosphate receptor agonist fingolimod, a drug that crosses the blood-brain barrier. In addition, fingolimod has recently been introduced as the first oral treatment for multiple sclerosis. In cultured neurons, fingolimod increases BDNF levels and counteracts NMDA-induced neuronal death in a BDNF-dependent manner. Ongoing synaptic activity and MAPK signaling is required for fingolimod-induced BDNF increase, a pathway that can also be activated in vivo by systemic fingolimod administration. Mice lacking Mecp2, a gene frequently mutated in Rett syndrome, show decreased levels of BDNF, and fingolimod administration was found to partially rescue these levels as well as the size of the striatum, a volumetric sensor of BDNF signaling in rodents. These changes correlate with increased locomotor activity of the Mecp2-deficient animals, suggesting that fingolimod may improve the functional output of the nervous system, in addition to its well-documented effects on lymphocyte egress from lymph nodes.     

Serum concentrations of antiphospholipid and anticardiolipin antibodies are higher in HIV-infected women

Manifestations of viral infections like human immune deficiency virus (HIV) differ between women and men. There are some reports due to a higher risk of thrombosis due to antiphospholipid syndrome in HIV-infected women compared with men. The purpose of this study was demonstrating the impact of gender on serum concentration of antiphospholipid and anticardiolipin antibodies in HIV-infected patients. A total of 58 HIV-infected patients and 58 age, sex-matched healthy adults were enrolled. We measured platelets count, hemoglobin, partial thromboplastin time (PTT); prothrombin time (PT), international normalized ratio (INR), antiphospholipid IgG/IgM and anticardiolipin IgG/IgM serotypes in our studied population. Age, male-to-female ratio, hemoglobin level, PT, INR, antiphospholipid IgM isotype, anticardiolipin IgM and IgG isotypes levels were not significantly different between HIV-infected patients and healthy individuals, when CD4+ T-cell count, CD8+ T-cell count, platelet count, and PTT were significantly lower, and antiphospholipid IgG isotype levels was significantly higher in HIV patients. Antiphospholipid IgG isotypes (3.2 [2.8–4.2] vs. 2.5 [2.3–3.1]; P?<?0.001) and anticardiolipin IgG isotypes (2.2 [1.9–2.7] vs. 1.4 [1.4–1.9]; P?<?0.001) were significantly higher in HIV-infected women than in HIV-infected men. Antiphospholipid IgG/IgM and anticardiolipin IgG/IgM were significantly correlated in HIV-infected men and women when they did not had any correlation in controls. We suggest that HIV infection accelerate thrombosis in women more profoundly than in men, as a result of differences in disease progression and response to therapy in these patients.     

Safety and Efficacy of Non-Cemented Femoral Fixation in Patients 75 Years of Age and Older

The aim of this study was to assess peri-operative complications, safety and efficacy of non-cemented femoral fixation in total hip arthroplasty (THA) as compared to cemented femoral fixation in the elderly population. Fifty-two matched pair analysis of patients with 75 years of age and older (104 patients), who underwent primary THA from June 1997 to December 2004, was performed based on age, sex, BMI, and Charnley classification. Mean age was 81 years (75–101) and the average follow up was 3.1 ± 2.9 years (1.2–6.4). There was no difference in peri-operative cardiopulmonary complications, pulmonary failures, deep venous thrombosis, pulmonary embolus, length of stay, or discharge deposition between the two groups. Non-cemented fixation is safe and effective in patients older than 75 years of age.     

Doxorubicin-conjugated D-glucosamine- and folate- bi-functionalised InP/ZnS quantum dots for cancer cells imaging and therapy

Nanoscaled quantum dots (QDs), with unique optical properties have been used for the development of theranostics. Here, InP/ZnS QDs were synthesised and functionalised with folate (QD-FA), D-glucosamine (QD-GA) or both (QD-FA-GA). The bi-functionalised QDs were further conjugated with doxorubicin (QD-FA-GA-DOX). Optimum Indium to fatty acid (In:MA) ratio was 1:3.5. Transmission electron microscopy (TEM) micrographs revealed spherical morphology for the QDs (11?nm). Energy-dispersive spectroscopy (EDS) spectrum confirmed the chemical composition of the QDs. MTT analysis in the OVCAR-3 cells treated with bare QDs, QD-FA, QD-GA, QD-FA-GA and QD-FA-GA-DOX (0.2?mg/mL of QDs) after 24?h indicated low toxicity for the bare QDs and functionalised QDs (about 80–90% cell viability). QD-FA-GA-DOX nanoparticles elicited toxicity in the cells. Cellular uptake of the engineered QDs were investigated in both folate receptor (FR)-positive OVCAR-3 cells and FR-negative A549 cells using fluorescence microscopy and FACS flow cytometry. The FA-functionalised QDs showed significantly higher uptake in the FR-positive OVCAR-3 cells, nonetheless the GA-functionalised QDs resulted in an indiscriminate uptake in both cell lines. In conclusion, our findings indicated that DOX-conjugated FA-armed QDs can be used as theranostics for simultaneous imaging and therapy of cancer.     

Chronic morphine and tramadol re‐exposure induced an anti‐anxiety effect in prepubertal rats exposed neonatally to the same drugs

Anxiety disorders are among the most common mental disorders. Drugs that are often administered to manage medical problems cause rebound anxiety. The use of morphine and tramadol has increased in recent decades. In the present study, the effects of morphine and tramadol exposure during the neonatal and prepubertal periods on anxiety‐like behaviours in prepubertal rats were investigated. Male neonate rats were injected subcutaneously with saline, morphine or tramadol (3–21 mg/kg) on a daily basis from postnatal Day (P) 8 to P14. On P22, rats were divided into seven groups (saline/saline, saline/tramadol, saline/morphine, tramadol/saline, tramadol/tramadol, morphine/saline and morphine/morphine) and were injected with saline, tramadol or morphine for seven consecutive days. All rats were tested in an elevated plus maze (EPM) on P24 (acute effects), P27 (chronic effects) and P29. Locomotor activity was increased by the second and third exposure to the EPM. Re‐exposure to chronic morphine and tramadol resulted in increased locomotor activity, whereas acute and chronic administration of these drugs induced no notable difference. Anxiety decreased markedly after re‐exposure to tramadol and this anxiolytic‐like behaviour was more dominant in EPM re‐exposure in rats that had received higher doses of tramadol. Re‐exposure to tramadol elicited a stronger anxiolytic‐like behaviour than re‐exposure to morphine. It can be concluded that repeated morphine and tramadol administration during the neonatal period followed by re‐exposure to these drugs at an immature stage produces considerable anxiolytic‐like behaviour. Exposure to chronic morphine and tramadol during the neonatal period may affect the developing brain, which may induce long‐term changes in the opioid response.