Skoochies and component substances induced testicular damage and impaired sperm functions via increase generation of reactive oxygen species and impairment of the glutathione system in rats.

OBJECTIVE: To study examined the effect of skoochies, an illicit cocktail drink, on testicular and sperm function in male rats. DESIGN: Twenty-five adult male Wistar rats were assigned randomly into five groups (n = 5), as follows: Normal saline (NS group), skoochies (SK group), cannabis sativa (CS group), codeine (CO group), and tramadol (TM group). The cocktail (skoochies) used for this study was formulated using the following composition: codeine (5mg/kg), tramadol (20mg/kg) and cannabis extract (2mg/kg). These doses are as previously reported. Administration was done once daily for twenty-eight (28) days. RESULTS: Skoochies increased reactive oxygen species generation and impaired the antioxidant system resulting in inflammation that eventually damage the testicular tissue. Skoochies causes oxido-inflammatory injury to the testicular tissues resulting in impaired testicular functions. This was evident by the distorted cytoarchitecture, reduced sperm count, motility and impaired testicular DNA integrity. CONCLUSION: Thus, our results infer that Skoochies induced the impairment of testicular and sperm function through the increased generation of reactive oxygen species and impairment of the glutathione system.

Lecithin and cardiovascular health: a comprehensive review.

BACKGROUND: Cardiovascular diseases are one of the prime causes of mortality globally. Therefore, concerted efforts are made to prevent or manage disruptions from normal functioning of the cardiovascular system. Disruption in lipid metabolism is a major contributor to cardiovascular dysfunction. This review examines how lecithin impacts lipid metabolism and cardiovascular health. It emphasizes lecithin's ability to reduce excess low-density lipoproteins (LDL) while specifically promoting the synthesis of high-density lipoprotein (HDL) particles, thus contributing to clearer understanding of its role in cardiovascular well-being. Emphasizing the importance of lecithin cholesterol acyltransferase (LCAT) in the reverse cholesterol transport (RCT) process, the article delves into its contribution in removing surplus cholesterol from cells. This review aims to clarify existing literature on lipid metabolism, providing insights for targeted strategies in the prevention and management of atherosclerotic cardiovascular disease (ASCVD). This review summarizes the potential of lecithin in cardiovascular health and the role of LCAT in cholesterol metabolism modulation, based on articles from 2000 to 2023 sourced from databases like MEDLINE, PubMed and the Scientific Electronic Library Online. MAIN BODY: While studies suggest a positive correlation between increased LCAT activities, reduced LDL particle size and elevated serum levels of triglyceride-rich lipoprotein (TRL) markers in individuals at risk of ASCVD, the review acknowledges existing controversies. The precise nature of LCAT's potential adverse effects remains uncertain, with varying reports in the literature. Notably, gastrointestinal symptoms such as diarrhea and nausea have been sporadically documented. CONCLUSIONS: The review calls for a comprehensive investigation into the complexities of LCAT's impact on cardiovascular health, recognizing the need for a nuanced understanding of its potential drawbacks. Despite indications of potential benefits, conflicting findings warrant further research to clarify LCAT's role in atherosclerosis.

Disruptive consequences of monosodium glutamate on male reproductive function: A review.

Monosodium glutamate (MSG) is one of the most extensively used flavour enhancers worldwide. Although it is widely regarded as a safe food additive with no recommended daily dosage, its over-consumption has been associated with notably pathophysiological events in various tissues and organs of the body. Previous studies have reported of the neuro- cardio- and hepato- toxic effects of its excessive exposure. Moreover, the food additive instigates metabolic dysfunction. It has been established that MSG damages male reproductive accessory organs like prostate glands and epididymis. In addition, it impairs serum enzymatic activities and serum levels of testosterone, gonadotropin-releasing hormone, luteinizing hormone and cholesterol. Reduced sperm count, sperm motility, sperm morphology, and sperm viability, imbalances in male reproductive hormones, alongside alteration in the histoarchitecture of the testes and other male reproductive tissues have also been connected with excessive exposure to MSG. Literature reports affirm the link between the over-consumption of MSG and reproductive organ weight and male sexual behaviour. This review article addresses the multi-systemic effects of exposure to MSG and the possible mechanism of action of the compound with a focus on the negative implications of the food additive on male reproductive functions and the possible role of natural antioxidants in male reproductive functions. carefully selected keywords were used during the literature search to gather credible and up-to-date information about the subject matter.

Mechanism associated with changes in male reproductive functions during ageing process.

Ageing is a natural process with physiological changes in different body parts and has been associated with decreased reproductive capacity. Factors such as imbalance in the antioxidant defence system, vascular diseases, diabetes mellitus, accessory reproductive glands infection, obesity as well as buildup of toxic substances play a role in age-related male reproductive malfunction. Age is inversely proportional to volume of semen, sperm count, sperm progressive motility, sperm viability, normal sperm morphology. The observed negative correlation between ageing and semen indices contributes to male infertility and reproductive decline. Normal levels of ROS, plays crucial role in facilitating sperm function, such as capacitation, hyper-activation, acrosome reaction as well as sperm-oocyte fusion; however, a substantial elevation in the endogenous level of ROS, especially in reproductive tissues, usually instigates destruction of sperm cells and heightened male infertility. Contrarily, antioxidants, such as vitamins C and E, beta-carotene, and micronutrients like zinc and folate, have been found by researchers to facilitate normal semen quality and male reproductive function. Furthermore, the role of hormonal imbalance as a result of the compromised hypothalamic-pituitary-gonadal axis, Sertoli and Leydig cells disorder, and nitric oxide-medicated erectile dysfunction during ageing cannot be undermined.

Catechin from Anonna senegalensis is a Potential Inhibitor of Erectile Dysfunction: Implication for Its Use in Male Sexual Enhancement.

Erectile dysfunction (ED) is a major challenge for men. The drugs for its treatment are associated with side effects. Hence, in phytomedicinal research, where Anonna senegalensis (A. senegalensis) is a candidate with abundant phytochemicals possessing various pharmacological properties, but the sex-enhancing phytochemical is elusive in the literature. This study aimed to understand the molecular interaction of its potent molecule mediating male sexual enhancement. A library of 69 compounds from A. senegalensis was docked against the ED-targeted proteins. Sildenafil citrate was used as the reference standard. Thereafter, the lead compound was screened for drug-likeness by applying the Lipinski rule of 5 (RO5), pharmacokinetic properties, and bioactivity using SwissADME and Molinspiration web servers, respectively. The results show catechin as the lead phytochemical compound with a stronger binding affinity for most of the proteins of ED. Also, catechin demonstrates good compliance with the RO5, great pharmacokinetic profiles, and could be said to be a polypharmacological molecule with good bioactivity scores. The research findings unravel the potential of catechin (a phytochemical belonging to the flavonoids class) from A. senegalensis leaf as a potential male sexual enhancement molecule via its high binding affinity for most erectile dysfunction-targeted proteins. They may require further toxicity and therapeutic evaluations in vivo.

Epidemiologic evidence linking oxidative stress and pulmonary function in healthy populations.

Respiratory health in the general population declines regardless of the presence of pulmonary diseases. Oxidative stress has been implicated as one of the mechanisms involved in respiratory dysfunction. This review was to evaluate studies that relate oxidative stress factors with pulmonary function among the general population without prior respiratory illnesses. The search yielded 54 citations. Twenty-one studies qualified for incorporation in this review. Owing to the heterogeneity of the review, studies were discussed based on identified oxidative stress factors responsible for pulmonary dysfunction. Oxidative stress biomarkers, including gene polymorphisms of nuclear factor erythroid 2-related factor 2, heme oxygenase 1, glutathione S transferase, superoxide dismutase, and lipid peroxidation products were involved in lung function decline. In addition, the antioxidant status of individuals in reference to dietary antioxidant intake and exposure to environmental pollutants affected oxidative stress and pulmonary function, as indicated by forced expired volume in one second, forced vital capacity, and forced expiratory flow at 25%-75%. This review indicated that oxidative stress is implicated in the gradual decline of lung function among the general population, and gene polymorphism along the antioxidant defense line and/or their interaction with air pollutants reduce lung function. Different polymorphic forms among individuals explain why the rate of lung function decline differs among people. Dietary antioxidants have respiratory health benefits in antioxidant gene polymorphic forms. Therefore, the genetic composition of an individual may be considered for monitoring and identifying people at risk of respiratory illnesses.

Designing a conserved peptide-based subunit vaccine against SARS-CoV-2 using immunoinformatics approach.

The widespread of coronavirus (COVID-19) is a new global health crisis that poses a threat to the world. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in bats and was discovered first in Wuhan, Hubei province, China in December 2019. Immunoinformatics and bioinformatics tools were employed for the construction of a multi-epitope subunit vaccine to prevent the diseases. The antigenicity, toxicity and allergenicity of all epitopes used in the construction of the vaccine were predicted and then conjugated with adjuvants and linkers. Vaccine Toll-Like Receptors (2, 3, 4, 8 and 9) complex was also evaluated. The vaccine construct was antigenic, non-toxic and non-allergic, which indicates the vaccines ability to induce antibodies in the host, making it an effective vaccine candidate. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40203-020-00062-x.

Rohypnol-induced sexual dysfunction is via suppression of hypothalamic-pituitary-testicular axis: An experimental study in rats.

Sexual activity is an essential part of reproductive functions and needed for the maintenance of fertility. Drugs, particularly substances of abuse, impair male reproductive function either by interrupting hormonal functions or through the nonhormonal pathways. This study evaluated the impact of Rohypnol use in sexual behaviour. Materials and methods: Thirty adult male Wistar rats of comparable weights (180-200 g) were randomly allocated into three groups, the control and low-dose and high-dose Rohypnol-treated groups. The control group received 0.5 ml of distilled water, while the low- and high-dose Rohypnol-treated groups received 2 mg/kg b.w and 4 mg/kg b.w of Rohypnol via oral lavage once daily for 28 days. Rohypnol significantly increased mount latency, intromission latency, ejaculation latency and post-ejaculatory interval, as well as lowered mount frequency, intromission frequency and ejaculation frequency. Rohypnol-induced sexual dysfunction was found to be associated with significant suppression of circulatory follicle-stimulating hormone, luteinising hormone, testosterone and oestrogen. The present study reveals that Rohypnol induces sexual dysfunction through suppression of hypothalamic-pituitary-testicular axis. It also implicates Rohypnol as a potential candidate for drug-induced infertility.

Dysthyroidism induces hepatorenal injury by modulating HSP70/HSP90 and VEGF signaling in male Wistar rats.

Thyroid hormones have been shown to promote the generation of reactive oxygen species (ROS), consumption of antioxidants, and induction of oxidative stress, which triggers the release of heat shock proteins (HSPs) and VEGF-dependent angiogenesis. The present study investigated the effect of altered thyroid states, hypothyroidism and hyperthyroidism on hepatic and renal functions, oxidative stress biomarkers, and hepatorenal expressions of HSP70, HSP90, and VEGF. Male Wistar rats were randomized into vehicle-treated control, carbimazole-induced hypothyroidism, or levothyroxine-induced hyperthyroidism. Altered thyroid states caused impaired hepatic and renal functions accompanied by elevated malondialdehyde and reduced glutathione content and superoxide dismutase and catalase activities in the hepatic and renal tissues. These derangements were associated with down-regulation of hepatic and renal HSP70 and HSP90 and upregulation of hepatic and renal VEGF expression. Findings of histopathological examinations of the hepatic and renal tissues align with the biochemical derangements observed.   This study reveals that dysthyroidism impairs hepatorenal function via induction of oxidative stress and modulation of HSP70/HSP90/VEGF signaling.

Exploration of surface glycoprotein to design multi-epitope vaccine for the prevention of Covid-19.

Stimulation and generation of T and B cell-mediated long-term immune response are essential for the curbing of a deadly virus such as SAR-CoV-2 (Severe Acute Respiratory Corona Virus 2). Immunoinformatics approach in vaccine design takes advantage of antigenic and non-allergenic epitopes present on the spike glycoprotein of SARS-CoV-2 to elicit immune responses. T cells and B cells epitopes were predicted, and the selected residues were subjected to allergenicity, antigenicity and toxicity screening which were linked by appropriate linkers to form a multi-epitope subunit vaccine. The physiochemical properties of the vaccine construct were analyzed, and the molecular weight, molecular formula, theoretical isoelectric point value, half-life, solubility score, instability index, aliphatic index and GRAVY were predicted. The vaccine structure was constructed, refined, validated, and disulfide engineered to get the best model. Molecular binding simulation and molecular dynamics simulation were carried out to predict the stability and binding affinity of the vaccine construct with TLRs. Codon acclimatization and in silico cloning were performed to confirm the vaccine expression and potency. Results obtained indicated that this novel vaccine candidate is non-toxic, capable of initiating the immunogenic response and will not induce an allergic reaction. The highest binding energy was observed in TLR4 (Toll-like Receptor 4) (-1398.1), and the least is TLR 2 (-1479.6). The steady rise in Th (T-helper) cell population with memory development was noticed, and IFN-g (Interferon gamma) was provoked after simulation. At this point, the vaccine candidate awaits animal trial to validate its efficacy and safety for use in the prevention of the novel COVID-19 (Coronavirus Disease 2019) infections.

Laboratory diagnosis of COVID-19 in Africa: availability, challenges and implications.

The COVID-19 infection has been a matter of urgency to tackle around the world today, there exist 200 countries around the world and 54 countries in Africa that the COVID-19 infection cases have been confirmed. This situation prompted us to look into the challenges African laboratories are facing in the diagnosis of novel COVID-19 infection. A limited supply of essential laboratory equipment and test kits are some of the challenges faced in combatting the novel virus in Africa. Also, there is inadequate skilled personnel, which might pose a significant danger in case there is a surge in COVID-19 infection cases. The choice of diagnostic method in Africa is limited as there are only two available diagnostic methods being used out of the six methods used globally, thereby reducing the opportunity of supplementary diagnosis, which will further lead to inappropriate diagnosis and affect the accuracy of diagnostic reports. Furthermore, challenges like inadequate power supply, the method used in sample collection, storage and transportation of specimens are also significant as they also pose their respective implication. From the observations, there is an urgent need for more investment into the laboratories for proper, timely, and accurate diagnosis of COVID-19.

The physiology of male reproduction: Impact of drugs and their abuse on male fertility.

Male factor accounts for about 30-50% of infertility. A common cause of male infertility is drug abuse; either illicit or prolonged use of prescribed drugs. This study provides a review of the physiology of the hypothalamic-pituitary-gonadal axis and recent literature on drugs that have been linked to male infertility and the associated mechanisms. Relevant peer-reviewed papers were assessed online using PubMed/PubMed Central, Scopus, AJOL, Google Scholar and DOAJ databases using Medical Subjects Headings (MeSH) indexes and relevant key word searches. Although drugs are beneficial when used at therapeutic levels, the abuse leads to impairment of hypothalamic-pituitary-gonadal functions, increased sperm DNA fragmentation and apoptosis, and reduced sperm quality. A good knowledge of the physiology of the hypothalamic-pituitary-gonadal axis and the influence of drugs on male fertility will guide healthcare providers in managing cases of infertility.

Staging of the estrous cycle and induction of estrus in experimental rodents: an update.

BACKGROUND: Determination of the phases of the estrous cycle and induction of estrus (heat) in experimental animals remains useful, especially in reproductive function research. MAIN BODY OF THE ABSTRACT: This review provides a detailed description and discusses extensively the variations observed in different phases of the estrous cycle in laboratory animals using rats and mice as examples. It also illustrates how these phases can be determined and how to induce estrus 'heat' when required. The phases of the estrous cycle can be determined using various methods such as visual assessment, vaginal smear/cytology, histology of female reproductive organs (vagina, uterus and ovaries), vaginal wall impedance assessment and determination of urine biochemical parameters. Female animals can be artificially brought to estrus phase 'heat' to make them receptive to male counterparts. CONCLUSION: Determination of the length and phases of the estrous cycle and induction of estrus are useful in teaching and research and evaluating the effects of drugs/chemicals on the reproductive functions.

A Critique of Computer Simulation Software's Used in Pharmacokinetics and Pharmacodynamics Analysis.

BACKGROUND: In the pharmaceutical sectors, the computer plays a crucial role as a commander of all the theoretical aspects and provides a workbench to improve the overall quality of pharmaceutical research and development. The aim of this article is to provide a computational approach to the development of numerous technology of computer software in the field of clinical pharmacokinetics. The computational technique practised by clinical pharmacist and scientist with the applied knowledge and skills in dealing with clinical pharmacokinetics problems can be applied in routine clinical practices. METHODS: To solve the various complicated pharmacokinetic equations and modeling of pharmacokinetic processes, various software were used like Population pharmacokinetics, Individual pharmacokinetics, Absorption, Distribution, Metabolism, and Excretion (ADME) pharmacokinetics, in - silico pharmacokinetics like Window-Based Non-linear model fitting (WinNonlin), Statistical Analysis Software (SAS), Non-linear Mixed Effects Modelling (NONMEM), PK Solution etc. Results: Various software's which was described in this paper help in the development of experimental study designs, statistical treatment of data and various simulation studies, etc. A robust software solution should be easy to use and address the three main parts of the PK-PD workflow like data management, analysis, and reporting. PK-PD software's allow researchers to predict ADME properties of new drug entity. For the study of the pharmacokinetic, the best software is WINBUGS where there is no limitation of dimensional array and size of the problem. The best software to be used for individual pharmacokinetics is T.D.M.S in which, we can apply Bayesian and least square method for curve fitting and it can be used for both linear and non-linear pharmacokinetic data. CONCLUSION: Various software were discussed here. This software not only help in knowing the history of the software but also help in gaining more knowledge about pharmacokinetics and pharmacodynamics simulation. Different software such as population pharmacokinetic, individual pharmacokinetic and others discussed in this article will help in the reporting and analyzing of data. The important points to be considered while selecting the software is also discussed which will help in easy accessing of software.