Barium chloride dose‐dependently induced heart and lung injury in Wistar rats

Barium (Ba) is one of the environmental pollutant metals that incite deleterious effects on human health. The present study investigated the effects of exposure to different doses of barium chloride (BaCl₂) on heart and lung of Wistar rats. Rats were exposed to BaCl₂ at 150, 300, and 600 mg/L for seven consecutive days. Results indicated that exposure to Ba caused heart and lung damage evidenced by significant increase in plasma lactate dehydrogenase and creatine kinase activities, total cholesterol, triglyceride, and low‐density lipoprotein‐cholesterol levels, while high‐density lipoprotein‐cholesterol level decreased when compared with control. Moreover, BaCl₂ significantly decreased superoxide dismutase, catalase, and acetylcholinesterase activities as well as glutathione level in heart and lung of the treated rats. Furthermore, the dose‐dependent increase in cardiac and lung lipid peroxidation, advanced oxidative protein product and nitric oxide levels were accompanied by marked increase in metallothionein in the BaCl₂‐treated rats. Administration of BaCl₂ altered hematological parameters and significantly increased concentrations of interleukin‐6 in the treated rats. Histology analysis showed significant alteration in the heart and lung tissues of Ba‐treated rats. In conclusion, BaCl₂‐induced heart and lung damages via disruption of antioxidant defense systems, and activation of inflammatory mediators and alteration in hematological parameters in rats.     

Dietary stigmastane-type saponins as promising dual-target directed inhibitors of SARS-CoV-2 proteases: a structure-based screening

Despite the development of COVID-19 vaccines, at present, there is still no approved antiviral drug against the pandemic. The SARS-CoV-2 3-chymotrypsin-like proteases (S-3CLpro) and papain-like protease (S-PLpro) are essential for the viral proliferation cycle, hence attractive drug targets. Plant-based dietary components that have been extensively reported for antiviral activities may serve as cheap sources of preventive nutraceuticals and/or antiviral drugs. A custom-made library of 176 phytochemicals from five West African antiviral culinary herbs was screened for potential dual-target-directed inhibitors of S-3CLpro and S-PLpro in silico. The docking analysis revealed fifteen steroidal saponins (FSS) from Vernonia amygdalina with the highest binding tendency for the active sites of S-3CLpro and S-PLpro. In an optimized docking analysis, the FSS were further docked against four equilibrated conformers of the S-3CLpro and S-PLpro. Three stigmastane-type steroidal saponins (vernonioside A2, vernonioside A4 and vernonioside D2) were revealed as the lead compounds. These compounds interacted with the catalytic residues of both S-3CLpro and S-PLpro, thereby exhibiting dual inhibitory potential against these SARS-CoV-2 cysteine proteases. The binding free energy calculations further corroborated the static and optimized docking analysis. The complexed proteases with these promising phytochemicals were stable during a full atomistic MD simulation while the phytochemicals exhibited favourable physicochemical and ADMET properties, hence, recommended as promising inhibitors of SARS-CoV-2 cysteine proteases.

Vernonia amygdalina derived phytochemicals as potential dual-target directed inhibitors of SARS-CoV-2 proteases from computational study perspective.     

Biosocial Profiles and Pattern of Complaints of New Intrauterine Device Acceptors at the University College Hospital, Ibadan, Nigeria

Objective To determine the pattern of biosocial characteristics of the new IUD acceptors and describe their concerns. Methods This was a retrospective review of records of new IUD acceptors at the University College Hospital, Ibadan, Nigeria from January to December 2007. Results The age range of subjects was 19 to 49 years with a mean of 33.5 ±% 2.4 years. The commonest source （46.0%） of clientele referral was through the health care providers -doctors and nurse/midwife. Other referral patterns were from friends/ relative （23.5%）, media -TV and radio （17.0%）, outreach programmes （7.3%）, self referral （5.2%） and others -the source was not indicated （1.2%）. Of the total participants, only 239 （56.1%） reported for follow-up visits. Majority had at least one visit; about a third had two, while others had three or four and above visits. About 43.2% of those at follow-up visits had complaints. The commonest （37.5%） complaint was menstrual irregularity. Other complaints were cramping abdominal pain （22.2%）, vaginal discharge （19.6%）, amenorrhoea （10.3%）, penile discomfort during sexual intercourse （4.3%）, expulsion of IUD （3.8%） and 2.2% of missing IUD. Conclusion This audit shows that new IUD acceptors are largely referred by health care providers and are mainly offered the TCu380A version. Community outreach programmes as alternative strategy is likely to boost the uptake of this particular method in Nigeria.     

Unilateral spinal nerve ligation leads to an asymmetrical distribution of mast cells in the thalamus of female but not male mice

Mast cells are restricted to the leptomeninges and thalamus of healthy mice. These populations are increased by stress and highly sensitive to reproductive hormones. To examine the influence of nociception, a form of stress, on thalamic mast cells, we ligated the left fifth lumbar spinal nerve of male and female mice to induce hyperalgesia. Two, 7 and 14 days later, mice were killed and thalami examined histologically using toluidine blue stain. The total number of thalamic mast cells was not influenced by ligation of the spinal nerve compared to sham-operation in either female or male mice. However, in females, the percent of thalamic mast cells located on the side of the thalamus contralateral to the ligation was greater on days 2 and 7, coincident with mechanical hyperalgesia. At these times, areas in which mast cells were most dense contralateral to nerve-injury included the posterior (Po) and lateral geniculate (LG) nuclei compared to their symmetrical distribution in sham-operated mice. These data suggest that local nociceptive signals to each side of the thalamus rather than stress hormones influence the location of mast cells during the development of allodynia and hyperalgesia. In addition, both hyperalgesia and mast cell distribution induced by nerve-ligation differ in females compared to males, reflecting a novel neuroimmune response to pain within the CNS.     

Primary Epstein-Barr virus infection does not erode preexisting CD8⁺ T cell memory in humans

Acute Epstein-Barr virus (EBV) infection results in an unusually robust CD8(+) T cell response in young adults. Based on mouse studies, such a response would be predicted to result in attrition of preexisting memory to heterologous infections like influenza A (Flu) and cytomegalovirus (CMV). Furthermore, many studies have attempted to define the lymphocytosis that occurs during acute EBV infection in humans, but it is unclear whether bystander T cells contribute to it. To address these issues, we performed a longitudinal prospective study of primary EBV infection in humans. During acute EBV infection, both preexisting CMV- and Flu-specific memory CD8(+) T cells showed signs of bystander activation, including up-regulation of granzyme B. However, they generally did not expand, suggesting that the profound CD8(+) lymphocytosis associated with acute EBV infection is composed largely of EBV-specific T cells. Importantly, the numbers of CMV- and Flu-specific T cells were comparable before and after acute EBV infection. The data support the concept that, in humans, a robust CD8(+) T cell response creates a new memory CD8(+) T cell niche without substantially depleting preexisting memory for heterologous infections.     

Cholera toxin B subunit linked to glutamic acid decarboxylase suppresses dendritic cell maturation and function

Dendritic cells are the largest population of antigen presenting cells in the body. One of their main functions is to regulate the delicate balance between immunity and tolerance responsible for maintenance of immunological homeostasis. Disruption of this delicate balance often results in chronic inflammation responsible for initiation of organ specific autoimmune diseases such as rheumatoid arthritis, multiple sclerosis and type I diabetes. The cholera toxin B subunit (CTB) is a weak mucosal adjuvant known for its ability to stimulate immunity to antigenic proteins. However, conjugation of CTB to many autoantigens can induce immunological tolerance resulting in suppression of autoimmunity. In this study, we examined whether linkage of CTB to a 5 kDa C-terminal protein fragment of the major diabetes autoantigen glutamic acid decarboxylase (GAD₃₅), can block dendritic cell (DC) functions such as biosynthesis of co-stimulatory factor proteins CD86, CD83, CD80 and CD40 and secretion of inflammatory cytokines. The results of human umbilical cord blood monocyte-derived DC-GAD₃₅ autoantigen incubation experiments showed that inoculation of immature DCs (iDCs), with CTB-GAD₃₅ protein dramatically suppressed levels of CD86, CD83, CD80 and CD40 co-stimulatory factor protein biosynthesis in comparison with GAD₃₅ alone inoculated iDCs. Surprisingly, incubation of iDCs in the presence of the CTB-autoantigen and the strong immunostimulatory molecules PMA and Ionomycin revealed that CTB-GAD₃₅ was capable of arresting PMA + Ionomycin induced DC maturation. Consistent with this finding, CTB-GAD₃₅ mediated suppression of DC maturation was accompanied by a dramatic decrease in the secretion of the pro-inflammatory cytokines IL-12/23p40 and IL-6 and a significant increase in secretion of the immunosuppressive cytokine IL-10. Taken together, our experimental data suggest that linkage of the weak adjuvant CTB to the dominant type 1 diabetes autoantigen GAD strongly inhibits DC maturation through the down regulation of major co-stimulatory factors and inflammatory cytokine biosynthesis. These results emphasize the possibility that CTB-autoantigen fusion proteins enhance DC priming of naïve Th0 cell development in the direction of immunosuppressive T lymphocytes. The immunological phenomena observed here establish a basis for improvement of adjuvant augmented multi-component subunit vaccine strategies capable of complete suppression of organ-specific autoimmune diseases in vivo.     

YouTube as a source of medical information on the novel coronavirus 2019 disease (COVID-19) pandemic

ABSTRACT

Media coverage on coronavirus disease 2019 (COVID-19) has been extensive, yet large gaps remain in our understanding of the role of social media platforms during worldwide health crisis. The purpose of this study was to assess the most viewed YouTube videos on COVID-19 for medical content. We coded video characteristics, source, and medical content of the 113 most-widely viewed videos about COVID-19. Seventy-nine (69.9%) videos were classified as useful, and 10 (8.8%) videos were classified as misleading. Independent users were more likely to post misleading videos than useful videos (60.0% vs 21.5%, P?=?0.009). News agencies were more likely to post useful videos than misleading videos (72.2% vs 40.0%, P?=?0.039). Useful videos were more likely to present any information on prevalence or incidence (79.7% vs 20.0%, P?<?0.001), as well as information on outcomes or prognosis (84.8% vs 30.0%, P?<?0.001) compared to misleading videos. The World Health Organization contributed one useful video (1.3%), while no videos from the Center for Disease Control were included. Although YouTube generally is a useful source of medical information on the COVID-19 pandemic, increased efforts to disseminate accurate information from reputable sources is desired to help mitigate disease spread and decrease unnecessary panic in the general population.     

Chronic daily intrathecal injections of a large volume of fluid increase mast cells in the thalamus of mice

Mast cells are found in the central nervous system (CNS) as well as in the periphery. In the brain of mice, they are localized primarily in the thalamus and meninges. Although their numbers increase in response to stress, the mediator of their recruitment is not known. During studies in which drugs were delivered intrathecally in a volume sufficiently large to distribute to the brain, we discovered that repeated daily injections of this large volume increased the number of mast cells in the thalamus. The increase was not due to changes in electrolyte composition of the cerebrospinal fluid (CSF) as chronically administered artificial CSF produced similar effects. Repeated injections of even small volumes (2 mul) increased mast cells in the medial intralaminar (Med), ventral posterior (VP) and posterior (Po) nuclei. Increasing the volume injected daily to 20 mul increased mast cells in the lateral intralaminar (Lat), laterodorsal (LD), ventrolateral (VL) and lateral geniculate (LG) nuclei and further increased those in the lateral extension of the Po nucleus. Thus, small and large volumes augment distinct populations of mast cells. While stem cell factor (SCF) is abundant in the CNS and is chemotactic to mast cells in the periphery, thalamic mast cells in the rodent do not express c-kit, the SCF receptor, suggesting that this factor may not be responsible for the effect. Consistent with this, centrally injected SCF was incapable of increasing thalamic mast cell populations after either single or chronic (21 days) daily injections compared to the effect of saline alone. Although the mechanism is not known, repeated injections of a large volume of fluid dramatically increase mast cells in the CNS, a phenomenon that may be relevant to clinical conditions of increased CSF pressure or volume.     

Langerhans cells activate naive self-antigen-specific CD8 T cells in the steady state

TCR transgenic mice that express a peptide antigen in keratinocytes develop a lethal CD8 T cell-dependent autoimmune disease. We employed an adoptive transfer system to understand this disease and show that transfer of low numbers of naive CD8 T cells into peptide transgenic mice caused chronic skin disease. The antigen-presenting cell that initiated this response was the epidermal Langerhans cell. Naive CD8 T cells proliferated extensively, migrated to tissues, developed effector function, and were capable of making a recall response. These features are very different from the abortive activation of CD8 T cells that occurred in response to the same antigen presented by APC from other tissues. Furthermore, tolerance was dominant when the antigen was presented by both Langerhans cells and other APC. These data suggest that Langerhans cells do not have tolerogenic properties in the steady state.