The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in 2019 in Wuhan, China. Clinically, respiratory tract symptoms as well as other organs disorders are observed in patients positively diagnosed coronavirus disease 2019 (COVID-19). In addition, neurological symptoms, mainly anosmia, ageusia and headache were observed in many patients. Once in the central nervous system (CNS), the SARS-CoV-2 can reside either in a quiescent latent state, or eventually in actively state leading to severe acute encephalitis, characterized by neuroinflammation and prolonged neuroimmune activation. SRAS-CoV-2 requires angiotensin-converting enzyme 2 (ACE2) as a cell entry receptor. The expression of this receptor in endothelial cells of blood-brain barrier (BBB) shows that SRAS-CoV-2 may have higher neuroinvasive potential compared to known coronaviruses. This review summarizes available information regarding the impact of SRAS-CoV-2 in the brain and tended to identify its potential pathways of neuroinvasion. We offer also an understanding of the long-term impact of latently form of SARS-CoV-2 on the development of neurodegenerative disorders. As a conclusion, the persistent infection of SRAS-CoV-2 in the brain could be involved on human neurodegenerative diseases that evolve a gradual process, perhapes, over several decades.
Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is undoubtedly the most challenging pandemic in the current century. A total of 73,953,702 confirmed cases of COVID-19 and 1,644,416 deaths were reported globally up to December 17, 2020. Therefore, in the absence of a safe and effective vaccine, it is urgent to identify a novel antiviral drug to effectively treat patients with COVID-19. On October 22, the U.S. Food and Drug Administration approved remdesivir, a nucleotide analog prodrug with broad antiviral activity, for adults and children (12 years of age and older and weighing at least 40 kg) who need to be admitted to hospital for covid-19 treatment. In order to monitor the optimization of patient clinical response profile, as well as address the challenges associated with remdesivir metabolism, highly sensitive, selective and accurate analytical methods are necessary. This review clearly covers all the analytical methods developed for the identification and quantitative determination of remdesivir and its metabolites in biological matrices, which helps the researchers in developing new methods for the analysis of remdesivir by considering the pros and cons of the previously reported methods.
Coronavirus disease 2019 (COVID-19) is a febrile respiratory illness that has spread rampantly across the globe and has emerged as one of the biggest pandemics of all time. Besides the direct effects of COVID-19 on mortality, collateral impacts on diagnosis and management of acute febrile illnesses (AFI) is a matter of great concern. The overlap in presentation, shunting of available resources and infection control precautions in patients with suspected COVID-19 result in a significant delay in diagnoses and management of AFI. This review highlights the challenges in the management of acute febrile illness during COVID pandemic and possible solutions for the same.
In vivo-mimic silkworm infection models with Mycobacterium avium and Mycobacterium intracellulare were newly established to evaluate the therapeutic effects of anti-M. avium complex (MAC) antibiotics. Silkworms raised at 37°C died within 72 hours of an injection of M. avium or M.intracellulare (2.5 × 107 colony-forming unit (CFU)/larva·g) into the hemolymph. Clinical anti-mycobacterial (tuberculosis) antibiotics were evaluated under these conditions. Clarithromycin, kanamycin, streptomycin, amikacin, and ciprofloxacin exerted therapeutic effects in a dose-dependent manner, which was consistent with those in the mouse model. Furthermore, three effective actinomycete culture broths were selected in the screening program of our microbial broth library using the silkworm model, and four active metabolites, ohmyungsamycins A and B (1 and 2), chartreusin (3), and griseoviridin (4), were identified. Among these compounds, 1 showed the lowest 50% effective dose (ED50) value (8.5 µg/larva·g), while 3 had the best ED50/minimum inhibitory concentration (MIC) ratio (7.4). These results indicate that silkworm models are a useful tool for identifying anti-MAC antibiotics candidates with veritable therapeutic effects.
Oligo L-lactates (oligolactates) that have low molecular weights less than 2000 have been reported to inhibit tumor growth and extend the survival of experimental animals. Because oligolactates are scarcely soluble in water, they require a solvent or a solubilizing agent, such as a surfactant, to be dissolved in water. However, these agents are generally cytotoxic, an in vitro assay appropriate to evaluate the inhibitory effect on tumor growth has not been developed yet. Here, we prepared a solid nanodispersion of oligolactates using an oil-in-water emulsion solvent evaporation method to evaluate its tumor inhibitory activity in vitro without a solvent or surfactant. Polyol solutions containing polyvinyl alcohol (PVA) were used as a continuous phase. The formation of nanoparticles depended on the concentrations of polyol and PVA in the continuous phase. The nanoparticles with a particle size of approximately 100 nm were obtained using 10-15% PVA and 60% propylene glycol. The obtained aqueous nanodispersion of oligolactates inhibited the growth of B16-BL6 melanoma cells in vitro, whereas the medium alone did not affect tumor cell growth. Therefore, oligo(L-lactate) nanoparticles may be useful in the research and development of oligolactates as a remedy for cancer.
Acute graft-versus-host disease (aGvHD) remains lethal as a life-threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT). Inflammatory responses play an important role in aGvHD. 5-Aminolevulinic acid combined with sodium ferrous citrate (5-ALA/SFC) has been widely reported to have a major effect on the anti-inflammatory response; however, these effects in aGvHD models have never been reported. In this study, a murine aGvHD model was developed by transferring spleen cells from donor B6/N (H-2kb) mice into recipient B6D2F1 (H-2kb/d) mice. In addition to evaluating manifestations in aGvHD mice, we analyzed the serum ALT/AST levels, liver pathological changes, infiltrating cells and mRNA expression of inflammation-related cytokines and chemokines. 5-ALA/SFC treatment significantly ameliorated liver injury due to aGvHD and decreased the population of liver-infiltrating T cells, resulting in a reduced expression of pro-inflammatory cytokines and chemokines. Furthermore, the mRNA expression proliferator-activated receptor-γcoactivator (PGC-1α) was enhanced, which might explain why 5-ALA/SFC treatment downregulates inflammatory signaling pathways. Our results indicated that 5-ALA/SFC can ameliorate liver injury induced by aGvHD through the activation of PGC-1α and modulation of the liver mRNA expression of inflammatory-related cytokines and chemokines. This may be a novel strategy for treating this disease.
The clinical profile and risk factors for mortality in dengue fever have evolved over the years. The all-cause mortality in admitted dengue patients is around 6%. We aimed to evaluate the recent change in trends of the clinical characteristics and risk factors for in-hospital mortality in adults with dengue fever. This is a retrospective study on adults with confirmed dengue fever admitted in a medical unit of a tertiary care center in North India. Medical records of confirmed dengue fever patients admitted between January 2011, and December 2016 were reviewed. Chi-squared tests with Bonferroni correction for multiple testing were used to identify risk factors for mortality. 232 records were included, of which 66.8% were males. The mean age was 31.6 ± 14 years. There were 17 deaths with an all-cause mortality rate of 7.3% with 76.5% being classified as severe dengue at admission. Among the 17 mortality cases, dyspnea (47%), tachypnea (86.7%), leucocytosis (58.8%), raised urea (80%), and elevated serum creatinine (52.9%) at presentation were significantly associated with mortality (p < 0.001). Shock at any time during the hospital stay (58.8%) was also found to be significantly associated with mortality (p < 0.001). We found that dyspnea, tachypnea, acute kidney injury, and leucocytosis at presentation was significantly associated with in-hospital mortality. Based on our results, we recommend aggressive management of patients with severe dengue and those with mild/moderate disease with the above risk factors.
Maintaining good oral health is important because oral diseases are related to systemic diseases, and community pharmacies play a key role in maintaining the health of local residents. This study aimed to examine the effects of oral health check-ups and information provision at community pharmacies on oral health-associated behaviors as well as patient satisfaction. We conducted oral health check-ups and provided information about oral health self-care to 84 patients at a community pharmacy, and then asked them to complete a questionnaire survey. One month later, we sent them a follow-up questionnaire and received responses from 66.7% (56/84) of the participants. The large majority were satisfied with the salivary test (95.2%) and the information (96.4%) we provided. Most of the participants (89.3%) indicated that they wanted to use the oral health check-up service again in the future. Compared with baseline, the ratio of participants restricting their intake of sugar-rich foods and drinks significantly increased 1 month later (p = 0.021). About 60% of those who had not undergone a regular dental examination at baseline reported newly visiting or planning to visit a dental clinic. The results revealed high satisfaction with the oral health check-up and information about oral self-care they received at the community pharmacy. The results suggested that oral health check-ups had the potential to change both oral self-care habits and dental consultation behavior. Our findings indicate that community pharmacies can contribute to the maintenance and promotion of oral health by providing oral health check-ups to local residents.
New strategies for early diagnosis and careful follow-up of systemic sclerosis are urgently needed. We unconventionally used a video capillaroscopy system to measure the amount of sweating on finger pads, and investigated its clinical significance. Thirty-three Japanese patients who were diagnosed with typical or pre-clinical stage patients of systemic sclerosis were included in this study. Five healthy subjects were also included. Among twenty-one patients with typical systemic sclerosis that fulfilled ACR/EULAR 2013 classification criteria, seven had increased sweating levels. On the other hand, among twelve pre-clinical stage patients that did not fulfill the classification criteria, no patient showed increase in finger sweating. We found that there was statistically significant difference. The ratio of diffuse cutaneous systemic sclerosis was also found to be significantly higher in subjects with increased amounts of sweating than in subjects with normal levels. Furthermore, the positivity of topoisomerase I antibody was statistically higher in patients with increased sweating levels than in those without. These results indicated that measurement of finger sweating levels may be a useful tool for early diagnosis and clarification of pathogenesis in this disease.
Traditionally attributed only to Plasmodium falciparum, Plasmodium vivax has recently been reported to cause a significant burden of complicated malaria cases. The present study aimed to delineate the clinical spectrum and identify predictors for severe disease. This was a prospective observational cohort study conducted at a tertiary care hospital in North India. Patients with acute febrile illness (AFI) aged at least 14 years were included if they were diagnosed with vivax malaria based on rapid kits or peripheral smears. Clinical data and investigations during hospital stay was recorded. 439 cases of acute febrile illness were screened, of whom 50 (11%) were diagnosed with malaria including eight P. falciparum infections. Forty-two vivax malaria cases, 22 (52%) of whom were severe, were followed till discharge or death. The median age of the cohort was 24.5 years (Q1-Q3, 19-36 years), including a total of 29 males (69%). Severe malaria was more frequently associated with historical complaints of oliguria or dyspnea, and examination findings of pallor, splenomegaly or altered sensorium. The following five factors were identified to predict severe disease: prolonged illness over 7 days, symptoms of oliguria or dyspnea, examination findings of pallor or crepitations on auscultation. Malaria accounts for 1 in 10 cases of AFI at our North Indian tertiary care center and approximately half of them present with severe disease. Prolonged duration of disease prior to presentation is a modifiable predictor for severe disease and should be targeted for reducing morbidity.