Xing SY, Wei LQ, Abushelaibi A
… +3 more, Lai KS, Lim SHE, Maran S
Drug Target Insights
· 2022 · PMID 36761068
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INTRODUCTION:: Detection and diagnosis of methicillin-resistant (MRSA) are important in ensuring a correct and effective treatment, further reducing its spread. A wide range of molecular approaches has been used for the...INTRODUCTION:: Detection and diagnosis of methicillin-resistant (MRSA) are important in ensuring a correct and effective treatment, further reducing its spread. A wide range of molecular approaches has been used for the diagnosis of antimicrobial resistance (AMR) in MRSA. This review aims to study and appraise widely used molecular diagnostic methods for detecting MRSA. METHODS:: This meta-narrative review was performed by searching PubMed using the following search terms: (molecular diagnosis) AND (antimicrobial resistance) AND (methicillin-resistant Staphylococcus aureus). Studies using molecular diagnostic techniques for the detection of MRSA were included, while non-English language, duplicates and non-article studies were excluded. After reviewing the libraries and a further manual search, 20 studies were included in this article. RAMESES publication standard for narrative reviews was used for this synthesis. RESULTS:: A total of 20 full papers were reviewed and appraised in this synthesis, consisting of PCR technique (n = 7), deoxyribonucleic acid (DNA) Microarray (n = 1), DNA sequencing (n = 2), Xpert MRSA/SA BC assay (n = 2), matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) (n = 2), MLST (n = 4), SCC typing (n = 1) and GENECUBE (n = 1). DISCUSSION:: Different diagnostic methods used to diagnose MRSA have been studied in this review. This study concludes that PCR has been extensively used due to its higher sensitivity and cost-effectiveness in the past five years
Drug Target Insights
· 2022 · PMID 36755640
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The enrichment and diversity of gut microbiota play an important role in sepsis, but the role of gut microbiota composition and early-life colonization in sepsis and septic shock has not yet been characterized. The impac...The enrichment and diversity of gut microbiota play an important role in sepsis, but the role of gut microbiota composition and early-life colonization in sepsis and septic shock has not yet been characterized. The impact of gut microbiota diversity on host immunological disorders and future treatments of inflammatory diseases are not yet fully elucidated. Further, the association between the microbiota and immune development in sepsis remains unknown, and the underlying mechanisms are not well understood. The altered composition of gut microbiota during sepsis is profoundly associated with a loss of commensal bacteria and an overgrowth of potentially pathogenic bacteria, especially AMR bacteria. Disruptions of gut microbiota diversity are directly associated with susceptibility to sepsis and a higher risk of adverse outcomes. Several studies have confirmed that a mutual association between gut microbiota and the host is important for the metabolism of essential nutrients for the organism, for gut development, and for the maturation and development of a fully functional immune system. Therefore, understanding the gut microbiota diversity, composition, and function during various inflammatory conditions and sepsis may provide a comprehensive knowledge of the mechanisms behind the pathogenesis of gut-derived infection in diseases and the design of new treatment options (e.g., probiotics or fecal microbiota transplantation). Emerging evidence displays an important role of gut microbiota and their derived metabolites in modulating the host mucosal immune response and determining the susceptibility to, as well as outcomes of sepsis.
Abidin IZ, Murphy EJ, Fehrenbach GW
… +3 more, Rezoagli E, Gately N, Major I
Drug Target Insights
· 2023 · PMID 36687797
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Drug administration through the vaginal tract is one of the oldest modalities of pharmacotherapy, and it is also one of the most explored. Since the vaginal cavity has a wide surface area, a plentiful blood supply, and a...Drug administration through the vaginal tract is one of the oldest modalities of pharmacotherapy, and it is also one of the most explored. Since the vaginal cavity has a wide surface area, a plentiful blood supply, and a complex network of blood arteries, it can evade hepatic first-pass metabolism and obtain high local drug concentrations. Vaginal pills look to be a good dose form since they are simple to use, portable, and can easily deliver the required amount of medicine. Vaginal formulations, on the other hand, are vulnerable to rapid expulsion due to the vaginal tract’s self-cleaning action, which reduces the formulation’s efficiency. Currently, there is an increasing amount of focus on mucoadhesive vaginal formulation research and development to fix the formulation at the place where the medicine can be released and/or absorbed. This article examines all of the strategies used by researchers to develop a mucoadhesive vaginal tablet that is safe, effective, and comfortable for the user.
Drug Target Insights
· 2022 · PMID 36644017
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Drug-resistant infections are a serious threat globally which demands cost-effective solutions to meet the unmet needs in their diagnosis and treatment. Gram-negative pathogens, drug-resistant tuberculosis, and multidrug...Drug-resistant infections are a serious threat globally which demands cost-effective solutions to meet the unmet needs in their diagnosis and treatment. Gram-negative pathogens, drug-resistant tuberculosis, and multidrug-resistant have been reported as cause of resistant infections in developing countries. Here, we discuss the priority pathogens and conditions for which feasible solutions adaptable to low-resource settings are required to address the antimicrobial resistance in pathogens. These solutions will be helpful in containing the spread of antimicrobial resistance and better patient outcomes.
Duong TB, Duong MC, Campbell JI
… +5 more, Nguyen HVM, Nguyen HH, Bui HTB, Nguyen CVV, Heywood A
Drug Target Insights
· 2022 · PMID 36636735
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BACKGROUND:: Little is known about the magnitude and patterns of methicillin-resistant (MRSA) carriage among intensive care unit (ICU) healthcare workers (HCWs), especially in lower-middle-income countries like Vietnam....BACKGROUND:: Little is known about the magnitude and patterns of methicillin-resistant (MRSA) carriage among intensive care unit (ICU) healthcare workers (HCWs), especially in lower-middle-income countries like Vietnam. MATERIALS AND METHODS:: A prospective cohort study was conducted on HCWs working in the adult ICU of the Hospital for Tropical Diseases in Vietnam between October 28 and December 20, 2019. These HCWs included physicians, nurses, and nursing assistants who were responsible for all essential medical activities and basic patient care. A questionnaire was used to collect participants’ information, including age, sex, profession, ICU working time, and underlying diseases. Hand and nasal swabs were collected weekly for 8 consecutive weeks for MRSA screening. Staphylococcal isolates were checked for catalase and coagulase and, for methicillin resistance using cefoxitin disk diffusion, then rechecked on the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. RESULTS:: Among 55 HCWs, 16 (29.1%) carried MRSA in their noses or hands. MRSA intermittent hand carriage was documented in 2 (3.6%) HCWs. Among 53 HCWs undertaking nasal swabs, 13 (24.5%) were MRSA persistent and 3 (5.6%) were intermittent carriers. The MRSA carriage rate was highest among nursing assistants (50%, 4/8). More HCWs with underlying diseases were found to be MRSA carriers (31.8%, 7/22) compared with those without comorbidities (27.3%, 9/33). CONCLUSION:: MRSA carriage among HCWs is not rare. The findings highlight an urgent need to review and update the local infection prevention and control measures to prevent MRSA transmission from HCWs to patients.
Shah SF, Paracha SA, Ullah W
… +6 more, Muhammad I, Iqbal S, Gul A, Hussain M, Ullah H, Zaman S
Drug Target Insights
· 2022 · PMID 36582782
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INTRODUCTION:: is an important medical pathogen present in more than half of the world’s population. Various treatment regimen are in use for the eradication of , but due to the emergence of antibiotic resistance, its m...INTRODUCTION:: is an important medical pathogen present in more than half of the world’s population. Various treatment regimen are in use for the eradication of , but due to the emergence of antibiotic resistance, its management is a big issue for clinicians. METHODS:: In this study all suspected cases that had visited District Headquarters Hospital Kohat were considered for screening of infections. Preliminary information about their age, gender, general health conditions, occupation, etc. was taken for consideration. After recording initial signs and symptoms, samples were considered for detection using stool antigen test and endoscopy. Fourteen-day proton pump inhibitor base triple and quadruple therapy were administered to each patient. RESULTS:: In total (n = 178), there were high numbers of positivity in patients aged below 30 years (82; 46.06%), most of whom belonged to rural areas. CONCLUSION:: This study concludes that there were high numbers of positive patients aged below 30 years, and according to this study MEL (Metronidazole + Esomeprazole + Levofloxacin) is the most effective treatment regimen for the eradication of .
Drug Target Insights
· 2022 · PMID 36582781
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The world is under the great threat of antimicrobial resistance (AMR) leading to premature deaths. Microorganisms can produce AMR via quorum sensing mechanisms utilizing -adenosyl homocysteine/methylthioadenosine nucleos...The world is under the great threat of antimicrobial resistance (AMR) leading to premature deaths. Microorganisms can produce AMR via quorum sensing mechanisms utilizing -adenosyl homocysteine/methylthioadenosine nucleosidase (SAH/MTAN) biosynthesis. But there is no specific drug developed to date to stop SAH/MTAN, which is a crucial target for the discovery of anti-quorum sensing compound. It has been shown that indazole compounds cause inhibition of SAH/MTAN-mediated quorum sensing, but the biochemical mechanisms have not yet been explored. Therefore, in this original research, an attempt has been made to explore essential structural features of these compounds by quantitative structure-activity relationship (QSAR) and molecular docking of indazole compounds having inhibition of SAH/MTAN-mediated quorum sensing. The validated QSAR predicted five essential descriptors and molecular docking helps to identify the active binding amino acid residues involved in ligand-receptor interactions that are responsible for producing the quorum sensing inhibitory mechanisms of indazole compounds against SAH/MTAN-mediated AMR.
Drug Target Insights
· 2022 · PMID 36479338
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OBJECTIVES:: Excessive use of antibiotics has increased antimicrobial resistance (AMR) worldwide, which is a major public concern among the countries. To control this threat proper monitoring of the antimicrobial usage w...OBJECTIVES:: Excessive use of antibiotics has increased antimicrobial resistance (AMR) worldwide, which is a major public concern among the countries. To control this threat proper monitoring of the antimicrobial usage with increasing rate of AMR is required. Moreover, alternatives for antibiotics are surveyed and are being researched for quick use in the future. Thus, multisector intervention is highly encouraged for better outcomes. In this research article, six different European countries are discussed in terms of antimicrobial usage and AMR in human and livestock sectors with the help of literature study and various reports published by different organizations. METHODS:: Data study has been conducted to collect data for comparison study. Data sources of AMR and antimicrobial usage are analyzed and both antimicrobial use and AMR are compared. RESULTS:: This article provides surveillance systems that are formed to keep a track on the upcoming situation of AMR and the consumption of antimicrobials by humans as well as animals. The article firmly allows the readers to get broad information about the AMR across six countries of Europe. These annual reports have hugely helped the government to decide for alternatives and have focused in many training activities to combat the AMR situation globally. CONCLUSION:: As antibiotic resistance genes persist on an interface between environment and animal and animal health, an approach is required in all three areas that stress the concept of “One Approach to Health.”
Sen P, Vijay M, Singh S
… +2 more, Hameed S, Vijayaraghavan P
Drug Target Insights
· 2022 · PMID 36458152
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Aspergilli are ubiquitous fungal pathogens associated with severe life-threatening infections, especially in immunocompromised patients. Azoles are the first line of defence in the fight against most -related infections....Aspergilli are ubiquitous fungal pathogens associated with severe life-threatening infections, especially in immunocompromised patients. Azoles are the first line of defence in the fight against most -related infections. However, resistance to these therapeutic compounds has developed, which is mainly due to the existence of mutations in lanosterol 14 alpha-demethylase (Cyp51A), a crucial enzyme in the pathway that produces ergosterol and is the target of azole antifungals. Azole-based antifungal medications are ineffective because of infections brought on by azole-resistant species, leading to a high fatality rate. However, resistant isolates have also been isolated from azole-naïve patients. Global agricultural practices promote the use of azole fungicides to protect crops from phytopathogens. Usage of azole fungicides on a large scale has been linked to the development of resistance among species prevalent in the environment. The infections caused by these azole-resistant species cannot be treated by the available azole drugs, in turn leading to high morbidity and mortality rates. Thus, knowledge of the environmental drivers and comprehending the genetic basis of fungal drug resistance evolution is pertinent, considering increasing numbers of patients with COVID-19 infections who are sensitive to opportunistic fungal infections. This article emphasises the prevalence and underlying mechanisms of azole resistance in species, with a focus on environmental triggers and resistance development. It also highlights the need for regular surveillance of pesticide use in agriculture, detection of triazole-resistant species in environmental and clinical settings and development of new antifungal drugs.
Drug Target Insights
· 2022 · PMID 36415217
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INTRODUCTION:: infection (CDI) is a leading cause of gastrointestinal infections and in the present day is a major concern for global health care system. The unavailability of specific antibiotics for CDI treatment and...INTRODUCTION:: infection (CDI) is a leading cause of gastrointestinal infections and in the present day is a major concern for global health care system. The unavailability of specific antibiotics for CDI treatment and its emerging cases worldwide further broaden the challenge to control CDI. METHODS:: The availability of a large number of genome sequences for and many bioinformatics tools for genome analysis provides the opportunity for pangenomic analysis. In the present study, 97 strains of were used for pangenomic studies and characterized for their phylogenomic and functional analysis. RESULTS:: Pangenome analysis reveals open pangenome of and high genetic diversity. Sequence and interactome analysis of 1,481 core genes was done and eight potent drug targets are identified. Three drug targets, namely, aminodeoxychorismate synthase (PabB), D-alanyl-D-alanine carboxypeptidase (DD-CPase) and undecaprenyl diphospho-muramoyl pentapeptide beta--acetylglucosaminyl transferase (MurG transferase), have been reported as drug targets for other human pathogens, and five targets, namely, bifunctional diguanylate cyclase/phosphodiesterase (cyclic-diGMP), sporulation transcription factor (Spo0A), histidinol-phosphate transaminase (HisC), 3-deoxy-7-phosphoheptulonate synthase (DAHP synthase) and c-di-GMP phosphodiesterase (PdcA), are novel. CONCLUSION:: The suggested potent targets could act as broad-spectrum drug targets for . However, further validation needs to be done before using them for lead compound discovery.
Phungoen P, Sarunyaparit J, Apiratwarakul K
… +3 more, Wonglakorn L, Meesing A, Sawanyawisuth K
Drug Target Insights
· 2022 · PMID 36304435
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BACKGROUND:: is a common bloodstream infection pathogen in the emergency department (ED). Patients with extended-spectrum beta-lactamase (ESBL) have a higher risk of morbidity. However, there is still debate surroundin...BACKGROUND:: is a common bloodstream infection pathogen in the emergency department (ED). Patients with extended-spectrum beta-lactamase (ESBL) have a higher risk of morbidity. However, there is still debate surrounding ESBL -associated mortality in community, intensive care unit, and tertiary care settings. In addition, there have been few studies regarding mortality in ESBL in ED settings, and results have been contradictory. METHODS:: This was a retrospective cohort study conducted at the Department of Emergency Medicine, Faculty of Medicine, Khon Kaen University in Thailand aimed at evaluating the possible association between ESBL bacteremia and mortality in the ED. The inclusion criteria were age 18 years or over, clinical presentation suspicious of infection, and positive blood culture for . Predictors for mortality were analyzed by logistic regression analysis. RESULTS:: During the study period, 273 patients presented at the ED with hemoculture positive for . Of those, 27 (9.89%) died. Five factors remained in the final model, of which plasma glucose levels, serum lactate levels, and ESBL were significantly associated with 28-day mortality in the ED with adjusted odds ratios of 0.970, 1.258, and 12.885, respectively. Plasma glucose of less than 113 mg/dL yielded a sensitivity of 80.95% and specificity of 64.29%, while serum lactate over 2.4 mmol/L had a sensitivity of 81.48% and specificity of 45.50%. CONCLUSION:: ESBL , plasma glucose, and serum lactate levels were associated with 28-day mortality in patients with bacteremia presenting at the ED.
Drug Target Insights
· 2022 · PMID 35360670
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INTRODUCTION:: Neovascular age-related macular degeneration (nAMD) is treated with antivascular endothelial growth factor (anti-VEGF) drugs. However, resistance to anti-VEGF therapy is observed in some patients. Broluciz...INTRODUCTION:: Neovascular age-related macular degeneration (nAMD) is treated with antivascular endothelial growth factor (anti-VEGF) drugs. However, resistance to anti-VEGF therapy is observed in some patients. Brolucizumab is a new-generation anti-VEGF drug for the treatment of nAMD, with proven efficacy in fluid resolution and long-lasting effects. METHODS:: We report here a case series of nAMD patients not responding to previous anti-VEGF therapy showing anatomical and functional response to a single intravitreal injection of brolucizumab. RESULTS:: Nine patients with nAMD, undergoing treatment with anti-VEGF therapy (aflibercept, bevacizumab, or ranibizumab) but with either fluid persistence or frequent fluid recurrences in retinal compartments, were switched to intravitreal brolucizumab and examined 4 weeks postinjection. No signs of active disease were observed in all but one patient, with complete retinal fluid resolution in seven patients. Central macular thickness and visual acuity significantly improved, and changes were sustained for up to 12 weeks in a subset of three patients. No adverse reactions were observed. CONCLUSIONS:: This new anti-VEGF drug showed great efficacy since the first week from the injection with a significative reduction of subretinal fluid and rapid improvement of visual acuity. In conclusion, brolucizumab administered intravitreally appears to be an effective treatment in nAMD patients, leading to both early anatomical and functional improvements.
Drug Target Insights
· 2022 · PMID 35309848
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INTRODUCTION:: Erythrodermic psoriasis (EP) is a rare and severe form of psoriasis that affects 1% to 2.25% of patients, increasing mortality risk. To date, very few therapies have been approved for the treatment of this...INTRODUCTION:: Erythrodermic psoriasis (EP) is a rare and severe form of psoriasis that affects 1% to 2.25% of patients, increasing mortality risk. To date, very few therapies have been approved for the treatment of this condition. Recently, biological therapies that specifically target inflammatory cytokines have improved the management and treatment of EP. Secukinumab, a human monoclonal antibody that specifically targets interleukin-17A (IL-17A), has been shown to be beneficial in different psoriasis settings. METHODS:: We report the case of a 72-year-old man affected by persistent EP and severe palmoplantar hyperkeratosis whose condition was not resolved after two rounds of treatment with prednisone and therapy with cyclosporine. RESULTS AND CONCLUSIONS:: Treatment with secukinumab significantly improved the symptoms of palmoplantar hyperkeratosis as early as the first week, with a decrease of psoriasis area and severity index (PASI) score from 60 to 10, showing almost complete remission after 1 month. Consistent with the current literature, secukinumab treatment showed promising and encouraging clinical outcomes in the treatment of the patient’s EP. However, more studies are needed to clarify the IL-17-dependent mechanism in the pathophysiology of EP.
Zambelli V, Rizzi L, Delvecchio P
… +11 more, Bresciani E, Rezoagli E, Molteni L, Meanti R, Cuttin MS, Bovo G, Coco S, Omeljaniuk RJ, Locatelli V, Bellani G, Torsello A
Drug Target Insights
· 2021 · PMID 34871336
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INTRODUCTION:: Acute respiratory distress syndrome (ARDS) is an acute form of diffuse lung injury characterized by (i) an intense inflammatory response, (ii) increased pulmonary vascular permeability, and (iii) the loss...INTRODUCTION:: Acute respiratory distress syndrome (ARDS) is an acute form of diffuse lung injury characterized by (i) an intense inflammatory response, (ii) increased pulmonary vascular permeability, and (iii) the loss of respiratory pulmonary tissue. In this article we explore the therapeutic potential of hexarelin, a synthetic hexapeptide growth hormone secretagogue (GHS), in an experimental model of ARDS. Hexarelin has anti-inflammatory properties and demonstrates cardiovascular-protective activities including the inhibition of cardiomyocyte apoptosis and cardiac fibrosis, both of which may involve the angiotensin-converting enzyme (ACE) system. METHODS:: In our experimental model, ARDS was induced by the instillation of 100 mM HCl into the right bronchus; these mice were treated with hexarelin (320 μg/kg, ip) before (Pre) or after (Post) HCl challenge, or with vehicle. Respiratory system compliance, blood gas analysis, and differential cell counts in a selective bronchoalveolar lavage (BAL) were determined 6 or 24 hours after HCl instillation. In an extended study, mice were observed for a subsequent 14 days in order to assess lung fibrosis. RESULTS:: Hexarelin induced a significant improvement in lung compliance and a reduction of the number of total immune cells in BAL 24 hours after HCl instillation, accompanied with a lower recruitment of neutrophils compared with the vehicle group. At day 14, hexarelin-treated mice presented with less pulmonary collagen deposition compared with vehicle-treated controls. CONCLUSIONS:: Our data suggest that hexarelin can inhibit the early phase of the inflammatory response in a murine model of HCl-induced ARDS, thereby blunting lung remodeling processes and fibrotic development.
Tongdee S, Sawunyavisuth B, Sukeepaisarnjaroen W
… +3 more, Boonsawat W, Khamsai S, Sawanyawisuth K
Drug Target Insights
· 2021 · PMID 34803374
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BACKGROUND:: Chronic obstructive pulmonary disease (COPD) is a common respiratory disease. The appropriate treatment according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline was 19-60%. Ho...BACKGROUND:: Chronic obstructive pulmonary disease (COPD) is a common respiratory disease. The appropriate treatment according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline was 19-60%. However, there are limited data on predictors of appropriate treatment in patients with COPD. This study aimed to evaluate risk factors of appropriate treatment in patients with COPD according to the GOLD guideline in a real-world community setting. METHODS:: This is a retrospective study conducted at a community hospital. Inclusion criteria were adult patients diagnosed as COPD treated at a COPD clinic. The primary outcome was the appropriate treatment, defined by correct pharmacological treatment by the GOLD guideline according to the ABCD severity assessment. Clinical predictors of appropriate treatment were executed by stepwise multivariate logistic regression analysis. RESULTS:: 136 patients with COPD met the study criteria. Of those, 100 patients had inappropriate treatment according to the GOLD guideline. Three factors were independently associated with the appropriate treatment including number of admissions, modified Medical Research Council (mMRC) score, and CAT score. These factors had adjusted odds ratio of 3.11, 2.86, and 1.26, respectively. Causes of inappropriate treatment were unavailability of long-acting muscarinic antagonist (LAMA) (51 patients; 79.69%), treated by inhaled corticosteroid (ICS) alone (12 patients; 18.75%), and treated with only bronchodilator (1 patient; 1.56%). CONCLUSIONS:: Appropriate COPD patients’ treatment according to the GOLD guideline was 26.47% in community setting. Factors associated with severity of COPD were associated with prescribing appropriate treatments.
Losi S, Berra CCF, Fornengo R
… +3 more, Pitocco D, Biricolti G, Federici MO
Drug Target Insights
· 2021 · PMID 34785884
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Adherence to prescribed medication is important to the management of all diseases, especially those of chronic nature. Drug effectiveness is substantially compromised by therapy nonadherence. We reviewed the available ev...Adherence to prescribed medication is important to the management of all diseases, especially those of chronic nature. Drug effectiveness is substantially compromised by therapy nonadherence. We reviewed the available evidences on the impact of patient preferences for therapy on adherence to a prescribed treatment in chronic diseases requiring long-term treatment. A search on PubMed retrieved 699 publications, leading to a selection of 12 publications: 6 on osteoporosis, 2 on moderate-to-severe asthma, 1 on type 1 diabetes, 1 on type 2 diabetes, 1 on kidney transplantation, and 1 on atrial fibrillation. Overall, 8 studies found a positive association between patient preference and adherence to therapy, while the others found no association. In general, overall adherence was considered to be high in the published studies. The reasons for a positive association included reduced dosing frequency, route of administration, lower costs, and favorable safety profile, which is related to the diverse nature of the pathology and its type and duration of treatment. A literature review suggests that achieving good adherence and persistence to therapy requires evaluation of patient preferences. In a period of increasingly limited resources, more effort is warranted to promote better adherence to therapy, especially when patients must self-manage their disease in the long term. Our results further highlight that insufficient attention has been given to the relationship between patient preference and adherence and point out the complex nature of adherence and the need for adequate patient education. More efforts are also needed to better understand the entity of cost savings for payers for specific treatments and the link with patient preference.
Morais AHA, de Medeiros AF, Medeiros I
… +4 more, de Lima VCO, Luz ABS, Maciel BLL, Passos TS
Drug Target Insights
· 2021 · PMID 33840996
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INTRODUCTION:: Obesity and coronavirus disease (COVID)-19 are overlapping pandemics, and one might worsen the other. METHODS:: This narrative review discusses one of the primary mechanisms to initiate acute respiratory d...INTRODUCTION:: Obesity and coronavirus disease (COVID)-19 are overlapping pandemics, and one might worsen the other. METHODS:: This narrative review discusses one of the primary mechanisms to initiate acute respiratory distress syndrome, uncontrolled systemic inflammation in COVID-19, and presents a potential candidate for adjuvant treatment. Blocking the S protein binding to angiotensin-converting enzyme 2 (ACE-2) and the 3C-like protease (3CL ) is an effective strategy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. RESULTS:: Host proteases such as FURIN, trypsin, and transmembrane serine protease 2 (TMPRSS) act in S protein activation. Tamarind trypsin inhibitor (TTI) shows several beneficial effects on the reduction of inflammatory markers (tumor necrosis factor α [TNF-α], leptin) and biochemical parameters (fasting glycemia, triglycerides, and very low-density lipoprotein [VLDL]), in addition to improving pancreatic function and mucosal integrity in an obesity model. TTI may inhibit the action of proteases that collaborate with SARS-CoV-2 infection and the neutrophil activity characteristic of lung injury promoted by the virus. CONCLUSION:: Thus, TTI may contribute to combating two severe overlapping problems with high cost and social complex implications, obesity and COVID-19.
Drug Target Insights
· 2021 · PMID 33840995
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BACKGROUND:: Eosinophilic meningitis (EOM) is an emerging parasitic disease that can be found worldwide, of which acute severe headache is a presenting symptom. Although such headaches may persist for up to 2 months, stu...BACKGROUND:: Eosinophilic meningitis (EOM) is an emerging parasitic disease that can be found worldwide, of which acute severe headache is a presenting symptom. Although such headaches may persist for up to 2 months, studies have found corticosteroid to be effective in reducing this symptom. As the most recent systematic review was published in 2015, the aim of this study was to provide a more up-to-date examination of the role of corticosteroids in EOM. METHODS:: We included randomized controlled trials of corticosteroid treatment for EOM regardless of comparators. Research articles published in five databases were searched and evaluated. The primary outcome was headache, which was compared among various treatment regimens. RESULTS:: We found a total of 257 articles after duplication removal. Of those, two met the study criteria. According to these studies, oral prednisolone alone or in a combination of albendazole resulted in fewer patients with headache after a 2-week course of treatment compared with placebo (maximum of 9.1% vs. 45.5%). The duration of headache was also shorter in the prednisolone arm vs. placebo (maximum of 5 vs. 13 days). There were no serious side effects reported. CONCLUSION:: A 2-week course of treatment with oral corticosteroid with or without albendazole reduced headaches in patients with EOM.