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1.
Antiviral Res ; 220: 105743, 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37949319

RESUMO

The COVID-19 pandemic caused by SARS-CoV-2, lead to mild to severe respiratory illness and resulted in 6.9 million deaths worldwide. Although vaccines are effective in preventing COVID-19, they may not be sufficient to protect immunocompromised individuals from this respiratory illness. Moreover, novel emerging variants of SARS-CoV-2 pose a risk of new COVID-19 waves. Therefore, identification of effective antivirals is critical in controlling SARS and other coronaviruses, such as MERS-CoV. We show that Fangchinoline (Fcn), a bisbenzylisoquinoline alkaloid, inhibits replication of SARS-CoV, SARS-CoV-2, and MERS-CoV in a range of in vitro assays, by blocking entry. Therapeutic use of Fcn inhibited viral loads in the lungs, and suppressed associated airway inflammation in hACE2. Tg mice and Syrian hamster infected with SARS-CoV-2. Combination of Fcn with remdesivir (RDV) or an anti-leprosy drug, Clofazimine, exhibited synergistic antiviral activity. Compared to Fcn, its synthetic derivative, MK-04-003, more effectively inhibited SARS-CoV-2 and its variants B.1.617.2 and BA.5 in mice. Taken together these data demonstrate that Fcn is a pan beta coronavirus inhibitor, which possibly can be used to combat novel emerging coronavirus diseases.

3.
BMC Infect Dis ; 23(1): 662, 2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37853318

RESUMO

BACKGROUND: Fortaleza (Brazil) is high endemic for coronavirus disease 2019 (COVID-19), tuberculosis (TB) and leprosy. These three diseases share respiratory droplets through coughing or sneezing as the main mode of transmission but differ in incubation time, with COVID-19 having a short and leprosy a long incubation time. Consequently, contacts of a patient are at higher risk of infection and developing these diseases. There might be scope for combined preventive measures, but a better understanding of the geographical distribution and relevant socioeconomic risk factors of the three diseases is needed first. This study aims to describe the geographic distribution of COVID-19, TB and leprosy incidence and to identify common socioeconomic risk factors. METHODS: The total number of new cases of COVID-19, TB and leprosy, as well as socioeconomic and demographic variables, were retrieved from official registers. The geographical distribution of COVID-19, TB and leprosy rates per neighbourhood was visualised in Quantum GIS, and spatial autocorrelation was measured with Moran's I in GeoDa. A spatial regression model was applied to understand the association between COVID-19, TB, leprosy rates, and socioeconomic factors. RESULTS: COVID-19 and TB showed a more homogenous distribution, whereas leprosy is located more in the south and west of Fortaleza. One neighbourhood (Pedras) in the southeast was identified as high endemic for all three diseases. Literacy was a socioeconomic risk factor for all three diseases: a high literacy rate increases the risk of COVID-19, and a low literacy rate (i.e., illiteracy) increases the risk of TB and leprosy. In addition, high income was associated with COVID-19, while low income with TB. CONCLUSIONS: Despite the similar mode of transmission, COVID-19, TB and leprosy show a different distribution of cases in Fortaleza. In addition, associated risk factors are related to wealth in COVID-19 and to poverty in TB and leprosy. These findings may support policymakers in developing (partially combined) primary and secondary prevention considering the efficient use of resources.


Assuntos
COVID-19 , Hanseníase , Tuberculose , Humanos , Brasil/epidemiologia , COVID-19/epidemiologia , Tuberculose/epidemiologia , Fatores de Risco , Fatores Socioeconômicos , Hanseníase/epidemiologia
4.
Indian Dermatol Online J ; 14(5): 643-652, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37727561

RESUMO

Background: Impact of COVID-19 pandemic has been immense. An innocent casualty of this disaster is medical education and training. Dermatology, which primarily deals with out-patient services, medical and surgical interventions, and in-patient services, was one of the worst hit. The National Medical Commission of India has implemented competency-based medical education (CBME) in Dermatology, Venereology, and Leprosy since 2019. The new curriculum relies on acquiring practical and procedural skills, training skills in research methodology, professionalism, attitude, and communication. Objectives: The study was undertaken to understand the implications of the COVID-19 pandemic on postgraduate dermatology CBME training in India. Materials and Methods: A questionnaire-based survey was carried out on postgraduate dermatology teachers and residents in India after obtaining ethics committee approval. An online semi-structured English questionnaire was administered by Google Forms. The calculated sample size was 366 dermatology faculty and 341 postgraduate students. Validity (Content validity ratio (CVR) ≥0.56) and reliability (Cronbach's alpha coefficient 0.7249) of the questionnaire were determined. Results: Among the 764 responses received, 51.4% reported that their institutes were converted to exclusive COVID hospitals. Domains of dermatology education affected were procedural training (n = 655), bedside clinical teaching (n = 613), outpatient department-based clinical teaching (n = 487), bedside laboratory procedures (n = 463), research activities (n = 453), histopathology (n = 412), and theory classes (n = 302). To keep up with the teaching-learning process, online platforms were mostly utilized: Zoom Meeting (n = 379), Google Meet (n = 287), and WhatsApp Interaction (n = 224). Teaching during ward rounds was significantly more affected in exclusively COVID institutes than non-exclusive COVID institutes (P < 0.001). Psychomotor skill development suffered a major jolt with 26.7% of respondents reporting a standstill (P < 0.001). Communication skills among students suffered due to social distancing, mask, and poor attendance of patients. According to 23.84% of respondents, formative assessment was discontinued. Conclusion: Online seminars, journal clubs, and assessments have been incorporated during the pandemic. Online modalities should be used as a supplementary method as psychomotor skills, communication skills, research work, and bedside clinics may not be replaced by the e-learning.

5.
Washington, D.C.; OPS; 2023-09-18. (PAHO/CDE/HT/23-0007).
em Espanhol | PAHOIRIS | ID: phr-58003

RESUMO

La Organización Panamericana de la Salud (OPS) es un líder reconocido en la eliminación de enfermedades, que trabaja de la mano con los países de la Región y sus asociados con el fin de impulsar los logros en materia de salud pública a nivel regional y mundial. Estos esfuerzos han contribuido a la erradicación de la viruela, la eliminación de la poliomielitis y el tétanos neonatal de la Región de las Américas, la eliminación de la transmisión endémica del sarampión, la rubéola y el síndrome de rubéola congénita, así a como la eliminación de la transmisión maternoinfantil del VIH y la sífilis en ocho países. La Región también ha avanzado de manera considerable hacia la eliminación de la malaria, la lepra, el tracoma, la filariasis linfática, la oncocercosis y la rabia humana transmitida por perros. En septiembre del 2019, el 57.° Consejo Directivo de la OPS aprobó la Iniciativa de la OPS para la Eliminación de Enfermedades, una política innovadora que promueve un enfoque integrado y sostenible encaminado a acelerar el avance de los países hacia la eliminación de las enfermedades transmisibles y otras afecciones relacionadas. La eliminación de enfermedades se basa en la trayectoria eficaz de eliminación de enfermedades en la Región de las Américas y tiene como objetivo catalizar la voluntad política y aprovechar la capacidad técnica necesaria para lograr un futuro sin la carga de 35 enfermedades transmisibles y otras afecciones relacionadas en la Región de las Américas en el 2030 y contribuir al progreso hacia los Objetivos de Desarrollo Sostenible (ODS). Al tiempo que los países se recuperan del impacto de la pandemia de COVID‑19, la OPS reconoció la importancia de convocar al Grupo Consultivo Estratégico y Técnico externo sobre eliminación de enfermedades con el objeto de hacer un balance del nuevo panorama de salud pública y las evoluciones recientes en la eliminación de enfermedades y buscar orientación y recomendaciones sobre temas prioritarios con el fin de respaldar la agenda de eliminación de enfermedades en la Región de las Américas. En el presente informe se presenta un resumen de los procedimientos, conclusiones y recomendaciones de la segunda reunión del Grupo Consultivo Estratégico y Técnico de la OPS sobre eliminación de enfermedades, que tuvo lugar el 29 y 30 de noviembre del 2022.


Assuntos
Erradicação de Doenças , Doenças Transmissíveis , COVID-19 , Sistemas de Saúde , Desenvolvimento Sustentável , América
6.
Sci Total Environ ; 904: 166672, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37657538

RESUMO

Microbial (bacteria and fungi) community structures and their distributions in urban household municipal solid waste (HMSW) were characterized in a sampling campaign in 38 cities of China covering 5 climatic zones. All samples were collected from garbage containers in residential communities during the Winter of 2022, from January 11 to 26. A total of 247 bacterial genera belonging to 22 phyla were identified among the samples. Firmicutes (44.3 %), Bacteroidetes (33.77 %) and Proteobacteria (21.54 %) were the top 3 dominant phyla, and Arcicella (33.11 %) and Leuconostoc (21.87 %) were the dominant genera. Meanwhile, 124 fungal genera from 7 fungal phyla were detected. Ascomycota was the most dominant phylum, with an average relative abundance of 77.31 %. Hanseniaspora (24.03 %), Debaryomyces (13.47 %), Candida (12.18) were the top 3 dominant fungal genera. Alpha-diversity analysis showed that the species richness and diversity of bacterial and fungal communities of HMSW samples belonging to different climatic zones did not differ significantly. Nonmetric multidimensional scaling (NMDS) analysis confirmed that climatic had an effect on microbial communities but did not show a significant correlation. In addition, the distribution of microbial community in different samples from the same climate zone varied considerably, suggesting the HMSW source play important role in shaping microbial community composition. Considering that residential HMSW is relatively fresh, we speculates that the original microorganisms residing in different components of HMSW are key influencing factor for the community, while the reshaping force driven by environmental conditions are relatively weak. In addition, the study identified 13 bacterial and 16 fungal pathogens with Pseudomonas putida (0.25 %) and Sclerotinia sclerotiorum (2.12 %) as the most abundant potential pathogenic bacteria and fungi, respectively. These findings provide valuable information for characterizing microbial features and potential risks of HMSW in its management system.


Assuntos
COVID-19 , Resíduos Sólidos , Humanos , Bactérias , China/epidemiologia , Surtos de Doenças
7.
PLoS Negl Trop Dis ; 17(8): e0011493, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37540711

RESUMO

BACKGROUND: Individuals with leprosy are at risk of leprosy reactions, T-cell mediated immunological complications, which lead to nerve function impairment. Leprosy reactions require systemic immunosuppression which is a risk factor for severe COVID-19. Vaccination for SARS-CoV-2 infection is recommended in the UK and became widely available in 2021 with individuals at increased risk of severe disease, including the immunosuppressed, prioritised. Vaccines for SARS-CoV-2 may provoke a T cell response. The latter poses a theoretical risk of provoking an immunological response to latent Mycobacterium leprae infection leading to clinical disease or in those with clinical disease triggering a leprosy reaction. BCG vaccination is associated with the development of leprosy in a small proportion of healthy contacts of people with leprosy within twelve weeks of administration. BCG causes a Th1 immune response. METHODOLOGY/PRINCIPAL FINDINGS: We performed a retrospective cohort study to determine the SARS-CoV-2 vaccination status of individuals diagnosed with leprosy attending the Leprosy Clinic in 2021 and whether any had developed leprosy or experienced a new leprosy reaction within twelve weeks of receiving a dose of a SARS-CoV-2 vaccine. The electronic patient records were used to retrieve data. Fifty-two individuals with leprosy attended the clinic in 2021 of which five people were newly diagnosed with leprosy. Thirty-seven (71%) were male and the median age was 48.5 years old (Range 27-85 years). Eight (15.4%) individuals were taking multi-drug therapy (MDT) and eight (15.4%) had completed MDT within three years of the study. Twenty-two (41.5%) individuals were prescribed a systemic immunosuppressant drug during 2021. Ten (18.9%) individuals have one or more risk factors for severe COVID-19. The SARS-CoV-2 vaccination status of fifty (96%) were recorded of which forty-nine were vaccinated (98%). One individual had declined vaccination. One individual was diagnosed with borderline tuberculoid (BT) leprosy having developed red skin lesions with reduced sensation (which increased in size and number) and thickened peripheral nerves one week after a second dose of BNT162b2 vaccine. Another individual who had completed MDT more than three years earlier developed red plaques and tender thickened nerves consistent with a leprosy Type 1 reaction eight weeks after a single dose of BNT162b2 vaccine (having received two doses of CoronaVac vaccine three months earlier). CONCLUSIONS/SIGNIFICANCE: The development of BT leprosy and a Type 1 reaction in another individual shortly after a dose of BNT162b2 vaccine may be associated with vaccine mediated T cell responses. The benefits of vaccination to reduce the risk of severe COVID-19 outweigh these unwanted events but data from leprosy endemic countries may provide further information about potential adverse effects of augmented T cell responses in individuals with leprosy or latent M. leprae infection.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Hipersensibilidade , Hanseníase , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vacina BCG/efeitos adversos , Vacina BNT162 , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Hipersensibilidade/tratamento farmacológico , Mycobacterium leprae , Estudos Retrospectivos , SARS-CoV-2 , Reino Unido/epidemiologia , Vacinação
8.
Int J Equity Health ; 22(1): 147, 2023 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-37542266

RESUMO

BACKGROUND: Research on the needs of people with disability is scarce, which promotes inadequate programs. Community Based Inclusive Development interventions aim to promote rights but demand a high level of community participation. This study aimed to identify prioritized needs as well as lessons learned for successful project implementation in different Latin American communities. METHODS: This study was based on a Community Based Inclusive Development project conducted from 2018 to 2021 led by a Columbian team in Columbia, Brazil and Bolivia. Within a sequential mixed methods design, we first retrospectively analyzed the project baseline data and then conducted Focus Group Discussions, together with ratings of community participation levels. Quantitative descriptive and between group analysis of the baseline survey were used to identify and compare sociodemographic characteristics and prioritized needs of participating communities. We conducted qualitative thematic analysis on Focus Group Discussions, using deductive main categories for triangulation: 1) prioritized needs and 2) lessons learned, with subcategories project impact, facilitators, barriers and community participation. Community participation was assessed via spidergrams. Key findings were compared with triangulation protocols. RESULTS: A total of 348 people with disability from 6 urban settings participated in the baseline survey, with a mean age of 37.6 years (SD 23.8). Out of these, 18 participated within the four Focus Group Discussions. Less than half of the survey participants were able to read and calculate (42.0%) and reported knowledge on health care routes (46.0%). Unemployment (87.9%) and inadequate housing (57.8%) were other prioritized needs across countries. Focus Group Discussions revealed needs within health, education, livelihood, social and empowerment domains. Participants highlighted positive project impact in work inclusion, self-esteem and ability for self-advocacy. Facilitators included individual leadership, community networks and previous reputation of participating organizations. Barriers against successful project implementation were inadequate contextualization, lack of resources and on-site support, mostly due to the COVID-19 pandemic. The overall level of community participation was high (mean score 4.0/5) with lower levels in Brazil (3.8/5) and Bolivia (3.2/5). CONCLUSION: People with disability still face significant needs. Community Based Inclusive Development can initiate positive changes, but adequate contextualization and on-site support should be assured.


Assuntos
COVID-19 , Pessoas com Deficiência , Humanos , Adulto , América Latina , Estudos Retrospectivos , Pandemias
9.
Am J Trop Med Hyg ; 109(2): 466-470, 2023 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-37364863

RESUMO

It remains unclear whether a previous history of tropical infectious diseases and a second SARS-COV-2 infection may influence the likelihood of later symptoms. In this prospective cohort study, individuals infected with SARS-CoV-2 were followed up by telephone shortly after diagnosis of COVID-19 and again 12 months later. Poisson regression was used to identify the predictors of the highest number of symptoms in the post-COVID-19 syndrome. A total of 1,371 patients with COVID-19, with a mean age of 39.7 ± 11.7 years and 50% female, were followed for 12 months. Reinfection was found in 32 (2.3%) participants, and 806 (58.8%) individuals reported a previous history of dengue, malaria, Zika, chikungunya, leprosy, and visceral leishmaniasis. Eight hundred seventy-seven (63.9%) participants reported late symptoms related to COVID-19. After adjusting for multiple factors, female sex, non-White race, number of acute-phase symptoms, body mass index, and reinfection were independent predictors of higher number of symptoms in post-COVID-19 syndrome. Female sex, non-White race, number of acute-phase symptoms, body mass index, and reinfection, but not previous endemic tropical diseases, were associated with long-term symptoms.


Assuntos
COVID-19 , Infecção por Zika virus , Zika virus , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Masculino , COVID-19/epidemiologia , Estudos de Coortes , Prevalência , SARS-CoV-2 , Síndrome Pós-COVID-19 Aguda , Estudos Prospectivos , Reinfecção
10.
Indian J Dermatol Venereol Leprol ; 89(6): 862-866, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37317744

RESUMO

Background Data on outcomes of Coronavirus disease 2019 (COVID-19) infection in autoimmune bullous diseases (AIBDs) patients is scarce. Materials and methods This single-centre survey-based-observational study included patients registered in the AIBD clinic of the Postgraduate Institute of Medical Education and Research, Chandigarh, India. All registered patients were contacted over telephone between June and October 2021. A survey was conducted after obtaining informed consent. Results Among 1389 registered patients, 409 completed the survey. Two hundred and twenty-two (55.3%) patients were females and 187 (45.7%) were males. The mean age was 48.52 ± 14.98 years. Active disease was reported by 34% patients. The frequency of COVID-19 infection in responders was 12.2% (50/409), with a case-fatality ratio of 18% (9/50). Rituximab infusion after the onset of pandemic significantly increased the risk of COVID-19 infection. Active AIBD and concomitant comorbidities were significantly associated with COVID-19 related death. Limitation Relative risk of COVID-19 infection and complications among AIBD patients could not be estimated due to lack of control group. The incidence of COVID-19 in AIBD could not be determined due to lack of denominator (source population) data. Other limitations include telephonic nature of the survey and lack of COVID-19 strain identification. Conclusion Use of rituximab is associated with higher probability of COVID-19 infection, while advanced age, active disease and presence of comorbidities may increase the risk of COVID-19 mortality in AIBD patients.


Assuntos
Doenças Autoimunes , COVID-19 , Dermatopatias Vesiculobolhosas , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Rituximab , Inquéritos e Questionários
11.
Turk Patoloji Derg ; 39(3): 206-211, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37218667

RESUMO

AIM: To document a case of lobomycosis and to discuss its epidemiology & diagnosis. CASE REPORT: A 53-year-old male presented with a history of nasal congestion, nasal discharge, and epistaxis following Covid 19 infection. On physical examination, there was necrotic slough in the nasal vestibule near the inferior turbinate. Scrapings and punch biopsy were taken from the lesion. Hematoxylin-eosin-stained sections showed necrotic and mucoid areas with mixed inflammatory cell infiltration and numerous budding yeasts 3- 7µm diameter in singles, and small clusters with single narrow based budding as well as multiple budding including sequential budding forming "chains of yeasts". A diagnosis of Lobomycosis was made. Yeasts of lobomycosis are often confused with other yeasts such as P. brasiliensis, Candida spp., B. dermatitidis, and Cryptococci, but characteristic 'sequential budding' with a 'chain of yeasts" aid in the final diagnosis. Demonstration of yeasts with characteristic chains either in tissue sections or in potassium hydroxide (KOH) preparation of scraped material, exudate, or exfoliative cytology is the mainstay in the diagnosis as the organisms are uncultivable in vitro in culture medium.


Assuntos
COVID-19 , Lobomicose , Masculino , Humanos , Pessoa de Meia-Idade , Lobomicose/diagnóstico , Lobomicose/patologia , COVID-19/complicações , Pele/patologia , Biópsia
12.
GigaByte ; 2023: gigabyte80, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37153490

RESUMO

Antibiotic resistance is increasing at an alarming rate, and three related mycobacteria are sources of widespread infections in humans. According to the World Health Organization, Mycobacterium leprae, which causes leprosy, is still endemic in tropical countries; Mycobacterium tuberculosis is the second leading infectious killer worldwide after COVID-19; and Mycobacteroides abscessus, a group of non-tuberculous mycobacteria, causes lung infections and other healthcare-associated infections in humans. Due to the rise in resistance to common antibacterial drugs, it is critical that we develop alternatives to traditional treatment procedures. Furthermore, an understanding of the biochemical mechanisms underlying pathogenic evolution is important for the treatment and management of these diseases. In this study, metabolic models have been developed for two bacterial pathogens, M. leprae and My. abscessus, and a new computational tool has been used to identify potential drug targets, which are referred to as bottleneck reactions. The genes, reactions, and pathways in each of these organisms have been highlighted; the potential drug targets can be further explored as broad-spectrum antibacterials and the unique drug targets for each pathogen are significant for precision medicine initiatives. The models and associated datasets described in this paper are available in GigaDB, Biomodels, and PatMeDB repositories.

13.
Curr Top Med Chem ; 23(19): 1850-1858, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37150990

RESUMO

Bacteria cells exhibit multidrug resistance in one of two ways: by raising the genetic expression of multidrug efflux pumps or by accumulating several drug-resistant components in many genes. Multidrug-resistive tuberculosis bacteria are treated by multidrug therapy, where a few certain antibacterial drugs are administered together to kill a bacterium jointly. A major drawback of conventional multidrug therapy is that the administration never ensures the reaching of different drug molecules to a particular bacterium cell at the same time, which promotes growing drug resistivity step-wise. As a result, it enhances the treatment time. With additional tabletability and plasticity, the formation of a cocrystal of multidrug can ensure administrating the multidrug chemically together to a target bacterium cell. With properly maintaining the basic philosophy of multidrug therapy here, the synergistic effects of drug molecules can ensure killing the bacteria, even before getting the option to raise the drug resistance against them. This can minimize the treatment span, expenditure and drug resistance. A potential threat of epidemic from tuberculosis has appeared after the Covid-19 outbreak. An unwanted loop of finding molecules with the potential to kill tuberculosis, getting their corresponding drug approvals, and abandoning the drug after facing drug resistance can be suppressed here. This perspective aims to develop the universal drug regimen by postulating the principles of drug molecule selection, cocrystallization, and subsequent harmonisation within a short period to address multidrug-resistant bacteria.


Assuntos
COVID-19 , Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose , Humanos , Quimioterapia Combinada , Proteínas de Bactérias/metabolismo , Hansenostáticos/farmacologia , Tuberculose/tratamento farmacológico , Bactérias/metabolismo , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia
15.
Eur J Pharm Biopharm ; 187: 141-155, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37076052

RESUMO

Clofazimine, an anti-leprosy drug, has been anticipated for a candidate to treat tuberculosis, cryptosporidiosis, and coronavirus infection, but its low oral bioavailability is considered a reason for its limited activity. In the current study, we have tried to improve the oral bioavailability of clofazimine by several SNEDDS formulations and characterized the absorption behavior from various aspects. Among four SNEDDS formulations prepared, SNEDDS A, prepared with castor oil as an oil component, provided the highest bioavailability (around 61%) and SNEDDS D, prepared with Capryol 90, gave the second highest bioavailability. SNEDDS A formed the finest nanoparticles, which were maintained under gastric and intestinal luminal conditions. The comparison in oral bioavailability between the SNEDDS formulation and its corresponding preformed nanoemulsion suggested that SNEDDS A would efficiently form nanoemulsion in the gastrointestinal tract after oral administration. AUC of mesenteric lymph node concentration was the highest for SNEDDS A, which would be one of the reasons for SNEDDS A to reveal the highest oral bioavailability. A cycloheximide-treated oral absorption study and single-pass perfusion study by utilizing a vascular-luminal perfused small intestine-liver preparation clearly indicated that over 90% of clofazimine absorbed to systemic circulation should be derived from lymphatic transport for both SNEDDS A and D. Furthermore, the fraction of dose absorbed was around 65% for SNEDDS D, but SNEDDS A achieved around 94%, indicating the excellent performance of SNEDDS A.


Assuntos
Clofazimina , Nanopartículas , Sistemas de Liberação de Medicamentos , Solubilidade , Preparações Farmacêuticas , Administração Oral , Disponibilidade Biológica , Nanopartículas/química , Emulsões/química , Tamanho da Partícula
16.
PLoS Negl Trop Dis ; 17(4): e0010888, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37018206

RESUMO

BACKGROUND: The effect of leprosy on the sense of smell is not yet fully established. Studies that have relied only on patients' perceptions may have under- or over-estimated the change in smell perception. A validated and psychophysical method is necessary to avoid these errors in assessment. OBJECTIVES: This study aimed to validate the existence of olfactory involvement in leprosy patients. METHODS: A cross-sectional, controlled study was conducted, in which individuals with leprosy (exposed individuals) and individuals without leprosy (control patients) were recruited. For each exposed individual, we selected two control patients. A total of 108 patients (72 control patients and 36 exposed individuals) with no history of infection with the new coronavirus (COVID-19) took the University of Pennsylvania Smell Identification Test (UPSIT). RESULTS: Most exposed individuals had olfactory dysfunction [n = 33, 91.7% (CI 95%: 77.5%-98.3%)] when compared with the control patients [n = 28, 38.9% (CI 95%: 27.6%-51.1%)], but only two (5.6%) had olfactory complaints. The olfactory function was significantly worse among exposed individuals [UPSIT leprosy = 25.2 (CI 95%: 23.1-27.3) when compared with the UPSIT control patients = 34.1 (CI 95%: 33.0-35.3); p<0.001]. The risk of olfactory loss was higher among the exposed individuals [OR: 19.5 (CI 95%: 5.18-105.70; p < 0.001)]. CONCLUSIONS: Olfactory dysfunction was highly prevalent among exposed individuals, although they had little or no self-knowledge of the disorder. The results show that it is important to assess the sense of smell in exposed individuals.


Assuntos
COVID-19 , Transtornos do Olfato , Humanos , Estudos Transversais , Prevalência , Transtornos do Olfato/epidemiologia , Olfato
17.
J Pak Med Assoc ; 73(Suppl 2)(2): S170-S174, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37096727

RESUMO

Objectives: To analyse the effect of using digital health technology on leprosy control programmes. Method: The systematic review comprised search on PubMed, Scopus, ScienceDirect, SAGE and ProQuest databases for interventional studies published in English language from 2013 to 2021 which used digital health technology for leprosy contact tracing, active leprosy detection, monitoring of multi-drug therapy and treatment management during the corona virus disease-2019 pandemic A standard risk of bias tool was used to evaluate bias in the studies, and the Joanna Briggs Institute protocol was used to assess the quality of the studies analysed. RESULTS: Of the 205 studies initially identified, 15(7.3%) were analysed in detail. Quasi-experimental studies had a low risk of bias compared to the rest. The e-leprosy framework was being used along with applications based on smartphones and artificial intelligence Digital health technology was found to be practical, accessible and effective in leprosy control programmes. CONCLUSIONS: Studies reported favourable findings regarding the use of digital health technology in services related to leprosy patients.


Assuntos
COVID-19 , Hanseníase , Humanos , Pandemias , Inteligência Artificial , Hanseníase/tratamento farmacológico , Tecnologia
19.
Inflammopharmacology ; 31(3): 1167-1182, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36966238

RESUMO

The "Thalidomide tragedy" is a landmark in the history of the pharmaceutical industry. Despite limited clinical trials, there is a continuous effort to investigate thalidomide as a drug for cancer and inflammatory diseases such as rheumatoid arthritis, lepromatous leprosy, and COVID-19. This review focuses on the possibilities of targeting inflammation by repurposing thalidomide for the treatment of idiopathic pulmonary fibrosis (IPF). Articles were searched from the Scopus database, sorted, and selected articles were reviewed. The content includes the proven mechanisms of action of thalidomide relevant to IPF. Inflammation, oxidative stress, and epigenetic mechanisms are major pathogenic factors in IPF. Transforming growth factor-ß (TGF-ß) is the major biomarker of IPF. Thalidomide is an effective anti-inflammatory drug in inhibiting TGF-ß, interleukins (IL-6 and IL-1ß), and tumour necrosis factor-α (TNF-α). Thalidomide binds cereblon, a process that is involved in the proposed mechanism in specific cancers such as breast cancer, colon cancer, multiple myeloma, and lung cancer. Cereblon is involved in activating AMP-activated protein kinase (AMPK)-TGF-ß/Smad signalling, thereby attenuating fibrosis. The past few years have witnessed an improvement in the identification of biomarkers and diagnostic technologies in respiratory diseases, partly because of the COVID-19 pandemic. Hence, investment in clinical trials with a systematic plan can help repurpose thalidomide for pulmonary fibrosis.


Assuntos
COVID-19 , Fibrose Pulmonar Idiopática , Humanos , Talidomida/uso terapêutico , Talidomida/metabolismo , Talidomida/farmacologia , Pandemias , COVID-19/metabolismo , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/metabolismo , Fibrose Pulmonar Idiopática/patologia , Inflamação/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Pulmão
20.
Rev. bras. med. fam. comunidade ; 18(45): 3232, 20230212. mapas, ilus
Artigo em Inglês, Português | LILACS, ColecionaSUS | ID: biblio-1451704

RESUMO

Introdução: A COVID-19 (coronavirus disease 2019) trouxe inúmeros desafios e sobrecarga ao Sistema Único de Saúde (SUS), gerando dificuldades no enfrentamento das outras enfermidades endêmicas e negligenciadas no território brasileiro, entre elas a hanseníase. Objetivo: Relatar a experiência de enfrentamento da prevalência oculta de hanseníase por uma equipe de atenção primária à saúde do interior do estado de Sergipe durante a pandemia de COVID-19. Métodos: O projeto foi desenvolvido entre os meses de setembro de 2020 e janeiro de 2021 e caracterizou-se pela oferta de exame dermatológico aos indivíduos que buscaram atendimento na unidade de saúde do bairro Cidade Nova, em Estância, Sergipe. Confirmado o diagnóstico de hanseníase, foi introduzido o tratamento com esquema de poliquimioterapia da Organização Mundial da Saúde (PQT-OMS) e os contatos foram examinados, respeitando-se as medidas sanitárias de prevenção à contaminação pela COVID-19. Resultados: No período analisado, foram avaliados 235 indivíduos, sendo feitos seis diagnósticos clínicos de hanseníase (2,5%), entre os quais um em menor de 15 anos de idade. No município, durante todo o ano de 2020, registrou-se o total de nove casos novos de hanseníase. Sem o projeto, o coeficiente de detecção de casos novos de hanseníase no município seria de 4,3/100 mil habitantes e, com o projeto, esse coeficiente foi três vezes superior (12,9/100 mil habitantes). Conclusão: A oferta de exame dermatoneurológico durante consultas médicas de rotina em áreas vulneráveis permitiu evidenciar a prevalência oculta de hanseníase no bairro Cidade Nova, Estância. Além disso, ações dessa natureza permitem o diagnóstico precoce, evitando-se a evolução para incapacidades físicas.


Introduction: COVID-19 (coronavirus disease 2019) has brought numerous challenges and burdens on the Unified Health System (SUS, acronym in Portuguese), creating difficulties for the facing of other endemic diseases in the Brazilian territory, such as leprosy. Objective: To report an experience of coping with the hidden prevalence of leprosy by a primary health care team in the countryside of the state of Sergipe during the COVID-19 pandemic. Methods: The project was developed from September 2020 to January 2021 and was characterized for offering a dermatological examination to individuals seeking care at the health unit in the Cidade Nova neighborhood, Estância, Sergipe. For confirmed cases, treatment was instituted and household contacts were examined, respecting the measures to prevent contamination by COVID-19. Results: In the analyzed period, 235 individuals were evaluated, with six diagnoses of leprosy (2.5%), one under the age of 15. In 2020, the municipality registered nine total cases. Without the project, the detection rate of new leprosy cases in the municipality would have been 4.3/100,000 inhabitants and, with the project, this coefficient was three times higher (12.9/100,000 inhabitants). Conclusion: The offer of dermato-neurological exams during routine medical appointments made it possible to show the hidden prevalence of leprosy in the neighborhood of Cidade Nova, Estância. In addition, actions of this nature allow early diagnosis, preventing the occurrence of physical disabilities.


Introducción: La COVID-19 (enfermedad por coronavirus 2019) trajo numerosos desafíos y cargas al Sistema Único de Salud (SUS), creando dificultades para enfrentar otras enfermedades endémicas en el territorio brasileño, como la lepra. Objetivo: Informar una experiencia de afrontamiento de la prevalencia oculta de lepra por parte de un equipo de atención primaria en el interior del estado de Sergipe durante la pandemia de COVID-19. Métodos: El proyecto se desarrolló desde septiembre de 2020 hasta enero de 2021 y se caracterizó por ofrecer un examen dermatológico a las personas que buscaban atención en la unidad de salud del barrio Cidade Nova, en Estância, Sergipe. En caso de confirmarse los casos, se instituyó el tratamiento y se examinaron los contactos domiciliarios, respetando las medidas para prevenir la contaminación por COVID-19. Resultados: En el período analizado se evaluaron 235 individuos, con 06 diagnósticos de lepra (2,5%), uno menor de 15 años. En 2020, el municipio registró nueve casos en total. Sin el proyecto, la tasa de detección de nuevos casos de lepra en el municipio sería de 4,3/100 mil habitantes y, con el proyecto, este coeficiente era tres veces mayor (12,9/100 mil habitantes). Conclusión: La oferta de exámenes dermatoneurológicos durante las consultas médicas de rutina permitió mostrar la prevalencia oculta de la lepra en el barrio Cidade Nova, Estância. Además, acciones de esta naturaleza permiten un diagnóstico precoz, evitando la aparición de discapacidades físicas.


Assuntos
Humanos , Feminino , Criança , Adulto , Atenção Primária à Saúde , Prevalência , COVID-19 , Hanseníase
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