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1.
Rev. Assoc. Méd. Rio Gd. do Sul ; 66(1): 01022105, 20220101.
Article in Portuguese | LILACS-Express | LILACS | ID: biblio-1395312

ABSTRACT

Introdução: A transmissão materno-fetal do vírus da imunodeficiência humana, no Brasil, atinge ainda grandes proporções, levando a elevadas taxas de morbimortalidade na infância e vida adulta dos indivíduos afetados. O objetivo do presente estudo foi analisar o perfil epidemiológico dos pacientes pediátricos em tratamento ou que foram expostos ao vírus do HIV no município de Criciúma/SC. Métodos: Foi realizado um estudo observacional transversal, retrospectivo, descritivo e de abordagem quantitativa. Foram analisadas 110 crianças e adolescentes, entre 0 e 18 anos, no período de julho de 2016 a junho de 2018. Resultados: Totalizaram-se 23 (20,9%) pacientes que são soropositivos confirmados e 87 (79,1%) que estão em acompanhamento para possível infecção ou que tiveram alta do serviço por não terem adquirido o vírus. Quanto ao diagnóstico materno prévio, 24 (21,8%) mães não tinham o diagnóstico prévio e representaram 16 (69,6%) das infecções verticais, 86 (78,2%) sabiam de sua soropositividade, resultando em 7 (30,4%) crianças infectadas pelo HIV. Já entre os não infectados, 8 (9,2%) eram filhos de mães que não tinham o diagnóstico, e em 79 (90,8%) crianças, a mãe já tinha o diagnóstico. O uso profilático de terapia antirretroviral (TARV) materno foi observado em 82 (74,5%) e não utilizado em 28 (25,5%) crianças. Conclusão: A transmissão vertical do HIV foi vista com maior prevalência nas crianças em que não foram utilizadas medidas profiláticas, demonstrando que o diagnóstico materno prévio, a profilaxia com TARV durante a gestação e a amamentação têm valor significativo na transmissão vertical do HIV.


Introduction: Maternal-fetal transmission of HIV in Brazil is still high, with high morbidity and mortality rates during childhood and adulthood in affected individuals. The objective of this study was to analyze the epidemiological profile of pediatric patients undergoing treatment for or who were exposed to the HIV virus in the city of Criciúma, SC, Brazil. Methods: A cross-sectional, retrospective, descriptive, and quantitative analysis of 110 children and adolescents between birth and 18 years of age was conducted between July 2016 and June 2018. Results: A total of 23 (20.9%) patients were confirmed seropositive, while 87 (79.1%) are being followed up for possible infection or were released for seronegativity. Regarding previous diagnosis, 24 (21.8%) previously undiagnosed mothers had 16 (69.6%) vertically infected children, and 86 (78.2%) mothers knew they were seropositive, resulting in 7 (30.4%) vertical infections. Among the uninfected, 8 (9.2%) were children of previously undiagnosed mothers, while the mothers of 79 (90.8%) had been diagnosed. Prophylactic maternal antiretroviral therapy was applied in 82 (74.5%) cases and was not applied in 28 (25.5%) cases. Conclusions: There was a higher prevalence of vertical HIV transmission when prophylactic measures were not used, which demonstrates that prior maternal diagnosis and antiretroviral prophylaxis during pregnancy and breastfeeding have significant value in vertical HIV transmission.

2.
S. Afr. j. psychiatry (Online) ; 27(0): 1-8, 2021. Tables
Article in English | AIM | ID: biblio-1284404

ABSTRACT

Background: Studies exploring HIV knowledge, attitudes and practices (KAP) of individuals with severe mental illness (SMI) have suggested their poorer knowledge about HIV. In KwaZulu-Natal (KZN) province, South Africa (SA), the epicentre of the country's HIV epidemic, improving KAP is essential for reduce its incidence amongst individuals with SMI. Comparing the KAP related to HIV between those with SMI and chronic medical illnesses (CMI) such as hypertension and diabetes may expose gaps in KAP related to HIV in the mentally ill who are more vulnerable to HIV. Aim: This study aimed to compare the KAP related to HIV between people living with SMI and CMI. Setting: Outpatient clinics in Durban, SA. Methods: A cross-sectional structured questionnaire survey was conducted amongst 214 adult outpatients with SMI and CMI attending two general public sector hospitals in Durban, KZN. The KAP questionnaire consisted of three sections: general information, prevention and transmission of HIV. Results: Interviews were conducted with 124 patients with SMI and 90 with CMI. Most were female (69.5%), single (57.5%) and unemployed (59.4%). The diagnosis of SMI was associated with poorer general information of HIV (p = 0.02), but not with its prevention and transmission compared with those with CMI. Educational level was associated with poorer performance in all three domains: general information of HIV (p = 0.01), prevention (p = 0.01) and transmission (p = 0.02) amongst all the participants. Conclusion: Gaps in the KAP of HIV amongst individuals with SMI compared with those with CMI suggested a need to provide focused health promotion regarding sexual health and HIV to the mentally ill at psychiatric facilities


Subject(s)
Humans , HIV Infections , Health Knowledge, Attitudes, Practice , South Africa , Chronic Disease , Acquired Immunodeficiency Syndrome , Mental Disorders
3.
Acta Pharmaceutica Sinica B ; (6): 2768-2782, 2021.
Article in English | WPRIM | ID: wpr-888886

ABSTRACT

Pyroptosis is the process of inflammatory cell death. The primary function of pyroptosis is to induce strong inflammatory responses that defend the host against microbe infection. Excessive pyroptosis, however, leads to several inflammatory diseases, including sepsis and autoimmune disorders. Pyroptosis can be canonical or noncanonical. Upon microbe infection, the canonical pathway responds to pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), while the noncanonical pathway responds to intracellular lipopolysaccharides (LPS) of Gram-negative bacteria. The last step of pyroptosis requires the cleavage of gasdermin D (GsdmD) at D275 (numbering after human GSDMD) into N- and C-termini by caspase 1 in the canonical pathway and caspase 4/5/11 (caspase 4/5 in humans, caspase 11 in mice) in the noncanonical pathway. Upon cleavage, the N-terminus of GsdmD (GsdmD-N) forms a transmembrane pore that releases cytokines such as IL-1

4.
Acta Pharmaceutica Sinica B ; (6): 2449-2468, 2021.
Article in English | WPRIM | ID: wpr-888869

ABSTRACT

Orally administered drug entities have to survive the harsh gastrointestinal environment, penetrate the enteric epithelia and circumvent hepatic metabolism before reaching the systemic circulation. Whereas the gastrointestinal stability can be well maintained by taking proper measures, hepatic metabolism presents as a formidable barrier to drugs suffering from first-pass metabolism. The pharmaceutical academia and industries are seeking alternative pathways for drug transport to circumvent problems associated with the portal pathway. Intestinal lymphatic transport is emerging as a promising pathway to this end. In this review, we intend to provide an updated overview on the rationale, strategies, factors and applications involved in intestinal lymphatic transport. There are mainly two pathways for peroral lymphatic transport-the chylomicron and the microfold cell pathways. The underlying mechanisms are being unraveled gradually and nowadays witness increasing research input and applications.

5.
Acta Pharmaceutica Sinica B ; (6): 2344-2361, 2021.
Article in English | WPRIM | ID: wpr-888806

ABSTRACT

Recent infectious disease outbreaks, such as COVID-19 and Ebola, have highlighted the need for rapid and accurate diagnosis to initiate treatment and curb transmission. Successful diagnostic strategies critically depend on the efficiency of biological sampling and timely analysis. However, current diagnostic techniques are invasive/intrusive and present a severe bottleneck by requiring specialist equipment and trained personnel. Moreover, centralised test facilities are poorly accessible and the requirement to travel may increase disease transmission. Self-administrable, point-of-care (PoC) microneedle diagnostic devices could provide a viable solution to these problems. These miniature needle arrays can detect biomarkers in/from the skin in a minimally invasive manner to provide (near-) real-time diagnosis. Few microneedle devices have been developed specifically for infectious disease diagnosis, though similar technologies are well established in other fields and generally adaptable for infectious disease diagnosis. These include microneedles for biofluid extraction, microneedle sensors and analyte-capturing microneedles, or combinations thereof. Analyte sampling/detection from both blood and dermal interstitial fluid is possible. These technologies are in their early stages of development for infectious disease diagnostics, and there is a vast scope for further development. In this review, we discuss the utility and future outlook of these microneedle technologies in infectious disease diagnosis.

6.
Acta Pharmaceutica Sinica B ; (6): 2973-2982, 2021.
Article in English | WPRIM | ID: wpr-922799

ABSTRACT

The 2020 Nobel Prize in Chemistry recognized CRISPR-Cas9, a super-selective and precise gene editing tool. CRISPR-Cas9 has an obvious advantage in editing multiple genes in the same cell, and presents great potential in disease treatment and animal model construction. In recent years, CRISPR-Cas9 has been used to establish a series of rat models of drug metabolism and pharmacokinetics (DMPK), such as

7.
Acta Pharmaceutica Sinica B ; (6): 810-822, 2021.
Article in English | WPRIM | ID: wpr-881170

ABSTRACT

Of all known small molecules targeting human immunodeficiency virus (HIV) capsid protein (CA), PF74 represents by far the best characterized chemotype, due to its ability to confer antiviral phenotypes in both early and late phases of viral replication. However, the prohibitively low metabolic stability renders PF74 a poor antiviral lead. We report herein our medicinal chemistry efforts toward identifying novel and metabolically stable small molecules targeting the PF74 binding site. Specifically, we replaced the inter-domain-interacting, electron-rich indole ring of PF74 with less electron-rich isosteres, including imidazolidine-2,4-dione, pyrimidine-2,4-dione, and benzamide, and identified four potent antiviral compounds (

8.
Acta Pharmaceutica Sinica B ; (6): 3035-3059, 2021.
Article in English | WPRIM | ID: wpr-922741

ABSTRACT

Various boron-containing drugs have been approved for clinical use over the past two decades, and more are currently in clinical trials. The increasing interest in boron-containing compounds is due to their unique binding properties to biological targets; for example, boron substitution can be used to modulate biological activity, pharmacokinetic properties, and drug resistance. In this perspective, we aim to comprehensively review the current status of boron compounds in drug discovery, focusing especially on progress from 2015 to December 2020. We classify these compounds into groups showing anticancer, antibacterial, antiviral, antiparasitic and other activities, and discuss the biological targets associated with each activity, as well as potential future developments.

9.
J. coloproctol. (Rio J., Impr.) ; 40(2): 156-162, Apr.-Jun. 2020. tab, graf
Article in English | LILACS | ID: biblio-1134969

ABSTRACT

ABSTRACT Study objectives To perform anal lesion and anal cancer screening in men living with HIV/AIDS. Methods This is a descriptive, observational, cross-sectional study. Data were obtained from the Specialized Assistance Service (SAE) in Divinópolis, Minas Gerais. A sociodemographic, epidemiological, and sexual behavior questionnaire was applied; material was collected for cytology, high-resolution anoscopy (AAR) was performed, and an acceptability questionnaire applied. Main results Of the 50 men living with HIV/AIDS invited to participate in this study, 6% were excluded because they were illiterate, 40% refused to participate, and 54% participated in the survey. Among these, all answered the self-administered questionnaire. However, ten (37.0%) underwent proctological examination and anal cytology. Of these, two did not respond to the acceptability questionnaire. No anal lesions were identified during AAR and no biopsy was required. A 10% change in anal cytology was found. Conclusions Through the study it was possible to construct a flow of referrals from the SAE to the UFSJ Coloproctology outpatient clinic. Moreover, the existence of internal stigmas on the part of the participants regarding the proctological examination and the lack of information about anal cancer screening are challenges to be overcome.


RESUMO Objetivos do estudo Realizar o rastreamento de lesões anais e câncer anal em homens vivendo com HIV/AIDS. Métodos Trata-se de estudo descritivo observacional transversal, cujos dados foram obtidos no Serviço de Assistência Especializada (SAE) em Divinópolis, Minas Gerais. Foi aplicado questionário sociodemográfico, epidemiológico e de comportamento sexual; realizada coleta de material para citologia, Anuscopia de Alta Resolução (AAR) e aplicado questionário de aceitabilidade do exame. Principais resultados Dos 50 homens vivendo com HIV/AIDS convidados a participar do presente estudo, 6% foram excluídos por serem analfabetos, 40% se recusaram a participar e 54% participaram da pesquisa. Entre estes, todos responderam o questionário autoaplicado. Entretanto, 10 (37.0%) realizaram o exame proctológico e a citologia anal. Desses, dois não responderam ao questionário de aceitabilidade. Não foram identificadas lesões anais durante a AAR, não sendo necessária a realização de biópsia. Foi encontrado 10% de alteração à citologia anal. Conclusões Por meio do estudo foi possível construir um fluxo de encaminhamentos do SAE para o ambulatório de Coloproctologia da UFSJ. Ademais, a existência de estigmas internos por parte dos participantes no que concerne à realização do exame proctológico e a falta de informação a respeito do rastreamento do câncer anal são desafios a serem vencidos.


Subject(s)
Humans , Male , Anus Neoplasms/prevention & control , Mass Screening , Anus Neoplasms/epidemiology , Papillomaviridae , Acquired Immunodeficiency Syndrome
10.
Acta Pharmaceutica Sinica B ; (6): 961-978, 2020.
Article in English | WPRIM | ID: wpr-828831

ABSTRACT

Human immunodeficiency virus (HIV) is the primary infectious agent of acquired immunodeficiency syndrome (AIDS), and non-nucleoside reverse transcriptase inhibitors (NNRTIs) are the cornerstone of HIV treatment. In the last 20 years, our medicinal chemistry group has made great strides in developing several distinct novel NNRTIs, including 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT), thio-dihydro-alkoxy-benzyl-oxopyrimidine (-DABO), diaryltriazine (DATA), diarylpyrimidine (DAPY) analogues, and their hybrid derivatives. Application of integrated modern medicinal strategies, including structure-based drug design, fragment-based optimization, scaffold/fragment hopping, molecular/fragment hybridization, and bioisosterism, led to the development of several highly potent analogues for further evaluations. In this paper, we review the development of NNRTIs in the last two decades using the above optimization strategies, including their structure-activity relationships, molecular modeling, and their binding modes with HIV-1 reverse transcriptase (RT). Future directions and perspectives on the design and associated challenges are also discussed.

11.
Acta Pharmaceutica Sinica B ; (6): 344-357, 2020.
Article in English | WPRIM | ID: wpr-787624

ABSTRACT

In order to improve the positional adaptability of our previously reported naphthyl diaryltriazines (NP-DATAs), synthesis of a series of novel biphenyl-substituted diaryltriazines (BP-DATAs) with a flexible side chain attached at the C-6 position is presented. These compounds exhibited excellent potency against wild-type (WT) HIV-1 with EC values ranging from 2.6 to 39 nmol/L and most of them showed low nanomolar anti-viral potency against a panel of HIV-1 mutant strains. Compounds and had the best activity against WT, single and double HIV-1 mutants and reverse transcriptase (RT) enzyme comparable to two reference drugs (EFV and ETR) and our lead compound NP-DATA (). Molecular modeling disclosed that the side chain at the C-6 position of DATAs occupied the entrance channel of the HIV-1 reverse transcriptase non-nucleoside binding pocket (NNIBP) attributing to the improved activity. The preliminary structure-activity relationship and PK profiles were also discussed.

12.
Acta Pharmaceutica Sinica B ; (6): 287-296, 2016.
Article in English | WPRIM | ID: wpr-309956

ABSTRACT

Exosomes are small intracellular membrane-based vesicles with different compositions that are involved in several biological and pathological processes. The exploitation of exosomes as drug delivery vehicles offers important advantages compared to other nanoparticulate drug delivery systems such as liposomes and polymeric nanoparticles; exosomes are non-immunogenic in nature due to similar composition as body׳s own cells. In this article, the origin and structure of exosomes as well as their biological functions are outlined. We will then focus on specific applications of exosomes as drug delivery systems in pharmaceutical drug development. An overview of the advantages and challenges faced when using exosomes as a pharmaceutical drug delivery vehicles will also be discussed.

13.
São Paulo; s.n; s.n; 2016. 92 p. tab, graf, ilus.
Thesis in Portuguese | LILACS | ID: biblio-846562

ABSTRACT

No advento dos antirretrovirais potentes, os indivíduos infectados pelo vírus da imunodeficiência humana (HIV) começaram a apresentar risco maior para o desenvolvimento de doença cardiovascular (DCV). Este aumento do risco cardiovascular pode ser associado tanto à infecção viral quanto ao tratamento antirretroviral (TARV), que provocam mudanças pró-aterogênicas como o aumento do colesterol total e da lipoproteína de baixa densidade (LDL), além da diminuição da lipoproteína de alta densidade (HDL). A ativação imune e as alterações lipídicas são mecanismos associados com a infecção pelo HIV e com o risco de DCV. Este trabalho utilizou ensaios imunoenzimáticos para a determinação plasmática de biomarcadores emergentes de risco cardiovascular relacionados com modificações da lipoproteína de baixa densidade, a saber: LDL eletronegativa [LDL(-)] e formas oxidadas da LDL, ou seja, LDL-oxi (resíduos lisina da apolipoproteína B100 modificados com malondialdeído), LDL-HNE (resíduos lisina da ApoB100 modificados com 4-hidroxinonenal) e LDL-CML (resíduos lisina da ApoB100 modificados por carboximetila), além de biomarcadores relacionados com a resposta imune-inflamatória, ou seja, autoanticorpos IgG e IgM anti-LDL(-), imunocomplexo de LDL(-) [IC-LDL(-)], proteína amiloide sérica A (SAA) e mieloperoxidase (MPO). Também foram determinadas as concentrações séricas dos biomarcadores de risco relacionados às apolipoproteínas: apolipoproteína A-I (ApoA-I), apolipoproteína B (ApoB) e apolipoproteína E (ApoE). A população estudada incluiu indivíduos com infecção pelo HIV, tratados (HIV-TARV) e não tratados (HIV-NT) com terapia antirretroviral e indivíduos sem infecção pelo HIV (controle). Não foram identificadas diferenças para as concentrações de LDL(-), IC-LDL(-), anti- LDL(-)-IgM, SAA, ApoA-I, ApoB e ApoE entre os grupos estudados (HIV-TARV, HIV-NT e controle). A ApoA-I correlacionou-se positivamente com ApoB e ApoE (rs= 0,418 e rs= 0,347, Spearman, p<0,01) e a ApoB com a ApoE (rs= 0,286, Spearman, p<0,01). Verificou-se correlação inversa entre as concentrações de LDL(-) e IC-LDL(-) (rs= -0,214, Spearman, p<0,05). Os níveis de anti-LDL(-)-IgG correlacionaram-se positivamente com IC-LDL(-) e anti-LDL(-)-IgM (rs= 0,240, Spearman, p<0,05 e rs= 0,348, Spearman, p<0,01). As concentrações de LDL-CML correlacionaram-se positivamente com LDL(-), LDL-oxi, LDL-HNE e IC-LDL(-) (rs= 0,212, Spearman, p<0,05; rs= 0,214, Spearman, p<0,05; rs= 0,573, Spearman, p<0,01 e rs= 0,219, Spearman, p<0,05). O grupo HIV-NT apresentou níveis mais elevados de anticorpos anti-LDL(-)-IgG comparado ao grupo controle (Kruskal-Wallis, p<0,01). Em contraste, observou-se no grupo HIV-NT diminuição das concentrações de MPO, LDL-HNE e LDL-CML em relação ao grupo controle (Kruskal-Wallis, p<0,01). A comparação dos grupos HIV-NT e HIV-TARV demonstrou que o TARV promoveu diminuição das concentrações dos anticorpos anti-LDL(-)-IgG e aumentou os níveis de LDL-oxi (Kruskal-Wallis, p<0,01). O grupo HIV-TARV apresentou aumento das concentrações de LDL-oxi e diminuição dos níveis de MPO, LDL-HNE e LDL-CML em relação ao controle (Kruskal-Wallis, p<0,01). Em conclusão, a infecção pelo HIV modificou o biomarcador de inflamação MPO e o perfil de biomarcadores relacionados às modificações da LDL (menor formação de LDL-HNE e LDL-CML), além aumentar a resposta imune-humoral à LDL eletronegativa [anti-LDL(-)-IgG], enquanto o tratamento com antirretrovirais inibiu esta resposta. Os outros biomarcadores estudados não foram modificados pela infecção viral ou pelo tratamento antirretroviral


In the advent of potent antiretroviral therapy, individuals infected with human immunodeficiency virus (HIV) have showed an increased risk for developing cardiovascular disease (DCV). Studies have discussed that the increased risk may be related to both the disease and antiretroviral treatment (TARV), that produced pro-atherogenic changes such as increased of total cholesterol and low density lipoprotein (LDL) and decreased high density lipoprotein. The immune activation and the lipid modifications are well known mechanisms related to HIV infection and the risk of DCV. This study used immunoassays for plasma quantification for emerging biomarkers of cardiovascular risk related to modification of low density lipoprotein: electronegative LDL [LDL(-)] and oxidized forms of LDL, LDL-oxi (lysine residues of apolipoprotein B100 modified by malondialdehyde), LDL-HNE (lysine residues of ApoB100 modified by 4-hydroxynonenal) and LDL-CML (lysine residues of ApoB100 modified by carboxymethyl) and biomarkers associated to immune and inflammatory responses, IgG and IgM autoantibodies anti-LDL(-) and immunecomplexe of LDL(-) [IC-LDL(-)], serum amyloid A protein (SAA) and myeloperoxidase (MPO). Also, were determined serum concentrations of risk biomarkers related to apolipoproteins: apolipoprotein A-I (ApoA-I), apolipoprotein B (ApoB) and apolipoprotein E (ApoE). The studied population included patients with HIV infection, treated (HIV-TARV) and untreated (HIV-NT) with antiretroviral therapy and individuals without HIV infection (controle). No differences were identified for concentrations of LDL(-), ICLDL(-), anti-LDL(-)-IgM, SAA, ApoA-I, ApoB and ApoE between studied groups (HIV-TARV, HIV-NT and controle). The ApoA-I was positively correlated to ApoB and ApoE (rs= 0,418 e rs= 0,347, Spearman, p<0,01) and ApoB to ApoE (rs= 0,286, Spearman, p<0,01). There was an inverted correlation between LDL(-) and IC-LDL(-) (rs= -0.214, Spearman, p<0,05). The levels of anti-LDL(-)-IgG were positively correlated to IC-LDL(-) and antibodies anti-LDL(-)-IgM (rs= 0.240; Spearman; p <0.05 and rs= 0.348; Spearman; p <0.01). The concentrations of LDL-CML were positively correlated to LDL(-), LDL-oxi, LDL-HNE e IC-LDL(-) (rs= 0,212, Spearman, p<0,05; rs= 0,214, Spearman, p<0,05; rs= 0,573, Spearman, p<0,01 e rs= 0,219, Spearman, p<0,05). The HIV-NT group showed higher levels of anti-LDL(-)-IgG compared to Control group (Kruskal-Wallis, p<0,01). In contrast, was observed lower levels for HIV-NT group to MPO, LDL-HNE and LDL-CML when compared to Control group (Kruskal-Wallis, p<0,01). The comparison of HIV-NT and HIV-TARV groups demonstrated that TARV caused a decrease of concentrations of anti-LDL(-)-IgG antibodies and an increased of LDL-oxi levels (Kruskal-Wallis, p <0.01). The HIV-TARV group showed increased LDL-oxi concentrations and decreased at levels of MPO, LDL-HNE e LDL-CML when compared to Control (Kruskal-Wallis, p<0,01). In conclusion, the HIV infection changed the biomarker of inflammation MPO and the profile of biomarkers related to modifications of LDL (lower concentrations of LDL-HNE and LDL-CML), as well as increased the humoral-immune response to electronegative LDL [anti-LDL(-)-IgG], while treatment with antiretroviral therapy inhibited this response. The other studied biomarkers were not modified either by viral infection or antiretroviral treatment


Subject(s)
Biomarkers/analysis , Cardiovascular System , HIV/metabolism , Immunoenzyme Techniques/methods , Antiretroviral Therapy, Highly Active/classification , Atherosclerosis/complications , Low Density Lipoprotein Receptor-Related Protein-1
14.
Acta Pharmaceutica Sinica B ; (6): 310-315, 2015.
Article in English | WPRIM | ID: wpr-310022

ABSTRACT

Licorice is a common herb which has been used in traditional Chinese medicine for centuries. More than 20 triterpenoids and nearly 300 flavonoids have been isolated from licorice. Recent studies have shown that these metabolites possess many pharmacological activities, such as antiviral, antimicrobial, anti-inflammatory, antitumor and other activities. This paper provides a summary of the antiviral and antimicrobial activities of licorice. The active components and the possible mechanisms for these activities are summarized in detail. This review will be helpful for the further studies of licorice for its potential therapeutic effects as an antiviral or an antimicrobial agent.

15.
Acta Pharmaceutica Sinica B ; (6): 493-499, 2015.
Article in English | WPRIM | ID: wpr-310001

ABSTRACT

Despite significant advances in antiretroviral therapy, increasing drug resistance and toxicities observed among many of the current approved human immunodeficiency virus (HIV) drugs indicate a need for discovery and development of potent and safe antivirals with a novel mechanism of action. Maturation inhibitors (MIs) represent one such new class of HIV therapies. MIs inhibit a late step in the HIV-1 Gag processing cascade, causing defective core condensation and the release of non-infectious virus particles from infected cells, thus blocking the spread of the infection to new cells. Clinical proof-of-concept for the MIs was established with betulinic acid derived bevirimat, the prototype HIV-1 MI. Despite the discontinuation of its further clinical development in 2010 due to a lack of uniform patient response caused by naturally occurring drug resistance Gag polymorphisms, several second-generation MIs with improved activity against viruses exhibiting Gag polymorphism mediated resistance have been recently discovered and are under clinical evaluation in HIV/AID patients. In this review, current understanding of HIV-1 MIs is described and recent progress made toward elucidating the mechanism of action, target identification and development of second-generation MIs is reviewed.

16.
Acta Pharmaceutica Sinica B ; (6): 284-294, 2014.
Article in English | WPRIM | ID: wpr-329723

ABSTRACT

Human enterovirus 71 (EV71) is the main causative pathogen of hand, foot, and mouth disease (HFMD) in children. The epidemic of HFMD has been a public health problem in Asia-Pacific region for decades, and no vaccine and effective antiviral medicine are available. Curcumin has been used as a traditional medicine for centuries to treat a diversity of disorders including viral infections. In this study, we demonstrated that curcumin showed potent antiviral effect again EV71. In Vero cells infected with EV71, the addition of curcumin significantly suppressed the synthesis of viral RNA, the expression of viral protein, and the overall production of viral progeny. Similar with the previous reports, curcumin reduced the production of ROS induced by viral infection. However, the antioxidant property of curcumin did not contribute to its antiviral activity, since N-acetyl-l-cysteine, the potent antioxidant failed to suppress viral replication. This study also showed that extracellular signal-regulated kinase (ERK) was activated by either viral infection or curcumin treatment, but the activated ERK did not interfere with the antiviral effect of curcumin, indicating ERK is not involved in the antiviral mechanism of curcumin. Unlike the previous reports that curcumin inhibited protein degradation through ubiquitin-proteasome system (UPS), we found that curcumin had no impact on UPS in control cells. However, curcumin did reduce the activity of proteasomes which was increased by viral infection. In addition, the accumulation of the short-lived proteins, p53 and p21, was increased by the treatment of curcumin in EV71-infected cells. We further probed the antiviral mechanism of curcumin by examining the expression of GBF1 and PI4KB, both of which are required for the formation of viral replication complex. We found that curcumin significantly reduced the level of both proteins. Moreover, the decreased expression of either GBF1 or PI4KB by the application of siRNAs was sufficient to suppress viral replication. We also demonstrated that curcumin showed anti-apoptotic activity at the early stage of viral infection. The results of this study provide solid evidence that curcumin has potent anti-EV71 activity. Whether or not the down-regulated GBF1 and PI4KB by curcumin contribute to its antiviral effect needs further studies.

17.
Article | IMSEAR | ID: sea-185926

ABSTRACT

This study was carried out from January 2006 to December 2008 in the rural district of Andhra Pradesh, India. It included counselling and spreading of awareness encouraging voluntary Human Immunovirus testing in antenatal cases and starting prophylactic treatment of seropositive cases with nevirapine for safe deliveries and for preventing the mother to child transmission with distinct improvement effectively.

19.
Article in Korean | WPRIM | ID: wpr-176082

ABSTRACT

BACKGROUND: Tuberculosis is the most frequent opportunistic infection in HIV-infected patients in Korea. We examined the incidence and risk factors for tuberculosis in HIV-infected patients. METHODS: We reviewed the medical records of 143 HIV-infected patients between January 1988 and June 1997 at the Seoul National University Hospita The incidence of tuberculosis was determined by the number of new tuberculosis per 100 patients divided by a total duration of follow-up (cases/100 person- years). The incidence of tuberculosis was analyzed with respect to CD4+ lymphocyte count, status of tuberculin skin reaction, and status of delayed hypersensitivity skin reaction. RESULTS: The total duration of follow-up was 229.6 person-years. During follow-up, 22 patients developed tuberculosis [9.6 cases per 100 person-years (95% CI, 6.0 to 14.5)]. The incidence of tuberculosis according to sex and transmission route showed no significant difference. Tuberculosis occurred more frequently in patients with minimum CD4+ T lympho-cyte counts of less than 200 cells/mm3 (14.2 cases/100 person-years) than in those with higher T lymphocyte counts (3.9 cases/100 person-years) [relative risk, 4.02 (95% CI 1.32 to 12.5), P=0.009]. The incidence of tuberculosis was higher among tuberculin- positive patients [17.0 cases/100 person-years (95% CI, 9.0 to 29.0)] than among tuberculin-negative [8.0 cases/100 person-years (95% CI, 3.2 to 16.6)], but the difference was not statistically significant [relative risk, 2.35 (95% CI, 0.88 to 6.26, P=0.078)]. The rate of tuberculosis in patients with negative delayed hypersensitivity test was not significantly different from that in patients with positive results (P=0.510). CONCLUSION: The incidence of tuberculosis was 9.6 cases per 100 person-years. CD4+ lymphocyte count (<200 cells/mm3) was the most useful predictor for the development of tuberculosis in HIV patients in Korea.


Subject(s)
Follow-Up Studies , HIV , Humans , Hypersensitivity, Delayed , Incidence , Korea , Lymphocyte Count , Medical Records , Opportunistic Infections , Risk Factors , Seoul , Skin , Tuberculin , Tuberculosis
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