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1.
Clin Exp Dent Res ; 10(2): e863, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38433297

RESUMO

OBJECTIVES: The study aimed to assess the effectiveness of anxiety reduction protocol using auditory distraction in alleviating dental anxiety among patients undergoing tooth extraction. MATERIALS AND METHODS: A randomized controlled trial was conducted at the Oral Surgery Department at Islamabad Dental Hospital from July to December 2022, involving 50 patients scheduled for tooth extraction. Participants were randomly divided into two groups: an interventional group, exposed to auditory distraction, and a noninterventional group, without exposure to auditory distraction before the dental extraction. Dental anxiety was measured using the modified dental anxiety scale (MDAS) questionnaire, which scores anxiety levels on a range from 5 (not anxious) to 25 (extremely anxious). Anxiety levels were assessed in the waiting room and just before extraction, and the results were compared across both groups to evaluate the effectiveness of auditory distraction in reducing dental anxiety. RESULTS: The sample size of 50 was randomly and equally allocated to the interventional and noninterventional groups. The study population consisted of 28 (56%) female and 22 (44%) male participants. No significant difference was observed between the anxiety scores of interventional and noninterventional groups at baseline. A significant reduction in anxiety scores was observed in the intervention group during postintervention assessment, while no significant difference was seen in the noninterventional group's anxiety scores. CONCLUSIONS: The study supports the efficacy of anxiety reduction protocol using auditory distraction as a practical tool for reducing dental anxiety among patients undergoing tooth extraction.


Assuntos
Ansiedade ao Tratamento Odontológico , Assistência Odontológica , Humanos , Feminino , Masculino , Ansiedade ao Tratamento Odontológico/prevenção & controle , Centros de Atenção Terciária , Extração Dentária/efeitos adversos
2.
Front Immunol ; 15: 1303115, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38420119

RESUMO

Many studies have investigated the antiviral activity of cytokines, including interleukin-6 (IL-6), interleukin-22 (IL-22), interleukin-32 gamma (IL-32γ), and interferon-lambda (IFN-λ) in diverse populations. This study aims to evaluate the role of these cytokines in inhibition of various human and animal viruses when administered exogenously. A comprehensive meta-analysis and systematic review were conducted on all the relevant studies from three databases. Standard mean differences (SMDs) of overall viral inhibition were used to generate the difference in the antiviral efficacy of these cytokines between control and experimental groups. A total of 4,618 abstracts for IL-6, 3,517 abstracts for IL-22, 2,160 abstracts for IL-32γ, and 1,026 abstracts for IFN-λ were identified, and 7, 4, 8, and 35 studies were included, respectively, for each cytokine. IFN-λ (SMD = 0.9540; 95% CI: 0.69-0.22) and IL-32γ (SMD = 0.459; 95% CI: 0.02-0.90) showed the highest influence followed by IL-6 (SMD = 0.456; CI: -0.04-0.95) and IL-22 (SMD = 0.244; 95% CI: -0.33-0.81). None of the cytokines represented heterogeneity (tau² > 0), but only IFN-λ indicated the funnel plot asymmetry (p = 0.0097). Results also indicated that IFN-λ and IL-32γ are more potent antivirals than IL-6 and IL-22. The collective findings of this study emphasize that exogenously administered pro-inflammatory cytokines, specifically IFN-λ and IL-32, exhibit a significant antiviral activity, thereby underscoring them as potent antiviral agents. Nonetheless, additional research is required to ascertain their clinical utility and potential for integration into combinatorial therapeutic regimens against viral infections.


Assuntos
Interleucina-6 , Vírus , Animais , Humanos , Interferon lambda , Interleucina 22 , Citocinas , Antivirais/farmacologia
3.
Community Dent Oral Epidemiol ; 51(2): 283-291, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-35238417

RESUMO

OBJECTIVES: To understand the magnitude of risk of health events, such as cardiovascular diseases (CVD), related to poor oral health, both relative and absolute risk measures should be reported. Our aim was to investigate the extent to which absolute and relative measures of risk are reported in longitudinal studies that assess the association between oral health indicators (OHIs) and CVD. METHODS: A systematic search of longitudinal studies investigating the association of any OHI with CVD was carried out using the Embase, Medline and Cochrane library databases. The search covered each database from its inception date to August 2021. Data about reporting relative and absolute risks of the relationship between CVD and OHI from the abstract were extracted. If the relative risk for OHIs and CVD was reported in the abstract, then the underlying absolute risks were searched from the full text, and it was assessed whether it was similarly adjusted for confounding than was the relative risk in the abstract. RESULTS: One hundred-six articles were included. From these, 85 (80%) studies reported the association of OHIs and CVD with one or more relative risks in the abstract. Of those 85 studies, the underlying absolute risks were accessible or calculable from the abstract or full text of 60 studies. However, of these 60 studies, in only 10 (12%), the underlying absolute risks were similarly adjusted, as were the relative risks in the abstract. The absolute risks of CVD by OHIs were rarely reported without corresponding relative risks in the abstract (n = 2, 2%). Median absolute risk difference in the CVD risk between exposure levels to which the first relative risk in the abstract referred was 1.8% (interquartile range 0.6-4.6, n = 63). CONCLUSIONS: Focusing on relative risks over absolute risks was a common practice in literature. Reporting similarly adjusted underlying absolute risks of relative risks was rare in most studies, despite those being helpful for comprehending the magnitude of CVD-risk increase related to poor oral health. Current reporting practices could lead to an overinterpretation of risk increase of CVD related to poor oral health.


Assuntos
Doenças Cardiovasculares , Saúde Bucal , Humanos , Risco , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia
4.
Community Dent Oral Epidemiol ; 50(3): 206-215, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-33961319

RESUMO

OBJECTIVE: The current study aimed to investigate the association of temporomandibular disorders (TMD)-related pain with the presence of migraine or tension-type headaches (TTH) over a follow-up period of 11 years. METHODS: Data sets from Finnish national health surveys, the Health 2000 Survey (baseline), and the Health 2011 Survey (follow-up) were utilized. Study participants are undergoing clinical TMD examination at baseline and answering questions related to the presence of migraine and TTH at follow-up were included in the study (n = 530). For analyses, the study sample was divided into two data sets: One with those excluded suffering from migraine at baseline (Data set I, n = 345), and the other excluding those having TTH at baseline (Data set II, n = 464). RESULTS: Based on logistic regression modelling, no consistent association between TMD-related pain and the presence of migraine was observed, although jTMD associated with elevated estimates for migraine. However, participants with muscle-related TMD pain (mTMD) at baseline had markedly higher odds for having TTH at follow-up than participants without mTMD at baseline (OR 2.1, 95% CI 1.2-3.8). Joint-related TMD pain (jTMD) at baseline was inversely associated with the presence of TTH at follow-up (OR 0.4, 95% CI 0.1-1.3). CONCLUSION: Contrasting patterns of the associations of TMD-related pain with different severe headaches point towards a more thorough and systematic research approach are needed to understand the mechanisms behind these associations.


Assuntos
Transtornos de Enxaqueca , Transtornos da Articulação Temporomandibular , Cefaleia do Tipo Tensional , Artralgia , Dor Facial/complicações , Dor Facial/epidemiologia , Cefaleia/complicações , Cefaleia/epidemiologia , Humanos , Transtornos de Enxaqueca/complicações , Transtornos de Enxaqueca/epidemiologia , Transtornos da Articulação Temporomandibular/complicações , Transtornos da Articulação Temporomandibular/diagnóstico , Transtornos da Articulação Temporomandibular/epidemiologia , Cefaleia do Tipo Tensional/complicações , Cefaleia do Tipo Tensional/diagnóstico , Cefaleia do Tipo Tensional/epidemiologia
5.
Clin Oral Investig ; 26(1): 729-738, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34224000

RESUMO

OBJECTIVES: Association of temporomandibular disorders (TMD)-related pain with severe headaches (migraine and tension-type headaches [TTH]) was studied over a follow-up period of 11 years. MATERIALS AND METHODS: The data used was from two nationally representative health surveys in Finland-the Health 2000 Survey (baseline) and the Health 2011 Survey (follow-up) (Bioresource Research Impact Factor [BRIF] 8901)-conducted by the Finnish Institute for Health and Welfare (THL). The primary dataset of the current study included a subset of the population undergoing a clinical oral examination, including TMD examination, at baseline, and answering the questions related to severe headaches, both at baseline and at follow-up (n = 530). From the primary dataset, two datasets were created to study the onset of migraine (dataset 1) and TTH (dataset 2) separately. Dataset 1 included participants healthy of migraine, but not other headaches, at baseline (n = 345), and dataset 2 participants healthy of TTH and other headaches, except migraine, at baseline (n = 464). Bayesian logistic regression models with weakly informative priors were utilized to assess the association of muscle-related TMD pain (mTMD) at baseline and temporomandibular joint-related TMD pain (jTMD) at baseline with the presence of migraine and TTH at follow-up. RESULTS: Neither of the baseline TMD-related pain variables were associated with the presence of migraine at follow-up (posterior effect estimates-0.12, 95% credible interval [CI] -0.49-0.24, and 0.11, 95% CI -0.38-0.59, for mTMD and jTMD, respectively), whereas mTMD at baseline (posterior effect estimate 0.36, 95% CI 0.02-0.69), but not jTMD at baseline (posterior effect estimate -0.32, 95% CI -0.94-0.25), was associated with the presence of TTH at follow-up. Bayesian sensitivity analyses revealed that the estimates of the regression models were stable, demonstrating sufficient validity and consistency of the estimates. CONCLUSION: These results indicate that diverse mechanisms may exist behind the associations of TMD-related painful conditions with different types of severe headaches. CLINICAL RELEVANCE: TMD-related pain is a frequent comorbidity of severe primary headaches. Therapy of severe primary headaches may thus benefit significantly with the incorporation of a multi-disciplinary clinical team.


Assuntos
Transtornos de Enxaqueca , Transtornos da Articulação Temporomandibular , Cefaleia do Tipo Tensional , Teorema de Bayes , Cefaleia/epidemiologia , Cefaleia/etiologia , Humanos , Transtornos de Enxaqueca/complicações , Transtornos de Enxaqueca/epidemiologia , Transtornos da Articulação Temporomandibular/complicações , Transtornos da Articulação Temporomandibular/epidemiologia
7.
J Oral Facial Pain Headache ; 33(4): 399­407, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31247056

RESUMO

AIMS: To study the possible associations of various clinically assessed painful signs of temporomandibular disorders (TMD) with the presence of migraine using a large population-based dataset. METHODS: The data were taken from the nationally representative Health 2000 Survey (BRIF8901). The sample consisted of 5,876 adults (age range 30 to 97 years, mean ± standard deviation 52.5 ± 14.8), 5,378 nonmigraineurs and 498 migraineurs. The study participants answered questions concerning migraine presence, migraine frequency, and migraine medication consumption during a home interview. They also underwent a clinical TMD examination. RESULTS: Based on the multivariate regression models, painful muscular TMD, but not joint-related TMD, was associated with the presence of migraine (odds ratio [OR] = 1.58; 95% confidence interval [CI] = 1.23 to 2.04; P < .01). Migraine with TMD was associated with increased migraine frequency (daily or a few attacks within a week) (OR = 1.93; 95% CI = 1.27 to 2.93; P < .01) and higher migraine medication consumption (OR = 2.37; 95% CI = 1.43 to 3.92; P < .01). CONCLUSION: According to the results of this study, muscle-related TMD pain is associated with the presence of migraine. Additionally, migraine along with painful TMD signs is associated with increased migraine frequency and migraine medication consumption.


Assuntos
Transtornos de Enxaqueca , Transtornos da Articulação Temporomandibular , Adulto , Idoso , Idoso de 80 Anos ou mais , Dor Facial , Humanos , Pessoa de Meia-Idade , Medição da Dor , Inquéritos e Questionários
8.
Pak J Pharm Sci ; 31(5): 1859-1863, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30150181

RESUMO

Macrotyloma uniflorum (Lam.) Verdc. (Papilionaceae) is commonly known as Horse gram and Kulthi. The seeds are reported as anthelmintic, diaphoretic, diuretic and emmenagogue. It is also useful in asthma, bronchitis and urolithiasis. In the present study, analgesic, anti-inflammatory and diuretic effects of the methanol extract of Macrotyloma uniflorum seeds were evaluated in doses of 200 and 400mg/kg. Significant results were obtained in all activities.


Assuntos
Analgésicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Diuréticos/uso terapêutico , Extratos Vegetais/uso terapêutico , Sementes , Analgésicos/isolamento & purificação , Analgésicos/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Diuréticos/isolamento & purificação , Diuréticos/farmacologia , Relação Dose-Resposta a Droga , Edema/tratamento farmacológico , Edema/metabolismo , Edema/patologia , Fabaceae , Camundongos , Medição da Dor/efeitos dos fármacos , Medição da Dor/métodos , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar
9.
Pak J Med Sci ; 33(5): 1236-1241, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29142571

RESUMO

OBJECTIVE: Mutations in HCV nonstructural protein 5A (NS5A) play a vital role in virus resistance. The aim of this study was to develop a correlation between NS5A mutations (genotype 3a) and virological response towards interferon alpha (IFN-α) plus ribavirin therapy. METHODS: In this study, which was conducted from 09-02-2013 to 25-11-2015 in the rural area of Province Sindh - Pakistan, total patients' responses to peg-IFN therapy were investigated. Patients were given peg-IFN therapy for 24 to 48 weeks and categorized as sustained virologic responders (SVR) or non-responders (NR) to HCV infection. HCV NS5A region (2215-2335) of genotype 3a was identified in both responders and non-responders. RESULTS: Twenty-four NR with 24 SVR isolates showed significant mutations within the nonstructural protein 5A region in HCV genotype 3a. The New Zealand (NZL1) (GenBank D17763) differences were observed by using gene. The ISDR mutations for nonstructural protein 5A in non-responders have been reported as a possible explanation of HCV interferon resistance. CONCLUSION: Based on these results, it is suggested that decreased SVR is caused by the increased mutations in nonstructural protein 5A sequences. When the sequence outside the Protein kinases R binding domain (PKRBD) (2281-2335) was examined, significant differentiations were observed among the SVR and NR classes at few amino acid strains.

10.
Catheter Cardiovasc Interv ; 90(3): 357-363, 2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28168845

RESUMO

OBJECTIVES: To assess patients' perspective about factors associated with stent choice. BACKGROUND: Drug eluting stents (DES) markedly reduce the risk of repeat percutaneous coronary intervention (PCI), but necessitate a longer duration of dual anti-platelet therapy (DAPT) as compared with bare metal stents (BMS). Thus, understanding patients' perspective about factors associated with stent choice is paramount. METHODS: Patients undergoing angiography rated, on a 10-point scale, the importance (1 = not important, 10 = most important) of avoiding repeat revascularization and avoiding the following potential DAPT drawbacks: bleeding/bruising, more pills/day, medication costs and delaying elective surgery. The factor, or group of factors, that was rated highest by each patient was identified. RESULTS: Among 311 patients, repeat revascularization was the single most important consideration to 14.4% of patients, while 20.6% considered avoiding one of the DAPT drawbacks as most important. Most patients (65%) considered avoiding at least one DAPT drawback as important as avoiding repeat revascularization. In no subgroup of patients did more than a quarter of patients prefer avoiding repeat revascularization above all other concerns. Among patients undergoing PCI, more than three quarters received a DES, regardless of their stated preferences (DES use among those most valuing DES benefits, avoiding DAPT drawbacks, or both equally were 78.7%, 86.2%, and 85.6%, respectively, P = 0.56). CONCLUSION: Most patients reported that avoiding DAPT drawbacks was as important as avoiding repeat revascularization. Eliciting patient preferences regarding stent type can enhance shared decision-making and allow physicians to better tailor stent choice to patients' goals and values. TRIAL REGISTRATION: Developing and Testing a Personalized Evidence-based Shared Decision-making Tool for Stent Selection (DECIDE-PCI). ClinicalTrials.gov Identifier: NCT02046902. URL: https://clinicaltrials.gov/ct2/show/NCT02046902 © 2017 Wiley Periodicals, Inc.


Assuntos
Técnicas de Apoio para a Decisão , Stents Farmacológicos , Metais , Preferência do Paciente , Intervenção Coronária Percutânea/instrumentação , Inibidores da Agregação Plaquetária/administração & dosagem , Stents , Tomada de Decisão Clínica , Angiografia Coronária , Reestenose Coronária/etiologia , Reestenose Coronária/terapia , Estudos Transversais , Custos de Medicamentos , Quimioterapia Combinada , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Missouri , Participação do Paciente , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/economia , Desenho de Prótese , Retratamento , Fatores de Risco , Resultado do Tratamento
11.
APMIS ; 124(10): 817-31, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27539675

RESUMO

Human immunodeficiency virus (HIV) infection is a major health burden across the world which leads to the development of acquired immune deficiency syndrome (AIDS). This review article discusses the prevalence of HIV, its major routes of transmission, natural immunity, and evasion from the host immune system. HIV is mostly prevalent in Sub-Saharan Africa and low income countries. It is mostly transmitted by sharing syringe needles, blood transfusion, and sexual routes. The host immune system is categorized into three main types; the innate, the adaptive, and the intrinsic immune system. Regarding the innate immune system against HIV, the key players are mucosal membrane, dendritic cells (DCs), complement system, interferon, and host Micro RNAs. The major components of the adaptive immune system exploited by HIV are T cells mainly CD4+ T cells and B cells. The intrinsic immune system confronted by HIV involves (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G) APOBEC3G, tripartite motif 5-α (TRIM5a), terherin, and (SAM-domain HD-domain containing protein) SAMHD1. HIV-1 efficiently interacts with the host immune system, exploits the host machinery, successfully replicates and transmits from one cell to another. Further research is required to explore evasion strategies of HIV to develop novel therapeutic approaches against HIV.


Assuntos
Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/fisiologia , Interações Hospedeiro-Patógeno , Evasão da Resposta Imune , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Humanos
12.
Tumour Biol ; 37(1): 105-14, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26541758

RESUMO

Hepatocellular carcinoma (HCC) is a growing concern all over the world. With the number of patients rising exponentially with each passing day, HCC is a problem that needs immediate attention. Currently, available treatment strategies focus on controlling the damage after the development of HCC. The options available from chemo- and radio-embolization to surgical resection and transplantation are not efficacious as required due to the complex nature of the disease. Liver regeneration and tissue healing are the subject of great interest today. Interleukin-22 (IL-22) is a cytokine with the ability to regenerate and therefore reverse the injuries caused by a wide range of agents. IL-22 acts via STAT molecule and controls the activity of a wide variety of cell survival and proliferation genes. Experimental data has given a positive insight into the role of IL-22 in inhibition of viral and alcohol-induced hepatocellular carcinoma. A further insight into the nature of IL-22 and the factors that can be manipulated in controlling the activity of IL-22 can help to counter the menace caused by the devastating effects of HCC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Interleucinas/metabolismo , Neoplasias Hepáticas/metabolismo , Animais , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/virologia , Proliferação de Células , Sobrevivência Celular , Citocinas/metabolismo , Progressão da Doença , Hepacivirus , Vírus da Hepatite B , Humanos , Inflamação , Fígado/patologia , Cirrose Hepática , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/virologia , Regeneração Hepática , Modelos Biológicos , Regeneração , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Interleucina 22
13.
World J Gastroenterol ; 21(44): 12558-75, 2015 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-26640332

RESUMO

Hepatitis B is one of the leading causes of liver cancer worldwide and unfortunately the number of people affected with hepatitis B virus (HBV) infection is still on the rise. Although the HBV has been known to cause fatal illness since decades but the population effected by this lethal virus have still only a few options for its management. The major treatment strategies include interferons and nucleos(t)ide analogues. These agents have so far produced unsatisfactory results in terms of complete virus eradication. Interferons cannot be used for long term therapy because of their potential side effects. Prolong treatment with nucleos(t)ide analogues has also been reported to cause serious side effects besides the increasing resistance by the virus. The need for new innovative solutions for treatment of HBV has been realized by global research institutes and pharmaceutical industry. Present review focuses in detail on the new ideas that are being transformed into therapeutic tools for use as future therapies in HBV infection. Modern drug designing and screening methods have made the drug discovery process shorter and more reliable. HBV therapeutics will take a new turn in coming years owing to these intelligent drug designing and screening methods. Future therapy of HBV is aiming to include the use of vaccines (both prophylactic and therapeutic), immunomodulators such as antibodies, non-nucleoside antivirals such as RNAi and inhibitors of viral life cycle.


Assuntos
Antivirais/uso terapêutico , Desenho de Fármacos , Descoberta de Drogas/tendências , Vacinas contra Hepatite B/uso terapêutico , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Animais , Antivirais/efeitos adversos , Difusão de Inovações , Hepatite B/diagnóstico , Hepatite B/imunologia , Vacinas contra Hepatite B/efeitos adversos , Vírus da Hepatite B/imunologia , Vírus da Hepatite B/patogenicidade , Interações Hospedeiro-Patógeno , Humanos , Fatores Imunológicos/efeitos adversos , Terapia de Alvo Molecular/tendências , Resultado do Tratamento
14.
J Geriatr Cardiol ; 12(3): 257-62, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-26089850

RESUMO

BACKGROUND: Sedatives and analgesics are often administered to achieve conscious sedation for diagnostic and therapeutic procedures. Appropriate concerns have been raised regarding post procedure delirium related to peri-procedural medication in the elderly. The objective of this study was to investigate the effect of premedication on new onset delirium and procedural care in elderly patients. METHODS: Patients ≥ 70 years old and scheduled for elective cardiac catheterization were randomly assigned to receive either oral diphenhydramine and diazepam (25 mg/5 mg) or no premedication. All patients underwent a mini mental state exam and delirium assessment using confusion assessment method prior to the procedure and repeated at 4 h after the procedure and prior to discharge. Patients' cooperation during the procedure and ease of post-procedure were measured using Visual Analog Scale (VAS). The degree of alertness was assessed immediately on arrival to the floor, and twice hourly afterwards using Observer's Assessment of Alertness/Sedation Scale (OAA/S). RESULTS: A total of 93 patients were enrolled. The mean age was 77 years, and 47 patients received premedication prior to the procedure. None of the patients in either group developed delirium. Patients' cooperation and the ease of procedure was greater and pain medication requirement less both during and after the procedure in the pre-medicated group (P < 0.05 for both). Nurses reported an improvement with patient management in the pre-medicated group (P = 0.08). CONCLUSIONS: In conclusion, premedication did not cause delirium in elderly patients undergoing cardiac catheterization. The reduced pain medication requirement, perceived procedural ease and post procedure management favors premedication in elderly patients undergoing cardiac catheterization.

15.
Viral Immunol ; 28(4): 222-8, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25798684

RESUMO

Hepatitis C virus (HCV) pathogenesis and treatment outcomes are multifactorial phenomena involving both viral and host factors. This study was designed to determine the role of tumor necrosis factor-related apoptosis-inducing ligand receptor 1(TRAIL-R1) and interferon gamma (IFN-γ) genetic mutations in susceptibility and response to interferon-based therapy of hepatitis C virus (HCV) infection. The detection of TRAIL-R1 rs4242392 and IFN-γ rs2069707 single nucleotide polymorphisms was completed in 118 chronic HCV patients and 96 healthy controls by allele-specific polymerase chain reaction and restriction fragment length polymorphisms polymerase chain reaction. Patients were further categorized into sustained virological responder (SVR) and nonresponder (NR) groups on the basis of their response to interferon-based therapy for HCV infection. Real-time PCR was used for HCV quantification. HCV genotyping was performed by Ohno's method. The results demonstrated that the distribution of the TRAIL-R1 rs4242392TT genotype was significantly higher in the SVR group (78%) compared to the NR group (36%). It showed that chronic HCV patients possessing the TRAIL-R1 rs4242392TT genotype are better responders to interferon-based therapy (p<0.05). The prevalence of the TRAIL-R1 rs4242392TT genotype in healthy controls and chronic HCV patients was 56% and 65% respectively. It indicated that there is the TRAIL-R1 rs4242392 genetic variation plays no role in the spontaneous clearance of HCV infection (p>0.05). The distribution of IFN-γ rs2069707 was the opposite to TRAIL-R1 rs4242392 prevalence, that is, there was high distribution of the IFN-γ rs2069707GG genotype in patients and healthy controls (p<0.05), while the prevalence of IFN-γ rs2069707GG in SVR and NR groups was comparable (p>0.05). In conclusion, genetic variation of TRAIL-R1 rs4242392 is linked with response to interferon-based therapy for HCV infection, and genetic variation IFN-γ rs2069707 is associated with natural clearance of HCV infection.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/imunologia , Interferon gama/genética , Interferons/uso terapêutico , Polimorfismo de Nucleotídeo Único , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/genética , Adulto , Feminino , Técnicas de Genotipagem , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição , Reação em Cadeia da Polimerase em Tempo Real , Resultado do Tratamento , Carga Viral
16.
Arch Virol ; 159(5): 831-46, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-23979177

RESUMO

Hepatitis C virus (HCV) infection is the most important problem across the world. It causes acute and chronic liver infection. Different approaches are in use to inhibit HCV infection, including small organic compounds, siRNA, shRNA and peptide inhibitors. This review article summarizes the current and future therapies for HCV infection. PubMed and Google Scholar were searched for articles published in English to give an insight into the current inhibitors against this life-threatening virus. HCV NS3/4A protease inhibitors and nucleoside/nucleotide inhibitors of NS5B polymerase are presently in the most progressive stage of clinical development, but they are linked with the development of resistance and viral breakthrough. Boceprevir and telaprevir are the two most important protease inhibitors that have been approved recently for the treatment of HCV infection. These two drugs are now the part of standard-of-care treatment (SOC). There are also many other drugs in phase III of clinical development. When exploring the various host-cell-targeting compounds, the most hopeful results have been demonstrated by cyclophilin inhibitors. The current SOC treatment of HCV infection is Peg-interferon, ribavirin and protease inhibitors (boceprevir or telaprevir). The future treatment of this life-threatening disease must involve combinations of therapies hitting multiple targets of HCV and host factors. It is strongly expected that the near future, treatment of HCV infection will be a combination of direct-acting agents (DAA) without the involvement of interferon to eliminate its side effects.


Assuntos
Antivirais/uso terapêutico , Hepacivirus , Hepatite C/tratamento farmacológico , Hepatite C/virologia , Regulação Viral da Expressão Gênica/efeitos dos fármacos , Inativação Gênica , Humanos
17.
Viral Immunol ; 26(5): 343-50, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24116708

RESUMO

BACKGROUND: After invasion of hepatocytes and immune cells, hepatitis C virus has the ability to escape from the host immune system, leading to the progression of disease into chronic infection with associated liver morbidities. Adenosine 5'triphosphate (ATP) is released in most of the pathological events from the affected cells and acts as a signaling molecule by binding to P2X receptors expressed on the host's immune cells and activates the immune system for pro-inflammatory response. Therefore, the present study was designed to analyze the transcript expression of the ionotropic purinergic P2X receptors on peripheral blood mononuclear cells (PBMCs) of chronic HCV patients to have study the immune responses mediated by P2X receptors in chronic HCV infections. METHODS: PBMCs were isolated from the collected blood samples. Transcript analysis of P2X receptors in PBMCs was done. The identity of amplified product was confirmed by sequencing PCR, while the quantification of the transcript expression was done by real time PCR. The relative expression of the P2X receptors was analyzed by unpaired Student's t test using GraphPad Prims 5 software. RESULTS: We found that out of seven isoforms of P2X receptors, P2X1, P2X4, P2X5, and P2X7 receptors are expressed on the PBMCs. P2X1 and P2X7 are significantly upregulated in treatment-naïve chronic HCV patients by 2.2- and 2.5-fold, respectively. However, only P2X7 expression is found increased by 2.7-fold in patients achieving sustained virological response (SVR) after antiviral treatment compared to healthy controls. The expression of P2X receptors remained unaltered in chronic HCV patients not responding to the treatment. CONCLUSION: The present study confirms the significant involvement of P2X receptors in the immune responses mediated by the PBMCs in the chronic HCV infection, which should be further investigated to devise strategies to augment the immune system against this chronic viral disease.


Assuntos
Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/imunologia , Leucócitos Mononucleares/metabolismo , Receptores Purinérgicos P2X/genética , Receptores Purinérgicos P2X/imunologia , Adulto , Antivirais/uso terapêutico , Citocinas/metabolismo , Feminino , Expressão Gênica , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepacivirus/imunologia , Humanos , Interferon-alfa/uso terapêutico , Masculino , Polietilenoglicóis/uso terapêutico , Isoformas de Proteínas/metabolismo , Proteínas Recombinantes/uso terapêutico , Ribavirina/uso terapêutico
18.
Virol J ; 10: 299, 2013 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-24079723

RESUMO

The current standard of care (SOC) for hepatitis C virus (HCV) infection is the combination of pegylated interferon (PEG-IFN), Ribavirin and protease inhibitor for HCV genotype 1. Nevertheless, this treatment is successful only in 70-80% of the patients. In addition, the treatment is not economical and is of immense physical burden for the subject. It has been established now, that virus-host interactions play a significant role in determining treatment outcomes. Therefore identifying biological markers that may predict the treatment response and hence treatment outcome would be useful. Both IFN and Ribavirin mainly act by modulating the immune system of the patient. Therefore, the treatment response is influenced by genetic variations of the human as well as the HCV genome. The goal of this review article is to summarize the impact of recent scientific advances in this area regarding the understanding of human and HCV genetic variations and their effect on treatment outcomes. Google scholar and PubMed have been used for literature research. Among the host factors, the most prominent associations are polymorphisms within the region of the interleukin 28B (IL28B) gene, but variations in other cytokine genes have also been linked with the treatment outcome. Among the viral factors, HCV genotypes are noteworthy. Moreover, for sustained virological responses (SVR), variations in core, p7, non-structural 2 (NS2), NS3 and NS5A genes are also important. However, all considered single nucleotide polymorphisms (SNPs) of IL28B and viral genotypes are the most important predictors for interferon based therapy of HCV infection.


Assuntos
Antivirais/uso terapêutico , Marcadores Genéticos , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Interferons/uso terapêutico , Variação Genética , Genótipo , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/virologia , Humanos , Prognóstico , Ribavirina/uso terapêutico , Resultado do Tratamento
19.
Indian J Virol ; 24(2): 151-6, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24426270

RESUMO

Hepatitis C virus (HCV) is involved in different liver pathologies worldwide. In contemporary scenario, HCV treatment is lagging behind owing to absence of vaccines against virus. The only consideration for HCV treatment is pegylated interferon-alpha and ribavirin that results in sustained virological response in 50 % of patients. Two feasible hosts for HCV infection are chimpanzee and humans. For decades, chimpanzees are sole host to study HCV pathogenesis, but their use is limited due to ethical issues. The dilemma behind HCV therapy is the need of sustainable animal models that can help simulate in vivo conditions. We have assembled recent advances in animal models to study liver diseases for targeted therapy.

20.
J Periodontol ; 83(11): 1382-7, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22324468

RESUMO

BACKGROUND: There is insufficient research on the relationship of oral health and coronary artery disease (CAD) from developing countries, such as Pakistan. This study observes the status of oral health in the CAD population. METHODS: A case-control study was conducted on 145 cases and 145 controls. Otherwise healthy patients with CAD (cases) and individuals free from previous/current history of CAD (controls), having ≥14 remaining teeth, were examined for oral health status through missing teeth, plaque index (PI), and community periodontal index (CPI). Student t test, χ2 test, and multivariate regression analysis were applied at significance level of 95% (P ≤ 0.05) to compare study parameters between cases and controls. RESULTS: A significant difference between cases and controls was observed in this study sample with respect to missing teeth (P = 0.027) and periodontal parameters of PI and CPI (P < 0.001). Cases were observed with significantly higher scores of PI (2 and 3) and CPI (3 and 4) compared with controls. Prevalence of periodontal parameters was observed to be higher in cases than controls at subgroup-level (sex and age group) analysis. A significant odds ratio (OR), unadjusted, between CAD and periodontal indicators of PI (mild to severe plaque/no plaque: OR = 5.04, 95% confidence interval [95% CI] = 2.24 to 11.36) and CPI (healthy/poor periodontal status: OR = 4.59, 95% CI = 1.81 to 11.61) scores was noted; cases were at odds of 1.20 (95% CI = 0.93 to 15.68, P = 0.017) for having poor oral health after adjusting age, sex, and education. CONCLUSION: Poor oral health was significantly associated with CAD in this study sample matched for sociodemographic characteristics.


Assuntos
Doença das Coronárias/complicações , Placa Dentária/complicações , Doenças Periodontais/complicações , Perda de Dente/complicações , Adulto , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Intervalos de Confiança , Índice de Placa Dentária , Países em Desenvolvimento , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Paquistão , Índice Periodontal
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