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1.
J Acquir Immune Defic Syndr ; 95(4): 305-312, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38416032

RESUMO

BACKGROUND: Key populations are disproportionately affected by HIV, viral hepatitis (VH), and sexually transmitted infections (STIs) and face barriers to care. Peer navigation programs are widely used, but evidence supporting their use has not been synthesized. SETTING: Peer navigation programs for sex workers, men who have sex with men, people who inject drugs, prisoners, and trans and gender diverse people globally. METHODS: To inform World Health Organization guidelines, we conducted a systematic review of effectiveness, values and preferences, and cost studies published between January 2010 and May 2021. We searched CINAHL, PsycINFO, PubMed, and EMBASE; screened abstracts; and extracted data in duplicate. The effectiveness review included randomized controlled trials and comparative observational studies evaluating time to diagnosis or linkage to care, treatment initiation, treatment retention/completion, viral load, cure, or mortality. We assessed risk of bias and summarized findings in GRADE evidence profiles. Values and preferences and cost data were summarized descriptively. RESULTS: Four studies evaluated the effectiveness of peer navigators for key populations. All were focused on HIV; none were designed for VH or STIs. These studies showed mixed effects on linkage to care, treatment retention/completion, and viral load; no studies measured treatment initiation, cure, or mortality. Two values and preferences studies with community-based organization staff and health workers suggested peer navigators for key populations were acceptable and valued, although continued challenges remained. No cost studies were identified. CONCLUSIONS: Although limited, available studies provide moderate certainty evidence for benefits of HIV/VH/STI peer navigation programs for key populations. Further evaluations are needed.


Assuntos
Infecções por HIV , Adesão à Medicação , Retenção nos Cuidados , Humanos , Masculino , Infecções por HIV/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Observacionais como Assunto , Populações Vulneráveis
2.
Tob Induc Dis ; 20: 23, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35342383

RESUMO

INTRODUCTION: Tobacco use is a major public health concern, particularly in low- and middle-income countries where 80% of the world's smokers reside. There is limited population-based data from rural Africa on patterns of tobacco smoking and smoker characteristics. We assessed trends in rates of smoking, characteristics of smokers, and factors associated with smoking using repeat population-based cross-sectional surveys in south-central Uganda. METHODS: Data accrued over five survey rounds (2010-2018) of the Rakai Community Cohort Study (RCCS) from consenting individuals aged 15-49 years including sociodemographic and behavioral characteristics and smoking status. Proportions of smokers per survey were compared using χ2 test for trends, and factors associated with smoking were assessed by multivariable logistic regression. RESULTS: The prevalence of tobacco smoking in the general population declined from 7.3% in 2010-2011 to 5.1% in 2016-2018, p<0.001. Smoking rates declined among males (13.9-9.2%) and females (2.2-1.8%) from 2010-2011 to 2016-2018. Smoking prevalence was higher among previously married (11.8-11.7%) compared to currently (8.4-5.3%) and never married persons (3.1-1.8%) from 2010-2011 to 2016-2018. Older age (≥35 years) was associated with higher odds of smoking (AOR=8.72; 95% CI: 5.68-13.39 in 2010-2011 and AOR=9.03; 95% CI: 5.42-15.06 in 2016-2018) compared to those aged <35 years (AOR=4.73; 95% CI: 3.15-7.12 in 2010-2011 and AOR=4.83; 95% CI: 2.95-7.91 in 2016-2018). Primary and secondary/higher education level was significantly associated with lower odds of smoking (AOR=0.20; 95% CI: 0.14-0.29 in 2010-2011 and AOR=0.26; 95% CI: 0.18-0.39 in 2016-2018) compared to no education (AOR=0.43; 95% CI: 0.31-0.59 in 2010-2011 and AOR=0.48; 95% CI: 0.34-0.68 in 2016-2018). Number of sexual partners and HIV status were not associated with smoking. CONCLUSIONS: We observed declining trends in tobacco smoking in the Rakai region of rural Uganda. Smoking was more prevalent in men, older individuals, individuals who were previously married, and individuals with lower education. The decline in smoking may be due to tobacco control efforts, but there is a continued need to target sub-populations with higher smoking prevalence.

3.
Contraception ; 111: 22-31, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34077748

RESUMO

OBJECTIVE: We sought to systematically review the literature on values and preferences for contraception among adolescents and young adults globally. STUDY DESIGN: We searched ten electronic databases for articles from January 1, 2005 through July 27, 2020 regarding end-users' values and preferences for contraception. We included studies that report specifically on people up to 25 years old. RESULTS: Fifty-five studies out of 7,846 met our inclusion criteria. These studies included participants aged 10-25 years and were conducted in 16 countries. Through open coding, we identified 18 content areas. The five most commonly discussed content areas were: (1) general preferences regarding contraception, (2) contraceptive method benefits, (3) contraceptive method drawbacks, (4) the influence of the social context, and (5) the influence of myths and misconceptions, including safety and side effects, on contraceptive choice. Privacy and autonomy were important overarching themes, along with safety of the method. These considerations affected participants' access to and use of contraception. CONCLUSION: Various social, cultural, and method-specific factors influence a young person's values and preferences around contraceptive methods. Understanding their values and preferences can help providers and programs improve contraceptive care for young people.


Assuntos
Anticoncepcionais , Dispositivos Anticoncepcionais , Adolescente , Anticoncepção/métodos , Comportamento Contraceptivo , Serviços de Planejamento Familiar , Humanos , Adulto Jovem
4.
Zhongguo Zhong Yao Za Zhi ; 45(18): 4510-4518, 2020 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-33164382

RESUMO

The names, basic sources, medicinal parts, efficacy and standards of the medicinal materials in Euphorbiaceae were systematically collated and analyzed by the textual research for Yao medicine monographs in this paper. The results showed that there were great differences in the names, basic sources, medicinal parts and efficacy of some medicinal materials recorded in different literatures. There were 19 genera and 60 species(including varieties) of Euphorbiaceae of Yao medicine, involving 50 kinds of medicinal materials. Among them, there were 42 kinds of single basic sources medicine, 8 kinds of multi basic sources medicine, 28 kinds of root medicine, 26 kinds of whole plant medicine, 25 kinds of unique Yao medicine, accounting for 50%, 11 kinds of cross with Chinese medicinal materials, accounting for 22%. There were 21 kinds of Yao medicine standards at all levels, but only 1 kind of Laoban medicine and 2 kinds of Yao medicine standards. The Yao medicine in Euphorbiaceae could be named by means of transliteration of Yao language/Yao language transliteration/Chinese medicine name, Laoban medicine, plant morphology, medicinal properties, color and smell of medicine, while the medicinal parts and efficacy of the same medicinal name were different from those of traditional Chinese medicine. Therefore, the name and basic sources of the medicinal materials in Euphorbiaceae were not standardized, and the quality standard is not perfect. The above results provided a reference for the construction and improvement of quality standard system, the promotion of the production of medicinal materials and clinical medication standards, and the further development and utilization of Euphorbiaceae.


Assuntos
Medicamentos de Ervas Chinesas , Euphorbiaceae , Plantas Medicinais , Humanos , Medicina Tradicional Chinesa , Registros , Padrões de Referência
6.
Epidemiol Rev ; 40(1): 12-26, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29688317

RESUMO

Prisons and other closed facilities create opportunities for transmission of human immunodeficiency virus (HIV) and viral hepatitis during detention and after release. We conducted a systematic review and meta-analysis of peer-reviewed publications (2005-2015) to describe the prevalence of HIV, hepatitis C virus, and hepatitis B virus among key populations in prisons worldwide and to compare estimates of infection with those of other prison populations. Most data were reported for people who inject drugs (PWID; n = 72) and for men who have sex with men (MSM; n = 21); few data were reported on sex workers (SW; n = 6), or transgender women (n = 2). Publications were identified from 29 countries, predominantly middle- and high-income countries. Globally, PWID had 6 times the prevalence of HIV (pooled prevalence ratio (PPR) = 6.0, 95% CI: 3.8, 9.4), 8 times the prevalence of hepatitis C virus (PPR = 8.1, 95% CI: 6.4, 10.4), and 2 times the prevalence of hepatitis B virus (PPR = 2.0, 95% CI: 1.5, 2.7) compared with noninjecting prisoner populations. Among these articles, only those from Iran, Scotland, Spain, and Italy included the availability of methadone therapy; 2 articles included information on access to needle exchange programs by PWID detainees. HIV prevalence was more than 2 times higher among SW (PPR = 2.6, 95% CI: 2.2, 3.1) and 5 times higher among MSM (PPR = 5.3, 95% CI: 3.5, 7.9) compared with other prisoners. None of these articles reported HIV prevention coverage among SW or transgender women; 1 described HIV and sexually transmitted infection screening for MSM in prison. Prevention programs specific to key populations are important, particularly for populations that are criminalized and/or may cycle in and out of prison.


Assuntos
Saúde Global/estatística & dados numéricos , Infecções por HIV/epidemiologia , Hepatite Viral Humana/epidemiologia , Prisioneiros/estatística & dados numéricos , Usuários de Drogas , Feminino , Infecções por HIV/etiologia , Infecções por HIV/transmissão , Hepatite Viral Humana/etiologia , Hepatite Viral Humana/transmissão , Humanos , Masculino , Modelos Estatísticos , Prevalência , Fatores de Risco , Profissionais do Sexo , Minorias Sexuais e de Gênero , Pessoas Transgênero
7.
AIDS ; 31(11): 1579-1591, 2017 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-28481770

RESUMO

OBJECTIVE AND DESIGN: To inform WHO guidelines, we conducted a systematic review and meta-analysis to assess maternal and perinatal outcomes comparing cesarean section (c-section) before labor and rupture of membranes [elective c-section (ECS)] with other modes of delivery for women living with HIV. METHODS: We searched PubMed, CINAHL, Embase, CENTRAL, and previous reviews to identify published trials and observational studies through October 2015. Results were synthesized using random-effects meta-analysis, stratifying for combination antiretroviral therapy (cART), CD4/viral load (VL), delivery at term, and low-income/middle-income countries. RESULTS: From 2567 citations identified, 36 articles met inclusion criteria. The single randomized trial, published in 1999, reported minimal maternal morbidity and significantly fewer infant HIV infections with ECS [odds ratio (OR) 0.2, 95% confidence interval (CI) 0.0-0.5]. Across observational studies, ECS was associated with increased maternal morbidity compared with vaginal delivery (OR 3.12, 95% CI 2.21-4.41). ECS was also associated with decreased infant HIV infection overall (OR 0.43, 95% CI 0.30-0.63) and in low-income/middle-income countries (OR 0.27, 95% CI 0.16-0.45), but not among women on cART (OR 0.82, 95% CI 0.47-1.43) or with CD4 cell count more than 200/VL less than 400/term delivery (OR 0.59, 95% CI 0.21-1.63). Infant morbidity moderately increased with ECS. CONCLUSION: Although ECS may reduce infant HIV infection, this effect was not statistically significant in the context of cART and viral suppression. As ECS poses other risks, routine ECS for all women living with HIV may not be appropriate. Risks and benefits will differ across settings, depending on underlying risks of ECS complications and vertical transmission during delivery. Understanding individual client risks and benefits and respecting women's autonomy remain important.


Assuntos
Cesárea , Procedimentos Cirúrgicos Eletivos , Fidelidade a Diretrizes , Infecções por HIV/transmissão , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez/cirurgia , Saúde Reprodutiva , Parto Obstétrico , Feminino , Humanos , Estudos Observacionais como Assunto , Gravidez , Medição de Risco
8.
Spinal Cord ; 54(1): 46-50, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26261074

RESUMO

OBJECTIVES: The objective of this study was to evaluate the effect and safety of trigonal injection of botulinum toxin A (BTX-A) for patients with neurological detrusor overactivity (NDO) with incontinence. METHODS: A prospective, multicenter, single-blind and randomized controlled trial was conducted between June 2011 and June 2014. Spinal cord injury patients with urinary incontinence secondary to NDO overactivity were recruited. At a 1:1 ratio, patients randomly received 200 U BTX-A intradetrusor injections excluding the trigone (the control group) or 160 U intradetrusor and 40 U intratrigonal injections (the experimental group). Patients were evaluated at baseline and at 4 and 12 weeks after injection. The efficacy and safety outcomes included Incontinence-Specific-Quality-of-Life Instrument (I-QoL), voiding volume, urinary incontinence episodes, complete dryness, maximum detrusor pressure (P(detmax)) and volume at first involuntary detrusor contraction (V(FIDC)). Vesicoureteral reflux (VUR) and other adverse events were recorded. RESULTS: Ninety-six patients were recruited and 91 of them completed the trial. Among the 91 patients, 47 were randomized to the experimental group and 44 to the control group. There were no significant differences in baseline evaluation items (gender, age, duration of spinal cord injury, level of neurological injury, AIS (the American Social Injury Association) scores) between the two groups. At 12 weeks, the improvement was significantly better in the experimental group compared with that in the control group for I-QoL (26.01 vs 18.75, P=0.01), mean urinary incontinence episodes (-5.22 vs -4.68 per day, P=0.01), complete dryness (13 vs 5, P=0.03), mean voiding volume (159.72 vs 139.07 ml, P=0.02), P(detmax) (-33.34 vs -28.02 cmH(2)O, P=0.04) and VFIDC (106.81 vs 97.86 ml, P=0.02), duration of first detrusor contraction (-41.54 vs -18.65 s, P=0.03) and the number of patients with detrusor contraction (-20 vs -9, P=0.02). In both the groups, no patients developed VUR. CONCLUSIONS: BTX-A intradetrusor and intratrigonal injections are more effective compared with those excluding the trigone for patients with NDO with incontinence. Intratrigonal injections do not induce VUR.


Assuntos
Toxinas Botulínicas Tipo A/uso terapêutico , Fármacos Neuromusculares/uso terapêutico , Bexiga Urinária Hiperativa/tratamento farmacológico , Incontinência Urinária/tratamento farmacológico , Feminino , Humanos , Masculino , Estudos Prospectivos , Qualidade de Vida/psicologia , Método Simples-Cego , Traumatismos da Medula Espinal/complicações , Resultado do Tratamento , Bexiga Urinária Hiperativa/etiologia , Incontinência Urinária/etiologia , Refluxo Vesicoureteral/tratamento farmacológico
9.
PLoS Genet ; 10(12): e1004872, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25501822

RESUMO

Adaptation to ecologically complex environments can provide insights into the evolutionary dynamics and functional constraints encountered by organisms during natural selection. Adaptation to a new environment with abundant and varied resources can be difficult to achieve by small incremental changes if many mutations are required to achieve even modest gains in fitness. Since changing complex environments are quite common in nature, we investigated how such an epistatic bottleneck can be avoided to allow rapid adaptation. We show that adaptive mutations arise repeatedly in independently evolved populations in the context of greatly increased genetic and phenotypic diversity. We go on to show that weak selection requiring substantial metabolic reprogramming can be readily achieved by mutations in the global response regulator arcA and the stress response regulator rpoS. We identified 46 unique single-nucleotide variants of arcA and 18 mutations in rpoS, nine of which resulted in stop codons or large deletions, suggesting that subtle modulations of ArcA function and knockouts of rpoS are largely responsible for the metabolic shifts leading to adaptation. These mutations allow a higher order metabolic selection that eliminates epistatic bottlenecks, which could occur when many changes would be required. Proteomic and carbohydrate analysis of adapting E. coli populations revealed an up-regulation of enzymes associated with the TCA cycle and amino acid metabolism, and an increase in the secretion of putrescine. The overall effect of adaptation across populations is to redirect and efficiently utilize uptake and catabolism of abundant amino acids. Concomitantly, there is a pronounced spread of more ecologically limited strains that results from specialization through metabolic erosion. Remarkably, the global regulators arcA and rpoS can provide a "one-step" mechanism of adaptation to a novel environment, which highlights the importance of global resource management as a powerful strategy to adaptation.


Assuntos
Citrobacter freundii/genética , Escherichia coli/genética , Evolução Molecular , Adaptação Biológica/genética , Proteínas da Membrana Bacteriana Externa/genética , Proteínas de Bactérias/genética , Ciclo do Ácido Cítrico/genética , Proteínas de Escherichia coli/genética , Trato Gastrointestinal/microbiologia , Regulação Bacteriana da Expressão Gênica , Interação Gene-Ambiente , Variação Genética , Humanos , Mutação , Fenótipo , Proteoma/genética , Proteoma/metabolismo , Proteínas Repressoras/genética , Fator sigma/genética , Regulação para Cima
10.
Clin Exp Dermatol ; 39(6): 696-707, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25039593

RESUMO

BACKGROUND: Psoriasis is a chronic, recurrent skin disease that affects approximately 2-3% of the world's population, and can significantly impair patients' wellbeing and their physical and mental functioning. AIM: To systematically evaluate the efficacy and safety of ustekinumab versus placebo for psoriasis. METHODS: We performed a systematic review of all the relevant published literature relating to randomized controlled trials (RCTs) of ustekinumab from 1990 to August 2013. Relative ratios (RRs) and 95% confidence intervals (CIs) were calculated, and meta-analysis was conducted with Revman5.2.6 software, while GRADE Profile 3.6 was used to evaluate the quality of the evidence. RESULTS: In total, 9 RCTs involving 11 381 patients were included. The meta-analysis results were as follows. (i) At the end of 12 weeks, the ustekinumab group had a larger number of patients with improvement in Psoriasis Area and Severity Index (PASI) of at least 50% (PASI50), at least 75% (PASI75) and at least 90% (PASI90); a larger number with improvement in Physician's Global Assessment (PGA), and a larger number with improvement in Dermatology Life Quality Index (DLQI) to a score of 0 or 1 (no effect at all on patient's life). (ii) There was no significant difference in efficacy between 45 mg and 90 mg ustekinumab at the end of 12 weeks. (iii) There was no obvious difference between the ustekinumab and placebo groups in the incidence of adverse events over 5 years. There was also no obvious difference between the two doses of ustekinumab after 5 years. CONCLUSION: Our results indicate that ustekinumab is safe for patients with moderate to severe plaque psoriasis over a period of 5 years, and it is effective after 12 weeks. There was no significant superiority in efficacy between the 45 mg and 90 mg doses for short-term therapy. Results of the long-term safety evaluation are consistent with short-term reports of ustekinumab safety. More long-term studies and RCTs are needed to validate these results.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Imunossupressores/uso terapêutico , Psoríase/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Ustekinumab
11.
Cell Calcium ; 56(2): 59-67, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24889371

RESUMO

Increased expression of specific calcium channels in some cancers and the role of calcium signaling in proliferation and invasion have led to studies assessing calcium channel inhibitors as potential therapies for some cancers. The use of channel activators to promote death of cancer cells has been suggested, but the risk of activators promoting cancer cell proliferation and the importance of the degree of channel over-expression is unclear. We developed an MCF-7 breast cancer cell line with inducible TRPV1 overexpression and assessed the role of TRPV1 levels on cell death mediated by the TRPV1 activator capsaicin and the potential for submaximal activation to promote proliferation. The TRPV1 level was a determinant of cell death induced by capsaicin. A concentration response curve with varying TRPV1 expression levels identified the minimum level of TRPV1 required for capsaicin induced cell death. At no level of TRPV1 over-expression or capsaicin concentration did TRPV1 activation enhance proliferation. Cell death induced by capsaicin was necrotic and associated with up-regulation of c-Fos and RIP3. These studies suggest that activators of specific calcium channels may be an effective way to induce necrosis and that this approach may not always be associated with enhancement of cancer cell proliferation.


Assuntos
Canais de Cátion TRPV/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Cálcio/metabolismo , Capsaicina/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/toxicidade , Feminino , Humanos , Células MCF-7 , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Canais de Cátion TRPV/genética , Regulação para Cima/efeitos dos fármacos
12.
J Surg Case Rep ; 2012(10): 7, 2012 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-24960747

RESUMO

Retropharyngeal or parapharyngeal abscesses developing after intubation are rare. This can present as surgical emergency post extubation. We report a case of retropharyngeal abscess that probably occurred as a complication of laryngeal mask insertion.

13.
Br J Pharmacol ; 153(6): 1177-84, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18264127

RESUMO

BACKGROUND AND PURPOSE: An oral, single dose of 7.5 mg kg(-1) of unfractionated heparin (UFH) reduces thrombosis by 50% in a rat model of venous thrombosis. As long-term use is required clinically, our objectives were to study the antithrombotic effects following repeated oral UFH administration. EXPERIMENTAL APPROACH: Bovine lung UFH was administered by oral gavage to rats in 3 doses of 7.5 mg kg(-1) each 12, 24, 48, and 72 h apart; and in 3 or 15 doses of 1 mg kg(-1) every 48 h. The last dose was given immediately after thrombus initiation where 10% formalin in methanol was applied to the jugular vein. The vessel was examined for thrombosis 4 h later. Amounts of heparin in tissue and endothelium, and plasma anticoagulant activity were measured. KEY RESULTS: When 3 x 7.5 mg kg(-1) heparin was given, thrombotic incidence was most reduced at 48 h dose-intervals and was significantly less than single dose treatment. There was a negative correlation between endothelial heparin content and thrombotic incidence, but not anticoagulant activity. When 3 doses of 1 mg kg(-1) every 48 h were given, thrombotic incidence was similar to single dose treatment. When 15 doses were given, total thrombotic incidence was less than for 3 doses and was similar to that after s.c. administration. CONCLUSIONS AND IMPLICATIONS: Antithrombotic activity increased with repeated doses of oral UFH, with antithrombotic effects similar to s.c. administration. Antithrombotic activity was related to heparin on endothelium.


Assuntos
Anticoagulantes/farmacologia , Heparina/farmacologia , Trombose/tratamento farmacológico , Administração Oral , Animais , Anticoagulantes/administração & dosagem , Anticoagulantes/farmacocinética , Bovinos , Modelos Animais de Doenças , Esquema de Medicação , Endotélio Vascular/metabolismo , Heparina/administração & dosagem , Heparina/farmacocinética , Injeções Subcutâneas , Masculino , Ratos , Ratos Wistar , Distribuição Tecidual
14.
J Clin Psychiatry ; 68(1): 29-36, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17284127

RESUMO

OBJECTIVE: Asian populations may differ from other races in response to antipsychotics. Studies of aripiprazole in Asian populations are scarce. This study aimed to investigate the efficacy, safety, and tolerability of aripiprazole in Chinese patients with acute schizophrenia or schizoaffective disorder. METHOD: This 4-week, double-blind, randomized, parallel study was conducted in 5 medical centers in Taiwan between March 2004 and January 2005. A total of 83 patients with a primary DSM-IV diagnosis of schizophrenia or schizoaffective disorder were randomly assigned (with a randomization ratio of 3:2) to 15 mg/day of aripiprazole (N = 49) or 6 mg/day of risperidone (N = 34). Efficacy measures included the Positive and Negative Syndrome Scale (PANSS) total, positive, and negative scores and Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement scale scores. Extrapyramidal symptoms (EPS), weight gain, serum prolactin level, QTc interval, and self-reported adverse events were assessed as measures of safety and tolerability. RESULTS: Both the aripiprazole and risperidone groups showed statistical improvement from baseline in PANSS total, PANSS positive, PANSS negative, and CGI-S scores at study endpoint (all p < .001). Significant improvement was noted in the first week of treatment for both treatment groups. There were no significant differences in efficacy measures between treatment groups. Aripiprazole showed significantly less EPS liability as assessed by the Simpson-Angus Scale (p < .005) and less serum prolactin level elevation (p < .001) than risperidone. Both groups showed mild weight gain. No patients showed clinically significant QTc interval prolongation in this study. CONCLUSION: Compared with risperidone 6 mg/day, aripiprazole 15 mg/day has comparable efficacy and favorable safety and tolerability profiles in the short-term treatment of Chinese patients with acute schizophrenia. In this group of Chinese patients, the overall response to aripiprazole did not differ from that of white patients. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT00283179.


Assuntos
Antipsicóticos/uso terapêutico , Piperazinas/uso terapêutico , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/etnologia , Quinolonas/uso terapêutico , Risperidona/uso terapêutico , Adulto , Antipsicóticos/efeitos adversos , Aripiprazol , China/etnologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Piperazinas/efeitos adversos , Quinolonas/efeitos adversos , Risperidona/efeitos adversos , Resultado do Tratamento
15.
Histol Histopathol ; 21(9): 941-50, 2006 09.
Artigo em Inglês | MEDLINE | ID: mdl-16763943

RESUMO

We previously reported that high glucose treated cultured endothelial cells (ECs) showed intercellular gaps by transmission electron microscopy (TEM). These gaps were abrogated with insulin and/or heparin treatment. Our aims were to assess the severity of injury in ECs treated with high glucose for variable duration, and to further study the protective effects of insulin and/or heparin. Cells were also treated with L-buthionine sulfoximine (BSO), a glutathione inhibitor, to help understand the mechanism of high glucose injury. Primary porcine ECs were treated with high glucose (30 mM) for 2, 6 or 10 days; and glucose plus insulin (1 U/ml), glucose plus heparin (5 microg/ml), glucose plus insulin plus heparin for 6 days. ECs were treated with BSO (0.001-0.05 mM) for 2 days. Pellets from trypsinized cells were processed for TEM. High glucose treatment revealed apoptosis or necrosis showing variable cell size, abnormal nuclei, condensation of nuclear chromatin, few mitochondria, cell membrane disruption and needle-shaped structures. Changes increased with duration of exposure. In high glucose plus heparin or insulin treated cultures at least one-half of the cells appeared normal. Most ECs were intact when treated with high glucose plus insulin plus heparin. BSO treatment showed dose-dependent changes with low doses showing apoptosis whereas higher doses revealed necrosis similar to high glucose treatment for 6 or 10 days. High glucose-induced EC injury increased with duration of exposure. These data demonstrate that high glucose injury resembles that of BSO treatment, suggesting that glutathione depletion may be involved in EC injury. Insulin and/or heparin protect against high glucose-induced injury.


Assuntos
Células Endoteliais/patologia , Células Endoteliais/ultraestrutura , Endotélio Vascular/patologia , Endotélio Vascular/ultraestrutura , Glucose/metabolismo , Animais , Apoptose , Butionina Sulfoximina/farmacologia , Células Cultivadas , Relação Dose-Resposta a Droga , Glutationa/antagonistas & inibidores , Glutationa/metabolismo , Heparina/metabolismo , Heparina/farmacologia , Insulina/metabolismo , Microscopia Eletrônica de Transmissão/métodos , Necrose , Suínos
16.
Clin Lab Haematol ; 28(2): 111-6, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16630215

RESUMO

Venous thromboembolism (VTE) is a common vascular disease that results in two major clinical manifestations: deep venous thrombosis (DVT) and pulmonary embolism (PE). Several genetic risk factors, especially factor V Leiden and prothrombin G20210A mutations have been reported to be related to VTE in Caucasians, but the relationship remains controversial in other populations. Thus, the objective of the present study was to compare the frequency of the two mutations and also to investigate whether acquired risk factors other than genetic mutations may play a different role in Chinese VTE patients. Thirty-five patients were diagnosed with DVT concomitant PE, 178 patients with DVT, 54 patients with PE and 102 control subjects were recruited. The mutation was determined by the polymerase chain reaction-restriction fragment length polymorphism method. Of all subjects, none was a carrier of factor V Leiden or prothrombin G20210A mutations. The frequency of surgery was significantly higher in the PE group than that in other groups. There was no significant difference among the three groups in other known risk factors. The data presented here indicate that factor V Leiden and prothrombin G20210A mutations are very rare in the Chinese population, and the genetic risk profile of VTE in the Chinese population is different from that in Caucasians.


Assuntos
Fator V/genética , Mutação , Protrombina/genética , Embolia Pulmonar/genética , Trombose Venosa/genética , Adulto , Povo Asiático/genética , Feminino , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Embolia Pulmonar/complicações , Fatores de Risco , Trombose Venosa/complicações
17.
J Nat Prod ; 66(3): 350-6, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12662091

RESUMO

Microbial transformation studies of the cardiovascular drugs mexrenone (1) and canrenone (2) were conducted. Thirty-nine biotransformations of mexrenone and 84 biotransformations of canrenone were analyzed. Metabolism of the substrate was observed in the majority of these cases. Several monohydroxylated derivatives were detected by HPLC-MS-UV and subsequently identified. Two new mexrenone derivatives, 11alpha- (3) and 12beta-hydroxymexrenone (4), and the known metabolite 6beta-hydroxymexrenone (5) were isolated as major products produced by the Beauveria bassiana ATCC 13144 bioconversion (3) and the Mortierella isabellina bioconversion (4 and 5), respectively. Single-elimination products were also sought; however, only the production of the known metabolite Delta(1,2)-mexrenone (6) by several bacteria was confirmed. One new monohydroxylated derivative of canrenone, 9alpha-hydroxycanrenone (7), was isolated as a major product from the Corynespora cassiicola bioconversion. Structure elucidation of all metabolites was based on NMR and HRMS analyses.


Assuntos
Canrenona/metabolismo , Fármacos Cardiovasculares/metabolismo , Fungos/metabolismo , Mortierella/metabolismo , Espironolactona/análogos & derivados , Espironolactona/metabolismo , Biotransformação , Cromatografia Líquida de Alta Pressão , Fermentação , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Estereoisomerismo
18.
Int J Radiat Biol ; 79(2): 107-18, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12569014

RESUMO

PURPOSE: Alpha-radiation from polonium-210 ((210)Po) can elevate background radiation dose by an order of magnitude in people consuming large quantities of meat and seafood, particularly caribou and reindeer. Because up to 50% of the ingested (210)Po body burden is initially found in the blood, a primary target for the short range alpha-particles is the endothelial cells lining the blood vessels. This study examined the relative biological effectiveness (RBE) of (210)Po alpha-particles versus 250 kVp X-rays in producing injury to cultured bovine aortic endothelial cells. MATERIALS AND METHODS: Radiation effects on cells were measured in four different ways: the percentage viable cells by trypan blue dye exclusion, the number of live cells, the lactate dehydrogenase (LDH) release to medium and the ability to form colonies (clonogenic survival). RESULTS: Comparison of dose-response curves yielded RBE values of 13.1+/-2.5 (SEM) for cell viability, 10.3+/-1.0 for live cell number and 11.1+/-3.0 for LDH activity. The RBE values for clonogenic survival were 14.0+/-1.0 based on the ratio of the initial slopes of the dose-response curves and 13.1, 9.9 and 7.7 for 50, 10 and 1% survival rate, respectively. At X-ray doses <0.25 Gy, a pronounced stimulatory effect on proliferation was noted. CONCLUSIONS: Exposure to (210)Po alpha-particles was seven to 14 times more effective than X-ray exposure in causing endothelial cell damage.


Assuntos
Endotélio Vascular/efeitos da radiação , Raios X/efeitos adversos , Partículas alfa/efeitos adversos , Animais , Bovinos , Sobrevivência Celular/efeitos da radiação , Células Cultivadas , Ensaio de Unidades Formadoras de Colônias , Endotélio Vascular/citologia , Endotélio Vascular/lesões , Cadeia Alimentar , Contaminação Radioativa de Alimentos , Humanos , Microscopia Eletrônica , Polônio/efeitos adversos , Polônio/sangue , Eficiência Biológica Relativa
19.
Dis Esophagus ; 15(3): 257-61, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12445002

RESUMO

Four families with a history of esophageal cancer were studied and their family trees analyzed. All the families had lived in Chaoshan for about 20 generations, speak Chanshan dialect, and generally have a predilection for drinking scalding Gong Fu tea and eating pickled Chinese cabbage. The majority of the esophageal cancer patients of the first generation were diagnosed 40 or 50 years ago after presenting with the typical symptom of dysphagia, whereas patients of the second and third generations were diagnosed mainly by means of radiography and pathology. The ratio of male to female patients was 14:5, which corresponds to that in the general population. The average age at occurrence of esophageal carcinoma in the patients studied was lower than in the general population and had progressively decreased from generation to generation.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Predisposição Genética para Doença , Idoso , Carcinoma de Células Escamosas/diagnóstico , China/epidemiologia , Doenças Endêmicas , Neoplasias Esofágicas/diagnóstico , Família , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Medição de Risco , Fatores de Risco , População Rural
20.
Thromb Haemost ; 85(1): 114-8, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11204561

RESUMO

Previous studies in rats show that unfractionated heparin and the low molecular weight heparin logiparin have a dose-dependent antithrombotic effect and are found in endothelium and plasma when administered orally. Objectives of the present study were to determine if similar evidence of absorption could be observed with oral reviparin sodium. Thrombosis incidence was determined 4 h after application of 10% formalin in methanol to the exposed jugular vein. A dose-dependent antithrombotic effect was observed when 0.01 to 7.5 mg/kg (20 rats/group) was administered by stomach tube immediately following thrombus initiation. Thrombotic incidence was also significantly reduced when 0.025 mg/kg was given 4 and 2 h prior to, immediately after, and 2 and 3 h following thrombus initiation. Reviparin was recovered from endothelium and plasma in trace amounts at all doses. At 0.025 mg/kg, peak aortic endothelial reviparin concentrations were found at 1 and 2 h and peak plasma anti-Xa activity was detected at 2 h. Trace amounts of plasma TFPI were found only at 8 h after administration. Dose-dependent antithrombotic activity and recovery from endothelium and plasma support the hypothesis that orally administered reviparin sodium is absorbed.


Assuntos
Heparina de Baixo Peso Molecular/farmacocinética , Trombose/prevenção & controle , Administração Oral , Animais , Aorta , Testes de Coagulação Sanguínea , Relação Dose-Resposta a Droga , Endotélio Vascular/metabolismo , Inibidores do Fator Xa , Fibrinolíticos/administração & dosagem , Fibrinolíticos/farmacocinética , Heparina de Baixo Peso Molecular/administração & dosagem , Heparina de Baixo Peso Molecular/farmacologia , Masculino , Modelos Animais , Ratos , Ratos Wistar , Equivalência Terapêutica , Trombose/induzido quimicamente , Trombose/tratamento farmacológico , Distribuição Tecidual , Veias Cavas
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