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1.
Med J Malaysia ; 79(2): 128-132, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38553915

RESUMO

INTRODUCTION: Domestic violence (DV) is a pervasive social and public health issue affecting millions globally, regardless of age, gender or socioeconomic background. Understanding victim and perpetrators' characteristics as well as the DV injury patterns are essential for developing targeted interventions and prevention strategies. Although past DV studies have often focused on female victims, it is increasingly recognised that DV affects a significant proportion of male victims as well. This study aimed to comprehensively examine both male and female DV victims and perpetrators, as well as the anatomical regions affected in DV cases in Kuching, Sarawak, so that a deeper understanding of DV within this community can be enhanced. MATERIALS AND METHODS: This prospective, observational study was conducted from March 2021 to March 2023, involving adult DV victims aged 18 years and above admitted to the One Stop Crisis Center (OSCC) of Sarawak General Hospital. Data were collected from the OSCC clerking sheet, focusing on the victims, perpetrators and the violence characteristics. RESULTS: A total of 133 DV victims were analysed, with 25.6% being male victims. Although majority of the perpetrators in cases involving male victims were male perpetrators, there was a significantly higher number of female perpetrators in these male DV cases (i.e., 5 out of 34 cases,14.7%) compared to in female DV cases (4 out of 99 cases, 4.0%) (p = 0.05). The commonest type of relationship between the victims and perpetrators was spouses or ex-spouses (56.4%). Male victims had more cases involving weapons (67.6%) compared to female victims (26.3%), p < 0.001. The most affected anatomical region was the head and neck (63.9%) region although no significant differences were observed. CONCLUSION: The study reveals that DV affects individuals across all societal classes and income groups. Although weapons were used more frequently in male DV cases, other injury characteristics and affected anatomical regions were not significantly different between genders, suggesting female perpetrators can inflict similar injuries as male perpetrators. Subgroup analysis showed that the majority of male victims faced abuse from their children or grandchildren, hinting at hidden geriatric abuse, that should be unmasked and treated as a separate entity.


Assuntos
Vítimas de Crime , Violência Doméstica , Adulto , Feminino , Humanos , Masculino , Malásia , Estudos Prospectivos
3.
J Bone Joint Surg Am ; 105(12): 924-932, 2023 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-37220180

RESUMO

BACKGROUND: Total knee arthroplasty (TKA) is a cost-effective procedure, but it is also associated with substantial postoperative pain. The present study aimed to compare pain relief and functional recovery after TKA among groups that received intravenous corticosteroids, periarticular corticosteroids, or a combination of both. METHODS: This randomized, double-blinded clinical trial in a local institution in Hong Kong recruited 178 patients who underwent primary unilateral TKA. Six of these patients were excluded because of changes in surgical technique; 4, because of their hepatitis B status; 2, because of a history of peptic ulcer; and 2, because they declined to participate in the study. Patients were randomized 1:1:1:1 to receive placebo (P), intravenous corticosteroids (IVS), periarticular corticosteroids (PAS), or a combination of intravenous and periarticular corticosteroids (IVSPAS). RESULTS: The pain scores at rest were significantly lower in the IVSPAS group than in the P group over the first 48 hours (p = 0.034) and 72 hours (p = 0.043) postoperatively. The pain scores during movement were also significantly lower in the IVS and IVSPAS groups than in the P group over the first 24, 48, and 72 hours (p ≤ 0.023 for all). The flexion range of the operatively treated knee was significantly better in the IVSPAS group than in the P group on postoperative day 3 (p = 0.027). Quadriceps power was also greater in the IVSPAS group than in the P group on postoperative days 2 (p = 0.005) and 3 (p = 0.007). Patients in the IVSPAS group were able to walk significantly further than patients in the P group in the first 3 postoperative days (p ≤ 0.003). Patients in the IVSPAS group also had a higher score on the Elderly Mobility Scale than those in the P group (p = 0.036). CONCLUSIONS: IVS and IVSPAS yielded similar pain relief, but IVSPAS yielded a larger number of rehabilitation parameters that were significantly better than those in the P group. This study provides new insights into pain management and postoperative rehabilitation following TKA. LEVEL OF EVIDENCE: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.


Assuntos
Artroplastia do Joelho , Manejo da Dor , Humanos , Idoso , Manejo da Dor/métodos , Artroplastia do Joelho/efeitos adversos , Resultado do Tratamento , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Corticosteroides , Anestésicos Locais , Método Duplo-Cego
5.
Med J Malaysia ; 78(1): 118-123, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36715201

RESUMO

INTRODUCTION: Although healthcare service industry has been thriving in Malaysia, the types of healthcare service quality models used in past research as well as their key messages had not been explored. A scoping review was performed to determine the validated healthcare service quality models, the key messages of these past studies and potential research gaps that should be addressed in future studies. MATERIALS AND METHODS: Relevant, peer-reviewed, Englishlanguage articles on healthcare service quality in Malaysia were independently searched by the authors using the SCOPUS and EMERALD databases. Articles that do not directly address healthcare service quality within the Malaysian setting were excluded. Additional articles were identified from the reference lists of the selected articles and from Google search engine. A total of 43 out of 2,749 articles were selected. RESULTS: Most of these studies (28 out of the 43 articles, 65.1%) in this scoping review used either the original or a modified version of SERVQUAL instrument to measure healthcare service quality. Significant positive relationships between tangibles, assurance and empathy with patient satisfaction were identified. As SERVQUAL primarily measures the functional dimension of service quality, this suggests that past studies on Malaysian healthcare services emphasised heavily on the functional dimension of healthcare service quality. Functional dimension refers to the expressive performance on how the healthcare service is rendered whereas technical dimension refers to the types of services rendered as well as its safety and efficacy. CONCLUSION: A pertinent research gap identified in this review is the lack of studies that measure both technical and functional dimensions comprehensively. Future research should adopt a more holistic (incorporating both technical dimension and functional dimension) measurement of healthcare service quality.


Assuntos
Lacunas de Evidências , Satisfação do Paciente , Humanos , Malásia
7.
Med J Malaysia ; 76(6): 814-819, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34806666

RESUMO

INTRODUCTION: Although menstruation is a physiological process, it is shrouded with socio-cultural and religious beliefs. Healthcare providers should be aware that these influences may affect how women perceive their menstrual disorders. The primary objective of this study was to develop a validated questionnaire measuring the sociocultural and religious beliefs during menstruation. METHODS: In the first stage, a preliminary list of items measuring socio-cultural and religious beliefs during menstruation was generated. In the second stage, exploratory factor analysis was performed. Finally, confirmatory factor analysis using reflective measurement model and structural equation modelling was performed using partial least squares. The practices of these beliefs were included as mediating effect. Biological symptoms of menstruation were added in as another factor. RESULTS: A total of 400 female students from the Universiti Malaysia Sarawak, Malaysia were recruited. A preliminary list of 22 items was first generated. From the confirmatory factor analysis, two factors were iteratively removed due to poor factor loadings. Four factors were retained, i.e., i) "religious beliefs"; ii) "unpleasant (or dirty) nature of menstruation"; iii) "personal restrictions (dietary and behavior)"; and iv) "restrictions of interactions with male gender". In structural equation modelling, only 2 factors, i.e., the practices of "personal restrictions (dietary and behavioural)" and "restriction of interactions with males" had significant negative impact on quality of life. CONCLUSION: Menstruation should not be viewed purely from a biological lens as there are layers of sociocultural and religious beliefs surrounding it.


Assuntos
Menstruação , Qualidade de Vida , Feminino , Humanos , Malásia , Masculino , Religião , Estudantes
8.
J Clin Tuberc Other Mycobact Dis ; 21: 100189, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32995571

RESUMO

INTRODUCTION: There is an increasing trend worldwide in the incidence of Mycobacterium avium complex pulmonary diseases (MAC-PD) and the diagnosis is sometimes complicated. Recently, an enzyme immunoassay (EIA) kit that detects serum IgA antibody against MAC-specific glycopeptidolipid (GPL) core antigen had been developed and found to be useful in discriminating MAC-PD from other lung diseases. The antibody was subsequently also found to be elevated in patients suffering Mycobacterium abscessus pulmonary diseases (MAB-PD). This study is to evaluate this EIA kit in the serological diagnosis of MAC-PD in Hong Kong Chinese patients. METHODS: The study was conducted in Grantham Hospital, Hong Kong between July 2017 and July 2018. Assay of the IgA antibody level using the EIA kit was done on blood samples collected from patients suffering from MAC-PD, MAB-PD, pulmonary tuberculosis and other lung diseases. RESULTS: There were 100 subjects recruited into the study, among which 11 were excluded. By using the cut-off value 0.7 U/mL provided by the manufacturer, the sensitivity and specificity for diagnosis were 73.7% and 77.6% for MAC-PD; 50% and 77.6% for MAB-PD. By receiver operating characteristic curves analysis, new cut-off for MAC-PD and MAB-PD were calculated as 1.771 U/mL and 0.172 U/m, respectively. The sensitivity and specificity were 68.4% and 86.2% for MAC-PD, whereas 66.7% and 72.4% for MAB-PD. CONCLUSIONS: Our study showed that the enzyme immunoassay of IgA antibodies against MAC-specific glycopeptidolipid core antigen could help to distinguishing MAC and M. abscessus pulmonary diseases from pulmonary tuberculosis and other lung diseases among Hong Kong Chinese patients. Further larger scale studies in our local population for the usefulness of this antibody test in the diagnosis and monitoring of MAC and M. abscessus lung diseases might be warranted.

10.
Anaesthesia ; 71(10): 1222-33, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27506326

RESUMO

Propofol is used both for induction and maintenance of anaesthesia. Recent evidence shows that propofol has analgesic properties. This meta-analysis evaluated differences in postoperative analgesia between general anaesthetic maintenance with intravenous propofol and inhalational anaesthetics. Fourteen trials met inclusion criteria and were included. Our outcomes were pain scores 2 and 24 h after surgery. No significant difference in pain scores was found at 2 h after surgery (Hedge's g (95% CI) -0.120 (-0.415-0.175) (p = 0.425). Propofol was associated with a statistically significant, albeit marginal, reduction in pain scores 24 h after surgery (Hedge's g (95% CI) -0.134 (-0.248 to -0.021) (p = 0.021). Data were insufficient to allow a meaningful analysis regarding 24-h morphine-equivalent consumption. Propofol was associated with reduced postoperative nausea and vomiting (relative risk (95%CI) 0.446 (0.304-0.656) (p < 0.0001). In conclusion, this meta-analysis suggests that propofol improves postoperative analgesia compared with inhalational anaesthesia 24 h after surgery, with a lower incidence of nausea and vomiting.


Assuntos
Anestesia Geral/métodos , Anestésicos Intravenosos , Cuidados Intraoperatórios/métodos , Dor Pós-Operatória/tratamento farmacológico , Propofol , Humanos
11.
Clin Exp Immunol ; 183(2): 239-47, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26425827

RESUMO

Vitamin A supports the induction of immunoglobulin (Ig)A responses at mucosal surfaces in mice, but much less is known about the influence of vitamins on antibody isotype expression in humans. To address this knowledge gap, we examined 46 residual blood samples from adults and children, some of whom were experiencing influenza virus infections of the respiratory tract. Assays were performed for retinol binding protein (RBP, a surrogate for vitamin A), vitamin D (a related vitamin) and antibody isotypes. Results showed that all but two tested samples exhibited RBP and/or vitamin D insufficiencies or deficiencies. Vitamin D correlated with blood IgM and IgG3, while RBP correlated with IgG4 and IgA. RBP also correlated positively with age and with influenza virus-specific antibody neutralization titres. Individuals with low blood RBP levels exhibited the highest frequencies of over-expressed cytokines and growth factors in nasal wash samples, an indication of inflamed mucosal tissues. While cause-effect relationships were not discerned, results support a hypothesis that vitamins directly influence B cell isotype expression in humans, and by so doing may help protect mucosal surfaces from respiratory viral disease.


Assuntos
Anticorpos Antivirais/sangue , Isotipos de Imunoglobulinas/sangue , Vírus da Influenza A/imunologia , Influenza Humana/imunologia , Sistema Respiratório/imunologia , Proteínas de Ligação ao Retinol/análise , Vitamina D/sangue , Adolescente , Adulto , Fatores Etários , Idoso , Anticorpos Neutralizantes/sangue , Criança , Citocinas/genética , Citocinas/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Isotipos de Imunoglobulinas/genética , Imunoglobulina M/sangue , Influenza Humana/virologia , Masculino , Pessoa de Meia-Idade , Sistema Respiratório/virologia , Vitamina D/genética , Adulto Jovem
12.
Anaesthesia ; 71 Suppl 1: 29-39, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26620144

RESUMO

Cardiovascular complications are an important cause of morbidity and mortality after non-cardiac surgery. Pre-operative identification of high-risk individuals and appropriate peri-operative management can reduce cardiovascular risk. It is important to continue chronic beta-blocker and statin therapy. Statins are relatively safe and peri-operative initiation may be beneficial in high-risk patients and those scheduled for vascular surgery. The pre-operative introduction of beta-blockers reduces myocardial injury but increases rates of stroke and mortality, possibly due to hypotension. They should only be considered in high-risk patients and the dose should be titrated to heart rate. Alpha-2 agonists may also contribute to hypotension. Aspirin continuation can increase the risk of major bleeding and offset the benefit of reduced myocardial risk. Contrary to the initial ENIGMA study, nitrous oxide does not seem to increase the risk of myocardial injury. Volatile anaesthetic agents and opioids have been shown to be cardioprotective in animal laboratory studies but these effects have, so far, not been conclusively reproduced clinically.


Assuntos
Cardiotônicos/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Assistência Perioperatória/métodos , Complicações Pós-Operatórias/prevenção & controle , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Humanos , Fatores de Risco
13.
Eur J Clin Microbiol Infect Dis ; 34(4): 713-8, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25413926

RESUMO

An increasing endemicity of multiple-drug-resistant Acinetobacter baumannii (MRAB) ST457 was noted in Hong Kong. The epidemiology, risk factors, and infection control measures to prevent nosocomial transmission of this epidemic clone were analyzed. A total of 5,058 patients cultured positive with A. baumannii between 1 January 2004 and 30 June 2014 were included, of which 297 (5.9 %) had bacteremia. The first case of MRAB bacteremia emerged in 2009, with an incidence that increased from 0.27 (one case) in 2009 to 1.86 (14 cases) per 100,000 patient-days in 2013 (p < 0.001). With the implementation of strict contact precautions and directly observed hand hygiene in conscious patients immediately before receiving meals and medications in July 2013, the incidence of MRAB bacteremia reduced from its peak to 0.77 (one case) per 100,000 patient-days in the first 6 months of 2014 (p < 0.001). Patients from long-term care facilities for the elderly [odds ratio (OR) 18.6, confidence interval (CI) 2.1-162.4, p = 0.008] and history of carbapenem (OR 7.0, CI 1.7-28.0, p = 0.006) and beta-lactam/beta-lactamase use (OR 5.6, CI 1.1-28.7, p = 0.038) 90 days prior to admission were independent risk factors for MRAB bacteremia by logistic regression when compared with carbapenem-susceptible A. baumannii bacteremia.


Assuntos
Infecções por Acinetobacter/prevenção & controle , Acinetobacter baumannii/efeitos dos fármacos , Bacteriemia/prevenção & controle , Farmacorresistência Bacteriana Múltipla , Doenças Endêmicas/prevenção & controle , Higiene das Mãos/métodos , Controle de Infecções/métodos , Infecções por Acinetobacter/epidemiologia , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Criança , Pré-Escolar , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Infecção Hospitalar/prevenção & controle , Feminino , Hong Kong/epidemiologia , Hospitais , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Adulto Jovem
16.
Ann Oncol ; 25(1): 143-8, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24356625

RESUMO

BACKGROUND: This Australian single-arm, multicenter, phase II trial evaluated feasibility, tolerability and activity of accelerated bleomycin, etoposide and cisplatin (BEP) as first-line chemotherapy for metastatic germ cell tumours. PATIENTS AND METHODS: Patients were planned to receive cisplatin 20 mg/m(2) and etoposide 100 mg/m(2) days 1-5, and pegfilgrastim 6 mg day 6, all repeated every 2 weeks for four cycles (three cycles for good prognosis). Bleomycin was given at 30 000 IU weekly to a total of 12 doses (9 doses for good prognosis). Primary end point was feasibility, defined as the proportion of patients able to complete the etoposide and cisplatin components of BEP and be eligible to receive a fourth cycle of BEP by day 50. RESULTS: Twelve poor, 16 intermediate and 15 good prognosis (n = 43) eligible patients were enrolled. Two patients aged >40 years were ineligible and excluded from analyses. The regimen was feasible in 86%, not feasible in 7% and not assessable in 7% of patients. Most common grade 3/4 adverse events were non-neutropenic infection (16%) and febrile neutropenia (12%). Complete response (CR) to chemotherapy and surgery was achieved in 33% poor-prognosis, 81% intermediate-prognosis and 100% good-prognosis patients. At median follow-up of 27 months (range 6-42), the 2-year progression-free survival was 50% for poor-prognosis, 94% for intermediate-prognosis and 92% for good-prognosis patients. CONCLUSION: Accelerated BEP is feasible and tolerable. Efficacy data appear to be promising. This trial and a similar UK study provide the rationale for a randomised trial comparing accelerated versus standard BEP. Australian New Zealand Clinical Trials Registry Registration number. ACTRN 12607000294459.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Testiculares/tratamento farmacológico , Adolescente , Adulto , Bleomicina/administração & dosagem , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Esquema de Medicação , Etoposídeo/administração & dosagem , Feminino , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/secundário , Prognóstico , Neoplasias Testiculares/patologia , Resultado do Tratamento , Adulto Jovem
17.
Clin Infect Dis ; 57(8): 1069-77, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23876395

RESUMO

BACKGROUND: Better understanding of complications and outcomes of adults hospitalized with respiratory syncytial virus (RSV) infection is necessary. METHODS: A retrospective cohort study was conducted on all adults (≥ 18 years) admitted to 3 acute care general hospitals in Hong Kong with virologically confirmed RSV infection during 2009-2011 (N = 607). Adults hospitalized for seasonal influenza during the period were used for comparison (n = 547). Both infections were prospectively diagnosed following a standard protocol. Independent reviews of chest radiographs were performed by radiologists. Main outcome measures were all-cause death, respiratory failure requiring ventilatory support, and hospitalization duration. Cox proportional hazards models were used for analyses. RESULTS: The mean age of RSV patients was 75 (SD, 16) years; 87% had underlying conditions. Lower respiratory and cardiovascular complications were diagnosed in 71.9% (pneumonia, 42.3%; acute bronchitis, 21.9%; chronic obstructive pulmonary disease/asthma exacerbation, 27.3%) and 14.3% of patients, respectively; 12.5% had bacterial superinfections. Supplemental oxygen and ventilatory support were required in 67.9% and 11.1%, respectively. Crude all-cause mortality was 9.1% and 11.9% within 30 days and 60 days, respectively; mean length of stay of survivors was 12 (SD, 13) days. Advanced age, radiographic pneumonia, requirement for ventilation, bacterial superinfection, and elevated urea level and white blood cell count were independently associated with poorer survival. Systemic corticosteroid use was associated with longer hospitalization and secondary infections. The overall outcomes of survival and length of stay were not significantly different from those in influenza. CONCLUSIONS: RSV can cause severe lower respiratory complications in older adults, resulting in respiratory failure, prolonged hospitalization, and high mortality similar to seasonal influenza. Corticosteroids did not seem to improve outcomes. The unmet need for antiviral therapy and vaccination against RSV in adults should be promptly addressed.


Assuntos
Infecções por Vírus Respiratório Sincicial/mortalidade , Infecções Respiratórias/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade , Estudos Retrospectivos
18.
Science ; 341(6142): 183-6, 2013 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-23704376

RESUMO

The emergence of the H7N9 influenza virus in humans in Eastern China has raised concerns that a new influenza pandemic could occur. Here, we used a ferret model to evaluate the infectivity and transmissibility of A/Shanghai/2/2013 (SH2), a human H7N9 virus isolate. This virus replicated in the upper and lower respiratory tracts of the ferrets and was shed at high titers for 6 to 7 days, with ferrets showing relatively mild clinical signs. SH2 was efficiently transmitted between ferrets via direct contact, but less efficiently by airborne exposure. Pigs were productively infected by SH2 and shed virus for 6 days but were unable to transmit the virus to naïve pigs or ferrets. Under appropriate conditions, human-to-human transmission of the H7N9 virus may be possible.


Assuntos
Doenças Transmissíveis Emergentes/transmissão , Doenças Transmissíveis Emergentes/virologia , Influenza Humana/transmissão , Influenza Humana/virologia , Orthomyxoviridae/patogenicidade , Animais , Modelos Animais de Doenças , Furões , Humanos , Influenza Humana/patologia , Orthomyxoviridae/classificação , Orthomyxoviridae/genética , Sistema Respiratório/patologia , Sistema Respiratório/virologia , Sus scrofa
19.
Surgeon ; 11(3): 153-7, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23507329

RESUMO

Hong Kong, a Special Administrative Region of People's Republic of China, is a metropolitan city in Asia with a population of over 7 million people. This paper reflects the current oral health and dental care situations in Hong Kong. Water fluoridation was commenced in 1961, with a current level at 0.5 ppm. And there has continuously been lower caries prevalence thereafter. Dental care is mainly provided by private practitioners. The School Dental Care Service, run by the Department of Health, provides dental care to enrolled primary school children through treatments by dental therapists. An Oral Health Education Unit is set up to promote dental health among the public, particularly preschool children. Government dentists serve mainly civil servants and their dependents. Limited emergency dental care is available to the public at designated government clinics for pain relief, most commonly in the form of extractions. There are about 2200 registered dentists and the dentist to population ratio is about 1:3200. Amongst the dental team, dental hygienists are trained in limited numbers. There are only less than 320 dental hygienists registered, working under the supervision of dentists. The Faculty of Dentistry of the University of Hong Kong has been providing 5-year undergraduate training in dentistry since 1981, and this is lengthened to 6 years from 2012 onwards. Specialty training requires at least a further 6 years. There are 8 specialties, which are Community Dentistry, Endodontics, Family Dentistry, Oral & Maxillofacial Surgery, Oral Rehabilitation, Orthodontics, Pediatric Dentistry, and Periodontics.


Assuntos
Assistência Odontológica , Saúde Bucal , Doenças Dentárias/prevenção & controle , Hong Kong/epidemiologia , Humanos , Morbidade/tendências , Doenças Dentárias/epidemiologia
20.
Thromb Haemost ; 110(3): 423-33, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23494059

RESUMO

The kallikrein kinin system (KKS) consists of serine proteases involved in the production of peptides called kinins, principally bradykinin and Lys-bradykinin (kallidin). The KKS contributes to a variety of physiological processes including inflammation, blood pressure control and coagulation. Here we review the protein structural data available for these serine proteases and examine the molecular mechanisms of zymogen activation and substrate recognition focusing on plasma kallikrein (PK) and tissue kallikrein (KLK1) cleavage of kininogens. PK circulates as a zymogen bound to high-molecular-weight kininogen (HK). PK is activated by coagulation factor XIIa and then cleaves HK to generate bradykinin and factor XII to generate further XIIa.A structure has been described for the activated PK protease domain in complex with the inhibitor benzamidine. Kallikrein-related peptidases (KLKs) have a distinct domain structure and exist as a family of 15 genes which are differentially expressed in many tissues and the central nervous system.They cleave a wide variety of substrates including low-molecular-weight kininogen (LK) and matrix proteins. Crystal structures are available for KLK1, 3, 4, 5, 6 and 7 activated protease domains typically in complex with S1 pocket inhibitors. A substrate mimetic complex is described for KLK3 which provides insight into substrate recognition. A zymogen crystal structure determined for KLK6 reveals a closed S1 pocket and a novel mechanism of zymogen activation. Overall these structures have proved highly informative in understanding the molecular mechanisms of the KKS and provide templates to design inhibitors for treatment of a variety of diseases.


Assuntos
Calicreína Plasmática/química , Calicreínas Teciduais/química , Sequência de Aminoácidos , Animais , Pressão Sanguínea , Catálise , Domínio Catalítico , Precursores Enzimáticos/química , Fator XIIa/química , Humanos , Inflamação , Sistema Calicreína-Cinina , Cininogênios/química , Modelos Moleculares , Dados de Sequência Molecular , Peptídeo Hidrolases/química , Homologia de Sequência de Aminoácidos , Serina Proteases/química , Especificidade por Substrato
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