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1.
Zhonghua Yi Xue Za Zhi ; 102(23): 1747-1752, 2022 Jun 21.
Artigo em Chinês | MEDLINE | ID: mdl-35705478

RESUMO

Objective: To investigate the value of dual-layer spectral detector CT(SDCT) in preoperative prediction of lymph node (LN) metastasis of gastric cancer. Methods: From January 2019 to January 2021, the clinical and imaging data of 130 gastric cancer patients(93 males and 37 females, aged from 37 to 84 years)confirmed by pathology in the Zhongshan hospital of Xiamen University were retrospectively collected. According to the status of lymph node metastasis, those patients were divided into metastatic LNs group (n=104) and nonmetastatic LNs group (n=26). The maximum diameter of gastric cancer on spectral CT images, CT Values of lesions in 40, 50, 60, 70. KeV monoenergetic image of arterial and Venous phase (CT40 keV, CT50 keV, CT60 keV, CT70 keV), iodine concentration (IC) and effective atomic number (Zeff) were measured, then the normalized IC(NIC) and spectral curve(K(40-70)) value were calculated. The differences of each parameter derived from spectral CT between the two groups were compared, and a logistic regression model was constructed. The ROC curves and area under the curve (AUC) were conducted to evaluate the diagnostic performance of each parameter and Delong test was used to compare the difference of each AUC. Results: Compared to nonmetastatic LNs group, metastatic LNs group had higher maximum diameter of tumor, CT40 keV, CT50 keV, CT60 keV, CT70 keV, IC, NIC, Zeff, and K(40-70) values on venous phase (the representative parameter is Zeff: 8.4 (8.2, 8.5) vs 8.2 (8.1, 8.3)) (all P<0.05). The proportion of patients with lower histology differentiated degree, higher T grade and positive carcino embryonic antigen (CEA)were higher than that in nonmetastatic LNs (the representative parameter was CEA: 34.6%(36/104) vs 7.7%(2/26) (all P<0.05). The regression model constructed by CEA and Zeff had the highest predictive value in predicting metastatic LNs, with an AUC of 0.835(0.759-0.894), sensitivity and specificity of 83.65% and 73.08%, respectively. Conclusion: SDCT quantitative parameters on venous phase and CEA facilitate the accurate prediction of metastatic LNs in patients with gastric cancer, and the multi-parameter regression model has the highest diagnostic performance.


Assuntos
Metástase Linfática , Neoplasias Gástricas , Antígeno Carcinoembrionário/química , Feminino , Humanos , Iodo/química , Linfonodos/diagnóstico por imagem , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Masculino , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/secundário , Tomografia Computadorizada por Raios X/métodos
2.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 57(6): 569-575, 2022 Jun 09.
Artigo em Chinês | MEDLINE | ID: mdl-35692000

RESUMO

Objective: To explore the effects of periodontitis and inflammatory factors toward the occurrence of gestational diabetes mellitus (GDM). Methods: Pregnant women who came to the Department of Obstetrics, Northwest Women's and Children's Hospital for prenatal examinations during March to November of 2021 were invited to participate in this study. Participants with GDM who met the inclusion criteria (n=100) were assigned into the case group; while healthy participants (n=100) were assigned into the control group. Information of participants from the two groups were collected by questionnaires and periodontal statuses were clinically recorded in the meantime. Gingival crevicular fluid (GCF) and venous blood were also collected from participants of two groups to analyze the expression levels of inflammatory factors like C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, IL-8, IL-10 and IL-33. Factors different between the two groups were included in the multivariate regression analysis model to determine the risk factors of GDM. Results: The age of participants was (33.4±5.1) years in case group and (30.5±4.5) years in control group respectively, which had statistical differences (t=4.33,P<0.001). Besides, the body mass index of participants from case group was also significantly higher than control group [(28.11±3.85) kg/m2 vs. (23.31±3.15) kg/m2, t=9.65, P<0.001]. Participants with GDM had more adverse periodontal clinical parameters. Prevalence of periodontitis in GDM group was 47.0% (47/100) compared with 29.0% (29/100) in control group (χ²=6.88, P=0.009). Multivariate regression analysis results indicated that periodontitis was a critical risk factor for the occurrence of GDM (OR=1.882, P<0.001). Besides, GCF IL-8, serum TNF-α, IL-8 and IL-10 were also risk factors of GDM due to their higher expressions. Among them, TNF-α in serum (OR=2.077) and IL-8 in serum (OR=2.060) had more significant impacts (P<0.001). Conclusions: This study demonstrated that periodontitis was associated with the occurrence of GDM. Up-regulation of serum pro-inflammatory mediators leaded by local periodontal inflammatory microenvironment might play a critical role in this pathological process.


Assuntos
Diabetes Gestacional , Periodontite , Adulto , Estudos de Casos e Controles , Feminino , Líquido do Sulco Gengival/química , Humanos , Interleucina-10/análise , Interleucina-8 , Periodontite/complicações , Gravidez , Fator de Necrose Tumoral alfa
3.
Hong Kong Med J ; 25(6): 438-443, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31796640

RESUMO

INTRODUCTION: Ketamine is known to cause urinary tract dysfunction. Recently, methamphetamine (MA) abuse has become a growing problem in Asia. We investigated the symptomatology and voiding function in patients who abused MA and ketamine and compared their urinary tract toxicity profiles. METHODS: In the period of 23 months from 1 October 2016, all consecutive new cases of patients presenting with MA- or ketamine-related urological disorder were recruited into a prospective cohort. Polysubstance abuse patients were excluded. Data were analysed by comparison between patients with ketamine abuse and MA abuse. Basic demographic data and initial symptomatology were recorded, and questionnaires on urinary symptoms and the Montreal Cognitive Assessment (MoCA) were used as assessment tools. RESULTS: Thirty-eight patients were included for analysis. There was a statistically significant difference in mean age between patients with MA and ketamine abuse (27.2 ± 7.2 years and 31.6 ± 4.8 years, respectively, P=0.011). Urinary frequency was the most common urological symptom in our cohort of patients. There was a significant difference in the prevalence of dysuria (ketamine 43.5%, MA 6.7%, P=0.026) and a significant trend in the difference in hesitancy (ketamine 4.3%, MA 26.7%, P=0.069). Overall, questionnaires assessing urinary storage symptoms and voiding symptoms did not find a statistically significant difference between the two groups. The MoCA revealed that both groups had cognitive impairment (ketamine 24.8 ± 2.5, MA 23.6 ± 2.9, P=0.298). CONCLUCSIONS. Abuse of MA caused urinary tract dysfunction, predominantly storage symptoms. Compared with ketamine abuse, MA abuse was not commonly associated with dysuria or pelvic pain.


Assuntos
Ketamina/efeitos adversos , Sintomas do Trato Urinário Inferior/induzido quimicamente , Metanfetamina/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias , Adulto , Estudos de Coortes , Feminino , Hong Kong , Humanos , Sintomas do Trato Urinário Inferior/patologia , Masculino , Estudos Prospectivos , Inquéritos e Questionários , Urodinâmica
4.
Hong Kong Med J ; 24(2): 175-181, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29632275

RESUMO

Ketamine is an N-methyl-d-aspartate receptor antagonist, a dissociative anaesthetic agent and a treatment option for major depression, treatment-resistant depression, and bipolar disorder. Its strong psychostimulant properties and easy absorption make it a favourable candidate for substance abuse. Ketamine entered Hong Kong as a club drug in 2000 and the first local report of ketamine-associated urinary cystitis was published in 2007. Ketamine-associated lower-urinary tract symptoms include frequency, urgency, nocturia, dysuria, urge incontinence, and occasionally painful haematuria. The exact prevalence of ketamine-associated urinary cystitis is difficult to assess because the abuse itself and many of the associated symptoms often go unnoticed until a very late stage. Additionally, upper-urinary tract pathology, such as hydronephrosis, and other complications involving neuropsychiatric, hepatobiliary, and gastrointestinal systems have also been reported. Gradual improvement can be expected after abstinence from ketamine use. Sustained abstinence is the key to recovery, as relapse usually leads to recurrence of symptoms. Both medical and surgical management can be used. The Youth Urological Treatment Centre at the Prince of Wales Hospital, Hong Kong, has developed a four-tier treatment protocol with initial non-invasive investigation and management for these patients. Multidisciplinary care is essential given the complex and diverse psychological factors and sociological background that underlie ketamine abuse and abstinence status.


Assuntos
Ketamina/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/terapia , Gastroenteropatias/induzido quimicamente , Humanos , Doenças Urológicas/induzido quimicamente
5.
Hong Kong Med J ; 24(1): 11-17, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29284159

RESUMO

INTRODUCTION: In Asia, few reports are available on the outcomes for living renal donors. We report the short- and long-term clinical outcomes of individuals following living donor nephrectomy in Hong Kong. METHODS: We retrospectively reviewed the characteristics and clinical outcomes of all living renal donors who underwent surgery from January 1990 to December 2015 at a teaching hospital in Hong Kong. Information was obtained from hospital records and territory-wide electronic patient records. RESULTS: During the study period, 83 individuals underwent donor nephrectomy. The mean (± standard deviation) follow-up time was 12.0 ± 8.3 years, and the mean age at nephrectomy was 37.3 ± 10.0 years. A total of 44 (53.0%), four (4.8%), and 35 (42.2%) donors underwent living donor nephrectomy via an open, hand-port assisted laparoscopic, and laparoscopic approach, respectively. The overall incidence of complications was 36.6%, with most being grade 1 or 2. There were three (9.4%) grade 3a complications; all were related to open donor nephrectomy. The mean glomerular filtration rate was 96.0 ± 17.5 mL/min/1.73 m2 at baseline and significantly lower at 66.8 ± 13.5 mL/min/1.73 m2 at first annual follow-up (P<0.01). The latest mean glomerular filtration rate was 75.6% ± 15.1% of baseline. No donor died or developed renal failure. Of the donors, 14 (18.2%) developed hypertension, two (2.6%) had diabetes mellitus, and three (4.0%) had experienced proteinuria. CONCLUSION: The overall perioperative outcomes are good, with very few serious complications. The introduction of a laparoscopic approach has decreased perioperative blood loss and also shortened hospital stay. Long-term kidney function is satisfactory and no patients developed end-stage renal disease. The incidences of new-onset medical diseases and pregnancy-related complications were also low.


Assuntos
Transplante de Rim , Rim/fisiopatologia , Doadores Vivos/estatística & dados numéricos , Nefrectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Adulto , Feminino , Seguimentos , Taxa de Filtração Glomerular , Hong Kong , Humanos , Falência Renal Crônica/cirurgia , Laparoscopia/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
6.
Hong Kong Med J ; 22(5): 454-63, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27516568

RESUMO

OBJECTIVE: To investigate the prevalence of lower urinary tract symptoms in adolescents and the effects of psychotropic substance use. METHODS: This was a population-based cross-sectional survey using a validated questionnaire in students from 45 secondary schools in Hong Kong randomly selected over the period of January 2012 to January 2014. A total of 11 938 secondary school students (response rate, 74.6%) completed and returned a questionnaire that was eligible for analysis. Individual lower urinary tract symptoms and history of psychotropic substance abuse were documented. RESULTS: In this study, 11 617 non-substance abusers were regarded as control subjects and 321 (2.7%) were psychotropic substance users. Among the control subjects, 2106 (18.5%) had experienced at least one lower urinary tract symptom with urinary frequency being the most prevalent symptom (10.2%). Females had more daytime urinary incontinence (P<0.001) and males had more voiding symptoms (P=0.01). Prevalence of lower urinary tract symptoms increased with age from 13.9% to 25.8% towards young adulthood and age of ≥18 years (P<0.001). Among the substance users, ketamine was most commonly abused. Substance users had significantly more lower urinary tract symptoms than control subjects (P<0.001). In multivariate analysis, increasing age and psychotropic substance abuse increased the odds for lower urinary tract symptoms. Non-ketamine substance users and ketamine users were respectively 2.8-fold (95% confidence interval, 2.0-3.9) and 6.2-fold (4.1-9.1) more likely than control subjects to develop lower urinary tract symptoms. Females (odds ratio=9.9; 95% confidence interval, 5.4-18.2) were more likely to develop lower urinary tract symptoms than males (4.2; 2.5-7.1) when ketamine was abused. CONCLUSIONS: Lower urinary tract symptoms are prevalent in the general adolescent population. It is important to obtain an accurate history regarding psychotropic substance use when treating teenagers with lower urinary tract symptoms.


Assuntos
Ketamina/administração & dosagem , Sintomas do Trato Urinário Inferior/epidemiologia , Psicotrópicos/administração & dosagem , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adolescente , Fatores Etários , Criança , Estudos Transversais , Feminino , Hong Kong/epidemiologia , Humanos , Masculino , Análise Multivariada , Prevalência , Fatores de Risco , Fatores Sexuais , Inquéritos e Questionários
7.
Appl Opt ; 53(5): 861-7, 2014 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-24663264

RESUMO

There are many variations of differential phase contrast imaging methods. Although these imaging methods are different in configuration, they are alike in imaging by extracting differential phase information through the evaluation of the refraction angles. In this paper, we investigate common characteristics shared by various different differential phase contrast imaging methods.

8.
Exp Ther Med ; 5(4): 1169-1173, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23596486

RESUMO

It has been demonstrated that ischemic postconditioning (IPO) is capable of attenuating ischemia/reperfusion (I/R) injury in the heart. However, the novel role of pharmacological postconditioning in the liver remains unclear. In this study, the hypothesis that diazoxide postconditioning reduces I/R-induced injury in rat liver was tested. Rats were assigned randomly to the sham-operated control, I/R (occlusion of the porta hepatis for 60 min, followed by a persistent reperfusion for 120 min), diazoxide ischemic postconditioning (DIPO; occlusion of the porta hepatis for 60 min, then treatment with diazoxide for 10 min reperfusion, followed by a persistent reperfusion for 110 min) or 5-hydroxydecanoate (5-HD)+DIPO (occlusion of the porta hepatis for 60 min, then treatment with diazoxide and 5-HD for 10 min reperfusion, followed by a persistent reperfusion for 110 min) groups. The alanine aminotransferase (ALT) and aspartate transaminase (AST) levels were assayed. The expression levels of protein kinase c-ε (pkc-ε), cytochrome c (cyt-c), caspase-3 and bcl-2 protein were determined by western blotting. The serum levels of ALT and AST and expression levels of cyt-c and caspase-3 were significantly lower in the DIPO group (P<0.05). However, the protein expression levels of pkc-ε and bcl-2 were markedly increased in the DIPO group (P<0.05). 5-HD abrogated the protective effects of DIPO. The data of the present study provide the first evidence that DIPO protects the liver from I/R injury by opening the mitochondrial KATP channels, activating and upregulating pkc-ε and inhibiting the activation of the apoptotic pathway by decreasing the release of cyt-c and the expression of caspase-3 and increasing bcl-2 expression.

10.
Anaerobe ; 12(2): 106-9, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16701623

RESUMO

The effect of metronidazole (ME) on sulfate-reducing bacteria (SRB) was studied by atomic force microscopy (AFM) in this paper. Topography images of SRB cell show that after exposure to ME individual cell shape is sharply modified. Topography and phase images of SRB cell wall show that after exposure to ME not only the roughness of the cell wall increases but also the physical performance of SRB surface is changed to be uniform. AFM frictional loops show that after exposure to ME, SRB surface friction is increased remarkably.


Assuntos
Anti-Infecciosos/farmacologia , Desulfovibrio vulgaris/efeitos dos fármacos , Metronidazol/farmacologia , Parede Celular/efeitos dos fármacos , Parede Celular/ultraestrutura , Desulfovibrio vulgaris/ultraestrutura , Fricção , Microscopia de Força Atômica/métodos
11.
Chin J Dent Res ; 3(1): 51-4, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-11314342

RESUMO

OBJECTIVE: Tooth enamel is formed by ameloblasts, which are derived from epitheliums and secrete an extracellular matrix containing a complex arrangement of protein components. The epithelial component, referred to as the enamel organ, contains a layer of cells that secrete an organic matrix that biomineralizes to become tooth enamel. Adjacent ectomesenchyme cells differentiate to become dentinproducing odontoblasts. These two mineralized matrices form the crown of the vertebrate tooth. Therefore, amelogenins play a critical role in tooth enamel formation. We have examined the expression patterns and tissue distribution of amelogenins in their developmental stages in order to build a foundation for further study. METHODS: Amelogenin expression patterns and tissue distribution in developing teeth of embryonic (E17E19) and neonatal (1 to 9 days old) Wistar rats were examined by immunohistochemistry. RESULTS: Positive immunostaining for amelogenin was first observed in the late embryonic stage, E18. The highest level of amelogenin was noted in neonatal secretary ameloblasts, fully engaged in enamel matrix deposition (3 to 5 days old). After that, amelogenin expression continued at a lower level (6, 7, 8 days old). There was no amelogenin staining observed in the maturation stage of development (9 days old). CONCLUSIONS: Amelogenin expression occurs as early as the polarization stage of pre-ameloblasts. Amelogenin was also expressed, but at a low level, in post-secretary stages of amelogenesis. Odontoblasts did not contain detectable amelogenin.


Assuntos
Proteínas do Esmalte Dentário/genética , Germe de Dente/embriologia , Dente/metabolismo , Ameloblastos/citologia , Ameloblastos/metabolismo , Amelogênese , Amelogenina , Animais , Animais Recém-Nascidos , Corantes , Esmalte Dentário/citologia , Esmalte Dentário/embriologia , Esmalte Dentário/metabolismo , Dentina/citologia , Dentina/embriologia , Dentina/metabolismo , Dentinogênese , Órgão do Esmalte/citologia , Órgão do Esmalte/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Imuno-Histoquímica , Odontoblastos/metabolismo , Ratos , Ratos Wistar , Dente/citologia , Coroa do Dente/citologia , Coroa do Dente/embriologia , Coroa do Dente/metabolismo , Germe de Dente/citologia , Germe de Dente/metabolismo
12.
Clin Biochem ; 33(8): 619-25, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11166008

RESUMO

OBJECTIVES: In determining the plasma malondialdehyde MDA levels in some Taiwanese college students, we found rather different results by using different thiobarbituric acid TBA tests, even by the high-performance liquid chromatography HPLC-based methods. Here, we re-evaluated four commonly used TBA tests and improved the HPLC-based test. DESIGN AND METHODS: We used the blood plasma of 16 college volunteers to determine plasma MDA by using four methods: a spectrophotometric measurement of thiobarbituric acid-reactive substances (TBARS) in the TCA-supernatant of plasma (Method A); a fluorescence measurement of plasma lipid peroxides (Method B); and two different HPLC-based measurements of MDA with either 532-nm measurement (Method C, HPLC/532 nm) or fluorescence measurement (Method D, HPLC/fluor.). RESULTS: The levels of MDA or TBA reactive substances obtained from the four methods differed substantially (0.39 +/- 0.15; 2.14 +/- 0.73; 0.75 +/- 0.22; and 0.38 +/- 0.15 microM for Methods A, B, C, and D, respectively). The results were positively correlated between Methods A and B (r = 0.740, p < 0.02) and between Methods C and D (r = 0.516, p < 0.05). However, results were negatively correlated between Methods B and D (r = -0.548, p < 0.05). Because most plasma MDA is bound to proteins, we modified the HPLC-based methods (C and D) by adding an alkaline hydrolysis step, and the plasma TBA-MDA adduct detected by HPLC/532 nm was referred to as total MDA. RESULTS show that alkaline hydrolysis was a critical step for measurement of total MDA in plasma because this treatment led to release of MDA from plasma proteins. We also adapted the potassium iodide (KI) treatment of plasma from Method D to reduce lipid hydroperoxides. Our modified method gave a total MDA level in the 16 volunteers of approximately 1.5 microM, which was equal to protein-bound MDA plus free MDA. This total MDA level was positively (p < 0.05) correlated with the level of TBA reactive substances obtained from Methods C (r = 0.63, p < 0.05) and D (r = 0.48, p < 0.07), but was not correlated with those from Methods A and B. The recovery (84 approximately 105%), precision (within-assay coefficient of variation: 2.4%, between-assay coefficient of variation: 4 approximately 8%) and sensitivity of the modified procedure were comparable to other HPLC-based methods. CONCLUSION: By using a validated modification of HPLC-based TBA method, the total plasma MDA in 16 Taiwanese college students was found to be 1.54 microM, which was relatively high compared to those obtained by other HPLC-based method, primarily due to the release of protein-bound MDA by alkaline hydrolysis. This level equaled the sum of protein-bound MDA and free MDA in plasma, confirming that this level represents total plasma MDA.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Colorimetria/métodos , Malondialdeído/sangue , Adulto , Proteínas Sanguíneas/metabolismo , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estudantes , Tiobarbitúricos
13.
AIDS Res Hum Retroviruses ; 15(18): 1667-72, 1999 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-10606089

RESUMO

The infection of human cells by HIV-1 virus can be mimicked by a fusion process between cells expressing the HIV envelope protein (Env) and cells expressing both human CD4 (huCD4) and appropriate human chemokine receptors. In this study, a macrophage-tropic (M-tropic) HIV cell-cell fusion assay was established that utilized huCD4, human CCR5 (huCCR5), and HIV ADAgpl60 as fusion components and a Gal4/VP16-activated luciferase as a reporter system. By combining CHO cells expressing huCD4 and huCCR5 with CHO cells expressing HIV ADAgpl60, a 300-fold increase in luciferase activity could be elicited relative to control. No luciferase activity was detected when HXB2gpl60 (T-tropic) was used instead of ADAgpl60 (M-tropic) as the fusion partner in the assay. Addition of anti-huCD4 (RPA-T4) or anti-huCCR5 (2D7) monoclonal antibodies in the assay significantly inhibited the fusion event; in contrast, an anti-CXCR4 (12G5) monoclonal antibody had little effect, indicating that the fusion assay was huCD4 and huCCR5 dependent. The cell-cell fusion occurred in a time-dependent manner; the maximum luciferase activity was detected about 8 hr after mixing the cells. The fusion events could also be monitored by another reporter system in which Gal4/VP16 activated green fluorescent protein (GFP) was used as the reporter instead of luciferase. In combination with fluorescence microscopy, the GFP reporter system allowed visualization of the fusion events in real time. Compared with previously described HIV fusion models, this system has several advantages, including simplicity, sensitivity, and the ability to allow continuous monitoring of the HIV cell-cell fusion event. Finally, this cell-cell fusion system is easily adapted to study other HIV fusion events.


Assuntos
Antígenos CD4/fisiologia , Fusão Celular , Genes Reporter , Proteína gp160 do Envelope de HIV/fisiologia , Luciferases/genética , Proteínas Luminescentes/genética , Macrófagos/virologia , Receptores CCR5/fisiologia , Animais , Anticorpos Monoclonais/farmacologia , Células CHO , Fusão Celular/efeitos dos fármacos , Cricetinae , Cricetulus , Proteínas de Fluorescência Verde , Humanos , Luciferases/biossíntese , Proteínas Luminescentes/biossíntese , Microscopia de Fluorescência , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/genética , Sensibilidade e Especificidade , Transfecção
15.
FEMS Microbiol Lett ; 134(2-3): 251-4, 1995 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-8586276

RESUMO

Pneumocystis carinii synthesizes folates de novo from exogenous p-aminobenzoic acid (pABA). Lung-derived organisms take up [3H]pABA in vitro except in the presence of sulfamethoxazole. Supernatants from spinner-flask cultures take up [3H]pABA if they were inoculated with lungs from infected rats, but not if they were inoculated with lungs from uninfected rats. P. carinii folates consist primarily of pteroylpentaglutamates. Plasmodium falciparum, in contrast, contains primarily pteroyltetraglutamates. Culture-derived organisms synthesize folates at a four-fold higher specific activity than lung-derived organisms, possibly because they contain less contaminating lung debris. These data suggest that P. carinii remains metabolically active in culture for at least 4 days.


Assuntos
Pneumocystis/metabolismo , Ácidos Pteroilpoliglutâmicos/biossíntese , Ácido 4-Aminobenzoico/metabolismo , Animais , Técnicas In Vitro , Pulmão/microbiologia , Micologia/métodos , Pneumocystis/crescimento & desenvolvimento , Pneumocystis/isolamento & purificação , Pneumonia por Pneumocystis/microbiologia , Ratos
16.
Antimicrob Agents Chemother ; 39(8): 1756-63, 1995 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-7486915

RESUMO

Forty-four sulfa drugs were screened against crude preparations of recombinant Pneumocystis carinii dihydropteroate synthetase. The apparent Michaelis-Menten constants (Km) for p-aminobenzoic acid and 7,8-dihydro-6-hydroxymethylpterin pyrophosphate were 0.34 +/- 0.02 and 2.50 +/- 0.71 microM, respectively. Several sulfa drugs, including sulfathiazole, sulfachlorpyridazine, sulfamethoxypyridazine, and sulfathiourea, inhibited dihydropteroate synthetase approximately as well as sulfamethoxazole, as determined by the concentrations which cause 50% inhibition and/or by Ki. For all sulfones and sulfonamides tested, unsubstituted p-amino groups were necessary for activity, and sulfonamides containing an N1-heterocyclic substituent were found to be the most effective inhibitors. Folate biosynthesis in isolated intact P. carinii was approximately equally sensitive to inhibition by sulfamethoxazole, sulfachlorpyridazine, sulfamethoxypyridazine, sulfisoxazole, and sulfathiazole. Two of these drugs, sulfamethoxypyridazine and sulfisoxazole, are known to be less toxic than sulfamethoxazole and should be further evaluated for the treatment of P. carinii pneumonia.


Assuntos
Anti-Infecciosos/uso terapêutico , Di-Hidropteroato Sintase/antagonistas & inibidores , Pneumocystis/enzimologia , Sulfonamidas/farmacologia , Animais , Ácido Fólico/biossíntese , Cinética , Pulmão/microbiologia , Masculino , Pneumocystis/efeitos dos fármacos , Pneumocystis/metabolismo , Infecções por Pneumocystis/tratamento farmacológico , Infecções por Pneumocystis/microbiologia , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes , Relação Estrutura-Atividade
17.
Mol Biochem Parasitol ; 63(1): 121-8, 1994 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8183310

RESUMO

[14C]Artemisinin was taken up by Plasmodium falciparum in culture and concentrated in hemozoin. In vitro, hemin and artemisinin were found to undergo a chemical reaction forming two major products which were isolated by high-performance liquid chromatography (HPLC). The m/z values of the two products were 856 and 871. Thin-layer chromatography (TLC) and HPLC of hemozoin isolated from [14C]artemisinin-treated parasites showed that the majority of the hemozoin-associated radioactivity comigrated with the synthetic adducts. When [14C]artemisinin was incubated with isolated hemozoin, [14C]artemisinin disappeared from the solution in a time-dependent manner. Some of the radioactivity present in the treated hemozoin also comigrated with the adducts on TLC. Thus, artemisinin appears to react covalently with heme in malaria hemozoin both in vitro and in situ.


Assuntos
Antimaláricos/metabolismo , Artemisininas , Hemeproteínas/metabolismo , Plasmodium falciparum/metabolismo , Sesquiterpenos/metabolismo , Animais , Antimaláricos/farmacocinética , Antimaláricos/farmacologia , Transporte Biológico Ativo , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Fina , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/farmacocinética , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Técnicas In Vitro , Malária Falciparum/tratamento farmacológico , Malária Falciparum/parasitologia , Plasmodium falciparum/efeitos dos fármacos , Sesquiterpenos/farmacocinética , Sesquiterpenos/farmacologia
19.
Free Radic Biol Med ; 12(3): 213-8, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1563647

RESUMO

Primaquine is an important antimalarial drug which causes hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PDH) deficiency, probably due to oxidant generation by its metabolites. One of primaquine's metabolites, 5,6-dihydroxy-8-aminoquinoline (AQD), was found to cause chemiluminescence (CL) in vitro when incubated in the presence of luminol. This CL is inhibited by catalase and deferoxamine, unaffected by mannitol, and stimulated by superoxide dismutase (SOD), suggesting that it is mediated by H2O2. Three antioxidants (daphnetin, ferulate, and maltol), derived from Chinese herbal remedies, inhibited AQD- and H2O2-mediated CL, whereas a fourth, anisodamine, had no effect. Daphnetin also potently inhibited H2O2-mediated lipid peroxidation as measured by the production of thibarbituric acid reacting substances (TBARS). Thus, the possibility is raised that an antioxidant might be able to mitigate the oxidant hemolytic effects of primaquine.


Assuntos
Antioxidantes/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Oxigênio/metabolismo , Primaquina/metabolismo , Aminoquinolinas/farmacologia , Membrana Eritrocítica/efeitos dos fármacos , Membrana Eritrocítica/metabolismo , Radicais Livres , Humanos , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Ferro/química , Peroxidação de Lipídeos/efeitos dos fármacos , Medições Luminescentes , Oxirredução , Oxigênio/antagonistas & inibidores , Primaquina/antagonistas & inibidores , Primaquina/farmacologia , Tiobarbitúricos/metabolismo
20.
Int J Epidemiol ; 19(2): 435-8, 1990 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-2165466

RESUMO

Investigation of an epidemic of hepatitis A which occurred in Shanghai in early 1988 was conducted at the Shanghai No. 2 Yarn Dyeing and Weaving Mill. In this factory the attack rate between January and April 1988 was 9%. The rate was highest among staff who ate raw clams (18%) and higher among those who ate cooked clams (7%) than among those who did not eat clams (2%). In addition, independent risk factors for infection were: age below 30 years (relative risk (RR) = 3.0, 95% Cl: 2.0, 4.5) shift work (RR = 3.3, 95% Cl: 1.9, 5.8) and eating out (RR = 4.7, 95% Cl: 2.3, 9.7). Consumption of clams contaminated with hepatitis A was the main risk factor in this episode. The study indicates that strengthening surveillance of shellfish hygiene is important in preventing future epidemics of hepatitis A.


Assuntos
Surtos de Doenças/estatística & dados numéricos , Hepatite A/epidemiologia , Adulto , Fatores Etários , Análise de Variância , Animais , Bivalves/microbiologia , China/epidemiologia , Estudos Transversais , Diarreia/etiologia , Feminino , Contaminação de Alimentos , Hepatite A/complicações , Hepatovirus/isolamento & purificação , Humanos , Modelos Logísticos , Masculino , Restaurantes , Fatores de Risco
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