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1.
Sci Rep ; 11(1): 1214, 2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441704

RESUMO

Chimpanzees are genetically and physiologically similar to humans. Several pharmacokinetic models of propofol are available and target controlled infusion (TCI) of propofol is established in humans, but not in chimpanzees. The purpose of this study was to investigate if human pharmacokinetic models can accurately predict propofol plasma concentration (Cp) in chimpanzees and if it is feasible to perform TCI in chimpanzees. Ten chimpanzees were anaesthetized for regular veterinary examinations. Propofol was used as an induction or maintenance agent. Blood samples were collected from a catheter in a cephalic vein at 3-7 time points between 1 and 100 min following the propofol bolus and/or infusion in five chimpanzees, or TCI in six chimpanzees. Cp was measured using high-performance liquid chromatography. The Marsh, Schnider and Eleveld human pharmacokinetic models were used to predict Cp for each case and we examined the predictive performances of these models using the Varvel criteria Median PE and Median APE. Median PE and Median APE for Marsh, Schnider and Eleveld models were within or close to the acceptable range. A human TCI pump was successfully maintained propofol Cp during general anesthesia in six chimpanzees. Human propofol pharmacokinetic models and TCI pumps can be applied in chimpanzees.


Assuntos
Anestésicos Intravenosos/administração & dosagem , Propofol/administração & dosagem , Anestesia Geral/métodos , Anestesia Intravenosa/métodos , Animais , Feminino , Humanos , Bombas de Infusão , Infusões Intravenosas/métodos , Masculino , Modelos Biológicos , Pan troglodytes
2.
J Comp Pathol ; 169: 1-4, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31159945

RESUMO

An 11-month-old female Japanese macaque (Macaca fuscata), born in captivity in a research institute, suddenly died without clinical signs. Necropsy examination revealed a nodular mass protruding from the left ventral aspect of the larynx, compressing the epiglottis anteriorly. Histopathologically, the laryngeal mass was comprised of medium- to large-sized atypical cells. Immunohistochemically, these were positive for CD20 and partially positive for CD79α. Among the atypical cells were CD3+ T cells and CD68+ histiocytes. Based on the findings, this case was diagnosed as T-cell/histiocyte-rich large B-cell lymphoma. Epstein-Barr virus (EBV)-encoded small RNAs were frequently detected in the atypical cells by in-situ hybridization, which was consistent with the finding that the macaque was seropositive for EBV antigen. This is the first report showing the potential association of simian lymphocryptovirus, the simian homologue of EBV, with lymphoma in a juvenile non-human primate.


Assuntos
Infecções por Herpesviridae/veterinária , Linfoma Difuso de Grandes Células B/veterinária , Doenças dos Primatas/patologia , Doenças dos Primatas/virologia , Infecções Tumorais por Vírus/veterinária , Animais , Feminino , Histiócitos/patologia , Lymphocryptovirus , Macaca fuscata , Linfócitos T/patologia
3.
J Hosp Infect ; 97(3): 296-300, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28756169

RESUMO

BACKGROUND: In recent years, installation of bidet toilets within hospitals in Japan has raised concerns regarding potential for cross-contamination by antimicrobial-resistant bacteria from patients who are hospitalized over an extended period. AIM: To investigate the distribution of antimicrobial-resistant bacteria recovered from bidet toilets at a university-affiliated hospital in Japan. METHODS: All 292 electric bidet toilets at a university hospital were sampled for contamination. Swabs for culture were used to sample water-jet nozzles and toilet seats. FINDINGS: Of the 292 toilet seats sampled, warm-water nozzles of 254 (86.9%) were found to be contaminated by one or more of the following organisms: Staphylococcus aureus, Streptococcus spp., Enterococcus spp., Enterobacteriaceae and non-Enterobacteriaceae Gram-negative bacteria. S. aureus was recovered from one water-jet nozzle and nine toilet seats; of these, meticillin-resistant S. aureus was recovered from the water-jet nozzle and from one toilet seat. Both the water-jet nozzle and seat of the same toilet were contaminated with a CTX-M-9 group extended-spectrum ß-lactamase-producing Escherichia coli. Of the Gram-negative isolates recovered from samples, the organism with the highest frequency of isolation was Stenotrophomonas maltophilia, which was recovered from 39 bidet toilets. CONCLUSION: Warm-water nozzles of bidet toilets are contaminated with a wide range of bacteria, making them a potential vehicle for cross-infection. In the hospital setting, shared use of bidet toilets must consider the clinical background of patients. Based on these findings, these devices must be part of the risk management programme, and steps should be included for monitoring and disinfection.


Assuntos
Microbiologia Ambiental , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/isolamento & purificação , Hospitais Universitários , Toaletes , Infecção Hospitalar/epidemiologia , Estudos Transversais , Bactérias Gram-Negativas/classificação , Bactérias Gram-Positivas/classificação , Humanos , Japão , Medição de Risco
4.
Epidemiol Infect ; 145(1): 41-45, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27609054

RESUMO

The risk of malaria outbreak surfaced in Vanuatu after Tropical Cyclone (TC) Pam in March 2015. In June and July 2015 we conducted malariometric surveys on the islands of Tanna, Aneityum, and Erromango in Tafea Province, where malaria elimination had been targeted, to determine if malaria incidence had increased after TC Pam. No Plasmodium infection was detected by microscopy and PCR in 3009 survey participants. Only 6·3% (190/3007) of participants had fever. Spleen rates in children aged ⩽12 years from Aneityum and Tanna were low, at 3·6% (14/387) and 5·3% (27/510), respectively. Overall bed net use was high at 72·8% (2175/2986); however, a significantly higher (P < 0·001) proportion of participants from Aneityum (85·9%, 796/927) reported net use than those from Tanna (67·1%, 751/1119) and Erromango (66·8%, 628/940). A recent decrease in malaria incidence in Tafea Province through comprehensive intervention measures had reduced the indigenous parasite reservoir and limited the latter's potential to spur an outbreak after TC Pam. The path towards malaria elimination in Tafea Province was not adversely affected by TC Pam.


Assuntos
Tempestades Ciclônicas , Surtos de Doenças , Malária/epidemiologia , Animais , Criança , Pré-Escolar , Testes Diagnósticos de Rotina , Monitoramento Epidemiológico , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Microscopia , Reação em Cadeia da Polimerase , Vanuatu/epidemiologia
5.
Neurogastroenterol Motil ; 28(12): 1792-1805, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27284001

RESUMO

BACKGROUND: Stimulation of transient receptor potential ankyrin 1 (TRPA1), which abundantly expressed in enterochromaffin cells (ECC), has been reported to exert apparently contradictory results in in vitro contractility and in vivo gastrointestinal (GI) transit evaluations. The pharmaceutical-grade Japanese traditional medicine daikenchuto (TU-100) has been reported to be beneficial for postoperative ileus (POI) and accelerate GI transit in animals and humans. TU-100 was recently shown to increase intestinal blood flow via stimulation of TRPA1 in the epithelial cells of the small intestine (SI). METHODS: The effects of various TRPA1 agonists on motility were examined in a manipulation-induced murine POI model, in vitro culture of SI segments and an ECC model cell line, RIN-14B. KEY RESULTS: Orally administered TRPA1 agonists, aryl isothiocyanate (AITC) and cinnamaldehyde (CA), TU-100 ingredients, [6]-shogaol (6S) and γ-sanshool (GS), improved SI transit in a POI model. The effects of AITC, 6S and GS but not CA were abrogated in TRPA1-deficient mice. SI segments show periodic peristaltic motor activity whose periodicity disappeared in TRPA1-deficient mice. TU-100 augmented the motility. AITC, CA and 6S increased 5-HT release from isolated SI segments and the effects of all these compounds except for CA were lost in TRPA1-deficient mice. 6S and GS induced a release of 5-HT from RIN-14B cells in a dose- and TRPA1-dependent manner. CONCLUSIONS & INFERENCES: Intraluminal TRPA1 stimulation is a potential therapeutic strategy for GI motility disorders. Further investigation is required to determine whether 5-HT and/or ECC are involved in the effect of TRPA1 on motility.


Assuntos
Modelos Animais de Doenças , Trânsito Gastrointestinal/efeitos dos fármacos , Trânsito Gastrointestinal/fisiologia , Íleus/tratamento farmacológico , Canal de Cátion TRPA1/agonistas , Canal de Cátion TRPA1/fisiologia , Acroleína/análogos & derivados , Acroleína/farmacologia , Acroleína/uso terapêutico , Amidas/farmacologia , Amidas/uso terapêutico , Animais , Células Cultivadas , Relação Dose-Resposta a Droga , Íleus/fisiopatologia , Masculino , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Naftoquinonas/farmacologia , Naftoquinonas/uso terapêutico , Técnicas de Cultura de Órgãos
6.
Vet Pathol ; 52(3): 566-72, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25248517

RESUMO

Lymphomas are common spontaneous tumors in nonhuman primates but remain poorly characterized in Japanese macaques (Macaca fuscata). This study examined 5 cases of spontaneous malignant lymphoma in Japanese macaques, focusing on the immunophenotypes and presence of simian lymphocryptoviruses, which are Epstein-Barr virus-related herpesviruses in nonhuman primates. The macaques with lymphoma were 5 to 28 years old, indicating that lymphomas develop over a wide age range. The common macroscopic findings were splenomegaly and enlargement of lymph nodes. Histologic and immunohistochemical analyses revealed that all cases were non-Hodgkin type and exhibited a T-cell phenotype, positive for CD3 but negative for CD20 and CD79α. The lymphomas exhibited diverse cellular morphologies and were subdivided into 3 types according to the World Health Organization classification. These included 3 cases of peripheral T-cell lymphoma, not otherwise specified; 1 case of T-cell prolymphocytic leukemia; and 1 case of an unclassifiable T-cell lymphoma. Positive signals were detected by in situ hybridization in 2 of the 4 examined cases using probes for the Epstein-Barr virus-encoded small RNA (EBER). Furthermore, the presence of M. fuscata lymphocryptovirus 2, a macaque homolog of Epstein-Barr virus, was demonstrated in EBER-positive cases by polymerase chain reaction amplification followed by direct sequencing. Immunohistochemistry using antibody to the Epstein-Barr virus-encoded nuclear antigen 2 was negative, even in the EBER-positive cases. The present study suggests that T-cell lymphoma is more common than B-cell lymphoma in Japanese macaques and that M. fuscata lymphocryptovirus 2 is present in some cases.


Assuntos
Linfoma/veterinária , Doenças dos Macacos/patologia , Animais , Feminino , Infecções por Herpesviridae/diagnóstico , Infecções por Herpesviridae/patologia , Infecções por Herpesviridae/veterinária , Hibridização In Situ/veterinária , Leucemia Prolinfocítica de Células T/diagnóstico , Leucemia Prolinfocítica de Células T/patologia , Leucemia Prolinfocítica de Células T/veterinária , Leucemia Prolinfocítica de Células T/virologia , Linfonodos/patologia , Lymphocryptovirus , Linfoma/complicações , Linfoma/patologia , Linfoma/virologia , Linfoma de Células T/diagnóstico , Linfoma de Células T/patologia , Linfoma de Células T/veterinária , Linfoma de Células T/virologia , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/patologia , Linfoma de Células T Periférico/veterinária , Linfoma de Células T Periférico/virologia , Macaca , Masculino , Doenças dos Macacos/diagnóstico , Doenças dos Macacos/virologia , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Esplenomegalia/etiologia , Esplenomegalia/patologia , Esplenomegalia/veterinária , Infecções Tumorais por Vírus/diagnóstico , Infecções Tumorais por Vírus/patologia , Infecções Tumorais por Vírus/veterinária , Infecções Tumorais por Vírus/virologia
7.
J Vet Pharmacol Ther ; 36(2): 169-73, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22568878

RESUMO

Propofol is a short-acting intravenous anesthetic used for induction/maintenance anesthesia. The objective of this study was to assess a population pharmacokinetic (PPK) model for Japanese macaques during a step-down infusion of propofol. Five male Japanese macaques were immobilized with ketamine (10 mg/kg) and atropine (0.02 mg/kg). A bolus dose of propofol (5 mg/kg) was administrated intravenously (360 mg/kg/h) followed by step-down infusion at 40 mg/kg/h for 10 min, 20 mg/kg/h for 10 min, and then 15 mg/kg/h for 100 min. Venous blood samples were repeatedly collected following the administration. The plasma concentration of propofol (Cp) was measured by high-speed LC-FL. PPK analyses were performed using NONMEM VII. Median absolute prediction error and median prediction error (MDPE), the indices of prediction inaccuracy and bias, respectively, were calculated, and PE - individual MDPE vs. time was depicted to show the variability of prediction errors. In addition, we developed another population pharmacokinetic model using previous and current datasets. The previous PK model achieved stable prediction of propofol Cp throughout the study period, although it underestimates Cp. The step-down infusion regimen described in this study would be feasible in macaques during noninvasive procedures.


Assuntos
Anestésicos Intravenosos/farmacocinética , Macaca/sangue , Propofol/farmacocinética , Anestésicos Intravenosos/sangue , Animais , Injeções Intravenosas , Masculino , Modelos Biológicos , Propofol/sangue
8.
J Comp Pathol ; 148(1): 43-6, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22789862

RESUMO

A 5-year-old female Japanese macaque (Macaca fuscata) was humanely destroyed because of severe anaemia with poor response to treatment. At necropsy examination, marked splenomegaly and systemic enlargement of lymph nodes were observed. Microscopical examination revealed diffuse proliferation of neoplastic lymphoid cells in the spleen and lymph nodes with infiltration of the liver, lung, gastrointestinal tract, kidney and bone marrow. Immunohistochemically, the neoplastic cells expressed CD3 and CD4, but not CD20, CD79α or CD8, consistent with a T helper phenotype. A portion of neoplastic cells expressed the natural killer (NK) cell marker CD56. In-situ hybridization detected Epstein-Barr virus (EBV)-encoded small RNAs in the neoplastic cells, indicating the involvement of simian lymphocryptovirus (LCV). This is the first report of simian LCV-associated T/NK-cell lymphoma with the predominant expression of T-cell antigens in non-human primates.


Assuntos
Infecções por Herpesviridae/veterinária , Lymphocryptovirus/patogenicidade , Linfoma Extranodal de Células T-NK/veterinária , Macaca , Infecções Tumorais por Vírus/veterinária , Animais , Antígenos CD/metabolismo , Biomarcadores Tumorais/metabolismo , Proliferação de Células , Eutanásia Animal , Evolução Fatal , Feminino , Infecções por Herpesviridae/patologia , Infecções por Herpesviridae/virologia , Linfoma Extranodal de Células T-NK/metabolismo , Linfoma Extranodal de Células T-NK/patologia , Esplenomegalia/patologia , Esplenomegalia/virologia , Linfócitos T Auxiliares-Indutores/metabolismo , Linfócitos T Auxiliares-Indutores/patologia , Infecções Tumorais por Vírus/patologia , Infecções Tumorais por Vírus/virologia
9.
Strahlenther Onkol ; 188(12): 1102-7, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23104519

RESUMO

BACKGROUND AND PURPOSE: Surgical excision remains the standard and most reliable curative treatment for eyelid carcinoma, but frequently causes functional and cosmetic impairment of the eyelid. We therefore investigated the efficacy and safety of radiation therapy in eyelid carcinoma. PATIENTS AND METHODS: Twenty-three patients with primary carcinoma of the eyelid underwent radiation therapy. Sebaceous carcinoma was histologically confirmed in 16 patients, squamous cell carcinoma in 6, and basal cell carcinoma in 1. A total dose of 50-66.6 Gy (median, 60 Gy) was delivered to tumor sites in 18-37 fractions (median, 30 fractions). RESULTS: All but 3 of the 23 patients had survived at a median follow-up period of 49 months. The overall survival and local progression-free rates were 87% and 93% at 2 years, and 80% and 93% at 5 years, respectively. Although radiation-induced cataracts developed in 3 patients, visual acuity in the other patients was relatively well preserved. There were no other therapy-related toxicities of grade 3 or greater. CONCLUSION: Radiation therapy is safe and effective for patients with primary carcinoma of the eyelid. It appears to contribute to prolonged survival as a result of good tumor control, and it also facilitates functional and cosmetic preservation of the eyelid.


Assuntos
Adenocarcinoma Sebáceo/radioterapia , Carcinoma Basocelular/radioterapia , Carcinoma de Células Escamosas/radioterapia , Neoplasias Palpebrais/radioterapia , Visão Ocular/efeitos da radiação , Adenocarcinoma Sebáceo/mortalidade , Adenocarcinoma Sebáceo/patologia , Adenocarcinoma Sebáceo/cirurgia , Idoso , Idoso de 80 Anos ou mais , Piscadela/efeitos da radiação , Carcinoma Basocelular/mortalidade , Carcinoma Basocelular/patologia , Carcinoma Basocelular/cirurgia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Causas de Morte , Estética , Neoplasias Palpebrais/mortalidade , Neoplasias Palpebrais/patologia , Neoplasias Palpebrais/cirurgia , Pálpebras/efeitos da radiação , Feminino , Seguimentos , Humanos , Técnicas In Vitro , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Proteção Radiológica/instrumentação , Radioterapia Adjuvante/instrumentação , Taxa de Sobrevida
10.
J Anim Physiol Anim Nutr (Berl) ; 96(4): 600-9, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21699584

RESUMO

Successful ostrich farming requires knowledge of the nutritional needs of the birds. While much information is available on the nutritional value of various feed ingredients fed to ostriches, there is little known about their specific nutrient requirements. In this study, we measured the maintenance nitrogen requirements (MNR) of ostriches by nitrogen balance. We predict, based on the previous analysis of nitrogen requirements of various species of birds, that ostriches would have a MNR of 13.6-19.1 g N/day and a total endogenous nitrogen loss (TENL) of 2.8-5.1 g N/day. Three adult female ostriches were fed five pelleted diets containing 0.6-2.3% N [4-14.6% crude protein (CP)], 17.5 kJ/g gross energy (11.4 kJ/g ME) and 30% neutral detergent fibre. Each dietary trial consisted of a 10-day adaptation period, followed by a 5-day total excreta collection period. Body mass (109 ± 3 kg) and metabolizable energy intake (20.5 ± 0.7 MJ/day) were unaffected by dietary nitrogen levels. After correcting for excreta nitrogen losses during drying, MNR was calculated to be 481 mg N/kg(0.75) /day or 16.2 g N/day (100 g CP/day), and TENL as 310 mg N/kg(0.75) /day or 10.5 g N/day. Failure to correct for the 10.9 ± 4.1% average N losses during drying would underpredict the 'true' MNR by 35% and TENL by 46%. Our estimate for MNR of ostriches predicts a dietary requirement of 6.7% protein. Our estimate of TENL was nearly twice that predicted, possibly reflecting the high fibre content of their diet.


Assuntos
Ração Animal/análise , Dieta/veterinária , Nitrogênio/metabolismo , Necessidades Nutricionais , Struthioniformes/metabolismo , Fenômenos Fisiológicos da Nutrição Animal , Animais , Peso Corporal , Ingestão de Alimentos , Feminino
11.
Xenobiotica ; 40(12): 791-9, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20863202

RESUMO

The purpose of this study was to construct a method to predict CYP3A4 induction in the clinical setting from in vitro data using cryopreserved human hepatocytes. We recently developed an approach with in vitro assays of HepaRG cell lines for predicting CYP3A4 induction by using a novel value, termed the relative factor (RF), determined from the ratio of the concentration of an inducer to the reference standard. In this study, the applicability of the RF approach was expanded to cryopreserved human hepatocytes. Induction assays were performed in vitro using hepatocytes from four individual donors and eight typical inducers. The obtained RF values were related to the free plasma concentration of each inducer (expressed as Css,u/RF). A good relationship between the Css,u/RF values and the in vivo induction response was found for all donors. Inducers were classified by the Css,u/RF values into three categories for CYP3A4 induction risk (high, medium and low potency), and thereby the degree of CYP3A4 induction in vivo in humans could be predicted from the Css,u/RF values. The RF approach is applicable to human cryopreserved hepatocytes. Thus, a method to predict the potency of CYP3A4 inducers was constructed using cryopreserved human hepatocytes.


Assuntos
Criopreservação , Citocromo P-450 CYP3A/biossíntese , Ensaios Enzimáticos/métodos , Hepatócitos/enzimologia , Adulto , Idoso , Indução Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doadores de Tecidos
12.
J Med Primatol ; 39(5): 336-46, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20444005

RESUMO

BACKGROUND: A 24-year-old, male chimpanzee (Pan troglodytes) developed acute tetraparesis. Magnetic resonance imaging showed a diffuse T2-weighted hyperintensive lesion, indicating inflammation at the C1-2 level. All infective, autoimmune, and vascular investigations were unremarkable. RESULTS AND CONCLUSIONS: The chimpanzee's condition most resembled acute transverse myelitis (ATM) in humans. The chimpanzee was in severe incapacitated neurological condition with bedridden status and required 24-hour attention for 2 months followed by special care for over a year. Initially, corticosteroid therapy was performed, and his neurological symptoms improved to some extent; however, the general condition of the chimpanzee deteriorated in the first 6 months after onset. Pressure ulcers had developed at various areas on the animal's body, as the bedridden status was protracted. Supportive therapy was continued, and the general condition, appetite, mobility, and pressure ulcers have slowly but synergistically recovered over the course of 2 years.


Assuntos
Doenças dos Símios Antropoides/diagnóstico , Mielite Transversa/veterinária , Pan troglodytes , Paresia/veterinária , Traumatismos da Medula Espinal/veterinária , Animais , Doenças dos Símios Antropoides/terapia , Diagnóstico Diferencial , Assistência de Longa Duração , Imageamento por Ressonância Magnética , Masculino , Mielite Transversa/diagnóstico , Estado Nutricional , Paresia/líquido cefalorraquidiano , Paresia/etiologia , Lesão por Pressão/etiologia , Lesão por Pressão/veterinária , Traumatismos da Medula Espinal/líquido cefalorraquidiano , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/diagnóstico , Traumatismos da Medula Espinal/terapia
13.
Xenobiotica ; 39(11): 803-10, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19845431

RESUMO

It is important to predict CYP3A enzyme induction in the drug-discovery process to avoid adverse effects in clinical. In the present study, we constructed a method to correct the variability of in vitro CYP3A induction assays and thereby a method for the prediction of CYP3A induction in the clinical setting. Induction assays were performed in vitro using HepaRG cells and seven typical inducers. An index value was determined for enzyme induction, termed the relative factor (RF), from the ratio of the concentration of the inducers to the reference standards. Using RF as an index, variation among the assays was reduced. A good relationship was obtained between the ratio of the free plasma concentration at steady-state (C(ss,u)) to RF (expressed as C(ss,u)/RF) and the in vivo induction response. Using rifampicin as a reference standard, compounds with a C(ss,u)/RF value greater than 7.31 nmol l(-1) may induce CYP3A in vivo in humans.


Assuntos
Citocromo P-450 CYP3A/biossíntese , Hepatócitos/efeitos dos fármacos , Anticonvulsivantes/farmacologia , Bioensaio , Carbamazepina/farmacologia , Linhagem Celular , Indução Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Hepatócitos/enzimologia , Humanos , Fenobarbital/farmacologia , Rifampina/farmacologia
14.
J Viral Hepat ; 16(8): 586-94, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19552664

RESUMO

The impact of ribavirin exposure on virologic relapse remains controversial in combination therapy with pegylated interferon (Peg-IFN) and ribavirin for patients with chronic hepatitis C (CH-C) genotype 1. The present study was conducted to investigate this. Nine hundred and eighty-four patients with CH-C genotype 1 were enrolled. The drug exposure of each medication was calculated by averaging the dose actually taken. For the 472 patients who were HCV RNA negative at week 24 and week 48, multivariate logistic regression analysis showed that the degree of fibrosis (P = 0.002), the timing of HCV RNA negativiation (P < 0.001) and the mean doses of ribavirin (P < 0.001) were significantly associated with relapse, but those of Peg-IFN were not. Stepwise reduction of the ribavirin dose was associated with a stepwise increase in relapse rate from 11% to 60%. For patients with complete early virologic response (c-EVR) defined as HCV RNA negativity at week 12, only 4% relapse was found in patients given > or = 12 mg/kg/day of ribavirin and ribavirin exposure affected the relapse even after treatment week 12, while Peg-IFN could be reduced to 0.6 microg/kg/week after week 12 without the increase of relapse rate. Ribavirin showed dose-dependent correlation with the relapse. Maintaining as high a ribavirin dose as possible (> or = 12 mg/kg/day) during the full treatment period can lead to suppression of the relapse in HCV genotype 1 patients responding to Peg-IFN alpha-2b plus ribavirin, especially in c-EVR patients.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/isolamento & purificação , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Idoso , Relação Dose-Resposta a Droga , Feminino , Genótipo , Hepacivirus/genética , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/administração & dosagem , RNA Viral/sangue , Proteínas Recombinantes , Recidiva , Ribavirina/administração & dosagem , Resultado do Tratamento
15.
J Med Entomol ; 44(4): 601-7, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17695014

RESUMO

The Anopheles punctulatus (Diptera: Culicidae) group is the main vector for malaria and Bancroftian filariasis in Vanuatu. Anopheles larvae were collected from 10 localities on five islands of Vanuatu during the 2004 dry season for species identification as well as for estimating population structure and gene flow within and among islands. Species identification was determined using polymerase chain reaction-restriction fragment length polymorphism analysis of the internal transcribed spacer 2 region. Population structure and gene flow were examined by sequencing a portion of the ND4/ND5 region of the mitochondrial genome. Only one species of the An. punctulatus group, An. farauti s.s., was identified, consistent with previous studies in Vanuatu. A nonrandom distribution of An. farauti s.s. lineages was observed with one cosmopolitan lineage shared by eight sites on all five islands and a preponderance of island-specific lineages (36/40), indicating the introduction of a single main lineage into Vanuatu followed by dispersal, diversification, and limited lineage exchange between islands. Network analysis suggests a possible second introduction of An. farauti s.s. into the northern islands of Gaua and Malekula. Gene flow was high on three of the five islands, whereas Tanna and Santo have significant population structure. Among islands, gene flow was limited, indicating active mosquito dispersal only over short distances and a paucity of passive human-mediated dispersal over long distances. Minimal risk of active dispersal among these islands indicates that vector control can be effectively initiated at the island level within the archipelago of Vanuatu.


Assuntos
Anopheles/crescimento & desenvolvimento , Anopheles/genética , Fluxo Gênico , Dinâmica Populacional , Migração Animal , Animais , Clima , Geografia , Humanos , Malária/parasitologia , Modelos Biológicos , Reação em Cadeia da Polimerase , Estações do Ano , Vanuatu
16.
Acta Trop ; 103(2): 102-7, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17662681

RESUMO

A comparison of the patterns of gene flow within and between islands and the genetic diversities of the three species required for malaria transmission (humans, Plasmodium falciparum, and Anopheles farauti s.s.) within the model island system of Vanuatu, shows that the active dispersal of An. farauti s.s. is responsible for within island movement of parasites. In contrast, since both P. falciparum and An. farauti s.s. populations are largely restricted to islands, movement of parasites between islands is likely due to human transport. Thus, control of vectors is crucial for controlling malaria within islands, while control of human movement is essential to control malaria transmission across the archipelago.


Assuntos
Anopheles/genética , Vetores Artrópodes/genética , Fluxo Gênico , Variação Genética , Malária Falciparum/genética , Plasmodium falciparum/genética , Animais , Anopheles/parasitologia , Vetores Artrópodes/parasitologia , Humanos , Malária Falciparum/epidemiologia , Malária Falciparum/parasitologia , Malária Falciparum/transmissão , Vanuatu/epidemiologia
17.
J Periodontal Res ; 42(4): 294-9, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17559624

RESUMO

BACKGROUND AND OBJECTIVE: To establish an in vivo experimental model for examining human periodontal tissue, the present study examined several transplant techniques that maintain the structure and characteristics of human gingival mucosa. MATERIAL AND METHODS: Human oral mucosal tissue samples were collected from the gingiva (n = 11), palate (n = 1), and tongue (n = 3). These mucosal grafts were transplanted onto BALB/c nu/scid mice with double-mutant immunodeficiency. Murine skin, twice the size of the graft, was cut open in an ' square superset'-shape. Next, the connective tissue side of the graft was placed onto the murine connective tissue. Immunohistochemical analysis was also performed, using polyclonal rabbit antibody to involucrin, monoclonal antibody to vimentin, monoclonal antibody to CD34, and monoclonal antibody to Ki-67, to determine whether the characteristics of human oral mucosa were maintained. RESULTS: When the connective tissue side of the graft was placed on the murine fascial membrane, the histological structure of the graft was maintained for 60 d. These grafts were examined for human characteristics using human-specific antibodies. Immunohistochemically, the expression patterns of involucrin, vimentin, and Ki-67 indicated that transplanted mucosa revealed normal human characteristics, including differentiation and proliferation up to 80 d. CD34 was not detected in the graft endothelial cells. CONCLUSION: The present study revealed that the novel technique of transplantation of human gingival mucosa in nu/scid mice may serve as an in vivo experimental model of periodontal disease.


Assuntos
Procedimentos Cirúrgicos Dermatológicos , Gengiva/transplante , Mucosa Bucal/transplante , Transplante Heterólogo/métodos , Animais , Feminino , Humanos , Antígeno Ki-67/análise , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos SCID , Pessoa de Meia-Idade , Modelos Animais , Palato/cirurgia , Precursores de Proteínas/análise , Coelhos , Receptores de Complemento 3b/análise , Pele/patologia , Língua/transplante , Vimentina/análise
18.
Ann Trop Med Parasitol ; 101(4): 281-95, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17524243

RESUMO

Malaria-associated anaemia is a major public-health problem. Although the treatment of uncomplicated, Plasmodium falciparum malaria aims to clear the parasites, relieve the symptoms and permit haematological recovery, data on the impact of antimalarial treatment on haematological recovery are few. Haematological recovery and the prevalence of anaemia were therefore evaluated in 600 Kenyan children with uncomplicated malaria who were randomly assigned to one of three treatment groups. The children were given sulfadoxine-pyrimethamine (SP) on day 0, SP plus artesunate on day 0 (AS1), or SP on day 0 and artesunate on each of days 0-2 (AS3). Haemoglobin (Hb) concentrations were measured on days 0, 7, 14, 21 and 28, with haematological recovery defined as a day-28 Hb concentration of at least 11 g/dl. Only 96 (18%) of the 543 children who were anaemic (i.e. with <11.0 g Hb/dl) at enrolment achieved haematological recovery. The prevalence of anaemia fell from 91% on day 0 to 74% (252/340) by day 28 (P=0.065). Compared with SP alone, neither artesunate regimen resulted in higher Hb concentrations on day 28 (with means of 10.2, 9.9 and 10.2 g/dl for AS3, AS1 and SP, respectively; P=0.254), a higher frequency of haematological recovery (19%, 14% and 20% for AS3, AS1 and SP, respectively; P=0.301) or a greater reduction in the prevalence of anaemia (prevalences in the AS3, AS1 and SP arms falling from 90%, 89% and 93%, respectively, on day 0, to corresponding values of 71%, 82% and 69% on day 28; P=0.40). In fact, between days 0 and 7, the children in the AS3 arm showed a larger drop in mean Hb than the children in the other two treatment arms. In general, haematological recovery was most likely in older children who had mild anaemia at presentation and were parasitologically cured. Overall, the frequencies of haematological recovery were modest and not influenced by the artesunate treatments. Other factors contributing to anaemia need to be explored more fully.


Assuntos
Anemia/epidemiologia , Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Malária Falciparum/tratamento farmacológico , Pirimetamina/uso terapêutico , Sesquiterpenos/uso terapêutico , Sulfadoxina/uso terapêutico , Anemia/tratamento farmacológico , Artesunato , Pré-Escolar , Combinação de Medicamentos , Feminino , Humanos , Lactente , Quênia/epidemiologia , Malária Falciparum/complicações , Masculino , Prevalência , Fatores de Risco
19.
Int J Oral Maxillofac Surg ; 35(7): 613-7, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16540287

RESUMO

The efficacy of the selective cyclooxygenase-2 (COX-2) inhibitor meloxicam for treatment of postoperative oral surgical pain was assessed in a randomized controlled trial. Patients undergoing unilateral mandibular 3rd molar extraction surgery were allocated to 3 groups, A, B and C. After oral premedication of meloxicam 10 mg in group A, ampiroxicam 27 mg in group B and placebo in group C, surgery was completed within 30 min under local anaesthesia using 2% lidocaine. For postoperative pain relief the patients were allowed to take oral loxoprofen (60 mg per tablet). Postoperative pain was evaluated at the clinic on the 1st, 7th and 14th postoperative day (POD) using a visual analogue scale (VAS), as was the number of loxoprofen tablets consumed, and the results were compared among the 3 groups with statistical significance of P<0.05. VAS scores on 1 POD were significantly lower in group A than in group C. Loxoprofen consumption on the day of surgery and 1 POD was significantly lower in group A than in group C (P<0.01). Total analgesic consumption was significantly lower in groups A and B than in group C (P<0.02). The COX-2 inhibitor, meloxicam 10 mg used for premedication reduced postoperative pain compared with control in oral surgery.


Assuntos
Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Dor Pós-Operatória/prevenção & controle , Tiazinas/administração & dosagem , Tiazóis/administração & dosagem , Extração Dentária , Administração Oral , Adulto , Análise de Variância , Anestesia Local , Anti-Inflamatórios não Esteroides/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Masculino , Meloxicam , Dente Serotino/cirurgia , Medição da Dor , Fenilpropionatos/uso terapêutico , Pré-Medicação , Estudos Prospectivos
20.
Ann Oncol ; 17(1): 135-40, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16236754

RESUMO

BACKGROUND: The majority of lymphomas in the ocular adnexa are low-grade B-cell lymphomas of mucosa-associated lymphoid tissue (MALT lymphoma). Although radiotherapy is the most frequently applied management, cataract and dry eye are problematic complications. PATIENTS AND METHODS: Between 1973 and 2003, the clinical features of 36 patients with ocular adnexal MALT lymphoma with no symptoms who were managed with no initial therapy after biopsy or surgical resection were retrospectively analyzed. RESULTS: The median patient age was 63 years (range 22-84) and all patients had stage I disease, consisting of 31 unilateral cases and five bilateral cases. With a median follow-up of 7.1 years, 25 (69%) did not require treatment. The median time until the initiation of treatment in the remaining 11 patients (31%) was 4.8 years. Six patients (17%) died, and among them only two (6%) died due to progressive lymphoma. Seventeen patients (47%) progressed, but histologic transformation was recognized in only one (3%). The estimated overall survival rates of the 36 patients after 5, 10 and 15 years were 94%, 94% and 71%, respectively. CONCLUSIONS: In selected patients with ocular adnexal MALT lymphoma, no initial therapy might be an acceptable approach, because 70% of patients remained untreated at a median of 8.6 years, and their survival was comparable to that of reports on immediate therapy.


Assuntos
Linfoma de Zona Marginal Tipo Células B/patologia , Neoplasias Orbitárias/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Linfoma de Zona Marginal Tipo Células B/química , Linfoma de Zona Marginal Tipo Células B/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Orbitárias/secundário , Neoplasias Orbitárias/cirurgia , Prognóstico , Estudos Retrospectivos
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