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1.
J Physiol Pharmacol ; 68(1): 79-90, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28456772

RESUMO

Intestinal mucositis accompanied by severe diarrhea is one of the most common side effects during cancer chemotherapy. Lafutidine, a histamine H2 receptor antagonist with mucosal protective properties via sensory afferent neurons, is used for the treatment of upper gastrointestinal diseases. The present study investigated the effects of lafutidine on 5-fluorouracil (5-FU)-induced intestinal mucositis induced in mice. Male C57BL/6 wild-type (WT), sensory deafferented mice, and transient receptor potential vanilloid subfamily 1 knockout (TRPV1KO) mice were used. Animals were administered 5-FU once daily, while lafutidine and famotidine were administered twice daily for 6 days. Repeated administration of 5-FU caused severe intestinal mucositis, characterized by shortening of villi and destruction of crypts and was accompanied by diarrhea and body weight loss. Daily administration of lafutidine reduced the severity of intestinal mucositis, diarrhea and body weight loss in a dose-dependent manner, while famotidine had no effect on intestinal mucositis. The preventive effects of lafutidine were completely abolished in sensory deafferented and TRPV1-KO mice. Lafutidine significantly suppressed 5-FU-increased MPO activity and inflammatory cytokine expression on day 6, but not apoptosis induction in intestinal crypts on day 1. Lafutidine induced Alcian Blue and PAS-positive mucus production in the small intestine. These findings suggest that lafutidine attenuates 5-FU-induced intestinal mucositis, most likely by increasing mucus production via activation of sensory afferent neurons. Furthermore, intact TRPV1 signaling is essential for the activation of sensory afferent neurons induced by lafutidine. Therefore, lafutidine is more useful than other common antacids for the treatment of intestinal mucositis during cancer chemotherapy.


Assuntos
Acetamidas/uso terapêutico , Diarreia/tratamento farmacológico , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Mucosite/tratamento farmacológico , Piperidinas/uso terapêutico , Piridinas/uso terapêutico , Acetamidas/farmacologia , Animais , Antimetabólitos Antineoplásicos , Diarreia/metabolismo , Diarreia/patologia , Famotidina/uso terapêutico , Fluoruracila , Antagonistas dos Receptores H2 da Histamina/farmacologia , Interleucina-1beta/genética , Mucosa Intestinal/metabolismo , Intestinos/efeitos dos fármacos , Intestinos/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mucosite/induzido quimicamente , Mucosite/patologia , Peroxidase/metabolismo , Piperidinas/farmacologia , Piridinas/farmacologia , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfa/genética
2.
Sci Total Environ ; 571: 323-31, 2016 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-27487448

RESUMO

The persistent organic pollutants (POPs), such as organochlorine pesticides and PCBs, are ordinarily monitored in the aquatic environment or in soil in the environmental quality monitoring programs in São Paulo, Brazil. One of the core matrices proposed in the POPs Global Monitoring Plan (GMP) from the Stockholm Convention list is the ambient air, which is not a usual matrix for POPs monitoring in the country. In this study POP levels were evaluated in the air samples from an urban site in São Paulo City over five years, starting in 2010 as a capacity building project for Latin America and the Caribbean region for POP monitoring in ambient air using passive samplers. Furthermore, after the end of the Project in 2012, the monitoring continued in the same sampling site as means to improving the analytical capacity building and contribute to the GMP data. The POPs monitored were 17 congeners of 2,3,7,8 chloro-substituted PCDDs and PCDFs, dioxin-like PCBs, indicator PCBs, organochlorine pesticides and toxaphene. The results show a slight decrease in PCDD/F, dl-PCBs and indicator PCBs levels along the five years. The organochlorine pesticide endosulfan was present at its highest concentration at the beginning of the monitoring period, but it was below detection level in the last year of the monitoring. Some other organochlorine pesticides were detected close to or below quantitation limits. The compounds identified were dieldrin, chlordane, α-HCH, γ-HCH, heptachlor, heptachlor epoxide, hexachlorobenzene and DDTs. Toxaphene congeners were not detected. These results have confirmed the efficacy of passive sampling for POP monitoring and the capacity building for POP analysis and monitoring was established. However more needs to be done, including expansion of sampling sites, new POPs and studies on sampling rates to be considered in calculating the concentration of POPs in ambient air using a passive sampler.


Assuntos
Poluentes Atmosféricos/análise , Dioxinas e Compostos Semelhantes a Dioxinas/análise , Monitoramento Ambiental/métodos , Hidrocarbonetos Clorados/análise , Brasil , Cidades , Praguicidas/análise
3.
Eur J Pain ; 20(7): 1155-65, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27030509

RESUMO

BACKGROUND: TRPA1 is a Ca-permeable nonselective cation channel expressed in sensory neurons and acts as a nocisensor. Recent reports show that some monoterpenes, a group of naturally occurring organic compounds, modulate TRP channel activity. Here, we report that limonene, being contained in citrus fruits and mushrooms, shows a unique bimodal action on TRPA1 channel. METHODS: We examine the effects of limonene on sensory neurons from wild-type, TRPV1- and TRPA1-gene-deficient mice and on heterologously expressed channels in vitro. Molecular determinants were identified with using mutated channels. Cellular excitability is monitored with ratiometric Ca imaging. Nociceptive and analgesic actions of limonene are also examined in vivo. RESULTS: In wild-type mouse sensory neurons, limonene increased the intracellular Ca(2+) concentration ([Ca(2+) ]i ), which was inhibited by selective inhibitors of TRPA1 but not TRPV1. Limonene-responsive neurons highly corresponded to TRPA1 agonist-sensitive ones. Limonene failed to stimulate sensory neurons from the TRPA1 (-/-) mouse. Heterologously expressed mouse TRPA1 was activated by limonene. Intraplantar injection of limonene elicited acute pain, which was significantly less in TRPA1 (-/-) mice. Systemic administration of limonene reduced nociceptive behaviours evoked by H2 O2 . In both heterologously and endogenously expressed TRPA1, a low concentration of limonene significantly inhibited H2 O2 -induced TRPA1 activation. TRPA1 activation by limonene was abolished in H2 O2 -insensitive cysteine-mutated channels. CONCLUSIONS: Topically applied limonene stimulates TRPA1, resulting in elicitation of acute pain, but its systemic application inhibits nociception induced by oxidative stress. Because limonene is a safe compound, it may be utilized for pain control due to its inhibition of TRPA1 channels. What does this study add: Limonene, a monoterpene in essential oils of various plants, has been known for its antitumor and anti-inflammatory properties. However, molecular basis of their actions has not been identified. This study shows that limonene activates nociceptive TRPA1 and elicits acute pain, when it is topically applied. In addition, systemic application of limonene exerts inhibitory effects on nociception induced by an oxidative stress-induced TRPA1 activation.


Assuntos
Dor Aguda/etiologia , Analgésicos/farmacologia , Cicloexenos/farmacologia , Nociceptividade/efeitos dos fármacos , Células Receptoras Sensoriais/efeitos dos fármacos , Canal de Cátion TRPA1/efeitos dos fármacos , Terpenos/farmacologia , Animais , Técnicas de Cultura de Células , Células HEK293 , Humanos , Limoneno , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Canal de Cátion TRPA1/fisiologia
4.
Neuroscience ; 218: 335-43, 2012 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-22641084

RESUMO

Hydrogen sulfide (H(2)S), an endogenous gasotransmitter, modulates various biological functions, including nociception. It is known that H(2)S causes neurogenic inflammation and elicits hyperalgesia. Here we show that H(2)S activates mouse transient receptor potential ankyrin 1 (TRPA1) channels and elicits acute pain, using TRPA1-gene deficient mice (TRPA1(-/-)) and heterologous expression system. In wild-type mouse sensory neurons, H(2)S increased the intracellular Ca(2+) concentration ([Ca(2+)](i)), which was inhibited by ruthenium red (a nonselective TRP channel blocker) and HC-030031 (a TRPA1 blocker). H(2)S-responsive neurons highly corresponded to TRPA1 agonist-sensitive ones. [Ca(2+)](i) responses to H(2)S were observed in neurons from transient receptor potential vanilloid 1 (TRPV1(-/-)) mice but not from TRPA1(-/-) mice. Heterologously expressed mouse TRPA1, but not mouse TRPV1, was activated by H(2)S. H(2)S-induced [Ca(2+)](i) responses were inhibited by dithiothreitol, a reducing agent. Analyses of the TRPA1 mutant channel revealed that two cysteine residues located in the N-terminal internal domain were responsible for the activation by H(2)S. Intraplantar injection of H(2)S into the mouse hind paw caused acute pain which was significantly less in TRPA1(-/-) mice. The [Ca(2+)](i) responses to H(2)S in sensory neurons and in heterologously expressed channels, and pain-related behavior induced by H(2)S were enhanced under acidic conditions. These results suggest that H(2)S functions as a nociceptive messenger through the activation of TRPA1 channels. TRPA1 may be a therapeutic target for H(2)S-related algesic action, especially under inflammatory conditions.


Assuntos
Sulfeto de Hidrogênio/metabolismo , Neurônios/metabolismo , Neurotransmissores/metabolismo , Nociceptividade/fisiologia , Canais de Potencial de Receptor Transitório/metabolismo , Animais , Feminino , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Canal de Cátion TRPA1
5.
J Vet Intern Med ; 22(4): 985-8, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18564222

RESUMO

BACKGROUND: Imatinib mesylate is a small molecule targeted at dysregulated protein-tyrosine kinase. Mutation of c-kit exon 11, which induces constitutive phosphorylation of KIT, is one of the mechanisms for the development or progression of mast cell tumor (MCT) in dogs. The purpose of this study was to examine the therapeutic potential of imatinib mesylate in canine MCT. HYPOTHESIS: Imatinib mesylate has activity against MCT in dogs, and response to treatment can be correlated to presence of mutation within exon 11 of c-kit. ANIMALS: Twenty-one dogs with MCT with gross tumor burden and median tumor size of 7.2 cm (range, 1.0-25.3 cm) before treatment. METHODS: Tumors were analyzed for mutation of c-kit exon 11. Imatinib mesylate was administered PO to the dogs at a dose of 10 mg/kg daily for 1-9 weeks. RESULTS: Ten of 21 dogs (48%) had some beneficial response to imatinib mesylate treatment within 14 days of treatment initiation. All 5 dogs with a demonstrable c-kit mutation in exon 11 responded to the drug (1 complete remission, 4 partial remission). CONCLUSIONS AND CLINICAL IMPORTANCE: Imatinib mesylate has clinical activity against MCT in dogs. Response could not be predicted based on presence of absence of a mutation in exon 11 of c-kit.


Assuntos
Antineoplásicos/uso terapêutico , Doenças do Cão/tratamento farmacológico , Sarcoma de Mastócitos/veterinária , Piperazinas/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , Pirimidinas/uso terapêutico , Animais , Sequência de Bases , Benzamidas , Cães , Feminino , Mesilato de Imatinib , Masculino , Sarcoma de Mastócitos/tratamento farmacológico , Mutação , Proteínas Tirosina Quinases/genética
7.
Br J Pharmacol ; 153(6): 1324-30, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18204483

RESUMO

BACKGROUND AND PURPOSE: Transient receptor potential melastatin 2 (TRPM2) is a non-selective Ca(2+)-permeable cation channel and is known to be activated by adenosine 5'-diphosphoribose (ADP-ribose) and hydrogen peroxide. TRPM2 current responses are reported to be drastically potentiated by the combination of each of these ligands with heat. Furthermore, the combination of cyclic ADP-ribose with heat also activates TRPM2. Although flufenamic acid, antifungal agents (miconazole and clotrimazole), and a phospholipase A(2) inhibitor (N-(p-amylcinnamoyl)anthranilic acid) inhibit TRPM2, their inhibition was either gradual or irreversible. EXPERIMENTAL APPROACH: To facilitate future research on TRPM2, we screened several compounds to investigate their potential to activate or inhibit the TRPM2 channels using the patch-clamp technique in HEK293 cells, transfected with human TRPM2. KEY RESULTS: 2-aminoethoxydiphenyl borate (2-APB) exhibited a rapid and reversible inhibition of TRPM2 channels that had been activated by its ADP-ribose or cADP-ribose and heat in a dose-dependent manner (IC(50) about 1 microM). 2-APB also inhibited heat-evoked insulin release from pancreatic islets, isolated from rats. CONCLUSIONS AND IMPLICATIONS: 2-APB proved to be a powerful and effective tool for studying the function of TRPM2.


Assuntos
Compostos de Boro/farmacologia , Insulina/metabolismo , Canais de Cátion TRPM/antagonistas & inibidores , Adenosina Difosfato Ribose/metabolismo , Animais , Antifúngicos/farmacologia , Compostos de Boro/administração & dosagem , Linhagem Celular , Cinamatos/farmacologia , ADP-Ribose Cíclica/metabolismo , Relação Dose-Resposta a Droga , Ácido Flufenâmico/farmacologia , Temperatura Alta , Humanos , Técnicas In Vitro , Concentração Inibidora 50 , Secreção de Insulina , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Masculino , Técnicas de Patch-Clamp , Ratos , Ratos Wistar , Transfecção , ortoaminobenzoatos/farmacologia
8.
Cancer Gene Ther ; 14(8): 696-705, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17514193

RESUMO

The number of tumor-infiltrating lymphocytes is known to be related to outcomes in patients with a variety of malignancies. Interferon (IFN) gamma-inducible protein-10 (IP-10) and monokine induced by IFNgamma (MIG) have chemotactic effects on activated T lymphocytes and natural killer (NK) cells. The aim of this study was to evaluate the antitumor effects of exogenous expression of the MIG and IP-10 genes delivered to solid tumors by poly [D,L-2,4-diaminobutyric acid] (PDBA). The murine MIG and IP-10 genes were transfected into mouse neuroblastoma cells with PDBA. MIG and IP-10 levels in supernatants of transfected cells were measured by enzyme-linked immunosorbent assay. The chemotactic activities of MIG and IP-10 in the supernatants of cell cultures were measured by chemotaxis assay. Tumors were injected in vivo with PDBA/pmMIGColon, two colonsIP-10 complexes to evaluate the effects of these genes on tumor volume and survival time of mice. Transfected PDBA/pmMIGColon, two colonsIP-10 complexes produced MIG and IP-10 protein in vitro. MIG and IP-10 proteins secreted into the culture medium showed chemotactic activity. MIG and IP-10 gene therapy with the PDBA system in vivo significantly inhibited tumor growth and prolonged survival time of mice. In conclusion, PDBA-mediated MIG and IP-10 gene therapy may be useful for treatment of solid tumors.


Assuntos
Aminobutiratos , Quimiocinas CXC/genética , Técnicas de Transferência de Genes , Neuroblastoma/terapia , Animais , Linhagem Celular Tumoral , Quimiocina CXCL10 , Quimiocina CXCL9 , Feminino , Linfócitos do Interstício Tumoral/imunologia , Camundongos , Camundongos Endogâmicos A , Neuroblastoma/genética , Neuroblastoma/imunologia , Polímeros
9.
Nihon Hoshasen Gijutsu Gakkai Zasshi ; 62(5): 711-3, 2006 May 20.
Artigo em Japonês | MEDLINE | ID: mdl-16770852

RESUMO

PURPOSE: Recent years, CT on rail system was reported to be useful as a tool for image-guided radiotherapy (IGRT). This system was clinically developed with the aim of stereotactic irradiation (STI) for brain, lung, liver, prostate and other sites. Quality assurance and quality control (QC) is an important issue in CT on rail system to assure geometric accuracies. The purpose of this study is to estimate the geometric accuracies of our CT on rail system using a detachable micro-multi leaf collimator (mMLC) with new type radiochromic films. Carrying out our original QC program, translational errors, setup reproducibility, beam misalignment and beam characteristics were evaluated. METHODS AND MATERIALS: We have studied with CT on rail system (FOCAL unit, Toshiba Medical systems, Tokyo, Japan) and mMLC unit (Accuknife, Direx Inc., Tokyo, Japan). We have developed original alignment phantom and small steel markers (2 mm phi) were implanted on its surface at certain intervals. Firstly, we have evaluated the accuracy of self-moving CT gantry and CT resolutions for cranio-caudal directions by changing slice thickness. And then using the phantom, we have measured the accuracy and reproducibility of geometric isocenter of the linac side and the CT gantry side by scanning the phantom. We have also measured the geometric changes of the common treatment couch by weight-loaded test (up to 135 kgw). To estimate dosimetric and geometric accuracies with the mMLC unit, the misalignment of the beam axes (gantry, collimator and couch rotation axis), mMLC leaf positions, and dose distributions for the verification plan were measured with new type GafChromic films (GafChromic-RTQA, ISP Inc., USA) and cylindrical phantom. The dose characteristics of the GafChromic film were also evaluated. RESULTS: The reproducibility of the self-moving CT gantry have a good agreement within 1 mm. Weight-load test have shown a good reliability within 2 mm at the common treatment couch. The translational precision of the common treatment couch was 0.0 +/- 0.1 mm at linac side and -0.2 +/- 0.5 mm at CT gantry side. The misalignments of beam axes have been kept within 0.4 mm at maximum. Gap test have shown the accuracies of the mMLC leaf positions, which is needed to keep within 1 mm by a routine calibration. CONCLUSIONS: To practice quality control program for the FOCAL unit and the mMLC unit is essential for a regular interval to reduce systematic errors. New type radiochromic film would be useful for a verification tool as alternative to conventional film.


Assuntos
Controle de Qualidade , Radiocirurgia/instrumentação , Tomografia Computadorizada por Raios X/instrumentação , Filme para Raios X , Radiocirurgia/métodos , Reprodutibilidade dos Testes , Tomografia Computadorizada por Raios X/métodos
10.
Histol Histopathol ; 20(3): 817-24, 2005 07.
Artigo em Inglês | MEDLINE | ID: mdl-15944931

RESUMO

Uterine expression of the epidermal growth factor (EGF) family of growth factors has not been studied in the dog. The present study looks at the presence of mRNA transcripts and immunohistochemical localization for transforming growth factor-alpha (TGF-alpha), which is the potent EGF family member, and for EGF receptor (EGF-R) in the canine uterus during the estrous cycle. The reverse transcriptase-polymerase chain reaction together with sequencing of the products confirmed the presence of their mRNA transcripts in the endometrium throughout the estrous cycle. Immunohistochemical analysis found clear positive staining for TGF-alpha and EGF-R in the luminal and glandular epithelia at proestrus and estrus. Immunoreactivity decreased at the early stage of diestrus. In the mid stage of diestrus, clear staining for TGF-alpha was again found in the glands of the luminal region, and staining for EGF-R was observed in all glands. Very little staining was seen at anestrus for either TGF-alpha or EGF-R. These results suggest that TGF-alpha expressed in the uterus may be involved in regulating growth, differentiation and regression in the endometrial epithelial cells during the estrous cycle in the dog.


Assuntos
Receptores ErbB/genética , Ciclo Estral , RNA Mensageiro/metabolismo , Fator de Crescimento Transformador alfa/genética , Útero/metabolismo , Animais , Sequência de Bases , DNA Complementar/química , DNA Complementar/genética , Cães , Receptores ErbB/análise , Feminino , Expressão Gênica , Imuno-Histoquímica , Dados de Sequência Molecular , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Alinhamento de Sequência , Análise de Sequência de DNA , Homologia de Sequência do Ácido Nucleico , Fator de Crescimento Transformador alfa/análise , Útero/química
12.
Br J Surg ; 90(9): 1072-5, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12945073

RESUMO

BACKGROUND: Compromised patients subjected to major digestive surgery frequently develop infective complications caused by methicillin-resistant Staphylococcus aureus (MRSA), which may have dangerous consequences. This was a prospective randomized study to determine whether intranasal mupirocin could reduce postoperative infective complications in patients having digestive surgery. METHODS: A total of 395 patients who underwent abdominal digestive surgery were assigned randomly into two groups: a treated group (193 patients) and controls (202). Patients in the treated group were given 30 mg mupirocin calcium hydrate ointment topically to each nostril three times a day on each of the 3 days before operation. The untreated group received no mupirocin treatment. RESULTS: Most infections were due to Gram-negative bacteria in both groups. There were 21 Gram-positive infections detected at the surgical site, ten in the treated group and 11 in control patients. The incidence of pneumonia was significantly different between the groups (none in the treated group and five in control patients; P = 0.028). Four of five patients with pneumonia had a sputum culture containing MRSA. CONCLUSION: Intranasal mupirocin treatment had no significant impact on surgical-site infection after digestive surgery.


Assuntos
Antibacterianos/administração & dosagem , Mupirocina/administração & dosagem , Infecções Estafilocócicas/prevenção & controle , Infecção da Ferida Cirúrgica/prevenção & controle , Administração Intranasal , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças do Sistema Digestório/cirurgia , Feminino , Humanos , Masculino , Resistência a Meticilina , Pessoa de Meia-Idade , Pomadas , Cuidados Pré-Operatórios/métodos , Estudos Prospectivos , Staphylococcus aureus
13.
Lung ; 180(2): 73-89, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12182159

RESUMO

14-membered ring macrolides have been reported to have anti-inflammatory effects and to decrease neutrophil infiltration into the airways in chronic lower respiratory tract diseases. This study investigated the potential inhibitory effects of macrolide antibiotics on bleomycin-induced acute lung injury. Four drugs were studied: two 14-membered ring macrolides, clarithromycin (CAM) and roxithromycin (RXM); a 15-membered ring macrolide, azithromycin (AZM); and a 16-membered ring macrolide, josamycin (JM). Their effects were compared with macrolide untreated, pretreated, and post-treated groups. An acute lung injury was inhibited by pretreatment with CAM or RXM, which significantly ameliorated the bleomycin-induced increases in the total cell and neutrophil counts in bronchoalveolar lavage (BAL) fluids and the wet lung weight. The pretreatment with CAM or RXM also suppressed inflammatory cell infiltration and interstitial lung edema in the histopathological study. These inhibitory effects were associated with a decreased KC concentration in the BAL fluid and a decreased number of apoptotic cells in the lungs. Posttreatment with CAM or RXM had no marked inhibitory effects. Pretreatment with AZM was much less effective, and JM showed no inhibitory effects. These findings suggest that 14-membered ring macrolides have different effects on inflammatory lung disease than 15- and 16-membered ring macrolides and may be therapeutic agents for acute lung injury and pulmonary fibrosis.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/antagonistas & inibidores , Antibióticos Antineoplásicos/efeitos adversos , Bleomicina/efeitos adversos , Quimiocinas CXC , Peptídeos e Proteínas de Sinalização Intercelular , Síndrome do Desconforto Respiratório/induzido quimicamente , Síndrome do Desconforto Respiratório/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Azitromicina/administração & dosagem , Azitromicina/antagonistas & inibidores , Líquido da Lavagem Broncoalveolar/citologia , Quimiocina CXCL1 , Fatores Quimiotáticos/metabolismo , Claritromicina/administração & dosagem , Claritromicina/antagonistas & inibidores , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Substâncias de Crescimento/metabolismo , Marcação In Situ das Extremidades Cortadas , Josamicina/administração & dosagem , Josamicina/antagonistas & inibidores , Pulmão/irrigação sanguínea , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Edema Pulmonar/tratamento farmacológico , Roxitromicina/administração & dosagem , Roxitromicina/antagonistas & inibidores , Fatores de Tempo , Resultado do Tratamento
14.
Br J Surg ; 89(1): 63-9, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11851665

RESUMO

BACKGROUND: Liver resection of segments VII and/or VIII sometimes requires segmental resection of the right hepatic vein in patients with liver tumours invading or located close to the hepatic vein. In this situation, hepatic vein reconstruction is thought to have an important role in the postoperative function of segment VI. This study investigated whether preoperative embolization of the major hepatic vein could obviate the need for hepatic vein reconstruction after cranial partial resection of the liver including the major hepatic vein trunk in a preclinical model. METHODS: Sixteen beagles were divided into two groups of eight: control group (hepatectomy alone) and hepatic venous embolization (HVE) group (hepatectomy after HVE). HVE was performed 2 weeks before hepatectomy. All dogs underwent resection of the cranial third of the left lateral liver lobe together with the major trunk of the left hepatic vein. Following hepatectomy, survival, histological features, portal venous pressure and serum aspartate aminotransferase (AST) levels were determined. RESULTS: Six control animals and seven in the HVE group were alive 1 week after hepatectomy. Immediately after hepatectomy, portal venous pressure was significantly higher in the control group compared with the HVE group (mean(s.d.) 14.0(1.1) versus 8.1(1.0) mmHg; P < 0.01). Histological examination of the remnant left lateral lobe demonstrated patchy parenchymal haemorrhage in the control group and normal parenchymal architecture in the HVE group. Peak AST levels were observed on day 1 in both groups and were significantly higher in the control group (mean(s.d.) 182(42) versus 67(40) units/l; P < 0.01). CONCLUSION: In this model, preoperative HVE facilitated interlobar venous collateral formation and minimized the untoward effects of segmental hepatic vein resection. This procedure may obviate the need for hepatic vein reconstruction after cranial partial liver resection including the major hepatic vein.


Assuntos
Embolização Terapêutica/métodos , Hepatectomia/métodos , Veias Hepáticas/cirurgia , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Pressão Sanguínea/fisiologia , Prótese Vascular , Cães , Feminino , Masculino , Modelos Animais , Cuidados Pré-Operatórios/métodos
15.
Hypertension ; 38(6): 1255-9, 2001 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-11751699

RESUMO

This study investigates the effects of candesartan, an angiotensin II type 1 receptor blockade, on carotid arterial intimal thickening and glucose tolerance in balloon-injured male Wistar fatty rats and their littermates (Wistar lean rats). Candesartan was orally administered to 12-week-old rats for 21 days, and age-matched rats without the agent were used as the respective controls. Balloon catheterization in the left common carotid artery was performed on day 7, and the artery was removed on day 14 for histological analysis. Compared with the area ratios of the neointima/media in fatty rats without treatment, the ratios in fatty rats treated with candesartan at 1 mg. kg(-1). d(-1) and lean rats without treatment were significantly decreased to 65%; on the other hand, the ratios of fatty rats treated with candesartan at 10 mg. kg(-1). d(-1) and lean rats treated with 1 mg. kg(-1). d(-1) were reduced to 35%, and those of lean rats treated with 10 mg. kg(-1). d(-1) were reduced to 28%. The administration of candesartan also decreased the level of plasma glucose time- and dose-dependently in fatty rats. In an intragastric glucose load, the levels of both glucose and insulin at 30 and 60 minutes were significantly decreased when fatty rats were treated with candesartan at 10 mg. kg(-1). d(-1). In cultured vascular smooth muscle cells from fatty rats, insulin-stimulated Akt (New England Biolabs) phosphorylation and 2-deoxy-D-glucose uptake were inhibited to 59% and 68%, respectively, by angiotensin II, but the effects were ameliorated by the addition of 10(-7) mol/L candesartan. We conclude that candesartan could be effective for the suppression of vascular smooth muscle cell growth dose-dependently in Wistar fatty and lean rats. Furthermore, the agent could improve insulin resistance in Wistar fatty rats.


Assuntos
Antagonistas de Receptores de Angiotensina , Benzimidazóis/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Resistência à Insulina , Proteínas Serina-Treonina Quinases , Tetrazóis/farmacologia , Túnica Íntima/efeitos dos fármacos , Animais , Compostos de Bifenilo , Artéria Carótida Primitiva , Células Cultivadas , Desoxiglucose/farmacocinética , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Relação Dose-Resposta a Droga , Masculino , Músculo Liso Vascular/patologia , Obesidade , Fosforilação , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-akt , Ratos , Ratos Wistar , Túnica Íntima/patologia
16.
Intern Med ; 40(10): 1064-7, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11688836

RESUMO

A 57-year-old man presented with pneumonia, respiratory distress, and myelodysplastic syndrome. A diagnosis of Legionnaires' disease due to Legionella pneumophila (L. pneumophila) was established. The patient had long been drinking tap water via a conduit from a hot spring resource, from which L. pneumophila was also isolated. Both the patient's strain and the water strain of L. pneumophila were identified as serogroup 1, and the genetic relatedness between the two strains as seen by pulsed-field gel electrophoresis was 87%. The patient was successfully treated with erythromycin, fluoroquinolone, and rifampicin. This case raises an important issue on public health represented by legionellosis in Japan.


Assuntos
Legionella pneumophila/isolamento & purificação , Doença dos Legionários/diagnóstico , Doença dos Legionários/etiologia , Microbiologia da Água , Comportamento de Ingestão de Líquido , Eletroforese em Gel de Campo Pulsado , Humanos , Japão , Legionella pneumophila/genética , Masculino , Pessoa de Meia-Idade
17.
Endocr J ; 48(4): 433-42, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11603565

RESUMO

The aim of this experiment was to examine the regulation of p38 mitogen-activated protein (MAP) kinase by platelet-derived growth factor (PDGF)-BB and its biological effects on rat cultured vascular smooth muscle cells (VSMCs). VSMCs were obtained from aortae of male Wistar rats by the media explant technique. After being stimulated by PDGF-BB with or without the p38 MAP kinase-specific inhibitor, SB-203580, the cells were solubilized, and the levels of phosphorylated p38 MAP kinase were examined by immunoblot analysis. The amounts of DNA synthesis and content were measured by using [3H]-thymidine and Hoechst-33258 dye, respectively. The detection of apoptotic cells was evaluated by the TUNEL method. PDGF-BB could phosphorylate p38 MAP kinase dose-dependently, and the phosphorylation was specifically inhibited by SB-203580 in a dose-dependent manner. However, PDGF-BB did not affect the protein level of p38 MAP kinase. Both [3H]-thymidine incorporation and total cellular DNA content were increased by PDGF-BB, and these elevations were prevented by SB-203580. In contrast, PDGF-BB-stimulated VSMCs did not show apoptotic change in spite of the presence or absence of SB-203580. These results established that PDGF-BB activated p38 MAP kinase and subsequently regulated cell growth in VSMCs, providing a molecular mechanism by which p38 MAP kinase can cause the development of cardiovascular diseases, including atherosclerosis.


Assuntos
Apoptose/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Músculo Liso Vascular/citologia , Fator de Crescimento Derivado de Plaquetas/farmacologia , Animais , Aorta , Becaplermina , DNA/análise , DNA/biossíntese , Ativação Enzimática/efeitos dos fármacos , Humanos , Imidazóis/farmacologia , Immunoblotting , Marcação In Situ das Extremidades Cortadas , Masculino , Músculo Liso Vascular/química , Músculo Liso Vascular/enzimologia , Fosforilação , Proteínas Proto-Oncogênicas c-sis , Piridinas/farmacologia , Ratos , Ratos Wistar , Timidina/metabolismo , Trítio , Proteínas Quinases p38 Ativadas por Mitógeno
18.
Pancreas ; 23(4): 393-8, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11668209

RESUMO

INTRODUCTION: Recently, results of the clinical application of the two-layer method have shown the morphologic quality of the human pancreas grafts after reperfusion to be excellent, although ischemia-reperfusion injury is related to early graft loss in pancreas transplantation. However, some reports have indicated that heat shock proteins (HSPs) have important functions in response to the stress-related events. AIM: To examine whether the two-layer method reduced ischemia-reperfusion injury in a canine pancreas autotransplantation model by investigating the expression of HSPs. METHODOLOGY: There were three experimental groups in which dogs received segmental autografts after preservation by the two-layer method using University of Wisconsin solution (UW) (group 1), simple storage in UW (group 2) for 24 hours, or no preservation (group 3). RESULTS: In group 1, pancreatic tissue perfusions were high, and pancreatic exocrine functions were well preserved after 1, 2, and 4 hours of reperfusion with low incidence of graft pancreatitis or vessel thrombosis compared with that in group 2. Moreover, ATP rapidly recovered, and HSP 60 was strongly enhanced after reperfusion in group 1. On the other hand, ATP recovery and the enhancement of HSP 60 were weak after reperfusion in group 2. CONCLUSION: The two-layer method reduced ischemia-reperfusion injury compared with UW simple storage in canine pancreas autotransplantation with a strong expression of HSP 60.


Assuntos
Chaperonina 60/fisiologia , Transplante de Pâncreas , Pâncreas/irrigação sanguínea , Traumatismo por Reperfusão/prevenção & controle , Trifosfato de Adenosina/metabolismo , Amilases/sangue , Animais , Chaperonina 60/análise , Cães , Feminino , Sobrevivência de Enxerto , Proteínas de Choque Térmico HSP90/análise , Imuno-Histoquímica , Lipase/sangue , Masculino , Pâncreas/química , Pâncreas/enzimologia , Transplante Autólogo
20.
Chem Pharm Bull (Tokyo) ; 49(9): 1089-92, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11558592

RESUMO

As an extension of our investigation of peptidyl-resin linkage stability towards different cleavage procedures used in the solid-phase peptide synthesis (SPPS) technique, the present paper evaluated the trifluoromethanesulfonic acid (TFMSA)/trifluoroacetic acid (TFA)/thioanisole method, varying the type of resin (benzhydrylamine-resin, BHAR; methylbenzhydrylamine-resin, MBHAR and 4-(oxymethyl)-phenylacetamidomethyl-resin, PAMR) and peptide resin-bound residue (Gly and Phe). The vasoactive angiotensin II (AII, DRVYIHPF) and its [Gly8]-AII analogue linked to those resins used routinely in tert-butyloxycarbonyl (Boc)-SPPS chemistry were submitted comparatively to a time course study towards TFMSA/TFA cleavage. At 0 degrees C, [Gly8]-AII was completely removed from all resins in less than 6 h, but the hydrophobic Phe8 moiety-containing AII sequence was only partially cleaved (not more than 15%) from BHAR or MBHAR in this period. At 25 degrees C, [Gly8]-AII cleavage time decreased to less than 2 h irrespective of the solid support, and quantitative removal of AII from PAMR and MBHAR occurred in less than 3 h. However, about 10-15 h seemed to be necessary for cleavage of AII from BHAR, and in this extended cleavage reaction a significant increase in peptide degradation rate was observed. Regardless of the cleavage temperature used, the decreasing order of acid stability measured for resins was BHAR>MBHAR>PAMR. Collectively, these findings demonstrated the feasibility of applying TFMSA/TFA solution as a substitute for anhydrous HF at the cleavage step in Boc-SPPS methodology. Care should be taken however, as the cleavage efficacy depends on multiple factors including the resin, peptide sequence, the time and temperature of reaction.


Assuntos
Peptídeos/síntese química , Sulfetos/química , Ácidos Sulfônicos/química , Ácido Trifluoracético/química , Aminoácidos/análise , Cromatografia Líquida de Alta Pressão , Indicadores e Reagentes , Espectrometria de Massas , Resinas Vegetais , Solventes
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