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1.
Artigo em Inglês | MEDLINE | ID: mdl-37458570

RESUMO

Summary: There are very few reports of syndrome of inappropriate antidiuresis hormone secretion (SIADH) after receiving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine. Herein, we present the case of an 84-year-old woman who developed severe hyponatremia following the second administration of the SARS-CoV-2 mRNA vaccine. The patient presented with nausea, vomiting, and headache. Laboratory tests showed a plasma sodium level of 119 mmol/L. After receiving 500 mL of intravenous saline over a 2-h period, her plasma sodium level raised to 121 mmol/L, but her symptoms persisted. Considering that rapid plasma sodium correction was necessary, we started 3% saline solution overnight. Her plasma sodium level raised to 132 mmol/L and her symptoms completely resolved. Clinical and laboratory findings were consistent with a diagnosis of SIADH. In the absence of any other triggering factors, we concluded that the condition was likely associated with the vaccination. Clinicians should be aware of the potential for hyponatremia, particularly SIADH, associated with SARS-CoV-2 mRNA vaccination. Learning points: Reports of syndrome of inappropriate antidiuresis hormone secretion after receiving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination are limited. If nausea, headache, and confusion are observed immediately after SARS-CoV-2 vaccination, clinicians should consider the presence of hyponatremia. As similar case reports to date have presented with severe hyponatremia, prompt treatment may be required.

2.
Cureus ; 15(12): e51149, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38283441

RESUMO

Systemic lupus erythematosus is known to cause autoimmune hyperlipidemia. We present a case in which hypertriglyceridemia was exacerbated by dermatomyositis. A 53-year-old woman with a medical history of undertreated hypertriglyceridemia complained of dyspnea and arthralgia. Despite the treatment, her triglyceride levels increased concurrently with the onset of arthralgia. She had characteristic skin manifestations and tested positive for anti-Jo-1 autoantibodies, leading to a diagnosis of dermatomyositis. Chronic inflammation may result in elevated triglyceride levels. When dermatomyositis is diagnosed, evaluating lipid abnormalities is important.

3.
J Radiat Res ; 63(1): 80-87, 2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-34718690

RESUMO

We hypothesize that there is a risk of ipsilateral breast tumor recurrence (IBTR) in surgical margin-free invasive ductal carcinoma (IDC) in the presence of ductal carcinoma in situ (DCIS) component affecting surgical margins in early stage. From 1990 to 2014, 343 patients with IDC in which the DCIS component constitute have received radiotherapy (RT) following breast-conserving surgery (BCS). All patients received whole breast irradiation with a prescribed dose of 50 Gy in 20 fractions (four times a week). This one-arm cohort with boost RT (253 patients) was compared for IBTR with a non-cohort group receiving no boost RT because of freedom from positive margins (90 patients). Median observation months were 98 (boost group) vs 119 (no boost group), respectively. The 15-year local recurrence-free survival (LRFS) rates were 98.5% and 85.6% in the boost and no boost groups, respectively (Cox proportional hazards model univariate analysis; p = 0.013, HR 0.13). Similarly, for other background factors, there was a significant difference in the LRFS between age groups. The 15-year LRFS rate was 91.8% in patients aged 45 years or younger and 94.6% in patients older than 46 years (p = 0.031, HR 0.21), respectively. Only these two factors were independently significant in Cox proportional hazards model multivariate analysis. IBTR risk in margin-free IDC with DCIS component was independently decreased by boost RT in the cohort setting. Tumor size, extensive intraductal component (EIC), boost dose, the presence of lymph node (LN) metastasis and hormonal therapy were not IBTR risk factors in this study.


Assuntos
Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/radioterapia , Carcinoma Intraductal não Infiltrante/cirurgia , Feminino , Humanos , Margens de Excisão , Mastectomia Segmentar/efeitos adversos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia
4.
Rinsho Shinkeigaku ; 61(6): 361-367, 2021 Jun 29.
Artigo em Japonês | MEDLINE | ID: mdl-34011812

RESUMO

OBJECTIVE: We proposed a novel palliative care scale (Amyotrophic Lateral Sclerosis Palliative Care Scale: ALSPCS) for patients with ALS, and analyzed the suffering reported by patients. METHODS: Thirty-one patients participated in the study. The ALSPCS has 15 items to evaluate physical and psychological suffering; patients scored their subjective suffering on a scale of 0-5 for each item. This study analyzed 13 of 15 items. RESULTS: The mean scores obtained from the patients were as follows: 'dyspnea', 2.5; 'pain', 2.4; 'restlessness', 2.4; 'thirst', 3.0; 'burning sensation', 2.0; 'choking', 2.0; 'nausea', 0.4; 'constipation', 1.5; 'insomnia', 2.5; 'anxiety', 3.5; 'loneliness', 2.4; 'irritation', 2.1; and 'communication difficulty', 2.3. Multiple correlation analysis using Spearman's rank correlation coefficient showed significant correlations of dyspnea with restlessness, thirst, burning sensation and anxiety; of restlessness with dyspnea, thirst, loneliness and irritation; and of anxiety with dyspnea, thirst and loneliness (P < 0.0038 after Bonferroni's correction). In the principal component analysis, every item showed a positive loading value in the first principal component. Dyspnea, restlessness, thirst, anxiety, loneliness and irritation had loading values >0.7; thus, these symptoms might be the main features in ALS patients. The total scores or each ALSPCS score showed no significant association with post-assessment survival period. CONCLUSION: This study, using ALSPCS, showed that the subjective suffering of ALS patients was variable and strongly correlated with each other. Appropriate and comprehensive assessment of physical and psychological affliction with ALSPCS could be potentially useful in verifying the effectiveness of palliative care for end-of-life stage ALS patients in the future.


Assuntos
Esclerose Lateral Amiotrófica , Esclerose Lateral Amiotrófica/terapia , Ansiedade , Dispneia/etiologia , Humanos , Cuidados Paliativos , Agitação Psicomotora
5.
Int J Hematol ; 107(5): 551-558, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29374827

RESUMO

In allogeneic hematopoietic stem cell transplantation (allo-HSCT) from unrelated donors, delays in donor search are adversely associated with patient outcome. However, the optimal duration for either waiting for an unrelated donor or selecting alternative sources remains undetermined. Using data from the Japan Marrow Donor Program (JMDP) registry, we retrospectively analyzed 349 adult patients who had searched for unrelated donors. Two hundred and three patients received allo-HSCT from JMDP donors (Group A) with a median of 140 days required to identify a donor, 60 received allo-HSCT from alternative sources (Group B) after a median of 111.5 days at which point either all donor candidates had failed or the patient achieved a second or subsequent complete remission, and 77 suspended allo-HSCT (Group C) after a median of 310 days. The 5-year overall survival (OS) rate in Group A was superior to that of Group C (48.6 vs 38.5%, P = 0.001). Although Group B included more patients with high or very high disease risk index (DRI) at the time of allo-HSCT compared with Group A, the 5-year OS was not significantly different between Groups A and B (48.6 vs 40.9%, P = 0.07), indicating that switching to alternative donors may benefit patients with high DRI.


Assuntos
Seleção do Doador , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Obtenção de Tecidos e Órgãos/métodos , Doadores não Relacionados , Adolescente , Adulto , Idoso , Aloenxertos , Progressão da Doença , Feminino , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Listas de Espera , Adulto Jovem
6.
Kekkaku ; 92(1): 21-26, 2017 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-30646469

RESUMO

[Objective] To contribute to countermeasures against pulmonary tuberculosis in patients with HIV infection through analyzing and evaluating its treatment outcomes and patient management. [Methods] The 'subjects were pulmonary tuberculosis patients newly registered between 2008 and 2014 in whom concomitant HIV infection was detected. For the control, sex- and generation-matched pulmonary tuberculosis patients newly registered in Osaka City -between 2012 and 2014 were adopted. On analysis, the X² test and Fisher's exact test were used, and a significance level below 5% was regarded as significant. [Results] 1) There were 25 pulmonary tuberculosis patients complicated by HIV. All were male -and the mean age was 43.2 years old. 2) The sputum smear positivity rate was 76.0% in the pulmonary tuberculosis patients complicated by HIV and 50.8 % in 250 control pulmonary tuberculosis patients, showing a significantly higher rate in the former. 3) Risk factors for the discontinuation of medication for tuberculosis: In the patients complicated by HIV, the follow- ing risks of the discontinuation of medication were noted in the order of a decreasing frequency: 'Lack of medication helpers' in 68.0%, 'Side effects' in 48.0%, 'Financial prob- lems' in 32.0%, and 'Liver damage' in 28.0%. Those in the control pulmonary tuberculosis patients were 33.2%, 22.8 %, 16.0%, and 11.6%, respectively, showing a significant difference in each factor. 4) The DOTS executing rates were 68.0% and 94.8% in the patients complicated by HIV and control patients, respectively, showing that it was significantly lower in the patients complicated by HIV. On comparison of the treatment outcomes excluding died, on treatment, transferred out, not evaluated, treatment succeeded in 72.7% in the patients complicated by HIV and 92.9% in the control patients, showing a significantly lower success rate in the patients complicated by HIV. The numbers of risk factors of discon- tinuation in. 16 and 6 patients complicated by HIV in whom treatment succeeded and treatment failed/defaulted were 3.8 and 2.8, respectively, showing that the number was higher in patients with successful treatment, and the DOTS execution rates were 75.0% and 33.3%, respectively, showing a higher rate in the successful treatment cases. [Conclusion] The treatment outcome was significantly poorer in pulmonary tuberculosis patients complicated by HIV than in the control pulmonary tuberculosis patients. More risk factors for the discontinuation of medication were observed and the DOTS execution rate was lower in the patients complicated by HIV, suggesting that risk assess- fient for the discontinuation of medication should be appro- priately performed, and support for medication should be strengthened.


Assuntos
Antituberculosos/uso terapêutico , Infecções por HIV/complicações , Tuberculose Pulmonar/tratamento farmacológico , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Japão , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do Tratamento , Tuberculose Pulmonar/complicações , Adulto Jovem
7.
Kekkaku ; 91(8): 587-591, 2016 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-30646463

RESUMO

[Purpose] To improve the treatment outcomes by analyzing/evaluating the association between DOTS and treatment outcomes in patients with extra-pulmonary tuber- culosis. [Methods] The subjects were patients with extra-pulmonary tuberculosis newly registered in Osaka City between 2012 and 2014. As controls, patients with pulmonary tuberculosis during this period were enrolled. Patients in whom compli- ance was confirmed once a month or more were regarded as completing DOTS. [Results] There were 434 patients with extra-pulmonary tuberculosis. Treatment was completed in 73.3% of these patients. Defaulted rates accounted for 9.4%. The mortality rate was 13.4%. Treatment is being conducted in 2.8%. Furthermore, 0.7% was transferred out. The results were unclear in 0.5%. We investigated changes in the DOTS and defaulted rates, excluding patients who died, those who were referred to other hospitals, those receiving treatment, and those whose results were unclear. The DOTS rates in 2012, 2013, and 2014 were 85.5, 87.5, and 91.2%, respectively, showing a slight increase. The defaulted rates were 14.5, 10.7, and 7.8%, respectively, showing a decrease. When compar- ing the results between the extra-pulmonary and pulmonary tuberculosis patients, the defaulted rates were 11.4 and 6.2 %, respectively; the percentage was significantly higher in the extra-pulmonary tuberculosis patients. The DOTS rates were 87.7 and 97.2%, respectively; the percentage was sig- nificantly lower in the extra-pulmonary tuberculosis patients. There were 41 defaulted cases. The reasons were "side effects" in 41.5%, "physicians' instructions" in 24.4%, "self- discontinuation/refusal" in 22.0%, and "preferential treatment for other diseases" in 12.2%. In the extra-pulmonary tuberculosis patients, the proportion of those in whom "side effects" led to defaulted was higher than in the pulmonary tubercu- losis patients, and that of those "self-discontinuation/refusal" was significantly lower. [Conclusion] Although the defaulted rate has decreased with an increase in the DOTS rate in patients with extra- pulmonary tuberculosis, both the DOTS and defaulted rates were less favorable than in patients with pulmonary tuber- culosis. In the future, it may be necessary to decrease the defaulted rate by intensifying DOTS. Of the reasons for defaulted, "side effects" and "physicians' instructions" account- ed for a high percentage. Therefore, it may be important to provide medical institutions with information.


Assuntos
Tuberculose Pulmonar/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
8.
Mol Pharmacol ; 85(1): 18-28, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24136992

RESUMO

The plasma membrane Na(+)/H(+) exchanger 1 (NHE1) is rapidly activated in response to various stimuli. The membrane-proximal cytoplasmic region (∼60 residues), termed the lipid-interacting domain (LID), is an important regulatory domain of NHE1. Here, we used a pharmacological approach to further characterize the role of LID in the regulation of NHE1. Pharmacological analysis using staurosporine-like indolocarbazole and bisindolylmaleimide compounds suggested that the phorbol ester- and receptor agonist-induced activation of NHE1 occurs through a protein kinase C-independent mechanism. In particular, only indolocarbazole compounds that inhibited NHE1 activation were able to interact with the LID, suggesting that the inhibition of NHE1 activation is achieved through the direct action of these compounds on the LID. Furthermore, in addition to phorbol esters and a receptor agonist, okadaic acid and hyperosmotic stress, which are known to activate NHE1 through unknown mechanisms, were found to promote membrane association of the LID concomitant with NHE1 activation; these effects were inhibited by staurosporine, as well as by a mutation in the LID. Binding experiments using the fluorescent ATP analog trinitrophenyl ATP revealed that ATP and the NHE1 activator phosphatidylinositol 4,5-bisphosphate bind competitively to the LID. These findings suggest that modulation of NHE1 activity by various activators and inhibitors occurs through the direct binding of these molecules to the LID, which alters the association of the LID with the plasma membrane.


Assuntos
Carbazóis/farmacologia , Proteínas de Transporte de Cátions/metabolismo , Indóis/farmacologia , Lipídeos/química , Maleimidas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Trocadores de Sódio-Hidrogênio/metabolismo , Agonistas de Receptores Adrenérgicos alfa 1/farmacologia , Animais , Ligação Competitiva , Carbazóis/química , Proteínas de Transporte de Cátions/antagonistas & inibidores , Proteínas de Transporte de Cátions/química , Proteínas de Transporte de Cátions/genética , Membrana Celular , Cricetinae , Cricetulus , Bases de Dados de Compostos Químicos , Indóis/química , Maleimidas/química , Camundongos , Mutação , Ácido Okadáico/farmacologia , Pressão Osmótica , Fosfatidilinositol 4,5-Difosfato/farmacologia , Proteína Quinase C/antagonistas & inibidores , Proteína Quinase C/metabolismo , Inibidores de Proteínas Quinases/química , Estrutura Terciária de Proteína , Transporte Proteico , Receptores Adrenérgicos alfa 1/genética , Receptores Adrenérgicos alfa 1/metabolismo , Trocador 1 de Sódio-Hidrogênio , Trocadores de Sódio-Hidrogênio/antagonistas & inibidores , Trocadores de Sódio-Hidrogênio/química , Trocadores de Sódio-Hidrogênio/genética , Estaurosporina/química , Estaurosporina/farmacologia , Transfecção
9.
FEBS J ; 280(6): 1430-42, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23331996

RESUMO

Na(+)/H(+) exchanger (NHE) 1 is a member of the solute carrier superfamily, which regulates intracellular ionic homeostasis. NHE1 is known to require cellular ATP for its activity, despite there being no requirement for energy input from ATP hydrolysis. In this study, we investigated whether NHE1 is an ATP-binding protein. We designed a baculovirus vector carrying both epitope-tagged NHE1 and its cytosolic subunit CHP1, and expressed the functional NHE1-CHP1 complex on the surface of Sf9 insect cells. Using the purified complex protein consisting of NHE1 and CHP1 from Sf9 cells, we examined a photoaffinity labeling reaction with 8-azido-ATP-biotin. UV irradiation promoted the incorporation of 8-azido-ATP into NHE1, but not into CHP1, with an apparent Kd of 29.1 µM in the presence of Mg(2+). The nonlabeled nucleotides ATP, GTP, TTP and CTP all inhibited this crosslinking. However, ATP had the strongest inhibitory effect, with an apparent inhibition constant (IC50) for ATP of 2.2 mM, close to the ATP concentration giving the half-maximal activation of NHE1 activity. Importantly, crosslinking was more strongly inhibited by ATP than by ADP, suggesting that ATP is dissociated from NHE1 upon ATP hydrolysis. Limited proteolysis with thrombin and deletion mutant analysis revealed that the 8-azido-ATP-binding site is within the C-terminal cytoplasmic domain of NHE1. Equilibrium dialysis with NHE1-derived peptides provided evidence that ATP directly binds to the proximal cytoplasmic region (Gly542-Pro598), which is critical for ATP-dependent regulation of NHE1. These findings suggest that NHE1 is an ATP-binding transporter. Thus, ATP may serve as a direct activator of NHE1.


Assuntos
Trifosfato de Adenosina/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Trocadores de Sódio-Hidrogênio/metabolismo , Difosfato de Adenosina/metabolismo , Trifosfato de Adenosina/análogos & derivados , Animais , Azidas/metabolismo , Baculoviridae/genética , Baculoviridae/metabolismo , Sítios de Ligação , Proteínas de Ligação ao Cálcio/isolamento & purificação , Proteínas de Transporte de Cátions/isolamento & purificação , Membrana Celular/metabolismo , Eletroforese em Gel de Poliacrilamida , Vetores Genéticos/genética , Vetores Genéticos/metabolismo , Guanosina Trifosfato/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Hidrólise , Magnésio/metabolismo , Marcadores de Fotoafinidade/metabolismo , Ligação Proteica , Mapeamento de Interação de Proteínas , Proteólise , Células Sf9 , Radioisótopos de Sódio/metabolismo , Trocador 1 de Sódio-Hidrogênio , Trocadores de Sódio-Hidrogênio/isolamento & purificação , Transfecção , Raios Ultravioleta
10.
Biol Pharm Bull ; 34(7): 1122-5, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21720024

RESUMO

Protease-activated receptor-2 (PAR-2) is activated by serine proteases, such as trypsin and mast cell tryptase. Previous studies have demonstrated that both trypsin and PAR-2 activating peptide contract isolated rat urinary bladder preparations, however, the mechanisms are not fully understood. In the present study, we examined the role of bradykinin in contractions induced by trypsin and the PAR-2 agonist 2-furoyl-LIGRL-NH(2) in urinary bladders isolated from control or cyclophosphamide (CYP)-induced cystitis rats. The contractile effects of trypsin were significantly greater in the preparations obtained from CYP-treated rats than in those from controls. The bradykinin B2 receptor antagonist Hoe 140 did not affect trypsin-induced contractions in control rat bladders, whereas it significantly reduced the contractile effects of trypsin on bladders from CYP-treated rats. On the other hand, Hoe 140 failed to affect contractions induced by the PAR-2 agonist 2-furoyl-LIGRL-NH(2). These results suggest that the actions of trypsin on urinary bladders in cystitis rats are partly exerted through stimulation of bradykinin B2 receptor in a PAR-2-independent manner. This mechanism seems to be involved in the enhancement of trypsin-induced bladder contractions observed after induction of cystitis with CYP in rats.


Assuntos
Bradicinina/farmacologia , Ciclofosfamida/farmacologia , Tripsina/farmacologia , Bexiga Urinária/efeitos dos fármacos , Animais , Técnicas In Vitro , Masculino , Contração Muscular/efeitos dos fármacos , Contração Muscular/fisiologia , Ratos , Ratos Wistar , Bexiga Urinária/fisiologia
11.
Jpn J Infect Dis ; 63(6): 427-32, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21099094

RESUMO

Periodontitis is a chronic inflammatory disease caused by the infection of periodontopathic bacteria in dental plaque. However, an individual's susceptibility to this disease appears to be associated with multiple genetic factors, as seen in the case of leprosy. In order to gain a better understanding of the pathophysiology of periodontal disease in subjects with leprosy, we investigated the clinical features of periodontitis and the immunological responses against periodontopathic bacteria in 382 subjects with a history of leprosy and 451 age-matched control subjects. The prevalence of periodontitis and the degree of periodontal pocket depth were found to be significantly higher in leprosy patients than in age-matched controls. Furthermore, a comparison of the clinical parameters of lepromatous leprosy (L-lep) and tuberculoid leprosy (T-lep) patients showed that the probing pocket depth of L-lep patients with periodontal disease was significantly higher than that for T-lep patients. In contrast, serum IgG titers against Porphyromonas gingivalis in L-lep patients were significantly lower than in T-lep patients. These results imply that L-lep patients show more severe periodontal disease than T-lep patients or age-matched control subjects, and that low humoral immunity against P. gingivalis might be one of the genetic factors determining periodontal disease susceptibility in leprosy patients.


Assuntos
Hanseníase Virchowiana/complicações , Hanseníase Tuberculoide/complicações , Periodontite/imunologia , Periodontite/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antibacterianos/sangue , Infecções por Bacteroidaceae/epidemiologia , Infecções por Bacteroidaceae/imunologia , Infecções por Bacteroidaceae/microbiologia , Infecções por Bacteroidaceae/fisiopatologia , Estudos de Casos e Controles , Feminino , Humanos , Japão/epidemiologia , Hanseníase Virchowiana/epidemiologia , Hanseníase Virchowiana/microbiologia , Hanseníase Tuberculoide/epidemiologia , Hanseníase Tuberculoide/microbiologia , Masculino , Pessoa de Meia-Idade , Bolsa Periodontal , Periodontite/epidemiologia , Periodontite/microbiologia , Porphyromonas gingivalis/imunologia , Prevalência , Índice de Gravidade de Doença
12.
Pharmacology ; 86(5-6): 281-6, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20980781

RESUMO

Donepezil, an inhibitor of acetylcholinesterase, is used to improve cholinergic neurotransmission and cognitive function in Alzheimer's disease. In the present study, contractile effects of donepezil on the rat urinary bladder were examined and compared with those of the nonselective cholinesterase inhibitor neostigmine. Both donepezil and neostigmine produced concentration-dependent contractile responses of the isolated rat urinary bladder strips. The neostigmine-induced contractions were abolished by atropine. However, donepezil produced contractions of urinary bladders partly through atropine-insensitive mechanisms. The atropine-resistant component of donepezil-induced contraction was significantly reduced by the cyclooxygenase inhibitor indomethacin. These results suggest that cyclooxygenase-derived prostanoids contribute, at least in part, to contractile effects of donepezil in the rat urinary bladder.


Assuntos
Inibidores da Colinesterase/farmacologia , Indanos/farmacologia , Contração Muscular/efeitos dos fármacos , Piperidinas/farmacologia , Bexiga Urinária/efeitos dos fármacos , Animais , Atropina/farmacologia , Donepezila , Indometacina/farmacologia , Masculino , Neostigmina/farmacologia , Prostaglandina-Endoperóxido Sintases/efeitos dos fármacos , Prostaglandina-Endoperóxido Sintases/metabolismo , Ratos , Ratos Sprague-Dawley , Bexiga Urinária/metabolismo
13.
14.
Eur J Pharmacol ; 569(1-2): 145-8, 2007 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-17588562

RESUMO

The capsaicin receptor, transient receptor potential vanilloid receptor 1 (TRPV1), colocalizes with protease-activated receptors (PARs) in the urinary bladder, but functional interaction between TRPV1 and PARs remains to be clarified. In the present study, the role of capsaicin-sensitive sensory neurons in contraction induced by activation of PAR-2 was investigated in the rat urinary bladders. The contractile responses to trypsin and the PAR-2 agonist 2-furoyl-LIGRL-NH(2) were significantly attenuated by either desensitization of sensory neurons achieved by capsaicin (10 microM) or by the TRPV1 antagonist capsazepine (30 microM). These results suggest that stimulation of capsaicin-sensitive sensory fibers contributes, at least in part, to PAR-2-mediated bladder contractions in rats.


Assuntos
Capsaicina/farmacologia , Contração Muscular/efeitos dos fármacos , Neurônios Aferentes/efeitos dos fármacos , Receptor PAR-2/fisiologia , Bexiga Urinária/efeitos dos fármacos , Acetilcolina/farmacologia , Analgésicos não Narcóticos/farmacologia , Análise de Variância , Animais , Capsaicina/análogos & derivados , Relação Dose-Resposta a Droga , Masculino , Músculo Liso/efeitos dos fármacos , Músculo Liso/inervação , Músculo Liso/fisiologia , Neurônios Aferentes/fisiologia , Oligopeptídeos/farmacologia , Ratos , Ratos Wistar , Receptor PAR-2/agonistas , Tripsina/química , Tripsina/farmacologia , Bexiga Urinária/inervação , Bexiga Urinária/fisiologia
15.
Congenit Anom (Kyoto) ; 46(2): 105-14, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16732769

RESUMO

DDT, an organochlorine pesticide, has been cited as a representative chemical suspected of having endocrine disrupting effects. In this study, the potential endocrine disrupting activities of p,p'-DDT, a major component of DDT, were investigated in rats in a 2-generation reproduction toxicity study in accordance with the most current test guidelines of the Ministry of Agriculture, Forestry and Fisheries in Japan, Organization for Economic Cooperation and Development (OECD) and United States Environmental Protection Agency (USEPA) with some modifications and additions. p,p'-DDT was given to parental rats at dietary levels of 0, 5, 50 or 350 ppm. Systemic toxicities in the parental animals consisted of tremors and subsequent deaths (females only) and/or pathological alterations of the liver (both sexes of animals) of the 2 higher dose groups. Reproductive and postnatal developmental toxicities were not evident up to the highest dose level except for the decreased pup viability index on postnatal day 21 in the 350 ppm group. Changes in serum estradiol and progesterone levels and/or a delay in male sexual maturation were noted in the 2 higher dose groups in a dose-dependent fashion, suggesting alterations of endogenous endocrine functions. However, these changes never resulted in substantial reproductive disorders.


Assuntos
DDT/toxicidade , Praguicidas/toxicidade , Anormalidades Induzidas por Medicamentos , Animais , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Estradiol/sangue , Estrogênios/metabolismo , Feminino , Fígado/efeitos dos fármacos , Masculino , Gravidez , Prenhez , Progesterona/sangue , Ratos , Ratos Sprague-Dawley
16.
J Nat Prod ; 68(8): 1238-42, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16124768

RESUMO

Alpha-1-C-hydroxymethylfagomine (7), 3-O-beta-D-glucopyranosyl-DMDP (12), and 2,5-dideoxy-2,5-imino-D-glucitol (13) were isolated from the Thai traditional crude drug "Non tai yak" (Stemona tuberosa), which also contains a high concentration level of alpha-homonojirimycin (0.1% dry weight). "Thopthaep" (Connarus ferrugineus) and "Cha em thai" (Albizia myriophylla) contained 1-deoxymannojirimycin (DMJ) (10) at levels of 0.083% (dry weight) and 0.17% (dry weight), respectively. 2-O-alpha-D-Galactopyranosyl-DMJ (20), 3-O-beta-D-glucopyranosyl-DMJ (21), 1,4-dideoxymannojirimycin (17), 1,4-dideoxyallonojirimycin (18), and 1,4-dideoxyaltronojirimycin (19) from C. ferrugineus and 2-O-beta-D-glucopyranosyl-DMJ (22) and 4-O-beta-D-glucopyranosyl-DMJ (23) from A. myriophylla were isolated as new compounds.


Assuntos
Amino Açúcares/isolamento & purificação , Inibidores Enzimáticos/isolamento & purificação , Glicosídeo Hidrolases/antagonistas & inibidores , Plantas Medicinais/química , Alcaloides/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Amino Açúcares/química , Amino Açúcares/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Estrutura Molecular , Estereoisomerismo , Tailândia
17.
J Toxicol Sci ; 30 Spec No.: 59-78, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16641544

RESUMO

A two-generation reproductive toxicity study was conducted with 2,4-dichlorophenol (2,4-DCP), an agent suspected of exerting endocrine disrupting effects. Wistar-Hannover rats, 24/sex/group, were given diet containing 2,4-DCP at dose levels of 0, 500, 2000 or 8000 ppm to examine the potential effects of the test substance on parental animals and their offspring over 2 successive generations. Neither clear systemic nor reproductive toxicity of 2,4-DCP was apparent in the 500 ppm group. In the 2000 ppm group, mean body weight gain and food consumption of females were lowered significantly during the treatment period. Effects on body weights and food consumption were more serious in the 8000 ppm group, both males and females being significantly affected. Reproductive effects of the test substance were also observed in the 2000 and 8000 ppm groups dose-dependently. Observations included significantly increased uterine weights of F1 and/or F2 female weanlings and reduced numbers of implantation sites and live births of F1 parental females. These results suggest that 2,4-DCP has weak reproductive toxicity, possibly based on endocrine activity. However, the basic mechanisms for apparent estrogenic effects of 2,4-DCP remain to be elucidated.


Assuntos
Clorofenóis/toxicidade , Disruptores Endócrinos/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Reprodução/efeitos dos fármacos , Testes de Toxicidade Crônica/métodos , Administração Oral , Animais , Relação Dose-Resposta a Droga , Feminino , Masculino , Gravidez , Ratos , Ratos Endogâmicos
18.
Jpn J Ophthalmol ; 47(1): 6-12, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12586171

RESUMO

PURPOSE: To investigate the refractive status and factors associated with myopia by a population-based survey of Japanese adults. METHODS: A total of 2168 subjects aged 40 to 79 years, randomly selected from a local community, were assessed in a cross-sectional study. The spherical equivalent of the refractive error was calculated and used in a multiple logistic regression analysis to evaluate the relationships between myopia and possible related factors. RESULTS: The mean (+/- SD) of the spherical equivalent was -0.70 +/- 1.40 diopters (D) in men, and -0.50 +/- 1.44 D in women. Based on +/- 0.5 D cutoff points, the prevalence of myopia, emmetropia, and hypermetropia were 45.7%, 40.8%, and 13.5% in men, and 38.3%, 43.1%, and 18.6% in women, respectively. A 10-year increase in age was associated with reduced risk of myopia [men: odds ratio (OR) = 0.53, 95% confidence interval (CI): 0.44-0.62; women: OR = 0.65, 95% CI: 0.54-0.78]. In men, myopia was significantly associated with higher education (high school: OR = 1.6, 95% CI: 1.1-2.3; college: OR = 2.0, 95% CI: 1.3-3.1) and management occupations (OR = 1.6, 95% CI: 1.0-2.4). For women, high income (OR = 1.5, 95% CI: 1.1-2.2), and clerical (OR = 1.5, 95% CI: 1.0-2.4) and sales/service occupations (OR = 1.7, 95% CI: 1.1-2.6) were also associated with myopia. CONCLUSIONS: The prevalence of myopia in a Japanese population was similar to that in other Asian surveys but higher than in black or white populations. Our study confirmed a higher prevalence of myopia among younger vs. older populations, and a significant association with education levels and socioeconomic factors.


Assuntos
Miopia/etnologia , Adulto , Idoso , Envelhecimento , Constituição Corporal , Estudos Transversais , Escolaridade , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Miopia/etiologia , Miopia/fisiopatologia , Ocupações , Razão de Chances , Prevalência , Refração Ocular/fisiologia , Fatores de Risco , Classe Social
19.
Congenit Anom (Kyoto) ; 42(3): 194-201, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12502899

RESUMO

Wistar Hannover rats, which have recently been introduced into Japan, are expected to be used in reproductive and developmental toxicity studies, yet the accumulation of background data is insufficient. This paper describes our historical data on the reproductive ability of this strain of rat. Three lots of sexually matured females (40 each) were received from CLEA JAPAN, Inc. with males of the same strain (30 or 36 each) and mated. A total of 47 dams were killed on gestation day 20 to examine their fetuses. The remaining 71 pregnant females were allowed to deliver spontaneously and observed for common reproductive parameters. The mating and fertility indices of females were both 99.2%. Overall mean numbers of implants and live fetuses at cesarean sectioning were 12.5 and 11.5, respectively. Fetal resorptions and deaths occurred at an incidence of 8.6%. Morphological examinations of fetuses revealed low incidences of spontaneous malformations (each one case of double aortic arch and absent cervical vertebral arch) and a variety of common variations. The followings are overall means of major reproductive parameters obtained from females with live birth: no. of implants, 12.5; no. of pups delivered, 11.8; viability index of pups at birth, 99.8%; and days of age at sexual maturation (vaginal opening and preputial separation), 30.3 and 42.8, respectively. Our present observations confirmed a minimal deviation among 3 lots of animals in terms of reproductive abilities. These results suggest that this strain of rat can be used in reproductive and developmental toxicity studies, although the sensitivity to toxicants remains to be elucidated.


Assuntos
Anormalidades Congênitas/epidemiologia , Fertilidade/fisiologia , Animais , Animais Endogâmicos , Anormalidades Congênitas/genética , Estro/fisiologia , Feminino , Fertilidade/genética , Variação Genética , Masculino , Gravidez , Ratos , Ratos Wistar
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