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1.
J Med Ultrason (2001) ; 46(3): 353-359, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30840213

RESUMO

PURPOSE: Rupture of the flexor pollicis longus (FPL) and index flexor digitorum profundus (FDP2) tendons often occurs after locking plate fixation for distal radius fracture. This study aimed to determine the shortest tendon-radius distances of different hand positions. METHODS: Fifty-nine hands of 30 healthy volunteers were studied. Distances between the FPL or FDP2 and distal radius were calculated in six wrist positions: 30° palmar flexion, neutral, 30° dorsiflexion, 60° dorsiflexion, maximum dorsiflexion, and 40° ulnar deviation with three finger positions (full extension and flexion of fingers, full flexion of the thumb or index finger, and full extension of the other four fingers). The shortest distance between the FPL or FDP2 and distal radius was noted. RESULTS: The shortest distance between the FPL and distal radius was during maximum wrist dorsiflexion with isolated thumb flexion. The distance between the FDP2 and distal radius was shortest with all-finger flexion in 30° wrist dorsiflexion. CONCLUSIONS: It is necessary to measure the distance between the FPL and distal radius in maximal wrist dorsiflexion with full flexion of the isolated thumb, as the shortest distance was observed with flexion of the isolated thumb. On the contrary, we recommend measuring the distance between the FDP2 and distal radius in 30° wrist dorsiflexion with flexion of all fingers.


Assuntos
Dedos/diagnóstico por imagem , Rádio (Anatomia)/diagnóstico por imagem , Amplitude de Movimento Articular/fisiologia , Tendões/diagnóstico por imagem , Articulação do Punho/fisiologia , Adulto , Feminino , Dedos/anatomia & histologia , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Rádio (Anatomia)/anatomia & histologia , Tendões/anatomia & histologia , Adulto Jovem
2.
Endocrine ; 51(1): 140-7, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26024973

RESUMO

Central diabetes insipidus (CDI) is characterized by polyuria and polydipsia due to a deficiency of vasopressin. Currently, the treatment goal for CDI is improvement of quality of life (QOL) by desmopressin (DDAVP) without developing hyponatremia. However, there is no reliable measure for QOL in CDI patients. We evaluate our original questionnaire for QOL, consisting of 12 questions focusing on polyuria, polydipsia, and DDAVP treatment, in CDI patients who underwent a switch from nasal spray to oral disintegrating tablets of DDAVP. Twenty-five CDI patients under nasal DDAVP treatment, six with newly developed CDI, and 18 healthy individuals without known polyuric/polydipsic disorders as control subjects were enrolled. QOL scores were determined by our questionnaire at the enrollment and 3 months after the start of oral DDAVP treatment and were examined by the Wilcoxon signed-rank test. Eleven questions detected improvement in QOL. The sum of the QOL scores of the eleven questions increased from 29.2 ± 5.6 under nasal to 36.8 ± 4.5 under oral DDAVP (p < 0.001). There were no clinically relevant changes in serum levels of Na. After eliminating two questions about DDAVP treatment, the sum of QOL scores was 15.3 ± 6.5 in untreated CDI patients, 24.4 ± 5.2 in those with nasal treatment, 28.9 ± 4.9 in those with oral DDAVP, and 29.5 ± 3.6 in healthy controls. The difference among groups was significant (p < 0.05 in Steel-Dwass test) except between patients treated with oral DDAVP and healthy controls. Our questionnaire can be used to accurately assess QOL in CDI patients.


Assuntos
Diabetes Insípido Neurogênico/epidemiologia , Qualidade de Vida , Inquéritos e Questionários , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Diabetes Insípido Neurogênico/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
3.
Diabetes Metab Res Rev ; 27(8): 895-8, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22069281

RESUMO

BACKGROUND: The aim of this study was to determine the prevalence and role of autoantibodies to zinc transporter 8 (ZnT8A) in three forms (fulminant, acute-onset, and slow-onset) of Japanese patients with type 1 diabetes. METHODS: One-hundred and ninety-six new-onset patients with type 1 diabetes were studied: 85 were fulminant, 81 acute-onset, and 30 slow-onset type 1 diabetes. ZnT8A were determined by radioimmunoassay using a hybrid ZnT8 carboxy-terminal construct (aa268-369) carrying 325Trp and 325Arg. Furthermore, ZnT8A epitopes were analysed using ZnT8 constructs incorporating the known aa325 variants (Trp, Arg, and Gln). RESULTS: ZnT8A were detected in 58% patients with acute-onset and 20% with slow-onset type 1 diabetes (p<0.0005). In contrast, none of sera from fulminant type 1 diabetes were reactive to ZnT8 construct. Conversion of Arg or Trp to Gln at aa325 abolished reactivity in 59% of patients with an age of onset>10 years, which was significantly higher than that in patients≤10 years of age (33%, p<0.05). CONCLUSIONS: These results suggest that ZnT8A are an additional useful marker for acute-onset type 1 diabetes, but not a diagnostic marker for fulminant type 1 diabetes, and ZnT8A epitope recognition is different according to the onset age.


Assuntos
Autoanticorpos/sangue , Proteínas de Transporte de Cátions/imunologia , Diabetes Mellitus Tipo 1/imunologia , Adolescente , Adulto , Idade de Início , Substituição de Aminoácidos , Povo Asiático , Biomarcadores/sangue , Proteínas de Transporte de Cátions/genética , Criança , Epitopos/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radioimunoensaio , Transportador 8 de Zinco
4.
Clin Immunol ; 138(2): 146-53, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21067978

RESUMO

The aim of this study was to evaluate the humoral autoreactivity to zinc transporter 8 (ZnT8) depending on the clinical phenotype of type 1 diabetes (T1D). ZnT8 autoantibodies (ZnT8A) were determined by radioimmunoassay using carboxy-terminal ZnT8 constructs in 57 childhood-onset, 97 adult-onset, and 85 fulminant T1D. The ZnT8A frequency was higher in childhood-onset patients and decreased with increasing age of onset from 70% to 24% (P(trend)<0.005). None of the patients with fulminant T1D was positive for ZnT8A. There were at least two distinct ZnT8A epitope patterns associated with the aa325-restriction, childhood-onset patients have aa325-nonrestricted response more frequently compared to the adult-onset group (P<0.05). The level of ZnT8A was inversely associated with the copy number of HLA-DR4 allele (P<0.05). These results suggest differences in the humoral autoreactivity to ZnT8 depending on the clinical phenotype, which should provide strategy for autoantibody measurement in subjects to allow early diagnosis of autoimmune T1D.


Assuntos
Autoanticorpos/imunologia , Autoimunidade , Proteínas de Transporte de Cátions/imunologia , Diabetes Mellitus Tipo 1/imunologia , Células Secretoras de Insulina/imunologia , Adolescente , Adulto , Povo Asiático , Autoanticorpos/sangue , Proteínas de Transporte de Cátions/genética , Criança , Estudos de Coortes , Variações do Número de Cópias de DNA/imunologia , Diabetes Mellitus Tipo 1/genética , Epitopos/imunologia , Feminino , Antígeno HLA-DR4/genética , Antígeno HLA-DR4/imunologia , Humanos , Imunidade Humoral , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Transportador 8 de Zinco
5.
Endocr J ; 57(11): 947-51, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20805634

RESUMO

Interferon-alpha (IFN-α) is widely used in the treatment of viral hepatitis, however, it is known that IFN-α therapy may induce type 1 diabetes. We report here on two cases of chronic viral hepatitis C who developed autoimmune type 1 diabetes during Peg-IFN-α plus ribavirin (RBV) therapy. Case 1: a 48-year-old male with chronic hepatitis C with chronic thyroiditis. The patient's plasma glucose level was normal and anti-islet autoantibody tests were negative before Peg-IFN-α+RBV therapy. The emergence of glutamic acid decarboxylase 65 autoantibody (GAD65Ab) was observed after five months of treatment. Autoantibodies to insulin and insulinoma-associated antigen-2 (IA-2) also became positive. Eleven months later, thirst and polydipsia occurred with increased fasting plasma glucose level and the patient was diagnosed with type 1A diabetes. Zinc transporter-8 autoantibody (ZnT8Ab) was not detectable at any point. The patient has type 1 diabetes-susceptible HLA-DRB1-DQB1 haplotypes *0405-*0401 and *0901-*0303. Case 2: a 65-year-old male with chronic hepatitis C with type 2 diabetes on insulin treatment. GAD65Ab and IA-2Ab were negative before Peg-IFN-α+RBV therapy, however, nine months later, a single appearance of GAD65Ab was observed. After twelve months, his plasma glucose control worsened rapidly, and he was diagnosed with type 1A diabetes. IA-2Ab and ZnT8Ab were negative throughout the clinical course. His HLA-DRB1-DQB1 haplotypes were *0410-*0402 and *1407-*0503. Both cases showed a unique GAD65Ab epitope (amino acids 360-442). These clinical courses suggest that IFN-α therapy provoked acute islet autoimmunity and onset of type 1 diabetes. Therefore, during IFN-α therapy, patients should be closely monitored for the occurrence of type 1 diabetes.


Assuntos
Autoanticorpos/sangue , Diabetes Mellitus Tipo 1/induzido quimicamente , Diabetes Mellitus Tipo 1/imunologia , Hepacivirus/imunologia , Hepatite C Crônica/imunologia , Interferon-alfa/uso terapêutico , Ilhotas Pancreáticas/imunologia , Idoso , Proteínas de Transporte de Cátions/imunologia , Glutamato Descarboxilase/imunologia , Hepatite C Crônica/tratamento farmacológico , Humanos , Interferon-alfa/efeitos adversos , Masculino , Pessoa de Meia-Idade , Transportador 8 de Zinco
6.
Endocr J ; 57(7): 623-8, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20505260

RESUMO

Circulating anti-islet autoantibodies in sera are used as a predictive marker for type 1 diabetes (T1D). We here report two Japanese patients with autoimmune thyroid disease complicated with T1D in whom the time course of anti-islet autoantibodies were observed before the clinical onset of diabetes. Case 1: A woman who had developed Graves' disease at age 25 was diagnosed with type 2 diabetes at age 31; six months later, insulin therapy was started. At age 36 she was diagnosed with T1D due to glutamic acid decarboxylase 65 autoantibodies (GAD65Ab)-positive status and decreased C-peptide levels. With stored sera we retrospectively followed her anti-islet autoantibodies. GAD65Ab, zinc transporter 8 autoantibodies (ZnT8Ab) and insulin autoantibodies (IAA) were found to be positive at age 25. IAA soon turned negative, but GAD65Ab and ZnT8Ab remained positive with high levels. Insulinoma-associated antigen-2 autoantibodies (IA-2Ab) emerged 2 years before the initiation of insulin therapy. She has T1D-susceptible HLA-DRB1-DQB1 haplotypes, (*)0405- (*)0401/(*)0802-(*)0302. Case 2: A 49-year-old woman with hypothyroidism due to 19 years' history of atrophic thyroiditis noticed marked thirst, polyuria and weight loss. On admission she was diagnosed as T1D due to GAD65Ab-positive findings and poor C-peptide response to i.v. glucagon. Retrospective serology revealed the emergence of GAD65Ab and IAA just after the clinical onset. IA-2Ab and ZnT8Ab never developed. She has T1D-susceptible and -resistant HLADRB1- DQB1 haplotypes, (*)0901-(*)0303/(*)1502-(*)0601. The autoantibody profile and the mode of diabetes onset in the two cases were remarkably different. These cases imply that anti-islet autoantibodies do not always precede the onset of T1D.


Assuntos
Autoanticorpos/sangue , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/imunologia , Ilhotas Pancreáticas/imunologia , Adulto , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/diagnóstico , Progressão da Doença , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Tireoidite Autoimune/sangue , Tireoidite Autoimune/complicações , Tireoidite Autoimune/imunologia
7.
J Clin Endocrinol Metab ; 95(2): 707-13, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20061424

RESUMO

OBJECTIVE: The aim of this study was to identify the predictive marker for early insulin requirement in adult-onset autoimmune diabetes in the Japanese populations. DESIGN/PATIENTS: We analyzed insulin autoantibodies (IAA), insulinoma-associated antigen-2 (IA-2) autoantibodies (IA-2icA), and zinc transporter 8 (ZnT8) autoantibodies (ZnT8A) by radioimmunoassay in 47 Japanese patients with adult-onset autoimmune diabetes who were identified by native GAD autoantibody (nGADA) screening of approximately 3000 non-insulin-requiring diabetes patients and 302 nGADA-negative type 2 diabetes patients. Furthermore, GAD65 autoantibody-specific epitopes were also analyzed using GAD65/GAD67 chimeric constructs. RESULTS: The prevalence of IAA, IA-2icA, and ZnT8A in nGADA-positive patients was 26, 15, and 19%, respectively, which was significantly higher than that in nGADA-negative type 2 diabetes (2, 2, and 2%; P < 0.0001). Among nGADA-positive patients, 38% had one or more of IAA, IA-2icA, or ZnT8A, and 15% had two or more of these autoantibodies, compared with none of the nGADA-negative patients (P < 0.0001). Thirty-six percent of nGADA-positive patients subsequently required insulin therapy; and high nGADA titer (log-rank P = 0.003), middle epitope recognition of GAD65A (P = 0.002), and the presence of one or more of IAA, IA-2icA, or ZnT8A (P = 0.002) at diagnosis marked the risk for early requirement of insulin therapy. Multivariate logistic regression analysis showed the multiple islet autoantibodies to be independently associated with the risk for insulin requirement (odds ratio = 13.77; 95% confidence interval, 2.77-68.45; P = 0.001). CONCLUSIONS: These results indicate that the determination of IAA, IA-2icA, and ZnT8A improves the prediction of a future insulin insufficiency in adult-onset autoimmune diabetes, which appears to be superior to GADA titer and GAD65A-specific epitopes.


Assuntos
Autoanticorpos/sangue , Proteínas de Transporte de Cátions/imunologia , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 2/imunologia , Insulina/imunologia , Insulina/uso terapêutico , Adulto , Idoso , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Progressão da Doença , Feminino , Glutamato Descarboxilase/imunologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Transportador 8 de Zinco
8.
Yakugaku Zasshi ; 129(9): 1013-23, 2009 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-19721376

RESUMO

Synthetic organic chemistry is a base of medicinal chemistry and the exploitation of new methods for carbon-carbon bond formation is of most importance in synthetic organic chemistry. Carbenes and carbenoids have long been known to be highly reactive carbon species that show a variety of unique reactivity. However, those reactive species are not fully used in organic synthesis. The reasons are as follows: one is the precursors for the generation of carbenes and carbenoids are quite limited and the other is that the reactivity of the species is too high to control. In order to solve the problem mentioned above, we used alpha-haloalkyl (or alkenyl) aryl sulfoxides as the precursors and used sulfoxide-magnesium exchange reaction for generation of much mild magnesium carbenoids. alpha-Haloalkyl (or alkenyl) aryl sulfoxides are quite easily synthesized in high overall yields. Magnesium carbenoids, cyclopropylmagnesium carbenoids, cyclobutylmagnesium carbenoids, magnesium beta-oxido carbenoids, and magnesium alkylidene carbenoids are generated at low temperature from the corresponding sulfoxides with a Grignard reagent in quantitative yields. They were found to be stable usually at below -60 degrees C for at least 30 min. The each magnesium carbenoids have their own unique reactivities and we could find many unprecedented reactions from these reactive species. Recent results for the developments of new synthetic methods based on the chemistry of magnesium carbenoids are described.


Assuntos
Carbono/química , Química Orgânica/métodos , Magnésio/química , Metano/análogos & derivados , Fenômenos de Química Orgânica , Metano/química , Sulfóxidos/síntese química , Temperatura
9.
Biochem Biophys Res Commun ; 367(4): 719-24, 2008 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-18194666

RESUMO

Insulin peptide B:9-23 is a major autoantigen in type 1 diabetes. Combined treatment with B:9-23 peptide and polyinosinic-polycytidylic acid (poly I:C), but neither alone, induce insulitis in normal BALB/c mice. In contrast, the combined treatment accelerated insulitis, but prevented diabetes in NOD mice. Our immunofluorescence study with anti-CD4/anti-Foxp3 revealed that the proportion of Foxp3 positive CD4(+)CD25(+) regulatory T cells (Tregs) was elevated in the islets of NOD mice treated with B:9-23 peptide and poly I:C, as compared to non-treated mice. Depletion of Tregs by anti-CD25 antibody hastened spontaneous development of diabetes in non-treated NOD mice, and abolished the protective effect of the combined treatment and conversely accelerated the onset of diabetes in the treated mice. These results indicate that poly I:C combined with B:9-23 peptide promotes infiltration of both pathogenic T cells and predominantly Tregs into the islets, thereby inhibiting progression from insulitis to overt diabetes in NOD mice.


Assuntos
Linfócitos T CD4-Positivos/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/patologia , Fatores de Transcrição Forkhead/metabolismo , Insulina/administração & dosagem , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/patologia , Fragmentos de Peptídeos/administração & dosagem , Poli I-C/administração & dosagem , Animais , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/patologia , Feminino , Ilhotas Pancreáticas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Obesidade/patologia
10.
Ann N Y Acad Sci ; 1150: 248-51, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19120305

RESUMO

In this study, we evaluated autoantibodies to IA-2 (IA-2As), glutamic acid decarboxylase 65 (GADAs), and islet cell antibodies (ICAs) in 233 patients with type 1 diabetes (M:F = 90:143, mean duration 4.0 +/- 6.7 yr) as a cross-sectional study. Of 233 patients with type 1 diabetes, IA-2A was detected in 58% of patients with duration within 2 weeks, 61% of patients with duration <1 yr, 41% of patients with diabetes for 1-3 yr, 29% for 4-9 yr, and 21% for >or=10 yr. These prevalences were similar to those of ICA, while the prevalence of GADA was not influenced by duration of diabetes with positivity of 63-74%. Thus, as the duration of diabetes became longer, the frequency of GADA(+)/IA-2A(-) patients increased and the frequency of GADA(+)/IA-2A(+) patients decreased. However, the frequency of GADA(-)/IA-2A(+) patients was not influenced by duration of diabetes. The prevalence of IA-2A was significantly higher in abrupt-onset group (68%, n= 79) compared to the slowly progressive group (23%, n= 22) in new-onset patients (P= 0.0001). However, there was no difference in the IA-2A frequency between these two groups (abrupt-onset 26%, n= 53 vs. slowly progressive 24%, n= 21) in patients with long-standing disease, suggesting that IA-2A positivity might persist in patients with slowly progressive type 1 diabetes. These results emphasize the heterogeneity of humoral autoimmunity to protein tyrosine phosphatase-like molecules, but not to GAD, in patients with type 1 diabetes.


Assuntos
Formação de Anticorpos/fisiologia , Autoantígenos/imunologia , Diabetes Mellitus Tipo 1/imunologia , Ilhotas Pancreáticas/imunologia , Adolescente , Adulto , Anticorpos/sangue , Criança , Estudos Transversais , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/epidemiologia , Progressão da Doença , Feminino , Glutamato Descarboxilase/imunologia , Humanos , Japão/epidemiologia , Masculino , Proteínas Tirosina Fosfatases Classe 8 Semelhantes a Receptores/imunologia , Estudos Soroepidemiológicos , Fatores de Tempo , Adulto Jovem
11.
Chem Soc Rev ; 36(10): 1561-72, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17721581

RESUMO

This tutorial review deals with recent advances in the chemistry and synthetic use of magnesium carbenoids. The reactivity of traditional carbenoids (alpha-haloalkyllithium species) was successfully reduced by using magnesium as the metal instead of lithium. Properties of these relatively stable carbenoids, magnesium carbenoids, were widely investigated and it was found that the magnesium carbenoids have very interesting reactivity toward several nucleophiles. The magnesium carbenoids, magnesium cyclopropylidenes, magnesium alkylidene carbenoids, and magnesium beta-oxido carbenoids are generated from alpha-chloroalkyl (or alpha-chloroalkenyl) aryl sulfoxides with a Grignard reagent at low temperature by sulfoxide-magnesium exchange reaction. The stability of the generated magnesium carbenoids and several new reactions based on the electrophilicity of the magnesium carbenoids, including 1,3-CH insertion, are reviewed. Magnesium carbenoids open up the new world of the chemistry of carbenoids.

12.
Biochem Biophys Res Commun ; 356(4): 1024-30, 2007 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-17399685

RESUMO

Adiponectin, an adipose tissue-specific plasma protein, has been shown to ameliorate insulin resistance and inhibit the process of atherosclerosis. Recently, several reports have stated that angiotensin type 1 receptor blockers (ARBs), increase adiponectin plasma level, and ameliorate insulin resistance. Telmisartan, a subclass of ARBs, has been shown to be a partial agonist of the peroxisome proliferator-activated receptor (PPAR)-gamma, and to increase the plasma adiponectin level. However, the transcriptional regulation of the human adiponectin gene by telmisartan has not been determined yet. To elucidate the effect of telmisartan on adiponectin, the stimulatory regulation of human adiponectin gene by telmisartan was investigated in 3T3-L1 adipocytes, utilizing adenovirus-mediated luciferase reporter gene-transferring technique. This study indicates that telmisartan may stimulate adiponectin transcription independent of PPAR-gamma.


Assuntos
Adipócitos/metabolismo , Adiponectina/metabolismo , Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Benzimidazóis/administração & dosagem , Benzoatos/administração & dosagem , PPAR gama/metabolismo , Ativação Transcricional/fisiologia , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Adiponectina/genética , Animais , Relação Dose-Resposta a Droga , Humanos , Camundongos , Telmisartan , Ativação Transcricional/efeitos dos fármacos
13.
Chem Pharm Bull (Tokyo) ; 54(12): 1734-8, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17139114

RESUMO

Reaction of lithium alpha-sulfinyl carbanions of 1-chloroalkyl p-tolyl sulfoxides with ketones or aldehydes at low temperature gave adducts in almost quantitative yields. Treatment of the adducts derived from ketones with trifluoroacetic anhydride (TFAA) in the presence of NaI in acetone gave alpha-sulfanyl allylic alcohols in good to quantitative yields. On the other hand, treatment of the adducts derived from aldehydes with TFAA and NaI resulted in the formation of alpha-sulfanyl ketones and/or alpha-sulfanyl allylic alcohols. These reactions offer a good method for the synthesis of the above-mentioned compounds from ketones and aldehydes with carbon-carbon bond-formation in two steps and in good yields.


Assuntos
Carbono/química , Cetonas/síntese química , Propanóis/síntese química , Compostos de Enxofre/síntese química , Aldeídos/química , Estrutura Molecular
14.
Arch Toxicol ; 80(9): 605-13, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16518644

RESUMO

Many cases of hepatopathy including deaths have frequently occurred after ingestion of Chinese dietary supplements for weight loss containing N-nitrosofenfluramine (N-fen), a nitroso derivative of fenfluramine (Fen), which was used for the treatment of obesity in the United States. Since Fen decreases appetite by decreasing the serotonin level and exhibits an antibiotic effect, N-fen may have been added, expecting a similar effect. Thus, we synthesized N-fen and orally administered it to mice, and investigated its effect on the liver as well as on the cerebral serotonin nervous system to investigate whether N-fen exhibits an anorectic effect. Three doses of N-fen were orally administered once daily to mice for 1 week. No significant changes in body weight, food intake, and general condition were noted. The liver and kidney weights were significantly increased. On blood chemistry, alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase activities were increased, and total bilirubin and albumin were slightly decreased. On histopathological examination, acidophilic changes and mild cellular swelling were noted in the liver. The liver drug-metabolizing enzyme (P-450) level was significantly higher. The effect of N-fen on the serotonin (5HT) nervous system was examined by quantitative autoradiography of the mouse brain, and it was found that N-fen did not decrease the 5HT nerve activity. Effects of reuptake and release of monoamine neurotransmitters [dopamine (DA), 5HT, and norepinephrine (NE)] were investigated. N-fen inhibited a little 5HT reuptake, and did not inhibit reuptakes of DA and NE. Moreover, N-fen did not affect release of the three monoamines. The above findings suggested that N-fen did not exhibit a serotonin nerve fiber-mediated anorectic effect in mice, but induced hepatopathy.


Assuntos
Fármacos Antiobesidade/toxicidade , Suplementos Nutricionais/toxicidade , Medicamentos de Ervas Chinesas/toxicidade , Fenfluramina/análogos & derivados , Testes de Toxicidade/métodos , Administração Oral , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Sistema Enzimático do Citocromo P-450/efeitos dos fármacos , Sistema Enzimático do Citocromo P-450/metabolismo , Relação Dose-Resposta a Droga , Fenfluramina/toxicidade , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Inibidores da Captação de Neurotransmissores/toxicidade , Tamanho do Órgão/efeitos dos fármacos , Serotonina/metabolismo
15.
Chem Pharm Bull (Tokyo) ; 52(8): 1009-12, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15305004

RESUMO

Benzeneseleninic anhydride in the presence of tert-butyl hydroperoxide in chlorobenzene at about 70 degrees C is an effective oxidizing agent for the selective oxidation of alcohols at the benzylic position.


Assuntos
Álcoois/química , Derivados de Benzeno/química , Benzeno/química , Compostos Organosselênicos/química , Oxidantes/química , Derivados de Benzeno/farmacologia , Clorobenzenos/química , Modelos Químicos , Compostos Organosselênicos/farmacologia , Oxidantes/farmacologia , Oxirredução , terc-Butil Hidroperóxido/química
16.
Chem Rec ; 3(6): 329-41, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-14991922

RESUMO

Aryl 1-chlorovinyl sulfoxides were easily synthesized from ketones and aldehydes with aryl chloromethyl sulfoxide in three-steps with high overall yields. Low-temperature treatment of the aryl 1-chlorovinyl sulfoxides with alkyllithium or a Grignard reagent gave alkylidene carbenoids via a sulfoxide-metal exchange reaction. From the alkylidene carbenoids, acetylenic compounds, tetra-substituted olefins, and allenes were synthesized. Enolization of alpha-chloro alpha-sulfinyl ketones, which were synthesized from methyl esters and chloromethyl phenyl sulfoxide, is another method for the generation of aryl 1-chloroalkyl sulfoxides. Treatment of 1-chlorovinyl phenyl sulfoxides so generated with t-BuLi followed by some nucleophiles having an acidic hydrogen gave one-carbon elongated carboxylic acids and their derivatives. Conjugate addition of some carbanions with 1-chlorovinyl p-tolyl sulfoxides was found to have taken place. For example, reaction of 1-chlorovinyl p-tolyl sulfoxides with cyanomethyllithium gave high yields of cyclic enaminonitriles. Acidic treatment of the enaminonitriles afforded good yields of 4,4-disubstituted 2-cyclopentenones. By using unsymmetrical ketones and optically pure chloromethyl p-tolyl sulfoxide, this procedure suggests a good method for an asymmetric synthesis of optically pure 4,4-disubstituted 2-cyclopentenones. This method achieved an asymmetric total synthesis of (+)-alpha-cuparenone starting from methyl 4-methylphenyl ketone and (R)-(-)-chloromethyl p-tolyl sulfoxide. A novel synthesis of 2,4,4-trisubstituted 2-cyclopentenones is also successful using cyanomethyllithium and its homologues. Conjugate addition of the lithium enolate of tert-butyl acetate and its homologues gave high yields of the adduct, 3,3-disubstituted esters. Synthesis of various kinds of carboxylic acids and their derivatives and lactones was realized from the adducts.

17.
Chem Pharm Bull (Tokyo) ; 51(8): 966-70, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12913237

RESUMO

Treatment of 1-chlorovinyl p-tolyl sulfoxides, which were synthesized from ketones and chloromethyl p-tolyl sulfoxide, with ethylmagnesium chloride or isopropylmagnesium chloride at below -78 degrees C gave magnesium alkylidene carbenoids in about 90% yields. The reaction of the generated carbenoids with lithium alpha-sulfonyl carbanions was found to afford tri- and tetra-substituted allenes. Both cyclic ketones and acyclic ketones were useful in this procedure. However, the 1-chlorovinyl p-tolyl sulfoxides derived from aldehydes gave only rearranged products, acetylenes, under the reaction conditions. The magnesium alkylidene carbenoid derived from an optically active 1-chlorovinyl p-tolyl sulfoxide was treated with lithium alpha-carbanion of 1-naphthyl phenyl sulfone; however, the obtained allene was found to be racemic. The mechanism of this reaction is also discussed.


Assuntos
Lítio/química , Magnésio/química , Sulfonas/síntese química , Sulfóxidos/síntese química
18.
Chem Pharm Bull (Tokyo) ; 51(5): 602-4, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12736466

RESUMO

The reaction of the dianion of phenylsulfinylacetone with alkyl halides afforded beta-keto sulfoxides, which were first chlorinated with hexachloroethane and then treated successively with KH and t-BuLi to give carboxylic acids in three-steps in moderate overall yields from the alkyl halides. This procedure affords a good method for a synthesis of carboxylic acids from alkyl halides with three-carbon elongation.


Assuntos
Acetona/química , Ácidos Carboxílicos/síntese química , Propionatos/química , Ácidos Sulfínicos/química , Ácidos Graxos/química , Indicadores e Reagentes , Espectroscopia de Ressonância Magnética , Espectrofotometria Infravermelho
19.
Chem Pharm Bull (Tokyo) ; 51(2): 181-6, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12576652

RESUMO

Dithioacetal monoxides were synthesized from aldehydes and cyclohexanone, and reaction of the dithioacetal monoxides with Grignard reagents was investigated. The dithioacetal monoxide synthesized from alkylaldehyde and 4-chlorobenzenethiol reacted with i-PrMgCl to afford the desired alpha-thiomagnesium in high yield. The generated alpha-thiomagnesium was found to be stable at room temperature and to be useful in organic synthesis. In contrast to this, the dithioacetal monoxides derived from benzaldehyde and cyclohexanone did not give satisfactory results.


Assuntos
Acetais/síntese química , Aldeídos/síntese química , Cicloexanonas/síntese química , Compostos de Magnésio/síntese química
20.
Artigo em Inglês | MEDLINE | ID: mdl-12182344

RESUMO

Methods are described for the synthesis of the 2'-tributylstannyl derivative of 2',3'-didehydro-2',3'-dideoxyuridine (d4U). Two approaches were investigated: radical-mediated desulfonylative stannylation of the 2'-benzenesulfonyl derivative of d4U and sulfoxide-metal exchange reaction of the 2'-benzenesulfinyl derivative. The latter approach was found to give the desired 2'-stannyl derivative in good yield. It was also shown that manipulations of the stannyl group allowed the introduction of a variety of carbon-substituents to the 2'-position by applying the Stille reaction. The whole reaction sequence has opened up a highly general entry to 2'-carbon-substituted analogues of d4U.


Assuntos
Fármacos Anti-HIV/síntese química , Didesoxinucleosídeos/síntese química , Nucleosídeos de Pirimidina/síntese química , Uridina/síntese química , Metais/química , Modelos Químicos , Estereoisomerismo , Sulfóxidos/química
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