RESUMO
OBJECTIVE: To study the effect of Lactobacillus helveticus fermented milk on sleep and health perception in elderly healthy subjects. SUBJECTS: The study included 29 healthy elderly subjects aged 60-81 years. METHODS: Prospective, randomized, double-blind and placebo-controlled, with a crossover design. The study included two intervention periods of 3 weeks each, separated by a 3-week washout period. Subjects took 100 g of fermented milk drink or a placebo drink (artificially acidified milk) daily in the first supplementary period and the other drink in the second supplementary period. For each period, we measured sleep quality by means of actigraphy and a sleep questionnaire, and assessed the quality of life (QOL) by SF-36 health survey. RESULTS: There was a significant improvement in sleep efficiency (P=0.03) and number of wakening episodes (P=0.007) in actigraph data after intake of fermented milk, whereas no significant changes were observed for the placebo. Fermented milk did not improve the SF-36 scores significantly from the baseline period. In the GH domain (general health perception) of the SF-36, however, there was marginal improvement as compared to the baseline period. Although the difference between fermented milk and placebo was not statistically significant for any of the sleep or QOL parameters, fermented milk produced slightly greater mean values for many parameters. CONCLUSION: This short-term (3-week) intervention study indicates that Lactobacillus helveticus fermented milk may have a more favorable effect on improving sleep in healthy elderly people as compared with placebo.
Assuntos
Produtos Fermentados do Leite , Lactobacillus helveticus , Distúrbios do Início e da Manutenção do Sono/dietoterapia , Idoso , Envelhecimento/fisiologia , Produtos Fermentados do Leite/microbiologia , Método Duplo-Cego , Fermentação , Nível de Saúde , Inquéritos Epidemiológicos , Humanos , Percepção , Estudos Prospectivos , Sono/fisiologiaRESUMO
Trophoblasts, a cell type found in the placenta, play a pivotal role in the function of the placenta as a barrier between the maternal fluid and the fetus. Recently, claudin, a 24-kDa transmembrane protein, was identified as being responsible for the barrier function of epithelia. In the present study, we investigated the expression profiles of claudin and the changes in expression during the differentiation of BeWo human trophoblast cells. Reverse transcriptase-polymerase chain reaction and immunoblotting demonstrated the expression of claudin-1, -3, -4, and -5 in BeWo cells. Forskolin, which induces the differentiation of BeWo cells from cytotrophoblast-like cells into syncytiotrophoblast-like cells, reduced slightly the expression of claudin-5. This is the first report to show changes in claudin-5 in forskolin-treated BeWo cells.
Assuntos
Colforsina/farmacologia , Proteínas de Membrana/biossíntese , Trofoblastos/metabolismo , Western Blotting , Linhagem Celular Tumoral , Claudina-5 , Depressão Química , Feminino , Humanos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Trofoblastos/efeitos dos fármacosRESUMO
Effects of Lactobacillus helveticus-fermented milk whey on the differentiation of normal human epidermal keratinocytes were studied. Analysis using real-time reverse transcription-polymerase chain reaction revealed that addition of Lactobacillus helveticus-fermented milk whey to the culture medium enhanced mRNA expression of keratin 10, an early differentiation marker, as well as involucrin, a late differentiation marker. Whey of artificially acidified milk, prepared by the addition of dl-lactic acid to milk instead of fermentation, also promoted expression of both markers, but Lactobacillus helveticus-fermented milk whey was more effective in increasing expression of those markers. These results indicate that milk whey has the potential to induce multiple stages of keratinocyte differentiation and that fermentation with Lactobacillus helveticus increases that activity. Furthermore, we examined the expression of profilaggrin, which increases with epidermal terminal differentiation, and found that Lactobacillus helveticus-fermented milk whey enhanced expression of profilaggrin mRNA in a dose-dependent manner. Expression also occurred to a greater extent than with artificially acidified milk whey or other whey samples prepared with several lactic acid bacterial species. Because the proteolytically processed form of profilaggrin, filaggrin, is very important for normal epidermal hydration and flexibility, our results indicate that Lactobacillus helveticus-fermented milk whey has the potential to enhance the production of filaggrin-related natural moisturizing factor, because of its effect on the induction of epidermal differentiation, and is expected to be a useful skin moisturizing agent.
Assuntos
Diferenciação Celular , Fermentação , Queratinócitos/citologia , Lactobacillus helveticus/metabolismo , Leite/química , Leite/microbiologia , Animais , Diferenciação Celular/efeitos dos fármacos , Cosméticos , Proteínas Filagrinas , Humanos , Proteínas de Filamentos Intermediários/genética , Proteínas de Filamentos Intermediários/metabolismo , Proteínas de Filamentos Intermediários/fisiologia , Queratina-10 , Queratinócitos/efeitos dos fármacos , Queratinas/genética , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
In this short review the methods of preparation of novel 1,2,4,5-tetraoxacycloalkanes and the related peroxides are summarized, with the emphasis on the usefulness of 1,1-bishydroperoxides as the precursor. Also, their antimalarial activities in vitro and in vivo are discussed.
Assuntos
Antimaláricos/síntese química , Antimaláricos/farmacologia , Cicloparafinas/síntese química , Cicloparafinas/farmacologia , Animais , Desenho de Fármacos , HumanosRESUMO
The transfer of genes of interest is a useful method for studying placental biology. Recombinant adenovirus (Ad) vector is an efficient vector for transgene expression. An interaction between the fiber of Ad and the coxsackievirus and adenovirus receptor on the cell membrane is the first step in infection. We previously developed fiber-modified Ad vectors and showed that they improved transgene activity in several cell lines when compared to wild-type vector. In the present study, we examined the ability of three fiber-modified Ad vectors to transduce human choriocarcinoma cell lines (JEG-3, JAR and BeWo) and rat trophoblast cell lines (Rcho-1, TR-TBT 18d-1 and TR-TBT 18d-2). We compared the transgene efficacy of wild-type Ad-L2 vector, Ad-RGD(HI)-L2 vector containing an Arg-Gly-Asp motif, Ad-K7(C)-L2 vector containing a 7-tandem lysine motif, and Ad-RGD(HI)K7(C)-L2 vector containing both motifs in the fiber. We used the luciferase gene as a reporter gene. In the human and rodent trophoblast cell lines, Ad-RGD(HI)-L2 had the greatest infectious potential, followed by Ad-RGD(HI)K7(C)-L2, Ad-K7(C)-L2 and Ad-L2. Compared to the amount of luciferase produced by wild-type vector, Ad-RGD(HI)-L2 mediated 8.1-fold the amount of luciferase in JEG-3 cells, 13.5-fold in JAR cells, 76.8-fold in BeWo cells, 5.0-fold in Rcho-1, 19.4-fold in TR-TBT 18d-1 and 15.0-fold in TR-TBT 18d-2. These results indicate that Ad-RGD(HI) is a potential recombinant Ad vector for transgene expression in some trophoblast cell lines.
Assuntos
Adenoviridae/genética , Vetores Genéticos/genética , Transdução Genética/métodos , Transgenes/genética , Trofoblastos/virologia , Animais , Linhagem Celular Tumoral , Coriocarcinoma/genética , Coriocarcinoma/metabolismo , Coriocarcinoma/virologia , Proteína de Membrana Semelhante a Receptor de Coxsackie e Adenovirus , Feminino , Humanos , Integrinas/biossíntese , Integrinas/genética , Integrinas/metabolismo , Gravidez , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Receptores Virais/biossíntese , Receptores Virais/genética , Receptores Virais/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Trofoblastos/metabolismo , Trofoblastos/fisiologiaRESUMO
CsOH- or Ag(2)O-mediated cycloalkylation of (alkylidene)bisperoxides 3 and 1,n-dihaloalkanes (n = 3-8) provided the corresponding medium-sized 1,2,4,5-tetraoxacycloalkanes 4-8 in moderate yields. Subsequent evaluation of the antimalarial activity of the cyclic peroxides 4-8 in vitro and in vivo revealed that 1,2,6,7-tetraoxaspiro[7.11]nonadecane 4a has considerable potential as a new, inexpensive, and potent antimalarial drug.
Assuntos
Antimaláricos/síntese química , Compostos Heterocíclicos com 2 Anéis/síntese química , Compostos de Espiro/síntese química , Animais , Antimaláricos/química , Antimaláricos/farmacologia , Césio , Ciclização , Avaliação Pré-Clínica de Medicamentos , Compostos Heterocíclicos com 2 Anéis/química , Compostos Heterocíclicos com 2 Anéis/farmacologia , Hidróxidos , Malária/tratamento farmacológico , Malária/parasitologia , Camundongos , Óxidos , Plasmodium berghei , Plasmodium falciparum/efeitos dos fármacos , Compostos de Prata , Compostos de Espiro/química , Compostos de Espiro/farmacologia , Relação Estrutura-AtividadeRESUMO
Monoozonolyses of dienes 2 in methanol gave in each case the corresponding unsaturated alpha-methoxy hydroperoxides 3. Capture of 2-alkyl-substituted cyclohexanone oxides by methanol was highly diastereoselective, thereby providing exclusively the hydroperoxides derived from attack by methanol from the less hindered face of the carbonyl oxide intermediates. Halonium ion-mediated reactions of the hydroperoxides 3 gave the novel methoxy- or hydroxy-migrated products, together with the expected halogen-substituted 1, 2-dioxanes and/or 1,2-dioxepanes, the composition of the product mixture being a function of the halogenating agent utilized and the structure of 3.
Assuntos
Acetais/síntese química , Antimaláricos/síntese química , Dioxanos/síntese química , Peróxidos/síntese química , Acetais/química , Antimaláricos/química , Ciclização , Dioxanos/química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Metanol/metabolismo , Modelos Moleculares , Peróxidos/químicaRESUMO
A variety of 1,2,4,5,7-pentoxocane and 1,2,4,5-tetroxane derivatives were prepared as potential peroxide antimalarial agents. In both series of cyclic peroxides, the steric and electronic effects of the substituents attached to the peroxide ring exert a remarkable influence on the antimalarial activity. For some cyclic peroxides, which were found to be highly effective in vitro, the study in vivo has been also conducted.
Assuntos
Antimaláricos/síntese química , Peróxidos/síntese química , Animais , Antimaláricos/química , Antimaláricos/farmacologia , Antimaláricos/toxicidade , Linhagem Celular , Malária/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos ICR , Peróxidos/química , Peróxidos/farmacologia , Peróxidos/toxicidade , Plasmodium berghei , Plasmodium falciparum/efeitos dos fármacosRESUMO
The emigration of leukocytes from calves with beta 2 integrin deficiency (BLAD) into bronchoalveolar spaces and scraped tissues was compared to that of normal calves. Polymorphonuclear neutrophils were found in bronchoalveolar lavage fluid from BLAD-affected calves showing chronic pneumonia. The neutrophils were complement receptor type 3 (CR3)-negative when characterized by flow cytometric analysis using anti-CD18 monoclonal antibody. Chemiluminescent response mediated by CR3 in neutrophils isolated from bronchoalveolar lavage fluid from BLAD-calves showed similar findings obtained from CR3-deficient neutrophils. Neutrophils from normal calves migrated into scraped tissue which was prepared in an upper gluteal surface area, whereas few leukocytes from calves with BLAD migrated to the scraped tissue, evaluated by skin window (Rebuck) method. These findings confirmed the extravasation of CR3-deficient leukocytes into bronchoalveolar lumen in BLAD calves, and demonstrated in vivo characteristics of extravasating property of normal and CR3-deficient neutrophils into scraped tissues.
Assuntos
Doenças dos Bovinos/sangue , Movimento Celular/fisiologia , Síndrome da Aderência Leucocítica Deficitária/veterinária , Neutrófilos/patologia , Animais , Líquido da Lavagem Broncoalveolar/citologia , Antígenos CD18/análise , Antígenos CD18/metabolismo , Bovinos , Doenças dos Bovinos/patologia , Adesão Celular/fisiologia , Feminino , Citometria de Fluxo/veterinária , Síndrome da Aderência Leucocítica Deficitária/sangue , Síndrome da Aderência Leucocítica Deficitária/patologia , Medições Luminescentes , Neutrófilos/química , Neutrófilos/fisiologia , Pneumonia/sangue , Pneumonia/patologia , Pneumonia/veterinária , Alvéolos Pulmonares/química , Alvéolos Pulmonares/patologia , Receptores de Complemento/análise , Receptores de Complemento/deficiência , Receptores de Complemento/metabolismo , Pele/citologiaRESUMO
The extracts from rat submandibular glands (SMGs) induced erythroid differentiation of K-562. The activity was non-dialysable and abolished by heat, trypsin or 2-mercaptoethanol. Follistatin, which neutralizes the erythroid differentiation factor (EDF), had no effects on this activity. Analysis by gel chromatography and polyacrylamide gel electrophoresis-isoelectric focussing showed that the characteristics of this substance were different from those of erythropoietin, TGF-beta 1, EDF, stem cell factor and insulin-like growth factor-1. These results suggest the presence of a novel substance in rat SMGs which induces erythroid differentiation of K-562.
Assuntos
Leucemia Eritroblástica Aguda/tratamento farmacológico , Leucemia Eritroblástica Aguda/patologia , Glândula Submandibular/química , Extratos de Tecidos/farmacologia , Animais , Benzidinas , Diferenciação Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Citocinas/metabolismo , Eletroforese em Gel de Poliacrilamida , Feminino , Hemoglobinas/análise , Hemoglobinas/biossíntese , Humanos , Focalização Isoelétrica , Cinética , Leucemia Eritroblástica Aguda/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ratos , Ratos Wistar , Glândula Submandibular/metabolismo , Extratos de Tecidos/análise , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
Oophorectomy (OOX) has been known to increase bone turnover, but its precise mechanism is not fully understood. In order to further investigate the mechanism, we determined insulinlike growth factor I (IGF-I) concentrations in serum and bone tissue and interleukin 1 (IL-1) release from spleen macrophages in oophorectomized rats because it has been demonstrated that IGF-I stimulates bone formation and IL-1 stimulates bone resorption. Female 8-week-old Wistar rats were divided into four groups: (1) control, (2) OOX, (3) OOX given estradiol, and (4) control given estradiol. Ten micrograms/kg of 17 beta-estradiol was given daily by subcutaneous injection. After 5 weeks of treatment, IGF-I concentrations in the extract from right femur and in serum were determined by specific radioimmunoassay. IL-1 activity released from lipopolysaccharide (LPS)-stimulated spleen macrophages was determined by bioassay. IGF-I contents in the femur and IGF-I concentrations in serum in oophorectomized rats were significantly higher than those in control rats. Treatment by estradiol inhibited the increase in IGF-I concentrations both in femur and in serum. IL-1 release from LPS-stimulated spleen macrophages in oophorectomized rats was increased, and treatment by estradiol also inhibited the stimulated IL-1 release. The ash weights and the calcium contents of left femur in oophorectomized rats were lower than those in control rats. These results suggest that both IGF-I and IL-1 may be involved in the mechanism of the regulation of bone turnover in oophorectomized rats.
Assuntos
Osso e Ossos/química , Terapia de Reposição de Estrogênios , Estrogênios/farmacologia , Fator de Crescimento Insulin-Like I/análise , Interleucina-1/metabolismo , Macrófagos/metabolismo , Ovariectomia , Baço/citologia , Animais , Peso Corporal/fisiologia , Desenvolvimento Ósseo/fisiologia , Osso e Ossos/metabolismo , Cálcio/análise , Células Cultivadas , Estradiol/sangue , Estradiol/farmacologia , Estrogênios/administração & dosagem , Feminino , Fêmur/química , Fêmur/metabolismo , Injeções Subcutâneas , Fator de Crescimento Insulin-Like I/metabolismo , Interleucina-1/fisiologia , Macrófagos/citologia , Osteocalcina/sangue , Radioimunoensaio , Ratos , Ratos WistarRESUMO
Terminal deoxynucleotidyl transferase (TdT) was purified from calf thymus and a monoclonal antibody-producing clone was produced by the fusion of mouse myeloma cells and spleen cells of mice immunized with the purified enzyme. The antigens recognized by an immunoadsorbent column revealed TdT, whose molecular weight was 62 kDa. The extensive study of TdT in 196 patients with hematological disorders was done. The results from immunofluorescent analysis corresponded well to the results of biochemical assays of this enzyme. This monoclonal antibody will provide a useful means for the survey of leukemia and lymphoma patients.
Assuntos
Anticorpos Monoclonais/biossíntese , Especificidade de Anticorpos , DNA Nucleotidilexotransferase/imunologia , Leucemia/enzimologia , Mieloma Múltiplo/enzimologia , Neoplasias Experimentais/enzimologia , Animais , Humanos , Camundongos , Células Tumorais CultivadasRESUMO
We examined the binding characteristics of three kinds of steroid hormones--estrogen, androgen, and glucocorticoid--in cultured MC3T3-E1 mouse osteoblastic cells by whole-cell binding assay. The binding studies revealed the presence of a single class of high-affinity binding sites for [3H]17 beta-estradiol, [3H]mibolerone (a synthetic androgen), and [3H]triamcinolone acetonide (a synthetic glucocorticoid). The numbers of binding sites for these steroid hormones were found to be 4534 +/- 819, 14312 +/- 1884, and 24898 +/- 655 sites/cell; and the Kd values were 8.57 +/- 0.62 x 10(-10) M, 1.12 +/- 0.19 x 10(-9) M, and 6.08 +/- 1.24 x 10(-10) M, respectively. We also examined the effects of steroid hormones on the proliferation of MC3T3-E1 cells. 17 beta-estradiol significantly stimulated the proliferation of the cells (130-150% of control). Dihydrotestosterone also significantly stimulated the proliferation of the cells (115% of control); the effect was, however, much less potent than that of 17 beta-estradiol, although the number of binding sites was approximately three times more than that of 17 beta estradiol. Triamcinolone acetonide and dexamethasone had no effect on cell proliferation. These results suggest that estrogen and androgen act directly on osteoblastic cells through a receptor-mediated mechanism, and that androgen is much less potent than estrogen in stimulating the proliferation of MC3T3-E1 osteoblastic cells.
Assuntos
Di-Hidrotestosterona/farmacologia , Estradiol/farmacologia , Osteoblastos/efeitos dos fármacos , Receptores de Esteroides/metabolismo , Animais , Sítios de Ligação , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Dexametasona/farmacologia , Estradiol/metabolismo , Camundongos , Nandrolona/análogos & derivados , Nandrolona/metabolismo , Osteoblastos/citologia , Osteoblastos/metabolismo , Receptores Androgênicos/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Glucocorticoides/metabolismo , Triancinolona Acetonida/metabolismo , Triancinolona Acetonida/farmacologiaRESUMO
This study was undertaken to examine the possibility that parathyroid hormone promotes the production of interleukin 1 and 6 in MC3T3-E1 osteoblastic cells derived from mouse calvaria. The cells were incubated in serum-free medium with or without synthetic human parathyroid hormone(1-34). The concentrations of interleukin 1 and 6 in the culture medium were determined by using specific bioassay. The cells cultured without parathyroid hormone for 24 hr released both of interleukins, and parathyroid hormone stimulated the release in a dose-dependent manner. When the cells were cultured with 10(-6) M parathyroid hormone, the release of both interleukins from the cells remained higher than control up to 144 hr. These results suggest that interleukin 1 and 6 release stimulated by parathyroid hormone may be involved in the bone resorbing activity of the hormone.