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1.
Andrologia ; 50(1)2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28295471

RESUMO

This study examined whether feeding hydroalcoholic extract of Lepidium meyenii (maca) to 8-week-old (sexually maturing) or 18-week-old (mature) male rats for more than a half year affects serum testosterone concentration and testosterone production by Leydig cells cultured with hCG, 22R-hydroxycholesterol or pregnenolone. Testosterone concentration was determined in the serum samples obtained before and 6, 12, 18 and 24 weeks after the feeding, and it was significantly increased only at the 6 weeks in the group fed with the maca extract to maturing rats when it was compared with controls. Testosterone production by Leydig cells significantly increased when cultured with hCG by feeding the maca extract to maturing rats for 27 weeks (35 weeks of age) and when cultured with 22R-hydroxycholesterol by feeding it to mature rats for 30 weeks (48 weeks of age). Overall testosterone production by cultured Leydig cells decreased to about a half from 35 to 48 weeks of age. These results suggest that feeding the maca extract for a long time to male rats may enhance the steroidogenic ability of Leydig cells to alleviate its decline with ageing, whereas it may cause only a transient increase in blood testosterone concentration in sexually maturing male rats.


Assuntos
Envelhecimento/efeitos dos fármacos , Lepidium , Células Intersticiais do Testículo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Testosterona/biossíntese , Envelhecimento/metabolismo , Animais , Gonadotropina Coriônica/farmacologia , Hidroxicolesteróis/farmacologia , Células Intersticiais do Testículo/metabolismo , Masculino , Pregnenolona/farmacologia , Ratos , Testosterona/sangue
2.
Water Sci Technol ; 75(9-10): 2149-2156, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28498127

RESUMO

Accelerated release of potassium (K), magnesium (Mg) and phosphorus (P) from surplus activated sludge (SAS) was investigated to develop a new system for the recovery of the elements. Anaerobic cultivation of SAS during 24 h released 78% of K and about 50% of Mg and P from SAS more effectively compared to aerobic cultivation (K: 40%, Mg: 15%, P: 15%). Furthermore, the addition of sodium acetate as an organic carbon source remarkably accelerated the release of K, Mg and P from SAS under anaerobic condition. However, no increase in the maximum release efficiencies was observed. The elements released from SAS could be transferred to separate liquid with the existing mechanical thickener and be recovered as MgKPO4 by some additional process. Furthermore, the removal of the elements from SAS would inhibit the formation of struvite causing the blockage of sludge transport pipe after anaerobic digestion process of thickened sludge.


Assuntos
Magnésio/química , Fósforo/química , Potássio/química , Esgotos/química , Estruvita/química , Eliminação de Resíduos Líquidos/métodos , Anaerobiose , Águas Residuárias
3.
Leukemia ; 31(6): 1269-1277, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-27840424

RESUMO

Chromosomal rearrangements of the mixed lineage leukemia (MLL/KMT2A) gene leading to oncogenic MLL-fusion proteins occur in ~10% of acute leukemias and are associated with poor clinical outcomes, emphasizing the need for new treatment modalities. Inhibition of the DOT1-like histone H3K79 methyltransferase (DOT1L) is a specific therapeutic approach for such leukemias that is currently being tested in clinical trials. However, in most MLL-rearranged leukemia models responses to DOT1L inhibitors are limited. Here, we performed deep-coverage short hairpin RNA sensitizer screens in DOT1L inhibitor-treated MLL-rearranged leukemia cell lines and discovered that targeting additional nodes of MLL complexes concomitantly with DOT1L inhibition bears great potential for superior therapeutic results. Most notably, combination of a DOT1L inhibitor with an inhibitor of the MLL-Menin interaction markedly enhanced induction of differentiation and cell killing in various MLL disease models including primary leukemia cells, while sparing normal hematopoiesis and leukemias without MLL rearrangements. Gene expression analysis on human and murine leukemic cells revealed that target genes of MLL-fusion proteins and MYC were suppressed more profoundly upon combination treatment. Our findings provide a strong rationale for a novel targeted combination therapy that is expected to improve therapeutic outcomes in patients with MLL-rearranged leukemia.


Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , Inibidores Enzimáticos/farmacologia , Rearranjo Gênico , Histona-Lisina N-Metiltransferase/genética , Leucemia/tratamento farmacológico , Metiltransferases/metabolismo , Proteína de Leucina Linfoide-Mieloide/genética , Proteínas Proto-Oncogênicas/antagonistas & inibidores , RNA Interferente Pequeno/genética , Animais , Apoptose , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Regulação Leucêmica da Expressão Gênica , Histona-Lisina N-Metiltransferase/metabolismo , Humanos , Leucemia/genética , Leucemia/patologia , Metiltransferases/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Proteína de Leucina Linfoide-Mieloide/metabolismo , Células Tumorais Cultivadas
4.
Andrologia ; 48(3): 347-54, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26174043

RESUMO

Although Lepidium meyenii (maca), a plant growing in Peru's central Andes, has been traditionally used for enhancing fertility and reproductive performance in domestic animals and human beings, effects of maca on reproductive organs are still unclear. This study examined whether feeding the hydroalcoholic extract powder of maca for 6 weeks affects weight of the reproductive organs, serum concentrations of testosterone and luteinising hormone (LH), number and cytoplasmic area of immunohistochemically stained Leydig cells, and steroidogenesis of cultured Leydig cells in 8-week-old male rats. Feeding the extract powder increased weight of seminal vesicles, serum testosterone level and cytoplasmic area of Leydig cells when compared with controls. Weight of prostate gland, serum LH concentration and number of Leydig cells were not affected by the maca treatment. The testosterone production by Leydig cells significantly increased when cultured with 22R-hydroxycholesterol or pregnenolone and tended to increase when cultured with hCG by feeding the extract powder. The results show that feeding the hydroalcoholic extract powder of maca for 6 weeks increases serum testosterone concentration associated with seminal vesicle stimulation in male rats, and this increase in testosterone level may be related to the enhanced ability of testosterone production by Leydig cells especially in the metabolic process following cholesterol.


Assuntos
Lepidium , Células Intersticiais do Testículo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Testosterona/sangue , Animais , Células Cultivadas , Estradiol/sangue , Células Intersticiais do Testículo/citologia , Células Intersticiais do Testículo/metabolismo , Hormônio Luteinizante/sangue , Masculino , Tamanho do Órgão/efeitos dos fármacos , Próstata/efeitos dos fármacos , Ratos , Ratos Wistar , Testosterona/biossíntese
5.
Osteoporos Int ; 26(3): 1193-202, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25592133

RESUMO

UNLABELLED: Combined treatment with alendronate and eldecalcitol was found to be more effective in reducing the bone turnover markers and increasing bone mineral density than alendronate treatment with vitamin D3 and calcium supplementation in the osteoporotic patients. INTRODUCTION: We compared the clinical efficacy and safety of combined treatment with alendronate plus eldecalcitol (ALN + ELD) with those of treatment with ALN plus vitamin D and calcium (ALN + VitD). METHODS: Osteoporotic 219 patients were randomly assigned to the ALN + ELD, or the ALN + VitD group. Primary endpoint was the inter-group differences in lumbar spine BMD (L-BMD) at patient's last visit. Secondary endpoints included the differences in BMD at other sites and the bone turnover marker (BTM) levels. RESULTS: L-BMD, total hip BMD and femoral neck (FN-BMD) increased from baseline by 7.30, 2.41, and 2.70 % in the ALN + ELD group, and by 6.52, 2.27, and 1.18% in the ALN + VitD group, respectively. Inter-group differences of the L-BMD and total hip BMD values were not significant. The increase of the FN-BMD was larger in the ALN + ELD group than the ALN + VitD group. Reductions of the BTMs were greater in the ALN + ELD group than the ALN + VitD group. Interaction of the percent increase of the L-BMD with the baseline values of the BTMs was observed in the ALN + VitD group only. The increases of the FN-BMD in patients with lower baseline values of type-I-collagen C-telopeptide (sCTX) and serum 25(OH) D levels <20 ng/mL were significantly larger in the ALN + ELD group than the other group. CONCLUSION: Combination treatment of ALN plus ELD was more effective in reducing the BTMs and increasing the FN-BMD than ALN treatment with vitamin D3 and calcium.


Assuntos
Alendronato/administração & dosagem , Conservadores da Densidade Óssea/administração & dosagem , Cálcio/administração & dosagem , Colecalciferol/administração & dosagem , Osteoporose/tratamento farmacológico , Vitamina D/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Densidade Óssea , Remodelação Óssea , Quimioterapia Combinada , Feminino , Humanos , Japão , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Radiografia , Resultado do Tratamento , Vitamina D/administração & dosagem
6.
Osteoporos Int ; 26(2): 765-74, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25403903

RESUMO

SUMMARY: A 12-month extension phase of DIRECT in Japanese subjects with osteoporosis showed that total 3 years of denosumab treatment in Japanese postmenopausal women and men with osteoporosis was associated with low fracture rates, persistent bone turnover marker (BTM) reductions, continuous bone mineral density (BMD) increases, and a favorable overall benefit/risk profile. INTRODUCTION: The DIRECT trial demonstrated that 2 years of treatment with denosumab 60 mg subcutaneously every 6 months significantly reduced the incidence of vertebral fracture compared to placebo in Japanese postmenopausal women and men with osteoporosis. The purpose of this study is to evaluate the efficacy and safety of denosumab treatment for up to 3 years. METHODS: This study includes a 2-year randomized, double-blind, placebo-controlled phase and a 1-year open-label extension phase in which all subjects received denosumab. The data correspond to 3 years of denosumab treatment in subjects who received denosumab (long-term group) and 1 year of denosumab treatment in subjects who received placebo (cross-over group) in the double-blind phase. RESULTS: Eight hundred and ten subjects who completed the double-blind phase enrolled into the extension phase, and 775 subjects completed the study. All subjects received denosumab with daily supplements of calcium and vitamin D. The cumulative 36-month incidences of new or worsening vertebral fractures and new vertebral fractures were 3.8 and 2.5 %, respectively, in the long-term group. In this group, the BMD continued to increase, and the reduction in BTMs was maintained. In the cross-over group, comparable BMD increases and BTMs reductions to those of in their first year of the long-term group were confirmed. Adverse events did not show a notable increase with long-term denosumab administration. One event of osteonecrosis of the jaw occurred in the cross-over group. CONCLUSIONS: Three-year denosumab treatment in Japanese subjects with osteoporosis showed a favorable benefit/risk profile.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Denosumab/administração & dosagem , Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Idoso , Biomarcadores/sangue , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Remodelação Óssea/efeitos dos fármacos , Remodelação Óssea/fisiologia , Cálcio/uso terapêutico , Denosumab/efeitos adversos , Denosumab/uso terapêutico , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Osteoporose/complicações , Osteoporose/fisiopatologia , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/fisiopatologia , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/fisiopatologia , Fraturas da Coluna Vertebral/etiologia , Fraturas da Coluna Vertebral/fisiopatologia , Fraturas da Coluna Vertebral/prevenção & controle , Vitamina D/uso terapêutico
7.
Artigo em Inglês | MEDLINE | ID: mdl-24701241

RESUMO

Pattern classification is very unique in traditional medicine. Kampo medical patterns have transformed over time during Japan's history. In the 17th to 18th centuries, Japanese doctors advocated elimination of the Ming medical theory and followed the basic concepts put forth by Shang Han Lun and Jin Gui Yao Lue in the later Han dynasty (25-220 AD). The physician Todo Yoshimasu (1702-1773) emphasized that an appropriate treatment could be administered if a set of patterns could be identified. This principle is still referred to as "matching of pattern and formula" and is the basic concept underlying Kampo medicine today. In 1868, the Meiji restoration occurred, and the new government changed its policies to follow that of the European countries, adopting only Western medicine. Physicians trained in Western medicine played an important role in the revival of Kampo medicine, modernizing Kampo patterns to avoid confusion with Western biomedical terminology. In order to understand the Japanese version of traditional disorders and patterns, background information on the history of Kampo and its role in the current health care system in Japan is important. In this paper we overviewed the formation of Kampo patterns.

8.
J Orthop Surg (Hong Kong) ; 15(1): 22-6, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17429112

RESUMO

PURPOSE: To assess the biomechanical and histological effects of a high-voltage electrical field on ligament healing. METHODS: 54 male Wistar rats were used. The medial collateral ligaments (MCLs) of 6 rats were measured for normal biomechanical failure load and stiffness. MCLs of the remaining 48 rats were transected and randomly assigned; half were subjected to a high-voltage electrical field for 8 hours a day (experimental group), and the other half were kept under normal conditions (control group). Eight rats from each group were killed 2, 4, and 6 weeks after the transection and their MCLs were tested biomechanically and histologically. RESULTS: Failure load and stiffness of the MCLs in the experimental group were significantly higher than those in the control group 2 weeks after transection, but not thereafter. At week 2, the granulation tissue completely occupied the space between the cut ends of the MCL in the experimental group, whereas some gaps remained in the control group. CONCLUSION: A high-voltage electrical field appear to accelerate ligament healing in the initial 2 weeks. Earlier initial healing may allow earlier start of the rehabilitation.


Assuntos
Terapia por Estimulação Elétrica , Membro Posterior/lesões , Ligamentos Articulares/lesões , Cicatrização , Animais , Fenômenos Biomecânicos , Colágeno Tipo I/metabolismo , Tecido de Granulação/patologia , Imuno-Histoquímica , Masculino , Ratos , Ratos Wistar
9.
J Oral Rehabil ; 33(5): 363-7, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16629895

RESUMO

The feasibility of using collagen as the base of miconazole was investigated. The addition of 33% collagen to a miconazole solution did not affect the minimal inhibitory concentration (MIC80) of the miconazole solution for Candida albicans. When 1 microg mL(-1) of miconazole in 33% collagen solution was plated on resin discs and dried to yield a thin membrane, the growth of C. albicans on the resin discs was nearly completely inhibited. In addition, we compared the antifungal effect of this collagen solution that contained 1 microg mL(-1) miconazole, with the antifungal effect of miconazole gel that had been diluted with glycerol (the main component of miconazole gel) to yield a final concentration of 1 microg mL(-1) of miconazole; as a result, we found that the collagen solution containing 1 microg mL(-1) miconazole had a stronger antifungal effect. In conclusion, our results demonstrated that it may be feasible to use collagen as the base of miconazole instead of glycerol, and suggest that a collagen-based miconazole solution would have a stronger antifungal effect than commercially available miconazole gel. Collagen-based miconazole solution may be useful for the treatment of Candida-associated denture stomatitis.


Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Colágeno/farmacologia , Portadores de Fármacos/farmacologia , Miconazol/farmacologia , Antifúngicos/química , Candida albicans/crescimento & desenvolvimento , Contagem de Colônia Microbiana , Avaliação Pré-Clínica de Medicamentos , Estudos de Viabilidade , Humanos , Miconazol/química , Testes de Sensibilidade Microbiana/métodos
10.
Calcif Tissue Int ; 78(3): 152-61, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16525749

RESUMO

The purpose of this study was to assess whether a nutritional supply of calcium (Ca) could be substituted for alfacalcidol (ALF) administration in preventing bone loss due to estrogen deficiency. Female Wistar-Imamichi rats (8 months old) were ovariectomized (OVX) or sham-operated. OVX rats received ALF administration (0.025, 0.5, or 0.1 microg/kg, p.o., 5 times a week) with standard rodent chow [Ca 1.2%, phosphorus (P) 1.04%], a Ca-enriched diet containing 2%, 4%, or 6% Ca (Ca/P ratio of 2, 4, and 6, respectively), or a Ca/P-enriched diet (Ca/P ratio of 1.2). After 12 weeks of treatment, all rats were killed to harvest the spine, serum, and urine samples. Neither the ALF treatment nor the Ca supplement caused hypercalcemia. In the spine, ALF prevented decreases in bone mineral density (BMD) and compressive strength of lumbar spine induced by OVX. Micro-computed tomographic analysis confirmed that ALF significantly improved the trabecular bone pattern factor and the structure model index and suppressed bone destruction. In contrast, of particular interest, high-dose Ca administration did not have marked effects on bone fragility. Also, when both Ca and P were administered in high doses, BMD and mechanical strength decreased dose-dependently, urinary P excretion significantly increased, and serum parathyroid hormone level increased. Together, it is difficult to adjust the Ca supply through diet alone without disrupting the balance between serum Ca and P levels. Consequently, we conclude that ALF is beneficial for the treatment of osteoporosis, which is not achieved by the use of a Ca supplement.


Assuntos
Conservadores da Densidade Óssea/farmacologia , Densidade Óssea/fisiologia , Cálcio da Dieta/administração & dosagem , Hidroxicolecalciferóis/farmacologia , Osteoporose/tratamento farmacológico , Aminoácidos/urina , Animais , Nitrogênio da Ureia Sanguínea , Densidade Óssea/efeitos dos fármacos , Cálcio/sangue , Cálcio/urina , Cálcio da Dieta/uso terapêutico , Força Compressiva , Creatinina/análise , Creatinina/urina , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática , Feminino , Ovariectomia , Hormônio Paratireóideo/sangue , Fósforo/sangue , Fósforo/urina , Ratos , Ratos Wistar , Tomografia Computadorizada por Raios X
11.
Exp Brain Res ; 160(1): 107-17, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15289965

RESUMO

The aim of the present study was to demonstrate the convergence of inputs from masseter muscle (MM) and tooth pulp (TP) onto C1 spinal neurons and to determine whether the afferent fibers express the functional vanilloid receptor (VR1). Extracellular single-unit recordings were made from 61 C1 units responding to TP electrical stimulation with a constant temporal relationship to a digastric electromyogram signal in pentobarbital anesthetized rats. Eighty-four percent of C1 neurons responding to TP stimulation also responded to the ipsilateral MM stimulation. Of these neurons, 61% were considered to be afferent inputs from Adelta-fibers and the remaining units (39%) were C-fibers, based on calculation of the nerve conduction velocity. Intramuscular injection of capsaicin (0.05 and 0.1%) produced a reduction in a MM-induced C1 neuronal activity in a dose-dependent manner and this effect was antagonized by pretreatment with an antagonist of VR1, capsazepine. Some of these units were also excited by noxious heat stimulation (> 43 degrees C). The trigeminal root ganglion (TRG) neurons that innervated the MM were retrogradely labeled with Fluorogold (FG) and the small-diameter FG-labeled TRG neurons expressed the immunoreactivity for VR1. After intramuscular mustard oil injection (noxious chemical stimulation), the C1 neuronal activity induced by both touch and pinch stimuli was enhanced and their receptive field sizes were significantly expanded. These changes were reversed within 15-20 min. These results suggest that there may be the convergence of noxious afferents inputs from the MM and TP afferents on the same C1 neurons in rats, and that the afferent fibers expressing the functional VR1 may contribute to the hyperalgesia and/or referred pain associated with temporomandibular joint disorder.


Assuntos
Vias Aferentes/fisiologia , Cavidade Pulpar/inervação , Músculo Masseter/inervação , Nociceptores/fisiologia , Dor/fisiopatologia , Células do Corno Posterior/fisiologia , Núcleo Inferior Caudal do Nervo Trigêmeo/fisiologia , Potenciais de Ação/fisiologia , Vias Aferentes/efeitos dos fármacos , Animais , Capsaicina/farmacologia , Atlas Cervical , Cavidade Pulpar/fisiologia , Relação Dose-Resposta a Droga , Estimulação Elétrica , Lateralidade Funcional/fisiologia , Temperatura Alta/efeitos adversos , Masculino , Músculo Masseter/fisiologia , Contração Muscular/fisiologia , Mostardeira , Músculos do Pescoço/inervação , Músculos do Pescoço/fisiologia , Fibras Nervosas Mielinizadas/efeitos dos fármacos , Fibras Nervosas Mielinizadas/fisiologia , Fibras Nervosas Amielínicas/efeitos dos fármacos , Fibras Nervosas Amielínicas/fisiologia , Nociceptores/efeitos dos fármacos , Dor/induzido quimicamente , Extratos Vegetais/efeitos adversos , Óleos de Plantas , Ratos , Ratos Wistar , Receptores de Droga/antagonistas & inibidores , Receptores de Droga/metabolismo , Transmissão Sináptica/fisiologia , Gânglio Trigeminal/citologia , Gânglio Trigeminal/metabolismo
12.
Evid Based Complement Alternat Med ; 1(3): 259-267, 2004 12.
Artigo em Inglês | MEDLINE | ID: mdl-15841259

RESUMO

Agaricus blazei Murill is an edible fungus used in traditional medicine, which has various well-documented medicinal properties. In the present study, we investigated the effects of hemicellulase-derived mycelia extract (Agaricus blazei fraction H: ABH) on the immune system. First, we examined the cytokine-inducing activity of ABH on human peripheral mononuclear cells (PBMC). The results indicated that ABH induced expression of IL-12, a cytokine known to be a critical regulator of cellular immune responses. Flow cytometric analysis demonstrated the induction of IL-12 production by the CD14-positive cell population, consisting of monocytes/macrophages (Mo/Mphi). Furthermore, the elimination of Mo/Mphi attenuated IL-12 production in PBMC. ABH-induced IL-12 production was inhibited by anti-CD14 and anti-TLR4 antibodies but not by anti-TLR2 antibody. The activity of ABH was not inhibited by polymyxin B, while the activity of lipopolysaccharide used as a reference was inhibited. Oral administration of ABH enhanced natural killer (NK) activity in the spleen. These findings suggest that ABH activated Mo/Mphi in a manner dependent on CD14/TLR4 and NK activity.

13.
Adv Space Res ; 32(8): 1453-7, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-15000081

RESUMO

The purpose of this study is to reveal the effect of chronic hypergravity exposure on the bone formation and the bone metabolism when mammals produce offspring in a 2 G environment. We measured the length and width of the thighbone, the length of the pelvis, the width of the pelvic cavity and the width of the fourth cervical vertebra on the second (F2) and the third (F3) generation mice bred in a 2 G environment every ten days from 20 days old to 60 days old in an experiment on bone formation. In an experiment on bone metabolism, we measured calcium and phosphorus in the bones of the F3 in the 2 G group. Ratios of the thighbone length, pelvis length, pelvic cavity width, and fourth cervical vertebra width versus the body length were calculated. These ratios were higher in the 2 G group than the control group during all measuring periods. Calcium and phosphorus concentrations in the thighbone and the lumbar vertebra were lower in the 2 G group than in the control group. However, the calcium and phosphorus concentrations in the cervical vertebrae of the 2 G group were higher. These results suggest that the influence of gravity load may vary in the bones.


Assuntos
Desenvolvimento Ósseo/fisiologia , Osso e Ossos/metabolismo , Cálcio/metabolismo , Hipergravidade , Fósforo/metabolismo , Animais , Tamanho Corporal , Osso e Ossos/fisiologia , Vértebras Cervicais , Fêmur , Vértebras Lombares , Masculino , Camundongos , Camundongos Endogâmicos ICR , Tamanho do Órgão , Fatores de Tempo
14.
Mech Dev ; 119(1): 21-34, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12385751

RESUMO

The Sonic hedgehog (Shh)-Gli signaling pathway regulates development of many organs, including teeth. We cloned a novel gene encoding a transcription factor that contains a zinc finger domain with highest homology to the Gli family of proteins (61-64% amino acid sequence identity) from incisor pulp. Consistent with this sequence conservation, gel mobility shift assays demonstrated that this new Gli homologous protein, GliH1, could bind previously characterized Gli DNA binding sites. Furthermore, transfection assays in dental pulp cells showed that whereas Gli1 induces a nearly 50-fold increase in activity of a luciferase reporter containing Gli DNA binding sites, coexpression of Gli1 with Gli3 and/or GliH1 results in inhibition of the Gli1-stimulated luciferase activity. In situ hybridization analysis of mouse embryos demonstrated that GliH1 expression is initiated later than the three Gli genes and has a more restricted expression pattern. GliH1 is first detected diffusely in the limb buds at 10.0 days post coitus and later is expressed in the branchial arches, craniofacial interface, ventral part of the tail, whisker follicles and hair, intervertebral discs, teeth, eyes and kidney. LacZ was inserted into the GliH1 allele in embryonic stem cells to produce mice lacking GliH1 function. While this produced indicator mice for GliH1-expression, analysis of mutant mice revealed no discernible phenotype or required function for GliH1. A search of the Celera Genomics and associated databases identified possible gene sequences encoding a zinc finger domain with approximately 90% homology to that of GliH1, indicating there is a family of GliH genes and raising the possibility of overlapping functions during development.


Assuntos
Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/fisiologia , Proteínas Oncogênicas/química , Proteínas Oncogênicas/fisiologia , Fatores de Transcrição/química , Fatores de Transcrição/fisiologia , Alelos , Sequência de Aminoácidos , Animais , Sítios de Ligação , Northern Blotting , Clonagem Molecular , DNA/metabolismo , DNA Complementar/metabolismo , Proteínas de Ligação a DNA/biossíntese , Bases de Dados como Assunto , Polpa Dentária/metabolismo , Marcação de Genes , Glutationa Transferase/metabolismo , Proteínas Hedgehog , Hibridização In Situ , Luciferases/metabolismo , Camundongos , Modelos Genéticos , Dados de Sequência Molecular , Filogenia , Regiões Promotoras Genéticas , Ligação Proteica , Estrutura Terciária de Proteína , RNA/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Homologia de Sequência de Aminoácidos , Fatores de Tempo , Transativadores/metabolismo , Transfecção , Proteína GLI1 em Dedos de Zinco , Dedos de Zinco
15.
Bone ; 30(6): 872-9, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12052456

RESUMO

Rheumatoid arthritis (RA) is a disease characterized by inflammatory polyarthritis leading to destruction of the joints and reduction in bone mass. However, the relationship between bone mass and turnover is not yet clear in RA patients. To clarify the effect of bone turnover and marrow osteogenic capacity on mass and structure during the development of arthritis, we examined DBA1/J mice for 8 weeks after the first immunization with bovine type II collagen at the age of 9 weeks. Localized arthritis developed at 4 weeks and advanced arthritis at 6 weeks postimmunization. Urinary deoxypyridinoline levels in arthritic mice were significantly higher at 4 weeks, and levels were maintained thereafter. Their serum osteocalcin levels were significantly reduced compared with controls at 2 and 6 weeks, but did not differ significantly from those in the control group at 4 and 8 weeks. Three-dimensional (3D) trabecular bone volume of the proximal tibia measured by 3D microcomputed tomography (micro-CT) in the arthritic mice became significantly lower at 4 weeks and decreased further at 6 weeks compared with controls. Parameters of 3D trabecular bone structure, such as structure model index and trabecular bone pattern factor, were increased at 4 and 6 weeks, respectively. Trabecular osteoclast number increased and bone formation rates decreased at 8 weeks. The number of total bone marrow cells (BMCs), adherent stromal cells, and area of mineralized nodule formation in the tibia of arthritic mice were significantly reduced compared with controls at 6 weeks. Numbers of total fibroblastic colony-forming units (CFU-f) and alkaline phosphatase (ALP)-positive CFU-f colonies also decreased. However, the values of these osteogenic parameters corrected for the total BMCs and/or adherent stromal cells did not differ significantly between the arthritic and control groups. These data indicate that an increase in bone resorption led to the reduction in trabecular bone mass and deterioration of 3D structure during the localized arthritic stage. The reduction in bone marrow osteogenic potential in the advanced arthritic stage was due to the reduction in the number of total bone marrow cells, and differentiation of osteogenic cells was apparently unaffected. The reduction in bone formation may not be substantial in this arthritic model.


Assuntos
Artrite Experimental/metabolismo , Artrite Experimental/fisiopatologia , Células da Medula Óssea/metabolismo , Remodelação Óssea/fisiologia , Colágeno Tipo II/administração & dosagem , Osteogênese/fisiologia , Animais , Artrite Experimental/etiologia , Artrite Experimental/patologia , Autoanticorpos/biossíntese , Peso Corporal , Células da Medula Óssea/patologia , Colágeno Tipo II/imunologia , Orelha Externa/patologia , Edema/etiologia , Edema/patologia , Hipersensibilidade Tardia/etiologia , Hipersensibilidade Tardia/patologia , Masculino , Camundongos , Camundongos Endogâmicos DBA
16.
Ann Hematol ; 81(1): 1-6, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11807627

RESUMO

To investigate the influence of iron deficiency and iron supplementation on nitric oxide (NO) production, we measured serum iron markers, serum nitrate and nitrite (NOx) concentrations, reticulocyte maturity index (RMI), and serum transferrin receptor (sTfR) levels in 369 females aged 14-19 years. RMI was analyzed by flow cytometry, sTfR concentrations were measured by enzyme immunoassay, and serum NOx levels were tested by the Griess reaction. NOx concentrations of the subjects in iron depletion phase were significantly higher than those of healthy controls. NOx concentrations increased gradually as iron deficiency progressed and were threefold higher than for the healthy controls, when the subjects attained a frank iron deficiency anemia. In particular, the NOx concentrations were 7.5-fold higher in the patients with severe iron deficiency anemia (Hb<80 g/l) than for the subjects with high hemoglobin value (Hb>or=140 g/l). The increased NOx concentrations (132.6+/-42.1 microM) observed in the group with severe anemia decreased significantly (46.3+/-15.8 microM) after hemoglobin levels were normalized by iron supplementation ( P<0.01). NOx concentrations correlated inversely with hemoglobin levels ( r(2)=0.202, P<0.01), but correlated positively with the sTfR concentrations ( r(2)=0.322, P<0.01) and the RMI ( r(2)=0.369, P<0.01). In conclusion, iron deficiency anemia increases NO production, and elevated NOx concentrations in iron deficiency anemia return to normal with iron supplementation.


Assuntos
Anemia Ferropriva/metabolismo , Compostos Ferrosos/administração & dosagem , Óxido Nítrico/sangue , Adolescente , Eritropoese , Feminino , Humanos , Ferro/metabolismo , Receptores da Transferrina/sangue , Valores de Referência
17.
No To Hattatsu ; 33(6): 498-504, 2001 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-11725517

RESUMO

Twenty patients with West syndrome were initially treated with high-dose vitamin B6 (40 to 50 mg/kg/day) and valproate (40 to 50 mg/kg/day). Three became seizure free. For the remaining 17 patients, low-dose synthetic ACTH (0.01 mg [0.4 IU]/kg/day) was added to the regimen. One month after the end of ACTH therapy, 13 patients were seizure free. Thus 16 patients in total(80%) were free of seizures(group A). The treatment was ineffective for the remaining 4 patients (20%; group B). During the following for a mean period of 64 months (range, 48 to 83 months), 9 in group A had a relapse of epileptic seizures. However, only 4 in this group had epileptic seizures at the end of the study (5-7 years of age), all of which were partial and infrequent. In group B, two had frequent intractable seizures, and one was seizure free at the end of the study. One died at the age of 1 year. In group A, 2 patients showed normal or subnormal mental development. Mild, moderate and severe mental retardation were seen in 3, 4 and 7 patients respectively. In group B, all patients showed severe mental retardation. In this study, the rate of evolution into intractable epilepsy was low, but long-term mental development was poor. Seizure control by itself seemed to be insufficient to improve long developmental prognosis of West syndrome.


Assuntos
Hormônio Adrenocorticotrópico/administração & dosagem , Espasmos Infantis/tratamento farmacológico , Ácido Valproico/administração & dosagem , Vitamina B 6/administração & dosagem , Criança , Pré-Escolar , Deficiências do Desenvolvimento/tratamento farmacológico , Esquema de Medicação , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Lactente , Masculino , Prognóstico , Fatores de Tempo
19.
Phytochemistry ; 58(5): 763-7, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11672742

RESUMO

Ethyl acetate extracts of the air-dried fruits of Ferula kuhistanica afforded three daucane esters: kuhistanicaol H, I and J, together with nine other known compounds. Their structures were established on the basis of spectroscopic evidence. Isolated compounds in this paper and previously reported compounds from the roots and stems of F. kuhistanica were tested for antibacterial activity. Some of them were selectively toxic against Gram-positive bacteria, including methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MSSA and MRSA).


Assuntos
Ferula/química , Sesquiterpenos/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus epidermidis/efeitos dos fármacos , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Frutas/química , Meticilina/farmacologia , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação
20.
J Gerontol A Biol Sci Med Sci ; 56(10): M650-5, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11584039

RESUMO

BACKGROUND: The purpose of this study was to determine the prevalence, patterns of reporting, and perceived effectiveness of alternative medical therapies (ATs) among older white American, African American, and Japanese outpatients. METHODS: This study used a questionnaire to interview participants (N = 593; age, >59 y), who were outpatients of geriatric outpatient clinics in Saint Louis, Missouri, and Tokyo, Japan (white Americans, n = 180; African Americans, n = 106; and Japanese, n = 307). RESULTS: Use of >1 AT was greatest among older Japanese (74.3%), followed by white Americans (61.1%) and African Americans (47.2%; p <.001). The most common ATs used among the Japanese (and significantly more than the white and African American groups) were lifestyle diet, herbal therapy, massage, acupressure, and acupuncture. The white and African American groups were more frequent users of relaxation techniques and spiritual healing compared with the Japanese group. Contrary to prior studies of the general population, the use of >1 AT did not correlate with any sociodemographic variables. Reported use of ATs to doctors was low but similar in all three groups (white Americans = 48%, African Americans = 42%, and Japanese = 46%). Perceived effectiveness was high but similar in all three groups (white Americans = 85%, African Americans = 92%, and Japanese = 84%). Although chronic conditions were common reasons for use of ATs, nonmedical reasons (e.g., general health or religious reasons) were also common. CONCLUSIONS: Use of ATs was greater in Japan than in the United States, but for both countries, use by older persons was greater than previous reports of the general population. Because sociodemographic variables do not predict use, and reported use to doctors is low and perceived effectiveness is high, increased awareness and understanding about ATs by health care professionals seems imperative.


Assuntos
Assistência Ambulatorial/estatística & dados numéricos , Terapias Complementares/estatística & dados numéricos , Satisfação do Paciente , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Assistência Ambulatorial/normas , Distribuição de Qui-Quadrado , Coleta de Dados , Feminino , Avaliação Geriátrica , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Sensibilidade e Especificidade , Distribuição por Sexo , Inquéritos e Questionários , Resultado do Tratamento , Estados Unidos
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