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PURPOSE OF INVESTIGATION: We investigated various factors affecting bone mineral density (BMD) in young women and predictive factors of low BMD. METHODS: Subjects were 105 nursing school students aged from 19 to 24 years old. Body weight (BW), pituitary hormones, sex steroid hormone and bone turnover markers were selected as factors. BMD was measured at the lumbar spine at L2-L4 by dual-energy X-ray absorptiometry (DXA). RESULTS: BW (p = 0.002), serum N-terminal telopeptide of type 1 collagen (NTx) (p = 0.006) and bone specific alkaline phosphatase (BAP) (p = 0.02) were significantly correlated with BMD. For identification of the low BMD group, all subjects were divided into four groups on the basis of BW and NTx concentrations. In the group with BW under 51 kg and Ntx concentrations over 11 nMBCE/1, BMD was significantly (p = 0.0013) decreased compared with the other three groups. In this group, the ratio of women with a low BMD was significantly higher (p = 0.004) than the other groups. CONCLUSION: In young women, BW and bone turnover markers significantly affected BMD. Low BMD can be indicated using BW and NTx concentrations without measurement by DXA.
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Peso Corporal , Densidade Óssea , Colágeno Tipo I/sangue , Peptídeos/sangue , Absorciometria de Fóton , Fosfatase Alcalina/sangue , Biomarcadores/sangue , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Valor Preditivo dos Testes , Prolactina/sangue , Fatores de Risco , Adulto JovemRESUMO
1. Inter-breed morphological comparisons were made among 11 breeds of Japanese native chickens (Gifujidori, Hinaidori, Shokoku, Totenko, Tomaru, Satsumadori, Shamo, Koshamo, Koeyoshi, Chabo and Nagoya), White Leghorn, broiler chickens (Chunky) and red junglefowl collected in the Philippines, based on results of direct measurements and analysis by computer vision techniques of the skull. 2. Analysis of direct measurements identified two groups of chicken: a small type that included the Chabo, Koshamo, red junglefowl, Gifujidori and Shokoku and a large type that included the remaining breeds studied. These groupings were made based on size determined both in the first (PC1) and second principal component (PC2). The greatest length of the cranium and condylobasal length greatly contributed to the morphological differences between these two groups. 3. Analysis by computer vision techniques, however, identified three groups: the Bantam group (which includes red junglefowl), Shokoku group and Shamo group. White Leghorn clustered within the Shokoku group while the broiler chicken belonged to the Shamo group. The region around the junction of the neural cranium and the visceral cranium contributed greatly to the morphological differences among breeds, both in the PC1 and PC2.
Assuntos
Galinhas/anatomia & histologia , Galinhas/genética , Crânio/anatomia & histologia , Animais , Galinhas/classificação , Gráficos por Computador , Simulação por Computador , Feminino , Variação Genética , Japão , Masculino , Filogenia , Especificidade da EspécieRESUMO
Understanding the overall features of magnetic excitation is essential for clarifying the mechanism of Cooper pair formation in iron-based superconductors. In particular, clarifying the relationship between magnetism and superconductivity is a central challenge because magnetism may play a key role in their exotic superconductivity. BaFe2As2 is one of ideal systems for such investigation because its superconductivity can be induced in several ways, allowing a comparative examination. Here we report a study on the spin fluctuations of the hole-overdoped iron-based superconductors Ba1-xKxFe2As2 (x = 0.5 and 1.0; Tc = 36 K and 3.4 K, respectively) over the entire Brillouin zone using inelastic neutron scattering. We find that their spin spectra consist of spin wave and chimney-like dispersions. The chimney-like dispersion can be attributed to the itinerant character of magnetism. The band width of the spin wave-like dispersion is almost constant from the non-doped to optimum-doped region, which is followed by a large reduction in the overdoped region. This suggests that the superconductivity is suppressed by the reduction of magnetic exchange couplings, indicating a strong relationship between magnetism and superconductivity in iron-based superconductors.
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In strongly correlated electron systems, enhanced fluctuations in the proximity of the ordered states of electronic degrees of freedom often induce anomalous electronic properties such as unconventional superconductivity. While spin fluctuations in the energy-momentum space have been studied widely using inelastic neutron scattering, other degrees of freedom, i.e., charge and orbital, have hardly been explored thus far. Here, we use resonant inelastic x-ray scattering to observe charge fluctuations proximate to the charge-order phase in transition metal oxides. In the two-leg ladder of Sr(14-x)Ca(x)Cu24O41, charge fluctuations are enhanced at the propagation vector of the charge order (qCO) when the order is melted by raising temperature or by doping holes. In contrast, charge fluctuations are observed not only at qCO but also at other momenta in a geometrically frustrated triangular bilayer lattice of LuFe2O4. The observed charge fluctuations have a high energy (~1 eV), suggesting that the Coulomb repulsion between electrons plays an important role in the formation of the charge order.
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Elucidating the nature of the magnetism of a high-temperature superconductor is crucial for establishing its pairing mechanism. The parent compounds of the cuprate and iron-pnictide superconductors exhibit Néel and stripe magnetic order, respectively. However, FeSe, the structurally simplest iron-based superconductor, shows nematic order (Ts=90 K), but not magnetic order in the parent phase, and its magnetic ground state is intensely debated. Here we report inelastic neutron-scattering experiments that reveal both stripe and Néel spin fluctuations over a wide energy range at 110 K. On entering the nematic phase, a substantial amount of spectral weight is transferred from the Néel to the stripe spin fluctuations. Moreover, the total fluctuating magnetic moment of FeSe is â¼60% larger than that in the iron pnictide BaFe2As2. Our results suggest that FeSe is a novel S=1 nematic quantum-disordered paramagnet interpolating between the Néel and stripe magnetic instabilities.
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In this paper, we tackle the problem of geometric and photometric modeling of large intricately shaped objects. Typical target objects we consider are cultural heritage objects. When constructing models of such objects, we are faced with several important issues that have not been addressed in the past-issues that mainly arise due to the large amount of data that has to be handled. We propose two novel approaches to efficiently handle such large amounts of data: A highly adaptive algorithm for merging range images and an adaptive nearest-neighbor search to be used with the algorithm. We construct an integrated mesh model of the target object in adaptive resolution, taking into account the geometric and/or photometric attributes associated with the range images. We use surface curvature for the geometric attributes and (laser) reflectance values for the photometric attributes. This adaptive merging framework leads to a significant reduction in the necessary amount of computational resources. Furthermore, the resulting adaptive mesh models can be of great use for applications such as texture mapping, as we will briefly demonstrate. Additionally, we propose an additional test for the k-d tree nearest-neighbor search algorithm. Our approach successfully omits back-tracking, which is controlled adaptively depending on the distance to the nearest neighbor. Since the main consumption of computational cost lies in the nearest-neighbor search, the proposed algorithm leads to a significant speed-up of the whole merging process. In this paper, we present the theories and algorithms of our approaches with pseudo code and apply them to several real objects, including large-scale cultural assets.
Assuntos
Algoritmos , Inteligência Artificial , Interpretação de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Armazenamento e Recuperação da Informação/métodos , Reconhecimento Automatizado de Padrão/métodos , Fotogrametria/métodos , Análise por Conglomerados , Bases de Dados Factuais , Retroalimentação , Aumento da Imagem/métodos , Fotometria/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Técnica de SubtraçãoRESUMO
In this work, the hypothesis that water content and substances present on the articular surface play an important role in lubrication through the formation of a layer with a high content of water on the articular surface is analysed. The hydrophilic properties of proteoglycans exposed at the articular surface and hydration of tissue are the main responsible factors for the formation of this layer. The role of the articular surface in the frictional characteristics of articular cartilage was examined using specimens (femoral condyles of pigs) with intact and wiped surfaces tested in intermittent friction tests. Results indicated that the intact condition presented low friction in comparison with the wiped condition. The measured water loss of the articular cartilage after sliding and loading indicated a gradual decrease in the water content as the time evolved, and rehydration was observed after the submersion of unloaded specimens in the saline bath solution. Micrographic analyses indicated the presence of a layer covering the articular surface, and histological analyses indicated the presence of proteoglycans in this superficial layer. The hydration of the cartilage surface layer and proteoglycan in this layer influence lubrication.
Assuntos
Água Corporal/química , Cartilagem Articular/citologia , Cartilagem Articular/fisiologia , Proteoglicanas/fisiologia , Água/fisiologia , Animais , Fricção , Articulação do Quadril/citologia , Articulação do Quadril/fisiologia , Técnicas In Vitro , Lubrificação , SuínosRESUMO
We report the results of inelastic neutron scattering measurements on particular phonons of a superconducting (SC) Ca10Pt4As8(Fe1-x Pt x As)10 with the onset transition temperature T c ~ 33 K to investigate mainly what roles orbital fluctuation plays in Cooper pairing, where we observed a slight softening of the in-plane transverse acoustic mode corresponding to the elastic constant C 66. This softening starts at temperature T well above the SC T c, as T decreases. An anomalously strong change of the scattering intensity of in-plane optical modes was observed at the M point of the pseudo tetragonal reciprocal space in the range of 35 < ω < 40 meV with decreasing T from far above T c. Because this ω region mainly corresponds to the motion of Fe and As atoms in the FeAs planes, the finding presents information on the coupling between the orbital fluctuation of Fe 3d electrons and the lattice system, useful for studying the possible roles of orbital fluctuation in the pairing mechanism and/or the appearance of the so-called nematic phase.
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Augmentation of anti-tumor effect of interleukin 2 (IL-2) with sizofiran (SPG) was demonstrated with in vivo and in vitro experiments. C3H/He mice with subcutaneously inoculated X5563 tumor were used as experimental models. IL-2 at a dose of 2 X 10(4) units per mouse by subcutaneous injection, and/or SPG at a dose of 0.1 g per mouse by intramuscular injection were given every other day for a total of ten times. Tumor infiltrating lymphocytes (TIL) were investigated with the avidin-biotin peroxidase complex method. Cytotoxic activity of mice spleen cells after the therapies against YAC-1, X5563 and MH134 were tested with 51Cr release assay. IL-2 or SPG alone suppressed tumor growth in vivo, although not significantly. Combination therapy with IL-2 and SPG suppressed tumor growth in vivo significantly (p = 0.04). Mice treated with the combination survived longer than the mice treated with the single drug (p less than 0.05) and the controls (p less than 0.001). Immunohistologically, more TILs were seen in the combination group than the other groups. In the cytotoxicity study, 3 days after initiation of the therapies, augmentation of natural killer (NK) activity was greater by the combination than by IL-2 or SPG alone. After incubation with IL-2, the spleen cells from mice treated with the combination showed higher cytotoxicity against X5563 or MH134 tumors than those treated with the single drug or controls. Obtained results suggested that combination therapy with IL-2 and SPG effectively induced NK cells and lymphokine-activated killer cells in vivo and may lead to greater clinical benefit in the treatment of malignancies.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Interleucina-2/uso terapêutico , Neoplasias Experimentais/tratamento farmacológico , Sizofirano/uso terapêutico , Animais , Citotoxicidade Imunológica , Sinergismo Farmacológico , Feminino , Células Matadoras Ativadas por Linfocina/fisiologia , Linfócitos/fisiologia , Camundongos , Camundongos Endogâmicos C3H , Neoplasias Experimentais/imunologia , Neoplasias Experimentais/patologia , Células Tumorais CultivadasRESUMO
Immunologic and antitumor effects of human recombinant interferon-gamma were studied in patients with renal cell carcinoma. A daily dose of 6 to 12 x 10(6) units/m2 of interferon-gamma was given by intravenous drip infusion or intramuscular injection to nine patients over a period varying from two to 16 weeks. Antibody-dependent cell-mediated cytotoxicity and OKIa1-positive monocytes count increased significantly after the therapy was started. Interferon-gamma transiently increased OKT3- and OKT4- positive lymphocyte count. Tumor regression was not observed when clinical response was evaluated in seven patients. Two others, who had no measurable metastases, were not evaluated, because interferon-gamma were given to them as post-operative adjuvant therapy. Our results indicate that interferon-gamma stimulated monocytes and enhanced cell-mediated cytotoxicity; they also suggest the necessity of combining monoclonal antibodies and other biological response modifiers that effect tumor-associated antigens.
Assuntos
Carcinoma de Células Renais/terapia , Interferon gama/uso terapêutico , Neoplasias Renais/terapia , Adulto , Idoso , Citotoxicidade Celular Dependente de Anticorpos , Carcinoma de Células Renais/imunologia , Feminino , Humanos , Neoplasias Renais/imunologia , Células Matadoras Naturais/imunologia , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Proteínas RecombinantesRESUMO
Natural killer (NK) cell activity and recycling capacity of NK cells in patients with carcinoma of the prostate (CaP) was determined by combining the 51Cr-release cytotoxicity assay and single cell cytotoxicity assay in agarose. The NK cell activity in patients with advanced CaP (stage D) was significantly lower than the NK cell activity of normal controls and that of patients with localized CaP (stage B and C). The number of active NK cells in the peripheral blood lymphocytes was similar in all groups tested including normal controls, patients with localized CaP, and patients with advanced CaP. Maximal killing potential (Vmax) and maximal recycling capacity (MRC) were significantly reduced in patients with advanced CaP as compared to patients with localized CaP or normal controls. Obtained results indicated that the depressed NK cell activity in advanced CaP was not due to a reduced number of active NK cells but due to the decreased recycling capacity of the individual NK cells.
Assuntos
Carcinoma/imunologia , Células Matadoras Naturais/imunologia , Neoplasias da Próstata/imunologia , Adulto , Idoso , Contagem de Células , Ciclo Celular , Citotoxicidade Imunológica , Humanos , Masculino , Pessoa de Meia-Idade , Células Tumorais CultivadasRESUMO
A 10-month-old Japanese male infant, with no history of being prone to infections, contracted an intrapulmonary mycobacterial infection. After 2 months of intermittent fever, radiological examinations revealed mass lesions in the lung and mediastinum. Biopsy specimens showed granulomas with caseous necrosis, from which Mycobacterium avium was isolated. There was no history of mycobacteriosis or immunodeficiency diseases among his relatives. Analyses of the O2- release and expression of NADPH oxidase components verified that he suffered from gp91-phox- chronic granulomatous disease (CGD), and that his mother was a carrier of the disease. This is a rare clinical presentation for the onset of CGD, suggesting that the invasive mycobacteriosis might result from defective intracellular killing of CGD-phagocytes.
Assuntos
Doença Granulomatosa Crônica/diagnóstico , Complexo Mycobacterium avium , Infecção por Mycobacterium avium-intracellulare/etiologia , Doença Granulomatosa Crônica/complicações , Humanos , Lactente , Masculino , NADPH Oxidases/deficiência , Neutrófilos/enzimologia , Explosão RespiratóriaRESUMO
Autosomal recessive juvenile parkinsonism (AR-JP) is a hereditary neurodegenerative disorder characterized by levodopa-responsive parkinsonism with onset before age 40 years and a slowly progressive course. Families with this condition have been described predominantly in Japanese population, occasionally under different names including an autosomal recessive early-onset parkinsonism with diurnal fluctuation (AR-EPDF) or a familial form of juvenile parkinsonism. Recently, the causative gene for AR-JP was mapped on chromosome 6q25.2-q27, and subsequently a novel gene 'parkin' was identified by means of positional cloning. In this manuscript, we review the clinical, pathological and genetical aspects of AR-JP. It would not only promise to provide important insights into the molecular mechanisms of selective degeneration of dopaminergic neurons in AR-JP, but also bring insights into the mechanisms of degeneration of these neurons in Parkinson's disease.
Assuntos
Ligases , Degeneração Neural/genética , Degeneração Neural/patologia , Transtornos Parkinsonianos/genética , Transtornos Parkinsonianos/patologia , Proteínas/genética , Ubiquitina-Proteína Ligases , Adolescente , Adulto , Criança , Análise Mutacional de DNA , Feminino , Humanos , MasculinoRESUMO
The orientation of patches on the surface of an object can be determined from multiple images taken with different illumination, but from the same viewing position. The method, referred to as photometric stereo, can be implemented using table lookup based on numerical inversion of reflectance maps. Here we concentrate on objects with specularly reflecting surfaces, since these are of importance in industrial applications. Previous methods, intended for diffusely reflecting surfaces, employed point source illumination, which is quite unsuitable in this case. Instead, we use a distributed light source obtained by uneven illumination of a diffusely reflecting planar surface. Experimental results are shown to verify analytic expressions obtained for a method employing three light source distributions.
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Cefmatilen hydrochloride hydrate (S-1090) at dosage levels of 6.25, 12.5 and 25 mg potency/kg/day was administered orally by gavage to groups of 13-16 pregnant rabbits daily during the period of organogenesis, and the effects of S-1090 on dams and fetuses were examined. Control animals were treated with a 0.5 w/v% aqueous solution of methylcellulose. Abortion was noted in 1 of the 16 females of the 12.5 mg potency/kg group and in 1 of the 14 females of the 25 mg potency/kg group, and death was noted in 1 of the 14 females of the 25 mg potency/kg group. Regarding the dams, decreased food consumption was noted in the 12.5 mg potency/kg group in the beginning of the dosing period. Suppressed body weight gain and decreased food consumption were noted in the 25 mg potency/kg group during the pregnancy period. At necropsy, thickening of the gastric mucosa, hemorrhage in the cecum, and higher values of cecum weight were also noted in this group. On the other hand, no effects of S-1090 were noted in general signs, body weight changes, food consumption, necropsy findings, or organ weights in the 6.25 mg potency/kg group. No effects of S-1090 were noted in the number of corpora lutea, number of implantations, implantation rate, death or resorption rate, number of live fetuses, sex ratio of live fetuses, fetal body weight of either sex, incidence of external anomalies, incidence of skeletal anomalies or variations, degree of ossification, or incidence of visceral anomalies. On the basis of the above results, the no observed adverse effect levels of S-1090 are estimated at 6.25 mg potency/kg/day for general toxicity and reproductive functions in dams, and at 25 mg potency/kg/day for development in fetuses under the conditions of the present study.
Assuntos
Cefalosporinas/toxicidade , Desenvolvimento Embrionário e Fetal/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Administração Oral , Animais , Peso Corporal/efeitos dos fármacos , Ceco/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Masculino , Tamanho do Órgão/efeitos dos fármacos , CoelhosRESUMO
The present study was designed to elucidate the correlation between findings from reproductive performance testing and those from histopathological examination of the testis and sperm analysis in rats given a benzodiazepine derivative, nitrazepam, for 2 and 4 weeks. The mechanisms of toxicological action of nitrazepam on the male reproductive organs were also investigated. Nitrazepam was given orally to Sprague-Dawley male rats (6-week-old) at a daily dose of 80 mg/kg for 2 weeks or at daily doses of 20, 40 or 80 mg/kg for 4 weeks. Treated males were mated to examine reproductive performance with untreated females after each dosing period, and after 4 and 9 week of recovery periods. Necropsy was performed for histopathological examination of the testis and epididymis and for sperm analysis after each dosing period and the final mating trial (total of 11 weeks recovery). In the findings from reproductive performance testing, significant decrease in the fertility index was observed in the 80 mg/kg group even after 2 weeks dosing and thereafter until 4 weeks recovery, though the mating index did not significantly differ from that of controls through the experiment. In the histopathological examination and sperm analysis, testicular signs of toxicity, decrease in number of sperm heads in the testis and increase in number of sperm with abnormal heads in the seminiferous tubules were noted in the 80 mg/kg group after 2 weeks dosing and in the 40 and 80 mg/kg groups after 4 weeks dosing. Concentrations of plasma testosterone and content of testis testosterone in nitrazepam-treated groups were not significantly different from those of controls. Plasma FSH concentration was significantly elevated in the 80 mg/kg group through the experiment, although significant elevation of plasma LH was observed only after 2 weeks dosing. These results indicate that histopathological examination is the most reliable approach to detect male reproductive adverse effects induced by nitrazepam rather than using parameters from mating trials. The four-week-dosing period is appropriate for their detection. Hypospermatogenesis induced by nitrazepam is suggested to be caused by direct action of nitrazepam on germ cells and/or Sertoli cells rather than by indirect action through inhibition of testosterone secretion.
Assuntos
Fertilidade/efeitos dos fármacos , Infertilidade Masculina/patologia , Nitrazepam/toxicidade , Espermatozoides/patologia , Animais , Esquema de Medicação , Feminino , Hormônio Foliculoestimulante/sangue , Imuno-Histoquímica , Infertilidade Masculina/induzido quimicamente , Hormônio Luteinizante/sangue , Masculino , Nitrazepam/administração & dosagem , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Espermatogênese/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Testículo/química , Testículo/efeitos dos fármacos , Testículo/patologia , Testosterona/sangueRESUMO
Cefmatilen hydrochloride hydrate (S-1090) was administered daily by gavage to rats at doses of 100, 300 or 1000 mg potency/kg/day prior to and in the early stage of pregnancy to assess its adverse effects on parental reproductive ability and embryo-fetal development. Loose and/or reddish brown feces were observed in both males and females of all the S-1090 dosing groups, and abdominal distention was also observed in males throughout the dosing period. No drug-related deaths occurred in either males or females. In males, body weight and food consumption were increased at a dose of 1000 mg potency/kg/day throughout the dosing period. In females, body weight gain was restrained during late pregnancy, and food consumption was decreased transiently following the initiation of dosing, and then remained high on the day before parturition in all the S-1090 dosing groups. Necropsy of male and female rats revealed an increase in the cecum weight. The reproductive ability of males and females was normal in all the S-1090 dosing groups. No effects of S-1090 were observed in the implantation ratio, embryo-fetal viability, fetal body weight, and incidence of external, skeletal and visceral anomalies. Based on these results, the no observed adverse effect levels of S-1090 are estimated to be less than 100 mg potency/kg/day for parental general toxicity, 1000 mg potency/kg/day for reproductive toxicity, and 1000 mg potency/kg/day for developmental toxicity in embryo-fetuses under the conditions of the present study.
Assuntos
Cefalosporinas/toxicidade , Embrião de Mamíferos/efeitos dos fármacos , Desenvolvimento Embrionário e Fetal/efeitos dos fármacos , Fertilidade/efeitos dos fármacos , Administração Oral , Animais , Peso Corporal/efeitos dos fármacos , Ceco/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Cefmatilen hydrochloride hydrate (S-1090) was administered daily by gavage to female rats at doses of 100, 300 or 1000 mg potency/kg/day from Days 7 to 17 of pregnancy to assess its effects on dams and on development of the embryo-fetuses and offspring. Loose or reddish-brown feces were observed in dams of all the S-1090 dosing groups. Body weight gain was increased from the early stage of administration to the end of pregnancy, food consumption was transiently decreased at the early stage of administration, and water consumption was increased from the middle to the end of pregnancy in all the S-1090 dosing groups. However, no effects on pregnancy, parturition and lactation were observed. Necrospy revealed an increased cecum weight in pregnant and lactating dams of all the S-1090 dosing groups. No effects of S-1090 were observed in viability, growth, incidences of external, skeletal and visceral anomalies, and degree of ossification in F1 fetuses. No effects of S-1090 were observed in such parameters as viability, incidence of external and skeletal anomalies, physical development, sensory functions/reflexes, behavior and reproductive function in F1 offspring. No adverse effects were observed in F2 offspring. On the basis of these results, the no observed adverse effect levels of S-1090 are estimated to be less than 100 mg potency/kg/day for maternal general toxicity, 1000 mg potency/kg/day for maternal reproductive toxicity and the developmental toxicity in the embryo-fetuses and offspring under the conditions of the present study.
Assuntos
Cefalosporinas/toxicidade , Desenvolvimento Embrionário e Fetal/efeitos dos fármacos , Anormalidades Induzidas por Medicamentos , Administração Oral , Animais , Peso Corporal/efeitos dos fármacos , Osso e Ossos/embriologia , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Feto/efeitos dos fármacos , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
Cefmatilen hydrochloride hydrate (S-1090) was administered daily by gavage to female rats at doses of 100, 300 or 1000 mg potency/kg/day from Day 17 of pregnancy to Day 20 of lactation to assess its effects on pregnant/lactating females and on development of the offspring. In dams, loose feces/reddish brown feces, increased cecum weight, decreased weights of the heart, spleen and submaxillary gland in all the S-1090 dosing groups and a decreased weight of the thymus in the 1000 mg potency/kg dosing group were observed. However, no effects on parturition and lactation were observed in any of the dosing groups. In F1 offspring, although increased cecum weight was found at weaning in all the S-1090 dosing groups, no abnormalities in viability, physical development, sensory functions/reflexes, behavior and reproductive function were observed. No adverse effects were observed in F2 fetuses and offspring. On the basis of these results, the no observed adverse effect levels of S-1090 are estimated to be less than 100 mg potency/kg/day for maternal general toxicity, and 1000 mg potency/kg/day for maternal reproductive toxicity and for developmental and reproductive toxicity in offspring under the conditions of the present study.