RESUMEN

AIM: This study aimed to examine the influence of the COVID-19 pandemic on physical components and activity, and its relationship to physical performance in older adults. METHODS: Sixty-seven participants aged 75 and older (81 ± 2 years, female: 66%), who underwent medical checkups continuously from 2018 to 2022 in one clinic, were enrolled. Muscle mass was assessed by the biometrical impedance analysis method, which was adjusted by height squared. Physical, oral, and cognitive performance data were obtained from Japanese standard questionnaires at medical checkups. Values obtained in 2018 and 2019 were defined as pre-pandemic, and those in 2021 and 2022 were defined as during the pandemic. RESULTS: Body weight, grip strength, and skeletal mass index did not change from 2018 to 2022, but trunk muscle mass index decreased significantly. A difference in the trunk muscle mass index (TMI) was observed between 2022 and 2018/2019 in men; however, a significant difference was found between 2021 and 2022 in women. Compared with the pre-pandemic period, TMI during the pandemic decreased only in men. The difference in TMI between the pre-pandemic period and during the pandemic (ΔTMI) was significantly decreased in participants with low physical activity and poor oral performance before the pandemic, and in those with falls and poor cognitive function during the pandemic only in men. CONCLUSION: Reduction of trunk muscle mass was related to falls and poor cognitive function during the COVID-19 pandemic in older male adults. These data suggest that the difference in response to the COVID-19 pandemic between men and women necessitates different types of support for older adults. Geriatr Gerontol Int 2024; ••: ••-••.

RESUMEN

Epigenetic reprogramming resets parental epigenetic memories and differentiates primordial germ cells (PGCs) into mitotic pro-spermatogonia or oogonia. This process ensures sexually dimorphic germ cell development for totipotency1. In vitro reconstitution of epigenetic reprogramming in humans remains a fundamental challenge. Here we establish a strategy for inducing epigenetic reprogramming and differentiation of pluripotent stem-cell-derived human PGC-like cells (hPGCLCs) into mitotic pro-spermatogonia or oogonia, coupled with their extensive amplification (about >1010-fold). Bone morphogenetic protein (BMP) signalling is a key driver of these processes. BMP-driven hPGCLC differentiation involves attenuation of the MAPK (ERK) pathway and both de novo and maintenance DNA methyltransferase activities, which probably promote replication-coupled, passive DNA demethylation. hPGCLCs deficient in TET1, an active DNA demethylase abundant in human germ cells2,3, differentiate into extraembryonic cells, including amnion, with de-repression of key genes that bear bivalent promoters. These cells fail to fully activate genes vital for spermatogenesis and oogenesis, and their promoters remain methylated. Our study provides a framework for epigenetic reprogramming in humans and an important advance in human biology. Through the generation of abundant mitotic pro-spermatogonia and oogonia-like cells, our results also represent a milestone for human in vitro gametogenesis research and its potential translation into reproductive medicine.

Asunto(s)

Reprogramación Celular , Epigénesis Genética , Células Germinativas , Técnicas In Vitro , Femenino , Humanos , Masculino , Amnios/citología , Proteínas Morfogenéticas Óseas/metabolismo , Reprogramación Celular/genética , Metilación de ADN/genética , Células Germinativas/metabolismo , Células Germinativas/citología , Sistema de Señalización de MAP Quinasas , Mitosis/genética , Oxigenasas de Función Mixta/deficiencia , Oogénesis/genética , Oogonios/citología , Oogonios/metabolismo , Células Madre Pluripotentes/citología , Células Madre Pluripotentes/metabolismo , Regiones Promotoras Genéticas/genética , Espermatogénesis/genética , Espermatogonias/citología , Espermatogonias/metabolismo , Regulación del Desarrollo de la Expresión Génica

RESUMEN

AIM: To examine the actual conditions of older patients receiving home medical care after hospitalization over a period of 2 years in Japan. METHODS: The study population included 102 participants, aged ≥65 years, receiving home medical care, who consented to participate in the Osaka Home Care Registry (OHCARE) study in Japan over a period of 2 years. We investigated the actual conditions for returning home after hospitalization. RESULTS: The median age of the 102 participants was 84 years, and 61 (59.8%) were women. In the group that returned home, 42 (55.3%) of the respondents desired to recuperate in a familiar place, as in advanced care planning (ACP). During the 2-year follow-up period, the group that did not return home had significantly more deaths. A multivariate analysis showed the association in the presence of ACP (odds ratio: 4.72, 95% confidence interval: 1.60-13.86) and cardiac disease (odds ratio: 0.25, 95% confidence interval: 0.08-0.76). The lack of ACP in the medical records when the patient was admitted to the hospital may have prevented the return home. CONCLUSION: In older patients who had difficulty returning home after hospitalization, the lack of ACP in home medical care may have been an influencing factor. ACP could help continue with home medical care. Geriatr Gerontol Int 2024; 24: 320-326.

Asunto(s)

Servicios de Atención de Salud a Domicilio , Humanos , Femenino , Anciano , Anciano de 80 o más Años , Masculino , Japón , Hospitalización , Hospitales

RESUMEN

AIM: The late-stage medical care system for older people provides medical examinations, including questionnaires for frailty. We examined whether or not this approach is useful in clinical practice. METHODS: We used this questionnaire for the screening of frailty as follows: according to the manual prepared by the Japan Geriatrics Society, each question was classified as concerning oral (Q4, 5), physical (Q6-9), cognitive (Q10, 11), or social (Q13-15) frailty. Each frailty was defined if there was at least one negative answer in each question. The grip power and skeletal muscle index (SMI) according to a bioelectrical impedance analysis were also evaluated. Subjects who showed a reduced grip strength and SMI were defined as having sarcopenia, and those who showed only a reduced grip strength were defined as having possible sarcopenia. RESULTS: One hundred and seventy-one subjects aged 81.0±4.2 years old (63.1% female) were enrolled. A total of 12.3% of subjects showed sarcopenia, and 17.5% showed possible sarcopenia. The prevalence of physical, cognitive, and social frailties was associated with sarcopenia. Oral frailty, defined as having decreased swallowing and mastication functions (Q4 and 5), was significantly related to sarcopenia. Physical frailty was associated with age. In patients with hypertension, a low incidence of cognitive frailty was found. Social frailty was related to a decreased body weight. CONCLUSIONS: A questionnaire during medical examinations for older subjects may be useful for screening various frailties and may lead to promotion of the preventive care activities in the community. Further studies are needed to elucidate the relationship between each type of frailty and background characteristics.

Asunto(s)

Fragilidad , Sarcopenia , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Anciano Frágil , Fragilidad/diagnóstico , Evaluación Geriátrica , Humanos , Masculino , Sarcopenia/epidemiología , Encuestas y Cuestionarios

RESUMEN

In vitro oogenesis is key to elucidating the mechanism of human female germ-cell development and its anomalies. Accordingly, pluripotent stem cells have been induced into primordial germ cell-like cells and into oogonia with epigenetic reprogramming, yet further reconstitutions remain a challenge. Here, we demonstrate ex vivo reconstitution of fetal oocyte development in both humans and cynomolgus monkeys (Macaca fascicularis). With an optimized culture of fetal ovary reaggregates over three months, human and monkey oogonia enter and complete the first meiotic prophase to differentiate into diplotene oocytes that form primordial follicles, the source for oogenesis in adults. The cytological and transcriptomic progressions of fetal oocyte development in vitro closely recapitulate those in vivo. A comparison of single-cell transcriptomes among humans, monkeys, and mice unravels primate-specific and conserved programs driving fetal oocyte development, the former including a distinct transcriptomic transformation upon oogonia-to-oocyte transition and the latter including two active X chromosomes with little X-chromosome upregulation. Our study provides a critical step forward for realizing human in vitro oogenesis and uncovers salient characteristics of fetal oocyte development in primates.

Asunto(s)

Meiosis , Oogénesis , Animales , Femenino , Humanos , Macaca fascicularis , Ratones , Oocitos , Oogénesis/fisiología , Ovario

RESUMEN

Male germ-cell development comprises primordial germ-cell (PGC) development, spermatogonium differentiation, and ensuing spermatogenesis. We present a step-by-step protocol for differentiation of mouse pluripotent stem cells (PSCs) into germline stem-cell-like cells (GSCLCs) via PGC-like cell and spermatogonium-like cell intermediates. The differentiation protocol has higher fidelity than our previous protocol. Upon transplantation into testes in vivo or culture for testis transplants, GSCLCs robustly contribute to spermatogenesis, providing a paradigm for PSC-based reconstitution of mammalian male germ-cell development. For complete details on the use and execution of this protocol, please refer to Ishikura et al. (2021).

Asunto(s)

Células Madre Pluripotentes , Animales , Diferenciación Celular , Masculino , Mamíferos , Ratones , Espermatogénesis , Espermatogonias , Testículo

RESUMEN

Germ cells are unique in engendering totipotency, yet the mechanisms underlying this capacity remain elusive. Here, we perform comprehensive and in-depth nucleome analysis of mouse germ-cell development in vitro, encompassing pluripotent precursors, primordial germ cells (PGCs) before and after epigenetic reprogramming, and spermatogonia/spermatogonial stem cells (SSCs). Although epigenetic reprogramming, including genome-wide DNA de-methylation, creates broadly open chromatin with abundant enhancer-like signatures, the augmented chromatin insulation safeguards transcriptional fidelity. These insulatory constraints are then erased en masse for spermatogonial development. Notably, despite distinguishing epigenetic programming, including global DNA re-methylation, the PGCs-to-spermatogonia/SSCs development entails further euchromatization. This accompanies substantial erasure of lamina-associated domains, generating spermatogonia/SSCs with a minimal peripheral attachment of chromatin except for pericentromeres-an architecture conserved in primates. Accordingly, faulty nucleome maturation, including persistent insulation and improper euchromatization, leads to impaired spermatogenic potential. Given that PGCs after epigenetic reprogramming serve as oogenic progenitors as well, our findings elucidate a principle for the nucleome programming that creates gametogenic progenitors in both sexes, defining a basis for nuclear totipotency.

Asunto(s)

Epigénesis Genética , Células Germinativas , Animales , Cromatina/genética , Cromatina/metabolismo , Metilación de ADN , Epigenómica , Femenino , Células Germinativas/metabolismo , Masculino , Mamíferos/genética , Ratones , Espermatogonias

RESUMEN

AIM: We investigated seasonal variations in blood pressure (BP) and factors related to these variations among older patients receiving home medical care. METHOD: A total 57 patients ≥ 65 years old receiving home medical care who participated in the Osaka Home Care REgistry study (OHCARE), a prospective cohort study, were included. We investigated the seasonal patient characteristics and variations in the BP. In addition, to determine the influence of seasonal variations in the systolic blood pressure (SBP) on the occurrence of clinical events (hospitalization, falls and death), we classified patients into larger- and smaller- change groups based on the median seasonal variations in SBP. RESULT: About 60% of subjects were very frail or bedridden. The mean BP was higher in winter than in summer (124.7±11/69.5±7 vs.120.5±12/66.9±8 mmHg) (P< 0.01). On comparing the characteristics of the two groups with larger and smaller changes in the SBP, the group with large BP changes had a significantly lower BP in summer than the group with small BP changes. In addition, the incidence of "hospitalization" was significantly higher in the group with large BP changes than in the group with small BP changes (P = 0.03). CONCLUSION: The present study revealed that there were seasonal changes in the BP in older patients receiving home medical care. It was also suggested that seasonal changes in the BP might be associated with the risk of hospitalization events. Given these BP variations, doctors and visiting nurses should be alert for systemic abnormalities, especially in frail patients receinving home medical care.

Asunto(s)

Servicios de Atención de Salud a Domicilio , Hipertensión , Anciano , Presión Sanguínea , Monitoreo Ambulatorio de la Presión Arterial , Humanos , Estudios Prospectivos , Estaciones del Año

RESUMEN

Here, we describe a new species of the genus Hynobius from Chugoku, Japan. In populations from central to eastern Shimane Prefecture, the Izumo Lineage of Hynobius utsunomiyaorum was clearly distinguished from the true Hynobius utsunomiyaorum based on morphological and molecular evidence. Thus, we describe the former lineage as a new species, Hynobius kunibiki sp. nov. Morphological comparisons revealed that H. utsunomiyaorum lacks a distinct yellow line on the ventral side of its tail, whereas the new species possesses this yellow line; most H. utsunomiyaorum individuals have distinct white spots on the lateral sides of their body and lack a fifth toe, whereas the new species largely lacks these spots, and all examined individuals had a fifth toe. The two species also differed significantly by several other morphological characteristics. The lentic species Hynobius setoi is morphologically similar to H. kunibiki sp. nov., but they differ significantly by various morphological characteristics. Despite their partial morphological similarity, these two species differed substantially in terms of their genetics. Finally, we show, in a phylogenetic tree including all Japanese Hynobius species, that the subgenus Hynobius can be divided into four genetic clades. Overall, this information will help develop conservation management strategies and policies for these species.

RESUMEN

Some studies reported that excessive blood pressure (BP) control was not appropriate for older people, especially from the viewpoint of quality of life and maintaining sufficient blood flow for tissue perfusion. However, the lower limit of the target BP is still unclear, and there has not yet been a sufficient consensus. Therefore, we investigated the associations of BP levels with clinical events in older patients ~85 years old receiving home medical care. A total of 144 patients were included, who were followed for longer than 3 months in the Osaka Home Care Registry study, a prospective cohort study targeting older patients receiving home medical care in Japan. BP levels were divided into lower and higher groups based on the average systolic blood pressure (SBP). The main outcomes were clinical events, including hospitalizations, falls, and deaths during follow-up. As a result, the hospitalization rate in the SBP below 124 mmHg group was significantly higher than that in the SBP over 124 mmHg group. When comparing the clinical events between the two groups only in participants with hypertension, the same results were obtained. Furthermore, in Cox proportional hazards regression models adjusted by age, sex, and current diseases, the SBP below 124 mmHg group showed a significantly higher rate of required hospitalization (hazard ratio: 7.25, 95% confidence interval: 1.79-29.45). Thus, in older and very frail patients requiring home medical care, an SBP level below 124 mmHg could be a predictive marker of clinical events leading to hospitalization.

Asunto(s)

Servicios de Atención de Salud a Domicilio , Hipertensión , Anciano , Anciano de 80 o más Años , Presión Sanguínea , Humanos , Hipertensión/epidemiología , Estudios Prospectivos , Calidad de Vida

RESUMEN

Hynobius dunni is a salamander species of the genus Hynobius endemically distributed in eastern Kyushu in southwestern Japan. In this study, we determined the complete mitochondrial genome sequence and clarified the phylogenetic position of this species. The mitochondrial genome was 16,47 bp in length and encoded 13 protein, 2 ribosomal RNA, and 22 transfer RNA genes. Phylogenetic tree based on 13 protein-coding genes revealed that H. nebulosus were the most closely related species within the Hynobius species. The data identified in this study will be useful for population and conservation genetic studies of Hynobius species.

RESUMEN

AIM: The present study investigated the behavioral and psychological symptoms of dementia (BPSD) and pharmacological therapy among elderly people with dementia who received home medical treatment. METHODS: This study was part of the Osaka Home Care Registry study (OHCARE-study). Participants were >65 years old with dementia. Demographic and medical data, BPSD, and the LTCI [long-term care insurance] care-need level were collected. A multiple logistic regression analysis was performed in order to clarify the factors associated with BPSD. RESULTS: Among 110 subjects (82.0±11.3 years old), 64.6% had a diagnosis of dementia, most commonly Alzheimer's dementia. Aside from home medical treatment, 58.1% had a nurse visit, 48.1% received home care, and 40.0% used a day service. The prevalence of BPSD was 53.0%. Those with BPSD most frequently had an LTCI care-need level of 3, and the prevalence of BPSD declined as the level increased after 3. Psychotropic drugs were prescribed in 61.5% of those with BPSD. Antipsychotic drugs were used significantly more frequently in those with nursing care resistance, assault and delusions than in others (all, p <0.005). A multivariate analysis showed that the positive predictor of BPSD was antipsychotic drug use, while negative predictors were an LTCI care-need level and the use of visiting rehabilitation. CONCLUSION: The BPSD in elderly dementia patients receiving home medical treatment were clarified. The LTCI care-need level is an independent predictor of BPSD after adjusting for the activities of daily life. Further longitudinal investigations including the BPSD severity and frequency are needed.

Asunto(s)

Enfermedad de Alzheimer , Demencia , Servicios de Atención de Salud a Domicilio , Seguro de Cuidados a Largo Plazo , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/psicología , Enfermedad de Alzheimer/terapia , Estudios Transversales , Demencia/psicología , Demencia/terapia , Humanos

RESUMEN

AIM: To clarify factors associated with changes in care needs level and mortality among disabled older people receiving home medical care over a period of 2.5 years. METHODS: The study included 179 participants, aged ≥65 years, receiving home medical care, who consented to join the Osaka Home Care Registry study. The main outcome was changes in the care needs level of participants eligible for the long-term care insurance system. We investigated the association of changes in care needs level with basic characteristics and care-receiving status. RESULTS: At the 2.5-year follow up, 20.0% of participants showed deteriorated levels, and 41.8% of participants died. In multiple logistic regression, age (odds ratio [OR] 1.10, 95% confidence interval [CI] 1.00-1.21; P = 0.051) and bone joint diseases (OR 0.34, CI 0.09-1.22; P = 0.098) were possible risks associated with deterioration of the care needs level. Male sex (OR 3.28, CI 0.91-11.74; P = 0.068) was a possible risk factor for mortality, and lower serum albumin (OR 0.22, CI 0.07-0.73) was a significant risk factor for mortality. CONCLUSIONS: We clarified the different factors associated with deterioration of the care needs level and mortality among disabled older people. Old age and bone joint diseases might be predictive factors for the further deterioration of independence of physical activity, and a low serum albumin level is considered to be strongly associated with increased mortality. Geriatr Gerontol Int 2019; 19: 1198-1205.

Asunto(s)

Evaluación de la Discapacidad , Personas con Discapacidad/estadística & datos numéricos , Servicios de Atención de Salud a Domicilio/estadística & datos numéricos , Evaluación de Necesidades , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Seguro de Cuidados a Largo Plazo/estadística & datos numéricos , Japón , Masculino , Estudios Prospectivos , Sistema de Registros , Factores de Tiempo

RESUMEN

Hashimoto's encephalopathy (HE) is a steroid-responsive autoimmune encephalopathy associated with Hashimoto thyroiditis. We herein report a case of HE manifesting "smoldering" limbic encephalitis with persisting symptoms and abnormalities on examinations. Although our patient experienced partial clinical remission after treatment, hippocampal hypermetabolism on [18F] fluorodeoxyglucose positron emission tomography (FDG-PET) and subclinical seizures on video electroencephalography persisted. Hypermetabolism on FDG-PET was improved by additional prednisolone therapy. Thus, as with other autoimmune limbic encephalitis cases, HE can take a course of "smoldering" encephalitis. FDG-PET and electroencephalogram findings can reflect the disease activity degree in such patients, although with certain neurophysiological and biochemical distinctions.

Asunto(s)

Enfermedades Autoinmunes/fisiopatología , Encefalitis/fisiopatología , Enfermedad de Hashimoto/fisiopatología , Encefalitis Límbica/fisiopatología , Anciano , Enfermedades Autoinmunes/diagnóstico , Biomarcadores/análisis , Electroencefalografía/métodos , Encefalitis/diagnóstico , Femenino , Enfermedad de Hashimoto/diagnóstico , Humanos , Encefalitis Límbica/complicaciones , Encefalitis Límbica/diagnóstico , Tomografía de Emisión de Positrones/métodos

RESUMEN

Primary central nervous system lymphoma (PCNSL) and chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) can share clinical features and may be indistinguishable, even after brain biopsy. We encountered a case of Epstein-Barr virus-positive (EBV+) PCNSL recurrence in a patient with clinical features of CLIPPERS, and repeat brain biopsy was required to reach the correct diagnosis. Four years after the initial diagnosis and treatment of PCNSL, "peppering" punctate enhanced lesions with transient steroid responsiveness were detected during brain magnetic resonance imaging (MRI). A second brain biopsy supported a diagnosis of CLIPPERS, while a third biopsy confirmed the diagnosis of recurrent PCNSL.

Asunto(s)

Neoplasias del Tronco Encefálico/tratamiento farmacológico , Neoplasias del Tronco Encefálico/genética , Neoplasias del Sistema Nervioso Central/genética , Herpesvirus Humano 4/genética , Inflamación/genética , Linfoma/genética , Metilprednisolona/uso terapéutico , Adulto , Antineoplásicos/uso terapéutico , Neoplasias del Tronco Encefálico/patología , Neoplasias del Sistema Nervioso Central/patología , Enfermedad Crónica , Herpesvirus Humano 4/patogenicidad , Humanos , Inflamación/patología , Linfocitos/efectos de los fármacos , Linfocitos/patología , Linfoma/patología , Masculino , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Resultado del Tratamiento

RESUMEN

We examine the phylogenetic structure and morphological differentiation within the Hynobius kimurae-H. boulengeri species complex-a widely-distributed group of stream-breeding hynobiid salamanders, inhabiting montane areas of western, central and eastern parts of Honshu Island, Japan. Phylogenetic relationships were assessed based on analyses of mitochondrial (mtDNA) and nuclear (nuDNA) gene fragments for a total of 51 samples representing 23 localities covering the entire range of the species complex. Morphological study included one-way analysis of variance (ANOVA) and principal components analysis (PCA) analyses of 26 morphometric and six meristic characters for 38 adult specimens of H. kimurae and three adult specimens of H. boulengeri. MtDNA genealogy supported monophyly of the H. kimurae-H. boulengeri complex, which is sister to all other Hynobius except H. retardatus. The complex is subdivided into three major clades, corresponding to the Eastern (Clade I) and Western (Clade II) populations of H. kimurae sensu lato, and to H. boulengeri (Clade III). Monophyly of H. kimurae sensu lato is only moderately supported by mtDNA, while nuDNA suggested that the Western form of H. kimurae is closer to H. boulengeri than to the eastern form. The time of the split of the H. kimurae-H. boulengeri complex is estimated as late Miocene and coincides with intensive crust movement in western Japan. Divergence between Clades I and II took place in early Pliocene and was likely influenced by the uplift of Central Japanese Highlands. All three clades were found to be different in a number of morphological characters, allowing us to describe the eastern form of H. kimurae as a new species, Hynobius fossigenussp. nov.

RESUMEN

Accurate estimation of tree and forest biomass is key to evaluating forest ecosystem functions and the global carbon cycle. Allometric equations that estimate tree biomass from a set of predictors, such as stem diameter and tree height, are commonly used. Most allometric equations are site specific, usually developed from a small number of trees harvested in a small area, and are either species specific or ignore interspecific differences in allometry. Due to lack of site-specific allometries, local equations are often applied to sites for which they were not originally developed (foreign sites), sometimes leading to large errors in biomass estimates. In this study, we developed generic allometric equations for aboveground biomass and component (stem, branch, leaf, and root) biomass using large, compiled data sets of 1203 harvested trees belonging to 102 species (60 deciduous angiosperm, 32 evergreen angiosperm, and 10 evergreen gymnosperm species) from 70 boreal, temperate, and subtropical natural forests in Japan. The best generic equations provided better biomass estimates than did local equations that were applied to foreign sites. The best generic equations included explanatory variables that represent interspecific differences in allometry in addition to stem diameter, reducing error by 4-12% compared to the generic equations that did not include the interspecific difference. Different explanatory variables were selected for different components. For aboveground and stem biomass, the best generic equations had species-specific wood specific gravity as an explanatory variable. For branch, leaf, and root biomass, the best equations had functional types (deciduous angiosperm, evergreen angiosperm, and evergreen gymnosperm) instead of functional traits (wood specific gravity or leaf mass per area), suggesting importance of other traits in addition to these traits, such as canopy and root architecture. Inclusion of tree height in addition to stem diameter improved the performance of the generic equation only for stem biomass and had no apparent effect on aboveground, branch, leaf, and root biomass at the site level. The development of a generic allometric equation taking account of interspecific differences is an effective approach for accurately estimating aboveground and component biomass in boreal, temperate, and subtropical natural forests.

Asunto(s)

Biomasa , Bosques , Modelos Biológicos , Monitoreo del Ambiente , Japón , Dinámica Poblacional

RESUMEN

Fixed-dose combination (FDC) therapy with telmisartan 40 mg+amlodipine 5 mg (T40/A5) is expected to achieve tight blood pressure (BP) control because of the strong efficacy and long half-life of each drug. The aims of this study were to evaluate the 24-h antihypertensive efficacy of T40/A5 FDC therapy and to explore differences that may arise owing to different administration times in Japanese patients whose hypertension was not controlled by 5 mg of amlodipine per day. In this randomized clinical trial, 44 patients who had been taking amlodipine 5 mg per day and did not achieve their optimal BP target were enrolled (mean age: 67.8±10.2 years). The subjects were then randomly assigned to a T40/A5 morning or evening administration group (22 patients per group). At baseline and 8 weeks after randomization, we evaluated clinical BP and various laboratory values and performed ambulatory BP monitoring (ABPM). Clinical and mean BP evaluated with ABPM at 8 weeks (24 h, daytime, nighttime and early morning) were significantly decreased compared with BP at baseline. There were no significant differences in the diurnal BP profile change from baseline to 8 weeks between subjects in the morning and evening administration groups. There were also no significant differences in the diurnal BP profile change from baseline to 8 weeks between subjects with or without metabolic syndrome. We conclude that T40/A5 FDC therapy significantly decreased the 24-h mean and clinical BP, independent of administration time, in patients whose hypertension was not controlled by 5 mg of amlodipine.

Asunto(s)

Amlodipino/administración & dosificación , Bloqueadores del Receptor Tipo 1 de Angiotensina II/administración & dosificación , Antihipertensivos/administración & dosificación , Bencimidazoles/administración & dosificación , Benzoatos/administración & dosificación , Bloqueadores de los Canales de Calcio/administración & dosificación , Hipertensión/tratamiento farmacológico , Anciano , Monitoreo Ambulatorio de la Presión Arterial , Combinación de Medicamentos , Epinefrina/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Comprimidos , Telmisartán

RESUMEN

Cholesterol 7alpha-hydroxylase (CYP7A1) is regulated by bile acids through the farnesoid X receptor (FXR) mechanism in a negative feedback fashion. However, the fact that CYP7A1 is down-regulated by intraduodenal administration of bile acid, but not by intravenous administration may not be explained only by this mechanism. The aim of this study was to establish a new rat model with reconstructed or simulated enterohepatic circulation to examine if intravenous or portal administration of bile acid can regulate CYP7A1. Under biliary drainage, taurocholate (0 or 6 micromol/h/100g body weight) was administered continuously for 48h into the duodenum (ID-0/ID-6), femoral vein (IV-0/IV-6), or portal vein (IP-0/IP-6) to create a condition in which biliary bile acids were continuously lost, and a similar dose of taurocholate was supplied to the liver simultaneously. CYP7A1 activity and mRNA expression of the ID-0 group were significantly increased compared with the no treatment (NT) group. CYP7A1 activity and mRNA expression of the ID-6 group were suppressed significantly to 41 and 46% of those of the ID-0 group, respectively. In the IV-6 and IP-6 groups, however, enzyme activity and mRNA expression were decreased slightly, but the suppression was not statistically significant. The results suggested that portal as well as intravenous administration of bile acids cannot suppress bile acid synthesis as effectively as intraduodenal administration. It was concluded that an unidentified regulatory factor other than the nuclear receptors may be involved in bile acid synthesis in vivo.

Asunto(s)

Ácidos y Sales Biliares/biosíntesis , Colesterol 7-alfa-Hidroxilasa/metabolismo , Circulación Enterohepática/fisiología , Alanina Transaminasa/sangre , Animales , Ácidos y Sales Biliares/sangre , Ácidos y Sales Biliares/metabolismo , Sistema Biliar/metabolismo , Bilirrubina/sangre , Catéteres de Permanencia , Coledocostomía , Colesterol 7-alfa-Hidroxilasa/genética , Duodeno , Vena Femoral , Expresión Génica/efectos de los fármacos , Infusiones Intravenosas , L-Lactato Deshidrogenasa/sangre , Hígado/anatomía & histología , Hígado/enzimología , Hígado/metabolismo , Masculino , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/enzimología , Microsomas Hepáticos/metabolismo , Modelos Animales , Tamaño de los Órganos/efectos de los fármacos , Vena Porta , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Ácido Taurocólico/administración & dosificación , Ácido Taurocólico/farmacología

RESUMEN

A novel urine tumor marker, diacetylspermine, was compared with two conventional serum tumor markers, carcinoembryonic antigen (CEA) (highly specific for pancreatic cancer) and carbohydrate antigen (CA) 19-9 (highly sensitive for pancreatic cancer), in 125 patients with bilio-pancreatic tumors. When the diagnoses of benign or malignant conditions were examined, the sensitivity of urine diacetylspermine (75%) was shown to be higher than that of CEA (44%; P = 0.044) and CA19-9 (75%). The specificity of urine diacetylspermine (81%) was lower than that of CEA (92%) and as high as that of CA19-9 (80%). These results suggest that urine discetylspermine is a highly sensitive and specific novel marker for bilio-pancreatic carcinoma.

Asunto(s)

Neoplasias del Sistema Biliar/diagnóstico , Biomarcadores de Tumor/orina , Neoplasias/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Espermidina/análogos & derivados , Espermidina/orina , Espermina/análogos & derivados , Espermina/orina , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Sistema Biliar/patología , Biomarcadores de Tumor/sangre , Antígeno CA-19-9/sangre , Antígeno Carcinoembrionario/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias/patología , Neoplasias Pancreáticas/patología , Sensibilidad y Especificidad