Effects of silymarin on the resolution of liver fibrosis induced by carbon tetrachloride in rats

Summary.  Silymarin, a standardized extract of the milk thistle ( Silybum marianum ), has a long tradition as a herbal remedy, and was introduced as a hepatoprotective agent a few years ago. However, the therapeutic effects of silymarin remain undefined. Carbon tetrachloride (CCl₄) is a xenobiotic used extensively to induce oxidative stress and is one of the most widely used hepatic toxins for experimental induction of liver fibrosis in the laboratory. In this study, we investigated the restoration of the CCl₄-induced hepatic fibrosis by high dose of silymarin in rats. After treatment with oil (as normal group; n  =   6) or CCl₄ [as model ( n  =   7) and therapeutic ( n  =   7) groups] by intragastric delivery for 8 weeks for the induction of liver fibrosis, the rats in the normal and model group were administered orally normal saline four times a week for 3 weeks whilst the therapeutic group received silymarin (200 mg/kg). The histopathological changes were observed with Masson staining. The results showed that the restoration of the CCl₄-induced damage of liver fibrosis in the therapeutic group was significantly increased as compared to that in the model group. Moreover, silymarin significantly decreased the elevation of aspartate aminotransferase (AST), alanine aminotransferase, and alkaline phosphatase in serum, and also reversed the altered expressions of α-smooth muscle actin in liver tissue. Therefore, these findings indicated that silymarin may have the potential to increase the resolution of the CCl₄-induced liver fibrosis in rats.     

The needs of family caregivers of frail elders during the transition from hospital to home: a Taiwanese sample

The needs of family caregivers of frail elders during the transition from hospital to home: a Taiwanese sample This study explored the needs of family caregivers during the transition from hospital to home. Data from 37 face-to-face interviews with 16 caregivers before discharge and at 2 weeks and 1 month after discharge were subjected to constant comparative analysis. Findings revealed changes in family caregivers' needs during the discharge transition. While preparing to take caregiving responsibility, caregivers reported a need for various types of information. After the discharge, but before home caregiving settled into a pattern, they needed help with caregiving practices. After reaching a pattern for providing family care, caregivers frequently reported needs for continuous emotional support. These findings provide a basis for transitional care services such as discharge planning and home health care services.     

Regulation of hypoxia-inducible factor-1alpha by cyclical mechanical stretch in rat vascular smooth muscle cells

Vascular smooth muscle cells (VSMCs) are exposed to hormonal and mechanical stress in vivo. Hormonal factors have been shown to affect hypoxia-inducible factor-1alpha (HIF-1alpha). How mechanical stress affects the regulation of HIF-1alpha in VSMCs has not been reported previously, and therefore we sought to investigate the regulation of HIF-1alpha by cyclical mechanical stretch in cultured rat VSMCs. Rat VSMCs grown on a flexible membrane base were stretched by vacuum to 20% of the maximum elongation at 60 cycles/min. The levels of HIF-1alpha protein began to increase as early as 2 h after stretch was applied and reached a maximum of 2.8-fold over the control by 4 h. Real-time PCR showed that the levels of HIF-1alpha mRNA increased 2.1-fold after cyclical stretch for 4 h. Cyclical mechanical stretch also increased the immunohistochemical labelling of HIF-1alpha in VSMCs after cyclical stretch for 4 h. The phosphorylation of p42/p44 mitogen-activated protein kinase (MAP kinase) increased after stretch and this was inhibited by the MAP kinase kinase inhibitors PD98059 and U0126. PD98059 and U0126 also blocked HIF-1alpha gene expression induced by cyclical stretch. In conclusion, cyclical mechanical stretch activates the gene expression of HIF-1alpha in cultured VSMCs and this mechanical effect is possibly mediated by the p42/p44 MAP kinase kinase pathway.     

Thrombomodulin is upregulated in cardiomyocytes during cardiac hypertrophy and prevents the progression of contractile dysfunction

BackgroundCardiac hypertrophy is a common response to pressure overload and leads to left ventricular (LV) dysfunction. Thrombomodulin (TM), an endothelial anticoagulant protein, was found to have direct effects on cellular proliferation and inflammation. We examined the TM expression in cardiomyocytes during cardiac hypertrophy and investigated its physiological significance.Methods and ResultsTM expression was evaluated in cardiomyocytes from hearts of mice that underwent transverse aortic constriction (TAC). The effects of recombinant TM protein on cardiomyocytes apoptosis and related signaling pathways were examined. Recombinant TM protein was administered continuously in mice that underwent TAC, and serial LV function was determined. There was significant TM expression in cardiomyocytes during cardiac hypertrophy elicited by TAC in mice. TM treatment decreased doxorubicin-induced apoptosis of cardiomyocytes and increased the Bcl-2/Bax ratio. It also increased cardiomyocytes hypertrophy, expression of atrial natriuretic peptide, and significantly activated the extracellular signal–regulated kinase 1/2 (ERK1/2) and the phosphatidylinositol-3-kinase (PI3-K)/protein kinase B (Akt) signaling pathways in cardiomyocytes. Continuous TM supply after TAC prevented the progression of LV contractile dysfunction in mice.ConclusionsTM treatment decreased cardiomyocyte apoptosis and maintained LV contractile function in response to pressure overload.     

Implantation of olfactory ensheathing cells promotes neuroplasticity in murine models of stroke

Murine olfactory ensheathing cells (OECs) promote central nervous system axonal regeneration in models of spinal cord injury. We investigated whether OECs could induce a neuroplastic effect to improve the neurological dysfunction caused by hypoxic/ischemic stress. In this study, human OECs/olfactory nerve fibroblasts (hOECs/ONFs) specifically secreted trophic factors including stromal cell-derived factor-1alpha (SDF-1alpha). Rats with intracerebral hOEC/ONF implantation showed more improvement on behavioral measures of neurological deficit following stroke than control rats. [18F]fluoro-2-deoxyglucose PET (FDG-PET) showed increased glucose metabolic activity in the hOEC/ONF-treated group compared with controls. In mice, transplanted hOECs/ONFs and endogenous homing stem cells including intrinsic neural progenitor cells and bone marrow stem cells colocalized with specific neural and vascular markers, indicating stem cell fusion. Both hOECs/ONFs and endogenous homing stem cells enhanced neuroplasticity in the rat and mouse ischemic brain. Upregulation of SDF-1alpha and CXCR4 in hOECs/ONFs promoted neurite outgrowth of cocultured primary cortical neurons under oxygen glucose deprivation conditions and in stroke animals through upregulation of cellular prion protein (PrP C) expression. Therefore, the upregulation of SDF-1alpha and the enhancement of CXCR4 and PrP C interaction induced by hOEC/ONF implantation mediated neuroplastic signals in response to hypoxia and ischemia.     

Corpus callosotomy in a patient of hemimegalencephaly and Lennox-Gastaut syndrome

We report the case of a girl with hemimegalencephaly (HME) and Lennox-Gastaut syndrome (LGS) treated by callosotomy at 1 year of age. Over 10 years, her seizure frequency and severity decreased markedly. Hemispherectomy is the main surgical option for HME although HME appears to correlate with a less favorable seizure outcome. However, the clinical presentation of LGS and possible generalized cortical dysplasia, which is indicative of a secondarily generalized epilepsy, might predict a favorable surgical outcome of corpus callosotomy in patients of HME, as in our case.     

A family caregiver-oriented discharge planning program for older stroke patients and their family caregivers

Aims. To test the effectiveness of a discharge planning program for dyads of older stroke survivors and their family caregivers in Taiwan. Background. Family caregivers of stroke survivors often feel inadequately prepared to deal with the physical, cognitive and emotional needs of the stroke survivors. However, little information could be found on discharge planning programs for caregivers of stroke survivors in Asian families. Design. A randomised experimental design was used to explore the effects of a discharge planning program for 158 dyads of older stroke patients and their family caregivers. Methods. The control group (n = 86 dyads) received only routine hospital discharge planning services and the experimental group (n = 72 dyads) received routine hospital discharge planning services plus the caregiver‐oriented discharge planning program. Outcome variables were measured at baseline, before discharge and one month after hospital discharge. Variables were measured by the Nurse Evaluation of Caregiver Preparation Scale, Preparedness for Caregiving Scale, Caregiver Discharge Needs Satisfaction Scale and Perception of Balance between Competing Needs Scale. Results. Caregivers in the experimental group had significantly better nurse evaluation and self‐evaluation of preparation after the program than before, and greater satisfaction of discharge needs one month after discharge than before discharge. Caregivers in the experimental group had significantly better nurse evaluations and self‐evaluations of preparation and better satisfaction of discharge needs after the program compared with the control group. However, no significant difference was found between caregiver groups in perceived balance of competing needs. Conclusions. This discharge planning program benefited family caregivers of older stroke patients during the transition from hospitalisation to one month after discharge. Relevance to clinical practice. This caregiver‐oriented discharge planning program, with its emphasis on individualised health education and home visits following discharge may improve caregivers’ preparation and the satisfaction of their needs during the discharge transition.     

Caregiver self‐efficacy for managing behavioural problems of older people with dementia in Taiwan correlates with care receivers’ behavioural problems

Aims and objective. To investigate the relationship between family caregivers’ self‐efficacy for managing behavioural problems of older people with dementia and their behavioural problems in Taiwan. Background. Older people with dementia commonly have at least one behavioural problem, which caregivers complain is difficult to handle. To provide interventions that can help caregivers more effectively manage the behavioural problems of care receivers with dementia, caregivers’ self‐efficacy on managing behavioural problems must be assessed. However, it is not clear yet how these behavioural problems of older people with dementia may influence caregivers’ self‐efficacy for managing behavioural problems. Design. A prospective, correlational study. Method. Eighty dyads of older people with dementia and their family caregivers were recruited from neurological clinics of a medical centre in Taiwan. Care receivers were assessed for behavioural problems using the Chinese version of Cohen‐Mansfield Agitation Inventory, community form. Caregivers’ self‐efficacy for managing care receivers’ agitation was measured by the research team‐developed Agitation Management Self‐Efficacy Scale. Results. Caregiver self‐efficacy for managing behavioural problems was significantly and positively associated with more caregiver education, greater duration of caregiving and with care receivers’ less physically non‐aggressive behaviours. When caregiver characteristics were controlled for in hierarchical regression analysis, physically non‐aggressive behaviours explained 6% of the variance in caregiver self‐efficacy. Conclusions. Results of this study contradict the general belief that physically aggressive behaviours of elders with dementia are more difficult for family caregivers to handle than other behavioural problems. Clinicians need to address physically non‐aggressive problem behaviours. Relevance to clinical practice. Nurses could assess older patients with dementia for physically non‐aggressive behaviours and train less educated caregivers to improve their self‐efficacy for managing problem behaviours, thus enhancing the quality of life for both caregivers and care receivers.     

Grade changes in peer influence on adolescent cigarette smoking: a comparison of two measures

The effects of peer influence on adolescent cigarette smoking were investigated in longitudinal study of 309 white, middle-class subjects in the 8th and 11th grades. Subjects provided data on their smoking behavior, the proportion of their friends who smoked, and the identity of their best friend. Data from the person named as best friend was used to measure peer smoking, rather than the adolescent's perceptions of the friend's smoking. Peer influence was defined as the difference between the subject's smoking behavior and that of their best friend. This definition (PI1) minimized the confounding of peer influence with selective association. The effects of peer influence on change in smoking behavior were found to be stronger for 8th than 11th graders and for boys than girls. When the proportion of friends who smoke (PI2) was used as the measure of peer influence, the effects of peer influence were stronger for 11th than 8th graders. The relative merits of the two measures are discussed, and the argument is made that the difference between friend and adolescent smoking is a more appropriate measure of peer influence than the proportion of friends who smoke.     

Assessment of neutralizing antibodies elicited by a vaccine (Nakayama) strain of Japanese encephalitis virus in Taiwan.

A total of 368 blood specimens were resampled from a serum collection containing 2914 blood samples which were collected by a random sampling in Taiwan in 1991. The plaque reduction neutralization test was applied to evaluate the neutralizing ability to two strains of Japanese encephalitis viruses, i.e. Nakayama (the present vaccine strain) and JE5 (a Taiwan isolate). The result revealed that antibodies against JE virus were present in each stratified age group. Antibody positive rates were both highest in the group older than 70 years although the lowest rates were located in different groups. In addition, the result showed that the immunogenicity potency of the antibody induced by the vaccine strain did not have a good coverage against JE5. The rate of neutralizing antibodies above the level of protective efficacy of the present vaccine was limited as low as 37.93%. Efficacy of the vaccine used at present was apparently not efficient. Consideration of a more promising vaccine may be necessary.