Magnesium lithospermate B possesses inhibitory activity on Na^＋,K^＋-ATPase and neuroprotective effects against ischemic stroke

AIM: To examine if magnesium lithospermate B (MLB) extracted from Danshen, the dried roots of Salvia miltiorrhiza, may act as an active component responsible for the cardiac therapeutic effect of this traditional Chinese herb via the same molecular mechanism triggered by cardiac glycosides, such as ouabain and digoxin. Moreover, we wanted to test if MLB may provide neuroprotection against ischemic stroke as observed for cardiac glycosides. METHODS: Similarity in the chemical structure and molecular configuration between MLB and ouabain was analyzed. The inhibition potency of MLB and ouabain on Na( +),K( +) -ATPase activity of a commercial product, as well as in purified membrane fractions from rat brain and heart tissues, was examined and compared. Neuroprotective effect of MLB against ischemic stroke was also evaluated using a cortical brain slice-based assay model. RESULTS: Dose-dependent inhibition on the commercial Na( +),K( +)-ATPase equivalent to that for ouabain was observed for MLB of approximately half dosage by weight. This relative potency of ouabain and MLB was also observed for their inhibition on Na( +),K( +)-ATPase activity of plasma membrane purified from rat tissues, although these 2 inhibitors exhibited somewhat lower competence in these crude extracts. In ischemic gerbil brains, post-treatment with MLB significantly reduced the infarct size, visualized by 2,3,5-triphenyltetrazolium chloride staining, by approximately 55% when compared with the control group. CONCLUSION: These results evidently suggest that the cardiac therapeutic effect of Danshen should be at least partly attributed to the effective inhibition of Na( +),K( +)-ATPase by MLB, and that MLB provides anti-ischemic neuroprotection in gerbils subjected to focal ischemia and reperfusion.     

Bacterial RNA induces myocyte cellular dysfunction through the activation of PKR

Severe sepsis and the ensuing septic shock are serious life threatening conditions. These diseases are triggered by the host's over exuberant systemic response to the infecting pathogen. Several surveillance mechanisms have evolved to discriminate self from foreign RNA and accordingly trigger effective cellular responses to target the pathogenic threats. The RNA-dependent protein kinase (PKR) is a key component of the cytoplasmic RNA sensors involved in the recognition of viral double-stranded RNA (dsRNA). Here, we identify bacterial RNA as a distinct pathogenic pattern recognized by PKR. Our results indicate that natural RNA derived from bacteria directly binds to and activates PKR. We further show that bacterial RNA induces human cardiac myocyte apoptosis and identify the requirement for PKR in mediating this response. In addition to bacterial immunity, the results presented here may also have implications in cardiac pathophysiology.     

Retroperitoneal endoscopic adrenalectomy vs. conventional adrenalectomy in treatment of benign adrenal lesions--comparative analysis

Minimally invasive adrenalectomy is considered to be the standard of care for the surgical treatment of the adrenal gland' s pathology. Since the initial report of laparoscopic adrenalectomy in 1992 and of retroperitoneal endoscopic adrenalectomy in 1994, it has evolved into a feasible and safe minimally invasive procedure for benign adrenal tumors. Clinical characteristics and outcomes of 63 retroperitoneal endoscopic adrenalectomies (REAs) and 45 conventional adrenalectomies (CAs) from 1996 to 2004 were evaluated. 61 patients underwent 63 REAs. Tumor size varied from 2 to 8 cm. Median age was 48.6 years. Median operative time was 135 min (45-240), median intraoperative blood loss - 85 ml (30-550). The complication rate was 17.77%. Median postoperative hospital stay was 5 days (2-10). 44 patients underwent 45 conventional adenalectomies. Median age was 44.5 years (16-71). Intraoperative complication rate was 17.77%, postoperative -22.22 %, Median operative time was 120 min (75-240). Median postoperative hospital stay was 10 days (6-21). No statistically significant difference was established between median operative times of REA- and CA-groups (p=0.91). Conventional adrenalectomy was associated with a significantly increased complication rate (p= 0.009). Hospitalization was also longer after the open tecnique (d). Introduced in 1994 and displaying all advantages of minimal access surgery REA has become the standard of care for benign adrenal tumors.     

What Does the Informal Caregiver of a Terminally Ill Cancer Patient Need? A Study from a Cancer Centre

Aims:

To assess the needs of informal caregivers of terminally ill cancer patients.

Materials and Methods:

Fifty four informal caregivers of patients registered in our palliative care service were interviewed 3–6 months after the death of the patient with the help of a semistructured questionnaire covering the physical, medical, psychological, social, and information domains.

Results:

Most of the caregivers were middle aged and had no prior experience of care giving. The caregivers were satisfied by the information and medical support provided to them by their treatment team. Most had an “emergency plan”. Caregivers had unmet needs including homecare, psychological support, and financial help.

Conclusions:

informal caregivers provide most of the nursing and psychological support to the patient. However, palliative care services need to recognize that the caregiver too may need psychological and technical support.     

Soy isoflavones supplementation alleviates disease severity in autoimmune-prone MRL-lpr/lpr mice

Soy isoflavones supplements, which are phyto-oestrogens widely used as alternatives to alleviate menopausal syndromes or prevent chronic diseases, may exert oestrogenic and anti-oestrogenic activities. This study aimed to investigate the effects of soy isoflavones supplement on oestrogen-related autoimmune disease, such as systemic lupus erythematosus, using autoimmune-prone female MRL-lpr/lpr mice. Eighty mice of 8 weeks were divided into five groups: 0 (Control), 2 (Isf 2), 10 (Isf 10) and 20 (Isf 20) mg/kg BW/day Phyto Soya isoflavones or 0.375 mg/kg BW/day tamoxifen (TAM) as the positive control, by tube-feeding. Some mice were killed at age 15 weeks for cellular cytokine secretion. The data suggested that the Isf 20 and TAM groups had higher weight gain and survival compared with the control group. At age 22 weeks, the Isf 20 group still had 75% survival comparable to mice treated with TAM. At age 14 weeks, the TAM group showed significantly lower serum anti-double-stranded (ds) DNA IgG and anti-cardiolipin IgG. The mice in the Isf 10 and Isf 20 groups also had lower anti-dsDNA IgG and anti-cardiolipin IgG. The interferon (IFN)-gamma secretion from mitogen-stimulated T cells in the Isf 20 and TAM groups were significantly lower than those of control mice. Furthermore, the oestrogenic activity of the methanol extracts of soy isoflavones for oestrogen receptor (ER)beta, but not ERalpha, significantly increased, suggesting that soy isoflavones have a selective modulation of ER activation. Thus, soy isoflavone supplementation did not aggravate murine lupus, but apparently ameliorated the disease.