Accumulation of exogenous polyamines in gerbil brain after ischemia

Regionally selective delayed neuronal degeneration is a characteristic sequel of cerebral ischemia. Recent evidence indicates that changes in brain polyamine metabolism may be critical for nerve cell survival after ischemia. Within hours after ischemia, intracellular putrescine levels are greatly increased and remain elevated for days, whereas only minor changes are noted in the levels of the polyamines spermine and spermidine. In contrast, the extracellular levels of all polyamines are low after ischemia. Injections of polyamines following ischemia, however, can protect neurons in the gerbil brain from delayed cell death, with spermine being the most potent of the polyamines. In the present study, therefore, we sought to determine if increased polyamine uptake occurs in the brain after ischemia. In the hippocampal slice preparation, temperature-dependent uptake was unique for spermine, but not for spermidine or putrescine. Uptake of [¹⁴C]spermine was transiently increased after ischemia, peaking at 150% of control by 12–13 h and subsiding by 24 h. Intravenous injections of [³H]spermidine resulted in a postischemic accumulation of this polyamine throughout the forebrain parenchyma. We conclude that:

1. Active cellular uptake of spermine is transiently increased early after ischemia;
2. A nonspecific accumulation of exogenous polyamines occurs early after ischemia probably owing to a compromised blood-brain barrier, and
3. The findings indicate that exogenous polyamines can exert their effect directly in the brain after ischemia.

     

Hormonal contraception,sexual behaviour and HIV prevalence among women in Cameroon

Background  

Data on the effect of contraceptive methods, other than the condom, on HIV acquisition is not clear. The aim of this study was to describe hormonal contraceptive use, sexual behaviour and HIV prevalence among women in Cameroon in order to provide baseline information for future analytical studies.     

The effect of electric stimulation treatment on the functional rehabilitation of acute geriatric patients with stroke--a preliminary study

The most common neurological damage in acute stroke/cerebrovascular accident (CVA) is a decline in the senso-motor capacities of both the upper and the lower extremities with a more severe injury in the upper ones. Motor improvement of the affected limb can be attained through frequent intensive exercise by electrical stimulation (ES). The objective of this study was to examine the effect of the ES treatment using Handmaster ES device on the functional rehabilitation of elderly patients after acute CVA. Twenty-two elderly with different levels of damage and partial movements in their upper limb joints underwent a 3-week treatment. Nine of them were treated for additional 3-weeks after a 3-week break. After the first 3-week treatment, significant improvements were observed, in all the subjects, in the active range of motion (ROM) of the shoulder and the wrist joints, on manual dexterity tests and on functional independence measure (FIM). After the two periods of treatment the nine subjects exhibited significant improvements in ROM and in manual dexterity. FIM score increased by the same rate after each of the three stages. This preliminary study has proven that the Handmaster treatment can improve the geriatric rehabilitation outcome of elderly patients with senso-motor deficit caused by acute CVA.     

Platinum-resistance in ovarian cancer cells is mediated by IL-6 secretion via the increased expression of its target cIAP-2

Ovarian carcinoma patients are initially responsive to platinum-based therapy, but eventually become refractory to treatment due to the development of platinum chemoresistance. Elevated levels of interleukin-6 (IL-6) in the sera and ascites of these patients predict poor clinical outcome. Our goal was to analyze the interaction between cisplatin and cisplatin-resistant ovarian cancer cells, and to identify means of circumventing platinum resistance. We studied ovarian carcinoma cell lines and cells drawn from ovarian carcinoma patients. Gene array analyses were performed on ovarian carcinoma cells upon treatment with cisplatin, and the results were validated by ELISA and Western blotting (WB). Cytotoxicity assays were performed on anti-IL-6 Ab-, IL-6-, and cellular inhibitor of apoptosis 2 (cIAP-2) siRNA-treated cells, following cisplatin addition. Our results revealed a highly significant increase in IL-6 and cIAP-2 mRNA and protein levels upon treatment with cisplatin. WB analysis of cisplatin-treated cells exhibited decreased cIAP-2 expression level following anti-IL-6 Ab addition. Furthermore, IL-6 by itself, significantly increased cIAP-2 levels in ovarian carcinoma cells. Finally, cytotoxicity assays showed sensitization to cisplatin following the addition of IL-6 and cIAP-2 inhibitors. In conclusion, cisplatin treatment of ovarian carcinoma cells upregulates IL-6 and cIAP-2 levels while their inhibition significantly sensitizes them to cisplatin. Here, we present cIAP-2 as a novel inducer of platinum resistance in ovarian carcinoma cells, and suggest an axis beginning with an encounter between cisplatin and these cells, mediated sequentially by IL-6 and cIAP-2, resulting in cisplatin resistance. Consequently, we propose that combining IL-6/cIAP-2 inhibitors with cisplatin will provide new hope for ovarian carcinoma patients by improving the current treatment.     

Mental health outcomes in elderly men with prostate cancer

ObjectiveTo examine the burden of mental health issues (MHI), namely anxiety, depressive disorders, and suicide, in a population-based cohort of older men with localized prostate cancer and to evaluate associations with primary treatment modality.Patients and methodsA total of 50,856 men, who were 65 years of age or older with clinically localized prostate cancer diagnosed between 1992 and 2005 and without a diagnosis of mental illness at baseline, were abstracted from the Surveillance, Epidemiology, and End Results–Medicare database. The primary outcome of interest was the development of MHI (anxiety, major depressive disorder, depressive disorder not elsewhere classified, neurotic depression, adjustment disorder with depressed mood, and suicide) after the diagnosis of prostate cancer.ResultsA total of 10,389 men (20.4%) developed MHI during the study period. Independent risk factors for MHI included age≥75 years (hazard ratio [HR] = 1.29); higher comorbidity (Charlson comorbidity index≥3, HR = 1.63); rural hospital location (HR = 1.14); being single, divorced, or widowed (HR = 1.12); later year of diagnosis (HR = 1.05); and urinary incontinence (HR = 1.47). Black race (HR = 0.79), very high-income status (HR = 0.87), and definitive treatment (radical prostatectomy [RP], HR = 0.79; radiotherapy [RT], HR= 0.85, all P<0.001) predicted a lower risk of MHI. The rates of MHI at 10 years were 29.7%, 29.0%, and 22.6% in men undergoing watchful waiting (WW), RT, and RP, respectively.ConclusionOlder men with localized prostate cancer had a significant burden of MHI. Men treated with RP or RT were at a lower risk of developing MHI, compared with those undergoing WW, with median time to development of MHI being significantly greater in those undergoing RP compared with those undergoing RT or WW.