Transport mechanism of L-[14C]glutamate in cortical slices and synaptosomes of rabbits exposed to brain ischemia and reperfusion

Molecular and chemical neuropathology - Changes in the functioning of the glutamatergic system in rabbit brain were studied after partial brain ischemia and reperfusion. In vitro studies were...     

Lipid nanoparticles for skin penetration enhancement-correlation to drug localization within the particle matrix as determined by fluorescence and parelectric spectroscopy.

With topical treatment of skin diseases, the requirement of a high and reproducible drug uptake often still is not met. Moreover, drug targeting to specific skin strata may improve the use of agents which are prone to cause local unwanted effects. Recent investigations have indicated that improved uptake and skin targeting may become feasible by means of nanoparticular systems such as solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and nanoemulsions (NE). Here we describe techniques to characterize drug loading to carrier systems and skin penetration profiles by using the lipophilic dye nile red as a model agent. Since the mode of drug association with the particle matrix may strongly influence the efficiency of skin targeting, parelectric spectroscopy (PS) was used to differentiate between matrix incorporation and attachment to the particle surface and fluorescence spectroscopy (FS) to solve dye distribution within NLC particles. Nile red was incorporated into the lipid matrix or the covering tensed shell, respectively, of SLN and NLC with all the lipids studied (Compritol, Precirol, oleic acid, Miglyol). In NLC, the dye was enriched in the liquid phase. Next, nile red concentrations were followed by image analysis of vertical sections of pigskin treated with dye-loaded nanoparticular dispersions and an oil-in-water cream for 4 and 8 h in vitro. Following the SLN dispersions, dye penetration increased about fourfold over the uptake obtained following the cream. NLC turned out less potent (相似文献   

Influence of pain and urinary symptoms on quality of life in young men with chronic prostatitis-like symptoms

BACKGROUND: Our aims in the present study were to estimate the influences of pain and urinary symptoms on quality of life, and to determine which of these two variables has the most predictive power with respect to quality of life in young men with chronic prostatitis-like symptoms. METHODS: Chronic prostatitis-like symptoms were measured by the National Institutes of Health-Chronic Prostatitis Symptom Index. Of the 28,841 men aged 20 years who lived in the study community, 18,495 men (a response rate 64.1%) agreed to participate in the study. A total of 1057 men who complained of symptoms indicative of chronic prostatitis were included in the study. The influences of pain and urinary symptoms on quality of life were determined using logistic regression analysis. The receiver operating characteristic (ROC) curve was used to estimate the predictive ability of each of these variables with respect to quality of life. RESULTS: Results from multivariate analysis showed that both pain and urinary symptoms were associated with an increased likelihood of impaired quality of life, although pain contributed more to a reduced quality of life than urinary symptoms. Relative to men who experienced mild pain, men who experienced moderate pain had a 3.9-fold risk of poor quality of life (odds ratio [OR], 3.87; 95% confidence interval [CI], 2.86-5.23; P < 0.001) and those who experienced severe pain had a 15.7-fold risk of reduced quality of life (OR, 15.68; 95% CI, 6.59-37.35; P < 0.001). Moderate urinary symptoms were associated with a 1.4-fold risk of bother (OR, 1.41; 95% CI, 1.01-1.99; P < 0.001) and severe urinary symptoms were associated with 2.4-fold risk (OR, 2.39; 95% CI, 1.37-4.12; P < 0.001), relative to mild urinary symptoms. Comparison of the effects of pain and urinary symptoms showed that pain severity had the most predictive power for bother, quality of life, and quality-of-life impact. The areas under the ROC curves for bother, quality of life, and quality-of-life impact were 71.3%, 69.3% and 72.5%, respectively. CONCLUSION: Urinary symptoms and pain might be associated with an increased likelihood of impaired quality of life in young men with chronic prostatitis-like symptoms. In addition, our findings suggest that pain severity is the most influential variable for determining quality of life in this population.     

Experimental isobaric subarachnoid hemorrhage: regional mitochondrial function during the acute and late phase

Patients treated for aneurysmal subarachnoid hemorrhage show, in the long-term follow up, an elevated rate of cognitive disturbances that are mainly related to the impact of the initial bleeding: the neurotoxic effects of blood deposition in subarachnoidal spaces may result in a diffuse encephalopathy, but the intrinsic mechanism and the biochemical correlates are not known. In the present study we have evaluated mitochondrial function after experimental induction of subarachnoid hemorrhage. Mitochondrial function was evaluated in four different rat brain areas (frontal cortex, occipital cortex, hippocampus, and brain stem) after experimental isobaric subarachnoid hemorrhage in rats. Subarachnoid hemorrhage was induced by injecting 0.07 mL of arterial autologous blood into the cisterna magna. Intracranial pressure did not significantly increase. The nonsynaptic mitochondrial fraction was isolated from different rat brain areas, and the maximal rate of enzymatic reactions of some key enzymatic activities related to the Krebs cycle [nicotinamide adenine dinucleotide (oxidized form) (NAD+)-isocitrate dehydrogenase, citrate synthase, and succinate dehydrogenase] and of the electron transfer chain (cytochrome oxidase) were evaluated. The nonsynaptic mitochondrial fraction was utilized also to check parameters related to the mitochondrial respiration: state 3, state 4, uncoupled state, respiratory control ratio, and adenosine 5'-diphosphate/oxygen ratio. The biochemical parameters were measured at 1 and 72 hours after the subarachnoidal injection of blood. Subarachnoid hemorrhage did not affect the mitochondrial enzymatic activities both at 1 and 72 hours, while the mitochondrial enzymatic activities parameters were significantly affected: in particular, a significant decrease of respiratory control ratio in all tested brain areas was demonstrated. The increased mitochondrial vulnerability in the delayed phases could be one of the biochemical correlates of post-hemorrhagic encephalopathy.     

Adrenal function under long-term raloxifene administration.

The aim of the present study was to evaluate the effect of long-term (12 months) administration of raloxifene hydrochloride (60 mg/day) on the steroid production of the adrenal cortex and on the hypothalamic-pituitary-adrenal axis in postmenopausal women. We performed a basal evaluation, a corticotropin releasing factor (CRF) (100 microg i.v. bolus) test and a dexamethasone (DXM) (0.25 mg) suppression-adrenocorticotropic hormone (ACTH) (10 microg i.v. bolus) stimulation test in 11 postmenopausal women, before and after 3, 6 and 12 months of raloxifene treatment. Raloxifene administration significantly modified circulating levels of adrenal steroids, decreasing cortisol (-24%), dehydroepiandrosterone (DHEA) (-36%), and its sulfate (DHEAS) (-41%), and androstenedione (-29%), and increasing circulating allopregnanolone (+39%) levels. Progesterone and 17OH-progesterone levels remained unmodified, while estradiol and estrone levels showed a significant decrease (-51% for estradiol and -61% for estrone). We also observed an increase in circulating ACTH (+58%) and beta-endorphin (+120%). No modifications in the hormonal responses to CRF were observed during the treatment. DXM significantly suppressed circulating steroids at any time with a lower suppression of cortisol from the third month and a higher suppression of DHEA at 12 months. ACTH administration was associated with a significantly blunted cortisol response from the sixth month and a significantly increased response of allopregnanolone from the third month. The present data exclude a raloxifene effect on pituitary sensitivity to CRF and demonstrate a reduced adrenal sensitivity to ACTH, sustained by the opposite changes in basal cortisol and Delta5 androgens, which were reduced, and in ACTH and beta-endorphin, which were increased, as well by the reduced response of cortisol to the direct ACTH stimulus. The reduction of circulating cortisol levels and cortisol response to the ACTH challenge suggests that raloxifene protects against the neurotoxic effects of endogenous glucocorticoids. Furthermore, the progressive increase in basal allopregnanolone and its increased response to ACTH indicate that chronic raloxifene administration exerts direct effects on the pattern of adrenal enzymes, leading to specific changes in the circulating levels of this anxiolytic progesterone metabolite. The important reduction in the circulating levels of estradiol and estrone under long-term raloxifene administration may represent a further mechanism by which this molecule may exert a protective effect against breast and endometrial malignancies.