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At least 811 records · Page 45Linked to original sources
PubMed2004

Cerebral neutrophil recruitment, histology, and outcome in acute ischemic stroke: an imaging-based study.

BACKGROUND AND PURPOSE: Evidence now exists for a pathogenic role for neutrophils in acute cerebral ischemia. We have studied the patterns and temporal profile of cerebral neutrophil recruitment to areas of acute ischemic stroke (IS) and have attempted to correlate this with neurological status and outcome. METHODS: Patients with cortical middle cerebral artery (MCA) IS were recruited within 24 hours of clinical onset. Neutrophil recruitment was studied using indium-111 (111In) troponolate-labeled neutrophils, planar imaging, and single-photon emission computed tomography (SPECT). Volume of brain infarction was calculated from concurrent computed tomography (CT). Hematoxylin and eosin sections were obtained postmortem (n=2). Outcome was measured using Barthel, Rankin, and National Institute of Health Stroke (NIHSS) scales. RESULTS: Fifteen patients were studied. Significant 111In-neutrophil recruitment to ipsilateral hemisphere, as measured by asymmetry index (AI), was demonstrated within 24 hours of onset in 9 patients; this response was heterogenous between patients and on repeated measurement attenuated over time. Histologically, recruitment was confirmed within intravascular, intramural, and intraparenchymal compartments. Interindividual heterogeneity in neutrophil response did not correlate with infarct volume or outcome. In an exploratory analysis, neutrophil accumulation appeared to correlate significantly with infarct expansion (Spearman rho=0.66; P=0.03, n=12). CONCLUSIONS: Neutrophils recruit to areas of ischemic brain within 24 hours of symptom onset. This recruitment attenuates over time and is confirmed histologically. While neutrophil accumulation may be associated with either the magnitude or the rate of infarct growth, these results require confirmation in future studies.

Brain Ischemia↗
PubMed2006

Oximetry-guided reoxygenation improves neurological outcome after experimental cardiac arrest.

BACKGROUND AND PURPOSE: Current guidelines suggest that cardiac arrest (CA) survivors should be ventilated with 100% O(2) after resuscitation. Breathing 100% O(2) may worsen neurological outcome after experimental CA. This study tested the hypothesis that graded reoxygenation, with oximetry guidance, can safely reduce FiO(2) after resuscitation, avoiding hypoxia while promoting neurological recovery. METHODS: Mature dogs underwent 10 minutes of CA and restoration of spontaneous circulation with 100% O(2.) Animals were randomized to 1-hour additional ventilation on 100% FiO(2) or to rapid lowering of arterial O(2) saturation to <96% but >94% with pulse oximeter guidance. Animals were awakened at hour 23, and the neurological deficit score (0=normal; 100=brain-dead) was measured. Reanesthetized animals were perfusion-fixed and the brains removed for histopathology. RESULTS: The neurological deficit score was significantly better in oximetry (O) dogs. O dogs appeared aware of their surroundings, whereas most hyperoxic (H) animals were stuporous (neurological deficit score=43.0+/-5.9 [O] versus 61.0+/-4.2 [H]; n=8, P<0.05). Stereological analysis revealed fewer injured CA1 neurons in O animals (cresyl violet: 35.5+/-4.3% [O] versus 60.5+/-3.3% [H]; P<0.05). There were also fewer fluoro-Jade B-stained degenerating CA1 neurons in O animals (3320+/-267 [O] versus 6633+/-356 [H] per 0.1 mm(3); P<0.001). CONCLUSIONS: A clinically applicable protocol designed to reduce postresuscitative hyperoxia after CA results in significant neuroprotection. Clinical trials of controlled normoxia after CA/restoration of spontaneous circulation should strongly be considered.

Animals↗
PubMed2003

The relation between the clinical subtypes of delirium and the urinary level of 6-SMT.

Delirium is a common syndrome among hospitalized elderly patients. In humans, sleep and circadian rhythms are disturbed during delirium, and both are influenced by the hormone melatonin. This prompted us to investigate the relationship of the clinical subtypes of delirium: 1). hyperactive, 2). hypoactive, and 3). mixed, with melatonin, as reflected by a patient's urinary metabolite 6-SMT. Results support our hypothesis that urinary 6-SMT during delirium was higher in hypoactive and lower in hyperactive patients. Because this is the first time a biochemical parameter related to the clinical subtypes of delirium has been reported, further research on the link between melatonin and delirium is necessary.

Aged↗
PubMed2005

Concomitant cyclosporine and micafungin pharmacokinetics in healthy volunteers.

Cyclosporine is a marketed immunosuppressive agent and a known substrate for CYP3A. Micafungin is an antifungal agent and a mild inhibitor of CYP3A-mediated metabolism in vitro. The objectives of this study were to evaluate the pharmacokinetics of cyclosporine and micafungin before and with concomitant administration. The pharmacokinetics of single-dose oral cyclosporine (5 mg/kg) were estimated on days 1, 9, and 15 (n = 27). Subjects received micafungin (100 mg/d over 1 hour) on days 7, 9, and 11 through 15. Micafungin pharmacokinetics were estimated on days 7, 9, and 15. Mean apparent oral cyclosporine clearances were estimated to be 645+/-236 mL/h/kg, 546+/-101 mL/h/kg (P = .01), and 540+/-104 mL/h/kg (P = .02) for days 1, 9, and 15, respectively. Micafungin appears to be a mild inhibitor of cyclosporine metabolism.

Adult↗
PubMed1985

Treatment of vaginal candidosis using clotrimazole vaginal cream: single dose versus 3-day therapy.

The effect of using a single dose of 10% clotrimazole cream was compared with that of using a twice-daily application of 2% clotrimazole cream for 3 days in 111 women with mycologically proven vaginal candidosis. The results, analyzed for 55 patients in each group, showed that 1 week after starting treatment, negative cultures were recorded for 91% of the patients who received single-dose therapy and 96% of patients treated with the 3-day regimen. Five weeks after treatment started, the figures were 84% and 81%, respectively, showing that both regimens were equally effective. No adverse events were recorded for either preparation.

Administration, Topical↗
PubMed2006

Pulmonary vasoconstrictor action of KCNQ potassium channel blockers.

BACKGROUND: KCNQ channels have been widely studied in the nervous system, heart and inner ear, where they have important physiological functions. Recent reports indicate that KCNQ channels may also be expressed in portal vein where they are suggested to influence spontaneous contractile activity. The biophysical properties of K+ currents mediated by KCNQ channels resemble a current underlying the resting K+ conductance and resting potential of pulmonary artery smooth muscle cells. We therefore investigated a possible role of KCNQ channels in regulating the function of pulmonary arteries by determining the ability of the selective KCNQ channel blockers, linopirdine and XE991, to promote pulmonary vasoconstriction. METHODS: The tension developed by rat and mouse intrapulmonary or mesenteric arteries was measured using small vessel myography. Contractile responses to linopirdine and XE991 were measured in intact and endothelium denuded vessels. Experiments were also carried out under conditions that prevent the contractile effects of nerve released noradrenaline or ATP, or block various Ca2+ influx pathways, in order to investigate the mechanisms underlying contraction. RESULTS: Linopirdine and XE991 both contracted rat and mouse pulmonary arteries but had little effect on mesenteric arteries. In each case the maximum contraction was almost as large as the response to 50 mM K+. Linopirdine had an EC50 of around 1 microM and XE991 was almost 10-fold more potent. Neither removal of the endothelium nor exposure to phentolamine or alpha,beta-methylene ATP, to block alpha1-adrenoceptors or P2X receptors, respectively, affected the contraction. Contraction was abolished in Ca2+-free solution and in the presence of 1 microM nifedipine or 10 microM levcromakalim. CONCLUSION: The KCNQ channel blockers are potent and powerful constrictors of pulmonary arteries. This action may be selective for the pulmonary circulation as mesenteric arteries showed little response. The results imply that the drugs act directly on smooth muscle cells and contraction requires voltage-dependent Ca2+ influx. It is concluded that the drugs probably act by blocking KCNQ channels in pulmonary artery myocytes, leading to membrane depolarization and Ca2+ influx through L-type Ca2+ channels. This implies a functional role for KCNQ channels in regulating the resting membrane potential of pulmonary artery myocytes.

Animals↗
PubMed2006

Psychiatric services utilization in completed suicides of a youth centres population.

BACKGROUND: From a retrospective study of youth centres (YCs) and coroner's files, we investigated youths' history of medical service utilization who died by suicide. This is the second of two papers on YCs population, the first paper having shown that the rate of psychopathology was higher in the YCs population compared to the general adolescent population. METHODS: From 1995 to 2000, 422 youths, aged 18 years and younger, died as a result of suicide in Quebec. More than one-third received services from YCs at some point. Using the provincial physician payment and hospitalization database, we examined physical and psychiatric service utilization according to time intervals, as well as hospitalization for psychiatric reasons in the individuals' lifetime and in the year preceding suicide. Suicides were matched to living YCs youths for age, sex, and geographic area. YCs controls were then subdivided into two groups based on file information pertaining to the presence or absence of suicidal behavior or ideation. RESULTS: Compared to living YCs youths, suicides had a higher rate of psychiatric service utilization in the week, month, 90 days, and year preceding suicide, as well as higher levels of lifetime hospitalization for psychiatric reasons than controls with or without a history of suicidal behavior or ideation. We found that 28.3% YCs suicides made use of psychiatric services in the year preceding suicide. CONCLUSION: The rate of psychiatric service utilization by YCs youth suicides is substantially inferior to the needs of this population. Our study underscores the need for appropriate recognition of psychiatric and suicidal problems among YCs population by social and psycho-educational professionals. At the same time, it highlights the issues of general practitioners' risk identification, psychiatric referral and treatment. Our findings suggest the need for improved organization and coordination of psychiatric services to ameliorate treatment delivery.

Adolescent↗
PubMed2006

The lectin jacalin plus costimulation with anti-CD28 antibody induces phosphorylation of p38 MAPK and IL-4 synthesis-I.

Costimulatory signals play an important role in the development of T helper cell type 1 (Th1) or Th2 type. Little is known about jacalin plus CD28-mediated signaling and cytokine secretion. In the present study, we analyzed the intracellular signaling events following stimulation of CD4+ T cells with jacalin plus CD28 cross-linking (CD28XL) with anti-CD28 antibody. Our results indicate enhanced phosphorylation of Tec and linker for activation of T cells when compared with stimulation with jacalin alone or CD28XL alone. Stimulation with jacalin or CD28XL appears to be insufficient to induce interleukin (IL)-4 secretion; however, CD28XL followed by stimulation with jacalin resulted in enhanced phosphorylation of p38 mitogen-activated protein kinase (MAPK) and increased secretion of IL-4. However, compared with stimulation with phorbol 12-myristate 13-acetate plus ionomycin, jacalin plus CD28XL resulted in decreased levels of tumor necrosis factor alpha secretion. Addition of p38 inhibitor, SB203580, inhibited p38 phosphorylation and IL-4 secretion. These data suggest that jacalin stimulation alone appears to be insufficient for Th2 development, and addition of CD28 costimulation induced Th2 generation. We propose that jacalin plus CD28XL induces Th2 differentiation via activation of p38 MAPK.

Antibodies↗
PubMed2006

p38 MAPK plays a role in IL-4 synthesis in jacalin plus CD28-stimulated CD4+ T cells--II.

We have previously shown that jacalin, a CD4+ T cell lectin, induces phosphorylation of intracellular events, moderate levels of interleukin (IL)-2 secretion. We have also shown that in the presence of CD28 costimulation, jacalin induces IL-4 secretion. In the present study, we showed that stimulation of normal CD4+ T cells with jacalin plus CD28 cross-linking (CD28XL) resulted in phosphorylation of signal transducer and activator of transcription (STAT)-6 and expression of Bcl-2 and Bcl-xL, which were inhibited significantly when cells were cultured in the presence of the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580. We further generated jacalin-induced CD4+ T cell blasts, examined the effects of CD28XL, and observed enhanced up-regulation of p38 and activation of STAT-6, Bcl-2, and Bcl-xL. Engagement of CD28 alone induced a marked degree of phosphorylation of p38 MAPK and IL-4 secretion in memory T cells (jacalin blasts), whereas in naïve T cells, jacalin plus CD28XL was required to induce these molecules. Incubation of cells with p38 inhibitor prior to CD28XL resulted in down-modulation of all these molecules. Further treatment with IL-4 has not reversed this trend. Our studies imply that p38 MAPK may play an important role in induction of these molecules and a putative role in protecting cells from undergoing apoptosis.

Antibodies, Monoclonal↗