The AMPA receptor potentiator LY404187 increases cerebral glucose utilization and c-fos expression in the rat.

AMPA receptor potentiators enhance AMPA receptor-mediated glutamatergic neurotransmission and may have therapeutic potential as cognitive enhancers or antidepressants. The anatomical basis for the action of AMPA receptor potentiators is unknown. The aim of this study was to determine the effects of the biarylpropylsulfonamide AMPA receptor potentiator, LY404187 (0.05 to 5 mg/kg subcutaneously), upon cerebral glucose utilization and c-fos expression using 14C-2-deoxglucose autoradiography and c-fos immunocytochemistry. LY404187 (0.5 mg/kg) produced significant elevations in glucose utilization in 28 of the 52 anatomical regions analyzed, which included rostral neocortical areas and the hippocampus, as well the dorsal raphe nucleus, lateral habenula, and locus coeruleus. No significant decreases in glucose utilization were observed in any region after LY404187 administration. The increases in glucose utilization with LY404187 (0.5 mg/kg) were blocked by pretreatment with the AMPA receptor antagonist LY293558 (25 mg/kg), indicating that LY404187 acts through AMPA receptor-mediated mechanisms. LY404187 (0.5 mg/kg) also produced increases in c-fos immunoreactivity in the cortex, locus coeruleus, and the dorsal raphe nucleus. These studies demonstrate neuronal activation in key brain areas that are associated with memory processes and thus provide an anatomical basis for the cognitive enhancing effects of AMPA receptor potentiators.     

The angiotensin II type 1-receptor blocker candesartan increases cerebral blood flow, reduces infarct size, and improves neurologic outcome after transient cerebral ischemia in rats.

The goal of the present study was to test the impact of administration time of the angiotensin II type 1-receptor blocker candesartan on cerebral blood flow (CBF), infarct size, and neuroscore in transient cerebral ischemia. Therefore, 1-hour middle cerebral artery occlusion (MCAO) was followed by reperfusion. Rats received 0.5-mg/kg candesartan intravenously 2 hours before MCAO (pretreatment), 24 hours after MCAO, every 24 hours after MCAO, or 2 hours before and every 24 hours after MCAO. Infarct size (mm3) and a neuroscore at day 7 were compared with controls. CBF was quantified by radiolabeled microspheres and laser-Doppler flowmetry. Compared with controls (95 +/- 8), infarct size in candesartan-treated groups was smaller (59 +/- 5, 68 +/- 10, 28 +/- 3, and 15 +/- 3, respectively; P<0.05). Although there was no difference in neuroscore between pretreatment and controls (1.55 +/- 0.18, 1.80 +/- 0.13), other treatment regimens resulted in improved neuroscores (1.33 +/- 0.16, 1.11 +/- 0.11, 0.73 +/- 0.15; P<0.05). CBF in pretreated animals at 0.5 hours after MCAO was significantly higher than in controls (0.58 +/- 0.09 mL x g(-1) x min(-1) and 44% +/- 7% of baseline compared with 0.49 +/- 0.06 mL x g(-1) x min(-1) and 37% +/- 6%, microspheres and laser-Doppler flowmetry; P<0.05). Thus, candesartan reduces infarct size even if administered only during reperfusion. Apart from pretreatment, other treatment regimens result in significantly improved neuroscores. In the acute phase of cerebral ischemia, candesartan increases CBF.     

Differential Stripping: Determination of the Amount of Topically Applied Substances Penetrated into the Hair Follicles

The determination of penetration pathways of topically applied substances into the skin is the subject of several investigations. Recently, follicular penetration has become a major focus of interest. To date, a direct, non-invasive quantification of the amount of topically applied substance penetrated into the follicles had not been possible. The development of such a method was the aim of this study. Therefore, the advantages of both stripping techniques, tape stripping and cyanoacrylate skin surface biopsy, were combined and evaluated. Tape stripping was used to remove the part of the stratum corneum that contained the topically applied dye. Subsequently, the follicular contents were ripped off by cyanoacrylate skin surface biopsy. The combined method termed "differential stripping" was evaluated in vitro and in vivo , and the amount of topically applied fluorescent dye penetrated into the hair follicles was quantified after different penetration times. After 30 min, 5% of the recovered concentration of sodium fluorescein was found in the follicular infundibula, where it was still detectable after 48 h. Altogether, the results of this investigation revealed that differential stripping is a new method that can be used to study the penetration of topically applied substances into the follicular infundibula non-invasively and selectively.     

Patterns of eye care use and expenditures among children with diagnosed eye conditions.

PURPOSE: Little is known about use and expenditure patterns of children's eye-care services and about possible disparities in care among children. This report describes the use and expenditure patterns of eye care and non-eye care services for children under 18 years old in the United States. METHODS: Levels of use and expenditure were estimated using self-reported information from the nationally representative Medical Expenditure Panel Surveys (1996-2001) for 48,304 subjects under 18 years old from randomly selected households in the United States. Means presented for children with and without diagnosed eye conditions were adjusted for child and family characteristics using generalized linear models. RESULTS: Children with diagnosed eye conditions had higher levels of use and expenditure than children without diagnosed conditions. Families of children with diagnosed eye conditions incurred higher out-of-pocket expenditures. Black children and children living below 400% of the federal poverty level had lower levels of use and expenditure, indicating that they received fewer and less intensive services. CONCLUSIONS: Children with diagnosed eye conditions experienced higher overall use of health care. Some groups of children appear to be underserved. Estimates of use and expenditure patterns, stratified by socioeconomic factors, will be needed to plan for future delivery of children's eye and vision care services and to assess progress toward Healthy People 2010 goals.     

Preventing the airborne spread of Staphylococcus aureus by persons with the common cold: effect of surgical scrubs, gowns, and masks.

OBJECTIVE: Transmission of Staphylococcus aureus via air may play an important role in healthcare settings. This study investigates the impact of barrier precautions on the spread of airborne S. aureus by volunteers with experimentally induced rhinovirus infection (ie, the common cold). DESIGN: Prospective nonrandomized study. SETTING: Wake Forest University School of Medicine (Winston-Salem, NC).Participants. A convenience sample of 10 individuals with nasal S. aureus carriage selected from 593 students screened for carriage. INTERVENTION: Airborne S. aureus dispersal was studied in the 10 participants under the following clothing conditions: street clothes, surgical scrubs, surgical scrubs and a gown, and the latter plus a face mask. After a 4-day baseline period, volunteers were exposed to a rhinovirus, and their clinical course was followed for 12 days. Daily swabs of nasal specimens, pharynx specimens, and skin specimens were obtained for quantitative culture, and cold symptoms were documented. Data were analyzed by random-effects negative binomial models. RESULTS: All participants developed a common cold. Incidence rate ratios (IRRs) indicated that, compared with airborne levels of S. aureus during sessions in which street clothes were worn, airborne levels decreased by 75% when surgical scrubs were worn (P<.001), by 80% when scrubs and a surgical gown were worn (P<.001), and by 82% when scrubs, a gown, and a face mask were worn (P<.001). The addition of a mask to the surgical scrubs and gown did not reduce the airborne dispersal significantly (IRR, 0.92; P>.05). Male volunteers shed twice as much S. aureus as females (incidence rate ratio, 2.04; P=.013). The cold did not alter the efficacy of the barrier precautions. CONCLUSIONS: Scrubs reduced the spread of airborne S. aureus, independent of the presence of a rhinovirus-induced cold. Airborne dispersal of S. aureus during sessions in which participants wore surgical scrubs was not significantly different from that during sessions in which gowns and gowns plus masks were also worn.     

Work disability in adults with cystic fibrosis and its relationship to quality of life.

With increasing numbers of cystic fibrosis (CF) patients surviving to adulthood, issues related to vocation inevitably arise and warrant specific attention. We examined the percentage of participants with CF currently working and explored risk factors for work disability among adults with CF. METHOD: We recruited 50 consecutive patients from an adult cystic fibrosis service. Demographic, employment history, illness severity indicators and CF-attributed work disability factors were evaluated. Demographic risk factors for work disability using the illness severity measures of FEV(1), S-K score, CRDQ, and recent hospitalisation as independent variables were determined. RESULTS: Factorial analysis of a disability index (DI) indicated no dependency on FEV(1) or S-K score, but dependency on quality of life indices (p<0.05), age (p<0.05) and hospital admission rate (p<0.05). Hours worked per week were dependent on quality of life (p<0.01) (mastery of disease domain), fewer hospital admissions (p<0.01) and age (p<0.05). Sixty-eight percent of the sample reported that CF resulted in significant impediments to employment. However, few had sought vocational guidance (6%). CONCLUSION: Determinants of workforce participation shows that hours worked and perceived disability are more dependent on mastery of disease, age, and time in hospital, than on clinical severity scores. Health professionals may assist productivity through career counselling or tailored programs.