DMPP-evoked increases in postganglionic sympathetic nerve activity and blood pressure occurs by two mechanisms in the rat

1 Intravenous administration of the ganglionic nicotinic receptor agonist DMPP (1,1-dimethyl-4-phenylpiperazinium iodide) into urethane-anaesthetized rats evoked dose-dependent increases in mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). 2 The ganglionic nicotinic receptor antagonists pentolinium and hexamethonium either alone or combined did not inhibit the increase in RSNA and MAP evoked by 50 to 200 μg kg^?1 doses of DMPP. The increase in renal sympathetic nerve activity evoked by DMPP occurred as a brief burst in firing. 3 The increase in MAP, but not RSNA, evoked by DMPP in the presence of pentolinium was inhibited by the selective α₁-adrenergic receptor antagonist prazosin. 4 The non-selective α-adrenoceptor and NPY receptor antagonist benextramine also inhibited the increase in MAP without inhibiting the increase in RSNA. Surprisingly, the combination of benextramine and pentolinium, or benextramine and hexamethonium, completely blocked the DMPP-evoked increase in RSNA and thus the increase in MAP. 5 The uptake₁ antagonist desipramine combined with pentolinium did not affect the DMPP-evoked increases in MAP or RSNA when compared to the responses evoked in the presence of pentolinium alone. 6 Adding the selective M₁ muscarinic receptor antagonist telenzepine to pentolinium and prazosin did not inhibit the increase in RSNA evoked by a 100 μg kg^?1 dose of DMPP. 7 While the DMPP-evoked increase in MAP in the presence of ganglionic nicotinic receptor antagonists is primarily dependent upon activation of α₁-adrenoceptors, the increase in RSNA occurs via activation of ganglionic nicotinic receptors and activation of a mechanism susceptible to blockade by benextramine.     

Influence of Inhaled Corticosteroids and Dietary Intake on Bone Density and Metabolism in Patients With Moderate to Severe Asthma

Objectives Compare the effect of high doses of inhaled corticosteroids on bone loss in subjects with moderate to severe asthma or mild asthma, and examine the influence of dietary intake on bone metabolism. Design A survey on the effects of corticotherapy and nutrition on bone density was conducted in 74 subjects currently being treated for asthma in the asthma clinic of Hospital Laval (Sainte-Foy, Quebec, Canada). Fifty-eight subjects completed the study (attrition RATE=15%).

Main outcome measures In all subjects expiratory volumes were determined and urinary analysis was conducted for hydroxyproline, calcium, phosphorus, and cortisol levels. Osteocalcin, calcium, phosphorus, cortisol, alkaline phosphatase, and γ-glutamyltransferase levels were measured in blood samples. Bone density of the lumbar spine was determined by means of dual-energy x-ray absorptiometry. Nutrition evaluation was based on a 3-day food diary analyzed using progiciel Nutri 91. The nutritional parameters examined were calcium; phosphorus; magnesium; zinc; vitamins A, C, and D; protein; total fiber; oxalates; energy; caffeine; and alcohol in relation to bone density.

Subjects Thirty-one patients with moderate to severe asthma who had been taking more than 1,000 μg beclomethasone per day or the equivalent for more than 2 years and 27 patients with mild asthma who were taking less than 500 μg beclomethasone per day or the equivalent.

Statistical analyses performed Four factor analysis of variance with hierarchized interactions of four levels, Duncan's test, Pearson correlation coefficients.

Results Blood levels of osteocalcin and protein intake were lower in patients with moderate to severe asthma than in those with mild asthma (P<.05). Significant correlations (P<.02) were observed between bone density and calcium intake (r=.40), phosphorus intake (r=.35), protein intake (r=.30), and serum alkaline phosphatase level (r=−.30). Bone density was not significantly different between the two groups of patients with asthma.

Applications A follow-up of patients with asthma who are taking inhaled corticosteroids is needed to assess bone density, osteocalcin levels, and dietary intakes of calcium. Verify if osteocalcin level decreases over time in patients with moderate to severe asthma, monitor possible modifications in bone density, and verify if the correlation between dietary calcium and bone density is maintained. J Am Diet Assoc. 1997;97:1401–1406.     

Functional MR of the primary auditory cortex: an analysis of pure tone activation and tone discrimination.

PURPOSETo use functional MR imaging to measure the effect of frequency (pitch), intensity (loudness), and complexity of auditory stimuli on activation in the primary and secondary auditory cortexes.METHODSMultiplanar echo-planar images were acquired in healthy subjects with normal hearing to whom auditory stimuli were presented intermittently. Functional images were processed from the echo-planar images with conventional postprocessing methods. The stimuli included pure tones with a single frequency and intensity, pure tones with the frequency stepped between 1,000, 2,000, 3,000, or 4,000 Hz, and spoken text. The pixels activated by each task in the transverse temporal gyrus (TTG) and the auditory association areas were tabulated.RESULTSThe pure tone task activated the TTG. The 1,000-Hz tone activated significantly more pixels in the TTG than did the 4,000-Hz tone. The 4,000-Hz tone activated pixels primarily in the medial TTG, whereas the 1,000-Hz tone activated more pixels in the lateral TTG. Higher intensity tones activated significantly more pixels than did lower intensity tones at the same frequency. The stepped tones activated more pixels than the pure tones, but the difference was not significant. The text task produced significantly more activation than did the pure tones in the TTG and in the auditory association areas. The more complex tasks (stepped tones and listening to text) tended to activate more pixels in the left hemisphere than in the right, whereas the simpler tasks activated similar numbers of pixels in each hemisphere.CONCLUSIONAuditory stimuli activate the TTG and the association areas. Activation in the primary auditory cortex depends on frequency, intensity, and complexity of the auditory stimulus. Activation of the auditory association areas requires more complex auditory stimuli, such as the stepped tone task or text reading.     

Repeated survey on changes in musculoskeletal complaints relative to age and work demands.

OBJECTIVES: To examine changes in musculoskeletal complaints over four years in groups of employees relative to age and work demands. METHODS: Repeated questionnaire data of male employees in heavy physical work (exposed group, n = 7324) and mental work (control group, n = 4686), stratified for age (20-9, 30-9, 40-9, 50-9), were analysed. For each employee, data on the occurrence of musculoskeletal complaints from two surveys with a mean interval of around four years were available. Changes in prevalences over the follow up interval were analysed. Proportions of new, recovered, and chronic cases as well as those free of complaints at both surveys were studied. RESULTS: For most complaints, there were significantly greater increases in prevalences in the exposed group compared with the control group over the follow up interval particularly within the group aged 40-9 for back, neck, and several sites of the upper and lower limbs. The 20-9 year age group also had significantly greater changes for several musculoskeletal complaints. Within the oldest age group (50-9) exposure to heavy physical work demands only affected changes in prevalences of neck and upper arm complaints. After four years in the cohort free of complaints at the start of the follow up the group aged 40-9 had the highest prevalence of complaints of the back, neck, and the upper and lower limbs. CONCLUSIONS: Middle aged and younger employees develop musculoskeletal complaints as a result of exposure to heavy physical work. In the oldest age group health related selection seems to mask the occupational health risks under study. To prevent the expected increase in musculoskeletal disorders and related work disability in our aging workforce, preventive measures should be taken at all stages of a working life.     

Regulation of fibroblast-induced collagen gel contraction by interleukin-1β

Fibroblasts incorporated within collagen gels induce a cell-mediated contraction of the gel to form a three-dimensional, tissue-like structure by a mechanism thought to mimic wound contraction in vivo . In this study a gel contraction model was used to investigate the ability of fibroblasts derived from adult gingiva, adult skin and fetal skin to organise a collagen matrix. In addition the effects of interleukin-1β (IL-1β) on the contraction process was also investigated. Over the concentration range 5-50 U/ml, IL-1β induced a statistically significant inhibition of gel contraction in all fibroblast cell types ( P <0.05), although fetal fibroblasts appeared least responsive and gingival fibroblasts most responsive to the inhibitory effects of this cytokine. Comparison of gel contraction by the different fibroblast strains indicated that fetal and gingival fibroblasts shared similar contraction kinetics. For the adult skin fibroblasts, three of five strains studied showed significantly diminished levels of gel contraction compared to fetal and gingival cells. This apparent difference in fibroblast phenotype may, at least in part, explain the fetal-like wound healing pattern seen in the oral mucosa.