School health talks. Update 1998.
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Adolescent↗
Biomedical subjects
D Platt
Publications and source records attributed to D Platt.
IL-1 beta induces the degradation of equine articular cartilage by a mechanism that is not mediated by nitric oxide.
Proteoglycan degradation was induced in young equine articular cartilage explants cultured for eight days in the presence of 50 ng/ml recombinant human interleukin-1 beta. Degradation was initiated after 6 hours of exposure to the cytokine. This was accompanied by an induction of nitric oxide synthesis and a decrease in the incorporation of [36S]sulphate into the glycosaminoglycan chains of proteoglycans. The addition of 1mM N-iminoethyl-L-ornithine (an inhibitor of nitric oxide synthase) to the explant cultures in the presence of rhIL-1 beta suppressed the synthesis of NO and restored proteoglycan synthesis to control levels. However, treatment of explants with LNIO did not overcome proteoglycan degradation. These results indicate that although IL1 beta regulates both proteoglycan synthesis and degradation in equine cartilage explants, only the inhibition of proteoglycan synthesis is mediated by nitric oxide.
Animals↗
Increased expression of microtubule-associated protein 1B in the hippocampus, subiculum, and perforant path of rats treated with a high dose of pentylenetetrazole.
A single administration of the convulsant pentylenetetrazole (PTZ) initiates a complex pattern of long-term changes in microtubule-associated protein 1B (MAP1B) expression across the hippocampal formation. Using Northern blot and in situ hybridization we show that the first increases in MAP1B mRNA were detected at 15 h following PTZ administration in the granule cells of the dentate gyrus and CA3 region of the hippocampus and reached a maximum at 44 h. The levels of MAP1B mRNA in the subiculum peaked at later times (5 days). At 72 h MAP1B immunoreactivity was mainly localized in the granule-cell bodies and dentate inner and midmolecular layer as well as in neuronal cell bodies and the stratum lucidum, including the mossy fiber pathway of the CA3 region. By 5-10 days the levels of MAP1B in the pyramidal cells in the CA3 region decreased to very low levels; rather, heavy staining of interneuron-like cells and "strings-of-bead" structures all over the hippocampus and at the stratum oriens/alveus border were seen. The levels of MAP1B in the hippocampus returned to control levels by 20 days after PTZ administration. MAP1B immunoreactivity in the alvear path was also evident at 5 days postinjection at the CA1/alveus border. The intensity of MAP1B staining increased gradually in the perforant path starting at 72 h and persisted at high levels until day 35. Our studies show that (i) MAP1B is a temporal and regional marker for rapid and acute epileptic seizures and (ii) long-term increases in MAP1B in the perforant path might play a role in PTZ-induced seizures.
Animals↗
The relationship between endothelin-1, event-related P300 potentials, and prognosis in cerebral arteriosclerosis.
OBJECTIVES: To search for a potential role of endothelin-1 (ET-1), a potent vasoconstrictor and presumably neurotoxic 21-amino acid peptide, for dysfunction of brain signal processing and cerebrovascular morbidity in nondemented patients with cerebral arteriosclerosis. DESIGN: Cross-sectional study with longitudinal follow-up. SETTING: University-affiliated teaching hospital. PARTICIPANTS: A total of 106 nondemented patients with significant stenosis of either the internal carotid (cAD, cases; n = 63, mean age +/- SD, 62 +/- 7 years) or peripheral arteries (pAD, disease controls; n = 43, 60 +/- 11 years) were investigated before carotid endarterectomy and bypass surgery, respectively. After a mean follow-up of about 19 months, cerebrovascular morbidity of the cAD and pAD patients was evaluated by phone. MEASUREMENTS: Brain signal processing functions by event-related visual P300 potentials; cerebrovascular events by a structured telephone interview; the extent of arteriosclerosis by venous ET-1 concentration. RESULTS: Venous ET-1 levels were elevated in both cAD and pAD patient groups, but to the same degree. In these patients, ET-1 concentration was correlated slightly with diastolic blood pressure (r = .334, P = .0326, stepwise regression). Only in cAD patients with ET-1 levels above the 75th percentile were P300 latencies markedly prolonged compared with their lower ET-1 level counterparts. Furthermore, the P300 latencies of the cAD patients, but not of the pAD patients, correlated positively with venous ET-1 concentration and inversely with pack years of smoking (r = .728, P = .0002; stepwise regression). In contrast to base-line P300 abnormalities and classical risk factors (e.g., hypertension), high ET-1 levels predicted an increased cerebrovascular morbidity of cAD, but not of pAD, patients (P = .0044; Mantel Cox test). CONCLUSIONS: In nondemented patients with cerebral arteriosclerosis, endothelin-1 is associated with P300 abnormalities reflecting subclinical dysfunction of brain signal processing. In the long-term, high venous ET-1 levels also appear to predict a higher cerebrovascular morbidity of cAD patients even after carotid endarterectomy.
Aged↗
Chronic tenosynovitis of the carpal extensor tendon sheaths in 15 horses.
The history, clinical features, radiological findings, treatment and outcome of 15 horses with chronic tenosynovitis of the carpal extensor tendon sheaths are reported. The condition was seen most commonly in horses used for jumping and penetration of the tendon sheaths by thorns was the most common aetiology. Treatment involved surgical resection of the hyperplastic synovial membrane, and adhesions within the tendon sheath, with primary closure. When combined with early postoperative physiotherapy this was found to be an effective method of treatment. All horses in this series were not lame at follow-up, with 14 horse returning to their former level of athletic performance.
Animals↗
In vitro antifungal activity of CAN-296: a naturally occurring complex carbohydrate.
The in vitro activity of a naturally occurring complex carbohydrate, CAN-296, was evaluated by testing 132 clinical and ATCC isolates of yeast and Aspergillus fumigatus, many of which were azole-resistant. The in vitro susceptibility tests were performed by standardized broth micro- and macrodilution methods and results were compared with those obtained for amphotericin B, fluconazole, ketoconazole, flucytosine and the pneumocandin L-733,560. All tested Candida species showed highly uniform susceptibility to CAN-296 at concentrations of 0.078 to 0.312 microgram/ml; non-albicans Candida were as susceptible to CAN-296 as the Candida albicans strains. Multi-azole-resistant Candida species were highly sensitive to CAN-296. Minimum inhibitory concentration measurements did not differ from minimum lethal concentrations by more than two-fold for all tested Candida species. Aspergillus fumigatus, on the other hand, showed only moderate susceptibility to CAN-296. The kinetics of the anti-Candida activity of CAN-296 was investigated by kill-curve experiments using C. albicans and C. glabrata and the results were compared with those obtain for amphotericin B. CAN-296 was found to be rapidly fungicidal in concentrations ranging from 4-16 fold the mean MIC value. The broad spectrum of anti-Candida activity together with the rapid fungicidal effect make this complex carbohydrate a promising agent for clinical use.
Antifungal Agents↗
School health talks and doctor/lawyer talks update 1997.
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Adolescent↗
V+ fibronectin mRNA is increased in the brains of aged rats: effect of food restriction.
Food restriction increases life-span in rodents. With regard to the central nervous system, underfeeding has been shown to have beneficial effects on synaptic transmission in old rats. However, the molecular events underlying functional changes in the brains of food-restricted rats are largely unknown. In the present study the levels of fibronectin mRNA containing the alternatively spliced segment V (FN-V+) as well as the levels of FN mRNA containing the alternatively spliced segment EIIIB (FN-EIIIB+), were examined by RNA gel blot hybridization in the brains of 3-day-old, 24-day-old, 10-month-old, 18-month-old, 30-month-old ad libitum (AL) fed, 30-month-old food-restricted (FR), and 35-37-month-old, FR rats. The hybridization signal for the FN-EIIIB+ mRNA was relatively abundant at early postnatal stages but very few transcripts were detected in the brains of adult, AL rats. The transcripts coding for FN-V+ mRNA were moderately expressed in the brains of 3-day-old, 24-day-old, 10-month-old, and 18-month-old rats. However, the FN-V+ mRNA signal was then prominently increased (approx. 3-fold) in the brains of the 30-month-old, AL rats vs. 10-month-old, AL rats, and further increased (approx. 2-fold) in the brains of 30-month-old, FR, as compared to 30-month-old, AL rats. However, the levels of FN-V+ mRNA were slightly decreased in the brains of very old (35-37-month) FR rats vs. 30-month-old FR rats. The distribution of fibronectin messenger RNA and protein was also investigated by non-radioactive in situ hybridization and immunohistochemistry, respectively. The most prominent expression of FN-V+ messenger RNA was seen in neurons of the hippocampus, including the granule cells of the dentate gyrus, and in layers III and V of the cortex of 30-month-old, FR rats. FN immunostaining closely paralleled the distribution of FN mRNA and was confined to the neuronal cell periphery. The upregulation of fibronectin gene expression upon exposure to glucocorticoids is well documented. Prolonged food restriction, acting as a stress factor, combined with decreased plasticity of glucocorticoid regulatory responses in the aged rats could cause an increase in the levels of FN mRNA and protein in the brains of old, FR rats. Since FN has been shown to provide an adhesive substrate for extending neurites, we conclude that food restriction may potentiate synaptic plasticity, via glucocorticoid receptor binding elements of the FN gene, in the brains of old rats.
Aging↗
Influence of age, frailty and liver function on the pharmacokinetics of brofaromine.
OBJECTIVE: The pharmacokinetics of brofaromine, a selective inhibitor of monoamine oxidase A, was evaluated in 12 frail elderly patients (66-92 y) and 12 healthy volunteers (20-35 y). METHODS: Quantitative liver function tests were performed to show whether brofaromine elimination in the elderly could be predicted from noninvasive assessment of CYP1A2 activity (caffeine clearance) or liver plasma flow (sorbitol clearance). RESULTS: In the elderly the AUC of brofaromine was significantly increased (e.g. for the 75 mg dose 43.2 vs 19.9 mumol*h.l-1, clearance was reduced (5.0 vs. 11.8 l.h-1), the volume of distribution was smaller (130 vs. 230 l), and the half-life was slightly increased (19.0 vs. 14.2 h). No significant correlation was observed between hepatic plasma flow and brofaromine clearance (r = 0.41, P = 0.05), whereas CYP1A2 activity and brofaromine clearance were tightly correlated (r = 0.94, P < 0.0001). CONCLUSION: Caffeine clearance, a simple, noninvasive test of CYP1A2 activity, is predictive of brofaromine clearance.
Administration, Oral↗
Age-related dynamics of cognitive brain functions in humans: an electrophysiological approach.
Event-related P300 potentials closely reflect cognitive functions such as stimulus discrimination (N250) and processing time (P300 latencies) as well as attention capabilities (P300 amplitudes). To delineate the age-related dynamics of P300 potentials, we investigated 250 healthy subjects between 18 and 98 years of age in a cross-sectional study. A total of 330 visual P300 tests was performed in two different paradigms (PI, passive condition, n = 80; PII, active condition, n = 250). In both P300 paradigms, the N250 and P300 latencies were markedly prolonged (p < .0001) in older age, whereas the N250 and P300 latency differences between PII and PI did not change (p > .05). The P300 amplitudes in paradigm I and II revealed only a slight age-related reduction. In fact, the P300 amplitude ratios between PII and PI remained constant. Third-order polynomial regressions provided the best fit of the aging-P300 interactions in paradigms I and II for both males and females. Interestingly, females showed a greater and possibly earlier P300 latency increase during aging than males. These age-related changes of P300 potentials indicate a rather mild cognitive decline that does not accelerate before old age and may be different between both sexes.
Adolescent↗
Training influence on age-dependent changes in the gait of rats.
Stride length, stance width and gait symmetry were measured as parameters of gait analysis in young (5 months) and old (28 months) Sprague-Dawley rats following 3 months of treadmill running as well as in sedentary controls. Stride length decreased significantly with age and increased significantly following training in both young and old rats. Means of stance width increased significantly with age, but were unaffected by training. Gait symmetry declined with age; however, treadmill running counteracted the decline of gait symmetry. It was concluded that treadmill running compensates for or prevents age-related changes in the neuromuscular function of rats, which lead to gait deterioration.
Aging↗
Acute spinal cord degeneration following general anaesthesia in a young pony.
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Acute Disease↗
[Age dependence of interleukin 6 and acute phase proteins].
In 59 healthy subjects of different age groups with no signs of inflammatory processes, the basal II-6 levels were measured. The II-6 concentrations were significantly higher in the oldest group (66-90 years) than in the two other age groups (24-40, 41-65 years). A positive correlation was found between age and II-6 concentration (r = 0.470). Otherwise, a statistically detectable relationship was found merely with alpha-2-macroglobulin and with total and LDL cholesterol.
Acute-Phase Proteins↗
Complement C1q and C3 mRNA expression in the frontal cortex of Alzheimer's patients.
The levels and cellular localization of mRNA for complement C1q and C3 were examined by RNA gel blot and nonradioactive in situ hybridization in the frontal cortex of patients with Alzheimer's disease (AD) and age-matched controls. We found that the hybridization signal for C1q mRNA was markedly increased (approx. 3.5-fold) in the frontal cortex of AD patients compared to that in age-matched controls. In contrast to previous reports we also found that the levels of C3 mRNA, although well expressed, did not differ significantly between AD cases and age-matched controls. Nonradioactive in situ hybridization using digoxigenin-labeled ribo-probes revealed that transcripts coding for both C1q and C3 were closely associated with neurons. These results support the hypothesis that complement could play a role in neuronal degeneration which has been observed in the brain of AD patients.
Aged↗
Pentylenetetrazole-induced seizure up-regulates levels of microtubule-associated protein 1B mRNA and protein in the hippocampus of the rat.
Stimuli that evoke seizure are capable of inducing structural changes in the hippocampus. However, late-acting genes related to these changes have not been described. Administration of pentylenetetrazole (PTZ; 50 mg/kg) to rats of various ages evoked tonic-clonic seizures. Using RNA gel blot analysis we found that the level of the mRNA for microtubule-associated protein 1B (MAP1B) was robustly increased in the hippocampus of 3-month-old rats. The levels of MAP1B mRNA in hippocampus peaked at 40 h and began to decline by 72 h following PTZ treatment. Immunoblotting with anti-MAP1B antibody demonstrates the increase in content of immunoreactive proteins 40-72 h after seizure onset in the hippocampus of PTZ-treated rats. These results indicate that MAP1B is a sensitive indicator of hippocampal structural changes occurring in response to PTZ-induced seizure activity.
Animals↗
Fibronectin mRNA (FN-V95+) is increased in the liver of old Sprague-Dawley rats: effect of food restriction.
Because fibronectin (FN) mRNA has been shown to be increased in the brain of old rats and during in vivo and in vitro aging of both endothelial cells and fibroblasts, it was of interest to determine what effect age and caloric restriction have on the ability of liver cells to express FN mRNA. The prevalence of fibronectin mRNA containing the alternatively spliced variant V95 (FN-V95) was examined by RNA gel blot hybridization in the liver of 10-mo, 18-mo, 30-mo ad lib-fed (AL) and 30-mo food-restricted (FR) rats. The transcripts coding for FN-V95 mRNA were well expressed in the liver of 10-mo and 18-mo-old rats. The hybridization signal then increased (1.3-fold, p < .05) in the liver of 30-mo AL rats vs 10-mo-old rats. However, the prevalence of FN-V95 mRNA was dramatically decreased (approximately 4.5-fold, p < .01) in the liver of 30-mo food-restricted rats as compared to 30-mo-old AL rats. The distribution of FN-V95 mRNA was also investigated by non-radioactive in situ hybridization (ISH) on liver frozen sections. The hybridization signal for FN-V95 mRNA was evenly distributed among liver cells of 10-mo and 18-mo-old rats, while weak hybridization signals were sparsely scattered on liver sections derived from 30-mo-old FR rats. In contrast, strong hybridization signals showing a localized distribution were detected on liver sections obtained from 30-mo-old AL rats. Histologic examination of cryostat sections also revealed a massive accumulation of lipid droplets in the liver of 30-mo-old AL rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Aging↗
Proteoglycan metabolism of equine articular cartilage and its modulation by insulin-like growth factors.
The effect of human recombinant insulin-like growth factor 1 (rhIGF-1) on proteoglycan (PG) metabolism of full thickness equine articular cartilage explants was investigated. PG synthesis was stimulated at all ages, but higher concentrations of rhIGF-1 were required for maximal stimulation of adult cartilage. There were no changes in the hydrodynamic size, electrophoretic heterogeneity or composition of proteoglycans isolated from rhIGF-1-stimulated cartilage. rhIGF-1 reduced the rate of turnover of both newly synthesized and endogenous proteoglycans in all ages of cartilage investigated. The structure of proteoglycan fragments retained within the matrix and those released into the culture medium was unaffected by IGF-1 stimulation, suggesting that this peptide is a key regulator of the proteoglycan composition of equine articular cartilage extracellular matrix.
Aging↗