Age-related changes in sympathetic modulation of sensory nerve activity in rat skin

OBJECTIVES: Sensory nerves play an important role in mediating neurogenic inflammation and subsequent tissue healing. A decrease in sensory nerve function with increasing age has been reported to correlate with poor tissue healing. Sympathetic nerves are known to modulate sensory nerve function, and changes in this modulation could also have important implications with ageing. The aims of this study were to examine the effect of different frequency electrical stimulation (ES) on the microvascular responses obtained to sensory nerve activation in young, aged and capsaicin-pretreated rats and modulation of these responses by sympathetic efferents. METHODS: Using laser Doppler flowmetry, vascular responses to antidromic ES of the sciatic nerve were monitored in the base of vacuum-induced blisters in the hind footpad. The non-selective alpha-adrenoceptor antagonist phentolamine (3 mg/kg, i.v.) was administered 20 min prior to ES. RESULTS: At high frequency ES (20V, 2ms, 15Hz for 1 min), the vascular response in old rats was significantly reduced (46 percent decrease, p < 0.05) compared to young control. At low frequency ES (20 V, 2 ms, 5 Hz for 1 min) however, older rats produced similar vascular responses to the young. Capsaicin-pretreated rats showed significantly reduced vascular responses to both high and low frequency ES, regardless of age. Pretreatment with phentolamine significantly increased the microvascular response in young rats at high (87 percent) and low (36 percent) frequency ES. In contrast, phentolamine significantly increased the ES-induced response in old rats at high frequency only (147 percent increase). CONCLUSIONS: The results suggest that the aged sensory nerve responds preferentially to low frequency ES and that sympathetic efferents exert an inhibitory modulatory effect on the vascular response evoked by sensory nerve stimulation. There are age-related changes in sympathetic modulation of sensory nerve-mediated responses which is dependent on stimulation frequency.     

Physiological phosphorylation of protein kinase A at Thr-197 is by a protein kinase A kinase

Phosphorylation of the catalytic subunit of cyclic AMP-dependent protein kinase, or protein kinase A, on Thr-197 is required for optimal enzyme activity, and enzyme isolated from either animal sources or bacterial expression strains is found phosphorylated at this site. Autophosphorylation of Thr-197 occurs in Escherichia coli and in vitro but is an inefficient intermolecular reaction catalyzed primarily by active, previously phosphorylated molecules. In contrast, the Thr-197 phosphorylation of newly synthesized protein kinase A in intact S49 mouse lymphoma cells is both efficient and insensitive to activators or inhibitors of intracellular protein kinase A. Using [35S]methionine-labeled, nonphosphorylated, recombinant catalytic subunit as the substrate in a gel mobility shift assay, we have identified an activity in extracts of protein kinase A-deficient S49 cells that phosphorylates catalytic subunit on Thr-197. The protein kinase A kinase activity partially purified by anion-exchange and hydroxylapatite chromatography is an efficient catalyst of protein kinase A phosphorylation in terms of both a low Km for ATP and a rapid time course. Phosphorylation of wild-type catalytic subunit by the kinase kinase activates the subunit for binding to a pseudosubstrate peptide inhibitor of protein kinase A. By both the gel shift assay and a [gamma-32P]ATP incorporation assay, the enzyme is active on wild-type catalytic subunit and on an inactive mutant with Met substituted for Lys-72 but inactive on a mutant with Ala substituted for Thr-197. Combined with the results from mutant subunits, phosphoamino acid analysis suggests that the enzyme is specific for phosphorylation of Thr-197.     

Cloning and characterization of the human and Caenorhabditis elegans homologs of the Saccharomyces cerevisiae MSH5 gene

Genetic variation among malaria parasites has important consequences with regard to drug resistance, pathogenicity, immunity, transmission, and speciation. In this regard, malaria parasites have been shown to display a high degree of inter- and intra-species genetic divergence. The nuclear genomes of Plasmodium falciparum, Plasmodium yoelii, and Plasmodium gallinaceum are vastly divergent yet share a similar codon usage and total A/T content of approximately 82%. This is in contrast to other primate-specific species including P. vivax which have an A/T content of approximately 67%. To assess the effects of this evolutionary divergence on the conservation of gene content, organization, and codon usage in the mitochondrial DNA (mtDNA) of malaria parasites, we have cloned and sequenced the mitochondrial genome of Plasmodium vivax, and compared it with the mtDNAs of P. falciparum, P. yoelii, and P. gallinaceum. The P. vivax mitochondrial genome was found to be 5990 base pairs in length, and displayed a gene organization identical to that of P. falciparum, P. yoelii, and P. gallinaceum. Furthermore, there was a remarkable 90% conservation of sequence identity between the mitochondrial genomes of all four species. As an example of intra-species conservation, comparison of mtDNAs from two independently cloned P. falciparum isolates, Malay Camp and C10, revealed only a single nucleotide substitution. A/T content of the P. vivax mitochondrial genome was found to be identical to other species of Plasmodium, hence, we have postulated that the mitochondrial genomes of malaria parasites were refractory to the evolutionary shifts in nucleotide content seen among the nuclear genomes of malaria parasites. Among different Plasmodium species, the second position of mitochondrial codons were found to be the least prone to substitutions and displayed a significant bias in pyrimidines. These aspects of mitochondrial codon usage were distinct from the nuclear genome and may reflect functional aspects of decoding by the mitochondrial translational system.     

Neuroleptic use and behavioral disturbance in nursing homes: a 1-year study

This article discusses a longitudinal study of change in disruptive behaviors among nursing home residents treated with neuroleptics compared with those not treated with neuroleptics. Observations were made of 201 participants on admission to and after 1 year in eight skilled nursing facilities. Nine disruptive behaviors were measured using the Psychogeriatric Dependency Rating Scale with nursing assistants. Neuroleptic use was documented from medication records. Odds ratios are reported for the association of behavior at baseline and use of neuroleptics on nine problem behaviors. For those who received neuroleptics during the year, there was greater change in both developing and resolving disruptive behaviors than for those not receiving neuroleptics. For both groups, restless or pacing behavior and belligerent behavior manifested by refusing instructions changed the most, both in developing and in apparently resolving. Our results show that change in disruptive behaviors occurs among nursing home residents regardless of neuroleptic use, but it occurs more frequently among those who receive neuroleptic medication. Knowledge of which disruptive behaviors are most likely to resolve or develop is important in training nursing home staff to cope with the behaviors as well as in planning interventions that may modify such behaviors.     

Hereditary neurocutaneous angiomatosis. Report of four cases

The authors report the coexistence of vascular nevi (hemangiomas and arteriovenous malformations (AVMs) of the skin) with AVMs and venous malformations of the brain in male siblings from two related but nonconsanguineous families of three generations. The proband, his siblings, parents, aunts, uncles, and cousins were examined, underwent magnetic resonance (MR) imaging and MR angiography, and when appropriate, cerebral angiography. A father had vascular nevi and a mother, his sister, had an azygos anterior cerebral artery. No other cutaneous or cerebrovascular malformations were present in the parents. Each of the two families had two boys and one girl, 9 to 18 years of age. All the children had vascular nevi and all of the boys had coexisting cerebrovascular malformations: AVMs in three, and a venous malformation in another. One boy had three cerebral AVMs. Two boys had a cerebral hemorrhage, and one also had focal motor seizures. The skin lesions were not those of the Sturge-Weber-Dimitri, Rendu-Osler-Weber, or Wybum-Mason syndromes. The association of cutaneous and cerebrovascular malformations was seen only in males in these families. but females have also been reported in the literature. The results obtained in these families and three other families reported from Western and Central Europe indicate that the association of cerebral and cutaneous vascular hamartomas constitutes a distinct, hereditary clinicopathological entity with autosomal dominant inheritance and variable penetrance. The clinical manifestations of this syndrome are visible, painful vascular nevi, epilepsy, cerebral hemorrhage, and focal neurological deficits. The preponderance of male patients with the full expression of the syndrome suggests a possible hormonal influence on the expression of the gene.     

3-D molecular assembly of function in titania-based composite material systems

Various examples of composite titania-based nanostructured materials exhibiting cooperative functionalities between different active components are presented. The fabrication of these integrated composite materials is based on one-pot supramolecular templating techniques combined with acidic sol-gel chemistry. The defined 3-D nanoscale organization and integration of various functional components results in advanced optoelectronic and photonic applications such as visible light sensitization of mesoporous titania photocatalysts with cadmium sulfide nanocrystals acting as sensitizing integral part of the mesopore wall structure, narrow bandwidth emission from rare earth ion activated nanocrystalline mesoporous titania films, and mirrorless lasing in dye-doped hybrid organic/inorganic mesostructured titania waveguides.     

A progressive deployment strategy for cooperative adaptive cruise control to improve traffic dynamics

Cooperative adaptive cruise control(CACC)vehicles are intelligent vehicles that use vehicular ad hoc networks(VANETs)to share trafc information in real time.Previous studies have shown that CACC could have an impact on increasing highway capacities at high market penetration.Since reaching a high CACC market penetration level is not occurring in the near future,this study presents a progressive deployment approach that demonstrates to have a great potential of reducing trafc congestions at low CACC penetration levels.Using a previously developed microscopic trafc simulation model of a freeway with an on-ramp—created to induce perturbations and trigger stop-and-go trafc,the CACC system s efect on the trafc performance is studied.The results show signifcance and indicate the potential of CACC systems to improve trafc characteristics which can be used to reduce trafc congestion.The study shows that the impact of CACC is positive and not only limited to a high market penetration.By giving CACC vehicles priority access to high-occupancy vehicle(HOV)lanes,the highway capacity could be signifcantly improved with a CACC penetration as low as 20%.     

A Progressive Deployment Strategy for Cooperative Adaptive Cruise Control to Improve Trafc Dynamics

Cooperative adaptive cruise control(CACC)vehicles are intelligent vehicles that use vehicular ad hoc networks(VANETs)to share trafc information in real time.Previous studies have shown that CACC could have an impact on increasing highway capacities at high market penetration.Since reaching a high CACC market penetration level is not occurring in the near future,this study presents a progressive deployment approach that demonstrates to have a great potential of reducing trafc congestions at low CACC penetration levels.Using a previously developed microscopic trafc simulation model of a freeway with an on-ramp—created to induce perturbations and trigger stop-and-go trafc,the CACC system s efect on the trafc performance is studied.The results show signifcance and indicate the potential of CACC systems to improve trafc characteristics which can be used to reduce trafc congestion.The study shows that the impact of CACC is positive and not only limited to a high market penetration.By giving CACC vehicles priority access to high-occupancy vehicle(HOV)lanes,the highway capacity could be signifcantly improved with a CACC penetration as low as 20%.     

Hedgerow species and environmental conditions effects on soil total C and N and C and N mineralization patterns of soils amended with their prunings

An important criterium in selecting species for alley cropping is themineralization pattern of their prunings. This study determined effects of 5years of hedgerow pruning applications on soil organic C and total N at threelocations in Haiti and mineralization patterns from soil amended with theprunings during an incubation using micro-lysimeters. Soils (0–5cm) under 5 hedgerows were collected at each site and analyzed fororganic C and total N. In the laboratory, ground leaves and stems (<1cm diameter) of the hedgerow species were mixed with soil at ratesof 3 and 1.5 Mg ha^–1, respectively, andaerobically incubated in the dark at 25 °C. A non-amended soilwas used as control. Soils were leached to determine mineral N at 1, 3, 7, 14,28, 42, 84 and 120 days of incubation. Evolved CO₂ was measuredfollowing each leaching procedure. At the calcareous site, application ofprunings from Leucaena leucocephala (Lam.) De Wit andDelonix regia (Boj. ex Hook. Raf.) resulted in 23 and 13%higher soil N than the control, respectively, after 5 years. There were nodifferences in total N at the other sites but soil N was highest underLeucaena hybrid and Acaciaangustissima (Mill.) Kuntze, respectively at the basaltic and highelevation sites. Soils under D. regia (calcareous) andA. angustissima and Leucaena hybrid(high elevation) had higher organic C than the respective controls. Carbon andNmineralization and C turnover were highest when soils were amended with leavesof Leucaena diversifolia (Schlecht.) Benth (calcareous andbasaltic soils) and A. angustissima (high elevation) andlowest in non-amended control soils. Stem-amended soils showed differences in Cmineralization for calcareous and high elevation soils whereas N mineralizationwas similar among treatments within sites. Carbon and N mineralization (highelevation soil) correlated positively with N concentrations of leaf prunings.Amendments with leaf prunings increased soil C and N mineralization andturnoverrates, suggesting greater nutrient availability for the crop during a shortperiod than in non-amended control soils.