The levels of the cyclic adenosine 3',5'-monophosphate (cyclic AMP)-phosphodiesterase (PDE) and the biochemical properties of its endogenous protein activator (PDEA) obtained from the human brain cortex and from different types of human cerebral tumours have been evaluated. The effects of the various PDEAs were studied measuring the activation of an activator-depleted cyclic AMP-PDE prepared from a normal brain cortex. The PDEA, obtained from normal and pathological tissues, did not change the affinity of the purified PDE for cyclic AMP, while it increased the Vmax of the enzyme. On the other hand, a cross-activation study showed that the PDEA lacked tissue specificity and was present in the tissue in excess over the enzyme. The levels of cyclic AMP-PDE and PDEA were much higher in normal than in tumoural tissues. The enzyme activity decreased in cerebral tumours more markedly than the protein activator. This biochemical pattern was more evident in the tumours of glial origin which are the most malignant.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMedDate not supplied

Risk factors for the development of pressure sores in hospitalized elderly patients: results of a prospective study.

Pressure sores are a serious and still common complication of immobility in the elderly. Despite the potential seriousness of the problem, factors that identify bedridden patients at the greatest risk for pressure sores have not been well characterized and the epidemiology is not yet well defined. The characteristics of 56 subjects with pressure sores and 92 at risk (confined to bed or chair for at least 1 week) were first compared in a cross-sectional analysis; subjects at risk were then followed up for 2 months to identify factors that may contribute to the appearance of pressure sores during hospitalization. In hospitalized patients at risk we found an incidence of 22.8% within 60 days. Our data suggest that age is not a risk factor for the development of pressure sores, while urinary incontinence, fecal incontinence, altered consciousness, impairment of cognitive function, poor functional status, time spent in bed, lack of caregivers and poor nutritional status are important factors associated with pressure sores in hospitalized elderly patients.

Journal Article↗

PubMedDate not supplied

Dihydroergokryptine vs. placebo in dementia of Alzheimer type: interim results of a randomized multicenter study after a 1-year follow-up.

In order to evaluate the efficacy of dihydroergokryptine mesylate (DEK) - a semisynthetic ergot alkaloid having a neuroprotective activity through the activation of antioxidant enzymatic systems - in dementia of Alzheimer type, a long-term, randomized, placebo-controlled, double-blind study was carried out. The interim analysis after 1-year follow-up is here reported. Two-hundred-and-fifteen patients fulfilling the NINCDS-ADRDA criteria for probable Alzheimer's disease were enrolled by 14 geriatric and neurologic Italian centers. The study design included a 1-month pre-treatment phase with placebo; 1-year double-blind treatment with DEK or placebo; a further 1-year open phase of treatment with DEK. The active drug dosage was 5 mg bid orally administered for the first 2 weeks, 10 mg bid for the following 2 weeks, 20 mg bid for the following 11 months. Efficacy was assessed by means of Gottfries-Bråne-Steen (GBS) Rating Scale for dementia and Mental Deterioration Battery. The univariate analysis showed a significant improvement of GBS subscales and factors (with the exception of the Factor III, depression-anxiety). Multivariate analysis showed a significant difference between treatments in GBS scale (P=0.002) without any influence of age and illness duration. These results were confirmed by the end-point analysis carried out on GBS scores using baseline value as covariate. Minor adverse events were observed in 9 out of 108 patients (8.3%) of the DEK group and in 7 out of 107 (6.5%) of the placebo group. No change in blood pressure, heart rate and routine laboratory tests was observed. These preliminary results suggest positive symptomatic effects of DEK on elderly patients with probable Alzheimer's disease indicating a slowing down of the cognitive decline.

Clinical Trial↗

PubMedDate not supplied

Association of chronic non-steroidal anti-inflammatory drugs use and cognitive decline in non-demented elderly patients admitted to a geriatric evaluation and rehabilitation unit.

In a geriatric evaluation and rehabilitation unit (GERU), 258 elderly patients (M: 71, F: 187; mean age 77.4 +/- 7.5) scoring 22 or more at Mini-Mental State Examination (MMSE) consecutively admitted were assessed in order to evaluate the effects of non-steroidal anti-inflammatory drugs (NSAID) chronic treatment on cognitive status in non-demented elderly patients. Sixty-six patients (25.6%) were considered chronic NSAID users. Patients chronically assuming NSAADs showed a significantly higher MMSE score than non-users (26.9+/-2.1 vs 25.7+/-2.5, P<0.0005 ). After controlling for potential confounders in a multivariate model, chronic NSAID use remained independently associated with MMSE score. The results support a positive association between chronic NSAID use and cognitive function in non-demented elderly patients. Randomized controlled trials will be needed to definitively prove this beneficial effect.

Journal Article↗

PubMedDate not supplied

Neuropeptidergic inhibitory regulation of Met-enkephalin immunoreactive material release from rat spinal cord in vitro.

The release of Met-enkephalin immunoreactive material (ME-IR) from rat spinal slices was measured in vitro. This release increased about 4 fold in response to the addition of K+ ions. K+-evoked release of ME-IR was Ca++ dependent. Veratridine, a depolarizing agent, also stimulated the release of ME-IR. Veratridine-induced ME-IR release was completely prevented by tetrodotoxin (TTX), a Na+ channel blocker. Somatostatin (SRIF) inhibited both basal and K+-evoked release of ME-IR at 10(-7) M. Substance P had a similar effect although higher concentrations were needed. gamma-Aminobutyric acid (GABA) and neurotensin (NT) did not affect the basal release but slightly decreased K+-evoked release at 10(-5) M. Serotonin (5-HT) and noradrenaline (NA), did not affect ME-IR release. These results suggest that some of the neuropeptides present in the spinal cord, especially SP and SRIF, may be potent modulators of ME-IR release at the spinal level.

Animals↗

PubMedDate not supplied

Drugs affecting calcium movements and the aging brain.

Drugs acting on neuronal calcium homeostasis may potentially affect the aging brain, but the risk/benefit ratio of this approach should be carefully evaluated.

Aged↗

PubMedDate not supplied

Omegaconotoxin binding decreases in aged rat brain.

Omegaconotoxin binding was studied in young (3 months) and old (24 months) male Sprague-Dawley rats. In both groups omegaconotoxin binding displayed high affinity, was specific and saturable. The age-related changes are mainly a decrease in the Bmax in striatum and cortex (-29% and -31%, respectively). Binding parameters were unmodified in hippocampus of the two age groups. These data are consistent with the decrease of calcium uptake and neurotransmitter release observed in the brain of aged rodents.

Age Factors↗

PubMedDate not supplied

Regulation of phorbol ester binding and protein kinase C activity in aged rat brain.

Protein kinase C (PKC) function was analyzed in aged male Sprague-Dawley rat brain using two different approaches: the binding of [3H]-phorbol-12,13-dibutyrate and the in vitro phosphorylation of histone H1. In cortex the binding was decreased while in cerebellum no age-related modifications were observed. In hippocampus the binding capacity was increased in old animals and the affinity decreased. The kinase activity in both soluble and particulate fractions was decreased in cortex, increased in hippocampus and unmodified in cerebellum. The area selective, age-dependent modifications in neuronal PKC may sustain short- and long-term regional changes of neuronal excitability.

Age Factors↗

PubMedDate not supplied

Protein kinase C activity, translocation, and conventional isoforms in aging rat brain.

Protein kinase C was studied in various brain areas in aging Wistar rats. Histone-directed kinase activity from the cortex, hippocampus and cerebellum did not change with aging. Using purified protein B-50 as a substrate, between 3 and 8 months a decrease in in vitro phosphorylation was detected in the membrane fraction of the cortex but after this age values remained stable. In hippocampal membranes, B-50 phosphorylation was increased in aged rats. PKC translocation was impaired in aged rats in both the cortex and the hippocampus. PKC alpha and beta mRNA decreased in the cortex between 3 and 8 months with no further decline in aged animals. Hippocampal mRNA for calcium-dependent PKC isoforms was not modified during aging, as assessed by Northern and in situ hybridization. Western blot analysis revealed a change in PKC gamma protein only, which was increased in hippocampal membranes from aged rats. The data indicate that the key PKC function that is impaired in aged rats is enzyme translocation irrespective of the brain area investigated.

Aging↗

PubMedDate not supplied

Chronic lead treatment differentially affects dopamine synthesis in various rat brain areas.

The effect of chronic dietary lead exposure on brain nigrostriatal, mesolimbic and mesocortial systems was studied. The results show no modification of the dopamine receptors measured either as dopamine sensitive adenylate cyclase or as [3H]spiroperidol binding. On the other hand, dopamine synthesis seems to be reduced in striatum, unaffected in substantia nigra and increased in nucleus accumbens and in the frontal cortex. The increase of DA synthesis observed in some brain areas might be involved in determining the hyperactive behaviour that follows lead intoxication.

Adenylyl Cyclases↗