Calmodulin-stimulated cyclic nucleotide phosphodiesterase (PDE1C) is induced in human arterial smooth muscle cells of the synthetic, proliferative phenotype.

The diversity among cyclic nucleotide phosphodiesterases provides multiple mechanisms for regulation of cAMP and cGMP in the cardiovascular system. Here we report that a calmodulin-stimulated phosphodiesterase (PDE1C) is highly expressed in proliferating human arterial smooth muscle cells (SMCs) in primary culture, but not in the quiescent SMCs of intact human aorta. High levels of PDE1C were found in primary cultures of SMCs derived from explants of human newborn and adult aortas, and in SMCs cultured from severe atherosclerotic lesions. PDE1C was the major cAMP hydrolytic activity in these SMCs. PDE expression patterns in primary SMC cultures from monkey and rat aortas were different from those from human cells. In monkey, high expression of PDE1B was found, whereas PDE1C was not detected. In rat SMCs, PDE1A was the only detectable calmodulin-stimulated PDE. These findings suggest that many of the commonly used animal species may not provide good models for studying the roles of PDEs in proliferation of human SMCs. More importantly, the observation that PDE1C is induced only in proliferating SMCs suggests that it may be both an indicator of proliferation and a possible target for treatment of atherosclerosis or restenosis after angioplasty, conditions in which proliferation of arterial SMCs is negatively modulated by cyclic nucleotides.     

Prospective Randomized Study Comparing the Efficacy of Bioequivalent Doses of glycosylated and nonglycosylated rG-CSF for Mobilizing Peripheral Blood Progenitor Cells

Thirty patients diagnosed with breast cancer were included in a prospective randomized study comparing the in vivo priming effect of bioequivalent doses of glycosylated (lenograstim) and nonglycosylated (filgrastim) rG-CSF administration. Analysis of the efficacy of equivalent biological doses of both rG-CSFs showed no significant differences either in the mobilization of the subpopulations of PBPC considered (CD34⁺, CD34⁺/38⁻, CD34⁺/DR⁻), the content of such CD34⁺ cell subsets in the leukapheresis product, or the cost of the mobilization and collection procedures between both recombinant molecules. These results suggest that priming with bioequivalent doses of the two commercially available forms of glycosylated or nonglycosylated rG-CSF has a similar in vivo effect on PBPC mobilization.     

Persistent platelet activation in patients with type 2 diabetes treated with low doses of aspirin

BACKGROUND: The percentage of diabetic patients who do not benefit from the protective effect of aspirin is larger than in other populations at cardiovascular risk. OBJECTIVE: We compared the ability of aspirin to suppress TxA2 and platelet activation in vivo, in type-2 diabetics vs. high-risk non-diabetic patients. METHODS: Urinary 11-dehydro-TXB2, plasma sCD40 L, and sP-selectin were measured, together with indices of low-grade inflammation, glycemic control, and lipid profile, in 82 patients with type-2 diabetes and 39 without diabetes, treated with low doses of aspirin. RESULTS: Urinary 11-dehydro-TxB2, plasma sCD40L and sP-selectin were significantly higher in diabetics than in controls: [38.9 (27.8-63.3) vs. 28.5 (22.5-43.9) ng mmol(-1) of creatinine, P = 0.02], [1.06 (0.42-3.06) vs. 0.35 (0.22-0.95) ng mL(-1); P = 0.0001], [37.0 (16.8-85.6) vs. 20.0 (11.2-35.6) ng mL(-1), P = 0.0001], respectively. The proportion of individuals with diabetes increased across quartiles of 11-dehydro-TxB2, sCD40L, and sP-selectin, with the highest quartiles of 11-dehydro-TxB2, sCD40L and sP-selectin, including 66%, 93.3%, and 93.3% of individuals with diabetes. Markers of platelet activation positively correlated with indices of glycemic control but not with markers of low-grade inflammation. CONCLUSIONS: Platelet dysfunction associated with insufficient glycemic control, may mediate persistent platelet activation under aspirin treatment.     

Paternal lineage of alcoholism, cohort effects, and alcoholism criteria

Adoption studies have led to the suggestion that there may be two distinct subgroups of alcoholics with differing genetic contributions. Among 249 male alcoholics we used discriminant analysis to relate the features of type 1 and type 2 alcoholism it the presence or absence of a family history of alcoholism in male paternal relatives. We found that guilt and hinging, features usually attributed to type 1 (milieu-limited) alcoholism, were in fact more prevalent m the family history positive group. An additional cohort analysis found cohort-related variations in type 1/type 2 characteristics. The possible implications of these findings are discussed.     

Effect of Policosanol on Foam-cell Formation in Carrageenan-induced Granulomas in Rats

Policosanol is a new cholesterol-lowering drug isolated and purified from sugar-cane wax. which prevents the development of lipofundin-induced lesions and foam-cell formation in New Zealand rabbits and Wistar rats. This study was conducted to examine the effects of policosanol on foam-cell formation in carrageenan-induced granulomas in rats. Eighteen Wistar rats were randomly distributed in three experimental groups which received orally for 20 days Tween 20 H₂O as vehicle (control group) or policosanol at 2.5 or 25 mg kg^?1. At the 11th day. lipofundin was injected intrapcritoneally for 8 days to induce formation of foam cells in the granuloma. At day 13, carrageenan was injected subcutaneously for granuloma induction and seven days later animals were killed. A significant reduction of the foam-cell formation in granulomas of policosanol-treated rats was observed. It is concluded that policosanol prevents the development of foam cells in carrageenan-induced granulomas (extravascular medium) in rats.     

EFFECTS OF ACUTE AND CHRONIC ADMINISTRATION OF TWO ANTIBIOTICS, AZTREONAM AND GENTAMICIN, ALONE OR IN COMBINATION, ON "OPEN-FIELD TEST" IN MICE

A study aimed at investigating the behavioural effects of aztreonam and gentamicin, given separately or in combination, was carried out in mice. Animals were randomly assigned to two test conditions: acute and chronic treatment. Those receiving acute treatment had a single IP injection 60 min before the test. Those receiving chronic treatment had IP injections once daily for 5 successive days prior to the test. Behavioural patterns (ambulation, rearing, grooming and defecation) were assessed using the "open-field" test. The results indicate that, both after single and multiple dosing, aztreonam (10, 40 and 80 mg/kg IP) and/or gentamicin (10 mg/kg IP) do produce changes in the behaviour of animals. A rate increasing effect for certain behaviours (rearing, grooming and defecation) and a reduction in other behaviours (ambulation) seems to occur.