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In older adults co-occurrence of multiple diseases often leads to use of multiple medications (polypharmacy). The aim of the present study is to describe how prescription of medications varies across age groups, with specific focus on the oldest old.We performed a cross-sectional study using 2013 data from the OsMed Health-DB database (mean number of medicines and defined daily doses prescribed in 15,931,642 individuals). There were 3,378,725 individuals age 65 years or older (21.2% of the study sample).The mean number of prescribed medications progressively rose from 1.9 in the age group65 years to 7.4 in the age group 80-84 years and then declined, with a more marked reduction in the age group 95 years or older with a mean number of 2.8 medications. A similar pattern was observed for the mean number of defined daily doses. Among participants age ≥65 years, proton pump inhibitors were the most commonly prescribed medication (40.9% of individuals ≥65 years), followed by platelet aggregation inhibitors (32.8%) and hydroxy-methylglutaryl-coenzyme A reductase inhibitors (26.1%). A decline in prescription was observed among individuals age 90 years or older, but this reduction was less consistent for medications used to treat acute conditions (ie, antibiotics and glucocorticoids) rather than preventive medicines commonly used to treat chronic diseases (ie, antihypertensive medications and hydroxy-methylglutaryl-coenzyme A reductase inhibitors).The burden of medication treatment progressively increases till age 85 and substantially declines after age of 90 years. Patterns of medication prescription widely vary across age groups.

We report that neutrophil function was impaired in former heroin addicts on chronic naltrexone maintenance. Of the subjects, 62.5% had elevated plasma ACTH, 25% had elevated plasma cortisol and one subject had increased urinary cortisol. All subjects showed enhanced expression of opioid receptors on monocytes, neutrophils and lymphocytes. In vitro, incubation with therapeutically relevant concentrations of naltrexone induced a slow increase of neutrophil cytoplasmatic free Ca(2+)concentrations ([Ca(2+)]()E2>i) and slowed down the [Ca(2+)]()E2>i rise induced by N-formyl-methionyl-leucyl-phenylalanine. Neither naltrexone nor its metabolite beta-naltrexol affected human neutrophil function in vitro. We conclude that impairment of neutrophil function during chronic naltrexone may be related to opioid receptor overexpression. With this regard, the possible role of naltrexone-induced [Ca(2+)]()E2>i changes deserves further investigation. 1999 Academic Press.

The aims of this study were to assess the possible role of peripheral benzodiazepine receptors (pBZrs)1 in mediating the in vitro effects of carbamazepine (CBZ) on some neutrophil functions in healthy volunteers and to investigate neutrophil function and pBZr expression in patients with epilepsia on CBZ monotherapy for at least 1 year. In vitro CBZ (42-168 microM) concentration-dependently inhibited chemotaxis induced by N-formyl-methionyl-leucyl-phenylalanine (FMLP) or lipopolysaccharide (LPS)-activated human serum. CBZ did not affect random migration, phagocytosis index, phagocytosis frequency, NBT reduction frequency, C. albicans lethality index and resting superoxide production. The pBZr antagonist PK 11195 (1 microM, per se ineffective) reversed the inhibitory effect of CBZ on chemotaxis induced by endotoxin-activated serum or FMLP. The pBZr agonist Ro 5-4864 (10-100 microM) mimicked the effect of CBZ on chemotaxis induced by endotoxin-activated serum or FMLP and had no effect on the other parameters. Neutrophils from epileptic patients on chronic CBZ monotherapy had impaired FMLP- and serum-induced chemotaxis and enhanced expression of pBZrs on neutrophils. These data strongly suggest an involvement of pBZrs in mediating the in vitro effects of CBZ on chemotaxis; furthermore, impairment of the same neutrophil function parameters and overexpression of pBZrs in patients are consistent with the hypothesis of an in vivo interaction of CBZ with pBZrs.

Epileptic patients on long-term therapy with a single anticonvulsant showed enhanced expression of peripheral benzodiazepine receptors (pBZrs) on neutrophils, monocytes and lymphocytes. N-Formyl-methionyl-leucyl-phenylalanine-induced chemotaxis was significantly impaired in neutrophils from patients on carbamazepine (p < 0.01 vs. controls). Neutrophils from patients on phenytoin had enhanced phorbol myristate acetate-stimulated O–2 production (p < 0.01 vs. controls) and neutrophils from patients on valproic acid had impaired phagocytosis frequency and Staphylococcus aureus lethality index (p < 0.01 vs. controls). Overexpression of pBZrs on leukocytes may reflect the clinical response to anticonvulsants and may play a role in the immunological effects of some of these drugs.

Peripheral benzodiazepine receptors (pBDZrs) are found in both brain and peripheral tissues and differ from the central BDZrs linked to the GABA-receptor-chloride channel complex in their different distribution, molecular structure and pharmacological sensitivity. The pBDZrs bind diazepam, but with low affinity, do not bind clonazepam, and bind the benzodiazepine (BDZ) Ro 5-4864 and the isoquinoline carboxamide PK 11195 with nanomolar affinity 1. Peripheral BDZrs have been shown on human neutrophils, monocytes and lymphocytes 2. Ligands for pBDZrs modulate a number of human leukocyte activities 3,4, however, no definite data are available yet concerning the intracellular signal transduction mechanisms of pBZr ligands in leukocytes. Ca++ is the most common signal transduction element modulating many crucial cellular processes. A role for BDZs as regulators of Ca++ channel activity has been suggested for both centrally and peripherally acting BDZ ligands5. However, the possible influence of BDZs on Ca++ movements in leukocytes has never been considered. The aim of the present study was to investigate the effect of BDZr ligands on [Ca]i in human neutrophils. In addition, the possible mechanisms responsible for such effect have also been examined.

On March 7 this year, Prof. Robert J. Domenjoz died at the age of 89 years. Pharmacology is extremely indebted to him. He founded the journal in 1959, which was named Medicina Experimentalis and some years later renamed Medicina et Pharmacologia Experimentalis still in the tradition that Latin was the medical language.

The functional properties of elongation factor 1 (EF1) in high viability and aged wheat embryos have been studied. The results show the presence of an inhibitory activity at the level of the translational machinery in aged germs: the significance of this activity on protein synthesis related to the physiological conditions of ageing seeds is discussed.

Elongation factor EF1 was found in a low salt homogenate of wheat embryos, either in the 100 000 × g supernatant or in the ribosome pellet. The ribosome-linked EF1 (EF1 R ), detached by high salt washing, was purified to electrophoretical homogeneity and its molecular and functional properties compared to those of a purified high molecular weight species of EF1 obtained from cytoplasm (EF1 H ). The two forms are associations of different polypeptides having in common only the polypeptide which can form the ternary complex with aminoacyl-tRNA and GTP. Whereas EF1 R is able to fulfill all the EF1 functions, EF1 H , incubated with ribosomes completely deprived of elongation factors, can catalyze the aminoacyl-tRNA binding to ribosomes, but, in the presence of EF2, forms only a very small amount of poly(Phe).