1,721,112 research outputs found
Terapia farmacologica dell'influenza e delle sue complicanze
L'influenza è una patologia respiratoria causata da virus influenzali di tipo A (più comuni) e di tipo B. La prevenzione mediante i vaccini è la procedura più pratica e più conveniente per il controllo dei virus influenzali. Attualmente è possibile attuare sia prevenzione che trattamento dell'influenza mediante farmaci antivirali, in alcune popolazioni particolari ed in soggetti ad alto rischio. I farmaci antivirali possono contrastare l'azione dei virus e per essere efficaci debbono essere assunti entro 36 ore dall'esposizione ai virus. I farmaci attualmente disponibili appartengono a due categorie: i bloccanti M2 e gli inibitori della neuraminidasi. I primi sono caratterizzati da elevata biodisponibilità orale e relativa tollerabilità ma sono attivi solo nei confronti di virus di tipo A. Inoltre presentano una relativamente rapido sviluppo di resistenza. I secondi sono ben tollerati e sono attivi nei confronti di virus di tipo A e B e possiedono un potenziale di resistenza inferiore a quello dei bloccanti M2. Le superinfezioni batteriche nel corso di patologie respiratorie virali rappresentano un fenomeno clinicamente ben documentato. Le epidemie di influenza sono accompagnate da un aumento di ricoveri per polmonite batterica sostenuta da pneumococco, H. influenzae e S. aureus e da un incremento di incidenza di infezioni da meningococco. Le complicanze batteriche dell'influenza necessitano terapia antibiotica ma non giustificano l'uso sistematico di antibiotici in corso di patologie esclusivamente virali
Humoral and cellular immunoresponse of mice treated with pyrazole-carboxamide-4-amino (PCA).
Effects of pinealectomy on the circadian rhythms of the activities of polyamine biosynthetic decarboxylases and tyrosine adminotransferase in different organs of the rat
The circadian rhythms of the activities of some enzymes were compared in liver, kidneys, and thymus of sham-pinealectomized and pinealectomized rats. Ornithine decarboxylase and tyrosine aminotransferase were chosen because of the well known fluctuations of their activities during the day. The diurnal behavior of S-adenosyl-L-methionine decarboxylase activity was first ascertained to display circadian rhythm in all of the above-mentioned organs of sham-pinealectomized rats and then was compared with that of pinealectomized rats. Before the operation and until killed, all of the animals were kept under rigidly standardized conditions. They were killed at 6-h intervals during the day. Chronobiologically in pinealectomized animals, the acrophase of the circadian rhythm of ornithine decarboxylase activity was markedly shifted in liver and, to a lesser degree, in kidneys. For the same enzyme, pinealectomy modified the amplitude in thymus and, even more so in kidneys. As for the circadian rhythm of S-adenosyl-L-methionine decarboxylase activity, pinealectomy induced an increase of the amplitude only in kidneys. No chronobiological parameter of the circadian rhythm of tyrosine aminotransferase activity was changed by pinealectomy in any of the chosen organs. The results of chronobiological analyses are supported by and in agreement with the results of analyses of variance of the effects of pinealectomy on the circadian rhythms tested. Two conclusions seem to be justified: 1) the pineal gland plays a part in the rat time-keeping machinery regulating enzyme circadian rhythms; and 2) in the circadian organization of the rat, the pineal gland plays the role of a coupling device, rather than that of master oscillator
Compartimenti intracellulari batterici e distribuzione intra-cellulare dei chemioantibiotici
IN VITRO COMPARATIVE DYNAMICS OF MODIFIED RELEASE CLARITHROMYCIN AND OF AZITHROMYCIN
Antibacterial kinetics of modified-release clarithromycin (CLA) and azithromycin (AZI) against respiratory tract pathogens were compared in relation to their pharmacokinetic profile. The study was carried out in three strains of Streptococcus pneumoniae, group A β-hemolytic Streptococcus pyogenes, Moraxella catarrhalis and Haemophilus influenzae, respectively, exposed to concentration gradients of CLA and AZI simulating human serum pharmacokinetics after administration of 500 mg p.o. in a single dose. Bactericidal kinetics were assessed by counting the number of survivors before each change in concentration over a period of 36 h. The minimal inhibitory concentrations (MICs) of CLA and AZI were evaluated at time 0 and after 36 h of exposure to antibiotics in the surviving organisms. The results showed that CLA and AZI, in the experimental conditions adopted, had different antibacterial kinetics. Moreover, the addition of the 14-OH metabolite of CLA at the same concentrations reached in human serum exerted a bactericidal effect against two strains of H. influenzae resistant to CLA and AZI. An increase in MICs was observed against S. pyogenes and H. influenzae, with higher values for AZI. Copyright (C) 2000 S. Karger AG, Basel
Enhancement of ornithine decarboxylase activity in rat adenohypophysis after pinealectomy
Pineal gland and polyamines
The activity of ornithine decarboxylase was assayed in several organs (thymus, testes, prostate gland, liver, kidneys, adenohypophysis, anterior hypothalamus, and adrenals) taken from adult male rats killed at seven day interval up to six weeks after pinealectomy. The absence of the pineal gland particularly influences the ornithine decarboxylase activity in the thymus, in which the level of the enzyme is decreased irreversibly by the fourth week after the operation. In other organs the ornithine decarboxylase activity was often significantly different from that of corresponding shampinealectomized controls at various weeks after the surgical removal of the gland. Moreover, these differences between operated and sham-operated animals are sometimes positive, sometimes negative. Thus, the polyamine biosynthetic pathway in different organs appears to be regulated, directly or indirectly, by a new neuroendocrine centre, the pineal gland, and this pineal gland has thus been shown to be active in adult life in correlating endocrine-enzymatic functions
Melatonin : positive effects on high-risk patients with desynchronized sleep-wake rhythm
Background
Melatonin (MT), a pineal gland hormone, mediates many processes, including the biorhythmic regulation of the organism physiology. The role of MT in the treatment of sleep disturbances, to prevent jet lag or as a part of the sepsis treatment is widely discussed. Circadian rhythm of MT is desynchronized in critically ill pts in intensive care unit (ICU). The restoration of MT levels has been recently proved to be useful. The aims of the investigation are: to confirm that MT is a molecule active in the regulation of sleep/wake rhythm in ICU patients and to compare the differences in the MT pharmacokinetics using different administration route and drug formulation.
Methodology
The clinical effects of long term (5 days) administration of oral MT, as well as the pharmacokinetics profiles as a function of different administration ways (os, os by SLN (solid lipid nanoparticles), transdermal by SLN) have been studied in ICU pts. From the second day of the ICU stay, serial withdrawal were taken to determine both the endogenous and the exogenous plasma MT content, for a total of 20 withdrawal for each patient. Each blood sample was centrifuged and the plasma stored at -20°C. To determine the MT concentration we used an ELISA kit that includes a pre-purification of the sample by SPE (solid phase extraction) cartridges.
Results
In this study, we have seen that administration of oral MT, is safe, reduces need for analgesic and sedative drugs and shows better neurological status indicators, also restoring the normal circadian rhythm. In patients who have received oral MT, the absorption is rapid: the peak plasma concentration has a median of 30 minutes and after only 5 minutes the MT levels were significantly higher than physiological ones. The group treated with transdermal MT presents a delayed peak plasma concentration (4 h).
Conclusions
In this study, we have proved that MT is able to normalize the sleep-wake cycle, to ameliorate the sleep quality and to reduce the number of sedative drugs used in ICU pts. We proved also that transdermal administration by SLN is effective in rising plasma MT levels as well as enteral administration and is more practicable in clinical setting
2-[125I]iodomelatonin binding sites in the bovine hippocampus are not sensitive to guanine nucleotides
The discrete distribution and pharmacological characteristics of melatonin binding sites in the bovine hippocampus were determined. Autoradiography revealed the presence of melatonin binding sites in the stratum lacunosum-molecularis of the hippocampus (CA1), stratum molecularis of the subiculum and in the enthorhinal cortex. Analysis of the kinetic parameters demonstrated that the binding was stable and reversible, represented by a single class high affinity binding sites (Kd 40 pM, Bmax = 3.9 fmol/mg protein). However, 2-iodomelatonin and 2-bromomelatonin inhibited 2-[125I]iodomelatonin binding in a biphasic manner. The presence of 4 mM CaCl2 did not cause changes in the affinity constant values. Finally, experiments performed with GTP gamma S revealed that binding affinity was not decreased even with high concentrations of the nucleotide. These findings show that 2-[125I]iodomelatonin binding sites in the bovine parahippocampal-hippocampal region possess some binding features not common to melatonin receptors described so far; moreover they seem not to be linked to a regulatory G-protein
A new model examining intracellular and extracellular activity of amoxicillin, azithromycin, and clarithromycin in infected cells
An in vitro infection model was created using a suspension of macrophages, polymorphonuclear leukocytes, lymphocytes, fibroblasts, and human serum to which pathogen and antibiotic were added. Separate intracellular and extracellular antibiotic concentrations and activity against Staphylococcus aureus and Legionella pneumophila were assessed for three antimicrobial agents: amoxicillin, azithromycin and clarithromycin. Amoxicillin was found almost exclusively in extracellular fluid, where it was active; intracellularly, it was ineffective. Azithromycin, in contrast, was primarily concentrated and active intracellularly, with little activity in extracellular fluid. Clarithromycin was present in both compartments and possessed significant activity both intracellularly and extracellularly
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