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Biomedical subjects

A Novelli

Publications and source records attributed to A Novelli.

At least 55 records · Page 3Linked to original sources
PubMed1999

Pharmacokinetics of dirithromycin in patients with mild or moderate cirrhosis.

The pharmacokinetics of dirithromycin were determined over a 72-h period following oral administration of a single 500-mg dose to 8 healthy volunteers and to 16 cirrhotic patients (8 patients with class A cirrhosis and 8 patients with class B cirrhosis according to Pugh's & Child's classification). Drug levels in plasma and urine were determined by microbiological assay. The mean maximum concentrations of drug in serum obtained 3 to 4 h after administration were 0.29 +/- 0.22 mg/liter in volunteers and 0.48 +/- 0.21 and 0.52 +/- 0.38 mg/liter in patients with class A and class B cirrhosis, respectively. The elimination half-life (t1/2beta) was 23.3 +/- 7.6 h in healthy subjects and 35.2 +/- 11.8 h and 39.5 +/- 11.0 h in patients with class A and class B cirrhosis, respectively. The mean area under the concentration-time curve (AUC) and t1/2beta were significantly higher in patients with class A and B cirrhosis than in healthy controls, while total and renal clearances were markedly reduced (P < 0.01). The time to the maximum concentration of drug in serum and the volume of distribution values appeared to be similar in all groups, and the mean recovery in urine at 72 h ranged from 3.7 to 5.7%, without significant differences among groups. These results demonstrate that some dirithromycin kinetic parameters are significantly different in cirrhotic patients in comparison to those in healthy volunteers. However, an increase in the t1/2beta or AUC, which is also observed with other semisynthetic macrolides (e.g., azithromycin), does seem to be not clinically relevant if one takes into account both the high therapeutic indices of these antibiotics and the usually short duration of therapy. Therefore, on the limited basis of single-dose administration, no modifications of dirithromycin dosage seem to be required even for patients with class B liver cirrhosis.

Adolescent↗
PubMed1999

Antimicrobial prophylaxis in surgery: the role of pharmacokinetics.

Even though surgical infection rates have decreased dramatically during the past 25 years, morbidity and mortality of infection in surgical treatment remains substantial. From a pharmacological point of view, the key factor of the efficacy of antibiotic prophylaxis is to attain bactericidal levels of antibiotic in serum and tissues (target site) during the whole intraoperative and early postoperative period. The success of antibiotic prophylaxis is assured only when the chosen antibiotic with a targeted spectrum and high antimicrobial efficacy is available at the critical moment, at the correct site and in sufficiently high concentration to prevent bacterial contamination of the surgical area. It would be desirable for reasons of convenience and cost if a single preoperative administration were sufficient. The pharmacokinetics and the half-life of antibiotics in the serum are directly related to the duration of activity of antibiotic in the tissue. Antibiotics with longer half-lives maintain levels in the tissues for longer periods than do antibiotics with shorter half-lives and they cover with a single dose the time required for prophylaxis even for longer operations. Finally, the application of the pharmacokinetic properties of antibiotics to surgical prophylaxis can provide the surgeon with certainty that adequate coverage and protection with antibiotics are achieved before and throughout the operation.

Anti-Bacterial Agents↗
PubMed1999

Detection of an atypical 7q11.23 deletion in Williams syndrome patients which does not include the STX1A and FZD3 genes.

We present two patients with the full Williams syndrome (WS) phenotype carrying a smaller deletion than typically observed. The deleted region spans from the elastin gene to marker D7S1870. This observation narrows the minimal region of deletion in WS and suggests that the syntaxin 1A and frizzled genes are not responsible for the major features of this developmental disorder and provides important insight into understanding the genotype-phenotype correlation in WS.

Antigens, Surface↗
PubMed1998

Increased burn patient survival with once-a-day high dose teicoplanin and netilmicin. An Italian multicenter study.

This is the final report of a large, controlled, multicenter Italian study on immuno- and chemotherapy in adult patients with burns affecting 20 to 95% of total body surface area (mean 35%). The antibiotic treatment of burn patients consisted of topical silver sulfadiazine, short-term antimicrobial chemoprophylaxis with pefloxacin (800 mg i.v. qd) for the first 4 days and polychemotherapy with teicoplanin (800 mg i.v. qd) together with netilmicin (300 mg i.m. qd) in one or more cycles of 5-12 days. At random, half of the patients received thymostimulin, 70 mg i.m. qd for the first month and every other day thereafter. The analysis at completion of 634 valid cases showed that when the results are stratified by means of the Roi risk index, 396 of the 530 patients who contracted wound infection (84%) after chemoprophylaxis were in the first three categories and a mean of 95% survived. Of the remaining 134 patients (Roi index 4-5) only 50% survived. There was no difference in survival of the immunotherapy group in comparison with the parallel group without thymostimulin. The short-term antimicrobial prophylaxis prevented wound infection in only 104 of 634 patients (16%) and they were at low risk (84% Roi index 1). Of the bacterial pathogens involved in septic complications Staphylococcus aureus and Pseudomonas aeruginosa were prevalent (86%): eradication was achieved in 43% of patients and clinical cure or improvement were seen with combination chemotherapy in 64% of all patients, mainly with only one treatment cycle. This value increased to 79% for the 395 protocol-complying patients and went down to 20% in the 135 non-compliers. The total survival of complier and non-complier patients was 447 of the 530 valid patients (84%). The overall mortality of the 634 evaluable patients was 13.1%, ranging from less than 2% to 68%. Burn mortality was directly proportional to the percentage of burned body surface area, to increasing age and other variables of the Roi index, a 50% mortality being associated with a 72.5% total body surface area burned. Normoergic burn patients had a mortality rate of 9.1% versus 35.7% in anergic patients.

Adolescent↗
PubMed1997

Effects of clenbuterol as a repartitioning agent on beta-adrenoceptor concentrations in heart, bronchi and brain of veal calves.

The effects induced by dietary clenbuterol (20 micrograms kg-1 body weight day-1 for 40 days) on beta-adrenergic receptor (beta-AR) subtypes in the heart, bronchial smooth muscles and the CNS of veal calves were investigated using a binding method. Clenbuterol exposure caused a significant (P < 0.05, P < 0.01, P < 0.001) decrease in beta 1-AR and beta 2-AR in both cardiac atria and ventricles of treated animals (excluding the beta 2-AR of the right atrium). Similarly, a significant (P < 0.01, P < 0.001) down-regulation of beta-AR subtypes in bronchial smooth muscles of treated calves was observed. In the CNS (cerebral cortex, hippocampus, hypothalamus and cerebellum) the down-regulation was limited to beta 2-AR, with the exception of the hippocampus in which both beta 1-AR and beta 2-AR concentrations were significantly (P < 0.05; P < 0.01) reduced. Scatchard analysis of the binding of the beta-AR antagonist, (-) [3H]CGP 12177, revealed that the down-regulation of beta-AR was not associated with any modification in binding affinity, as Kd values were unaffected by clenbuterol treatment. Data obtained indicated that prolonged clenbuterol exposure induced a remarkable beta-AR down-regulation in the heart, bronchi and brain of veal calves.

Adrenergic beta-Agonists↗
PubMed1997

Identification of beta-adrenergic receptor subtypes mediating relaxation in isolated equine ileum.

OBJECTIVE: To identify beta-adrenergic receptor subtypes in ileum smooth muscle of the horse. SAMPLE POPULATION: Isolated strips of equine longitudinal ileum smooth muscle and membrane preparations from smooth muscle of the intestinal wall. PROCEDURE: Functional assays and radioligand binding assays. RESULTS: Relaxation of ileum longitudinal smooth muscle proved to be mainly caused by stimulation of beta-atypical and beta 2-adrenergic receptors. Binding studies on cell membranes indicated that the total beta-adrenergic receptors population consists of 54% beta-atypical, 34% beta 2- and 12% beta 1-subtypes. CONCLUSIONS: The data suggest that sympathetic relaxation of equine ileum smooth muscle depends mainly on beta-atypical receptor subtypes activation, with a minor contribution by beta 2-subtypes. CLINICAL RELEVANCE: The important role of beta-atypical adrenergic receptor subtypes in the relaxation of equine ileum suggests possible clinical use of selective beta-atypical receptor agonists to control intestinal disturbances.

Adrenergic beta-Agonists↗
PubMed1996

Inhibition of protein phosphatases induces IGF-1-blocked neurotrophin-insensitive neuronal apoptosis.

We have previously described the marine toxin okadaic acid (OKA) to be a potent neurotoxin for cultured rat cerebellar neurons. Here we show that OKA-induced neurodegeneration involves the DNA fragmentation characteristic of apoptosis and is protein synthesis-dependent. DNA fragmentation and neurotoxicity correlated with inhibition of protein phosphatase (PP) 2A rather than PP1 activity. Neurotrophins NT-3 and BDNF failed to protect from OKA-induced apoptotic neurotoxicity that was, however, totally prevented by insulin-like growth factor-1. Neuronal death by OKA was significantly reduced by protein kinase C inhibitors and by the L-type calcium channel agonist Bay K8644, while it was potentiated by the reduction of free extracellular calcium concentrations.

Animals↗
PubMed1996

The development of oxidative metabolism in diencephalic structures of the rat: a quantitative study.

A new method for quantitative determination of cytochrome oxidase (C.O.) activity was applied to diencephalic structures of the limbic system that are closely connected anatomically, that is, the mammillary bodies (MB) and the anterior nucleus of the thalamus (AT). This method makes it possible to easily evaluate the oxidative metabolic capacity of brain regions, an index of their functionality. By using this technique, we studied the postnatal development of both structures in Wistar rats of 14, 21, 30, and 120 days of age. Furthermore, animals of 730 days were included in order to evaluate the effects of aging on C.O. activity of these structures. The results showed a significant increase in the C.O. activity of the subdivisions of the AT, its levels remaining constant until the adult age, with a significant decrease in its activity in aged animals. In the MB, only the increase in C.O. activity of the medial mammillary nucleus (pars medialis) was significant until the adult age. A decrease of C.O. values with aging was significant only in the lateral mammillary nucleus. These data suggest that there is a wide heterogeneity in the maturation and aging of brain oxidative metabolism in diencephalic structures.

Aging↗
PubMed1996

Clinical pharmacokinetics of meropenem after the first and tenth intramuscular administration.

We investigated the pharmacokinetics of meropenem after the first and tenth i.m. administration in patients with respiratory tract infections. Ten patients (mean age 63.8 +/- 5.2 years) received meropenem 500 mg tds for at least ten doses, and plasma and urine antibiotic concentrations were determined by microbiological assay. After the first injection a mean peak plasma concentration of 7.93 +/- 1.29 mg/L was observed at 1 h. Trough levels at 8 h (0.29 +/- 0.16 mg/L) were detectable in five of ten treated patients. The mean terminal half-life was 1.08 +/- 0.2 h with an area under the curve (AUC) value of 23.8 +/- 4.59 mg/L.h, and a cumulative urinary recovery at 8 h of 48.43 +/- 3.12%. There was no evidence of change in the pharmacokinetics of meropenem after repeated i.m. administration, though the mean peak plasma concentration and AUC value were slightly increased. The accumulation ratio (assessed using AUC values) was 1.18 +/- 0.19 after multiple doses and was considered to be of little kinetic and clinical importance. Moreover, many of the trough concentrations of meropenem were below the limit of detection of the assay. After i.m. administration meropenem concentrations exceeded 0.5 mg/L for longer than previously described following i.v. infusion. No adverse events were reported.

Aged↗
PubMed1996

[A new high definition histologic coloration method based on formic nigrosin].

Nigrosin, an aqueous blue-black acid dye of the azine series, in conjunction with Biebrich scarlet, orange G and formic acid as mordant, it is found an excellent triple panchromatic rapid stain for histological purposes. The staining so obtained permits a more brighter and well differentiated picture if the latter is observed by means of a microscope connected with a monitor, tuning colour strength adjustment.

Aniline Compounds↗
PubMed1996

Myoclonic epilepsy, neuroblast migration disorders, and maternally derived partial duplication 14q/deletion 15q.

A large maternally inherited duplication of 14q and deletion of proximal 15q was observed in a child with myoclonic epilepsy, mental retardation and neuroblast migration disorders (NMDs) detected by MRI. Genetic syndromes associated with NMDs have previously been described. In additional our observations support the connection between major chromosomal imbalances, developmental brain disorders and epilepsy. Thus, in patients with these combinations of symptoms, careful chromosome investigations are recommended.

Cell Movement↗
PubMed1995

Distribution of cytosolic oestrogen and progesterone receptors in the genital tract of the mare.

The distribution of oestrogen and progesterone receptors in the equine genital tract was investigated by means of a modified dextran-coated charcoal method on samples collected from the vagina, the cervix and the uterus of 30 healthy adult Polish mares, divided into two groups on the basis of their serum progesterone levels. The concentrations of oestrogen and progesterone receptors were significantly (P < 0.05) lower in the vagina and the cervix than in the uterus, in agreement with data from human beings, cattle and pigs, which showed that the highest concentrations of oestrogen and progesterone receptors were localised respectively in the body and in the horns of the uterus.

Animals↗
PubMed1995

Impairment of vitamin A uptake by rat hepatocytes and fat storing cells determined by Monensin--morphological observations.

The action of the Na+/H+ antiport monensin on vitamin A uptake by rat liver has been studied in vivo. The quickfading autofluorescence of vitamin A has been used for the determination of vitamin A uptake by the liver. Pretreatment of rats intraperitoneally with monensin decreases the uptake of vitamin A by hepatocytes and its transfer for storage to fat storing cells. Pretreatment of rats intraperitoneally with vitamin A for a short time, then with monensin, shows that the hepatocytes no longer transfer vitamin A to fat storing cells for storage. These results might indicate that monensin impairs the uptake of vitamin A by the hepatocytes and might also impair the transport of vitamin A from parenchymal to perisinusoidal cells.

Adipocytes↗
PubMed1995

In vitro postantibiotic effect and postantibiotic leukocyte enhancement of tobramycin.

The occurrence of a postantibiotic effect (PAE) and postantibiotic leukocyte enhancement (PALE) of tobramycin, a natural aminoglycoside clinically used since the early 1970s, has been investigated in comparison to gentamicin on recent clinical isolates of Staphylococcus aureus (both methicillin-susceptible and -resistant strains) and of Gram-negative fermenting and non-fermenting rods. A concentration-dependent PAE was observed with both antibiotics, regardless of the bacterial species used, with some variability based on their intrinsic resistance. Tobramycin, at concentrations equal to or higher than the minimum inhibitory concentration (MIC), exhibited a rather long PAE (ranging from 1.9 to 10.9 h) which was often significantly longer than that observed with gentamicin (ranging from 1.0 to 7.5h). Moreover, pre-exposure to tobramycin led to enhanced polymorphonuclear leukocyte phagocytosis and killing with a 2- to 27-fold increase in activity compared to controls. These results suggest that tobramycin might be conveniently used with once-daily dosing for the treatment of infections due to sensitive pathogens.

Analysis of Variance↗
PubMed1995

Tissue penetration and pulmonary disposition of tobramycin.

The pharmacokinetics of tobramycin, including the penetration into suction blister fluid (SBF), has been investigated in 12 patients with a mean age of 69.8 +/- 4.6 yrs, after a single i.m. administration of either 150 or 300 mg. Tobramycin demonstrated a concentration-independent pharmacokinetics and a high diffusion into the extravascular compartment with a penetration index (obtained by the SBF and serum AUC ratio) of 135% with no significant differences between the two groups of patients. Tobramycin was also administered as a single or multiple i.m. dose of 300 mg in 10 intensive care patients undergoing fiberoptic bronchoscopy for diagnostic purposes. The aminoglycoside mean concentration 6h after the single or last administration ranged from 5.3 to 5.5 mg/l and from 3.0 to 3.3 mg/l in alveolar lining fluid (ALF) and macrophages (AM), respectively, thus demonstrating that the once-daily dosage schedule leads to high and persistent levels in the bronchial alveolar tree, exceeding the minimum inhibitory concentrations in vitro for susceptible respiratory pathogens.

Adolescent↗
PubMed1995

[Perisinusoidal stellate cells in a model of experimental liver cirrhosis].

The association of the common bile duct (CBD) ligation followed by CCl4 and progesterone treatment leads to liver cirrhosis in rats in 28 days. The resulting cirrhosis shows mixed aspects: it starts as biliary cirrhosis and goes on to nodular and periportal pseudolobular form of cirrhosis. Because Ito cells are the main source of extracellular matrix components, changing their phenotype from quiescent Ito cells to myofibroblast like cells, the purpose of this study was to evaluate the behaviour of Ito cells by the immunohistochemistry technique of desmin and alpha-SM-actin after these treatments. After CBD ligation alone, positive Ito cells for desmin remarkably proliferate around adenomateous areas; after treatment with CCl4 alone desmin positive stellate cells are more numerous. Desmin positive Ito cells in CBD ligation and CCl4 treatment were even larger than those of the previous lots. Significant differences were not observed after progesterone and for the alpha-SM-actin positive cells.

Animals↗
PubMed1995

Down-regulation of beta-adrenergic receptors and up-regulation of estrogen and progesterone receptors induced in the reproductive system of female veal calves by dietary clenbuterol.

Effects induced by long-term administration of clenbuterol at anabolic dosages (20 micrograms/kg of body weight for 40 days) on beta-adrenergic receptor (beta-AR) subtypes, estrogen receptors (ER), and progesterone receptors (PgR) in the reproductive system of female veal calves were investigated. Clenbuterol treatment induced a significant (P < 0.01) down-regulation of beta-AR subtypes (beta 1-AR, beta 2-AR, myometrial high-affinity beta 2-AR, and ovarian low-affinity beta 2-AR). On the other hand, a significant (P < 0.01) increase of uterine and ovarian ER and PgR receptors was observed in treated calves. Treatment did not affect dissociation constant values of beta-AR, ER, or PgR. In similar manner, clenbuterol did not significantly modify distribution of ER and PgR in the various tissues of the genital tract. In fact, these receptors were significantly (P < 0.05) more concentrated in the uterus than in the vagina in treated and untreated calves. Data indicated that prolonged clenbuterol exposure induced homologous beta-AR down-regulation (down-regulation of its specific receptors) and heterologous ER and PgR up-regulation (up-regulation of different types of receptors, not specifically bound by clenbuterol) in the genital tract of veal calves. Modification of the receptorial status could be reasonably related to the pathologic changes observed in long-term treated calves (eg, hydrometra, dilatation of uterine glands, cystic ovaries). The increased concentrations of ER and PgR suggested the possible existence of subcellular mechanisms regulated by repeated beta-adrenergic stimulation.

Adrenergic beta-Agonists↗