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Biomedical subjects

A Novelli

Publications and source records attributed to A Novelli.

At least 109 records · Page 6Linked to original sources
PubMed1989

Clinical pharmacokinetics and tissue penetration of teicoplanin.

The pharmacokinetic properties were investigated of teicoplanin, including its penetration into suction blister fluid (SBF), after a single intravenous bolus administration of 600 mg in seven pneumological patients with normal renal and hepatic function. Blood and SBF samples were collected during the 60-hour period drug administration. Teicoplanin was assayed microbiologically and the mean serum concentration at the end of the i.v. injection was 98.7 +/- 16 mg/l falling to 2.3 +/- 0.4 mg/l at 60 h. The antibiotic was rapidly distributed into a fast equilibrating peripheral compartment and, at a lower rate, into a slowly equilibrating peripheral compartment, while the mean elimination half-life (t1/2 beta) was 34.1 +/- 6.8 h. Penetration into the SBF, though slow, was good, reaching a mean peak level of 8.7 +/- 1.7 mg/l at a mean time of 2.1 h, with a penetration index (obtained by percentage ratio of the area under curve in the SBF to that of serum) of 42.9%.

Adult↗
PubMed1989

Pharmacokinetics of teicoplanin during cardiopulmonary bypass surgery.

Teicoplanin is a recently introduced long-acting glycopeptide antibiotic effective against Gram-positive aerobic and anaerobic bacteria. The effects of hypothermic extracorporeal circulation on teicoplanin serum pharmacokinetics have been studied in 18 patients undergoing open-heart surgery for coronary artery bypass graft or prosthetic cardiac valve insertion. The patients received a single 600 mg dose of teicoplanin by intravenous (i.v.) bolus (five cases) or by i.v. infusion over 20 min (13 cases) approximately 1 h before the anticipated skin incision and 2 h before the anticipated extracorporeal circulation. Serum drug concentrations were measured by a microbiological method using Bacillus subtilis ATCC 6633 as the test organism. Following i.v. bolus injection and i.v. infusion, teicoplanin levels in serum (mean +/- s.d.) were respectively 13.9 +/- 6.8 and 11.4 +/- 2.4 mg/l at the beginning of extracorporeal circulation, 8.8 +/- 3.5 and 10.2 +/- 2.3 mg/l at the end of this procedure and 2.8 +/- 0.6 and 2.9 +/- 1.0 mg/l at 24 h after surgery. Mean AUCs were 378.1 +/- 52.5 and 328.9 +/- 88.0/l.h and mean elimination half-life values were 27.9 +/- 12.7 and 30.3 +/- 11.0 h, respectively under the same conditions. These differences in plasma pharmacokinetic parameters were not significant. Teicoplanin pharmacokinetics in patients undergoing cardiopulmonary bypass surgery were similar to those observed in non-surgical patients with normal renal and hepatic function, confirming experimental evidence for lack of effects of extracorporeal circulation.

Bacterial Infections↗
PubMed1989

[The effect of hypophysectomy on liver regeneration in the rat].

Liver regeneration after partial hepatectomy in Wistar rats, hypophysectomised and otherwise has been studied. In almost all hypophysectomised rats, the regenerative processes were much less evident than in the non-hypophysectomised controls; only some hypophysectomised animals showed effective liver regeneration through an as yet unclear mechanism.

Animals↗
PubMed1988

Glutamate becomes neurotoxic via the N-methyl-D-aspartate receptor when intracellular energy levels are reduced.

The N-methyl-D-aspartate (NMDA) subtype of glutamate receptor appears to play a pivotal role in enabling glutamate to express its neurotoxic potential in a variety of neurological disorders. Our results show that the transition of glutamate from neurotransmitter to neurotoxin is facilitated when cellular energy is limited in cultured cerebellar neurons. Omission of glucose, exclusion of oxygen, or inclusion of inhibitors of oxidative phosphorylation or of the sodium/potassium pump, enables the excitatory amino acids glutamate or NMDA to express their neurotoxic potential. We interpret these results as demonstrating that glucose metabolism, ATP production, and functioning Na+,K+-ATPases are necessary to generate a resting potential sufficient to maintain the voltage-dependent Mg2+ block of the NMDA receptor channel; relief of the Mg2+ block enables the excitatory amino acids to act persistently at the NMDA receptor, resulting in the opening of ion channels and subsequent neuronal damage. These findings are discussed in the context of perturbations or abnormalities which lead to decreased availability or utilization of glucose and oxygen in the brain which may trigger endogenous excitatory amino acids to become neurotoxic by this mechanism.

Amino Acids↗
PubMed1988

In vitro activity of temafloxacin, a new difluoro quinolone antimicrobial agent.

Temafloxacin, a new difluoro quinolone, inhibited the majority of Enterobacteriaceae at less than or equal to 1 microgram/ml. It was 4-8-fold less active than ciprofloxacin and 2-fold less active than ofloxacin. Cefotaxime and imipenem-resistant isolates such as Enterobacter cloacae, Citrobacter freundii, Pseudomonas aeruginosa, and Acinetobacter spp. were inhibited. Temafloxacin inhibited Neisseria, Branhamella, and Haemophilus species at less than 0.25 microgram/ml. Methicillin-susceptible and methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis and Clostridium spp. were inhibited at concentrations less or equal to that of ciprofloxacin and ofloxacin.

Anti-Bacterial Agents↗
PubMed1988

In vitro activity of E-1040, a novel cephalosporin with potent activity against Pseudomonas aeruginosa.

The in vitro activity of E-1040 [(6R,7R)-3-[(4-carbamoyl-1-quinuclidinio)methyl]-7-[2-(5-amino-1,2 ,4- thiadiazol-3-yl)-(Z)-2-methoxyiminoacetoamido]-8-oxo-5-thia- 1- azabicyclo(4,2,0)oct-2-ene-2-carboxylate], a novel cephalosporin, was compared with that of ceftazidime, cefpirome, cefepime, imipenem, and gentamicin. E-1040 inhibited 50% of members of the family Enterobacteriaceae, Pseudomonas aeruginosa, and Haemophilus and Neisseria species at less than or equal to 0.25 microgram/ml, and the MIC for 90% of strains tested ranged from 0.06 to 2 micrograms/ml. It was two- to fourfold more active than ceftazidime and similar in activity to cefepime and cefpirome. It inhibited Enterobacter, Citrobacter, Serratia, and Morganella species that were resistant to ceftazidime. E-1040 inhibited imipenem-, piperacillin-, aztreonam-, and tobramycin-resistant P. aeruginosa. It was less active against Xanthomonas maltophilia and P. cepacia but inhibited other Pseudomonas species. The activity of E-1040 against staphylococci and hemolytic streptococci was similar to that of ceftazidime, but E-1040 was less active than cefepime and cefpirome. It did not inhibit Bacteroides spp. There was no inoculum effect or medium effect, and MBCs were within a dilution of MICs. Plasmid beta-lactamases TEM-1, TEM-2, TEM-3 (CTX-1), SHV-1, Staphylococcus aureus, PSE, and CARB did not hydrolyze E-1040. Chromosomal beta-lactamases P99 and K-1 did not hydrolyze E-1040; E-1040 had poor affinity for these enzymes, with a Ki of greater than 100 microM.

Aminoglycosides↗
PubMed1988

In vitro activities of two oxazolidinone antimicrobial agents, DuP 721 and DuP 105.

The antibacterial activities of DuP 105 and DuP 721, new oxazolidinone antimicrobial agents, were compared with those of beta-lactams and glycopeptides. Ninety percent of Staphylococcus aureus and Staphylococcus epidermidis isolates, including methicillin-resistant isolates, were inhibited by 4 micrograms of DuP 105 and 1 microgram of DuP 721 per ml. DuP 721 inhibited hemolytic streptococcus groups A, B, C, F, and G at a concentration of less than or equal to 1 microgram/ml, and it inhibited viridans group streptococci at a concentration of 2 micrograms/ml. Both agents inhibited Listeria monocytogenes, Corynebacterium group JK species, anaerobic cocci, and Clostridium spp. including Clostridium difficile. They did not inhibit members of the family Enterobacteriaceae or Pseudomonas aeruginosa, but the MIC for 90% of Bacteroides fragilis isolates was 8 micrograms of DuP 721 per ml.

Anti-Bacterial Agents↗
PubMed1988

In vitro activity of lomefloxacin (SC-47111; NY-198), a difluoroquinolone 3-carboxylic acid, compared with those of other quinolones.

Lomefloxacin (SC-47111; NY-198) is a new difluoroquinolone agent. It inhibited 90% of Escherichia coli, Klebsiella spp., Enterobacter spp., Citrobacter spp., Proteus mirabilis, Morganella morganii, Proteus vulgaris, Serratia marcescens, Salmonella spp., Shigella spp., Aeromonas spp., Yersinia spp., Haemophilus influenzae, and Neisseria gonorrhoeae at less than or equal to 2 micrograms/ml. Lomefloxacin inhibited 90% of Pseudomonas aeruginosa at 4 micrograms/ml. Lomefloxacin was equal in activity to norfloxacin against Escherichia coli, Klebsiella spp., Enterobacter spp., Haemophilus influenzae, and Neisseria gonorrhoeae but was twofold less active against Proteus spp., Providencia spp., Serratia marcescens, Salmonella spp., and Shigella spp. Ofloxacin was generally 2- to 4-fold more active, and ciprofloxacin was 4- to 16-fold more active. Lomefloxacin inhibited Staphylococcus aureus, including methicillin-resistant isolates, but MICs for 90% of streptococcal species tested were 8 micrograms/ml. In the presence of 9 mM Mg2+, MICs for Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, and Pseudomonas aeruginosa were increased, as they were when they were tested in urine. A single-step increase in resistance to eightfold above the MIC occurred at a frequency of less than 10(-10), but serial transfer of bacteria in the presence of the agent produced MIC increases. Lomefloxacin had activity and properties comparable to those of many of the new quinolones.

Anaerobiosis↗
PubMed1988

Comparative in vitro activity of a new fluorinated 4-quinolone, T-3262 (A-60969).

The in vitro activity of a new quinolone, T-3262 [A-60969; DL-7-(3-amino-1-pyrrolidinyl)-1-(2,4-difluorophenyl)-6-fluoro-1-, 4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid monohydrate], was compared with those of ciprofloxacin, ofloxacin, ceftazidime, imipenem, and gentamicin. T-3262 inhibited 90% of isolates of the family Enterobacteriaceae at a concentration of less than or equal to 0.25 micrograms/ml. It was two to four times more active than ofloxacin and similarly or slightly less active than ciprofloxacin. Ninety percent of isolates of Pseudomonas aeruginosa were inhibited at 0.5 micrograms/ml. It was 4- to 8-fold more active than ciprofloxacin and 8- to 16-fold more active than ofloxacin against Pseudomonas cepacia and Pseudomonas maltophilia, which were resistant to imipenem and gentamicin. Most Haemophilus influenzae, Neisseria gonorrhoeae, and Branhamella catarrhalis isolates were inhibited at concentrations of less than or equal to 0.008 micrograms/ml. The MIC for 90% of the Staphylococcus aureus isolates, including methicillin-resistant S. aureus, was 0.12 micrograms/ml; that for Staphylococcus epidermidis was 0.5 micrograms/ml, as was that for Enterococcus faecalis. It inhibited 90% of Bacteroides fragilis isolates at 2 micrograms/ml, considerably more active than ciprofloxacin and ofloxacin. The frequency of spontaneous point mutational resistance was less than 10(-10) for members of the family Enterobacteriaceae and Pseudomonas spp. Resistant strains could be selected by repeated subculture. Similar to other quinolones, its activity could be affected by culture conditions. T-3262 showed a postantibiotic suppressive effect on Escherichia coli, P. aeruginosa, and S. aureus.

Anti-Bacterial Agents↗
PubMed1988

Ceftizoxime concentrations in human aqueous humor following intravenous administration.

The aqueous humor penetration of the third-generation cephalosporin, ceftizoxime, was determined in 21 patients awaiting cataract extraction, after an intravenous bolus injection of 2 g. The beta-lactam compound achieved a mean peak aqueous humor concentration of 7.8 mg/l two hours after administration with a serum/humor percent ratio ranging between 7 and 16% during the four-hour sampling interval. Therefore, ceftizoxime levels in this extravascular fluid were above the minimum inhibitory concentrations for the majority of sensitive organisms.

Adult↗
PubMed1987

Characterization of cells from invaded lymph nodes in patients with solid tumors. Lymphokine requirement for tumor-specific lymphoproliferative response.

The specific immune response against the malignant cells was investigated in patients with urinary bladder or larynx cancer. Lymphocytes from lymph nodes that drain the tumor site were tested for their proliferative and cytotoxic capacities against autologous malignant cells isolated from the primary tumor. In no occasion was a proliferative or a cytotoxic response observed. However, when the lymph node cell suspensions were depleted of cells expressing both OKM1 and Leu-7 markers by rosetting with the appropriate mAbs, a proliferative response could be observed. The lymphocytes responded to autologous tumor cells only if IL-2 was added to the cultures. IL-2 alone induced some cell proliferation, which was not, however, comparable to that observed in response to both IL-2 and tumor cells. A panel of allogeneic tumor cells consistently failed to stimulate OKM1-, Leu-7- cells in vitro. Response to autologous tumor cells was not caused by HLA-encoded molecules, as occurs in the autologous mixed lymphocyte reaction, since OKM1-, Leu-7- cells failed to be stimulated by autologous non-T cells. A proliferative response was observed only with cells from lymph nodes that had been classified as invaded by malignant cells according to histopathologic criteria. Cells from noninvaded lymph nodes consistently failed to respond. Cells stimulated with autologous tumor cells could be expanded in short-term lines by continuous addition of IL-2 and malignant cells. One of these lines, which comprised mainly T8+ cells, was stimulated to proliferate only by autologous tumor cells, and its proliferative response was inhibitable by anti-class I and not by anti-class II mAbs. This line showed lytic capacities against autologous malignant targets, while it was inefficient against all of the other allogeneic cells tested. In another set of experiments, the mechanisms whereby exogenous IL-2 had to be added to the cultures to sustain a proliferative response against neoplastic cells were investigated. When cocultured with autologous malignant cells, OKM1-, Leu-7- lymphocytes expressed IL-2 receptors, as could be assessed by anti-Tac fluorescent staining. Under these culture conditions, these cells did not produce IL-2, and no proliferation was observed. Addition of purified IL-1 to the cultures induced IL-2 production and cell proliferation. It is concluded that metastatic lymph nodes contain a T cell population that can be detected in a proliferative assay when both suppressor cells are removed and the appropriate molecular signals are supplied.

Antigens, Surface↗
PubMed1987

Uptake of imipramine in neurons cultured from rat cerebellum.

Imipramine was taken up by rat cerebellar neurons in primary culture. The process was dependent on time, temperature and pH and was reduced in the presence of the adenosine triphosphatase (ATPase) inhibitor dicyclohexylcarbodiimide or in the absence of glucose. Uptake approached saturation at 100 microM imipramine where approximately 42 nmol of the drug accumulated intracellularly per mg cell protein. Propranolol, but not serotonin, competed for imipramine uptake and uptake was inhibited by the 'lysosomotropic' amine chloroquine and by the Na+/H+ ionophore monensin, both of which dissipate proton gradients. Neurons were fractionated on Percoll gradients and the fractions exposed to [3H]imipramine. MgATP-dependent accumulation of [3H]imipramine was found mainly in fractions enriched for dense lysosomes. We conclude that imipramine was taken up by cerebellar neurons in primary culture and accumulated at high concentrations in intracellular compartments.

Animals↗
PubMed1987

cGmp synthesis in cultured cerebellar neurons is stimulated by glutamate via a Ca2+-mediated, differentiation-dependent mechanism.

Sensitivity of cyclic GMP synthesis to stimulation by excitatory amino acids, depolarizing agents, and divalent cation ionophores develops during the differentiation of cerebellar neurons in culture; in each case calcium influx appears responsible for activating guanylate cyclase. The developmental event being followed is not the appearance of either the soluble or the particulate form of the enzyme since both are present throughout. The possible role of a differentiation-dependent calcium-modulating protein is discussed.

Animals↗
PubMed1987

Prophylactic chemotherapy with fosfomycin trometamol salt during transurethral prostatic surgery: a controlled multicenter clinical trial.

A prospective, randomized controlled study was carried out in 24 Italian urology wards in 675 patients undergoing transurethral prostatic resection, utilizing three different chemoprophylactic treatments with either amoxycillin (AMX), co-trimoxazole (CTX) or fosfomycin trometamol salt (FT) in order to prevent postoperative urinary tract infections. FT significantly lowered the incidence of both postoperative bacteriuria and symptomatic infections in comparison to AMX and CTX. Transient side effects, mild or moderate, were observed in 6.6% of cases. Similar safety and protective results were obtained in 233 patients undergoing different transurethral instrumentations who were chemoprophylactically treated with FT.

Aminoglycosides↗
PubMed1987

Excitatory amino acid receptors coupled with guanylate cyclase in primary cultures of cerebellar granule cells.

Primary cultures of cerebellar granule cells have been used in pharmacologically and functionally characterizing excitatory amino acid recognition sites coupled with guanylate cyclase. When granule cells were incubated in physiological culture conditions (Locke's solution, pH 7.4), only kainate and, to a lesser extent, L-glutamate increased cyclic GMP (cGMP) levels. Under these conditions, L-aspartate, N-methyl-D-aspartate (NMDA), and quisqualate were inactive. When granule cells were incubated in the absence of extracellular Mg2+ or in the presence of the depolarizing agent veratrine, L-glutamate, L-aspartate, and NMDA became as effective as kainate in enhancing cGMP formation. The action of kainate was preferentially antagonized by 2,3-cis-piperidindicarboxylate, whereas the action of L-glutamate was preferentially antagonized by (+/-)2-amino-5-phosphonovalerate. These data suggest that 2 different excitatory amino acid recognition sites (activated by kainate or by L-glutamate, L-aspartate, and NMDA, respectively) are coupled with guanylate cyclase in primary cultures of cerebellar granule cells: While the coupling of the recognition site for kainate with guanylate cyclase operates under resting conditions and in the presence of Mg2+, the coupling of the recognition site for L-glutamate, L-aspartate, and NMDA with guanylate cyclase requires depolarizing conditions or the absence of extracellular Mg2+.

Amino Acids↗
PubMed1987

Ciprofloxacin inhibition of cefoxitin betalactamase induction in an Enterobacter cloacae strain.

The betalactamase activity of an Enterobacter cloacae strain was measured using subinhibitory concentrations of cefoxitin and ciprofloxacin respectively as enzyme inducer and induction inhibitor. Cultures of this strain were also exposed to different ceftriaxone concentrations either alone or in the presence of cefoxitin and/or ciprofloxacin. Ciprofloxacin at subinhibitory concentrations does not interfere with ceftriaxone's activity and is capable of neutralizing the antagonistic effect of cefoxitin on ceftriaxone. The enzyme assay and MS-2 System demonstrate ciprofloxacin's partial suppression of cefoxitin betalactamase induction in the E. cloacae strain tested.

Cefoxitin↗
PubMed1986

The activation of inositol phospholipid metabolism as a signal-transducing system for excitatory amino acids in primary cultures of cerebellar granule cells.

L-Glutamic, L-aspartic acids and a number of their structural analogs, including quisqualic, kainic, ibotenic, quinolinic, and N-methyl-D-aspartic (NMDA) acids, increase inositol phospholipid hydrolysis when added to primary cultures of cerebellar granule cells, as is reflected by an enhanced formation of 3H-inositolmonophosphate (3H-IP1) in the presence of Li+. L-Glutamic acid also enhances the formation of the initial products of inositol phospholipid hydrolysis, 3H-inositol di-(3H-IP2) and triphosphate (3H-IP3). In the absence of extracellular Ca2+, L-glutamic acid fails to enhance 3H-IP1 formation, but still increases 3H-IP2 and 3H-IP3 formation. The stimulation of 3H-IP1 formation elicited by L-glutamic acid is reduced by DL-2-amino-5-phosphonovaleric acid (APV) and gamma-glutamylglycine and, to a lesser extent, by 2,3-cis-piperidindicarboxylic acid (PDA). The stimulation of 3H-IP1 formation by kainic acid is antagonized by PDA and gamma-glutamylglycine, but it is almost unaffected by APV. The increase in 3H-IP1 formation elicited by quisqualic acid is not reduced by any of the dicarboxylic amino acid receptor antagonists that we have tested. We conclude that different subtypes of excitatory amino acid recognition sites are associated with inositol phospholipid metabolism in primary cultures of cerebellar granule cells.

Amino Acids↗