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Biomedical subjects

G Ziv

Publications and source records attributed to G Ziv.

At least 19 recordsLinked to original sources
PubMed2003

Subgraphs in random networks.

Understanding the subgraph distribution in random networks is important for modeling complex systems. In classic Erdos networks, which exhibit a Poissonian degree distribution, the number of appearances of a subgraph G with n nodes and g edges scales with network size as approximately N(n-g). However, many natural networks have a non-Poissonian degree distribution. Here we present approximate equations for the average number of subgraphs in an ensemble of random sparse directed networks, characterized by an arbitrary degree sequence. We find scaling rules for the commonly occurring case of directed scale-free networks, in which the outgoing degree distribution scales as P(k) approximately k(-gamma). Considering the power exponent of the degree distribution, gamma, as a control parameter, we show that random networks exhibit transitions between three regimes. In each regime, the subgraph number of appearances follows a different scaling law, approximately Nalpha, where alpha=n-g+s-1 for gamma<2, alpha=n-g+s+1-gamma for 2 gamma(c), where s is the maximal outdegree in the subgraph, and gamma(c)=s+1. We find that certain subgraphs appear much more frequently than in Erdos networks. These results are in very good agreement with numerical simulations. This has implications for detecting network motifs, subgraphs that occur in natural networks significantly more than in their randomized counterparts.

Journal Article↗
PubMed1999

Pharmacokinetics of clindamycin HCl administered intravenously, intramuscularly and subcutaneously to dogs.

A buffered aqueous solution of clindamycin Hcl (200 mg/mL) was injected intravenously (i.v.) intramuscularly (i.m.) and subcutaneously (s.c.) in a non-randomized, partial cross-over trial involving six male and six female dogs. Blood samples were collected at conventional, predetermined time periods and serum drug concentrations were determined by microbiological assay. Dogs were observed clinically for signs of pain, and activity of serum creatine phosphokinase (CPK) was monitored after i.m. dosing. The i.v. data from five of the dogs best fitted a two-compartment open-system pharmacokinetic model whereas a non-compartment model was most suitable for analysis of the data from the remaining seven dogs. The mean i.v. elimination half-life (t1/2 beta) and the mean residence time (MRT) were 124 and 143 min, respectively. The mean volume of distribution at steady state (Vss) was 0.86 L/kg. Little pain was recorded upon i.m. injection; mean peak serum drug concentration (Cmax) was 4.4 micrograms/mL, the elimination half-life (t1/2el) was 247 min and the calculated bioavailability (F) was 115% of the i.v. dose. Serum CPK activity was elevated to 25-fold the pretreatment level in samples collected 4, 8 and 12 h after i.m. injection. Pain was not recorded after s.c. drug administration; the mean Cmax of 20.8 micrograms/mL was significantly greater than the corresponding value for the i.m. route, and F was 310%. The s.c. route appears to be superior to the i.m. route in terms of local tolerance and serum drug level; a 10 mg/kg SID treatment regimen is suggested for treatment of canine infections due to clindamycin sensitive bacteria.

Absorption↗
PubMed1998

Clinical, bacteriological and epidemiological aspects of clinical mastitis in Israeli dairy herds.

A 4-year retrospective study was performed to determine the clinical, bacteriological and epidemiological aspects of acute clinical mastitis in seven Israeli dairy herds. A total of 1124 clinical mastitis cases were detected by abnormal changes in the milk and udder with concurrent decrease of at least 25% in daily milk production. A total of 1190 quarters were affected with clinical mastitis in 1089 cows. The rear quarters had a higher incidence risk (64.7% of quarter cases) than the front quarters. The annual herd-year-incidence varied from 4.2 to 126.8 cases/100 cows/year. The whole-lactation incidence risk (LIR) was 20.8 per 100 lactations. LIR increased from the first to fifth lactation and then decreased. Most clinical mastitis cases were associated with coliform bacteria (60.2% of cases), environmental streptococci (18.6%), coagulase-negative staphylococci (8.7%) and samples from which no bacterial growth was detected (8.1%). Most cases of clinical mastitis occurred in the early stages of lactation, with 51.4% of all cases, 52.3% of coliform cases and 54.6% of environmental streptococci mastitis cases occurring during the first 4 months of lactation. The median days in milk at diagnosis was 118 days. The incidence was lower in the dry summer months. The ratio of peak to low incidence was 1.62 with a calculated peak incidence in January.

Animals↗
PubMed1998

Relationship between in vitro sensitivity of coliform pathogens in the udder and the outcome of treatment for clinical mastitis.

The relationship between in vitro sensitivity to antimicrobials and the outcome of treatment was studied in 228 cows with coliform mastitis. All the cows were treated with a preparation containing sulphonamide and trimethoprim, and 197 of them were also treated with a non-steroidal anti-inflammatory drug (NSAID). The relationship between in vitro sensitivity to sulphonamide/trimethoprim and recovery was analysed by multivariate logistic regression. The possible confounding effects of treatment with an NSAID, days in lactation, parity, herd, and type of infecting organism were tested. Only treatment with an NSAID had a significant confounding effect and was included in the final statistical model. The recovery rate of the 165 cows infected by coliforms that were sensitive to sulphonamide/trimethoprim (89.1 per cent) was higher than that of the 63 cows infected by coliforms that were resistant to sulphonamide/trimethoprim (74.6 per cent). The odds ratio of recovery for the cases associated with organisms that were sensitive to sulphonamide/trimethoprim relative to the cases associated with organisms that were resistant to sulphonamide/trimethoprim was 2.75, with a 95 per cent confidence from 1.25 to 5.85. The odds ratio of recovery for the cases treated with an NSAID relative to the cases treated with sulphonamide/trimethoprim only was 2.76 with a 95 per cent confidence interval from 1.12 to 6.79.

Animals↗
PubMed1998

Pharmacokinetics and penetration of danofloxacin from the blood into the milk of cows.

The single-dose disposition kinetics of danofloxacin were determined in clinically normal lactating cows after intravenous (i.v.) and intramuscular (i.m.) administration of the drug at 1.25 mg/kg. The drug concentrations in blood serum and milk were determined by microbiological assay methods and the data were subjected to kinetic analysis. The mean i.v. and i.m. elimination half-lives (t1/2el) in serum were 54.9 and 135.7 min, respectively. The steady-state volume of distribution (Vss) was 2.04 L/kg. The drug was quickly absorbed after i.m. injection but a 'flip flop' effect was clearly evident and bioavailability was > 100%. Penetration of danofloxacin from blood into milk was rapid and extensive with drug concentrations in milk exceeding those in serum beginning 90-120 min after i.v. and i.m. administration and onwards. Milk danofloxacin concentrations equal to or higher than the minimal inhibitory concentrations (MIC) for pathogenic Gram-negative bacteria and Mycoplasma species were maintained over approximately 24 h. Concentrations greater than the MIC for Staphylococcus aureus were maintained in the milk for 12 h.

Animals↗
PubMed1997

Pharmacokinetics and penetration of marbofloxacin from blood into the milk of cows and ewes.

The single-dose disposition kinetics of marbofloxacin were determined in lactating cows and ewes after intravenous (i.v.) and intramuscular (i.m.) administration of 2, 2.5 and 4 mg/kg. Drug concentrations in blood and milk were determined by microbiological assay and the data were subjected to compartmental and non-compartmental kinetic analyses. In cows, the i.v. serum elimination half-life (t1/2 beta) was approximately 2 h and the i.m. serum elimination half-life (t1/2el) was approximately 3 h. The mean steady-state volume of distribution (Vss) was 1.5 l/kg for the cows and 0.6 l/kg for the ewes. The i.m. availability was nearly 100% for both cows and ewes. Drug penetration into the milk was rapid and extensive with milk marbofloxacin concentrations exceeding those in serum 2 h after administration. Milk drug concentrations equal to or greater than the minimal inhibitory concentrations for the majority of gram-negative udder pathogens were maintained for approximately 12 h after i.v. and i.m. treatment of 2-4 mg/kg. The drug was not detected in milk 24 h after treatment (sensitivity limit of assay = 0.05 microgram/ml).

Animals↗
PubMed1997

Efficacy of cefquinome for treatment of cows with mastitis experimentally induced using Escherichia coli.

The efficacy of intramuscularly and intramammarily administered cefquinome was evaluated in experimental Escherichia coli mastitis in dairy cows. Forty-seven multiparous, Israeli Holstein cows in early lactation that produced at least 25 L/d of milk were used, and 400 to 750 cfu of E. coli were infused into two healthy quarters of each cow. Cows were randomly assigned to one of the following treatment groups: 1) 75 mg of cefquinome administered intramammarily three times at 12-h intervals, 2) 75 mg of cefquinome administered intramammarily three times at 12-h intervals and 1 mg/kg of cefquinome administered intramuscularly two times at a 24-h interval, 3) 1 mg/kg of cefquinome administered intramuscularly two times at a 24-h interval, and 4) 75 mg of ampicillin and 200 mg of cloxacillin administered intramammarily three times at 12-h intervals. All cows developed typical signs of acute clinical mastitis by 12 to 16 h postinoculation. Parenteral cefquinome therapy, with or without intramammary cefquinome (groups 2 and 3), significantly improved clinical recovery and return to milk production. The bacteriological cure rates were considerably and significantly higher for cows in the groups treated with cefquinome than for cows in the group treated with ampicillin and cloxacillin. This study supported the efficacy of cefquinome in the treatment of clinical coliform mastitis in dairy cows.

Animals↗
PubMed1996

The anti-inflammatory drugs phenylbutazone and dipyrone in the treatment of field cases of bovine mastitis.

The efficacy of phenylbutazone vs. dipyrone for the treatment of acute clinical mastitis were compared in a clinical trial. All cows were treated with 20 g sulfadiazine and 4 g trimethoprim i.m. upon diagnosis and half dosage once daily thereafter. In addition, the NSAIDs treated cows received once daily either 4 g phenylbutazone or 20 g dipyrone i.m. for the duration of the antimicrobial therapy. In all treatment groups the major causative organisms were coliforms. Recovery rates for the controls, the phenylbutazone and dipyrone treatment groups were 81.8%, 89.4% and 86.6%, respectively. Recovery was evaluated by the logistic regression analysis, the odds ratios (OR) and their 95% confidence interval (CI) of treatment success for phenylbutazone and dipyrone treatments relative to the control treatment were calculated. Odds ratio of recovery was high for phenylbutazone (OR = 2.42; CI = 0.98-5.96; P = 0.054) as well as for dipyrone (OR = 1.71; CI = 0.98-3.00; P = 0.060), demonstrating a strong trend towards improved recovery in NSAID groups. The odds of treatment failure for the phenylbutazone group relative to the dipyrone group was 0.71 with 95% CI of 0.28-1.78. Clearly no significant difference could be demonstrated between phenylbutazone and dipyrone in this field trial.

Animals↗
PubMed1996

Isolation and antimicrobial susceptibility of obligate anaerobic bacteria recovered from the uteri of dairy cows with retained fetal membranes and postparturient endometritis.

The uteri of 77 postparturient dairy cows were sampled. Samples were cultured aerobically and anaerobically, and the nature of bacterial growth was identified. A mixed aerobic and anaerobic bacterial infection was found in 55% of the samples. Actinomyces pyogenes was the predominant aerobic species; it was found in 70% of the samples, whereas Bacteroides melaninogenicus was the most frequent anaerobic species isolated. Altogether, 16 species belonging to the genus Bacteroides were identified with variable frequencies. It appears that more than one Bacteroides species colonizes the uterus of a given cow postpartum. The minimal inhibitory concentrations (MICs) of clindamycin, metronidazole, tetracycline and ciprofloxacin for 83 anaerobic isolates were determined. All isolates were susceptible to clindamycin (MIC90 of 0.064 microgram/ml) and all but two to metronidazole. Susceptibility to ciprofloxacin was variable, with a bimodal distribution of MIC values. The MIC of tetracycline for 90% of the isolates was > 256 micrograms/ml.

Animals↗
PubMed1995

Pharmacokinetics of ampicillin administered intravenously and intraosseously to kittens.

An aqueous solution of ampicillin sodium (100 mg ml-1) was administered intravenously and intraosseously to six kitten at 50 mg kg-1 in a crossover study. Jugular vein blood samples were taken at intervals up to eight hours after treatment and the serum ampicillin concentration-time data, derived from a microbiological assay, were analysed pharmacokinetically. The disposition kinetics of ampicillin administered by the two routes were very similar. The mean elimination half-life (t1/2 beta), the area-derived volume of distribution (Varea) and the total body clearance (ClB) values after the intravenous and intraosseous treatment were 86.3 and 79.0 minutes, 0.9 and 0.8 litre kg-1 and 7.3 and 7.6 ml min-1 kg-1, respectively. No side-effects related to the intraosseous administration of the drug were observed.

Ampicillin↗
PubMed1995

Clinical pharmacology of cefixime in unweaned calves.

Cefixime is a unique third-generation oral cephalosporin. Its in vitro activity and pharmacokinetic properties have been studied to assess its potential for use in the therapy of newborn calf infections due to gram-negative bacteria. The minimum inhibitory concentrations of cefixime for 90% (MIC90) of field isolates of Escherichia coli, Salmonella and Pasteurella were 0.10-0.40 micrograms/mL. The serum disposition kinetics of cefixime following intravenous and oral administration was evaluated. The elimination half-life of cefixime after intravenous and oral administration was 3.5-4.0 h, the steady-state volume of distribution was 0.34 L/kg and approximately 90% of the drug was bound to serum proteins. Oral absorption was comparatively slow and bioavailability values for single 5 mg/kg doses were 20.2% after the administration of 200 mg of cefixime in capsules, 28.3% after dosing an aqueous solution of cefixime and 35.7% after fasted calves received the solution of cefixime. Mean serum drug concentrations 12 h after the cefixime solution was administered orally (5 mg/kg) were 1.05 micrograms/mL for the milk-fed calves and 1.76 micrograms/mL for the fasted calves. Computations showed that mean free drug concentrations equal to the MIC50 of the drug for gram-negative pathogens associated with newborn calf infections can be maintained in tissues by multiple treatments at 5 mg/kg every 12 h or 10 mg/kg every 24 h.

Administration, Oral↗
PubMed1995

Intravenous disposition kinetics, oral and intramuscular bioavailability and urinary excretion of norfloxacin nicotinate in donkeys.

An aqueous solution of norfloxacin nicotinate (NFN) was administered to donkeys (Aquus asinus) intravenously (once at 10 mg/kg), intramuscularly and orally (both routes once at 10 and 20 mg/kg, and for 5 days at 20 mg/kg/day). Blood samples were collected at predetermined times after each treatment and urine was sampled after intravenous drug administration. Serum NFN concentrations were determined by microbiological assay. Intravenous injection of NFN over 45-60 s resulted in seizures, profuse sweating and tachycardia. The intravenous half-life (t1/2 beta) was 209 +/- 36 min, the apparent volume of distribution (Vd(area)) was 3.34 +/- 0.58 L/kg, the total body clearance (ClB) was 1.092 +/- 0.123 x 10(-2) mL/min/kg and the renal clearance (C1R) was 0.411 +/- 0.057 x 10(-2) mL/min/kg. Oral bioavailability was rather poor (9.6% and 6.4% for the 10 and 20 mg/kg doses respectively). Multiple oral treatments did not result in any clinical gastrointestinal disturbances. After intramuscular administration (20 mg/kg), serum NFN concentrations > 0.25 microgram/mL (necessary to inhibit the majority of gram-negative bacteria isolated from horses) were maintained for 12 h. The intramuscular bioavailability was 31.5% and 18.8% for the 10 and 20 mg/kg doses respectively. After multiple dosing some local swelling was observed at the injection site. About 40% of the intravenous dose was recovered in the urine as parent drug. The results of comprehensive haematological and blood biochemistry tests indicated no abnormal findings except elevation in serum CPK (creatine phosphokinase) values after multiple intramuscular dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1995

Disposition kinetics of tylosin tartrate administered intravenously and intramuscularly to normal and water-deprived camels.

The disposition kinetics of tylosin tartrate administered intravenously (i.v.) at 10 mg/kg and intramuscularly (i.m.) at 20 mg/kg were studied in normal camels and in the same camels at the end of a 14 day water-deprivation period. After i.v. treatment, serum tylosin concentrations in the water-deprived camels were significantly higher, rate of drug elimination was slower, the volume of distribution was significantly smaller, and total body clearance was significantly slower than in the normal camels. On the other hand, serum drug concentrations were lower in the water deprived camels after i.m. dosing, the mean absorption time was significantly shorter and the i.m. availability was significantly smaller than in the normal camels. Water-deprivation was thought to cause reduced rate of tylosin elimination by the liver, as was shown for antipyrine--a drug which is eliminated from the body exclusively by the liver. Redistribution of tylosin in tissues concomitant with a greater proportion of drug in blood and extracellular fluid of water-deprived camels was suggested as a partial explanation for the higher serum drug levels seen after i.v. dosing. The low i.m. availability observed in the water-deprived camels implies that i.v. is the route of choice for tylosin administration to ill, dehydrated camels.

Animals↗
PubMed1995

Effect of water deprivation on the disposition kinetics of enrofloxacin in camels.

Concentrations of enrofloxacin equivalent activity were determined (by microbiological assay) in the serum of normal camels and camels at the end of a 14-day water-deprivation period following single intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) administrations at 2.5 mg/kg. Also, normal camels were given an oral drench of the drug at 5 mg/kg. Pharmacokinetic variables were determined using compartmental and non-compartmental analytical methods. Camels lost on average 12.5% of body weight at the end of the water-deprivation period. The disposition kinetics of i.v. administered drug in normal and water-deprived camels were very similar. The t1/2 beta was 3.0-3.5 h; MRT was 4.0-4.5 h; Vc was 0.3 L/kg; Vss was 1.0 L/kg and ClB was 4.0-4.6 mL/min/kg. The effect of water deprivation on the rate of drug absorption and elimination after i.m. administration was inconsistent, and there was also a large degree of variability in the normal animals that precluded statistical significance. After s.c. administration, the mean absorption half-life (t1/2abs) in the water-deprived camels was significantly longer than in the normal camels. Systemic availability (F) was similar in both normal and water-deprived camels after i.m. dosing but was significantly greater (P < 0.05) in normal camels (0.92 compared with 0.65 in water-deprived camels) after s.c. treatment. In normal camels, urinary recovery at 12 h after i.v. and s.c. dosing was 25% and 15%, respectively, and the extent of serum protein binding ranged between 1.7% at 1.8 micrograms/mL and 24% at 0.33 microgram/mL. The drug was not detected in serum after oral administration. Serum and milk enrofloxacin equivalent activities were determined after i.v. (one camel) and i.m. (one camel) drug administration. Serum drug concentrations were consistently higher than in the milk. The AUCmilk/AUCserum ratios were 0.27 and 0.39 after i.v. and i.m. drug administration, respectively. An i.m. or s.c. treatment regimen of 2.5 mg/kg q.12 h is suggested for clinical and bacteriological efficacy trials with enrofloxacin in normally hydrated and dehydrated camels.

Absorption↗
PubMed1995

Tilmicosin antibacterial activity and pharmacokinetics in cows.

The minimal inhibitory concentration (MIC) of tilmicosin for 90% of 112 Staphylococcus aureus isolates from the bovine udder was 0.78 microgram/mL and 149 of 164 (90.8%) other gram-positive udder pathogens were inhibited by tilmicosin concentrations < 3.12 micrograms/mL. The MIC of the drug for 19 of 22 S. aureus isolates was < 0.78 microgram/mL when the test was conducted using Mueller-Hinton (MH) agar or MH agar containing 7.5% skimmed milk. Acute cardiac toxicity followed intravenous (i.v.) injection of the drug at 10 mg/kg to 3 cows, but animals appeared clinically normal within 30 min after treatment. The pharmacokinetics of i.v.-administered tilmicosin is typical for the macrolide class of antibiotics, i.e. low serum drug concentrations and a large volume of distribution (> 2.0 L/kg). The elimination half-life (t1/2 beta) values for 3 cows were 46.4, 56.0 and 72.8 min. The drug was administered subcutaneously (s.c.) to 5 cows at 10 mg/kg; the elimination half-life (t1/2el) was 4.18 +/- 0.55 h and the mean s.c. bioavailability was 22%. Rapid and extensive penetration of tilmicosin from blood into milk, and slow elimination from the milk were among the characteristic kinetic features of the drug after i.v. and s.c. administration. Tilmicosin was injected s.c. at 10 mg/kg once to 9 cows after the last milking of lactation; dry udder secretion samples were collected daily for 11 consecutive days and assayed microbiologically. Concentrations of drug > 0.78 microgram/mL were found in the secretion for 8-9 days after dosing. Systemic side-effects were not observed after s.c. drug administration.

Animals↗
PubMed1995

Serum and milk concentrations of apramycin in lactating cows, ewes and goats.

A 20% solution of apramycin was administered intravenously (i.v.) and intramuscularly (i.m.) to lactating cows with clinically normal and acutely inflamed udders, to lactating ewes with normal or subclinically infected, inflamed udders and i.v. to lactating goats with normal udders. The i.v. disposition kinetics of apramycin was very similar in cows, ewes and goats. The elimination half-life was approximately 2 h and the steady-state volume of distribution was 1.26-1.45 L/kg. The absorption rate of the drug from the i.m. injection site was rapid, the i.m. bioavailability was 60-70% and the mean elimination half-life was 265 min in cows and 145.5 min in ewes. The binding percentage of apramycin to serum protein was low (< 22.5%). Concentrations of apramycin in milk produced by clinically normal mammary glands of cows, ewes and goats were consistently lower than in serum; the kinetic value AUCmilk/AUCserum was < 0.32. Drug penetration into the milk from the acutely inflamed quarters of cows was extensive; mastitis milk Cmax values were more than tenfold greater than the Cmax in normal milk. On the other hand, the drug had limited access to the milk produced by subclinically infected inflamed half-udders of ewes.

Animals↗