Mitochondrial metabolism in neural stem cells and implications for neurodevelopmental and neurodegenerative diseases.

Mitochondria are cytoplasmic organelles having a fundamental role in the regulation of neural stem cell (NSC) fate during neural development and maintenance.During embryonic and adult neurogenesis, NSCs undergo a metabolic switch from glycolytic to oxidative phosphorylation with a rise in mitochondrial DNA (mtDNA) content, changes in mitochondria shape and size, and a physiological augmentation of mitochondrial reactive oxygen species which together drive NSCs to proliferate and differentiate. Genetic and epigenetic modifications of proteins involved in cellular differentiation (Mechanistic Target of Rapamycin), proliferation (Wingless-type), and hypoxia (Mitogen-activated protein kinase)-and all connected by the common key regulatory factor Hypoxia Inducible Factor-1A-are deemed to be responsible for the metabolic shift and, consequently, NSC fate in physiological and pathological conditions.Both primary mitochondrial dysfunction due to mutations in nuclear DNA or mtDNA or secondary mitochondrial dysfunction in oxidative phosphorylation (OXPHOS) metabolism, mitochondrial dynamics, and organelle interplay pathways can contribute to the development of neurodevelopmental or progressive neurodegenerative disorders.This review analyses the physiology and pathology of neural development starting from the available in vitro and in vivo models and highlights the current knowledge concerning key mitochondrial pathways involved in this process.

Non-lactose-fermenting uropathogenic Escherichia coli from dogs: virulence profile characterization.

Non-lactose-fermenting Escherichia coli (NLFEC) has a few descriptive studies restricted to human infections. In the present study, isolates of NLFEC obtained from urine samples of dogs with hyperadrenocorticism were characterized regarding their virulence ability, biofilm formation capacity and antimicrobial susceptibility profile. Escherichia coli lactose-fermenting strains from urinary infection in dogs with the same conditions were analysed to provide comparisons. The non-lactose-fermenting E. coli strains were classified as belonging to clade I E. coli, whereas the lactose-fermenting strains were classified in phylogroup B2. All strains presented virulence markers to adhesion, iron acquisition, toxins, colicin and cytotoxin production, and biofilm regulation. Components of the extracellular matrix in addition to the in vitro biofilm formation ability were observed in the strains. Multidrug resistance (MDR) profiles were observed by in vitro susceptibility tests to all NLFEC strains. In summary, non-lactose-fermenting uropathogenic E. coli from dogs behaves similar to lactose-fermenting E. coli, exhibiting MDR profile, and pathogenic potential of promote animal infections.

Molecular detection of Salmonella serovars Enteritidis, Heidelberg and Typhimurium directly from pre-enriched poultry samples.

1. Salmonella is one of the most important pathogens in public health and it is usually associated with food-borne diseases. Salmonella serovars Enteritidis and Typhimurium are widespread in the world with outbreaks frequently associated with consumption of poultry products; furthermore, there is an increasing public health concern with the wide dissemination of the serovar Heidelberg in poultry flocks. 2. The aim of the experiment was to develop and to validate rapid methods to detect Salmonella serovars Enteritidis, Typhimurium, and Heidelberg by real-time PCRs and test isolates from pre-enriched poultry samples. 3. Three real-time PCRs were developed and used in combination to detect the serovars Enteritidis, Typhimurium and Heidelberg. These assays were validated by the analysis of 126 Salmonella isolates, eight other enteric bacterial species and 34 naturally contaminated poultry samples after pre-enrichment with buffered peptone water (BPW). 4. Real-time PCRs detected the isolates of the most important poultry serovars (Enteritidis, Typhimurium and Heidelberg) with 100% inclusivity and exclusivity in each assay. The PCR identified monophasic variants of the serovars Typhimurium and Heidelberg. All PCRs were validated in detecting these specific serovars directly from pre-enriched poultry samples. The whole analytical procedure was performed in less than 24 h in a veterinary diagnostic laboratory.

Pharmacokinetics and perioperative efficacy of intravenous ketorolac in dogs.

Ketorolac (KET) is a nonsteroidal anti-inflammatory drug approved for the use in humans that possesses a potent analgesic activity, comparable to morphine, and could represent a useful tool to control acute pain also in animals. The clinical efficacy and pharmacokinetic profile of intravenous (IV) ketorolac tromethamine (0.5 mg/kg) were studied in 15 dogs undergoing gonadectomy. Intra-operative cardiorespiratory variables were monitored, and post-operative pain was assessed using a subjective pain score (0-24) in all dogs, whereas the pharmacokinetic profile of the drug was determined in 10 animals. During surgery, mean minimal alveolar concentration of isoflurane was 1.69 ± 0.11%, and normocapnia and spontaneous ventilation were maintained in all animals. During pain assessment, no significant differences between males and females were found, and in no case rescue analgesia was necessary. No adverse effects were reported. Serum samples were purified by solid-phase extraction and analysed by HPLC with UV-Vis detection. A large variability was observed in serum concentrations. The kinetics of ketorolac was described by a noncompartmental analysis. The elimination half-life (t½λz ) and ClB were 10.95 ± 7.06 h and 92.66 ± 84.49 mL/h/kg, respectively, and Vdss and Vz were 1030.09 ± 620.50 mL/kg and 1512.25 ± 799.13 mL/kg, respectively. AUC(0→last) and MRT(0→last) were 6.08 ± 3.28 h × µg/mL and 5.59 ± 2.12 h, respectively. The results indicate that ketorolac possess good post-operative analgesic effects until about 6 h after administration in dogs undergoing moderately painful surgery.

Pharmacokinetics of ketamine and propofol combination administered as ketofol via continuous infusion in cats.

The pharmacokinetics of the extemporaneous combination of low doses of ketamine and propofol, known as 'ketofol', frequently used for emergency procedures in humans to achieve safe sedation and analgesia was studied in cats. The study was performed to assess propofol, ketamine and norketamine kinetics in six female cats that received ketamine and propofol (1:1 ratio) as a loading dose (2 mg/kg each, IV) followed by a continuous infusion (10 mg/kg/h each, IV, 25 min of length). Blood samples were collected during the infusion period and up to 24 h afterwards. Drug quantification was achieved by HPLC analysis using UV-visible detection for ketamine and fluorimetric detection for propofol. The pharmacokinetic parameters were deduced by a two-compartment bolus plus infusion model for propofol and ketamine and a monocompartmental model for norketamine. Additional data were derived by a noncompartmental analysis. Propofol and ketamine were quantifiable in most animals until 24 and 8 h after the end of infusion, respectively. Propofol showed a long elimination half-life (t(1/2λ2) 7.55 ± 9.86 h), whereas ketamine was characterized by shorter half-life (t(1/2λ2) 4 ± 3.4 h) owing to its rapid biotransformation into norketamine. The clinical significance of propofol's long elimination half-life and low clearance is negligible when the drug is administered as short-term and low-dosage infusion. The concurrent administration of ketamine and propofol in cats did not produce adverse effects although it was not possible to exclude interference in the metabolism.

Arthroscopic repair of massive rotator cuff tear. The role of the LHB distal tenotomy.

PURPOSE: The aim of the study was to evaluate the results of an all arthroscopic technique for the treatment of massive rotator cuff tears using the long head of biceps as a graft to reconstruct the superior capsule and to reinforce the cuff. METHODS: A retrospective review of a consecutive series of arthroscopic repair of massive rotator cuff tears using the long head of biceps tendon was conducted. Twenty-five patients underwent surgery, and none were lost at follow-up. Minimum follow-up period was more than 12 months. Constant, UCLA and VAS scores as clinical outcome were analyzed. Time for surgical procedures was also registered. Two alternative procedures (transosseous or anchors) were employed to fix laterally the long head of biceps to the greater tuberosity and to reinforce the cuff. This choice was essentially determined by the bone quality of the greater tuberosity. RESULTS: All patients of both groups (Transosseous: 15 and Anchors: 10) showed a significant improvement of clinical and functional scores. Difference of the operative times between two procedures was statistically significant in favor of the anchor approach. No intraoperative complications were recorded. Postoperative shoulder stiffness was found in two male patients. In no case biceps tenodesis was performed: Popeye sign was easily detected in 16 patients but they did not complain any superior arm pain and weakness. CONCLUSION: This technique represents a valid solution for treatment of massive rotator cuff tears resulting safe, easier and cost saving in comparison with other published techniques.

The neutrophil/lymphocyte ratio as a prognostic factor in COVID-19 patients: a case-control study.

OBJECTIVE: SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) has been identified in China as responsible for viral pneumonia, now called COVID-19 (Coronavirus Disease 2019). Patients infected can develop common symptoms like cough and sore throat, and, in severe cases, acute respiratory syndrome and even death. To optimize the available resources, it is necessary to identify in advance the subjects that will develop a more serious illness, therefore requiring intensive care.The neutrophil / lymphocyte ratio (NLR) parameter, resulting from the blood count, could be a significant marker for the diagnosis and management of risk stratification. PATIENTS AND METHODS: A retrospective, single-center case-control observational study was conducted. The differential cell count of leukocytes, the NLR and the clinical course of patients hospitalized in intensive care with COVID-19 were analyzed, comparing them with other patients (COVID-19 and non-COVID-19) and healthy individuals selected among workers of the Teaching Hospital Policlinico Umberto I in Rome. RESULTS: 370 patients (145 cases and 225 controls) were included in the case-control study, 211 males (57%) and 159 females (43%). The average age of the population was 63 years (SD 16.35). In the group of cases, out of 145 patients, 57 deaths and 88 survivors were recorded, with a lethality rate of 39.3%. The group of cases has an NLR of 7.83 (SD = 8.07), a much higher value than the control group where an NLR of 2.58 was recorded (SD = 1.93) (p <0.001). The Neutrophils / Lymphocytes ratio may prove to be a diagnostic factor for COVID-19, an NLR> 3.68 revealed an OR 10.84 (95% CI = 6.47 - 18.13) (p <0.005). CONCLUSIONS: The value of NLR considered together with the age variable allows a risk stratification and allows the development of diagnostic and treatment protocols for patients affected by COVID-19. A high neutrophil to lymphocyte ratio suggests worse survival. Risk stratification and management help alleviate the shortage of medical resources and reduce the mortality of critically ill patients.

Laparoscopic transperitoneal hernia repair (TAPP) in emergency: long-term follow-up in a high volume centre.

PURPOSE: Aim of this study was to analyse feasibility, safety and effectiveness of laparoscopic transperitoneal hernia repair (TAPP) approach to inguinal hernias in the emergency setting, with a longer follow-up than the studies present in literature. METHODS: We retrospectively analysed all patients who underwent emergency TAPP hernia repair in San Marco Hospital (Zingonia, Italy), from September 2010 to June 2020. A prospectively collected database of 685 consecutive TAPP hernia repair was reviewed. Feasibility and safety were evaluated through operative time, conversion rate, perioperative mortality, morbidity and prosthesis infection rate. Effectiveness was assessed by recurrence and complication rate, acute (during admission) and chronic (during follow-up) pain by Visual Analogic Scale (VAS), and recovery to normal activity in a long-term follow-up (mean period 1718 days). RESULTS: The final study group included 47 patients. The mean age was 59.6 years (range 22-89), 29 patients were male and 18 were female. The mean operation time was 64 min. Two cases were converted to open approach (4%). In four cases bowel resection became necessary (8.5%). Appendicectomy and omentectomy occurred once and twice, respectively (2% and 4%), and orchiectomy was required in two patients (4%). Seroma was the only postoperative complication that we registered in four patients. During a mean follow-up period of 1718 days, there was no recurrence of the hernia or other complications. Five patients referred mild occasional groin pain (VAS < 3), with quick relief without taking any pain killers. CONCLUSION: TAPP approach is a safe, feasible and effective therapeutic option for groin hernias in emergency setting. No recurrence or severe complications were reported in over 4 years of follow-up.

Cefquinome sulfate behavior after intramammary administration in healthy and infected cows.

Maintenance of adequate drug concentration at the site of infection is an important problem in mastitis antibiotic therapy, and the efficacy of intramammary ß-lactams can be optimized by maintaining the drug concentration at the site of infection above the minimum inhibitory concentration (MIC) as long as possible. The most important pharmacokinetic and pharmacodynamic parameter for efficacy evaluation is time during which drug concentrations exceed the MIC (t>MIC). In this study, we assessed the pharmacokinetic profile of cefquinome (CFQ) after repeated intramammary administration in healthy cows and cows subclinically infected with Staphylococcus aureus as well as the MIC of Staph. aureus field strains. In addition, the degree of drug passage was investigated from udder to bloodstream by measuring systemic drug absorption in healthy and infected animals. Cefquinome concentrations were quantified by HPLC (UV-visible detection) in milk samples collected from quarters and from blood serum samples. The systemic drug absorption was negligible in healthy and subclinically infected animals (maximum concentration 0.09±0.02 and 0.1±0.01 µg/mL in healthy and subclinically infected animals, respectively). The MIC(90) value for CFQ in Staph. aureus field strains (n=20) was 0.24 µg/mL. The pharmacokinetic and pharmacodynamic evaluation, determined by t>MIC, showed an equal persistence of CFQ in all quarters, indicating an equivalent activity of the drug regardless of the pathological status of the udder. Moreover, with literature data regarding CFQ MIC, the t>MIC has been calculated for other bacterial species.

Cefoperazone sodium preparation behavior after intramammary administration in healthy and infected cows.

Selection of the antimicrobial agent and maintenance of adequate drug concentrations at the site of infection are the most relevant problems in mastitis antibiotic therapy. Intramammary drug efficacy can be maximized by keeping drug concentrations at the site of infection above the minimum inhibitory concentration (MIC) as long as possible; the most important pharmacokinetic and pharmacodynamic (PK/PD) measure for efficacy evaluation is time during which drug concentrations exceed the MIC (t>MIC). To evaluate this measure, the PK profile of cefoperazone (CFP) after single intramammary administration in healthy and subclinical infected Staphylococcus aureus cows and the MIC of Staph. aureus field strains were assessed. In addition, the degree of drug passage from udder to bloodstream was investigated by measuring systemic drug absorption in healthy and infected animals. Cefoperazone concentrations were quantified by HPLC in quarter milk samples and blood serum samples. Systemic drug absorption was negligible in healthy animals (0.020+/-0.006 microg/mL serum at 4 h), whereas it was higher in infected animals (0.102+/-0.079 microg/mL at 4h and 0.025 microg/mL at 24 h), probably due to the damage of epithelial cell junctions caused by subclinical infections. The MIC90 value for CFP in Staph. aureus field strains (n=24) was 0.64 microg/mL. The PK/PD evaluation, determined by t>MIC, showed a longer persistence of CFP in infected quarters than in healthy ones (mean residence time was 8.37+/-1.51 vs. 11.42+/-5.74 h in September and 2.07+/-0.43 vs. 3.31+/-0.91 h in October), with a t>MIC of 45+/-6 h for infected quarters versus 38+/-5 h for healthy quarters different only in October. This could mean a prolonged time in which microorganisms are exposed to drug activity and thus, a greater efficacy of the drug.

Insights on the genetic features of endometrial pathogenic Escherichia coli strains from pyometra in companion animals: Improving the knowledge about pathogenesis.

Endometrial pathogenic E. coli (EnPEC) isolates are involved in endometrial infections in animals and humans. Besides the high aggressiveness of the endometrial infections, the EnPEC virulence profile and pathogenesis are still little known. In this study, we have sequenced and analyzed an EnPEC strain from canine pyometra (E. coli_LBV005/17), following a molecular characterization of the virulence profile and phylogenetic evolution of an EnPEC collection from canines and felines (45 strains). Most of the strains belonged to phylo-group B2, and display a high virulence profile. In particular we highlight the classification of the E. coli_LBV005/17 as sequence type 131 (ST131), in addition to other five strains, as observed by gyrB phylogenetic analysis. Also, the phylogenetic position of EnPEC strains from pyometra in companion animals suggests that their origins are from both extraintestinal and commensal E. coli strains. Accordingly to Principal Coordinates Analysis (PCoA) and phylogenetic analysis we can propose that EnPEC strains have neither the same genetic profile, nor a unique common ancestral. In summary, the present work characterize an EnPEC genome from bitch pyometra and the genetic profile of 45 EnPEC strains from companion animals pyometra, being the commonest virulence pattern: fimA, papC, hlyA, hlyE, cnf1, entB, iroN, irp1, bssS, bssR, and hmsP. These data improving the background knowledge of this E. coli pathotype related to pyometra in companion animals and may support new methods to prevent the disease evolution.

Pharmacokinetics and efficacy of teicoplanin against intramammary infections in sheep.

The pharmacokinetics of teicoplanin were evaluated in 10 healthy sheep. After intravenous injection it showed monophasic behaviour, with a short mean (sd) elimination half-life (5 [0.24] hours). After intramuscular injection its bioavailability was 100 per cent but it was absorbed slowly; its elimination half-life was satisfactorily slow (9.23 [0.74] hours). Its efficacy was evaluated in 26 crossbreed sheep with milk positive to strains of Staphylococcus aureus, coagulase-negative staphylococci and Streptococcus agalactiae, and clinical signs of disease. In 19 of them a single intramuscular dose of 6 mg/kg bodyweight resulted in a complete resolution of the clinical signs, and no microorganisms were detected in milk by the fifth day; in the other seven sheep, with more severe intramammary infections, three consecutive daily intramuscular doses of 6 mg/kg bodyweight were necessary. There were no local or systemic side effects and no relapses during 30 days after the treatments in any of the sheep.

Asthma induced by inhalation of flour in adults with food allergy to wheat.

BACKGROUND: Wheat is one of the major food allergens and it is also an inhalant allergen in workers exposed to flour dusts. Food allergy to wheat in adulthood seems to be rare and has never been reported to be associated with asthma induced by flour inhalation. OBJECTIVE: The study aimed at detecting adults with food allergy to wheat and screening them for the presence of specific bronchial reactivity to inhaled wheat proteins. METHODS: Adults with a history of adverse reactions to ingestion of wheat underwent skin prick test with commercial wheat extract and were assessed for the presence of specific wheat IgE in the sera. Food sensitivity to wheat was confirmed by double-blind, placebo-controlled food challenge (DBPCFC). Specific bronchial reactivity was investigated through a specific bronchial challenge with wheat proteins. RESULTS: In nine patients with evidence of specific IgE response to wheat, a diagnosis of food allergy was made by DBPCFC. Only two subjects had asthma as disease induced by ingestion of wheat. Seven subjects reported a history of respiratory symptoms when exposed to flour dusts. A significant reduction of forced expiratory volume in 1 s (FEV(1)) was detected in these seven patients when a specific bronchial challenge with flour proteins was performed. Only three out of seven subjects with asthma induced by flour could be considered occupationally exposed to flour dusts. CONCLUSION: For the first time, it has been shown that specific bronchial reactivity to wheat proteins can be detected in patients with different disorders associated with food allergy to wheat. The presence of asthma induced by inhaled flour is not strictly related to occupational exposure and it may also occur in subjects not displaying asthma among symptoms induced by wheat ingestion.

Stapled hemorrhoidopexy: day surgery or one day surgery?

Hemorrhoidal disease is one of the most common anorectal disorders, from 10% to 20% of all patients admitted at a clinical investigation need to undergo surgery, stapled haemorrhoidopexy is gaining wide acceptance as an interesting, safe and less painful technique, but hemorrhage is one of the most serious early complications and is a severe complication in day surgery. In our day surgery proctology, surgical procedures represent about 32%. Of these, 24% are for hemorrhoidal disease, we present our protocol and experience for early and safe discharge, 6h after stapled hemorrhoidopexy surgery.

Outcomes of laparoscopic Miles' operation in very low rectal adenocarcinoma. Analysis of 32 cases.

AIMS: Minivasive techniques for excision of low rectal tumours have spread worldwide with good results, but their employment is still under discussion. The purpose of this study is to assess short term results and survival of laparoscopic abdominoperineal resection (LAPR) in very low rectal cancers. METHODS: The charts of 32 patients undergoing LAPR for very low rectal adenocarcinoma (0-2cm from dentata line) were reviewed retrospectively. Outcomes were evaluated considering surgical procedure, short and long-term results and survival. RESULTS: A thorough LAPR was performed in 31 patients and conversion to laparotomy was required in 1 patient. Mean operating time was 244min. The length of hospital stay (LOS) was 13,3days. The mean number of nodes collected was 12 and the distal margin was 3,6cm on average. There was 1 post-operative death. In the follow up no pelvic recurrence was observed, while metachronous metastases were observed in 5 patients and peritoneal carcinosis in 2 patients. No port site metastasis was registered. Cumulative 5year survival probability was 0,50. CONCLUSIONS: The outcomes of this study suggest that LAPR in very low rectal cancer is a reliable procedure, operating time and LOS were acceptable. Oncologic principles were respected: length of specimen, distal margin and number of nodes retrieved were quite acceptable. Pelvic recurrence frequency was nil. Long term results were comparable with those of other series.

Oral and intravenous administration of nimesulide in the horse: rational dosage regimen from pharmacokinetic and pharmacodynamic data.

REASONS FOR PERFORMING STUDY: The selective COX-2-inhibitor nimesulide is used extra-label in equine veterinary practice as an anti-inflammatory agent. However, there are no data on which to base the rational use of the drug in this species. OBJECTIVES: To determine the effective COX selectivity of nimesulide in the horse, and suggest a suitable dosing schedule. METHODS: The pharmacokinetics of nimesulide in the horse after oral administration (1 mg/kg bwt), and oral and i.v. administration (1.5 mg/kg bwt) were investigated, effects of feeding status on bioavailability determined, and plasma protein binding of the drug and its principal metabolites measured. Compartmental and noncompartmental pharmacokinetic analyses were performed. The plasma concentration-time profile was used, together with in vitro literature data on nimesulide inhibition of COX isoforms, to determine the effective COX selectivity of nimesulide in the horse, and suggest a suitable dosing schedule. RESULTS AND CONCLUSIONS: The findings suggest that 1.5 mg/kg bwt may produce adequate clinical effects, and the dosing interval should be 12-24 h depending on condition severity. However, at that dose, the concentration in the animal exceeds the in vitro IC50 for both isoforms, so that COX-1/COX-2 selectivity is lost and side-effects due to COX-1 inhibition are a possibility. Nimesulide should therefore be used with caution in equine clinical practice.

A new ruthenium black dye design with improved optical properties for transparent dye sensitized solar devices.

We report here on the preparation and on the electronic properties of a panchromatic Ru(ii) sensitizer based on a new ligand which allows for higher molar extinction coefficients in the visible and better performances (32% efficiency improvement) over conventional "black dye" in transparent DSSC.

Short communication: antimicrobial drug susceptibility of Staphylococcus aureus from subclinical bovine mastitis in Italy.

The antimicrobial susceptibility of 68 Staphylococcus aureus isolates collected during 2004 from milk of cows affected by subclinical mastitis was examined. The antimicrobial agents tested were the beta-lactams, penicillin G, amoxicillin, ampicillin, cloxacillin, amoxicillin + clavulanate, cephalonium, and cefoperazone; and other drugs including lincomycin, oxytetracycline, doxycycline, and kanamycin. Minimum inhibitory concentrations recorded show that only certain beta-lactamase-resistant penicillins (specifically cloxacillin) or penicillin combinations (amoxicillin + clavulanate) were consistently effective against Staph. aureus, whereas the other beta-lactam derivatives and drugs from other pharmacological groups were either moderately effective or ineffective. Thus, beta-lactamase-resistant penicillins are to be considered the antimicrobial agents of choice for treatment of bovine mastitis resulting from infection by Staph. aureus.

Pharmacodynamics and pharmacokinetics of flumequine in pigs after single intravenous and intramuscular administration.

The pharmacokinetics and intramuscular (IM) bioavailability of flumequine (15 mgkg(-1)) were investigated in healthy pigs and the findings related to published minimal inhibitory concentrations (MICs) for susceptible bacteria of animal origin, and to experimentally determined MICs for susceptible strains of porcine origin. We found MICs for Escherichia coli, Salmonella spp., Pasteurella spp. and Bordetella spp. in the range 0.5 to >64 microg mL(-1) isolated from infected pigs in the Forli area of Italy; only the Pasteurella multocida strains were sensitive (MIC(90)=0.5 microg mL(-1)). After intravenous (IV) injection, flumequine was slowly distributed and eliminated (t(1/2lambda(1))1.40+/-0.16 h and t(1/2lambda(2))6.35+/-1.69 h). The distribution volume at steady state (V(dss)) was 752.59+/-84.03 mL kg(-1) and clearance (Cl(B)) was 237.19+/-17.88 mL kg(-1)h(-1). After IM administration, peak serum concentration (4.99+/-0.92 microg mL(-1)) was reached between the 2nd and the 3rd hour. The results on MIC of isolated bacteria, although only indicative, suggest that the efficacy of flumequine on Gram-negative bacteria may be impaired by the emergence of less sensitive or resistant strains.

Flumequine in the goat: pharmacokinetics after intravenous and intramuscular administration.

The pharmacokinetics of flumequine, administered intravenously and intramuscularly at a single dose of 20 mg/kg, was investigated in healthy goats. After intravenous injection, flumequine distributed rapidly (t1/2alpha = 0.87+/-0.15 h) but was eliminated slowly (t1/2beta = 7.12+/-1.27 h); mean clearance (Cl) and volume of distribution (Vdss) were 0.32+/-0.03 (L/(h x kg) and 1.22+/-029 (L/kg), respectively. After intramuscular administration, the peakserum concentration (Cmax = 7.40+/-0.5 microg/ml) was reached in about 1.5 h (Tmax) and bioavailability was about 93%. Estimated flumequine serum levels following repeated intramuscular administration of the aqueous suspension used in the study (7.23+/-0.7 microg/ml and 4.82+/-0.47 microg/ml at intervals of 8 and 12 h, respectively) indicated that to maintain serum levels above MIC values for susceptible bacteria a dosage regimen of 20 mg/kg every 12 h is necessary by the intramuscular route.