Molecular epidemiology and phylogenetic analysis of Tams I gene of Theileria annulata in Khyber Pakhtunkhwa, Pakistan.

Theileriosis is a hemoparasitic disease that affects a wide range of different animal species and is caused by various species of Theileria. This study aimed to determine the molecular epidemiology of Theileria annulata through microscopy and PCR, in crossbred cattle in some districts of Khyber Pakhtunkhwa, Pakistan. For this study, a total of 384 blood samples were collected from cattle in the Peshawar (n=120), Charsadda (n=94), Nowshera (n=84), and Swabi (n=86) districts. Microscopy and PCR were used to determine the overall prevalence of theileriosis, which was found to be 15.8 and 22.6%, respectively. Theileria annulata was detected in blood samples through PCR in the study area, and the target gene i.e., Tams 1, of positive samples was sequenced. The sequences in the current study revealed high sequence homology (ranging from 96 to 100%) with Tams 1 sequences of neighboring countries present in the NCBI database. Season, breed, age, and sex were found to be important risk factors among the several risk factors examined, whereas, among different clinical manifestations, lymphadenopathy showed a strong association with theileriosis. According to Cohen's kappa and ROC analysis, microscopy was proven to be a fair diagnostic test for detecting theileriosis in cattle, and may be used in combination with molecular techniques for screening a large number of animals.

Anesthesia for left ventricular assisted device insertion in a patient with multiple organ failure.

Technological advances in mechanical circulatory support have enabled more patients with end-stage heart failure to benefit from left ventricular assist devices (LVAD). Indications for LVAD implantation have evolved to include patients who are deemed unsuitable for cardiac transplantation, otherwise known as destination therapy. This case report describes such patient with multi-organ failure who underwent LVAD insertion after nine days of extra-corporeal membrane oxygenation, intra-aortic balloon pump and maximal inotropic support. Strategies for perioperative management, as well as intra-operative monitoring and interventions are discussed.

COVID-19 pandemic and its positive impacts on environment: an updated review.

In December, 2019 in Wuhan city of China, a novel coronavirus (SARS-CoV-2) has garnered global attention due to its rapid transmission. World Health Organization (WHO) termed the infection as Coronavirus Disease 2019 (COVID-19) after phylogenic studies with SARS-CoV. The virus causes severe respiratory infections with dry cough, high fever, body ache and fatigue. The virus is primarily transmitted among people through respiratory droplets from COVID-19 infected person. WHO declared this COVID-19 outbreak a pandemic and since February, 2020 affected countries have locked down their cities, industries and restricted the movement of their citizens to minimize the spread of the virus. In spite of the negative aspects of coronavirus on the globe, the coronavirus crises brought a positive impact on the natural environment. Countries where the movement of citizens was seized to stop the spread of coronavirus infection have experienced a noticeable decline in pollution and greenhouse gases emission. Recent research also indicated that this COVID-19-induced lockdown has reduced the environmental pollution drastically worldwide. In this review, we have discussed some important positive impacts of coronavirus on environmental quality by compiling the recently published data from research articles, NASA (National Aeronautics and Space Administration) and ESA (European Space Agency).

Access-Site Complications in Mechanical Thrombectomy for Acute Ischemic Stroke: A Review of Prospective Trials.

BACKGROUND: A shift has occurred in interventional cardiology from transfemoral to transradial access due to a 70%-80% decrease in complications. This shift has not yet taken place in other interventional specialties, perhaps owing to the lack of generalizability of findings in the cardiology data. PURPOSE: Our aim was to assess data from the recent mechanical thrombectomy prospective trials to better understand the access-site complication rate. DATA SOURCES: Articles were systematically sourced from the National Center for Biotechnology Information PubMed archive. STUDY SELECTION: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, prospective, randomized controlled trials published after 2008 with mention of major and/or minor femoral access-site complications in neuroendovascular mechanical thrombectomies were included. DATA ANALYSIS: Major and minor femoral access-site complications were extracted. A total complication rate was calculated with major access-site complications alone and combined with minor access-site complications. DATA SYNTHESIS: Seven prospective studies of 339 total screened met the inclusion criteria. Eleven major access-site complications were identified in of 660 total interventions, revealing a major access-site complication rate of 1.67% for patients undergoing mechanical thrombectomy with transfemoral access. If minor access-site complications were included, 35 total incidents were detected in 763 interventions, resulting in a total complication rate of 4.59%. LIMITATIONS: Multiple unspecified vessel and procedure-related complications were mentioned in the studies. CONCLUSIONS: The overall rate of major access-site complications was 1.67% in this review, which is not low and poses a risk to patients. We suggest further investigation into the feasibility and complication rates of alternative access sites for neurointerventional procedures.

SPOP regulates prostate epithelial cell proliferation and promotes ubiquitination and turnover of c-MYC oncoprotein.

The E3 ubiquitin ligase adaptor speckle-type POZ protein (SPOP) is frequently dysregulated in prostate adenocarcinoma (PC), via either somatic mutations or mRNA downregulation, suggesting an important tumour suppressor function. To examine its physiologic role in the prostate epithelium in vivo, we generated mice with prostate-specific biallelic ablation of Spop. These mice exhibited increased prostate mass, prostate epithelial cell proliferation, and expression of c-MYC protein compared to littermate controls, and eventually developed prostatic intraepithelial neoplasia (PIN). We found that SPOPWT can physically interact with c-MYC protein and, upon exogenous expression in vitro, can promote c-MYC ubiquitination and degradation. This effect was attenuated in PC cells by introducing PC-associated SPOP mutants or upon knockdown of SPOP via short-hairpin-RNA, suggesting that SPOP inactivation directly increases c-MYC protein levels. Gene Set Enrichment Analysis revealed enrichment of Myc-induced genes in transcriptomic signatures associated with SPOPMT. Likewise, we observed strong inverse correlation between c-MYC activity and SPOP mRNA levels in two independent PC patient cohorts. The core SPOPMT;MYCHigh transcriptomic response, defined by the overlap between the SPOPMT and c-MYC transcriptomic programmes, was also associated with inferior clinical outcome in human PCs. Finally, the organoid-forming capacity of Spop-null murine prostate cells was more sensitive to c-MYC inhibition than that of Spop-WT cells, suggesting that c-MYC upregulation functionally contributes to the proliferative phenotype of Spop knock-out prostates. Taken together, our data highlight SPOP as an important regulator of luminal epithelial cell proliferation and c-MYC expression in prostate physiology, identify c-MYC as a novel bona fide SPOP substrate, and help explain the frequent inactivation of SPOP in human PC. We propose SPOPMT-induced stabilization of c-MYC protein as a novel mechanism that can increase total c-MYC levels in PC cells, in addition to amplification of c-MYC locus.

Comprehensive proteomic profiling identifies the androgen receptor axis and other signaling pathways as targets of microRNAs suppressed in metastatic prostate cancer.

MicroRNAs are important epigenetic regulators of protein expression by triggering degradation of target mRNAs and/or inhibiting their translation. Dysregulation of microRNA expression has been reported in several cancers, including prostate cancer (PC). We comprehensively characterized the proteomic footprint of a panel of 12 microRNAs that are potently suppressed in metastatic PC (SiM-miRNAs: miR-1, miR-133a, miR-133b, miR-135a, miR-143-3p, miR-145-3p, miR-205, miR-221-3p, miR-221-5p, miR-222-3p, miR-24-1-5p, and miR-31) using reverse-phase proteomic arrays. Re-expression of these SiM-miRNAs in PC cells suppressed cell proliferation and targeted key oncogenic pathways, including cell cycle, apoptosis, Akt/mammalian target of rapamycin signaling, metastasis and the androgen receptor (AR) axis. However, only 12%, at most, of these observed protein expression changes could be explained by predicted direct binding of miRNAs to corresponding mRNAs, suggesting that the majority of these proteomic effects result indirectly. AR and its steroid receptor coactivators (SRCs; SRC-1, -2 and -3) were recurrently affected by these SiM-miRNAs. In agreement, we identified inverse correlations between expression of these SiM-miRNAs and early clinical recurrence, as well as with AR transcriptional activity in human PC tissues. We also identified robust induction of miR-135a by androgen and strong direct binding of AR to the miR-135a locus. As miR-135a potently suppresses AR expression, this results in a negative feedback loop that suppresses AR protein expression in an androgen-dependent manner, while de-repressing AR expression upon androgen deprivation. Our results demonstrate that epigenetic silencing of these SiM-miRNAs can result in increased AR axis activity and cell proliferation, thus contributing to disease progression. We further demonstrate that a negative feedback loop involving miR-135a can restore AR expression under androgen-deprivation conditions, thus contributing to the upregulation of AR protein expression in castration-resistant PC. Finally, our unbiased proteomic profiling demonstrates that the majority of actual protein expression changes induced by SiM-miRNAs cannot be explained based on predicted direct interactions.

The effect of exposure to wood smoke on outcomes of childhood pneumonia in Botswana.

SETTING: Tertiary hospital in Gaborone, Botswana. OBJECTIVE: To examine whether exposure to wood smoke worsens outcomes of childhood pneumonia. DESIGN: Prospective cohort study of children aged 1-23 months meeting clinical criteria for pneumonia. Household use of wood as a cooking fuel was assessed during a face-to-face questionnaire with care givers. We estimated crude and adjusted risk ratios (RRs) and 95% confidence intervals (CIs) for treatment failure at 48 h by household use of wood as a cooking fuel. We assessed for effect modification by age (1-5 vs. 6-23 months) and malnutrition (none vs. moderate vs. severe). RESULTS: The median age of the 284 enrolled children was 5.9 months; 17% had moderate or severe malnutrition. Ninety-nine (35%) children failed treatment at 48 h and 17 (6%) died. In multivariable analyses, household use of wood as a cooking fuel increased the risk of treatment failure at 48 h (RR 1.44, 95%CI 1.09-1.92, P = 0.01). This association differed by child nutritional status (P = 0.02), with a detrimental effect observed only among children with no or moderate malnutrition. CONCLUSIONS: Exposure to wood smoke worsens outcomes for childhood pneumonia. Efforts to prevent exposure to smoke from unprocessed fuels may improve pneumonia outcomes among children.

DNA binding mode of transition metal complexes, a relationship to tumor cell toxicity.

Transition metal-based compounds constitute a distinct class of chemotherapeutics extensively used in the clinic as antitumor and antiviral agents. However, drug resistance and side effects of established antitumor metallodrugs such as cisplatin [cis-diamminedichloroplatinum(II)] and its analogues, carboplatin and oxaliplatin, have limited their clinical utility. These limitations have prompted a search for more effective and less toxic metal-based antitumor agents. The unique properties of metal ions, such as redox transfer/electron shuttling, and versatile coordination geometries arising from various oxidation states, result in metal ions and complexes that have potential medicinal applications that could be complementary to organic compounds and which are widely sought in drug discovery efforts. This review summarizes the results that show that transition metal complexes exhibit antitumor effects that differ from cisplatin or its analogues.

Synthetic thioamide, benzimidazole, quinolone and derivatives with carboxylic acid and ester moieties: a strategy in the design of antituberculosis agents.

Synthetic heterocyclic compounds have remarkable potential activity against diseases; thioamides, benzimidazoles, quinolones and derivatives with carboxylic acid and esters moieties have shown excellent activity against Mycobacterium tuberculosis. We reviewed antituberculosis activities of above compounds with reference to half maximal inhibitory concentration, minimum inhibitory concentration and structural-activity relationship which clearly indicate that electron-withdrawing groups are the main inducers of antimycobacterium activity. Comparison between clinically used drugs and new synthetic derivatives showed recent advances made in the last decade.

Cationic agent contrast-enhanced computed tomography imaging of cartilage correlates with the compressive modulus and coefficient of friction.

OBJECTIVE: The aim of this study is to evaluate whether contrast-enhanced computed tomography (CECT) attenuation, using a cationic contrast agent (CA4+), correlates with the equilibrium compressive modulus (E) and coefficient of friction (µ) of ex vivo bovine articular cartilage. METHODS: Correlations between CECT attenuation and E (Group 1, n = 12) and µ (Group 2, n = 10) were determined using 7 mm diameter bovine osteochondral plugs from the stifle joints of six freshly slaughtered, skeletally mature cows. The equilibrium compressive modulus was measured using a four-step, unconfined, compressive stress-relaxation test, and the coefficients of friction were determined from a torsional friction test. Following mechanical testing, samples were immersed in CA4+, imaged using µCT, rinsed, and analyzed for glycosaminoglycan (GAG) content using the 1,9-dimethylmethylene blue (DMMB) assay. RESULTS: The CECT attenuation was positively correlated with the GAG content of bovine cartilage (R(2) = 0.87, P < 0.0001 for Group 1 and R(2) = 0.74, P = 0.001 for Group 2). Strong and significant positive correlations were observed between E and GAG content (R(2) = 0.90, P < 0.0001) as well as CECT attenuation and E (R(2) = 0.90, P < 0.0001). The CECT attenuation was negatively correlated with the three coefficients of friction: CECT vs µ(static) (R(2) = 0.71, P = 0.002), CECT vs µ(static_equilibrium) (R(2) = 0.79, P < 0.001), and CECT vs µ(kinetic) (R(2) = 0.69, P = 0.003). CONCLUSIONS: CECT with CA4+ is a useful tool for determining the mechanical properties of ex vivo cartilage tissue as the attenuation significantly correlates with the compressive modulus and coefficient of friction.

The use of vacuum-assisted wound closure therapy in thoracic operations.

BACKGROUND: Conventional treatment of complex, nonresolving empyemas after an episode of pneumonia or a chest operation often requires an open-window thoracostomy. This necessitates frequent, often painful dressing changes and is associated with prolonged hospitalization. The wound is often malodorous, causing significant social distress to patients and unquestionably affects their quality of life. We assessed the value of using vacuum-assisted closure (VAC) therapy in managing patients with a persistent infected pleural space. METHODS: The study included 10 patients. All patients signed an informed consent and were debriefed before the procedure. An empyema developed in 1 patient after an episode of pneumonia. The other 9 had recently undergone a thoracic surgical procedure. All patients underwent initial open drainage of the pleural cavity and debridement. A VAC therapy system was then inserted intraoperatively or on the first postoperative day. The patients were discharged home with a portable VAC therapy system in situ. Subsequent dressing changes were managed by tissue-viability nurses in the community, without the need for further anesthesia or analgesia. Over a period of time, the cavity was sterilized and eventually obliterated spontaneously. RESULTS: All patients were mobilized early and fast-tracked through the hospital. This prevented the need for daily dressing changes; hence, minimizing the disruption of normal activities and reducing the need for nursing care. Overall, the length of hospitalization was shorter, and the VAC therapy facilitated closure of the infected wound cavity. The use of the VAC therapy system negated the need for a second surgical procedure to close the wound cavity. None of the patients reported pain, odor, or inconvenience associated with the VAC therapy system. CONCLUSIONS: Our observations suggest that the use of VAC therapy to treat such patients is safe, facilitates early discharge and recovery, and offers a "civilized," cost-effective treatment in a community setting.

Acute kidney injury after cardiac surgery in eastern Saudi Arabia.

Acute kidney injury is a serious complication after cardiac surgery. This study was conducted to determine the frequency of acute kidney injury and the associated risk factors following cardiac surgery at Dhahran health centre in eastern Saudi Arabia. All patients who underwent cardiac surgery between June 2005 and December 2008 were included. Of 293 patients who fulfilled the criteria and were included in the final analysis, 85 (29.0%) developed acute kidney injury. Using multivariate analysis, the factors significantly associated with acute kidney injury were age, diabetes, preoperative chronic kidney disease and emergent surgery. Mortality associated with acute kidney injury was 10.5% overall and 42.9% when dialysis was required. Acute kidney injury following cardiac surgery is a serious problem among patients in eastern Saudi Arabia. Measures to prevent this complication are essential.

CSF opening pressure in children with optic nerve head edema.

BACKGROUND: We previously reported that an abnormal CSF opening pressure (OP) in children was greater than 28 cm H(2)O. Since elevated intracranial pressure can cause optic nerve head edema (ONHE), we would expect that most patients with ONHE would have an OP greater than 28 cm H(2)O. This study describes the range of OP for children with ONHE and compared them to age-matched controls without ONHE. METHODS: Case subjects were children (1-18 years of age) enrolled in a prospective study of CSF OP that demonstrated ONHE at time of lumbar puncture and that the ONHE later resolved. Patients with ONHE secondary to infectious, inflammatory, or ischemic conditions were excluded. Control subjects from the same study, but without ONHE, were matched to cases. RESULTS: Of the 472 subjects enrolled in the study, 41 OP measurements were obtained from 33 patients with ONHE who did not have any exclusionary criteria and matched to 41 control subjects without ONHE. Case subjects had a significantly higher OP (mean, 41.4 cm H(2)0; range, 22-56) than control subjects (mean, 18.9 cm H(2)O; range, 9-29; p < 0.01). Forty of 41 (97.6%) case subjects and 2 of 41 (4.8%) control subjects had OP measures >28 cm H(2)O. CONCLUSIONS: Children with ONHE not related to infectious, inflammatory, or ischemic causes typically have an OP >28 cm H(2)O, significantly higher than age-matched controls without ONHE. This study provides further support to our previously published findings that suggests an abnormal OP in children is typically above 28 cm H(2)O.

Acute kidney injury after cardiac surgery in eastern Saudi Arabia

Acute kidney injury is a serious complication after cardiac surgery. This study was conducted to determine the frequency of acute kidney injury and the associated risk factors following cardiac surgery at Dhahran health centre in eastern Saudi Arabia. All patients who underwent cardiac surgery between June 2005 and December 2008 were included. Of 293 patients who fulfilled the criteria and were included in the final analysis, 85 [29.0%] developed acute kidney injury. Using multivariate analysis, the factors significantly associated with acute kidney injury were age, diabetes, preoperative chronic kidney disease and emergent surgery. Mortality associated with acute kidney injury was 10.5% overall and 42.9% when dialysis was required. Acute kidney injury following cardiac surgery is a serious problem among patients in eastern Saudi Arabia. Measures to prevent this complication are essential

Inhaled versus systemic corticosteroids for the treatment of chronic lung disease in ventilated very low birth weight preterm infants.

BACKGROUND: Chronic lung disease (CLD) remains a serious and common problem among very low birth weight infants despite the use of antenatal steroids and postnatal surfactant therapy to decrease the incidence and severity of respiratory distress syndrome. Due to their anti-inflammatory properties, corticosteroids have been widely used to treat or prevent CLD. However, the use of systemic steroids has been associated with serious short and long-term adverse effects. Administration of corticosteroids topically through the respiratory tract might result in beneficial effects on the pulmonary system with fewer undesirable systemic side effects. OBJECTIVES: To determine the effect of inhaled versus systemic corticosteroids administered to ventilator dependent preterm neonates with birth weight < 1500 g or gestational age < 32 weeks after two weeks of life for the treatment of evolving CLD. SEARCH STRATEGY: Randomized and quasi-randomized trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2007), MEDLINE (1966 - June 2007), EMBASE (1980 - June 2007), CINAHL (1982 - June 2007), reference lists of published trials and abstracts published in Pediatric Research or electronically on the Pediatric Academic Societies website (1990 - April 2007). SELECTION CRITERIA: Randomized or quasi-randomized trials comparing inhaled versus systemic corticosteroid therapy (irrespective of the dose and duration of therapy) starting after the first two weeks of life in ventilator dependent very low birth weight preterm infants. DATA COLLECTION AND ANALYSIS: Data were extracted regarding clinical outcomes including CLD at 28 days or 36 weeks postmenstrual age (PMA), mortality, combined outcome of death or CLD at 28 days of age or 36 weeks PMA, other pulmonary outcomes and adverse effects. All data were analyzed using RevMan 4.2.10. When appropriate, meta-analysis was performed using relative risk (RR), risk difference (RD), and weighted mean difference (WMD) along with their 95% confidence intervals (CI). If RD was statistically significant, the number needed to treat (NNT) was calculated. MAIN RESULTS: Data from one additional trial were available for inclusion in this update. Thus, five trials comparing inhaled versus systemic corticosteroids in the treatment of CLD were identified. Two trials were excluded as both included non-ventilator dependent patients and three trials qualified for inclusion in this review. Halliday et al (Halliday 2001) randomized infants at < 72 hours, while Rozycki et al (Rozycki 2003) and Suchomski et al (Suchomski 2002) randomized at 12 - 21 days. The data from the two trials of Rozycki et al and Suchmoski et al are combined using meta-analytic techniques. The data from the trial by Halliday et al are reported separately, as outcomes were measured over different time periods from the age at randomization. In none of the trials was there a statistically significant difference between the groups in the incidence of CLD at 36 weeks PMA among all randomized infants. The estimates for the trial by Halliday et al (Halliday 2001) were RR 1.10 (95% CI 0.82, 1.47), RD 0.03 (95% CI -0.08, 0.15); number of infants (n = 292). For the trials by Rozycki et al (Rozycki 2003) and Suchomski et al (Suchomski 2002) the typical RR was 1.02 (95% CI 0.83, 1.25) and the typical RD 0.01 (95% CI -0.11, 0.14); (number of infants = 139 ). There were no statistically significant differences between the groups in either trial for oxygen dependency at 28 days of age, death by 28 days or 36 weeks PMA, the combined outcome of death by or CLD at 28 days or 36 weeks PMA, duration of intubation, duration of oxygen dependence, or adverse effects. Information on the long-term neurodevelopmental outcomes was not available. AUTHORS' CONCLUSIONS: This review found no evidence that inhaled corticosteroids confer net advantages over systemic corticosteroids in the management of ventilator dependent preterm infants. Neither inhaled steroids nor systemic steroids can be recommended as standard treatment for ventilated preterm infants. There was no evidence of difference in effectiveness or side-effect profiles for inhaled versus systemic steroids. A better delivery system guaranteeing selective delivery of inhaled steroids to the alveoli might result in beneficial clinical effects without increasing side-effects. To resolve this issue, studies are needed to identify the risk/benefit ratio of different delivery techniques and dosing schedules for the administration of these medications. The long-term effects of inhaled steroids, with particular attention to neurodevelopmental outcome, should be addressed in future studies.

Characterization of cytochrome P450-mediated drug metabolism in cats.

In this study we examined activities of cytochrome P450 (CYP)1A, 2C, 2D and 3A using hepatic microsomes from five male and five female cats. CYP1A, 2C, 2D and 3A activities were referred by ethoxyresorufin O-deethylation (EROD), tolbutamide hydroxylation (TBH), bufuralol 1'-hydroxylation (BLH) and midazolam 1'- and 4-hydroxylation respectively. The anti-rat CYP1A2 and CYP3A2 serum significantly inhibited EROD and midazolam 1'- and 4-hydroxylation, suggesting that EROD and midazolam 1'- and 4-hydroxylation were catalysed by CYP1A and 3A in cats respectively. Quinidine inhibited BLH in cats microsomes at quite low concentrations, suggesting that BLH was catalysed by CYP2D in cats. Tolbutamide hydroxylation activities were negligible in hepatic microsomes from both male and female cats, suggesting CYP2C activities of cats are extremely low. This suggests that CYP2C substrates should be carefully administered to cats. Although there is no sexual difference in CYP1A activities, there are differences in CYP2D and 3A activities of cats. CYP2D activities were higher (3-fold), but CYP3A activities were lower (one-fifth) in female cats. These results might suggest that CYP2D and 3A substrates should be prescribed for male and female cats using different dosage regimen.

Renal vein thrombosis.

OBJECTIVE: The aim of this article is to review the published English literature on aetiology, pathology, clinical presentation, diagnostic methods and treatment of renal vein thrombosis. MATERIALS AND METHODS: We searched the published literature from Medline & Pubmed using keywords renal vein thrombosis, anti-phospholipid syndrome and nephrotic syndrome. Data was extracted from individual case reports, case series, articles on pathology, diagnostic tests, treatment modalities, and previous reviews. Case reports which did not add any new information were excluded. RESULTS: We selected 60 references based on the above criteria. Renal vein thrombosis is relatively rare. CT angiography is considered the investigation of choice. Alternatives include MR angiography or renal venography in highly selected patients. As the condition is relatively uncommon, consensus on the best form of therapy for this condition has been slow to evolve. The trend in management has shifted to non-surgical therapies particularly systemic anticoagulation except in highly selected group of patients.

Lack of inhibitory effects of several fluoroquinolones on cytochrome P-450 3A activities at clinical dosage in dogs.

Inhibitory effects of several fluoroquinolones (FQs) on liver CYP3A activities were examined by in vitro and in vivo tests in dogs. Midazolam (MDZ) hydroxylation rate was used to determine the CYP3A activities in liver microsomes. Enrofloxacin (EFX), ofloxacin (OFX) orbifloxacin (OBFX) and ciprofloxacin (CFX) were tested. None of the FQs changed Vmax, Km or intrinsic clearance (Vmax/Km) of MDZ. For in vivo test, we examined the effects of oral administration of EFX and OFX on the pharmacokinetics of quinidine (QN), a CYP3A substrate. EFX or OFX (10 mg/kg) was administered once a day for 3 days. QN (2 mg/kg) was intravenously injected at 2 h after the final dose of FQs administration. The same dose of QN was intravenously injected 3 weeks before the start of FQs administration for control. Neither EFX nor OFX changed the pharmacokinetic parameters of QN. These in vitro and in vivo consisted results suggest that these FQs lack the inhibitory effects on CYP3A activities in dogs. Hence, given these results, the risk of drug-drug interaction is unlikely to occur between FQs and CYP3A substrates in clinical situation in dogs.