Os níveis plasmáticos, farmacocinética e regime de dosagem de gatifloxacina administrado por via intravenosa em bezerros búfalos (Bubalus bubalis) na administração concomitante com meloxicam

The pharmacokinetics of intravenously administered gatifloxacin, upon concomitant administration with meloxicam was investigated in buffalo calves. Meloxicam was administered subcutaneously (0.5 mg.kg-1) immediately followed by intravenous administration of Gatifloxacin (4 mg.kg-1). The concentration of gatifloxacin was estimated in plasma by microbiological assay. Pharmacokinetic parameters were calculated and appropriate dosage schedule was computed. The therapeutic plasma drug concentration was maintained up to 12 h. Gatifloxacin was rapidly distributed from blood to tissue compartment, which was evident from the high values of distribution rate constant, α1 (11.9 ± 0.52 h-1) and the ratio of rate constant of transfer of drug from central to peripheral compartments and vice versa, K12/K21 (3.05 ± 0.36) and K13/K31 (2.04 ± 0.12). The area under the plasma drug concentration-time curve and apparent volume of distribution were 12.0 ± 0.68 µg.ml-1.h and 2.69 ± 0.14 L.kg-1, respectively. The elimination half-life (t1/2β), total body clearance (ClB) and the ratio of drug present in peripheral to central compartment (P/C) were 5.59 ± 0.40 h, 337.6 ± 19.9 ml.kg-1.h-1 and 8.04 ± 0.50, respectively. The present study revealed that the most suitable dosage regimen of gatifloxacin when concomitantly administered with meloxicam in buffalo calves would be 2.5 mg.kg-1 followed by 2.0 mg.kg-1 at 12 h intervals.Investigou-se a farmacocinética da gatifloxacina, administrada por via intravenosa, concomitante à aplicação de meloxicam em bezerros búfalos. O meloxicam foi administrado por via subcutânea (0,5 mg.kg-1), imediatamente seguido pela administração intravenosa de gatifloxacina (4 mg.kg-1). A concentração plasmática de gatifloxacina foi estimada por ensaio microbiológico. Os parâmetros farmacocinéticos foram calculados e a posologia adequada foi computada. A concentração plasmática do fármaco-terapêutico foi mantida por 12 h. A gatifloxacina foi rapidamente distribuída a partir de sangue para o compartimento de tecido, o que ficou evidente a partir dos valores elevados da taxa constante de distribuição, α1 (11.9 ± 0.52 h-1) e a proporção de velocidade constante de transferência de droga a partir de centrais para os compartimentos periféricos e vice-versa, K12/K21 (3.05 ± 0.36) e K13/K31 (2.04 ± 0.12). A área sob a curva plasmática de concentração-tempo da droga e o volume aparente de distribuição foi de 12.0 ± 0.68 µg.ml-1.h e 2.69 ± 0.14 L.kg-1, respectivamente. A meia-vida (t1/2β), a depuração corporal total (ClB) e relação da droga presente no sangue periférico para o compartimento central (P/C) foram 5.59 ± 0.40 h, 337.6 ± 19.9 ml.kg-1.h-1 e 8.04 ± 0.50, respectivamente. O presente estudo revelou que o regime de dosagem mais adequado de gatifloxacina quando administrada concomitantemente com meloxicam em bezerros búfalos seria 2,5 mg.kg-1 seguida de 2,0 mg.kg-1 em intervalos de 12 h

Farmakokinetika gatifloksacina u bivolje teladi nakon jednokratne intramuskularne primjene

The pharmacokinetics and in vivo plasma protein binding of gatifloxacin after a single intramuscular injection of 4 mg/kg were studied in buffalo calves. The minimum therapeutic concentration of drug was maintained in plasma from 1 min to 12 h. Gatifloxacin was rapidly absorbed from the extravascular site of injection, as evident from the high value of absorption rate constant (4.91 ± 0.22 /h) and attained a Cmax of 2.98 ± 0.08 μg/mL at 1h. The area under the plasma concentration-time curve and apparent volume of distribution were 10.8 ± 0.64 μg/mL/h and 3.2 ± 0.08 L/kg, respectively. Elimination half-life and total body clearance were 7.45 ± 0.55 h and 301.5 ± 34.4 mL/kg/h, respectively. Cmax/MIC ratio was 14.9 ± 0.3 and systemic bioavailability was 79.7 ± 3.35 per cent. Gatifloxacin was bound to plasma proteins of buffalo calves to the extent of 25.0 ± 1.05 per cent. A suitable intramuscular dosage regimen of gatifloxacin in buffalo calves would be 6.0 mg/kg followed by 5.3 mg/kg at 24 h intervals.Farmakokinetika i in vivo vezanje gatifloksacina na proteine plazme istraživani su u bivolje teladi nakon jednokratne intramuskularne primjene u dozi od 4 mg/kg. Minimalna terapijska koncentracija lijeka održavana je u plazmi u tijeku od 1 minute do 12 sati. Gatifloksacin se brzo resorbirao s mjesta ubrizgavanja što je vidljivo po visokoj vrijednosti konstante brzine apsorpcije (4,91 ± 0,22 sati) i postignute Cmax 2,98 ± 0,08 μg/mL/sat. Površina ispod koncentracijske krivulje u plazmi iznosila je 10,8 ± 0,64 μg/mL/sat, a prividni volumen raspodjele 3,2 ± 0,08 L/kg. Poluvrijeme izlučivanja iznosilo je 7,45 ± 0,55 sati, a ukupni tjelesni klirens 301,5 ± 34,4 mL/kg/sat. Omjer Cmax/MIC bio je 14,9 ± 0,3, a sustavna bioraspoloživost iznosila je 79,7 ± 3,35%. Gatifloksacin je bio vezan na bjelančevine plazme do 25,0 ± 1,05%. Prikladno intramuskularno doziranje u bivolje teladi bilo bi 6,0 mg/kg, a u sljedećim dozama treba davati 5,3 mg/kg u razmacima od 24 sata

Patohistološke promjene kod subakutnoga otrovanja nakon oralne primjene tiakloprida u kokoši (Gallus domesticus)

Repeated oral administration of 10 mg/kg/day thiacloprid, a neonicotinoid insecticide, for 28 consecutive days in Gallus domesticus, resulted in significant changes in the gross morphology of liver, lungs and intestine but no alterations in the kidneys, brain, heart and ovaries. Histopathologically significant alterations in the liver were observed, such as mild fatty changes, congestion and degeneration of hepatocytes. Alterations in the histoarchitecture of the kidneys included marked congestion, tubular cell degeneration and sloughing of epithelial cells. The cerebral hemisphere revealed changes comprising of mild neuronal degeneration with surrounding glial cells, satellitosis and vacuolation. Mild congestion and haemorrhage was observed in the lungs and myocardial tissues following oral administration of thiacloprid. No adverse effect on the ovarian histoarchitecture and thus the reproductive performance of Gallus domesticus was seen. The oral sub-acute toxicity study of thiacloprid revealed that this neonicotinoid insecticide is of moderate risk in Gallus domesticusPonovljena oralna primjena neonikotinoidnog insekticida tiakloprida u količini od 10 mg/kg/dan uzastopno tijekom 28 dana u kokoši je dovela do značajnih patomorfoloških promjena u jetrima, plućima i crijevima, ali neznatnih u bubrezima, mozgu, srcu i jajnicima. U jetrima su ustanovljene znatne patohistološke promjene poput blage masne degeneracije, kongestije i degeneracije hepatocita. Promjene u bubrezima uključivale su znatnu kongestiju, degeneraciju tubularnih stanica i ljuštenje epitelnih stanica. U mozgu su ustanovljene promjene u smislu blage degeneracije živčanih stanica okruženih glijalnim stanicama te satelitoza i vakuolacija. Blaga kongestija i krvarenje ustanovljeni su u plućima i u srčanom mišiću nakon oralne primjene tiakloprida. Nije ustanovljen štetan učinak na histološku građu jajnika i time na reprodukcijsku sposobnost kokoši. Subakutno otrovanje kokoši tiaklopridom pokazalo je da je taj neonikotinoidni insekticid umjereno štetan za koko

Kinetika raspodjele cefpiroma i njegovo in vitro vezanje na proteine plazme u goveda.

The disposition of cefpirome after single intramuscular (i.m.) administration (10 mg.kg-1) was investigated in five male cross-bred calves and in vitro plasma protein binding was determined. The concentration of cefpirome in the plasma was estimated by the microbiological assay technique. Binding of cefpirome to plasma proteins was determined at different concentration levels by the equilibrium dialysis technique. The peak plasma level of cefpirome after i.m. administration to cattle was attained at 45 min post-dose and the drug was detected in plasma above MIC of 0.5 μg.mL-1 for up to 10 h. The drug disposition followed a one-compartment open model. The values of t1/2Ka, t1/2β and AUC were 0.21 ± 0.01 h, 2.06 ± 0.02 h and 31.7 ± 0.95 μg.mL-1.h, respectively. Cefpirome was bound to the plasma proteins to the extent of 26.0 ± 2.84 percent at the concentration range of 1-100 μg.mL-1. The binding capacity of cefpirome to plasma proteins and the dissociation rate constant of the protein-drug complex were 3.71 ×10-8 ± 0.31 ×10-8 mole.g-1 and 3.43 ×10-7 ± 0.46 ×10-7 mole, respectively.Istražena je raspodjela cefpiroma i njegovo in vitro vezanje na proteine plazme u petero muške bivolje teladi nakon jednokratne intramuskularne primjene u dozi od 10 mg/kg. Koncentracija cefpiroma u plazmi bila je procijenjena pomoću mikrobioloških testova. Njegovo vezanje na proteine plazme određeno je za različite koncentracije pomoću dijalize. Vršna razina cefpiroma u plazmi nakon intramuskularne primjene postignuta je 45 minuta nakon davanja, a lijek je u plazmi bio dokazan iznad MIC od 0,5 μg/mL do 10 sati nakon davanja. Raspodjela lijeka bila je sukladna modelu otvorenosti jednog odjeljka. Vrijednost t1/2Ka iznosila je 0,21 ± 0,01 h, t1/2β 2,06 ± 0,02 h, a AUC 31,7 ± 0,95 μg/mL/h. Cefpirom se vezao na proteine plazme u visini od 26,0 ± 2,84 % u razmaku koncentracije od 1-100 μg/mL. Sposobnost vezanja cefpiroma na proteine plazme bila je 3,71 ×10-8 ± 0,31 ×10-8 mol/g, a konstanta njegova oslobađanja od kompleksa protein-lijek iznosila je 3,43 ×10 7± 0,46 ×10-7 mola

Automated Diagnosis and Grading of Diabetic Retinopathy Using Optical Coherence Tomography

Purpose: We determine the feasibility and accuracy of a computer-assisted diagnostic (CAD) system to diagnose and grade nonproliferative diabetic retinopathy (NPDR) from optical coherence tomography (OCT) images. Methods: A cross-sectional, single-center study was done of type II diabetics who presented for routine screening and/or monitoring exams. Inclusion criteria were age 18 or older, diagnosis of diabetes mellitus type II, and clear media allowing for OCT imaging. Exclusion criteria were inability to image the macula, posterior staphylomas, proliferative diabetic retinopathy, and concurrent retinovascular disease. All patients underwent a full dilated eye exam and spectral-domain OCT of a 6 x 6 mm area of the macula in both eyes. These images then were analyzed by a novel CAD system that segments the retina into 12 layers; quantifies the reflectivity, curvature, and thickness of each layer; and ultimately uses this information to train a neural network that classifies images as either normal or having NPDR, and then further grades the level of retinopathy. A first dataset was tested by leave-one-subject-out (LOSO) methods and by 2- and 4-fold cross-validation. The system then was tested on a second, independent dataset. Results: Using LOSO experiments on a dataset of images from 80 patients, the proposed CAD system distinguished normal from NPDR subjects with 93.8% accuracy (sensitivity = 92.5%, specificity = 95%) and achieved 97.4% correct classification between subclinical and mild/moderate DR. When tested on an independent dataset of 40 patients, the proposed system distinguished between normal and NPDR subjects with 92.5% accuracy and between subclinical and mild/moderate NPDR with 95% accuracy. Conclusions: A CAD system for automated diagnosis of NPDR based on macular OCT images from type II diabetics is feasible, reliable, and accurate

Farmakokinetika i doziranje levofloksacina u bivolje teladi nakon jednokratne potkožne primjene

The present study was conducted on six male buffalo calves to investigate the pharmacokinetics of levofloxacin following a single subcutaneous administration at the dose rate of 3 mg/kg body weight. Appreciable plasma concentration of levofloxacin (0.28 ± 0.01 μg/mL) was detected 2.5 min after injection and the peak plasma level of 2.94 ± 0.07 μg/mL was observed at 1 h. Drug levels of 0.28 ± 0.01 μg/mL in plasma were detected up to 12 h from administration. Rapid absorption of the drug was also evident by the high value of the absorption rate constant (2.53 ± 0.53 /h). The absolute bioavailability of levofloxacin after subcutaneous administration calculated on the basis of AUC (10.5 ± 0.11 μg/mL/h) and Ke (0.272 ± 0.009 /h) after a single intravenous injection in buffalo calves was 44.3 ± 1.76 per cent. The high value of AUC (8.02 ± 0.2 μg/mL/h) reflected major exposure in the buffalo calves. Extensive distribution of the drug into various body fluids and tissues was reflected by the high value of Vdarea (1.06 ± 0.04 L.kg-1). The elimination half-life and MRT were 4.43 ± 0.1 h and 6.71 ± 0.17 h, respectively. On the basis of the pharmacokinetic parameters, the calculated subcutaneous dosage regimen for levofloxacin in buffalo calves was 4.6 mg/kg at 24 h intervals.Farmakokinetika levofloksacina nakon njegove jednokratne supkutane primjene u dozi od 3 mg/kg tjelesne mase određivana je na šest muške bivolje teladi. Mjerljiva koncentracija levofloksacina u plazmi (0,28 ± 0,01 μg/mL) bila je ustanovljena 2,5 minute nakon primjene, a vršna razina od 2,94 ± 0,07 μg/mL ustanovljena je jedan sat nakon primjene. Razina lijeka od 0,28 ± 0,01 μg/mL bila je u plazmi dokazana do 12 sati nakon primjene. Brza apsorpcija lijeka očitovala se u visokoj vrijednosti stupnja apsorpcije (2,53 ± 0,53/h). Apsolutna biološka raspoloživost levofloksacina nakon supkutane primjene izračunana na osnovi AUC (10,5 ± 0,11 μg/mL/h) i Ke (0,272 ± 0,009 /h) nakon jednokratne intravenske primjene iznosila je 44,3 ± 1,76%. Visoka vrijednost AUC (8,02 ± 0,2 μg/mL/h) bila je posljedica velike količine primijenjenoga lijeka. Široka raspodjela lijeka u različitim tjelesnim tekućinama i tkivima očitovala se velikom vrijednošću Vdarea (1,06 ± 0,04 L/kg). Poluživot izlučivanja lijeka iznosio je 4,43 ± 0,1 h, a MRT 6,71 ± 0,17 h. Na osnovi farmakokinetičkih pokazatelja, izračunana supkutana doza levofloksacina u bivolje teladi iznosila je 4,6 mg/kg u razmacima od 24 sata

Farmakokinetika gatifloksacina u bivolje teladi nakon jednokratne intramuskularne primjene

The pharmacokinetics and in vivo plasma protein binding of gatifloxacin after a single intramuscular injection of 4 mg/kg were studied in buffalo calves. The minimum therapeutic concentration of drug was maintained in plasma from 1 min to 12 h. Gatifloxacin was rapidly absorbed from the extravascular site of injection, as evident from the high value of absorption rate constant (4.91 ± 0.22 /h) and attained a Cmax of 2.98 ± 0.08 μg/mL at 1h. The area under the plasma concentration-time curve and apparent volume of distribution were 10.8 ± 0.64 μg/mL/h and 3.2 ± 0.08 L/kg, respectively. Elimination half-life and total body clearance were 7.45 ± 0.55 h and 301.5 ± 34.4 mL/kg/h, respectively. Cmax/MIC ratio was 14.9 ± 0.3 and systemic bioavailability was 79.7 ± 3.35 per cent. Gatifloxacin was bound to plasma proteins of buffalo calves to the extent of 25.0 ± 1.05 per cent. A suitable intramuscular dosage regimen of gatifloxacin in buffalo calves would be 6.0 mg/kg followed by 5.3 mg/kg at 24 h intervals.Farmakokinetika i in vivo vezanje gatifloksacina na proteine plazme istraživani su u bivolje teladi nakon jednokratne intramuskularne primjene u dozi od 4 mg/kg. Minimalna terapijska koncentracija lijeka održavana je u plazmi u tijeku od 1 minute do 12 sati. Gatifloksacin se brzo resorbirao s mjesta ubrizgavanja što je vidljivo po visokoj vrijednosti konstante brzine apsorpcije (4,91 ± 0,22 sati) i postignute Cmax 2,98 ± 0,08 μg/mL/sat. Površina ispod koncentracijske krivulje u plazmi iznosila je 10,8 ± 0,64 μg/mL/sat, a prividni volumen raspodjele 3,2 ± 0,08 L/kg. Poluvrijeme izlučivanja iznosilo je 7,45 ± 0,55 sati, a ukupni tjelesni klirens 301,5 ± 34,4 mL/kg/sat. Omjer Cmax/MIC bio je 14,9 ± 0,3, a sustavna bioraspoloživost iznosila je 79,7 ± 3,35%. Gatifloksacin je bio vezan na bjelančevine plazme do 25,0 ± 1,05%. Prikladno intramuskularno doziranje u bivolje teladi bilo bi 6,0 mg/kg, a u sljedećim dozama treba davati 5,3 mg/kg u razmacima od 24 sata

A strategy to identify event specific hospitalizations in large health claims databases

Background: Health insurance claims data offer a unique opportunity to study disease distribution on a large scale. Challenges arise in the process of accurately analyzing these raw data. One important challenge to overcome is the accurate classification of study outcomes. For example, using claims data, there is no clear way of classifying hospitalizations due to a specific event. This is because of the inherent disjointedness and lack of context that typically come with raw claims data. Methods: In this paper, we propose a framework for classifying hospitalizations due to a specific event. We then tested this framework in a private health insurance claims database (Symphony) with approximately 4 million US adults who tested positive with COVID-19 between March and December 2020. Our claims specific COVID-19 related hospitalizations proportion is then compared to nationally reported rates from the Centers for Disease Control by age. Results: Across all ages (18 +) the total percentage of Symphony patients who met our definition of hospitalized due to COVID-19 was 7.3% which was similar to the CDC’s estimate of 7.5%. By age group, defined by the CDC, our estimates vs. the CDC’s estimates were 18–49: 2.7% vs. 3%, 50–64: 8.2% vs. 9.2%, and 65 + : 14.6% vs. 28.1%. Conclusions: The proposed methodology is a rigorous way to define event specific hospitalizations in claims data. This methodology can be extended to many different types of events and used on a variety of different types of claims databases

Predicting the Level of Respiratory Support in COVID-19 Patients Using Machine Learning

In this paper, a machine learning-based system for the prediction of the required level of respiratory support in COVID-19 patients is proposed. The level of respiratory support is divided into three classes: class 0 which refers to minimal support, class 1 which refers to non-invasive support, and class 2 which refers to invasive support. A two-stage classification system is built. First, the classification between class 0 and others is performed. Then, the classification between class 1 and class 2 is performed. The system is built using a dataset collected retrospectively from 3491 patients admitted to tertiary care hospitals at the University of Louisville Medical Center. The use of the feature selection method based on analysis of variance is demonstrated in the paper. Furthermore, a dimensionality reduction method called principal component analysis is used. XGBoost classifier achieves the best classification accuracy (84%) in the first stage. It also achieved optimal performance in the second stage, with a classification accuracy of 83%

The Role of Medical Image Modalities and AI in the Early Detection, Diagnosis and Grading of Retinal Diseases: A Survey.

Traditional dilated ophthalmoscopy can reveal diseases, such as age-related macular degeneration (AMD), diabetic retinopathy (DR), diabetic macular edema (DME), retinal tear, epiretinal membrane, macular hole, retinal detachment, retinitis pigmentosa, retinal vein occlusion (RVO), and retinal artery occlusion (RAO). Among these diseases, AMD and DR are the major causes of progressive vision loss, while the latter is recognized as a world-wide epidemic. Advances in retinal imaging have improved the diagnosis and management of DR and AMD. In this review article, we focus on the variable imaging modalities for accurate diagnosis, early detection, and staging of both AMD and DR. In addition, the role of artificial intelligence (AI) in providing automated detection, diagnosis, and staging of these diseases will be surveyed. Furthermore, current works are summarized and discussed. Finally, projected future trends are outlined. The work done on this survey indicates the effective role of AI in the early detection, diagnosis, and staging of DR and/or AMD. In the future, more AI solutions will be presented that hold promise for clinical applications