Učinak pretkondicioniranja piperinom na farmakokinetiku peroralno primijenjenog marbofloksacina u štakora

The present study was carried out to evaluate the effect of piperine pre-conditioning on the pharmacokinetics of marbofloxacin in Wistar rats. Marbofloxacin was administrated at a dose rate of 5 mg/kg body weight alone, and along with piperine pre-conditioning at a dose of 10 mg/kg of body weight, orally for 5 days in Wistar rats. The mean values of the half-life (t1⁄2β), maximum drug concentration (Cmax) and area under the curve (AUC) were 1.19 ± 0.17 h, 2.71 ± 0.09 μg/mL and 12.25 ± 0.77 μg.h/mL, respectively, in piperine pretreated rats. The values were significantly higher than the values observed in rats administered with marbofloxacin alone (1.12 ± 0.31 h, 2.28 ± 0.20 μg/mL and 9.24 ± 0.59 μg.h/mL, respectively). The drug clearance (ClB) in piperine pretreated rats was 0.04 ± 0.02 L/h/kg, which was significantly lower than the clearance rate of the drug (0.53 ± 0.03 L/h/kg) in the animals administered with marbofloxacin alone. The study reveals that piperine has a significant effect on the pharmacokinetics of marbofloxacin, which may be due to an increase in the drug absorption and inhibition of elimination of the drug in rats.U ovom je radu istražen učinak pretkondicioniranja piperinom na farmakokinetiku marbofloksacina Wistar štakora. Marbofloksacin je apliciran u dozi od 5 mg/kg tjelesne mase peroralno, samostalno i nakon pretkondicioniranja piperinom u dozi od 10 mg/kg tjelesne mase peroralno tijekom 5 dana. U štakora tretiranih piperinom prosječne vrijednosti poluživota (t1⁄2β) bile su 1,19 ± 0,17 h, maksimalna koncentracija lijeka (Cmax) 2,71 ± 0,09 μg/mL, a površina ispod krivulje (AUC) 12,25 ± 0,77 μg.h/mL. Navedene vrijednosti bile su znakovito više od onih utvrđenih u štakora tretiranih samo marbofloksacin (1,12 ± 0,31 h, 2,28 ± 0,20 μg/mL i 9,24 ± 0,59 μg.h/mL). Klirens lijeka (ClB) u štakora tretiranih piperinom bio je 0,04 ± 0,02 L/h/kg što je bilo znakovito niže od klirensa lijeka (0,53 ± 0,03 L/h/ kg) u životinja koje su dobivale samo marbofloksacin. Ovo istraživanje pokazuje da piperin znakovito utječe na farmakokinetiku marbofloksacina, što može biti posljedica povećane apsorpcije lijeka i inhibicije uklanjanja lijeka u štakora

The Impact of a Brief Intervention on Medical Students\u27 Readiness to Screen for DV - Changes in Decisional Balance and Self-Efficacy

Introduction: Domestic violence (DV) affects millions of Americans each year. Yet, there is a dearth of theory-based DV curricula, resulting in physicians unprepared to screen for DV. This study utilized a survey based on constructs from the Transtheoretical Model to assess the readiness of first- and second-year medical students to screen for DV. Information from this survey will be used to help institutionalize DV education into the medical curriculum. [See PDF for complete abstract

Analysis and Implementation of Malicious Node in AODV Routing Protocol

The Mobile Ad-hoc Network (MANET) is constructed based on wireless medium and it is of self organizing behaviour. MANET is easy to establish and having dynamic topology. The mobile Ad-hoc networks are vulnerable to various networks attacks because MANET operational environment is open and dynamic or live. MANET uses the Routing protocols for data transfer. Two different types of Routing protocols are available: Table Driven and On Demand Routing Protocols. Malicious node is the one type of mobile node but its work is completely different compared to normal Mobile nodes. Malicious nodes have capability to change or remove Routing Information. It also sends or advertises the fake Route Request to attract user’s data. Malicious node disturbs the Network to carry correct flow of operation. It is responsible for attacks on the existing normal mobile nodes and creates receiver collision, limited transmission power, false misbehaviour etc. Malicious or selfish node carries attacks on the networks so it directly effects to the routing Performance. The objective of this work is to check Network performance in malicious environment and provide prevention for the attack. Throughput and Delay are analysed for Denial of Service (DoS) attack and prevention scenarios. Keywords: MANET, AODV, Selfish Node, DoS Attack, Routing Protocol

Farmakokinetika eprinomektina u ovaca nakon potkožne primjene.

The pharmacokinetics of eprinomectin was determined in lactating sheep following subcutaneous administration at a dose rate of 0.2 mg kg-1. The eprinomectin concentration in plasma was determined using High Performance Liquid Chromatography (HPLC) with a fluorescence detector. The kinetics of plasma concentrations were analysed using the non-compartment model. The maximum plasma concentration of 24.44 ng/mL occurred 2 days post-administration. Following subcutaneous administration of eprinomectin in sheep, the value of plasma elimination half-life, the area under the plasma concentration time curve (AUC) and mean residence time (MRT) were 388.52 ± 0.25 h. 4282.10 ng.h/mL and 374.50 h, respectively. The values of V (area), Vd(ss) and Cl(B) were 20.50 mL/kg, 13.70 mL/kg and 0.04 mL/h/kg, respectively. This study demonstrates that subcutaneous administration of eprinomectin led to higher bioavailability and longer mean residence time with a lower dose than a pour-on application, and that an injectable formulation may be applied in lactating sheep with zero withdrawal period.Farmakokinetika eprinomektina određivana je u ovaca u laktaciji nakon potkožne primjene u dozi od 0,2 mg/kg. Njegova koncentracija u plazmi utvrđena je visoko učinkovitom tekućinskom kromatografijom s fluorescentnim detektorom. Kinetika koncentracija u plazmi analizirana je na osnovi modela bez odjeljaka. Najveća koncentracija u plazmi od 24,44 ng/mL dokazana je dva dana nakon primjene. Poluživot eliminacije iz plazme iznosio je 388,52 ± 0,25 sati, površina ispod krivulje koncentracije u plazmi (AUC) 4282,10 ng/h/mL, a prosječno vrijeme zadržavanja iznosilo je 374,50 sati. Vrijednost prividnog volumena raspodjele, Vd(area), iznosila je 20,50 mL/kg, prosječni vidljivi volumen raspodjele, Vd(ss), 13,70 mL/kg, a ukupni klirens 0,04 mL/sat/kg. Istraživanje je pokazalo da potkožna primjena eprinomektina pruža veću bioraspoloživost, duže vrijeme zadržavanja s manjom dozom u odnosu na veliku te da se injekcijska formulacija može primijeniti u ovaca u laktaciji

Robotic-Assisted Laparoscopic “Salvage” Rectopexy for Recurrent Ileoanal J-Pouch Prolapse

Total restorative proctocolectomy with ileal pouch-anal anastomosis (RP/IPAA) has become the standard of care for the surgical treatment of ulcerative colitis. Despite its correlation with an excellent quality of life and favorable long-term outcomes, RP/IPAA has been associated with several complications. Prolapse of the ileoanal pouch is a rare and debilitating complication that should be considered in the differential diagnosis of pouch failure. Limited data exist regarding the prevalence and treatment of pouch prolapse. We present the case of a recurrent J-pouch prolapse treated with a novel minimally invasive “salvage” approach involving a robotic-assisted laparoscopic rectopexy with mesh

Learning curve for robotic-assisted laparoscopic colorectal surgery.

BACKGROUND: Robotic-assisted laparoscopic surgery (RALS) is evolving as an important surgical approach in the field of colorectal surgery. We aimed to evaluate the learning curve for RALS procedures involving resections of the rectum and rectosigmoid. METHODS: A series of 50 consecutive RALS procedures were performed between August 2008 and September 2009. Data were entered into a retrospective database and later abstracted for analysis. The surgical procedures included abdominoperineal resection (APR), anterior rectosigmoidectomy (AR), low anterior resection (LAR), and rectopexy (RP). Demographic data and intraoperative parameters including docking time (DT), surgeon console time (SCT), and total operative time (OT) were analyzed. The learning curve was evaluated using the cumulative sum (CUSUM) method. RESULTS: The procedures performed for 50 patients (54% male) included 25 AR (50%), 15 LAR (30%), 6 APR (12%), and 4 RP (8%). The mean age of the patients was 54.4 years, the mean BMI was 27.8 kg/m(2), and the median American Society of Anesthesiologists (ASA) classification was 2. The series had a mean DT of 14 min, a mean SCT of 115.1 min, and a mean OT of 246.1 min. The DT and SCT accounted for 6.3% and 46.8% of the OT, respectively. The SCT learning curve was analyzed. The CUSUM(SCT) learning curve was best modeled as a parabola, with equation CUSUM(SCT) in minutes equal to 0.73 × case number(2) - 31.54 × case number - 107.72 (R = 0.93). The learning curve consisted of three unique phases: phase 1 (the initial 15 cases), phase 2 (the middle 10 cases), and phase 3 (the subsequent cases). Phase 1 represented the initial learning curve, which spanned 15 cases. The phase 2 plateau represented increased competence with the robotic technology. Phase 3 was achieved after 25 cases and represented the mastery phase in which more challenging cases were managed. CONCLUSIONS: The three phases identified with CUSUM analysis of surgeon console time represented characteristic stages of the learning curve for robotic colorectal procedures. The data suggest that the learning phase was achieved after 15 to 25 cases

Xenon Upregulates Hypoxia Inducible Factor 1 Alpha in Neonatal Rat Brain under Normoxic Conditions

Xenon can induce cell and organ protection through different molecular mechanisms related to oxygen level. We explored the effect of xenon on oxygen-related signalling in the central nervous system via hypoxia inducible factor 1 alpha (HIF-1α) and mammalian target of rapamycin (mTOR). Methods. Postnatal day 7 (P7) Sprague Dawley rats were exposed to 25% oxygen/75% nitrogen (air group) or 25% oxygen/75% xenon (treatment group) for 120 min. Brains were collected immediately (transcript analysis—relative real-time polymerase chain reaction) or 24 hours (protein analysis—immunohistochemistry) after the 120-minute exposure period; peak anesthetic preconditioning has been previously identified at 24 hours post-exposure. Results. HIF-1α transcript and protein levels were found to be increased in xenon-exposed compared to air-exposed brains. Sustained nuclear translocation of the protein, accounting for an increased activity of HIF-1α, was also noted. mTOR transcript analysis revealed no significant difference between xenon-exposed and air-exposed brains immediately after the 120-minute exposure. Conclusion. Our data suggest that xenon induces the upregulation of HIF-1α transcription and translation, which may contribute to xenon's neuroprotective preconditioning effect. However, given that xenon exposure did not affect mTOR transcription, further investigation into other signalling cascades mediating xenon's effects on HIF-1α in developing brain is warranted

Using Pupillometry to Characterize Visual Perception in Autistic Mouse Models

Fragile X syndrome (FXS) is the leading genetic cause of autism. Individuals with Fragile X Syndrome (FXS) commonly display social, behavioral, and intellectual disabilities. Perceptual deficits and their underlying neural activity remain poorly characterized in FXS and other autism spectrum disorders (ASD’s). To explore visual perception in autism, we developed camera based pupil tracking software using OpenCV (an open-source computer vision library) capable of measuring visually evoked changes in pupil area and position in the FXS mouse model (Fmr1 KO). Changes in pupil area and position are believed to correlate with changes in arousal or visual processing and may serve as an indirect readout of brain state. To explore visually evoked changes in pupil area, head-restrained wild type or Fragile X mice were exposed to visual stimulation consisting of sinusoidal gratings. The average pupil area of Fragile X mice was increased compared to wild type controls. Our results suggest that online pupillometry has a high potential to serve as a diagnostic tool for autism spectrum disorders

Farmakokinetika eprinomektina u ovaca nakon potkožne primjene.

The pharmacokinetics of eprinomectin was determined in lactating sheep following subcutaneous administration at a dose rate of 0.2 mg kg-1. The eprinomectin concentration in plasma was determined using High Performance Liquid Chromatography (HPLC) with a fluorescence detector. The kinetics of plasma concentrations were analysed using the non-compartment model. The maximum plasma concentration of 24.44 ng/mL occurred 2 days post-administration. Following subcutaneous administration of eprinomectin in sheep, the value of plasma elimination half-life, the area under the plasma concentration time curve (AUC) and mean residence time (MRT) were 388.52 ± 0.25 h. 4282.10 ng.h/mL and 374.50 h, respectively. The values of V (area), Vd(ss) and Cl(B) were 20.50 mL/kg, 13.70 mL/kg and 0.04 mL/h/kg, respectively. This study demonstrates that subcutaneous administration of eprinomectin led to higher bioavailability and longer mean residence time with a lower dose than a pour-on application, and that an injectable formulation may be applied in lactating sheep with zero withdrawal period.Farmakokinetika eprinomektina određivana je u ovaca u laktaciji nakon potkožne primjene u dozi od 0,2 mg/kg. Njegova koncentracija u plazmi utvrđena je visoko učinkovitom tekućinskom kromatografijom s fluorescentnim detektorom. Kinetika koncentracija u plazmi analizirana je na osnovi modela bez odjeljaka. Najveća koncentracija u plazmi od 24,44 ng/mL dokazana je dva dana nakon primjene. Poluživot eliminacije iz plazme iznosio je 388,52 ± 0,25 sati, površina ispod krivulje koncentracije u plazmi (AUC) 4282,10 ng/h/mL, a prosječno vrijeme zadržavanja iznosilo je 374,50 sati. Vrijednost prividnog volumena raspodjele, Vd(area), iznosila je 20,50 mL/kg, prosječni vidljivi volumen raspodjele, Vd(ss), 13,70 mL/kg, a ukupni klirens 0,04 mL/sat/kg. Istraživanje je pokazalo da potkožna primjena eprinomektina pruža veću bioraspoloživost, duže vrijeme zadržavanja s manjom dozom u odnosu na veliku te da se injekcijska formulacija može primijeniti u ovaca u laktaciji

A Student-Initiated Elective in Medical Ethics: Innovations in Design and Institutionalization

Introduction: This study addresses how to best approach the instruction and evaluation of clinical ethics with preclinical medical students. [See PDF for complete abstract