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April 21, 2009

Determination of reference intervals for plasma biochemical values in clinically normal adult domestic shorthair cats by use of a dry-slide biochemical analyzer.

Filed under: Veterinary Science and Veterinary Medicine — Tags: , — medical insurance @ 7:12 am

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Objective-To establish reference intervals of plasma biochemical values in healthy adult domestic shorthair (DSH) cats by use of controlled conditions. Animals-95 healthy client-owned cats. Procedures-Food was withheld from the cats overnight. All blood samples were obtained on the same day, at the same location, and by the same investigator. Blood samples were collected from a cephalic vein into lithium heparin tubes. After centrifugation of blood samples, plasma supernatants were harvested and stored at -20 degrees C until assayed for total proteins, albumin, creatinine, urea, glucose, calcium, phosphates, sodium, chloride, potassium, and CO(2) concentrations and alkaline phosphatase and alanine aminotransferase activities. Results-Reference intervals in healthy adult DSH cats were 65 to 85 g/L for total proteins, 27 to 39 g/L for albumin, 89 to 207 mumol/L for creatinine, 6.6 to 11.3 mmol/L for urea, 4.1 to 8.2 mmol/L for glucose, 2.4 to 2.9 mmol/L for calcium, 1.1 to 2.1 mmol/L for phosphates, 153 to 161 mmol/L for sodium, 120 to 127 mmol/L for chloride, 3.3 to 4.2 mmol/L for potassium, 15 to 21 mmol/L for CO(2), 32 to 147 U/L for alkaline phosphatase, and 34 to 123 U/L for alanine aminotransferase. Conclusions and Clinical Relevance-This study provided reference intervals for plasma analytes in adult DSH cats. The influence of potential confounding factors was minimized through use of controlled preanalytic and analytic conditions. However, these results cannot be extrapolated to other feline breeds or used to interpret results from other biochemical analyzers.

Reynolds BS Boudet KG Germain CA Braun JP Lefebvre HP
Department of Clinical Sciences, National Veterinary School of Toulouse, 23, chemin des Capelles, BP 87614, 31076 Toulouse cedex 03, France.

Intraocular pharmacokinetics of intravenously administered marbofloxacin in rabbits with experimentally induced acute endophthalmitis.

Filed under: Veterinary Science and Veterinary Medicine — Tags: , — medical insurance @ 6:02 am

OBJECTIVE: To compare penetration of IV administered marbofloxacin in intraocular fluids of healthy and inflamed eyes in rabbits with endotoxin-induced endophthalmitis. ANIMALS: 35 pigmented rabbits. PROCEDURES: Endophthalmitis was induced in the right eye via intravitreal administration of Escherichia coli endotoxin. The left eye was a control eye. After 24 hours, a single dose of marbofloxacin (4 mg/kg, IV) was administered. Groups of rabbits (n = 5/group) were euthanized 0.5, 1, 2, 4, 6, 10, and 18 hours later, and blood and ocular fluids were collected. Marbofloxacin concentrations were determined via reverse-phase high-performance liquid chromatography, and pharmacokinetic analysis of the data was performed with a mono-compartmental model. RESULTS: Mean area under the aqueous concentration-time curve was significantly lower in control eyes (1.64 +/- 0.07 microg*h/mL) than in inflamed eyes (3.31 +/- 0.11 microg*h/mL). Similarly, drug penetration into aqueous humor was 33% and 65% for control eyes and inflamed eyes, respectively. Mean area under the vitreous humor concentration-time curve for control eyes(1.75 +/- 0.05 microg*h/mL) was significantly less than for inflamed eyes (2.39 +/- 0.16 microg*h/mL). In the vitreous humor, corresponding penetrations were 34% and 47%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Penetration of marbofloxacin into the aqueous and vitreous humor after IV administration was significantly enhanced by intraocular inflammation, suggesting a role for this antimicrobial in the prophylaxis or treatment of bacterial endophthalmitis caused by susceptible pathogens.

Regnier ASchneider MConcordet DToutain PL
UMR181 Physiopathologie et Toxicologie Experimentales, INRA, ENVT, Ecole Nationale Veterinaire,Toulouse Cedex 3, France.

April 10, 2009

Homeoproteins as natural Penetratin cargoes with signaling properties

Filed under: Pharmacology, Toxicology and Pharmaceutical Science — Tags: , — medical insurance @ 10:23 am

Most of this volume is dedicated to a very important and pragmatic issue which is to design ways of internalizing active pharmacological compounds into cells. In fact, many vectors have now been developed and the improvement in the technology can be seen on two main fronts. A first one is the identification of extremely efficient cargoes, for example siRNAs, which can enter the cells once attached to the vectors. A second one is the development of chemical vectors designed after the properties of the peptides and of tags allowing in vivo addressing to specific organs, for example the brain, cell types or sub-cellular compartments.This chapter is of a different nature, as it is devoted to the physiological significance of protein transduction and to the comparative analysis of the Penetratin PTD with its parental proteins, the homeoproteins. Although very academic, these two issues are of practical interest for the rational design of new vectors and the identification of unforeseen pathological mechanisms and pharmacological targets.

Alain JoliotaEmail:joliot@biologie.ens.fr Alain ProchiantzbEmail:prochian@biologie.ens.fr
[a]Homeoprotein Cell Biology Group, UMR CNRS 8542, Ecole Normale Supérieure, 46 rue d’Ulm 75230 Paris Cedex 05, France;[b]Development and Neuropharmacology, UMR CNRS 8542, Ecole Normale Supérieure, 46 rue d’Ulm 75230 Paris Cedex 05, France

2008.60,12-4

Protein and peptide transduction, twenty years later a happy birthday

Filed under: Pharmacology, Toxicology and Pharmaceutical Science — Tags: , — medical insurance @ 9:23 am

This commentary underscores the following aspects of Cell Permeable Peptides/Transduction Peptides (CPP/PTD) research. First the discovery of CPP/PTD takes its origin in the observation that some full-length transcription factors navigate between cells. The latter physiological origin is of interest as the significance of this new mode of signal transduction is not yet fully understood. A second point is that most breakthroughs in the domain have been made possible by long lasting collaborations between biologists, chemists and physicists. It is beyond doubt that the understanding of the mechanisms of secretion and internalization, in parallel with the development of new transduction compounds, not only peptides, will require that such collaborative efforts be amplified. Finally, although the domain is flourishing and our minds full of hope, it must be said that many points need to be resolved before getting close to bedside. Among these points are bio-disponibility, toxicity and specific addressing to body regions, cell types and intracellular compartments. In brief, beyond this happy birthday, there is still plenty of home work!

Alain ProchiantzaEmail:prochian@biologie.ens.fr
[a]Development and Neuropharmacology, UMR CNRS 8542, Ecole normale supérieure, 46 rue d’Ulm 75230 Paris Cedex 05, France

April 6, 2009

Staging of peritoneal carcinomatosis: enhanced CT vs. PET/CT.

Filed under: Medicine and Dentistry — Tags: , — medical insurance @ 3:14 pm

PURPOSE: To assess and compare the performance of CT and 18F-FDG-PET/CT in the evaluation of peritoneal carcinomatosis (PC). METHOD AND MATERIALS: Thirty consecutive patients with PC and scheduled for a surgery underwent a CT of the abdomen and pelvis and a whole-body 18F-FDG PET/CT. The extent of PC was assessed precisely using the peritoneal cancer index combining the distribution of tumor throughout 11 abdominopelvic regions with a lesion size score. CT and PET/CT imaging results were compared in all patients with intraoperative findings using an interclass correlation test. RESULTS: The presence of PC was correctly determined on CT and PET/CT in 23/28 and 16/28 patients, respectively. The extent of PC was understaged with CT and PET/CT in 27 patients and overstaged with CT and PET/CT in 1 and 2 patients, respectively. The interclass correlation was 0.53 (moderate) between CT and surgery and 0.12 (low) between PET/CT and surgery. The interclass correlation was higher for mucinous tumor (0.63) than for non-mucinous (0.16) on CT imaging whereas no difference was found in PET/CT. CONCLUSION: The intraperitoneal assessment of the extent of carcinomatosis, necessary to assess prognosis and treatment planning, is not accurate enough with CT and PET/CT imaging.

Dromain C Leboulleux S Auperin A Goere D Malka D Lumbroso J Schumberger M Sigal R Elias D
Department of Radiology, Institut Gustave-Roussy, 39, rue Camille Desmoulins, 94805, Villejuif Cedex, France. dromain@igr.fr

2008,33,000,1

March 24, 2009

Challenges and opportunities in the encapsulation of liquid and semi-solid formulations into capsules for oral administration

Filed under: Pharmacology, Toxicology and Pharmaceutical Science — Tags: , — medical insurance @ 12:52 pm

The encapsulation of liquids and semi-solids provides solutions for convenient delivery through improved oral absorption of poorly water-soluble drugs. In addition, low dose (content uniformity), highly potent (containment), low melting point drugs, those with a critical stability profile and those for which a delayed release is required are candidates for liquid or semi-solid formulations. Both hard and soft capsules can be considered and in each case the capsule wall may comprise gelatin or some other suitable polymer such as hypromellose. The choice of a hard or soft capsule will depend primarily on the components of the formulation which provides the best absorption characteristics as well as on the physical characteristics, such as the viscosity of the formulation and the temperature at which the product needs to be filled. Numerous excipients are available for formulation of lipid-based systems and their compatibilities with hard gelatin capsules have been tested. The availability of new enhanced manufacturing equipment has brought new opportunities for liquid-filled hard capsules. Filling and sealing technologies for hard capsules, provides the formulator with the flexibility of developing formulations in-house from small scale, as required for Phase I studies, up to production.

Ewart T. ColeaEmail:etc.consulting@bluewin.ch Dominique CadébEmail:Dominique.cade@pfizer.com Hassan BenameurbEmail:Hassan.benameur@pfizer.com
[a]Capsugel Division of Pfizer, CH-4114 Hofstetten, Switzerland;[b]Capsugel Division of Pfizer, 10 Rue Timken, Colmar, France

March 22, 2009

Paradoxical increase of positive answers to the Cut-down, Annoyed, Guilt, Eye-opener (CAGE) questionnaire during a period of decreasing alcohol consumption: results from two population-based surveys in Ile-de-France, 1991 and 2005.

Filed under: Nursing and Health Professions — Tags: , — medical insurance @ 11:53 am

AIMS: To describe trends of responses to the Cut-down, Annoyed, Guilt, Eye-opener (CAGE) questionnaire during a period of declining alcohol consumption, in a country with no temperance history. DESIGN: Two random-sample surveys, conducted in 1991 and 2005, respectively. SETTING: The adult population of Ile-de-France. PARTICIPANTS: A total of 1183 subjects in 1991 and 5382 subjects in 2005. MEASUREMENTS: Responses to CAGE questions, obtained by face-to-face interviews in 1991 and by telephone in 2005. RESULTS: were standardized on the 2005 population structure. FINDINGS: The proportion of subjects giving at least two positive answers has increased by 4.2 times; the biggest increase was observed for the Guilt question (4.8 times) and the smallest for the Eye-opener question (2.6 times). Several increases were higher for women than for men: 12.9 times versus 3.3 times for two or more positive answers, 9.8 times versus 3.8 times for the Guilt question. Increases did not vary consistently by age. CONCLUSION: These paradoxical trends do not support the use of CAGE in general population surveys. They confirm previous reports suggesting that CAGE was sensitive to community temperance level. They might reflect the emergence of a temperance movement in France, with stronger impact among women. This movement might be responsible for the fall in alcohol consumption.

Messiah,A Encrenaz,G Sapinho,D Gilbert,F Carmona,E Kovess-Masfety,V
INSERM, Research Center U-897, Equipe Avenir, Prevention et prise en charge des Traumatismes/Injury Prevention and Control, Bordeaux, France. antoine.messiah@isped.u-bordeaux2.fr

Staging of peritoneal carcinomatosis: enhanced CT vs. PET/CT.

Filed under: Medicine and Dentistry — Tags: , — medical insurance @ 11:43 am

PURPOSE: To assess and compare the performance of CT and 18F-FDG-PET/CT in the evaluation of peritoneal carcinomatosis (PC). METHOD AND MATERIALS: Thirty consecutive patients with PC and scheduled for a surgery underwent a CT of the abdomen and pelvis and a whole-body 18F-FDG PET/CT. The extent of PC was assessed precisely using the peritoneal cancer index combining the distribution of tumor throughout 11 abdominopelvic regions with a lesion size score. CT and PET/CT imaging results were compared in all patients with intraoperative findings using an interclass correlation test. RESULTS: The presence of PC was correctly determined on CT and PET/CT in 23/28 and 16/28 patients, respectively. The extent of PC was understaged with CT and PET/CT in 27 patients and overstaged with CT and PET/CT in 1 and 2 patients, respectively. The interclass correlation was 0.53 (moderate) between CT and surgery and 0.12 (low) between PET/CT and surgery. The interclass correlation was higher for mucinous tumor (0.63) than for non-mucinous (0.16) on CT imaging whereas no difference was found in PET/CT. CONCLUSION: The intraperitoneal assessment of the extent of carcinomatosis, necessary to assess prognosis and treatment planning, is not accurate enough with CT and PET/CT imaging.

Dromain C Leboulleux S Auperin A Goere D Malka D Lumbroso J Schumberger M Sigal R Elias D
Department of Radiology, Institut Gustave-Roussy, 39, rue Camille Desmoulins, 94805, Villejuif Cedex, France. dromain@igr.fr

March 16, 2009

Efficiency of MR imaging to orientate surgical treatment of posterior deep pelvic endometriosis

Filed under: Medicine and Dentistry — Tags: , — medical insurance @ 6:57 pm

OBJECTIVE: The purpose of this retrospective study was to evaluate the accuracy of MRI using pelvic-phased-array and endocavitary coils in detecting intestinal wall invasion by an endometriotic nodule. MATERIALS AND METHODS: Forty-seven patients (32.1 +/- 4.2 years) who were planned for a surgical cure of deep endometriosis underwent MRI with conventional sequences using both coils. A thin bright layer on T(2)-w with enhancement on post-Gd T(1)-w defined our MR pattern for muscular layer involvement. MR results were correlated with surgical and pathological findings of the removed nodule. RESULTS: MR results for Group 1 (both coils) achieved a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 100-63%, 96-92%, 90-70%, 100-85%, and 97-83% for endovaginal coil and phased-array coil, respectively. Group 2 (phased-array coil) had a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 73%, 93%, 84%, 88%, and 87% for this coil, respectively. CONCLUSION: Combined pelvic-phased-array and endovaginal coils are better than phased array alone in the detection of intestinal wall invasion. Easy to perform, it has to be considered as a preoperative staging for deep posterior endometriosis to orientate the surgical management.

Roy C Balzan C Thoma V Sauer B Wattiez A Leroy J
Department of Radiology B, Universitary Hospital of Strasbourg – Civil Hospital, 1, place de l’hopital BP 426, 67091, Strasbourg Cedex, France, catherine.roy@chru-strasbourg.fr.

March 15, 2009

Challenges and opportunities in the encapsulation of liquid and semi-solid formulations into capsules for oral administration

Filed under: Pharmacology, Toxicology and Pharmaceutical Science — Tags: , — medical insurance @ 11:22 pm

The encapsulation of liquids and semi-solids provides solutions for convenient delivery through improved oral absorption of poorly water-soluble drugs. In addition, low dose (content uniformity), highly potent (containment), low melting point drugs, those with a critical stability profile and those for which a delayed release is required are candidates for liquid or semi-solid formulations. Both hard and soft capsules can be considered and in each case the capsule wall may comprise gelatin or some other suitable polymer such as hypromellose. The choice of a hard or soft capsule will depend primarily on the components of the formulation which provides the best absorption characteristics as well as on the physical characteristics, such as the viscosity of the formulation and the temperature at which the product needs to be filled. Numerous excipients are available for formulation of lipid-based systems and their compatibilities with hard gelatin capsules have been tested. The availability of new enhanced manufacturing equipment has brought new opportunities for liquid-filled hard capsules. Filling and sealing technologies for hard capsules, provides the formulator with the flexibility of developing formulations in-house from small scale, as required for Phase I studies, up to production.

Ewart T. ColeaEmail:etc.consulting@bluewin.ch Dominique CadébEmail:Dominique.cade@pfizer.com Hassan BenameurbEmail:Hassan.benameur@pfizer.com
[a]Capsugel Division of Pfizer, CH-4114 Hofstetten, Switzerland;[b]Capsugel Division of Pfizer, 10 Rue Timken, Colmar, France

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