The importance of the cosolvent propylene glycol on the antimicrobial preservative efficacy of a pharmaceutical formulation by DOE-ruggedness testing.

The aim of this study was to statistically evaluate the influence of the concentration of the co-solvent propylene glycol on the preservative efficacy of a complex pharmaceutical suspension-emulsion formulation containing methyl- and propylparaben. Preservative Efficacy Tests (PETs) were performed using the validated pharmacopoeial methodology with five test organisms over 1 month on lab-scale test formulations. These were independently prepared according to a Box-Behnken experimental design with a triplicate central point at 0.22% m/m methylparaben, 0.22% m/m propylparaben, and 2.75% m/m propylene glycol, and with an additional corner point of the Box-Behnken cube. We evaluated the preservative efficacies against the criteria of the United States Pharmacopeia (USP) and European Pharmacopoeias (PhEur) for formulations for oral use, as well as by the statistical comparison of the slopes obtained by linear regression of log (CFU/g) vs. time. With an initial bacterial challenge of 10(6) CFU/g for each of the three bacterial strains, no survivals were detected after 7 days. For the two fungal strains, box plots and analysis of variance showed significant, concentration-dependent, main effects: the three variables significantly influenced the kill-rate of C. albicans, while A. niger was predominantly influenced by the cosolvent propylene glycol, and only to a minor extent by methylparaben and not at all by propylparaben. These findings were confirmed by taking the pharmacopoeial criteria as the evaluation basis, where the dominant influence of propylene glycol concentration is apparent. It was concluded that the cosolvent propylene glycol is at least of equal preservative importance than both parabens.

Effect of 5-hydroxytryptamine type-2 receptor blockade on pulmonary function in calves with experimentally induced Pasteurella haemolytica pneumonia.

OBJECTIVE: To evaluate a 5-hydroxytryptamine type-2 receptor antagonist, metrenperone (MET), in alleviating respiratory distress associated with experimentally induced Pasteurella haemolytica pneumonia in feedlot calves. DESIGN: Double-blind controlled clinical trial. ANIMALS: 30 healthy 6- to 8-month-old Hereford-type calves (250 to 450 kg). PROCEDURE: Initial measurements were made of rectal temperature (RT), arterial blood gas (ABG) tensions, and pulmonary mechanics. Calves were then infected with P haemolytica in logarithmic phase of growth by intratracheal inoculation. 18 hours later, determination of RT and ABG tensions, and pulmonary function testing were repeated and calves were selected for inclusion in the study on the basis of having 2 of the following: respiratory rate > 50 breaths/min, RT > 40 C, or PaO2 > 20 mm of Hg below the baseline value. MET (0.1 mg/kg of body weight, IM) or an equivalent vehicle dose was then administered. RT, ABG, and pulmonary mechanics measurements were repeated at 0.5, 1, 2, 3, 4, 6, 12, and 24 hours after treatment. Calves were then euthanatized, and gross necropsy scoring and histologic examination were performed on the lungs. RESULTS: Infection with P haemolytica caused significant increases in RT and respiratory rate, and reduction in PaO2, PaCO2, and tidal volume 18 hours after inoculation. MET-treated calves and significantly reduced rectal temperature between 1 and 12 hours, compared with vehicle-treated calves. In addition, MET-treated calves had reduced respiratory rate with concomitantly increased tidal volume between 0.5 and 2 hours after treatment, compared with vehicle-treated calves. Necropsy revealed acute lobar bronchopneumonia in all 30 calves, but there was no difference in necropsy score between treatment groups. CONCLUSIONS AND CLINICAL RELEVANCE: MET may have an antipyretic effect on calves with pneumonia caused by P haemolytica. Its influence on pulmonary mechanics was minimal however, and it did not induce lung lesions in the short term.

[Clazuril: a new anticoccidial agent for pigeons]. / Clazuril: een nieuw anti-coccidiosemiddel voor duiven.

The effectiveness of clazuril (Appertex), a new anticoccidial agent for the treatment of pigeons is described in the present study. Clazuril, a benzene-acetonitrile derivative, is administered in a single dose. In laboratory studies, 121 carrier pigeons infected with E. labbeana and E. columbarum were treated once with clazuril in gelatin capsules at dose levels of 10 mg, 5 mg, 2.5 mg, 1.25 mg, 0.63 mg or with a placebo. When a single dose of 2.5 mg and higher was administered, all faecal samples became negative for oocysts within seven days after treatment. In the field studies, 1531 young and full-grown carrier pigeons, from 116 infected dove-cotes, were treated with 1 tablet of 2.5 mg clazuril. Seven days after treatment, the faecal samples of 105 dove-cotes were negative for oocysts of E. Labbeana and E. columbarum; in six dove-cotes, infection was also virtually reduced to zero. Performance in racing was not affected by treatment and side-effects were not observed.

Potassium concentration in equine red blood cells: normal values and correlation with potassium levels in plasma.

The concentration of potassium in plasma and in red blood cells was determined in 948 horses. The coefficient of correlation between the two parameters was low. In 436 of these horses, which were clinically healthy, the red blood cell potassium (RBCK+) levels did not fit within a normal distribution curve, but a bimodal distribution was observed with a section point at 90 mmol/litre. In 90 per cent of these normal horses, mean RBCK+ content was 97.5 mmol/litre. In the remaining 10 per cent, mean RBCK+ concentration was 93.8 mmol/litre. A subdivision into a 'low potassium group' and a 'high potassium group' was made. In 10 out of 15 horses in the 'low potassium group', bimonthly sampling over a period of one year showed that RBCK+ content remained low. In the remaining five horses an increase was observed.

Staphylococcus hyicus in skin lesions of horses.

Staphylococcus hyicus (subspecies hyicus) was isolated as the only pathogenic organism from two independent cases of dermatitis of the lower parts of the limbs (grease heel) in horses. The organism was recovered together with other pathogenic staphylococci from similar conditions in two other horses of different origins. These conditions were characterised by epidermolysis, alopecia and crust formation. They responded quickly to antibiotic treatment. The organism was also isolated from a long standing case of "summer eczema" which healed without antibiotic treatment, and from a horse with dermatophilosis (streptotrichosis, Dermatophilus congolensis infection). Experimentally, Staph hyicus caused epidermolysis, exudation and inflammation in the superficial layers of the skin.

[Halothane-induced malignant hyperthermia (MH) in the Belgian Landrace breed of pigs: some findings concerning the role of subcellular fractions (author's transl)]. / Halothaan geïnduceerde maligne hyperthermie (MH) bij het Belgisch Landvarken: enkele gegevens in verband met de rol van subcellulaire fracties.

Both calcium ++-activated magnesium++ adenosine triphosphatase and the calcium++-accumulating activity of SR isolated from white skeletal muscle of pigs of the Yorkshire breed resistant to MH and pigs of the Belgian Landrace breed susceptible to MH continue to be stable throughout the process of growth. There was not any detectable difference between the two breeds and therefore it could not be concluded that there was a defective SR membrane. Abnormal contractions induced by halothane and caffeine in biopsy specimens of muscle of MH-susceptible pigs of the Belgian Landrace breed are mainly produced by external calcium++, CN--not having any inhibitory effect in these cases. The contractions induced by combined caffeine and halothane in susceptible animals are more marked than those occurring in resistant animals. These increased contractions are mainly due to external Ca++ and, to a less extent, to CN--sensitive mitochondrial Ca++ fluxes.