Clinical responses in cows vaccinated with a developed prototype killed Staphylococcus aureus mastitis vaccine.

Mastitis is an inflammatory condition of the udder that occurs as a result of the release of leucocytes into the udder in a response to bacterial invasion. The major causes of mastitis are an array of gram positive and negative bacteria, however, algae, virus, fungi, mechanical or thermal injury to the gland have also been identified as possible causes. Mastitis vaccines are yet to be developed using Malaysian local isolate of bacteria. The objective of the present experimental trial was to develop a monovalent vaccine against mastitis using S. aureus of Malaysian isolate and to evaluate the clinical responses such as temperature, respiratory rates and heart rates in vaccinated cows. S. aureus is a major causative bacteria in clinical and subclinical types of mastitis in cows. Four concentrations of the bacterin (106, 107, 108 and 109 cfu/ml of the local isolate of S. aureus) were prepared using Aluminium potassium sulfate adjuvant. Thirty cows were grouped into four treatment groups (B, C, D and E) with a fifth group as control (A). These groups were vaccinated intramuscularly(IM) with the prepared monovalent vaccine and its influence on the vital signs were intermittently measured. The mean of rectal temperature was significantly different (p˂ 0.05) at 0hr Post Vaccination [1]" in groups D and E (39.5 ±â€¯0.15 °C and 39.4 ±â€¯0.15 °C respectively) and at 3 h PV in groups C, D and E (39.8 ±â€¯0.14 °C, 39.9 ±â€¯0.14 °C and 40.3 ±â€¯0.14 °C respectively) compared to the control group. This indicated a sharp increased rectal temperatures between 0hr and 3 h PV in groups C, D and E which later declined at 24 h PV. The mean of rectal temperature of group E was significantly different (p˂ 0.05) at weeks 1 and 2 PV (39.87 ±â€¯0.19 °C and 39.80 ±â€¯0.18 °C respectively) compared to the control group. The mean of heart rate was significantly different (p˂ 0.05) at week 1 PV in groups D and E (83.0 ±â€¯3.8 beats/minute and 80.0 ±â€¯3.8 °C respectively) compared to control. A trending decrease was however observed in heart rates of group E from weeks through 4 PV and in group D from weeks 1 through 3 PV. The mean of respiratory rates was significantly different (p˂ 0.05) at week 3 PV in group B and D (31.0 ±â€¯1.2 breaths/minute and 28.0 ±â€¯1.2 breaths/minute) compared to control. In conclusion, this study highlights responses of these vital signs due to vaccination against S. aureus causing mastitis in cows. To the best of our knowledge the findings of this study adds value to the shallow literature on vital signs alterations in cows vaccinated against mastitis as elevated levels of temperature and heart rates of group D and E indicated obvious response.

Evaluation and selection of bio-relevant dissolution media for a poorly water-soluble new chemical entity.

The purpose of this work is to develop a bio-relevant dissolution method for formulation screening in order to select an enhanced bioavailable formulation for a poorly water-soluble drug. The methods used included a modified rotating disk apparatus for measuring intrinsic dissolution rate of the new chemical entity (NCE) and the USP dissolution method II for evaluating dissolution profiles of the drug in three different dosage forms. The in vitro dissolution results were compared with the in vivo bioavailability for selecting a bio-relevant medium. The results showed that the solubility of the NCE was proportional to the concentration of sodium lauryl sulfate (SLS) in the media. The apparent intrinsic dissolution rate of the NCE was linear to the rotational speed of the disk, which indicated that the dissolution of the drug is a diffusion-controlled mechanism. The apparent intrinsic dissolution rate was also linear to the surfactant concentration in the media, which was interpreted using the Noyes and Whitney Empirical Theory. Three formulations were studied in three different SLS media using the bulk drug as a reference. The dissolution results were compared with the corresponding bioavailability results in dogs. In the 1% SLS--sink conditions--the drug release from all the formulations was complete and the dissolution results were discriminative for the difference in particle size of the drug in the formulations. However, the data showed poor IVIV correlation. In the 0.5% SLS medium--non-sink conditions--the dissolution results showed the same rank order among the tested formulations as the bioavailability. The best IVIV correlation was obtained from the dissolution in 0.25% SLS medium, an over-saturated condition. The conclusions are: a surfactant medium increases the apparent intrinsic dissolution rate of the NCE linearly due to an increase in solubility. A low concentration of surfactant in the medium (0.25%) is more bio-relevant than higher concentrations of surfactant in the media for the poorly water-soluble drug. Creating sink conditions (based on bulk drug solubilities) by using a high concentration of a surfactant in the dissolution medium may not be a proper approach in developing a bio-relevant dissolution method for a poorly water-soluble drug.