Thymus sipyleus Boiss. subsp. rosulans (Borbas) Jalas (TS) is a commonly used plant in the treatment of various complaints, including skin wounds in Turkish folk medicine. Despite the widespread traditional use of TS, there is not any scientific report confirming the effectiveness of this plant on the healing process. This research aimed to investigate the effects of different extracts obtained from TS on biological events during wound healing, on a cellular basis. In this context, proliferative activities of the extracts, as well as the effects on wound closure and hydroxyproline synthesis, were determined. In addition to wound healing properties, the antioxidant, antibacterial and anti-inflammatory activities of the extracts were evaluated. Decoction (D) and infusion (I) extracts contained the highest amount of phenolic content and showed the most potent activity against DPPH radical. All extracts exhibited complete protection against the damage induced by hydrogen peroxide (H2O2) by increasing cell viability compared to only H2O2-treated groups, both in co-treatment and pre-treatment protocols. None of the extracts exhibited cytotoxic activity, and most of the extracts from the TS stimulated fibroblast proliferation and migration. All TS extracts exert anti-inflammatory activity by suppressing the overproduction of tumor necrosis factor-alpha (TNF-α) and nitric oxide (NO). The most pronounced activity on hydroxyproline synthesis was observed in D extract. In summary, it was observed that TS extracts can promote the healing process by enhancing fibroblast migration, proliferation and collagen synthesis as well as suppressing pro-inflammatory cytokines. The obtained data in this work support the traditional use of TS as a valuable plant-based compound for the treatment of wounds.

In this study, amoxicillin (AMO)-loaded poly(vinyl alcohol)/sodium alginate (PVA/NaAlg) nanoparticles were prepared as a polymer-based controlled release system. The physicochemical properties of the obtained nanoparticles were investigated by XRD, DSC/TGA, particle size analyses and zeta potential measurements. The average particle sizes were in the range from 336.3 ± 25.66 to 558.3 ± 31.39 nm with negative zeta potential values from -41.86 ± 0.55 to -47.3 ± 2.76 mV. The influences of PVA/NaAlg ratio, span 80 concentration, exposure time to glutaraldehyde (GA) and the drug/polymer ratio on AMO release profiles were evaluated. In vitro drug release studies showed a controlled and pH dependent AMO release with an initial burst effect. XRD patterns and DSC thermograms of AMO-loaded nanoparticles revealed that the drug in the nanoparticles was in amorphous form, which was more stable than the crystalline form. The antibacterial activity of the optimal formulation was also investigated. The minimum inhibitory concentration (MIC) values of this formulation had the comparable antibacterial activity with that of pure AMO. These results indicate that the developed nanoparticles could be a promising candidate drug delivery system for AMO.

Cyclooxygenase (COX) inhibitors, already widely used for the treatment of pain and inflammation, are considered as promising compounds for the prevention and treatment of neoplasia. The aim of our study was to determine the direct antiproliferative effects of nonsteroidal anti-inflammatory drugs (NSAIDs), piroxicam and deracoxib, at a variety of concentrations as both single and combined treatments on canine mammary carcinoma cell line CMT-U27 and to understand the mechanisms of cell death. MTT assay was performed to determine cell viability, and flow cytometric analyses were performed to evaluate apoptosis and cell cycle alterations. Significant decrease in cell viability was observed at high concentrations of piroxicam and deracoxib in both single and combined treatments after 72 h incubation. Combined treatment produced a significantly greater inhibition than that caused by either agent alone. Also apoptotic cell number was increased by both drugs at the cytotoxic concentrations. However, concomitant treatment of cells with piroxicam and deracoxib resulted in significant induction of apoptosis at lower concentrations and accumulation of cells in the G0/G1 phase. Significant cytotoxic effects exhibited by the combination of piroxicam and deracoxib against canine mammary carcinoma cells in vitro suggest an attractive approach for the treatment of canine mammary carcinoma.

Cyclooxygenase (COX) inhibitors have been shown to exert anti-angiogenic and anti-tumor activities on many types of malignant tumors. These anticancer properties make it worthwhile to examine the possible benefit of combining COX inhibitors with other anti-cancer agents. In the present study, we evaluated the potential of deracoxib (DER) in potentiating antitumor activity of doxorubicin (DOX) in canine mammary carcinoma cells (CMT-U27). DER (50–250 µM) enhanced the antiproliferative activity of DOX by reducing the IC50 (approximately 3- to 3.5 fold). Interaction analysis of the data showed that combinations of DOX at 0.9 µM with DER (100–250 µM) produced synergism in the CMT-U27 cell line, with a ratio index ranging from 1.98 to 2.33. In additional studies identifying the mechanism of observed synergistic effect, we found that DER strongly potentiated DOX-caused G0/G1 arrest in cell cycle progression. Also, DER (100–250 µM) augmented apoptosis induction with approximately 1.35- and 1.37- fold increases in apoptotic response caused by DOX in the cells. DER enhanced the antiproliferative effect of DOX in conjunction with induction of apoptosis by modulation of Bcl-2 expression and changes in the cell cycle of the CMT-U27 cell line. Although the exact molecular mechanism of the alterations in the cell cycle and apoptosis observed with DER and DOX combinations require further investigations, the results suggest that the synergistic effect of DOX and DER combinations in CMT therapy may be achieved at relatively lower doses of DOX with lesser side effects. Therefore, combining DER with DOX may prove beneficial in the clinical treatment of canine mammary cancer.

Emboli of central nervous tissue were detected in the jugular venous blood of two of 15 sheep stunned with a conventional cartridge-operated captive bolt gun and in two of 15 sheep stunned with a pneumatically activated gun. No emboli were detected in arterial blood from these sheep or in venous blood from sheep stunned electrically. Emboli from an animal with BSE could transmit the disease to people.

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The present study evaluated the effects of doxorubicin (DOX) and deracoxib (DER), as single agents and in combination treatments, on antioxidant parameters in the canine mammary carcinoma cell line CMT-U27. The cells were exposed to DOX and DER for 24, 48 and 72 h. The viability and malondialdehyde (MDA), nitric oxide (NO), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and total glutathione (GSH) activities of CMT-U27 cells were determined. The half inhibition concentration (IC 50 ) of DOX was found to be ~0.9 μM in the 72-h period. IC 50 and 1/10 IC 50 concentrations of DOX were combined with all concentrations of DER (50-1000 µM) in the combination experiments. The results showed increased oxidative status associated with significant decreases of CAT and GSH levels in CMT-U27 cells exposed to 10-µM and higher concentrations of DOX compared to control cells. In contrast, there were no significant changes in the groups tested with any of the concentrations of DER (50-1000 µM). In combination treatments, DER attenuated DOX-induced oxidative damage by modulating the enzymatic and non-enzymatic components in CMT-U27 cells. We suggest that the combination of DOX and DER can be beneficial in the treatment of cancer cells by increasing cellular responses to oxidative stress. In conclusion, the use of COX inhibitor in conjunction with a chemotherapeutic agent may provide a basis for new concepts of cancer treatment through systematic modulation of the antioxidant defence systems in mammary cancers of animals.

This study was conducted to compare the pharmacokinetic profiles of conventional Liposomal amphotericin B showed markedly higher peak plasma concentrations (approximately ninefold greater) and higher area under the plasma concentration curve values (approximately 14-fold higher) compared to conventional formulation. It is concluded that AmBisome ® reached higher plasma concentration and lower distribution volume and had a longer half-life compared to Fungizone ® , and therefore, AmBisome ® is reported to be an appropriate and effective choice for the treatment of systemic mycotic infections in dogs.