Investigation of efficacy of two different chemotherapy protocols used in neoadjuvant chemotherapy in clinical stages II-IV canine malignant mammary tumours.

The first aim of this study is to demonstrate the clinical efficacy and reliability of two different neoadjuvant chemotherapy (NAC) protocols consisting of doxorubicin/cyclophosphamide (AC) and paclitaxel in dogs with clinical stages II-IV canine malignant mammary tumours (CMTs). Secondly, to determine the Luminal A, Luminal B, HER2-positive and triple-negative molecular subtypes and their value in predicting clinical response to NAC in biopsy samples, and thirdly, to reveal the changes in Ki-67, human epidermal growth factor receptor type 2 (HER2), oestrogen receptor (ER), and progesterone receptor (PgR) expression levels induced by NAC. Thirty dogs with clinical stages II-IV CMTs (T1-3N0-1M0) according to the modified TNM system were included in the study. Dogs in group-1 (n = 15) AC combination and dogs in group-2 (n = 15) were administered paclitaxel. Partial response (PR) was the most common clinical response in both treatment groups (66.66% and 86.66%, respectively). There was no difference between the groups regarding clinical response parameters (p = .001). The rate of treatment responders was higher than the rate of non-responders in both groups (p < .001). The adverse effects observed in both groups were mostly limited to grades 1 and 2 and all were easy to manage. The most frequently detected molecular subtype was Luminal A (59.25%). Complete response (CR) was achieved in 33.33% of dogs with triple-negative CMT in the AC group and 14.29% of the Luminal A subtype in the paclitaxel group. Alterations in Ki-67, HER2, ER, and PgR expressions after chemotherapy were not statistically significant (p > .05). As a result, we have shown that these neoadjuvant chemotherapy protocols are effective and safe alternative treatment options for CMTs.

Evaluation of serum anti-Müllerian hormone concentrations following treatment with vitamin D in Holstein Friesian heifers.

Anti-Müllerian hormone (AMH) levels in the blood of dairy cattle are associated with the count of antral follicles (AFC), ovarian function. Numerous studies, particularly in human medicine, have shown that vitamin D3 (Vit D3) has a positive effect on AMH levels. To our knowledge, the effects of Vit D3 on serum AMH levels in heifers have not been investigated. The goal of the current study was to evaluate the concentrations of serum AMH in dairy heifers following Vit D3 treatment. The study included 20 healthy non-pregnant Holstein Friesian heifers. These animals came to estrus at least once. All heifers received a single intramuscular dosage of 5 million IU Vit D3 (Cholecalciferol). Blood samples were collected from the coccygeal veins of all animals before and after Vit D3 injection (days 7, 14, and 28) for the measurement of AMH and 25(OH)D concentrations. In our analysis, we observed that after exogenous Vit D3 administration, circular 25(OH)D increased constantly (up to day 28 after Vit D3 injection) in all animals. On day 28, AMH concentrations saw a 10% increase in comparison with those measured the day before the Vit D3 injection. However, a comparison of AMH concentrations measured across days did not reveal statistically significant differences between Day 0, 7, 14, and 28 levels (p = .10). Furthermore, no statistical correlation was observed between the pairs (age-AMH) and (weight-AMH). Considering all times, no correlation was found between 25(OH)D and blood AMH levels. These findings demonstrated that exogenous Vit D3 did not affect serum AMH in Holstein Friesian heifers.

First isolation and molecular characterization of pseudorabies virus detected in Turkey.

BACKGROUND: Pigs are the main host species for the pseudorabies virus. It causes fatal encephalitis in many species, including humans. This article aims to report the first clinical case of pseudorabies as well as isolation and molecular characterization of the virus from a hunting dog in Bursa province, Turkey. METHODS AND RESULTS: The dog shows clinical signs including pruritus and neurological signs such as stumbling and inability to stand up compatible with pseudorabies. The virus isolates were obtained from the supernatant of fresh tissue samples from the cerebellum, cornu ammonis, spleen, salivary gland, conjunctival swab, serum, and PBMC samples. The glycoprotein C region is targeted for viral DNA amplification. Pseudorabies virus genome detected both in fresh tissues and supernatants of third passage on Vero cells. The number of PCR positive samples was dramatically increased after cell culture inoculations. Genome sequencing of strain Bursa-10303, which was isolated from a non-endemic area, identified it to belong to clade A. CONCLUSIONS: This study confirms the possible presence of pseudorabies infection in the wildlife reservoirs in Turkey. Future studies may clarify the importance of the infection in Turkey region, where there is no prevalent pig production.

Chlorogenic Acid Enhances Abdominal Skin Flap Survival Based on Epigastric Artery in Nondiabetic and Diabetic Rats.

Previous studies showed that chlorogenic acid (CGA) accelerates wound healing via its antioxidant activity. We aimed to investigate the effect of CGA in an experimental epigastric abdominal skin flap model in nondiabetic and diabetic rats. Rats were firstly divided into 2 groups: nondiabetic and diabetic. Diabetes was induced by streptozotocin. Then, 4 subgroups were created for each group: vehicle as well as 0.2 mg/0.5 mL, 1 mg/0.5 mL, and 5 mg/0.5 mL CGA treatments. Right epigastric artery-based abdominal skin flaps were elevated and sutured back into their original position. Chlorogenic acid or vehicle was injected once into the femoral arteries by leaving the epigastric artery as the single artery feeding the flaps during the injection. On postoperative day 7, flap survivals were evaluated, and the rats were killed. Distal flap tissues were collected for histopathological and biochemical assays. Chlorogenic acid showed greater flap survival in both nondiabetic and diabetic rats. Capillary density was increased, and necrosis was reduced in the CGA-treated rats. Chlorogenic acid decreased malondialdehyde levels as well as increased reduced glutathione and superoxide dismutase levels in the flap tissues. This study showed that CGA significantly improved flap survival by its antioxidant activities with intra-arterial local injections.

In vivo systemic chlorogenic acid therapy under diabetic conditions: Wound healing effects and cytotoxicity/genotoxicity profile.

Oxidative stress occurs following the impairment of pro-oxidant/antioxidant balance in chronic wounds and leads to harmful delays in healing progress. A fine balance between oxidative stress and endogenous antioxidant defense system may be beneficial for wound healing under redox control. This study tested the hypothesis that oxidative stress in wound area can be controlled with systemic antioxidant therapy and therefore wound healing can be accelerated. We used chlorogenic acid (CGA), a dietary antioxidant, in experimental diabetic wounds that are characterized by delayed healing. Additionally, we aimed to understand possible side effects of CGA on pivotal organs and bone marrow during therapy. Wounds were created on backs of streptozotocin-induced diabetic rats. CGA (50 mg/kg/day) was injected intraperitoneally. Animals were sacrificed on different days. Biochemical and histopathological examinations were performed. Side effects of chronic antioxidant treatment were tested. CGA accelerated wound healing, enhanced hydroxyproline content, decreased malondialdehyde/nitric oxide levels, elevated reduced-glutathione, and did not affect superoxide dismutase/catalase levels in wound bed. While CGA induced side effects such as cyto/genotoxicity, 15 days of treatment attenuated blood glucose levels. CGA decreased lipid peroxidation levels of main organs. This study provides a better understanding for antioxidant intake on diabetic wound repair and possible pro-oxidative effects.

Pharmacologic overview of systemic chlorogenic acid therapy on experimental wound healing.

Chlorogenic acid (CGA) is a well-known natural antioxidant in human diet. To understand the effects of CGA on wound healing by enhancing antioxidant defense in the body, the present study sought to investigate the potential role of systemic CGA therapy on wound healing and oxidative stress markers of the skin. We also aimed to understand whether chronic CGA treatment has side effects on pivotal organs or rat bone marrow during therapy. Full-thickness experimental wounds were created on the backs of rats. CGA (25, 50, 100, 200 mg/kg) or vehicle was administered intraperitoneally for 15 days. All rats were sacrificed on the 16th day. Biochemical, histopathological, and immunohistochemical examinations were performed. Possible side effects were also investigated. The results suggested that CGA accelerated wound healing in a dose-dependent manner. CGA enhanced hydroxyproline content, decreased malondialdehyde and nitric oxide levels. and elevated reduced glutathione, superoxide dismutase, and catalase levels in wound tissues. Epithelialization, angiogenesis, fibroblast proliferation, and collagen formation increased by CGA while polymorph nuclear leukocytes infiltration decreased. CGA modulated matrix metalloproteinase-9 and tissue inhibitor-2 expression in biopsies. Otherwise, high dose of CGA increased lipid peroxidation of liver and kidney without affecting the heart and muscle samples. Chronic CGA increased micronuclei formation and induced cytotoxicity in the bone marrow. In conclusion, systemic CGA has beneficial effects in improving wound repair. Antioxidant, free radical scavenger, angiogenesis, and anti-inflammatory effects of CGA may ameliorate wound healing. High dose of CGA may induce side effects. In light of these observations, CGA supplementation or dietary CGA may have benefit on wound healing.

Effects of systemic chlorogenic acid on random-pattern dorsal skin flap survival in diabetic rats.

There has been considerable interest in understanding the effects of antioxidants in flap survival during diabetes. Previous studies showed that chlorogenic acid (CGA) exhibits potent antioxidant effects. We aimed to determine the effects of systemic CGA treatment on skin flap survival in an experimental random-pattern dorsal skin flap model in diabetic rats. Twenty-eight male Wistar rats were divided into four groups: phosphate buffered saline (PBS)-treated or CGA-treated nondiabetic rats, PBS-treated or CGA-treated diabetic rats. Diabetes was induced by streptozotocin (45 mg/kg). Caudally based bipedicled dorsal skin flaps were elevated. CGA (100 mg/kg) or PBS (mL/kg; as vehicle) was administered intraperitoneally once daily. On postoperative day 7, flap survival, regional blood perfusion and microangiography were evaluated. The malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and nitric oxide (NO) levels were evaluated from the flap tissue. Capillary density and vascular endothelial growth factor (VEGF) expression were assessed. Harmful effects of diabetes on flap survival were observed. CGA attenuated these effects and allowed greater survival and blood perfusion. CGA decreased MDA and NO levels and increased GSH and SOD levels. CGA elevated capillary density and VEGF expression. This study showed that peripherally administered CGA significantly improved flap survival in diabetic and nondiabetic rats.

Antihyperalgesic activity of chlorogenic acid in experimental neuropathic pain.

Chlorogenic acid (CGA) is a natural organic phenolic compound that is found in many plants, fruits and vegetables. CGA has beneficial bioactivities and strong therapeutic effects in inflammatory processes. CGA-rich fractions have analgesic activity but CGA has not been tested previously in neuropathic pain, which results from tissue damage, inflammation or injury of the nervous system. Chronic constrictive nerve injury (CCI) is a peripheral neuropathic pain model which initiates an inflammatory cascade. We aimed to determine possible antihyperalgesic effects of CGA in neuropathic pain. Our study showed for the first time that CGA [50, 100 and 200 mg/kg; intraperitoneally (i.p.)] produced significant dose- and time-dependent antihyperalgesic activity in CCI-induced neuropathic pain. In addition, chronic administration of CGA (100 mg/kg/day; i.p. for 14 days) prevented the development of mechanical hyperalgesia and attenuated CCI-induced histopathological changes. On the other hand, CGA (200 mg/kg) did not affect falling latencies of rats in the rota rod test. Hence, CGA might represent a novel potential therapeutic option for the management of neuropathic pain.

HER-2/neu (c-erbB-2) oncoprotein in hyperplastic endometrial polyps detected in two cats.

The presence of HER-2/neu (c-erbB-2) oncoprotein, oestrogen-alpha receptor (ER), and progesterone receptor (PR) in hyperplastic endometrial polyps (EPs) of two cats with cystic endometrial hyperplasia-pyometra (CEH-P) complex was investigated. Immunohistochemistry assay for ER, PR and c-erbB-2 oncoprotein in the glandular and stromal tissue of the EPs was performed. ER and c-erbB-2 immunoreactivity was observed in the glandular epithelium of the EPs whereas PR immunoreactivity was detected only in the stromal fibroblasts. The c-erbB-2 oncoprotein may play a role with the ER in the pathogenesis of the hyperplastic EPs, although the role of this oncoprotein in the pathogenesis of EPs has yet to be determined.