Nihal Y. Gul

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.

The effects of topical tripeptide copper complex and helium-neon laser on wound healing in rabbits

The aim of this study was to compare the clinical and histopathological effects of tripeptide copper complex (TCC) and two different doses of laser application (helium-neon laser, 1 and 3 J cm(-2)) on wound healing with untreated control wounds. Experimental wounds were created on a total of 24 New Zealand white rabbits and topical TCC or laser was applied for 28 days. The wounds were observed daily, and planimetry was performed on days 7, 14, 21 and 28 to measure the unhealed wound area and percentage of total wound healing. Biopsies were taken weekly to evaluate the inflammatory response and the level of neovascularization. The median time for the first observable granulation tissue was shorter (P < 0.05) in the low and high dose laser groups than in the control group (3 and 2.66 vs. 4.5 days), but was not different between the TCC and control groups (4.16 vs. 4.5 days). Filling of the open wound to skin level with granulation tissue was faster (P < 0.05) in the TCC and high dose laser groups than in the control group (14 and 16 vs. 25 days), but was not different between the low dose laser and control groups (23 vs. 25 days). The average time for healing was shorter (P < 0.05) in the TCC and high dose laser groups (29.8 and 30.2 vs. 34.6 days), but was not different between the low dose laser and control groups (33.8 vs. 34.6 days). Histopathologically, wound healing was characterized by a decrease in the neutrophil counts and an increase in neovascularization. The TCC and high dose laser groups had greater neutrophil and vessel counts than in the control group, suggesting a more beneficial effect for wound healing.

Intracoronary Shunt Versus Bulldog Clamp in Off-Pump Bypass Surgery. Endothelial Trauma: Shunt Versus Clamp

BACKGROUND During off-pump coronary bypass grafting, local vascular control of the target vessel and a bloodless field are crucial. The aim of this study is to asses the histopathological outcomes of intracoronary shunts and bulldog clamping on the beating heart in a canine model. METHODS Twelve healthy adult mongrel dogs weighing between 15 to 25 kg were included in the study. Following left thoracotomy, proximal left anterior descending artery segment 1 cm to distal of diagonal branch was marked. Arteriotomy at this site was performed and a shunt was inserted for 10 min in the shunt group. The bulldog clamp was applied 3 cm distal to the mark for 10 min after heparinization in the bulldog group. Thirty days after the procedure, the specimens of left anterior descending artery from both regions were collected and were examined. Vascular damage, presence of intimal hyperplasia, and denudation were noted. RESULTS Only intimal denudation was found significantly higher in the shunt group (P < 0.05). In this group, only one case had grade 0 endothelial damage. In the bulldog group, all cases had endothelial damage of various grades. CONCLUSION The proven advantages of temporary intracoronary shunts are well-known, e.g., preserving the ventricular functions. Despite these advantages, our study revealed an ultimate bad result for an off-pump coronary by pass patient: intimal denudation. We conclude that further studies with a larger number of subjects are needed to decide whether routine shunt insertion into coronary arteries during off-pump coronary bypass surgery is appropriate or not.

Effect of the P2Y12 antagonist ticagrelor on neointimal hyperplasia in a rabbit carotid anastomosis model

OBJECTIVES In the present study, we aimed to deterimine the dose-related effects of ticagrelor, the first reversible inhibitor of the P2Y12 receptor, found in smooth muscle cells as well as platelets, during neointimal hyperplasia in a rabbit carotid anastomosis model. METHODS This study was an experimental, prospective, randomized controlled study including 20 New Zealand white female rabbits (6-months old; weighing 2300 ± 300 g). Under general anaesthesia, the rabbits underwent transection of the right carotid artery and subsequent anastomosis of both ends. The study animals were divided into the following 4 groups: T1 (ticagrelor 5 mg/kg, orally, daily), T2 (ticagrelor 10 mg/kg, orally, daily), T3 (ticagrelor 20 mg/kg, orally, daily) and control (no ticagrelor treatment). The single oral doses were administered in phosphate-buffered saline. The control group received sterile phosphate-buffered saline (2 ml/kg/day, orally) for 3 weeks postoperatively. At the end of the study, the animals were killed, and the anastomosed segment of the right carotid artery and part of the left carotid artery were excised from each animal. Antibodies against transforming growth factor-β were used in staining of arterial sections, which was followed by histomorphological and immunohistochemical studies. RESULTS The median intimal thickness (2.0 ± 0.14 µm left vs 73.4 ± 35.8 µm anastomosed right arteries; P <0.05), the median medial thickness (70.8 ± 5.6 µm left vs 92.3 ± 4.5 µm anastomosed right arteries; P <0.05) and the index ratio of intimal thickness to medial thickness (0.03 ± 0.00 left vs 0.8 ± 0.35 anastomosed control right arteries; P <0.05) increased significantly in the anastomosed right arteries compared with the left carotid arteries in the control group. In the treatment groups, the intimal thickness (73.4 ± 35.8 µm in control group vs T1 32.7 ± 19;1 µm, T2 1.9 ± 0.09 µm and T3 2.2 ± 0.5 µm; P = 0.047, P = 0.009 and P = 0.009, respectively), carotid artery intima/media ratio (0.8 ± 0.35 in control group vs T1 0.4 ± 0.2, T2 0.03 ± 0.01 and T3 0.03 ± 0.01 in ticagrelor groups; P = 0.028, P = 0.009 and P = 0.009, respectively) and medial thickness (92.3 ± 4.5 µm in control group vs T2 65.6 ± 7.1 and T3 66.1 ± 7.6 µm; P = 0.009 and P = 0.009, respectively) decreased significantly in the anastomosed right arteries. CONCLUSIONS This study indicates that effective doses (10 and 20 mg/kg, daily) of the antiplatelet agent ticagrelor in a rabbit model may be beneficial in prevention of intimal hyperplasia. Restenosis due to intimal hyperplasia has been high. Ticagrelor has also been linked to inhibition of smooth muscle cell proliferation and, hence, reduced intimal hyperplasia.

comparison of the arterial blood gas, arterial oxyhaemoglobin saturation and end-tidal carbon dioxide tension during sevoflurane or isoflurane anaesthesia in rabbits

The effects of sevoflurane or isoflurane on arterial blood gas, arterial oxyhaemoglobin saturation and end-tidal CO2 tension were monitored during induction and maintenance of anaesthesia in 10 premedicated New Zealand White (NZW) rabbits.For induction, the anaesthetic agents were delivered via a face-mask. After induction was completed, an endotracheal tube was introduced for maintenance of anaesthesia for a period of 90 minutes. Changes in heart rate, respiratory rate, arterial blood gas, arterial oxyhaemoglobin saturation, blood pH and end-tidal CO2 tension were recorded. Although sevoflurane and isoflurane produce similar cardiopulmonary effects in premedicated rabbits, sevoflurane provides a smoother and faster induction because of its lower blood/gas partition coefficient. Thus sevoflurane is probably a more suitable agent than isoflurane for mask induction and maintenance. Its lower blood solubility also makes sevoflurane more satisfactory than isoflurane for maintenance of anaesthesia because it allows the anaesthetist to change the depth of anaesthesia more rapidly.