Effect of Intrathecal Eugenol on Cerebral Vasospasm in an Experimental Subarachnoid Hemorrhage Model.

BACKGROUND: Eugenol has various curative properties. It affects the dilatation of cerebral arteries through voltage-dependent Ca2+ channel inhibition. This study is the first to explore the impact of eugenol on neuroprotection and vasospasm in an experimental subarachnoid hemorrhage (SAH) model. METHODS: Twenty-four adult male Sprague-Dawley rats were indiscriminately separated into 3 groups: the control group (n = 8), the SAH group (n = 8), and the eugenol group (n = 8). A double-bleeding method was used. The eugenol group received intracisternal eugenol (Sigma-Aldrich, St. Louis, MO, USA) at 30 µg/20 µl after induction of SAH. On the day 7, all groups were euthanized. Measurements were taken for basilar artery wall thickness, lumen diameter, serum endothelin-1 (ET-1), and caspase-3 levels. RESULTS: The eugenol group exhibited significantly lower wall thickness, ET-1, oxidative stress index, and caspase-3 levels compared to the SAH group. In comparison to the control group, the eugenol group showed a higher oxidative stress index along with higher ET-1 and caspase-3 levels, but these differences were not statistically significant. Wall thickness was significantly higher in the eugenol group than in the control group. CONCLUSIONS: This study represents the first literature exploration of intrathecal eugenol's impact on vasospasm induced after experimental SAH. Administration of intrathecal eugenol demonstrates a positive effect on the treatment of experimental vasospasm as well as on the reduction of oxidative stress and apoptosis.

The Biocompatibility of a New Type of 45S5 Bioactive Graft in a Sheep Model: A Pilot Study.

Background Bone is a dramatically regenerating tissue with the ability to heal after trauma, although intensive surgical management is required to treat considerable damage. In this study, 45S5 bioactive grafts were prepared through the melt-quenched method in compliance with the guidelines on medical product requirements (MDD regulations; 93/42/EEC Annex-II section 3&4 and ISO standardizations; ISO 13485:2016) for bone repair and regeneration. Methodology After preparing the graft/scaffold, it was evaluated for biocompatibility according to the principles of "lSO 10993-6 2015 Biological evaluation of medical devices: Tests for local effects after implantation, Annex D 'Test method for implantation in bone,'" "lSO 10993-2:2005 Biological evaluation of medical devices: Animal welfare requirements," and "lSO 10993-12 2012 Biological evaluation of medical devices sample preparation rules and standards." Defects were created on the tibia of the right hind leg. The defects were filled with 3-mm bioactive granules, and a cylindrical polypropylene biocompatible material was used as a negative control. After 120 days, the sheep were sacrificed, and the tibia were analyzed. Results The results demonstrated the safety of 45S5 bioactive grafts. Histological evaluation showed no signs of pathological changes around the implant area. Hematoxylin and eosin sections demonstrated the presence of a few multinucleated giant cells, macrophages, and non-irritant mild fibrotic changes on the surface of the biomaterial. Conclusions 45S5 bioactive glass was found to be biocompatible in a sheep model, demonstrating its capacity to promote bone consolidation while also justifying its further preclinical application as a bone-bonded material owing to the layer formation of the growing bone mineral.

The effect of pharmacological treatment in combination with vitamin K on healing in an experimental rat model of osteoporosis.

OBJECTIVES: This study aims to compare the effects of teriparatide, zoledronic acid, and their combination therapy with vitamin K on osteoporotic rats. MATERIALS AND METHODS: We divided a total of 50 female Sprague-Dawley rats into five groups: A (the control group), B and D (the teriparatide group), and C and E (the zoledronic acid group). Following ovariectomy and subcutaneous heparin administration at a dose of 2 IU/kg for four weeks, osteoporosis was created. Groups A, B, and C were fed with standard feed, while Groups D and E were fed with vitamin K-rich feed. After four weeks of treatment, sacrification was performed. The right and left femurs were separated for histopathological and biomechanical evaluation, respectively. For histopathological evaluation, the femurs were decalcified, and the sections were stained with hematoxylin-eosin and evaluated under a light microscope. Fracture healing was evaluated using the classification system as described previously. For biomechanical evaluation, the 3-point stress test and torsion stress test were applied to 10 femurs from each group. RESULTS: Groups B-E were histopathologically and biomechanically superior to Group A in fracture healing of osteoporotic rats; however, it was not statistically significant (p>0.05). The group that received additional vitamin K was histopathologically and biomechanically superior to the group which was fed with standard feed, although it was not statistically significant (p>0.05). CONCLUSION: Our study results indicated that both teriparatide and zoledronic acid had beneficial effects on osteoporotic fractures with comparable histological and biochemical results. Vitamin K promoted teriparatide and zoledronic acid treatment on osteoporotic fracture healing. Based on these findings, combination therapies may yield the most optimal results in biomechanical and histological examinations.

The preventive effect of omega-3 fish oil on peritoneal adhesion formation.

INTRODUCTION: Postoperative peritoneal adhesions formed after abdominal surgery still continue to exist as an unresolved health problem. AIM: The aim of the present study is to examine whether omega -3 fish oil has a preventive effect on postoperative peritoneal adhesions. METHODS: Twenty-one female Wistar-Albino rats were separated into 3 groups (sham, control, and experimental group), each consisting of 7 rats. In sham group, only laparotomy was performed. Both in control and experimental group rats; the right parietal peritoneum and cecum were traumatized to form petechiae. Following this procedure, unlike the control group, the abdomen was irrigated with omega-3 fish oil in the experimental group. Rats were re-explored on the 14th postoperative day and adhesions were scored. Tissue samples and blood samples were taken for histopathological and biochemical analysis. RESULTS: None of the omega-3 fish oil given rats developed macroscopically postoperative peritoneal adhesion (P=0.005). Omega-3 fish oil formed an anti-adhesive lipid barrier on injured tissue surfaces. Microscopic evaluation revealed diffuse inflammation with excessive connective tissue and fibroblastic activity in control group rats while foreign body reactions were common in omega-3 given rats. The mean amount of hydroxyproline in samples from injured tissues was significantly lower in omega-3 given rats than in control rats. (P=0.004). CONCLUSION: Intraperitoneal application of omega-3 fish oil prevents postoperative peritoneal adhesions by forming an anti-adhesive lipid barrier on injured tissue surfaces. However, further studies are needed to determine whether this adipose layer is permanent or will be resorbed over time.

Effect of protection of enoxaparin against experimental ischemia/reperfusion injury in the rat ovary on in vitro fertilization outcomes.

OBJECTIVE: The study aimed to investigate the protection of enoxaparin (E) against experimental ischemic (I) and ischemic-reperfusion (I/R) injury in rat ovaries on in vitro fertilization outcomes. METHODS: In total, 56 adult female Sprague-Dawley albino rats were randomly assigned to 6 groups of 8 animals each: Sham, Ischemia, I/R, Sham+E, I+E, and I/R+E. Ischemia groups were subjected to bilateral adnexal torsion for 3 h. In contrast, I/R and I/R+E groups received subsequent detorsion for 3 h. Enoxaparin (0.5 mg/kg s.c.) was administered 30 min prior to ischemia (I+platelet-rich plasma) or reperfusion (I/R+I+platelet-rich plasma). Ovaries were stimulated through intraperitoneal injection of 150-300 internal units IU/kg pregnant mare serum gonadotropin. Anti-Müllerian hormone levels were measured before and after surgery in all groups. RESULTS: When the number of metaphase II oocytes was evaluated, statistically significant differences were observed between the I and I+E (p=0.001) and I/R and I/R+E (p=0.000) groups. When both I and I+E groups and I/R and I/R+E groups were compared, it was found that E application increased the number of fertilized oocytes. The number of embryos on the second day was higher in the I/R+E group than that in the I/R group. Statistically significant differences were found in the number of grade 1 embryos between the I/R and I/R+E groups (p=0.003). In comparing anti-Müllerian hormone values within the group, the highest decrease was observed in the I and I/R groups. CONCLUSION: Enoxaparin effectively minimizes ovarian damage and preserves ovarian reserve following ovarian torsion.

The Effectiveness of Granulocyte Colony-Stimulating Factor (G-CSF) Against Experimental Ischemia-Reperfusion Injury in Rat Ovaries and Its Effect on In Vitro Fertilization Outcomes.

Local ischemic damage resulting from ovarian torsion is a common cause of decreased follicular activity and infertility. It was aimed to evaluate the effect of granulocyte colony-stimulating factor (G-CSF) protection on in vitro fertilization (IVF) results against experimental ischemic (I) and ischemic-reperfusion (I/R) injury in rat ovaries. The study consisted of 35 adult female Sprague-Dawley albino rats (sham, ischemia, I/R, I + G-CSF, and I/R + G-CSF) randomly assigned to 5 groups, each containing 7 rats. While bilateral adnexal torsion was applied to the ischemia groups for 3 h, detorsion was applied to the reperfusion groups. Intraperitoneal 100 IU/kg G-CSF was administered 30 min prior to ischemia (I + G-CSF) or reperfusion (I/R + G-CSF). After ovulation induction (intraperitoneal 150-300 IU/kg PMSG), the oocytes were collected and IVF was applied. Statistically significant differences were observed between the collected oocyte numbers in I and I + G-CSF, I/R, and I/R + G-CSF groups (P values were P = 0.001 for the I-I + G-SCF groups and P = 0.003 for I/R-IR + G-CSF, respectively). An increase in the number of MII oocytes obtained was observed in the I + G-CSF and I/R + G-CSF groups compared to the I and I/R groups. Grade 1 and grade 2 embryo numbers were statically different between the I/R and I/R + G-CSF groups (P values were P = 0.023 for grade 1 embryos and P = 0.045 for grade 2 embryos, respectively). G-CSF treatment was found to be effective in reducing I- and I/R-induced ovarian damage.

The preventive effect of omega-3 fish oil on the formation of peritoneal adhesions.

<br><b>Introduction:</b> Postoperative peritoneal adhesions that form after abdominal surgery still continue to exist as an unresolved health problem.</br> <br><b>Aim:</b> The aim of the study is to examine whether omega-3 fish oil has a preventive effect on postoperative peritoneal adhesions.</br> <br><b>Material and methods:</b> Twenty-one female Wistar albino rats were separated into 3 groups (sham, control and experimental), each consisting of 7 rats. In the sham group, only laparotomy was performed. In both the control and experimental group rats, the right parietal peritoneum and cecum were traumatised to form petechiae. Following this procedure, the abdomen was irrigated with omega-3 fish oil in the experimental group. The rats were re-explored on the 14^th postoperative day and any adhesions were scored. Tissue samples and blood samples were taken for histopathological and biochemical analysis.</br> <br><b>Results:</b> None of the rats that were administered omega-3 fish oil developed macroscopic postoperative peritoneal adhesions (P = 0.005). The omega-3 fish oil formed an anti-adhesive lipid barrier on the injured tissue surfaces. Microscopic evaluation revealed diffuse inflammation with excessive connective tissue and fibroblastic activity in the control group rats, while foreign body reactions were common in the omega-3 rats. The mean amount of hydroxyproline in samples from injured tissues was significantly lower in the omega-3 rats than in the control rats (P = 0.004).</br> <br><b>Conclusion:</b> Intraperitoneal application of omega-3 fish oil prevents postoperative peritoneal adhesions by forming an anti-adhesive lipid barrier on injured tissue surfaces. However, further studies are needed to determine whether this adipose layer is permanent or will be resorbed over time.</br>.

The protective effect of cilostazol on experimental ischemia/reperfusion injury in rats ovaries on in vitro fertilization outcomes.

Objective: Ovarian torsion decreases ovarian reserve because of ischemic and reperfusion damage it causes. In this study, we investigated the protective effect of cilostazol (CIL) on experimental ischemia (I) and ischemic-reperfusion (I/R) damage in rat ovaries with in vitro fertilization (IVF) results. Materials and Methods: Forty-eight adult female Sprague-Dawley albino rats were randomly assigned to 6 groups with 8 animals in each group: Sham (S), I, I/R, S + CIL, I + CIL and I/R + CIL. The I groups were subjected to bilateral adnexal torsion for 3 h, while the I/R and I/R + CIL groups received subsequent detorsion for 3 h. Twenty-two mg/kg of CIL was given via oral gavage 30 min before surgery on the I (I+ CIL) or reperfusion (I/R + CIL) groups. Oocytes were collected before the IVF procedure and after ovulation induction with 150-300 IU/kg pregnant mare serum gonadotropin. Results: The metaphase oocytes reached their highest value of 4.73±0.96 in the S+ CIL group and reached their lowest value of 0.51±0.55 in the I/R group. There were statistically significant differences in the number of second-day embryos among the I, I+ CIL, and I/R and I/R+ CIL groups (p=0.000). When the groups were compared in terms of Anti-Müllerian hormone change, the highest decrease was observed in the I and I/R groups. Conclusion: CIL pretreatment before surgery has a protective effect against I and I/R in rats with ovarian torsion.

The effect of protection of platelet-rich plasma against experimental ischemia/reperfusion injury in the rat ovary on in vitro fertilization outcomes.

OBJECTIVE: Ovarian torsion is a common cause of local ischemic damage, reduced follicular activity and infertility. This study aimed to investigate how well platelet-rich plasma (PRP) protects against experimental ischemic (I) and ischemia-reperfusion (I/R) injury in rat ovaries and its effect on in vitro fertilization (IVF) outcomes. METHOD: Fifty-six adult female Sprague-Dawley albino rats were randomly assigned to six groups of eight animals each: Sham, Ischemia, I/R, Sham + PRP, I + PRP, and I/R + PRP. The remaining eight animals were used to prepare the PRP. The ischemia groups were subjected to bilateral adnexal torsion for 3 h, while the I/R and I/R + PRP groups received subsequent detorsion for 3 h. Intraperitoneal (i.p.) PRP was administered 30 min prior to ischemia (I + PRP) or reperfusion (I/R + PRP). The ovaries were stimulated through an intraperitoneal injection of 150-300 internal units of IU/kg PMSG. After ovulation induction, oocytes were taken from the ovaries, and IVF was performed. RESULTS: The number of MII oocytes reached the highest number with 4.63 ± 0.74 in the S group and had the lowest number with 0.50 ± 0.53 in the I/R group. There were statistically significant differences for the number of embryos obtained on the second day between the I and I + PRP groups and the I/R and I/R + PRP groups (p = 0.000). In comparing anti-Müllerian hormone 1 (AMH1) and AMH2 values within the group, the highest decrease was observed in the I and I/R groups. CONCLUSION: PRP is effective in minimizing ovarian damage and preserving ovarian reserves following ovarian torsion.

The effect of Propofol versus Dexmedetomidine as anesthetic agents for oocyte pick-up on in vitro fertilization (IVF) outcomes.

This study aimed to evaluate the effects of propofol and dexmedetomidine over different timescales on the IVF outcomes for transvaginal oocyte retrieval (TVOR). Twenty-four rats included in the study were divided into two main groups and three subgroups were subjected to the ovulation induction process. Group 1 was administered propofol (100 mg/kg i.v.) and group 2 were administered dexmedetomidine (25 µg/kg i.p.) The oviduct collection procedure was completed within 15 min for subgroup Pro15min, Dex15min (n = 4), within 16 to 30 min for subgroup Pro30min, Dex30min (n = 4) and within 31 to 60 min for subgroup Pro60min, Dex60min (n = 4) after euthanasia. The total number of oocytes was counted. After in vitro fertilization, the number and quality of embryos were evaluated. The number of pups born were evaluated after embryo transfer. The embryo number, quality and pup count decreased as the administration time for propofol increased (p < 0.05). No statistically significant difference was found between the dexmedetomidine subgroups for embryo number, quality and pup count(p > 0.05). As the exposure time to propofol increased, the number and quality of embryos obtained, and the pup count, decreased. The use of dexmedetomidine had no negative impacts on the number of embryos, their quality or the number of pups.

Investigation of the effect of melatonin administration on inflammatory mediators; MMP-2, TGF-ß and VEGF levels in rats with sepsis.

AIMS: Sepsis causes life-threatening tissue and organ dysfunctions caused by endogenous mediators in response to infection. Melatonin is a powerful endogenous anti-inflammatory agent and effective in reducing cellular damage. This study aimed to evaluate the changes in serum and liver tissue levels of VEGF, TGF-ß and MMP-2 in melatonin-treated septic rats. MATERIALS AND METHODS: Twenty-one Wistar-albino male rats were included in this study. Rats were randomly divided into three groups. Group 1 is sham-operated control (C) group, Group 2 is caecal ligation and puncture (CLP) group and Group 3 is melatonin-treated (10 mg/kg) (M-CLP) group. Serum and tissue samples were analysed. All procedures were carried out according to the ethical rules specified in Helsinki Declaration. RESULTS: Sera MMP-2 levels were found higher than tissue MMP-2 levels in C and CLP (respectively, P = .048, P = .01). In CLP and M-CLP, serum TGF-ß levels were higher than tissue TGF-ß levels(respectively, P = .05, P = .01). Serum VEGF levels in CLP were found to be significantly higher than both C and M-CLP(P < .01). CONCLUSION: MMP-2 levels may have increased because of the prevention of oxidative damage in sepsis, and this may increase the anti-inflammatory effect. Melatonin treatment may have a therapeutic effect against sepsis since it prevents the increase in serum VEGF level. A powerful endogenous antioxidant, may be a promising therapeutic agent on the mortality and morbidity of the disease, because of its lowering effect on serum VEGF, which is a poor prognostic factor in sepsis.

The Short-Term Effect of Eugenol on the Prevention of Experimentally Induced Myringosclerosis in a Rat Model.

OBJECTIVE: The aim of our study was to assess the possible short-term effects of topical and oral eugenol on the suppression of experimentally developed myringosclerosis (MS). METHODS: Four groups of seven male Wistar albino rats were used in the study. The tympanic membranes (TMs) of all subjects were myringotomized, and group 1 was given no treatment (as control group), group 2 received saline, group 3 had received topical eugenol and group 4 received oral eugenol. RESULTS: In macroscopic evaluation the control and saline groups showed much more MS compared to the topical and oral eugenol groups which had statistically significantly less changes (p<0.05). Fibrosis and inflammation regarding the lamina propria (LP) of the eardrums of the topical and oral eugenol groups were significantly less than those of the control and saline groups (p<0.001). In microscopic evaluation, TMs were found to be thicker in the control and saline groups (p<0.001). CONCLUSION: Our study showed that the application of topical and oral forms of eugenol reduced fibrosis and prevented the advancement of MS in the LP of the TMs in the short-term. More studies with different extracts are needed to investigate the efficacy of phytotherapeutic agents for preventing MS development following myringotomy.

One-Step, Rapid, 18F-19F Isotopic Exchange Radiolabeling of Difluoro-dioxaborinins: Substituent Effect on Stability and In Vivo Applications.

The ß-diketone moiety is commonly present in many anticancer drugs, antibiotics, and natural products. We describe a general method for radiolabeling ß-diketone-bearing molecules with fluoride-18. Radiolabeling was carried out via 18F-19F isotopic exchange on nonradioactive difluoro-dioxaborinins, which were generated by minimally modifying the ß-diketone as a difluoroborate. Radiochemistry was one-step, rapid (<10 min), and high-yielding (>80%) and proceeded at room temperature to accommodate the half-life of F-18 (t1/2 = 110 min). High molar activities (7.4 Ci/µmol) were achieved with relatively low starting activities (16.4 mCi). It was found that substituents affected both the solvolytic stability and fluorescence properties of difluoro-dioxaborinins. An F-18 radiolabeled difluoro-dioxaborinin probe that was simultaneously fluorescent showed sufficient stability for in vivo positron emission tomography (PET)/fluorescence imaging in mice, rabbits, and patients. These findings will guide the design of probes with specific PET/fluorescence properties; the development of new PET/fluorescence dual-modality reporters; and accurate in vivo tracking of ß-diketone molecules.

Vitamin C is effective for the prevention and regression of endometriotic implants in an experimentally induced rat model of endometriosis.

OBJECTIVE: Endometriosis is a chronic inflammatory disease pathologically defined as the presence of endometrial-like tissue outside the uterine cavity. It is one of the most important diseases affecting women of reproductive age. The process of endometriotic implant growth is mediated by many complex interactions of immunologic, hormonal, genetic, and environmental mediators. Vitamin C (ascorbic acid), besides playing a role in preventing invasion and metastasis, is an antioxidant having anti-inflammatory and -angiogenic effects. In this study, we aimed to investigate the effect of vitamin C on the prevention and regression of endometriotic implants in a rat model of endometriosis. MATERIALS AND METHODS: This was a prospective, comparative, experimental animal study. After endometriotic implants were induced simultaneously, rats were divided into three groups. Group A was given 500 mg/kg of intravenous vitamin C every 2 days, starting immediately after implantation (n = 11). All rats had a second operation 21 days after the initial one and had the lesion volumes measured. Group B was given 500 mg/kg of intravenous vitamin C every 2 days, starting 21 days after this operation (n = 11). All rats were sacrificed 21 days after the third operation. Implant volume, weight measurements, and histopathological evaluation of the lesions were carried out. Group A received vitamin C throughout the study, while Group C (n = 11) was not given any medication. The findings in the three groups were compared. RESULTS: At the second laparotomy after the induction, Group A had the smallest implant volume with a statistically significant difference compared to Group B (p = 0.012). The end-of-study volumes of endometriotic implants of group B were significantly smaller than the first volumes (p < 0.05). CONCLUSION: Intravenous vitamin C treatment might have a suppressive effect on the prevention of endometriotic implant induction and regression of endometriotic implant volumes.