Saim Ozdamar

Prevention of paclitaxel and cisplatin induced ovarian damage in rats by a gonadotropin-releasing hormone agonist.

OBJECTIVE To evaluate the protective effect of GnRH agonist for the prevention of ovarian reserve during treatment with paclitaxel and cisplatin. DESIGN Experimental study. SETTINGS University-based research laboratory. ANIMAL(S) Seventy female Wistar-Albino rats. INTERVENTION(S) Each group consisted of 10 rats. Group 1 served as controls. Groups without GnRH agonist (groups 2, 3, and 4) were administered paclitaxel and cisplatin, respectively; the remaining groups (groups 5, 6, and 7) were given the same regimens with GnRH agonist. The GnRH agonist (leuprolide acetate; 2.5 microg/d subcutaneously for 5 weeks) was started four weeks before chemotherapy to achieve anovulation. Paclitaxel (7.5 mg/kg) and cisplatin (5 mg/kg) were administered intraperitoneally on the 28th day as a single dose. MAIN OUTCOME MEASURE(S) One week after the chemotherapy, the animals were euthanized and primordial, primary, secondary, and tertiary follicle counts were evaluated. RESULT(S) Primordial, primary, and tertiary follicle counts in group 5 (paclitaxel plus GnRH agonist) and tertiary follicles in groups 2 and 3 had not decreased, but there was a significant decrease in other treatment groups compared with controls (P < 0.05). Binary comparison between all groups demonstrated that the primordial follicle count in group 5 was comparable to those of the controls. CONCLUSION(S) Paclitaxel plus GnRH agonist treatment may be an appropriate option for patients deserving further fertility in the preservation of primordial follicles.

Effect of platelet-rich plasma on fibrocartilage, cartilage, and bone repair in temporomandibular joint.

PURPOSE The purpose of the present study was to explore the potential use of platelet-rich-plasma (PRP) in the treatment of temporomandibular joint osteoarthritis (TMJ-OA). MATERIALS AND METHODS Surgical defects were created bilaterally on the condylar fibrocartilage, hyaline cartilage, and bone to induce an osteoarthritic TMJ in rabbits. PRP was applied to the right joints of the rabbits (PRP group), and the left joints received physiologic saline (control group). After 4 weeks, the rabbits were sacrificed for histologic and scanning electron microscopy (SEM) examinations. The data were analyzed statistically. RESULTS The new bone regeneration was significantly greater in the PRP group (P < .011). Although the regeneration of the fibrocartilage and hyaline cartilage was greater in the PRP group, no statistically significant difference was found between the 2 groups. SEM showed better ultrastructural architecture of the collagen fibrils in the PRP group. CONCLUSIONS PRP might enhance the regeneration of bone in TMJ-OA.

In vitro effects of l-carnitine and glutamine on motility, acrosomal abnormality, and plasma membrane integrity of rabbit sperm during liquid-storage.

This study was designed to evaluate the in vitro effects of l-carnitine and glutamine (Gln) on the sperm quality parameters of liquid-stored rabbit semen maintained up to 24 h at 5°C. Pooled and extended ejaculates were divided into two equal portions. l-Carnitine doses of 0.5, 1 and 2mM were added to the first portion, and glutamine was added at the same doses to the second portion. All samples were cooled to 5°C and examined at 0, 6, 12 and 24 h of liquid storage. Supplementation of the semen extender with three different doses of l-carnitine provided significant increases in the percentage of motile sperm at 12 h (P<0.01), and 24h (P<0.001) and enabled significant protection of the sperm plasma membrane (P<0.01) at 12 and 24h of cool-storage, in comparison to the control samples. Only the 2mM dose of l-carnitine significantly (P<0.01) decreased the rate of acrosomal damage when compared to the control group. Furthermore, all doses of Gln caused a significant (P<0.01) decrease in acrosomal damage at 6h, and provided significant improvement (P<0.01) in sperm motility, acrosomal and plasma membrane integrities at 12 and 24h of liquid storage, when compared to the controls. In conclusion, the supplementation of liquid-stored rabbit semen with l-carnitine and Gln provided a protection for sperm against cool storage-induced functional and structural damages.

The effects of different sugars on motility, morphology and DNA damage during the liquid storage of rat epididymal sperm at 4 C

This study evaluated the protective effects of supplementation with three different sugars on the motility, morphology and DNA integrity of rat epididymal sperm chilled and stored at 4°C Epididymides were obtained from each donor. Rat epididymal sperm was diluted in Hams F10 plus raffinose, Hams F10 plus trehalose, Hams F10 plus fructose, and Hams F10 medium for control purposes. Thereafter, the extended sperm were chilled and stored in liquid form at 4°C. Sperm motility, morphological abnormalities and DNA damage were determined at 0 and 12h after chilling. No significant difference was observed in any of the parameters evaluated at 0h, before storage (P>0.05). After 12h of storage, all sugar additives led to statistically higher motility, normal sperm morphology and DNA integrity in comparison to the control group. Raffinose gave the best motility percentages (32.86±1.84%) after 12h of storage at 4°C, compared to the other groups (P<0.001). In conclusion, Raffinose, trehalose and fructose provided a better protection of sperm functional parameters against chilling injury, in comparison to the control group.

Ovarian morphology of rats after fallopian tube sterilization

This study was conducted to study poststerilization menstrual changes. For this purpose, 60 rats were divided into 2 groups. In the first group, rats underwent bilateral uterine horn ligation with Pomeroy method, and one ovary of each rat was excised and weighed. The other ligated ovary was left intact. In the second group, only unilateral oophorectomy was performed. Histopathological studies revealed the presence of primary, secondary, and tertiary follicles in the ovaries of all the rats at the beginning of the study. Such follicles were found in 20 of the 22 rats in the first group and 23 of the 26 rats in the second group at the end of the study. Poststerilization ovarian weight remained unchanged in both groups. There was no difference in terms of histologic examination between pre- and post-ligation. These findings suggest that tubal ligation in the rats performed using surgical method does not cause any alteration in the ovarian morphology.

Effects of Cinnamon (C. zeylanicum) Bark Oil Against Taxanes-Induced Damages in Sperm Quality, Testicular and Epididymal Oxidant/Antioxidant Balance, Testicular Apoptosis, and Sperm DNA Integrity

ABSTRACT The aim of this study was to investigate whether cinnamon bark oil (CBO) has protective effect on taxanes-induced adverse changes in sperm quality, testicular and epididymal oxidant/antioxidant balance, testicular apoptosis, and sperm DNA integrity. For this purpose, 88 adult male rats were equally divided into 8 groups: control, CBO, docetaxel (DTX), paclitaxel (PTX), DTX+PTX, DTX+CBO, PTX+CBO, and DTX+PTX+CBO. CBO was given by gavage daily for 10 weeks at the dose of 100 mg/kg. DTX and PTX were administered by intraperitoneal injection at the doses of 5 and 4 mg/kg/week, respectively, for 10 weeks. DTX+PTX and DTX+PTX+CBO groups were treated with DTX during first 5 weeks and PTX during next 5 weeks. DTX, PTX, and their mixed administrations caused significant decreases in absolute and relative weights of all reproductive organs, testosterone level, sperm motility, concentration, glutathione level, and catalase activity in testicular and epididymal tissues. They also significantly increased abnormal sperm rate, testicular and epididymal malondialdehyde level, apoptotic germ cell number, and sperm DNA fragmentation and significantly damaged the histological structure of testes. CBO consumption by DTX-, PTX-, and DTX+PTX-treated rats provided significant ameliorations in decreased relative weights of reproductive organs, decreased testosterone, decreased sperm quality, imbalanced oxidant/antioxidant system, increased apoptotic germ cell number, rate of sperm with fragmented DNA, and severity of testicular histopathological lesions induced by taxanes. In conclusion, taxanes cause impairments in sperm quality, testicular and epididymal oxidant/antioxidant balance, testicular histopathological structure, and sperm DNA integrity, and long-term CBO consumption protects male reproductive system of rats.

Comparison of Bovine Bone-Autogenic Bone Mixture Versus Platelet-Rich Fibrin for Maxillary Sinus Grafting: Histologic and Histomorphologic Study

&NA; Numerous grafting materials have been used to augment the maxillary sinus floor for long‐term stability and success for implant‐supported prosthesis. To enhance bone formation, adjunctive blood‐born growth factor sources have gained popularity during the recent years. The present study compared the use of platelet‐rich fibrin (PRF) and bovine‐autogenous bone mixture for maxillary sinus floor elevation. A split‐face model was used to apply 2 different filling materials for maxillary sinus floor elevation in 22 healthy adult sheep. In group 1, bovine and autogenous bone mixture; and in group 2, PRF was used. The animals were killed at 3, 6, and 9 months. Histologic and histomorphologic examinations revealed new bone formation in group 1 at the third and sixth months. In group 2, new bone formation was observed only at the sixth month, and residual PRF remnants were identified. At the ninth month, host bone and new bone could not be distinguished from each other in group 1, and bone formation was found to be proceeding in group 2. PRF remnants still existed at the ninth month. In conclusion, bovine bone and autogenous bone mixture is superior to PRF as a grafting material in sinus‐lifting procedures.

Protective effect of N-acetylcysteine against cisplatin ototoxicity in rats: a study with hearing tests and scanning electron microscopy

INTRODUCTION Ototoxicity is a health problem appearing after powerful treatments in serious health conditions. It is sometimes inevitable when treatment of the serious disease is required. Cisplatin is an antineoplastic agent which was investigated previously to reveal increased nitrogen and reactive oxygen radicals that damages hair cells, resulting in ototoxicity. N-acetylcysteine, previously shown to decrease ototoxicity caused by different agents, is known to be a powerful in vitro antioxidant. Probably N-acetylcysteine, in addition to its antioxidant effect, blocks a cascade where reactive oxygen species result in apoptosis in the cochlea. OBJECTIVES The possible preventive effect of N-acetylcysteine in cisplatin ototoxicity was studied with auditory brain stem responses, otoacoustic emissions, and histopathological investigation of the cochlea in a scanning electron microscopy. METHODS This study was conducted on 21 Wistar Albino rats in four groups. 1mL/kg/day three times in total intraperitoneal (i.p.) Saline (n=5), 500mg/kg/day i.p. three times in total N-acetylcysteine (n=5), i.p. 15mg/kg cisplatin alone (single dose) (n=5) and i.p. 15mg/kg cisplatin plus 500mg/kg/day N-acetylcysteine (n=6) were administered. The rats were anesthetized to study the hearing tests before and after the experiment. The rats were sacrificed to investigate the cochleas by scanning electron microscopy. RESULTS Auditory brain stem responses and otoacoustic emissions values were attenuated in the cisplatin group. The group that received N-acetylcysteine in addition to cisplatin had better auditory brain stem responses thresholds and otoacoustic emissions. The samples obtained from the cisplatin group showed surface irregularities, degeneration areas, and total or partial severe stereocilia losses. The changes were milder in the cisplatin+N-acetylcysteine group. CONCLUSION Cisplatin ototoxicity can be detected by auditory brain stem responses and otoacoustic emissions testing in rats. N-acetylcysteine may protect the cochlear cells from histopathological changes. We concluded that N-acetylcysteine given 4h after cisplatin injection has a potential otoprotective effect against cisplatin ototoxicity. which suggests it could be used in clinical trials.

Assessment of markers expressed in human hair follicles according to different skin regions

BACKGROUND Body region-dependent hair follicle (HF) characteristics are concerned with follicular size and distribution, and have been demonstrated to have characteristics for each region of the body. OBJECTIVES The aim of the present study was to investigate the expression patterns of the markers called cytokeratin 15 (K15), cytokeratin 6 (K6) and monoclonal antibody Ki-67, and also apoptosis in HFs, which can be observed in different parts of the human body. MATERIAL AND METHODS In this study, healthy human HFs were taken by biopsy from 5 various donor sites of the human body: the scalp, the leg, the abdomen, the back and waist. HF-containing skin specimens taken using cryosection were stained with hematoxylin & eosin (H&E) and K15, K6, Ki-67 and terminal deoxynucleotidyl transferase-mediated digoxigenin-dNTP nick end-labelling (TUNEL) immunofluorescence staining protocol was performed. RESULTS Different skin regions from the human body were examined histologically. While the HFs of scalp tissue showed anatomically obvious hair layers, some hair sections from other regions, like the leg, the abdomen, back and waist, were not as distinct as in the scalp region. According to our findings, K15 expression was highest in the scalp. In addition, the immunoreactivity (IR) intensity of K15 was significantly decreased in the HFs on the waist and abdominal regions, compared to the scalp and back regions (p < 0.001). However, the IR intensity of K6 in the scalp region was statistically significantly higher than the IR intensity of K6 in the abdomen region (p < 0.05). Moreover, we showed intraepithelial apoptosis and proliferation of keratinocytes in the bulge of HF. In the study, Ki-67-positive and TUNEL-positive cell numbers were not statistically significant (p > 0.05). CONCLUSIONS Our findings are important for further investigation of molecular aspects of the human hair follicle stem cells compartments in health and disease, which might be a promising model for comparative studies with different human diseases.

Progesterone decreases the extent of ovarian damagecaused by cisplatin in an experimental rat model

BACKGROUND Apart from the role of progesterone in reproductive physiology, the protective role of exogenously administered progesterone was observed in various injuries, such as neurologic defects and acute kidney injury. OBJECTIVES The aim of the present study was to investigate the effects of progesterone therapy on the immunoexpression of anti-Müllerian hormone (AMH) and the number of apoptotic cells in ovarian damage induced with cisplatin, a chemotherapeutic agent, in an experimental rat model. MATERIAL AND METHODS Forty rats were randomly divided into 4 groups; the control group (the saline group), the cisplatin-treated group (rats were injected with 5 mg/kg/week cisplatin intraperitoneally (i.p.)), the cisplatin + progesterone-treated group (the rats were pretreated with 8 mg/kg progesterone intramuscularly (i.m.) (8 mg/kg) before they were injected with 5 mg/kg/week cisplatin i.p.), and the progesteronetreated group (the rats were treated with 8 mg/kg progesterone i.m.). The ovaries were removed from the rats in all groups 5 days after the final injection of cisplatin. RESULTS Histopathologic examination and follicle counting were performed. The immunoreactivity intensity of AMH and apoptosis were compared. Histological analysis of the ovaries treated with cisplatin showed ovarian damage. Immunohistochemical analysis showed that the immunoreactivity intensity of AMH, a biomarker that discriminates the degree of ovarian damage, was lower in the cisplatin-treated groups than in other groups. Terminal deoxynucleotide transferase-mediated 20-deoxyuridine 50-triphosphate nick endlabeling (TUNEL) assays showed that the increase in the number of apoptotic cells was statistically significant in the cisplatin-treated group compared to the control group (p < 0.05). Progesterone administration with cisplatin resulted in decreases in TUNEL-positive cells. The decrease in the number of apoptotic cells was statistically significant in the cisplatin + progesterone-treated group compared to the control group (p < 0.001). CONCLUSIONS Our results showed that using progesterone as an adjuvant agent against ovarian damage in patients undergoing cancer chemotherapy with cisplatin is beneficial.