Anti-cancer effects of alpha lipoic acid, cisplatin and paclitaxel combination in the OVCAR-3 ovarian adenocarcinoma cell line.

BACKGROUND: Ovarian cancer is the leading cause of gynecological cancer deaths. One of the major challenges in treating ovarian cancer with chemotherapy is managing the resistance developed by cancer cells to drugs, while also minimizing the side effects caused by these agents In the present study, we aimed to examine the effects of a combination of alpha lipoic acid (ALA), with cisplatin and paclitaxel in ovarian cancer(OVCAR-3). METHODS: The cytotoxic effects of ALA, cisplatin and paclitaxel on OVCAR-3 cells were determined. Four groups were formed: Control, ALA, Cisplatin + Paclitaxel, ALA + Cisplatin + Paclitaxel. The effects of single and combined therapy on cell migration, invasion and colony formation were analyzed. Changes in the expression of genes related to apoptosis, cell adhesion and cell cycle were analyzed with Real-time polymerase chain reaction(RT-PCR). The oxidative stress index and The Annexin V test were performed. RESULTS: The reduction in rapamycin-insensitive companion of mTOR(RICTOR) expression in the ALA + Cisplatin + Paclitaxel group was found statistically significant(p < 0.05). The decrease in MMP-9 and - 11 expressions the ALA + Cisplatin + Paclitaxel group was statistically significant(p < 0.05). The lowest values for mitogen-activated protein kinase(MAPK) proteins were found in the ALA + Cisplatin + Paclitaxel group. No colony formation was observed in the Cisplatin + Paclitaxel and ALA + Cisplatin + Paclitaxel groups. The lowest wound healing at 24 h was seen in the ALA + Cisplatin + Paclitaxel group. CONCLUSIONS: This study is the first one to investigate the combined treatment of ALA, Cisplatin, Paclitaxel on OVCAR-3. While ALA alone was not effective, combined therapy with ALA, has been found to reduce cell invasion, especially wound healing in the first 24 h, along with tumor cell adhesion.

In Vitro Effects of Boric Acid on Cell Cycle, Apoptosis, and miRNAs in Medullary Thyroid Cancer Cells.

Medullary thyroid cancer (MTC) is a highly aggressive and chemotherapy-resistant cancer originating from the thyroid's parafollicular C cells. Due to its resistance to conventional treatments, alternative therapies such as boric acid have been explored. Boric acid, a boron-based compound, has shown anticarcinogenic effects, positioning it as a potential treatment option for MTC. TT medullary thyroid carcinoma cell line (TT cells) and human thyroid fibroblast (HThF cells) were utilized for the cell culture experiments. Cell viability was assessed using the 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay. Total RNA was extracted using Trizol reagent for gene expression and microRNA (miRNA) analysis via reverse transcription-polymerase chain reaction (RT-PCR). The extent of apoptosis induced by boric acid was determined using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Colony formation assays were conducted to evaluate the impact of boric acid on the colony-forming ability of MTC cells. At 48 h, 50% inhibitory concentration (IC50) of boric acid was found to be 35 µM. Treatment with boric acid resulted in significant modulation of apoptosis-related genes and miRNAs, including increased expression of phorbol-12-myristate-13-acetate-induced protein 1(NOXA), apoptotic protease activating factor 1 (APAF-1), Bcl-2-associated X protein (Bax), caspase-3, and caspase-9. In contrast, the expression of B cell lymphoma 2 (Bcl2), B cell lymphoma- extra-large (Bcl-xl), and microRNA-21 (miR-21), which are linked to the aggressiveness of MTC, was significantly reduced. The TUNEL assay indicated a 14% apoptosis rate, and there was a 67.9% reduction in colony formation, as shown by the colony formation assay. Our study suggests that boric acid may have anticancer activity in MTC by modulating apoptotic pathways. These findings suggest that boric acid could be a potential therapeutic agent for MTC and possibly for other malignancies with similar pathogenic mechanisms.

Anti-inflammatory effects of sericin and swimming exercise in treating experimental Achilles tendinopathy in rat.

The aim of this study was to assess the effectiveness of combining sericin with swimming exercise as a treatment for type-I collagenase-induced Achilles tendinopathy (AT) in rats, with a focus on inflammatory cytokines. An experimental AT model was established using type-I collagenase in male Sprague-Dawley rats, categorized into five groups: Group 1 (Control + Saline), Group 2 (AT), Group 3 (AT + exercise), Group 4 (AT + sericin), and Group 5 (AT + sericin + exercise). Intratendinous sericin administration (0.8 g/kg/mL) took place from days 3 to 6, coupled with 30 min daily swimming exercise sessions (5 days/week, 4 weeks). Serum samples were analyzed using ELISA for tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), interleukin-10 (IL-10), and total antioxidant-oxidant status (TAS-TOS), alongside histopathological and immunohistochemical assessments of Achilles tendon samples. Elevated TNF-α and IL-1ß and decreased IL-10 levels were evident in Group 2; Of these, TNF-α and IL-1ß were effectively reduced and IL-10 increased across all treatment groups, particularly groups 4 and 5. Serum TAS was notably lower in Group 2 and significantly increased in Group 5 compared to Group 2. Histopathologically, Group 2 displayed severe degeneration, irregular fibers, and round cell nuclei, while Group 5 exhibited decreased degeneration and spindle-shaped fibers. The Bonar score increased in Group 2 and decreased in groups 4 and 5. Collagen type-I alpha-1 (Col1A1) expression was notably lower in Group 2 (P = 0.001) and significantly increased in groups 4 and 5 compared to Group 2 (P = 0.011 and 0.028, respectively). This study underscores the potential of sericin and swimming exercises in mitigating inflammation and oxidative stress linked to AT pathogenesis, presenting a promising combined therapeutic strategy.

Silk protein sericin: a promising therapy for Achilles tendinopathy-evidence from an experimental rat model.

OBJECTIVE: This study investigated the efficacy of sericin in treating experimental Achilles tendinopathy (AT) in rats via the transforming growth factor-beta (TGF-ß)/mothers against decapentaplegic (Smad) pathway compared with diclofenac sodium (DS). METHOD: An AT model was induced in rats using collagenase enzyme type I and divided into 5 groups: C (control), AT (diseased control), ATS (AT treated with sericin), ATN (AT treated with DS), and ATSN (AT treated with sericin and DS). Sericin injection was given on the 3rd and 6th days by intratendinous injection (0.8 g/kg/mL), and DS was administered for 14 days by oral gavage (1.1 mg/kg/day). Serum concentrations of total oxidant-antioxidant status (TOS-TAS), TGF-ß1, decorin, Smad2, and connective tissue growth factor (CTGF) were measured. Histopathologic and immunohistochemical (IHC) studies were conducted on Achilles tendon samples. RESULTS: The TOS, oxidative stress index (OSI), TGF-ß1, Smad2, CTGF, and decorin serum concentrations were significantly higher in AT than in C and significantly lower in ATS than in AT (P<0.05). Histopathological examination revealed that irregular fibers, degeneration, and round cell nuclei were significantly elevated in AT. Spindle-shaped fibers were similar to those in C, and degeneration was reduced in ATS. TGF-ß1 and Smad2/3 expression was increased, and collagen type I alpha-1 (Col1A1) expression was decreased in AT vs. C (P=0.001). In the ATS, TGF-ß1 and Smad2/3 expression decreased, and Col1A1 expression increased. The Bonar score significantly increased in the AT group (P =0.001) and significantly decreased in the ATS group (P =0.027). CONCLUSION: Sericin shows potential efficacy in reducing oxidative stress and modulating the TGF-ß/Smad pathway in experimental AT models in rats. It may be a promising therapeutic agent for AT, warranting further clinical studies for validation. Key Points • This study revealed that sericin mitigates AT-induced damage through the TGF-ß/Smad pathway in an AT rat model. • ELISA and IHC investigations corroborated the effectiveness of sericin via the pivotal TGF-ß/Smad pathway in tissue repair. • Evidence indicates that sericin enhances collagen synthesis,shapes tendon fiber structure, and diminishes histopathological degeneration. • Sericin's antioxidant properties were reaffirmed in its AT treatment application.

Relationship between embryo development and apoptotic gene expression of cumulus cells in poor responders and polycystic ovary syndrome.

RESEARCH QUESTION: Is there a relationship between embryo quality, pregnancy rates and apoptotic gene expression in cumulus cells of oocytes collected from patients with poor ovarian response and polycystic ovary syndrome? DESIGN: Fifty infertile couples who underwent assisted reproductive technology treatment were included in the study (Approval date 4 February 2020, number 03). The patients were divided into four group: control (n = 9; 90 oocytes), unexplained infertility (n = 8; 86 oocytes), polycystic ovary syndrome (PCOS) (n = 6; 137 oocytes) and poor ovarian response (POR) (n = 27; 124 oocytes). Cumulus cells were isolated individually from 437 oocytes obtained. Intracytoplasmic sperm injection was undertaken on 365 mature oocytes. The embryos were monitored. Caspase-3, Bax and Bcl-2 gene expressions of the cumulus cells were measured by real-time polymerase chain reaction. RESULTS: A significant and negative correlation was found between Bax and Bcl-2 expressions of the cumulus cells of poor-quality embryos. The increase in Caspase-3 gene expression in the POR group statistically decreases the pregnancy rates. Fertilization and good-quality embryo development of 365 oocytes whose cumulus cells were examined, however, were not associated with apoptotic gene expression. The Bax/Bcl-2 ratio was found to be significantly lower in cumulus cells of mature oocytes. CONCLUSIONS: Our results demonstrated no significant associations between fertilization, quality embryo development and apoptotic gene expression. Bax expression and the Bax/Bcl-2 ratio are high in immature oocyte cumulus cells has shown us that the apoptotic process may begin when the cumulus-oocyte connection exists.

Retrospective comparison of the semen preparation techniques for intrauterine insemination: Swim-up versus density gradient method.

OBJECTIVE: Our study aims to retrospectively examine the relationship between two different sperm preparation methods used in IUI among eight years in terms of pregnancy and live birth rates. METHODS: We evaluated the data of semen samples between December 2012 and March 2020. Three hundred eighty-four samples prepared with Conventional Swim-up (CSW) and 361 samples prepared with Density Gradient-Swim up (DGC-SW) obtained from men applying for IUI were analyzed. Spermiogram results of the semen samples given by men applying for IUI were examined. Data about sperm preparation method, post washed sperm parameters, pregnancy, and live birth rate were collected. Statistical analysis was performed. RESULTS: Basal progressive sperm count was significantly higher in pregnant couples in both CSW and DGC-SW groups (p = 0,032, p = 0,035, respectively). In each group, the post washed total progressive motile sperm count obtained by CSW and DGC-SW methods were significantly higher in pregnant patients (p < 0.05). There was no significant difference between CSW and DGC-SW methods in pregnancy achievement (p = 0,399, χ2 = 0,712). Live birth and miscarriage rates were not different between the groups (p = 0,243, χ2 = 2.827). CONCLUSION: In conclusion, there is no significant difference between CSW and DGC-SW for pregnancy and live birth rates. Our results suggest that both sperm preparation techniques used in IUI are not superior to each other. In other words, the choice of sperm preparation method does not affect the pregnancy rate in couples undergoing IUI.

Effects of low-density pulsed ultrasound treatment on transforming growth factor-beta, collagen level, histology, biomechanics, and function in repaired rat tendons.

OBJECTIVES: The aim of this study is to compare the effects of low-density pulsed ultrasound (LIPUS) treatment on growth factors/collagen production, histological, biomechanical, and function of rats with Achilles tendon injury. MATERIALS AND METHODS: A total of 44 Wistar Albino rats were used in the study between April 2017 and June 2018. The rats were randomized to two treatment groups. Group 1 (n=6) received LIPUS treatment (0.3 Watt/cm2; 1 MHz, 1:5 pulse mode) and Group 2 (n=6)received sham ultrasound (US) treatment following Achilles tendon surgery. Transforming growth factor-beta 1 (TGF-ß1) and collagen gene expression levels were evaluated using polymerase chain reaction. The histological evaluation was performed with the Bonar scoring system. The tensile strength was measured by biomechanical testing and the function was evaluated with the Achilles Functional Index (AFI). RESULTS: Although TGF-ß1 expression and tensile strength evaluation showed a tendency to improve in favor of the LIPUS group, no statistically significant difference was found (p=0.065 and p=0.053, respectively). The COL3 gene expression in the LIPUS group and the COL1 expression in the sham US group were significantly higher. Bonar scores and AFI scores showed a statistically significant improvement in the LIPUS group, compared to the sham US group. CONCLUSION: Our study results show that LIPUS yields positive effects on tendon histology and functional status in repaired Achilles tendon in rats.

Effects of different doses of melatonin on rat adipose derived mesenchymal stem cells.

OBJECTIVES: Stem cell treatment is based on Melatonin which is crucial for lots of pathological and physiological pathways. Our aim is determining the most appropriate dose of melatonin affecting the rat adipose tissue mesenchymal stem cells. METHODS: Stem cells were isolated from male rat adipose tissue. Differentiation and characterization experiments were performed. Cell viability analyses in stem cells were used the XTT [2,3-Bis-(2-methoxy-4-Nitro-5-Sulfophenyl)-2H-Tetrazolium-5-Carboxanilide] assay. After 24 h incubation, different concentrations (0.5, 1, 5, 10, 50 µM) of extract were treated to the stem cells for 24 h, 48 and 72 h considering time and dose dependent manner. Total antioxidant status (TAS) and the total oxidant status (TOS) in control cells and melatonin treated cells (5, 10 µM) were determined Rel Assay commercial kits. RESULTS: In 24 h, melatonin increased cell viability in all groups. When we evaluate the effect of melatonin in 48 h, the most proliferation increase was seen at 5, 10 µM doses. When the total oxidant activity melatonin was found to be significantly lower in 5 and 10 µM dose groups of melatonin. CONCLUSIONS: Melatonin increases the survivor of stem cells and the most effective dose is 5 and 10 µM. The reduction of the oxidative stress index as a result of treating melatonin to mesenchymal stem cells showed that melatonin is a powerful antioxidant for stem cells.

Boric acid as a promising agent in the treatment of ovarian cancer: Molecular mechanisms.

PURPOSE: The aim of this study is to determine the therapeutic effects of boric acid cell proliferation, invasion, migration, colony formation, cell cycle and apoptosis mechanisms in ovarian cancer cell line under in vitro conditions. METHODS: MDAH-2774 ovarian cancer cells were employed. Real-time PCR test was used to investigate changes in genes and proteins of cell cycle and apoptosis and identified miRNAs under the addition of boric acid. The apoptosis rates were calculated by TUNEL assay. Matrigel invasion, colony formation and Wound healing tests were used to determine invasion and migration. Oxidative stress index value was calculated for oxidative stress. RESULTS: Boric acid inhibited cell proliferation, invasion, migration and colony formation, but induces apoptosis and oxidative stress. Also, the expression of miRNA-21, miRNA-200a, miRNA-130a and mi-RNA-224 (which are indicators of poor prognosis of ovarian cancer) decreased significantly. CONCLUSION: The potential of boric acid as a natural molecule may supports its effectiveness in reducing adverse effects arising from conventional ovarian cancer treatments.

The effect of adipose-derived mesenchymal stem cell treatment on mTOR and p-mTOR expression in ovarian damage due to cyclophosphomide.

Our aim is to investigate the effect of the Mesenchymal stem cell (MSC) administration on the release of Mammalian Target of Rapamycin (mTOR) and Phosphorylated- mTOR(p-mTOR) in Cyclophosphomide (CTX) induced ovarian damage. Rats divided into three groups. The first group was categorized as the control(C group;n = 6), the second group as CTX-administered group (CTX group;n = 6), and the third group as CTX and MSC-administered group (CTX + SC group;n = 6). CTX was injected intraperitoneally at 50 mg/kg on the first day and at 8 mg/kg during the following 13 days. In Group 3, adipose-derived MSCs (5 × 104) were injected locally into the ovary. Both ovaries were removed at the end of the 8th week. The follicle count was made. The expression of mTOR and p-mTOR was analyzed immunohistochemically. The follicles in the ovary of Group C were observed in normal structures. Degeneration was evident in the CTX group. In the CTX + SC group, the degenerative appearance monitored in the CTX group vanished in most areas, and fibrosis was greatly reduced. The number of follicles in the CTX group was lower than that of both C and CTX + SC groups (p < 005). In the C group, mTOR showed strong positive staining while mTOR and p-mTOR expression was negative in all follicles in the CTX group. Both mTOR and p-mTOR revealed moderate positive expression in the CTX + SC group. MSC therapy rescued the damage ovarian function created by CTX, reducing follicle loss. MSCs were shown to inhibit the loss of mTOR and p-mTOR signaling, which is key to meiosis in oocytes.

Determination of the pathways of potential muscle damage and regeneration in response to acute and long-term swimming exercise in mice.

The objective of the current study was examining early and late (3, 24 h) responses to acute, chronic swimming exercise as muscle damage and regeneration in gastrocnemius-soleus muscle complexes. We also aimed to reveal the signaling pathways involved. 8-12 weeks old mice were grouped as control, exercise. Exercising groups were firstly divided into two as acute and chronic, later every group was again divided in terms of time (3, 24 h) passed from the last exercise session until exsanguination. Acute exercise groups swam 30 min, while chronic swimming groups exercised 30 min/day, 5 days/week, 6 weeks. Histological investigations were performed to determine muscle damage and regeneration. Whole-genome expression analysis was applied to total RNA samples. Microarray data was confirmed by quantitative real-time PCR. Exercising mice muscle revealed enhanced damage, leukocyte infiltration. Increments in acute and chronic 3 h groups were statistically significant. Car3, Neb, Obscn, Ttn, Igfbp5, Igfbp7, Gsk3ß, and Usp2 were down-regulated in muscles of swimming mice. The exercise-induced signaling pathways involved in muscle damage and regeneration were drawn. Our findings demonstrate that swimming induces muscle damage. Samples were obtained at 3 and 24 h following exercise, this time duration seems not sufficient for the development of myofibrillogenesis.

Do seasonal variations in ambient temperature, humidity and daylight duration affect semen parameters? A retrospective analysis over eight years.

We aimed to evaluate the possible effects of seasonal variation on semen parameters. We retrospectively analysed the data of 6,116 semen samples collected at a university hospital for eight years. The past ambient temperature, relative humidity and daylight duration records, and birth registry of the province were obtained to examine the relationship of seasonal changes in semen parameters with annual birth rates and environmental factors. The mean age was 33.03 ± 6.86 years. We found a significant difference between months for sperm concentration (p < .0001), total sperm count (p < .0001), progressively motile sperm count (p < .0001) and normal sperm morphology (p = .028). The sperm concentration and total count were significantly lower in July and August compared with December, May and June. The progressively motile sperm count in October was 23.6% less than the value of May. The temperature and temperature-humidity index were negatively correlated with semen parameters. The highest number of births was in the summer. However, no correlation was present between deliveries and the semen concentration regarding months (rs  = 0.199, p = .083). In conclusion, we observed significant seasonal and monthly differences in sperm concentration, sperm count and progressively motile sperm count. Increased ambient temperature due to seasonal changes may be a detrimental factor for semen parameters.

Adipose derived mesenchymal stem cell treatment in experimental asherman syndrome induced rats.

Asherman syndrome (AS) occurs due to fibrosis or uterine adhesions as a result of damage to the basal layer of the endometrium. The aim of this study is investigating the effects of adipose tissue-derived mesenchymal stem cell (ADMSC) application on the expression of vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF-1), miRNA-98, miRNA199a in endometrial tissue in rats with AS. Study groups were designed as, control (C), Asherman syndrome (AS), AS + oral estrogen (ASO), AS + ADMSC (ASSC), AS + oral estrogen + ADMSC (ASSCO) with 7 samples in each group. Characterization and differentiation experiments were performed in ADMSC obtained. Two weeks after the development of the AS, ADMSC therapy was applied. BrdU (5-bromo-2'-deoxyuridine) labeling was performed to show the presence of ADMSC in the tissues. Rats were sacrificed after 8 weeks and bilateral uterine horn resection was performed. Tissues were fixed in formaldehyde. After routine tissue follow-up, sections were taken and evaluated with hematoxylin eosin staining. VEGF1 and IGF1 expressions were evaluated by immunohistochemical staining and western blot analysis. Expression changes of miR-98 and miR-199a were detected by RT-PCR. Our results showed that stem cells and estrogen giving together reduced inflammation and fibrosis in the endometrium. Immunohistochemistry and western blot results suggested that this effect was achieved especially through IGF-1. In our study, decreased miR-98 and miR-199a expressions were determined in Asherman syndrome. Furthermore, no changes of miRNA expressions were observed in treatment groups.

Contribution of Heme Oxygenase 2 to Blood Pressure Regulation in Response to Swimming Exercise and Detraining in Spontaneously Hypertensive Rats.

BACKGROUND We aimed to determine the effects of exercise followed by detraining on systolic blood pressure (SBP), heme oxygenase 2 (HO-2) expression, and carboxyhemoglobin (COHb) concentration in spontaneously hypertensive rats (SHR) to explain the role of carbon monoxide (CO) in this process. MATERIAL AND METHODS Animals were randomized into exercised and detrained groups. Corresponding sedentary rats were grouped as Time 1-2. Swimming of 60 min/5 days/week for 10 weeks was applied. Detraining rats discontinued training for an additional 5 weeks. Gene and protein expressions were determined by real-time PCR and immunohistochemistry. RESULTS Aorta HO-2 histological scores (HSCORE) of hypertensive rats were lower, while SBP was higher. Swimming caused enhancement of HO-2 immunostaining in aorta endothelium and adventitia of SHR. Exercise induced elevation of blood COHb index in SHR. Synchronous BP lowering effect of exercise was observed. HO-2 mRNA expression, HSCORE, and blood COHb index were unaltered during detraining, while SBP was still low in SHR. CONCLUSIONS CO synthesized by HO-2 at least partly plays a role in SBP regulation in the SHR- and BP-lowering effect of exercise. Regular exercise with short-term pauses may be advised to both hypertensives and individuals who are at risk.

Chronic Exposure to Static Magnetic Fields from Magnetic Resonance Imaging Devices Deserves Screening for Osteoporosis and Vitamin D Levels: A Rat Model.

Technicians often receive chronic magnetic exposures from magnetic resonance imaging (MRI) devices, mainly due to static magnetic fields (SMFs). Here, we ascertain the biological effects of chronic exposure to SMFs from MRI devices on the bone quality using rats exposed to SMFs in MRI examining rooms. Eighteen Wistar albino male rats were randomly assigned to SMF exposure (A), sham (B), and control (C) groups. Group A rats were positioned within 50 centimeters of the bore of the magnet of 1.5 T MRI machine during the nighttime for 8 weeks. We collected blood samples for biochemical analysis, and bone tissue samples for electron microscopic and histological analysis. The mean vitamin D level in Group A was lower than in the other groups (p = 0.002). The mean cortical thickness, the mean trabecular wall thickness, and number of trabeculae per 1 mm2 were significantly lower in Group A (p = 0.003). TUNEL assay revealed that apoptosis of osteocytes were significantly greater in Group A than the other groups (p = 0.005). The effect of SMFs in chronic exposure is related to movement within the magnetic field that induces low-frequency fields within the tissues. These fields can exceed the exposure limits necessary to deteriorate bone microstructure and vitamin D metabolism.

[Investigation of the effect of ibuprofen on wound healing in experimental Staphylococcus aureus soft tissue infections]. / Deneysel Staphylococcus aureus yumusak doku enfeksiyonlarinda ibuprofenin yara iyilesmesi üzerindeki etkisinin arastirilmasi.

Soft tissue infections (STIs) occur as a result of the colonization of pathogenic bacteria upon the destruction of normal skin microbial flora and the skin integrity. Streptococci and staphylococci are the most frequent causes of bacterial STIs. Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen are often used in STIs because of their analgesic and antipyretic effects. However, evidence suggests that these drugs might delay both epithelization and angiogenesis in the early phases of wound healing because of an antiproliferative effect. The aim of this study was to investigate the effect of ibuprofen on the wound healing in STIs caused by Staphylococcus aureus in immunosuppressed mice. A total of 120 female Balb/c mice were used in the study and the mice were assigned to four test groups and two control groups. The test groups were defined as follows; B (Bacteria group, n= 23), BI (Bacteria + Ibuprofen group, n= 23), BA (Bacteria + Ampicillin group, n= 23), BIA (Bacteria + Ampicillin + Ibuprofen group, n= 21); and the control groups were defined as follows; S1B2 (only immunosuppressed controls, n= 15) and S2B2 (Sham group). Immunosupression was induced with cyclophosphamide and the experimental infection was generated by subcutaneous inoculation of bacterial suspension (2 x 10(8) cfu/ml) of methicillin-sensitive S.aureus ATCC 25923 to the right hind leg. Ibuprofen was given to the mice by gastric gavage (50 mg/kg/day), and ampicillin (100 mg/kg/day) by intramuscular injection. Wound sizes that appear in the animals were measured on a daily basis. Serum and tissue (epithelial tissue, connective tissue, sebaceous glands, sweat glands) samples were obtained on the first, third and seventh days. The tissue samples were examined histopathologically by hematoxylin-eosin (HE) staining method and IL-1, IL-6, TNF-α and VEGF (Vascular Endothelial Growth Factor) levels were determined in serum samples by ELISA method. The tissue cytokine reactions were also evaluated by immunohistochemical (immunoperoxidase staining) method in tissue samples. In our study, no significant change was detected in the wound sizes of B and BI groups from the second day to the end of study period (p> 0.05). On the other hand the wound dimensions of BA and BIA groups gradually decreased and remained superficial. The average serum levels of TNF-α and IL-1 was detected low in all groups. The mean value of serum IL-6 on the first day in group B was determined to be higher compared to other groups, and when this difference was compared to groups BI and BA, and the control group, it was found statistically significant (p< 0.05). In addition, the VEGF levels which were detected low in all groups in the third day of infection increased significantly at the seventh day. The results of histopathologic and immunohistochemical studies have supported the results of ELISA and yielded similar results with serum cytokine patterns. In conclusion, our data indicated that ibuprofen has no negative effect on the wound healing in soft-tissue infections caused by S.aureus.

Effects of menopause, diabetes mellitus and steroid use on type I mesh-induced tissue reaction in a rat model.

OBJECTIVE: To evaluate the effects of menopause, use of steroids, diabetes mellitus, and site of implantation on the tissue response to type I polypropylene mesh used in pelvic reconstructive surgery. STUDY DESIGN: Forty mature female albino rats were used in the study. Inflammatory reaction and mesh-tissue detachment strength were studied in 4 different animal models; control (GI), menopause (GII), steroid+menopause (GIII), and diabetes mellitus+menopause (GIV) groups. Two pieces of 1cm×1cm type I macro porous polypropylene monofilament mesh were fixed over rectus abdominis muscle on both sides of the midline, and 0.5cm×0.5cm in size was placed into paravaginal area. Nine weeks later, implanted sling materials in the vaginal region and the right abdominal side were harvested with surrounding tissue for histopathologic examination, whereas the left sided meshes were used for the mechanical testing of detachment strength. RESULTS: The mean detachment strengths in groups were, 595±274g for GI, 410±161g for GII, 610±202g for GIII, and 457±250g for GIV (p>0.008). Inflammatory process was more intense in menopause and DM+menopause groups for both abdominal and vaginal tissues (p<0.008). There was no difference between control and steroid+menopause groups, and DM+menopause and menopause groups (p>0.008). Comparison of tissue reaction caused by meshes in abdominal and vaginal area showed more intense granulocyte infiltration in abdominal region whereas more prominent inflammation and necrosis in the vaginal site (p<0.05). CONCLUSION: The abdominal and vaginal region show differences in tissue reaction to type I mesh, and menopause was the most determining factor on the intensity of mesh induced inflammatory response.

Effect of testosterone propionate on hippocampal pyramidal neuron number in female rats.

INTRODUCTION: The hippocampus is an important region of the brain that regulates cognitive and emotional functions. In this study, we examined the impact of perinatal administration of testosterone propionate (TP) on the number of pyramidal neurons in the CA1 and CA3 regions of the hippocampi of female rats. METHODS: Five groups of rats were used in this study. Three groups of female rats were administered TP in either both the prenatal and the postnatal periods (Group 1), only the prenatal period (Group 2) or only the postnatal period (Group 3). The other two groups of rats included control females (Group 4) and control males (Group 5). The rats were sacrificed on postnatal Day 120 and their brains were analysed for hippocampal pyramidal neuron number using stereological methods. RESULTS: Control male rats (Group 5; p = 0.043) and TP-treated female rats in Groups 1 (p = 0.012) and 2 (p = 0.037), but not Group 3 (p > 0.05), had a significantly higher number of pyramidal neurons than control female rats (Group 4). The rats in Group 1 had the highest number of pyramidal neurons among the female rats. CONCLUSION: Perinatal TP treatment has an augmenting effect on the number of pyramidal neurons in the hippocampi of female rats. We also found gender-based differences in the hippocampi of male and female rats, with a higher number of pyramidal neurons seen in male rats. Continuous TP administration during the prenatal and postnatal periods is more effective than administration only in the prenatal or postnatal period.