Evaluation of therapeutic use of a combination of pentoxifylline and vitamin E in radiation-induced renal fibrosis.

Radiation-induced renal fibrosis (RIRF) is a progressive, irreversible condition causing chronic kidney disease. Pentoxifylline (PTX) and vitamin E may mitigate radiation-induced damage and fibrosis. This study assesses their effectiveness. We used four groups, each with six rats: radiation therapy alone (RT-only), radiation therapy plus drug treatment (RT + drug), drug treatment alone (drug-only), and a control group. Rats were monitored for three months, with weight measurements every four weeks. Afterward, rats were analyzed biochemically and histologically, with blood and tissue samples taken for statistical comparison. No significant differences in serum creatinine levels and body weight were observed. RT-only group had more severe kidney tubule effects. Histomorphological, immunohistochemical, and TUNEL analyses showed significant RIRF mitigation in the RT + drug group. Our study highlighted molecular pathways (SMAD, TGF-beta, VEGF) and histological markers (collagens, a-SMA, fibronectin, metalloproteinases) associated with RIRF. PTX and vitamin E reduced ionizing radiation's impact on renal cells and mitigated radiation-induced kidney fibrosis. Further human studies are needed to confirm these findings.

A rat study on the PTEN expression in ovarian tissue in PCOS and folliculogenesis.

The objective of this investigation was to examine alterations in PTEN expression within ovarian tissue in a rat model of polycystic ovary syndrome (PCOS). The analysis also encompassed the examination of PTEN alterations in the ovarian tissue throughout the process of folliculogenesis in rats with normal ovulatory cycles. The study involved 12 adult female Sprague‒Dawley rats randomly assigned to the letrozole-induced polycystic ovary syndrome (PCOS) group as part of an animal-based research endeavour. The sections derived from the ovaries were subjected to immunohistochemical staining for PTEN. The evaluation of PTEN staining levels in ovarian tissues was conducted using electron microscopy. Follicle counts, as well as hormonal and biochemical analyses (serum luteinising hormone (LH), follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), testosterone, oestradiol levels and serum glucose, triglyceride, HDL and LDL-cholesterol levels), were conducted to provide evidence of the manifestation of polycystic ovary syndrome (PCOS) in rats. The number of primordial and Graafian follicles in the PCOS group decreased significantly, and the number of primary, secondary and antral follicles increased significantly. PTEN expression was found to be significantly higher in the PCOS group than in the control group in the primordial follicle oocyte cytoplasm, primordial follicle granulosa cells, primary follicle oocyte cytoplasm, primary follicle granulosa cells, antral follicle oocyte cytoplasm, antral follicle granulosa cells, and corpus luteum (p = 0.007, p = 0.001, p = 0.001, p = 0.001, p = 0.001, p = 0.002, and p = 0.018, respectively). In the non-PCOS group, a time-dependent comparison of the amount of oocyte cytoplasm and PTEN staining in granulosa cells of the oocytes at different stages of development was performed. While the follicles were developing from the primordial follicle to the primary and antral follicle, the amount of PTEN staining in the oocyte cytoplasm decreased, whereas the PTEN activity in the granulosa cells increased as the oocyte developed (p = 0.001 and p = 0.001, respectively). The current investigation demonstrated changes in PTEN expression in ovarian tissue throughout the course of normal folliculogenesis, as well as in instances of disrupted folliculogenesis, with a focus on rats with PCOS.

Effects of recurrent ketamine exposure on brain histopathology in juvenile rats.

BACKGROUND: Ketamine (KET) is a commonly used anesthetic agent. However, several previous studies reported that KET leads to neuronal damage in neurodevelopmental stages and has neuroprotective effects. The present experimental study aimed to determine the undesirable histopathological effects of KET in the cerebral cortex, striatum, and hippocampus after recurrent KET administration in juvenile rats. METHODS: After ethical approval was obtained, 32 juvenile male Wistar Albino rats were randomized into four groups: 1 mg/kg serum saline intraperitoneally (i.p.), 5 mg/kg KET i.p., 20 mg/kg KET i.p., and 50 mg/kg KET i.p. KET was administered for three consecutive days at three-h intervals in three doses. Ten days after the last KET dose, the rats were sacrificed. Cerebral hemispheres were fixed. Hematoxylin and eosin stain was used for morphometric analysis. Hippocampi were evaluated by immunohistochemistry with anticleaved caspase-3 antibodies. Statistical analysis was conducted with SPSS 21 software using the ANOVA test and Bonferroni post hoc analysis method. RESULTS: The experimental study findings revealed no difference between the groups' cell counts or sizes in cortical morphometry. No degenerative changes were observed in pyramidal and granular cells in the striatum. Mild gliosis was observed in the 20 mg/kg and 50 mg/kg KET administration groups. Immuno-histo-chemical analysis was conducted to determine apoptosis in the CA1 region of the hippocampus and revealed that caspase-3 positivity increased with the KET dose. However, there was no statistical difference between the groups. While it was lower than the control group in the 5 mg/kg KET group, it was similar to the control group in the 20 mg/kg KET group and higher in the 50 mg/kg KET group (p > 0.05). DISCUSSION: : Repetitive KET exposure did not significantly affect juvenile cerebral morphology and apoptosis in hippocampal cells.

Immunohistochemical analysis with apoptosis and autophagy markers in periodontitis and peri-implantitis: Clinical comparative study.

BACKGROUND AND OBJECTIVES: Recently, the terms autophagy and apoptosis have been studied on implants, especially in cell culture and in vitro studies, but in vivo evaluations are limited. The aim of this study was to compare the differences in apoptosis and autophagy intensity at the molecular and cellular level in periodontal and peri-implant diseases. METHODS: Sixty-four biopsy samples were obtained from 52 patients, 36 female and 16 male, whose mean age was between 18 and 75, and were included in the study. The periodontitis group was defined as PG (n:30 sample) and the peri-implantitis group as IG (n:34 samples). Granulation tissues as biopsy materials were collected, and immunohistochemical analysis was performed with hematoxylin-eosin, Masson's trichrome, anti-MAP1LC3A, anti-beclin, and anti-active caspase-3 antibodies and terminal TdT-mediated dUTP-biotin nick end labeling (TUNEL) methods. The histological slide images were evaluated with the ImageJ software program. Inflammatory cell density in epithelial tissue, inflammatory cell density in connective tissue, the density of necrotic tissue debris, and collagen density in connective tissue were scored between 0 and 3 (0: none, 1: minimal, 2: moderate, 3: severe by hematoxylin-eosin and Masson's trichrome). The antibody binding reaction areas were evaluated per unit area (mm2 ) in connective tissue by immunohistochemical examination. RESULTS: As histochemical evaluations, there was no statistically significant differences the mean inflammatory cell density value in the epithelial tissue, inflammatory cell density value in the connective tissue, density value of necrotic tissue debris, collagen density value in the connective tissue between the groups. There was no statistically significant difference on immunohistochemical staining with LC3, caspase-3, Beclin-1 and TUNEL between the two groups (p > .05). CONCLUSIONS: A higher rate of inflammatory accumulation was shown on peri-implantitis, but no difference was found between periodontitis and peri-implantitis according to autophagy and apoptosis markers. Studies with high sample sizes with different markers are needed.

Comparison of the Effects of Skin Microneedling with Cupping Therapy and Microneedling Alone: An Experimental Study.

BACKGROUND: Microneedling promotes percutaneous collagen induction; cupping therapy creates negative pressure and leads to increased blood flow in the applied area. The addition of cupping therapy to microneedling is thought to contribute positively to microneedling's effects. This study was carried out to investigate the histologic effects of adding cupping therapy to microneedling. METHODS: Thirty Wistar rats were divided into five groups, with six rats in each group. One control group and four experimental groups were formed, which are defined as follows: the control group; the single-session microneedling applied to the dorsal trunk group; the 15-minute cupping therapy added to the single-session microneedling group; the microneedling applied over a total of three sessions at 3-week intervals group; and the microneedling with cupping therapy applied over a total of three sessions at 3-week intervals group. Each animal was euthanized at the end of the fourth week following the last treatment, and skin samples were evaluated histologically with hematoxylin and eosin stain and type I and III collagen antibody immunostaining. RESULTS: The addition of cupping therapy to microneedling increased the thickness of the epidermis and dermis. A significant increase in type I collagen immunostaining and the type-I-to-type III collagen ratio was seen only in the single-session microneedling applied to the dorsal trunk group. Cupping therapy did not generate a significant difference in type I collagen immunostaining. No treatment was found to produce a significant increase in type III collagen immunostaining. CONCLUSION: Cupping therapy can be added to microneedling therapy and used to increase certain desired effects on skin. CLINICAL RELEVANCE STATEMENT: Microneedling is an easy and effective method to improve skin quality in clinical practice.

Electron microscopic investigation of benzo(a)pyrene-induced alterations in the rat kidney tissue and the protective effects of curcumin.

Benzo(a)pyrene (BaP) is a polycyclic hydrocarbon with carcinogenic and DNA damaging properties. Curcumin, primary yellow pigment in turmeric, has a wide range of biological, pharmacological properties in addition to being a powerful antioxidant. The aim of this study was to investigate protective effects of curcumin against benzo(a)pyrene damage in rat kidney. Thirty-six male Wistar albino rats were divided into six groups (n = 6) as: control, corn oil, Dimethyl sulfoxide (DMSO), BaP (10 mg/kg/day), Curcumin (100 mg/kg/day), Curcumin+BaP (100 mg/kg/day+10 mg/kg/day). Agents were daily and orally administered for six weeks. Kidney tissues were removed and examined ultrastructurally. Glomerular and tubular structures in control, corn oil, and DMSO groups demonstrated normal features. Glomerular capillary dilation, thickening, and folding of basement membrane and disruption of organelle contents were distinguished in BaP group. Deletion of podocyte cell and pedicels also sponge-like appearance of glomerular surface were remarkable in this group. Tissue components were protected in curcumin treated group. Proximal tubules and glomerular basement membrane exhibited normal features in Curcumin+BaP group. The abnormalities that accompanied BaP administration clearly revealed the detrimental effects of this agent. Therefore, this study provided substantial evidence that curcumin protects against benzo(a)pyrene nephrotoxicity.

The effect of controlled ovarian hyperstimulation on ovarian reserve via PTEN pathway.

Abstract: This study was carried out to investigate whether repeated controlled ovarian hyperstimulation (COH) affects ovarian reserve. For this reason, we aimed to show possible changes in the expression of PTEN and FOXO3, which are involved in preserving the over-reserve, after applying the COH protocol methods. For this purpose, 18 young Wistar albino female rats (8 weeks old) were randomly assigned as group 1 (control), group 2, and group 3 as 6 subjects in each group. Experimental groups were treated with 10 IU/0.1 mL pregnant mare's serum gonadotropin and a COH protocol consisting of 10 IU/0.1 mL human chorionic gonadotropin injection after 48 h. This procedure was applied three and five times to group 2 and group 3, respectively. For the control groups, the same procedures were performed with 0.1 mL of 0.9% sodium chloride solution. At the end of the experiment, the ovarium tissues were placed in a 10% neutral formaldehyde solution for light microscopic examinations. In histological sections stained with hematoxylin and eosin, the number of ovarian follicles was determined using the physical dissector method. However, the expression of PTEN, FOXO3, and LH-R molecules was evaluated by immunohistochemical methods. As a result of our study, it was concluded that COH administration reduces the expression levels of PTEN and FOXO3 proteins and LH-R, which are among the essential components of the PIK3 intracellular signaling pathway and also increased the levels of hormones such as follicle-stimulating hormone, estradiol, and luteinizing hormone, which are over-reserve markers, and causes adverse effects on the histological structure, oocyte morphology, and number of ovaries. Lay summary: Today, approximately 10-15% of couples experience fertility problems. However, assisted reproductive techniques help people with fertility problems to get pregnant. The main purpose of these techniques is to put the sperm and egg together outside the woman's body where the eggs are fertilized and then to return the fertilized eggs (embryos) to the womb. During a woman's menstrual cycle, several hormones influence the growth of the eggs. This process can be mimicked by using various medications. Medication is given to increase the number of eggs that develop. However, this method is not the same as normal ovulation. Therefore, in our study, we wanted to examine the effect that developing multiple follicles has on the number and quality of eggs remaining for the future.

Analysis of potential protective effects of caffeic acid phenethyl ester against gentamicin ototoxicity: An experimental study.

Objectives: In this study, it is aimed to investigate the potential protective effect of caffeic acid phenethyl ester (CAPE) on ototoxicity caused by gentamicin in a rat model. Materials and Methods: Thirty Wistar albino rats were divided into 3 groups. Group I was selected as the control group. Gentamicin was administered intraperitoneally in group II, gentamicin and CAPE in group III. Audiological assessment was performed by the distortion product otoacoustic emission (DPOAE) and auditory brainstem response (ABR) measurements before and after treatment of each group. At the end of the study all rats were decapitated, cochlea was removed and electron microscopic examination was performed. Results: In group II post-treatment DPOAE levels were found to be lower than pretreatment DPOAE levels (P<0.05). However, in group III, there is no significant difference between pre- and post-treatment DPOAE levels (P>0.05). Except for Group I, ABR thresholds increased after the procedure and this increase was statistically significant (P<0.0001). According to histological examination by transmission electron microscopy, CAPE has a cellular protective effect against gentamicin ototoxicity. Conclusion: CAPE may ameliorate hearing deterioration caused by gentamicin ototoxicity and protect the cochlear cells from apoptosis due to the strong antioxidant effect.

Efficiency of hypericum perforatum, povidone iodine, tincture benzoin and tretinoin on wound healing.

Different topical agents have been used to accelerate wound healing. The purpose of this study is to compare the safety and efficacy of topical application of the extract of Hypericum perforatum (HPE), povidone iodine (PI), tincture benzoin (TB) and tretinoin (T) on surgical wound healing. Ten adult female, Wistar albino rats were included in the study. HPE, PI, TB and T solutions were applied on the wounds. After seven days, tissue samples were collected and inflammatory cells, re-epithelialization, granulation tissue, angiogenesis, collagen accumulation, hemorrhage and lysis of cells were investigated histopathologically. No dermal toxicity was noted. HPE, TB, PI have all showed good epithelialization and granulation, but HPE showed the most advanced stage of healing within a short period of time. HPE had significantly higher values of re-epithelialization and collagen accumulation, but lower inflammatory cell count and granulation tissue. TB had the second best in re-epithelialization, collagen accumulation and the highest granulation tissue. PI induced better reepithelialization and granulation than the control group with remarkable cell lysis. As a result, HPE can be a safe, effective, and cheap agent that can be used for surgical wounds.

The Effect of Ultrasonic Liposuction Energy Levels on Fat Graft Viability.

BACKGROUND: The use of fat obtained from ultrasound-assisted liposuction is popular. However, no study has considered the effect of different energy levels on fat grafts. OBJECTIVES: We hypothesized that different ultrasonic energy levels could change the fat graft viability. METHODS: Both flanks of 15 CD1 nude mice (30 experimental areas) were used, with experimental areas randomly distributed into five groups. Using different energy settings, fat grafts were obtained from a patient's abdominoplasty material and applied to the mouse flank regions. Device settings were intermittent mode with 50% vibration amplitude in group 1, continuous mode with 50% vibration amplitude in group 2, intermittent mode with 90% vibration amplitude in group 3, and continuous mode with 90% vibration amplitude in group 4. The control group was grafted with fat obtained via the conventional method. After 6 weeks, all mice were sacrificed, and fat grafts were excised. Sections were stained with hematoxylin-eosin, Masson's trichrome, and anti-perilipin A antibody. RESULTS: The perilipin A immunostaining result was lowest in group 4, indicating the lowest viable cell count (p < 0.01). There was no significant difference between groups for the other parameters (p > 0.05). CONCLUSION: High ultrasonic energy may affect fat graft survival. If fat injection is planned, avoiding high energy settings (our recommendation is not to exceed 16 Watts.) should be considered. We also recommend increasing the vibration amplitude rather than switching from intermittent to continuous mode in body parts that are relatively resistant to liposuction. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Effects of chitosan and platelet-rich plasma on facial nerve regeneration in an animal model.

PURPOSE: There is still no widely-accepted local agent proven to be effective in nerve regeneration. We aimed to investigate the effects of chitosan gel and platelet-rich plasma MATERIALS AND METHODS: Electrophysiological measurements were performed before and immediately after injury. The injured nerves were covered with spongostan impregnated with the following agents: Group 1 (Control Group): Saline at a dose of 50 µl; Group 2: Chitosan (CHT) at a dose of 50 µl; Group 3: PRP at a dose of 50 ml; and Group 4: a solution of CHT with PRP (1:1). The final measurements were performed after 3 weeks and the injured nerve of each rat was removed. RESULTS: There were statistically-significant differences between the groups regarding the measurements of the after-treatment values of stimulus threshold (p < 0.05). The best improvement in electrophysiological measurement and histopathological evaluation was found in Group 4 (CHT-PRP). CONCLUSION: Chitosan gel has a positive effect on nerve healing and applying it along with PRP can enhance the effect of chitosan.

The relationship between good quality embryo rates and IVF outcomes/embryo transfer policies in extended embryo culture.

This study aims to investigate which parameters affect the change in good quality embryo rates during the cleavage stage and whether they have any effect on embryo transfer policies and IVF results. We analysed changes in good quality embryo (grades 1 and 2) rates during the period on days 2, 3 and 5; patients with five or fewer embryos (group 1), 6-10 embryos (group 2) and more than 10 embryos (group 3). The good quality embryo rates decreased in all groups on day 5. When the infertility reasons are studied among all of the groups, ovulatory dysfunction is found to be significantly higher in group 2 compared to group 1 and unexplained infertility was found to be significantly higher in group 2 compared to group 1 and group 3. Total antral follicle, mature oocyte and total oocyte counts were found to be significantly lower in group 1. However, there is no significant difference found among all of the groups for ß-HCG levels and clinical pregnancies. Changes in good quality embryo rates at the cleavage stage in extended embryo culture do not have an impact on IVF results.IMPACT STATEMENTWhat is already known on this subject? The number and quality of embryos in the cleavage stage are important parameters affecting the embryo transfer decision on day 5. There is still insufficient knowledge concerning changes in the percentage of increased good quality embryo transfers associated with IVF outcomes during the second to the third day, and the third to the fifth day.What do the results of this study add? Day 5 embryo transfer is possible in patients with a low number of embryos, according to our results. The good quality embryo rates of patients with a low number of embryos at the cleavage stage are more promising compared to patients having more than five embryos.What are the implications of these findings for clinical practice and/or further research? An extended embryo culture option can be used on patients with a low number of embryos for clinical practice.

Use of Erythropoietin and Fibrin Glue Mixture for Peripheral Nerve Repair.

BACKGROUND: Erythropoietin has neuroregenerative effects. Fibrin glue may be used for nerve repair and controlled release of substances. In this study, the authors investigated the effects of erythropoietin-containing fibrin glue on nerve repair, based on the hypothesis that erythropoietin-containing fibrin glue would positively affect nerve regeneration. METHODS: Thirty-six Long-Evans rats were used. The animals were divided into six groups. Their left sciatic nerves were isolated, transected, and repaired with saline-containing fibrin glue in group 1, with erythropoietin-containing fibrin glue in group 2, with saline-containing fibrin glue and two sutures in group 3, with erythropoietin-containing fibrin glue and two sutures in group 4, with two sutures in group 5, and with four sutures in group 6. Sciatic Functional Index calculation, pin-prick test, and toe-spread test were performed on days 21, 42, and 63. All animals were killed on day 63. The nerve sections were analyzed histologically. RESULTS: The Sciatic Functional Index, pin-prick test, and toe-spread test results were the best in group 4 and the worst in group 5. Group 4 showed superior Schwann cell proliferation (p < 0.05). Groups with epineural suture use (groups 3, 4, 5, and 6) had higher endoneurial collagen synthesis scores than the groups without suture use (groups 1 and 2) (p < 0.05). The myelin protein zero immunostaining results were significantly higher in the erythropoietin-treated groups (groups 2 and 4) (p < 0.05). CONCLUSION: The combined use of erythropoietin-containing fibrin glue and two epineural sutures (group 4) showed a statistically significant improvement in many parameters. CLINICAL RELEVANCE STATEMENT: Fibrin glue is already used in nerve repair. Adding erythropoietin to fibrin glue could be a safe and easy option to improve nerve regeneration.

Arterial Occlusion After Hyaluronic Acid Injection: Treatment With Hyaluronidase and Streptokinase.

ABSTRACT: The most feared complication of the hyaluronic acid injections in the periorbital region is embolism of the central retinal artery. The present study aimed to compare the effectiveness of hyaluronidase administered intravenously (systemically) alone or in combination with streptokinase with that of intra-arterial revascularization. Thirty rats were divided into 5 groups. The bilateral oblique groin flap of the rats was raised; the right side was the experiment group, and the left side was the sham control. The right superficial epigastric artery was occluded with a hyaluronic acid injection. After occlusion, no additional procedures were performed in group 1, whereas group 2 received systemic hyaluronidase, group 3 received intra-arterial hyaluronidase, group 4 received systemic hyaluronidase and streptokinase, and group 5 received intra-arterial hyaluronidase and streptokinase. On the seventh day, the rats were killed, flap necrosis rate was calculated, and histological examination was performed. There was no significant difference in the necrosis rates of the rats in groups 2, 3, 4, and 5 (P > 0.05). In histological evaluation, the histological view closest to normal arterial structure was observed in group 4. Immunohistochemical analysis revealed that the ischemia scores of systemic therapy were significantly lower than those of intra-arterial therapy. These results have shown that hyaluronidase and streptokinase administered systemically is as effective as intra-arterial revascularization and does not cause arterial wall degeneration. It has been shown that systemic administration of hyaluronidase and streptokinase is as successful as intra-arterial revascularization in the treatment of arterial embolism with hyaluronic acid.

Comparison of Large-Gauge Needle, Corneal Knife, and No. 11 Blade for Percutaneous Achillotomy.

BACKGROUND: In the Ponseti technique, the residual equinus deformity is corrected with percutaneous tenotomy. This experimental study aimed to compare the safety and effectiveness of a large-gauge needle, a corneal knife, and a No. 11 blade in percutaneous achillotomy performed in rats. METHODS: Ninety Achilles tendons of 45 Sprague-Dawley rats were analyzed, following division into three study groups. In the study, group I (needle), group II (corneal knife), and group III (No. 11 blade) were compared on the basis of bleeding, incision length, requirement for primary suture, range of motion, and resulting neurovascular injury at day 0. Moreover, the groups were compared in terms of range of motion, macroscopic and microscopic adhesions, and tenocyte morphology at days 21 and 42 postoperatively. RESULTS: On day 0, one suture was required in group III, whereas in groups I and II, no sutures were required. Postoperative bleeding was greater in group III and similar in groups I and II. Neurovascular injury was not observed in any of the groups. Three incomplete tenotomies were observed in group III and one incomplete tenotomy was observed in group II. Importantly, all tenotomies were complete in group I. In all groups, the range of motion was similar. The macroscopic adhesion score revealed high adhesion in group III (P = .009). According to Tang's criteria, microscopic adhesion was significantly higher on day 21 in group III compared with the other groups (P <0.001). No significant differences were observed in tenocyte morphology based on the Bonar criteria (P = .850). CONCLUSIONS: In the results obtained from this animal study, we observed less bleeding, less adhesion, and less incomplete tenotomy in the large-gauge needle and corneal knife groups compared with the No. 11 blade group during the percutaneous Achilles tenotomy performed in rats.

Angiotensin-Converting Enzyme Inhibitor Reduces Radiation-Induced Periprosthetic Capsular Fibrosis.

BACKGROUND: The capsular contracture is one of the main complications after radiotherapy in patients with implant-based reconstruction. The aim of this study is to evaluate the efficacy of ramipril for the prevention of radiation-induced fibrosis around the silicone implant. MATERIALS AND METHODS: Thirty Wistar rats in 5 groups were used. Group 1: implant; group 2: implant + radiation; group 3: ramipril + implant; group 4: ramipril + implant + radiation; group 5: sham. Ramipril treatment was started 5 d before surgery and continued for 12 wk after surgery. A mini silicone implant was placed in the back of the rats. A single fraction of 21.5 Gy radiation was applied. Tissues were examined histologically and immunohistochemically (TGF-ß1, MMP-2, and TIMP-2 expression). The alteration of plasma TGF-ß1 levels was examined before and after the experiment. RESULTS: After applying implant or implant + radiation, capsular thickness, percentage of fibrotic area, tissue and plasma TGF-ß1 levels significantly increased, and MMP-2/TIMP-2 ratio significantly decreased compared with the sham group. In ramipril-treated groups, the decrease in capsular thickness, fibrosis, TGF-ß1 positivity, and an increase in MMP-2/TIMP-2 ratio were found significant. In the ramipril + implant + radiation group, the alteration values of TGF-ß1 dramatically decreased. CONCLUSIONS: Our results show that ramipril reduces radiation-induced fibrosis and contracture. The results of our study may be important for the design of the clinical trials required to investigate the effective and safe doses of ramipril, which is an inexpensive and easily tolerated drug, on humans.

[Investigation of Pseudomonas aeruginosa Biofilm Formation and Quorum Sensing Genes in Piperacillin/Tazobactam and Ciprofloxacin Sub-minimal Inhibitory Concentrations]. / TPiperasilin/Tazobaktam ve Siprofloksasin Sub-minimal Inhibitör Konsantrasyonlarinda Pseudomonas aeruginosa Biyofilm Olusumunun ve Quorum Sensing Genlerinin Arastirilmasi.

Pseudomonas aeruginosa is a non-fermentative, oxidase-positive, motile gram-negative bacillus widespread in nature. The virulence factors of P.aeruginosa including the ability to grow under minimal growth conditions, the widespread presence in nature, and the ability to form biofilms make P.aeruginosa a highly important bacterium along with its resistance mechanisms against many antibiotics. The ability to form biofilms increases the symptom severity in diseases caused by P.aeruginosa and causes difficulties in the treatment. The aim of this study was to investigate the effects of sub-minimal inhibitory concentrations (sub-MIC) of piperacillin/tazobactam (TZP) and ciprofloxacin (CIP) which are used for the treatment of P.aeruginosa infections on biofilm formation and to investigate the relationship between the severity of biofilm formation and Quorum Sensing (QS) genes. The study included 24 P.aeruginosa isolates from the culture collection of Medical Microbiology Laboratory of Gazi University Faculty of Medicine. MIC values of TZP and CIP antibiotics were determined by the microdilution method. The biofilm layers in the antibiotic-free medium and in the sub-MIC (MIC/2, MIC/4 ve MIC/8) concentrations of antibiotics were visualized by using a scanning electron microscope (SEM). The QS genes (lasI, lasR, rhlI, and rhlR) of the 24 isolates with known biofilm characteristics were identified via the amplification of chromosomal DNA by using PCR method. In the study, it was foundthat both antibiotics reduced biofilm formation in a dose-dependent manner in sub-MIC concentrations compared to the antibiotic-free condition and that MIC/2 was the concentration, which reduced the biofilm formation most. These results were further confirmed by viewing the SEM images. The QS genes lasI, lasR, and rhlI were detected in a total of 19 isolates with moderately strong and strong biofilm formation, the rhlR gene was detected in six of the strong biofilm-forming isolates, in four of the moderately strong biofilm-forming isolates, and in three of the weak biofilm-forming isolates, respectively. The investigation of the effects of sub-MIC concentrations of antimicrobials, used for the treatment of P.aeruginosa infections, on the biofilm formation of P.aeruginosa and the investigation and better understanding of the QS systems associated with biofilm production will allow for finding out new treatment approaches and offer different options in combating infections with high morbidity and mortality.

A Comparison of Ramipril and Bevacizumab to Mitigate Radiation-Induced Brain Necrosis: An Experimental Study.

BACKGROUND: Bevacizumab, an anti-vascular endothelial growth factor (VEGF) antibody, is a new treatment approach for radionecrosis. In our study, we compared the prophylactic and therapeutic usage of a promising agent, ramipril (an angiotensin-converting enzyme inhibitor), with that of bevacizumab for reducing radiation-induced brain injury after high-dose stereotactic radiosurgery (SRS). METHODS: A total of 60 Wistar rats were used. The rats were irradiated with a single dose of 50 Gy using a Leksell Gamma Knife device. Bevacizumab and ramipril were administered in the prophylactic protocol (starting the first day of SRS) and in the therapeutic protocol (starting the fourth week of SRS). Their usage was continued until 12 weeks, and the right frontal lobes of the rats were examined histologically (hematoxylin and eosin stain) and immunohistochemically (hypoxia-inducible factor [HIF]-1α, VEGF, and CD31 antibody expression). RESULTS: The expression of VEGF, HIF-1α, and CD31 had significantly increased at 12 weeks after SRS compared with the control group. The addition of bevacizumab or ramipril to SRS significantly mitigated the histological severity of radiation injury and the expression of VEGF, HIF-1α, and CD31. However, the prophylactic use of bevacizumab and ramipril seemed to be more effective than therapeutic administration. Our results also revealed that the greatest benefit was achieved with the use of prophylactic administration of bevacizumab compared with other treatment protocols. CONCLUSIONS: Ramipril might be a promising agent for patients with radionecrosis. Clinical studies are required to investigate the effective and safe doses of ramipril, which is an inexpensive, well-tolerated drug that can cross the blood-brain barrier.

Capsular contracture around silicone miniimplants following bacterial contamination: an in vivo comparative experimental study between textured and polyurethane implants.

BACKGROUND: Capsular contracture remains a problem following breast implant surgery. Although impact of biofilm and implant surface on capsule formation has been demonstrated, interaction of microorganisms with different surface types has not been clarified yet. We aimed to compare the ability of biofilm formation of implants with different surfaces, under standard conditions and to demonstrate its impact on capsular contracture. METHODS: Twenty-four rats were divided into four groups. Mini-implants with three different surfaces (fine-textured, rough-textured and polyurethane) were placed on the dorsum of each rat. In Group-1, sterile implants were placed in submuscular pockets. In Group-2, implants were incubated in Staphylococcus epidermidis medium before implantation. In Group-3, before implantation, implants were immersed in Rifamycin solution following bacterial contamination. In Group-4, sterile implants were immersed in Rifamycin solution before implantation, and served as the control group. Rats were sacrificed at three months. Clinical, microbiological, histological and immunohistochemical evaluations were performed. RESULTS: Capsule contracture developed only on infected rough-textured implants. Rough-textured and polyurethane implants showed more biofilm formation than fine-textured implants. Capsule thickness and inflammatory cell density were higher on rough-textured implants compared to fine-textured implants (p = 0.004). Actin sequence was parallel and concentric on fine-textured and rough-textured implants; but was in irregular array on polyurethane implants. CONCLUSION: In presence of bacterial contamination, rough-textured implants have the most propensity of developing capsular contracture comparing to fine-textured and polyurethane implants at three months after implantation. Despite high bacterial load and biofilm formation, polyurethane implants are resistant to capsule contracture due to surface characteristics.