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.

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.

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.

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 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 .

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.

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.

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.

[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 Novel Stitching Technique: Adjustable Closed-Loop Sewing Machine Lock Stitching Technique to Bend or Unbend Cartilages.

This study aimed to evaluate the effect of a novel adjustable, closed-loop sewing machine lock stitching technique on cartilage shape. This study was performed on 18 rabbits that were divided into 3 groups to evaluate the short- (Group I), medium- (Group II), and long-term (Group III) effects of the technique on cartilage shape. Three cartilage grafts were obtained from the right and left ears of the rabbits and measured angularly. For the cartilage grafts obtained from the right ears, contours were corrected using the stitching technique proposed herein. The cartilage grafts obtained from the left ears were not stitched; these were maintained as the control group. Angular measurements were performed for the stitched cartilage grafts, and all the cartilages grafts obtained were finally embedded into the rabbits' backs. The rabbits in Groups I, II, and III were euthanized at week 2, 6, and 12, respectively, after which the cartilages were reevaluated for angular measurement and submitted for histopathological examination. A significant improvement from baseline was detected in the angular measurements of the stitched cartilage grafts obtained from the rabbits in each group. For the stitched cartilage grafts obtained from Group II and III rabbits, the angular measurements obtained immediately after stitching were found to be better than those obtained after euthanasia. In histopathological evaluation elevated collagen, perichondrium, and connective tissue levels were detected in grafts obtained from Group III rabbits. The novel stitching technique proposed herein appears to have beneficial long-term effects on the maintenance of cartilage contour.

The Effect of Minocycline on Fat Graft Survival and Apoptotic Pathway.

Variable absorption rate is one of the biggest problems of fat grafting and one of the most important causes of fat graft volume loss is apoptosis. Minocycline is a tetracycline derivative and besides its antibacterial capacity, it has been widely using for anti-apoptotic effects. This study was designed to investigate the effect of minocycline on fat graft survival and adipocyte apoptosis. A total of two main and eight subgroups were designed and a total of 48 experimental animals, 6 in each group, were used. Fat grafts are obtained from Wistar albino rats and implanted to dorsal area of rats. Local and systemic minocycline was applied in the study groups. On the 9th day, apoptotic cells were detected by the terminal deoxynucleotidyl transferase dUTP nick end labeling method and on the 90th day morphologic characteristics and viability of adipocytes were evaluated using histologic and immunohistochemical methods and statistically compared. This study revealed that the fat grafts were bigger, and they kept their structures better and they were more vascular in the minocycline groups and apoptosis was significantly lower in the minocycline groups. The authors demonstrated that minocycline increases fat graft survival and statistical improvement in apoptosis inhibition via using minocycline therapy has been shown.

Maternal nutrition and reproductive functions of female and male offspring

This study aimed to investigate the effects of maternal unhealthy nutrition on the reproductive functions of female and male adult offspring. This was an animal study carried out with 24 virgin female Wistar rats (dams) and their male and female offspring. Rats were divided standard diet (SD) or cafeteria diet (CD) groups, after 10 weeks of feeding, all rats were paired with a Wistar stud male, and each group was again divided into CD and SD groups during the pregnancy and lactation periods. After birth, six female and six male pups in each group, were subjected to study. Following 3 weeks of lactation, the pups were fed with SD for 8 weeks and killed when they were considered adult at 11th week for analysis. Primordial and antral follicle counts, serum anti-Mullerian hormone (AMH) and phosphatase and tensin homolog (PTEN) in the oocyte cytoplasm were examined to evaluate ovarian function, and E-cadherin and integrin-ß1 levels were examined in endometrial tissues for the evaluation of endometrial receptivity in female offspring. Sperm analysis was performed in male offspring. In groups in which the dams were fed CD, primordial follicular pool, PTEN, and endometrial receptivity were reduced. In contrast, AMH and the number of antral follicles were not changed. In male offspring, the testicles were smaller, testosterone production decreased, AMH increased and the number and function of sperm were not changed. Sperm analysis results were not changed. All negative effects on reproductive functions were more apparent in groups fed with the CD during the pregestational period.

Effects of Low-Level Laser Therapy With a Herbal Extract on Alveolar Bone Healing.

PURPOSE: This study investigated the effect of a gallium-aluminum-arsenide (GaAlAs) diode laser used in low-level laser therapy (LLLT) with the application of Mecsina Hemostopper on mandibular alveolar bone healing. MATERIALS AND METHODS: Standard semispherical bone defects were created in left mandibular diastema sites of 32 female Long-Evans rats. Experimental animals were allocated to 1 of 4 groups: control group (no treatment), laser group (GaAlAs LLLT), Mecsina group, and laser-Mecsina combination group. Liquid Mecsina 0.01 mL was applied to the bone defects. Laser treatment was performed for 7 days after surgery at an energy dose of 10 J/cm2. All animals were sacrificed to observe hard tissue healing histologically, immunohistochemically, and radiologically at 30 days after surgery. RESULTS: Histologic assessment showed significantly more calcified tissue areas and significantly more osteoblast cells in the laser and laser-Mecsina groups than in the other groups (P < .01). Qualitative morphologic assessment showed that more bone tissue was present in the laser-Mecsina group than in the other groups. CONCLUSION: This study showed that LLLT, Mecsina application, and combined treatments were effective in healing alveolar bone among all tested treatment modalities.

Botulinum Toxin Type A: Assessing The Effects on The Brain Stem.

BACKGROUND: In this study, our aim is to investigate the possible effects of Botulinum toxin type A administrations in the early and late periods on the brain stem. METHODS: Eighteen white New Zealand rabbits were used in this study with the subjects being divided into three groups. Group I received 0.05 mL sterile saline to the left anterior auricular muscles. Group II and III were injected with Botulinum toxin type A (Botox, Allergan) to the left anterior auricular muscles. Group II was sacrificed 5 days after application and Group III was sacrificed 12 weeks after application; brain stem tissues were then taken. The samples were examined with Caspase 3, 8, and 9 immunohistochemical stainings. RESULTS: In the control group with Caspase-3 immune staining, moderate-to-strong immune reactivity was seen in a small number of neurons. In the Caspase-8 and 9 immune stainings, the immune reactive neurons were seen in greater numbers when compared with the Caspase-3 immune reactive neurons. In the early and late period, groups with Caspase-8 and 9 immune stainings, the immune reactive neurons were seen in greater numbers and in the wider area when compared with the Caspase-3 immune reactive neurons. No significant differences were recognized in the Caspase immune stainings between the early and late period groups. The results were statistically supported. CONCLUSION: It was concluded that Botulinum toxin type A application did not trigger apoptosis in stem cell tissues. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each article. 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 Rat Bone Marrow-Derived Mesenchymal Stem Cells and Demineralized Bone Matrix on Cranial Bone Healing.

BACKGROUND: Studies in tissue engineering about mesenchymal stem cells (MSCs) provide promising results for bone regeneration. The aim of this study was to evaluate the effects of rat bone marrow-derived MSCs (rMSCs) alone and when combined with demineralized bone matrix (DBM) on critical-sized cranial defects of rats. METHODS: Ten rats were used to obtain allogeneic rMSCs. Forty rats were separated equally into 4 groups. A full-thickness circular bone defect was created in the frontal bone of the rats. Group 1 was an operative control group. In group 2 DBM, in group 3 rMSCs, and in group 4 DBM combined with rMSCs were applied into the defects. Bone regeneration was evaluated by computed tomographic analysis and immunohistochemistry. RESULTS: In radiological evaluation, the percentage of area healed in group 3 at the 12th week was statistically significantly greater than in group 1. In group 3 and group 4, distributed healing patterns were observed more than in group 2 and in group 1. Immunohistochemical evaluation revealed that group 4 had the best osteoinductive potential. Osteoinductive potential of group 3 was similar to group 2 and was better than group 1. CONCLUSIONS: Allogeneic rMSC applications have created a statistically significant radiologic reduction of the bone defect areas at the end of the 12 weeks. The MSC applications have also increased the bone density and changed the healing patterns. Combined use of the DBM and rMSCs has created more osteoinductive responses. This combination can provide better results in craniofacial bone reconstruction.

The Effect of Hyaluronic Acid Application on the Perisilicon Capsule Structure.

BACKGROUND: Silicon implants constitute a major part of plastic surgery practice. Although materials with high biocompatibility have been used around the implants, capsule formation still develops and progressive nature of this process results in capsule contraction. The aim of this study is to evaluate the effects of hyaluronic acid injected around the silicon block on the capsule structure. METHODS: Twenty Wistar albino rats were used in the study. Rats were divided into two main groups (group 1 and group 2) and two subgroups. Rats in group 1 were sacrificed in week 4 and rats in group 2 were sacrificed in week 8. A subcutaneous pouch was created in the dorsum of the rats and a silicon block was placed into the pouch in groups 1A and 2A. 0.2 ml of hyaluronic acid was injected around the silicon block in group 1B and group 2B. Rats were sacrificed and capsule structure and thickness were analyzed following macroscopic evaluation. Concentrations of transforming growth factor-ß1 (TGF-ß1) and heat shock protein-47 (HSP-47) were evaluated immunohistochemically, and statistical comparisons were made. RESULT: Capsule structure consisted of three layers in all the groups. A more intense collagen structure was observed in the middle layer. The capsule was thinnest in group 1A and thickest in group 2B; the difference between the groups was statistically significant. TGF-ß1 was most intense in group 2B and it was correlated with the amount of collagen. Involvement of HSP-47 was observed mainly in collagen and also in fibroblasts and vascular structures, and its concentration was found to be lower in groups 2A and 2B. CONCLUSION: Exogenously added cross-linked hyaluronic acid increased the capsular thickness and may increase the risk of developing capsular contracture around silicone implants. LEVEL OF EVIDENCE II: Evidence was obtained from the well-designed controlled trials without randomization.

The Effect of Thrombolytic, Anticoagulant, and Vasodilator Agents on the Survival of Random Pattern Skin Flap.

BACKGROUND: The aim of this study was to investigate the effect of subcutaneously applied thrombolytic, anticoagulant, and vasodilator agents on the survival of random-pattern skin flap. METHODS: A caudally based dorsal flap model was used in 24 rats in four groups. In group 1 (n = 6), flap was elevated and sutured. In group 2 (n = 6), enoxaparin sodium was injected subcutaneously immediately after surgery, on days 1 and 2. In group 3 (n = 6), a transdermal nitroglycerin was applied directly following surgery, on days 1 and 2. In group 4 (n = 6), alteplase was injected subcutaneously immediately after surgery, on days 1 and 2. Blood flow was measured with laser Doppler flowmetry at the proximal and distal halves of flap before, immediately after surgery, and on days 3 and 7. Histologic samples were taken from the same locations on day 3 and day 7 postoperatively. Vessel and lymphocyte count was obtained. Photographs were taken to determine flap necrosis areas at day 7 postoperatively. RESULTS: Area of skin necrosis was found to be less in all medication groups. But only enoxaparin sodium group showed significant decrease in skin necrosis (p < 0.05). Laser Doppler flowmetry showed a gradual decrease in all groups over time, with no statistically significant result. The histologic findings revealed the induction of angiogenesis in all experimental groups. CONCLUSION: Subcutaneously applied thrombolytic, anticoagulant, and vasodilator agents increase random-pattern skin flap survival with only enoxaparin sodium showing significant decrease in flap necrosis.

The effect of folic acid supplementation and folate deficiency on embryo implantation.

Implantation is a critical stage of pregnancy, which occurs in a short period of interaction between the receptive endometrium and the embryo. Folic acid (FA) is a synthetic derivative of folate and is recommended as a pre-conceptional supplement. However, the impact of different doses of FA supplementation and folate deficiency during the early stages of pregnancy requires further investigation. The aim of this study was to investigate the possible effects of FA supplementation and folate deficiency on expression of Estrogen Receptor Alpha (ER-α), Vascular Endothelial Growth Factor-A (VEGFA), and Integrin alpha V and beta3 (Integrin αVß3). A total of 32, 6-8-week old Wistar albino rats were divided into four groups of control, folate-deficiency, low-dose, and high-dose FA supplement groups. After five weeks of FA supplementation and folate deficiency model formation, mated rats were sacrificed on the 5th gestational day (GD), and implantation sites were collected. The expression of ER- α, VEGFA, and Integrin αVß3 in the implantation sites were examined with immunohistochemistry and real-time PCR. The results revealed that the mRNA levels of ESR1, VEGFA, and Integrin αV and ß3 were significantly increased in the high-dose FA group and significantly decreased in the folate deficiency group compared to the control group (p < 0.05). Based on these results, it can be concluded that FA supplementation before pregnancy has positive effects on the maintenance of pregnancy, and folate deficiency may lead to implantation disorders.

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.

The treatment of segmental bone defects in rabbit tibiae with vascular endothelial growth factor (VEGF)-loaded gelatin/hydroxyapatite "cryogel" scaffold.

The aim of this study was to investigate the effectiveness of a novel hydroxyapatite containing gelatin scaffold--with and without local vascular endothelial growth factor (VEGF) administration--as the synthetic graft material in treatment of critical-sized bone defects. An experimental nonunion model was established by creating critical-sized (10 mm. in length) bone defects in the proximal tibiae of 30 skeletally mature New Zealand white rabbits. Following tibial intramedullary fixation, the rabbits were grouped into three: The defects were left empty in the first (control) group, the defects were grafted with synthetic scaffolds in the second group, and synthetic scaffolds loaded with VEGF were administered at bone defects in the third group. Five rabbits in each group were killed on 6th and 12th weeks, and new bone growth was assessed radiologically, histologically and with dual-energy X-ray absorptiometry (DEXA). At 6 weeks, VEGF-administered group had significantly better scores than the other two groups. The second group also had significantly better scores than the control group. At 12 weeks, while no significant difference was noted between the second and third groups, these two groups both had significantly better scores in all criteria compared with the control group. There were no signs of complete fracture healing in the control group. The administration of hydroxyapatite containing gelatin scaffold yielded favorable results in grafting the critical-sized bone defects in this experimental model. The local administration of VEGF on the graft had a positive effect in the early phase of fracture healing.