The Effect of Zinc Deficiency and Supplementation on Elements in the Kidney Tissue of Ovariectomized Rats: Histopathologic Changes.

The objective of the present study is to determine the effects of zinc deficiency in and zinc supplementation to ovariectomized rats on some elements in kidney tissue. The study included 40 Sprague-Dawley type adult female rats. The experimental animals were randomized into four groups with equal numbers as follows: Group 1: Control (10). Group 2: Ovariectomized control (10). Group 3: Ovariectomized + zinc supplemented (10). Group 4: Ovariectomized + zinc deficient (10). After the animals were decapitated at the end of the experiment, element levels were determined by Atomic Emission (ICP-AES) as mg/g/wet tissue for calcium, phosphate, zinc, aluminum, copper, iron, lithium, and manganese and µg/g/wet tissue for magnesium in the kidney tissue. Additionally, the tissue samples were subjected to a histopathologic assessment. An examination of the study results showed that ovariectomy significantly reduced calcium, phosphorus, and zinc levels, while zinc supplementation to the rats following ovariectomy restored the reduced element levels to normal (0.10 ± 0.03, 0.85 ± 0.16, 0.11 ± 0.03 vs 0.19 ± 0.06, 1.86 ± 0.18, 0.52 ± 0.05). Group 4, which was both ovariectomized and fed on a zinc-deficient diet, had significantly lower aluminum, copper, and lithium values. Calcification, inflammation, and sclerotic changes in group 4, the group which was fed on a zinc-deficient diet, were greater in comparison to other groups (p < 0.05). Results of the study suggest that ovariectomy + zinc deficiency leads to calcification, inflammation, and sclerotic changes in renal tissue and significantly reduces element levels, whereas zinc supplementation after ovariectomy restores the lowered element levels to normal.

Lateral Orbital Wall Destruction Due to Pilonidal Sinus.

Pilonidal sinus is a chronic inflammatory disease commonly observed in the sacrococcygeal region. The authors report a patient of a pilonidal sinus in a rare location-the lateral orbital region. The authors' patient was misdiagnosed with an epidermal cyst, and the subsequent incomplete excision of the sinus tract led a pilonidal sinus with a high morbidity resulting in the destruction of bone tissue in the lateral orbital wall. It was, therefore, crucial to accurately diagnose and treat before the infection progressed through the bone and caused osteomyelitis.

Effects of strontium ranelate on sutural bone formation: a histological and immunohistochemical study.

AIM: Rapid maxillary expansion is performed to correct a skeletal transverse deficiency of the maxilla, which is a frequently- encountered orthodontic anomaly. Strontium ranelate (SrR) is a novel agent that has a dual action, involving anti-resorptive and bone-forming effects. The aim of this study was to evaluate the effects of systemically applied SrR on osteoblastic bone formation after maxillary expansion on the mid-palatal suture of rats using histological and immunohistochemical tests. MATERIALS AND METHODS: A total of 24 Wistar rats were randomly divided into two equal groups. In all animals, five-day inter-premaxillary expansion was applied and maintained for a seven-day retention period, during which 625mg/kg/day SrR diluted with saline solution was administered orally to the experimental group. The rats were sacrificed and the tissues prepared for histological and immunohistochemical examinations after the retention period. RESULTS: Osteoblastic activity and the width of the blood vessels in the suture area were significantly increased in the SrR group compared with the control group (p < 0.051. Ossification was also observed to be active under light microscopy by staining with hematoxylin and eosin in the experimental group. Immunohistochemical labelling performed using osteonectin, osteocalcin, TGF-P and VEGF antibodies revealed significant immunoreactivity in the experimental group (p < 0.05). CONCLUSION: It may be concluded that SrR contributed to stimulatory osteogenesis in the expansion region. Therefore, a retention period may be shortened and relapse possibly reduced, following the application of SrR after the expansion.

Prognostic value of preoperative neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios, and multiphasic renal tomography findings in histological subtypes of renal cell carcinoma.

BACKGROUND: To determine the relationship between renal cell carcinoma subtypes and the associated mortality and biochemical parameters. An additional aim was to analyze multiphasic multidetector computed tomography findings. METHODS: This study is a hospital-based retrospective investigation, using 211 patients with a diagnosis of renal cell carcinoma upon computed tomography examination. The histological subtypes included clear cell in 119 patients, chromophobe cell in 30 patients, papillary cell in 25 patients, mixed cell in 32 patients, and sarcomatoid cell in 4 patients. RESULTS: The mean age of the patients participating in this study was 61.18 ± 11.81 years, and the mortality rate was 10.4% (n = 22) through the 2-year follow-up. The ratios of both the neutrophil-to-lymphocyte upon admission to the hospital and platelet-to-lymphocyte of the non-surviving group were significantly higher than those of the surviving group (p < 0.05). When the analysis of the 2-year survival of the patients was examined according to the median platelet-to-lymphocyte ratio values, the Kaplan-Meier survival curves were significantly different between the surviving and non-surviving groups (p = 0.01). In two-way analysis of variance test, statistically significant results which were influenced by mortality (p = 0.028) and were found between renal cell carcinoma subtypes in the computed tomography density of corticomedullary phase (p = 0.001). CONCLUSIONS: The neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio may represent widely available biomarkers in renal cell carcinoma, and the logistic regression model indicated that neutrophil-to-lymphocyte ratio was a significant predictor for mortality. According to the median platelet-to-lymphocyte ratio values, the Kaplan-Meier survival curves were significantly different between the surviving and non-surviving groups.

Complete response and long-term remission to anti-HER2 combined therapy in a patient with breast cancer presented with bone marrow metastases.

Presentation with bone marrow metastasis at diagnosis is a rare event in breast carcinoma. Here, we report a rare presentation of metastatic breast cancer patient with bone marrow metastases, who was successfully treated with trastuzumab combined chemotherapy. The regimens initially applied for bone marrow metastasis were docetaxel/adriamycin, gemcitabine/vinorelbine, epirubicin/cyclophosphamide, capecitabine, docetaxel, gemcitabine, and paclitaxel. But, the best response to these regimens was not satisfactory. Our patient was completely treated with etoposide-cisplatin and trastuzumab combination. She is still on remission after five years of metastatic breast cancer diagnosis using letrozole and trastuzumab without complication. Physicians should be careful in treating bone marrow metastases in breast cancer, since patients can show improved marrow function after chemotherapy and long-lasting survival is possible.

Is it necrotizing fasciitis or necrotizing cellulitis after varicella zoster infection? Two case reports.

Necrotizing fasciitis and necrotizing cellulitis are serious cutaneous complications in varicella patients. Differentiation of necrotizing cellulitis from necrotizing fasciitis can initially be challenging because of indistinct clinical course at the onset of infection and the lack of definitive diagnostic criteria. This paper reports 2 children with necrotizing cellulitis that developed after varicella infection to draw the attention of health care providers to necrotizing cellulitis that showed slower clinical course than necrotizing fasciitis and recovered with conservative treatment approaches without aggressive surgical intervention.

Comparison of bone dust with other types of bone grafts for cranioplasty.

PURPOSE: Split calvarial bone graft is preferred in the reconstruction of calvarial defects. However, it is not feasible for use in some challenging cases and in children. Particulate bone graft containing viable osteoblasts could be an attractive alternative. MATERIALS AND METHODS: A total of 32 female rats were randomly separated into 4 groups. Full-thickness bone graft from rat calvaria was harvested in diameters of 8 × 8 mm. In group 1, the periosteum and skin were closed without any bone graft; bone dust particles were placed in group 2; bone fragments were placed in group 3; and full-thickness cranial bone graft was placed in group 4. After 12 weeks, all rats were killed. Degrees of resorption, foreign body reaction, and bone spicule length were assessed histologically, and an immunohistochemical study was used to show bone graft viability. RESULTS: In graft viability, osteogenesis, and osteoblastic differentiation, groups 3 and 4 were similar and superior to groups 1 and 2. No osteoblastic activity and no viable bone dust were detected in groups 1 and 2. Resorption was observed in every preparate that contains bone tissue, and foreign body reaction was prominent in small bone groups, such as in group 2. CONCLUSIONS: In the full-thickness cranial bone graft group and the bone fragment group, the preservation of bone viability was obviously superior to the bone dust group and the periosteum-only group. In conclusion, bone dust behaved like the periosteum and could not create new bone, whereas bone particles behaved like the full-thickness cranial bone graft and were capable of preserving viability.

Prevention of retrosternal pericardial adhesions after cardiac surgery with mitomycin C.

BACKGROUND: Retrosternal pericardial adhesions may cause significant injuries to the heart and great vessels in cases that require reoperation. Fibroblast proliferation is one of the mechanisms for adhesion formation. Inhibition of fibroblast proliferation is important in reduction of retrosternal adhesions. Mitomycin C (MMC) is able to reduce fibroblast proliferation. We aimed to determine the effect of MMC on prevention of retrosternal pericardial adhesions after primary cardiac operations. METHODS: Thirty Sprague-Dawley female rats were used in the study. The rats were divided into two groups. First group was control (n=10) and second group was MMC study group (n=20). Xiphoid cartilage resection and retrosternal abrasion via subxiphoidal incision was performed. In the study group, MMC (1mg/kg) was topically applied to the retrosternal space. After 15 days, rats were taken into reoperation and adhesion was graded. Tissue and blood samples were taken before termination procedure. Standard staining procedures and fibroblast growth factor receptor 3 antibody staining, were applied immunohistochemically to tissue samples. RESULTS: The average adhesion scores of the control (n=10) and study (n=20) (MMC; 1mg/kg) groups were 2.50 ± 1.27 and 0.70 ± 0.86, respectively. The adhesion score of the study group was lower than the control group (p<0.05). Immunohistochemical samples revealed that tissue fibroblast intensity was significantly higher in the control group than the study group (p<0.05). There was no statistical significance between two groups in case of hydroxyproline levels (p>0.05). CONCLUSION: MMC was found to be effective in the prevention of retrosternal pericardial adhesions without any delay in normal tissue regeneration.

Effects of low-intensity pulsed ultrasound on bone formation after the expansion of the inter-premaxillary suture in rats: a histologic and immunohistochemical study.

BACKGROUND: Orthodontic maxillary expansion is a commonly-performed treatment approach to correct transverse maxillary deficiencies by separating the mid-palatal suture. To obtain a successful treatment result and prevent relapse, the expanded maxillary sutures require maintenance by means of qualified bone reorganisation. AIM: To assess the effects of low-intensity pulsed ultrasound (LIPUS) on sutural bone formation after the expansion of the interpremaxillary suture in rats. METHODS: Sixteen male Wistar rats, 6 to 8-week old, were used. The expansion appliance comprised a helical spring fabricated from 0.014 inch stainless steel wire (Dentaurum, Ispringen, Germany). The rats were divided into two equal groups and randomly assigned to the LIPUS treatment group or a sham-operation group. LIPUS was delivered via a 2.5 cm diameter ultrasound transducer (Exogen, Smith and Nephews, Inc., Memphis, TN, USA) for 20 minutes per day during 7 days of post-expansion retention. Following retention, the rats' maxillae were surgically removed and histologic and immunohistochemical specimens were prepared and examined. RESULTS: The number of osteoblasts and blood vessel dimensions in the ultrasound group increased but was not significant, compared with the control group. A statistically significant difference in osteocalcin, VEGF and TGF-ß immunoreactivities (p < 0.01) was found in the area of the mineralising tissue. Only VEGF immunoreactivity was significant between two groups (p < 0.01) in the fibrous tissue area. CONCLUSIONS: The area of mineralising tissue in the LIPUS-applied group expressed activity markers for osteocalcin, VEGF and TGF-ß compared with a surrounding area of fibrous tissue. Cellular activation in the LIPUS group was greater than that of controls. Therefore, LIPUS may be accepted as a useful approach to enhance sutural bone formation.

Comparison of the effects of aromatase inhibitors and tamoxifen on radiation-induced lung toxicity: results of an experimental study.

PURPOSE: The purpose of this study is to compare the effects of anastrozole, letrozole and tamoxifen on radiation-induced pulmonary fibrosis. METHODS: Eighty female Wistar albino rats were divided into eight groups. Group (G) 1 was defined as control group. G2 was radiation therapy (RT) only group. Groups 3, 4 and 5 were tamoxifen, anastrozole and letrozole control groups respectively. Groups 6, 7 and 8 were RT plus tamoxifen, anastrozole and letrozole groups, respectively. A single dose of 12 Gy RT was given to both lungs. Tamoxifen, anastrozole and letrozole were started 1 week before the RT and continued until the animals were sacrificed 16 weeks after the RT. As an end point, the extent of pulmonary fibrosis for each rat was quantified with image analysis of histological sections of the lung. Kruskal-Wallis and Mann-Whitney U tests were used for statistical analyses. RESULTS: The congestion, inflammation and pulmonary fibrosis scores were significantly different between all the study groups (p values were <0.001 for each). When compared with RT only group, concomitant RT and tamoxifen group increased the radiation-induced pulmonary fibrosis (p = 0.005). However, using either anastrozole or letrozole with RT did not increase the radiation-induced pulmonary fibrosis (p values were 0.768 and 0.752, respectively). CONCLUSION: Concomitant use of tamoxifen with RT seems to increase radiation-induced pulmonary toxicity. However, the use of both anastrozole and letrozole appears to be safe with concomitant RT, without increasing the risk of pulmonary fibrosis. This finding should be clarified with further clinical studies.

Amelioration of radiation-induced acute inflammation and mucosal atrophy by beta-hydroxy-beta-methylbutyrate, L-glutamine, and L-arginine: results of an experimental study.

PURPOSE: We aimed to evaluate the effects of ß-hydroxy-ß-methylbutyrate, L-glutamine, and L-arginine (HMB/Glu/Arg) on radiation-induced acute inflammation and mucosal atrophy in the oral mucosa. METHODS: Twenty-eight rats were divided into four groups. group (G) 1 was defined as control group, and G2 was the radiation therapy (RT) group. G3 and G4 were HMB/Glu/Arg control and 17 Gy RT plus HMB/Glu/Arg groups, respectively. A single dose of 17 Gy RT was given to the head and neck area, and the active supplement consisting of 5.2 g of HMB, 29.6 g arginine, and 29.6 g of glutamine which was equivalent to 60 kg adult dose was calculated for each rat and administrated orally. HMB/Glu/Arg started from the day of RT and continued until the animals were sacrificed 7 days after the RT. The extent of acute inflammation and mucosal atrophy for each rat was quantified with image analysis of histological sections of the oral mucosa. RESULTS: There were significant differences in terms of epithelial thickness, subepithelial edema, inflammation, and congestion between all groups (p values were <0.001, 0.003, <0.001, and 0.001 for each parameter, respectively). Using HMB/Glu/Arg alone led to hypertrophic changes in the epithelial layer. Moreover, when used with RT, HMB/Glu/Arg reversed radiation-induced epithelial atrophy (p, 0.006) and decreased radiation-induced inflammation at a significant level (p, 0.007). CONCLUSION: Concomitant use of HMB/Glu/Arg appears to ameliorate the radiation-induced acute inflammation and mucosal atrophy which represent the early phase of acute oral mucositis; however, this finding should be clarified with further clinical studies.

Efficacy of aprotinin treatment on bilateral blunt chest trauma created in rabbits.

OBJECTIVES: To investigate the effects of aprotinin, on blood gasses, oxidant-antioxidant status, and lung histopathology in an experimental bilateral blunt chest trauma model. METHODS: Conducted at the Experimental Animal Laboratory of Meram Medical School at Selcuk University, Konya, Turkey, the study comprised 21 New Zealand female albino rabbits who were divided into three groups.Trauma was applied on the sham and aprotinin groups, which was administered intravenous Aprotinin 20.000 U/kg. Arterial blood samples were obtained from all rabbits at hours 0, 3, 24, and 96. At hour 96 after trauma, all rabbits were sacrificed using the decapitation method, and then blood and lung tissue samples were obtained. Blood nitric oxide, malondialdehyde and blood gas measurements were made. Histopathological changes in the lung were examined with a light microscope. RESULTS: While no positive effect of aprotinin was observed on nitric oxide malondialdehyde and partial pressure of carbon dioxide values, it was seen to have an increasing effect on partial oxygen pressure level. Aprotinin had a partial effect on lung histopathology. CONCLUSION: Aprotinin was determined to have a positive effect on PO2 levels. We could not find any positive effects especially on alveolar haemorrhage.

The effect of hyaluronan combined with microfracture on the treatment of chondral defects: an experimental study in a rabbit model.

Because articular hyaline cartilage has low potential for regeneration, numerous methods and techniques have been proposed to induce the reparation process. Microfracture is a convenient procedure for this purpose. However, the quality of the new cartilage after microfracture is still not as proper as original. In this experimental study, we used microfracture in combination with intraarticular application of hyaluronan in rabbit knee articular defect. Bilateral knee arthrotomies, chondral defects, and microfracture were created on each intercondylar notch in thirty rabbits. Rabbits received intraarticular injections of hyaluronan once a week for 3 weeks in the right knee, started from 1 week after injury. The left knees, which served as controls, were injected with normal saline. Biopsy was taken from both knees at the 4th and 6th weeks. In comparison with the control group, after 6 weeks we observed a higher potential for healing in the experimental group, with thicker and more organized repair tissue filling the defect. The current study reveals that application of hyaluronan after the microfracture might be beneficial in inducing articular cartilage defect reparation.

A comparison of the application of fibrin glue and adhesive film for repair of anastomotic leaks in the rat.

BACKGROUND: Anastomotic leaks constitute one of the most serious intraoperative complications and although many studies have been devoted to finding a solution for this problem, none of them has yet been able offer a decisive, successful method. In this study, the ability of fibrin glue and adhesive film to repair anastomotic leaks in an experimental model was compared. MATERIALS AND METHODS: The sample comprised four groups of seven rats: Group 1 (Control): the distal colon was transected and anastomosis was performed. Group 2 (Primary repair): incomplete anastomosis produced a leak that was closed by primary repair on day 3. Group 3 (Fibrin glue): incomplete anastomosis produced a leak that was closed by primary repair and fibrin glue applied on day 3. Group 4 (Adhesive film): incomplete anastomosis produced a leak that was closed by primary repair and adhesive film was applied on day 3. The rats were sacrificed on day 6 following anastomosis. Anastomotic blast compressions were measured and fibroblast activation, inflammation, neovascularization and levels of collagen were evaluated. RESULTS: The results from Group 4 showed that blast compression values were high and statistically significantly increased over control values (p < 0.05). Inflammation in Group 2 was significantly higher than the other groups (p < 0.05). No significant differences were detected in the comparison of the groups regarding the other scoring criteria (p > 0.05). CONCLUSION: Adhesive film is more effective in reducing anastomotic leakage than fibrin glue.

Effects of simvastatin on bleomycin-induced pulmonary fibrosis in female rats.

Statins reduce cholesterol levels by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase and have a major place in the treatment of atherosclerotic disease. Recent studies have shown anti-inflammatory properties of statins. The purpose of this study was to evaluate the anti-inflammatory effect of simvastatin on bleomycin (BLM)-induced pulmonary fibrosis in rats. A total of 31 female Sprague-Dawley rats were divided into four groups: (1) intratracheal (IT) phosphate-buffered saline (PBS) + intraperitoneal (IP) PBS (n=7); (2) IT BLM + IP PBS (n=8); (3) IT BLM + low dose (LD) simvastatin (1 mg/kg daily, n=8); (4) IT BLM + high dose (HD) simvastatin (5 mg/kg daily, n=8). Simvastatin was administered IP for 15 days, beginning 1 day prior to IT BLM. The effect of simvastatin on pulmonary fibrosis was studied by measurements of IL-13, PDGF, IFN-γ, TGF-p1 levels in bronchoalveolar lavage (BAL) fluid and lung tissue hydroxyproline (HPL) content and by histopathological examination (Ashcroft score). BLM caused significant change in BAL fluid cytokine levels and increased both HPL content and histopathological score (p<0.001 for all). While LD simvastatin had no effect on cytokine levels, HD significantly reduced IL-13 (15.12 ±7.08 pg/ml vs. 4.43±2.34 pg/mL; p<0.05) and TGF-ß1 levels (269.25 ±65.42 pg/mL vs. 131.75±32.65 pg/mL; p<0.05). Neither HD nor LD simvastatin attenuated HPL content or Ashcroft score. In conclusion, this study showed that LD simvastatin had no effect on a BLM-induced pulmonary fibrosis model, while the high dose caused partial improvement in profibrotic cytokine levels.

Evaluation of patients with Behçet's disease by cervical cytology and colposcopic examination.

PURPOSE: We evaluated the genital involvement in women with Behçet's disease (BD) by cervical cytology and colposcopy, and compared these findings with healthy controls. METHODS: A total of 152 women were referred to the Gynecology Clinic of Meram School of Medicine between March 2008 and December 2009. The study group was composed of 78 women with BD, and the control group included 74 healthy women admitted for routine gynecologic examination. These patients were subjected to cervical cytology and colposcopic examination. Cervical biopsy was performed in cases with abnormal cytology. These findings and some gynecologic complaints were compared. RESULTS: The demographic features were similar between each group. Genital involvement (scar + ulcer) was detected in 58 (74.3%) patients. The most common sites of ulcers (55.1%) and scars (7.6%) were the labia majora. Abnormal cytology in study and control groups was detected in nine (11.5%) and three (4%) of the patients, respectively, and a slight statistical significance was obtained (p = 0.048). Acetowhite and iodine-negative epithelium were higher in the study group than in controls (p = 0.015 and p = 0.042). Dyspareunia was higher in BD patients (p = 0.001). CONCLUSION: Patients with BD are more prone to having an abnormal cervical cytology and acetowhite and iodine-negative epithelium on colposcopic examination. However, these findings are mostly benign conditions. The complaint of dyspareunia should be considered during treatment of female patients with BD.

Serum intestinal fatty acid binding protein and phosphate levels in the diagnosis of acute intestinal ischemia: an experimental study in rabbits.

BACKGROUND: Acute intestinal ischemia is a serious clinical disorder with mesenteric infarction, which has high mortality. It is important to establish a biochemical marker for the early diagnosis of acute intestinal ischemia. OBJECTIVES: The aim of this experimental study was to assess the changes in the serum levels of intestinal fatty acid binding protein (IFABP) and phosphate by time using the acute intestinal ischemia model in rabbits. METHODS: In this study, 21 New Zealand rabbits were randomly divided into three groups. Blood samples were obtained at 0, 1, 3, and 6 h in the control group. Blood samples were obtained at 0, 1, 3, and 6 h in the sham group after simple laparotomy. Blood samples were obtained at the same hours in the ischemia group after simple laparotomy and ligation of the superior mesenteric artery. RESULTS: There was no significant difference between the control, the sham, and the ischemia groups in terms of serum IFABP levels at any time (p > 0.05). Serum phosphate levels significantly increased in the ischemia group (p < 0.001). Studies on IFABP have begun emerging in the literature, and there is no standard approach for the technique to measure the IFABP level. No studies on IFABP were found in the literature on rabbits. CONCLUSION: Based on our results, the role that IFABP levels play in the diagnosis of acute intestinal ischemia is unclear at this time. Serum phosphate levels continued to rise as the duration of ischemia was prolonged. These findings support the suggestion that serum phosphate levels are valuable for the diagnosis of acute intestinal ischemia.

The effects of botulinum toxin A and papaverine on human saphenous vein and internal mammary artery grafts: an in vitro study.

Introduction: Autologous saphenous vein (SV) and internal mammary artery (IMA) are used as bypass conduits during coronary artery bypass graft surgery. Vasospasm of the arterial and venous grafts may constitute a significant clinical problem. Pretreatment with a vasodilator drug of the graft ex vivo or intraluminal injection before implantation may be used for spasm prophylaxis. This in vitro study was designed to assess the vasoactive effects and time-dependent changes of botulinum toxin A (BTX-A) and papaverine pretreatment on vasospasm of human SV and IMA grafts. Also, histomorphology of the vessels was assessed. Material and methods: SV and IMA segments were suspended in organ baths, and isometric contraction responses to 2 different concentrations of 5-hydroxytryptamine (5-HT) and endothelin-1 (ET-1) were recorded after incubation with 2 different concentrations of BTX-A and papaverine at 2 time points (0 h and 2 h). Results: The results revealed the following: 1) incubation with BTX-A and papaverine relaxes both SV and IMA rings contracted with 5-HT and ET-1; 2) the duration of the relaxant effect of BTX-A lasts longer than papaverine; and 3) no apparent histomorphological changes were observed in the grafts under light microscopy. Conclusions: This study demonstrates that in human SV and IMA grafts, pretreatment with both BTX-A and papaverine are safe and have a potent inhibitory effect depending on the vessel and vasoconstrictor agent. The long-lasting vasodilatory effect of BTX-A on vascular smooth muscle may provide promising results in the prevention of venous and arterial graft spasm.

Anti-inflammatory and anti-fibrotic effects of sirolimus on bleomycin-induced pulmonary fibrosis in rats.

PURPOSE: Pulmonary fibrosis is a devastating disease with a poor prognosis. Although the diagnosis and pathophysiology of this disease have been better characterized over the past few years, there is no effective therapy for the disease. The aim of this study was to evaluate the anti-inflammatory and anti-fibrotic effects of sirolimus (SRL), which is a potential anti-fibrotic agent, by using bleomycin (BLM)-induced pulmonary fibrosis model in rats. METHODS: A single intra-tracheal injection of BLM (2.5 U/kg) was administered and sirolimus (2.5 mg/kg/day) was given orally, beginning either one day before (early SRL) or nine days after (late SRL) the BLM administration. The effect of SRL on fibrosis was studied by analysis of cytokine levels in BAL fluid, measurement of lung tissue hydroxyproline (HPL) content and histopathological examination. RESULTS: Both early and late SRL administrations caused a decrease in the levels of IL-13, PDGF-A and TGF-ß1 (p=0.001) and an increase in IFN-γ levels (p=0.001) in BAL fluid. Early and late SRL also caused a decrease in HPL content (p=0.001). Early sirolimus caused a significant decrease in fibrosis score (p=0.001), while late SRL did not. CONCLUSION: Sirolimus was effective in BLM-induced pulmonary fibrosis model, especially in the early phases of the disease.