Effects of polymer-based, silver nanoparticle-coated silicone splints on the nasal mucosa of rats.

Infection is a serious complication after nasal packing that otolaryngologists seek to avoid. The aim of this study is to investigate the use of silver (Ag) nanoparticle, which serves as antimicrobial agents, with nasal tampons. The study design is an experimental animal model and the setting is tertiary referral center. Twenty-four rats were randomized into the following four groups: (1) control group (n = 6); (2) silicone nasal splint (SNS) group (n  =  6); (3) polypropylene-grafted polyethylene glycol (PP-g-PEG) amphiphilic graft copolymer-coated SNS group (n  =  6); and (4) Ag nanoparticle-embedded PP-g-PEG (Ag-PP-g-PEG) amphiphilic graft copolymer-coated SNS group (n  =  6). These tampons were applied to rats for 48 h, after which they were removed in a sterile manner, and the rats were sacrificed. The nasal septa of the rats were excised, and assessments of tissue changes in the nasal mucosa were compared among the groups. The removed tampons were microbiologically examined, and quantitative analyses were made. When the groups were compared microbiologically, there were no significant differences in bacterial colonization rates of coagulase-negative Staphylococcus spp. among the three groups (p = 0.519), but there was a statistically significant difference among bacterial colonization rates of Heamophilus parainfluenzae and Corynebacterium spp. (p = 0.018, p = 0.004). We found that H. parainfluenzae grew less robustly in the Ag-PP-g-PEG than the PP-g-PEG group (p = 0.017). However, we found no significant difference between the Ag-PP-g-PEG and SNS groups, or between the SNS and PP-g-PEG groups. The growth of Corynebacterium spp. did not differ significantly between the Ag-PP-g-PEG and SNS groups (p = 1.000). When Group 4 was compared with Group 2, the former showed less inflammation. Compared with other tampons, Ag-PP-g-PEG amphiphilic graft copolymer-coated silicone nasal tampons caused less microbiological colonization and inflammation. Therefore, the use of these tampons may prevent secondary infections and reduce the risk of developing complications by minimizing tissue damage.

The effects of ketamine, midazolam and ketamine/xylazine on acute lung injury induced by α-naphthylthiourea in rats.

OBJECTIVES: Ketamine is a drug used in human and veterinary medicine, primarily for the induction and maintenance of general anesthesia, analgesia (particularly in emergency medicine), and treatment of bronchospasm. Midazolam is the preferred drug in intensive care units for sedation and anesthesia. Ketamine/xylazine combination is used as an anesthetic agent in veterinary medicine and experimental animals. Aside from anaesthetic properties, these agents can cause physiologic and metabolic alterations and modulate and improve the inflammatory responses. The objective of the present study was to investigate the effects of ketamine, midazolam, and veterinary and experimentally used ketamine/xylazine combination in acute lung injury induced by α-naphthylthiourea (ANTU). MATERIAL AND METHODS: ANTU was injected intraperitoneally (i.p.) in rats at the dose of 10 mg/kg. Ketamine (15, and 50 mg/kg, i.p.), midazolam (2 and 4 mg/kg, i.p.), and ketamine/xylazine (50/10 mg/kg, i.p.) administered to rats 30 min prior to ANTU. Four hours later, the lung weight/body weight (LW/BW) ratio and pleural effusion (PE) were measured. Histopathological changes were documented in each lung tissue, including intra-alveolar hemorrhage, alveolar edema and inflammation. The severity of the lung injury was scored (0-3). RESULTS: Ketamine, midazolam and ketamine/xylazine had a significant prophylactic effect on pleural effusion formation at all doses and significantly reduced pleural effusion. Ketamine caused a significant reduction of inflammation, hemorrhage and edema scoring and midazolam (2 mg/kg) and ketamine/xylazine caused a significant reduction of inflammation and edema scoring. CONCLUSIONS: It can be concluded that ketamine and midazolam may attenuate lung injuries induced by ANTU. In addition to their anesthetic or sedative properties, the prophylactic effects of these agents on lung tissue damage will contribute to the treatment of intensive care unit diseases including acute lung injury. Similarly, the effects of these agents on lung pathophysiology should be considered in experimental applications.

Histopathologic evaluation of anti-ulcerogenic effect of montelukast in indomethacin-induced experimental ulcer model.

BACKGROUND/AIMS: The effects of anti-ulcerogenic drugs are dependent on the increase in prostaglandin production and reduction in leukotriene production in the gastric mucosa. Montelukast is an anti-asthmatic drug, a selective reversible cysteinyl leukotriene D4 receptor antagonist. In this study, we aimed to evaluate the anti-ulcerogenic effect of montelukast and to investigate the relationship between its anti-ulcerogenic effect and polymorphonuclear leukocyte infiltration in the gastric tissues. MATERIALS AND METHODS: Male Sprague-Dawley rats were separated into five groups. Distilled water (control group), famotidine (40 mg/kg), and montelukast (5, 10 and 20 mg/kg) were given orally (gavage). Thirty minutes later, indomethacin (25 mg/kg) was administered to all the groups. Six hours later, the animals were sacrificed by decapitation. The ulcer indexes for each stomach and the ulcer inhibition rates for each group were calculated, and the stomachs were later evaluated histopathologically (polymorphonuclear leukocyte infiltration). RESULTS: Ulcer inhibition rates were as follows: famotidine 96.14% and montelukast 59.96%, 72.65% and 76.97% (5, 10 and 20 mg/kg, respectively). Montelukast (10 and 20 mg/kg) showed effects similar to those of famotidine histopathologically. CONCLUSIONS: In this study, it was observed that there was a relationship between the anti-ulcerogenic effect of montelukast and polymorphonuclear leukocyte infiltration in the gastric mucosa, and montelukast behaved as an anti-ulcerogenic drug both macroscopically and microscopically.

Effects of ozone oxidative preconditioning on liver regeneration after partial hepatectomy in rats.

AIM: Similar protective effect of ischemic and ozone oxidative preconditioning (OzoneOP) in hepatic ischemia-reperfusion (I/R) injury was demonstrated, providing evidences that both preconditioning settings shared similar biochemical mechanisms of protection. We investigated the effects of OzoneOP on liver regeneration after 70% partial hepatectomy (PHx) in rats. METHODS: Rats were divided into three groups: PHx, I/R + PHx, and OzoneOP + I/R + PHx groups. Ozone (intraperitoneal, 1.2 mg/kg) was given to rats subjected to I/R and 70% hepatectomy daily five times before operation. At 24 hr and 48 hr after resection, samples were collected for the measurement of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6). Moreover, liver regeneration rate, proliferating cell nuclear antigen (PCNA) labeling index, mitotic index, and histopathological examination were evaluated. RESULTS: OzoneOP reduced liver injury determined by liver histology and serum transaminases. There was a rise in serum TNF-α and IL-6 levels in the I/R + PHx group whereas OzoneOP significantly decreased the rise in the level of TNF-α but not IL-6 on the 24 hr and 48 hr of reperfusion. Moreover, liver regeneration in OzoneOP + PHx group, as assessed by the regenerated liver weight, mitotic, and PCNA-labeling index, was significantly improved when compared to I/R + PHx group. CONCLUSION: These results suggest that OzoneOP ameliorates the hepatic injury associated with I/R and has a stimulatory effect on liver cell regeneration that may make it valuable as a hepatoprotective modality.

Effects of peripheral benzodiazepine receptor ligand Ro5-4864 in four animal models of acute lung injury.

BACKGROUND: Acute lung injury (ALI) is a syndrome of inflammation and increased permeability of the blood-gas barrier. It is associated with high morbidity and mortality. Despite intensive research, treatments remain limited. The aim of the present study was to investigate the protective efficacy of a specific peripheral benzodiazepine receptor ligand, Ro5-4864, in experimental models of ALI in rats. METHODS: ALI was generated by four different methods: (1) intravenous (tail vein) injection of Escherichia coli (0111:B4) lipopolysaccaride (LPS), (2) cecal ligation and puncture (CLP), (3) mesenteric ischemia/reperfusion, and (4) intraperitoneal injection of α-naphthylthiourea (ANTU). Ro5-4864 was administered to rats intraperitoneally 30 min before ANTU and LPS administration or intravenously 15 min before reperfusion and CLP. The levels of pulmonary edema (lung weight/body weight ratio) and pleural effusion were measured, and the severity of ALI was scored (0-3). RESULTS: Ro5-4864 showed a dose-dependent and significant prophylactic effect on the ANTU-induced lung weight/body weight and pleural effusion/body weight ratios and histopathologic scores. Ro5-4864 also showed significant prophylactic effects against the LPS-induced lung weight/body weight ratio and histopathologic scores. Ro5-4864 significantly decreased the intra-alveolar edema and perialveolar hemorrhage scores in the CLP group. However, we found no prophylactic effect of Ro5-4864 on mesenteric ischemia/reperfusion-induced ALI at the dose used (2 mg/kg intraperitoneally). CONCLUSIONS: These results have demonstrated, for the first time, a protective effect of Ro5-4864 on experimental ALI induced by ANTU, LPS, and CLP. Ro5-4864 might be a useful therapeutic agent for lung diseases, including ALI, in intensive care patients.

Clinicopathological significance of fascin and CD44v6 expression in endometrioid carcinoma.

BACKGROUND: Fascin and CD44v6 may have significant roles as biomarkers in tumour progression and metastasis. In endometrioid carcinomas, the fascin expression profile is less defined, and the significance of CD44v6 is uncertain. We aimed to investigate the expressions of both fascin and CD44v6 in endometrioid carcinomas and to evaluate their inter-relation with clinicopathological parameters. METHODS: Fascin and CD44v6 expressions were evaluated, individually and in combination, in a series of 47 endometrioid carcinomas and 10 proliferative endometrium samples. The staining extent and intensity of both markers in tumour cells were scored semiquantitatively. The relationship between immunoexpressions and clinicopathological variables was assessed. RESULTS: The expression rates of fascin and CD44v6 in endometrioid carcinoma were 72.34% and 46.80%, respectively. Although these expression rates were higher than those in proliferative endometrial samples, fascin expression showed a statistically significant difference from the normal group (p = 0.02), but CD44v6 did not differ (p = 0.54). Fascin expression was significantly correlated with tumour grade (p = 0.003) and neural invasion (p = 0.036) in a univariate analysis. In contrast, no significant correlation was found between CD44v6 and any of the clinicopathological parameters. CONCLUSIONS: Our findings suggest that fascin might be an independent prognostic indicator in the different steps of extracellular matrix invasion. On the other hand, CD44v6 was not a predictive factor in endometrioid cancer. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8511594927206899.

Protective effect of dexmedetomidine in a rat model of α-naphthylthiourea-induced acute lung injury.

BACKGROUND: We assessed the effects of dexmedetomidine in a rat model of α-naphthylthiourea (ANTU)-induced acute lung injury. METHODS: Forty Wistar Albino male rats weighing 200-240 g were divided into 5 groups (n = 8 each), including a control group. Thus, there were one ANTU group and three dexmedetomidine groups (10-, 50-, and 100-µg/kg treatment groups), plus a control group. The control group provided the normal base values. The rats in the ANTU group were given 10 mg/kg of ANTU intraperitoneally and the three treatment groups received 10, 50, or 100 µg/kg of dexmedetomidine intraperitoneally 30 min before ANTU application. The rat body weight (BW), pleural effusion (PE), and lung weight (LW) of each group were measured 4 h after ANTU administration. The histopathologic changes were evaluated using hematoxylin-eosin staining. RESULTS: The mean PE, LW, LW/BW, and PE/BW measurements in the ANTU group were significantly greater than in the control groups and all dexmedetomidine treatment groups (P < 0.05). There were also significant decreases in the mean PE, LW, LW/BW and PE/BW values in the dexmedetomidine 50-µg/kg group compared with those in the ANTU group (P < 0.01). The inflammation, hemorrhage, and edema scores in the ANTU group were significantly greater than those in the control or dexmedetomidine 50-µg/kg group (P < 0.01). CONCLUSION: Dexmedetomidine treatment has demonstrated a potential benefit by preventing ANTU-induced acute lung injury in an experimental rat model. Dexmedetomidine could have a potential protective effect on acute lung injury in intensive care patients.

Effect of the endothelin receptor antagonist tezosentan on alpha-naphthylthiourea-induced lung injury in rats.

Acute lung injury is an inflammatory syndrome that increases the permeability of the blood-gas barrier, resulting in high morbidity and mortality. Despite intensive research, treatment options remain limited. We investigated the protective efficacy of tezosentan, a novel, dual endothelin receptor antagonist, in an experimental model of alpha-naphthylthiourea (ANTU)-induced acute lung injury in rats. ANTU was intraperitoneally (i.p.) injected into rats at a dose of 10 mg/kg. Tezosentan was injected 30 minutes before ANTU was subcutaneously (s.c.) injected at doses of 2, 10, or 30 mg/kg, 60 minutes before ANTU was injected at doses of 2, 10, or 30 mg/kg (i.p.), and 90 minutes before ANTU at a dose of 10 mg/kg (i.p.). Four hours later, the lung weight/body weight (LW/BW) ratio and pleural effusion (PE) were measured. When injected 30 minutes before ANTU at doses of 2, 10, or 30 mg/kg (s.c.), tezosentan had no effect on lung pathology. When injected 60 minutes before ANTU at doses of 2, 10, or 30 mg/kg (i.p.) or 90 minutes before ANTU (10 mg/kg, i.p.), tezosentan significantly decreased the PE/BW ratio and had a prophylactic effect on PE formation at all doses. Therefore, tezosentan may attenuate lung injury. Furthermore, its acute and inhibitory effects on fluid accumulation were more effective in the pleural cavity than in the interstitial compartment in this experimental model.

The presence of oxidized low-density lipoprotein and inducible nitric oxide synthase expression in renal damage after intestinal ischemia reperfusion.

Intestinal ischemia/reperfusion (I/R) is a complex phenomenon that causes destruction of both local and remote tissues. The objective of this study was to investigate the possible participation of oxidized low-density lipoproteins (oxLDLs) and inducible nitric oxide synthase (iNOS) expression in renal tissue damage after intestinal I/R. The superior mesenteric artery was blocked for 30 minutes, followed by 24 hours of reperfusion. At the end of the reperfusion period, renal tissues were removed; the presence of oxLDL, superoxide dismutase enzyme activity, malondialdehyde levels, and iNOS expression were evaluated. I/R resulted in positive oxLDL staining in renal tissue. Compared with control rats, tissue from the I/R group showed significantly higher malondialdehyde levels and lower superoxide dismutase enzyme activity. Strong and diffuse iNOS expression was present in the I/R group. Our findings support the hypothesis that I/R of intestinal tissue results in oxidative and nitrosative stress and enhances lipid peroxidation in the end organ. These data show that oxLDL accumulates in rat renal tissue after intestinal I/R. Antioxidant strategies may provide organ protection in patients with reperfusion injury, at least by affecting interactions with free radicals, nitric oxide, and oxLDL. This study demonstrates for the first time that oxLDL may play a role in renal tissue damage after intestinal I/R. Antioxidant strategies may be beneficial for protection from reperfusion injury.

Malignant melanoma associated with congenital melanocytic nevus and diagnosed with intestinal metastases: Two case reports.

Congenital melanocytic nevi are hamartomatous lesions that develop from the neural crest and arise during odontogenesis. In this report, we present two malignant melanoma cases developed from congenital melanocytic nevi and revealed by gastrointestinal system metastases. The first case was a 71-year-old female who presented with pleural and peritoneal effusion and underwent biopsy due to detection of nodular lesions in the duodenum by endoscopic examination. The second case was a 36-year-old male patient who presented with abdominal pain in whom segmental ileal resection was performed due to mass lesions causing invaginations in the ileum. Histopathological examination of the lesions showed a diffuse neoplastic infiltration comprising the entire mucosal layers. In neoplastic cells having a marked atypia and pleomorphism, immunoreactions with S-100, HMB-45, and Melan A were detected. Both cases were diagnosed as malignant melanoma. Abdominal skin in the first case and the femoral region in the second case exhibited congenital melanocytic nevi, and those lesions were determined to show a transformation towards malignant melanoma in the histopathological studies. Malignant melanoma development in gastrointestinal system may have a primary or metastatic character. Definitive diagnosis always requires detailed clinical, histopathological and immunohistochemical analyses.

The effect of the Botulinum toxin-A on craniofacial development: an experimental study.

In this study, we developed a novel experimental model to evaluate muscular action on bone formation and remodeling by the help of Botulinum toxin-A (BTX). Forty-nine 15-day-old male Wistar rats were put into 4 groups randomly. Group 1 was the control group. BTX 0.4 IU (0.05 mL) was injected into the right masseter muscle in group 2 and into right temporalis muscle in group 3. The same volume of sterile saline was given into the both above-mentioned muscles in group 4. At the end of the fourth month, all animals were killed. Histology and weight of the masseter and temporalis muscles were studied. Thirty different osteometric measurements were also taken from skulls. Significant atrophy in BTX injected muscles was observed in groups 2 and 3. In group 4 (saline injection), only few osteometric measurements were significantly reduced, indicating the effect of the injection itself. Both groups 2 and 3 have apparent decrease in nasal bone, premaxilla, maxilla, and zygomatic dimensions on the injected side. When masseter group was compared with control and saline groups, no significant difference was found in skull base dimensions and mandibular length. In contrast, temporal group has also shown significant decrease in skull base dimensions. Our conclusions are as follows: (1) With this model, it is possible to study muscular action on bone formation and modeling without any surgical intervention, that is, by avoiding surgical artifacts, such as scar and contracture; (2) denervation of the skeletal muscles with BTX during the growing phase does effect bone development in a negative way; (3) pediatric use of the BTX deserves reevaluation under the light of these findings.

Classic Kaposi sarcoma with sarcoid-like granulomas: a case report and literature review.

The occurrence of granulomatous reactions within lymph nodes that drain carcinomas is well known but uncommon. Even more rarely, granulomas may occur within the stroma of tumors. These lesions, called sarcoid-like reactions, commonly accompany carcinomas but are very rare in sarcomas. This study presents a case of classic Kaposi sarcoma that contained sarcoid-like granulomas, with a literature review. A soft tissue lesion of the foot was excised from a 74-year-old male. Histopathological examination showed that the tumor tissue consisted of spindle cells, areas of atypical vascular proliferation, and extravasated erythrocytes surrounded by non-caseating granulomas. The patient had no clinical or laboratory findings of sarcoidosis. The case was interpreted as "Kaposi sarcoma containing sarcoid-like granulomas". The association of soft tissue sarcomas with a granulomatous reaction is very rare. A granulomatous reaction is reported to be a good prognostic indicator in several carcinoma types, although its importance in sarcomas is unclear.

Low-density lipoproteins oxidized after intestinal ischemia/reperfusion in rats.

BACKGROUND: Intestinal ischemia/reperfusion (I/R) is a complex phenomenon causing destruction of both local and remote tissues, as well as multiple-organ failure. We investigated the role of lipid peroxidation in damage to intestinal, liver, and lung tissues in this pathology. MATERIALS AND METHODS: The superior mesenteric artery was blocked for 30 min followed by 24 h of reperfusion. Tissues were removed and the presence of oxidized LDL, the activities of the superoxide dismutase enzyme, malondialdehyde levels, and inducible nitric oxide synthase expression were each evaluated in the intestinal, liver, and lung tissues. RESULTS: While there was no staining in the control group tissues, ischemia/reperfusion resulted in positive oxidized LDL staining in all of the I/R test group tissue samples. Inducible nitric oxide synthase expression was significantly increased in the ischemia/reperfusion group tissues. Compared with those of the control group rats, the ischemia/reperfusion group tissues showed significantly higher malondialdehyde levels and lower superoxide dismutase activities. CONCLUSIONS: This study demonstrated for the first time that oxidized LDL accumulated in the terminal ileum, liver, and lung tissues after intestinal ischemia/reperfusion. This occurrence (or the presence of oxidized LDL) may be an indicator of ongoing oxidative stress and enhanced lipid peroxidation. Augmentation of inducible nitric oxide synthase expression may play a role in progression of inflammation and LDL oxidation. These data support the hypothesis that cellular oxidative stress is a critical step in reperfusion-mediated injury in both the intestine and end organs, and that antioxidant strategies may provide organ protection in patients with reperfusion injury, at least through affecting interaction with free radicals, nitric oxide, and oxidized LDL.

Expression of adhesion molecules in first trimester spontaneous abortions and their role in abortion pathogenesis.

BACKGROUND: Early placental development is associated with complex regulatory mechanisms, and molecular communication problems that arise during the developmental process are dangerous for continuation of the pregnancy. As studies on the process of invasion and migration of trophoblast cells have shown the importance of cell-cell and cell-matrix interactions, we examined the effects of adhesion molecules on the mechanism(s) of spontaneous abortions and compared them to elective abortion materials using histopathological and immunohistochemical methods. To the best of our knowledge, this is the first study to investigate adhesion molecules in spontaneous abortions. METHODS: Curettage materials from abortions were examined retrospectively in the Department of Pathology, Zonguldak Karaelmas University School of Medicine, Zonguldak, Turkey. CD31/PECAM-1 (endothelial cell marker), CD44v (variant 3), E-cadherin, CD54/ICAM-1, and CD106/VCAM-1 expression profiles were evaluated by immunohistochemistry, and cellular localization was determined under light microscopy. The results of spontaneous abortions were compared to those of elective abortions. RESULTS: The staining percentages of CD31, CD44, CD106, and E-cadherin decreased in cases of spontaneous abortion, but CD54 (ICAM-1) expression increased. Statistically significant differences were detected between spontaneous and elective abortion materials with regard to cytotrophoblasts (CTs), syncytiotrophoblasts (STs), and extravillous trophoblasts (EVTs) with the anti-CD31 antibody (p=0.0001). In addition, CD54 (p=0.007 and p=0.002) and E-cadherin (p=0.002 and p=0.02) expression in CTs and STs, respectively, were significantly different. Furthermore, CD44 expression (p=0.003) in decidual (D) cells and CD106 (p=0.0001) expression in vessels of endometrial (E) and villous tissues were also significantly different. CONCLUSIONS: Decreased CD31 expression in CTs that invade the spiral arterioles and mimic E cells in spontaneous abortion cases suggests that CD31/PECAM-1 is an important molecule in uteroplacental adequacy. Moreover, diminished expression of CD44 in D cells caused impaired stroma-villous connections. Enhancement of ICAM-1 in placental and invading STs may be useful as a diagnostic marker for patients who may have a tendency to have spontaneous abortions. A down-regulation of E-cadherin was observed, which may be responsible for impaired CT differentiation and loss of the pregnancy. Furthermore, decreased VCAM-1 expression in spontaneous abortions may be consistent with the importance of VCAM-1 in trophoblast-endothelial cell interactions. Many adhesion molecules are known to be effective in the normal development of a pregnancy, and the analysis of adhesion molecules in spontaneous abortions will provide useful information for clarifying the physiopathology of spontaneous abortions.