The Effect of the iNOS Inhibitor S-Methylisothiourea and Hyperbaric Oxygen Treatment on Radiation Colitis in Rats.

INTRODUCTION: External radiotherapy is one of the main treatment modalities for a variety of malignancies. However, the lower gastrointestinal tract is sensitive to the ionizing radiation. Hyperbaric oxygen treatment (HOT) has been suggested as a viable treatment for refractory radiation colitis, but the effect of S-Methylisothiourea (SMT) in the radiation colitis have not reported. To investigate the effect of SMT, HOT and the combination of both in an acute radiation-induced enterocolitis model. METHODS: Sixty Sprague-Dawley rats were divided randomly into five equal groups. A single dose of gamma irradiation (25 Gy) was administered through the colorectal region to anesthetized rats. In the control group, we applied 2 ml of saline solution intraperitoneally for five days. In the HOT group, 100-per-cent oxygen at 2.5 atm pressure was applied for five days. In the SMT group, 10 mg/kg/day of SMT was applied intraperitoneally for five days. In the HOT+SMT group, HOT and SMT were both applied in the same dosages as in the preceding two groups. At the end of five days, the rats were sacrificed and colon samples were collected for histological grading. Blood samples were collected to test for : tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), IL-1ß, transforming growth factor-ß (TGF-ß) and intercellular adhesion molecule-1 (ICAM-1) mRNA. RESULTS: The TNF-α, IL-1ß, IL-10 and TGF-ß levels were reduced by SMT, HOT and HOT+SMT applications (p < 0.05). However ICAM-1 mRNA levels were not significantly lower (p:0.19). The microscopic scores differed significantly between the SMT, HOT and HOT+SMT groups and the control group. There was significant improvement histologically, especially in the HOT+SMT group. When we compared the weight of the rats before and after the study, weight loss was significantly lower in the SMT, HOT and HOT+SMT groups compared with the control group (p < 0.05). CONCLUSION: HOT and SMT together were significantly more effective in preventing weight loss and in reducing inflammation and the severity of colitis histology when compared with HOT and SMT separately.

The relation between oxidative stress, inflammation, and neopterin in the paraquat-induced lung toxicity.

Paraquat (PQ) is a well-known quaternary nitrogen herbicide. The major target organ in PQ poisoning is the lung. Reactive oxygen species (ROS) and inflammation play a crucial role in the development of PQ-induced pulmonary injury. Neopterin is synthesized in macrophage by interferon γ and other cytokines. We aimed to evaluate the utility of neopterin as a diagnostic marker in PQ-induced lung toxicity. Sprague Dawley rats were randomly divided into two groups (sham and PQ), administered intraperitoneally 1 mL saline and PQ (15 mg/kg/mL) respectively. Blood samples and lungs were collected for analyses. Lung injury and fibrosis were seen in the PQ group. Serum total antioxidant capacity, lactate dehydrogenase (LDH), and lung transforming growth factor-1ß (TGF-1ß) levels were significantly higher than the sham group (in all, p < 0.001). In addition, in the PQ group, serum neopterin and lung malondialdehyde (MDA) levels were also significantly higher than the sham group (in all, p = 0.001). Serum neopterin levels were correlated with LDH activities, lung MDA, lung TGF-1ß levels, and the degree of lung injury. These findings demonstrated that oxidative stress, reduction of antioxidant capacity, and inflammation play a crucial role in the PQ-induced lung injury. Elevated serum neopterin levels may be a prognostic parameter to determine extends of PQ-induced lung toxicity. Further studies may be performed to clarify the role of neopterin by different doses of PQ.

Effect of resveratrol on bone formation in the expanded inter-premaxillary suture: early bone changes.

OBJECTIVE: The aim of this study was to evaluate the effects of local resveratrol (RSVL) administration on bone formation in response to expansion of the inter-premaxillary suture, in rats. MATERIAL AND METHODS: Twenty 50- to 60-day-old male Wistar rats were separated into two equal groups. Both groups were subjected to expansion, and 30 cN of force was applied to the maxillary incisors with helical-spring. Twenty-four hours after appliance placement, single-dose 10 µmol/kg RSVL in the dimethylsulfoxide (DMSO) was injected to the inter-premaxillary suture in the experimental group. In the control group, the same amount of DMSO was injected to the suture of rats. Bone formation in the suture was evaluated histomorphometrically. The area of new bone (µm(2)), the perimeter around the new bone (µm), Feret's diameter (µm), the percentage of new bone to non-ossified tissue (%), and the number of osteoblast were measured and compared. Mann-Whitney U-test was used for statistical evaluation at p < 0.05 level. RESULTS: Statistically significant differences were found between the groups for all histomorphometric parameters. New bone area (p < 0.001), bone perimeter (p < 0.001), Feret's diameter (p < 0.001), percentage of new bone (p < 0.001), and the number of osteoblast (p < 0.001) were significantly larger in the experimental group when compared with the control. Bone histomorphometric measurements revealed that bone architecture in the RSVL treated rats was improved. CONCLUSIONS: Local application of RSVL during the early stages to orthopedically expanded inter-premaxillary suture area may stimulate bone formation and shorten the retention period, in rats.

The effect of gained experience on postoperative complications and mortality in cadaveric liver transplantation: a single-center experience.

AIM: Liver transplantation (OLT) has become the treatment of choice for end-stage liver failure, as well as for selected cases of malignancies and metabolic disorders. Decreased postoperative complications and mortality rates are expected to correlate with improvements in the interdisciplinary team approach, the perioperative anesthesiologic and intensive care management, and careful follow-up after transplantation. In this study, we have evaluated the effect of gained experience on postoperative complications and mortality in cadaveric OLT performed in our institution. MATERIALS AND METHODS: Data from cadaveric OLT patients (n = 34) since 2003 were retrospectively evaluated. Patients were divided into 2 groups: Early (2003-2006; n = 15) and late (2007-2010; n = 19). Age, gender, cold and warm ischemia times, intraoperative transfusion rates, infectious complications, biliary and vascular complication rates, and early and late postoperative mortality rates were compared in the 2 groups. RESULTS: The age and gender distribution was similar among both groups. Mean cold and warm ischemia times, intraoperative transfusion rates, and operative times were significantly lower in the late period group (P = .004, .012, and 0.008, respectively; CI=%95). T-tube usage was also significantly lower in the late period group (P < .001). There was no significant change for postoperative intensive care period (P = .404), but the overall length of stay in hospital was shorter for the patients in the late period group (P = .019). The nonsurgical early postoperative complication rate was lower (P = .001) and early postoperative mortality was nearly significant (P = .06) in patients who comprised the late period group. There was no difference in terms of biliary and vascular complication rates and overall survival rates between patients in the early and late groups (P = .664, .264, and .107, respectively). CONCLUSION: Our results indicate that the institutional improvements toward an interdisciplinary team approach in cadaveric OLT correlate with better results in ischemia and operative times and lower intraoperative transfusion rates and hospital stays. Early postoperative complication and mortality rates were found to decline in parallel to the team experience.

Anti-apoptotic and growth-promoting markers in adult medulloblastomas.

AIM: the aim of this study was to investigate the pathologic features, proliferation potential and expression of some anti-apoptotic and growth-promoting markers in adult medulloblastomas. METHOD: we analyzed the immunohistochemical expression of survivin, c-KIT, Bcl-2, fascin, p-53 and Ki-67 in 18 adult medulloblastomas (> 16 years of age). RESULTS: study included 14 males and 4 females (mean age: 22.9 ± 8.2). 14 cases were classical, 2 desmoplastic/nodular and 2 large cell medulloblastomas. Moderate-to-high nuclear survivin expression was observed with high percentages (55 - 100%) in all medulloblastomas while Bcl-2 was mildly positive in only 1 case. Interestingly, mild-to-moderate cytoplasmic c-KIT expression was demonstrated in 16 cases (89%) without membranous accentuation. Fascin expression was observed in 13 medulloblastomas (72%), 9 of which showing moderate to high immunoreactivity. Mild p53 expression was present in only 4 cases (22%). Mean Ki-67 index was 20.6% (range 8 - 55%). CONCLUSION: frequent nuclear survivin expression implies the predominance of anti-apoptotic factors in pathogenesis of adult medulloblastomas. It may also be a potential therapeutic target for adult medulloblastomas. Although Blc-2 immunoreactivity was previously reported in approximately 30% in medulloblastomas, we have observed that it is rarely expressed in the present series of adult medulloblastomas. To our knowledge, this is the first study evaluating fascin expression in medulloblastomas. Its presence may be related to the neuronal differentiation. Mild-to-moderate cytoplasmic c-KIT immunoreactivity without membranous staining in adult medulloblastomas may support the previous studies reporting low level of c-KIT protein expression with lack of activating mutations in medulloblastomas. It seems p53 is rarely involved in the course of develepment of adult medulloblastomas.

Effect of periosteal stimulation therapy on bone formation in orthopedically expanded suture in rats.

OBJECTIVE: The aim of this experimental study was to evaluate the effects of periosteal stimulation therapy (PST), on bone regeneration in response to expansion of the interpremaxillary suture, in rats. MATERIAL AND METHODS: Sixteen male, 50-60 days old Wistar rats were divided into two equal groups (control and experimental). Both groups were subjected to expansion for 5 days, and 30 cN of force was applied to the maxillary incisors with helical spring. On the 2nd day of the expansion procedure in the experimental group, the periosteum over the interpremaxillary suture was stimulated locally by intraperiosteal penetrations with a hypodermic needle. Bone regeneration in the interpremaxillary suture was evaluated by bone histomorphometry and the new bone area, bone perimeter, feret's diameter and new bone/old bone percentage parameters were evaluated. Mann-Whitney U-test was used for statistical evaluation at p < 0.05 level. RESULTS: Significant differences were found between groups for all investigated histomorphometric parameters. New bone area (p < 0.01), bone perimeter (p < 0.05), feret's diameter (p < 0.01) and new bone/old bone percentage (p < 0.01) measurements were significantly higher in the experimental group than that in the control. Bone histomorphometric measurements revealed that bone architecture in the PST group was improved. CONCLUSIONS: Local stimulation of the periosteum of the sutural area during expansion stimulates bone formation and improves healing.

Adrenomedullin worsens skin necrosis in rats subjected to vincristine-induced extravasation.

BACKGROUND: Extravasation of vesicant drugs such as vinca alkaloids causes severe injury, which may range from erythema to skin necrosis or ulceration. The skin necrosis may not be fully evident until several weeks or months after the initial damage, and may require surgical intervention. The main treatments for vincristine extravasation are hyaluronidase injection and topical warming, and the aim of treatment is to increase the clearance of the drug from the extravasation site. AIM: To investigate the effect of adrenomedullin, a potent vasodilatory peptide, in rats subjected to vincristine-induced extravasation. METHODS: In total, 36 Wistar albino rats were given intradermal injection of vincristine and saline. The rats were assigned to one of three treatment groups (adrenomedullin, adrenomedullin + hyaluronidase, or hyaluronidase), a control group given vincristine only, or a sham group (saline). Tissue superoxide dismutase (SOD), glutathione peroxidase, malondialdehyde (MDA) and protein content were evaluated in skin biopsies taken on day 22. The ulcer size and histopathological grading scores were also recorded. RESULTS: SOD levels were significantly increased by adrenomedullin and increased by hyaluronidase. Glutathione peroxidase levels were significantly decreased in all four vincristine groups. Tissue MDA levels were highest in the adrenomedullin group. In all four vincristine groups, MDA levels were reduced, indicating preservation from tissue injury. Protein carbonyl (PCO) content levels in the adrenomedullin group were significantly greater than in the other three study groups (P < 0.05). In contrast, PCO levels in the hyaluronidase group were significantly lower than in the other three groups. CONCLUSIONS: In this animal model of vincristine-induced extravasation, antioxidant status and histology were preserved by hyaluronidase but worsened by adrenomedullin.

Adenoid hypertrophy in adults: clinical and morphological characteristics.

This study compared the aetiology and pathological characteristics of adult and childhood adenoid hypertrophy (AH). Clinical and morphological features and accompanying otolaryngological pathologies were recorded in 40 adults and 23 children undergoing adenoidectomy for obstructive AH. Both AH forms were similar in terms of symptomatology and associated inflammations. There were, however, significant differences in otitis media rate, with effusion and dullness, and retraction in the eardrum both more prevalent in childhood AH. Adult AH was associated with nasal septum deviation in 25.0% of patients. Histopathological features of adenoidal lymphoid tissue were dissimilar in the two groups: numerous lymph follicles with prominent germinal centres was the chief finding in childhood adenoids, whereas adult adenoids showed chronic inflammatory cell infiltration and secondary changes (e.g. squamous metaplasia). These results underline the importance of considering AH as a cause or contributing factor in nasal obstruction and related pathologies in adults and supports the theory that it represents a long-standing inflammatory process rather than being a novel clinical entity.

Histomorphometrical analysis of new bone obtained by distraction osteogenesis and osteogenesis by periosteal distraction in rabbits.

The aim of this study was to compare histomorphometrically the new bone tissue obtained using two different distraction methods, and evaluate these two methods in terms of their advantages and disadvantages. In 36 New Zealand adult male rabbits, divided into two groups, a gradual distraction was performed using a device placed on the lateral surface of the mandibular corpus. In one group osteotomy was not performed and osteogenesis by periosteal distraction (OPD) only was used. In the other group, conventional distraction osteogenesis (DO) was performed. After a 7-day latent phase, the same distraction protocol was applied to both groups. Each group of rabbits was further divided into three sub-groups killed on the 15th, 30th and 60th days of the consolidation period, and histological analysis was performed. The mean extent of newly formed bone tissue was 14.4 mm2 in the OPD groups and 25.4 mm2 in the DO groups. When compared statistically, there were significant differences between all the DO and OPD sub-groups. The newly formed bone tissue obtained by OPD was rich in interstitial fatty tissue. These results indicate that bone tissue newly formed by OPD is not suitable for occlusal forces.

Hypericin-enhanced argon laser photocoagulation for subfoveal choroidal neovascular membrane in age-related macular degeneration: a pilot study.

PURPOSE: To evaluate the efficacy and safety of hypericin-enhanced argon laser photocoagulation (H-ALP) in the treatment of subfoveal choroidal neovascular membrane (CNM) secondary to age-related macular degeneration (ARMD). METHODS: After preliminary studies for definition of parameters, argon-green laser was administered 4 hours after single dose of oral 1800 mg hypericin (Saint-John's wort tablets, 0.3%, 300 mg) with a subthreshold light fluence, 24 J/cm2 in 34 eyes (20 with subfoveal classical and 14 with subfoveal occult CNM). Additionally, histopathologic examination was done in two eyes destined for enucleation and exenteration. Maintenance therapy (one tablet, twice a day) was performed for the following 6 months. Anatomic (complete closure of CNM) and functional success (improvement of final visual acuity in three or more Snellen lines) were analyzed with minimum 6-month follow-ups. RESULTS: Histopathologic examinations revealed photothrombosed choriocapillaries together with minimal retinal pigment epithelial disruption in H-ALP exposed areas. One to four (mean 1.88+/-0.91) treatment sessions were applied in 6 to 29 months (mean 12.2+/-5.1 months) follow-up period. Twenty-three (67.6%) eyes had 12 months follow-up. Two eyes in each group had functional success (20% in subfoveal classical and 14.3% in subfoveal occult CNM), which had a minimum 12-month follow-up. Anatomic success was achieved in 16 of 20 (80%) eyes with subfoveal classical and 10 of 14 (71.4%) eyes with subfoveal occult CNM. Severe gastric irritation was noted in 1 (2.9%) and pigment epithelial rupture in 2 (5.9%) patients. CONCLUSIONS: H-ALP is a novel and low-cost treatment for subfoveal CNM secondary to ARMD. It seems its efficacy depends on the photodynamic and antiproliferative properties of hypericin. Comparative studies are required to apply this new technique in ophthalmic practice.

Hypericin-enhanced argon laser photocoagulation for subfoveal choroidal neovascular membrane in age-related macular degeneration: a pilot study.

PURPOSE: To evaluate the efficacy and safety of hypericin-enhanced argon laser photocoagulation (H-ALP) in the treatment of subfoveal choroidal neovascular membrane (CNM) secondary to age-related macular degeneration (ARMD). METHODS: After preliminary studies for definition of parameters, argon-green laser was administered 4 hours after single dose of oral 1800 mg hypericin (Saint-John's wort tablets, 0.3%, 300 mg) with a subthreshold light fluence, 24 J/cm2 in 34 eyes (20 with subfoveal classical and 14 with subfoveal occult CNM). Additionally, histopathologic examination was done in two eyes destined for enucleation and exenteration. Maintenance therapy (one tablet, twice a day) was performed for the following 6 months. Anatomic (complete closure of CNM) and functional success (improvement of final visual acuity in three or more Snellen lines) were analyzed with minimum 6-month follow-ups. RESULTS: Histopathologic examinations revealed photothrombosed choriocapillaries together with minimal retinal pigment epithelial disruption in H-ALP exposed areas. One to four (mean 1.88+/-0.91) treatment sessions were applied in 6 to 29 months (mean 12.2+/-5.1 months) follow-up period. Twenty-three (67.6%) eyes had 12 months follow-up. Two eyes in each group had functional success (20% in subfoveal classical and 14.3% in subfoveal occult CNM), which had a minimum 12-month follow-up. Anatomic success was achieved in 16 of 20 (80%) eyes with subfoveal classical and 10 of 14 (71.4%) eyes with subfoveal occult CNM. Severe gastric irritation was noted in 1 (2.9%) and pigment epithelial rupture in 2 (5.9%) patients. CONCLUSIONS: H-ALP is a novel and low-cost treatment for subfoveal CNM secondary to ARMD. It seems its efficacy depends on the photodynamic and antiproliferative properties of hypericin. Comparative studies are required to apply this new technique in ophthalmic practice. (Eur J Ophthalmol 2006; 16: 119-28).