Prognostic risk factors for rare oncocytic variantin 101 cases of papillary thyroid carcinoma.

OBJECTIVE: Oncocytic variant (OV) is an unusual subtype of papillary thyroid cancer whose histopathologic diagnostic criteria, clinicopathologic features and biological behavior are different and have not been comprehensively studied, characterized in literature. Previous studies present conflicting results upon its prognosis. We investigated demographic and clinicopathologic risk factors affecting its prognosis while presenting our clinical experience. SUBJECTS AND METHODS: This is a retrospective cohort study reviewing 101 patients of OV from an archive of 4500 well-differentiated thyroid cancer patients treated with iodine-131 (131I) between 1991 and 2017. Predefined parameters of age, gender, tumor size (TS), total 131I dose, time to recurrent disease, overall survival, extrathyroidal extension, multifocality, vascular invasion, accompanying other variants, capsular status of thyroid gland, initial cervical lymph node (LN) metastases, preablation stimulated thyroglobulin level, background thyroiditis and stage were evaluated by statistical comparison between metastatic and nonmetastatic groups. RESULTS: Seventeen cases (17%) developed metastases/recurrence, 70% of the recurrences occured before 24 months. Four patients (4%) died during the follow-up. Metastatic sites were usually cervical LN, local recurrence in thyroid bed and lungs. Multivariate analysis revealed stage (IV) and TS were the main parameters impacting recurrence/metastases. In the follow-up, isolated cervical LN metastases were found in 41% of metastatic cases, while 12% had sole recurrence in thyroid bed. Eighty eight percent of the metastatic disease included locoregional (cervical) and/or remote LN. The recurrences were associated with initial thyroid masses greater than 3.5cm in diameter. CONCLUSION: We found that the prognosis of OV is not poor in our series. Stage (IV) and tumor size are the main risk factors in metastatic development.

Gammagrafía paratiroidea con 99mTc-MIBI: valor complementario de la paratohormona en el aspirado y análisis histopatológico de los tipos de células en los adenomas paratiroideos / Complementary role of parathormone washout test to 99mTc-MIBI parathyroid scintigraphy and histopathologic analysis of cell types in parathyroid adenomas

Objetivo: La gammagrafía paratiroidea (GP) puede ser negativa o equívoca (N/E) en un número considerable de casos con alta sospecha clínica y bioquímica de adenoma de paratiroides (AP). Los objetivos de este estudio fueron investigar el papel complementario de la determinación de paratohormona en punción con aguja fina (PTH en PAAF) con la GP en pacientes con hiperparatiroidismo primario (HPTP) y evaluar los aspectos histopatológicos de los AP en comparación con los resultados de GP. Material y métodos: Fueron incluidos en el estudio 38 pacientes con HPTP remitidos para realizar GP. Diecisiete pacientes tuvieron resultados gammagráficos y ecográficos concordantes con AP (grupo A). Veintiún pacientes con GP N/E pero sospecha de AP en la ecografía formaron el grupo B. Se realizó PTH en PAAF en todos los pacientes y todos fueron operados. Se extirpó un adenoma en cada uno de ellos y en todos los casos se establecieron las características histopatológicas. Resultados: El tamaño del tumor en la ecografía fue mayor en aquellos pacientes cuyos adenomas se vieron en la GP (p<0,001). Los porcentajes de células principales, oxífilas y claras en AP no fueron estadísticamente diferentes entre los grupos. El nivel de paratohormona sérica y PTH en PAAF no fueron estadísticamente significativos entre los grupos A y B (p=0,095 y p=0,04, respectivamente). Conclusión: Aunque no existe un valor umbral definitivo, la sensibilidad de la GP aumenta con el tamaño de la lesión. Mientras que el contenido de células principales y oxífilas tiende a reducirse en los AP con GP N/E EP, la tasa de células claras aumenta sustancialmente. La combinación de GP con la ecografía y la PTH en PAAF aumenta la sensibilidad de detección y localización de los AP

Objective: Parathyroid scintigraphy (PS) can be negative or equivocal (N/E) in a considerable number of cases with highly suspicious clinical findings and biochemical results for parathyroid adenoma (PA). The aims of this study were to investigate the complementary role of parathormone washout test (PWT) to PS in patients with primary hyperparathyroidism (PHPT) and evaluate histopathologic aspects of PAs in comparison with PS results. Material and methods: Thirty-eight patients with PHPT referred for PS were included in the study. Seventeen patients had both scintigraphic and ultrasonographic findings concordant with PA (Group A). Twenty-one patients having N/E PS, but suspected lesions for PA on ultrasonography (US) formed Group B. PWT was performed for all patients and they underwent the surgical intervention. An adenoma was removed in all patients and the histopathologic cell characteristics were established. Results: The tumor size on US was larger in those patients whose adenomas were seen on the PS (P<.001). The percentages of chief (or principal), oxyphilic and clear cells in PAs were not statistically different between the groups. Serum parathormone level and PWT were not statistically significant between Group A and Group B (P=.095 and P=.04, respectively). Conclusion: Although there is not a definitive threshold value, the sensitivity of PS increases with lesion size. While chief cell and oxyphilic cell content of PAs tend to deplete in N/E PS, clear cell rate increases substantially. Combining PS with both US and PWT increases the sensitivity of detection and localization of PAs

Complementary role of parathormone washout test to 99mTc-MIBI parathyroid scintigraphy and histopathologic analysis of cell types in parathyroid adenomas. / Gammagrafía paratiroidea con 99mTc-MIBI: valor complementario de la paratohormona en el aspirado y análisis histopatológico de los tipos de células en los adenomas paratiroideos.

OBJECTIVE: Parathyroid scintigraphy (PS) can be negative or equivocal (N/E) in a considerable number of cases with highly suspicious clinical findings and biochemical results for parathyroid adenoma (PA). The aims of this study were to investigate the complementary role of parathormone washout test (PWT) to PS in patients with primary hyperparathyroidism (PHPT) and evaluate histopathologic aspects of PAs in comparison with PS results. MATERIAL AND METHODS: Thirty-eight patients with PHPT referred for PS were included in the study. Seventeen patients had both scintigraphic and ultrasonographic findings concordant with PA (Group A). Twenty-one patients having N/E PS, but suspected lesions for PA on ultrasonography (US) formed Group B. PWT was performed for all patients and they underwent the surgical intervention. An adenoma was removed in all patients and the histopathologic cell characteristics were established. RESULTS: The tumor size on US was larger in those patients whose adenomas were seen on the PS (P<.001). The percentages of chief (or principal), oxyphilic and clear cells in PAs were not statistically different between the groups. Serum parathormone level and PWT were not statistically significant between Group A and Group B (P=.095 and P=.04, respectively). CONCLUSION: Although there is not a definitive threshold value, the sensitivity of PS increases with lesion size. While chief cell and oxyphilic cell content of PAs tend to deplete in N/E PS, clear cell rate increases substantially. Combining PS with both US and PWT increases the sensitivity of detection and localization of PAs.

Clinicopathologic features and prognostic factors of tall cell variant of papillary thyroid carcinoma: comparison with classic variant of papillary thyroid carcinoma.

OBJECTIVE: Tall cell variant (TCV), an aggressive form of papillary thyroid carcinoma (PTC), frequently presents with extrathyroidal disease and recurrence. The aim of this study was to evaluate the clinicopathologic features and outcomes of patients with TCV by comparing them with a larger group of patients with classic variant of papillary thyroid carcinoma (cPTC). PATIENTS AND METHODS: A total of 2500 patients with differentiated thyroid carcinoma were treated and monitored during a 23-year period (1992-2015). Of them, 2250 (90%) had PTC and 235 (9.5%) had follicular thyroid carcinoma. Of the 2250 patients, 862 (38.3%) and 70 (3.1%) had cPTC and TCV, respectively. Cases of TCV and cPTC of PTC were compared on the basis of risk factors. RESULTS: Patients with TCV were significantly older compared with cPTC patients (P<0.001). Tumor size was significantly bigger (P=0.01) and preablation thyroglobulin level was significantly higher (P<0.001) in TCV patients than in cPTC patients. The incidence of capsule invasion, extrathyroidal extension, and vascular invasion was significantly higher in TCV (P=0.003, <0.001, and 0.011, respectively). The incidence of initial lymph node metastasis was significantly higher in TCV (P<0.001). Patients with TCV were mostly at an advanced stage compared with patients with cPTC (P<0.001). Development of local or distant metastasis during the follow-up was significantly higher in TCV than in cPTC. Sex and multifocality were not statistically significant. CONCLUSION: TCV has a higher incidence of local or distant metastasis and mortality rate. Thus, it must be treated with the highest possible I ablation doses and followed up carefully.

Heterotopic brain tissue on the face and neck in a neonate: a rare case report and literature review.

Heterotopic brain tissue (HBT) most commonly occurs in the nasal region and it is often referred to as a nasal glioma. Nonnasal locations for ectopic brain tissue are less commonly described. In English literature, only six cases have been reported that share some features (face or neck location) of this case. The presented case is the fourth case, located in both face and neck, and the one, which is the most extensive with its dimensions. According to location of heterotopic brain may lead to dystocia. We reported HBT of the face and neck in a neonate and the differential diagnosis, etiopathogenic mechanisms and clinical courses are reviewed and discussed.

Effects of infliximab on bacterial translocation in experimental acute necrotizing pancreatitis.

BACKGROUND & OBJECTIVES: Translocation of bacteria from the gut is an important factor in the development of septic complications and mortality in acute pancreatitis (AP). The present study was designed to assess the effects of infliximab treatment on bacterial translocation (BT) in experimental acute necrotizing pancreatitis. METHODS: Male Sprague-Dawley rats (n=45) were allocated into three groups. AP was induced in group II (positive control, n=15) and group III (Infliximab; n=15) by retrograde injection of taurocholate into the common biliopancreatic duct. Group I rats (Sham; n=15) received normal saline infusion into the common biliopancreatic duct as placebo. Groups I and II were treated by normal saline and group III was treated with infliximab intraperitoneally on 6, 30 and 54 h after induction of pancreatitis. All surviving animals were killed 60 h after the induction of pancreatitis, and specimens were collected for amylase measurement as well as histopathologic and microbiologic examinations. RESULTS: Oedema, acinar cell necrosis, inflammatory infiltration, haemorrhage, fat necrosis and perivascular inflammation in group III rats were decreased with infliximab treatment when compared with group II (P<0.001). BT to mesentery lymph node in groups I, II and III were 20, 100 and 46 per cent, respectively. BT to peritoneum and pancreas in group III was lower than group II (P<0.05). INTERPRETATION & CONCLUSIONS: Infliximab administration resulted in beneficial effects on BT and histopathologic changes in the experimental necrotizing pancreatitis. Whether anti-TNF therapy has a role in prevention of complications of ANP needs to be established.

Effect of alpha-tocopherol on bone formation during distraction osteogenesis: a rabbit model.

PURPOSE: The purpose of this study was to evaluate the effects of alpha-tocopherol on distraction osteogenesis. MATERIALS AND METHODS: Right tibias of 30 New Zealand white rabbits were distracted at a rate of 0.5 mm/day for 20 days with a circular external fixator. Experimental group rabbits (n = 15) were administered i.m. 20 mg/kg/day alpha-tocopherol for 30 days. Radiographic examinations were performed at the 20th, 30th and 40th days. Bone scintigraphy was performed at the 5th and 20th days. Serum total antioxidant capacity (TAC) was measured at the 5th and 30th days. All animals were sacrificed and the right tibias of all animals were harvested for histopathologic examination at the 40th day. RESULTS: Radiologic scores were statistically similar at the 20th day. However, the experimental group demonstrated higher radiologic scores at the 30th and 40th days. A scintigraphic baseline study at the 5th day of the study showed statistically similar osteoblastic activities in both groups. However, at the 20th day, osteoblastic activity was significantly higher in the experimental group. Serum TAC values were also significantly higher in the experimental group at the 30th day. At necropsy, histopathologic examination revealed statistically significantly higher scores in the experimental group. CONCLUSION: The results of this study show that alpha-tocopherol has beneficial effects on new bone formation during distraction osteogenesis.

Diffusion-weighted imaging in the characterization of focal liver lesions: efficacy of visual assessment.

OBJECTIVES: The objective of the study was to assess the value of visual assessment of signal intensities on b800 diffusion-weighted images and apparent diffusion coefficient (ADC) maps in differentiation of benign and malignant focal liver lesions (FLLs). METHODS: Approval for this retrospective study was obtained from the institutional review board. One hundred forty-three FLLs in 65 patients (38 women, 27 men; mean age, 50.8 years) underwent magnetic resonance (MR) imaging and diffusion-weighted imaging (DWI) with a respiratory-triggered single-shot echo-planar imaging sequence. Focal liver lesions were evaluated visually according to the signal intensities on b800 and ADC map images, and ADC values were also calculated. The conventional MR imaging, follow-up imaging findings, and histopathologic data were regarded as gold standard. Normal distribution was assessed with Kolmogorov-Smirnov test. The accuracies of visual assessment and ADC values in differentiating benign and malignant FLLs were assessed with the Student t test, and threshold values were determined with receiver operating characteristic curve analysis. RESULTS: By using a cutoff value of 1.21 × 10⁻³ mm²/s, ADC had a sensitivity of 100%, a specificity of 89.3%, and an accuracy of 92.3% in the discrimination of malignant FLLs. With the visual assessment of the DWIs and ADC maps, malignant lesions were differentiated from benign ones, with 100% sensitivity, 92.2% specificity, and 94.4% accuracy. Although some benign lesions were interpreted as malignant, no malignant lesion was determined as benign in visual assessment. CONCLUSIONS: Most FLLs are benign ones such as hemangiomas and cysts, which can be readily and practically characterized only by using visual assessment of DWIs without requiring time-consuming conventional and dynamic contrast-enhanced imaging sequences. Some benign lesions that are falsely interpreted as malignant can be further characterized by using conventional and contrast-enhanced MR studies.

Combination of preoperative ultrasonographic mapping and radioguided occult lesion localization in patients with locally recurrent/persistent papillary thyroid carcinoma: a practical method for central compartment reoperations.

PURPOSE: To improve the surgical success and reduce the complication rates, we combine our routine preoperative ultrasound (US) mapping technique with radioguided occult lesion localization (ROLL) in patients with papillary thyroid cancer recurrences in central compartment. MATERIALS AND METHODS: In the morning of surgery, biopsy proven recurrent/persistent tumoral lesions were plotted on a sketch and injected with Tc-99m labeled macroaggregated albumin under US guidance. Thyroid bed exploration was carried out based on the location of biopsy proven lesion with the guidance of intraoperative gamma probe and neck map. The lymphoadipose tissues showing high count rates were resected and labeled separately for histopathologic study. RESULTS: Despite extensive scarring in some patients probe safely guided to lesions. Noninjected tumor foci were searched and successfully resected in the light of neck map that showing topographic relation of injected and noninjected lesions. Among total of 41 excised lesions, 28 metastatic foci ranging from 3 to 38 mm in largest diameter were recognized at final histologic examination. Combination of preoperative mapping with ROLL was found helpful by the operating surgeons in all patients, respectively. Except 2 patients with known distant metastases, undetectable thyroglobulin levels were reached 6 weeks after surgery. CONCLUSIONS: The use of preoperative US-mapping with ROLL in patients with nonpalpable recurrent/persistent papillary thyroid cancer in central compartment is technically safe and effective method. Combination of techniques provides better information about topographical relations of recurrent/persistent lesions during surgery.

Myoepithelioma of the parotid gland in a child: a case report.

Myoepitheliomas of the parotid glands are very rare in the pediatric population. Only a few cases of myoepitheliomas of the salivary glands have been reported in children. They have some similar features with pleomorphic adenoma. However, they may be malignant and infiltrate locally. Hence, histopathologic examination should be considered to differentiate these tumors. The treatment of myoepitheliomas is complete removal of the tumor. We report a child with myoepithelioma of the parotid gland and review the related literature.

Synergistic effects of hyperbaric oxygen and granulocytecolony stimulating factor on postoperative adhesion formation in a rat cecal abrasion model.

PURPOSE: We investigated the synergistic effect of hyperbaric oxygen (HBO) and granulocyte-colony stimulating factor (G-CSF) on adhesion formation in rats. METHODS: 40 adult male Sprague-Dawley rats (250-350 g) were divided into 4 groups. In group-1, no further management was undertaken. Group-2 received HBO therapy, group-3 was treated with 50 ug/kg subcutaneous G-CSF once daily for 7 days following laparatomy and cecal abrasion and group-4 was given both G-CSF and HBO therapies. On the 7th day, all rats were sacrificed and adhesions were scored. Tissue samples from adhesions and peritonea and cecum wall were examined both pathologically and biochemically for tissue hydroxyproline content. RESULTS: No mortality occurred in study groups. When the groups were evaluated according to the adhesion numbers and grades, there was a statistically significant difference between the control and groups 3 and 4 (P < 0.001). There was no statistically significant difference between groups 1 and 2 (p > 0.05). HBO + G-CSF group was significantly different from control, HBO and G-CSF groups, regarding hydroxyproline contents (p = 0.005). Inflammation and fibrosis did not differ significantly among the groups (p = 0.248), (p = 0.213). CONCLUSION: HBO treatment could not reduce the adhesion formation alone. Combined use of HBO and G-CSF, has a markedly preventive effect on postoperative adhesion formation (Tab. 1, Fig. 2, Ref. 57).

A case of pancreatic Burkitt lymphoma: radiological findings.

Burkitt lymphoma predominantly involving the pancreas is very rare. There is no specific clinical, laboratory, or radiological sign of the disease. Thus, the diagnosis, especially of focal involvement, is usually difficult. We here report ultrasonography, computed tomography and magnetic resonance imaging findings of primary pancreatic Burkitt lymphoma in a case with unusual radiological presentation.

Does the 3-aminobenzamide effect on bacterial translocation affect experimental acute necrotizing pancreatitis?

BACKGROUND/AIMS: One of the most important complications of acute pancreatitis is the secondary bacterial infections of the pancreas and gut. Translocation of bacteria from the gut is accepted as being responsible for the development of septic complications in acute pancreatitis. In this study, our aim was to investigate the effect of PARP inhibition via 3-aminobenzamide on the bacterial translocation in acute pancreatitis. METHODS: 45 male Sprague-Dawley rats were randomly allocated into three groups. Group I (Sham+saline) received normal saline infusion into the common biliopancreatic duct. Acute pancreatitis was induced in Group II (acute pancreatitis+saline) and Group III (acute pancreatitis+ 3-aminobenzamide) by the retrograde injection of taurocholate into the common biliopancreatic duct. Six hours after induction of pancreatitis, the rats in Group I and II were treated with saline (1 ml, every 12 hours), while the rats in Group III were treated with 3-aminobenzamide (10 mg/kg/day every 12 hours), intraperitoneally. In the 54th hour of the study, blood and tissue samples were taken for biochemical, microbiological and histopathological analysis. RESULTS: Acute pancreatitis developed in Groups II and III. Pathologic score [median (25-75% percentiles)] of the pancreatitis in Group III [8 (7-9)] was significantly lower than in Group II [19 (18-21)] (p<0.001). Bacterial translocation to mesenteric lymph node (53.3%), peritoneum (60%) and pancreas (46.7%) in Group III was significantly lower than in Group II (100% for all) (p<0.02, p<0.03, p<0.005, respectively). Pancreatic tissue glutathione peroxidase, superoxide dismutase, and malondialdehyde levels were better in Group III compared to Group II (p<0.001 for all). Comparison of Groups II and III demonstrated reduced severity of inflammation of the gut in Group III (p>0.05). Improvement in bacterial translocation was correlated with reducing oxidative stress. CONCLUSIONS: We demonstrated that 3-aminobenzamide therapy improved histopathologic score and oxidative stress in experimental pancreatitis. In addition, it was demonstrated microbiologically and histopathologically that 3-aminobenzamide therapy improves bacterial translocation. Further survival studies demonstrating the efficacy of 3-aminobenzamide therapy and explaining the potential mechanisms of bacterial translocation prevention in acute necrotizing pancreatitis will be beneficial.

Nuclear planimetry on the samples from cytologically overlapping proliferative breast lesions.

Differentiation of low-grade breast carcinomas from fibroadenomas with atypia on fine-needle aspiration cytology material may sometimes be problematic. In some cytological samples of these lesions, both the nuclei of cells and patterns of cell clusters display substantial overlapping morphological characteristics. Nuclear morphometry on cytological material is suggested as an ancillary method for the differential diagnosis in many lesions, including breast tumors. Twenty-five cytological samples obtained from patients with breast lesions, which were histopathologically confirmed as grade I ductal carcinomas (n=10), tubular carcinomas (n=5), and fibroadenomas with atypia (n=10), were utilized in this study. Eight geometric features of about 2002 nuclei from these tumors were measured. Discriminant analysis was performed on this data set in order to test the correct classification based on the eight measured variables. Statistical analyses were carried out with two fundamentally different approaches: in the first one, the entire data from all measured nuclei were used for classification. In the second one, a subset of data representing the 10% most deviated values of variables was extracted from the entire dataset to simulate the "selective examination" performed during classical morphologic evaluation. When the entire data was used in discriminant analysis, the overall performance in the correct classification rate was found to be approximately 50%, which was considered an unacceptable value in routine diagnostic practice. In the subset of data constructed with our systematic and reproducible "selection bias", the overall performance of correct classification rate of the same discriminant model improved substantially to 97%. Morphologic examination is actually based on selection. The use of data obtained from all of the cells in morphometry, as previously used in nearly all of the statistical methods, may cause a masking effect in diagnostically important features. Morphometric studies may seem to be useless when this effect is not taken into account. However, with a systematic and reproducible selection of the values with a proper "bias", morphometry may provide some discriminatory information in overlapping lesions.

Serous psammocarcinoma of the ovary and peritoneum: two case reports and review of the literature.

Serous psammocarcinoma (SPC) is a rare variant of ovarian carcinoma or peritoneum that may present with features consistent with malignancy, or tumors of low malignant potential. This is two-case reports of a SPC of the ovary and peritoneum and review of the literature. A 41-year-old woman was referred to our clinic for adnexal mass. Ultrasonography revealed endometrioma. Endometriotic cyst excision and sacrouterine biopsy were performed via laparoscopy. Histological examination revealed endometrioma and psammocarcinoma of the peritoneum. Staging laparotomy was performed. She received six courses of chemotherapy. She has no evidence of disease after 6 years from surgical therapy and chemotherapy. A 50-year-old woman presented with pelvic pain and discomfort in the upper abdomen with nausea and emesis. CT scan showed extensive tumor in the lower abdomen, and free fluid in the abdomen and pelvis which appeared to be an ovarian tumor. She underwent a laparotomy and a right and left ovarian tumor measuring about 20 x 15 and 8 x 8 cm, respectively, were seen. Staging procedure was performed. Microscopic examination revealed SPC of the ovary. Chemotherapy was planned. The biologic behavior of this disease remains unresolved. Primary surgical debulking should be attempted, while the utility of postoperative chemotherapy remains unknown.

Enhanced efficacy of diclofenac sodium-loaded lipogelosome formulation in intra-articular treatment of rheumatoid arthritis.

Recent research into the complex and varied components of rheumatoid arthritis (RA) is leading to the development of more effective targets for pharmaceutical approach than even before. Current treatment of RA frequently includes the use of nonsteroidal anti-inflammatory drugs, such as Diclofenac sodium (DFNa) in spite of the severe adverse effects. Local application and incorporation of the drugs in liposome based formulations may reduce those side effects and improve the efficacy of drugs by reducing the availability of them in systemic circulation and increasing accumulation and retention time in the sites of inflammation. Herein, anti-inflammatory efficacy of the DFNa containing lipogelosome formulations (L1J1) was evaluated and found that L1J1 elicits a better anti-inflammatory efficacy after a single dose i.a. administration in comparison with commercial product, VE-CP, which is used topically. Histopathological examination of the opened joints showed that joints treated with L1J1, had significantly (p < 0.05) lower scores than contra lateral control joints for inflammatory changes in the synovium. These results were also confirmed by biodistribution studies.

Combination of allopurinol and hyperbaric oxygen therapy: a new treatment in experimental acute necrotizing pancreatitis?

AIM: To investigate the individual and combined effects of allopurinol and hyperbaric oxygen (HBO) therapy on biochemical and histopathological changes, oxidative stress, and bacterial translocation (BT) in the experimental rat acute pancreatitis (AP). METHODS: Eighty-five Sprague-Dawley rats were included in the study. Fifteen of the eighty-five rats were used as controls (sham, Group I). AP was induced via intraductal taurocholate infusion in the remaining seventy rats. Rats that survived to induction of acute necrotizing pancreatitis were randomized into four groups. Group II received saline, Group III allopurinol, Group IV allopurinol plus HBO and Group V HBO alone. Serum amylase levels, oxidative stress parameters, BT and histopathologic scores were determined. RESULTS: Serum amylase levels were lower in Groups III, IV and V compared to Group II (974 +/- 110, 384 +/- 40, 851 +/- 56, and 1664 +/- 234 U/L, respectively, P < 0.05, for all). Combining the two treatment options revealed significantly lower median [25-75 percentiles] histopathological scores when compared to individual administrations (13 [12.5-15] in allopurinol group, 9.5 [7-11.75] in HBO group, and 6 [4.5-7.5] in combined group, P < 0.01). Oxidative stress markers were significantly better in all treatment groups compared to the controls. Bacterial translocation into the pancreas and mesenteric lymph nodes was lower in Groups III, IV and V compared to Group II (54%, 23%, 50% vs 100% for translocation to pancreas, and 62%, 46%, 58% vs 100% for translocation to mesenteric lymph nodes, respectively, P < 0.05 for all). CONCLUSION: The present study confirms the benefit of HBO and allopurinol treatment when administered separately in experimental rat AP. Combination of these treatment options appears to prevent progression of pancreatic injury parameters more effectively.

Allopurinol in rat chronic pancreatitis: effects on pancreatic stellate cell activation.

OBJECTIVES: Activation of pancreatic stellate cells (PSCs) is a key event in pancreatic fibrosis. Xanthine oxidase-derived free radicals are involved in the mechanism of chronic pancreatitis (CP). We here searched the in vivo effects of allopurinol on PSC activation and its relation to tissue oxidative stress and histological findings in rat CP. METHODS: Rat CP was induced with intraductal trinitrobenzene sulfonic acid in groups 1 (n = 16) and 2 (n = 10). Group 3 (n = 10) received intraductal saline. Four weeks after induction, group 1 received allopurinol (200 mg/kg, s.c.), and groups 2 and 3 received saline. After 4 weeks, oxidative stress parameters, histological evaluation, and immunostaining for alpha-smooth muscle actin (+) PSCs were performed in the pancreata. RESULTS: Oxidative stress parameters improved significantly in group 1 compared with groups 2 and 3. Collagen deposition and lobular/sublobular atrophy were significantly lower in group 1 than in group 2. Alpha-smooth muscle actin (+) PSCs counts in group 1 were significantly lower than in group 2, and were in correlation with the degree of fibrosis and atrophy. CONCLUSIONS: Allopurinol inhibits PSC activation in vivo. Pancreatic fibrosis can be prevented, at least in part, by antioxidant treatment through xanthine oxidase metabolism. Long-term use of allopurinol and its analogs may be considered in clinical trials with CP.

Pegylated interferon-alpha plus taurine in treatment of rat liver fibrosis.

AIM: To investigate the antifibrotic effects of peginterferon-alpha 2b and taurine on oxidative stress markers and hepatocellular apoptosis. METHODS: Sixty rats with CCl4-induced liver fibrosis were divided into 4 groups (n=15). Group 1 was left for spontaneous recovery (SR). Groups 2-4 received peginterferon-alpha 2b, taurine, and their combination, respectively, for four weeks. Histological fibrosis scores, histomorphometric analysis, tissue hydroxyproline, tissue MDA, GPx and SOD activities were determined. Activated stellate cells and hepatocellular apoptosis were also evaluated. RESULTS: The degree of fibrosis decreased in all treatment groups compared to spontaneous recovery group. Taurine alone and in combination with peginterferon-alpha 2b reduced oxidative stress markers, but peginterferon-alpha 2b alone did not. Apoptotic hepatocytes and activated stellate cells were higher in groups 2-4 than in group 1. Combined taurine and peginterferon-alpha 2b further reduced fibrosis and increased activated stellate cell apoptosis, but could not improve oxidative stress more than taurine alone. CONCLUSION: Peginterferon-alpha 2b exerts anti-fibrotic effects on rat liver fibrosis. It seems ineffective against oxidative stress in vivo. Peginterferon-alpha 2b in combination with taurine seems to be an antifibrotic strategy.

Alpha-tocopherol, beta-carotene and melatonin administration protects cyclophosphamide-induced oxidative damage to bladder tissue in rats.

Cyclophosphamide (CP) has potential urotoxicity such as hemorrhagic cystitis (HC). 2-Mercaptoethane sulfonate (mesna) has been widely used as an effective agent against CP-induced cystitis, but significant HC has still been encountered clinically. In recent studies, mesna was shown to be more effective if combined with antioxidants. The purpose of this study was to evaluate the effects of antioxidants, alpha-tocopherol, beta-carotene and melatonin on CP-induced bladder damage in rats, even if used without mesna administration. Male Sprague-Dawley rats weighing 180-210 g were divided into 5 groups. Four groups received a single dose of CP (100 mg/kg) intraperitoneally with the same time intervals. Group 2 received CP only, group 3 received beta-carotene (40 mg/kg/day), group 4 received alpha-tocopherol (40 mg/kg/day) and group 5 received melatonin (10 mg/kg/day) both before and the day after CP injection. Group 1 served as control. Bladder histopathology, as well as malondialdehyde (MDA) and iNOS levels, and excretion of nitrite-nitrates (NO(x)) in urine were evaluated. CP injection resulted in severe histological changes and macroscopic hematuria. alpha-Tocopherol and melatonin showed meaningful protection against bladder damage. Protection by beta-carotene was also significant but weaker. MDA levels increased significantly with CP injection and all antioxidants ameliorated this increase in bladder tissue. CP also elevated the NO(x) level in urine and iNOS activity in bladder. Only melatonin was able to decrease these parameters. In conclusion, there is no doubt that oxidants have a role in the pathogenesis of CP-cystitis. Antioxidants, especially melatonin and alpha-tocopherol, may help to ameliorate bladder damage induced by CP.