The clinicopathological significance of Bax and Bcl-2 protein expression with tumor infiltrating lymphocytes in ovarian carcinoma.

The aim of the study was to establish the prognostic and predictive value of Bax and Bcl-2 proteins in conjunction with the host immune response in primary epithelial ovarian carcinoma.83 patients were evaluated. Immunohistochemical staining was performed using anti-Bcl-2 (Dako; clone 124) and anti-Bax (Springbio; E17994) monoclonal antibodies. Additionally, the number of lymphocytes within tumor stroma lymphocyte nests were counted. Bcl-2 protein expression was lower in advanced stage than early stage (p= 0.005). High (H) Bax expression was associated with longer overall survival (OS) than lower (L) Bax expression (p=0.03). The OS of the (L) Bax/(L) Bcl-2 group was shorter than (H) Bax/(L) Bcl-2 group in advanced stage (p=0.05). The platinum-sensitive group had a statistically significant tendency for high Bax expression (p=0.04). Furthermore, the intensity of the lymphocyte infiltration was associated with tumor differentiation (p= 0.003). Our data suggests that (H) Bax protein expression prolongs survival, predicts platinum sensitivity and can be used after confirmation of this hypothesis in further prospective studies. The combined evaluation of Bax and Bcl-2 protein expression may provide additional significant prognostic information. The quantity of lymphocyte infiltration could be important for prognostic outcome.

Mast cells positive for cluster of differentiation 117 protein: are they players or conductor in the orchestra of cholesteatoma?

BACKGROUND: The pathogenesis of cholesteatoma remains unclear, despite several theories. Alterations in the density of mast cells positive for cluster of differentiation 117 protein (also known as CD117) can be critical to cholesteatoma formation, due to the effect on keratinocyte growth factor production. This study aimed to investigate the potential role of these mast cells in cholesteatoma pathogenesis. METHODS: The number and density of mast cells positive for cluster of differentiation 117 protein were immunohistochemically analysed in 52 patients: 22 with chronic otitis media alone (group one), 25 with chronic otitis media with cholesteatoma (group two) and five controls. RESULTS: The number of these mast cells was much higher in group two (in cholesteatoma matrix tissue) than in group one (in chronic otitis media granulation tissue) or the controls (in normal post-auricular skin). The density of these mast cells was significantly greater in group two than in group one or the controls (p < 0.05). The number and density of these mast cells was much greater in group one than in controls (p < 0.01). CONCLUSION: Mast cells positive for cluster of differentiation 117 protein could play a role in cholesteatoma formation. Further investigation of the role of these mast cells in cholesteatoma may suggest new ways of addressing this disorder, and may enable the development of targeted treatments.

Honey as a substitute for formalin?

Formalin has long been the standard fixative for clinical routines worldwide. After the Formaldehyde Standard became law in the US in 1987, as a result of increasing concerns about the potential carcinogenicity of formaldehyde, attempts have been made to find safer alternatives. Alcoholic formalin is a useful fixative, because in addition to fixation, dehydration also is begun. For centuries, honey has been known to be an antibacterial agent with the potential to preserve compounds without harmful effects on its users. We compared the effects of honey fixation with other routine fixatives using conventional histochemical and immunohistochemical staining methods. Our results demonstrated that tissues fixed in either honey or alcoholic formalin and 10% neutral buffered formalin (NBF) have similar histomorphology. Honey fixation showed minor histomorphological differences among the various tissues; however, it did not influence affect correct diagnostic conclusions. Our results suggested that honey can be used as a safe alternative to formalin in histopathology.

JC virus-associated nephropathy in a renal transplant recipient and comparative analysis of previous cases.

We report JC virus (JCV)-associated nephropathy in a renal allograft recipient and summarize the clinical and laboratory data of the 8 previous cases. A 28-year-old male renal allograft recipient received a preemptive transplant from his father. Six months later, a kidney biopsy was performed because of deterioration of allograft function. Biopsy revealed tubulointerstitial mononuclear infiltrates with normal glomeruli; on hematoxylin and eosin staining, basophilic nuclear inclusions were seen in the nucleus of tubular cells. Urinary cytology failed to demonstrate decoy cells, but polymerase chain reaction of a urinary sample was positive for JCV 3.15 × 10(10) copies/mL. Additionally, polyomavirus (SV40) immunohistochemical staining was performed and was positive in the enlarged nuclei of tubular epithelial cells in the kidney biopsy sample. After the diagnosis of polyomavirus-associated nephropathy (PVAN) was confirmed by kidney biopsy, immunosuppressive agents were reduced. Intravenous immunoglobulin was administered 5 times at a dose of 500 mg/kg every other 3 weeks. Two months after diagnosis, the serum creatinine became stable and urinary viral load of JCV was decreased. Because viruria was still present, tacrolimus was converted to sirolimus. Four months after immunosuppressive agent conversion from tacrolimus to sirolimus, the viruria had disappeared. Review of the literature and our case demonstrates that male gender, previous acute rejection episode, low incidence of JCV viremia, PVAN pattern B histology, and reducing immunosuppression are the diagnostic touchstones for PVAN due to JCV.

Effects of spironolactone in an experimental model of chronic cyclosporine nephrotoxicity.

BACKGROUND: Cyclosporine (CsA)-associated nephrotoxicity is a long-term complication in transplant patients. Chronic CsA nephrotoxicity is associated with renal fibrosis and hyaline arteriolopathy. The aim of this study was to investigate the effect of spironolactone on functional and structural alterations as well as on platelet-derived growth factor B (PDGF-B) and transforming growth factor (TGF) beta expression induced by CsA in a rat model of chronic CsA nephrotoxicity. MATERIALS AND METHODS: Twenty-four rats were divided into 3 groups. Group 1 (G1) received vehicle only (V); G2, CsA (15 mg/kg/d; CsA) by intraperitoneal (IP) injection; and G3, a similar CsA dosage + spironolactone (20 mg/kg/d; CsA + Ald.) by the oral route. At the end of 28 days, glomerular filtration rate (GFR) and blood CsA levels were measured as well as histopathological and immunohistochemical analyses performed on renal tissue. RESULTS: Mean CsA trough levels in G2 and G3 were both above 2000 ng/mL. In G2, GFR was lower than G1 and G3 (0.35 +/- 0.05, 1.64 +/- 0.24, and 1.20 +/- 0.25 mL/min, respectively; P < .001). There was a significantly increased number of arteriolopathic changes in G2 and G3 vs G1 (16% +/- 3.7%, 15% +/- 6.8%, 3% +/- 1.2%, respectively; P < .001). Interstitial fibrosis was significantly increased in G2 vs G1 and G3 (52%, 0%, 27%, respectively; P < .05). Marked by up-regulated PDGF-B and TGF beta expressions were observed in G2 vs G1 or G3: 100%, 0%, 37.5%, respectively, for PDGF-B (P < .001) and 87.5%, 0%, 12.5%, respectively, for TGF beta (P < .001). CONCLUSION: Our results suggested that chronic CsA nephrotoxicity may be mitigated by aldosterone receptor blockade which seemed to be associated with down-regulation of PDGF-B and TGF beta expression.

Renal protective effects of leukotriene receptor blockers in an experimental model of cyclosporine nephrotoxicity.

BACKGROUND: Chronic cyclosporine (CsA) nephrotoxicity is associated with renal fibrosis and hyaline arteriolopathy. Fibrogenic cytokines, such as transforming growth factor-beta (TGF-beta) and vascular endothelial growth factor (VEGF), play a pivotal role in CsA nephrotoxicity. Previous studies have demonstrated the possible role of leukotrienes (LT) in chronic CsA nephrotoxicity. The aim of this study was to examine the possible beneficial effects of LT blockers in attenuating the morphological and histochemical effects induced by CsA in a rat model of CsA nephrotoxicity. MATERIALS AND METHODS: Twenty-four male Wistar rats were divided into 3 groups (n = 8). The first group (G1) was treated with vehicle intraperitoneally (IP) for 60 days. The second group (G2) was treated with 15 mg/kg CsA IP for 60 days. The third group (G3) was treated with the same dose of CsA plus 4 mg/kg montelukast administered by oral gavage for 60 days. RESULTS: There was a statistically significant decrease in glomerular filtration rate (GFR) among G2 compared with G1 animals: 0.41 +/- 0.03 vs 1.63 +/- 0.12 mL/min (P < .001), or G3 hosts: 0.41 +/- 0.03 vs 0.95 +/- 0.05 mL/min (P < .005), respectively. The percentage of hyaline arteriolopathic changes was higher in G2 than G1 or G3: 81.66% +/- 8.2% vs 11.83% +/- 0.87% (P < .01) or 37.0% +/- 8.8% (P < .01), respectively. Fibrosis score was higher in G2 compared with G1 or G3: 1.5 +/- 0.04 vs 0.16 +/- 0.02 (P < .001) and 1.0 +/- 0.05 (P < .05), respectively. TGF-beta and VEGF immunoexpression were significantly increased in G2 compared with G1 (P < .05) or G3 (P < .05). CONCLUSIONS: Our study suggested that LT may play a critical role in the pathogenesis of chronic CsA nephrotoxicity; the administration of montelukast, a LT receptor blocker, may prevent CsA-induced nephrotoxicity.

A rare case of early onset nephrotic syndrome in pregnancy.

Nephrotic syndrome occurs very rarely, about 0.012-0.025% of all pregnancies. Here, we report a rare case of early onset nephrotic syndrome developing de novo in the 17th week of pregnancy. A renal biopsy was done and the specimens revealed typical features of focal segmental glomerulosclerosis. The patient had a progressive clinical course of disease despite steroid treatment. Suffering from severe intrauterine growth restriction, the fetus died in utero. After delivery, steroid treatment was continued. The patient had normal renal function with a decrease in proteinuria in the second and fifth month postpartum. This report points out the poor fetal prognosis associated with an early onset nephrotic syndrome. Pregnant patients with early onset nephrotic syndrome should be carefully evaluated for the presence of chronic renal disease, and primary renal pathology should be included in the differential diagnosis of massive proteinuria in early pregnancy.

Inhibition of the renin angiotensin system decreases fibrogenic cytokine expression in tacrolimus nephrotoxicity in rats.

The aim of our study was to investigate the influence of angiotensin-converting enzyme (ACE) inhibition and angiotensin II receptor blockage on the renal function by light microscopic and immunohistochemical findings in a rat model of tacrolimus nephrotoxicity. Thirty-two male Wistar rats were divided into four groups of eight: G1 = control group; G2-G3, G4 = Tacrolimus (Tac) 1 mg/kg/d intraperitoneally (ip); G3 (Tac + Q) = ip Tac and peroral quinapril 10 mg/kg; and G4 (Tac + V) = Tac and valsartan 40 mg/d. Serum blood urea nitrogen (BUN), creatinine, and creatinine clearance were measured before and at the end of the study period. Renal tissues were assessed for light microscopic findings of tacrolimus toxicity. Transforming growth factor-beta, VEGF, PDGF, BMP-7, and interleukin-6 (IL-6) expression were semiquantitatively scored after immunohistochemical staining. At the end of the study period serum BUN and creatinine levels were increased in all groups, but creatinine clearance was not significantly changed between the groups. Afferent arteriolopathy was significantly less pronounced in G3 versus G2 and G4. Interstial fibrosis was significantly less pronounced in G3 and G4 versus G2. TGF-beta, PDGF, and IL-6 expression were significantly increased in G2, G3, and G4 compared to G1, and in G2 compared to G3 and G4. BMP-7 expression was significantly decreased in G2, G3, and G4 compared to G1, whereas the differences between G2, G3, and G4 failed to reach statistical significance. In conclusion, the results of our study suggested that renin angiotensin inhibition down-regulates fibrogenic cytokine expression in rats displaying tacrolimus nephrotoxicity.

Transforming growth factor-beta1, vascular endothelial growth factor, and bone morphogenic protein-7 expression in tacrolimus-induced nephrotoxicity in rats.

The aim of our study was to investigate transforming growth factor (TGF)-beta1, vascular endothelial growth factor (VEGF), and bone morphogenic protein-7 (BMP-7) expression in the rat model of chronic tacrolimus (TAC) toxicity compared to healthy controls. Seventeen male Wistar rats were divided into two groups: group 1 animals were healthy controls and Group 2 animals were treated with TAC (1 mg/kg per day intraperitoneally for 8 weeks). At the end of the study period the animals were sacrificed following renal function studies including blood urea nitrogen (BUN), serum creatinine, and creatinine clearance, and renal tissues were examined by light microscopy for the findings of tacrolimus toxicity, specifically for afferent arteriolopathy and interstitial fibrosis. TGF-beta1, VEGF, and BMP-7 expression were assessed by semiquantitative scoring of the immunohistochemically stained specimens. Mean TAC levels were 5.53 +/- 2.38 ng/mL in group 2. BUN, creatinine levels, and creatinine clearance were 57.99 +/- 11.13 vs 39.49 +/- 5.64 mg/dL; 0.60 +/- 0.16 vs 0.65 +/- 0.09 mg/dL; 0.97 +/- 0.39 vs 1.17 +/- 0.32 mL/min in group 2 versus group 1. Only the BUN level was significantly higher in group 2 compared to group 1. Afferent arteriolopathy and interstitial fibrosis were significantly increased in group 2 compared to group 1. TGF-beta1 and VEGF expression was significantly increased while BMP-7 expression was significantly decreased in group 2 versus group 1. In conclusion, our findings suggest that TAC-induced nephrotoxicity is associated with increased TGF-beta1 and VEGF and decreased BMP-7 expression.

Diffuse malignant epithelial peritoneal mesothelioma in pregnancy. A case report and literature review.

A 33-year-old pregnant woman of 38 weeks' gestation with massive peritoneal ascites presented. A cesarean section was performed and a viable 3.100 g male infant was delivered. Biopsy of the nodular enlargements from the omentum revealed a malignant epithelial peritoneal mesothelioma. Malignant mesothelioma is a rare malignancy which has not been described in term pregnancy and appears to be unaffected by the pregnant state.

Cyclosporine-A induced nephrotoxicity is associated with decreased renal bone morphogenetic protein-7 expression in rats.

The aim of our study was to investigate bone morphogenetic protein-7 (BMP-7) expression in a rat model of chronic cyclosporine (CsA) toxicity compare with healthy controls, as well as the influence of treatment with the angiotensin-converting enzyme inhibitor (ACEI) quinapril. Twenty-four male Wistar rats were divided into groups of eight animals treated with CsA (15 mg/kg intraperitoneally) for 8 weeks (CsA group) without or with quinapril (10 mg/kg per day in the drinking water: CsA group + Q) for comparison with healthy controls (H group). The renal tissues were examined by light microscopy for CsA toxicity; specifically, tubulointerstitial damage and afferent arteriolopathy as well as BMP-7 expression were semiquantitatively scored by immunohistochemical staining. Mean CsA levels were 1982 ng/mL and 1968 ng/mL for the CsA and CsA + Q groups, respectively. At the end of the study period, the mean serum creatinine levels were 0.8 +/- 0.2 mg/dL, 1.6 +/- 0.8 mg/dL, and 1.4 +/- 0.8 mg/dL for the H, CsA, and CsA + Q groups, respectively. Interstitial fibrosis, tubular atrophy, and afferent arteriolar hyalinization were present in the CsA group and, to a lesser degree, in the CsA + Q group, compared with the H group. CsA-treated rats displayed significantly decreased BMP-7 expression compared with healthy controls (P <.0005). BMP-7 expression was higher among the CsA + Q group than the the group CsA group. In a rat model histologic changes characteristic of CsA-induced nephrotoxicity are associated with decreased expression of BMP-7, which seems to be at least partially restored by ACE inhibition.

Accelerated atherosclerosis in tertiary syphilis and successful treatment with saphenous vein grafting--a case report.

A 48-year-old male patient having none of the known risk factors for atherosclerosis underwent coronary artery bypass graft (CABG) surgery because of double-vessel coronary artery disease. During the operation, the aorta, both internal thoracic arteries (L/R-ITA), and the femoral artery were sclerotic, and CABG was performed using only saphenous vein grafts. A diagnosis of tertiary syphilis had been confirmed by either microscopic or serologic tests. There were different degrees of sclerosis in different arteries of different sizes. The presence of coronary artery disease with no known atherosclerotic risk factors should include preoperative testing for connective tissue disorders, chronic inflammatory disease, and cold hemagglutinins, because of the possible use of obligatory deep hypothermia or total circulatory arrest due to a diseased ascending aorta.

Comparison of omentum, pleura and diaphragm for tracheal autograft survival in rats.

Pleura, diaphragm, pericardial fat pad, intercostal muscles and omentum can be used to protect and revascularize the bronchial suture line. To compare the efficiency of pleura, diaphragm and omentum, an experimental study was designed. Heterotopic tracheal autotransplantation was performed in 15 rats. Animals were divided into three groups; omentum, diaphragm and pleura. Tracheal Segment Necrosis Scoring System was used for pathologic examinations. Pleural and diaphragmatic groups showed the least necrosis and there was significant statistical difference among these groups and omental group (P < 0.05). Our study showed that pleura and diaphragm could be used as safely as omentum for protection and survival of bronchial suture lines.

Use of fascial grafts as an interface in flap prefabrication: an experimental study.

An experimental study was conducted to investigate whether a fascial graft can be used as an interface between a vascular pedicle and target tissue to augment tissue survival in a prefabricated flap. Thirty-six male Sprague-Dawley rats were divided into three experimental groups according to the type of the recipient bed prepared for the vascular implantation. The left saphenous vascular pedicle was used as the vascular source. A 9 x 9-cm inferiorly based peninsular abdominal flap was elevated in each animal. In group I, the pedicle was tacked beneath the abdominal flap, in which the epigastric fascial layer was untouched. In group II, a 3 x 5-cm graft of epigastric fascia was harvested from the abdominal flaps under loupe magnification. The graft was sutured back into its original position after a 180-deg rotation. The vascular pedicle was then implanted just beneath the center of the fascial graft. In group III, the same size of epigastric fascia was removed in the same manner as group II, exposing the subcutaneous layer for pedicle implantation. Four weeks later, abdominal flaps were raised as island flaps connected only to the saphenous pedicle and were sutured in place. Flap viability was assessed visually on day 7. Overall, the ultimate flap survival in group I was the largest, with some necrotic areas at the periphery of the flaps. In group II, flap survival was typically centralized over the fascial graft, and crescent-shaped necrosis was noted superiorly. In group III, an almost linear pattern of survival overlying the vascular pedicle was observed. The mean surviving flap area of group I (12.13 +/- 1.615 cm2) was statistically greater than that of group II (8.83 +/- 0.663 cm2, p < 0.001) and group III (6.3 +/- 0.815 cm2; p < 0.001). There was a statistically significant difference between the mean flap survival in groups II and III (p < 0.001). Vascular arborization was examined by microangiography, and specimens were processed for histological staining. In group II, vascularization was distributed in a larger area along the fascial graft in comparison with limited vascularization around the pedicle in group III. In this study it was revealed that the interposition of a fascial graft as an interface between the vascular source and the target tissue seems to increase the size of the prefabricated flap.