Colonic fibronectin and E-cadherin in mild ulcerative colitis.

BACKGROUND: Although fibronectin has an important role in wound repair, nearly no human studies to date have investigated its condition in ulcerative colitis (UC) histologically. E-cadherin plays a critical role in the repair of normal epithelial tissues. This study aims to find out the condition of these two molecules in UC. MATERIAL AND METHODS: The records of 22 UC patients during the period of 2004‒2009 were retrospectively analyzed. We also included 24 patients with sporadic colorectal cancer (SCC) and 24 patients with normal colonoscopic biopsies who served as the control group. Colonoscopic biopsies were stained with E-cadherin and fibronectin. RESULTS: The E-cadherin loss was significantly more prominent in the SCC group, followed by the UC group and control group. The situation was reverse for fibronectin. We also observed that while the E-cadherin loss was still ongoing in all of the endoscopically inactive cases, the fibronectin staining resembled the staining pattern of normal individuals in ten out of thirteen UC patients. CONCLUSION: We suggest that the decrease in E-cadherin, even in the inactive period, might be the cause of why UC is not just a compensatory change in repair of inflammation. The results of staining with fibronectin in UC patients were between normal individuals and SCC patients. Further studies are necessary to confirm our results (Tab. 2, Fig. 6, Ref. 15). Text in PDF www.elis.sk Keywords: ulcerative colitis, fibronectin, E-cadherin.

Diagnostic value of MDCT in determining the perinephric fat tissue and renal sinus invasion in patients with clear cell renal cell carcinoma.

AIMS: To investigate the accuracy of multidetector computed tomography (MDCT) findings, and the effect of tumor volume in determining the perinephric and renal sinus invasion in clear cell renal cell carcinomas (ccRCCs). METHOD: Fifty patients with ccRCCs underwent non-contrast and nephrographic-phase contrast-enhanced MDCT examination before total nephrectomy. The following MDCT features were used to diagnose perinephric fat tissue invasion: perinephric stranding, perinephric vascularity, and irregular contour. The following MDCT features were used to diagnose renal sinus fat invasion: elongation of tumor into renal sinus, invasion, or compression of pelvicalyceal system. Histopathologic examinations were used as a gold standard. RESULTS: Fourteen out of 50 ccRCCs patients (28%) had histopathological-proven perinephric fat tissue invasion. The sensitivity, specificity, PPV, NPV, and accuracy of MDCT in the detection of perinephric fat tissue invasion were found 64%, 58%, 38%, 80%, and 60%, respectively. Seven out of 50 ccRCCs patient (14%) had histopathological-proven renal sinus invasion. The sensitivity, specificity, PPV, NPV, and accuracy of MDCT in the detection of renal sinus invasion were found 85%, 65%, 28%, 96%, and 68%, respectively. The area under of curve (AUC) value of tumor volume in the detection of perinephric fat invasion was 0.631. The AUC value of tumor volume in the detection of renal sinus invasion was 0.803. CONCLUSION: MDCT has a good sensitivity for detection of renal sinus fat invasion, but low PPV and specificity in patients with ccRCC. Tumor volume, and invasion into the pelvicalyceal structures can aid in the diagnosis of renal sinus fat invasion preoperatively.

Can platelet-rich plasma be used safely in intra-abdominal operations?

OBJECTIVES: In this study, it was aimed to investigate whether or not platelet­rich plasma (PRP) causes intra-abdominal adhesions and therefore, whether or not PRP can be used safely in intra-abdominal operations. METHODS: Of the total of 35 animals, 5 were used as donors for the preparation of platelet­rich plasma (PRP). The surgical procedures were performed on the remaining 30 animals. These rats were randomized and divided into 3 groups of 10. In Group 1, no adhesion induction was performed. Adhesion was induced by cecal abrasion and peritoneal resection model in Groups II and IIII. In Group 2, no treatment was given. In Group 3, 1 cc PRP was applied on the cecum. The rats were sacrificed on postoperative day 21. RESULTS: According to adhesion scores, the difference between the sham and PRP groups was not statistically significant. There was also no significant difference between the control and PRP groups, but the adhesion scores in the PRP group was lower than those in the control group. On histopathological evaluation, the difference between the sham and PRP groups was not statistically significant. There was also no significant difference between the control and PRP groups, but the average fibrosis and inflammation scores in the PRP group were lower than those in the control group. CONCLUSION: The results of the present study have demonstrated that PRP neither reduced nor exacerbated postoperative adhesions. Thus, PRP can be used safely in experimental and clinical studies where it will be applied intra-abdominally (Tab. 2, Fig. 3, Ref. 11).

Effects of Ankaferd Blood Stopper and calcium alginate in experimental model of hepatic parenchymal bleeding.

BACKGROUND: This experimental study compared the hemostatic effects of calcium alginate and Anka-ferd Blood Stopper in hepatic parenchymal bleedings. MATERIAL AND METHOD: The study comprised 39 male Wistar albino rats (weight 230±30 g). Laceration model was created in the left lateral lobe of the liver. Standard cotton gauze that was impregnated 0.9% NaCl solution and Calcium alginate cover was compared to ABS tampon. The amount of preoperative bleeding, preoperative and postoperative Day 1 hematocrit levels, and the difference between them were assessed and statistically analyzed. RESULTS: Comparing the hematocrit levels between the groups, we found that the amount of bleeding was significantly higher in the control group versus the study groups (p<0.001). Histopathological examination revealed the portal area enlargement and biliary canaliculi proliferation. In the Ca2+ Alginate group, it was observed that the fibres were still present in the incision line with massive fibrotic area around. In the Ankaferd group, examination of the preparations revealed patchy focal necrosis areas but no fibrotic area. CONCLUSION: With this study, we demonstrated that both calcium alginate and Ankaferd have hemostatic effect in preventing hepatic parenchymal bleeding and that calcium alginate causes fibrosis in the liver, where ABS causes focal necrosis areas(Tab. 2, Fig. 4, Ref. 19).

Effect of ozone therapy on autogenous bone graft healing in calvarial defects: a histologic and histometric study in rats.

AIM: The purpose of this study was to analyze histologically the effect of ozone therapy in combination with autogenous bone graft on bone healing in rat calvaria. METHODS: Critical size defects were created in calvaria of 27 male Wistar rats. The animals were divided into three groups of nine animals each: autogenous bone graft group (n = 9); autogenous bone graft with ozone therapy group (80%, 30 s 3 d for 2 wk, n = 9); non-treatment (control) group (n = 9). Animals were killed after 8 wk. Histomorphometric assessments, using image analysis software, and histological analyses were performed. Primary outcome was total bone area. Secondary outcomes (osteoblast number, new bone formation) were also measured. RESULTS: Histomorphometrically, the total bone area in the autogenous bone graft with ozone therapy group (9.3 ± 2.2) were significantly higher than that of the autogenous bone graft group (5.1 ± 1.8) (p < 0.05). Also, the ozone therapy group significantly increased the percentage of total bone area compared to the autogenous bone graft group (p < 0.05). The osteoblast number significantly increased in the autogenous bone graft with the ozone therapy group (58 ± 12.3) compared to the autogenous bone graft group (9.3 ± 3.5) (p < 0.05). Also, it was observed that autogenous bone graft with ozone therapy group showed significant new bone formation when compared to the autogenous bone graft group (p < 0.05). CONCLUSION: Ozone therapy enhances new bone formation by autogenous bone graft in the rat calvarial defect model.

Antitumor effects of Origanum acutidens extracts on human breast cancer.

PURPOSE: There has been a long-standing interest in the identification of medicinal plants and derived natural products for developing anticancer agents. This work aimed at investigating the antiprolipherative properties of Origanum acutidens (OA) on breast cancer. METHODS: OA water extracts were studied for cytotoxicity against the breast cancer cell lines MCF-7, MDA-MB-468 and MDA-MB-231. In vitro apoptosis studies of these cancer cell lines were performed by annexin V staining in flow cytometry analyses. Immunohistochemistry studies for Ki-67 and caspase-7 of tumor tissue sections of dimethylbenzanthracene (DMBA) -induced mammary cancer in rats were also performed. TUNEL assay was used to detect apoptotic cells of tumor tissue. In vivo anticancer activity testing was carried out by inhibiting the growth of DMBA-induced mammary cancer in rats. RESULTS: OA showed cytotoxicity on all 3 cancer cell lines. Annexin-positive cells level in OA-treated cell lines were significantly higher compared with untreated control cells (p=0.002). The expressions of caspase-7 protein and TUNEL-positive cells were much higher for the rats treated by OA, compared with the untreated control group (p<0.05). The expressions of the Ki-67 decreased in the treated groups compared with the control group (p<0.05). In vivo studies showed that the mean tumor volume inhibition ratio in OA-treated group was 41 % compared with the untreated rats (p<0.05). CONCLUSION: These results indicate that OA has antitumor activity against breast cancer cell lines.

Poly(glycidyl methacrylate) modified cellulose nanocrystals and their PBAT-based nanocomposites.

Melt processing of cellulose nanocrystals (CNCs) reinforced nanocomposites is still a serious challenge due to the hydrophilic nature of CNCs and their severe agglomeration tendency within the polymer melt. In this study, chemical modification of CNC through grafting poly(glycidyl methacrylate) (PGMA) with various degrees was implemented. Wettability of the modified CNCs (mCNCs) were controlled and their structure was characterized through Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), optical microscopy, X-ray diffraction (XRD), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). The nanocomposites of polybutylene adipate terephthalate (PBAT) with 3 wt% CNC and mCNC were prepared using an internal melt mixer. To differentiate the effects of CNC and PGMA molecules on the final properties of nanocomposites, PBAT/PGMA compounds were separately prepared. To confirm the chain characterization and molecular weight of the synthesized PGMAs, 1H NMR and gel permeation chromatography (GPC) analysis were conducted. Melt rheological analysis, dynamic mechanical analysis (DMA), DSC, and atomic force microscopy (AFM) were used to monitor the mCNC dispersion quality and the effect of PGMA modification in PBAT compounds. The results revealed that grafting CNC with longer PGMA considerably improved the CNCs' dispersion quality within PBAT. Such dispersion enhancement of long-chain mCNCs and interfacial interaction of PGMA and PBAT resulted in a noticeable increase in storage modulus and complex viscosity of the final nanocomposites.

Could immune cells be associated with nephropathy in Fabry disease patients?

BACKGROUND: In Fabry Disease (FD), although the primary factor initiating kidney damage is glycosphingolipid accumulation, secondary conditions such as increased inflammation and fibrosis may cause this damage to progress. These processes may be induced by immune cells. Therefore, we aimed to investigate the peripheral lymphocyte subgroup analysis of the patients with FD and compare these results with healthy individuals. In addition, we performed T, B, NK, and plasma cell analyses in kidney biopsy materials and compared these kidney biopsy results with the biopsy results of patients whose kidney functions were impaired after 4 years of regular ERT. MATERIALS AND METHODS: 18 FD and 16 healthy individuals were included in the study. T-B lymphocyte and NK-cell populations were determined. We performed kidney biopsies (KBx) on 13 patients with FD prior to ERT. Of these, 4 patients had rebiopsy after 4 years of regular ERT. Immunohistochemical staining was performed to define immune cell infiltration. RESULTS: There was no statistically significant difference in terms of total, helper and cytotoxic T-lymphocyte and CD3-CD16+CD56+ natural killer (NK)-cell count (p = 0.20; p = 0.12; p = 0.76; p = 0.75, respectively).According to KBx findings prior to ERT, all patients had interstitial fibrosis (IF), podocyte vacuoles (PV), and podocyte inclusion (PI), CD3, CD4, CD8, CD16, and CD56 positivity at different levels. None of the patients had CD19, CD20, and CD138 positivity at the first biopsies. When we compared the first and the second KBx results of the two progressors, we also demonstrated that CD3+4+T-cells infiltration remained the same, whereas CD8+T cells, CD16+ and 56+NK-cells infiltration were significantly decreased. In contrast, CD20+B cells and CD138+plasma cell infiltration were significantly increased despite 4 years of ERT (15 fold and sixfold, respectively). The CD20+B and CD138+ plasma cells and IF were positively correlated with proteinuria. CONCLUSIONS: The progression of FD nephropathy and proteinuria is increased despite a long-term ERT. Immune cells, primarily B and plasma cells, might cause these unwanted consequences.

The impact of smoking on clinical features of Behçet's disease patients with glutathione S-transferase polymorphisms.

OBJECTIVES: Various cancer studies have suggested that polymorphism of GSTM1 may influence the ability to detoxify chemicals in cigarette smoke. In the present study the effect of smoking on clinical features of Behçet's disease were investigated in patients having GST-M1 and/or -T1 null polymorphisms. METHODS: Ninety-seven patients meeting International Study Group Criteria for Behçet's disease (63 male, 34 female) and 172 healthy controls (94 male, 78 female) were included into the study. GST-M1 and -T1 polymorphisms were investigated using polymerase chain reaction-restriction fragment length polymorphism technique. RESULTS: Frequency of GSTM1- and/or GSTT1-null polymorphisms were comparable between the Behçet and the control groups. Smoking patients with GSTM1 null-polymorphism have decreased risk of developing papulopustuler lesions (OR=0.227 [0.063-0.818], χ2=5.463, p=0.019). Non-smoking patients with GSTM1 null-polymorphism has increased risk for having chronic arthritis (OR=5.988 [0.845-43.478]) but smoking patients with GSTM1 null-polymorphism have decreased risk (OR=0.741 [0.593-0.926]). GSTT1 null-polymorphism is associated with the presence of venous insufficiency (χ2=6.273, p=0.012, OR=2.740 [1.224-6.135]); smoking further increases the risk (χ2=7.840, OR=3.333 [1.412-7.874], p=0.005). GSTM1 null-polymorphism seemed to effect development of large vessel vasculitis (OR=1.158 [0.981-1.367], χ2=4.760, p=0.029). Male smoker Behçet patients even have more risk (OR=1.250 [0.971-1.610]). CONCLUSIONS: Several manifestations of Behçet's disease may be influenced by smoking, and this effect can be augmented in patients carrying GST gene polymorphism, which code enzymes crucial for the detoxification of chemicals.

N-acetylcysteine decreases alveolar bone loss on experimental periodontitis in streptozotocin-induced diabetic rats.

BACKGROUND AND OBJECTIVE: The purpose of this study was to evaluate the morphometric and histopathological changes associated with experimental periodontitis in diabetic rats in response to systemic administration of N-acetylcysteine (NAC), a sulfhydryl-containing thiol antioxidant. MATERIAL AND METHODS: Sixty Wistar rats were divided into six experimental groups: nonligated (NL) group; ligature-only (L) group; streptozotocin-only (STZ) group; STZ and ligature (STZ + L) group; and systemic administration of NAC and ligature (70 and 100 mg/kg body weight per day, respectively) (NAC70 and NAC100 groups). Diabetes mellitus was induced by 60 mg/kg of streptozotocin. Silk ligatures were placed at the gingival margin of the lower first molars of the mandibular quadrant. The study duration was 30 d and the animals were killed at the end of this period. Changes in alveolar bone levels were clinically measured and tissues were histopathologically examined to assess the differences among the study groups. RESULTS: At the end of the 30-d study period, alveolar bone loss was significantly higher in the STZ + L group compared with the other groups (p < 0.05). Also, alveolar bone loss in all the NAC groups was significantly lower than in the STZ + L and L groups (p < 0.05). The osteoblastic activity in the NAC100 group was significantly higher than in the other groups (p < 0.05). CONCLUSION: Within the limits of this study, it can be suggested that NAC, when administered systemically, prevents alveolar bone loss in the diabetic rat model.

Preventive effects of thymoquinone in a rat periodontitis model: a morphometric and histopathological study.

BACKGROUND AND OBJECTIVE: Thymoquinone has a variety of pharmacologic properties, including antihistaminic, antibacterial, antihypertensive, hypoglycemic, anti-inflammatory and anti-oxidative activities. Through its anti-inflammatory and antioxidant properties, thymoquinone may play an important role in preventing periodontal diseases. The aim of this study was to evaluate the effectiveness of thymoquinone in preventing the initiation and progression of periodontitis in a rat periodontitis model. MATERIAL AND METHODS: Twenty-four rats were randomly divided into three experimental groups: a nonligated (NL) treatment group (n = 8), a ligature-only (LO) treatment group (n = 8) and a ligature plus thymoquinone (10 mg/kg, daily for 11 d) (TQ) treatment group. In order to induce experimental periodontitis, a 4/0 silk suture was placed at the gingival margin of the right-mandibular first molars of the rats. Thymoquinone was administered by gastric feeding until the animals were killed on day 11. Changes in the alveolar bone levels of rats in each group were measured clinically, and tissues of rats in each group were examined histopathologically to determine inflammatory cell infiltration (ICI), osteoblast and osteoclast activities, and osteoclast morphology. RESULTS: Alveolar bone loss around the mandibular molar tooth was significantly higher in the LO group compared with NL and TQ groups (p < 0.05). The ratio of the presence of ICI and osteoclast numbers was significantly higher in the LO group than in the NL and TQ groups (p < 0.05). Osteoblastic activity was significantly lower in the LO group than in the NL and TQ groups (p < 0.05). CONCLUSION: The present study showed that the oral administration of thymoquinone diminishes alveolar bone resorption in a rat periodontitis model.

The effect of sorafenib in postoperative adhesion formation in a rat uterine horn model.

OBJECTIVE: Postoperative adhesions are a serious problem. In this study, we aimed to observe the effects of sorafenib in postoperative adhesions and, to examine the effects of sorafenib on tissue levels of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). MATERIAL AND METHODS: Twenty female Wistar albino rats were randomized into two equal groups; sorafenib group (sorafenib treated) and control group; then all rats underwent laparotomy. Adhesions were developed by scalping on the anti-mesenteric surfaces of the right uterine horns. After 14 days, adhesions were investigated by using macroscopic, histopathological and immunohistochemical (for VEGF and PDGF) methods. RESULTS: The sorafenib group had lower scores of total adhesions [1 (0-2.5) vs 1.5 (1-4); p: 0.037], staining of VEGF [1 (0-1) vs 1 (1-3); p: 0.029] and PDGF [1 (0-2) vs 2 (1-3); p: 0.006], and vascular proliferation [1 (0-2) vs 2 (1-3); p: 0.038] than the control group. CONCLUSION: The findings of the present study show that sorafenib, a tyrosine kinase inhibitor, significantly reduced postoperative adhesion formation. This effect may be explained by inhibition of VEGF, PDGF, and thus vascular proliferation.

Effect of fibrin glue and comparison with suture on experimental induction of endometriosis in a rat endometrial autograft model.

OBJECTIVE: The effects of fibrin glue (FG) and suture were investigated and compared with experimental induction in an endometriosis model. MATERIAL AND METHODS: A randomized, controlled, and double-blind study was performed with 25 adult female Wistar Albino rats. Two autologous endometrial grafts were obtained from each of the rats. The endometrial grafts were transplanted by gluing with FG on the right abdominal wall and suturing with only 5/0 prolene on the left in ten rats. Gluing+suturing and after suturing over the covering with FG of the endometrial graft were performed, respectively, on the right and left in another ten rats. Covering with FG glue of the endometrial graft was performed in another five rats. The endometriosis-like lesions and intraperitoneal adhesions were evaluated macroscopically and histopathologically. RESULTS: The mean volume (31.4 +/- 17.3), adhesion (0.8 +/- 0.7) and inflammatory reaction (1.2 +/- 0.7) score of the implants in the group using only FG were significantly lower than in the group using suture [respectively, (49.2 +/- 20.6), (2.4 +/- 0.8), (2.2 +/- 0.8)] (p < 0.05). CONCLUSIONS: Our results demonstrate the general feasibility of reproducible and reliable endometrial graft fixation with FG onto the inner abdominal surface in rats. Furthermore, several advantageous characteristics could be demonstrated such as less inflammation and fewer adhesions.

Neonatal non-ketotic hyperglycinemia.

The typical imaging findings of neonatal non-ketotic hyperglycinemia have rarely been described in the radiologic literature with only few individual cases or small series reported. In this article, we present a case of neonatal onset non-ketotic hyperglycinemia, imaged at 6 days of age, and discuss characteristic MRI and MR spectroscopic findings.

In vitro effects of 4-hydroperoxycyclophosphamide on human immunoregulatory T subset function. I. Selective effects on lymphocyte function in T-B cell collaboration.

The alkylating agent cyclophosphamide may suppress or enhance immune responses in vivo but is inactive in vitro unless metabolized by microsomal enzyme activation. 4-hydroperoxycyclophosphamide (4-HC) is a synthetic compound that is spontaneously converted in aqueous solution to the active metabolites. In this report, we examined the in vitro sensitivity of functional human T cell subsets to 4-HC in a polyclonal B cell differentiation assay and in the generation of mitogen-induced suppressor cells for effector B cell function. Con A-induced T suppression of B cell differentiation is completely abrogated by a 1-h pretreatment of T cells at very low concentrations of between 10(-2) and 20 nmol/ml, whereas inducer T cell function is sensitive only to concentrations in greater than 40 nmol/ml. The effects of 4-HC on suppressor T cells appear to occur at concentrations that do not result in DNA cross-linking or decreased blastogenesis. Con A-induced T suppressors are generated from within the OKT4+, OKT8- subset and are sensitive to low-dose 4-HC only before activation, whereas differentiated suppressor cells are resistant to concentrations in greater than 80 nmol/ml. Low-dose 4-HC pretreatment of the B cell population results in abrogation of immunoglobulin secretion when treated B cells are cocultured with unfractionated T cells, however, this effect is completely reversible if pretreated B cells are cocultured with T cells devoid of suppressor activity. These results demonstrate that human presuppressor cells for B-effector function differentiate in response to Con A from the OKT4+, OKT8- subset and are exquisitely sensitive to low concentrations of CYP whereas mature suppressor and inducer functions are resistant to all but very high concentrations in vitro. The differential sensitivity of functional T and B cell subsets to 4-HC in vitro can be a very useful probe in dissecting immunoregulatory interactions with man.

A transformation-associated 130-kD cell surface glycoprotein is growth controlled in normal human cells.

Two characteristics of cell surface molecules involved in the regulation of cell proliferation are altered expression in relation to growth phase in normal cells and overexpression in transformed cells. Here, we describe a similar pattern of expression for a 130-kD cell surface glycoprotein (gp 130) in human cells. Synthesis and cell surface expression of gp130 were greatly increased in both virally and chemically transformed fibroblasts, fibrosarcomas, a squamous cell carcinoma of the skin, and T cell leukemia lines. Furthermore, gp130 expression was induced in serum-starved fetal fibroblasts by serum stimulation, and in fresh T cells by various activating agents. Expression in response to serum stimulation was associated primarily with the transition from a quiescent state (G0) into the cell cycle (G1).

PHF10 is required for cell proliferation in normal and SV40-immortalized human fibroblast cells.

Normal human diploid fibroblasts have limited life span in culture and undergo replicative senescence after 50-60 population doublings. On the contrary, cancer cells typically divide indefinitely and are immortal. Expression of SV40 large T and small t antigens in human fibroblasts transiently extends their life span by 20-30 population doublings and facilitates immortalization. We have identified a rearrangement in chromosome 6 shared by SV40-transformed human fibroblasts. Rearrangements involving chromosome 6 are among the most frequent in human carcinogenesis. In this paper, we extend analysis of the 6q26-q27 region, a putative site for a growth suppressor gene designated SEN6 involved in immortalization of SV40-transformed cells. Detailed molecular characterization of the rearranged chromosomes (6q*, normal appearing; and 6q(t), translocated) in the SV40-immortalized cell line HALneo by isolating each of these 2 chromosomes in mouse/HAL somatic cell hybrids is presented. Analysis of these mouse/HAL somatic cell hybrids with polymorphic and nonpolymorphic markers revealed that the 6q* has undergone a chromosomal break in the MLLT4 gene (alias AF6). This result in conjunction with previous published observations leads us to conclude that SEN6 lies between MLLT4 and TBP at chromosomal region 6q27. Examination of different genes (MLLT4, DLL1, FAM120B, PHF10) located within this interval that are expressed in HS74 normal fibroblast cells reveals that overexpression of epitope-tagged truncated PHF10 cDNAs resulted in reduced cell proliferation in multiple cell lines. Paradoxically, down-regulation of PHF10 by RNAi also resulted in loss of cell proliferation in normal fibroblast cells, indicating PHF10 function is required for cell growth. Taken together, these observations suggest that decreased cell proliferation with epitope-tagged truncated PHF10 proteins may be due to dominant negative effects or due to unregulated expression of these mutant proteins. Hence we conclude that PHF10 is not SEN6 but is required for cell growth.

Takayasu's arteritis in Turkey - clinical and angiographic features of 248 patients.

OBJECTIVE: Takayasu's arteritis (TA) is a chronic, inflammatory vasculitis affecting the aorta and its major branches. Although it is more prevalent in Far-East Asia, the distribution of the disease is worldwide with different vascular involvement patterns and clinical manifestations. The objective of this study was to evaluate the demographic, clinical, angiographic and prognostic features of TA patients in Turkey. METHODS: Clinical and angiographic findings of 248 TA patients (228 female, 27 male) followed at 15 Rheumatology Centers were prospectively evaluated according to a predefined protocol. RESULTS: The mean age was 40.1 years (30.2 years at the clinical onset). Clinical manifestations included constitutional symptoms in 66%, absent or diminished pulses in 88%, bruits in 77%, extremity pain in 69%, claudication in 48%, hypertension in 43% and cerebrovascular accidents (CVA) in 18% of the patients. Renal artery stenosis, aortic regurgitation and pulmonary hypertension were present in 26%, 33% and 12%, respectively. According to the new angiographic classification, type V (50.8%) and Type I (32%) were the most frequent types of involvement. Corticosteroids were the main treatment in 93% of the patients alone (9%) or in combination with immunosuppressive agents (84%). Most frequently preferred immunosuppressive agents were methotrexate (63%), azathioprine (22%) and cyclophosphamide (13%). Remission was observed at least once in 94% of the patients and sustained remission in 71% during follow-up. CONCLUSION: The demographical, clinical and angiographic findings of TA patients in our series were similar to those reported from Japan, Brazil and Colombia. Combination therapies with immunosuppressive agents were the preferred choice of treatment in Turkey.

Expression of retinoblastoma and cyclin D1 in gastric carcinoma.

Abnormal regulation of the cell cycle is a feature of many neoplasms. The role of cell cycle regulators in oncogenesis has been investigated in many human tumors. Alteration of the retinoblastoma (pRb) and cyclin D1 disrupt the Rb pathway and occur in many carcinomas. However the expression of the Rb and cyclin D1 in intestinal type gastric carcinoma is unclear. The purpose of this study was to investigate the expression of Rb and cyclinD1 in resected gastric carcinoma, their adjacent nonneoplastic mucosa and normal gastric mucosa, and finally to provide insights into the role of the Rb and cyclin D1 in gastric carcinogenesis. We investigated Rb and cyclin D1 expression in 43 patients (32 men, 11 women; mean age: 64) with primary gastric adenocarcinoma and compared the results with adjacent nonneoplastic mucosa. Adjacent nonneoplastic mucosa consisted of atrophy, dysplasia, intestinal metaplasia and gastritis. Expression of Rb was detected in 30 (69.7%) of gastric carcinoma, 18 (41.8%) of the adjacent nonneoplastic mucosa. Expression of cyclinD1 protein was detected in 31 (72%) of gastric carcinoma, 24 (55.8%) of adjacent nonneoplastic mucosa. Expression of Rb and cyclinD1 was not detected in normal gastric mucosa. The positive rate of Rb and cyclin D1 expression in gastric carcinoma was significantly higher than that adjacent nonneoplastic mucosa (p<0.05). There were significant trends for increased expression of Rb and cyclinD1 from nonneoplastic mucosa including atrophy, dyplasia, intestinal metaplasia and gastritis to carcinoma. These results suggested that positive expression of pRb and cyclinD1 might be an early event in gastric carcinoma and it tend to begin at precursor lesions and maintain throughout the progression of infiltration. Key words: Retinoblastoma, cyclin D1, gastric carcinoma, dysplasia, atrophy, intestinal metaplasia.

Effect of nitric oxide/cyclic guanosine mono-phosphate pathway on gallbladder relaxant response in bile duct-ligated guinea pigs.

BACKGROUND/AIMS: Common bile duct ligation (CBDL) in the guinea pig is a well-defined model of acalculous cholecystitis. Nitric oxide (NO) mediates smooth muscle relaxation by stimulating the activity of soluble guanylate cyclase. The aim of this study was to determine whether the NO/cyclic guanosine monophosphate pathway plays a role in gallbladder relaxant response after CBDL. METHODS: Relaxant response of gallbladder muscle strips from CBDL and sham-operated guinea pigs was studied in vitro. Animals were treated with saline, aminoguanidine or an aminoguanidine + L-arginine combination in vivo. Concentration-response curves of papaverine, diethylamine/NO, YC-1, sildenafil and amrinone were obtained and relaxations in each group were calculated as the percent of the contractions induced by carbachol (10(-6) M). RESULTS: There was a significant decrease in the gallbladder muscle relaxant responses to these substances in CBDL and aminoguanidine groups compared with sham surgical controls. The decreased relaxant response was reversed by aminoguanidine + L-arginine but not by aminoguanidine alone. CONCLUSION: Decreased relaxant responses might be due to the reduced guanylate cyclase enzyme activity, but further studies are required.