Fish: A Promising Screening Tool for Malignancy After Augmentation Cystoplasty?

INTRODUCTION: Malignancy after augmentation cystoplasty (AC) is reported up to 5.5 %. We assessed the use of urine fluorescence in situ hybridization (FISH) screening for bladder malignancy after AC. PATIENTS AND METHODS: In this study, 36/98 patients under follow-up who have completed tenth year after ileal AC were included prospectively. Twenty-four (66.7 %) patients were tested with FISH initially and overall 28 (77.8 %) patients with conventional cytology (CC). Twenty-four (66.7 %) patients with FISH analysis also had cytology analysis. Blinded from the cytology results, 32 (88.9 %) patients who were consented underwent cystoscopy with random biopsy (native bladder, ileal segment, ileovesical junction). Two patients those were tested with FISH did not consented cystoscopy. This study was registred to the government registry (No: 71146310). RESULTS: Mean follow-up time after AC was 15.4 ± 4.8 years. 2/32 (5.6 %) patients were diagnosed with adenocarcinoma in cyctoscopic biopsy. FISH analysis of 3/24 (12.5 %) patients demonstrated abnormal findings consistent with malignancy. Two FISH malignant patients were patients who had adenocarcinoma. The third patient's biopsy was benign and the third year control cystoscopy was normal. 2/4 patients with malignant CC had adenocarcinoma and 2/4 patients had benign biopsy. The sensitivity and specificity of FISH in our series were 100 % and 95 % respectively. Whereas the sensitivity and specificity of CC was 100 % and 91.6 % respectively. CONCLUSION: Despite limited number of patients in this study, FISH showed higher specificity than CC in this series. FISH is a promising tool for malignancy screening after AC. TYPE OF STUDY: Diagnostic Studies. LEVEL OF EVIDENCE: II.

The effect of mitochondria-targeted slow hydrogen sulfide releasing donor AP39-treatment on airway inflammation.

Mitochondrial dysfunction has been shown to contribute to the pathophysiology of airway diseases. Therefore, mitochondria are targeted in the development of new therapeutic approaches. Hydrogen sulfide (H2S) has been shown to be involved in the pathophysiological processes of airway inflammation. We aimed to evaluate the effect of mitochondria-targeted slow H2S releasing donor AP39 [(10-oxo-10-(4-(3-thioxo-3H-1,2-dithiol5yl)phenoxy)decyl)triphenylphosphoniumbromide)] on lipopolysaccharide (LPS)-induced airway inflammation in mice. LPS was applied to female Balb/c mice by intranasal (i.n.) route to induce airway inflammation and the subgroups of mice were treated with i.n. AP39 (250-1000 nmol/kg). 48 h after LPS administration airway reactivity was evaluated in vivo, then bronchoalveolar lavage (BAL) fluid and lungs were collected. LPS application led to bronchial hyperreactivity and neutrophil infiltration into the lung tissues along with increased TNF-α, IL-1ß and IL-6 levels in BAL fluid. LPS also induced an increase in the rate of glycolysis, glycogenolysis and Krebs-cycle. AP39 treatment prevented the LPS-induced bronchial hyperreactivity and reversed the increase in TNF-α and IL-6 levels in BAL fluid. The increase in neutrophil numbers in BAL fluid was also prevented by AP39 treatment at the highest dose. Our results indicate that AP39 can prevent bronchial hyperreactivity and decrease airway inflammation. Targeting H2S to the mitochondria may be a new therapeutic approach in airway inflammation.

An unexpected intracardiac location of yolk sac tumor.

PURPOSE: In the pediatric population, intracardiac tumors are rare, usually benign, and mostly diagnosed as rhabdomyoma. Yolk sac tumors (YSTs) are a rare malignant type of germ celltumor that typically occurs in gonads. It can also be seen in midline locations but the intracardiac location is extremely rare. METHODS: The case herein comprises an asymptomatic 2.5-year-old girl with a murmur detected under general examination. RESULTS: Echocardiography showed a 3 × 3-cm mass in the right ventricle. Cardiac magnetic resonance imaging revealed a smooth contoured mass in the right ventricle lumen, which was compatible with rhabdomyoma. After surgical resection, the histopathological results showed a YST. This diagnosis was supported by high values of subsequent serum alpha feto-protein. There was no evidence for any other primary location. CONCLUSION: When an intracardiac mass is observed, a YST should be considered. The increase in the alpha feto-protein level can help in the differential diagnosis.

Endocannabinoid metabolism inhibition ameliorates ovalbumin-induced allergic airway inflammation and hyperreactivity in Guinea pigs.

AIMS: Endocannabinoids are biologically active cannabinoid-related substances endogenously synthesized in many mammalian tissues. Mainly two enzymes carry out their degradation; Fatty Acid Amide Hydrolase (FAAH) and Monoacylglycerol Lipase (MAGL). Endocannabinoids are shown to affect the modulation of inflammatory processes and airway responsiveness. In the present study, we investigated the effects of FAAH and MAGL inhibitor treatments in experimental allergic airway inflammation in guinea pigs. MATERIALS AND METHODS: Guinea pigs were sensitized and challenged by ovalbumin to induce an allergic asthma model. Then, the effects of FAAH inhibitor URB597, MAGL inhibitor JZL184, and dual (FAAH/MAGL) inhibitor JZL195 on airway inflammation and hyperreactivity were evaluated. KEY FINDINGS: Ovalbumin challenge increased airway reactivity, IgE in serum, IL-4, and IL-13, and the percentage of eosinophils in bronchoalveolar lavage (BAL). In addition, inhibition of FAAH or MAGL enzymes leads to an increase in endocannabinoid levels. The selective inhibition of the FAAH enzyme prevented inflammation indicators such as cytokine production and inflammatory cell infiltration but had a negligible effect on airway hyperreactivity. However, the inhibition of the MAGL enzyme or dual inhibition of both FAAH and MAGL enzymes tent to moderate both pulmonary inflammation and airway hyperreactivity. SIGNIFICANCE: We have previously demonstrated that modulation of endocannabinoid levels in the airways by FAAH or MAGL inhibition can be useful in preventing acute lung inflammation. The results of the present study further suggest that FAAH and MAGL inhibitor treatment can also be a promising strategy for bronchial hyperreactivity and airway inflammation in allergic asthma.

Mitochondrial Dysfunction in Cyanotic Congenital Heart Disease: A Promising Therapeutic Approach for the Future.

Congenital heart disease (CHD) is one of the most specific and yet challenging fields of heart surgery. Apart from the known clinical approaches, including surgery, a significant scale of regenerative therapeutic options is available, which increase the number of cardiomyocytes and restore cardiac function. Although it has been revealed in recent years that mitochondrial transplantation can be used as a promising treatment option in this disease group, there is no clinical evidence for the significance of mitochondrial function in myocardial tissue of patients with CHD regarding cardiac surgery. In this study, mitochondrial morphology and function, myocardial fibrosis, and myocyte atypia were evaluated in myocardial biopsy tissue of pediatric patients with cyanotic and acyanotic CHD, five from each group. After histopathological evaluation of myocardial tissue specimens, mitochondrial morphology and network were analyzed by immunofluorescence staining using an anti-Tom20 antibody, electron transport chain complexes of myocardium were examined by cytochrome c oxidase/succinate dehydrogenase staining, and the amount of ATP was measured by bioluminescence assay. In addition, cardiac markers have been tested to be reviewed as a potential indicator for postoperative follow-up. Myocyte atypia and fibrosis were classified on a scale of 1 to 4. In this study, unlike patients with acyanotic CHD, alterations in mitochondrial network and reduction in ATP production were detected in all pediatric patients with cyanotic CHD. A statistically significant correlation was also determined between mitochondrial dysfunction and cardiac markers. These findings may be assumed as a promising pathway for evaluating the relationship between mitochondrial dysfunction and cyanotic CHD.

Trypsin-induced elevated contractile responses in a rat model of interstitial cystitis/bladder pain syndrome: Involvement of PAR2 and intracellular Ca2+ release pathways.

AIMS: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic inflammatory disease with unclear etiology. Different receptors play a role in the pathophysiology including protease activated receptors (PARs). The present study aimed to investigate the subtypes and the effects of PARs on contractility using permeabilized detrusor smooth muscle strips in IC/BPS. MAIN METHODS: IC/BPS was induced by cyclophosphamide injection. Histopathological analysis, PCR for detecting PAR proteins, western blotting for indicating PAR2 protein expression levels and myograph recording for measuring contractile force were used. KEY FINDINGS: The present study reveals that in rat bladder PAR1 and PAR2 but not PAR4 were found to be expressed. The first evidence was revealed where trypsin-induced contractions in rat permeabilized detrusor were potentiated in CYP-induced cystitis. Moreover, the functional inhibition of trypsin-induced contractions by selective PAR2 antagonist (ENMD-1068) and the supporting immunoblotting results emphasized that the main PAR subtype involved in IC/BPS model in rat bladder is PAR2. Our data emphasize the prominent role of IP3 in cystitis pathology besides ryanodine channels. Trypsin-induced Ca2+sensitization contractions were also higher in cystitis. Both Rho kinase and protein kinase C played a role in this increased Ca2+sensitization situation. SIGNIFICANCE: The present paper highlights the intracellular pathways that are involved in trypsin-induced contractions mainly via PAR2 in permeabilized bladder detrusor smooth muscle in a rat model of IC/BPS.

The effects of systemic and local fatty acid amide hydrolase and monoacylglycerol lipase inhibitor treatments on the metabolomic profile of lungs.

The contribution of the endocannabinoid system to both physiology and pathological processes in the respiratory system makes it a promising target for inflammatory airway diseases. Previously, we have shown that increasing the tissue endocannabinoid levels by fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) inhibitors can prevent airway inflammation and hyperreactivity. In this study, the changes in the levels of major metabolites of endocannabinoids by systemic and local FAAH or MAGL inhibitor treatments were evaluated. Mice were treated with either the FAAH inhibitor URB597 or the MAGL inhibitor JZL184 by local (intranasal) or systemic (intraperitoneal) application. Bronchoalveolar lavage (BAL) fluids and lungs were isolated afterward in order to perform histopathological and metabolomic analyses. There were no significant histopathological changes in the lungs and neutrophil, and macrophage and lymphocyte numbers in BAL fluid were not altered after local and systemic treatments. However, GC-MS-based metabolomics profile allowed us to identify 102 metabolites in lung samples, among which levels of 75 metabolites were significantly different from the control. The metabolites whose levels were changed by treatments were mostly related to the endocannabinoid system and energy metabolism. Therefore, these changes may contribute to the anti-inflammatory effects of URB597 and JZL184 treatments in mice.

The effects of fatty acid amide hydrolase and monoacylglycerol lipase inhibitor treatments on lipopolysaccharide-induced airway inflammation in mice.

Cannabinoids and the endocannabinoid system significantly contributes to the airway inflammation. Fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) are two main enzymes responsible for the metabolism of the endocannabinoids anandamide (AEA) and 2-arachydonoyl glycerol (2-AG), respectively. In the present study, we aimed to investigate the effects of local and systemic FAAH and MAGL inhibitor treatments in experimental airway inflammation and tracheal hyperreactivity in mice. Airway inflammation was induced by intranasal (i.n.) lipopolysaccharide (LPS) application (60 µl; 0,1 mg/ml in PBS) to mice and the control group received PBS. Systemic (intraperitoneal (i.p.)) or local (i.n.) FAAH inhibitor URB597 and MAGL inhibitor JZL184 treatments were administered 1h before LPS/PBS application. Fourty 8 h after LPS/PBS application, tracheas were removed to assess airway reactivity, and the lungs and bronchoalveolar lavage (BAL) fluids were isolated for histopathological evaluation, cytokine and endocannabinoid measurements. LPS application lead to an increase in 5-hydroxytryptamine (5-HT) contractions in isolated tracheal rings while carbachol contractions remained unchanged. The increased 5-HT contractions were prevented by both systemic and local URB597 and JZL184 treatments. Systemic treatment with URB597 and JZL184, and local treatment with JZL184 reduced peribronchial and paranchymal inflammation in the LPS group while i.n. application of URB597 worsened the inflammation in the lungs. Systemic URB597 treatment increased lung AEA level whereas it had no effect on 2-AG level. However, JZL184 treatment increased 2-AG level by either systemic or local application, and also elevated AEA level. Inflammation-induced increase in neutrophil numbers was only prevented by systemic URB597 treatment. However, both URB597 and JZL184 treatments abolished the increased TNF-α level either they are administered systemically or locally. These results indicate that FAAH and MAGL inhibition may have a protective effect in airway inflammation and airway hyperreactivity, and therefore their therapeutic potential for airway diseases should be further investigated.

Is bacterial vaginosis associated with autoimmune antibody positivity?

OBJECTIVE: To evaluate the association between bacterial vaginosis (BV) and autoimmune antibody positivity. METHOD: We evaluated Papanicolaou-stained cervicovaginal smears of 210 patients with poor obstetric history who were admitted to a special preconception counselling programme. Cytological specimens with various types of microorganisms except for BV, epithelial cell abnormalities and other non-neoplastic findings, including inflammation were excluded from the cohort in addition to patients with autoimmune and chronic inflammatory diseases. The remaining study population (n = 121) was divided into two groups of patients with autoimmune antibody positivity (study group, n = 80) and patients without antibody positivity (control group, n = 41). RESULTS: The rate of BV was demonstrated to be 13.8% and 2.4% in the study and control groups respectively (P = .042). We also demonstrated that the anti-nuclear antibody was positive in 58.3% of the cases with BV. CONCLUSION: BV was found more frequently in patients with autoimmune antibody positivity to a statistically significant degree.

Human papillomavirus infection and autoimmune disorders: a tertiary center experience.

This study aimed to investigate the relationship between HPV and autoimmune disorders. We retrospectively evaluated 62 women who had HPV-DNA positivity in terms of autoimmune disorders (autoimmune antibody positivity, chronic inflammatory diseases and autoimmune diseases). The patients were divided into two groups according to autoimmune disorder positivity (autoimmune positive (n = 30), autoimmune negative (n = 32)) and compared with each other in terms of single and multiple HPV-DNA types, high and low-risk HPV-DNA types, and Pap smear findings. We determined that 48.4% of the HPV-DNA positive patients had autoimmune disorders. We found that 15 of 62 (24.2%) women had more than one type of HPV and HPV type 16 was the dominant type in this study (58.2%). A total of 27.4% of HPV-DNA positive patients had abnormal cytological findings. There was no statistically significant difference between autoimmune groups in terms of the presence of high-risk HPV types, multiple HPV types and abnormal cytological findings (P = 0.531, P = 0.558 and P = 0.234, respectively). The prevalence of autoimmune disorders was high among HPV-DNA positive women. On the other hand, the rate of high-risk HPV type positivity, multiple HPV infections and cytopathological findings were similar between the autoimmune positive and negative groups.

Effects of intranasal treatment with slow (GYY4137) and rapid (NaHS) donors of hydrogen sulfide in lipopolysaccharide-induced airway inflammation in mice.

We have investigated the effects of slow (GYY4137) and rapid (NaHS) hydrogen sulfide (H2S) releasing donors in lipopolysaccharide (LPS)-induced airway inflammation in mice. LPS (0.1 mg/ml) in 60 µl PBS was administered by the intranasal (i.n.) route and control group received vehicle, whereas the subgroups of mice were treated with i.n. GYY4137 or NaHS. The tracheal reactivity, inflammatory cell count in bronchoalveolar lavage (BAL) fluid and lung histopathology were evaluated in all groups 48 h after LPS/PBS applications. 5-Hydroxytryptamine (5-HT)-induced contraction response in isolated tracheas was enhanced after LPS treatment but carbachol response was not altered. Incubation with atropine (10-6 M), 5-HT2A receptor antagonist ketanserin (10-9-10-7 M) and 5-HT3 receptor antagonist alosetron (10-8 and 10-7 M) prevented 5-HT-induced hyperreactivity whereas 5-HT4 receptor antagonist GR113808 (10-7 M, 10-6 M) did not have any effect in LPS-treated group. Electrical field stimulation (EFS) of isolated tracheas elicited frequency-dependent contractile response, which was not altered by LPS treatment alone but was enhanced in the presence of 5-HT (10-9-10-4 M). This data indicated that 5-HT2A and 5-HT3 receptors, and acetylcholine released from cholinergic nerves were contributing to 5-HT-induced hyperreactivity in the present experiments. The increase in neutrophil count along with cytokine (IL-1ß, TNF-α) levels in bronchoalveolar lavage (BAL) fluid and histopathological changes like paranchymal inflammation and interalveolar thickening were determined in LPS-treated mice. H2S production in lung homogenates were determined by the methylene blue assay, and found to be similar in both LPS and control groups. The experiments conducted after i.n. treatment with H2S donors has shown that only GYY4137 (1 mg/kg) inhibited 5-HT-induced hyperreactivity, and both GYY4137 and NaHS (1 mg/kg) prevented the neutrophil increase in BAL fluid in LPS-induced airway inflammation. IL-1ß increase in BAL fluid was abolished by both GYY4137 and NaHS treatments whereas TNF-α levels remained unchanged. Furthermore, GYY4137 treatment did not have any effect in LPS-induced changes of lung pathology whereas NaHS prevented the paranchymal inflammation. The different H2S releasing pattern of these donors may explain the difference of their effects in this model. Compounds that provide stable H2S levels via local application may be a new therapeutic approach in airway inflammation.

HPV types and E6/E7 mRNA expression in cervical samples from Turkish women with abnormal cytology in Ankara, Turkey.

BACKGROUND/AIM: Human papillomaviruses have been established as a risk factor for invasive carcinoma of the uterine cervix. HPV E6/E7 oncogene expression has recently emerged as a promising biomarker to determine the risk for progression to high-grade cervical lesions. The aim of this study was to evaluate HPV mRNA and DNA detection in samples with abnormal cytology. MATERIALS AND METHODS: Cervical specimens were obtained at the Department of Obstetrics and Gynecology via cervical brushes during January-October 2011. Liquid-based cytology slides were evaluated according to the 2001 Bethesda System. Cytology specimens from a total of 81 women with abnormal cytology were included. Real-time PCR and NASBA assays were performed to detect HPV DNA and E6/E7 mRNA, respectively. RESULTS: HPV DNA was identified in 73 samples (90.1%). HPV E6/E7 mRNA expression was observed in 45 samples (55.6%). A statistically significant difference was observed among cytological diagnosis groups. In 25 patients, a biopsy was performed during the follow-up. HPV DNA was detected in all of these patients. HPV E6/E7 expression was present only in CIN I-III diagnosed patients. CONCLUSION: The E6/E7 mRNA test is a robust indicator of cytological atypia and correlates better with progressive lesions than DNA assays.

Evaluation of the effect of changes in dose rate on rat lung cells.

The aim of this study is to evaluate the effect of dose rate (DR) on lung tissue. The rats included in the study were randomly grouped into 3 groups: Group (G) 1 was defined as control group, and in this group rats were sham irradiated. G2 was the group receiving a single dose of 12 Gy in DR of 300 monitor unit (MU)/min. G3 was the group receiving a single dose of 12 Gy in DR of 600 MU/min. Radiotherapy (RT) was applied under general anesthesia with 6-MV photon beams to both lungs. At the 6th and 16th week of the RT, animals from each group were killed for light and electron microscopy evaluation. We evaluated the scores of each group in the 6th and the 16th week and found that in G2, there were significant increases in the perivascular fibrosis (P = .018), interstitial fibrosis (P = .002), total inflammation (P = .040), and total fibrosis (P = .003) scores. In G3, we found statistically significant increases in perivascular fibrosis (P = .001), interstitial fibrosis (P = .002), and total fibrosis scores (P = .029). There was no significant difference in the total inflammation score in G3 (P = .225). When we compare G2 and G3 in the 6th week, we found significant increase in the interstitial thickening (P = .039) and total inflammation (P = .035) scores in G3. Dose rate per fraction may have an impact on normal tissue toxicity. The prominent effect of increased DR in lung tissue is fibrosis which should be kept in mind, especially in cases where higher doses per fraction are used.

Efficiency of ultrasound and ultrasound-guided fine needle aspiration cytology in preoperative assessment of axillary lymph node metastases in breast cancer.

PURPOSE: We performed this study to detect preoperative axillary metastases with ultrasound (US)-guided fine needle aspiration biopsy (FNAB), to eliminate the need for time-consuming and costly sentinel lymph node (SLN) scintigraphy and biopsy steps in the treatment of breast cancer patients, and in that of with suspicious US findings, and to evaluate the accuracy of preoperative US-guided FNAB for patients with suspicious lymph node metastases on US. METHODS: Patients with a suspicious breast lump or histopathologically proven breast cancer underwent breast-axillary US. Increase in lymph node size, cortical thickening, non-hilar cortical flow, and hilar changes were evaluated with gray scale-color Doppler US. FNAB was performed if US results were suspicious for malignancy. RESULTS: Thirty-eight axillary lymph nodes (ALN) underwent FNAB. ALN dissection, SLN scintigraphy, and biopsy steps were bypassed in 23 axillas with positive ALN FNAB (60.5%). The sensitivity of ALN FNAB was 88.46%; specificity and positive predictive value were 100%; and negative predictive value was 66.6% (inadequate cytology included; 76.7%, 100%, 100%, 53.3%, respectively). Asymmetrical cortical thickening, non-hilar cortical flow, and increase in hypoechogenity were only detected in metastatic nodes. Cortical thickening, and lymph node and breast mass size was higher in the metastatic group. CONCLUSION: By performing FNAB on suspicious lymph nodes, the routine, high-cost SLN scintigraphy and intraoperative gamma probe steps may be skipped, and axilla dissection can be performed directly. This leads to the elimination of the need for SLN investigation in more than half of the patients. The assessment of ALN metastases with preoperative US-guided FNAB is a cost-effective method with high specificity, that eliminates the need for costly and time-consuming SLN scintigraphy and biopsy steps, and helps in preoperative staging.

Stump appendicitis, rare complication after appendectomy: report of a case.

Appendectomy is one of the most common procedures in surgical practice. Stump appendicitis is an acute inflammation of the residual part of the appendix and a rare complication of incomplete appendectomy. It may present clinically as acute abdomen. We report a case of stump appendicitis 12 years after open appendectomy. After the diagnosis of acute appendicitis, the patient was operated and discharged from the hospital four days after operation without any complications. Stump appendicitis is a rare cause of acute abdomen and should be taken into consideration in the differential diagnosis.