Time interval between self-expandable metal stent placement or creation of a decompressing stoma and elective resection of left-sided obstructive colon cancer

Background The optimal timing of resection after decompression of left-sided obstructive colon cancer is unknown. Revised expert-based guideline recommendations have shifted from an interval of 5-10 days to approximately 2 weeks following self-expandable metal stent (SEMS) placement, and recommendations after decompressing stoma are lacking. We aimed to evaluate the recommended bridging intervals after SEMS and explore the timing of resection after decompressing stoma. Methods This nationwide study included patients registered between 2009 and 2016 in the prospective, mandatory Dutch ColoRectal Audit. Additional data were collected through patient records in 75 hospitals. Only patients who underwent either SEMS placement or decompressing stoma as a bridge to surgery were selected. Technical SEMS failure and unsuccessful decompression within 48 hours were exclusion criteria. Results 510 patients were included (182 SEMS, 328 decompressing stoma). Median bridging interval was 23 days (interquartile range [IQR] 13-31) for SEMS and 36 days (IQR 22-65) for decompressing stoma. Following SEMS placement, no significant differences in post-resection complications, hospital stay, or laparoscopic resections were observed with resection after 11-17 days compared with 5-10 days. Of SEMS-related complications, 48% occurred in patients operated on beyond 17 days. Compared with resection within 14 days, an interval of 14-28 days following decompressing stoma resulted in significantly more laparoscopic resections, more primary anastomoses, and shorter hospital stays. No impact of bridging interval on mortality, disease-free survival, or overall survival was demonstrated. Conclusions Based on an overview of the data with balancing of surgical outcomes and timing of adverse events, a bridging interval of approximately 2 weeks seems appropriate after SEMS placement, while waiting 2-4 weeks after decompressing stoma further optimizes surgical conditions for laparoscopic resection with restoration of bowel continuity

Dose-dependent differential mechanism of quercetin-induced vasodilatations in isolated perfused rat mesenteric vascular bed

Epidemiological studies indicate that low incidence of cardiovascular disease is associated with dietary intake of polyphenolic compounds, which are abundantly present in fruits and vegetables. There is solid evidence that quercetin, a polyphenolic compound, exerts vasodilator effects in addition to its antioxidant activity. Therefore, in this study, the contribution of shear stress-induced nitric oxide to the vasodilator effect of quercetin in mesenteric bed was investigated. Dose-dependent vasodilator effects of quercetin on the perfusion pressure increased by phenylephrine were recorded in the presence of L-arginine/cGMP pathway inhibitors or superoxide dismutase in the perfused mesenteric vascular beds isolated from rats. Quercetin (1, 5 and 10 µM) concentration-dependently decreased the perfusion pressure raised by phenylephrine (3-6 µM) in the endothelium-intact mesenteric bed. The relaxations occured at 1 and 5 µM quercetin were significantly inhibited by nitric oxide synthase inhibitor, N?-nitro-L-arginine (L-NA,100 µM) or the guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 5 µM), while relaxations to 10 µM quercetin were not affected. Removal of endothelium significantly reduced the relaxations at lower concentrations of quercetin but was without effect on relaxations induced by 10 µM. Calmidazolium (0.5 µM), a calmodulin inhibitor did not significantly affect the quercetin responses but a superoxide anion scavanger, superoxide dismutase (SOD, 100 U mL-1) significantly improved the quercetin-induced relaxations especially at 1 and 5 µM. These findings suggest that quercetin induces endothelium-dependent vasodilatations at lower concentrations by increasing the bioactivity of sustained nitric oxide release evoked by perfusion pressure. However, the vasodilatations induced by high concentrations of quercetin are endothelium-independent. © 2016 Ozlem Yorulmaz Ozü et al

Possible interactions between neomycin and calcium channels in abdominal skeletal muscle

The present study was performed to investigate whether neomycin, an aminoglycoside, interacts with calcium channels in the frog rectus abdominis muscle. We thus examined the effects of methoxyverapamil (D600), a dihydropyridine-sensitive calcium channel antagonist, and neomycin on contractions induced by acetylcholine (ACh; 10-6, 3 × 10 -6, 5 × 10-6, 10-5 and 5 × 10 -5 M), electrical field stimulation (EFS; 5, 8, 10 Hz, 15 V, 1 ms) and potassium chloride (KCl; 40 mM) in isolated frog rectus abdominis muscle. D600 (10-6 - 3 × 10-4 M) exhibited a concentration dependent inhibitory action on contractions evoked by ACh, EFS and KCl. Neomycin (10-5-5 × 10-4 M) significantly inhibited the contractions elicited by ACh and EFS in a concentration dependent manner but it failed to reduce the KCl-evoked contractions. These results suggest that the inhibitory action of D600 on ACh-, EFS- and KCl-induced contractions reflect the action of this agent on Ca2+-channel activity in the isolated frog rectus abdominis muscle. A similar mechanism may also be involved in the action of neomycin on the frog abdominal skeletal muscle

The effect of sub-chronic systemic ethanol treatment on corpus cavernosal smooth muscle contraction: The contribution of RhoA/Rho-kinase

PubMedID: 26728616The aim of this study was to evaluate whether the sub-chronic systemic ethanol exposure has direct effect on cavernosal smooth muscle contractions induced by KCl (depolarizing) and phenylephrine (?1-receptor agonist), and the possible involvement of RhoA/Rho-kinase pathway. Sub-chronic systemic ethanol was applied to mice with inhalation route for 14 days. The blood levels in ethanol-treated mice averaged 121.2 ± 9.1 mg/dl. KCl (80 mM) and phenylephrine (10 nM-100 µM) induced sustained contractions in corpus corporal strips from sham-treated mice. Sub-chronic ethanol treatment reduced the contractions to KCl. However, phenylephrine-induced contractions were not affected by ethanol treatment. Rho-kinase inhibitor fasudil (50 µM) and Y-27632 (50 µM) inhibited contractions to KCl and phenylephrine in sham-treated mice. Ethanol treatment increased the inhibitory effect of Rho-kinase inhibitors on contractions to phenylephrine. The relaxations induced by fasudil (100 µM) and Y-27632 (500 µM) did not change in ethanol treatment group. In ethanol-treated group, the expression of RhoA decreased compared to sham-treated group. Also, ROCK1 expression was reduced by ethanol but not statically significant to sham-treated group; however, the expression of ROCK2 increased in ethanol group. From these findings, it seems that phenylephrine and KCl-induced contractions depends on RhoA/Rho-kinase-mediated Ca2+ sensitization. Also, these results suggest that the ethanol treatment decreased the expression of RhoA, and the inhibitory effect of ethanol on KCl-induced contractions may be due to, at least in part, the inhibition of a RhoA/Rho-kinase in mouse corpus cavernosum. © 2016 Springer-Verlag Berlin Heidelberg

Effect of phosphodiesterase type 4 inhibitor rolipram on cyclophosphamide-induced bladder over activity

WOS: 000253839801176

Stromal podoplanin expression and its clinicopathological role in breast carcinoma

Introduction: Breast cancer is still a serious health problem in 21 st century and diagnosis, treatment and prognosis of this malignant disease are subject to many research. While cancer research has been focused on tumour cells primarily, recent studies showed that tumour stroma contribute to carcinogenesis as well as tumour cells. Especially fibroblasts adjacent to epithelial tumour cells are not ordinary fibroblasts and play the critical role. Studies showed that these cancer associated fibroblasts (CAFs) have different genetic profile and protein expression. One of the differently expressed molecules recently found is podoplanin. Podoplanin, utilised as a lymphatic endothelial marker, is found to be expressed in CAFs. The aim of this study is to evaluate the relationship between the stromal expression of podoplanin in invasive breast carcinoma and clinicopathological parameters. Materials & Methods: Podoplanin expression was evaluated immunohistochemically in 153 breast cancers. Tumours with ? 10% distinct cytoplasmic podoplanin staining in CAFs were considered as positive. Results: In 65.3% of analysed tumours, podoplanin expression was found positive in CAFs. According to our results, podoplanin positive CAFs correlated significantly with tumour size (p= 0.012), tumour grade (p= 0.032) and cerbB2 score (p= 0.032). Discussion: Our results suggest that podoplanin expression by CAFs could predict poor patient outcome in breast carcinoma. © 2018, Malaysian Society of Pathologists. All rights reserved

Neocuproine, a copper (I) chelator, potentiates purinergic component of vas deferens contractions elicited by electrical field stimulation

PubMedID: 16020948Effects of the specific copper (I) chelator, neocuproine, on the purinergic and adrenergic components of nerve-evoked contractions were investigated in the prostatic rat vas deferens. Electrical field stimulation (EFS; 4 Hz) induced bimodal contractions of vas deferens tissue in the presence of ?1-adrenoceptor antagonist prazosin (to isolate the purinergic component) or purinoceptor antagonist suramin (to isolate the adrenergic component). Neocuproine significantly potentiated the purinergic component of the contractile responses to EFS. However, the same agent failed to elicit any significant effect on the adrenergic component of nerve-evoked contractions. The copper (II) chelator cuprizone could not affect the purinergic component of contractions. The potentiating effect of neocuproine which was reversible after washout of the drug, did not occur following the application of the pre-prepared neocuproine-copper (I) complex. A nitric oxide synthase inhibitor, L-nitroarginine; a cyclooxygenase inhibitor, indomethacin or an ?2-adrenoceptor antagonist, yohimbine, failed to alter the responses to neocuproine on the purinergic component of the contraction to EFS. Neocuproine did not elicit any significant effect on preparations in which the purinergic receptors were desensitized with ?,ß-methylene ATP. In conclusion, our results suggest that neocuproine potentiates the purinergic component of rat vas deferens contractions elicited by EFS, presumably by facilitating purinergic neurotransmission and that copper (I)-sensitive mechanisms can modulate purinergic transmission in this tissue. Copyright © 2005 S. Karger AG

Effects of some divalent cations on nitrergic relaxations in the mouse corpus cavernosum

PubMedID: 11903503Acute effects of some divalent cations (Cd2+, Ni2+, Co2+, Zn2+, Mn2+ and Sn2+) were investigated on neurogenic and endothelium-dependent relaxations in the isolated mouse corpus cavernosum. Neither neurogenic nor endothelium-dependent relaxation was affected by cations at the concentrations used (up to 100 µM), except Cd2+. Although Cd2+ (20 and 40 µM) did not cause any significant alteration in the acetylcholine- (ACh) or sodium nitroprusside- (SNP) induced relaxation, it inhibited electrical field stimulation-(EFS) produced relaxation significantly. Zn2+ and selenium could not reverse this inhibitory action. Cd2+ did block the EFS-evoked guanethidine-sensitive contraction in the presence of NG-nitro-L-arginine. Elevation of external Ca2+ content significantly reduced the inhibitions due to Cd2+ on the EFS-induced relaxation and on the EFS-evoked guanethidine-sensitive contraction. In the Ca2+-omitted medium, EFS-induced relaxation disappeared, while acetylcholine-elicited relaxation resisted. Verapamil was ineffective on the relaxation produced by EFS or acetylcholine. However, it significantly diminished phenylephrine-induced contractions. These findings suggest that unlike other cations at the concentrations used in the present study, Cd2+ may have an effect on an external Ca2+-dependent mechanism at the neuronal level, and this effect may be responsible for its acute inhibitory action on the neurogenic relaxation in the mouse corpus cavernosum