Urotensin II receptor determines prognosis of bladder cancer regulating cell motility/invasion

Background

Non Muscle Invasive Bladder Transitional Cancer (NMIBC) and Muscle Invasive Bladder Transitional Cancer (MIBC)/invasive have different gene profile and clinical course. NMIBC prognosis is not completely predictable, since the relapse rate is higher than 20%, even in the form of MIBC. The aim of this study is to evaluate if UTR expression can discriminate between NMIBC and MIBC and predict the risk of relapses in NMIBCs.

Methods

We have investigated upon urotensin-II (UII) receptor (UTR) expression in vivo in 159 patients affected by NMIBC. The biological role of UTR was also investigated in vitro. UTR expression was evaluated in a tissue-micro-array, consisting of normal, NMIBC and invasive bTCC samples.

Results

UTR discriminated between NMIBC and MIBC and showed a significant correlation between low UTR expression and shorter disease free survival in NMIBC. The superagonist UPG84 induced growth suppression at nM concentrations on 3/4 cell lines. Bladder cancer cell treatment with the antagonist urantide or the knock-down of UTR with a specific shRNA significantly blocked both the motility and invasion of bladder cancer cells.

Conclusions

The evaluation of UTR expression can discriminate between NMIBC at high and low risk of relapse. Moreover, our data suggest that UTR is involved in the regulation of motility, invasion and proliferation of bladder cancer cells. High UTR expression is an independent prognostic factor of good prognosis for NMIBC regulating motility and invasion of bladder cancer cells.     

Role of epidermal growth factor receptor (EGFR) in corneal remodelling in diabetes

Purpose: This study examined the role of epidermal growth factor receptor (EGFR) signalling on the organization and remodelling of collagen fibrils (CFs) and proteoglycans (PGs) in the stroma of diabetic rat cornea. Methods: Diabetes was induced in female Wistar rats (n = 5) by streptozotocin (STZ) injection (55 mg/kg). Treatment with a selective inhibitor of EGFR tyrosine kinase, AG1478, was started on the same day as the induction of diabetes and administered every other day for 4 weeks. Corneas were fixed in 4% paraformaldehyde at 4 ° to allow for analysis of CF diameters and in 2.5% glutaraldehyde in sodium acetate buffer containing cuprolinic blue to enable the study of PG distribution. AnalySIS soft imaging software was used to analyse CFs and PGs. Results: Epithelial thickness, and median diameter and area fraction of CF in corneal stroma were decreased in diabetic rat cornea compared with normal cornea (p < 0.001), whereas the median PG area and area fractions were significantly increased (p < 0.001). Treatment with AG1478, although it had no action on normal cornea, prevented these diameter and area fraction changes in CFs and PGs. The cornea of AG1478‐treated diabetic rats showed a slight increase in CF diameter and area fraction and a decreased number density. Conclusions: These data show that the distribution of corneal stroma CFs and PGs was altered after 4 weeks of diabetes and that, furthermore, treatment with an EGFR signalling inhibitor normalized these abnormalities. The data suggest that EGFR plays an important role in the development of diabetes‐induced corneal remodelling.     

Prognosis of radiologically non-functioning obstructed kidneys

Twenty patients found to have unilateral radiologically non-functioning obstructed kidneys on excretory urography (IVU), and who had normal contralateral kidneys, were further evaluated. Ultrasonography, radionuclide imaging and CT scan were carried out pre-operatively to try to predict which of the kidneys were potentially recoverable after relief of obstruction. Percutaneous nephrostomy was also performed on the last consecutive 7 patients 4 weeks before definitive treatment and the function of the kidneys determined daily. The patients were re-evaluated 2 months after the relief of obstruction. Ultrasonography, radionuclide imaging and CT scan were not found to be reliable in predicting whether these kidneys were potentially recoverable. We consider percutaneous nephrostomy a good procedure for obtaining prognostic information prior to definitive surgery.     

Novel 1-phenylpiperazine and 4-phenylpiperidine derivatives as high-affinity sigma ligands.

sigma receptors may represent an exciting new approach for the development of novel psychotherapeutic agents. Unfortunately, many of the commonly used sigma ligands lack selectivity (e.g., many bind at phencyclidine or dopamine receptors) or suffer from other serious drawbacks. Recently, we described a series of 2-phenylaminoethanes that bind at sigma receptors with high affinity and selectivity. Because there is evidence that 1-phenylpiperazines can structurally mimic the 2-phenylaminoethane moiety, we prepared a series of 1-phenylpiperazines and related analogues and incorporated structural features already shown to enhance the sigma binding of the 2-phenylaminoethanes. Several of these derivatives bind at sigma receptors with high affinity (Ki = 1-10 nM) and lack appreciable affinity for phencyclidine and dopamine receptors. In as much as certain of these agents structurally resemble the high-affinity, but nonselective, sigma ligand haloperidol, and because they bind with 10 times the affinity of haloperidol, we have apparently identified what appears to be the primary sigma pharmacophore of that agent.     

Identification of Acutely Isolated Cells from Developing Rat Cerebellum

Immunocytochemical staining was used to identify nerve and glial cells from postnatal rat cerebelli in situ and following tissue dissociation. Purkinje cells were identified using antibodies for the calcium-binding proteins calbindin and PEP19. Purkinje cells isolated during the second postnatal week were 15-20 μm in diameter and relatively abundant and displayed thin perisomatic processes. These features were used to identify Purkinje cells with scanning electron microscopy, which revealed extensive membrane infoldings. Golgi and nuclear cells were identified using antibodies against rat-303 antigen. Pale, nuclear, and Purkinje cells were identified using antibodies for rat-302 antigen. Although staining for rat-302 and rat-303 was weak during the second postnatal week, we were able to identify Golgi and pale cells even after tissue dissociation. Isolated Golgi cells were 8-10 μm in diameter and fewer in number than Purkinje cells and did not counterstain with calbindin antibodies. Isolated pale cells were 8-10 μm in diameter, rare, and resistant to calbindin antibodies. Isolated neurons from cerebellar nuclei were not located with either 302 or 303 staining, suggesting that they remained in the tissue. Golgi-Bergmann cells and astrocytes were identified using antibodies for glial fibrillary acidic protein. Isolated glial cells were 12-15 μm in diameter, more numerous than Purkinje cells, and unstained with calbindin antibodies. With phase-contrast optics, glial cells appeared flatter than neuronal cell types and had acentric nuclei. These results demonstrate that specific cell types in developing rat cerebellum can be identified after acute isolation, which should facilitate analysis of their endogenous properties.     

Proximal phalangeal fracture after tendon pulley reconstruction

A case is presented in which an A2 pulley reconstruction was done, encircling a previously fractured, multiply-operated proximal phalanx. Bone resorption occurred directly under the pulley, and the bone then fractured. It is postulated that the cumulative effect of these operations on the blood supply to the bone and abnormal pressure forces led to resorption of bone and subsequent fracture.     

Unique Outbreak of Rift Valley Fever in Sudan, 2019

We report a unique outbreak of Rift Valley fever in the Eldamar area, Sudan, May–July 2019, that resulted in 1,129 case-patients and 19 (1.7%) deaths. Patients exhibited clinical signs including fever (100%), headache (79%), and bleeding (4%). Most (98%) patients also reported death and abortions among their livestock.     

Safety and efficacy of ultrasound ciliary plasty as a primary intervention in glaucoma patients

AIM: To evaluate the safety and the efficacy of the ultrasound ciliary plasty (UCP) on the intraocular pressure (IOP) control in glaucomatous eyes without previous glaucoma surgery. METHODS: A retrospective study included patients with primary and secondary glaucoma who underwent UCP in Dar AlShifa Hospital, Kuwait between January 2017 to June 2018. High-intensity focused ultrasound procedures were performed under peribulbar anesthesia using the 2nd generation probe with 8s duration of each of the 6 shots. Complete ophthalmologic examinations were scheduled pre-treatment, and at 1d, 1wk, 1, 3, 6 and 12mo post-treatment. Primary outcomes were the IOP reduction and success rates at 12mo, while the secondary outcomes were the occurrence of vision threatening complications and visual acuity. RESULTS: The records of 62 eyes of 62 patients were analyzed with mean age of 63.8y (67.7% males). There was statistically significant reduction in the mean IOP from 35.2±8.3 mm Hg before treatment to 20.6±8.7 mm Hg at 12th month (P<0.0005) with a mean percentage IOP reduction of 42.3% with significant reduction in the mean number of antiglaucomatous drugs from 3.2±0.4 before treatment to 2.1±1.02 at 12mo (P<0.0005). Qualified success was achieved in 77.4% of eyes at 12mo. No major intra- or post-treatment complications were reported. CONCLUSION: Second-generation UCP prove to be effective in reducing IOP in naive glaucoma patients with lower success rates in cases of neovascular and uveitic glaucomas.     

Correlation between Olive Oil Intake and Gut Microbiota in Colorectal Cancer Prevention

Extra virgin olive oil (EVOO) is a mainstay of the Mediterranean diet with its excellent balance of fats and antioxidant bioactive compounds. Both the phenolic and lipid fractions of EVOO contain a variety of antioxidant and anticancer substances which might protect from the development of colorectal cancer (CRC). The function of the intestinal microbiome is essential for the integrity of the intestinal epithelium, being protective against pathogens and maintaining immunity. Indeed, dysbiosis of the microbiota alters the physiological functions of the organ, leading to the onset of different diseases including CRC. It is known that some factors, including diet, could deeply influence and modulate the colon microenvironment. Although coming from animal models, there is increasing evidence that a diet rich in EVOO is linked to a significant reduction in the diversity of gut microbiome (GM), causing a switch from predominant bacteria to a more protective group of bacteria. The potential beneficial effect of the EVOO compounds in the carcinogenesis of CRC is only partially known and further trials are needed in order to clarify this issue. With this narrative review, we aim at discussing the available evidence on the effect of olive oil consumption on GM in the prevention of CRC.