Robot-assisted laparoscopic placement of extravascular stent for nutcracker syndrome.

A 20-year-old man complained of debilitating left flank pain for 6 months with an episode of gross hematuria. Computed tomography showed compression of the left renal vein between the aorta and superior mesenteric artery with an aortomesenteric angle of 25 degrees. Venography showed a gradient of 3 mm Hg across the compression and 94.4% luminal compression of the left renal vein. After discussion of all surgical and endovascular options, robot-assisted laparoscopic placement of an extravascular cuff around the left renal vein was performed using the da Vinci X Surgical System (Intuitive Surgical, Sunnyvale, Calif). The patient did well with full resolution of the left flank pain.

Renocolic fistula: A rare complication of obstructive uropathy.

Renocolic fistulas are abnormal connections between the upper urinary tract and the colon. Chronic renal obstruction and delayed treatment of obstructive renal stones can lead to loss of renal function, inflammation of the kidney and surrounding structures, and the development of fistulas. However, due to the increased availability of CT scans and cystoscopy for diagnosis and treatment, renocolic fistulas resulting from obstructing renal stones have become rare. This article describes a patient who was found to have a renocolic fistula on antegrade percutaneous nephrostogram. The patient was treated with a laparoscopic nephrectomy and minimally invasive colon repair and recovered.

Relationship between voided volume and the urge to void among patients with lower urinary tract symptoms.

OBJECTIVE: The aim of this study was to explore the relationship between voided volume (VV) and urge to void among patients with lower urinary tract symptoms. MATERIAL AND METHODS: Consecutive adult patients (aged 23-90 years) were enrolled, and completed a 24 h bladder diary and the Urgency Perception Scale (UPS). Patients were categorized as urgency or non-urgency based on the Overactive Bladder Symptom Score. The relationship between UPS and VV (based on the bladder diary) was analyzed by Spearman's rho and proportional odds model. RESULTS: In total, 1265 micturitions were evaluated in 117 individuals (41 men, 76 women; 56 individuals in the urgency and 61 in the non-urgency group). The mean (± SD) VV and UPS were 192 ± 127 ml and 2.4 ± 1.2 ml in the urgency group and 173 ± 124 ml and 1.7 ± 1.1 ml in the non-urgency group, respectively. Spearman's rho (between UPS and VV) was 0.21 [95% confidence interval (CI) 0.13-029, p < 0.001] for the urgency group, 0.32 (95% CI 0.25-0.39, p < 0.001) for the non-urgency group, and 0.28 (95% CI 0.23-0.33, p < 0.001) for the total cohort. Urgency patients had higher UPS [odds ratio (OR) 3.1, 95% CI 2.5-3.8]. Overall, each additional 50 ml VV increased the odds of having a higher UPS with OR 1.2 (95% CI 1.2-1.3). The relationship between VV and UPS score was similar in both groups (p = 0.548 for interaction). CONCLUSION: Although urgency patients void with a higher UPS score, among both urgency and non-urgency patients there is only a weak correlation between VV and the urge to void. This suggests that there are factors other than VV that cause the urge to void.

Erk1/2-dependent phosphorylation of PKCalpha at threonine 638 in hippocampal 5-HT(1A) receptor-mediated signaling.

Stimulation of the serotonin 1A receptor (5-HT(1A)-R) causes activation of extracellular signal-regulated protein kinase (Erk) and protein kinase C alpha (PKCalpha) in both hippocampal HN2-5 cells and cultured hippocampal slices from postnatal day-15 (P15) mice. Our earlier studies demonstrated that PKCalpha is co-immunoprecipitated with Erk and the phosphorylation of PKCalpha in this Erk-PKCalpha complex is dependent on the Erk pathway. Furthermore, the T(638) residue, which must be phosphorylated for the complete activation of PKCalpha, is within an authentic Erk consensus domain (S/TP), and the PKCalpha protein also contains two docking sites for Erk such as KRGRIYL and KRGIIYRDLKL. Using Föster Resonance Energy Transfer (FRET) we have confirmed an association between Erk and PKCalpha. Employing PKCalpha and Erk mutants we next demonstrated that Erk causes direct phosphorylation and activation of PKCalpha. By mutating the phosphoinositide-dependent kinase-1 (PDK-1)-promoted phosphorylation site (S(497)) and the kinase site (K(368)) in PKCalpha, we observed that both of these autophosphorylation-deficient mutants are phosphorylated at T(638) in an Erk-dependent manner. To confirm that Erk indeed catalyzes phosphorylation of PKCalpha at T(638), we used a mutant Erk construct in which a relatively large amino acid residue in the ATP binding site (Q(103)) had been replaced with glycine, enabling this mutant to utilize a bulky analog of ATP, cyclopentyl ATP. An in vitro kinase assay using this mutant Erk protein, radiolabeled cyclopentyl ATP, and a synthetic oligopeptide containing the S/TP site of PKCalpha demonstrated phosphorylation of the peptide by Erk1/2. These results confirm the novel possibility that PKCalpha is a direct substrate of Erk1/2 in neuronal cells and help link two important signaling molecules that regulate maturation and protection of hippocampal neurons as well as many other cell types.

Regulation of protein kinase C isozymes during early postnatal hippocampal development.

During neonatal hippocampal development, serotonin 1A receptor-mediated signaling initially employs PKCepsilon to boost neuronal proliferation and then uses PKCalpha to promote synaptogenesis. Such stage-specific involvement of a PKC isozyme could be determined by its relative expression level. In mouse hippocampi, we detected relatively low levels of alpha, beta, gamma, and delta isozymes at postnatal days 2-6 (P2-6), which was followed by a large increase in their expression. In contrast, the PKC isozymes epsilon and theta were relatively abundant at P6, following which they underwent a further increase by P15. Comparison with purified proteins confirmed that the PKCepsilon levels at P6 and P15 were respectively 1.75 and 7.36 ng per 60 microg of protein, whereas PKCalpha levels at P6 and P15 were respectively 160 pg and 1.186 ng per 60 microg of protein. Therefore, at P6, PKCepsilon was about 11-fold more abundant than PKCalpha. Consequently, signaling cascades could use the relatively abundant PKCepsilon (and possibly PKCtheta) molecules for early events at P2-6 (e.g. neurogenesis), following which PKCalpha (and the beta, gamma, or delta isozymes) could guide maturation or apoptosis. Notably, at P6 but not P15, PKCepsilon, was localized to the nuclei of neuroblasts, probably directing mitosis. In contrast, at P15 but not P6, PKCalpha was highly expressed in the processes of the differentiated hippocampal neurons. In summary, PKC isozymes follow differential profiles of expression in neonatal hippocampus and the relative abundance of each may determine its mode and stage of involvement in hippocampal development.

Curcumin blocks brain tumor formation.

Turmeric, an essential ingredient of culinary preparations of Southeast Asia, contains a major polyphenolic compound, named curcumin or diferuloylmethane, which eliminates cancer cells derived from a variety of peripheral tissues. Although in vitro experiments have addressed its anti-tumor property, no in vivo studies have explored its anti-cancer activity in the brain. Oral delivery of this food component has been less effective because of its low solubility in water.We show that a soluble formulation of curcumin crosses the blood­brain barrier but does not suppress normal brain cell viability. Furthermore, tail vein injection, or more effectively, intracerebral injection through a cannula, blocks brain tumor formation in mice that had already received an intracerebral bolus of mouse melanoma cells (B16F10).While exploring the mechanism of its action in vitro we observed that the solubilized curcumin causes activation of proapoptotic enzymes caspase 3/7 in human oligodendroglioma (HOG) and lung carcinoma (A549) cells, and mouse tumor cells N18(neuroblastoma), GL261 (glioma), and B16F10. A simultaneous decrease in cell viability is also revealed by MTT [3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide]assays. Further examination of the B16F10 cells showed that curcumin effectively suppresses Cyclin D1, P-NF-kB, BclXL, P-Akt, and VEGF, which explains its efficacy in blocking proliferation, survival, and invasion of the B16F10 cells in the brain. Taken together,solubilized curcumin effectively blocks brain tumor formation and also eliminates brain tumor cells. Therefore, judicious application of such injectable formulations of curcumin could be developed into a safe therapeutic strategy for treating brain tumors.

Transmembrane signaling in the brain by serotonin, a key regulator of physiology and emotion.

Serotonin (5-HT) is an ancient chemical that plays a crucial functional role in almost every living organism. It regulates platelet aggregation, activation of immune cells, and contraction of stomach and intestinal muscles. In addition, serotonin acts as a neurotransmitter in the brain and the peripheral nervous system. These activities are initiated by the binding of serotonin to 15 or more receptors that are pharmacologically classified into seven groups, 5-HT1 through 5-HT7. Each group is further divided into subgroups of receptors that are homologous but are encoded by discrete genes. With the exception of the 5-HT3 receptor--a cation channel--all of the others are G protein-coupled receptors that potentially activate or inhibit a large number of biochemical cascades. This review will endeavor to compare and contrast such signaling pathways with special attention to their tissue-specific occurrence, their possible role in immediate effects on covalent modification of other proteins, and relatively slower effects on gene expression, physiology and behavior.