Sexual Dysfunction in Patients With Urinary Bladder Stones but no Bladder Outlet Obstruction.

Objective: To explore the correlates of sexual dysfunction and lower urinary tract symptoms (LUTS) in male patients with urinary bladder stones and to determine the effect of stone extraction on recovery of sexual function. Materials and Methods: A total of 87 male patients with primary bladder stones were studied from January 2015 to May 2016. All patients underwent pneumatic lithotripsy for bladder stones. Sexual dysfunction was assessed based on sexual function assessment scales. The relationship of bladder stones with sexual dysfunction or LUTS was assessed using a two-sample t-test. Postoperative improvement of sexual function was assessed by repeated measures Analysis of Variance (ANOVA). Results: Forty-one patients had primary bladder stones and 46 had secondary stones from the kidneys. Eighty-three of 87 patients (95%) had sexual dysfunction; 79 patients (91%) had both sexual dysfunction and LUTS. There was a significant association between bladder stones and sexual dysfunction, between sexual dysfunction and LUTS, and between bladder stone and LUTS (p < 0.05). There was no significant association between the course of illness, size and number of bladder stones, or urinary tract infection with sexual function (p > 0.05). In addition, among 83 patients with both bladder stone and sexual dysfunction, 61 patients (73%) had benign prostatic hyperplasia (BPH) and 22 patients (27%) had no BPH. On postoperative evaluation at 3 months, sexual dysfunction scores were significantly improved in 77 patients (88.5%) Conclusion: Patients with bladder stones have a high incidence of sexual dysfunction, particularly those with co-existing LUTS and BPH. About 1/3 patients without BPH had sexual dysfunction and surgical removal of bladder stones significantly improved sexual function and LUTS.

Preconcentration and analysis of Rhodamine B in water and red wine samples by using magnesium hydroxide/carbon nanotube composites as a solid-phase extractant.

A convenient and accurate analysis approach that combined solid-phase extraction and high-performance liquid chromatography was developed to determine the amount of Rhodamine B in red wine and Xiang-jiang river water samples. A novel composite, magnesium hydroxide/carbon nanotube composites, was synthesized and used as the solid-phase extractant for the preconcentration/analysis of Rhodamine B. Magnesium hydroxide/carbon nanotube composites, which combined the merits of carbon nanotubes and magnesium hydroxide, exhibited acceptable adsorption and desorption efficiencies for Rhodamine B. The linear range of the proposed solid-phase extraction with high-performance liquid chromatography method for Rhodamine B was 0.05-20.0 mg/L, with a limit of detection of 3.6 µg/L. The precision and reproducibility of the developed solid-phase extraction with high-performance liquid chromatography method and the batch-to-batch reproducibility of the solid-phase extractant were also validated at spiking levels of 0.5 and 2.0 mg/L. The recovery of Rhodamine B was 94.33-106.7%, and the recovery relative standard deviations of the intra- and interday precisions were ≤ 3.83 and ≤ 6.01%, respectively. The relative standard deviation of the batch-to-batch reproducibility was ≤ 7.98%.

The impact of the metabotropic glutamate receptor and other gene family interaction networks on autism.

Although multiple reports show that defective genetic networks underlie the aetiology of autism, few have translated into pharmacotherapeutic opportunities. Since drugs compete with endogenous small molecules for protein binding, many successful drugs target large gene families with multiple drug binding sites. Here we search for defective gene family interaction networks (GFINs) in 6,742 patients with the ASDs relative to 12,544 neurologically normal controls, to find potentially druggable genetic targets. We find significant enrichment of structural defects (P ≤ 2.40E-09, 1.8-fold enrichment) in the metabotropic glutamate receptor (GRM) GFIN, previously observed to impact attention deficit hyperactivity disorder (ADHD) and schizophrenia. Also, the MXD-MYC-MAX network of genes, previously implicated in cancer, is significantly enriched (P ≤ 3.83E-23, 2.5-fold enrichment), as is the calmodulin 1 (CALM1) gene interaction network (P ≤ 4.16E-04, 14.4-fold enrichment), which regulates voltage-independent calcium-activated action potentials at the neuronal synapse. We find that multiple defective gene family interactions underlie autism, presenting new translational opportunities to explore for therapeutic interventions.

[Investigation into the serum uric acid level of the residents in Henglan town of Zhongshan city].

OBJECTIVE: To investigate the relationship between cardiac Cerebrovascular disease and serum uric acid(SUA) in the coastal inhabitant, and try to provide base for prevention of the local metabolic disease and cardiac Cerebrovascular disease. METHOD: We got 3111 local people who had participated in the annual physical examination in the perch hospital for the research on the level of SUA and the relative risk factor. According to SUA level we divided the cases into two groups. One is hyperuricemia group and the other is control group. RESULTS: (1)The average SUA level was (380.2-/+62.58) micromol/L in the males, while (290.82-/+60.32) micromlo/L in the female. The sick rate of hyperuricaemia rate, was 21.8% for male, and the 17.6% of female. This disease affected more men than women. It has significant difference (P<0.01); (2)The SUA level of the showed a positive correlation with the indexes of the total cholesterol, the triglyceride, the blood pressure and the body weight index. The SUA level in overweight/obesity people was obviously higher than that of the normal weight people. CONCLUSIONS: (1)The sick rate of hyperuricaemia is high in Zhongshan coastal area, which due to many related factors. As far as, few people know it, so we should adopt the synthesis measure to prevent and control it to reduce the sick rate; (2)the rise of The SUA level possibly becomes one of the independent dangerous and predictive factor for the heart cerebral von disease.

The phosphatidylinositol 3-kinase inhibitor LY 294002 inhibits GlyT1-mediated glycine uptake.

The actions of neurotransmitter glycine are regulated by the Na+/Cl(-) dependent high-affinity glycine transporters, GlyT1 and GlyT2. These two members of the SLC6 transport family have been cloned and extensively characterized, however relatively little is known regarding their modulation. In the present study, glycine uptake in primary cultures of rat embryonic cortex has been characterized and the effects of the phosphatidylinositol 3 (PI3) kinase inhibitors LY 294002 and wortmannin on GlyT1- and GlyT2-mediated glycine uptake were investigated. GlyT1 inhibitors ALX 5407 and sarcosine reduced total glycine uptake to 80% whereas the specific GlyT2 inhibitor Org 25543 had no effect. In the presence of alanine, glycine uptake was completely blocked by the GlyT1 inhibitors ALX 5407 and sarcosine, suggesting that the high-affinity glycine uptake occurs predominantly via GlyT1. Kinetic analysis of GlyT1 revealed the Km value of 27+/-1.5 microM and Vmax value of 157+/-14 pmol/mg/min. LY 294002, a PI3 kinase inhibitor, blocked the GlyT1-mediated glycine uptake with an IC50 value of 81+/-2 microM, whereas another inhibitor wortmannin did not show any effect. In human placental choriocarcinoma (JAR) cells, which have been previously shown to predominantly express GlyT1a, LY 294002 showed a similar potency with an IC50 value of 86+/-3 microM. Immunoblots demonstrated that LY 294002 and wortmannin inhibited PI3 kinase-dependent Akt phosphorylation in the primary cultures with IC50 values of 10+/-4 microM and 7+/-1 nM, respectively. These results suggest that the commonly used PI3 kinase blocker LY 294002 may modulate GlyT1 function independent of PI3 kinase inhibition. Kinetic analysis in the presence of LY 294002 demonstrated significant decreases of both Km and Vmax values, suggesting a mechanism of uncompetitive inhibition on GlyT1-mediated glycine uptake. In addition, glycine release was blocked by LY 294002. These results raised a possibility that LY 294002 might interact with GlyT1.

Comparative analysis of cortical gene expression in mouse models of Alzheimer's disease.

Three mouse models of Alzheimer's disease (AD) were used to assess changes in gene expression potentially critical to amyloid beta-peptide (Abeta)-induced neuronal dysfunction. One mouse model harbored homozygous familial AD (FAD) knock-in mutations in both, amyloid precursor protein (APP) and presenilin 1 (PS-1) genes (APP(NLh/NLh)/PS-1(P264L/P264L)), the other two models harbored APP over-expression of FAD mutations (Tg2576) with the PS-1 knock-in mutation at either one or two alleles. These mouse models of AD had varying levels of Abeta40 and Abeta42 and different latencies and rates of Abeta deposition in brain. To assess changes in gene expression associated with Abeta accumulation, the Affymetrix murine genome array U74A was used to survey gene expression in the cortex of these three models both prior to and following Abeta deposition. Altered genes were identified by comparing the AD models with age-matched control littermates. Thirty-four gene changes were identified in common among the three models in mice with Abeta deposition. Among the up-regulated genes, three major classes were identified that encoded for proteins involved in immune responses, carbohydrate metabolism, and proteolysis. Down-regulated genes of note included pituitary adenylate cyclase-activating peptide (PACAP), brain-derived neurotrophic factor (BDNF), and insulin-like growth factor I receptor (IGF-IR). In young mice without detectable Abeta deposition, there were no regulated genes common among the three models, although 40 genes were similarly altered between the two Tg2576 models with the PS-1 FAD knock-in. Finally, changes in gene expression among the three mouse models of AD were compared with those reported in human AD samples. Sixty-nine up-regulated and 147 down-regulated genes were found in common with human AD brain. These comparisons across different genetic mouse models of AD and human AD brain provide greater support for the involvement of identified gene expression changes in the neuronal dysfunction and cognitive deficits accompanying amyloid deposition in mammalian brain.

Inhibition of mixed lineage kinase 3 attenuates MPP+-induced neurotoxicity in SH-SY5Y cells.

The neuropathology of Parkinson's Disease has been modeled in experimental animals following MPTP treatment and in dopaminergic cells in culture treated with the MPTP neurotoxic metabolite, MPP(+). MPTP through MPP(+) activates the stress-activated c-Jun N-terminal kinase (JNK) pathway in mice and SH-SY5Y neuroblastoma cells. Recently, it was demonstrated that CEP-1347/KT7515 attenuated MPTP-induced nigrostriatal dopaminergic neuron degeneration in mice, as well as MPTP-induced JNK phosphorylation. Presumably, CEP-1347 acts through inhibition of at least one upstream kinase within the mixed lineage kinase (MLK) family since it has been shown to inhibit MLK 1, 2 and 3 in vitro. Activation of the MLK family leads to JNK activation. In this study, the potential role of MLK and the JNK pathway was examined in MPP(+)-induced cell death of differentiated SH-SY5Y cells using CEP-1347 as a pharmacological probe and dominant negative adenoviral constructs to MLKs. CEP-1347 inhibited MPP(+)-induced cell death and the morphological features of apoptosis. CEP-1347 also prevented MPP(+)-induced JNK activation in SH-SY5Y cells. Endogenous MLK 3 expression was demonstrated in SH-SY5Y cells through protein levels and RT-PCR. Adenoviral infection of SH-SY5Y cells with a dominant negative MLK 3 construct attenuated the MPP(+)-mediated increase in activated JNK levels and inhibited neuronal death following MPP(+) addition compared to cultures infected with a control construct. Adenoviral dominant negative constructs of two other MLK family members (MLK 2 and DLK) did not protect against MPP(+)-induced cell death. These studies show that inhibition of the MLK 3/JNK pathway attenuates MPP(+)-mediated SH-SY5Y cell death in culture and supports the mechanism of action of CEP-1347 as an MLK family inhibitor.

Protein tyrosine phosphatases are up-regulated and participate in cell death induced by polyglutamine expansion.

Polyglutamine expansion is the cause of several neurodegenerative diseases. An in vitro model of polyglutamine-induced neuronal cell death was developed using truncated mutant huntingtin (Htt) and PC12 cells. Cell death was specifically observed in cells expressing a truncated mutant huntingtin-green fluorescence protein (GFP) fusion protein with 118 glutamine repeats (Gln(118)), as demonstrated by the release of lactate dehydrogenase (LDH). To gain further insights into the mechanisms of polyglutamine expansion-induced cell death, the Affymetrix rat genome array U34A was used to investigate gene expression changes associated with polyglutamine-mediated protein aggregation and cell death. Among the up-regulated genes, the increase of four protein tyrosine phosphatases (PTPs) was further confirmed by real-time quantitative reverse transcription PCR. Protein expression of mitogen activated protein (MAP) kinase phosphatase 1 (MKP1) was also increased as demonstrated by Western blot. Furthermore, phosphorylation of MAP kinase extracellular signal-regulated kinase 1/2 (ERK1/2) was substantially reduced in association with protein aggregation, and two general PTP inhibitors, sodium orthovanadate and bpV(pic), dramatically rescued the cells from polyglutamine-induced cell death. These results suggest that one or more of the PTPs are involved in the polyglutamine-induced cell death.