The cardiovascular risk factors in men with lower urinary tract symptoms.

OBJECTIVE: It has been hypothesized that endothelial dysfunction and pelvic atherosclerosis may contribute to lower urinary tract symptoms (LUTS). We assessed the relationship between cardiovascular risk factors and LUTS severity in male patients presented to urology clinic. METHODS: It is a cross-sectional study on patients who presented between 2013 and 2015 with LUTS. A total of 1176 male patients were encountered, and 966 were included for analysis after excluding patients with urinary tract malignancy, urethral stricture, bladder stone and history of urinary tract surgery. Cardiovascular risk factors including components of Framingham risk score, body mass index, uroflowmetry, International Prostate Symptoms Score, fasting blood glucose and serum prostate-specific antigen (PSA) were assessed. Correlation between Framingham risk score, cardiovascular risk factors and severity of LUTS was investigated. RESULTS: Multinomial logistic regression analysis showed that severe LUTS significantly associated with Framingham score (P = 0.008) and its components of total cholesterol (OR = 1.318; P = 0.010) and age (OR = 1.032; P = 0.006) compare with mild symptoms. Framingham risk score was found to correlate with storage symptoms (CC = 0.083; P < 0.0001) but not voiding symptoms (CC = - 0.029; P = 0.185). CONCLUSIONS: Severity of LUTS and storage symptom significantly increases Framingham risk score, particularly with the components of total cholesterol level and age.

Protein phosphatase 2A (PP2A) regulates low density lipoprotein uptake through regulating sterol response element-binding protein-2 (SREBP-2) DNA binding.

LDL-cholesterol (LDL-C) uptake by Ldlr is regulated at the transcriptional level by the cleavage-dependent activation of membrane-associated sterol response element-binding protein (SREBP-2). Activated SREBP-2 translocates to the nucleus, where it binds to an LDLR promoter sterol response element (SRE), increasing LDLR gene expression and LDL-C uptake. SREBP-2 cleavage and translocation steps are well established. Several SREBP-2 phosphorylation sites have been mapped and functionally characterized. The phosphatases dephosphorylating these sites remain elusive. The phosphatase(s) regulating SREBP-2 represents a novel pharmacological target for treating hypercholesterolemia. Here we show that protein phosphatase 2A (PP2A) promotes SREBP-2 LDLR promoter binding in response to cholesterol depletion. No binding to an LDLR SRE was observed in the presence of the HMG-CoA reductase inhibitor, lovastatin, when PP2A activity was inhibited by okadaic acid or depleted by siRNA methods. SREBP-2 cleavage and nuclear translocation were not affected by loss of PP2A. PP2A activity was required for SREBP-2 DNA binding. In response to cholesterol depletion, PP2A directly interacted with SREBP-2 and altered its phosphorylation state, causing an increase in SREBP-2 binding to an LDLR SRE site. Increased binding resulted in induced LDLR gene expression and increased LDL uptake. We conclude that PP2A activity regulates cholesterol homeostasis and LDL-C uptake.

Effects of intensive cognitive-behavioral therapy on cingulate neurochemistry in obsessive-compulsive disorder.

The neurophysiological bases of cognitive-behavioral therapy (CBT) for obsessive-compulsive disorder (OCD) are incompletely understood. Previous studies, though sparse, implicate metabolic changes in pregenual anterior cingulate cortex (pACC) and anterior middle cingulate cortex (aMCC) as neural correlates of response to CBT. The goal of this pilot study was to determine the relationship between levels of the neurochemically interlinked metabolites glutamate + glutamine (Glx) and N-acetyl-aspartate + N-acetyl-aspartyl-glutamate (tNAA) in pACC and aMCC to pretreatment OCD diagnostic status and OCD response to CBT. Proton magnetic resonance spectroscopic imaging ((1)H MRSI) was acquired from pACC and aMCC in 10 OCD patients at baseline, 8 of whom had a repeat scan after 4 weeks of intensive CBT. pACC was also scanned (baseline only) in 8 age-matched healthy controls. OCD symptoms improved markedly in 8/8 patients after CBT. In right pACC, tNAA was significantly lower in OCD patients than controls at baseline and then increased significantly after CBT. Baseline tNAA also correlated with post-CBT change in OCD symptom severity. In left aMCC, Glx decreased significantly after intensive CBT. These findings add to evidence implicating the pACC and aMCC as loci of the metabolic effects of CBT in OCD, particularly effects on glutamatergic and N-acetyl compounds. Moreover, these metabolic responses occurred after just 4 weeks of intensive CBT, compared to 3 months for standard weekly CBT. Baseline levels of tNAA in the pACC may be associated with response to CBT for OCD. Lateralization of metabolite effects of CBT, previously observed in subcortical nuclei and white matter, may also occur in cingulate cortex. Tentative mechanisms for these effects are discussed. Comorbid depressive symptoms in OCD patients may have contributed to metabolite effects, although baseline and post-CBT change in depression ratings varied with choline-compounds and myo-inositol rather than Glx or tNAA.