Interstitial cystitis (IC), also known as painful bladder syndrome or bladder pain syndrome, is a chronic lower urinary tract syndrome characterized by pelvic pain, urinary urgency, and increased urinary frequency in the absence of bacterial infection or identifiable clinicopathology. IC can lead to long-term adverse effects on the patient's quality of life. Therefore, early diagnosis and better understanding of the mechanisms underlying IC are needed. Metabolomic studies of biofluids have become a powerful method for assessing disease mechanisms and biomarker discovery, which potentially address these important clinical needs. However, limited intensive metabolic profiles have been elucidated in IC. The article is a short review on metabolomic analyses that provide a unique fingerprint of IC with a focus on its use in determining a potential diagnostic biomarker associated with symptoms, a response predictor of therapy, and a prognostic marker.
Bacterial Infections ; Biomarkers ; Cystitis, Interstitial* ; Dermatoglyphics ; Early Diagnosis ; Magnetic Resonance Spectroscopy ; Mass Spectrometry ; Metabolome ; Metabolomics* ; Pelvic Pain ; Quality of Life ; Urinary Bladder ; Urinary Tract

One suggested mechanism underlying copper (Cu) deficiency teratogenicity is a low availability of nitric oxide (NO), a signaling molecule which is essential in developmental processes. Increased superoxide anions secondary to decreased activities of Cu-zinc superoxide dismutase (Cu-Zn SOD) in Cu deficiency can interact with NO to form peroxynitrite, which can nitrate proteins at tyrosine residues. In addition, peroxynitrite formation can limit NO bioavailability. We previously reported low NO availability and increased protein nitration in Cu deficient (Cu-) embryos. In the current study, we tested whether Cu deficiency alters downstream signaling of NO by assessing cyclic GMP (cGMP) and phosphorylated vasodilator-stimulating phosphoprotein (VASP) levels, and whether NO supplementation can affect these targets as well as protein nitration. Gestation day 8.5 embryos from Cu adequate (Cu+) or Cu- dams were collected and cultured in either Cu+ or Cu- media for 48 hr. A subset of embryos was cultured in Cu- media supplemented with a NO donor (DETA/NONOate; 20 micrometer) and/or Cu-Zn SOD. Cu-/Cu- embryos showed a higher incidence of embryonic and yolk sac abnormalities, low NO availability, blunted dose-response in NO concentrations to increasing doses of acetylcholine, low mRNA expression of endothelial nitric oxide synthase (eNOS), increased levels of 3-nitrotyrosine (3-NT) compared to Cu+/Cu+ controls. cGMP concentrations tended to be low in Cu-/Cu- embryos, and they were significantly lower in Cu-/Cu- yolk sacs than in controls. Levels of phosphorylated VASP at serine 239 (P-VASP) were similar in all groups. NO donor supplementation to the Cu- media ameliorated embryonic and yolk sac abnormalities, and resulted in increased levels of cGMP without altering levels of P-VASP and 3-NT. Taken together, these data support the concept that Cu deficiency limits NO availability and alters NO/cGMP-dependent signaling in Cu- embryos and yolk sacs, which contributes to Cu deficiency-induced abnormal development.
Acetylcholine ; Biological Availability ; Copper ; Cyclic GMP ; Embryonic Structures ; Humans ; Incidence ; Nitric Oxide ; Nitric Oxide Synthase Type III ; Oxidative Stress ; Peroxynitrous Acid ; Pregnancy ; Proteins ; RNA, Messenger ; Serine ; Superoxide Dismutase ; Superoxides ; Tissue Donors ; Tyrosine ; Yolk Sac

Capsaicin in chili peppers bestows the sensation of spiciness. Since the discovery of its receptor, transient receptor potential vanilloid 1 (TRPV1) ion channel, how capsaicin activates this channel has been under extensive investigation using a variety of experimental techniques including mutagenesis, patch-clamp recording, crystallography, cryo-electron microscopy, computational docking and molecular dynamic simulation. A framework of how capsaicin binds and activates TRPV1 has started to merge: capsaicin binds to a pocket formed by the channel's transmembrane segments, where it takes a "tail-up, head-down" configuration. Binding is mediated by both hydrogen bonds and van der Waals interactions. Upon binding, capsaicin stabilizes the open state of TRPV1 by "pull-and-contact" with the S4-S5 linker. Understanding the ligand-host interaction will greatly facilitate pharmaceutical efforts to develop novel analgesics targeting TRPV1.
Binding Sites ; Capsaicin ; chemistry ; pharmacokinetics ; Humans ; Hydrogen Bonding ; Protein Binding ; TRPV Cation Channels ; chemistry ; genetics ; metabolism

No abstract available.
Posterior Cerebral Artery* ; Stroke*

No abstract available.

No abstract available.
Animals ; Marek Disease*

Important roles for reactive oxygen species (ROS) in physiology and pathophysiology have been increasingly recognized. Under normal conditions, ROS serve as signaling molecules in the regulation of cellular functions. However, enhanced ROS production as a result of the activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase contributes significantly to the pathogeneses of vascular diseases. Although it has become evident that increased ROS is associated with erectile dysfunction (ED), the sources of ROS in the penis remain largely unknown. In recent years, emergent evidence suggests the possible role of NADPH oxidase in inducing ED. In this review, we examine the relationship between ROS and ED in different disease models and discuss the current evidence basis for NADPH oxidase-derived ROS in ED.
Aging ; Animals ; Diabetes Mellitus ; Erectile Dysfunction ; enzymology ; etiology ; Humans ; Hyperhomocysteinemia ; Hyperlipidemias ; Hypertension ; Male ; NADPH Oxidases ; physiology ; Reactive Oxygen Species

Purpose: To assess the potential advantage of intensity-modulated radiotherapy (IMRT) over 3D-conformal radiotherapy (3D-CRT) planning in postoperative adjuvant radiotherapy for patients with gastric carcinoma. Methods and materials: In a retrospective study, for plan comparison, dose distribution was recalculated in 15 patients treated with 3D-CRT on the contoured structures of same CT images using an IMRT technique. 3D-conformal plans with three fields and four-fields were compared with seven-field dynamic IMRT plans. The different plans were compared by analyzing the dose coverage of planning target volume using TV95, Dmean, uniformity index, conformity index and homogeneity index parameters. To assess critical organ sparing, Dmean, Dmax, dose to one-third and two-third volumes of the OARs and percentage of volumes receiving more than their tolerance doses were compared. Results: The average dose coverage values of PTV with 3F-CRT and 4F-CRT plans were comparable, where as IMRT plans achieved better target coverage(p<0.001) with higher conformity index value of 0.81±0.07 compared to both the 3D-CRT plans. The doses to the liver and bowel reduced significantly (p<0.001) with IMRT plans compared to other 3D-CRT plans. For all OARs the percentage of volumes receiving more than their tolerance doses were reduced with the IMRT plans. Conclusion: This study showed that a better target coverage and significant dose reduction to OARs could be achieved with the IMRT plans. The IMRT can be preferred with caution for organ motion. The authors are currently studying organ motion in the upper abdomen to use IMRT for patient treatment.

Motor posturing in acutely comatose patient is suggestive of an evolving brain herniation. In the presence of a unilateral pupillary abnormality, a metabolic or drug induced coma can be excluded. Neuroimaging studies in such cases will likely reveal underlying mass or acute ventricular obstruction. We recently encountered a patient who presented in stupor with repetitive motor posturing and a transient right oval pupil to light stimulus. Surprisingly, an urgent brain CT revealed only mild global atrophy for age. Further evaluation disclosed cryptococcus meningitis as the underlying cause.

Background/Aims: Optimal small bowel (SB) preparation for video capsule endoscopy (VCE) is controversial. Our study aimed to support the use of a specified volume of 4 liters of clear liquids for bowel preparation for VCE. Methods: A retrospective review of 284 patients who underwent SB preparation with 2 liters of polyethylene glycol (PEG) and 284 patients who had 4 liters of clear liquid preparation. We analyzed image quality, endoscopic findings, completion rate, and transit times. Results: The 4-liter clear liquid group had significantly higher mean image quality scores when compared to the PEG group (2.908±0.77 to 2.669±0.64, p<0.0001), as well as more studies with adequate preparation (72% to 64%, p=0.0214). Although the PEG group had more endoscopic findings on VCE (40% to 23%, p<0.0001), there was a significant difference in the indications for the procedure between the groups. There was no difference in the capsule completion rate or SB transit time. Conclusions Our data demonstrate significantly higher mean image quality scores when using a specified volume of 4 liters of clear liquid compared to 2 liters of PEG. This study supports the growing evidence of the effectiveness of a 4-liter clear liquid SB preparation as opposed to PEG for VCE.