The role of transcorporal cuff placement in high-risk and ultra-high-risk patients: are they actually helpful?

Purpose: To assess the incidence of artificial urinary sphincter (AUS) explant in high-risk patients and to evaluate the relationship between transcorporal cuff (TCC) placement and explant risk in this population.

Methods: We retrospectively reviewed all AUS insertions performed on high-risk patients by a single surgeon from 2010 to 2020. "High-risk" was defined as having ≥ 1 urethral risk factor: pelvic radiation, urethroplasty, recalcitrant urethral/bladder neck stenosis, urethral stenting, or previous AUS erosion/infection.

Inhibition of protein glycosylation is a novel pro-angiogenic strategy that acts via activation of stress pathways.

Endothelial cell (EC) metabolism is thought to be one of the driving forces for angiogenesis. Here we report the identification of the hexosamine D-mannosamine (ManN) as an EC mitogen and survival factor for bovine and human microvascular EC, with an additivity with VEGF. ManN inhibits glycosylation in ECs and induces significant changes in N-glycan and O-glycan profiles.

Role of urinary cations in the etiology of interstitial cystitis: A multisite study.

Objective: To determine whether patients with interstitial cystitis have elevated levels of toxic urinary cations, to identify and quantify these cationic metabolites, and to assess their cytotoxicity.

Methods: Isolation of cationic fraction was achieved by solid phase extraction using an Oasis MCX cartridge on urine specimens from interstitial cystitis patients and controls. C reverse phase high-performance liquid chromatography was used to profile cationic metabolites, and they were quantified by the area under the peaks and normalized to creatinine.

Structural similarity, characterization of Poly Ethylene Glycol linkage and identification of product related variants in biosimilar pegfilgrastim.

The approval of biosimilars requires demonstration of biosimilarity, which rests on the base of thorough analytical characterization of the biosimilar product. In addition to demonstration of biosimilarity, the product related impurities need to be thoroughly characterized and controlled at minimal levels. Pegylation of peptides and proteins creates significant challenges for detailed structural characterization, such as PEG (Poly Ethylene Glycol) heterogeneity, site of addition and number of attached pegylated moieties.

A gut microbial factor modulates locomotor behaviour in Drosophila.

While research into the biology of animal behaviour has primarily focused on the central nervous system, cues from peripheral tissues and the environment have been implicated in brain development and function. There is emerging evidence that bidirectional communication between the gut and the brain affects behaviours including anxiety, cognition, nociception and social interaction. Coordinated locomotor behaviour is critical for the survival and propagation of animals, and is regulated by internal and external sensory inputs.

Increased toxic urinary cations in males with interstitial cystitis: a possible cause of bladder symptoms.

Purpose: To identify and quantify toxic urinary cations in male patients with bladder pain syndrome/interstitial cystitis versus male controls, to compare them in symptomatic patients to those significantly improved, and to evaluate cytotoxicity of these cations to cultured urothelial cells to determine whether Tamm-Horsfall protein (THP) can neutralize the cations.

Methods: Isolation of cationic fraction (CFs) was achieved by solid phase extraction on urine specimens of 51 male patients with IC and 33 male controls. C reverse-phase high-performance liquid chromatography was used to profile and quantify cationic metabolites.

An evaluation of Tamm-Horsfall protein glycans in kidney stone formers using novel techniques.

Tamm-Horsfall protein (THP) is theorized to play a critical role in preventing kidney stone formation. There is conflicting literature on THP analysis in kidney stone patients; therefore, this study was conducted using sensitive and specific bio-analytical techniques to better understand differences in THP, which play a potential role in nephrolithiasis pathogenesis. THP was isolated from urine samples of 34 male and 19 female kidney stone patients and 30 male and 24 female control subjects using diatomaceous earth.

Heparin and alkalinized lidocaine versus alkalinized lidocaine for treatment of interstitial cystitis symptoms.

Introduction: Interstitial cystitis (IC), sometimes referred to as IC/bladder pain syndrome, is a substantial health care problem. Once considered a rare, orphan disease, it is now believed to be relatively common. This pilot study was undertaken to determine if the combination of heparin and alkalinized lidocaine (heparin-lidocaine) was more efficacious than alkalinized lidocaine at relieving pain and urgency symptoms associated with IC and also capable of yielding higher lidocaine absorption.

Patient-derived skeletal dysplasia induced pluripotent stem cells display abnormal chondrogenic marker expression and regulation by BMP2 and TGFβ1.

Skeletal dysplasias (SDs) are caused by abnormal chondrogenesis during cartilage growth plate differentiation. To study early stages of aberrant cartilage formation in vitro, we generated the first induced pluripotent stem cells (iPSCs) from fibroblasts of an SD patient with a lethal form of metatropic dysplasia, caused by a dominant mutation (I604M) in the calcium channel gene TRPV4. When micromasses were grown in chondrogenic differentiation conditions and compared with control iPSCs, mutant TRPV4-iPSCs showed significantly (P<0.

Solubility of ammonium acid urate nephroliths from bottlenose dolphins (Tursiops truncatus).

Nephrolithiasis has been identified in managed populations of bottlenose dolphins (Tursiops truncatus); most of these nephroliths are composed of 100% ammonium acid urate (AAU). Several therapies are being investigated to treat and prevent nephrolithiasis in dolphins including the alkalization of urine for dissolution of nephroliths. This study evaluates the solubility of AAU nephroliths in a phosphate buffer, pH range 6.

Role of urinary cations in the aetiology of bladder symptoms and interstitial cystitis.

Objectives: To identify and characterise urinary cationic metabolites, defined as toxic factors, in patients with interstitial cystitis (IC) and in control subjects. To evaluate the cytotoxicity of the urinary cationic metabolite fraction of patients with IC vs control subjects and of individual metabolites in cultured urothelial cells.

Subjects And Methods: Cationic fractions (CFs) were isolated from the urine specimens of 62 patients with IC and 33 control subjects by solid-phase extraction.

Tamm-Horsfall protein-associated nucleotides in patients with interstitial cystitis.

Unlabelled: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The nucleotides associated with Tamm-Horsfall protein (THP) identified in this study are 2'(3') isomers, which are uncommon and very little is known about their biochemical pathway and role in interstitial cystitis (IC). The current study provides additional evidence of our earlier finding that THP is abnormal in IC patients. This can adversely affect THP's protective function, and suggests that THP plays a role in the pathogenesis of the disease.

A multi-site study confirms abnormal glycosylation in the Tamm-Horsfall protein of patients with interstitial cystitis.

Purpose: We confirm the single site observation of decreased sialylation and abnormal glycosylation of Tamm-Horsfall protein in patients with interstitial cystitis compared to control subjects.

Materials And Methods: Urine samples from 41 controls and 48 patients with interstitial cystitis from a total of 5 North American sites were obtained in blinded fashion as to participant status. Tamm-Horsfall protein was isolated from urine samples by salt precipitation.

Abnormal glycosylation of Tamm-Horsfall protein in patients with interstitial cystitis.

Objective: To confirm abnormal glycosylation of Tamm-Horsfall protein (THP) in patients with interstitial cystitis (IC).

Patients, Subjects And Methods: The sialic acid content of THP, a critical component of its biological activity, is reduced in patients with IC. N-glycan shows reduced levels of high molecular weight tri- and tetra-antennary sialylated oligosaccharides.

Defective Tamm-Horsfall protein in patients with interstitial cystitis.

Purpose: Normal urinary Tamm-Horsfall protein shows a urothelial cytoprotective effect against potentially toxic compounds in urine that may injure the urothelium and cause bladder disease. One such disease is interstitial cystitis. In patients with interstitial cystitis this protective effect is decreased.

A chemical reporter strategy to probe glycoprotein fucosylation.

Fucosylated glycoproteins are involved in many cell-cell recognition events and are markers of embryonic and malignant tissue. Here we report a method for rapid profiling of fucosylated glycoproteins from human cells using 6-azido fucose as a metabolic label.

Metabolic functionalization of recombinant glycoproteins.

Glycoproteins are essential for cellular communication and are the most rapidly growing class of therapeutic agents. Chemical modification of glycoproteins has been employed to improve their in vivo efficacy or to label them for detection. Methods for the controlled derivatization of glycoproteins are presently limited by the repertoire of natural amino acid side chain and carbohydrate functionalities.

Development of monoclonal antibody based antigen capture ELISA to detect chikungunya virus antigen in mosquitoes.

Background & Objectives: Chikungunya (CHIK) virus has caused numerous large outbreaks in India. No active or passive surveillance has been carried out since the last epidemic which occurred in 1971. For active surveillance, it is necessary to have a test, which can detect the virus from a large number of field-collected mosquitoes.

Exploring the glycan repertoire of genetically modified mice by isolation and profiling of the major glycan classes and nano-NMR analysis of glycan mixtures.

The production of mice with genetic alterations in glycosyltransferases has highlighted the need to isolate and study complex mixtures of the major classes of oligosaccharides (glycans) from intact tissues. We have found that nano-NMR spectroscopy of whole mixtures of N- and O-glycans can complement HPLC profiling methods for elucidating structural details. Working toward obtaining such glycan mixtures from mouse tissues, we decided to develop an approach to isolate not only N- and O-glycans, but also to separate out glycosphingolipids, glycosaminoglycans and glycosylphosphatidylinositol anchors.

Plasma lactic dehydrogenase in mice infected with Japanese encephalitis & West Nile viruses.

A study of the total and isoenzymes fractions of lactic dehydrogenase (LDH) enzyme was carried out in the plasma of mice infected with Japanese encephalitis (JE) and West Nile (WN) viruses. Only 2 isoenzymes (LDH 4 and LDH 5) were present in control mice. There was a rapid increase of total LDH in the animals infected with the wild strain of viruses.

The effect of alkaline borohydride treatment on N-linked carbohydrates of glycoproteins.

The effects of treatments of the glycoprotein ribonuclease-B, the proteins ribonuclease-A and myoglobin, and the glyco-amino acid GlcNAc beta(1-N)Asn with alkali, alkaline sodium borohydride, and aqueous sodium borohydride were systematically studied as a function of the concentration of the reagents, the temperature, and the length of the treatment. High-field 1H-NMR spectroscopy, chromatographic methods and amino-acid analysis were used to characterize products of the treatments of the various compounds. Our results indicate that mild alkaline borohydride treatment, as well as aqueous borohydride treatment alone, is capable of extensively degrading polypeptides and of partially releasing the N-linked glycans from ribonuclease-B.

Structural studies on the carbohydrate moieties of human liver alpha-L-fucosidase.

alpha-L-Fucosidase was purified from human liver to apparent homogeneity and subjected to exhaustive digestion with Pronase. The resulting glycopeptides were isolated by gel filtration on Sephadex G-50 and further fractionated by Bio-Gel P-4 chromatography. Five glycopeptide fractions were obtained.