Binding of steroid substrates reveals the key to the productive transition of the cytochrome P450 OleP.

OleP is a bacterial cytochrome P450 involved in oleandomycin biosynthesis as it catalyzes regioselective epoxidation on macrolide intermediates. OleP has recently been reported to convert lithocholic acid (LCA) into murideoxycholic acid through a highly regioselective reaction and to unspecifically hydroxylate testosterone (TES). Since LCA and TES mainly differ by the substituent group at the C17, here we used X-ray crystallography, equilibrium binding assays, and molecular dynamics simulations to investigate the molecular basis of the diverse reactivity observed with the two steroids.

Non-covalent inhibitors of thioredoxin glutathione reductase with schistosomicidal activity in vivo.

Only praziquantel is available for treating schistosomiasis, a disease affecting more than 200 million people. Praziquantel-resistant worms have been selected for in the lab and low cure rates from mass drug administration programs suggest that resistance is evolving in the field. Thioredoxin glutathione reductase (TGR) is essential for schistosome survival and a validated drug target.

Bio-Tailored Sensing at the Nanoscale: Biochemical Aspects and Applications.

The demonstration of the first enzyme-based electrode to detect glucose, published in 1967 by S. J. Updike and G.

Immediate repeated testing (IRT) for BPPV: A cost-effective examination.

Objective: To show that a negative Dix-Hallpike test or Pagnini-McClure test may convert into positive after head shaking in cases of semicircular canalith jam.

Methods: This is a retrospective study, where 768 cases of BPPV were studied of which 36 were found to have canalith jam.

Results: Thirty-six patients (4.

Biochemical and structural characterizations of thioredoxin reductase selenoproteins of the parasitic filarial nematodes Brugia malayi and Onchocerca volvulus.

Enzymes in the thiol redox systems of microbial pathogens are promising targets for drug development. In this study we characterized the thioredoxin reductase (TrxR) selenoproteins from Brugia malayi and Onchocerca volvulus, filarial nematode parasites and causative agents of lymphatic filariasis and onchocerciasis, respectively. The two filarial enzymes showed similar turnover numbers and affinities for different thioredoxin (Trx) proteins, but with a clear preference for the autologous Trx.

Unusual presentation of a clinically isolated temporal region mass: Non-Hodgkin lymphoma.

Non-hodgkins lymphoma is a systemic disease that may present in multiple sites, rarely does it present primarily as a temporal fossa swelling. Only four cases have been reported in the English literature. We report a case of a patient who presented with a rapidly progressive swelling of the temporal fossa.

Probing the Surface of a Parasite Drug Target Thioredoxin Glutathione Reductase Using Small Molecule Fragments.

Fragment screening is a powerful drug discovery approach particularly useful for enzymes difficult to inhibit selectively, such as the thiol/selenol-dependent thioredoxin reductases (TrxRs), which are essential and druggable in several infectious diseases. Several known inhibitors are reactive electrophiles targeting the selenocysteine-containing C-terminus and thus often suffering from off-target reactivity . The lack of structural information on the interaction modalities of the C-terminus-targeting inhibitors, due to the high mobility of this domain and the lack of alternative druggable sites, prevents the development of selective inhibitors for TrxRs.

The folding and aggregation properties of a single KH-domain protein: Ribosome binding factor A (RbfA) from Pseudomonas aeruginosa.

Background: Ribosome-binding factor A from the pathogenic bacterium Pseudomonas aeruginosa (PaRbfA) is a small ribosome assembly factor, composed by a single KH domain, involved in the maturation of the 30S subunit. These domains are characterized by the ability to bind RNA or ssDNA and are often located in proteins involved in a variety of cellular functions. However, although the ability of proteins to fold properly, to misfold or to aggregate is of paramount importance for their cellular functions, limited information is available on these dynamic properties in the case of KH domains.

A ring-shaped protein clusters gold nanoparticles acting as molecular scaffold for plasmonic surfaces.

Background: Proteins are efficient supramolecular scaffolds to drive self-assembly of nanomaterials into regular colloidal structures suitable for several purposes, including cell imaging and drug delivery. Proteins, in particular, can bind to gold nanoparticles (AuNPs) through van der Waals and electrostatic forces as well as coordination and hydrogen bonds leading their assembly into responsive nanostructures.

Methods: Bioconjugation of alkyne Raman tag-labeled 20 nm AuNPs with the ring-shaped protein Peroxiredoxin (Prx), characterized by a symmetric homo-oligomeric circular arrangement, has been investigated by absorption spectroscopy, transmission and scanning electron microscopy.

Fragment-Based Discovery of a Regulatory Site in Thioredoxin Glutathione Reductase Acting as "Doorstop" for NADPH Entry.

Members of the FAD/NAD-linked reductase family are recognized as crucial targets in drug development for cancers, inflammatory disorders, and infectious diseases. However, individual FAD/NAD reductases are difficult to inhibit in a selective manner with off-target inhibition reducing usefulness of identified compounds. Thioredoxin glutathione reductase (TGR), a high molecular weight thioredoxin reductase-like enzyme, has emerged as a promising drug target for the treatment of schistosomiasis, a parasitosis afflicting more than 200 million people.

Baseline PSA in a Spanish male population aged 40-49 years anticipates detection of prostate cancer.

Introduction: We researched the usefulness of optimizing prostate cancer (PC) screening in our community using baseline PSA readings in men between 40-49 years of age.

Material And Method: A retrospective study was performed that analyzed baseline PSA in the fifth decade of life and its ability to predict the development of PC in a population of Madrid (Spain). An ROC curve was created and a cutoff was proposed.

Second transurethral resection and prognosis of high-grade non-muscle invasive bladder cancer in patients not receiving bacillus Calmette-Guérin.

Objective: To define the natural history of T1G3 bladder tumor not receiving intravesical Bacillus Calmette-Guerin (BCG) and assess the diagnostic and therapeutic value of a second transurethral resection (Re-TUR) in these patients.

Patients And Methods: Retrospective study on the natural history of 210 patients treated at two institutions for T1G3 bladder carcinoma without associated CIS. In no case was BCG administered; 79 (37.

Acute Generalized Exanthematous Pustulosis Induced by Erlotinib (Tarceva) with Superimposed Staphylococcus aureus Skin Infection in a Pancreatic Cancer Patient: A Case Report.

Acute generalized exanthematous pustulosis (AGEP) is a rare acute reaction that is drug induced in 90% of the cases and characterized by a widespread, sterile pustular rash. Erlotinib, a small-molecule EGFR tyrosine kinase inhibitor, has been approved by the FDA for patients with pancreatic cancer and non-small cell lung cancer. Skin rash is a well-known side effect related with all EGFR blocking agents.

Is intratympanic injection of erdosteine protective against cisplatin-induced ototoxicity?

Cisplatin induces ototoxicity in adult and pediatric population. Our aim was (1) to assess the protective effect of intratympanic injections of erdosteine in the prevention of cisplatin-induced ototoxicity and (2) to investigate inner ear protection using a scanning electron microscope. Ears of 20 Hartley guinea pigs were assigned to four subgroups and received an intratympanic injection of: E1-erdosteine 1.

[Upper urinary tract tumors: endourological management and treatment].

The propensity of upper tract transitional cell carcinoma towards recurrence and the limitations of upper tract endoscopy have led to nephroureterectomy being the gold standard treatment, even though major open surgery risks outweigh the risks of cancer. Thus, removal of the entire unit may not be warranted when the tumor can be safely controlled endoscopically. Recent advances in technology and techniques have permitted the effective endourologic management of upper transitional cell carcinoma.

[Laparoscopic radical cystectomy and orthotopic urinary diversion in the male patient: technique].

Radical cystectomy with extended pelvic lymphadenectomy remains the treatment of choice for muscle invasive bladder cancer and non-metastatic chorion-invasive high grade tumors resistant to treatment with intravesical chemotherapy. During the last decade the procedure has been refined and we have acquired the skills necessary to perform it using the laparoscopic approach. In this way, the oncologic and functional outcomes obtained can be compared to those of its open counterpart.

[Laparoscopic extraperitoneal prostatic adenomectomy: description of the surgical technique].

Historically, the surgical treatment of benign prostatic hyperplasia (BPH)in glands with volumes over 75-80 grams was performed using the conventional surgical approaches described by Terence Millin and Peter Freyer. Due to technological advancement over the past three decades, at present, minimally invasive techniques are being used with good results in the treatment of BPH. The incorporation of the laparoscopic approach to urologic surgery has allowed the technical development of adenomectomy using the same guidelines followed by conventional approaches.

[Detection and molecular staging of bladder cancer using real-time RT-PCR for gelatinases (MMP-2, MMP-9) and TIMP-2 in peripheral blood].

Introduction: Molecular staging of bladder cancer based on the detection of mRNA of urothelial specific genes in circulating cancer cells has been inconclusive. We analyze whether real-time RT-PCR evaluation of gelatinases (MMP-9, MMP-2) and TIMP-2 in peripheral blood to diagnose and characterize patients with bladder neoplasm.

Material And Method: Total RNA is extracted from circulating blood cells in 42 individuals (11 healthy controls, 31 patients with bladder cancer of different stages) and real-time RT-PCR performed using specific primers for MMP-9, MMP-2, TIMP-2 and ribosomal 18S.

Bone anchored hearing aid in single sided deafness: outcome in right-handed patients.

Objective: To assess the benefits in terms of sound localization, to evaluate speech discrimination in noise, to appraise the prosthesis benefit and to identify outcome in right and left handed patients when BAHA are implanted on the right or on the left deaf side.

Methods: Two years prospective study in a tertiary referral center. Tests consist on Hearing in Noise Test (HINT) and sound localization after 6 months of BAHA use.

Are intratympanic injections of N-acetylcysteine and methylprednisolone protective against Cisplatin-induced ototoxicity?

Objective: To identify and to compare the protective effect of intratympanic injections of N-acetylcysteine (NAC) or methylprednisolone to prevent cisplatin-induced ototoxicity, to investigate inner ear protection using an electron microscope and to evaluate the effect of 4% NAC on the middle ear.

Design: Experimental study.

Setting: Basic ear research center at Sainte-Justine hospital.

How much residual hearing is 'useful' for music perception with cochlear implants?

Aim: To compare performance on a song recognition task of bilaterally combined electric and acoustic hearing (bimodal stimulation) with electric or acoustic hearing alone.

Methods: Subjects were 14 adults with cochlear implants (CI) who continued to use a hearing aid (HA) in one/both ears. Subjects were asked to identify excerpts from 15 popular songs, which were familiar to them, presented in a random order via a single loudspeaker.

Trigeminal nerve haemangioma eroding the petrous carotid canal.

Objective: To report the first case of mandibular branch haemangioma of the trigeminal nerve causing erosion of the petrous carotid canal. The radiological and histological findings in this case are reviewed.

Case Report: A 60-year-old woman presented with severe, right-sided facial pain and paraesthesia.

Ossicular reconstruction: incus versus universal titanium prosthesis.

Objectives: The main purpose of this study is to compare audiological outcomes of incus reconstruction, Xomed Medtronic universal titanium partial ossicular replacement prosthesis (PORP) and total ossicular replacement prosthesis (TORP). We also compared results based on surgical technique, history of previous surgery, form of the prosthesis head, pathology and frequency.

Methods: A chart review was performed and included reconstructions performed between June 2003 and December 2006.