Methionine aminopeptidases: Potential therapeutic target for microsporidia and other microbes.

Methionine aminopeptidases (MetAPs) have emerged as a target for medicinal chemists in the quest for novel therapeutic agents for treating cancer, obesity, and other disorders. Methionine aminopeptidase is a metalloenzyme with two structurally distinct forms in humans, MetAP-1 and MetAP-2. The MetAP2 inhibitor fumagillin, which was used as an amebicide in the 1950s, has been used for the successful treatment of microsporidiosis in humans; however, it is no longer commercially available.

Canal-Centering and Apical Transportation Ability of Similar Cross-Section NiTi Instruments Working with Different Kinematics-Micro-CT-based Analysis.

Objective: Evaluating the canal-centering and apical transportation ability of endodontic file systems working with different kinematics but of similar cross section.

Materials And Methods: Sixty human maxillary first molar mesiobuccal (MB) roots were assigned to three experimental groups based on instrumentation techniques: Reciproc Blue (RB), Mtwo (M2), and OneShape (OS). Pre- and post-instrumentation micro-computed tomographic analysis was performed.

Sequential Release and Muscle Slide of Irreparable Rotator Cuff Tears Results in Linear Gains in Tendon Mobility.

Purpose: The purposes of this study were to examine the technique of the supraspinatus and infraspinatus muscle slide for the treatment of rotator cuff tears and to quantify the amount of release and resultant tendon excursion at their insertion sites in cadavers.

Methods: Twelve shoulders in 6 human cadavers were dissected. Their average age at time of death was 84 years.

Classical Seminoma With Secondary Undescended Testis in an Elderly Patient: An Incidental Finding With a Penile Fracture.

Cryptorchidism is a common condition among children; however, it is rare in adults and is associated with an increased risk of malignancy. The development of secondary undescended testes is recognized as a complication following inguinal surgeries such as hernia repair and orchidopexy. Herein, we describe the case of a 64-year-old male with a known past surgical history of right indirect inguinal hernia repair complaining of penile swelling.

Remnant mullerian structure with transverse testicular ectopia.

29-year-old male patient with infertility, presented to emergency room with recurrent testicular pain. Patient had MRI done with suspicion of TTE. Laparoscopic exploration showed right spermatic vessels crossing the midline toward the left side with normal course of left vas.

Does end-tidal capnography confirm tracheal intubation in fresh-frozen cadavers?

Background: Life-like end-tidal capnography (ETCO) waveforms have been demonstrated in recently deceased and fresh-frozen cadavers following tracheal intubation, offering potential for high fidelity airway simulation training. As the mechanism for carbon dioxide production is not fully understood, it is possible that oesophageal intubation may also generate a capnograph. Our aim was to measure ETCO levels following (1) oesophageal and (2) tracheal intubation in fresh-frozen cadavers, and to observe the size, shape and duration of any capnographic waveform.

A human cadaveric workshop: One solution to competence in the face of rarity.

Competent performance of cricothyroidotomy, lateral canthotomy and resuscitative thoracostomy is an expected standard for Australasian emergency physicians, but infrequent exposure to these procedures could impair physician confidence, reducing the likelihood of their execution in a critical timeframe. Training to perform these procedures is a recognised challenge for non-surgeons, and cadaver-based training is one method of addressing this need. We describe a 1 day cadaver-based workshop for emergency medicine doctors and briefly report on its impact on physician confidence.

Edelfosine Promotes Apoptosis in Androgen-Deprived Prostate Tumors by Increasing ATF3 and Inhibiting Androgen Receptor Activity.

Edelfosine is a synthetic alkyl-lysophospholipid that possesses significant antitumor activity in several human tumor models. Here, we investigated the effects of edelfosine combined with androgen deprivation (AD) in LNCaP and VCaP human prostate cancer cells. This treatment regimen greatly decreased cell proliferation compared with single agent or AD alone, resulting in higher levels of apoptosis in LNCaP compared with VCaP cells.

Physical performance and markers of muscle damage following sport-specific sprints in male collegiate soccer players: repeated bout effect.

Background: This is the first study to examine the repeated bout effect (RBE) on physical performance parameters in an athletic population. Protocols used by previous studies to induce muscle injury and assess performance following injury, are dissimilar from those utilized by physically trained individuals or are impractical in relation to athletic performance. The present study uses a sport specific protocol to study the effects of exercise induced muscle damage (EIMD) on physical performance to provide a more systematic analysis of the extent of muscle injury.

Fulminant hepatic failure with virtually undetectable serum alkaline phosphatase.

Wilson's disease presenting as fulminant hepatic failure is a rare presentation that carries a high morbidity and mortality. We report a young patient who developed fulminant hepatic failure as the initial manifestation of Wilson's disease. Virtually undetectable serum alkaline phosphatase provided the first clue to the diagnosis.

Interaction of HIF-1α and Notch3 Is Required for the Expression of Carbonic Anhydrase 9 in Breast Carcinoma Cells.

Expression of carbonic anhydrase 9 (CA9) is associated with poor prognosis and increased tumor aggressiveness and does not always correlate with HIF-1α expression. Presently, we analyzed the regulation of CA9 expression during hypoxia by HIF-1α, Notch3, and the von Hippel-Lindau (VHL) in breast carcinoma cells. Both HIF-1α and Notch3 were absolutely required for the expression of CA9 mRNA, protein, and reporter.

Heat-induced fibrillation of BclXL apoptotic repressor.

The BclXL apoptotic repressor bears the propensity to associate into megadalton oligomers in solution, particularly under acidic pH. Herein, using various biophysical methods, we analyze the effect of temperature on the oligomerization of BclXL. Our data show that BclXL undergoes irreversible aggregation and assembles into highly-ordered rope-like homogeneous fibrils with length in the order of mm and a diameter in the μm-range under elevated temperatures.

The E2F1/Rb and p53/MDM2 pathways in DNA repair and apoptosis: understanding the crosstalk to develop novel strategies for prostate cancer radiotherapy.

Both the p53- and E2F1-signaling pathways are defective in almost all types of tumors, suggesting very important roles for their signaling networks in regulating the process of tumorigenesis and therapy response. Studies on Radiation Therapy Oncology Group tissue samples have identified aberrant expression of p53, MDM2 (an E3 ubiquitin ligase that targets p53 for proteosomal degradation), and p16 (an upstream regulator of retinoblastoma and hence E2F1 in prostate cancer); abnormal expression of these biomarkers has been associated with clinical outcome after radiotherapy ± androgen deprivation therapy. Although the proapoptotic properties of p53 are well documented, a relatively new aspect of p53 function as an active mediator of prosurvival signaling pathways is now emerging.

Photopatch testing negative in systemic quinine phototoxicity.

Drug-induced phototoxicity can be caused by topical or systemic agents and is diagnosed on the basis of clinical history, examination and appropriate investigations. Photopatch testing is the investigation of choice for topical photocontact allergic dermatitis, but its use in drug-induced phototoxicity has not been validated. We retrospectively analyzed the results of photopatch testing to the drug quinine sulfate in three patients in whom a diagnosis of drug-induced phototoxicity to this agent had been made.

Human Prostate Cancer Cells Secrete Neuro-Protective Factors in Response to Cryotherapy.

Cryoablation is one of the established treatment modalities for prostate cancer management. Although, it is target specific, it may still lead to damage to the nerve fibers around the prostate tumor. In this study, by directly exposing the co-cultures of prostate cancer cells, PC-3 and Schwann cell-Dorsal Root Ganglion neuron (SC-DRG) to cryo-shock and by exposing SC-DRG to cryo-shock conditioned media (CSCM) obtained from PC-3 cells, robust neuro-protective effects were observed.

Role of Radiation-induced TGF-beta Signaling in Cancer Therapy.

TGF-β signaling regulates several different biological processes involving cell-growth, differentiation, apoptosis, motility, angiogenesis, epithelial mesenchymal transition and extracellular matrix production that affects embryonic development and pathogenesis of various diseases, including cancer, its effects depending on the cellular context and physiological environment. Growth suppression mediated by TGF-β signaling often associated with inhibition of c-myc, cdks and induction of p15, p27, Bax and p21. Despite its growth inhibitory effect, in certain conditions TGF-β may act as a promoter of cell proliferation and invasion.

A noncommercial polymerase chain reaction-based method to approach one hundred percent recombinant clone selection efficiency.

Molecular cloning is an important procedure in molecular biology, but this is often a rate-limiting step and can be very time-consuming, possibly due to low ligation efficiency. Here, we describe a simple polymerase chain reaction (PCR)-based strategy to approach 100% selection efficiency. The post-ligation mixture containing the recombinant was subjected to insert-specific primer-mediated PCR amplification using a high-fidelity DNA Pfu polymerase generating a plasmid containing staggered nicks.

Lack of P-glycoprotein expression by low-dose fractionated radiation results from loss of nuclear factor-kappaB and NF-Y activation in oral carcinoma cells.

Multidrug resistance (MDR) is associated with the overproduction of the 170-kDa transmembrane protein P-glycoprotein (MDR1) caused by transcriptional activation. However, the activity of the MDR1 promoter in response to different doses of ionizing radiation has not been investigated. In this study, two squamous cell carcinoma oral cavity cell lines, T-167 and T-409, were exposed to either a standard clinical dose of 2 Gy or low-dose fractionated radiation therapy (LDFRT), delivered as 0.

Role of tumor necrosis factor-alpha and TRAIL in high-dose radiation-induced bystander signaling in lung adenocarcinoma.

In the present study, ionizing radiation (IR)-induced bystander effects were investigated in two lung cancer cell lines. A549 cells were found to be more resistant to radiation-conditioned medium (RCM) obtained from A549 cells when compared with the H460 exposed to RCM procured from H460 cells. Significant release of tumor necrosis factor-alpha (TNF-alpha) was observed in A549 cells after IR/RCM exposure, and the survival was reversed with neutralizing antibody against TNF-alpha.

Inhibition of transforming growth factor-beta signaling in normal lung epithelial cells confers resistance to ionizing radiation.

Purpose: To address the functional role of radiation-induced transforming growth factor-beta (TGF-beta) signaling in a normal epithelial background, we selected a spontaneously immortalized lung epithelial cell line derived from the normal lung tissue of a dominant-negative mutant of the TGF-beta RII (DeltaRII) transgenic mouse that conditionally expressed DeltaRII under the control of the metallothionein promoter (MT-1), and assessed this cell line's response to radiation.

Methods And Materials: A spontaneously immortalized lung epithelial cell culture (SILECC) was established and all analyses were performed within 50 passages. Colony-forming and terminal transferase dUPT nick end labeling (TUNEL) assays were used to assess clonogenic inhibition and apoptosis, respectively.

Obesity and cardiovascular risk factors in Saudi adult soldiers.

Objective: To examine the relationship between obesity and cardiovascular risk factors among men aged 20 years and above.

Methods: The study involved a cross-sectional survey of 2,250 Saudi male soldiers aged between 20 and 60 years residing in a military city in northern Saudi Arabia conducted in 2004. Anthropometric measurements, blood pressure, and a brief medical history were obtained in a pre-set questionnaire.