Release and hemodynamic influence of nitro-glycerine-derived nitric oxide in endotoxemic rats.

Background And Aim: Nitric oxide released from nitro-glycerine (NG) has been considered to improve the microcirculation. Septic conditions are, however, associated with excessive formation of nitric oxide (NO), which is formed from l-arginine by the inducible NO synthase (iNOS) activity. Since the characteristics and influence of NG-derived NO in sepsis remains unclear, the major aims of the present study were to quantify the release and to determine the effects of NO formed from NG on systemic blood pressure under endotoxemic conditions.

Efficacy of ultrasound in the diagnosis of pleurodesis in rabbits.

Introduction: The treatment of recurrent pleural effusion or recurrent pneumothorax frequently involves the creation of a pleurodesis. Ultrasound is being used more frequently to assess the presence of pleural fluid or pneumothorax. With ultrasound, the gliding sign displays the gliding of the visceral pleura over the parietal pleura during respiration.

Murine double minute 2 as a therapeutic target for radiation sensitization of lung cancer.

Murine double minute 2 (MDM2) inhibits p53-mediated functions, which are essential for therapies using DNA-damaging agents. The purpose of this study was to determine whether MDM2 inhibition enhances the radiosensitivity of a lung cancer model. The effects of MDM2 inhibition on tumor vasculature were also studied.

Induction of cytokinesis is independent of precisely regulated microtubule dynamics.

Astral microtubules (MTs) emanating from the mitotic apparatus (MA) during anaphase are required for stimulation of cytokinesis in eggs. We have used green fluorescent protein-labeled EB1 to observe MT dynamics during mitosis and cytokinesis in normal sea urchin eggs. Analysis of astral MT growth rates during anaphase shows that MTs contact the polar cortex earlier than the equatorial cortex after anaphase onset but that a normal cleavage furrow is not induced until contact with MTs has been achieved throughout the cortex.

Effects of motexafin gadolinium on DNA damage and X-ray-induced DNA damage repair, as assessed by the Comet assay.

Purpose: To investigate the effects of motexafin gadolinium (MGd) on the levels of reactive oxygen species (ROS), glutathione (GSH), and DNA damage in EMT6 mouse mammary carcinoma cells. The ability of MGd to alter radiosensitivity and to inhibit DNA damage repair after X-ray irradiation was also evaluated.

Methods And Materials: Reactive oxygen species and GSH levels were assessed by 2,7-dichlorofluorescein fluorescence flow cytometry and the Tietze method, respectively.

Metallothionein crypt-restricted immunopositivity indices (MTCRII) correlate with aberrant crypt foci (ACF) in mouse colon.

Metallothionein (MT) crypt-restricted immunopositivity indices (MTCRII) are colonic crypt stem cell mutation markers that may be induced early and in abundance after mutagen treatment. Metallothionein is the endogenous reporter gene for MTCRII, but is not typically implicated in the classical pathway of colorectal tumorigenesis. Hence, the oncological relevance of MTCRII is unclear.

Sonographic depiction of changes of tumor vascularity in response to various therapies.

Purpose: To evaluate the diagnostic accuracy of power Doppler sonography for the depiction of changes in tumor vascularity with various therapeutic regimens.

Materials And Methods: Tumor cells were implanted subcutaneously in thirty-two mice and assigned to four treatment groups: control, radiation therapy, antiangiogenesis therapy (VEGF [vascular endothelial growth factor] receptor antagonist, SU11248), or combined antiangiogenesis and radiation therapy. Twenty of these mice were scanned with power Doppler sonography at two time points over the course of treatment, and power-weighted pixel densities were assessed.

Experimental validation of the Wigner distributions theory of phase-contrast imaging.

Recently, a new theory of phase-contrast imaging has been proposed by Wu and Liu [Med. Phys. 31, 2378-2384 (2004)].

Gene therapy targeting the Tie2 function ameliorates collagen-induced arthritis and protects against bone destruction.

Objective: In a previous study, we demonstrated that Tie2 regulates angiogenesis in arthritis. The current study was performed to determine whether systemic delivery of a soluble Tie2 receptor (ExTek) using an adenoviral vector (AdExTek) as a Tie2 inhibitor affects arthritis development and progression in an animal model.

Methods: We used a collagen-induced arthritis (CIA) mouse model to study the outcome of treatment with either AdExTek or a control vector.

Sauvagine analogs selective for corticotropin releasing factor 2 receptor: effect of substitutions at positions 35 and 39 on CRF2R selectivity.

Corticotropin releasing factor 2 receptor selective analogs of the amphibian peptide sauvagine, a member of the corticotropin releasing factor (CRF) peptide family, have therapeutic potential for the treatment of skeletal muscle atrophy. Previously, we demonstrated that [P11X12X13]Svg peptides have improved CRF2R selectivity, although not to the level of CRF2R selective hormones such as urocortin 2 and urocortin 3. Since we also demonstrated a potential for improvement in selectivity of sauvagine by modifications of residues 35 and 39, we investigated substitutions of these amino acids in selected [P11X12X13]Svg peptides.

Corticotropin releasing factor 2 receptor agonists reduce the denervation-induced loss of rat skeletal muscle mass and force and increase non-atrophying skeletal muscle mass and force.

Of the two corticotropin releasing factor receptors known, corticotrophin releasing factor 2 receptor (CRF2R) is expressed in skeletal muscle. The function of this receptor in skeletal muscle is at present unknown. In order to better understand the role of the CRF2R in skeletal muscle, we treated rats with CRF2R agonists and evaluated the effect of these agents on normal and denervated muscle mass.

Activation of the vasoactive intestinal peptide 2 receptor modulates normal and atrophying skeletal muscle mass and force.

Of the two known vasoactive intestinal peptide receptors (VPAC1R and VPAC2R), the VPAC2R is expressed in skeletal muscle. To evaluate the function of the VPAC2R in the physiological control of skeletal muscle mass, we utilized the VPAC1R selective agonist [K15,R16,L27]VIP(1-7) GRF(8-27)-NH2 and the VPAC2R selective agonist Ro-25-1553 to treat mice and rats undergoing either nerve damage-, corticosteroid-, or disuse-induced skeletal muscle atrophy. These analyses demonstrated that activation of VPAC2R, but not VPAC1R, reduced the loss of skeletal muscle mass and force during conditions of skeletal muscle atrophy resulting from corticosteroid administration, denervation, casting-induced disuse, increased skeletal muscle mass, and force of nonatrophying muscles.

Discovery of corticotropin releasing factor 2 receptor selective sauvagine analogues for treatment of skeletal muscle atrophy.

The corticotropin release factor 2 receptor (CRF2R) has many biological activities including modulation of the stress response. Recently, we have demonstrated that CRF2R activation functions to prevent skeletal muscle wasting resulting from a variety of physiological stimuli. Thus we are interested in identifying CRF2R selective agonists with optimal pharmacological properties for use in treating muscle wasting diseases.

Linking pharmacovigilance with pharmacogenetics.

The ability to identify individuals who are susceptible to adverse drug reactions (ADRs) has the potential to reduce the personal and population costs of drug-related morbidity. Some individuals may show an increased susceptibility to certain ADRs through genetic polymorphisms that alter their responses to various drugs. We wished to establish a methodology that would be acceptable to members of the general population and that would enable estimation of the risks that specific genetic factors confer on susceptibility to specific ADRs.

Preview: Lyme disease vaccines.

Lyme disease is a tick-borne spirochetal disease that is common in Rhode Island. The OSP A based vaccine against Lyme disease that has been shown effective in animal models has now been tested by two manufacturers in thousands of people. The vaccines appear to be safe and effective.

Sonographic depiction of microvessel perfusion: principles and potential.

Objective: To provide an overview of the technical aspects and potential clinical applications of microvessel perfusion as depicted by microbubble-enhanced sonography.

Methods: Sonographic depiction of microvessel perfusion was obtained by microbubble-enhanced sonography. This technique was used for imaging in vivo murine tumors and was correlated with magnetic resonance and fluorodeoxyglucose autoradiography.

Long-term outcome of clozapine use for psychosis in parkinsonian patients.

A retrospective analysis was carried out on 39 parkinsonian patients on clozapine treatment >/=24 months for psychosis. The cohort had a mean age of 76 years and an average clozapine dose of 47 mg/day over 60 months of clozapine use. Of 39 patients, 13 (33%) patients were eventually admitted to nursing homes, 6 (46%) of whom died over a period of 5 years.

Determinants of corticotropin releasing factor. Receptor selectivity of corticotropin releasing factor related peptides.

The corticotropin-releasing factor (CRF) peptide family is an important target in pharmaceutical research. The CRF system consists of two receptors, corticotropin releasing factor receptor 1 (CRF1R) and corticotropin releasing factor receptor 2 (CRF2R), a nonreceptor binding protein, and the peptide agonists of these receptors. The recent discovery of the CRF2R selective peptide agonists, UCN2, UCN3 and URP, prompted investigations into the structural source of CRF1R versus CRF2R selectivity of CRF peptide family members.

Effects of texaphyrins on the oxygenation of EMT6 mouse mammary tumors.

Purpose: To investigate the effects of texaphyrins on the oxygenation of EMT6 mouse mammary tumors in Balb/c Rw mice. Texaphyrins are synthetic, porphyrin-like molecules capable of stably coordinating lanthanide and nonlanthanide metals. Metallotexaphyrin compounds containing gadolinium (MGd), lutetium (MLu), europium (Eu-Tex), dysprosium (Dy-Tex), and manganese (Mn-Tex) were evaluated.

Broad spectrum receptor tyrosine kinase inhibitor, SU6668, sensitizes radiation via targeting survival pathway of vascular endothelium.

Purpose: Recent studies have demonstrated radiosensitization by inhibiting receptor tyrosine kinases (RTKs). Irradiation activates RTKs and their downstream prosurvival molecule, Akt. In this study, we investigated the mechanism by which SU6668, an inhibitor of RTKs involved in angiogenic pathways, enhances effects of irradiation.

Quantification of tumor vascularity with contrast-enhanced sonography: correlation with magnetic resonance imaging and fluorodeoxyglucose autoradiography in an implanted tumor.

Objective: To correlate the quantitated tumor vascularity of implanted murine tumors as depicted by contrast-enhanced sonography with estimates made with magnetic resonance imaging and with estimates of the percentage of viable (metabolically active) tumor as depicted by fluorodeoxyglucose autoradiography.

Methods: Implanted tumors in 10 mice were imaged with contrast-enhanced sonography, magnetic resonance imaging, and fluorodeoxyglucose autoradiography. Tumor vascularity was estimated with each modality and compared with the percentage of viable tumor.

Modulation of N-methyl-N-nitrosourea-induced crypt restricted metallothionein immunopositivity in mouse colon by a non-genotoxic diet-related chemical.

Red meat consumption is associated with endogenous metabolic generation of mutagenic N-nitroso compounds (NOC) and may be implicated in causation of colorectal cancer. Assessment of a biologically relevant dose of NOCs is hampered by imperfect understanding of NOC interactions with other dietary components. This study tests the hypothesis that NOC effects upon mutational biomarkers in mouse colon may be modulated by a non-genotoxic diet-related compound.

Effects of cryopreservation on testicular sperm nuclear DNA fragmentation and its relationship with assisted conception outcome following ICSI with testicular spermatozoa.

The objective of the study was to investigate the effects of freeze-thawing on testicular sperm DNA fragmentation, fertilization rates and pregnancy rates following intracytoplasmic sperm injection with testicular spermatozoa (TESE). This ongoing prospective study included 88 couples attending for infertility treatment where the man presented with obstructive azoospermia at the Regional Fertility Centre, Belfast, UK. Patients were allocated to receive TESE treatment with fresh or freeze-thawed spermatozoa.

Quantification of the effect of system and object parameters on edge enhancement in phase-contrast radiography.

The purpose of this study was to evaluate the effects of system parameters (focal spot size, tube voltage, geometry, detector resolution, and image noise) and object characteristics (edge gradient/ shape, composition, thickness, and overlying attenuating material) upon the edge enhancement effect in phase-contrast radiography. Each variable of interest was adjusted and images of a 3 mm lucite phantom were obtained with the other variables remaining constant. A microfocus x-ray source coupled to a CCD camera with an intensifying screen was used to acquire the digital images.