Rosuvastatin provides pleiotropic protection against pulmonary hypertension, right ventricular hypertrophy, and coronary endothelial dysfunction in rats.

We recently reported that increased vascular endothelial nitric oxide production could protect against the development of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) and right ventricular hypertrophy (RVH) in rats (32). The present study investigated whether the pleiotropic action of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors in upregulating endothelial function could also protect against the MCT-induced end-organ damages. Rosuvastatin (2 mg kg(-1) day(-1) via oral gavage) or placebo was initiated 1 wk before or 1 wk after MCT (60 mg/kg ip) administration.

T cells of the gammadelta T-cell receptor lineage play an important role in the postburn wound healing process.

Although gammadelta T cells have been implicated in various aspects of the dermal wound healing process, their role in postburn wound healing processes has not been investigated. To study this, we subjected mice deficient in gammadelta T cells (ie, T-cell receptor delta gene [delta TCR]) and wild-type (WT; C57BL6J) mice to burn injury (25% TBSA) or sham treatment; skin samples were isolated 3 days later. Marked inflammation of the injury site was observed in WT mice but was markedly reduced in delta TCR mice.

Evidence for roles of the activating function in electric stimulation.

The hypothesis that the activating function drives transmembrane voltage changes (delta Vm) has been tested in hearts. Optical delta Vm were measured during activating functions produced with nonuniform and uniform transparent electrodes. When a nonuniform electrode was used to produce [equation: see text], the signs of delta Vm and [equation: see text] matched.

Morphological variability and specializations in bovine extraocular muscle spindles.

Bovine extraocular muscles were examined to determine whether the structure of their muscle spindles was notably different from those commonly encountered in mammalian limb muscles. Extraocular muscle spindles on the whole were shorter, and intrafusal fiber counts/spindle were more variable than in somatic muscles. No pronounced nuclear bags were seen in intrafusal fibers.

Lessons learned from the mouse model of short-chain acyl-CoA dehydrogenase deficiency.

The SCAD deficient mouse model has been useful to investigate mechanisms of deficient fatty acid oxidation disease in human patients. This mouse model has been thoroughly characterized and is readily available from the Jackson Laboratory. Using the new technologies of gene-knockout mouse modeling, we envisage developing additional members of the acyl-CoA dehydrogenase family of enzyme deficiencies in mice and furthering our understanding of fatty acid metabolism in health and disease.

High-resolution mapping and histologic examination of long radiofrequency lesions in canine atria.

Introduction: Catheter ablation may prevent conduction of multiple atrial wavefronts and/or reduce the critical mass of atrial myocardium required to sustain fibrillation. The purpose of this study was to examine the effect of radiofrequency (RF) energy application on conduction in canine atria by performing high-density epicardial mapping and careful histologic examination of the ablation zone.

Methods And Results: RF energy was applied to the right atrial endocardium in nine anesthetized mongrel dogs in an attempt to create a line of conduction block spanning the vertical length of a 504-channel epicardial mapping plaque.

Isolation and microinjection of somatic cell-derived mitochondria and germline heteroplasmy in transmitochondrial mice.

At present, there are no means for creation of relevant animal models of human mitochondrial DNA (mtDNA)-based diseases in a directed fashion. As an initial step towards this end, we have developed a microinjection technique for transfer of isolated, viable mitochondria between two mouse species. Previously, we reported detection, by nested PCR with species-specific primer sets, of Mus spretus mtDNA in Mus musculus domesticus blastocyts following zygote microinjection and culture.

Effects of pyrrolidine dithiocarbamate on endothelial cells: protection against oxidative stress.

The dithiocarbamates are well known for their antioxidant properties and effects on cellular transcriptional events. For example, pyrrolidine dithiocarbamate (PDTC) is widely used as an inhibitor of nuclear factor kappa B (NFkappaB) and this, or related compounds may have therapeutic potential in inhibiting atherosclerosis. However, the precise molecular mechanisms through which PDTC could elicit antioxidant or cell signaling effects in a cellular setting remain unclear.

Defects in mitochondrial beta-oxidation of fatty acids.

Mitochondrial beta-oxidation of fatty acids generates energy by direct electron transfer at the dehydrogenase steps along with the ultimate product of acetyl-coenzyme A that can be further oxidized for ATP synthesis, or conversion to ketone bodies. This review describes the human inborn errors of this pathway and recent results concerning the development and use of mouse models of these inherited enzyme deficiencies.

Mucosal vaccination with recombinant poxvirus vaccines protects ferrets against symptomatic CDV infection.

Canine distemper virus (CDV) infection of ferrets causes a disease characterized by fever, erythema, conjunctivitis and leukocytopenia, similar clinically to measles except for the fatal neurologic sequelae of CDV. We vaccinated juvenile ferrets twice at 4-week intervals by the intranasal or intraduodenal route with attenuated vaccinia (NYVAC) or canarypox virus (ALVAC) constructs containing the CDV hemagglutinin and fusion genes. Controls were vaccinated with the same vectors expressing rabies glycoprotein.

Nitric oxide--cyclic GMP pathway regulates vascular smooth muscle cell phenotypic modulation: implications in vascular diseases.

The role of cGMP-dependent protein kinase (PKG) in the regulation of rat aortic vascular smooth muscle cells (VSMC) phenotype was examined using a transfected cell culture system. Repetitively passaged VSMC do not express PKG and exist in the synthetic phenotype. Transfection of PKG-l alpha cDNA, or the active catalytic domain of PKG-l alpha, resulted in the appearance of VSMC having a morphology consistent with the contractile phenotype.

Syndecans: synergistic activators of cell adhesion.

Cell-surface proteoglycans participate in cell adhesion, growth-factor signalling, lipase activity and anticoagulation. Until recently, only the roles of the glycosaminoglycan chains were investigated. Now, with molecular characterization of several core proteins, the roles of each individual proteoglycan species in cellular signalling pathways are being determined.

Elastic protein-based materials in tissue reconstruction.

In natural tissues, cells form multiple attachment sites to their extracellular matrix. By means of those attachments, cells deform as the tissue deforms in response to the natural mechanical stresses and strains that the tissue must sustain during function. These mechanical forces are the energy input that instruct the cells to produce the extracellular matrix sufficient to sustain those forces.

Primary structure and expression of a chicken laminin beta chain: evidence for four beta chains in birds.

Characterization of a full length cDNA sequence for a chicken laminin beta chain is described which is most closely related to the mammalian beta 2 chain. Comparison with published sequences shows that the chicken beta 2-like chain corresponds to a fragment of a previously described laminin beta chain called B1-2 (O'Rear, 1992). The sequence of the chicken beta 2-like chain differed from fragments of two other chicken laminin beta chains that were previously described and designated B1-1 (now called beta 1; O'Rear, 1992) and beta x (Ybot-Gonzalez et a1.

Mitochondria transfer into mouse ova by microinjection.

A method for mitochondria isolation and interspecific transfer of mitochondria was developed in mice. Mitochondria were isolated from Mus spretus liver samples for microinjection into fertilized ova obtained from superovulated M. musculus domesticus females.

Prevention of action potentials during extracellular electrical stimulation of long duration.

Introduction: This study investigated if action potentials can be prevented by electrical field stimuli of long duration.

Methods And Results: The transmembrane potential was recorded by a double-barrel micro-electrode during field stimulation given across a papillary muscle from 10 guinea pigs. After 10 stimuli (S) with a 200-msec S-S interval, a 400-msec square wave shock was given just before or after the end of the effective refractory period following the 10th stimulus through electrodes 1 cm on either side of the papillary muscles.

Can catheter ablation in cardiac arrest survivors prevent ventricular fibrillation recurrence?

Ventricular tachyarrhythmias are the most common cause for sudden cardiac death. The success of catheter ablation for supraventricular tachycardias led to the supposition that ablation could also be used in the treatment of ventricular tachycardias. Despite the promising results in bundle branch reentry and some forms of idiopathic ventricular tachycardia, the success rate in patients with coronary artery disease is still low.

Disruption of vascular signalling by the reaction of nitric oxide with superoxide: implications for cardiovascular disease.

Oxidation reactions are used in controlled enzymatic pathways to form intracellular messengers such as the prostaglandins, leukotrienes, and the simplest signalling molecule known, nitric oxide. In inflammation, non-enzymatic oxidation appears to produce compounds which compete with or inhibit the mediators derived from endogenous enzymatic oxidative processes. Many of these compounds could be derived from the reaction of NO with superoxide to form peroxynitrite and the ensuing oxidation, nitration and nitrosation reactions.

Interspecies variability of TNP-470 metabolism, using primary monkey, rat, and dog cultured hepatocytes.

The biotransformation of TNP-470 [O-(chloroacetylcarbamoyl)fumagillol; AGM 1470], a potent in vitro inhibitor of angiogenesis, was investigated in primary cultured hepatocytes isolated from different species, including monkey, dog, and rat, as well as in microsomal fractions of various monkey tissues. Previous metabolic studies by our group using human hepatocytes in primary culture demonstrated that TNP-470 was primarily metabolized to M-IV through an ester cleavage, with subsequent conversion of M-IV to M-II by microsomal epoxide hydrolase. Additional studies using monkey liver microsomes demonstrated that M-II was then glucuronidated by uridine-5'-diphosphoglucuronyl transferase, leading to the formation of M-III.

Cyclic GMP-dependent protein kinase is required for thrombospondin and tenascin mediated focal adhesion disassembly.

Focal adhesions are specialized regions of cell membranes that are foci for the transmission of signals between the outside and the inside of the cell. Intracellular signaling events are important in the organization and stability of these structures. In previous work, we showed that the counter-adhesive extracellular matrix proteins, thrombospondin, tenascin, and SPARC, induce the disassembly of focal adhesion plaques and we identified the active regions of these proteins.

Identification of transgenic mice by PCR analysis of saliva.

As an alternative to surgically obtaining samples (e.g., tail or tissue biopsy, toe dock, or blood sampling) from weanling mice to screen for transgene integration or other genetic monitoring procedures, we offer a simpler, nonsurgical method.

Evidence that embryonic kidney cells expressing flk-1 are intrinsic, vasculogenic angioblasts.

Renal glomerular capillary tufts have been believed to arise from angiogenic ingrowth of extrinsic vessels. We found, however, that when embryonic day 12 (E12) mouse kidneys were maintained in culture for 6 days and then grafted into anterior eye chambers of adult transgenic ROSA26 host mice (which carry the beta-galactosidase transgene), glomerular endothelial cells within the grafts were predominantly of intrinsic, kidney origin. To identify potential endothelial precursors, we immunolabled kidneys with antibodies against the vascular endothelial growth factor receptor, flk-1.

Prepubertal genistein exposure suppresses mammary cancer and enhances gland differentiation in rats.

Genistein, a component of soy, was administered to prepubertal female Sprague-Dawley CD rats and investigated for chemoprevention against mammary cancer. Genistein, at 500 microgram/g body wt or an equivalent volume of the vehicle, dimethylsulfoxide (DMSO), was injected (s.c.