Insulin Therapy is Associated With Increased Myocardial Interstitial Fibrosis and Cardiomyocyte Apoptosis in a Rodent Model of Experimental Diabetes.

The incidence of diabetes mellitus (DM) is rising. DM is a risk factor for developing left ventricular (LV) dysfunction and adverse cardiovascular outcomes. Insulin, commonly used to treat DM, is associated with further worsening of such outcomes.

Membrane lipid peroxidation in neurodegeneration: Role of thrombin and proteinase-activated receptor-1.

Thrombin and membrane lipid peroxidation (MLP) have been implicated in various central nervous system (CNS) disorders from CNS trauma to stroke, Alzheimer's (AD) and Parkinson's (PD) diseases. Because thrombin also induces MLP in platelets and its involvement in neurodegenerative diseases we hypothesized that its deleterious effects might, in part, involve formation of MLP in neuronal cells. We previously showed that thrombin induced caspase-3 mediated apoptosis in motor neurons, via a proteinase-activated receptor (PAR1).

The effect of the brain-type natriuretic peptide single-nucleotide polymorphism rs198389 on test characteristics of common assays.

Objective: To assess in a US general adult population the effect of the functional single-nucleotide polymorphism rs198389 in the promoter region of the gene of brain-type natriuretic peptide (BNP) on 3 commonly used BNP assays, clinical phenotype, disease prevalence, overall survival, and diagnostic test characteristics of BNP as a biomarker.

Patients And Methods: We genotyped for rs198389 in a random sample of the general population (aged ≥ 45 years; n = 1970; enrolled between June 1, 1997, and September 30, 2000) from Olmsted County, Minnesota. Patients were characterized biochemically, clinically, echocardiographically, and regarding BNP molecular forms (2 assays for BNP and 1 assay for amino-terminal proBNP).

In vivo biodegradation and biocompatibility of PEG/sebacic acid-based hydrogels using a cage implant system.

Comprehensive in vivo biodegradability and biocompatibility of unmodified and Arg-Gly-Asp (RGD) peptide-modified PEG/sebacic acid-based hydrogels were evaluated and compared to the control material poly(lactide-co-glycolide) (PLGA) using a cage implantation system, as well as direct subcutaneous implantation for up to 12 weeks. The total weight loss after 12 weeks of implantation for unmodified PEGSDA and RGD-modified PEGSDA in the cage was approximately 42% and 52%, respectively, with no statistical difference (p > 0.05).

Importance of the vasculature in cyst formation after spinal cord injury.

Object: Glial scar and cystic formation greatly contribute to the inhibition of axonal regeneration after spinal cord injury (SCI). Attempts to promote axonal regeneration are extremely challenging in this type of hostile environment. The objective of this study was to examine the surgical methods that may be used to assess the factors that influence the level of scar and cystic formation in SCI.

Relationship between scaffold channel diameter and number of regenerating axons in the transected rat spinal cord.

Regeneration of endogenous axons through a Schwann cell (SC)-seeded scaffold implant has been demonstrated in the transected rat spinal cord. The formation of a cellular lining in the scaffold channel may limit the degree of axonal regeneration. Spinal cords of adult rats were transected and implanted with the SC-loaded polylactic co-glycollic acid (PLGA) scaffold implants containing seven parallel-aligned channels, either 450mum (n=19) or 660microm in diameter (n=14).

Rigid fixation of the spinal column improves scaffold alignment and prevents scoliosis in the transected rat spinal cord.

Study Design: A controlled study to evaluate a new technique for spinal rod fixation after spinal cord injury in rats. Alignment of implanted tissue-engineered scaffolds was assessed radiographically and by magnetic resonance imaging.

Objective: To evaluate the stability of implanted scaffolds and the extent of kyphoscoliotic deformities after spinal fixation.

Neuroprotective effects of caspase-3 inhibition on functional recovery and tissue sparing after acute spinal cord injury.

Study Design: We used gene microarrays and found that caspase-related death genes were upregulated. We tested caspase inhibition and evaluated its effect on the spinal cord after traumatic injury.

Objective: The logical extension of previous studies was to determine whether downstream CASP genes might also be involved and whether inhibition might prevent injury-induced cell death.

Dynamic role of kallikrein 6 in traumatic spinal cord injury.

Kallikrein 6 (K6) is a member of the kallikrein gene family that comprises 15 structurally and functionally related serine proteases. In prior studies we showed that, while this trypsin-like enzyme is preferentially expressed in neurons and oligodendroglia of the adult central nervous system (CNS), it is up-regulated at sites of injury due to expression by infiltrating immune and resident CNS cells. Given this background we hypothesized that K6 is a key contributor to the pathophysiology of traumatic spinal cord injury (SCI), influencing neural repair and regeneration.

Minocycline neuroprotects, reduces microgliosis, and inhibits caspase protease expression early after spinal cord injury.

Minocycline, a clinically used tetracycline for over 40 years, crosses the blood-brain barrier and prevents caspase up-regulation. It reduces apoptosis in mouse models of Huntington's disease and familial amyotrophic lateral sclerosis (ALS) and is in clinical trial for sporadic ALS. Because apoptosis also occurs after brain and spinal cord (SCI) injury, its prevention may be useful in improving recovery.

Synthesis, material properties, and biocompatibility of a novel self-cross-linkable poly(caprolactone fumarate) as an injectable tissue engineering scaffold.

A novel self-cross-linkable and biodegradable macromer, poly(caprolactone fumarate) (PCLF), has been developed for guided bone regeneration. This macromer is a copolymer of fumaryl chloride, which contains double bonds for in-situ cross-linking, and poly(epsilon-caprolactone), which has a flexible chain to facilitate self-cross-linkability. PCLF was characterized with Fourier transform infrared spectroscopy, 1H and 13C nuclear magnetic resonance spectroscopy, and gel permeation chromatography.

Multiple-channel scaffolds to promote spinal cord axon regeneration.

As molecular, cellular, and tissue-level treatments for spinal cord injury are discovered, it is likely that combinations of such treatments will be necessary to elicit functional recovery in animal models or patients. We describe multiple-channel, biodegradable scaffolds that serve as the basis for a model to investigate simultaneously the effects on axon regeneration of scaffold architecture, transplanted cells, and locally delivered molecular agents. Poly(lactic-co-glycolic acid) (PLGA) with copolymer ratio 85:15 was used for these initial experiments.

Neuroprotective effects of recombinant thrombomodulin in controlled contusion spinal cord injury implicates thrombin signaling.

Although the central nervous system (CNS) of mammals has had poor prospects for regeneration, recent studies suggest this might improve from blocking "secondary cell loss" or apoptosis. In this regard, intravenous activated protein C (aPC) improved neurologic outcomes in a rat compression spinal cord injury (SCI) model. Protein C activation occurs when the serine protease thrombin binds to the cell surface proteoglycan thrombomodulin (TM) forming a complex that halts coagulation.

Participation of protease-activated receptor-1 in thrombin-induced microglial activation.

Activation of microglia, the resident macrophages in the CNS, plays a significant role in neuronal death or degeneration in a broad spectrum of CNS disorders. Recent studies indicate that nanomolar concentrations of the serine protease, thrombin, can activate microglia in culture. However, in contrast to other neural cells responsive to thrombin, the participation of novel protease-activated receptors (PARs), such as the prototypic thrombin receptor PAR1, in thrombin-induced microglial activation was cast in doubt.

Rapid upregulation of caspase-3 in rat spinal cord after injury: mRNA, protein, and cellular localization correlates with apoptotic cell death.

Although the precise mechanisms explaining loss of, and failure to regain, function after spinal cord injury are unknown, there is increasing interest in the role of "secondary cell death." One prevalent theme in cell loss in other regions of the CNS involves apoptosis executed by the intracellular caspase proteases. A recent study demonstrated that spinal cord injury rapidly increased the activation of caspase-3.

The effect of a low essential fatty acid diet on hibernation in marmots.

We investigated the effect of an essential fatty acid (EFA)-deficient diet on hibernation patterns in yellow-bellied marmots (Marmota flaviventris). Fatty acid (FA) analysis of white adipose tissue (WAT) from animals maintained for 2 mo on the EFA-deficient diet suggested that little or no EFAs were present in the gonadal or omental fat depots. Hibernation about lengths of the EFA-deficient animals were significantly shorter (P < 0.

Lack of response of bone mineralization of chicks fed egg yolks from hens on dietary 1,25 dihydroxycholecalciferol.

White Leghorn hens, age 34 wk, fed 0 to 3 micrograms/kg of 1,25 dihydroxycholecalciferol (1,25(OH)2D3) as the only source of dietary vitamin D3 with 2.5 or 3.5% calcium failed to achieve normal embryonic survival and hatchability of their fertile eggs.

Excessive cholecalciferol in a layers diet: decline in some aspects of reproductive performance and increased bone mineralisation of progeny.

Feeding hens a diet containing 5,000 micrograms (200,000 ICU)/kg of cholecalciferol for four 28-d periods had no adverse effect on hen-day egg production or hatchability. Egg weight, shell quality, food consumption and fertility were significantly decreased in hens fed 5,000 micrograms/kg. of cholecalciferol compared with those fed 24 micrograms (960 ICU) cholecalciferol/kg diet.

Sensitivity of chick embryo to various solvents used in egg injection studies.

Two experiments were conducted to study the sensitivity of developing chicken embryos to various solvents used as vehicles and their effect on hatchability. No significant differences on embryonic mortality were observed between the sham-injected control and corn oil-injected groups. Acetone, ethylene glycol, and ethanol (0.

Support of embryonic chick survival by vitamin D metabolites.

The provision of 1,25-dihydroxyvitamin D3 as the only source of dietary vitamin D3 to laying hens failed to support normal embryonic development in their fertile eggs. Significant (P less than .001) improvement in embryonic survival to hatching in these eggs resulted from injections of 1,25-dihydroxyvitamin D3, 24,25-dihydroxyvitamin D3, 25-hydroxyvitamin D3, or 24,24-difluoro-25-hydroxyvitamin D3 prior to incubation.

Live monovular twin chicks from a single yolk chicken egg.

Monovular fully formed twin chicks were recorded from a single-yolked egg. The chicks were attached to a common umbilical cord. One of the twin chicks survived for 10 weeks and the other for 4 days.

Effect of added methionine and lysine on the performance of chicks fed different alfalfa protein concentrates.

Experiments were conducted to determine the limiting amino acids in chick diets containing 40% spray-dried heat coagulated alfalfa protein concentrate (APC) and 40% spray-dried fermented alfalfa protein concentrate (FAPC). Significant improvements in chick gains were observed when methionine (met) was supplemented to the 40% APC (82 vs. 119 g) and 40% FAPC (72 vs.

Studies on the utilization of leaf protein concentrates as a protein source in poultry nutrition.

Spray-dried leaf protein concentrate prepared from Red Clover and alfalfa with low or high saponin content were evaluated by studying their effect on growth and feed efficiency of broiler chicks at the 40% level. Excellent growth and feed efficiency were recorded when 40% of low saponin alfalfa protein concentrate (APC) prepared from fresh alfalfa was incorporated in the diets. Saponin in APC estimated by hemolysis test was an important factor affecting the growth, feed efficiency, and mortality of chicks.

24-hydroxylation of 25-hydroxyvitamin D3: is it required for embryonic development in chicks?

As shown previously, laying hens given 1,25-dihydroxyvitamin D3 as their sole source of vitamin D produce fertile eggs having normal shells, but only 35 to 55 percent of the embryos are normal. Giving these hens additional 25-hydroxyvitamin D3, 24,25-dihydroxyvitamin D3, or 24,24-difluoro-25-hydroxyvitamin D3 at 1.25 nanomoles per day resulted in 90 to 100 percent normal embryos, and hence, hatchability.