Biodistribution of Infused Human Umbilical Cord Blood Cells in Alzheimer's Disease-Like Murine Model.

Human umbilical cord blood cells (HUCBCs), a prolific source of non-embryonic or adult stem cells, have emerged as effective and relatively safe immunomodulators and neuroprotectors, reducing behavioral impairment in animal models of Alzheimer's disease (AD), Parkinson's disease, amyotrophic lateral sclerosis, traumatic brain injury, spinal cord injury, and stroke. In this report, we followed the bioavailability of HUCBCs in AD-like transgenic PSAPP mice and nontransgenic Sprague-Dawley rats. HUCBCs were injected into tail veins of mice or rats at a single dose of 1 × 10(6) or 2.

Elevated [Ca2+]i levels occur with decreased calpain activity in aged fibroblasts and their reversal by energy-rich compounds: new paradigm for Alzheimer's disease prevention.

Elevated intracellular Ca2+ levels in the aging brain are widely thought to hyperactivate Ca2+ signaling and Ca2+-dependent enzymes, leading to neuronal death through an excitatory mechanism in Alzheimer's disease (AD). This "Ca2+ overload" hypothesis has been questioned by our theoretical analyses. To better understand the relationship between the "level" and functionality of Ca2+ in aging, in this study we simultaneously measured intracellular Ca2+ transients and calpain activity in cultured human fibroblasts.

High-energy compounds promote physiological processing of Alzheimer's amyloid-β precursor protein and boost cell survival in culture.

Physiological or α-processing of amyloid-β precursor protein (APP) prevents the formation of Aβ, which is deposited in the aging brain and may contribute to Alzheimer's disease. As such, drugs promoting this pathway could be useful for prevention of the disease. Along this line, we searched through a number of substances and unexpectedly found that a group of high-energy compounds (HECs), namely ATP, phosphocreatine, and acetyl coenzyme A, potently increased APP α-processing in cultured SH-SY5Y cells, whereas their cognate counterparts, i.

Evidence supporting the role of calpain in the α-processing of amyloid-β precursor protein.

Amyloid plaques are a hallmark of the aging and senile dementia brains, yet their mechanism of origins has remained elusive. A central issue is the regulatory mechanism and identity of α-secretase, a protease responsible for α-processing of amyloid-β precursor protein (APP). A remarkable feature of this enzyme is its high sensitivity to a wide range of cellular stimulators, many of which are agonists for Ca(2+) signaling.

What to look for beyond "pathogenic" factors in senile dementia? A functional deficiency of Ca²⁺ signaling.

We have contended that senile conditions--illnesses after age 60 and fully age-penetrating, such as tooth, hearing or memory loss--are not distinct "diseases" in medical nature, because they are caused by aging. Since the pace of aging varies among individuals and is much influenced by risk factors, senile conditions will only affect some but not all elderly. However, perhaps due to its unusually heavy burdens and tremendous social pressures, senile dementia (SD) has been singled out from other senile conditions and redefined as a curable "disease" (Alzheimer's).

Mechanisms of vasoactive intestinal peptide-elicited coronary vasodilation in the isolated perfused rat heart.

The present study investigated the potential role of vasoactive intestinal peptide (VIP) receptors, VPAC1 and VPAC2, in VIP-elicited coronary vasodilation of the isolated perfused rat heart. Additional studies determined the role of ATP-sensitive (K(ATP)) and voltage-gated K(+) (K(V)) channels in the VIP-elicited coronary vasodilation. Both the selective VPAC1 agonist, K15,R16,L27VIPl-7GRF8-27, and the selective VPAC2 agonist, RO25-1553, decreased coronary vascular resistance (CVR) in a dose-dependent manner, with EC(50) values of 1.

Coronary vascular effects of vasoactive intestinal peptide in the isolated perfused rat heart.

The potency and mechanism of action of vasoactive intestinal peptide (VIP) for producing coronary vasodilation was investigated in the isolated perfused heart of the rat. VIP reduced coronary vascular resistance in a dose-dependent manner, starting at 1 x 10(-10) M, and maximally reduced coronary vascular resistance by 49% at 1 x 10(-8) M. The potency of VIP for reducing coronary vascular resistance (EC50=3.

Phosphodiesterase 3 activity is reduced in dog lung following pacing-induced heart failure.

We hypothesized that decreases in expression and/or activity of cAMP-specific phosphodiesterases (PDE) contribute to protective adaptations observed in lung after heart failure. In this study, we compared PDE activity in lung parenchyma isolated from control dogs and those paced to heart failure by assaying cyclic nucleotide hydrolysis in fractions of homogenate supernatant eluted from DEAE-Trisacryl columns. Cyclic nucleotide hydrolysis due to PDE3, PDE4, and PDE5 isoforms was predominant in both control and paced groups.