The convergence in distribution of some simple epidemics

A group of n susceptible individuals exposed to a contagious disease isconsidered. It is assumed that at each point in time one or more susceptible individuals can contract the disease. The progress of this simple batch epidemic is modeled by a stochastic process X_n(t), t[0, ∞), representing the number of infectiveindividuals at time t. In this paper our analysis is restricted to simple batch epidemics with transition rates given by [α²X_n(t){n −X_n(t) +X_n(0)}]^1/2, t[0, ∞), α(0, ∞). This class of simple batch epidemics generalizes a model used and motivated by McNeil (1972) to describe simple epidemic situations. It is shown for this class of simple batch epidemics, that X_n(t), with suitable standardization, converges in distribution as n→∞ to a normal random variable for all t(0, t₀), and t₀ is evaluated.     

Human and porcine early kidney precursors as a new source for transplantation

Kidney transplantation has been one of the major medical advances of the past 30 years. However, tissue availability remains a major obstacle. This can potentially be overcome by the use of undifferentiated or partially developed kidney precursor cells derived from early embryos and fetal tissue. Here, transplantation in mice reveals the earliest gestational time point at which kidney precursor cells, of both human and pig origin, differentiate into functional nephrons and not into other, non-renal professional cell types. Moreover, successful organogenesis is achieved when using the early kidney precursors, but not later-gestation kidneys. The formed, miniature kidneys are functional as evidenced by the dilute urine they produce. In addition, decreased immunogenicity of the transplants of early human and pig kidney precursors compared with adult kidney transplants is demonstrated in vivo. Our data pinpoint a window of human and pig kidney organogenesis that may be optimal for transplantation in humans.     

Penetrability of orally toxic protein from cobra venom through the gut of a blowfly

The oral toxicity of a radioiodinated toxic polypeptide isolated from a cobra snake venom as assayed by Sarcophaga falculata blowflies coupled with assays on competitive displacement have indicated that: (a) During 3–4 h 8% of the orally active toxin is able to pass through the digestive system of the fly; (b) the orally active toxin after passing the gut binds to body tissues. The strong affinity of the toxin to tissue membranes explains its absence in the insect's hemolymph following oral applications as well as injection.The removal of traces of phospholipase A, which is extremely toxic, by injection of the orally active toxin has significantly lowered its injection toxicity without affecting its oral toxicity, thus indicating the absence of any interaction with phospholipases in oral toxicity. This conclusion was supported by additional experimentation.     

Aldosterone up‐regulates 12‐ and 15‐lipoxygenase expression and LDL oxidation in human vascular smooth muscle cells

Several lines of evidence suggest that aldosterone excess may have detrimental effects in the cardiovascular system, independent of its interaction with the renal epithelial cells. Here we examined the possibility that aldosterone modulates 12‐ and/or 15‐lipoxygenase (LO) expression/activity in human vascular smooth muscle cells (VSMC), in vitro, thereby potentially contributing to both vascular reactivity and atherogenesis. Following 24 h treatment of VSMC with aldosterone (1 nmol/L), there was a ～2‐fold increase in the generation rate of 12 hydroxyeicosatetraenoic acid (12‐HETE), 70% increase in platelet type 12‐LO mRNA expression (P < 0.001) along with a ～3‐fold increase in 12‐LO protein expression, which were blocked by the mineralocorticoid receptor (MR) antagonists spironolactone (100 nmol/L) and eplerelone (100 nmol/ml). Additionally, aldosterone (1 nmol/L; 24 h) increased the production of 15‐HETE (50%; P < 0.001) and the expression of 15‐LO type 2 mRNA (50%; P < 0.05) (in VSMC). Aldosterone also increased the 12‐ and 15‐LO type 2 mRNA expression in a line of human aortic smooth muscle cells (T/G HA‐VSMC) (60% and 50%, respectively). Aldosterone‐induced 12‐ and 15‐LO type 2 mRNA expressions were blocked by the EGF‐receptor antagonist AG 1478 and by the MAPK‐kinase inhibitor UO126. Aldosterone‐treated VSMC also showed increased LDL oxidation, (～2‐fold; P < 0.001), which was blocked by spironolactone. In conclusion, aldosterone increased 12‐ and 15‐LO expression in human VSMC, in association with increased 12‐ and 15‐HETE generation and enhanced LDL oxidation and may directly augment VSMC contractility, hypertrophy, and migration through 12‐HETE and promote LDL oxidation via the pro‐oxidative properties of these enzymes. J. Cell. Biochem. 108: 1203–1210, 2009. © 2009 Wiley‐Liss, Inc.     

The Influence of Radiographic Phenotype and Smoking Status on Peripheral Blood Biomarker Patterns in Chronic Obstructive Pulmonary Disease

Background

Chronic obstructive pulmonary disease (COPD) is characterized by both airway remodeling and parenchymal destruction. The identification of unique biomarker patterns associated with airway dominant versus parenchymal dominant patterns would support the existence of unique phenotypes representing independent biologic processes. A cross-sectional study was performed to examine the association of serum biomarkers with radiographic airway and parenchymal phenotypes of COPD.

Methodology/Principal Findings

Serum from 234 subjects enrolled in a CT screening cohort was analyzed for 33 cytokines and growth factors using a multiplex protein array. The association of serum markers with forced expiratory volume in one second percent predicted (FEV1%) and quantitative CT measurements of airway thickening and emphysema was assessed with and without stratification for current smoking status. Significant associations were found with several serum inflammatory proteins and measurements of FEV1%, airway thickening, and parenchymal emphysema independent of smoking status. The association of select analytes with airway thickening and emphysema was independent of FEV1%. Furthermore, the relationship between other inflammatory markers and measurements of physiologic obstruction or airway thickening was dependent on current smoking status.

Conclusions/Significance

Airway and parenchymal phenotypes of COPD are associated with unique systemic serum biomarker profiles. Serum biomarker patterns may provide a more precise classification of the COPD syndrome, provide insights into disease pathogenesis and identify targets for novel patient-specific biological therapies.     

Estrogen-like activity of licorice root constituents: glabridin and glabrene, in vascular tissues in vitro and in vivo

Post-menopausal women have higher incidence of heart diseases compared to pre-menopausal women, suggesting a protective role for estrogen. The recently Women's Health Initiative (WHI) randomized controlled trial concluded that the overall heart risk exceeded benefits from use of combined estrogen and progestin as hormone replacement therapy for an average of five years among healthy postmenopausal US women. Therefore, there is an urgent need for new agents with tissue-selective activity with no deleterious effects. In the present study, we tested the effects on vascular tissues in vitro and in vivo of two natural compounds derived from licorice root: glabridin, the major isoflavan, and glabrene, an isoflavene, both demonstrated estrogen-like activities. Similar to estradiol-17beta (E2), glabridin (gla) stimulated DNA synthesis in human endothelial cells (ECV-304; E304) and had a bi-phasic effect on proliferation of human vascular smooth muscle cells (VSMC). Raloxifene inhibited gla as well as E2 activities. In animal studies, both intact females or after ovariectomy, gla similar to E2 stimulated the specific activity of creatine kinase (CK) in aorta (Ao) and in left ventricle of the heart (Lv). Glabrene (glb), on the other hand, had only the stimulatory effect on DNA synthesis in vascular cells, with no inhibition by raloxifene, suggesting a different mechanism of action. To further elucidate the mechanism of action of glb, cells were pre-incubated with glb and then exposed to either E2 or to gla; the DNA stimulation at low doses was unchanged but there was abolishment of the inhibition of VSMC cell proliferation at high doses as well as inhibition of CK stimulation by both E2 and by gla. We conclude that glb behaved differently than E2 or gla, but similarly to raloxifene, being a partial agonist/antagonist of E2. Glabridin, on the other hand, demonstrated only estrogenic activity. Therefore, we suggest the use of glb with or without E2 as a new agent for modulation of vascular injury and atherogenesis for the prevention of cardiovascular diseases in post-menopausal women.