Quantitative demonstration of the existence of two isoforms of canine hepcidin in the serum & urine of dogs.

Hepcidin-25 is the key peptide hormone controlling vertebrate iron metabolism. However, in the last twenty years there was some disagreement in the literature over the structure of this compound. The aim of this research was to study whether more than one isoform of canine hepcidin-25 exists. For the purpose of comparison serum concentrations of hepcidin-25 were determined in the samples of 47 dogs sick with acute/chronic inflammation too. The study demonstrated that two isoforms of canine hepcidin-25 exist. A statistical correlation may indicate that both molecules are synthesised by dogs together. No statistically significant correlations were found between the measured concentrations of the two canine hepcidin-25 isoforms and the measured serum iron parameters in the sampled dogs, irrespective of the measurements were made in serum or urine. The mean urinary total hepcidin-25/creatinine ratio in healthy dogs was 1.08 ± 0.10. The mean serum total hepcidin-25 concentration was 79.8 ± 4.9 ng/ml, about 65% of which was the 25ß version. The presence of inflammation results in a statistically significant increase in the serum concentration of both hepcidin varieties. The role and fate of the two molecules may need to be researched further to provide better understanding of their relation.

Pairwise approximation for SIR-type network epidemics with non-Markovian recovery.

We present the generalized mean-field and pairwise models for non-Markovian epidemics on networks with arbitrary recovery time distributions. First we consider a hyperbolic partial differential equation (PDE) system, where the population of infective nodes and links are structured by age since infection. We show that the PDE system can be reduced to a system of integro-differential equations, which is analysed analytically and numerically. We investigate the asymptotic behaviour of the generalized model and provide an implicit analytical expression involving the final epidemic size and pairwise reproduction number. As an illustration of the applicability of the general model, we recover known results for the exponentially distributed and fixed recovery time cases. For gamma- and uniformly distributed infectious periods, new pairwise models are derived. Theoretical findings are confirmed by comparing results from the new pairwise model and explicit stochastic network simulation. A major benefit of the generalized pairwise model lies in approximating the time evolution of the epidemic.

Effects of brain natriuretic peptide on effects of morphine in mice.

Brain natriuretic peptide (BNP) is a member of the natriuretic peptide family. The effects of intracerebroventricularly administered BNP (in 0.002-200 ng doses) on the analgesic, tolerance-inducing and dependence-inducing actions of morphine were investigated in adult male CFLP mice. Graded doses of BNP centrally did not affect pain sensitivity itself in a tail-flick test. However, different doses of BNP depressed the acute nociceptive effect of a single subcutaneous dose of morphine (5 mg/kg), and BNP attenuated the development of acute and chronic tolerance to morphine. Withdrawal signs were studied by injecting naloxone (1 mg/kg s.c.). There was no significant difference in symptoms between the tolerant group and animals treated with BNP. The data obtained indicate that BNP can modify the analgesic action of morphine.

C-type natriuretic peptide can modify the acute and chronic effects of morphine.

Different doses (0.2-200 ng) of C-type natriuretic peptide (CNP) were administered into the lateral brain ventricle, and morphine (5 mg/kg) was injected subcutaneously. The analgesic effect was measured in a tail-flick test, in CFLP mice. CNP administered centrally did not itself affect pain sensitivity, but it depressed the acute antinociceptive effect of morphine 30 min after icv (0.2, 2 or 20 ng) CNP administration and the 2 and 20 ng doses also decreased this action after 60 min. CNP in a 0.2 or 200 ng dose blocked the development of acute tolerance to morphine after 30 min, as did the 200 ng dose at 60 min. CNP in a 0.2 ng dose blocked the development of chronic tolerance to morphine after 30 min, but there was no effect at 60 min. Morphine withdrawal signs were studied by injecting naloxone (1 mg/kg sc). There was no significant difference in symptoms between the tolerant group and the animals treated with CNP.