Prenatal hypoxia leads to increased muscle sympathetic nerve activity, sympathetic hyperinnervation, premature blunting of NPY signalling and hypertension in adult life

Adverse conditions prenatally increase the risk of cardiovascular disease, including hypertension. Chronic hypoxia in utero (CHU) causes endothelial dysfunction, but whether sympathetic vasoconstrictor nerve functioning is altered is unknown. We, therefore, compared in male CHU and control (N) rats muscle sympathetic nerve activity, vascular sympathetic innervation density, and mechanisms of sympathetic vasoconstriction. In young (Y)-CHU and Y-N rats (≈3 months), baseline arterial blood pressure was similar. However, tonic muscle sympathetic nerve activity recorded focally from arterial vessels of spinotrapezius muscle had higher mean frequency in Y-CHU than in Y-N rats (0.56±0.075 versus 0.33±0.036 Hz), and the proportions of single units with high instantaneous frequencies (1–5 and 6–10 Hz) being greater in Y-CHU rats. Sympathetic innervation density of tibial arteries was ≈50% greater in Y-CHU than in Y-N rats. Increases in femoral vascular resistance evoked by sympathetic stimulation at low frequency (2 Hz for 2 minutes) and bursts at 20 Hz were substantially smaller in Y-CHU than in Y-N rats. In Y-N only, the neuropeptide Y Y1-receptor antagonist BIBP3226 attenuated these responses. By contrast, baseline arterial blood pressure was higher in middle-aged (M)-CHU than in M-N rats (≈9 months; 139±3 versus 126±3 mmHg, respectively). BIBP3226 had no effect on femoral vascular resistance increases evoked by 2 Hz or 20 Hz bursts in M-N or M-CHU rats. These results indicate that fetal programming induced by prenatal hypoxia causes an increase in centrally generated muscle sympathetic nerve activity in youth and hypertension by middle age. This is associated with blunting of sympathetically evoked vasoconstriction and its neuropeptide Y component that may reflect premature vascular aging and contribute to increased risk of cardiovascular disease

Electrical conduction and rheological behaviour of composites of poly(epsilon-caprolactone) and MWCNTs

Two mechanisms of conduction were identified from temperature dependent (120 K-340 K) DC electrical resistivity measurements of composites of poly(c-caprolactone) (PCL) and multi-walled carbon nanotubes (MWCNTs). Activation of variable range hopping (VRH) occurred at lower temperatures than that for temperature fluctuation induced tunneling (TFIT). Experimental data was in good agreement with the VRH model in contrast to the TFIT model, where broadening of tunnel junctions and increasing electrical resistivity at T > T-g is a consequence of a large difference in the coefficients of thermal expansion of PCL and MWCNTs. A numerical model was developed to explain this behavior accounting for a thermal expansion effect by supposing the large increase in electrical resistivity corresponds to the larger relative deformation due to thermal expansion associated with disintegration of the conductive MWCNT network. MWCNTs had a significant nucleating effect on PCL resulting in increased PCL crystallinity and an electrically insulating layer between MWCNTs. The onset of rheological percolation at similar to 0.18 vol% MWCNTs was clearly evident as storage modulus, G' and complex viscosity, vertical bar eta*vertical bar increased by several orders of magnitude. From Cole-Cole and Van Gurp-Palmen plots, and extraction of crossover points (G(c)) from overlaying plots of G' and G '' as a function of frequency, the onset of rheological percolation at 0.18 vol% MWCNTs was confirmed, a similar MWCNT loading to that determined for electrical percolation. 

Neuromusculature of Gyrodactylus rysavyi, a monogenean gill and skin parasite of the catfish Clarias gariepinus

Phalloidin fluorescence technique, enzyme cytochemistry and immunocytochemistry in conjunction with confocal scanning laser microscopy were used for the first time to describe the nervous and muscle systems of the viviparous monogenean parasite, Gyrodactylus rysavyi inhabiting the gills and skin of the Nile catfish Clarias gariepinus. The body wall muscles are composed of an outer layer of circular fibres, an intermediate layer of paired longitudinal fibres and an inner layer of well-spaced bands of diagonal fibres arranged in two crossed directions. The musculature of the pharynx, intestine, reproductive tract and the most prominent muscles of the haptor were also described. Two characteristic muscular pads were found lying in the anterior region of the haptor in close contact with the hamuli. To each one of these pads, a group of ventral extrinsic muscles was connected. The role of this ventral extrinsic muscle in the body movement was discussed. The mechanism operating the marginal hooklets was also discussed. The central nervous system (CNS) consists of paired cerebral ganglia from which three pairs of longitudinal ventral, lateral and dorsal nerve cords arise. The nerve cords are connected at intervals by many transverse connectives. The CNS is better developed ventrally than dorsally or laterally and it has the highest reactivity for all neuroactive substances examined. Both the central and the peripheral nervous system (PNS) are bilaterally symmetrical. Structural and functional correlates of the neuromusculature of the pharynx, haptor and reproductive tracts were explained. The results implicated acetylcholine, FMRFamide-related peptides (FaRPs) and serotonin in sensory and motor function. The results were compared with those of the monogeneans Macrogyrodactylus clarii and M. congolensis inhabiting the gills and skin respectively of the same host fish C. gariepinus.

Neuromusculature of Macrogyrodactylus congolensis, a monogenean skin parasite of the Nile catfish Clarias gariepinus

Phalloidin fluorescence technique, enzyme cytochemistry and immunocytochemistry, in conjunction with confocal scanning laser microscopy, were used to describe the neuromusculature of the monogenean skin parasite Macrogyrodactylus congolensis from the Nile catfish Clarias gariepinus. The body wall muscles are composed of an outer layer of compactly arranged circular fibres, an intermediate layer of paired longitudinal fibres and an inner layer of well-spaced bands of diagonal fibres arranged in two crossed directions. The central nervous system consists of paired cerebral ganglia from which three pairs of longitudinal ventral, lateral and dorsal nerve cords arise. The nerve cords are connected at intervals by many transverse connectives. Both central and peripheral nervous systems are bilaterally symmetrical and better developed ventrally than laterally and dorsally. Structural and functional correlates of the neuromusculature of the pharynx, haptor and reproductive tracts were examined. Results implicate acetylcholine, FMRFamide-related peptides and serotonin in sensory and motor function. The results were compared with those of Macrogyrodactylus clarii, a gill parasite of the same host fish C. gariepinus.

Neuromusculature of Macrogyrodactylus clarii, a monogenean gill parasite of the Nile catfish Clarias gariepinus in Egypt

Phalloidin fluorescence technique, enzyme cytochemistry and immunocytochemistry in conjunction with confocal scanning laser microscopy have been used for the first time to describe the nervous and muscle systems of the viviparous monogenean gill parasite, Macrogyrodactylus clarii. The gross spatial arrangement of muscle and associated cholinergic, peptidergic and aminergic innervations has been examined. The central nervous system (CNS) consists of paired cerebral ganglia from which emanate three pairs of longitudinal ventral, lateral and dorsal nerve cords, connected at intervals by transverse connectives. The CNS is better developed ventrally than dorsally or laterally, and has the strongest reactivity for all neuroactive substances examined. Structural and functional correlates of the neuromusculature of the pharynx, haptor and reproductive tracts have been examined. Results implicate acetylcholine, FMRFamide-related peptides (FaRPs) and serotonin in sensory and motor function in this monogenean, although confirmatory physiological data are obviously required.

Parasite neuropeptide biology:Seeding rational drug target selection?

The rationale for identifying drug targets within helminth neuromuscular signalling systems is based on the premise that adequate nerve and muscle function is essential for many of the key behavioural determinants of helminth parasitism, including sensory perception/host location, invasion, locomotion/orientation, attachment, feeding and reproduction. This premise is validated by the tendency of current anthelmintics to act on classical neurotransmitter-gated ion channels present on helminth nerve and/or muscle, yielding therapeutic endpoints associated with paralysis and/or death. Supplementary to classical neurotransmitters, helminth nervous systems are peptide-rich and encompass associated biosynthetic and signal transduction components - putative drug targets that remain to be exploited by anthelmintic chemotherapy. At this time, no neuropeptide system-targeting lead compounds have been reported, and given that our basic knowledge of neuropeptide biology in parasitic helminths remains inadequate, the short-term prospects for such drugs remain poor. Here, we review current knowledge of neuropeptide signalling in Nematoda and Platyhelminthes, and highlight a suite of 19 protein families that yield deleterious phenotypes in helminth reverse genetics screens. We suggest that orthologues of some of these peptidergic signalling components represent appealing therapeutic targets in parasitic helminths.