Influence of CGRP (8-37), but not adrenomedullin (22-52), on the haemodynamic responses to lipopolysaccharide in conscious rats.

1. The functional involvement of the vasodilator peptides, adrenomedullin (ADM) and calcitonin gene-related peptide (CGRP), in the haemodynamic sequelae of continuous infusion of lipopolysaccharide (LPS) was assessed in conscious, male, Long Evans rats, by the use of peptide antagonists. 2. It was demonstrated that ADM (22-52) at a dose of 500 nmol kg-1 h-1 caused significant inhibition of the effects of ADM (1 nmol kg-1), without affecting responses to CGRP (0.1 or 1 nmol kg-1). 3. Even when the regional vasodilator responses to LPS infusion were enhanced (by pre-treatment with dexamethasone and the endothelin antagonist, SB 209670, or by pretreatment with SB 209670 and the AT1-receptor antagonist, losartan), ADM (22-52) had no significant cardiovascular effects. In contrast, the CGRP1-receptor antagonist, CGRP (8-37), caused small, but significant, inhibitions of the hypotensive and renal and mesenteric vasodilator effects of LPS, but only 6 h after onset of infusion in the presence of dexamethasone and SB 209670. 4. The results indicate that, in this model of endotoxaemia, the marked regional vasodilatations seen in the presence of dexamethasone and SB 209670 do not involve ADM, but do involve CGRP, albeit only to a small extent.     

Regional haemodynamic responses to infusion of lipopolysaccharide in conscious rats: effects of pre- or post-treatment with glibenclamide

1. To determine the putative contribution of K(ATP)-channels to the haemodynamic sequelae of endotoxaemia, three experiments were carried out in different groups of conscious, chronically-instrumented, unrestrained, male Long Evans rats. 2. In the first experiment, pretreatment with the K(ATP)-channel antagonist, glibenclamide, abolished the initial hypotension, but not the renal vasodilatation caused by LPS infusion. Subsequently, however, in the presence of glibenclamide and LPS there was a significant increase in mean arterial blood pressure, and a bradycardia, in contrast to the fall in mean arterial blood pressure and the tachycardia seen in the presence of vehicle and LPS. The pressor and bradycardic changes in the presence of glibenclamide and LPS were accompanied by significant reductions in hindquarters flow and vascular conductance, and these were significantly greater than those seen in the presence of vehicle and LPS, or glibenclamide and saline. 3. Administration of glibenclamide 6 h after the onset of saline and LPS infusion, or 6 h after the onset of saline and LPS infusion in the presence of the AT(1)-receptor antagonist, losartan, and the ET(A)-, ET(B)- receptor antagonist, SB 209670, in the absence or presence of dexamethasone, caused a significant increase in mean arterial blood pressure and reductions in renal, mesenteric and hindquarters conductances, although the latter was the only vascular bed in which there was a reduction in flow. 4. The results are consistent with a contribution from K(ATP)-channels to the vasodilatation caused by LPS, particularly in the hindquarters vascular bed.     

Cardiovascular responses to angiotensins I and II in normotensive and hypertensive rats; effects of NO synthase inhibition or ET receptor antagonism

1. We compared the cardiovascular responses to angiotensins (I and II), and any possible modulatory influences thereupon of nitric oxide (NO) or endothelin (ET) in conscious male, normotensive, Hannover Sprague-Dawley (SD) rats, and hypertensive, heterozygous ((mRen-2)27), transgenic (TG) rats. 2. The pressor effects of angiotensin I or of angiotensin II were not consistently different in SD and TG rats. The accompanying absolute reductions in renal and mesenteric vascular conductances were smaller in TG rats, but probably due to the baseline vasoconstriction in those animals. 3. Inhibition of NO synthase with L-NAME had no significant effects on the pressor responses to angiotensin I or angiotensin II in either SD or TG rats. L-NAME reduced the absolute, but not percentage, reductions in renal and mesenteric vascular conductances in response to angiotensin I and angiotensin II. L-NAME abolished the hindquarters vasodilator effects of angiotensin I and angiotensin II in both strains of rat. 4. ET receptor antagonism (with SB209670) had no significant influence on the pressor or renal or mesenteric vasoconstrictor effects of angiotensin II in SD rats. In TG rats, the pressor responses to angiotensin II were unaffected by SB209670; the accompanying falls in renal and mesenteric vascular conductances were enhanced in absolute, but not in percentage terms. 5. These results provide no evidence for a buffering action of NO, or a modulatory influence of ET, on the pressor or vasoconstrictor effects of angiotensin I and/or angiotensin II in SD rats. Furthermore, there is no evidence for an altered sensitivity to angiotensin I or angiotensin II, and no evidence for a differential modulatory influence of either NO or ET in TG, compared to SD, rats.     

Induction of LTD in the adult hippocampus by the synaptic activation of AMPA/kainate and metabotropic glutamate receptors

It has been suggested that the induction of long-term depression (LTD) may be developmentally regulated since LTD can be readily induced by LFS in slices from young but not adult animals. However, we have recently reported that paired pulse low frequency stimulation (PP-LFS) can reliably induce LTD in the CA1 region of adult hippocampal slices. We now describe the role of glutamate receptors in the induction of LTD in adult hippocampus. The induction of LTD was prevented by the combined application of AMPA/kainate and metabotropic glutamate (mGlu) receptor antagonists (CNQX and LY341495). However, LTD was not blocked by the co-application of NMDA and mGlu receptor antagonists nor by the co-application of NMDA and AMPA/kainate receptor antagonists. Taken together, the above results suggest that activation of either AMPA/kainate or mGlu receptors is sufficient to induce LTD. Therefore, these results suggest that PP-LFS can efficiently activate AMPA/kainate and mGlu receptors in order to induce long-lasting synaptic depression in the CA1 region of the adult hippocampus in vitro.     

Snail shape and growth rates: Evidence for plastic shell allometry in Littorina littorea

The periwinkle Littorina littorea exhibits morphological variation among southern New England populations that appear to be genetically continuous. In dense populations, individuals have relatively elongate shells in comparison to individuals in sparse populations, which have rounder, globose shells. We experimentally demonstrate that this shell variation is a function of snail growth rate. Rapidly growing snails develop thin, globose shells that accommodate more body mass than thicker, more elongate shells. The implications of these results are discussed in relation to interpreting morphological variation in extant gastropods and in the molluscan fossil record.     

Optimal detection of the alpha state in a model of the human electroencephalogram

A mole of the EEG with waxing, waning and blocking alpha rhythm is described. One parameter is time dependent and simulates the "physiological alpha state' of the EEG generating network. A theoretically optimal detector of this state appears to be prescribed by the model and the statistics of the alpha state parameter. It minimizes the expected false decision rate.     

Primary bone tumors. MR morphologic appearance correlated with pathologic examinations.

Eighty-three MR studies for primary bone tumors, performed with both spin echo and short time inversion recovery (STIR) sequences, were reviewed. Twenty-six patients underwent surgery within 10 days after MR imaging. Specimens were cut and directly compared with MR images. In the remainder, pathologic slides were compared in order to obtain a better understanding of MR pattern. All MR images were examined with a traditional morphologic approach and, upon comparison with surgical macroslides and with pathology samples, some MR distinctive patterns were identified: the bulky appearance of osteosarcoma surrounded by muscle edema, the multilobular high signal intensity (SI) chondroid lesions, the subtle infiltration of Ewing's sarcoma, rarely accompanied by muscle edema and prone to MR underestimation, the well defined "multiple shells" pattern of giant cell tumor, and the ill defined "storiform" appearance of malignant fibrous histocytoma are all typical MR features strictly corresponding to pathologic findings. The chondroid origin tumors may be identified based on the lobular high SI pattern whereas a benign fibrous lesion was the only one in this series to be distinguished relying on the SI. Peritumoral soft tissue edema was found by the STIR sequence only in malignant tumors (69%) of this series, and particularly in osteosarcoma (96%), chondrosarcoma (83%), and giant cell tumor (100%): this associate finding may further contribute to the diagnosis.     

Immune deviation and the hygiene hypothesis: A review of the epidemiological evidence

The epidemiological evidence for the proposal that early life immune deviation is the principal mechanism by which microbial agents prevent the development of atopy has been reviewed. Seven criteria are proposed which should ideally be fulfilled. The majority of studies only fulfill two or three criteria. For mycobacteria, measles and respiratory viruses there are studies that demonstrate a significant increase in atopy or allergic disease. Parasite infections, which provide a strong TH2 stimulus, are associated with reduced rather than enhanced allergen sensitization. The available epidemiological evidence does not provide support for a mechanism of early life immune deviation. The principal environmental influences on atopic disease are likely to occur throughout life and involve interactions between microbes and other non-infective and lifestyle factors.