Sex Disparities in Risk of Mortality Among Children With ESRD

1. Download high-res image (377KB)
2. Download full-size image

     

Calcitonin gene-related peptide: functional role in cerebrovascular regulation.

Distribution studies disclosed that all major cerebral arteries and cortical arterioles of the cat were invested with fine varicose nerve fibers that contained calcitonin gene-related peptide (CGRP)-like immunoreactivity; the trigeminal ganglia likewise contained CGRP immunoreactivity. Sequential immunostaining with antibodies to CGRP and to substance P (SP) revealed identical distributions of these two peptides in trigeminal ganglia and cerebrovascular nerve fibers, suggesting that CGRP and SP are colocalized in these nerves. CGRP completely disappeared from ipsilateral blood vessels after unilateral section of the trigeminal nerve. Exogenous CGRP was a potent relaxant of feline middle cerebral arteries in vitro (maximum relaxation, 10.5 +/- 1.5 mN; concentration eliciting half-maximal response, 9.6 +/- 1.3 nM). Perivascular microapplication of CGRP to individual cortical arterioles of chloralose-anesthetized cats provoked dose-dependent dilatations (maximum increase in diameter, 38 +/- 5%; concentration eliciting half-maximal response, approximately equal to 3 nM). CGRP was significantly more potent than SP as a cerebrovascular dilator, both in vitro and in situ. Chronic division of the ipsilateral trigeminal nerve in cats did not modify the magnitude of arteriolar responses to perivascular microapplication of either vasoconstrictor or vasodilator agents, but the duration of vasoconstrictor responses to norepinephrine (0.1 mM) or alkaline solutions (pH 7.6) was significantly increased. The cerebrovascular trigeminal neuronal system, in which CGRP is the most potent vasoactive constituent, may participate in a reflex or local response to excessive cerebral vasoconstriction that restores normal vascular diameter.     

Nonprogression of subclinical beta-cell dysfunction among first-degree relatives of IDDM patients. 5-yr follow-up of the Seattle Family Study

It is unknown among first-degree relatives of individuals with insulin-dependent diabetes mellitus (IDDM) whether the disease process occurs in relatively few but always progresses to clinical IDDM or whether subclinical disease is more common but remains nonprogressive in many cases. Islet cell antibodies (ICAs) were found in 21 of 724 (2.9%) first-degree relatives during screening in the greater Seattle area between 1983 and 1988. Measures of beta-cell function (glucose disappearance rate [Kg], fasting insulin, acute insulin response to intravenous arginine [AIRarg], acute insulin response to intravenous glucose [AIRgluc], slope of glucose potentiation of AIRarg) and insulin sensitivity were obtained. Twenty individuals, 9 ICA+ relatives and 11 ICA- relatives, were evaluated prospectively. When expressed in relation to the expected AIRgluc based on each subject's sensitivity index, AIRgluc in 18 of 20 relatives fell below 100%, indicating inappropriately low insulin secretion (subclinical beta-cell dysfunction). After a median follow-up of 42 mo, 10 of 11 ICA- relatives remained ICA-. None showed deteriorating beta-cell dysfunction, and none developed diabetes. Five ICA+ relatives showed persistent immunologic positivity. beta-Cell function remained remarkably stable in all except 2 relatives. One was a 15-yr-old boy who developed IDDM shortly after screening and before evaluation of beta-cell function could be carried out. The other was an 18-yr-old monozygotic twin who developed IDDM after 27 mo. Both of these individuals had ICAs of 80 Juvenile Diabetes Foundation U and had been discordant for less than 5 yr.(ABSTRACT TRUNCATED AT 250 WORDS)     

The AMPA receptor potentiator LY404187 increases cerebral glucose utilization and c-fos expression in the rat.

AMPA receptor potentiators enhance AMPA receptor-mediated glutamatergic neurotransmission and may have therapeutic potential as cognitive enhancers or antidepressants. The anatomical basis for the action of AMPA receptor potentiators is unknown. The aim of this study was to determine the effects of the biarylpropylsulfonamide AMPA receptor potentiator, LY404187 (0.05 to 5 mg/kg subcutaneously), upon cerebral glucose utilization and c-fos expression using 14C-2-deoxglucose autoradiography and c-fos immunocytochemistry. LY404187 (0.5 mg/kg) produced significant elevations in glucose utilization in 28 of the 52 anatomical regions analyzed, which included rostral neocortical areas and the hippocampus, as well the dorsal raphe nucleus, lateral habenula, and locus coeruleus. No significant decreases in glucose utilization were observed in any region after LY404187 administration. The increases in glucose utilization with LY404187 (0.5 mg/kg) were blocked by pretreatment with the AMPA receptor antagonist LY293558 (25 mg/kg), indicating that LY404187 acts through AMPA receptor-mediated mechanisms. LY404187 (0.5 mg/kg) also produced increases in c-fos immunoreactivity in the cortex, locus coeruleus, and the dorsal raphe nucleus. These studies demonstrate neuronal activation in key brain areas that are associated with memory processes and thus provide an anatomical basis for the cognitive enhancing effects of AMPA receptor potentiators.     

Protoporphyrinogen oxidase in porphyria variegata. A report of the findings in 7 families

Protoporphyrinogen oxidase (PPO) activity was determined in 7 families with porphyria variegata (PV). Enzyme activity was reduced by 50% in 8 propositi and in 8 out of 16 prepubertal children. These results are in keeping with the concept that PV is inherited as an autosomal dominant disease. Enzyme activity was also reduced in the fathers of 2 of the propositi, who were suspected on family history of carrying the PV trait, but who had no clinical manifestations. Determination of PPO activity provides a reliable means of identifying PV and of identifying offspring who could, at puberty, become PV patients.     

The effect of the kappa-opioid receptor agonist CI-977 in a rat model of focal cerebral ischaemia.

The effect of a novel, highly potent and selective kappa-opioid receptor agonist CI-977 upon ischaemic brain damage and brain swelling has been examined in a rat model of focal cerebral ischaemia. Focal ischaemia was produced by the permanent occlusion of the left middle cerebral artery (MCA) during a brief period of halothane anaesthesia. The animals were sacrificed 24 h after MCA occlusion and the amount of ischaemic brain damage and swelling was assessed in coronal sections at 8 predetermined stereotactic planes. Treatment with CI-977 (0.03, 0.3 or 3 mg/kg), initiated 30 min prior to MCA occlusion (and at multiple times thereafter) produced dose-dependent reductions in the volumes of infarction and of brain swelling, with the most marked reductions being noted with CI-977 (0.3 mg/kg) in both infarction (reduced by 38% from controls; P less than 0.02) and swelling (reduced by 31%; P less than 0.002). There was an excellent correlation between the volume of brain swelling and ischaemic damage which was similar with saline-treated and CI-977-treated animals (overall correlation coefficient r = 0.896). These results indicate that CI-977 is effective in reducing infarction in a model of focal cerebral ischaemia, and that the reduction in brain swelling occurs in parallel with the reduction in ischaemic damage.