Upregulation of cardiac cell plasma membrane calcium pump in a canine model of Chagas disease.

We have previously demonstrated that cardiac myocytes isolated from the hearts of adult dogs develop rapid repetitive cytosolic Ca2+ transients, membrane depolarization, and cell contraction by mobilization of sarcoplasmic reticulum Ca2+ stores when exposed to a soluble factor from the trypomastigotes of Trypanosoma cruzi. These findings led us to investigate the regulatory mechanisms of cytosolic Ca2+ in cardiac tissues from dogs chronically infected with T. cruzi. Expression of the plasma membrane calcium pump (PMCA) RNA and protein was determined by Northern and Western blotting, respectively, followed by densitometric analyses. A 642-bp PMCA 1b complementary DNA probe derived from canine epicardial tissue hybridized to 2 major transcripts (7.3 and 5.3 kb) in canine epicardium. Expression of the dominant transcript (7.3 kb) was 77% greater in cardiac tissues obtained from dogs with chronic T. cruzi infection (140 days after inoculation) in comparison with constitutive expression levels in normal dogs. Monoclonal antibody 5F10, known to recognize all isoforms of the PMCA, was used to detect expression of the PMCA protein in epicardial tissue. Expression of a 142-kDa protein was increased by 58% in the cardiac tissues of infected dogs when compared with those from uninfected dogs. To establish a link between the upregulation of PMCA in dogs chronically infected with Chagas disease and the ventricular-based arrhythmias and myocardial failure that occur during this stage of disease both in dogs and humans, further study will be required.

Modulation of the excitability of avian peripheral nerves by vitamin D: relation to calbindin-D28k, calcium status and lipid composition.

Calbindin-D28k (CaBP), previously localized in some of the cell bodies of ganglia of the avian intestinal (Remark's) nerve, was shown to be vitamin D-dependent. In the present studies, the effect of vitamin D3 on electrophysiological properties of this nerve was examined in vitro. Electrical stimulation of the nerve yielded a compound action potential with two primary components, Peaks I and II. Peak II, suppressed by hexamethonium bromide or Ca(2+)-free buffer, is synaptically mediated. The transit time between the two peaks was unaffected by vitamin D3. The apparent conduction velocity, defined as [(activation time + transit time)/nerve length], was increased by vitamin D-deficiency and decreased by vitamin D3 repletion, the latter decrease due entirely to an increase in activation time. Activation time after vitamin D-repletion was correlated with an increase in CaBP and plasma Ca2+ levels. However, normalization of plasma Ca2+ by supplementation of vitamin D-deficient diets with excess calcium (2.5 and 4.0%) also resulted in an increase in activation time, without affecting neuronal CaBP levels. Vitamin D3 also decreased the conduction velocity and increased CaBP of the vagus nerve and, by lipid analysis, was shown to increase and decrease its phosphatidylcholine and phosphatidylethanolamine content, respectively, and to decrease its phospholipid/cholesterol ratio. Modulation of peripheral nerve activity by vitamin D3 is related to calcium status and perhaps to changes in lipid composition. The functional role of CaBP in the behaviour of this complex nerve remains unknown.

Continence following electrical stimulation and EMG biofeedback in a teenager with imperforate anus.

A teenage boy with repaired high imperforate anus relied on daily enemas for social continence. After treatment with low intensity transcutaneous electrical stimulation and electromyographic biofeedback home programs, he achieved improved fecal continence requiring only one enema per month.

OPC-88117 suppresses early and delayed afterdepolarizations and arrhythmias induced by cesium, 4-aminopyridine and digitalis in canine Purkinje fibers and in the canine heart in situ.

The effects of OPC-88117, a new investigational antiarrhythmic drug, on early and delayed afterdepolarizations (EAD and DAD, respectively) were assessed in vitro in canine Purkinje fibers and in vivo in the canine right ventricle. OPC-88117 had similar electrophysiologic properties to class I antiarrhythmic agents in that it decreased Vmax. OPC-88117 decreased the amplitude and prolonged the coupling interval of DAD induced by acetylstrophanthidin. Likewise, OPC-88117 suppressed EAD induced in vitro by 4-aminopyridine. In vivo, cesium-induced EAD, ventricular arrhythmia, and atrioventricular block were suppressed by OPC-88117. In summary, OPC-88117 suppressed DAD and EAD in vitro and inhibited EAD and triggered activity in the in situ canine heart.

The enema continence catheter in spina bifida: successful bowel management.

Patients with spina bifida who have fecal incontinence are managed by means of a large-volume saline enema. To facilitate administration of the enema, a special catheter has been devised that prevents leakage of the enema fluid. Continence has been achieved in 112 children and youths with spina bifida who were managed in this fashion.

Anaphylactoid and systemic reactions following saline enema administration. Six case reports.

This report describes six children with spina bifida who have experienced a total of 13 episodes of generalized hives, angioedema and in two cases, anaphylactoid reactions immediately following saline enema infusions. The enemas were administered using a kit comprised of a plastic bag, tubing, and rectal end-piece. The reactions always occurred with the first use of new kits. A third child developed a systemic reaction with only the rectal end-piece in situ and without infusion of fluid. An in-hospital challenge using a new end-piece in one patient, who was clinically the most sensitive, produced an acute anaphylactoid reaction implicating the end-piece as the most likely source of the problem. The definitive mechanism(s) of the reactions and the agent(s) responsible for them presently remain unknown.