Endothelin receptor blockade prevents the rise in pulmonary vascular resistance after cardiopulmonary bypass in lambs with increased pulmonary blood flow

BACKGROUND: Children with increased pulmonary blood flow may experience morbidity as the result of increased pulmonary vascular resistance after operations in which cardiopulmonary bypass is used. Plasma levels of endothelin-1, a potent vasoactive substance implicated in pulmonary hypertension, are increased after cardiopulmonary bypass. OBJECTIVES: In a lamb model of increased pulmonary blood flow after in utero placement of an aortopulmonary shunt, we characterized the changes in pulmonary vascular resistance induced by hypothermic cardiopulmonary bypass and investigated the role of endothelin-1 and endothelin-A receptor activation in postbypass pulmonary hypertension. METHODS: In eleven 1-month-old lambs, the shunt was closed, and vascular pressures and blood flows were monitored. An infusion of a selective endothelin-A receptor blocker (PD 156707; 1.0 mg/kg/h) or drug vehicle (saline solution) was then begun 30 minutes before cardiopulmonary bypass and continued for 4 hours after bypass. The hemodynamic variables were monitored, and plasma endothelin-1 concentrations were determined before, during, and for 6 hours after cardiopulmonary bypass. RESULTS: After 90 minutes of hypothermic cardiopulmonary bypass, both pulmonary arterial pressure and pulmonary vascular resistance increased significantly in saline-treated lambs during the 6-hour study period (P <.05). In lambs pretreated with PD 156707, pulmonary arterial pressure and pulmonary vascular resistance decreased (P <. 05). After bypass, plasma endothelin-1 concentrations increased in all lambs; there was a positive correlation between postbypass pulmonary vascular resistance and plasma endothelin-1 concentrations (P <.05). CONCLUSIONS: This study suggests that endothelin-A receptor-induced pulmonary vasoconstriction mediates, in part, the rise in pulmonary vascular resistance after cardiopulmonary bypass. Endothelin-A receptor antagonists may decrease morbidity in children at risk for postbypass pulmonary hypertension. This potential therapy warrants further investigation.     

Acidic urine pH is associated with elevated levels of free urinary benzidine and N-acetylbenzidine and urothelial cell DNA adducts in exposed workers

We evaluated the influence of urine pH on the proportion of urinary benzidine (BZ) and N-acetylbenzidine present in the free, unconjugated state and on exfoliated urothelial cell DNA adduct levels in 32 workers exposed to BZ in India. Postworkshift urine pH was inversely correlated with the proportions of BZ (r = -0.78; P < 0.0001) and N-acetylbenzidine (r = -0.67; P < 0.0001) present as free compounds. Furthermore, the average of each subject's pre- and postworkshift urine pH was negatively associated with the predominant urothelial DNA adduct (P = 0.0037, adjusted for urinary BZ and metabolites), which has been shown to cochromatograph with a N-(3'-phosphodeoxyguanosin-8-yl)-N'-acetylbenzidine adduct standard. Controlling for internal dose, individuals with urine pH < 6 had 10-fold higher DNA adduct levels compared to subjects with urine pH > or = 7. As reported previously, polymorphisms in NAT1, NAT2, and GSTM1 had no impact on DNA adduct levels. This is the first study to demonstrate that urine pH has a strong influence on the presence of free urinary aromatic amine compounds and on urothelial cell DNA adduct levels in exposed humans. Because there is evidence that acidic urine has a similar influence on aromatic amines derived from cigarette smoke, urine pH, which is influenced by diet, may be an important susceptibility factor for bladder cancer caused by tobacco in the general population.     

Interaction of L-glutamic acid with human T-lymphocytes

A specific interaction of [3H]Glu with T lymphocytes from the blood of healthy donors (Kd = 0.236 microM) was revealed and described. It was found that unlabeled quisqualate, a structural analogue of L-glutamic acid, and unlabeled dipeptides Ala-Glu, Glu-Ala, and Glu-Glu competitively inhibit the specific binding of [3H]Glu to T lymphocytes (with Ki 0.19, 2.4, 3.4, and 1.2 microM, respectively). Binding experiments with conjugates of labeled and unlabeled glutamic acid with dextran showed that the receptors of [3H]Glu are localized on the outer surface of the plasma membrane of T lymphocytes.     

Clinical manifestations and treatment of intestinal dysbacteriosis in patients with Flexner's dysentery

Flexner's dysentery is often accompanied with intestinal dysbacteriosis. Disbiotic changes in the intestine contribute to specific shigella endotoxins entering blood flow thus prolonging clinical symptoms of the underlying disease. Administration of bacterial biological preparations (bifidumbacterin forte, lactobacterin) relieves specific endotoxemia, reduces the duration of the disease and has an immunomodulating action.     

Variability in function measurements of three sensory foot nerves in neuropathic diabetic patients

Although most short, linear peptide fragments of proteins are unstructured in aqueous solution, a number of immunogenic and antigenic peptides have been shown to have conformational preferences for structured forms. By using mainly NMR and CD spectroscopy, it has been possible to detect and quantify quite small populations of beta-turn, helical, and nascent helical conformations. Recent studies have been published indicating that the presence of structured forms is correlated with the location of T cell and/or B cell epitopes in peptide sequences. X-ray crystal structures of complexes between peptides and anti-peptide antibodies frequently show the peptides bound in beta-turn conformations, and the presence of helix in one peptide-antibody complex has been shown by NMR spectroscopy. Studies of peptides free in solution and bound to anti-peptide antibodies in the crystal indicate that the structure of the principal neutralizing determinant of HIV-1 probably includes at least one beta-turn in a highly conserved region. These results can potentially be used in the design of peptide-based vaccines.     

Suppression of inward-rectifying K+ channels KAT1 and AKT2 by dominant negative point mutations in the KAT1 alpha-subunit

Na(+)-glucose transport and transepithelial permeability were investigated during symptomatic acute cryptosporidiosis in newborn rats. The infection resulted in a significant (P < 0.01) decrease in the ileal short-circuit current and a nonsignificant fall in the transepithelial potential difference and conductance. In glucose-stimulated conditions, the rise in ileal short-circuit current and transepithelial permeability were significantly lower in Cryptosporidium parvum-infected rats than in controls (delta Isc = 3.24 +/- 1.21 microA.cm-2 vs delta Isc = 5.09 +/- 2.23 microA.cm-2 in infected and control animals, respectively; P < 0.001; delta PD = -0.35 +/- 0.13 mV vs delta PD = -0.44 +/- 0.14 mV for infected and control animals, respectively; P < 0.01). Electrical parameters were not affected by addition of the cyclooxygenase inhibitor indomethacin in either Cryptosporidium-infected newborn rats or controls. Horseradish peroxidase and mannitol flux studies demonstrated a significant decrease (P < 0.05) in transepithelial molecular permeability in infected enterocyte rats, HRP flux = 380, range 68-5570 ng.cm-2, and mannitol flux = 1.06, range, 0.34-1.44%.cm-2.min-1, compared with controls rats, HRP flux = 4446 range, 1121-124,363 ng.cm-2, and mannitol flux = 1.99, range, 0.57-5.09%.cm-2.min-1; P < 0.05. These effects could originate from C. parvum-induced alteration of intracellular trafficking of pinocytosis vesicles and therefore account for the decrease in permeability to solute and macromolecules, together with impaired transcellular nutrient transport, in suckling rats.     

Magnetic resonance imaging with implanted neurostimulators: an in vitro and in vivo study

OBJECTIVE: The goal was to assess the safety of magnetic resonance imaging (MRI) with implanted neurostimulators, in an in vitro and in vivo study. METHODS: Two different implantable pulse generators (IPGs) (ITREL II and 3; Medtronic, Minneapolis, MN) and different leads (separately and connected to an IPG) were tested in three different MRI scanners (0.2, 0.25, and 1.5 T). Measurements of the induced voltages (using an external oscilloscope) and the induced heat (using an infrared camera) were performed in an in vitro study. Finally, 38 patients with implanted neurostimulator systems (leads and IPGs) underwent MRI in 50 examinations, with continuous monitoring by a physician with uninterrupted visual and vocal contact with the patient. Twenty-five patients were studied prospectively, with documented printouts of the parameter settings before and after MRI. RESULTS: An induced voltage of 2.4 to 5.5 V was measured in the experimental configuration with a lead connected to an IPG. The voltage was higher with the leads alone, compared with the leads connected to the IPG, and was dependent on the MRI scanner, the sequences, and the type of lead. No heat induction was observed in any part of the hardware. No change of pulse shape or change of IPG parameters was observed during MRI. No adverse effects occurred in patients with chronically implanted deep brain leads connected to an IPG. CONCLUSION: MRI can be safely performed in patients with implanted neurostimulation systems with the tested deep brain leads connected to an IPG (ITREL II and 3), with running parameters. No heat induction was detected, and the experimentally measured induced voltage did not seem to harm the patients. Only the reed switch of the IPGs was activated; the other parameters remained unchanged. Further investigations must be performed to study the local electrical effects in larger plate electrodes; these effects might cause slight discomfort. There is no danger with any type of electrode during MRI examinations if the electrodes lie outside the region of interest. These observations are restricted to the tested devices. A conscientious estimation of the risks and benefits of MRI for patients with implanted devices is recommended. If the type of device is not known to the examiner, MRI should still be considered to be contraindicated.