Vasoactive intestinal peptide inhibits luteinizing hormone secretion: the inhibition is not mediated by dopamine

Vasoactive intestinal peptide (VIP) is a neuropeptide that is present in the hypothalamus and is probably a neuroendocrine regulator. The effect of VIP on pulsatile LH secretion in the long-term ovariectomized rat was re-examined in the light of earlier conflicting reports. VIP or saline was infused into the third ventricle at the rat of 15 microliters/h and blood was sampled frequently before and during the infusion. VIP at 3.5 nmol/h significantly depressed mean LH levels (p less than 0.05) and lowered pulse frequency (p less than 0.05), but had no effect on LH pulse amplitude (p greater than 0.05). VIP at lower levels was not consistently effective, and intraventricular saline was without influence. We examined indirectly whether the site of action of VIP (3.5 nmol/h) was the brain or pituitary by injecting various doses of gonadotropin-releasing hormone (GnRH; 0.5-4.0 ng/100 g BW i.v.) during VIP-induced inhibition of LH secretion and in saline-infused controls. VIP did not alter the response of the pituitary to GnRH or the slope of the GnRH-LH dose-response curve (p greater than 0.05). We conclude that the inhibitory action of VIP on pulsatile LH secretion is probably exerted in the hypothalamus. To test the hypothesis that dopamine mediates the inhibitory effects of VIP (3.5 nmol/h), animals were pretreated with the dopamine receptor blocking agent pimozide (1.26 mg/kg) in an attempt to block the actions of VIP. Pimozide did not affect the response of LH to VIP infusion (p greater than 0.05). We conclude that dopamine is not a likely mediator of the action of VIP.     

Singlet oxygen-induced arrhythmias. Dose- and light-response studies for photoactivation of rose bengal in the rat heart

In a study of aerobically perfused rat hearts, the in situ photoactivation (530-590 nm) of rose bengal (a process that leads to the production of singlet oxygen and superoxide) has been shown to lead to the rapid development of electrocardiographic abnormalities and arrhythmias. With rose bengal concentrations of 1,000, 500, 250, 100, and 50 nmol/l (n = 6/group), photoactivation (3,600 lx) led to electrocardiographic changes (inversion of the T wave, Q-T prolongation, or both) after 3.8 +/- 0.9, 4.5 +/- 0.7, 11.8 +/- 2.1, 24.8 +/- 3.9, and 65.3 +/- 6.0 seconds), respectively; ventricular premature beats occurred in 100% of hearts after 0.5 +/- 0.2, 1.1 +/- 0.3, 2.2 +/- 0.7, 4.4 +/- 0.8, and 6.6 +/- 1.2 minutes, respectively. Ventricular tachycardia occurred in 83%, 83%, 83%, 67%, and 50% of hearts after 2.1 +/- 0.2, 2.1 +/- 0.4, 2.8 +/- 0.7, 5.7 +/- 2.0, and 11.2 +/- 1.9 minutes, respectively, and complete atrioventricular block in 100%, 100%, 100%, 100%, and 67% of hearts after 3.8 +/- 0.7, 6.5 +/- 1.0, 5.5 +/- 0.9, 13.8 +/- 1.0, and 14.1 +/- 0.9 minutes, respectively. With a fixed concentration (250 nmol/l) of rose bengal, similar light-response relations were observed. Photoactivation of rose bengal had no effect on heart rate but caused a transient (0-4 minutes) vasodilation followed by a progressive vasoconstriction. In further studies in which rose bengal was washed out for 10 minutes before photoactivation, several arrhythmias still developed, indicating that rose bengal binds strongly to tissue and acts as a cellular level rather than in the vascular compartment. To assess the reversibility of rose bengal-induced effects, hearts (n = 6/group) were perfused with rose bengal (250 nmol/l) for 1, 2, 4, 6, and 20 minutes followed by perfusion in the dark for 19, 18, 16, 14, and 0 minutes, respectively. During dark perfusion, the incidence of arrhythmias declined and any decrease in coronary flow was reversed. However, analysis of contents of adenosine triphosphate, creatine phosphate, lactate, and creatine kinase leakage indicated the occurrence of severe injury that did not abate on termination of photoactivation. Finally, although many arrhythmias developed before the onset of vasoconstriction, the reduction in flow with consequent ischemia was shown to exacerbate vulnerability to arrhythmias. In conclusion, short-lived reactive oxygen intermediates such as singlet oxygen and superoxide, which are produced during the photoactivation of rose bengal, can cause rapid and major damage to the heart and its function.     

The utility of the presence or absence of chest pain in patients with suspected acute myocardial infarction

In 422 patients admitted from the emergency department (ED) for suspected acute myocardial infarction, the hypothesis that chest pain that persists on arrival in the ED or recurs during the initial ED evaluation is a useful predictor of acute myocardial infarction (AMI) and complications of coronary ischemia was tested. Compared with patients whose chest pain spontaneously ceased before arrival in the ED, patients whose chest pain persisted or recurred during the initial ED evaluation had a 2.3 times greater risk of interventions (P less than .001), a 1.7 times greater risk of complications (P = .045), a 3.8 times greater risk of life-threatening complications (P = .04), and a 2.4 times greater risk of AMI (P = .005). A third group of patients with suspected AMI never experienced chest pain. This group of patients who never experienced chest pain had a three times higher risk of death (P = .02) compared with patients whose chest pain persisted or recurred in the ED, and a 2.1 times greater risk of intervention (P = .01), a 5.2 times greater risk of life-threatening complication (P = .015), and a 7.9 times greater risk of death (P = .025) compared with patients whose chest pain resolved before arrival in the ED. It was concluded that patients with chest pain that resolves spontaneously before arrival to the ED have a better in-hospital prognosis than any other group.     

Portal thrombosis: Percutaneous transhepatic treatment with urokinase — A case report

We present a case report of a patient suffering from portal and superior mesenteric vein thrombosis secondary to splenectomy. No surgical procedure could be performed due to the extension of thrombus.Local fibrinolysis treatment with urokinase through a percutaneous transhepatic approach was decided upon, and this procedure had a successful patient outcome.     

Beta-2 microglobulin and amyloid osteoarthropathy in patients undergoing chronic hemodialysis

The incidence of beta-2 microglobulin amyloidosis was assessed in two populations of chronic hemodialysis patients. Out of 34 patients who underwent biopsy during orthopedic surgery (33 cases) or autopsy (1 case), 26 had amyloid deposits which fixed anti-beta microglobulin serum. Out of 55 unselected patients treated for over months at the dialysis centre, 14 (25%) had clinical symptoms suggesting amyloidosis and out of 43 patients who had a systematic radiological skeletal survey, 23 (53%) had bone deposits. The plasma beta microglobulin concentrations (about 20 times the normal value) we not significantly different whether or not the patients had histological proven amyloidosis, clinically or radiologically probable amyloidosis, no detectable amyloidosis. However, the duration of hemodialysis was longer in those with proven or highly probable amyloidosis. The finding illustrate the indirect role of elevation of beta-2 microglobulin in the genesis of this pathology and also the necessity of lowering its concentration in order to avoid the long term complications of osteoarticular deposits, the functional consequences of which may be very serious.     

Antibodies to the ADP/ATP carrier, an autoantigen in myocarditis and dilated cardiomyopathy, penetrate into myocardial cells and disturb energy metabolism in vivo

We identified the ADP/ATP carrier, located within the inner mitochondrial membrane, to be an organ- and conformation-specific autoantigen in myocarditis and dilated cardiomyopathy. We also showed that autoantibodies to the ADP/ATP carrier inhibit the nucleotide transport in vitro. Specific binding of the autoantibodies to the carrier was demonstrated by radioimmunoassay and the immunoblot technique; the inhibition of the nucleotide transport was determined by the inhibitor stop method. To establish if these autoantibodies might also affect cardiac energy metabolism in vivo, we measured whether they are capable of penetrating into myocytes and whether subcellular ATP/ADP ratios and phosphorylation potentials of ATP change in hearts of guinea pigs that have been immunized with the isolated ADP/ATP carrier. An intracellular deposition of autoantibodies was observed by direct immunofluorescence and by immunoperoxidase staining on cryosections of the myocardial tissue of animals immunized with the ADP/ATP carrier. Furthermore, binding of autoantibodies to mitochondrial membrane structures was shown by immunoelectron-microscopic methods. The cytosolic and intramitochondrial distribution of adenine nucleotides in stimulated, isolated perfused hearts of guinea pigs immunized with the ADP/ATP carrier was measured by nonaqueous fractionation. Compared with controls performing equal external heart work, the cytosolic ATP decreased in the immunized animals, whereas the mitochondrial ATP increased strongly; ADP concentrations showed an opposite change. Thus, a resultant cytosolic decrease and a marked mitochondrial increase of the ATP/ADP ratio was established. As a consequence, the cytosolic-mitochondrial phosphorylation potential of ATP was diminished. These findings demonstrate that antibodies against intracellular antigens are able to penetrate into living cells, and that autoimmunity to the ADP/ATP carrier may contribute to the pathophysiology of myocarditis and dilated cardiomyopathy by causing an autoantibody-mediated imbalance between intracellular energy delivery and demand.     

Ontogeny of serum insulin-like growth factor binding proteins in the rat

Insulin-like growth factors (IGF-I and -II) are peptide growth factors that may be important for neonatal development. Specific high affinity IGF binding proteins (BPs) have been characterized in serum and extracellular fluids. The major serum binding complex in the adult has an apparent Mr of 150 K, while the predominant BP in the neonate is approximately 30 K. In the rat, the transition from the neonatal BP to the adult form occurs during the third postnatal week, concomitant with an increase in serum IGF-I and a decrease in serum IGF-II concentrations. Using specific RIAs and Western ligand blot analyses we have characterized the changes in serum IGF and IGF BPs, respectively, during the early postnatal period. Seven BPs were identified in serum with apparent Mr values of 42, 41, 40, 38, 28, 26, and 22 K. After deglycosylation, the 42, 41, 40, and 38 K BPs were reduced to two bands with apparent Mr values of 35 and 32 K, while the 28, 26, and 22 K BP were unchanged. In the neonate, the 28, 26, and 22 K BPs were present, with the 28 K BP in highest concentration. With increasing age, the 28 K BP decreased and the 42, 41, 40, and 38 K BPs appeared at approximately 19 days of age. Comparison of Western ligand blots of neonatal serum, BRL-3A conditioned media, rat amniotic fluid, and rat cerebrospinal fluid (CSF) demonstrated that all contained a prominent 28 K BP. A polyclonal antibody (alpha Hec 1) developed against the 31 K human IGF-BP (hBP-31) immunoprecipitated the 28 K BP from neonatal rat serum, BRL-3A media, rat amniotic fluid, and rat CSF, but did not react with adult rat serum. These findings suggest that, in the rat, the predominant neonatal serum BP is structurally and immunologically similar to the major BRL-3A, amniotic fluid, and CSF BPs, but distinct from the predominant adult serum BP.     

Subacute cutaneous lupus erythematosus during PUVA therapy for psoriasis: case report and review of the literature

Lesions typical of subacute cutaneous lupus erythematosus developed in an elderly woman after 6 months of PUVA (8-methoxypsoralen and longwave ultraviolet light) therapy for psoriasis. Pancytopenia, antibodies to double-stranded DNA, and hypocomplementemia developed concurrently with the appearance of the cutaneous lesions. With discontinuation of photochemotherapy, the cutaneous lesions disappeared and the pancytopenia improved.