Serotonergic receptors in the brain of in utero undernourished rats

In this study, we report that 5-HT(1A) receptors are already present in fractions of axonal growth cones, from the normal rat fetal brain (E-17). Also, in utero undernourished (UN) rat pups at birth show a noteworthy enhancement in the B(max) of [3H]5-hydroxytryptamine (5-HT) and [3H]8-hydroxy-(2-N,N-dipropilamin)-tetralin (([3H])8-OH-DPAT), in the brainstem and cerebral cortex up to the second week after birth. Afterwards, there is a significant decrease in the binding of these ligands. [125I]Cyanopindolo binding in the cerebral cortex only showed a decrease in the same period. An elevation of brain serotonin in both regions was also present. These findings together, suggest that the mechanisms of regulation of serotonergic receptors' expression during the period studied, may not depend on the amount of neurotransmitter in the synaptic cleft, because in the early UN brain it would be expected only a lower receptor's density due to the chronic serotonin increase. On this basis, we propose that developmental activation of brain serotonin biosynthesis observed in early UN animals may disrupt the mechanism regulating the expression of 5-HT receptors during development.     

Ninety-one Cases of Breast Cancer and Chronic Lymphoproliferative Neoplasm: A Retrospective Review of a Population at High Risk for Multiple Malignancies

Abstract: We performed a retrospective analysis of clinical course of 91 patients who developed both breast cancer and a chronic lymphoproliferative neoplasm and were seen at the M. D. Anderson Cancer Center between January 1, 1970 and December 30, 1991. The sample included 24 individuals who developed lymphoproliferative neoplasm first (Group A), 22 individuals with concurrent diagnosis of both malignancies (Group B), and 45 individuals who developed breast cancer first (Group C). The median time to diagnosis of secondary breast cancer and lymphoproliferative neoplasm was 66 months (range, 7–459) and 65 months (range, 0–334), respectively. A higher proportion of Group B lymphomas were low-grade (77% vs. 47% [Group A] vs. 37% [Group C] p = 0.009). Prior occurrence of either one of these malignancies did not affect the disease-specific survival from the second malignancy. However, continuing mortality from the first malignancy appeared to contribute to a poor overall survival following second malignancy. Group A included 8 patients who developed breast cancer following radiation therapy for Hodgkin's disease after a mean interval of 18 (± 4.3) years. Three of these individuals had coexisting ductal and lobular histology (vs. none of the individuals in Groups B and C, p = 0.02). Another interesting finding was the high incidence of multiple additional malignancies in this patient population. A total of 29 additional neoplasms occurred in 21 (23%) of the 91 study subjects. These malignancies involved a wide variety of organ sites and could not be attributed to the therapy for either the breast cancer or the lymphoma in most cases. The data suggest that individuals who develop both breast cancer and a lymphoproliferative neoplasm are at a high risk for multiple malignancies. Close surveillance of such individuals for additional malignancies and further studies to understand the molecular basis of this predisposition are warranted.?     

Biphasic Shocks Compared with Monophasic Damped Sine Wave Shocks for Direct Ventricular Defibrillation during Open Heart Surgery

Background: Biphasic waveform shocks are more effective than monophasic shocks for transchest ventricular defibrillation, atrial cardioversion, and defibrillation with implantable defibrillators but have not been studied for open chest, intraoperative defibrillation. This prospective, blinded, randomized clinical study compares biphasic and monophasic shock effectiveness and establishes intraoperative energy dose-response curves.

Methods: Patients undergoing cardiothoracic surgery with bypass cardioplegia were randomly assigned to the monophasic or biphasic shock group. Ventricular fibrillation occurring after aortic clamp removal was treated with escalating energies of 2, 5, 7, 10, and 20 J until defibrillation occurred. If ventricular fibrillation persisted, a 20-J crossover shock of the other waveform was used.

Results: Cumulative defibrillation success at 5 J, the primary end point of the study, was higher in the biphasic group than in the monophasic group (25 of 50 vs. 9 of 41 defibrillated;P = 0.011). In addition, the biphasic group required lower threshold energy (6.8 vs. 11.0 J;P = 0.003), less cumulative energy (12.6 vs. 23.4 J;P = 0.002), and fewer shocks (2.5 vs. 3.5;P = 0.002). Crossover-shock effectiveness did not differ between groups. Dose-response curves show biphasic shocks to have higher cumulative success rates at all energies tested.     

Effects on Behaviour and EEG of Single Chain Phospholipases A2 from Snake and Bee Venoms Injected into Rat Brain: Search for a Functional Antagonism

Abstract: Three phospholipase A₂ (PLA₂s), OS₁ and OS₁ purified from the taipan snake venom Oxyuranus scutellatus scutellatus and bee venom PLA₂ were injected to rats by the intracerebroventricular route. OS₁ showed no sign of neurotoxicity at doses at which OS₂ and bee venom PLA₂ produced multiform dose-dependent behavioural effects including motor disturbances (stereotyped movements), compulsive scratching, convulsions and breathing difficulties. EEG recordings showed at the very time when the animal was motionless the induction of several episodes of a low frequency hippocampal theta rhythm, index of long-term changes in synaptic neuroplasticity. Spike-wave discharges were also produced but the occurrence was not systematic. These seizures were often accompanied with behavioural convulsions. Blockers of NMDA receptors and drugs modifying the GABAergic transmission could not abolish the neurotoxic effects of PLA₂s except for diazepam (10 mg/kg intraperitoneally) that prevented only OS₂-induced disturbances. Blockers of L-type Ca²⁺ channels and K⁺ channel openers were also without effect. The toxicity of OS₂ and bee venom PLA₂ is probably due to their initial specific binding to their neuronal receptor sites.     

Feedback from luminosity horizontal cells mediates depolarizing responses of chromaticity horizontal cells in the Xenopus retina.

It has been proposed that the depolarizing responses of chromaticity horizontal cells (C-HCs) to red light depend on a feedback signal from luminosity horizontal cells (L-HCs) to short-wavelength-sensitive cones in the retinas of lower vertebrates. In this regard we studied the C-HCs of the Xenopus retina. C-HCs and L-HCs were identified by physiological criteria and then injected with neurobiotin. The retina then was incubated with peanut agglutinin, which stains red-but not blue-sensitive cones. Electron microscopic examination revealed that L-HCs contact all cone classes, whereas C-HCs contact only blue-sensitive cones. Simultaneous recordings from C-HC/L-HC pairs established that when the L-HC was saturated by a steady bright red light, C-HCs alone responded to a superimposed blue stimulus. In response to red test flashes, the C-HC response was delayed by approximately 30 msec with respect to the L-HC response. Isolated HCs of both subtypes were examined by whole-cell patch clamp. Both responded to kainate with sustained inward currents and to quisqualate or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) with desensitizing currents from a negative holding potential; i.e., both have AMPA-type glutamate receptors. gamma-Aminobutyric acid or glycine opened a chloride channel in the L-HC, whereas the C-HC was unresponsive to either inhibitory amino acid. Since glycine has been shown to abolish selectively the depolarizing response of the C-HC, this finding and other pharmacological data strongly implicate the L-HC in the underlying circuit. Moreover, because the C-HC does not respond to gamma-aminobutyric acid, the neurotransmitter of the L-HC, by elimination, a feedback synapse from L-HC to blue cone is the most plausible mechanism for the creation of depolarizing responses in C-HCs.