Intermittent versus continuous neuroleptic treatment in a rat model

The treatment schedule for neuroleptic therapy is of relevance when evaluating the development of side-effects. Seventy-five rats were treated discontinuously or continuously with the predominantly dopamine D₂ receptor blocker haloperidol or the combined dopamine D₁/D₂ receptor blocker zuclopenthixol for 15 weeks. During and after treatment, a broad spectrum of behavioural parameters including vacuous chewing movements and tongue protrusions were observed. Discontinuous neuroteptic treatment as opposed to continuous neuroleptic treatment produced a significant long-lasting increase in oral activity. The changes were most pronounced in haloperidol-treated rats. The differences observed may have methodological implications for animal models of neuroleptic-induced movement disorders. Our finding are consistent with the hypothesis that pharmacological sensitization to the dyskinetic side-effects of neuroleptics develops when the drug effect is allowed to wear off between repeated administration.     

Absence of an Effect of Naloxone on Ethanol Intoxication and Withdrawal Reactions

Abstract Experimental and clinical results suggest a relationship between the action of ethanol and opiates. Therefore, we have tested whether the specific morphine antagonist naloxone (2 mg/kg intraperitoneally every six hours) affects signs of severe ethanol intoxication or modifies the withdrawal syndrome following chronic ethanol intoxication in rats. Using a double blind technique, we did not find any difference between saline treated and naloxone treated animals with respect to level of intoxication and severity of withdrawal symptoms. We must therefore conclude that naloxone does not modify signs of severe ethanol intoxication or change the ethanol withdrawal syndrome in the rat. These findings do not rule out that there might be a biochemical link between actions of ethanol and opiates, but this link is probably not localized at the level of specific drug receptor interaction.     

Long-term bone marrow culture in persons with Fanconi anemia and bone marrow failure

Fanconi anemia is an autosomal recessive disease characterized by a high risk of developing bone marrow (BM) failure and acute myelogenous leukemia. We studied growth of hematopoietic progenitor cells in long- term BM culture (LTBMC) in 8 persons with Fanconi anemia and BM failure. Although LTBMC were initiated with very few BM cells, an adherent layer formed in cultures from 7 persons. In these cultures, the number of nonadherent cells increased for 10 to 15 days. Cell growth continued until cultures were terminated at day 35 to 40. During the first 2 weeks of culture, most nonadherent cells were differentiated myeloid cells. By days 35 to 40, the adherent layer contained cells able to initiate secondary LTBMCs. These data indicate that hematopoietic precursors cells able to proliferate and differentiate in vitro are present in the BM of persons with Fanconi anemia and BM failure. They suggest that mechanisms other than absent precursor cells are responsible for BM failure in Fanconi anemia.     

Activation of cytotoxic T cells by nonstimulating tumor cells and spleen cell factor(s).

The ability of three cultured mouse tumor lines to stimulate a cytotoxic response in 5-day cultures of allogeneic lymph node cells was studied with a 51Cr release assay. Two lines of mesenchymal origin, P815 and EL-4, were found to be highly stimulatory, whereas the third cell line, CaD2, a mammary gland epithelial tumor, did not stimulate over a wide range of cell concentration. CaD2 cells were shown to contain major antigens similar to those of P815 cells by the specific lysis of both cells by lymphocytes activated to H-2d-bearing peritoneal cells.UV-irradiated P815-cells, like gamma-irradiated CaD2 cells, did not stimulate a cytotoxic response, but both cell lines were found to stimulate a full and specific response to allogeneic lymph node cells if these mixed cultures were supplemented with a supernatant harvested from concanavalin A-stimulated spleen cells.     

A direct test for the survival of gaseous nuclei in vivo

It has recently been demonstrated that bubble formation in the crab Pachygrapsus crassipes is induced by limb motions following decompression from nitrogen pressures as low as 2 atm. Preformed gaseous nuclei are not involved in this process and are absent from this animal. We further demonstrate here that nuclei do not remain in the body fluids when the motion-induced bubbles dissolve. This shows that gas phases do not become protected against dissolution in vivo as has been proposed by other workers. This may have important implications concerning the origin of bubbles causing decompression sickness in higher animals.     

Magnesium concentrations in blood and cerebrospinal fluid during delirium tremens.

Magnesium in plasma, erythrocytes, and cerebrospinal fluid (CSF) was measured immediately after hospital admission in 9 patients with delirium tremens (DT) and 11 patients with impending DT. Blood samples were taken daily during the acute state; a second lumbar puncture was performed when the patient's condition had improved. Plasma magnesium was low in patients with DT during the first days of the acute state and then spontaneously normalized. Normal plasma magnesium was consistently seen among patients with impending DT. Magnesium in erythrocytes and CSF was normal in both diagnostic categories. Patients with a high blood-alcohol concentration (BAC) at admission had a decreasing plasma magnesium, patients with a low BAC had a moderately increasing plasma magnesium, and patients with a BAC at nil had a more marked increase in plasma toms or with their duration. This finding, combined with the normal CSF magnesium and the lack of correlation between plasma and CSF magnesium, indicates that disturbances in magnesium metabolism do not play a role in the etiology or pathogenesis of DT; but it may be that disturbances in magnesium metabolism contribute to the development of alcoholic encephalopathy.