Neuronal spike activity in the nucleus accumbens of behaving rats during ethanol self-administration

Many lines of evidence support the importance of the nucleus accumbens (NAC) for ethanol-reinforced behavior. The nature of the neuronal activity that occurs in this region during ethanol self-administration is not known. We recorded from ensembles of single-units primarily located within the shell of the NAC during operant responding for oral ethanol solutions by well-trained rats. Of 90 units recorded from seven sessions from seven rats, 41 (46%) did not exhibit significant changes in relation to the experimental events. Of the 49 units (54%) that did exhibit significant phasic changes, alterations in firing rate occurred in relation to the following experimental events: operant response (63%), tone stimulus (20%), and ethanol delivery (63%). In addition, changes in spike activity during the intervals between the three experimental events were noted in 33% of the units. Most units (55% of responsive units) responded to multiple experimental events. Thus different but overlapping populations of neurons in the NAC represent each event that occurs along the temporal dimension of a single trial performed to obtain ethanol reward. The data suggest that the NAC plays a crucial role in linking together conditioned and unconditioned internal and external stimuli with motor plans to allow for ethanol-seeking behavior to occur.     

Crystalloids vs. colloids in fluid resuscitation: a systematic review

OBJECTIVE: To systematically review the effects of isotonic crystalloids compared with colloids in fluid resuscitation. DATA SOURCES: Computerized bibliographic search of published research and citation review of relevant articles. STUDY SELECTION: All randomized clinical trials of adult patients requiring fluid resuscitation comparing isotonic crystalloids vs. colloids were included. Pulmonary edema, mortality, and length of stay were evaluated. Independent review of 105 articles identified 17 relevant primary studies of 814 patients. Weighted c about article inclusion was high (0.76). DATA EXTRACTION: Data on population, interventions, outcomes, and methodologic quality of the studies were obtained by duplicate independent review with differences resolved by consensus. Weighted ic on the validity assessment was moderate (0.54). DATA SYNTHESIS: No difference was observed overall between crystalloid and colloid resuscitation with respect to mortality and pulmonary edema; however, the power of the aggregated data was insufficient to detect small but potentially clinically important differences. Subgroup analysis suggested a statistically significant difference in mortality in trauma in favor of crystalloid resuscitation (relative risk 0.39, 95% confidence intervals: 0.17 to 0.89). Several methodologic issues are noteworthy regarding the primary studies, including lack of blinding (except in three studies). The type, dose, and duration of fluid administration and outcomes measured were different across these trials. CONCLUSIONS: Overall, there is no apparent difference in pulmonary edema, mortality, or length of stay between isotonic crystalloid and colloid resuscitation. Crystalloid resuscitation is associated with a lower mortality in trauma patients. Methodologic limitations preclude any evidence-based clinical recommendations. Larger well-designed randomized trials are needed to achieve sufficient power to detect potentially small differences in treatment effects if they truly exist.     

Physical and functional interactions between the herpes simplex virus UL15 and UL28 DNA cleavage and packaging proteins

Herpes simplex virus (HSV) DNA is cleaved from concatemers and packaged into capsids in infected cell nuclei. This process requires seven viral proteins, including UL15 and UL28. UL15 expressed alone displays a nuclear localization, while UL28 remains cytoplasmic. Coexpression with UL15 enables UL28 to enter nuclei, suggesting an interaction between the two proteins. Additionally, UL28 copurified with UL15 from HSV-infected cells after ion-exchange and DNA affinity chromatography, and the complex sedimented as a 1:1 heterodimer upon sucrose gradient centrifugation. These findings are evidence of a physical interaction of UL15 and UL28 and a functional role for UL15 in directing UL28 to the nucleus.     

Thalassaemia and malaria, revisited

Haldane's attractive hypothesis that the high gene frequencies for thalassaemia in the Mediterranean population may have resulted from heterozygote advantage in regions where Plasmodium falciparum malaria was common in the past has been extremely difficult to verify at the population or experimental level. However, the molecular era has provided some powerful new tools to attack this old problem. It is now clear that the thalassaemias are the commonest monogenic diseases in man, with a broad distribution throughout the Mediterranean, Middle East, Indian sub-continent and South-east Asia. All these populations have specific types of thalassaemia mutations which, presumably, have arisen locally and been expanded by selection together with drift and founder effect. Recent work indicates that alpha thalassaemia provides protection against severe malaria. Quite unexpectedly at least some of this protection may be mediated by rendering very young children more susceptible to both P. vivax and P. falciparum malaria; such early immunization may provide some protection against the disease in later life.