Central opioid receptors differentially regulate the nalmefene-induced suppression of ethanol- and saccharin-reinforced behaviors in alcohol-preferring (P) rats.

The exact opioid-sensitive receptors participating in EtOH-seeking behaviors remains unclear. Previous studies have reported higher densities of micro-opioid receptor binding in the nucleus accumbens (NACC) of P relative to NP rats; however, no differences were seen in delta-receptor binding. In contrast to the NACC, substantially lower levels of micro-receptor binding have been observed in the ventral tegmental area (VTA) of both P and NP rats, albeit no line differences have been observed. In the present study, opioid receptors in the NACC, VTA, and hippocampus were evaluated for their capacity to regulate both EtOH- and saccharin-motivated behaviors in the genetically selected alcohol-preferring (P) rat. To accomplish this, nalmefene, an opiate antagonist with preferential binding affinity for the micro-opioid receptor was unilaterally or bilaterally infused during concurrent availability of 1 h daily EtOH (10% v/v) and saccharin (0.025 or 0.050% w/v) solutions. Rats performed under a two-lever fixed ratio (FR) schedule in which four responses on one lever produced the EtOH solution, and four on a second lever produced the saccharin solution. The results demonstrated that when responding maintained by both EtOH and saccharin are matched at basal levels, unilateral (1-60 microg) or bilateral (0.5-10 microg) microinjections of nalmefene into the NACC produced selective dose-dependent reductions on responding maintained by EtOH. Unilateral (40, 60 microg) and bilateral (10 microg) VTA infusions were also observed to selectively reduced EtOH responding; however, greater nalmefene doses were required and the magnitude of suppression on EtOH responding was markedly less compared with the NACC. The greater sensitivity of nalmefene to suppress EtOH responding in the NACC is likely due to the greater number of opioid receptors in the NACC relative to the VTA. Only bilateral infusion of the 40 microg dose in the NACC and VTA suppressed responding maintained by both EtOH and saccharin. In contrast, intrahippocampal infusions dose dependently suppressed EtOH- and saccharin-maintained responding over a range of doses (1-20 microg). The present study provides evidence that nalmefene suppresses EtOH-motivated behaviors via blockade of opioid receptors within the NACC and VTA, and under various dose conditions both reinforcer and neuroanatomical specificity can be observed.     

Prevention for those who have freedom of choice – or among the choice-disabled: confronting equity in the AIDS epidemic

With the exception of post-exposure prophylaxis for reported rape, no preventive strategy addresses the choice disabled – those who might like to benefit from AIDS prevention but who are unable to do so because they do not have the power to make and to act on prevention decisions. In southern African countries, where one in every three has been forced to have sex by the age of 18 years, a very large proportion of the population is choice disabled. This group is at higher risk of HIV infection and unable to respond to AIDS prevention programmes; they represent a reservoir of infection. Reduction of sexual violence would probably decrease HIV transmission directly, but also indirectly as more people can respond to existing AIDS prevention programmes.     

Germline mutations in the neurofibromatosis type 2 tumour suppressor gene

The recent identification of the NF2 tumour suppressor genehas enabled large scale screening for pathological mutationsin the gene. We have sought germline mutations In the NF2 geneby SSCP and heteroduplex analysis of cDNA and genomic DNA samplesfollowed by cloning and sequencing of mutant alleles. In thepresent report we describe 11 putative pathological mutations,including five nonsense mutations, three short insertions ordeletions cauing frameshifts and three missense mutations. Moststop mutations and frameshift mutations were found In Individualsexpressing a severe phenotype while one of the three missensemutations was associated with a mild phenotype. Four unrelatedNF2 patients of the 93 tested were found to have identical nonsensemutations caused by a C to T transition (C169) in a CpG dinucleotide,which is a potential mutational hotspot in the NF2 tumour suppressorgene.     

Serum erythropoietin quantitation in pregnancy using an enzyme-linked immunoassay.

During normal pregnancy there is a decrease in the hematocrit due to a disproportionate increase in the blood volume compared with the red cell mass. Using a new enzyme-linked immunoassay (Amgen Diagnostics), serum erythropoietin was quantified in normal nonanemic pregnancies throughout gestation and in third trimester anemic patients. We found that the mean hematocrit in normal pregnancy reached a nadir late in the second trimester and the serum erythropoietin plateaued at a 50% increase. Those pregnancies complicated by anemia defined by a hematocrit less than 30 vol% demonstrated a statistically significant increase in serum erythropoietin above those not anemic.     

Ureteral pseudodiverticulosis associated with carcinoma of renal pelvis

We describe a patient with bilateral ureteral pseudodiverticulosis of 10 years’ duration before developing transitional carcinoma of the pelvis.