MDMA ('Ecstasy') enhances 5-HT1A receptor density and 8-OH-DPAT-induced hypothermia: blockade by drugs preventing 5-hydroxytryptamine depletion

One week after a single administration of 3,4-methylenedioxymethamphetamine (MDMA HCI, 30 mg/kg i.p.), 5-HT1A receptor density was significantly increased by approximately 25-30% in the frontal cortex and hypothalamus of rats. The increased density correlated with the potentiation of the hypothermic response to the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 1 mg/kg s.c.). Hypothalamic 5-HT7 receptors, which also bind 8-OH-DPAT, were not changed, however, by MDMA. Fluoxetine (5 mg/kg s.c.), ketanserin (5 mg/kg s.c.) or haloperidol (2 mg/kg i.p.), given 15 min prior to MDMA, prevented the depletion of 5-hydroxytryptamine (5-HT) induced by MDMA and also blocked the effects of this neurotoxin on 5-HT1A receptor density and on 8-OH-DPAT-induced hypothermia. The protection afforded by drugs against 5-HT loss did not correlate, however, with the antagonism of the acute hyperthermic effect of MDMA. The present results indicate that drugs able to prevent or to attenuate MDMA-induced 5-HT loss also prevent the changes in 5-HT1A receptor density as well as the enhanced hypothermic response to the 5-HT1A receptor agonist 8-OH-DPAT in MDMA-treated rats.     

Neonatal sciatic palsy: etiology and outcome of 21 cases

INTRODUCTION: Sciatic nerve paralysis is a rare entity in the newborn. Few reference in specialized tests indicate that in the majority of cases the sciatic palsy has been observed after misplaced injections into the buttocks. The prognosis is variable and appears to be better after umbilical vessel catheterization for injection of medications than after misplaced muscular injections. In case of recovery it takes place within 3 to 12 months. OBJECTIVE: The objective of the present study is to know the evolution of neonatal sciatic palsy and to determine their injury noxe in regard to perinatal factors, and their relationship with long-time outcome, and to look for prognostic clues of clinical utility. MATERIAL AND METHODS: We evaluated perinatal factors of newborn children with sciatic nerve paralysis, followed for more than 18 months of clinical evolution, in a neuropediatric centre. RESULTS: Twenty one newborn with such criteria were evaluated. Gestational age was within 32 and 42 weeks (median 38.2). The birth weight was between 2,100 and 4,100 g (median 2,973). The majority of cases obtained total recovery (16 of 21). The time of recovery was 4 to 14 months (median 8.8). Free ambulation was obtained by all cases (at 10 to 24 months). No apparent cause was observed in the majority of cases. Cesarean delivery was more frequent specially in cases with permanent consequences. CONCLUSION: Long-time prognostic of neonatal sciatic palsy is generally good. In our series all the cases with consequences were associated to cesarean delivery. The duration of cesarean intervention and the anesthesic hypotony of the newborn could be implicated in the sciatic nerve injury of poor outcome.     

Cellular mechanisms of intestine regeneration in the sea cucumber, Holothuria glaberrima Selenka (Holothuroidea:Echinodermata)

Echinoderms are the deuterostome group with the most striking capacity to regenerate lost body parts. In particular, members of the class Holothuroidea are able to regenerate most of their internal organs following a typical evisceration process. Such formation of new viscera in an adult organism provides a unique model to study the process of organogenesis. We have studied this process in the sea cucumber Holothuria glabberrima by describing the spatial and temporal pattern of cellular events that occur during intestine regeneration following chemically induced evisceration. Regeneration begins as a thickening of the mesenteries that supported the autotomized organs to the body wall. The mesenterial thickening consists of tissues where most of the cellular populations found in the normal intestine are already present. However, the cell numbers differ, particularly those of hemocytes and amoebocytes, suggesting that some of these cells play an important role in the formation of the solid rod of hypertrophic mesentery that characterizes the intestinal primordia. The appearance of the luminal epithelium, together with the formation of the lumen, occurs during the second week of regeneration by proliferation and extensive migration of cells from the esophagus and cloacal ends into the thickenings. At this stage all tissue layers are present, but it takes an additional week for them to exhibit the proportions typical of the normal organ. Cell division, as determined by BrdU labeling, mainly occurs in the coelomic epithelia of the hypertrophic mesentery and in the regenerating luminal epithelium. Our study provides evidence that the process of new organ formation in holothurians can be described as an intermediate process showing characteristics of both epimorphic and morphallactic phenomena.     

Obstetric analgesia using continuous epidural perfusion of bupivacaine, adrenaline, and fentanyl

OBJECTIVES: To determine the efficacy and complications of continuous epidural perfusion of bupivacaine, adrenaline and fentanyl in the relief of pain during first and second stage labour during vaginal birth. PATIENTS AND METHODS: Between January 1990 and March 1993 we used continuous epidural perfusion for control of pain during labor in 1307 women. The solution administered through an epidural catheter and maintained until expulsion was one 10 ml bolus of bupivacaine 0.25% with adrenaline 1:200,000 and fentanyl 25 micrograms followed by continuous perfusion of bupivacaine 0.0625% with adrenaline 1:200,000 and fentanyl 2 micrograms/ml at an infusion rate of 12 ml/h. When analgesia was insufficient, a bolus of local anesthetic was administered or a pudendal block was carried out. RESULTS: Ninety-two percent of the birthing women reported good analgesic effect during the first stage; for 7% the effect was fair and for 0.55% it was poor. During the second stage 88% reported satisfactory analgesia, and 8% fair or poor. Assessment was not possible for the remaining women, who underwent cesarean sections. Complications were few and easily controllable. CONCLUSIONS: Maintenance of epidural perfusion with 0.0625% bupivacaine with adrenaline 1:200,000 and fentanyl 2 micrograms/ml provides sufficient analgesia during all stages of childbirth.     

New species of Aeromonas isolated in Cuba

One hundred and fifty-five strains of Aeromonas isolated in the stools of children under 5 years presenting with acute diarrheal disease were studied. Using the Aerokey II system for the identification of species, 47 strains were identified as Aeromonas caviae, 58 as Aeromonas hydrophila, 23 as Aeromonas veronii biovar sobria, 14 as Aeromonas trota, 9 as Aeromonas veronii biovar veronii, 2 as Aeromonas jandaei and 2 as Aeromonas shubertii, Emphasis is placed on the advantages of this method which allowed for the classification of new species not identified previously in our country.     

Cathepsin L2, a novel human cysteine proteinase produced by breast and colorectal carcinomas

We have identified and cloned a new member of the papain family of cysteine proteinases from a human brain cDNA library. The isolated cDNA codes for a polypeptide of 334 amino acids that exhibits all of the structural features characteristic of cysteine proteinases, including the active site cysteine residue essential for peptide hydrolysis. Pairwise comparisons of this amino acid sequence with the remaining human cysteine proteinases identified to date showed a high percentage of identity (78%) with cathepsin L; the percentage of identity with all other members of the family was much lower (<40%). On the basis of these structural characteristics, we have tentatively called this novel protein cathepsin L2. The cDNA encoding the mature cathepsin L2 was expressed in Escherichia coli, and after purification, the recombinant protein was able to degrade the synthetic peptide benzyloxycarbonyl-L-phenylalanyl-L-arginine-7-amido-4-methylcoumarin, which is commonly used as a substrate for cysteine proteinases. Cathepsin L2 proteolytic activity on this substrate was abolished by trans-epoxysuccinyl-L-leucylamido-(4-guanidino)butane, an inhibitor of cysteine proteinases, thus providing additional evidence that the isolated cDNA encodes a functional cysteine proteinase. Northern blot analysis of polyadenylated RNAs isolated from a variety of human tissues demonstrated that cathepsin L2 is predominantly expressed in the thymus and testis. This finding is in marked contrast with the wide tissue distribution of most cysteine proteinases characterized to date, including cathepsin L, and suggests that cathepsin L2 may play a specialized role in the thymus and testis. Expression analysis of cathepsin L2 in human tumors revealed a widespread expression in colorectal and breast carcinomas but not in normal colon or mammary gland or in peritumoral tissues. Cathepsin L2 was also expressed by colorectal and breast cancer cell lines as well as by some tumors of diverse origin, including ovarian and renal carcinomas. These results open the possibility that this novel enzyme may be involved in tumor processes, as already reported for other cysteine proteinases, including cathepsin L.