Sex differences on spontaneous alternation in prepubertal rats: implications for an animal model of obsessive-compulsive disorder

Sex differences in the prevalence of obsessive-compulsive disorder (OCD) in prepubertal children have been described. Deficits on spontaneous alternation behavior (SAB) have been proposed as an animal model of OCD. OBJECTIVES: To explore possible sex differences in the ontogeny of SAB and in the effect of the 5-HT1A agonist, 8-OH-hydroxy-2 (di-n-propylamino)-tetralin (8-OH-DPAT) in an animal model of OCD. METHODS: The ontogeny of SAB and the perseveration produced by 8-OH-DPAT were compared between male and female prepubertal rats. RESULTS: Males alternated their arm choose from postnatal day 32 onwards, while females perseverated in the chosen arm until postnatal day 38. The mean number of repetitive choices remained close to 1 in males from postnatal day 23 onwards, but females showed a mean number of repetitive choices higher than 1.5 until the end of the test. The 8-OH-DPAT (0.125, 0.5 and 2.0 mg/kg, 15 min) produced perseveration in males but not in females. CONCLUSIONS: These data show important sex differences in the ontogeny of SAB and the effect of 8-OH-DPAT in a model of OCD. Such differences could be relevant for the sex differences in the prevalence of childhood OCD.     

Efficacy of AT in pre-eclampsia: a case-control prospective trial

Pre-eclampsia is an extremely severe condition. It is associated with vasospasm, activation of the coagulation system and abnormal haemostasis. In pre-eclamptic patients increased plasmatic concentrations of fibronectin, laminin, von Willebrand factor (VWF) and endothelin are observed. Experimental studies on rats have also shown that the doses of antithrombin III (AT) needed to mediate anti-inflammatory processes are much higher than those required to obtain the anti-coagulant effect. The study aimed to evaluate the clinical efficacy of treatment with high AT doses (HD) in comparison with standard doses (SD). The primary endpoint was the prolongation of pregnancy defined as time (in days) from enrollment to delivery and to assess the maternal bleeding at and after delivery. The secondary endpoint was to demonstrate a role for AT in controlling haemostasis at conventional doses, and the inflammatory state at higher doses. The biochemical parameters assessed were: AT activity (%), Fibronectin (Fn), Fibrinogen, D-dimer, Uricemia, Proteinuria 24h, Protein C Reactive (PCR), Granulocyte Elastase and Endothelin. This study included 23 pre-eclamptic women. Patients were randomly subdivided into two groups: 10 patients ("cases") were treated with high doses of AT (6 vials: 3000 units) once daily for 5 days, or until delivery, while 13 women ("controls") were treated with doses of AT sufficient to maintain at least 80% of the activity. High-dose therapy was associated with prolongation of pregnancy by 2.5 days more when compared with controls (p = 0.03; Mann-Whitney test). The incidence of clinical significant bleeding was lower in cases than in controls (mean 550 mL vs. 650 mL, respectively). Preventive- and conservative-type treatment of moderate-severe pre-eclampsia, based on the administration high doses of AT, allows a significant prolongation of pregnancy, and thus a better neonatal outcome, as well as less maternal intra- and post-operative bleeding. Fn, PCR and elastase levels (markers of inflammation) decrease in the HD group in comparison with SD group. In the HD group, the AT plasma levels were obviously higher both at the end of the treatment (p < 0.0001) and after delivery (p = 0.03), in comparison with SD group. The fibrinogen and D-dimer levels were above the reference interval in both groups. TPA and PAI 1 were found to be significantly raised in the course of pre-eclampsia. In conclusion, the bio-chemical findings support a role for AT in controlling the haemostasis at conventional doses, and the inflammatory state at higher doses.     

Prenatal diagnosis of vein of Galen aneurysmal malformations

Vein of Galen aneurysmal malformations are rarely seen intracranial malformations. They represent less than 1% of the cerebral arteriovenous malformations. Prenatal diagnosis of an arteriovenous fistula malformation may be achieved by real-time and Doppler sonography with color flow imaging, by identifying dilated veins and arteriovenous shunts with turbulent flow. In addition, an elevated cardiac output may be observed and correlated with the magnitude of the cerebral arteriovenous shunt. The high incidence of cardiomegaly in neonates with arteriovenous malformations also suggests that high-output cardiac failure is already present in a significant number of cases during the 3rd trimester, and, therefore, treatment in utero may need to be considered to improve the hemodynamic status. In our case, all the above cardiovascular features were present during prenatal ultrasonography. The information on outcome compiled from the literature suggests that when an arteriovenous malformation is large enough to be detected prenatally, as in our case, it is likely to lead to cardiac failure either during the antenatal period or soon after birth. In this paper, we present the management of a case of 3rd-trimester diagnosis of a vein of Galen aneurysm associated with cardiac decompensation.     

Neurologic symptoms after great saphenous vein harvesting for coronary artery bypass grafting

AIM: Incidence evaluation of cutaneous neurologic symptoms in the lower limbs as a new event after great saphenous vein (GSV) harvesting for coronary artery bypass grafting (CABG). Each day we harvest the GSV for CABG. Some authors have reported the onset of saphenous neuralgia complex as a new event of which we would evaluate the incidence. METHODS: From January 2000, until June 2001, 2,091 patients underwent cardiac surgery; 1,326 underwent CABG, 1,227 of them using the GSV as a conduit for almost one graft. These patients were prospectively reviewed; all were preoperatively examined to determine the presence of normal sensation in the lower limbs and elude the presence of saphenous neuralgia. Then, we evaluated sensations in the lower limbs at 5 days, 8 weeks, and 5 months after operation to determine the new onset of saphenous neuralgia. The areas of sensory loss were recorded each time and reported in a diagram to obtain 3 areas. RESULTS: Hyperaesthesia and pain were noted in a few patients, especially at 5 days and 8 weeks control, but at 5 months none of them complained of real pain. CONCLUSION: This study demonstrates that saphenous neuralgia after harvesting the GSV for CABG is a rare consequence. The main symptom is anaesthesia but its duration is generally no longer than 2 months. Hyperaesthesia and pain, for the early onset and the early disappearance, are considered as a normal consequence of surgical procedure.     

Minimum effective doses of haloperidol for the treatment of first psychotic episode: a comparative study with risperidone and olanzapine

Minimum doses of haloperidol might show similar efficacy and side-effects compared to atypical antipsychotics. The objectives of this study were to compare the efficacy of minimum doses of haloperidol with standard doses of risperidone and olanzapine on a 6-month open trial in first psychotic episode patients and to examine the effect of compliance on their outcome. Forty-two patients were recruited and started on flexible doses of these drugs. Olanzapine was given with no cost to the patients. Efficacy and side-effects were monitored every 3 months using standardized assessments. Thirty patients completed the study. All treatment groups showed improvement in positive, negative and depressive symptoms. There were no differences in side-effects among them. The haloperidol group required higher doses of anticholinergics. The rate of treatment discontinuation was higher in the risperidone group due to the direct cost. Minimum doses of haloperidol might prove to be a good choice of treatment for patients with a first episode of psychosis.     

Growth of cultured porcine retinal pigment epithelial cells

PURPOSE: To establish and characterize cultures of porcine retinal pigment epithelial (pRPE) cells in order to produce confluent monolayers of cells for transplantation. METHODS: Primary pRPE cell cultures were established. Cell morphology was assessed by phase contrast and electron microscopy. Growth was determined by the crystal violet dye uptake assay. DNA synthesis and content were measured by incorporation of 3H-thymidine and flow cytometry. RESULTS: This primary culture resulted in cells with well-preserved morphology that could be propagated in up to six passages. The deterioration observed over time in cultures was not due to a constant high rate of cell turnover as postconfluency cell proliferation was limited. However, a large fraction of the cells had a high DNA content despite a lack of active DNA synthesis. CONCLUSIONS: The present method yields pRPE cells of high purity and proliferative capacity with preserved epithelial phenotype. However, aberrant DNA profiles and the deterioration of cell morphology observed over time in this graft material represent serious problems in RPE transplantation.     

Malnutrition is not related to alterations in energy balance in patients with stable liver cirrhosis

BACKGROUND AND AIMS: Little information are available on the relationship between energy balance and the alterations in nutritional status occurring in cirrhotic patients. The aim of the present study was to evaluate the daily energy balance in clinically stable cirrhotic patients with or without malnutrition.PATIENTS: Seventy-four consecutive cirrhotic patients and nine healthy controls were studied.METHODS: Basal energy expenditure was measured by indirect calorimetry and adjusted according to the patients' physical activity to estimate the daily energy expenditure. Food intake was evaluated based on a 3-day dietary diary. Nutritional status and body composition were assessed using skinfold anthropometry and dual energy X-ray absorptiometry, respectively.RESULTS: Thirty-two patients in the cirrhotic group were classified as severely malnourished according to anthropometric parameters. Two different patterns of soft-tissue loss were observed in the malnourished cirrhotic group: a significant reduction in fat mass and in fat-free mass was observed in males, whereas, females showed a significant reduction in fat mass only. Basal energy expenditure was similar in all groups, while the non-protein respiratory quotient was lower in cirrhotics notwithstanding their nutritional status. This suggests that lipids were the preferred oxidized fuel in the post-absorptive state in these patients. No difference in the estimated daily energy expenditure and energy intake was observed among groups. Lipid content of the diet was significantly lower in malnourished cirrhotics than in controls (33.1+/-1% vs 37.8+/-1%, P=0.02).CONCLUSIONS: Cirrhotic patients in stable clinical condition with malnutrition show a normal energy balance.     

Paracetamol effectively reduces prostaglandin E2 synthesis in brain macrophages by inhibiting enzymatic activity of cyclooxygenase but not phospholipase and prostaglandin E synthase

Epidemiological studies indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) are neuroprotective, although the mechanisms underlying their beneficial effect remain largely unknown. Given their well-known adverse effects, which of the NSAIDs is the best for neurodegenerative disease management remains a matter of debate. Paracetamol is a widely used analgesic/antipyretic drug with low peripheral adverse effects, possibly related to its weak activity as inhibitor of peripheral cyclooxygenase (COX), the main target of NSAIDs. As microglia play an important role in CNS inflammation and pathogenesis of neurodegenerative diseases, we investigate the effect of paracetamol on rat microglial cultures. Although less potent than other NSAIDs, (indomethacin approximately NS-398 > flurbiprofen approximately piroxicam > paracetamol approximately acetylsalicylic acid), paracetamol completely inhibited the synthesis of prostaglandin E(2) (PGE(2)) in lipopolysaccharide-stimulated microglia, when used at concentrations comparable to therapeutic doses. The drug did not affect the expression of the enzymes involved in PGE(2) synthesis, i.e., COX-1, COX-2, and microsomal PGE synthase, or the release of the precursor arachidonic acid (AA). Paracetamol inhibited the conversion of exogenous AA, but not PGH(2), into PGE(2) indicating that the target of the drug is COX activity. Consistently, paracetamol inhibited with similar IC(50) the synthesis of PGF(2alpha) and thromboxane B(2), two other COX metabolites. Finally, none of the NSAIDs affected the productions of nitric oxide and tumor necrosis factor(alpha), two inflammatory mediators released by activated microglia. As paracetamol was reported to inhibit PG synthesis in peripheral macrophages with an IC(50) at least three orders of magnitude higher than in microglia, we suggest that this drug represents a good tool for treating brain inflammation without compromising peripheral PG synthesis.