Lrrk2 G2019S substitution in frontotemporal lobar degeneration with ubiquitin-immunoreactive neuronal inclusions

Leucine-rich repeat kinase 2 (LRRK2) mutation carriers can develop clinical symptoms other than typical parkinsonism such as dementia, amyotrophy or dystonia. To determine if LRRK2 mutations might be involved in frontotemporal dementia (FTD), 5 individuals with multiplex familial FTD kindreds and 41 pathologically confirmed cases of FTD, including 23 with a family history of dementia, were screened for genetic variations in the LRRK2 gene. We identified a LRRK2 mutation leading to the G2019S amino acid substitution in a 79-year-old woman with frontotemporal lobar degeneration with ubiquitinated neuronal intranuclear inclusions (FTLD-U/NII) and a possible family history of tremor. These findings may be coincidental; however, there is a small nucleus of LRRK2-positive patients displaying atypical features suggesting a role for this protein in other neurodegenerative disorders.     

Angiotensin-(1-7) through receptor Mas mediates endothelial nitric oxide synthase activation via Akt-dependent pathways

Angiotensin-(1-7) [Ang-(1-7)] causes endothelial-dependent vasodilation mediated, in part, by NO release. However, the molecular mechanisms involved in endothelial NO synthase (eNOS) activation by Ang-(1-7) remain unknown. Using Chinese hamster ovary cells stably transfected with Mas cDNA (Chinese hamster ovary-Mas), we evaluated the underlying mechanisms related to receptor Mas-mediated posttranslational eNOS activation and NO release. We further examined the Ang-(1-7) profile of eNOS activation in human aortic endothelial cells, which constitutively express the Mas receptor. Chinese hamster ovary-Mas cells and human aortic endothelial cell were stimulated with Ang-(1-7; 10(-7) mol/L; 1 to 30 minutes) in the absence or presence of A-779 (10(-6) mol/L). Additional experiments were performed in the presence of the phosphatidylinositol 3-kinase inhibitor wortmannin (10(-6) mol/L). Changes in eNOS (at Ser1177/Thr495 residues) and Akt phosphorylation were evaluated by Western blotting. NO release was measured using both the fluorochrome 2,3-diaminonaphthalene and an NO analyzer. Ang-(1-7) significantly stimulated eNOS activation (reciprocal phosphorylation/dephosphorylation at Ser1177/Thr495) and induced a sustained Akt phosphorylation (P<0.05). Concomitantly, a significant increase in NO release was observed (2-fold increase in relation to control). These effects were blocked by A-779. Wortmannin suppressed eNOS activation in both Chinese hamster ovary-Mas and human aortic endothelial cells. Our findings demonstrate that Ang-(1-7), through Mas, stimulates eNOS activation and NO production via Akt-dependent pathways. These novel data highlight the importance of the Ang-(1-7)/Mas axis as a putative regulator of endothelial function.     

Evidence for Mas-mediated bradykinin potentiation by the angiotensin-(1-7) nonpeptide mimic AVE 0991 in normotensive rats

We evaluated the effect of the nonpeptide mimic of angiotensin (Ang)-(1-7), AVE 0991, on the hypotensive effect of bradykinin (BK). Increasing doses of intra-arterial or intravenous BK were administered before and 30 minutes after the beginning of AVE 0991 infusion. The effect of AVE 0991 on plasma Ang-converting enzyme activity was tested using Hip-His-Leu as the substrate. The interaction of AVE 0991 with Ang-converting enzyme in vivo was tested by determining its effect on the pressor action of Ang I or Ang II. AVE 0991 produced a significant and similar potentiation of intra-arterial or intravenous bradykinin. AVE 0991 did not inhibit plasma Ang-converting enzyme activity in vitro or the pressor effect of Ang I in vivo. N(W)-nitro-l-arginine methyl ester or D-Ala(7)-Ang-(1-7) administration abolished the BK potentiating effect of AVE 0991. We further examined the BK-potentiating effect of AVE 0991, evaluating its effect on NO production in rabbit endothelial cells. The NO release was measured using the 4-amino-5-methylamino-2'-7'-difluorofluorescein diacetate. A synergistic effect of AVE 0991 and BK on NO release was observed. These results suggest that AVE 0991 potentiates bradykinin through an Ang-converting enzyme-independent, NO-dependent receptor Mas-mediated mechanism. This effect may contribute to the improvement of endothelial function by AVE 0991 in vivo.     

1-year follow-up study of cognitive function in first-episode non-affective psychosis

The longitudinal course of primary cognitive dysfunction seen in schizophrenia has yet to be fully clarified. Whereas some studies in chronic patients have revealed a progressive decline in cognitive abilities, those studies with first-episode patients have indicated that initial cognitive deficits might remain stable over time. The aim of this study was to examine the longitudinal course of cognitive functioning in patients with a first episode of schizophrenia. 112 patients with a first episode of schizophrenia-spectrum disorders and 22 healthy controls completed clinical and cognitive evaluations at baseline and again after 1 year. An extensive neuropsychological battery that comprised seven cognitive domains was used. Patients and controls improved their cognitive performance in virtually all the cognitive domains after one year. However, patients continued to show marked cognitive deficits after one year, unlike healthy volunteers. The longitudinal cognitive changes were similar in patients and controls in all domains except Verbal Memory (F = 11.67; df = 1; P = 0.001). The increase in cognitive scores found during early phases of the illness seems to be associated to practice-related changes and would not reflect a real cognitive enhancement but rather stability of deficit. Patients' deficits remained stable over time in all cognitive domains except Verbal Memory, in which less performance improvement was found. Further investigations are warranted to discern the variability in patterns of specific cognitive deficits over time.     

Prostate adenocarcinoma and synchcronous multiple myeloma: a case report

PurposeTo report a case of syncrhronous prostatic cancer with multiple myeloma as inusual neoplasm presentation. To indicate the clinical data that they help to suspect the myeloma presence in the prostate bone metastatic disease.Case reportPatient 63 years old diagnosed of prostatic carcinoma with bone metastasis and BAC good responsive, who have clinical deterioration, hypercalcemia and renal insufficiency.ResultsThe presacred mass biopsy and extension study to find one second tumour (myeloma).ConclusionThe presence of multiple myeloma must be to rule out when there are bone lytics injuries, well biochemical evolution with therapy and clinical deterioration, hypercalcemia and quickly progressive renal insufficiency.     

Evaluation of guidelines for the assessment of success after vasectomy and needed improvements

ObjectivesThe evaluation of a recently established guidelines about the assessment of semen samples after vasectomy in the laboratory of the Hospital General of Albacete and to modify them to optimize the number of semen samples provided per patient but keeping in concordande with the international recommendations.Patients and MethodsThe records of seminal analysis results from vasectomies performed from January 2002 to December 2004 were reviewed. Our vasectomy guidelines are based upon those of the British Andrology Society (BAS) and those of the World Health Organization for seminal assessment.ResultsDuring the 3 years 984 patients underwent vasectomy. At follow up, 67% of them returned postvasectomy semen samples, but just 55,5% of them get the clearance criteria; the other patient abandoned before getting them. A mean of 2 samples per patient were received, but 39,6% of them provided one and more than 23% brought more than 3 semen samples. We had 43 technical failures, 4 early recanalization (0,5%) and one late recanalization (0,1%), and 13 patients underwent revasectomy (1,7%).ConclusionA high percentage of our patients failed to fulfill the clearance criteria recommended by the BAS and almost a quarter of them had to deliver more than 3 semen samples. So we find convenient to modify our guides and propose that our patients should receive 2 request forms from the practitioner for semen analysis in the 6th and the 7th month postoperatively and should return to global evaluation of both reports. In that moment most patients will be able to meet the applied criteria for success with just 2 semen samples. Those who fail to become sterile because of either technical failure or early recanalizatione may be advised to go to the urologist with just 2 semen analysis without unnecesary delay.     

Treatment of the first episode of schizophrenia: An update on pharmacologic and psychological interventions

This review emphasizes the recent findings on different pharmacologic and psychological interventions in the treatment of first-episode schizophrenia. Most controlled studies demonstrate that first-and second-generation antipsychotics produce a similar reduction in symptom severity and an overall equal likelihood of clinical response. The cognitive improvements found across atypical antipsychotics were similar and consistent in magnitude with practice effects observed in healthy controls. However, the differential effect of low doses of haloperidol on cognitive function compared with that of second-generation antipsychotics is still debated. The different pattern of metabolic side effects induced by long-term use of antipsychotics is a crucial concern when selecting an antipsychotic treatment for a first-episode patient. More long-term studies are necessary to elucidate the metabolic effects of the different antipsychotic drugs. Cognitive-behavioral therapy and family interventions seem to be effective adjunctive treatments in early phases of schizophrenia in some patients.