Hypertension induces brain β-amyloid accumulation, cognitive impairment, and memory deterioration through activation of receptor for advanced glycation end products in brain vasculature

Although epidemiological data associate hypertension with a strong predisposition to develop Alzheimer disease, no mechanistic explanation exists so far. We developed a model of hypertension, obtained by transverse aortic constriction, leading to alterations typical of Alzheimer disease, such as amyloid plaques, neuroinflammation, blood-brain barrier dysfunction, and cognitive impairment, shown here for the first time. The aim of this work was to investigate the mechanisms involved in Alzheimer disease of hypertensive mice. We focused on receptor for advanced glycation end products (RAGE) that critically regulates Aβ transport at the blood-brain barrier and could be influenced by vascular factors. The hypertensive challenge had an early and sustained effect on RAGE upregulation in brain vessels of the cortex and hippocampus. Interestingly, RAGE inhibition protected from hypertension-induced Alzheimer pathology, as showed by rescue from cognitive impairment and parenchymal Aβ deposition. The increased RAGE expression in transverse aortic coarctation mice was induced by increased circulating advanced glycation end products and sustained by their later deposition in brain vessels. Interestingly, a daily treatment with an advanced glycation end product inhibitor or antioxidant prevented the development of Alzheimer traits. So far, Alzheimer pathology in experimental animal models has been recognized using only transgenic mice overexpressing amyloid precursor. This is the first study demonstrating that a chronic vascular insult can activate brain vascular RAGE, favoring parenchymal Aβ deposition and the onset of cognitive deterioration. Overall we demonstrate that RAGE activation in brain vessels is a crucial pathogenetic event in hypertension-induced Alzheimer disease, suggesting that inhibiting this target can limit the onset of vascular-related Alzheimer disease.     

Hypocomplementemic tubulointerstitial nephritis in IgG4-related disease

A novel lymphoproliferative disorder producing plasma cell expansion in the affected organ with fibrotic or sclerosing changes, known as 'IgG4-related disease', was defined in Japan by Umehara's group in 2010. We present the first case reported in Italy. In 2007, a 63-year-old man presented with epigastric pain and elevated serum lipase levels. Computed tomography of the abdomen revealed a Kuttner's tumor of the pancreas. The patient underwent a biliary-enteric anastomosis, and biopsy of the pancreas revealed massive infiltration of lymphocytes and plasma cells. The patient was diagnosed with chronic sclerosing pancreatitis. After one year, he began to show signs of sicca syndrome and at the same time developed progressive renal failure. Immunological tests revealed hypocomplementemia, and the renal biopsy specimen showed diffuse interstitial inflammation. The infiltrate was composed of lymphocytes, while infiltrating plasma cells showed immunoreactivity to IgG-4. Sialography using a radioisotope revealed severe involvement of the salivary glands, and Schirmer's test gave a positive result. This led us to diagnose hypocomplementemic tubulointerstitial nephritis in IgG4-related disease. Corticosteroid treatment resulted in rapid improvement including disappearance of the sicca syndrome and progressive amelioration of renal function. After six months, we discontinued steroid administration and started mycophenolate mofetil to maintain a low degree of immunosuppression. Follow-up after two years showed that this therapy continued to be quite effective in our patient.     

Emotion recognition impairment is present early and is stable throughout the course of schizophrenia

Individuals with schizophrenia experience problems in the perception of emotion throughout the course of the disorder. Few studies have addressed the progression of the deficit over time. The present investigation explores face emotion recognition (FER) performance throughout the course of schizophrenia. The aim of the study was to test the hypotheses that: 1) FER impairment was present in ultra high-risk (putatively prodromal) individuals, and that 2) impairment was stable across the course of the illness. Forty-three individuals with a putative prodromal syndrome, 50 patients with first episode of schizophrenia, 44 patients with multi-episode schizophrenia and 86 unaffected healthy control subjects were assessed to examine emotion recognition ability. ANCOVA analysis adjusted for possible confounder factors and subsequent planned contrasts with healthy controls was undertaken. The results revealed deficits in recognition of sadness and disgust in prodromal individuals, and of all negative emotions in both first-episode and multi-episode patients. Furthermore, there were no significant differences between clinical groups. Within the framework of the neurodevelopmental model of schizophrenia, our results suggest the presence of emotional recognition impairment before the onset of full-blown psychosis. Moreover, the deficit remains stable over the course of illness, fitting the pattern of a vulnerability indicator in contrast to an indicator of chronicity or severity.     

Fine-tuning of social play in juvenile lowland gorillas (gorilla gorilla gorilla)

Social play, which involves cooperation, communication, and learning, may represent a suitable field for the investigation of cognitive ability in a given species. We collected data on a captive group of gorillas in order to evaluate the potential cognitive skill of juveniles in fine-tuning play behavior. This study revealed that juvenile gorillas are able to "place" the play session in a proper spatial/temporal context, thus evaluating a complex net of factors (e.g., play partner, play roughness, group activity, space availability). When animals play fight, they use patterns of agonistic functional contexts. Since these actions are not intrinsically different from their "serious" context, it may be hard to distinguish them. One of the most important function of play in the ontogeny of primate social cognition may be to recognize stimuli, which may indicate the intentions of conspecifics. Accordingly, we found that juvenile gorillas are able to use play signals appropriately when a clear statement of purpose is necessary (i.e., during male-male competitive play sessions and when the escape opportunities are limited). The ability to interpret such ambiguous features of social signaling could represent a central issue in the evolution of behavioral flexibility and intelligence in primates.     

Lurasidone: efficacy and safety in the treatment of psychotic and mood disorders

Introduction: Lurasidone ([3aR,4S,7R,7aS]-2-[(1R,2R)-2-[4-(1,2-benzisothiazol-3-yl)piperazin-1yl-methyl] cyclohexylmethyl]-hexahydro-4,7-methano-2H-isoindole-1,3-dione hydrochloride; Latuda®) is a novel benzisothiazole, second-generation antipsychotic drug developed by Dainippon Sumitomo Pharma Corporation in Japan. Similar to other atypical antipsychotics it has a distinctive pharmacodynamic profile,

Areas covered: This review updates reported research findings on the efficacy, safety and tolerability of LRSD for treatment of psychotic and major affective disorders, with meta-analyses. Short-term efficacy of LRSD in schizophrenia is supported by several randomized, controlled trials with daily doses of 40–160 mg, yielding relatively modest symptomatic improvements. Lurasidone has regulatory approval for treatment of undefined duration in schizophrenia. Long-term benefits and effects in schizophrenia, and both short- and long-term use for other psychotic disorders and mania have not been tested. LRSD shows unusual efficacy in acute bipolar depression even without psychotic features. However, trials of adding LRSD to lithium or valproate for bipolar disorder have yielded inconsistent findings.

Expert opinion: Available research findings indicate that LRSD is effective and well-tolerated for short-term treatment of schizophrenia, and for acute bipolar depression. It has low risk of inducing weight-gain, metabolic, or cardiac abnormalities, but its risk of akathisia may exceed that of other modern antipsychotics. Needed is adequate long-term testing in schizophrenia and bipolar disorder and testing for other indications, including against alternative treatments.     

How to evaluate the outflow tract of LVAD after minimally invasive implantation by 3D CT-scan

During a minimally invasive implantation technique, the outflow graft of left ventricular assist device (LVAD) is tunnelled blindly through the pericardium or left pleura, with an inability to assess for twisting or malposition. Three-dimensional computed tomography scan (CT-scan) has a role in qualitative evaluation of the different outflow tract configurations. The different surgical minimally invasive approaches include: (a) mini-sternotomy and left mini-thoracotomy, (b) right mini-thoracotomy and left mini-thoracotomy, (c) subclavian artery access and left mini-thoracotomy. The outflow graft could be anastomosed to the left axillary artery or the ascending aorta. CT-scan reconstruction using syngo InSpace4D (Siemens, Muenchen, Germany) was used to provide fast segmentation and high-resolution images. The 3D reconstructions permit an evaluation of different anastomosis configurations and to assess the route of outflow graft.     

Tilt testing potentiated with sublingual nitroglycerin in children with unexplained syncope.

AIMS: The aim of this prospective study was to assess the diagnostic value of a sublingual nitroglycerin (NTG) potentiated head-up tilt (HUT) testing protocol in children with unexplained syncope. METHODS AND RESULTS: One hundred and sixty-four consecutive paediatric patients with syncope of unknown origin and no evidence of organic heart disease (115 female, mean age 13 +/- 3 years) and 29 control children underwent a sublingual NTG-potentiated tilt testing protocol. Paediatric patients and controls were tilted at 60 degrees for 20 min and, if no symptom occurred, for other 15 min after sublingual 400 mug spray NTG administration. During the drug-free phase of the test, 13 patients (8%) and no controls had a positive response. After drug administration, a positive response occurred in another 88 patients (55%) and in four controls (14%), whereas an exaggerated response was observed in nine patients (5%) and in four controls (14%). Thus, the positive rate and specificity of sublingual NTG HUT test in children were 63 and 86%, respectively. No relevant adverse events were observed during the test. CONCLUSION: Tilt testing potentiated with sublingual NTG has proved to be effective and safe in unmasking the neurally mediated origin of unexplained syncope in children. The NTG challenge greatly increased the positive rate of passive tilt, with a small decrease in specificity.