Effects of oxytocin microinjected into the central amygdaloid nucleus and bed nucleus of stria terminalis on maternal aggressive behavior in rats

The central effect of oxytocin (OT) on the aggressive behavior of lactating rats was studied. Female rats are more aggressive than nonlactating resident females, vigorously attacking conspecific intruder male or females. This behavior is considered important for pup protection against infanticide. The present work aimed to test the effects on maternal aggressive behavior of OT infused into the central amygdaloid nucleus (CeM) or bed nucleus of stria terminalis (BNST). The surgeries for bilateral cannula implantation were performed between the 2nd and 4th postpartum day. Three days after the surgery, saline or OT was infused and 5 min later a male intruder was placed in the home-cage and the behaviors were videotaped for 10 min. The frequency of the aggressive behaviors and the duration of locomotion during the aggressive behavior test were measured. The latency to retrieve the pups was also evaluated. The results showed that OT injected into CeM (10 and 20 ng/nucleus) decreased frequency of biting and frontal attack while in the BNST (10 and 20 ng/nucleus) decreased the frequency of biting. No significant change on retrieval activity was detected. OT in CeM and BNST has an inhibitory effect on the aggressive behavior of lactating female rats.     

Establishing a national HTA program for medical devices in Italy: Overhauling a fragmented system to ensure value and equal access to new medical technologies

Differing contexts have greatly influenced HTA development in various countries, with considerable effort recently made by international HTA networks (e.g., EUnetHTA) and the European Union (EU) to make HTA a more coherent, equal, and efficient process. Medical devices (MDs) present particular challenges for HTA because of frequent, rapid innovation, outcomes influenced by end-user competence, dynamic pricing and often low-quality scientific evidence. Our objective is to describe the development, structure and governance of a National HTA Program for MDs (PNHTADM) in Italy, a highly participatory, stakeholder-engaged, evidence-based process to reform a fragmented system of appraisal and approval. Based largely on EUnetHTA methods, the resulting process delineates a standardized system for proposing MDs by any stakeholders, accrediting HTA producers, setting criteria for prioritization and appraisals, and innovatively linking recommendations with coverage, reimbursement and procurement of MDs. Expected benefits include reduced disparities in pricing and reimbursement policies and improved access to new technologies across 21 regional healthcare systems in Italy's decentralized, universal system, complete with provisions to require additional evidence collection and centrally monitor diffusion. Though devised for Italy, the design, resources and underlying analysis provide a framework for other nations seeking to consolidate HTA initiatives, particularly in light of new EU regulation.     

Bulbectomy Enhances Neurogenesis and Cell Turnover of Primary Olfactory Neurons But Does Not Abolish Carnosine Expression

Primary olfactory neurons located in the olfactory neuroepithelium project to the ipsilateral olfactory bulb and undergo a continuous process of neurogenesis and differentiation. We describe, in the adult rat, the kinetics of proliferation, differentiation and survival of primary olfactory neurons either in the presence or absence of their target, the olfactory bulb. The experimental design included unilateral bulbectomy, coupled with a single bromodeoxyuridine pulse 35 days after surgery. The rate of proliferation and survival of olfactory neurons was then examined by immunohistochemistry for bromodeoxyuridine, and the differentiation status by in situ hybridization for calmodulin messenger RNA in immature and mature olfactory neurons and immunohistochemistry for the dipeptide carnosine in mature olfactory neurons. We show that primary olfactory neurons can synthesize carnosine in the absence of the olfactory bulb. However, the number of carnosine-immunopositive neurons in the absence of their target is dramatically reduced to less than one-fourth, whereas the number of olfactory neurons expressing calmodulin messenger RNA is only slightly reduced. The numeric reduction of camosine-positive neurons in the target-deprived neuroepithelium is correlated with a dramatic reduction in the survival rate of olfactory neurons, since newly generated olfactory neurons are completely lost 35 days after the bromodeoxyuridine pulse. In contrast, in the normal olfactory neuroepithelium almost one-third of newly generated olfactory neurons survive 35 days after the bromodeoxyuridine pulse. On the whole, these data indicate that most of the primary olfactory neurons have a short lifespan but that once they have connected with the olfactory bulb they may persist longer, and suggest that throughout adulthood olfactory neurons are overproduced, differentiate independently from their target, and then undergo a process of target-induced neuronal selection.     

Trastuzumab down-regulates Bcl-2 expression and potentiates apoptosis induction by Bcl-2/Bcl-XL bispecific antisense oligonucleotides in HER-2 gene--amplified breast cancer cells.

PURPOSE: To investigate the possible existence of an antiapoptotic cross-talk between HER-2 and antiapoptotic Bcl-2 family members. EXPERIMENTAL DESIGN: Bcl-2 and Bcl-XL expression and apoptosis induction were analyzed in HER-2 gene-amplified (BT474) and nonamplified (ZR 75-1) breast cancer cell lines exposed to trastuzumab, alone or in combination with either Bcl-2/Bcl-XL bispecific antisense oligonucleotides (AS-4625) or the small-molecule Bcl-2 antagonist HA14-1. RESULTS: In addition to HER-2 and epidermal growth factor receptor, trastuzumab down-regulated Bcl-2, but not Bcl-XL, protein, and mRNA expression in BT474 cells. Interestingly, trastuzumab-induced down-regulation of HER-2 and Bcl-2 was also observed in three of five and two of three breast cancer patients undergoing trastuzumab treatment, respectively. Despite Bcl-2 down-regulation, however, trastuzumab only marginally increased the rate of apoptosis (7.3 +/- 3.5%). We therefore investigated whether a combination of AS-4625 and trastuzumab might increase proapoptotic efficiency. AS-4625 treatment of BT474 cells decreased both Bcl-2 and Bcl-XL expression, resulting in a 21 +/- 7% net apoptosis induction; the combination of AS-4625 followed by trastuzumab resulted in a significantly stronger induction of apoptosis (37 +/- 6%, P <0.01) that was not observed with the reverse treatment sequence (trastuzumab followed by AS-4625). Similar results were obtained with the Bcl-2 antagonist HA14-1; indeed, exposure of BT474 cells to HA14-1 followed by trastuzumab resulted in a striking proapoptotic synergism (combination index=0.58 +/- 0.18), as assessed by isobologram analysis. CONCLUSIONS: Altogether our findings suggest that combined targeting of HER-2 and Bcl-2 may represent a novel, rational approach to more effective breast cancer therapy.     

DEFB-1 genetic polymorphism screening in HIV-1 positive pregnant women and their children.

OBJECTIVE: In our study we evaluated the frequency of three SNPs (-52 G/A, -44 C/G; -20 G/A) in the 5' UTR of DEFB-1 gene, in a cohort of 130 HIV-1 infected mothers and their children, collected by the Italian group SIGO in Obstetrics and Gynecology. METHODS: The three SNPs (-52 G/A, -44 C/G; -20 G/A) in the 5' UTR of DEFB-1 gene were genotyped by direct sequencing of PCR products. RESULTS: The C allele at position -44 was shown to be significantly different in both HIV-1 positive mothers and their children when compared to the healthy controls. The odds ratio for -44 C allele in children born to HIV-1 infected mothers is 7.09 (confidence interval 3.38-15.3) while the odds ratio for this allele in HIV-1 infected mothers is 6.42 (confidence interval 3.14-13.4). CONCLUSIONS: Our results evidence a high frequency of the -44 CC allele in HIV-1 infected mothers and their children with augmented potential risk of maternal fetal transmission. This potential vertical transmission risk has been successfully prevented by antiretroviral drug treatment and cesarian section of the HIV-1 positive mothers.     

Effects of dark chocolate on endothelial function in patients with non-alcoholic steatohepatitis

Background and Aim

Oxidative stress plays a pivotal role in inducing endothelial dysfunction and progression from simple fatty liver steatosis (FLD) to non-alcoholic steatohepatitis (NASH). Polyphenols could reduce oxidative stress and restore endothelial function by inhibiting the nicotinamide-adenine-dinucleotide-phosphate (NADPH) oxidase isoform Nox2.The aim of this study was to assess endothelial function and oxidative stress in a population affected by simple FLD and NASH. Furthermore, we analysed the effect of high vs low content of cocoa polyphenols on endothelial function and oxidative stress in patients with NASH.