Jessenbernstein3338

Heparanase, the sole heparan sulfate degrading endoglycosidase, regulates multiple biological activities that enhance tumor growth, angiogenesis and metastasis. Much of the impact of heparanase on tumor progression is related to its function in mediating tumor-host crosstalk, priming the tumor microenvironment to better support tumor growth and metastasis. We have utilized mice over-expressing (Hpa-tg) heparanase to reveal the role of host heparanase in tumor initiation, growth and metastasis. While in wild type mice tumor development in response to DMBA carcinogenesis was restricted to the mammary gland, Hpa-tg mice developed tumors also in their lungs and liver, associating with reduced survival of the tumor-bearing mice. Consistently, xenograft tumors (lymphoma, melanoma, lung carcinoma, pancreatic carcinoma) transplanted in Hpa-tg mice exhibited accelerated tumor growth and shorter survival of the tumor-bearing mice compared with wild type mice. Hpa-tg mice were also more prone to the development of metaso the primary tumor. Collectively, our results emphasize the significance of host heparanase in mediating the pro-tumorigenic and pro-metastatic interactions between the tumor cells and the host tumor microenvironment, immune cells and systemic factors.Introduction The present study was designed to clarify the effects of resveratrol (RSV) on social behavioral alterations and nociceptive reactivity in valproic acid (VPA)-induced autistic-like model in female and male rats. Methods Pregnant Wistar rats were randomly divided in five groups. Animals received saline, DMSO, VPA, RSV and RSV + VPA. VPA was administered (600 mg/kg, i. p.) on embryonic day 12.5 (E12.5) and pretreatment by resveratrol (3.6 mg/kg, s. c.) was applied on E6.5 until E18.5. All offspring were weaned on postnatal day 21 and the experiments were done in male and female rats on day 60. Social interaction, hot plate and tail flick tests were set out to assess social deficits and pain threshold, respectively. Sociability index (SI), Social novelty index (SNI) and latency time were calculated as the standard indices of social behaviors and pain threshold, respectively. Results The results indicated that systemic intraperitoneal administration of VPA (600 mg/kg) significantly decreased SI and SNI in social interaction test (SIT) especially in male rats, indicating the social impairments caused by VPA. RSV (3.6 mg/kg, s. c.) reversed VPA-induced social deficits in male rats, but not in female group. VPA administration resulted in significant increase in latency time in the hot plate and tail flick tests in male rats, whereas it had no such dramatic effect in females. RSV administration in combination with VPA had no significant effect on latency time compared to the valproic acid group in male rats. It is important to note that RSV by itself had no significant effect on SI, SNI and latency time in female and male rats. Conclusion It can be concluded that valproic acid produces autistic-like behaviors and increases pain threshold in male rats which may be ameliorated at least in part by resveratrol administration. Further studies are needed to elucidate the molecular mechanisms involved in valproic acid and resveratrol-induced effects.Background Hereditary angioedema (HAE) symptoms may be triggered by dental procedures thereby complicating dental care in individuals affected by the condition. Objective This study investigated the self-perceived dental care needs, perceived susceptibility to acute angioedema (AE) attacks after dental procedures and dental care behavior of HAE patients. Methods A self-administered semi-structured web-based questionnaire was distributed to 250 adult HAE patients (Type-1 or -2; 88% Type-1) and 256 matched non-HAE controls. Data was analyzed using stratified chi-square tests, logistic regression, and classification trees. Results 46.4% of HAE vs. 55.5% of control patients had dental visits within 6 months (p=0.04). Dental insurance was a barrier to seeking routine dental visits among both groups. However, significantly fewer HAE patients had routine dental visits within 6 months despite having dental insurance compared to control patients (48% vs. 60%, p=0.01). Within the HAE group, a significantly greater number of patients with dental visits at intervals greater than 6 months had a history of recurrent post-procedural AE attacks (OR3.9 [1.7, 8.8], p=0.0005) and used anti-bacterial toothpaste more frequently than those without recurrent AE attacks (OR 4.7 [1.5, 15.4], p=0.005). Conclusions These data support the hypothesis that HAE patients who are predisposed to having AE episodes in response to medical or physical trauma, visit the dentist less and engage in specific oral hygiene practices more frequently than matched control patients and HAE patients who reported they were less likely to swell after a dental procedure.Background Patients with mastocytosis have an increased risk for severe anaphylaxis, particularly to hymenoptera venoms. These patients may also develop more often systemic hypersensitivity reactions to certain foods. RK701 However, this issue has not been systematically investigated. Objective We aimed to determine prevalence and severity of food-related hypersensitivity (FH) reactions among patients with clonal mast cell disorders (CMD). Methods A retrospective study was conducted among 204 (≥ 18 years) consecutive patients who presented with confirmed CMD (170 with mastocytosis and 34 with monoclonal mast cell activation syndrome [MMAS]). All patients underwent thorough allergy work-up where self-reported FH-reactions were evaluated. Results The prevalence of self-reported FH was 20.6%. The frequency of immunologically mediated reactions was uncommon, as only 3.4% were confirmed by relevant history and IgE-sensitization. Among patients with FH, five had severe anaphylaxis corresponding to an overall prevalence of 2.5%. Most symptoms were restricted to skin (86%), followed by gastrointestinal tract (45%); similar to symptoms that occur in mastocytosis patients also without food-intake. Nuts, spicy foods, seafood and alcohol were the most common incriminated elicitors. There was no significant difference between the groups regarding age, gender, atopic status or IgE levels. Conclusion Anaphylaxis from foods in mastocytosis does exist and is severe, although foods are less frequent elicitor than insect venoms. Further, the frequency of overall FH-reactions is comparable to the general population and most reactions are mild, non-allergic and unconfirmed. Consequently, our results do not support the elimination of any diet in CMD patients without history of FH.