Tailored treatment for signet ring cell gastric cancer

Gastric cancer with Laur\ue8n diffuse types is increasing in the West. The raising trend is more evident when considering signet ring cells (SRC) histology. However, to control the biologic potential of this GC subtype, some hypotheses of tailored therapeutic strategies for SRC cancers have been made. A review of the literature was performed using the key words "signet ring cells" AND "gastric cancer". Results of literature review were descriptively reported. Endoscopic submucosal dissection (ESD), according to the Japanese extended criteria, could be a therapeutic option for early SRC tumours. However, according to the evidences from more recent studies, indications for ESD to these tumours types should be carefully considered. Concerning the optimal surgical treatment, considering the high lymphotropism and infiltrating behaviour of SRC histotype, the extension of gastric resection should be wider than for intestinal type cancer and laparoscopic surgery should be performed carefully. Moreover, D3 lymphadenectomy could provide a benefit in diffuse-type and SRC histology. The role of surgery in gastric cancer with peritoneal carcinomatosis is still debated and studies on this topic should stratify the good results according to GC histotype. Finally, despite the evidences of chemoresistance in SRC, ongoing randomized trials suggest that multimodal therapy could be the best treatment. Based on the assumption that SRC tumours have specific features, they deserve a specific multimodal treatment. However, a preliminary step to generate strong evidences in this field is the standardization of terminology used to define signet ring cells carcinoma

Efficacy of Conventional and Organic Insecticides against Scaphoideus titanus: Field and Semi-Field Trials

Scaphoideus titanus is the main vector of phytoplasmas associated with Flavescence dorée (FD), one of the most serious threats to viticulture in many European countries. To minimize the spread of this disease, mandatory control measures against S. titanus were decided in Europe. In the 1990s, the repeated application of insecticides (mainly organophosphates) proved to be an effective measure to control the vector and the related disease in north-eastern Italy. These insecticides and most of the neonicotinoids were recently banned from European viticulture. Serious FD issues detected in the recent years in northern Italy could be related to the use of less effective insecticides. Trials aimed at evaluating the efficacy of the most used conventional and organic insecticides in the control of S. titanus have been performed in semi-field and field conditions to test this hypothesis. In efficacy trials, carried out in four vineyards, etofenprox and deltamethrin proved to be the best conventional insecticides, while pyrethrins were the most impactful among organic insecticides. Insecticide residual activity was evaluated in semi-field and field conditions. Acrinathrin showed the most significant residual effects in both conditions. In semi-field trials, most of the pyrethroids were associated with good results in terms of residual activity. However, these effects declined in field conditions, probably due to high temperatures. Organic insecticides showed poor results in terms of residual efficacy. Implications of these results in the context of Integrated Pest Management in conventional and organic viticulture are discussed

The genetic study of three population microisolates in South Tyrol (MICROS): study design and epidemiological perspectives

<p>Abstract</p> <p>Background</p> <p>There is increasing evidence of the important role that small, isolated populations could play in finding genes involved in the etiology of diseases. For historical and political reasons, South Tyrol, the northern most Italian region, includes several villages of small dimensions which remained isolated over the centuries.</p> <p>Methods</p> <p>The MICROS study is a population-based survey on three small, isolated villages, characterized by: old settlement; small number of founders; high endogamy rates; slow/null population expansion. During the stage-1 (2002/03) genealogical data, screening questionnaires, clinical measurements, blood and urine samples, and DNA were collected for 1175 adult volunteers. Stage-2, concerning trait diagnoses, linkage analysis and association studies, is ongoing. The selection of the traits is being driven by expert clinicians. Preliminary, descriptive statistics were obtained. Power simulations for finding linkage on a quantitative trait locus (QTL) were undertaken.</p> <p>Results</p> <p>Starting from participants, genealogies were reconstructed for 50,037 subjects, going back to the early 1600s. Within the last five generations, subjects were clustered in one pedigree of 7049 subjects plus 178 smaller pedigrees (3 to 85 subjects each). A significant probability of familial clustering was assessed for many traits, especially among the cardiovascular, neurological and respiratory traits. Simulations showed that the MICROS pedigree has a substantial power to detect a LOD score ≥ 3 when the QTL specific heritability is ≥ 20%.</p> <p>Conclusion</p> <p>The MICROS study is an extensive, ongoing, two-stage survey aimed at characterizing the genetic epidemiology of Mendelian and complex diseases. Our approach, involving different scientific disciplines, is an advantageous strategy to define and to study population isolates. The isolation of the Alpine populations, together with the extensive data collected so far, make the MICROS study a powerful resource for the study of diseases in many fields of medicine. Recent successes and simulation studies give us confidence that our pedigrees can be valuable both in finding new candidates loci and to confirm existing candidate genes.</p

Postoperative outcomes in oesophagectomy with trainee involvement

BACKGROUND: The complexity of oesophageal surgery and the significant risk of morbidity necessitates that oesophagectomy is predominantly performed by a consultant surgeon, or a senior trainee under their supervision. The aim of this study was to determine the impact of trainee involvement in oesophagectomy on postoperative outcomes in an international multicentre setting. METHODS: Data from the multicentre Oesophago-Gastric Anastomosis Study Group (OGAA) cohort study were analysed, which comprised prospectively collected data from patients undergoing oesophagectomy for oesophageal cancer between April 2018 and December 2018. Procedures were grouped by the level of trainee involvement, and univariable and multivariable analyses were performed to compare patient outcomes across groups. RESULTS: Of 2232 oesophagectomies from 137 centres in 41 countries, trainees were involved in 29.1 per cent of them (n = 650), performing only the abdominal phase in 230, only the chest and/or neck phases in 130, and all phases in 315 procedures. For procedures with a chest anastomosis, those with trainee involvement had similar 90-day mortality, complication and reoperation rates to consultant-performed oesophagectomies (P = 0.451, P = 0.318, and P = 0.382, respectively), while anastomotic leak rates were significantly lower in the trainee groups (P = 0.030). Procedures with a neck anastomosis had equivalent complication, anastomotic leak, and reoperation rates (P = 0.150, P = 0.430, and P = 0.632, respectively) in trainee-involved versus consultant-performed oesophagectomies, with significantly lower 90-day mortality in the trainee groups (P = 0.005). CONCLUSION: Trainee involvement was not found to be associated with significantly inferior postoperative outcomes for selected patients undergoing oesophagectomy. The results support continued supervised trainee involvement in oesophageal cancer surgery

Effect of Matricaria recutita L. water extract on human cAMP and cGMP phosphodiesterases

Tea infusion of Matricaria recutita L. flowers is a herbal remedy used for the treatment of gastrointestinal (GI) complaints, including minor spasms, epigastric distension, flatulence and belching [1]. The spasmolytic activity has been shown in vitro and in clinical studies [1]. cAMP and cGMP levels regulate the GI smooth muscle tone causing relaxation. Inhibition of phosphodiesterases (PDEs) which catalyze the hydrolysis of cAMP and cGMP to 5’AMP and 5’ GMP, respectively [2], is one of the mechanisms operated by spasmolytic drugs. In the GI tract, PDE3A isoform is the main cAMP-PDE, whereas PDE5A is the main cGMP-specific PDE [2]. In this study the effect of water extracts of dried capitula and sifted flowers on the activity of cAMP- and cGMP-PDEs was investigated. For this purpose, human recombinant PDE5A1 was prepared by expression of the full-length cDNA of PDE5A1 into COS-7 cells [3] and cAMP-PDE was evaluated in human platelet homogenate. PDE activity was determined according to the method described in [4]. Tea infusions (1g dried drug/60ml water at boiling temperature) were prepared from both capitula and sifted chamomile, and lyophilized. The recovery was 19.8 ± 2.0 and 26.1 ± 2.7 respectively (% vs dried drug, mean ± SD, n=6). Infusions were tested at concentrations of 5-100 µg/ml. The extracts did not affect PDE5A1 while inhibited cAMP-PDE in a concentration-dependent fashion; the IC50 values were 30.8 ± 6.3 µg/ml and 31.4 ± 4.2 µg/ml (mean ± S.D.) for capitula and sifted flowers, respectively. To investigate which component/s could be responsible for the effect, we tested apigenin-7-glucoside, luteolin-7-glucoside, the corresponding aglycons, and α-bisabolol. At 10 µM, only flavone derivatives inhibited cAMP-PDE, while α-bisabolol was inactive. Aglycons showed higher activity than the corresponding glucosides. Apigenin-7-glucoside, the main flavone present in chamomile [1], was tested then on cAMP-PDE in the range 1-100 µM and the IC50 was calculated (10.2 ± 1.7 µM ± S.D.). On the contrary, apigenin-7-glucoside was inactive on PDE5A1, even at 50 μM, the maximal concentration assayed, indicating that this flavone may specifically inhibit different PDE isoforms. In addition, these results suggest that apigenin-7-glucoside is the constituent mainly responsible for this pharmacological effect. Analytical studies are ongoing to identify and quantify the extract components. In conclusion, the inhibition of cAMP-PDE could in part explain the mechanism of the spasmolytic action of chamomile

Manejo pós-colheita de uvas de mesa BRS Clara e BRS Morena.

O objetivo do presente trabalho foi avaliar o comportamento pós-colheita de uvas sem sementes lançadas pelo programa de melhoramento genético da Embrapa Uva e Vinho. Para isso, frutos (cachos) das variedades BRS Clara e BRS Morena foram colhidas em vinhedo comercial existente no Vale dos Vinhedos, Bento Gonçalves, RS

Inhibition of human cAMP-phosphodiesterase as a mechanism of the spasmolytic effect of Matricaria recutita L.

Mechanisms underlying the spasmolytic activity of chamomile still remain unclear. Inhibition of cAMP-and cGMP-phosphodiesterases (PDE) is one of the mechanisms operated by spasmolytic drugs. In this study, the effect of chamomile on PDE was investigated. Human platelet cAMP-PDE and recombinant PDE5A1 were assayed in the presence of infusions prepared from sifted flowers and capitula. LC-ESI-MS/MS analysis showed different compositions in infusions made with sifted flowers and capitula. Chamomile inhibited cAMP-PDE activity (IC 50 = 17.9-40.5 μg/mL), while CGMP-PDE5 was less affected (-15% at 50 μg/mL). Among the individual compounds tested, only flavonoids showed an inhibitory effect (IC50 = 1.3-14.9 μM), contributing to around 39% of the infusion inhibition; other compounds responsible for cAMP-PDE inhibition still remain unknown. Although experimental evidence supporting the use of chamomile for gastrointestinal minor spasms dates back to the fifties, cAMP-PDE inhibition as a likely mechanism underlying the spasmolytic activity is reported for the first time

Potent inhibition of human phosphodiesterase-5 by icariin derivatives

Plant extracts traditionally used for male impotence (Tribulus terrestris, Ferula hermonis, Epimedium breVicornum, Cinnamomum cassia), and the individual compounds cinnamaldehyde, ferutinin, and icariin, were screened against phosphodiesterase-5A1 (PDE5A1) activity. Human recombinant PDE5A1 was used as the enzyme source. Only E. breVicornum extract (80% inhibition at 50 &#956;g/mL) and its active principle icariin (1) (IC50 5.9 &#956;M) were active. To improve its inhibitory activity, 1 was subjected to various structural modifications. Thus, 3,7-bis(2-hydroxyethyl)icaritin (5), where both sugars in 1 were replaced with hydroxyethyl residues, potently inhibited PDE5A1 with an IC50 very close to that of sildenafil (IC50 75 vs 74 nM). Thus, 5 was 80 times more potent than 1, and its selectivity versus phosphodiesterase-6 (PDE6) and cyclic adenosine monophosphate-phosphodiesterase (cAMP-PDE) was much higher in comparison with sildenafil. The improved pharmacodynamic profile and lack of cytotoxicity on human fibroblasts make compound 5 a promising candidate for further development