New treatment strategies for non-metastatic rectal cancer.

The most widely practiced (standard) treatment of non-metastatic rectal cancer is based on proctectomy with mesorectal excision (partial or total according to the location of the tumor and commonly called TME). Surgery is preceded by CAP50-type chemoradiotherapy (capecitabineand 50 Grays radiation) and performed 6-8 weeks after the end of chemoradiotherapy. The development of new endoscopic, surgical, radiation-based and chemotherapeutic modalities leads surgeons to envisage customized treatment to find the best compromise between functional and oncologic results according to the locoregional extension of the tumor. Superficial lesions are amenable to transanal excision. T2-3 tumors<4cm are amenable to rectal preservation when neoadjuvant treatment obtains a complete response, allowing local excision or close surveillance. Intensification endocavitary radiotherapy and induction and consolidation chemotherapy regimens to avoid recourse to salvage abdomino-perineal resection (APR) are under investigation. For locally advanced rectal cancers (T3-4 and all N+ irrespective of T), the following scenarios can be envisaged: for initially resectable tumors (T3N0, T1-T3N+, circumferential resection margin>2mm), neoadjuvant chemotherapy alone aims to minimize the risk of local recurrence while avoiding the sequelae of radiotherapy. In case of initially non-resectable tumors (T4, circumferential resection margin<1mm), induction chemotherapy before chemoradiotherapy and consolidation chemotherapy after short course radiotherapy provide better results than standard treatment in terms of complete response and recurrence-free survival, and should be routinely proposed in this indication.

Social deprivation aggravates post-operative morbidity in carcinologic colorectal surgery: Results of the COINCIDE multicenter study.

AIM OF THE STUDY: Evaluate the impact of social deprivation on morbidity and mortality in surgery for colorectal cancer. METHODS: The COINCIDE prospective cohort included nearly 2,000 consecutive patients operated on for colorectal cancer at the Assistance Publique-Hospitals of Paris (AP-HP) from 2008 to 2010. The data on these patients were crossed with the PMSI administrative database. The European Social Deprivation Index (EDI) was calculated for each patient and classified into five quintiles (quintiles 4 and 5 being the most disadvantaged patients). Thirty-day post-operative morbidity was determined according to the Dindo-Clavien classification, with a Had®Hoc re-analysis of each file. Statistical analysis was performed using the proprietary Q-finder® algorithm. RESULTS: One thousand two hundred and fifty nine curative colorectal resections were analyzed. Mortality was 2.7% and severe morbidity (Dindo-Clavien≥3) occurred in 16.4%. Mortality was not statistically significantly increased among the most disadvantaged who made up almost two thirds of the population (64.2%). Patients in quintiles 4 and 5 had a statistically significant increase in severe morbidity. The relative risk remained 1.5 even after adjustment for the known risk factors found in the analysis: age>70 years, ASA score, urgency, and laparotomy. CONCLUSIONS: The EDI represents an independent risk factor for severe morbidity after carcinologic colorectal resection. This study suggests that the determinants of health are multidimensional and do not depend solely on the quality and performance of the care system. The inclusion of this index in our surgical databases is therefore necessary, as is its use in health policy for the distribution of resources.

COVID-19-associated cardiovascular morbidity in older adults: a position paper from the Italian Society of Cardiovascular Researches.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells following binding with the cell surface ACE2 receptors, thereby leading to coronavirus disease 2019 (COVID-19). SARS-CoV-2 causes viral pneumonia with additional extrapulmonary manifestations and major complications, including acute myocardial injury, arrhythmia, and shock mainly in elderly patients. Furthermore, patients with existing cardiovascular comorbidities, such as hypertension and coronary heart disease, have a worse clinical outcome following contraction of the viral illness. A striking feature of COVID-19 pandemics is the high incidence of fatalities in advanced aged patients: this might be due to the prevalence of frailty and cardiovascular disease increase with age due to endothelial dysfunction and loss of endogenous cardioprotective mechanisms. Although experimental evidence on this topic is still at its infancy, the aim of this position paper is to hypothesize and discuss more suggestive cellular and molecular mechanisms whereby SARS-CoV-2 may lead to detrimental consequences to the cardiovascular system. We will focus on aging, cytokine storm, NLRP3/inflammasome, hypoxemia, and air pollution, which is an emerging cardiovascular risk factor associated with rapid urbanization and globalization. We will finally discuss the impact of clinically available CV drugs on the clinical course of COVID-19 patients. Understanding the role played by SARS-CoV2 on the CV system is indeed mandatory to get further insights into COVID-19 pathogenesis and to design a therapeutic strategy of cardio-protection for frail patients.

Índice de CMP em leite pasteurizado comercializado em Minas Gerais, Brasil, durante os anos de 2011 a 2017 / Caseinomacropeptide index in pasteurized milk retailed in Minas Gerais, Brazil from 2011 to 2017

Cheese whey is a nutritious byproduct in the dairy industry, however, due to low commercial value, its use as a milk adulterant is a common practice not easily detected by routine analysis. In Brazil, quantification of caseinomacropeptide (CMP) index, using High Performance Liquid Chromatography (HPLC), is officially used to investigate illegal cheese whey addition to milk. Milk with CMP index above 30mg/L is considered not suitable for human consumption. The objective of this research was to report the CMP index in 185 samples of pasteurized milk, representing 73 commercial brands produced in 51 counties and ten mesoregions of the state of Minas Gerais, from 2011 to 2013 (58 samples) and 2015 to 2017 (127 samples). CMP index was considered normal (up to 30mg/L) in 75.1% of the samples. However, 21.1% presented CMP index above 75mg/L and 3.8% from 31 to 75mg/L. CMP index above 75mg/L was found in 17.4% of the samples produced during the dry season (April to September) and in 24.7% during the rainy season (October to March). These data point to the need of more efficient monitoring and inspection processes to hinder adulteration with cheese whey addition to milk.(AU)

Elective surgery for tumours of the splenic flexure: a French inter-group (AFC, SFCD, FRENCH, GRECCAR) survey.

BACKGROUND: In an elective setting, there is no consensus regarding the type of colectomy that is best for patients with tumors of the splenic flexure: segmental left colectomy (or splenic flexure colectomy), left hemicolectomy or subtotal colectomy (or extended right hemicolectomy). In the United Kingdom, extended right hemicolectomy is preferred by surgeons. The aim of the present survey was to report on the practices in France for this particular tumor location. METHODS: Between 15/07/17 and 15/10/17, members of two French surgical societies [the French Association of Surgery (AFC) and the French Society of Digestive Surgery (SFCD)] and two French surgical cooperative groups [the French Federation of Surgical Research (FRENCH) and the French Research Group of Rectal Cancer Surgery (GRECCAR)] were solicited by email to answer an online anonymous questionnaire. RESULTS: A total of 190 out of 420 surgeons participated in this study (response rate 45%). The preferred procedure was splenic flexure colectomy (70%), followed by left hemicolectomy (17%) and subtotal colectomy (13%). The most used surgical approach was laparoscopy (63%), followed by laparotomy (31%) and hand-assisted laparoscopy (6%). Lymph node dissection was extended to the middle colic artery in 29% of splenic flexure colectomies and in 33% of left hemicolectomies. Twenty-nine percent of responders thought that tumors of the splenic flexure had a worse prognosis in comparison with other colonic sites, because of insufficient lymph node dissection (73%) or a more advanced stage (50%) at diagnosis. However, this opinion did not change the type of colectomy performed. CONCLUSIONS: There is a strong consensus in France to operate tumors of the splenic flexure with a splenic flexure colectomy and lymph node dissection limited to the left colic artery.

Short communication: In vitro and in vivo probiotic potential of Lactobacillus plantarum B7 and Lactobacillus rhamnosus D1 isolated from Minas artisanal cheese.

Some Lactobacillus strains may contribute to the health of the host when administered in adequate concentrations, demonstrating their probiotic potential. In contrast, Listeria monocytogenes is a foodborne pathogen that can cause enteropathy, meningoencephalitis, abortion, and septicemia. The aim of this survey was to evaluate the in vitro and in vivo probiotic potential of Lactobacillus plantarum B7 and Lactobacillus rhamnosus D1, isolated from Minas artisanal cheese of the Serra da Canastra (Minas Gerais, Brazil), against Lis. monocytogenes. We submitted B7 and D1 to in vitro testing (antibiogram, tolerance to bile salts and artificial gastric fluid, and spot-on-lawn) and in vivo testing (relative weight gain in mice). Both Lactobacillus strains demonstrated in vitro inhibitory activity against Lis. monocytogenes, as well as sensitivity to antimicrobials and resistance to gastric acids and bile salts. In the in vivo assays, mice treated with D1 gained more weight than mice in the other groups. These results indicate that D1 could have higher probiotic potential than B7 because improvements in feed conversion may help animals fight infection.

What is the impact of neoadjuvant chemoradiation on outcomes in gastro-intestinal cancer?

Multimodal therapeutic strategies combining chemotherapy, radiation therapy and surgery have been shown to be feasible and to have a positive impact on outcomes by decreasing the risk of locoregional recurrence and often by increasing overall survival. The advantages of neoadjuvant chemo(radio)therapy include optimal tumor control combined with better tolerance and compliance to treatment while also increasing the number of candidates for surgery. Whereas indications for neoadjuvant therapy are increasing, its impact on surgical treatment and postoperative outcomes are not well-known. Surgeons frequently believe that chemo(radio)therapy may amplify intraoperative difficulties, thereby increasing postoperative morbidity and mortality. The aim of this review was to report the state of the art regarding: (i) the role of chemo(radio)therapy; (ii) its impact on surgical indications and modalities; and (iii) its impact on postoperative outcomes for the most frequently encountered gastro-intestinal cancers, i.e. esophageal, rectal, pancreatic, and anal canal cancer.

Trocar-guided trans-vaginal mesh surgery for pelvic organ prolapse: effects on urinary continence and anatomical and functional outcomes. A prospective observational study.

OBJECTIVE: Primary objective of this study was to assess the effects of trocar-guided transvaginal mesh surgery (TVM) on cure and prevention rates for incontinence, without concomitant surgery for Stress Urinary Incontinence (SUI). Our secondary objectives were anatomical outcomes, relief of symptoms and effect on quality of life (QoL). STUDY DESIGN: This prospective observational study evaluated women who underwent TVM for symptomatic stage >2 Pelvic Organ Prolapse (POP). SUI was evaluated objectively using the cough stress test with prolapse reduced. SUI and urge urinary incontinence (UUI) were subjectively evaluated using ICIQ-SF. Anatomical cure was defined as stage <2 at POP-Q. STATISTICAL ANALYSIS: McNemar chi-square test; paired t-test; Mann-Whitney test. RESULTS: Seventy-two patients reached final evaluation (mean follow-up 72 months). In the 40 pre-op continent patients, 34 (85%) remained continent postoperatively and 6 (15%) showed de novo SUI. Only 1 patient chose to undergo subsequent TVT. The number needed to treat was 6 to prevent 1 women developing de novo objective SUI and 39 to prevent 1 woman having to undergo SUI surgery. In the 32 pre-op incontinent patients, 18 (56.3%) became continent postoperatively. Only 1 patient chose to undergo subsequent TVT. UUI was present in 44 patients pre-operatively and 15 (20.8%) post-operatively (1 de novo). Forty-four patients (61.1%) were continent post-operatively for SUI and UUI. We observed a significant improvement in storage, voiding, post-micturition and prolapse-related symptoms. The anatomical cure rate was 87.5% for the anterior compartment and 90.3%.for the apical segment. The apical recurrence was 8.3% in the patients previously hysterectomised, 18.8% in the patients with uterus preservation and 0% in the patients with concomitant hysterectomy. QoL scores improved in all domains except sleep and personal relationships. We observed mesh exposure in 10 patients (13.9%), in 5 of whom it was associated with a concomitant hysterectomy CONCLUSIONS: TVM showed excellent results in terms of continence and can be performed without contemporary anti-incontinence surgery, for both continent and incontinent women. Patients should have pre-operative counselling before POP surgery. For severe uterine prolapse the Perigee™ System should be employed with concomitant hysterectomy because uterus preservation is associated with significantly higher apical recurrence rates.

The accuracy of preoperative imaging in measuring the length of the ileocolic segment affected by Crohn's disease: a prospective cohort study.

AIM: The study aimed to evaluate the accuracy of imaging for measurement of the length of the ileocolic segment affected by Crohn's disease. METHOD: Fifty-four consecutive patients who underwent resection between 2011 and 2014 for ileocolic Crohn's disease were prospectively studied. All had preoperative MR or CT enterography. Two independent radiologists measured the length of the diseased intestinal segment. The measurements were compared with the length of disease assessed on pathology of the non-fixed surgical specimen. RESULTS: The median preoperative length of the Crohn's disease segment on imaging was 20.5 (2-73) cm and 20 (3-90) cm, as measured by the two radiologists. Interobserver agreement was substantial (κ = 0.69) with a correlation coefficient (r) of 0.82 (P < 0.001). The median length of the Crohn's disease segment on pathological examination was 16.5 (2-75) cm and was closely correlated with the radiological measurement (r = 0.76, P < 0.001). The length of the Crohn's disease segment on imaging was correct to within 5 cm of the value on pathology. It was correct in 30 (55%) patients and was underestimated and overestimated in 6 (11.1%) and 18 (33.3%). A length of disease of less than 20 cm found on imaging in 26 patients was confirmed in 25 (96%) on pathology, whereas a length of more than 20 cm found on imaging in 28 patients was confirmed in 18 (64%) on pathology. The sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy of imaging for predicting a length of less than 20 cm were 71%, 95%, 96%, 64% and 79%. CONCLUSION: Imaging accurately identifies the length of the ileocolic segment of Crohn's disease when it is 20 cm or less on pathological examination. In patients with more extensive disease, imaging tends to overestimate the length and should be interpreted with caution.

Nanoprecipitated catestatin released from pharmacologically active microcarriers (PAMs) exerts pro-survival effects on MSC.

Catestatin (CST), a fragment of Chromogranin-A, exerts angiogenic, arteriogenic, vasculogenic and cardioprotective effects. CST is a very promising agent for revascularization purposes, in "NOOPTION" patients. However, peptides have a very short half-life after administration and must be conveniently protected. Fibronectin-coated pharmacologically active microcarriers (FN-PAM), are biodegradable and biocompatible polymeric microspheres that can convey mesenchymal stem cell (MSCs) and therapeutic proteins delivered in a prolonged manner. In this study, we first evaluated whether a small peptide such as CST could be nanoprecipitated and incorporated within FN-PAMs. Subsequently, whether CST may be released in a prolonged manner by functionalized FN-PAMs (FN-PAM-CST). Finally, we assessed the effect of CST released by FN-PAM-CST on the survival of MSCs under stress conditions of hypoxia-reoxygenation. An experimental design, modifying three key parameters (ionic strength, mixing and centrifugation time) of protein nanoprecipitation, was used to define the optimum condition for CST. An optimal nanoprecipitation yield of 76% was obtained allowing encapsulation of solid CST within FN-PAM-CST, which released CST in a prolonged manner. In vitro, MSCs adhered to FN-PAMs, and the controlled release of CST from FN-PAM-CST greatly limited hypoxic MSC-death and enhanced MSC-survival in post-hypoxic environment. These results suggest that FN-PAM-CST are promising tools for cell-therapy.

Milk, caseinate and lactoferrin addition to equine semen cooling extenders.

Cooled semen has been used routinely to prolong sperm viability until artificial insemination time. However, spermatozoa are subjected to oxidative stress. The aim of the present work was to investigate the protective and antioxidant effect of the milk proteins lactoferrin (Lf) and caseinate added to equine semen cooling extenders. Semen from six stallions was cooled at 5 °C after resuspension with C1) milk- and glucose-based, C2) 0.6% caseinate, C3) C2 + Lf 200 µg ml-1 , C4) C2 + Lf 500 µg ml-1 and C5) C2 + Lf 1000 µg ml-1 extenders, and kept at 5 °C for 24 h. Sperm motility characteristics and intact membrane rates were not different among the treatments (P > 0.05). As a result of the cooling process, the nitrite concentration increased significantly in the cooled semen (69.6 ± 78.9 µm per ×106 spermatozoa) compared with the fresh semen (8.6 ± 1.9 µm per ×106 spermatozoa). In contrast, the H2 O2 concentrations were lower in the 0.6% caseinate extender (265.9 ± 221.3 µm per ×106 spermatozoa) than in the milk extender (430.9 ± 199.8 µm per ×106 spermatozoa, P < 0.05), showing an antioxidative effect of the caseinate compared with the milk. However, in all groups, hydrogen peroxide concentrations were similar to the undiluted fresh semen (332.8 ± 151.3 µm per ×106 spermatozoa). Caseinate showed to be as efficient as milk to protect equine-cooled spermatozoon.

Lactic acid microbiota identification in water, raw milk, endogenous starter culture, and fresh Minas artisanal cheese from the Campo das Vertentes region of Brazil during the dry and rainy seasons.

Minas artisanal cheese, produced in the Campo das Vertentes region of Brazil, is made from raw milk and endogenous starter cultures. Although this cheese is of great historical and socioeconomic importance, little information is available about its microbiological and physical-chemical qualities, or about its beneficial microbiota. This work was aimed at evaluating the qualities of the cheese and the components used for its production, comparing samples collected during the dry and rainy seasons. We also conducted molecular identification and isolated 50 samples of lactic acid bacteria from cheese (n=21), water (n=3), raw milk (n=9), and endogenous starter culture (n=17). The microbiological quality of the cheese, water, raw milk, and endogenous starter culture was lower during the rainy period, given the higher counts of coagulase-positive Staphylococcus and total and thermotolerant coliforms. Enterococcus faecalis was the lactic acid bacteria isolated most frequently (42.86%) in cheese samples, followed by Lactococcus lactis (28.57%) and Lactobacillus plantarum (14.29%). Lactobacillus brevis (5.88%), Enterococcus pseudoavium (5.88%), Enterococcus durans (5.88%), and Aerococcus viridans (5.88%) were isolated from endogenous starter cultures and are described for the first time in the literature. The lactic acid bacteria identified in the analyzed cheeses may inhibit undesirable microbiota and contribute to the safety and flavor of the cheese, but this needs to be evaluated in future research.

Outcome of emergency surgery for severe neuroleptic-induced colitis: results of a prospective cohort.

AIM: The study evaluated the outcome of severe acute antipsychotic (neuroleptic) drug related colitis requiring emergency surgery. METHOD: From 2009 to 2014, 20 patients underwent emergency surgery for acute and severe neuroleptic-related ischaemic colitis. Neuroleptic-induced colitis was defined as another cause besides inflammatory, infectious or ischaemic colitis with a relationship to treatment by antipsychotic drugs. RESULTS: The main drugs involved were cyamemazine (n = 9, 45%), loxapine (n = 5, 25%), haloperidol (n = 4, 20%) and alimemazine (n = 4, 20%). Most (n = 14, 70%) patients presented with haemodynamic instability requiring massive resuscitation and vasopressive drugs. CT signs of digestive impairment were found in 13 (65%) patients having emergency surgery. The lesions were pancolonic in 40%; transparietal necrosis was found in 45% and 15% had colonic perforation. Twelve (60%) patients had total or subtotal colectomy and eight (40%) a segmental colectomy with colostomy or ileostomy in all cases. The postoperative mortality was 15% and morbidity was 70%, necessitating surgical reintervention in two (10%) patients. Of the 17 surviving patients, 11 (64.7%) had restoration of intestinal continuity after a median delay of 103 days, with a postoperative morbidity rate of 36.3%. In the intent-to-treat population, the permanent stoma rate was 30%. CONCLUSION: The morbidity and mortality of surgery for neuroleptic-drug-induced colitis is higher than for colitis due to other causes. A better knowledge of this condition should lead to early diagnosis.

The innovative "Bio-Oil Spread" prevents metabolic disorders and mediates preconditioning-like cardioprotection in rats.

BACKGROUND AND AIMS: Obesity is often associated with an increased cardiovascular risk. The food industry and the associated research activities focus on formulating products that are a perfect mix between an adequate fat content and health. We evaluated whether a diet enriched with Bio-Oil Spread (SD), an olive oil-based innovative food, is cardioprotective in the presence of high-fat diet (HFD)-dependent obesity. METHODS AND RESULTS: Rats were fed for 16 weeks with normolipidic diet (ND; fat: 6.2%), HFD (fat: 42%), and ND enriched with SD (6.2% of fat + 35.8% of SD). Metabolic and anthropometric parameters were measured. Heart and liver structures were analyzed by histochemical examination. Ischemic susceptibility was evaluated on isolated and Langendorff-perfused cardiac preparations. Signaling was assessed by Western blotting. Compared to ND rats, HFD rats showed increased body weight and abdominal obesity, dyslipidemia, and impaired glucose tolerance. Morphological analyses showed that HFD is associated with heart and liver modifications (hypertrophy and steatosis, respectively), lesser evident in the SD group, together with metabolic and anthropometric alterations. In particular, IGF-1R immunodetection revealed a reduction of hypertrophy in SD heart sections. Notably, SD diet significantly reduced myocardial susceptibility against ischemia/reperfusion (I/R) with respect to HFD through the activation of survival signals (Akt, ERK1/2, and Bcl2). Systolic and diastolic performance was preserved in the SD group. CONCLUSIONS: We suggest that SD may contribute to the prevention of metabolic disorders and cardiovascular alterations typical of severe obesity induced by an HFD, including the increased ischemic susceptibility of the myocardium. Our results pave the way to evaluate the introduction of SD in human alimentary guidelines as a strategy to reduce saturated fat intake.

Cardiophrenic angle lymph node is an indicator of metastatic spread but not specifically peritoneal carcinomatosis in colorectal cancer patients: Results of a prospective validation study in 91 patients.

BACKGROUND: The presence of cardiophrenic angle lymph node (CPALN) has been associated with the risk of peritoneal carcinomatosis (PC) in high risk colon cancer patients. Its accuracy to predict PC and its prognostic value in non-selected CRC patients has not been validated prospectively. METHODS: From 2011 to 2013, all patients undergoing colectomy for colon cancer were included prospectively. Presence of CPALN was assessed on preoperative computed tomography scan by two radiologists. Surgical exploration was used as reference for the diagnosis of PC. Factors associated with presence of CPALN and progression-free survival were analyzed. RESULTS: Ninety one patients fulfilled inclusion criteria. CPALN was detected in 36 patients (39.5%) on CT scan. At surgical exploration, PC was found in 6 patients (6.5%). Sensitivity, specificity, negative predictive value, positive predictive value and overall accuracy of CPALN on CT scan for predicting PC were 67%, 62%, 96%, 11% and 63% respectively. In multivariate analysis, the presence of distant metastases whatever the site was associated with the presence of CPALN (p = 0.03; hazard ratio HR = 3.8; confidence interval CI 95% = 1.1-13.3). In the multivariate analysis, only vascular involvement (p = 0.034, HR = 3.574, CI 95% = 1.10-11.60) was associated with progression-free survival whereas CPALN was not found to predict outcome (p = 0.893). CONCLUSION: CPALN is a common finding in non-selected colon cancer patients. Although in the absence of CPALN, PC can almost be excluded, its value for the diagnosis of PC is limited. Our findings support that CPALN is mainly an indicator of metastatic spread of the tumor.

Microbiological and physical-chemical characteristics of fermented milk beverages / Características microbiológicas e físico-químicas de bebidas lácteas fermentadas

This study aimed to evaluate some microbiological and physical-chemical characteristics of fermented milk beverages collected at the main supermarkets in Belo Horizonte (MG). 40 samples of the products corresponding to five distinct brands were collected. They were submitted to the following analyses: Most Probable Number (MPN) of total (30ºC) and thermal tolerant coliforms (45ºC), Salmonella spp., coagulase positive Staphylococcus, molds and yeasts, lactic acid bacteria, pH, titratable acidity and contents of moisture, total solids, protein and fat. The analyses were carried out during the last week of shelf life. The microbiological quality of the samples was good and the counts of lactic bacteria were above the minimum established by the official legislation. Streptococcus and Lactobacillus were isolated and identified from the products and Lactobacillus delbrueckii was molecularly identified in three samples. The mean values for the contents of fat and protein, titratable acidity, pH, moisture and total solids ranged from 1.24 to 1.98%; 1.88 to 2.22%; 0.54 to 0.66%; 3.91 to 4.16; 81.18 to 83.25% and 16.75 to 18.82%, respectively. All samples had protein content in agreement with the official legislation.

O objetivo do presente trabalho foi avaliar as características microbiológicas e físico-químicas de bebidas lácteas fermentadas. Foram coletadas 40 amostras de bebidas lácteas fermentadas pertencentes a cinco marcas distintas, em grandes redes de supermercados de Belo Horizonte. Em cada amostra, foram avaliados os seguintes parâmetros: número mais provável de coliformes totais (30ºC), número mais provável de coliformes termotolerantes (45ºC), pesquisa de Salmonella spp., contagem de Staphylococcus coagulase positiva, contagem de bolores e leveduras, contagem total de bactérias lácticas viáveis, umidade, sólidos totais, teor de proteína, teor de gordura, pH e acidez titulável. As análises foram realizadas na última semana do período de validade. As amostras apresentaram qualidade microbiológica satisfatória, bem como contagens totais de bactérias lácticas viáveis superiores ao mínimo estabelecido pela legislação. Streptococcus e Lactobacillus foram identificados em todas as marcas de bebidas lácteas fermentadas analisadas, e em três delas foi possível identificar a espécie Lactobacillus delbrueckii. Os valores médios encontrados para os teores de gordura, proteína, acidez titulável, pH, umidade e sólidos totais variaram de 1,24 a 1,98%, 1,88 a 2,22%, 0,54 a 0,66%, 3,91 a 4,16, 81,18 a 83,25% e 16,75 a 18,82%, respectivamente. Todas as marcas de bebidas lácteas fermentadas apresentaram teor médio de proteína superior ao mínimo preconizado pela legislação.

pGlu-serpinin protects the normotensive and hypertensive heart from ischemic injury.

Serpinin peptides derive from proteolytic cleavage of Chromogranin-A at C-terminus. Serpinin and the more potent pyroglutaminated-serpinin (pGlu-Serp) are positive cardiac ß-adrenergic-like modulators, acting through ß1-AR/AC/cAMP/PKA pathway. Because in some conditions this pathway and/or other pro-survival pathways, activated by other Chromogranin-A fragments, may cross-talk and may be protective, here we explored whether pGlu-Serp cardioprotects against ischemia/reperfusion injury under normotensive and hypertensive conditions. In the latter condition, cardioprotection is often blunted because of the limitations on pro-survival Reperfusion Injury Salvage Kinases (RISK) pathway activation. The effects of pGlu-Serp were evaluated on infarct size (IS) and cardiac function by using the isolated and Langendorff perfused heart of normotensive (Wistar Kyoto, WKY) and spontaneously hypertensive (SHR) rats exposed to ischemic pre-conditioning (PreC) and post-conditioning (PostC). In both WKY and SHR rat, pGlu-Serp induced mild cardioprotection in both PreC and PostC. pGlu-Serp administered at the reperfusion (Serp-PostC) significantly reduced IS, being more protective in SHR than in WKY. Conversely, left ventricular developed pressure (LVDevP) post-ischemic recovery was greater in WKY than in SHR. pGlu-Serp-PostC reduced contracture in both strains. Co-infusion with specific RISK inhibitors (PI3K/Akt, MitoKATP channels and PKC) blocked the pGlu-Serp-PostC protective effects. To show direct effect on cardiomyocytes, we pre-treated H9c2 cells with pGlu-Serp, which were thus protected against hypoxia/reoxygenation. These results suggest pGlu-Serp as a potential modulatory agent implicated in the protective processes that can limit infarct size and overcome the hypertension-induced failure of PostC.

Pathological response of locally advanced rectal cancer to preoperative chemotherapy without pelvic irradiation.

AIM: Pathological response to chemotherapy without pelvic irradiation is not well defined in rectal cancer. This study aimed to evaluate the objective pathological response to preoperative chemotherapy without pelvic irradiation in middle or low locally advanced rectal cancer (LARC). METHODS: Between 2008 and 2013, 22 patients with middle or low LARC (T3/4 and/or N+ and circumferential resection margin < 2 mm) and synchronous metastatic disease or a contraindication to pelvic irradiation underwent rectal resection after preoperative chemotherapy. The pathological response of rectal tumour was analysed according to the Rödel tumour regression grading (TRG) system. Predictive factors of objective pathological response (TRG 2-4) were analysed. RESULTS: All patients underwent rectal surgery after a median of six cycles of preoperative chemotherapy. Of these, 20 (91%) had sphincter saving surgery and an R0 resection. Twelve (55%) patients had an objective pathological response (TRG 2-4), including one complete response. Poor response (TRG 0-1) to chemotherapy was noted in 10 (45%) patients. In univariate analyses, none of the factors examined was found to be predictive of an objective pathological response to chemotherapy. At a median follow-up of 37.2 months, none of the 22 patients experienced local recurrence. Of the 19 patients with Stage IV rectal cancer, 15 (79%) had liver surgery with curative intent. CONCLUSION: Preoperative chemotherapy without pelvic irradiation is associated with objective pathological response and adequate local control in selected patients with LARC. Further prospective controlled studies will address the question of whether it can be used as a valuable alternative to radiochemotherapy in LARC.

Redox signalling and cardioprotection: translatability and mechanism.

The morbidity and mortality from coronary artery disease (CAD) remain significant worldwide. The treatment for acute myocardial infarction has improved over the past decades, including early reperfusion of culprit coronary arteries. Although it is mandatory to reperfuse the ischaemic territory as soon as possible, paradoxically this leads to additional myocardial injury, namely ischaemia/reperfusion (I/R) injury, in which redox stress plays a pivotal role and for which no effective therapy is currently available. In this review, we report evidence that the redox environment plays a pivotal role not only in I/R injury but also in cardioprotection. In fact, cardioprotective strategies, such as pre- and post-conditioning, result in a robust reduction in infarct size in animals and the role of redox signalling is of paramount importance in these conditioning strategies. Nitrosative signalling and cysteine redox modifications, such as S-nitrosation/S-nitrosylation, are also emerging as very important mechanisms in conditioning cardioprotection. The reasons for the switch from protective oxidative/nitrosative signalling to deleterious oxidative/nitrosative/nitrative stress are not fully understood. The complex regulation of this switch is, at least in part, responsible for the diminished or lack of cardioprotection induced by conditioning protocols observed in ageing animals and with co-morbidities as well as in humans. Therefore, it is important to understand at a mechanistic level the reasons for these differences before proposing a safe and useful transition of ischaemic or pharmacological conditioning. Indeed, more mechanistic novel therapeutic strategies are required to protect the heart from I/R injury and to improve clinical outcomes in patients with CAD.

Propriedades probióticas in vitro de Lactobacillus spp. isolados de queijos minas artesanais da Serra da Canastra - MG / In vitro probiotic properties of Lactobacillus spp. isolated from Minas artisanal cheese from Serra da Canastra - MG

O objetivo deste estudo foi determinar o potencial probiótico in vitro de Lactobacillus spp. isolados de queijos minas artesanais da Serra da Canastra, considerando-se o antagonismo entre amostras isoladas frente a microrganismos indicadores, a susceptibilidade a antimicrobianos, a sensibilidade ao ácido gástrico e a sensibilidade a sais biliares. Todas as bactérias ácido-lácticas testadas apresentaram resistência ao ácido gástrico (pH 2,0) e aos sais biliares (0,3%), bem como atividade antagonista contra Escherichia coli, Staphylococcus aureus, Listeria monocytogenes, Salmonella enterica var. Typhimurium, Enterococcus faecalis e bactérias ácido-lácticas isoladas dos próprios queijos - Lactobacillus plantarum (D27) e Lactobacillus rhamnosus (B25). Todas as amostras foram sensíveis à eritromicina e tetraciclina e resistentes à ciprofloxacina, gentamicina, oxacilina, estreptomicina e vancomicina. L. plantarum (B17) apresentou melhor potencial probiótico, pois obteve resultados satisfatórios em todas as propriedades avaliadas. Mais estudos são necessários para verificar a presença e a capacidade de transmissão de genes de resistência antimicrobiana a outros microrganismos e para avaliar o potencial dos microrganismos in vivo. As bactérias selecionadas poderão ser utilizadas na elaboração de queijos em que sejam mantidos o sabor e a tradição do queijo minas artesanal do estado de Minas Gerais...

The aim of this study was to determine some in vitro probiotic features of Lactobacillus spp. isolated from Minas artisanal cheese from Serra da Canastra in order to select some bacteria for future production of safer cheeses keeping their natural flavor and tradition. The evaluated properties were antagonism against indicator microorganisms, antimicrobial susceptibility and also sensitivity to gastric acid and to bile salts. All lactic acid bacteria tested were resistant to gastric acid (pH 2.0) and bile salts (0.3%). Antagonistic activities were detected against Escherichia coli, Staphylococcus aureus, Listeria monocytogenes, Salmonella entericavar. Typhimurium, Enterococcus faecalis and other lactic bacteria isolated from the same cheese - Lactobacillus plantarum (D27) and Lactobacillus rhamnosus (B25). All samples were sensitive to the antimicrobials erythromycin, tetracycline and resistant to ciprofloxacin, gentamycin, oxacillin, streptomycin and vancomycin. L.plantarum (B17) presented the best probiotic potential. Further studies are needed to verify the presence and the capacity of transmission of antimicrobial resistance genes to other microorganisms and evaluate the in vivo probiotic potential of the selected microorganisms...