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Two studies were done to study detoxification of aflatoxin (AF)-contaminated chick feed with Nocardia corynebacteroides (NC). In the first study, pathogenicity of the bacteria was studied; in the second, the nutritional value of detoxified feed was evaluated. Commercial corn was divided into 2 sublots, one of which was contaminated with AF. Both lots were divided into 2 parts; the first was inoculated with NC. Four corn-soybean diets were prepared from the 4 corn lots. A completely randomized design was used with 2 × 2 factorial arrangement in which the factors were AF contaminated or not and NC inoculated or not. One hundred Ross 308 chicks (1-d-old, male) were used in 4 treatments with 5 repetitions and 5 chickens per cage. Bird weight and feed consumption were recorded weekly. Each week, 1 chick per treatment repetition was killed for histopathologic analysis of liver, kidney, bursa of Fabricius, pancreas, and small intestine (duodenum, jejunum, and ileum) and for analysis by scanning electron microscopy of the 3 sections of the intestine. At 21 d (the end of both experiments), 1 chick per treatment repetition was killed, and moisture, lipid content, and residual AF in liver were detected. Results at 3 wk did not show differences between treatments (P > 0.05) in any of the variables. In the second study, the same methodology was used except that greater levels of AF were used (800 and 1,200 µg of AFB1/kg of feed). Results showed differences (P < 0.05) in body weight, lipid content, and residual AF in liver. Histopathologic studies showed statistical differences in lesion severity in liver, duodenum, and kidney. Scanning electron microscopy analysis showed severe lesions of intestinal mucosa that mainly affected tight junctions in AF treatments. It can be concluded that NC is safe for chicks and may be used to partly detoxify chicken feed contaminated with AF. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic sleeve gastrectomy (LSG) has become the most frequently performed bariatric procedure to date. However, LSG is known to worsen pre-operative and result in de novo gastroesophageal reflux disease (GERD). Pre-operative evaluation reveals a high percentage of silent GERD of so far unknown influence on post-operative GERD., Methods: Prospective data of patients undergoing primary LSG between 01/2012 and 12/2015 were evaluated. Pre-operative GERD-specific evaluation consisted of validated questionnaires, upper endoscopy, 24 h-pH-manometry, and esophagograms. Patients were followed-up with questionnaires every 6 months, upper endoscopies after 1 year and 24 h-pH-metry after 2 years. Silent GERD was defined as esophagitis grade > B and/or abnormal esophageal acid exposure in absence of symptoms. LSG was performed over a 32F bougie, hiatal hernias > 1 cm were addressed with posterior hiatoplasty. Excluded were patients with hiatal hernias > 4 cm, patients with incorrect anatomy (stenosis, fundus too large) and conversion to RYGB for early leaks., Results: 222 patients were included. Mean follow-up was 32 ± 16 months, mean preoperative body mass index 49.6 ± 7.2 kg/m 2 . 116 patients (52%) presented with post-operative GERD-symptoms, of which 85 (73%) had de novo symptoms. Of those, 48 (of 85, 56%) had no preoperative GERD and 37 (of 85, 44%) silent GERD. 57 patients (26%) had neither pre- nor post-operative GERD, 7 (3%) had silent pre-operative and no postop GERD, and in 19 patients (9%) GERD was cured with LSG. 31 patients (14%) stayed symptomatic. Of 56 patients (25%) with pre-operative silent GERD, 37 (of 54, 66%) became symptomatic., Conclusion: LSG leads to a considerable rate of post-operative GERD. De novo-GERD consist of around half of pre-operative silent GERD and completely de novo-GERD. Most patients with pre-operative silent GERD became symptomatic.

Meprin-α is a metalloprotease overexpressed in cancer cells, leading to the accumulation of this protease in a subset of colorectal tumors. The impact of increased meprin-α levels on tumor progression is not known. We investigated the effect of this protease on cell migration and angiogenesis in vitro and studied the expression of meprin-α mRNA, protein and proteolytic activity in primary tumors at progressive stages and in liver metastases of patients with colorectal cancer, as well as inhibitory activity towards meprin-α in sera of cancer patient as compared to healthy controls. We found that the hepatocyte growth factor (HGF)-induced migratory response of meprin-transfected epithelial cells was increased compared to wild-type cells in the presence of plasminogen, and that the angiogenic response in organ-cultured rat aortic explants was enhanced in the presence of exogenous human meprin-α. In patients, meprin-α mRNA was expressed in colonic adenomas, primary tumors UICC (International Union Against Cancer) stage I, II, III and IV, as well as in liver metastases. In contrast, the corresponding protein accumulated only in primary tumors and liver metastases, but not in adenomas. However, liver metastases lacked meprin-α activity despite increased expression of the corresponding protein, which correlated with inefficient zymogen activation. Sera from cancer patients exhibited reduced meprin-α inhibition compared to healthy controls. In conclusion, meprin-α activity is regulated differently in primary tumors and metastases, leading to high proteolytic activity in primary tumors and low activity in liver metastases. By virtue of its pro-migratory and pro-angiogenic activity, meprin-α may promote tumor progression in colorectal cancer.

We have previously discovered a unique mechanism of epigenetic transcriptional gene silencing in the Entamoeba histolytica trophozoites of strain HM-1:IMSS that resulted in the persistent downregulation of the amoebapore A (ap-a) gene, and that could be successfully applied to silence other virulence genes (cpA5, lgl1). In order to understand how the silencing is maintained throughout generations, we analysed whether modifications occurred at the chromatin level. Chromatin immunoprecipitation assays were done with antibodies specific to the methylated lysine 4 of E. histolytica histone H3. When the genes were in a transcriptionally silent state, the methylation levels of H3K4 in their coding region were significantly reduced. In contrast, the levels of core histone H3 were consistently higher in the silenced genes. Controlled chromatin digestion with micrococcal nuclease was used to assess changes in nucleosome compaction. We found a significant resistance to digestion in the promoter region of the silenced ap-a and cpA5 genes as compared to the parental strain that expresses those genes. Our data lend further support to the idea that histone modifications and heterochromatin formations are at the basis of the transcriptional silencing of genes in E. histolytica.

In the past, protease-substrate finding proved to be rather haphazard and was executed by in vitro cleavage assays using singly selected targets. In the present study, we report the first protease proteomic approach applied to meprin, an astacin-like metalloendopeptidase, to determine physiological substrates in a cell-based system of Madin-Darby canine kidney epithelial cells. A simple 2D IEF/SDS/PAGE-based image analysis procedure was designed to find candidate substrates in conditioned media of Madin-Darby canine kidney cells expressing meprin in zymogen or in active form. The method enabled the discovery of hitherto unknown meprin substrates with shortened (non-trypsin-generated) N- and C-terminally truncated cleavage products in peptide fragments upon LC-MS/MS analysis. Of 22 (17 nonredundant) candidate substrates identified, the proteolytic processing of vinculin, lysyl oxidase, collagen type V and annexin A1 was analysed by means of immunoblotting validation experiments. The classification of substrates into functional groups may propose new functions for meprins in the regulation of cell homeostasis and the extracellular environment, and in innate immunity, respectively.

Meprin (EC 3.4.24.18) is an oligomeric metalloendopeptidase found in microvillar membranes of kidney proximal tubular epithelial cells. Here, we present the first report on the expression of meprin beta in rat glomerular epithelial cells and suggest a potential involvement in experimental glomerular disease. We detected meprin beta in glomeruli of immunostained rat kidney sections on the protein level and by quantitative RT-PCR of laser-capture microdissected glomeruli on the mRNA level. Using immuno-gold staining we identified the membrane of podocyte foot processes as the main site of meprin beta expression. The glomerular meprin beta expression pattern was altered in anti-Thy 1.1 and passive Heymann nephritis (PHN). In addition, the meprin beta staining pattern in the latter was reminiscent of immunostaining with the sheep anti-Fx1A antiserum, commonly used in PHN induction. Using Western blot and immunoprecipitation assays we demonstrated that meprin beta is recognized by Fx1A antiserum and may therefore represent an auto-antigen in PHN. In anti-Thy 1.1 glomerulonephritis we observed a striking redistribution of meprin beta in tubular epithelial cells from the apical to the basolateral side and the cytosol. This might point to an involvement of meprin beta in this form of glomerulonephritis.

Background: Meprin (EC 3.4.24.18), an astacin-like metalloprotease, is expressed in the epithelium of the intestine and kidney tubules and has been related to cancer, but the mechanistic links are unknown., Methodology/principal Findings: We used MDCK and Caco-2 cells stably transfected with meprin alpha and or meprin beta to establish models of renal and intestinal epithelial cells expressing this protease at physiological levels. In both models E-cadherin was cleaved, producing a cell-associated 97-kDa E-cadherin fragment, which was enhanced upon activation of the meprin zymogen and reduced in the presence of a meprin inhibitor. The cleavage site was localized in the extracellular domain adjacent to the plasma membrane. In vitro assays with purified components showed that the 97-kDa fragment was specifically generated by meprin beta, but not by ADAM-10 or MMP-7. Concomitantly with E-cadherin cleavage and degradation of the E-cadherin cytoplasmic tail, the plaque proteins beta-catenin and plakoglobin were processed by an intracellular protease, whereas alpha-catenin, which does not bind directly to E-cadherin, remained intact. Using confocal microscopy, we observed a partial colocalization of meprin beta and E-cadherin at lateral membranes of incompletely polarized cells at preconfluent or early confluent stages. Meprin beta-expressing cells displayed a reduced strength of cell-cell contacts and a significantly lower tendency to form multicellular aggregates., Conclusions/significance: By identifying E-cadherin as a substrate for meprin beta in a cellular context, this study reveals a novel biological role of this protease in epithelial cells. Our results suggest a crucial role for meprin beta in the control of adhesiveness via cleavage of E-cadherin with potential implications in a wide range of biological processes including epithelial barrier function and cancer progression.

Sentinel pigeons, Columba livia, were installed in lard-can traps at heights of 1.5 m and 7.6-9.1 m within differing canopy cover classes in New York City. Adult mosquitoes were collected weekly from July to October 2002, as were serum samples from each pigeon. Culex pipiens L. and Culex restuans Theobald comprised 97% of mosquitoes collected and were most numerous in canopy-level, forested traps. The West Nile virus (family Flaviviridae, genus Flavivirus, WNV) seroconversion rate was significantly greater for pigeons in canopy-level traps, although seroconversions occurred concurrently with human cases in the city and were of little prognostic value to public health agencies. Our results indicate that sentinel pigeons were most effective for monitoring enzootic transmission of WNV when placed in single-sentinel caging 7.6-9.1 m above ground level.

Objectives: to evaluate potential systemic effects of a single epidural injection of dexamethasone., Patients and Methods: each of nine patients (five males and four females, mean age 47 +/- 11.8 years) admitted for sciatica was given a single epidural injection of 15 mg dexamethasone acetate. Before the injection (D0) and two (D2), seven (D7) and 21 (D21) days after the injection, the following laboratory tests were performed: serum cortisol and ACTH in the morning after an overnight fast, free cortisol in a 24-hour urine collection, fasting serum levels of glucose, triglycerides and cholesterol, serum levels of sodium and potassium. Blood pressure was measured on D0, D2, and D7., Results: Serum cortisol, ACTH and urinary cortisol were profoundly decreased on D2 and D7 but normal on D21. There were no changes in fasting serum glucose, triglycerides, cholesterol, sodium or potassium levels., Conclusion: a single epidural injection of 15 mg dexamethasone acetate is associated with transient adrenal suppression, denoting passage of the steroid into the systemic bloodstream. However, evidence of hypercorticism is usually lacking.

There have been few studies and case-reports of bone metastases from hepatocellular carcinoma. To determine the characteristics of these metastases, we retrospectively studied 22 patients in whom the diagnosis was established either on the basis of concomitant occurrence of malignant bone lesions and hepatocellular carcinoma in the absence of other detectable malignant disease (n = 15) or on the basis of histological evidence of bone metastasis from an hepatocellular carcinoma (n = 7). There were 21 males and one female. Mean age was 62.5 years. Most patients (88.2%) had chronic alcohol abuse. The bone metastases occurred as the first manifestation of the liver cancer in half the cases (11/22). Time interval between onset of bone symptoms and admission was less than one month in 6 of 11 patients; mean interval was 7.4 weeks. Hepatomegaly was found upon initial physical evaluation in 9 of 11 patients. Pain was the main symptom of bone disease (18/22). Palpable bone masses were found in 6 of 22 patients. Purely osteolytic lesions were seen on roentgenograms in every case; rupture of the cortex and spread to adjacent soft tissues were common findings. The radionuclide bone scan was normal in four of 12 patients. An advanced primary hepatic tumor was found in 84.2% of cases. Histologic examination of bone specimens established the diagnosis of metastasis from a hepatocellular carcinoma in 7 of 9 patients (77.8%). Severe bleeding occurred during one of the nine biopsy procedures. Patients were given symptomatic treatment. Systemic chemotherapy was used in five patients, unsuccessfully. Median survival was three months.

The first anaesthetic record was introduced into medical practice in 1940. Since then few changes have been made to it and it remains a rudimentary memorandum. However, since the beginning of the 1980s, interest in automatic recording of the anaesthetic file has been increasing and numerous arguments can be put forward in its favour. Apart from theoretical and experimental arguments, in practice one has to master the automatic collection of data, management of alarms and the technology of the networks involved in order to manage the flow of information by channelling it and organizing it into a hierarchy. Four other objectives can be added to the clinical recording and its medico-legal applications: anaesthetic cost evaluation, quality of care, research and clinical teaching which will provide the basis of anaesthetic epidemiological research.

A survey was undertaken among a representative sample of the female population, aged 20 to 74, of the Canton of Vaud, Switzerland (total population 550,000) to assess the knowledge, attitudes and practices of women in respect to breast cancer and its prevention. The present study focuses on access by women to medical preventive measures (breast examination by physician and information on breast self-examination). The data are analyzed in relation to the individual risk factors affecting women, in particular age. While with age the risk of breast cancer grows in a linear fashion, the proportion of women having their breast examined by a physician declines. Women over 50 who had no children before the age of 30 constitute an especially high risk category, with the lowest access to information and prevention. This is explained in large part by the fact that they consult gynecologists less often. In this regard it should be noted that a visit to a gynecologist's office is associated much more often with breast examination than a visit to a family physician. It is important to take such findings into account in providing more appropriate and complete care for those groups. This involves sensitization of the physician and improved information for the women themselves.

A survey by personal interviews on this subject was carried out in 1984 with a representative sample of 499 women living in the Canton of Vaud. The response rate was 76.6%. Among the respondents, 61.3% practice BSE, but only 27% do so regularly. A complementary inquiry of a group of women who refused the interviews shows a lower practice rate. Women aged 40-49 years, who have benefited more than other groups from related information through their physicians, are those who do BSE most. Our results indicate that such personalized information from a doctor is strongly and positively associated with BSE practice (p less than .001), when compared with "extra-medical" information (mainly from the mass media). There are some negative reactions (fear, reluctance) when the question of BSE is taken up, but they are not major ones and do not influence the interest of the majority of the women (63.3%) in wanting to be better informed on the subject.

Proximal tubular reabsorption was studied by the split drop micropuncture technique in HgCl2-induced severe as well as mild acute renal failure. 4 mg/kg of HgCl2 given subcutaneously to normal rats resulted in severe and usually oliguric acute renale failure at 48 h, mean plasma creatinine and urea having risen to 6.9 +/- 0.4 and 420 +/- 30 mg%. On inspection of the kidney surface, usually more than 50% of the convolutions appeared white opaque and collapased. Split drop reabsorption of 0.9% NaCl, 20% mannitol and 20% albumin was markedly accelerated in these necrotic tubular segments, while reabsorptive rates were usually quite reduced in the normal-looking red transparent convolutions. DOCA/saline-pretreated rats developed mild renal failure, with plasma creatinine and urea rising slightly to 1.6 +/-0.3 and 83 +/- 14 mg%, respectively, at 48 h after 4 mg/kh HgCl2. Reabsorptive rates were almost uniformly reduced from 0.55 +/- 0.02 in controls to 0.32 +/- 0.03 nl-mm-2 sec-1 in mild HgCl2-induced acute renale failure. Mild proximal tubular injury features decreased reabsorptive rate while severely damaged tubules appear to be leaky to the extent of allowing rapid disappearance from the tubular lument of the normally barely reabsorbable 20% albumin. Although compatible with unrestricted passive backflow being an additional factor in the pathogenesis of HgCl2-induced acute renal failure, these results do not challenge the importance of primary filtration failure.

A population survey devoted to the self examination of breast (SEB) in the Canton Vaud provided some insights regarding the attitude of women toward prevention and medicine. Unpublished data related to this survey are presented, regarding the embarassment experienced by the patients, the attitude toward prevention and SEB. The specific role of SEB is commented as a tool for secondary prevention and as an autonomous attitude of the patient. A comparison is done with the prevention of the cancer of testis and the peculiar place of the female body in medicine is emphasized. The conclusion stresses the importance of subjective attitude of patients, physicians or researchers in areas related to sexuality.

A marked increase in preglomerular resistance mediated through the renin-angiotensin system has been proposed as the mechanism for the sustained decrease in glomerular filtration rate seen following release of 24-hour ureteral obstruction. The importance of the renin-angiotensin system in mediating this response was evaluated by determining whole kidney and single nephron function following release of 24-hour ureteral obstruction in rats with normal renal renin content and in rats depleted of renal renin by desoxycorticosterone acetate acetate (DOCA) and saline treatment. The DOCA and saline treatment was effective in reducing renal renin content to less than 10% of the normal values. However, when compared to nonobstructed kidneys, both whole kidney filtration rate and single nephron filtration rate were similarly and significantly reduced in both groups following release of 24-hour ureteral obstruction. Single nephron stopflow techniques were used to determine the net hydrostatic force for filtration. The net hydrostatic force for filtration in control nonobstructed nephrons averaged 37.8 +/- 1.1 mm. Hg, but was significantly decreased to 22.5 +/- 2.2 mm. Hg in the normal renin obstructed kidney and to 18.8 +/- 1.0 mm. Hg in the renin-depleted obstructed kidney. It is concluded that the marked depression in glomerular filtration rate seen following release of 24-hour ureteral obstruction is due to increased afferent arteriole resistance and that the renin-angiotensin system is apparently not important in mediating the response.