Peptides and multiple antigen peptides from Schistosoma mansoni glyceraldehyde 3-phosphate dehydrogenase: preparation, immunogenicity and immunoprotective capacity in C57BL/6 mice.

Four monoepitopic MAPs (MAP A, B, C and E) and one bis-diepitopic MAP B-E derived fromthe primary sequence of Schistosoma mansoni glyceraldehyde 3-phosphate dehydrogenase, previously tested in BALB/c mice, were examined for their immunogenicity and protective capacity in C57BL/6 mice. Despite multimerization into MAPs, MAP Aand MAP C were poorly immunogenic. In contrast toBALB/c mice, MAP E was non-immunogenic in C57BL/6 mice. Peptide B in the form of MAP B orbis-diepitopic MAPB-E elicited immune responses in C57BL/6 mice that were associated with a significant decrease in worm burden. The MAPs were prepared by the stepwise solid-phase peptide synthesis using Boc/Bzl chemistry, successfully purified on the RP-HPLC column and characterized by RP-HPLC, HPCE and MALDI-TOF MS techniques. A general strategy for MAPs purification is discussed here and the purification of MAP Band MAP E is documented in detail.     

Determination and Health-Risk Evaluation of Nitroxynil Residues in the Edible Tissue of Cattle

A specific Polarographic method with a sensitivity of ≥ 2 jig/kg (ppb) has been used to determine the plasma and tissue concentrations of nitroxynil (NTX), which is used against Parafilaria bovicola in cattle. After treatment with the therapeutic dose on NTX (2 × 20 mg/kg b.w., s,c), there was an initial rapid decrease in the plasma concentration followed by a slower elimination phase. The plasma levels of NTX were 8 mg/kg (ppm) and 3 mg/kg after 6 weeks and 2 months, respectively. The muscle and other edible tissue from treated cattle contained 0.1–0.3 mg/kg NTX after 2 months, and jxg/kg amounts were still detectable 3 months after the injection. Based on available pharmacological and toxicological data, a 3-months withdrawal time for NTX in cattle is proposed.     

Evaluation of gas chromatograph packings for the separation of butyric acid from serum-catalyzed hydrolysis of ethyl butyrate

Twelve synthetic and pilot adsorbents of different polarity and varying chemical composition were tested for the separation and quantitative determination of butyric acid from serum-catalyzed hydrolysis of ethyl butyrate. A gas chromatographic procedure with flame ionization detector (fld) using these adsorbents is satisfactory for the separation of butyric acid. The best results were obtained with Spheron SDA, Spheron BD, and Porapak R.     

LVV-hemorphin-7 lowers blood pressure in spontaneously hypertensive rats: radiotelemetry study

Cardiovascular effects of LVV-hemorphin-7, a member of the family of fragments from beta-chain of human or bovine hemoglobin, were studied in conscious spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats by radiotelemetry. Intraperitoneal injection of hemorphin in a dose of 100 microg/kg significantly decreased blood pressure in SHR, whereas negligible effect was seen in normotensive WKY rats. Blood pressure changes were accompanied by reduction of heart rate. In conclusion, a direct effect of LVV-hemorphin-7 on blood pressure was demonstrated in SHR. These biologically active peptides could be involved in blood pressure regulation especially in hypertensive rats, but the precise mechanism should be elucidated.     

Lack of pyloric interstitial cells of Cajal explains distinct peristaltic motor patterns in stomach and small intestine

The frequency and propagation velocity of distension-induced peristaltic contractions in the antrum and duodenum are distinctly different and depend on activation of intrinsic excitatory motoneurons as well as pacemaker cells, the interstitial cells of Cajal associated with Auerbach's plexus (ICC-AP). Because ICC are critical for coordination of motor activities along the long axis of many regions in the gut, the role of ICC in antroduodenal coordination was investigated. We used immunohistochemistry, electron microscopy, simultaneous multiple electrical recordings in vitro, and videofluoroscopy in vivo in mice and rats. A strongly reduced number of ICC-AP with loss of network characteristics was observed in a 4-mm area in the rat and a 1-mm area in the mouse pyloric region. The pyloric region showed a slow wave-free gap of 4.1 mm in rats and 1.3 mm in mice. Between antrum and duodenum, there was no interaction of electrical activities and in the absence of gastric emptying, there was no coordination of motor activities. When the pyloric sphincter opened, 2.4 s before the front of the antral wave reached the pylorus, the duodenum distended after receiving gastric content and aboral duodenal peristalsis was initiated, often disrupting other motor patterns. The absence of ICC-AP and slow wave activity in the pyloric region allows the antrum and duodenum to have distinct uncoordinated motor activities. Coordination of aborally propagating peristaltic antral and duodenal activity is initiated by opening of the pylorus, which is followed by distention-induced duodenal peristalsis. Throughout this coordinated motor activity, the pacemaker systems in antrum and duodenum remain independent.     

TGF-beta1 gene transfer to the mouse colon leads to intestinal fibrosis

Crohn's disease (CD) is a chronic, relapsing inflammatory bowel disease, characterized by transmural inflammation. In CD, the recurrent inflammatory injury and tissue repair that occurs in the intestine can progress uncontrollably, leading to the proliferation of mesenchymal cells as well as fibrosis, characterized by excessive extracellular matrix deposition. These processes thicken the bowel wall, reducing flexibility, and often culminate in obstructive strictures. Because no effective measures are currently available to specifically treat or prevent intestinal stricturing, we sought to gain a better understanding of its pathogenesis by developing a mouse model of intestinal fibrosis. Because transforming growth factor (TGF)-beta1 can mediate both fibrosis and mesenchymal cell proliferation; we studied the effects of delivering adenoviral vectors encoding spontaneously active TGF-beta1 into the colons of mice. We first demonstrated that enema delivery of marker adenoviral vectors led to the transfection of the colonic epithelium and transient transgene expression. Histologically, control vectors caused an acute inflammatory response, involving the recruitment of neutrophils and mononuclear cells into the colonic lamina propria; however, infection caused little if any fibrosis. In contrast, the TGF-beta1 vector caused a more severe and prolonged inflammatory response as well as localized collagen deposition, leading to severe and progressive fibrosis. This was accompanied by the emergence of cells with a myofibroblast phenotype. Ultimately the fibrosis resulted in many of the TGF-beta1-transfected mice developing profound colonic obstruction. Through adenoviral gene transfer technology, we describe a novel mouse model of colitis and implicate TGF-beta1 in the pathogenesis of obstructive intestinal fibrosis.     

Prevalence and determinants of healthcare avoidance during the COVID-19 pandemic: A population-based cross-sectional study

BackgroundDuring the Coronavirus Disease 2019 (COVID-19) pandemic, the number of consultations and diagnoses in primary care and referrals to specialist care declined substantially compared to prepandemic levels. Beyond deferral of elective non-COVID-19 care by healthcare providers, it is unclear to what extent healthcare avoidance by community-dwelling individuals contributed to this decline in routine healthcare utilisation. Moreover, it is uncertain which specific symptoms were left unheeded by patients and which determinants predispose to healthcare avoidance in the general population. In this cross-sectional study, we assessed prevalence of healthcare avoidance during the pandemic from a patient perspective, including symptoms that were left unheeded, as well as determinants of healthcare avoidance.Methods and findingsOn April 20, 2020, a paper COVID-19 survey addressing healthcare utilisation, socioeconomic factors, mental and physical health, medication use, and COVID-19–specific symptoms was sent out to 8,732 participants from the population-based Rotterdam Study (response rate 73%). All questionnaires were returned before July 10, 2020. By hand, prevalence of healthcare avoidance was subsequently verified through free text analysis of medical records of general practitioners. Odds ratios (ORs) for avoidance were determined using logistic regression models, adjusted for age, sex, and history of chronic diseases. We found that 1,142 of 5,656 included participants (20.2%) reported having avoided healthcare. Of those, 414 participants (36.3%) reported symptoms that potentially warranted urgent evaluation, including limb weakness (13.6%), palpitations (10.8%), and chest pain (10.2%). Determinants related to avoidance were older age (adjusted OR 1.14 [95% confidence interval (CI) 1.08 to 1.21]), female sex (1.58 [1.38 to 1.82]), low educational level (primary education versus higher vocational/university 1.21 [1.01 to 1.46), poor self-appreciated health (per level decrease 2.00 [1.80 to 2.22]), unemployment (versus employed 2.29 [1.54 to 3.39]), smoking (1.34 [1.08 to 1.65]), concern about contracting COVID-19 (per level increase 1.28 [1.19 to 1.38]) and symptoms of depression (per point increase 1.13 [1.11 to 1.14]) and anxiety (per point increase 1.16 [1.14 to 1.18]). Study limitations included uncertainty about (perceived) severity of the reported symptoms and potentially limited generalisability given the ethnically homogeneous study population.ConclusionsIn this population-based cross-sectional study, 1 in 5 individuals avoided healthcare during lockdown in the COVID-19 pandemic, often for potentially urgent symptoms. Healthcare avoidance was strongly associated with female sex, fragile self-appreciated health, and high levels of depression and anxiety. These results emphasise the need for targeted public education urging these vulnerable patients to timely seek medical care for their symptoms to mitigate major health consequences.

Marije J. Splinter and colleagues assess the prevalence of healthcare avoidance during the COIVD-19 pandemic and investigate related determinants