The development of a Defense System against Coxsackievirus B5 Infection in Suckling Mice

There are many viruses that are able to infect the alimentary tract of man. Little is known, however, about the mechanism of infection itself or the pathophysiology of the gut during infection. 'The research reported here is concerned with the differences in susceptibility among suckling mice of various ages inoculated by the intraperitoneal and intragastric routes. Since the normal mode of entry of many viruses to the gut is via the oral route, Coxsackievirus B5, a human enterovirus which does attack this way, was utilized. It is a non-tumor producing RNA virus that has been shown to act similarly in the mouse and human. The virus was pooled in HeLa cell cultures and titered by a plaquing assay in the same cell cultures. CD-l mice, 10, 14, 18, and 22 days old , were infected either orally or intraperitoneally with 5.0 x 10^10 (10 day old animals) and 1.0 x10^9 plaque forming units per animal. Dissections were done at 1 and 3 days post infection with samples of the blood, heart, liver, and gut being taken from each animal. Each sample was titered individually and the data presented as an average of six samples. As a result of previous work, it is known that the gut of a newborn mouse isn't able to decrease the concentration of the infecting dose and therefore provides no defense against an enteric infection with Coxsackievirus B5. In contrat, mature mice are able to reduce the amount of viral dissemination across the gut as well as inhibit replication after absorption has occurred. The results of this study indicate that there is a double barrier system developing in suckling mice that is involved with and directly related to the gastrointestinal tract The first part of this defense is the inhibition of penetration of virus across the gut when the primary site of' infection is the intestinal mucosa. This mechanism develops sometime around 20 to 22 days after birth. At about 16-18 days of age, suckling mice that were challenged intragastrically are able to stop active replication and initiate clearance of virus from the systemic circulation. There are many factors that might contribute to the marked decrease in susceptibility with age of suckling mice. Some of these or possibly a combination of these factors might explain the defense mechanisms described above, but to date, the chemistry or mechanical functioning of the gastrointestinal barrier to enteric viral infection is unknown.

Serotonin discontinuation syndrome following utero exposure to antidepressant medication : prospective controlled study

Objectives: The aim of the present study was to examine neonatal symptoms previously reported to be associated with exposure to antidepressant medication in late pregnancy in a group of infants exposed to antidepressants, using a prospective and controlled design.

Method: A prospective case-control study recruited 27 pregnant women taking antidepressant medication and 27 matched controls who were not taking antidepressant medication in pregnancy. Of the 27 women taking medication, 25 remained on medication in the third trimester and, of these, 23 women had complete data available. In pregnancy and after delivery women were assessed with the Beck Depression Inventory-II and a purpose-designed questionnaire. After delivery mothers were asked a set of nine questions pertaining to symptoms of discontinuation in their newborn and questions about pregnancy and delivery complications.

Results: There was an increased risk of discontinuation symptoms in neonates exposed to antidepressant medication in late pregnancy and an association with higher dose medication. The study group were found to be significantly more likely to display behaviour such as crying, jitteriness, tremor, feeding, reflux and sneezing and sleep for <3 h after a feed. They also had significantly higher rates of jaundice and admissions to the special care nursery.

Conclusions: Exposure to antidepressants in late pregnancy is associated with a range of symptoms in the neonate that are consistent with the effects of exposure to antidepressants in late pregnancy. The clusters of symptoms most highly correlated are the gastrointestinal and central nervous system symptoms. These finding helps to identify the common symptoms associated with a neonatal serotonin discontinuation syndrome.

The role of fatty acids in satiation and satiety

Background – Satiation and satiety describe the events which lead to meal termination and the maintenance of hunger induced by physical and metabolic events following food ingestion. Fatty acids, components of dietary fat (triglyceride) may be important, if not essential components of satiation and satiety. Emerging evidence suggests fatty acid now constitutes a sixth taste modality and orally sensed fatty acids mediate unique cephalic and hormonal responses priming the body for fat digestion, and may contribute to sensory specific satiety. Once ingested, fatty acids are sensed in the gastrointestinal tract (GIT) where they cause the release of hormones, stimulate the vagus and enter the blood stream where they act a number of organs (brain, liver) to influence satiety.
Objective – To review the role of fatty acids in sensory and metabolic satiation and satiety.
Design – Literature search and review of papers from the past decade on satiety, satiation, fat taste and fatty acids.
Outcomes – The physiological significance of gustatory fat detection is still unclear, but it may signal the nutritious content of fat similar to the tastes of sweet or umami which signal the presence of carbohydrate or proteins. Like other tastants, fatty acid taste sensitivity is thought to vary in the population and differences in sensitivity may influence dietary choice and fat intake. Fatty acid taste may contribute to sensory specific satiety as foods are eaten. Animal models have observed an inverse relationship between oral fatty acid sensitivity and fat consumption, which leads to obesity. Observations that the obese have heightened preferences for, and consume more fat than lean individuals questions whether such a relationship may also be apparent in humans. At the GIT, fatty acids are sensed by enterocytes and bind to receptors, transporters or ion channels where they initiate gut-brain communication over nutrient status through the vagus and cause the release of satiety hormones which lead to meal termination. Inefficient fatty acid sensing at either or both locations is thought to accompany the aetiology of obesity.
Conclusion – Variations in sensitivity to fatty acids may alter preferences and consumption of fats or hormonal responses to fat ingestion which influence sensory-specific, metabolic and subjective satiety.

Development of a salmon protein hydrolysate that lowers blood pressure

A salmon protein hydrolysate (SPH) was developed containing several angiotensin I-converting enzyme (ACE) inhibitory tripeptides the most abundant of which were Val-Leu-Trp, Val-Phe-Tyr, and Leu-Ala-Phe. Simulated digestion experiments showed that active constituents of SPH would survive in the digestive tract and be available for absorption into the bloodstream. In fact, ACE inhibitory activity was improved following simulated digestion suggesting that there were larger peptides in SPH that might contribute to bioactivity in vivo. A single oral dose (1,500 mg/kg body mass) of SPH significantly lowered blood pressure in spontaneously hypertensive rats (SHR). The treatment of SHR with either SPH fraction (<3,000 Da) or SPH fraction (>3,000 Da) reduced blood pressure. We conclude that the ability of SPH to lower blood pressure is due to a combination of ACE inhibitory tripeptides as identified, as well as additional unknown, peptide species that are generated during digestion of SPH in the gastrointestinal tract.

Bovine muc1 inhibits binding of enteric bacteria to caco-2 cells

Inhibition of bacterial adhesion to intestinal epithelial receptors by the consumption of natural food components is an attractive strategy for the prevention of microbial related gastrointestinal illness. We hypothesised that Muc1, a highly glycosylated mucin present in cows’ milk, may be one such food component. Purified bovine Muc1 was tested for its ability to inhibit binding of common enteric bacterial pathogens to Caco-2 cells grown in vitro. Muc1 caused dose-dependent binding inhibition of Escherichia coli, Salmonella enterica serovar Typhimurium (S. Typhimurium), Staphylococcus aureus and Bacillus subtilis. This inhibition was more pronounced for the Gram negative compared with Gram positive bacteria. It was also demonstrated that Muc1, immobilised on a membrane, bound all these bacterial species in a dose-dependent manner, although there was greater interaction with the Gram negative bacteria. A range of monosaccharides, representative of the Muc1 oligosaccharide composition, were tested for their ability to prevent binding of E. coli and S. Typhimurium to Caco-2 cells. Inhibition was structure dependent with sialic acid, L(-) fucose and D(+) mannose significantly inhibiting binding of both Gram negative species. N-acetylglucosamine and N-acetylgalactosamine significantly inhibited binding of E. coli whilst galactose, one of the most abundant Muc1 monosaccharides, showed the strongest inhibition against S. Typhimurium. Treatment with sialidase significantly decreased the inhibitory properties of Muc1, demonstrating the importance of sialic acid in adhesion inhibition. It is concluded that bovine Muc1 prevents binding of bacteria to human intestinal cells and may have a role in preventing the binding of common enteropathogenic bacteria to human intestinal epithelial surfaces.

Relationship between alcohol abuse upper gastro-intestinal haemorrhage and nutritional status during acute hospital admission

This thesis is concerned with the effect of alcohol consumption on the pathogenesis of bleeding from the upper gastrointestinal tract via nutritional pathways. Altered nutritional status is a frequently recognised clinical accompaniement of heavy alcohol consumption in hospitalized patients. Similarly, upper gastrointestinal bleeding is frequently accompanied by the presence of heavy alcohol consumption. Nevertheless, the clinical quantification of alcohol intake is often descriptive, so that a link between alcohol use and upper gastrointestinal haemorrhage via nutritional mechanisms has been only generally defined. In the literature review, the methods of defining alcohol use and abuse, using interview, biochemical and haematological techniques are noted. The relationship between alcohol abuse and nutrient imbalances is reviewed, especially in relation to possible effects on the gastrointestinal tract, appetite and eating habits. A further section reviews the relationship between alcohol use and anatomical lesions of the upper gastrointestinal tract likely to lead to bleeding. Following the chapter in which the methods used in this thesis are described. Chapter 4 seeks to describe the study population and its subgroups in this thesis in relation to interview, biochemical and haematological methods. Alcohol use is defined in relation to (1) a clinical classification of heavy or light drinking, based on a questionnaire administered in Casualty, (2) a quantified method of determining alcohol consumption during a subsequent ward dietetic assessment, (3) in relation to a biochemical definition (recent drinking and non-drinking), and a classification of (1) and (2) called, for the purposes of this thesis, 'alcohol abusers' and 'nonabusers'. Heavy, regular and recent drinkers and alcohol abusers tend to be male and younger than light, infrequent and nonrecent drinkers and nonabusers. Chapter 5 relates the nutritional status of those patients admitted acutely to hospital in relation to the groups defined in Chapter 4, Nutritional status is defined in terms of food intake, anthropometry, biochemical and haematological parameters. Different methods of defining alcohol use give rise to different patterns of nutritional impairment. Chapter 6 relates the nutritional status of those patients admitted acutely to hospital in relation to the presence or absence of an endoscopically defined site of upper gastrointestinal bleeding. A difference is seen between those bleeding from a Mailory-weiss tear and other sites of bleeding, similarly, biochemical differences in nutritional status emerge between those patients who presented in shock, and those who did not. Chapter 7 explores the relationships between biochemical markers of nutritional status and haemostatic variables in the groups of abusers/non-abusers, the various sites of primary bleeding/controls, and shock/non-shock. Serum copper appears to be related to altered haemostasis in a manner not apparently described elsewhere.

β-Thalassaemia : emergence of new and improved iron chelators for treatment

β-Thalassaemia is an inherited blood disorder which through repeated blood transfusions and enhanced iron uptake from the gastrointestinal tract, results in marked iron overload. Untreated, the iron accumulation results in the dysfunction of vital organs such as the heart and liver. At present, the most effective treatment for β-thalassaemia is the use of the iron chelator, desferrioxamine, which is expensive, orally inactive and requires long subcutaneous infusions. In this concise review, we will focus on novel chelators which show therapeutic potential to replace desferrioxamine. Furthermore, we will discuss the potential of combined iron chelation therapy and the principle that, in the future, the use of more than just one chelator may be beneficial in tailoring individual iron chelation regimens.

Manipulation of dietary short chain carbohydrates alters the pattern of gas production and genesis of symptoms in irritable bowel syndrome

Background and Aim:  Reduction of short-chain poorly absorbed carbohydrates (FODMAPs) in the diet reduces symptoms of irritable bowel syndrome (IBS). In the present study, we aimed to compare the patterns of breath hydrogen and methane and symptoms produced in response to diets that differed only in FODMAP content.
Methods:  Fifteen healthy subjects and 15 with IBS (Rome III criteria) undertook a single-blind, crossover intervention trial involving consuming provided diets that were either low (9 g/day) or high (50 g/day) in FODMAPs for 2 days. Food and gastrointestinal symptom diaries were kept and breath samples collected hourly over 14 h on day 2 of each diet.
Results:  Higher levels of breath hydrogen were produced over the entire day with the high FODMAP diet for healthy volunteers (181 ± 77 ppm.14 h vs 43 ± 18; mean ± SD P < 0.0001) and patients with IBS (242 ± 79 vs 62 ± 23; P < 0.0001), who had higher levels during each dietary period than the controls (P < 0.05). Breath methane, produced by 10 subjects within each group, was reduced with the high FODMAP intake in healthy subjects (47 ± 29 vs 109 ± 77; P = 0.043), but was not different in patients with IBS (126 ± 153 vs 86 ± 72). Gastrointestinal symptoms and lethargy were significantly induced by the high FODMAP diet in patients with IBS, while only increased flatus production was reported by healthy volunteers.
Conclusions:  Dietary FODMAPs induce prolonged hydrogen production in the intestine that is greater in IBS, influence the amount of methane produced, and induce gastrointestinal and systemic symptoms experienced by patients with IBS. The results offer mechanisms underlying the efficacy of the low FODMAP diet in IBS.

Fat taste sensitivity

Hyposensitivity to fatty acid taste is associated with greater intake of fat, higher BMI and attenuated gastrointestinal (GI) function. These observations are consistent amongst healthy and overweight/obese subjects, who display attenuated taste and GI function, and consume excess fat.

Review : nurses can improve patient nutrition in intensive care

Aims and objectives. To review the literature and identify opportunities for nutritional practice improvement in the critically ill and opportunities to improve nurses’ knowledge relating to enteral feeding.

Background. The literature reports varying nutritional practices in intensive care.

Design. Systematic review.

Methods. A systematic search, selection, analysis and review of nursing, medical and dietetic primary research articles was undertaken. Fifteen studies met the selection criteria.

Results. Delivery of nutrition to the critically ill varied widely. Patients were frequently underfed and less frequently, overfed. Both under- and overfeeding have been linked with unacceptable consequences including infections, extended weaning from mechanical ventilation, increased length of stay and increased mortality. Underfeeding was related to slow initiation and advancement of nutrition support and avoidable feed interruptions. The most common reasons for interrupting feeds were gastrointestinal intolerance and fasting for procedures. Certain nursing practices contributed to underfeeding such as the management of gastric residual volumes.

Conclusions. Consistent and reliable nutrition support in intensive care units is hampered by a lack of evidence leading to varying nutrition practices. Factors impeding delivery of enteral nutrition were considered avoidable. A new concept of a therapeutic range of energy delivery in the critically ill has emerged implying the need for re-evaluation of energy recommendations and improved delivery of enteral nutrition.

Relevance to clinical practice. This review supports the multi-disciplinary development and implementation of an evidence-based enteral feeding protocol in intensive care units as a strategy to improve adequacy of nutritional intake. Critical care nurses are well placed to improve this process.

A review of clozapine safety

Clozapine is a distinctive antipsychotic agent, having a unique clinical profile and an idiosyncratic safety profile. More so than with other agents, the weighting of its adverse event profile is critical, in order to counterbalance its clear clinical advantages. The safety issues with clozapine are in a number of areas, some of which are considered medical emergencies and potentially life-threatening. These include haematological (neutropenia and agranulocytosis), CNS (seizures), cardiovascular (myocarditis and cardiomyopathy), metabolic (diabetes), gastrointestinal and neuromuscular. Understanding the safety profile of clozapine allows an informed use of the agent that can maximise its clear clinical benefit and minimise the known risks.

Bovine lactoferrin : potential antioxidant effector molecule in colon carcinoma

This research generated important insight into the antioxidant capacity and effector molecule capability of bovine lactoferrin in both its Apo- (iron free) and metal saturated forms within the gastrointestinal system, giving rise to bovine lactoferrin's potential at regulating oxidative stress associated signalling molecules within colon carcinoma.

Conservation of the ST6Gal I gene and its expression in the mammary gland

Milk sialoglycoconjugates can protect the gastrointestinal tract of the suckling neonate by competitively binding to invading pathogens and promoting growth of beneficial flora, and their potential role in postnatal brain development is of particular interest in human infant nutrition. Although the concentration and the distribution of sialoglycoconjugates have been extensively studied in the milk of various species, the investigation of sialyltransferase gene expression in the mammary gland, in the context of lactation, has been limited. The sialyltransferase enzyme ST6Gal I transfers sialic acid from CMP-sialic acid to type 2 (Galβ1,4GlcNAc) free disaccharides or the termini of N- or O-linked oligosaccharides using an α2,6-linkage. Expression of the ST6Gal I gene is primarily regulated at the level of transcription through the use of several cell and development- specific promoters, producing transcripts with divergent 5′ untranslated regions (UTR). In the mouse mammary gland, the novel 5′UTR exon (L) appears to be associated with a drastic increase in ST6Gal I gene expression during lactation. We find that rats also possess an exon (L), suggesting conservation of this regulatory mechanism in rodents. In contrast, an exon (L)-containing transcript was not detected in the lactating bovine or human mammary gland. We also observed a trend of increasing ST6Gal I gene expression in the bovine mammary gland, culminating in involution. This is in contrast to species such as mice where the greatest change in ST6Gal I gene expression occurs between pregnancy and lactation, suggesting different roles in rodents vs. other mammals for α2,6-sialylated oligosaccharides present in milk.

Mycoplasmas in Australian fur seals (Arctocephalus pusillus doriferus) : identification and association with abortion

Bacteria from the genus Mycoplasma are common inhabitants of the respiratory, gastrointestinal, and genital tracts of mammals. The understanding of the pathological significance of mycoplasmas in seals is poor, as few studies have utilized the specific culture techniques required to isolate these bacteria. The current study surveyed for the Mycoplasma species present in Australian fur seals (Arctocephalus pusillus doriferus) and investigated the association between infection and pathology. Mycoplasmas were found in the nasal cavities of 55/80 (69%) of apparently healthy individuals. Isolates from 18 individuals were investigated through 16S ribosomal RNA sequencing, and 3 species were identified: M. zalophi, M. phocae, and Mycoplasma sp. (GenBank no. EU714238.1), all of which had previously been isolated from Northern Hemisphere pinnipeds. In addition, mycoplasmas were isolated from the lungs of 4 out of 16 juveniles and 1 out of 5 adults sampled at necropsy. Isolates obtained were M. zalophi, Mycoplasma sp. EU714238.1, and M. phocicerebrale, but infection was not associated with lung pathology in these age classes. Inflammatory disease processes of the heart and/or lungs were present in 12 out of 32 (38%) aborted fetuses on microscopic examination. Predominant findings were interstitial pneumonia, pericarditis, and myocarditis. Mycoplasma phocicerebrale was isolated from the thymus of an aborted fetus, and 3 out of 11 (27%) fetuses with inflammatory heart or lung lesions were PCR-positive for Mycoplasma. In conclusion, several species of Mycoplasma are part of the normal flora of the nasal cavity of Australian fur seals, and some mycoplasmas may be associated with abortion in this species of seal.

The use of cyclodextrins nanoparticles for oral delivery

This review aims to highlight many of the difficulties encountered in trying to achieve the task of delivering proteins and peptides through oral administration. The necessity of controlled protein and peptide release, protection and stability in the gastrointestinal tract, and ability to target specific areas are only a handful of the many problems associated with trying to engineer a useful solution. Current research gives strong indication that both cyclodextrins and nanoparticles could be highly useful in the search for a suitable method for such successful oral delivery of proteins and peptides. This review focuses on the use of cyclodextrins in pharmaceuticals, aiming to discuss the use of cyclodextrins in conjunction with nanoparticles for oral delivery of proteins. Both classical applications and more advanced "nanomedical" approaches are discussed. In order to achieve a complete overview this review will include background information about cyclodextrins, nanomedicine and their role in oral delivery systems. The use of absorption enhancers like cyclodextrins, bile salts and surfactants was used to facilitate bio-availability into the system. The state-of-the-art technology and challenges in this area are discussed, with typical examples.