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1. The science of micronutrients in clinical practice – Report on the ESPEN symposium

Author

Berger, Mette M., Amrein, Karin, Barazzoni, Rocco, Bindels, Laure, Bretón, Irene, Calder, Philip C., Cappa, Stefano, Cuerda, Cristina, D'Amelio, Patrizia, de Man, Angélique, Delzenne, Nathalie M., Forbes, Alastair, Genton, Laurence, Gombart, Adrian F., Joly, Francisca, Laviano, Alessandro, Matthys, Christophe, Phyo, Pyi Pyi, Ravasco, Paula, Serlie, Mireille J., Shenkin, Alan, Stoffel, Nicole U., Talwar, Dinesh, van Zanten, Arthur R.H., Berger, Mette M., Amrein, Karin, Barazzoni, Rocco, Bindels, Laure, Bretón, Irene, Calder, Philip C., Cappa, Stefano, Cuerda, Cristina, D'Amelio, Patrizia, de Man, Angélique, Delzenne, Nathalie M., Forbes, Alastair, Genton, Laurence, Gombart, Adrian F., Joly, Francisca, Laviano, Alessandro, Matthys, Christophe, Phyo, Pyi Pyi, Ravasco, Paula, Serlie, Mireille J., Shenkin, Alan, Stoffel, Nicole U., Talwar, Dinesh, and van Zanten, Arthur R.H.

Abstract

Background & aims: The European Society for Clinical Nutrition and Metabolism published its first clinical guidelines for use of micronutrients (MNs) in 2022. A two-day web symposium was organized in November 2022 discussing how to apply the guidelines in clinical practice. The present paper reports the main findings of this symposium. Methods: Current evidence was discussed, the first day being devoted to clarifying the biology underlying the guidelines, especially regarding the definition of deficiency, the impact of inflammation, and the roles in antioxidant defences and immunity. The second day focused on clinical situations with high prevalence of MN depletion and deficiency. Results: The importance of the determination of MN status in patients at risk and diagnosis of deficiencies is still insufficiently perceived, considering the essential role of MNs in immune and antioxidant defences. Epidemiological data show that deficiencies of several MNs (iron, iodine, vitamin D) are a global problem that affects human health and well-being including immune responses such as to vaccination. Clinical conditions frequently associated with MN deficiencies were discussed including cancer, obesity with impact of bariatric surgery, diseases of the gastrointestinal tract, critical illness, and aging. In all these conditions, MN deficiency is associated with worsening of outcomes. The recurrent problem of shortage of MN products, but also lack of individual MN-products is a worldwide problem. Conclusion: Despite important progress in epidemiology and clinical nutrition, numerous gaps in practice persist. MN depletion and deficiency are frequently insufficiently searched for in clinical conditions, leading to inadequate treatment. The symposium concluded that more research and continued education are required to improve patient outcome.

Published
2024

2. How to deal with micronutrient product shortage - Editorial

Author

Joly, Francisca, Mundi, Manpreet, Barazzoni, Rocco, Berger, Mette M., Bozzetti, Frederico, Cuerda, Cristina, Jeppesen, Palle B., Lal, Simon, Lamprecht, Georg, Szczepanek, Kinga, Van Gossum, André, Schneider, Stéphane, Shenkin, Alan, Wanten, Geert, Pironi, Loris, Joly, Francisca, Mundi, Manpreet, Barazzoni, Rocco, Berger, Mette M., Bozzetti, Frederico, Cuerda, Cristina, Jeppesen, Palle B., Lal, Simon, Lamprecht, Georg, Szczepanek, Kinga, Van Gossum, André, Schneider, Stéphane, Shenkin, Alan, Wanten, Geert, and Pironi, Loris

Published
2023

10. Homopolymer-rich regions in mammalian DNA

Author

Shenkin, Alan

Subjects
572.85
Abstract

The presence of deoxyadenylate-rich (dA-rich) and deoxyguanylate-rich (dG-rich) regions in mammalian DNA has been demonstrated by hybridisation with [5H] poly(U) and [5H] poly(C). For BHK-21/CI3 cells, the maximum levels of these homopolymer-rich regions, as detected by the hybridisation technique, are about 0.41% of the DNA for dA-rich, and 0.1% of the DNA for dG-rich regions. Since the hybrids are largely sensitive to digestion with RNase, it is probable that the majority of hybrid molecules contain mismatched base-pairs. 0.13% of the DNA consists of dA-rich regions ranging in size from 25-130 nucleotides long and containing about 2-6% of bases other than adenine. On the other hand, dG-rich regions less than 40 nucleotides long comprise 0.07% of the DNA and contain 10-30% of bases other than guanine. Exhaustive RNase digestion of the hybrids enables detection of pure deoxyhomopolymeric regions in the DNA. Pure sequences of poly(dA) of average size about 31 nucleotides long account for 0.008% of BHK-21/C13 DNA, whereas poly(dG) sequences about 17 nucleotides long comprise 0.0016% of the-DNA. The organisation of these sequences within the genome has been investigated. Both dA-rich and dG-rich regions are present within DNA sequences of widely varying base composition. Extensive shearing of the DNA is required to produce some enrichment for dA-rich sequences in the A + T rich fraction, although dG-rich sequences are slightly enriched in the (3- + C rich fraction of even unsheared DNA. The buoyant density of hybrid molecules was found to be significantly greater than that of the unhybridised DNA only when highly sheared. DNA was used. Furthermore, dA- rich and dG-rich regions were shown to be associated with rapidly, intermediately, and slowly renaturing DNA sequences. These findings all suggest that the dA-rich and dA-rich regions have a widespread distribution throughout DNA molecules. The pure poly(dA) and poly(dG) sequences also appear to be scattered throughout DNA molecules. In situ hybridisation studies with C5H] poly(U) further suggest that the dA~rich regions are not localised to any particular chromosome or to any specific region of the chromosomes. Analysis of DNA from a number of different species has shown that, in general, the dA-rich and dG-rich regions are present to a much higher level in mammalian DNA than in bacterial, bacteriophage, and mammalian viral DNAs. Evidence for the existence of A-rich, U-rich and G-rich RNA species in BHK-21/015 cells has also been obtained. The characteristics of the homopolymer-rich regions in DNA suggest that the dA-rich and pure poly(dA) sequences are more likely to have a significant role than dG-rich and poly(dG) sequences. The possible functions of these unusual deoxynucleotide sequences are reviewed.

Published
1974

11. Fish oil-enriched nutritional supplement attenuates progression of the acute-phase response in weight-losing patients with advanced pancreatic cancer

Author

Barber, Matthew D., Ross, James A., Preston, Tom, Shenkin, Alan, and Fearon, Kenneth C.H.

Subjects
Fish oils -- Health aspects, Dietary supplements -- Physiological aspects, Weight loss -- Health aspects, Pancreatic cancer -- Health aspects, Acute phase reaction -- Health aspects, Nutrition -- Physiological aspects, Cancer patients -- Food and nutrition, Food/cooking/nutrition
Abstract

The presence of an acute-phase protein response (APPR) has been suggested to shorten survival and contribute to weight loss in patients with pancreatic cancer. Fatty acids derived from fish oil have been shown to alter proinflammatory cytokine production and acute-phase protein synthesis in vitro. The present study was designed to determine the effects of a fish oil-enriched nutritional supplement on the concentrations of a range of individual acute-phase proteins (APP) in patients with advanced pancreatic cancer. In a sequential series, 18 patients with pancreatic cancer received the supplement (providing 2 g eicosapentaenoic acid and 1 g docosahexaenoic acid/d) for 3 wk while another 18 received full supportive care alone. Six healthy subjects served as additional controls. Acute-phase proteins were measured before and after the 3-wk intervention period in cancer patients. At baseline, albumin, transferrin and pre-albumin were significantly reduced and fibrinogen, haptoglobin, [Alpha]-1-acid glycoprotein, [Alpha]-1-antitrypsin, ceruloplasmin and C-reactive protein (CRP) were significantly elevated in the cancer patients compared with healthy controls, reflecting their roles as negative and positive acute phase proteins, respectively. In the supplemented cancer group, the only significant change in APP concentrations over the 4-wk study period was an increase in transferrin. In the control cancer group there were further significant reductions in albumin, transferrin and pre-albumin, and a significant increase in CRP concentration. These results suggest that many positive and negative APP are altered in advanced pancreatic cancer. The APPR tends to progress in untreated patients but may be stabilized by the administration of a fish oil-enriched nutritional supplement. This may have implications for reducing wasting in such patients. KEYWORDS: cancer cachexia; acute-phase protein response; fish oil; eicosapentaenoic acid; humans

Published
1999

12. Fibrinogen synthesis is elevated in fasting cancer patients with an acute phase response

Author

Preston, Tom, Slater, Christine, McMillan, Donald C., Falconer, J. Stuart, Shenkin, Alan, and Fearon, Kenneth C.H.

Subjects
Fibrinogen -- Physiological aspects, Cancer patients -- Physiological aspects, Acute phase reaction -- Analysis, Amino acids -- Analysis, Pancreatic cancer -- Analysis, Proteins -- Synthesis, Food/cooking/nutrition
Published
1998

14. Trace element supplementation modulates pulmonary infection rates after major burns: a double-blind, placebo-controlled trial

Author

Berger, Mette M., Spertini, Francois, Shenkin, Alan, Wardle, Catherine, Wiesner, Lucie, Schindler, Charles, and Chiolero, Rene L.

Subjects
Burns and scalds -- Health aspects, Dietary supplements -- Health aspects, Pneumonia -- Prevention, Food/cooking/nutrition, Health
Abstract

Infections remain the leading cause of death after major burns. Trace elements are involved in immunity and burn patients suffer acute trace element depletion after injury. In a previous nonrandomized study, trace element supplementation was associated with increased leukocyte counts and shortened hospital stays. This randomized, placebo-controlled trial studied clinical and immune effects of trace element supplements. Twenty patients, aged 40 [+ or -] 16 y (x [+ or -] SD), burned on 48 [+ or -] 17% of their body surfaces, were studied for 30 d after injury. They consumed either standard trace element intakes plus supplements (40.4 [micro]mol Cu, 2.9 [micro]mol Se, and 406 [micro]mol Zn; group TE) or standard trace element intakes plus placebo (20 [micro]mol Cu, 0.4 [micro]mol Se, and 100 [micro]mol Zn; group C) for 8 d. Demographic data were similar for both groups. Mean plasma copper and zinc concentrations were below normal until days 20 and 15, respectively (NS). Plasma selenium remained normal for group TE but decreased for group C (P [is less than] 0.05 on days 1 and 5). Total leukocyte counts tended to be higher in group TE because of higher neutrophil counts. Proliferation to mitogens was depressed compared with healthy control subjects (NS). The number of infections per patient was significantly (P [is less than] 0.05) lower in group TE (1.9 [+ or -] 0.9) than in group C (3.1 [+ or -] 1.1) because of fewer pulmonary infections. Early trace element supplementation appears beneficial after major burns; it was associated with a significant decrease in the number of bronchopneumonia infections and with a shorter hospital stay when data were normalized for burn size. Am J Clin Nutr 1998;68:365-71.

Published
1998

15. Lipoprotein(a): an independent risk factor for ischemic heart disease that is dependent on triglycerides in subjects with type 2 diabetes mellitus

Author

Marks Eileen, Alkindi Mohammed, AlBahrani Ali, AlYahyaee Said, and Shenkin Alan

Subjects
Nutritional diseases. Deficiency diseases, RC620-627
Abstract

Abstract Lipoprotein(a) is an independent risk factor for Ischaemic Heart Disease (IHD) in the general population. There are conflicting reports in the extent of its association with IHD among subjects with Type 2 diabetes mellitus (T2DM). The aim was to determine the concentration of Lp(a) and its relationship with other lipids parameters among Omani T2DM subjects with and without IHD. An over-night fasting blood sample from 221 T2DM subjects (86 females and 135 males) and 156 non-diabetics (69 females and 87 males) aged 30–70 years (as control) was taken for lipid profile studies. Results Lp(a) was significantly lower (p = 0.012) among T2DM subjects 0.123(1.12) g/L compared to non-diabetics 0.246 (1.18)g/L, irrespective of gender. A significant correlation (Spearman correlation, P = 0.047) was revealed between Lp(a) and IHD among Omani T2DM subjects. The proportions of T2DM subjects with IHD and an Lp(a) >0.3 g/L was higher compared to T2DM without IHD irrespective of gender, for women 42% vs. 27% and for men 17.5 vs. 8%, respectively. A significant negative correlation existed between Lp(a) and triglycerides (r = 0.41, P = 0.002) among T2DM subjects. In contrast, a significant positive correlation existed between Lp(a) and LDL-chol among the non-diabetic subjects. Women had significantly higher Lp(a) concentration compared to men ( 0.30 Vs. 0.16 g/L, P < 0.0001) irrespective of the diabetic status. Conclusion Lp(a) is an independent risk factor for IHD among Omani T2DM subjects. Lp(a) concentration was significantly lower and negatively correlated with triglycerides among Omani diabetic compared to non-diabetic subjects.

Published
2007
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16. Atypical presentation of a middle age male with severe hypertriglyceridaemia: a case report

Author

Albahrani Ali I, Usher J Jannette, Marks Eileen, Ranganath L, and Shenkin Alan

Subjects
Medicine
Abstract

Abstract Background Severe hypertriglyceridaemia (HTG) is uncommon but most prevalent in subjects with type 2 diabetes mellitus (T2DM) and excess ethanol intake. Case presentation We describe a case of a middle age male (53 y) presenting to the emergency room with acute atypical central chest pain and severe HTG in the absence of evidence of overt ischaemic heart disease (IHD). Admission ECG and EET (exercise tolerance test) were negative for reversible ischaemic changes. His admission glucose was 12.2 mmol/l, triglycerides (TG) were 103 mmol/l, total cholesterol 37 mmol/l. Cardiac Troponin T could not be measured on three occasions but CK MB mass was normal at 3 μg/l. The patient was started on Bezafibrate 400 mg OD, Simvastatin 20 mg nocte, Omacor (Omega-3 fish oil) 1 gm bd and Metformin 500 mg tds. Four weeks after admission, lipid and liver profiles showed remarkable improvement, TG 2.9 mmol/l, Tchol 6.3 mmol/l and HDLc 1.5 mmol/l, ALAT and GGT were normal. Conclusion A case report of severe hypertriglyceridaemia with atypical presentation demonstrate the role of combined lipid modifying agents in lowering triglycerides and cholesterol as well as improving liver enzymes.

Published
2007
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17. Elevated circulating interleukin-6 is associated with an acute-phase response but reduced fixed hepatic protein synthesis in patients with cancer

Author

Fearon, Kenneth C.H., McMillan, Donald C., Preston, Thomas, Winstanley, F. Peter, Cruickshank, Anne M., and Shenkin, Alan

Subjects
Proteins -- Synthesis, Cancer invasiveness -- Physiological aspects, Interleukin-6 -- Measurement, Colorectal cancer -- Metastasis, Liver cancer -- Physiological aspects, Health
Abstract

Patients with advanced cancer seem to die of cachexia, or severe weight loss and malnutrition. The mechanism of this nutritional and metabolic syndrome is not well understood. It is known that the normal liver forms two types of protein, fixed protein and export protein; this accounts for up to 15 percent of total-body protein synthesis. In cancer patients the concentrations of export protein or acute-phase proteins (APPs) is increased. It is possible that the tumor evokes an inflammatory response and influences the production of cytokines (chemicals involved in growth regulation), which in turn cause the liver to synthesize APPs. It is not known how this process affects fixed protein synthesis in the liver. An experiment was carried out to compare circulating levels of various cytokines, interleukin-1, interleukin-6, and tumor necrosis factor and synthesis rates of fixed hepatic protein. (Interleukins function in acute-phase and immune responses and tumor necrosis factor is produced by macrophages.) Six healthy control subjects and six patients with a known APP response, due to colon cancer with metastasis to the liver, were assessed. Fixed liver protein synthesis rates were measured and the liver was biopsied. Patients with advanced cancer and ongoing APP responses had elevated levels of circulating interleukin-6 concentrations, but their rate of fixed hepatic protein synthesis was 30 percent lower than that of controls. These findings indicate that patients with liver metastasis may have an increased synthesis of certain APPs, but their fixed protein synthesis is reduced. The role of interleukin-6 in this process is not known. (Consumer Summary produced by Reliance Medical Information, Inc.)

Published
1991

22. Effect of intraocular surgery and ketamine on aqueous and serum cytokines

Author

Tu, Kyaw Lin, Kaye, Stephen B., Sidaras, Gediminas, Taylor, William, and Shenkin, Alan

Subjects
Male, Anesthetics, Dissociative, Time Factors, Osmolar Concentration, Lidocaine, Cataract Extraction, Anesthesia, General, Bupivacaine, Specimen Handling, Aqueous Humor, Preoperative Care, Cytokines, Humans, Female, Ketamine, Postoperative Period, Anesthetics, Local, Research Article, Aged, Anesthesia, Local, Levobupivacaine
Abstract

Purpose To determine the effect of intraocular surgery and anesthesia on aqueous and serum cytokines. Methods Patients undergoing routine cataract surgery under general and local (peribulbar) anesthesia were randomized to those given general anesthetic with and without the use of ketamine and those having local anesthesia. Aqueous and serum levels of cytokines were collected at commencement of surgery and were determined by an immunoassay using multi-analyte biochip array technology at 18 h post-operatively. Results At 18 h postoperative, all patients (37) showed significant and many fold increases in their aqueous levels of interleukin (IL)-1α, IL-1β, IL-4, IL-6, IL-8, vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-α, interferon (IFN)-γ, epidermal growth factor (EGF), and monocyte chemotactic protein (MCP)-1. There was little to no increase in IL-2 and IL-10. Significant increases in some cytokines (EGF, IL-6, and IFN-γ) in the serum were also found (p=0.038). There were no significant differences in aqueous cytokine levels following the use of ketamine or between those patients who had general and local anesthesia (0.11

Published
2007

23. ESPEN Guidelines on Parenteral Nutrition: Home Parenteral Nutrition (HPN) in adult patients

Author

Staun, Michael, Pironi, Loris, Bozzetti, Federico, Baxter, Janet, Forbes, Alastair, Joly, Francisca, Jeppesen, Palle, Moreno, Jose, Hébuterne, Xavier, Pertkiewicz, Marek, Mühlebach, Stefan, Shenkin, Alan, Van Gossum, André, Staun, Michael, Pironi, Loris, Bozzetti, Federico, Baxter, Janet, Forbes, Alastair, Joly, Francisca, Jeppesen, Palle, Moreno, Jose, Hébuterne, Xavier, Pertkiewicz, Marek, Mühlebach, Stefan, Shenkin, Alan, and Van Gossum, André

Abstract

Home parenteral nutrition (HPN) was introduced as a treatment modality in the early 1970s primarily for the treatment of chronic intestinal failure in patients with benign disease. The relatively low morbidity and mortality associated with HPN has encouraged its widespread use in western countries. Thus there is huge clinical experience, but there are still few controlled clinical studies of treatment effects and management of complications. The purpose of these guidelines is to highlight areas of good practice and promote the use of standardized treatment protocols between centers. The guidelines may serve as a framework for development of policies and procedures.{A table is presented}. © 2009 European Society for Clinical Nutrition and Metabolism., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2009

24. ESPEN guidelines on parenteral nutrition:hepatology

Author

Plauth, Mathias, Cabré, Eduard, Campillo, Bernard, Kondrup, Jens, Marchesini, Giulio, Schütz, Tatjana, Shenkin, Alan, Wendon, Julia, Plauth, Mathias, Cabré, Eduard, Campillo, Bernard, Kondrup, Jens, Marchesini, Giulio, Schütz, Tatjana, Shenkin, Alan, and Wendon, Julia

Published
2009

33. Homopolymer-rich regions in mammalian DNA

Author

Shenkin, Alan and Shenkin, Alan

Abstract

The presence of deoxyadenylate-rich (dA-rich) and deoxyguanylate-rich (dG-rich) regions in mammalian DNA has been demonstrated by hybridisation with [5H] poly(U) and [5H] poly(C). For BHK-21/CI3 cells, the maximum levels of these homopolymer-rich regions, as detected by the hybridisation technique, are about 0.41% of the DNA for dA-rich, and 0.1% of the DNA for dG-rich regions. Since the hybrids are largely sensitive to digestion with RNase, it is probable that the majority of hybrid molecules contain mismatched base-pairs. 0.13% of the DNA consists of dA-rich regions ranging in size from 25-130 nucleotides long and containing about 2-6% of bases other than adenine. On the other hand, dG-rich regions less than 40 nucleotides long comprise 0.07% of the DNA and contain 10-30% of bases other than guanine. Exhaustive RNase digestion of the hybrids enables detection of pure deoxyhomopolymeric regions in the DNA. Pure sequences of poly(dA) of average size about 31 nucleotides long account for 0.008% of BHK-21/C13 DNA, whereas poly(dG) sequences about 17 nucleotides long comprise 0.0016% of the-DNA. The organisation of these sequences within the genome has been investigated. Both dA-rich and dG-rich regions are present within DNA sequences of widely varying base composition. Extensive shearing of the DNA is required to produce some enrichment for dA-rich sequences in the A + T rich fraction, although dG-rich sequences are slightly enriched in the (3- + C rich fraction of even unsheared DNA. The buoyant density of hybrid molecules was found to be significantly greater than that of the unhybridised DNA only when highly sheared. DNA was used. Furthermore, dA- rich and dG-rich regions were shown to be associated with rapidly, intermediately, and slowly renaturing DNA sequences. These findings all suggest that the dA-rich and dA-rich regions have a widespread distribution throughout DNA molecules. The pure poly(dA) and poly(dG) sequences also appear to be scattered throughout D

35. Reduction of nosocomial pneumonia after major burns by trace element supplementation: aggregation of two randomised trials

Author

Berger, Mette, Eggimann, Philippe, Heyland, Daren, Chioléro, René, Revelly, Jean-Pierre, Day, Andrew, Raffoul, Wassim, and Shenkin, Alan

Abstract

Introduction Nosocomial pneumonia is a major source of morbidity and mortality after severe burns. Burned patients suffer trace element deficiencies and depressed antioxidant and immune defences. This study aimed at determining the effect of trace element supplementation on nosocomial or intensive care unit (ICU)-acquired pneumonia.Methods Two consecutive, randomised, double-blinded, supplementation studies including two homogeneous groups of 41 severely burned patients (20 placebo and 21 intervention) admitted to the burn centre of a university hospital were combined. Intervention consisted of intravenous trace element supplements (copper 2.5 to 3.1 mg/day, selenium 315 to 380 μg/day, and zinc 26.2 to 31.4 mg/day) for 8 to 21 days versus placebo. Endpoints were infections during the first 30 days (predefined criteria for pneumonia, bacteraemia, wound, urine, and other), wound healing, and length of ICU stay. Plasma and skin (study 2) concentrations of selenium and zinc were determined on days 3, 10, and 20.Results The patients, 42 ± 15 years old, were burned on 46% ± 19% of body surface: the combined characteristics of the patients did not differ between the groups. Plasma trace element concentrations and antioxidative capacity were significantly enhanced with normalisation of plasma selenium, zinc, and glutathione peroxidase concentrations in plasma and skin in the trace element-supplemented group. A significant reduction in number of infections was observed in the supplemented patients, which decreased from 3.5 ± 1.2 to 2.0 ± 1.0 episodes per patient in placebo group (p < 0.001). This was related to a reduction of nosocomial pneumonia, which occurred in 16 (80%) patients versus seven (33%) patients, respectively (p < 0.001), and of ventilator-associated pneumonia from 13 to six episodes, respectively (p = 0.023).Conclusion Enhancing trace element status and antioxidant defences by selenium, zinc, and copper supplementation was associated with a decrease of nosocomial pneumonia in critically ill, severely burned patients.

Published
2006
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