| 1. |
- Ekelund, Mikael, et al.
(författare)
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Effects of total parenteral nutrition on rat enteric nervous system, intestinal morphology, and motility.
- 2005
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Ingår i: Journal of Surgical Research. - : Elsevier BV. - 1095-8673 .- 0022-4804. ; 124:2, s. 187-193
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Tidskriftsartikel (refereegranskat)abstract
- Total parenteral nutrition (TPN) is often crucial for patients not being able to feed enterally or having intestinal absorptive deficits. Enteral nutrition is, however, frequently regarded vital for maintaining functional and structural intestinal integrity. The aim of this study was to investigate possible effects of TPN on rat distal small intestine compared to enterally fed identically housed controls, regarding the enteric nervous system (ENS), motility in vitro, and morphology. This study shows that motor responses evoked by electrical stimulation or exposure to vasoactive intestinal peptide (VIP), pituitary adenylate cyclase activating peptide-27 (PACAP-27), and nitric oxide (NO) donor were unchanged. By using immunohistochemistry, the numbers of submucous (P < 0.05) and myenteric (P < 0.05) nerve cells were found to increase, expressed as numbers per unit length. The percentage of neurons expressing VIP, PACAP-27, NO-synthase, and galanin remained unchanged, however. By in situ hybridization the number of submucous neurons expressing neuropeptide Y-mRNA was found to decrease (P < 0.05); the other populations were unaltered. Morphometry revealed an increased submucosal thickness (P < 0.05), while intestinal circumference markedly decreased (P < 0.0001) in TPN-treated rats. In conclusion, TPN treatment resulted in reduced intestinal circumference leading to condensation of enteric neurons. No marked changes in neurotransmitter expression of the enteric neurons or in motor activity were noted.
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| 2. |
- Ekelund, Mats, et al.
(författare)
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Selective induction of inducible nitric oxide synthase in pancreatic islet of rat after an intravenous glucose or intralipid challenge.
- 2006
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Ingår i: Nutrition. - : Elsevier BV. - 1873-1244 .- 0899-9007. ; 22:2006 Apr 22, s. 652-660
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Constant exposure of pancreatic islets to high levels of glucose or free fatty acids can lead to irreversible beta-cell dysfunction, a process referred to as glucotoxicity or lipotoxicity, respectively. In this context a role for nitric oxide generated by pancreatic islet has been suggested. The present investigation examined whether the route of glucose administration, i.e., given orally (OG) or infused intravenously (IVG), could have any effect on the expression and activity of inducible nitric oxide synthase (iNOS) in pancreatic islets. Methods: Rats were infused with glucose (50%) or Intralipid intravenously for 24 h or given glucose orally. A freely fed control group (FF) was also included. At 24 h rats were killed and blood samples were drawn for analysis of plasma insulin, glucagon, and glucose. Pancreatic islets were harvested from each animal and investigated for the occurrence of iNOS by the use of confocal microscopy, western blot, and high-performance liquid chromatographic analysis. The effect of intravenously infused glucose was then compared with the effect of an intravenous infusion of Intralipid (IL). Results: Plasma insulin levels were markedly decreased after 24 h of infusion of glucose (IVG group) or Intralipid (IL group) compared with the FF or OG group. Plasma glucagon and glucose levels were markedly increased in the IVG group, whereas both parameters were decreased in the IL group. No significant differences in plasma insulin, glucagon, or glucose were found between the OG and FF groups. Immunocytochemical (confocal microscopy), western blot, and biochemical (high-performance liquid chromatographic) analyses showed that a sustained increase in plasma level of glucose or free fatty acids by an intravenous infusion of either nutrient for 24 h resulted in a marked expression and activity of iNOS in pancreatic islets. No sign of iNOS expression could, however, be detected in the islets of FF control or OG rats. Conclusion: The data suggest that impaired beta-cell function found after 24 It of an intravenous infusion of glucose or Intralipid might be mediated, at least in part, by the induction of iNOS in pancreatic islets. This may subsequently result in an exclusive production of nitric oxide, which is deleterious for beta-cells. (C) 2006 Elsevier Inc. All rights reserved.
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| 3. |
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| 4. |
- Njuguna, J., et al.
(författare)
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Challenges Associated with Scaling up Artemisinin Combination Therapy in Sub-Saharan Africa A Review Article
- 2008
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Ingår i: Libyan Journal of Medicine. - 1993-2820. ; 3:1, s. 42-48
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Forskningsöversikt (refereegranskat)abstract
- Malaria is the leading cause of morbidity and mortality in Sub-Saharan Africa. One key strategic intervention is provision of early diagnosis and prompt effective treatment. A major setback has been the development of drug resistance to commonly used antimalarials. To overcome this, most countries in Sub-Saharan Africa have adopted Artemisinin Combination Therapy (ACT) as a first line treatment for uncomplicated malaria. Artemether Lumefantrine (AL) and Artesunate Amodiaquine (ASAQ) are the main drugs of choice. There are key implementation issues, which may have a bearing on the scaling up of this new treatment. This article reviewed the published papers on ACT with focus on sustainability, compliance, and diagnosis. ACTs are costly, but highly effective. Their scaling up is the most cost effective malaria intervention currently available. Most countries rely heavily on the Global Fund for their scaling up. AL has a short shelf life, a complicated six-dose regimen that requires intake with fat to ensure sufficient bioavailability. High rates of adherence have been reported. Use of parasitic diagnosis is advocated to ensure rational use. Parasitic diagnostics like rapid test and microscopy are currently inadequate. The majority of malaria cases may continue to be diagnosed clinically leading to over prescription of drugs. ACTs are currently not available at the community level for home based management of malaria. Issues related to safety and rational use need to be addressed before their use in the informal health sector like community drug sellers and community health workers. The majority of malaria cases at the community level could go untreated or continue to be treated using less effective drugs. We conclude that ACTs are highly effective. A major challenge is ensuring rational use and access at the household level. It is hoped that addressing these issues will increase the likelihood that ACT achieves its intended goals of reducing morbidity and mortality due to malaria, and delaying the onset of drug resistance.
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| 5. |
- Qader, Saleem, et al.
(författare)
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Could Quality of Life Impact the Prevalence of Metabolic Syndrome? Results from a Population-Based Study of Swedish Women: The Women's Health in the Lund Area Study.
- 2008
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Ingår i: Metabolic syndrome and related disorders. - : Mary Ann Liebert Inc. - 1557-8518 .- 1540-4196.
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Background: The metabolic syndrome is regarded as an important risk factor for diabetes mellitus and cardiovascular disease. Metabolic syndrome could be associated with impaired quality of life (QoL). Methods: The Women's Health in the Lund Area (WHILA) project covers 10,766 women born between December 2, 1935, and December 1, 1945, living in the Lund area, of Sweden by December 1, 1995. The primary objectives of this project were to survey perimenopausal women in this area and to evaluate their health status and lifestyles. We used the criteria for the metabolic syndrome, as defined by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III), which include three or more of five risk factors: central obesity, elevated serum triglycerides, low high-density lipoprotein cholesterol (HDL-C), and elevated blood pressure and fasting glucose. Analysis of most aspects of daily life and QoL according to the Gothenburg Quality of Life Instrument (GQL) was done. GQL refers to the WHO definition of health. Results: A total number of 6913 (64.2%) women with a mean age (56.1) years fulfilled the criteria for screening procedure in the WHILA study. A positive association between women with metabolic syndrome and the following aspects of quality of life were found: "Partnership," "free time," "memory," and being "appreciated outside home." However, "economy," "health," "body image," and "fitness" had a negative association to the metabolic syndrome. Conclusion: QoL is an important factor for metabolic syndrome. Apart from traditional biological factors, prevention of metabolic syndrome should also encompass QoL.
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| 6. |
- Qader, Saleem, et al.
(författare)
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Could Spontaneous Retroperitoneal Haematoma Present with Scrotal Mass?
- 2009
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Ingår i: Libyan Journal of Medicine. - : Informa UK Limited. - 1993-2820 .- 1819-6357. ; 4:3, s. 117-119
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Tidskriftsartikel (refereegranskat)abstract
- Background: Retroperitoneal haematoma could be caused by different factors. It is increasing due to an increase in the use of antithrombotic and anticoagulant therapy. Diagnosis of retroperitoneal haematoma forms a big challenge in daily clinical practice. Patients with retroperitoneal haematoma could present with leg paresis, abdominal pain, shock or abdominal compartment syndrome. Retroperitoneal haematoma could be treated conservatively but surgical interference or embolization of the bleeding vessels is always an option. Objectives: To present a case with spontaneous retroperitoneal haematoma presenting with scrotal haematoma together with a mini- review of retroperitoneal haematoma. Conclusions: Retroperitoneal haematoma may present with a scrotal swelling and could be treated conservatively depending on the presentation and severity of the bleeding.
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| 7. |
- Qader, Saleem, et al.
(författare)
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Expression of islet iNOS and inhibition of glucose stimulated insulin release after long-term lipid infusion in the rat is counteracted by PACAP27.
- 2007
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Ingår i: American Journal of Physiology: Endocrinology and Metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 292:5, s. 1447-1455
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Tidskriftsartikel (refereegranskat)abstract
- Chronic exposure of pancreatic islets to elevated plasma lipids ( lipotoxicity) can lead to beta-cell dysfunction, with overtime becoming irreversible. We examined, by confocal microscopy and biochemistry, whether the expression of islet inducible nitric oxide synthase ( iNOS) and the concomitant inhibition of glucose-stimulated insulin release seen after lipid infusion in rats was modulated by the islet neuropeptide pituitary adenylate cyclase-activating polypeptide ( PACAP) 27. Lipid infusion for 8 days induced a strong expression of islet iNOS, which was mainly confined to beta-cells and was still evident after incubating islets at 8.3 mmol/l glucose. This was accompanied by a high iNOS-derived NO generation, a decreased insulin release, and increased cyclic GMP accumulation. No iNOS expression was found in control islets. Addition of PACAP27 to incubated islets from lipid-infused rats resulted in loss of iNOS protein expression, increased cyclic AMP, decreased cyclic GMP, and suppression of the activities of neuronal constitutive ( nc) NOS and iNOS and increased glucose-stimulated insulin response. These effects were reversed by the PKA inhibitor H-89. The suppression of islet iNOS expression induced by PACAP27 was not affected by the proteasome inhibitor MG-132, which by itself induced the loss of iNOS protein, making a direct proteasomal involvement less likely. Our results suggest that PACAP27 through its cyclic AMP- and PKA-stimulating capacity strongly suppresses not only ncNOS but, importantly, also the lipid-induced stimulation of iNOS expression, possibly by a nonproteasomal mechanism. Thus PACAP27 restores the impairment of glucose-stimulated insulin release and additionally might induce cytoprotection against deleterious actions of iNOS-derived NO in beta-cells.
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| 8. |
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| 9. |
- Qader, Saleem, et al.
(författare)
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Long-term infusion of nutrients (total parenteral nutrition) suppresses circulating ghrelin in food-deprived rats.
- 2005
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Ingår i: Regulatory Peptides. - : Elsevier BV. - 1873-1686 .- 0167-0115. ; 131:Aug 12, s. 82-88
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Tidskriftsartikel (refereegranskat)abstract
- Background: Ghrelin derives from endocrine cells (A-like cells) in the stomach (mainly the oxyntic mucosa). Its concentration in the circulation increases during fasting and decreases upon re-feeding. This has fostered the notion that the absence of food in the upper gastrointestinal (GI) tract stimulates the secretion of ghrelin. The purpose of the present study was to determine the concentration of ghrelin in serum and oxyntic mucosa after replacing food with intravenous (iv) infusion of nutrients for 8 days using the technique known as total parenteral nutrition (TPN). Materials and methods: Male Sprague-Dawley rats (200-250 g) were given nutrients (lipids, glucose, amino acids, minerals and vitamins) by iv infusion for 8 days during which time they were deprived of food and water; another group was deprived of food for 24-48 h (fasted controls), while fed controls had free access to food and water. Serum ghrelin, gastrin and pancreastatin concentrations were measured together with the ghrelin content of the oxyntic mucosa. Plasma insulin and glucose as well as serum lipid concentrations were also determined. Results: Fasted rats had higher serum ghrelin than TPN rats and fed controls. The oxyntic mucosal ghrelin concentration (and content) was lower in TPN rats than in fasted rats or fed controls. The serum gastrin and pancreastatin concentrations were lower in TPN rats and fasted rats than in fed controls. The plasma insulin concentration was 87 pmol/l +/- 8 (SEM) in TPN rats compared to 101 16 pmol/l in fed controls; it was 26 14 pmol/l in fasted rats. The basal plasma glucose level was 11 +/- 0.6 mmol/l in TPN rats and 12 +/- 0.8 mmol/l in fed controls; it was 7 +/- 0.3 mmol/l in fasted rats. In TPN rats, the serum concentrations of free fatty acids, triglycerides and cholesterol were increased by 100%, 50% and 25%, respectively, compared to fed controls. Fasted rats had higher circulating concentrations of free fatty acids (20%) and lower concentrations of triglycerides (- 40%) than fed controls; fasted rats did not differ from fed controls with respect to serum cholesterol. Conclusion: The circulating ghrelin concentration is high in situations of nutritional deficiency (starvation) and low in situations of nutritional plenty (free access to food or TPN). The actual presence or absence of food in the GI tract seems irrelevant. Circulating insulin and glucose concentrations did not differ much between TPN rats and fed controls, serum lipids, however, were elevated in the TPN rats. We suggest that elevated blood lipid levels contribute to the suppression of circulating ghrelin in rats subjected to TPN for 8 days.
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| 10. |
- Qader, Saleem, et al.
(författare)
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Proghrelin-derived peptides influence the secretion of insulin, glucagon, pancreatic polypeptide and somatostatin: A study on isolated islets from mouse and rat pancreas.
- 2008
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Ingår i: Regulatory Peptides. - : Elsevier BV. - 1873-1686 .- 0167-0115. ; 146:1-3, s. 230-237
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Tidskriftsartikel (refereegranskat)abstract
- Proghrelin, the precursor of the orexigenic and adipogenic peptide hormone ghrelin, is synthetized in endocrine (A-like) cells in the gastric mucosa. During its cellular processing, proghrelin gives rise to the 28-amino acid peptide desacyl ghrelin, which after octanoylation becomes active acyl ghrelin, and to the 23-amino acid peptide obestatin, claimed to be a physiological opponent of acyl ghrelin. This study examines the effects of the proghrelin products, alone and in combinations, on the secretion of insulin, glucagon, pancreatic polypeptide (PP) and somatostatin from isolated islets of mice and rats. Surprisingly, acyl ghrelin and obestatin had almost identical effects in that they stimulated the secretion of glucagon and inhibited that of PP and somatostatin from both mouse and rat islets. Obestatin inhibited insulin secretion more effectively than acyl ghrelin. In mouse islets, acyl ghrelin inhibited insulin secretion at low doses and stimulated at high. In rat islets, acyl ghrelin inhibited insulin secretion in a dose-dependent manner but the IC50 for the acyl ghrelin-induced inhibition of insulin release was 7.5 × 10− 8 M, while the EC50 and IC50 values, with respect to stimulation of glucagon release and to inhibition of PP and somatostatin release, were in the 3 × 10− 12–15 × 10− 12 M range. The corresponding EC50 and IC50 values for obestatin ranged from 5 × 10− 12 to 20 × 10− 12 M. Desacyl ghrelin per se did not affect islet hormone secretion. However, at a ten times higher concentration than acyl ghrelin (corresponding to the ratio of the two peptides in circulation), desacyl ghrelin abolished the effects of acyl ghrelin but not those of obestatin. Acyl ghrelin and obestatin affected the secretion of glucagon, PP and somatostatin at physiologically relevant concentrations; with obestatin this was the case also for insulin secretion. The combination of obestatin, acyl ghrelin and desacyl ghrelin in concentrations and proportions similar to those found in plasma resulted in effects that were indistinguishable from those induced by obestatin alone. From the data it seems that the effects of endogenous, circulating acyl ghrelin may be overshadowed by obestatin or blunted by desacyl ghrelin.
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