| 1. |
- Gelosa, P., et al.
(författare)
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Stimulation of AT2 receptor exerts beneficial effects in stroke-prone rats: focus on renal damage
- 2009
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Ingår i: J Hypertens. ; 27:12, s. 2444-2451
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIM: Angiotensin II acts through two major receptors: AT1-R and AT2-R. It is known that the stimulation of AT1-R mediates vasoconstriction, cell proliferation and fibrosis, aldosterone release and inflammatory response but, although the stimulation of AT2-R is thought to promote vasodilation and anti-inflammatory effects, its real in-vivo functions are still unclear. The aim of this study was to investigate the effects of specific and selective AT2-R stimulation on the pathological events occurring in spontaneously hypertensive stroke-prone rats (SHRSPs). METHODS AND RESULTS: SHRSPs who were fed a high-salt diet underwent long-term treatment with vehicle or compound 21 (C21), a nonpeptide selective AT2-R agonist, at doses of 0.75, 5 and 10 mg/kg per day. The vehicle-treated rats developed brain abnormalities detectable by magnetic resonance imaging after 42.5 +/- 7.5 days, and died 43 +/- 9.5 days after the start of the dietary treatment. The highest C21 dose delayed the occurrence of brain damage (P < 0.001 vs. vehicle-treated SHRSPs) and prolonged survival (P < 0.001) without affecting blood pressure. These beneficial effects of C21 were abolished by the administration of PD123319, an AT2-R antagonist. C21 treatment preserved renal structure by preventing inflammatory cell infiltration, collagen accumulation, and the neo-expression of vimentin; it also prevented the increased plasma renin activity and accumulation of urinary acute-phase proteins observed in the vehicle-treated rats. CONCLUSION: Specific and selective AT2-R stimulation has beneficial effects on the pathological events occurring in SHRSPs. These data indicate a new avenue for the pharmacological treatment of diseases in which modulation of the renin-angiotensin system is required.
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| 2. |
- Casselbrant, Anna, 1970, et al.
(författare)
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Actions by angiotensin II on esophageal contractility in humans
- 2007
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085. ; 132:1, s. 249-60
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Angiotensin II is a potent activator of smooth muscles but has not been much investigated with regard to gastrointestinal motor activity. This study explores expression of the renin-angiotensin system (RAS) in human esophageal musculature and actions by Angiotensin II both in vitro and in vivo. METHODS: Muscular specimens of esophageal body and lower esophageal sphincter were obtained from patients undergoing resection as a result of mucosal neoplasm. Healthy volunteers participated in functional examinations of esophageal motility assessed by high-resolution manometry and multiple transmucosal potential-difference measurements. RESULTS: Gene transcripts of key components of RAS were found in the esophageal musculature. Immunohistochemistry revealed a distinct staining for Angiotensin II type 1 (AT(1)) receptors in the muscular bundles and blood-vessel walls, whereas Angiotensin II type 2 receptors were confined to blood vessels only. Angiotensin II caused concentration-dependent contractions in vitro, which were inhibited by the AT(1) receptor antagonist losartan but not by the Angiotensin II type 2 receptor antagonist PD123319. Administration of the AT(1) receptor antagonist candesartan reduced the amplitude of swallow-induced peristaltic contractions and both the length and pressure amplitude of baseline high-pressure zone at the esophagogastric junction. Neither swallow-induced axial movements, nor the contraction after transient lower esophageal sphincter relaxations, were influenced by candesartan pretreatment. CONCLUSIONS: The study demonstrates a local RAS in the musculature of the distal esophagus and that Angiotensin II is a potent stimulator of esophageal contractions via the AT(1) receptor. The results suggest that Angiotensin II participates in the physiological control of the human esophageal motor activity.
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| 3. |
- Fändriks, Lars, 1956, et al.
(författare)
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Bariatric surgery for diabetes mellitus type 2 control in adults with BMI<35 kg/m2
- 2016
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Background: Obesity is strongly linked to diabetes and premature mortality, mainly from cardiovascular causes. In 2013, the prevalence of obesity (BMI ≥ 30 kg/m2) in adults in Sweden was 14 %. The prevalence of diabetes mellitus in Sweden is approximately 5 % with a slow increase due to an ageing population. In 2015, 73,225 patients in VGR had a diagnosis of diabetes mellitus. The treatment of overweight and obesity in adults is based on three principles: lifestyle changes, pharmacological treatment and surgery. Today, weight reducing (bariatric) surgery can be offered to individuals with BMI ≥40 kg/m2, and patients with BMI ≥35 kg/m2 with an obesity associated disease, in particular diabetes mellitus type 2 (T2D). Bariatric surgery in persons with BMI < 35 kg/m2 is currently not endorsed in Swedish national guidelines (National Board of Health and Welfare, 2015). Glycaemic stabilisation is reported to occur very early after surgery, before any significant weight loss. In a recent joint statement by several international diabetes organizations, it was proposed that bariatric surgery should be considered to be an option to treat T2D in patients with BMI 30.0–34.99 kg/m2 and inadequately controlled hyperglycaemia despite optimal medical treatment. Objective: To study if bariatric surgery in patients with T2D and a BMI <35 kg/m2 is superior to standard treatment with regard to diabetes control. Search methods and study selection criteria: During January 2016 two authors performed systematic searches in PubMed, Embase, the Cochrane Library and a number of HTA-databases for systematic reviews, randomized (RCT) and non-randomised controlled studies. Due to the small number of original articles fulfilling the inclusion criteria we chose to only include and critically appraise original articles. Main results: The literature search resulted in four RCTs and six cohort studies (two reporting on the same population) comparing results of bariatric surgery with medical treatment in T2D patients with BMI <35 kg/m2. The studies had limitations mainly related to, e.g., short follow-up, some inconsistency, indirectness due to different interventions or unclear patient selection, and imprecision. Mortality was reported in two studies with only one reported death. Remission of T2D was studied in three RCTs and four cohort studies. The frequency of T2D remission during 1–3 years follow-up may be higher after bariatric surgery compared with non-surgical standard care (GRADE ⊕⊕ ). Diabetes related and cardiovascular complications were not studied. Health related quality of life (SF-36) was reported in one RCT and physical wellbeing may improve after bariatric surgery compared with medical treatment (GRADE ⊕⊕ ). Regarding glycaemic control, bariatric surgery compared with non-surgical standard care probably reduces HbA1c (GRADE ⊕⊕⊕ ), may reduce fasting plasma glucose (GRADE ⊕⊕ ) but the effect on the number of glucose-lowering medications is uncertain (GRADE ⊕ ). Bariatric surgery compared with non-surgical standard care probably reduces BMI (GRADE ⊕⊕⊕ ) but the effects on other metabolic risk factors are uncertain (GRADE ⊕ ). Risks and complications: The rate of surgical complications was reported from four to 17% ranging from mild to more severe complications requiring surgical intervention. Concluding remarks: This systematic review shows that bariatric surgery compared with medical treatment may increase the frequency of diabetes remission and probably results in improved glycaemic control in adults with overweight or obesity (BMI< 35 kg/m2, mainly 30 – 34.99 kg/m2) during 1–3 years follow-up. The bariatric surgical procedures mainly performed in Sweden today (Roux-en-Y gastric bypass, vertical sleeve gastrectomy) were investigated in only half of the current studies. Data on long term efficacy and safety are lacking and there are no results indicating reduced risk of cardiovascular disease, cancer or death. No relevant health economic analyses are available.
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| 4. |
- Fändriks, L, et al.
(författare)
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Sympatho-adrenergic inhibition of basal and acid-induced changes in duodenal motility, mucosal net fluid and alkaline secretion in the anaesthetized cat
- 1995
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Ingår i: Acta Physiologica Scandinavica. - : Wiley. - 0001-6772 .- 1365-201X. ; 153:3, s. 211-219
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Tidskriftsartikel (refereegranskat)abstract
- Experiments were performed on chloralose anaesthetized cats. A 2-cm segment of the proximal duodenum was isolated between two luminally situated balloons and perfused with isotonic saline containing [14C]-PEG 4000 as a non-absorbable marker. The perfusate was analysed with regard to alkalinity (back titration) and concentration of marker (liquid scintillation). Net alkalinization and net fluid transport were calculated with conventional equations. Motor activity in the duodenal wall was recorded as changes in volume of the proximal balloon. In presence of sympathetic neural activity (spontaneous or electrically stimulated) basal motor activity and mucosal alkaline secretion was low and increased minimally in response to luminal HCl (30 mM). Net fluid transport was in an absorptive state and shifted to a small secretion upon the acid-exposure. Subsequent to bilateral acute splanchnicotomy, or the administration of the adrenolytic guanethidine (3-4 mg kg-1, i.v.), spontaneous duodenal contractions occurred and the alkaline secretion was increased. Furthermore, both parameters were then markedly stimulated by luminal perfusion with 30 mM HCl. Basal net fluid transport was zero and turned into secretion upon the acid-exposure. No morphological changes of the duodenal surface epithelium could be detected. The study demonstrates the existence of splanchnic nerve-mediated, adrenergic inhibition of basal, as well as of acid-induced duodenal motility, fluid and alkaline secretion.
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| 5. |
- Granstam, S O, et al.
(författare)
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Effects of cigarette smoke and nicotine on duodenal bicarbonate secretion in the rabbit and the rat.
- 1990
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Ingår i: Journal of Clinical Gastroenterology. - 0192-0790 .- 1539-2031. ; 12 Suppl 1, s. S19-24
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Tidskriftsartikel (refereegranskat)abstract
- The effects of short-time exposure to cigarette smoke on duodenal mucosal bicarbonate secretion were studied in anesthetized rabbits and rats. The bicarbonate secretion was measured by continuous titration of recirculating luminal perfusate. In artificially ventilated rabbits, intermittent exposure to cigarette smoke during two 10-min periods caused a marked (approximately 40%) decrease (p less than 0.01) in duodenal bicarbonate secretion. After the exposures, secretion gradually recovered and had returned to the pre-exposure rate after 50 min. The decrease in secretion was associated with decreases in heart rate (approximately 15%) and blood pressure (approximately 30%) that, however, were of shorter duration. Neither reduced amounts of smoke (1/6 or 1/3) nor nicotine (25-1,000 micrograms/kg, intravenously) had any major effect on the bicarbonate secretion. In the spontaneously breathing rat, smoke was administered for 1-2 breaths every 30 s during a 5-min period. This exposure resulted in a significant (p less than 0.05) decrease in bicarbonate secretion and some increase in the blood pressure. Exposure to smoke had no effect on the secretion in rats with both splanchnic nerves cut, suggesting neural sympathetic mediation of the smoke-induced inhibition.
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| 6. |
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| 7. |
- Jönson, C, et al.
(författare)
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Effects of hypovolemia on blood flow, arterial [HCO3-], and HCO3- output in the rat duodenum.
- 1990
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Ingår i: American Journal of Physiology. - 0002-9513 .- 2163-5773. ; 259:2 Pt 1, s. G179-83
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Tidskriftsartikel (refereegranskat)abstract
- The effects of bleeding-induced hypovolemia on duodenal blood flow (microsphere technique), arterial [HCO3-], and duodenal HCO3- secretion (in situ titration) were investigated in chloralose-anesthetized rats. A 10% decrease in blood volume reduced duodenal HCO3- secretion by 44%, duodenal blood flow by 31%, and arterial [HCO3-] by 11%. In a group with cervically cut vagal nerves, basal duodenal HCO3- secretion was greater than 50% lower compared with controls. Basal blood flow and arterial [HCO3-] were on similar levels as in nonvagotomized animals. Furthermore, bleeding failed to lower duodenal alkaline output in rats with cut vagal nerves, although blood flow and arterial [HCO3-] were reduced to a similar extent as in the vagally intact controls. In a yohimbine-treated group, a 10% bleeding reduced duodenal blood flow by 28% and arterial [HCO3-] by 7% without influencing duodenal HCO3- secretion. We suggest that the hypovolemia-induced inhibition of duodenal alkaline secretion is not caused by a decrease in blood and/or arterial [HCO3-]. Instead, other factors may be of importance, for example, neural effects on enteric secretomotor neurons or directly on the secreting epithelium.
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| 8. |
- Maleckas, Almantas, et al.
(författare)
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Surgery in the treatment of type 2 diabetes mellitus.
- 2015
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Ingår i: Scandinavian journal of surgery : SJS : official organ for the Finnish Surgical Society and the Scandinavian Surgical Society. - : SAGE Publications. - 1799-7267. ; 104:1, s. 40-47
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Tidskriftsartikel (refereegranskat)abstract
- The prevalence of diabetes is increasing worldwide, and most of the cases are type 2 diabetes mellitus. The relationship between type 2 diabetes mellitus and obesity is well established, and surgical treatment is widely used for obese patients with type 2 diabetes mellitus. The aim was to present current knowledge about the possible mechanisms responsible for glucose control after surgical procedures and to review the surgical treatment results.
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| 9. |
- Martin, W. P., et al.
(författare)
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Urinary Metabolomic Changes Accompanying Albuminuria Remission following Gastric Bypass Surgery for Type 2 Diabetic Kidney Disease
- 2022
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Ingår i: Metabolites. - : MDPI AG. - 2218-1989. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- In the Microvascular Outcomes after Metabolic Surgery randomised clinical trial (MOMS RCT, NCT01821508), combined metabolic surgery (gastric bypass) plus medical therapy (CSM) was superior to medical therapy alone (MTA) as a means of achieving albuminuria remission at 2‐year follow‐up in patients with obesity and early diabetic kidney disease (DKD). In the present study, we assessed the urinary1H‐NMR metabolome in a subgroup of patients from both arms of the MOMS RCT at baseline and 6‐month follow‐up. Whilst CSM and MTA both reduced the urinary excretion of sugars, CSM generated a distinctive urinary metabolomic profile characterised by increases in host–microbial co‐metabolites (N‐phenylacetylglycine, trimethylamine N‐oxide, and 4‐ aminobutyrate (GABA)) and amino acids (arginine and glutamine). Furthermore, reductions in aromatic amino acids (phenylalanine and tyrosine), as well as branched‐chain amino acids (BCAAs) and related catabolites (valine, leucine, 3‐hydroxyisobutyrate, 3‐hydroxyisovalerate, and 3‐methyl‐ 2‐oxovalerate), were observed following CSM but not MTA. Improvements in BMI did not correlate with improvements in metabolic and renal indices following CSM. Conversely, urinary metabolites changed by CSM at 6 months were moderately to strongly correlated with improvements in blood pressure, glycaemia, triglycerides, and albuminuria up to 24 months following treatment initiation, highlighting the potential involvement of these shifts in the urinary metabolomic profile in the metabolic and renoprotective effects of CSM. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
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