The clearance concept with special reference to determination of glomerular filtration rate in patients with fluid retention

In subjects without fluid retention, the total plasma clearance of a renal filtration indicator (inulin, ^99mTc‐DTPA, ⁵¹Cr‐EDTA) is close to the urinary plasma clearance. Conversely, in patients with fluid retention (oedema, pleural effusions, ascites), there is a substantial discrepancy between the total plasma clearance and the urinary plasma clearance. This is owing to delayed indicator distribution to smaller or larger parts of the interstitial space, which in patients with ascites may simulate a peritoneal dialysator. In patients with fluid retention, urinary plasma clearance should be assessed to obtain a correct measurement of the glomerular filtration rate (GFR). In theory, total plasma clearance with late samples (24‐h, 48‐h) may be applied in patients with fluid retention, but validation hereof has not been performed. Until such studies are completed, it is recommended that patients with fluid retention have their GFR measured by a urinary plasma clearance technique with controlled quantitative urinary sampling within a few hours after indicator injection.     

In‐Solution Structural Considerations by 1H NMR and Solid‐State Thermal Properties of Inulin‐d‐α‐Tocopherol Succinate (INVITE) Micelles as Drug Delivery Systems for Hydrophobic Drugs

¹H NMR is a suitable method to clarify the kind of interactions leading to the self‐assembly of amphiphilic polymers. This work shows, from ¹H NMR studies performed in solution, that the self‐assembly ability of the synthesized Inulin‐d ‐α‐tocopherol succinate (INVITE) amphiphilic polymers, can be addressed to specific π–π interactions between the aromatic regions of d ‐α‐tocopherol. This result suggests the use of INVITE systems for the preferential loading of aromatic group bearing drugs such as curcumin. The preparation conditions, effect of drug loading, and lyophilization on the INVITE systems are evaluated by DSC and thermogravimetric analysis (TGA) analysis to assess whether common pharmaceutical processes could influence the physical properties of the amphiphilic polymers, such as crystallinity, glass‐transition temperature or thermal degradation, to predict the physical stability of the systems upon administration. Furthermore, the size stability of the micelle systems up to 60 days is monitored to assess the feasibility of the INVITE micelles’ long‐term storage upon reconstitution with water.

     

Soluble Fiber Inulin Consumption Limits Alterations of the Gut Microbiota and Hepatic Fatty Acid Metabolism Caused by High-Fat Diet

Diet shapes the gut microbiota which impacts hepatic lipid metabolism. Modifications in liver fat content are associated with metabolic disorders. We investigated the extent of dietary fat and fiber-induced alterations in the composition of gut microbiota and hepatic fatty acids (FAs). Mice were fed a purified low-fat diet (LFD) or high-fat diet (HFD) containing non-soluble fiber cellulose or soluble fiber inulin. HFD induced hepatic decreases in the amounts of C14:0, C16:1n-7, C18:1n-7 and increases in the amounts of C17:0, C20:0, C16:1n-9, C22:5n-3, C20:2n-6, C20:3n-6, and C22:4n-6. When incorporated in a LFD, inulin poorly affected the profile of FAs. However, when incorporated in a HFD, it (i) specifically led to an increase in the amounts of hepatic C18:0, C22:0, total polyunsaturated FAs (PUFAs), total n-6 PUFAs, C18:3n-3, and C18:2n-6, (ii) exacerbated the HFD-induced increase in the amount of C17:0, and (iii) prevented the HFD-induced increases in C16:1n-9 and C20:3n-6. Importantly, the expression/activity of some elongases and desaturases, as well as the gut microbiota composition, were impacted by the dietary fat and fiber content. To conclude, inulin modulated gut microbiota and hepatic fatty acid composition, and further investigations will determine whether a causal relationship exists between these two parameters.     

Comparison of enzymatically synthesized inulin, resistant maltodextrin and clofibrate effects on biomarkers of metabolic disease in rats fed a high-fat and high-sucrose (cafeteria) diet

BACKGROUND: While naturally occurring inulin has anti-hyperlipidemic effects in animals and humans, health effects of synthetic inulin with different degrees of fructose polymerization remain poorly understood. AIM OF THE STUDY: Our study aimed at distinguishing health effects of synthetic inulin with different degrees of fructose polymerization (DP) from those of resistant maltodextrin and clofibrate. METHODS: We examined effects of synthetic inulin on serum and liver lipid profiles and blood biochemical parameters in rats fed a high-fat and high-sucrose (HF, cafeteria) diet when compared to resistant maltodextrin and clofibrate. RESULTS: Treatment with inulin (average DP = 6-8, 16-17 and 23) and resistant maltodextrin for 3 weeks reduced the elevation in liver levels of triacylglycerol and total cholesterol of rats fed the cafeteria diet but not the standard diet. In these groups, inulin (average DP = 16-17) significantly reduced the portal plasma glucose level. Moreover, the levels of portal plasma propionate and circulating serum adiponectin, which were decreased in cafeteria rats, recovered to nearly normal levels after administration of inulin (average DP = 16-17). In addition, the dietary inulin suppressed elevation in levels of portal plasma insulin and circulating serum leptin and induction of acetyl-CoA carboxylase and fatty acid synthase mRNAs in the liver of cafeteria rats, consistent with the reduction of liver lipids. The dietary inulin and clofibrate markedly reduced triacylglycerol levels in serum very low density lipoprotein (VLDL) and liver and epididymal adipose tissue weights of cafeteria rats; the extent of suppression by the dietary inulin was higher than that by clofibrate. No additive or synergistic effect of the dietary inulin and clofibrate was found in decrease in circulating serum VLDL and liver lipid levels. CONCLUSION: These observations indicate that the dietary inulin may prevent the development of metabolic disease such as hyperlipidemia and hyperinsulinemia caused by intake of cafeteria diet, in association with suppression of liver lipogenesis.     

RENAL FUNCTION IN RELATION TO METABOLIC CONTROL IN CHILDREN WITH DIABETES OF DIFFERENT DURATION

ABSTRACT. To evaluate the interpretation of different kidney function tests in diabetic children and teenagers we have studied 47 children with a duration of diabetes up to 5 years, 61 children with a duration of 5.1-10 years and 49 children with a duration of >10 years. Glomerular filtration rate (GFR) measuerd as inulin clearance or creatinine clearance, clearance PAH (C_PAH), filtration fraction (FF), 24-hour urinary excretion of β₂-microglobulin and albumin were examined and correlated with short- and longterm indices of metabolic control. In all groups of duration GFR as measured by inulin clearance was increased compared with reference values from age matched controls. In patients who had had diabetes for 0-5 years a significant positive correlation was found between inulin clearance and blood glucose during the examination. Inulin clearance was also correlated to HBA_1c as well as to 24-hour urinary glucose (mean of 4-6 samples during two years). No such correlation was found in the group who had had diabetes for 5-10 years but in patients with a duration of diabetes >10 years a significant inverse relation was found between GFR and HbA_1c. The 24-hour urinary excretion of albumin was significantly higher in all groups of diabetics compared with controls. The urinary excretion of β₂-microglobulin was similar in diabetics and controls. In the total material no significant correlation could be found between inulin clearance and creatinine clearance. On the other hand significant inverse correlations were found between creatinine clearance and indices of metabolic control. It is concluded that GFR as measured by inulin clearance is related to indices of metabolic control in a different way with different duration of diabetes. As long as the relation between the increased GFR detectable early in the disease to diabetic nephropathy is unknown the predictable value of this kidney function test is low and prospective studies are necessary. Creatinine clearancee assayed by the method of Jaffé is a poor indicator of GFR in diabetics with a poor metabolic control. 24-hour urinary excretion of albumin measured by sensitive techniques might be predictive for diabetic nephropathy.     

EVALUATION OF GLOMERULAR FILTRATION RATE IN INFANTS

Bäcklund, L., Göransson, M., Müller-Suur, R. (Department of Clinical Physiology, University Hospital, Uppsala, Sweden) and Olsen, L. (Department of Paediatric Surgery, University Hospital, Uppsala, Sweden). Evaluation of glomerular filtration in infants. Acta Paediatr Scand, Suppl. 305: 77–78, 1983.—In the present study we investigated if inulin with single injection technique and capillary blood sampling can be used to determine glomerular filtration rate. Inulin single injection clearances using both venous and capillary samples were compared to standard inulin clearance (constant infusion) and to the clinical routine method, i.e. ⁵¹Cr-EDTA clearance. Good agreement was obtained between these different methods and it is concluded that the inulin single injection clearance is a reliable method for GFR estimation. Especially in children this method is recommended as capillary blood samples can be used and thus the high doses of radioactivity necessary for a ⁵¹Cr-EDTA capillary method can be avoided.     

Hypercalcaemia and glucagon-mediated urinary electrolyte excretion in minipigs

Summary The effects of glucagon (G) on glomerular filtration rate (GFR) and the urinary excretion of electrolytes were studied during sequentially increasing hypercalcaemia in minipigs. G has no specific effect on GFR. The observed increase in the excretion of electrolytes was probably due to increased amounts of calcium in the glomerular filtrate rather than to any specific hormonal effects. The results obtained in parathyroid suppression experiments (using i. v. infusion of calcium) suggest that the renal effects of G may somehow be related to intact thyroid-parathyroid activity and normal circulating levels of these hormones.     

Jicama (Pachyrhizus erosus) extract increases insulin sensitivity and regulates hepatic glucose in C57BL/Ksj-db/db mice

This study investigated the effect of jicama extract on hyperglycemia and insulin sensitivity in an animal model of type 2 diabetes. Male C57BL/Ksj-db/db mice were divided into groups subsequently fed a regular diet (controls), or diet supplemented with jicama extract, and rosiglitazone. After 6 weeks, blood levels of glucose and glycosylated hemoglobin were significantly lower in animals administered the jicama extract than the control group. Additionally, glucose and insulin tolerance tests showed that jicama extract increased insulin sensitivity. The homeostatic index of insulin resistance was lower in the jicama extract-treated group than in the diabetic control group. Administration of jicama extract significantly enhanced the expressions of the phosphorylated AMP-activated protein kinase and Akt substrate of 160 kDa, and plasma membrane glucose transporter type 4 in skeletal muscle. Jicama extract administration also decreased the expressions of glucose 6-phosphatase and phosphoenol pyruvate carboxykinase in the liver. Jicama extract may increases insulin sensitivity and inhibites the gluconeogenesis in the liver.     

Differential Influence of Soluble Dietary Fibres on Intestinal and Hepatic Carbohydrate Response

Refined foods are commonly depleted in certain bioactive components that are abundant in ‘natural’ (plant) foods. Identification and addition of these ‘missing’ bioactives in the diet is, therefore, necessary to counteract the deleterious impact of convenience food. In this study, multiomics approaches were employed to assess the addition of the popular supplementary soluble dietary fibers inulin and psyllium, both in isolation and in combination with a refined animal feed. A 16S rRNA sequencing and ¹H NMR metabolomic investigation revealed that, whilst inulin mediated an increase in Bifidobacteria, psyllium elicited a broader microbial shift, with Parasutterella and Akkermansia being increased and Enterorhabdus and Odoribacter decreased. Interestingly, the combination diet benefited from both inulin and psyllium related microbial changes. Psyllium mediated microbial changes correlated with a reduction of glucose (R −0.67, −0.73, respectively, p < 0.05) and type 2 diabetes associated metabolites: 3-methyl-2-oxovaleric acid (R −0.72, −0.78, respectively, p < 0.05), and citrulline (R −0.77, −0.71, respectively, p < 0.05). This was in line with intestinal and hepatic carbohydrate response (e.g., Slc2a2, Slc2a5, Khk and Fbp1) and hepatic lipogenesis (e.g., Srebf1 and Fasn), which were significantly reduced under psyllium addition. Although established in the liver, the intestinal response associated with psyllium was absent in the combination diet, placing greater significance upon the established microbial, and subsequent metabolomic, shift. Our results therefore highlight the heterogeneity that exists between distinct dietary fibers in the context of carbohydrate uptake and metabolism, and supports psyllium containing combination diets, for their ability to negate the impact of a refined diet.