Multi-omics signatures in new-onset diabetes predict metabolic response to dietary inulin: findings from an observational study followed by an interventional trial.

AIM: The metabolic performance of the gut microbiota contributes to the onset of type 2 diabetes. However, targeted dietary interventions are limited by the highly variable inter-individual response. We hypothesized (1) that the composition of the complex gut microbiome and metabolome (MIME) differ across metabolic spectra (lean-obese-diabetes); (2) that specific MIME patterns could explain the differential responses to dietary inulin; and (3) that the response can be predicted based on baseline MIME signature and clinical characteristics. METHOD: Forty-nine patients with newly diagnosed pre/diabetes (DM), 66 metabolically healthy overweight/obese (OB), and 32 healthy lean (LH) volunteers were compared in a cross-sectional case-control study integrating clinical variables, dietary intake, gut microbiome, and fecal/serum metabolomes (16 S rRNA sequencing, metabolomics profiling). Subsequently, 27 DM were recruited for a predictive study: 3 months of dietary inulin (10 g/day) intervention. RESULTS: MIME composition was different between groups. While the DM and LH groups represented opposite poles of the abundance spectrum, OB was closer to DM. Inulin supplementation was associated with an overall improvement in glycemic indices, though the response was very variable, with a shift in microbiome composition toward a more favorable profile and increased serum butyric and propionic acid concentrations. The improved glycemic outcomes of inulin treatment were dependent on better baseline glycemic status and variables related to the gut microbiota, including the abundance of certain bacterial taxa (i.e., Blautia, Eubacterium halii group, Lachnoclostridium, Ruminiclostridium, Dialister, or Phascolarctobacterium), serum concentrations of branched-chain amino acid derivatives and asparagine, and fecal concentrations of indole and several other volatile organic compounds. CONCLUSION: We demonstrated that obesity is a stronger determinant of different MIME patterns than impaired glucose metabolism. The large inter-individual variability in the metabolic effects of dietary inulin was explained by differences in baseline glycemic status and MIME signatures. These could be further validated to personalize nutritional interventions in patients with newly diagnosed diabetes.

Direct and indirect impacts of the COVID-19 pandemic on patients with pulmonary and pleural malignancies - a retrospective analysis of patient outcomes treated at Department of Respiratory Diseases, University Hospital Brno, during the 2nd and 3rd coronavirus waves.

BACKGROUND: The pandemic of COVID-19 has significantly influenced the dia-gnostics and treatment of patients with lung and pleural malignancies. This group of patients is the riskiest, compared to patients with other cancers, both in morbidity and mortality. STUDY POPULATION AND METHODS: The data of patients with lung/pleural malignancies and proved COVID-19 positivity were analyzed at the Department of Respiratory Diseases and Tuberculosis, University Hospital Brno, during the period from October 2020 to May 2021. Demographic data, information about the course of SARS-CoV-2 infection and oncological disease as well as mortality were monitored. Together with the data from the study population, three case reports are also presented. RESULTS: Fifty-three patients were found (79% males), mean age 69.4 years, mainly with adenocarcinoma histology. A total of 47.1% patients experienced mild course of SARS-CoV-2 infection, 56.6% needed hospitalization, 24.5% died. Active anticancer treatment was delayed in 62.4% cases due to SARS-CoV-2 infection; the mean time of the delay reached 14.5 days. CONCLUSION: Patients with lung and pleural malignancies have a high risk of severe course of SARS-CoV-2 infection and mortality. Moreover, the ongoing SARS-CoV-2 infection as well as postcovid changes can complicate the anticancer treatment itself.

MicroRNAs as potential markers of parenteral nutrition associated liver disease in adult patients.

Parenteral nutrition-associated liver disease (PNALD) is a severe complication in patients completely dependent on parenteral nutrition (PN). The gold diagnostic standard, liver biopsy, is associated with significant health risk and therefore its use is limited. MicroRNAs (miRNAs) are small non-coding regulatory RNA molecules with highly tissue-specific expression and the secreted miRNAs may serve as non-invasive diagnostic biomarkers. The aim of this study was to evaluate the expression of a panel of specific miRNAs associated with liver diseases of different origin in PN-dependent adult patients in order to design miRNA panel enabling to precise monitoring of PNALD progression. Twelve PN-dependent patients with short bowel syndrome (SBS) were monitored on three/four-month basis for up to 24 months. Forty-five age- and sex-matched subjects without any known liver pathology served as controls. Specific miRNAs expression was determined by RT-qPCR using TaqMan probes (Thermofisher). Liver function test parameters were determined in certified clinical laboratories. Six of the tested miRNAs exhibited significantly altered expression compared with healthy controls, three of them (MIR122, MIR1273g, and MIR500a) were upregulated while three were down-regulated (MIR505, MIR199a, MIR139). MIR122 positively correlated with serum AST and ALT activities while MIR1273g positively correlated with serum CRP concentration and GGT activity. MIR505, MIR199a, and MIR139 negatively correlated with serum GGT activity. Fluctuation of these parameters well paralleled serum miRNA concentrations in all patients throughout the whole observation period. We identified six miRNAs whose serum concentrations are significantly altered in PN-dependent patients with PNALD and correlate with markers of inflammation, cholestasis or hepatic injury. Their reliability as markers of PNALD progression needs to be further evaluated.

Vegetarian diet-induced increase in linoleic acid in serum phospholipids is associated with improved insulin sensitivity in subjects with type 2 diabetes.

BACKGROUND AND AIMS: Fatty acids are important cellular constituents that may affect many metabolic processes relevant for the development of diabetes and its complications. We showed previously that vegetarian diet leads to greater increase in metabolic clearance rate of glucose (MCR) than conventional hypocaloric diet. The aim of this secondary analysis was to explore the role of changes in fatty acid composition of serum phospholipids in diet- and exercise-induced changes in MCR in subjects with type 2 diabetes (T2D). METHODS: Subjects with T2D (n=74) were randomly assigned into a vegetarian group (VG, n=37) following vegetarian diet or a control group (CG, n=37) following a conventional diet. Both diets were calorie restricted (-500 kcal day(-1)). Participants were examined at baseline, 12 weeks of diet intervention and 24 weeks (subsequent 12 weeks of diet were combined with aerobic exercise). The fatty acid composition of serum phospholipids was measured by gas liquid chromatography. MCR was measured by hyperinsulinemic isoglycemic clamp. Visceral fat (VF) was measured by magnetic resonance imaging. RESULTS: Linoleic acid (LA; 18:2n6) increased in VG (P=0.04), whereas it decreased in CG (P=0.04) in response to dietary interventions. It did not change significantly after the addition of exercise in either group (group × time P<0.001). In VG, changes in 18:2n6 correlated positively with changes in MCR (r=+0.22; P=0.04) and negatively with changes in VF (r=-0.43; P=0.01). After adjustment for changes in body mass index, the association between 18:2n6 and MCR was no longer significant. The addition of exercise resulted in greater changes of phospholipid fatty acids composition in VG than in CG. CONCLUSION: We demonstrated that the insulin-sensitizing effect of a vegetarian diet might be related to the increased proportion of LA in serum phospholipids.

Intestinal permeability in patients with chemotherapy-induced stomatitis.

PURPOSE: Mucositis represents one of the most common side effects of chemotherapy, and may affect any part of the gastrointestinal tract, resulting in stomatitis, dysphagia, dyspepsia, or diarrhea. The aim of the present study was to evaluate intestinal permeability in patients with stomatitis during treatment with oral granulocyte-monocyte colony-stimulating factor (GM-CSF, Leucomax). METHODS: Ten patients with chemotherapy-induced stomatitis and 21 control cancer patients were included in the study. Intestinal permeability in patients with stomatitis was evaluated before and after the treatment with oral GM-CSF (200 micrograms for 4 consecutive days) by measuring urinary lactulose, D-xylose, and mannitol after oral challenge in collected urine using capillary gas chromatography. RESULTS: Mean grade of stomatitis (3, range 2-3) improved during treatment by a mean of 1 grade (range 0-2, sign test P < 0.05) with an improvement observed in eight of ten patients. Lactulose excretion, lactulose/mannitol, and lactulose/xylose ratios were markedly elevated in the patients with mucositis compared with 21 control cancer patients (1.60 +/- 1.04%, 0.2446 +/- 0.2937, and 0.3877 +/- 0.6808 vs 0.35 +/- 0.20%, 0.0332 +/- 0.0148, and 0.0255 +/- 0.0086, respectively, Mann Whitney U-test, P < 0.001). After treatment, lactulose excretion, lactulose/mannitol, and lactulose/xylose ratio decreased significantly (1.60 +/- 1.04 vs 0.63 +/- 0.42%; 0.2446 +/- 0.2937 vs 0.1303 +/- 0.1149; and 0.3877 +/- 0.6808 vs 0.1126 +/- 0.1146, respectively, P < 0.05). CONCLUSIONS: Lactulose excretion after oral challenge, lactulose/mannitol, or lactulose/xylose ratio may be useful markers for intestinal involvement in chemotherapy-induced mucositis. Improvement of oral mucositis was associated with a significant decrease of intestinal permeability to lactulose. Testing of intestinal permeability by the present method may be useful to evaluate the effect of therapeutic interventions in patients with chemotherapy-induced mucositis.

Bioanalysis of age-related changes of lipid metabolism in nonagenarians.

The aim of the present study was the bioanalysis of lipid metabolism in the aged patients and to study the relationship between these biochemical markers and longevity. Eleven nonagenarians, nine women and two men, aged 94+/-3 years and ten control patients, six women and four men, aged 84+/-5 years, followed at the Department of Metabolic Care and Gerontology, Charles University, Teaching Hospital entered the study. All subjects were self-sufficient, without major illnesses and free living. At the start of the project the free fatty acids (FFA), thiobarbituric reactive substances (TBARS), retinol, alpha tocopherol, ascorbic acid, cholesterol, triacylglycerols, phospholipids in serum, in lipoprotein fractions and fatty acids (FA) and phospholipids in erythrocyte membrane were determined. We used capillary gas chromatography for determination of fatty acids. Retinol and alpha tocopherol were analysed by reversed-phase high-performance liquid chromatography, other parameters were determined spectrophotometrically or spectrofluorometrically. We found significantly higher LDL polyunsaturated fatty acids (PUFA) 22:4n--3 (P=0.028) and 22:6n--3 (P=0.018) and a significant increase of HDL alpha tocopherol/cholesterol ratio (P=0.034) in nonagenarians. There were not any significant differences in erythrocyte membrane fatty acids and phospholipids. In serum we found significantly higher level of TBARS (3.22+/-1.22 vs 1.98+/-0.71 micromol/l, P=0.012) in nonagenarians, other parameters were not changed significantly. The higher concentration of PUFAs in LDL and alpha tocopherol in HDL might be parameters related to longevity.

Bioanalysis of PUFA metabolism and lipid peroxidation in coronary atherosclerosis.

Twenty eight men (age 34-77 years) who underwent an elective coronary angiography for coronary artery disease (CAD), were studied. They were divided into group A (luminal narrowing < 50%; n = 11) and group B (luminal narrowing > 50%; n = 17). Capillary gas chromatography was used for determination of fatty acids. Retinol and alpha-tocopherol were analyzed by reversed-phase high-performance liquid chromatography (HPLC), other parameters were determined spectrofluorometrically and spectrophotometrically. Severe coronary atherosclerosis in group B was associated with higher serum low density lipoprotein/high density lipoprotein (LDL/HDL) cholesterol ratio, triacylglycerols, and phospholipids (P < 0.05). Erythrocyte membrane fatty acids C14:0, C16:1 and C22:6n3 were significantly higher in group B (P < 0.05). We found significantly higher plasma polyunsaturated fatty acids (PUFA) C18:3n6 in group B, whereas plasma linoleic acid was not changed significantly. There was a significant increase of IDL-C18:0, LDL-C14:0 and HDL-C22:6n3 PUFA in group B. We conclude that disturbances in saturated fatty acids (SUFA) and PUFA metabolism are associated with coronary atherogenesis. Such abnormalities may include enhanced extrahepatic transport of C14:0 SUFA via LDL and its incorporation into cell membranes, and enhanced clearance of anti atherosclerotic C22:6n3 PUFA via serum HDL.

Small bowel permeability in patients with cytostatic therapy.

The purpose of this study was to examine the influence of cytostatic therapy on the barrier function of the small bowel. In 16 patients with tumors in the gastrointestinal tract with metastatic involvement of the liver, small bowel permeability was measured using the lactulose/mannitol test. The patients were treated for 5 d with fluorouracil (750-1000 mg/d) and leucovorin (25-50 mg/d). The examination was performed on the first day, at the beginning of the cytostatic therapy, and also 5, 12, and 28 d after the therapy had begun. In comparing the start and the end of this therapy, the index of permeability was significantly increased (as measured 7 d after the end of therapy). These results show the damage of small bowel barrier after cytostatic therapy.

[Intestinal permeability in patients with food allergy]. / Vysetrení strevní propustnosti u pacientu s potravinovou alergií.

The authors examined the intestinal permeability using the lactulose mannitol test in 13 women, mean age 45.7 years with a confirmed food allergy before they were on an elimination diet. The intestinal permeability did not differ significantly in these patients as compared with healthy volunteers. The intestinal permeabiity test with lactulose and mannitol thus cannot be recommended on the basis of these results for the diagnosis of food allergy.

[Selection criteria for treatment of severe hyperlipoproteinemias with LDL apheresis]. / Selekcní kritéria k léc be závazných hyperlipoproteinémií metodou LDL aferéz.

LDL (low density lipoprotein) - apheresis has been established as an alternative management of severe hypercholesterolaemia after failure of conventional diet and drug therapy. General indication criteria for LDL-apheresis have yet been established. Indication guidelines in USA, Europe and japan are based on whether coronary heart disease is present and on the degree of lDL cholesterol elevation after treatment with diet and maximal drug therapy. It is reasonable to consider LDL apheresis therapy for: 1. patient with coronary heart disease and LDL cholesterol 4.9 mmol/l (190 mg/dl); 2. patients without coronary heart disease, but at high risk for disease (due to an LDL cholesterol above 6.4 mmol/l (250 mg/dl), a first-degree relative with premature coronary heart disease, and the presence of one or more additional risk factor. The therapeutical goal with present coronary heart disease is lDL cholesterol less than 3.4 mmol/l (130 mg/dl), with asymptomatic coronary heart less than 5.2 mmol/l (200 mg/dl). In addition, LDL apheresis is recommended for the management of all patients with homozygous familial hypercholesterolaemia due to the very high risk of coronary heart disease and the poor response to usual lipid-lowering treatments. In the end present two typical cases, treated by LDL-apheresis.

Hypocholesterolemic effect of pravastatin is associated with increased content of antioxidant vitamin-E in cholesterol fractions.

Metabolic studies support the findings that antioxidants inhibit atherosclerosis. Treatment with vitamin E reduced both the susceptibility of low density lipoprotein cholesterol (LDL-C) to in vivo lipid peroxidation and atherosclerosis and smooth muscle proliferation. Thus the aim of present study was to examine metabolic consequences of reduced plasma LDL-C during hypolipidemic therapy and the distribution of antioxidant vitamin E. A group of 10 patients (4 men, 6 women, age 35-65y) with familial hypercholesterolaemia was treated using pravastatin (Lipostat Bristol Myers Squibb, 40 mg daily at 6:00 PM). Blood samples were examined before treatment, after 4 and 8 weeks of therapy. After ultracentrifugation, samples were analyzed for lipoprotein fractions and the content of vitamin E and cholesterol. Pravastatin reduced both total cholesterol (9.85 +/- 0.74 vs. 6.81 +/- 0.51 mmol/1; p < 0.01), LDL-C (6.42 +/- 0.45 vs. 4.51 +/- 0.45 mmol/l; p < 0.01), light LDL1-C (4.56 +/- 0.50 vs. 3.11 +/- 0.34 mmol/l; p < 0.05) and dense LDL2-C (1.86 +/- 0.27 vs. 1.42 +/- 0.17 mmol/l; ns). Serum vitamin E was reduced during hypolipidemic therapy in the fraction of total, LDL1, LDL2, and VLDL-cholesterol. However, the ratio of serum vitamin E/total serum cholesterol (4.57 +/- 0.32 vs. 5.12 +/- 0.37 mmol/l/mmol/l; p < 0.05) and ratio of LDL2-C vitamin E/LDL2-C (3.92 +/- 0.07 vs. 4.64 +/- 0.37 mmol/l/mmol/l; p = 0.08) increased in comparison to pre-treatment values. We conclude that pravastatin therapy may possess anti-atherogenic properties which involve not only its hypocholesterolemic effect, but also its favorable effects on the distribution of LDL subclasses and the content of antioxidant vitamin E in atherogenic lipoproteins.

Distribution of fenofibric acid in lipoprotein fractions of patients.

The antidyslipidemic agent fenofibrate (procetofen) is hydrolysed in vivo to its main active metabolite--fenofibric (procetofenic) acid. This metabolite is usually determined in pharmacokinetic studies, because plasma concentrations of fenofibrate are practically undetectable. Presented study is focussed on the distribution of fenofibric acid into lipoprotein (VLDL, LDL, IDL and HDL) fractions of human and (for comparison) minipig blood plasma, which has not been studied yet. In order to obtain more accurate results, a new HPLC method based on the use of newly synthetized internal standards was developed. Four homologues of fenofibric acid prepared have identical chromophoric part of their molecules and hence the same UV spectra as fenofibric acid. From this point of view, these standards are more suitable for determination of fenofibric acid than the formerly used ones--naproxen or bezafibrate. Fenofibric acid levels in the high density lipoprotein fraction has been shown to be significantly higher (in both human and minipig plasma) than in the other lipoprotein fractions. This fact may be explained by higher affinity of the fenofibric acid to proteins constituting major part of the high density lipoprotein fraction.

Screening for organic acid disorders.

The detection of organic acidurias is a part of our screening programme for inherited metabolic diseases. Adapted procedure is differentiated and involves several steps: 1) thin-layer chromatography (TLC) in the case of an abnormal finding followed by 2) gas chromatography (GC). The next step of the investigation, using 3) gas chromatography mass-spectrometry (GS-MS) is reserved for more complicated and dubious analyses. In acutely sick patients and in the case of discrepancies between TLC results on the one hand, and clinical symptoms, supported by other laboratory findings on the other, the GC or GC-MS-analysis is performed immediately. Some examples of metabolic disorders, identified by this procedure, are presented.

Inulin as the soluble fiber in liquid enteral nutrition.

Dietary fibers are a necessary part of human nutrition. Inulin is a fermentable fiber that improves bacterial ecology in the large bowel and is also a relevant substrate for short-chain fatty acid (SCFA) production. The aim of the present study was to evaluate the clinical effect of inulin, added as dietary fiber into the fiber-free enteral nutrition (Nutrition Standard). Inulin (30-35 g/d) was administered for 1 wk to a group of patients requiring the nutritional support of a liquid enteral diet. A significant increase in flatulence, an indication of rapid bacterial fermentation, was apparent during its infusion in comparison with a fiber-free enteral diet. Moreover, an increment in ability to dehydrate the cecal stream (stool consistency) was apparent in nearly half of patients. No changes in SCFA concentration in stool and indican output in urine were apparent after 1 wk of inulin administration. Intestinal permeability (51Cr-EDTA absorption test) was not influenced by either enteral nutrition or inulin and enteral nutrition administration. Because of good tolerance inulin seems to be a potential source of dietary fiber in clinical enteral nutrition.

Evidence for the anti-hyperlipidaemic activity of the edible fungus Pleurotus ostreatus.

The effects are described of adding either the dried fruiting bodies of the oyster fungus Pleurotus ostreatus, or an ethanolic extract of it, to the diet of normal Wistar male rats and a strain with hereditary hypercholesterolaemia. Addition of the dry oyster fungus to the diet significantly increased, by more than two-fold, the triacylglycerol (TAG) level in the plasma of both groups of rats compared with their respective controls. In contrast, the ethanolic extract did not significantly change TAG levels. Values for total cholesterol and its high- and low-density lipoprotein fractions in the plasma, as well as the calculated atherogenic index, did not show any significant change. Levels of liver cholesterol were significantly lowered by the dried oyster fungus in both hypercholesterolaemic and normal groups of rats, and by the ethanolic extract in normal rats. A significantly increased phospholipid-to-cholesterol ratio in the aortas of both groups of rats, after the administration of either dried oyster fungus or the ethanolic extract of it, suggests a favourable anti-atherogenic effect for both.

[Dystrophic changes in the macular pigment epithelium as a sequela of exudative diabetic maculopathy]. / Dystrofické zmeny pigmentového epitelu makuly jako následek exsudativní diabetické makulopatie.

This work is concerned with the treatment of diabetic exsudative maculopathy using hypolipemic and laser therapy. It shows correlation between the decrease of lipemia and the reduction of the area of hard exsudates in the central region of retina after the hypolipemic therapy. But the corresponding improvement of the vision could not be reached because in 31.2% of cases there were permanent changes of the pigment epithelium of central retina in the original locations of the hard exsudates.

Kinetics of phenols in body fluid compartments during hemodialysis.

On the basis of direct quantification of hemodialysis (HD), the kinetics of phenols (Ph) were followed in 13 patients on regular HD treatment. The average plasma levels of Ph before and after HD were 627 +/- 109 mumol/L and 416 +/- 81 mumol/L, respectively. The total amount of Ph removed during 5-h HD was 7,481 +/- 1,894 mumol. For calculation of the generation rate (G), a new formula has been derived not requiring knowledge of the corresponding volume of distribution. The G of Ph was 2.9 +/- 0.7 mumol/min on average. The mean dialysis clearance (K) of Ph was 48.2 +/- 10.2 ml/min.

Pharmacokinetic parameters of verapamil and its active metabolite norverapamil in patients with hepatopathy.

Verapamil (CAS 52-53-9) is a calcium channel blocker with a vasodilatatory effect. Because of its significant first-pass effect, verapamil might be advantageous in the treatment of portal hypertension. It does not produce any excessive systemic effects, provided the doses are suitably adjusted. A decision was made to examine the pharmacokinetic parameters, independent of compartmental analysis of verapamil and its active metabolite norverapamil, in patients with portal hypertension. Their biological half-lives of the terminal phase were significantly prolonged as compared with the control group. However, no statistically significant differences were found in the values of tmax and Cmax. The calculated pharmacokinetic parameters of norverapamil were not significantly different from those of verapamil, except for the tmax of norverapamil, which was significantly longer in patients suffering from portal hypertension as compared with verapamil. The ratio of areas under the plasma concentration-time curve (AUC) of verapamil and norverapamil was comparable in both groups of patients. No relationship between the changes in the pharmacokinetic parameters and the extent of hepatic insufficiency was observed.

[Determination of lactoferrin in the diagnosis of pancreatopathy in patients with chronic kidney failure]. / Stanovení laktoferinu v diagnostice pankreatopatií u nemocných s chronickým selháním ledvin.

The authors investigated in patients with renal disease the lactoferrin content in duodenal aspirate. The aspirate was obtained after previous stimulation of the pancreas with pancreozymin. Lactoferrin estimation is described in the literature as a sensitive examination of changes of exocrine pancreatic secretion. The authors provided evidence that by assessing lactoferrin it is possible to detect initial changes of reduced exocrine pancreatic capacity already in subjects who are on the waiting list of chronic intermittent haemodialyzation programmes (CHIDP); maximum increase of the lactoferrin content in the duodenal aspirate corresponds with the severity of chronic renal failure. Transplantation of the kidneys leads to normalization of the amount of lactoferrin secreted by the pancreas which is evidence of normalization of pancreatic secretion. In patients with chronic renal failure lactoferrin is a sensitive marker of developing uraemic pancreatopathy.

[Vitamin A and metabolic disorders of calcium and phosphorus in patients on a long-term dialysis program]. / Vitamín A a metabolické poruchy vápnika a fosforu u chorych v dlhodobom dialyzacnom programe.

The aim of the present work was to reveal the relationship between vitamin A serum levels and some indicators of metabolic calcium and phosphorus disorders in patients in a long-term dialyzation programme. Thirty-six patients in a long-term dialyzation programme were divided into three groups. Group A comprised 11 patients who were treated for 3-9 months but without specific treatment, group B was formed by 10 patients treated for 2-5 years who were given calcium carbonate, 3 g/24 h, by the oral route for a period of six months and group C which comprised 15 patients treated for 3-10 years who were given 1 alpha, 25-dihydroxycholecalciferol (Rocaltrol), 0.25 micrograms/24 h for a period of six months. At the end of the investigation a significant rise of total calcium and serum Ca2+ occurred in all three groups of patients an a significant decrease of increased value of phosphorus, C-PTH and vitamin A in serum in groups B and C. In group A which was without treatment there was a significant increase of serum C-PTH and vitamin A after six months. The concentration of retinyl esters in serum was within the reference range of there were undetectable values throughout the investigation in all patients. A direct relationship was found between total calcium and vitamin A, alkaline phosphatase and C-PTH in serum in all 36 patients at the onset of the dialyzation programme. Moreover there was a direct relationship between C-PTH and vitamin A in groups, A, B and C at the onset of the investigation and in groups and vitamin C at the end of the investigation.(ABSTRACT TRUNCATED AT 250 WORDS)