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K H Usadel

Publications and source records attributed to K H Usadel.

At least 55 records · Page 3Linked to original sources
PubMed1999

HLA-DMA and HLA-DMB alleles in German patients with type 1 diabetes mellitus.

The HLA-DMA and HLA-DMB genes are located in the HLA-D region between DQ and DP. Four variants of DMA (DMA*0101-0104) and five of the DMB (DMB*0101-0105) have so far been identified. HLA-DM molecules are required in the process of peptide loading to HLA class II antigens, both regulating the dissociation of class II-associated invariant chain peptides (CLIP) and the subsequent binding of exogenous peptides to HLA class II molecules. In order to investigate the immunogenetic heterogeneity within the HLA-D susceptibility region, we analysed the distribution of DMA alleles in 125 patients with type 1 diabetes mellitus and 90 healthy controls, and of DMB alleles in 102 patients and 89 healthy controls. Patients and controls were all from central Germany. The polymerase chain reaction (PCR) amplified products were purified and separated on a 10% polyacrylamide gel electrophoresis. Among the four recognized DMA alleles, DMA*0102 was significantly less frequent (12% vs. 28.9%, P<0.01) in patients with type 1 diabetes mellitus. DMB*0101 (70.6% vs. 97.8%, P<5.5x10(-3)) was also reduced in frequency compared to controls. Comparing patients and controls positive for the type 1 diabetes high-risk markers we found a significant association between DMA*0102 and DQA*0501 (9.5% vs. 39.1%, P<0.02), as well as DMB*0101 and DQA*0501 (62.5% vs. 96.2%, P<0.03). In conclusion, DMA*0102 and DMB*0101 contribute to genetic protection to type 1 diabetes mellitus in individuals with high-risk DQA markers in the German population.

Alleles↗
PubMed1999

The effects of interleukin-2 treatment on endothelin and the activation of the hypothalamic-pituitary-adrenal axis.

OBJECTIVE: Recent reports suggest that complex interactions exist between the neuroendocrine and immune systems. It has been shown for example that cytokines are able to stimulate the hypothalamo-pituitary-adrenal axis. In addition, some studies present evidence that endothelin is able to modulate the activity of several hypothalamic-pituitary axes, e.g. by inducing the ACTH production. DESIGN: We investigated the effects of interleukin-2 on endothelin levels and the hypothalamo-pituitary-adrenal axis. We determined the interleukin-6, big-endothelin, endothelin-1, ACTH, cortisol and AVP responses to intravenously and subcutaneously administered interleukin-2 in 8 cancer patients in a randomized placebo controlled trial. PATIENTS: 8 Patients (2 female and 6 male), age 44 +/- 4.8 years, were enrolled. All patients had a World Health Organization performance status of 1 or less and a Karnofsky Index of at least 80%. MEASUREMENTS: Blood-samples were taken before and 15, 30, 45, 60, 120, 180, 240, 300 and 360 min after interleukin-2 injection. Cytokine serum levels and the plasma levels of big-endothelin, endothelin, ACTH and AVP were analysed using radioimmuno-assays. Cortisol was assayed by an enzyme-linked immunosorbent assay. RESULTS: Interleukin-2 treatment significantly increased plasma big-endothelin levels (P < 0.01 vs basal) and endothelin-1 levels (P < 0.05 vs basal) within two hours and this was followed by an increase in ACTH (P < 0.01 vs basal) and cortisol (P < 0.05 vs basal) within three hours. Interleukin-6 levels increased two hours after interleukin-2 administration (P < 0.01 vs basal). Interleukin-2 had no detectable effect on AVP, blood pressure or heart rate. CONCLUSIONS: Our data demonstrate that cytokines are able to activate the human hypothalamo-pituitary-adrenal axis in vivo. On the basis of the observed time kinetics and in connection with previous findings from in vitro and animal models, we conclude that endothelin may be a link between cytokines and corticotrophin-releasing hormone, most probably functioning as a cytokine-induced neuromodulator controlling pituitary functions.

Adrenocorticotropic Hormone↗
PubMed1999

In vivo microscopy of murine islets of Langerhans: increased adhesion of transferred lymphocytes to islets depends on macrophage-derived cytokines in a model of organ-specific insulitis.

Environmental factors contribute to the pathogenesis of type 1 diabetes (insulin-dependent diabetes mellitus). Multiple low doses of streptozotocin (MLDS) induce hyperglycaemia and insulitis in mice. Previously we demonstrated that adhesion of lymphocytes to endothelium of islets is only increased when donor animals were diabetic and recipient mice had received 5 mg/kg streptozotocin (STZ). Therefore we used streptozotocin to evaluate the immunological relevance of such an irritation of islets. Lymphocytes, separated from diabetic mice (MLDS), were fluorescently labelled and injected to recipient mice that had received 5 mg/kg STZ. With in vivo microscopy we measured lymphocyte flow and adherence in islets. Expression of vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) in the pancreas was assessed using immunohistochemistry. Very late antigen-4 (VLA-4) and leucocyte function-associated antigen-1 (LFA-1) expression on transferred lymphocytes was measured with flow cytometry. Pretreatment of recipients with antibodies to cytokines or silica reduced lymphocyte adherence to islet endothelium from 2.04% (goat immunoglobulin G; IgG) or 1.82% (rat IgG) to 0.47, 0.58, 0.39 or 0. 19% for monoclonal antibody (mAb) interferon-gamma (IFN-gamma), polyclonal antibody (pAb) tumour necrosis factor-alpha (TNF-alpha), pAb interleukin (IL)-1alpha or silica, respectively. Reduced adhesion was associated with a decreased expression of VCAM-1 and ICAM-1 in islets of treated recipients compared with mice treated with 5 mg/kg STZ alone. In conclusion, pretreatment of recipients with 5 mg/kg STZ leads to an increased expression of adhesion molecules in the islets and lymphocyte adhesion to islet endothelium in vivo, demonstrating an immune response of the islets. Prevention of increased expression of ICAM-1 or VCAM-1 and reduction of lymphocyte adhesion in islets by silica or antibody indicate an involvement of macrophages and macrophage derived cytokines in the generation of this immune response.

Animals↗
PubMed1999

Interferon-alpha improves glucose tolerance in diabetic and non-diabetic patients with HCV-induced liver disease.

This pilot study was initiated to evaluate factors controlling glucose tolerance in patients with hepatitis C virus-induced liver disease before and after therapy with recombinant interferon-alpha (r-INF-alpha). Fifteen patients with histologically and serologically proven hepatitis C infection underwent oral and frequently sampled intravenous glucose tolerance tests (FSIGTT) before and after four months of therapy (6 x 106 U r-INF-alpha, subcutaneously, three times a week). Glucose, insulin and C-peptide data from FSIGTT were analysed using the minimal modeling technique to determine insulin sensitivity, glucose effectiveness and first and second phase insulin secretion. According to the WHO criteria 13 patients, had normal glucose tolerance; diabetes mellitus was diagnosed in 2 patients. In the morning following the last r-INF-alpha injection four months later, insulin sensitivity improved significantly in hepatitis C virus-infected patients with normal glucose tolerance (2.17 +/- 0.37 vs. 6.18 +/- 0.94 10(-4) min(-1) per microU/ml, p < 0.001) and with diabetes mellitus (0.86 to 2.61; 0.46 to 1.06 10(-4) min(-1) per microU/ml). This effect was independent of the extent of fibrosis, virus load before treatment and therapy response. First phase insulin secretion increased in non-diabetic (139.2 +/- 17.1 vs. 200.0 +/- 32.7, p < 0.05) and diabetic patients with HCV infection (55.24 to 118.5; 84.23 to 261.1). Moreover, free fatty acid concentrations in all HCV-infected patients were significantly reduced (0.48 +/- 0.01 vs 0.21 +/- 0.03 mmol/l, p < 0.01). Therapy with recombinant interferon-alpha is associated with an amelioration of glucose tolerance in non-diabetic and diabetic HCV-infected patients.

Adult↗
PubMed1999

No association between the deltaF508 cystic fibrosis mutation and type 2 diabetes mellitus.

Cystic fibrosis (CF) is one of the most common recessively inherited disorders in Caucasian populations and is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. A three base deletion known as deltaF508 occurs on about 70%, of CF chromosomes and accounts for the high prevalence of the disease. Since type 2 diabetes mellitus occurs more frequently in relatives of patients with CF than in the normal population, we addressed the hypothesis whether heterozygosity for deltaF508 might be a genetic risk factor for type 2 diabetes. We screened 301 patients with type 2 diabetes mellitus which had been treated for at least three years from diagnosis by diet or oral antihyperglycemic agents. Healthy controls (n = 282) had no family history for diabetes. The genotype distribution did not differ significantly between patients with type 2 diabetes (2% heterozygotes) and controls (3% heterozygotes). According to these results, we conclude, that the deltaF508 mutation in its heterozygous form does not represent a major genetic risk factor for type 2 diabetes mellitus.

Body Mass Index↗
PubMed1999

Immunologic effects of human peripheral and intrathyroidal lymphocytes on xenotransplanted human thyroid tissue in athymic nude mice.

T cells are intimately involved in the etiology and pathogenesis of human autoimmune thyroid disease. In order to further elucidate the immunologic mechanisms leading to Graves' disease (GD), we investigated the effects of human lymphocytes derived from patients with autoimmune and nonautoimmune thyroid diseases on human thyroid tissue xenotransplanted into nude mice. Eight weeks after transplantation of thyroid tissue from 26 patients with nonautoimmune thyroid disease (nontoxic nodular goiter [NTG]) into nude mice, peripheral (PBL) and intrathyroidal lymphocytes (ITL) from 14 patients with NTG and 12 patients with GD were engrafted into the animals. ITL and PBL subsets were analyzed by flow cytometer before engraftment. Two days after lymphocyte engraftment, the thyroid transplants were examined histologically (HE) as well as immunohistologically by staining with monoclonal antibodies directed against CD3 (T-cell activation and signal transduction), immunoglobulin G (IgG), HLA class II and CD31 (human endothelium). After injection of GD lymphocytes, thyroid transplants contained significantly more CD3, HLA class II, and CD4 expressing cells. Engrafted PBL and especially ITL from patients with GD specifically migrated into human thyroid transplants but not into the mouse thyroids, induced expression of class II products and led to IgG production by plasma cells. Persistence of human endothelium has been proven by positive CD31 staining. In conclusion, our data demonstrate that an organ-specific immune response is induced only by GD lymphocytes that migrate specifically into the thyroid transplants. Persistence of human endothelial cells in the transplants suggests that homing in this in vivo model reflects the situation in GD patients.

Adult↗
PubMed1999

Second generation assay for thyrotropin receptor antibodies has superior diagnostic sensitivity for Graves' disease.

Detection of autoantibodies to the TSH receptor (TSH-R) in Graves' disease has found widespread use in clinical routine and is performed mostly by commercial RRAs measuring TSH binding inhibitory activity. We report in this study on a second generation TSH binding inhibitory assay using the human recombinant TSH-R with two major improvements: 1) superior diagnostic sensitivity for Graves' disease, and 2) for the first time, nonradioactive and radioactive coated tube (CT) technology. Full-length human recombinant TSH-R was expressed in the K562 leukemia cell line and grown in suspension at a high density. A murine monoclonal antibody was selected for binding to the native TSH-R without interfering with autoantibodies or TSH and was coated to polystyrene tubes. After detergent extraction, TSH-R was affinity immobilized on antibody-coated tubes. The binding of TSH to the TSH-R could be demonstrated by the addition of 125I- or acridinium ester-labeled bovine TSH, and this binding could be inhibited by sera from patients with Graves' disease up to 95%. Subsequently, these novel assays, a CT RRA and a CT luminescence receptor assay, were compared to the conventional RRA based on porcine antigen in a blinded clinical multicenter trial. Sera from 328 patients with Graves' disease (86 untreated, 116 treated, and 126 in remission) and 520 controls (comprised of healthy blood donors and patients with autoimmune diseases or goiter) were tested in all 3 assays. Receiver-operating characteristic plot analysis resulted in a specificity of 99.6% with a sensitivity of 98.8% for both CT assays, compared to 99.6% specificity and 80.2% sensitivity for the conventional RRA (P < 0.001). In all 3 groups of patients with Graves' disease, the 2 CT assays were significantly more sensitive for the disease than the conventional assay, without loss of specificity in the control groups. This increase in sensitivity and the nonradioactive or radioactive CT format constitute a significant improvement over the currently available assays.

Adolescent↗
PubMed1999

The presence or absence of a retroviral long terminal repeat influences the genetic risk for type 1 diabetes conferred by human leukocyte antigen DQ haplotypes. Belgian Diabetes Registry.

Major genetic susceptibility to type 1 diabetes mellitus maps to the human leukocyte antigen (HLA) region on chromosome 6p. During evolution, endogenous retroviral long terminal repeats (LTR) have been integrated at several sites within this region. We analyzed the presence of a solitary HERV-K LTR in the HLA DQ region (DQ-LTR3) and its linkage to DRB1, DQA1, and DQB1 haplotypes derived from 246 German and Belgian families with a patient suffering from type 1 diabetes mellitus. Segregation analysis of 984 HLA DQA1/B1 haplotypes showed that DQ-LTR3 is linked to distinct DQA1 and DQB1 haplotypes but is absent in others. The presence of DQ-LTR3 on HLA DQB1*0302 haplotypes was preferentially transmitted to patients from heterozygous parents (82%; P < 10(-6)), in contrast to only 2 of 7 DQB1*0302 haplotypes without DQ-LTR3. Also, the extended HLA DRB1*0401, DQB1*0302 DQ-LTR3-positive haplotypes were preferentially transmitted (84%; P < 10(-6)) compared with 1 of 6 DR-DQ matched DQ-LTR3 negative haplotypes. DQ-LTR3 is missing on most DQB1*0201 haplotypes, and those LTR3 negative haplotypes were also preferentially transmitted to patients (80%; P < 10(-6)), whereas DQB1*0201 DQ-LTR3-positive haplotypes were less often transmitted to patients (36%). Other DQA1/B1 haplotypes did not differ for DQ-LTR3 between transmitted and nontransmitted haplotypes. Thus, the presence of DQLTR3 on HLA DQB1*0302 and its absence on DQB1*0201 haplotypes are independent genetic risk markers for type 1 diabetes.

Diabetes Mellitus, Type 1↗
PubMed1999

Kleine-Levin and Munchausen syndromes in a patient with recurrent acromegaly.

Hypothalamic disease often affects the patients' personality and this also applies to pituitary tumors with suprasellar extension. We report on a patient with a 12-year history of recurrent acromegaly, treated with three transphenoidal operations, single field radiation therapy and bromocriptine/octreotide administration. During the course of follow-up she presented with self-inflicted anemia and Kleine-Levin syndrome (hypersomnia, hyperphagia and hypersexuality). Furthermore, she developed post-radiation necrosis within the right temporal lobe. Whether her neurological and personality disorders result - at least partially - from the acromegaly or the temporal lobe necrosis remains unclear.

Acromegaly↗
PubMed1999

IDDM patients neither show humoral reactivities against endogenous retroviral envelope protein nor do they differ in retroviral mRNA expression from healthy relatives or normal individuals.

Recently, human endogenous retrovirus type K (HERV-K [IDDMK(1,2)22]) was isolated from an IDDM patient's beta-cell supernatant and shown to be implicated in expression as a superantigen. Furthermore, HERV-K RNA was found in plasma samples from newly diagnosed patients but not in those from healthy control subjects. We had earlier identified the presence of a HERV-K long terminal repeat element of the HLA DQ gene (DQ-LTR) to be positively associated with IDDM, which led us to investigate whether DQ-LTR is related to transcription of the putative retroviral superantigen. Additionally, we sought immunological evidence to determine whether those retroviral antigens could evoke an antibody response. Patients with IDDM (n = 14), Hashimoto's thyroiditits (n = 5), and Graves' disease (n = 12), as well as healthy control subjects (n = 12), were investigated, as were four nuclear families of Graves' disease patients and two of IDDM patients. RNA was isolated from plasma and peripheral blood lymphocytes and subjected to reverse transcription-polymerase chain reaction for transcripts of the env region of the HERV-K (IDDMK(1,2)22) sequence. We identified env transcripts in both plasma and peripheral blood lymphocytes in all individuals studied: patients with recent-onset or long-standing IDDM, their relatives, and healthy control subjects, as well as patients with thyroid autoimmune disorders. Furthermore, we screened the sera of patients (n = 62) and control subjects (n = 35) for evidence of humoral immunity against HERV-K by Western blot specific for the ENV protein. Similar frequencies of antibody-positives were observed both in patients with IDDM (29%) and in healthy control subjects (26%). We conclude that neither the ubiquitous HERV-K transcripts nor the comparable percentage of ENV protein antibodies are associated with IDDM. An earlier, presymptomatic antibody response against HERV-K (IDDMK(1,22)22) ENV cannot be ruled out. However, the superantigen hypothesis of an endogenous retrovirus in beta-cell autoimmunity awaits confirmation.

Antibody Formation↗
PubMed1999

alpha-Lipoic acid treatment decreases serum lactate and pyruvate concentrations and improves glucose effectiveness in lean and obese patients with type 2 diabetes.

OBJECTIVE: We examined the effect of lipoic acid (LA), a cofactor of the pyruvate dehydrogenase complex (PDH), on insulin sensitivity (SI) and glucose effectiveness (SG) and on serum lactate and pyruvate levels after oral glucose tolerance tests (OGTTs) and modified frequently sampled intravenous glucose tolerance tests (FSIGTTs) in lean (n = 10) and obese (n = 10) patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: FSIGTT data were analyzed by minimal modeling technique to determine SI and SG before and after oral treatment (600 mg, twice a day, for 4 weeks). Serum lactate and pyruvate levels of diabetic patients after glucose loading were compared with those of lean (n = 10) and obese (n = 10) healthy control subjects in which SI and SG were also determined from FSIGTT data. RESULTS: Fasting lactate and pyruvate levels were significantly increased in patients with type 2 diabetes. These metabolites did not exceed elevated fasting concentrations after glucose loading in lean patients with type 2 diabetes. However, a twofold increase of lactate and pyruvate levels was measured in obese diabetic patients. LA treatment was associated with increased SG in both diabetic groups (lean 1.28 +/- 0.14 to 1.93 +/- 0.13; obese 1.07 +/- 0.11 to 1.53 +/- 0.08 x 10(-2) min-1, P < 0.05). Higher SI and lower fasting glucose were measured in lean diabetic patients only (P < 0.05). Lactate and pyruvate before and after glucose loading were approximately 45% lower in lean and obese diabetic patients after LA treatment. CONCLUSIONS: Treatment of lean and obese diabetic patients with LA prevents hyperglycemia-induced increments of serum lactate and pyruvate levels and increases SG.

Blood Glucose↗
PubMed1999

Vitamin D binding protein alleles and susceptibility for type 1 diabetes in Germans.

Vitamin D has been shown to modulate the immune system thereby preventing the development of diabetes in NOD mice. Since the vitamin D binding protein (DBP) is the main transporter for vitamin D and DBP has immunomodulatory properties itself, we investigated three polymorphic sites within the DBP gene as candidates for type 1 diabetes susceptibility for the first time. 152 Caucasian families with at least one affected offspring were genotyped for intron 8 [(TAAA)n repeat] and exon 11 (HaeIII, StyI) polymorphisms. Transmission disequilibrium testing was used to detect preferential transmission to affected offspring. We found no significant transmission disequilibrium for DBP alleles. The strongest deviation from expected values was observed for the "10" allele (relative risk = 0.57, transmitted 13 of 36 times (corrected p = 0.249)). Although we cannot exclude an association of the studied DBP alleles with type 1 diabetes at present, these data do not suggest their contribution to this disease in Germans.

Alleles↗
PubMed1999

[Genetic risk markers in Graves' disease].

Graves' disease is exceptional as a disorder of stimulatory autoimmunity in comparison with all other endocrine autoimmunopathies. Research into its pathogenesis has so far focussed on the genetics next to characterisation of antibody-antigen as well as T-lymphocyte interactions. A multigenic predisposition similar to other autoimmune diseases has been proposed. Such polygenic disorders are frequent in the population and require special genetic epidemiological tools to dissect the many gene loci, where polymorphisms are readily detectable by several molecular typing assays. This review presents these tools and methods as well as the currently identified main susceptibility loci in the Human Leukocyte Antigen (HLA DQA1*0501), cytotoxic T-lymphocyte antigen 4 (CTLA4-ala17) as well as interferon-gamma (IFN-gamma *2) regions. Most of these predisposing alleles are shared risk factors in several endocrine autoimmune diseases. Further research is required to identify those gene variants that determine the individual course of thyroid stimulation or destruction.

Genetic Markers↗
PubMed1999

Graves' disease: xenotransplantation model (athymic nude mice).

The immunological mechanisms leading to Graves' disease are not yet fully understood. The athymic nude mouse has immunological properties which allow in vivo studies concerning autoimmune thyroid diseases with special regard to the interaction of TSH, TSH receptor antibodies, cytokines, antithyroid drugs, TSH receptor antagonists and human lymphocytes. In our own studies thyroid tissues of patients with Graves' disease, toxic adenomas and non-toxic nodular goiter were xenotransplanted to athymic nude mice. Histology, morphology and function of the transplants were examined 2 days to 2 weeks after injection of bovine TSH, interferon-gamma, Graves' sera with or without addition of a TSH-receptor antagonist and lymphocytes of patients with Graves' disease. Thyroid transplants can be stimulated by TSH, interferon-gamma, Graves' sera and immunoglobulin G. Additional treatment with asialoagalacto-hCG inhibits stimulation of the immunoglobulin. Furthermore, preliminary results show, that engrafted peripheral and especially intrathyroidal lymphocytes from patients with Graves' disease specifically migrate into human thyroid transplants ("homing") and are able to induce functional and histological changes in these tissues. In summary, the xenotransplantation model is well suited for studies concerning pathogenesis, diagnosis and therapy of autoimmune thyroid diseases.

Animals↗
PubMed1998

[Treatment costs in a medical intensive care unit: a comparison of 1992 and 1997].

BACKGROUND AND OBJECTIVE: Treatment in an intensive care unit (ICU) is very expensive. Aim of this study was to determine the exact composition of costs and to analyse what factors are responsible for the rise in costs over the last 5 years. METHODS: In a prospective investigation all 790 patients who had been treated at the ICU of the Medical Department of Frankfurt University during 1992 were included, findings being compared with data on all 208 patients treated in the ICU in May and June 1997. All important diagnostic and therapeutic measures were quantitatively determined each day. RESULTS: The mean age of the ICU patients rose in the 5 years from 55 to 59 years (P < 0.001). Mean period of stay in the ICU remained unchanged (4.1 days), total duration of hospital stay (15 and 12 days, respectively), and treatment intensity (sum of points according to the "Therapeutic Intervention Scoring System" per ICU stay: 96 and 77, respectively). The mortality rate in the ICU fell from 16.3% to 10.6% (P = 0.02), hospital mortality rate from 23% to 14% (P = 0.01). Total cost rose from DM 797,860 to DM 1,148,945 per 100 patients (+44%). Of this total, personnel costs were DM 286,885 in 1992 and 356,091 in 1997 (+24%), costs for apparatus-based diagnostic and therapeutic tests were DM 169,743 and 245,156, respectively (+44%), DM 98,496 and 129,222 for drugs (+31%), and DM 60,399 and 186,671 (+209%) for blood and clotting products (in each category per 100 patients). Per case costs rose from DM 7970 to 11,489, per day costs from DM 1943 to 2831. 90% of cost increases were due to new strategies in the treatment of patients with myocardial infractions and those with severe clotting disorders and a rise in personnel costs. CONCLUSION: The costs of a stay in the ICU has greatly increased over the last 5 years, the main causes being a change to new forms of treatment, especially in patients with myocardial infarction and those with haemophilia.

Adult↗
PubMed1998

Fenofibrate improves microcirculation in patients with hyperlipidemia.

In order to investigate the effect of fenofibrate on microcirculation, 16 patients (5 female, 11 male, age 58 +/- 8 years) were studied with the aid of nailfold capillaroscopy before and after treatment with 200 mg fenofibrate per day over six weeks. Fenofibrate resulted in a significant decrease in triglycerides, total and LDL-cholesterol and apolipoprotein B and an increase in apolipoprotein A. As a parameter of an improved microcirculation the time to peak capillary blood cell velocity during postreactive hyperemia (occlusion of the lower arm for 2 minutes, 200 mmHg) decreased markedly from 45 +/- 5 to 16 +/- 3 s, p < 0.0001). Fibrinogen levels were significantly decreased (p < 0.04) in contrast to other parameters with a possible impact on microvascular perfusion (hemoglobin, hematocrit, mean platelet volume, total protein) and to blood pressure and heart rate. These findings suggest that fenofibrate treatment improves microcirculation in patients with hyperlipidemia. This beneficial effect of fenofibrate may arise from two leading mechanisms. One of these might be the decrease in fibrinogen levels reducing plasma viscosity, the other mechanism might be an indirect effect on functional abnormalities of the vascular endothelium arising from hyperlipdidemia. By lowering plasma lipids fenofibrate is likely to restore the impaired formation or efficacy of the endothelium derived relaxing factor (nitric oxide, NO).

Adult↗