716 research outputs found
Lipoprotein metabolism in hypothyroidism : the contribution of growth hormone
Current data suggest a role for GH in the regulation of lipoprotein
metabolism. In hypothyroidism not only the secretion of thyroid hormone, but
also of GH is decreased. Generally the effects on plasma lipids seen in
hypothyroid individuals are considered to be a consequence of decreased
thyroid hormone levels. More then twenty years ago evidence was found that
treatment of hypothyroid rats with GH in supraphysiologic doses affects
plasma lipid concentrations, but whether a lack of GH (activity) is involved in
the pathophysiology of lipid metabolism in hypothyroidism can not be
answered from the present literature. The first aim was to investigate whether
the changes occurring in lipid metabolism during hypothyroidism, merely
result from a lack of thyroid hormone or are also attributable to a deficiency
in GH-activity. In hypothyroid women the relationship between GH-activity
(lGF-1) and plasma lipoproteins was evaluated (Chapter 2). The effects of a
physiological dose of GH on lipoprotein concentrations during the
hypothyroid status were studied in hypothyroid and hypophysectomized rats,
as reported in Chapter 3. Furthermore, the effects on IGF-I and lipoproteins
of substitution of hypothyroid rats with varying doses of thyroid hormone
were studied (Chapter 4).
The second aim was to investigate the mechanism by which GH can affect lipid
metabolism, especially during hypothyroidism. The major cause of hypercholesterolemia
in hypothyroidism is a decreased LDL catabolism in the liver.
Hypothyroid rats were treated with GH and the effects of the hypothyroid
status and GH treatment on liver cell LDL-receptor mRNA, LDL receptor
expression and HMG-CoA reductase was studied, as described in Chapter 5.
In Chapter 6 the effects of IGF-1, GH and T3 on the expression and function
of the LDL-receptor in a human hepatoma derived cell line (HepG2) are
described
Recognition of genetic predisposition in pediatric cancer patients: An easy-to-use selection tool
Genetic predisposition for childhood cancer is under diagnosed. Identifying these patients may lead to therapy adjustments in case of syndrome-related increased toxicity or resistant disease and syndrome-specific screening programs may lead to early detection of a further independent malignancy. Cancer surveillance might also be warranted for affected relatives and detection of a genetic mutation can allow for reproductive counseling.Here we present an easy-to-use selection tool, based on a systematic review of pediatric cancer predisposing syndromes, to identify patients who may benefit from genetic counseling. The selection tool involves five questions concerning family history, the type of malignancy, multiple primary malignancies, specific features and excessive toxicity, which results in the selection of those patients that may benefit from referral to a clinical geneticist
Boosting care and knowledge about hereditary cancer: European Reference Network on Genetic Tumour Risk Syndromes.
Approximately 27-36 million patients in Europe have one of the ~ 5.000-8.000 known rare diseases. These patients often do not receive the care they need or they have a substantial delay from diagnosis to treatment. In March 2017, twenty-four European Reference Networks (ERNs) were launched with the aim to improve the care for these patients through cross border healthcare, in a way that the medical knowledge and expertise travels across the borders, rather than the patients. It is expected that through the ERNs, European patients with a rare disease get access to expert care more often and more quickly, and that research and guideline development will be accelerated resulting in improved diagnostics and therapies. The ERN on Genetic Tumour Risk Syndromes (ERN GENTURIS) aims to improve the identification, genetic diagnostics, prevention of cancer, and treatment of European patients with a genetic predisposition for cancer. The ERN GENTURIS focuses on syndromes such as hereditary breast cancer, hereditary colorectal cancer and polyposis, neurofibromatosis and more rare syndromes e.g. PTEN Hamartoma Tumour Syndrome, Li Fraumeni Syndrome and hereditary diffuse gastric cancer
Significance of various parameters derived from biological variability of lipoprotein(a), homocysteine, cysteine, and total antioxidant status
Analytical and biological components of variability and various derived
indices have been determined for lipoprotein(a) [Lp(a)], homocysteine
(Hcy), cysteine (Cys), and total antioxidant status (TAOS) in ostensibly
healthy adult Caucasians and in stable outpatients with an increased serum
Lp(a). In healthy Caucasians, average intraindividual biological CVs (CVb)
were 20.0% for Lp(a), 9.4% for Hcy, 5.9% for Cys, and 2.8% for TAOS, CVbs
being similar in men and women. In the outpatient group, CVbs were
comparable for Hcy, Cys, and TAOS, but significantly lower for Lp(a) (7.5%
vs 20.0%; P <0.0001). Moreover, a significant inverse relation between
both biological and analytical CVs (CVa) and serum Lp(a) concentrations
was demonstrated. We conclude that average CVa and CVb values, and hence
average derived indices, are adequate for Hcy, Cys, and TAOS, whereas
individual values should be used for Lp(a)
Systematic coarse-graining of the dynamics of entangled polymer melts: the road from chemistry to rheology
For optimal processing and design of entangled polymeric materials it is
important to establish a rigorous link between the detailed molecular
composition of the polymer and the viscoelastic properties of the macroscopic
melt. We review current and past computer simulation techniques and critically
assess their ability to provide such a link between chemistry and rheology. We
distinguish between two classes of coarse-graining levels, which we term
coarse-grained molecular dynamics (CGMD) and coarse-grained stochastic dynamics
(CGSD). In CGMD the coarse-grained beads are still relatively hard, thus
automatically preventing bond crossing. This also implies an upper limit on the
number of atoms that can be lumped together and therefore on the longest chain
lengths that can be studied. To reach a higher degree of coarse-graining, in
CGSD many more atoms are lumped together, leading to relatively soft beads. In
that case friction and stochastic forces dominate the interactions, and actions
must be undertaken to prevent bond crossing. We also review alternative methods
that make use of the tube model of polymer dynamics, by obtaining the
entanglement characteristics through a primitive path analysis and by
simulation of a primitive chain network. We finally review super-coarse-grained
methods in which an entire polymer is represented by a single particle, and
comment on ways to include memory effects and transient forces.Comment: Topical review, 31 pages, 10 figure
Growth hormone normalizes low-density lipoprotein receptor gene expression in hypothyroid rats
The effect of tibolone on the lipoprotein profile of postmenopausal women with type III hyperlipoproteinemia
OBJECTIVE: To investigate the short-term effect of treatment with tibolone on plasma lipid and lipoprotein levels in postmenopausal women with type III hyperlipoproteinemia (HLP).DESIGN AND INTERVENTION: Patients were randomized to receive, in a double-blind cross-over fashion, a fixed dose of tibolone, 2.5 mg once daily or placebo for 8 weeks. The two treatment periods were separated by a wash-out period of 6 weeks. At each visit body weight and blood pressure were determined. Before and after each treatment period, fasting venous blood samples were obtained from the patients for biochemical measurements.SETTING: The Leiden University Medical Center.SUBJECTS: Postmenopausal women with type III HLP (aged ≤ 65 years) were recruited from the Lipid Clinics of the Leiden University Medical Center, the Amsterdam Medical Center, the Utrecht Medical Center and the University Hospital Rotterdam. Five out of 25 women with type III HLP were eligible to be included in the study. Four of the five included patients completed the study according to the protocol. One patient was excluded from blinded therapy because total cholesterol levels increased above 20 mmol L-1.MAIN OUTCOME MEASURES: A significant reduction of plasma triglyceride, total cholesterol, VLDL cholesterol and VLDL triglyceride levels.RESULTS: Plasma triglyceride and total cholesterol levels decreased from 6.82 +/- 3.58 to 2.45 +/- 1.36 mmol L-1 and from 13.53 +/- 3.64 to 6.61 +/- 2.03 mmol L-1, respectively (both P < 0.05). The body mass index remained unchanged. The glycated haemoglobin percentage decreased significantly from 5.8 to 5.3%. Treatment with tibolone resulted in a profound reduction in plasma apolipoprotein E, VLDL cholesterol and VLDL triglyceride levels (mean reductions of 66, 77 and 70%, respectively, P < 0.05).CONCLUSIONS: Tibolone is a valuable adjuvant to current therapy in postmenopausal women with type III HLP.</p
Dissipative Particle Dynamics with Energy Conservation
The stochastic differential equations for a model of dissipative particle
dynamics with both total energy and total momentum conservation in the
particle-particle interactions are presented. The corresponding Fokker-Planck
equation for the evolution of the probability distribution for the system is
deduced together with the corresponding fluctuation-dissipation theorems
ensuring that the ab initio chosen equilibrium probability distribution for the
relevant variables is a stationary solution. When energy conservation is
included, the system can sustain temperature gradients and heat flow can be
modeled.Comment: 7 pages, submitted to Europhys. Let
The effect of tibolone on the lipoprotein profile of postmenopausal women with type III hyperlipoproteinemia
OBJECTIVE: To investigate the short-term effect of treatment with tibolone on plasma lipid and lipoprotein levels in postmenopausal women with type III hyperlipoproteinemia (HLP).DESIGN AND INTERVENTION: Patients were randomized to receive, in a double-blind cross-over fashion, a fixed dose of tibolone, 2.5 mg once daily or placebo for 8 weeks. The two treatment periods were separated by a wash-out period of 6 weeks. At each visit body weight and blood pressure were determined. Before and after each treatment period, fasting venous blood samples were obtained from the patients for biochemical measurements.SETTING: The Leiden University Medical Center.SUBJECTS: Postmenopausal women with type III HLP (aged ≤ 65 years) were recruited from the Lipid Clinics of the Leiden University Medical Center, the Amsterdam Medical Center, the Utrecht Medical Center and the University Hospital Rotterdam. Five out of 25 women with type III HLP were eligible to be included in the study. Four of the five included patients completed the study according to the protocol. One patient was excluded from blinded therapy because total cholesterol levels increased above 20 mmol L-1.MAIN OUTCOME MEASURES: A significant reduction of plasma triglyceride, total cholesterol, VLDL cholesterol and VLDL triglyceride levels.RESULTS: Plasma triglyceride and total cholesterol levels decreased from 6.82 +/- 3.58 to 2.45 +/- 1.36 mmol L-1 and from 13.53 +/- 3.64 to 6.61 +/- 2.03 mmol L-1, respectively (both P < 0.05). The body mass index remained unchanged. The glycated haemoglobin percentage decreased significantly from 5.8 to 5.3%. Treatment with tibolone resulted in a profound reduction in plasma apolipoprotein E, VLDL cholesterol and VLDL triglyceride levels (mean reductions of 66, 77 and 70%, respectively, P < 0.05).CONCLUSIONS: Tibolone is a valuable adjuvant to current therapy in postmenopausal women with type III HLP.</p
Particle-Based Mesoscale Hydrodynamic Techniques
Dissipative particle dynamics (DPD) and multi-particle collision (MPC)
dynamics are powerful tools to study mesoscale hydrodynamic phenomena
accompanied by thermal fluctuations. To understand the advantages of these
types of mesoscale simulation techniques in more detail, we propose new two
methods, which are intermediate between DPD and MPC -- DPD with a multibody
thermostat (DPD-MT), and MPC-Langevin dynamics (MPC-LD). The key features are
applying a Langevin thermostat to the relative velocities of pairs of particles
or multi-particle collisions, and whether or not to employ collision cells. The
viscosity of MPC-LD is derived analytically, in very good agreement with the
results of numerical simulations.Comment: 7 pages, 2 figures, 1 tabl
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