The effect of submicron fat droplets in a drink on satiety,food intake,and cholecystokinin in healthy volunteers

Purpose

Small fat droplets infused into the gut reduce food intake and hunger more than bigger ones, at levels as low as 6 g, and these effects are hypothesized to occur via satiety hormones such as cholecystokinin. It is, however, unknown whether the effect of droplet size would persist after oral consumption. It is also unknown whether an even smaller droplet size can affect hunger and food intake and at what minimum amount of fat. Therefore, the aim of the study was to test the effect of very fine fat droplets on satiety and food intake in two different quantities.

Methods

In a balanced-order 4-way crossover design, 24 volunteers consumed a fat-free meal replacement drink with either 5 or 9 g oil (rapeseed) and either 3 or 0.1 μm droplet size. Appetite scores and plasma cholecystokinin levels (in n = 12 subset) were measured for 180 min, when food intake was assessed during an ad libitum meal. Data were analyzed by ANCOVA, followed by Dunnett’s test and paired t test. The behavior of the emulsions was also characterized in a simulated gastrointestinal model.

Results

Despite faster in vitro lipolysis of the smallest droplets, neither droplet size nor fat amount affected satiety or food intake. From t = 45–150 min, cholecystokinin response was 50 % higher (P < 0.05) after the 0.1 versus 3 μm, but only with 9 g fat.

Conclusion

When this particular fat at these amounts is delivered in a meal replacement drink, droplet size does not influence appetite or food intake. This effect is independent of the amount of fat or plasma cholecystokinin changes.     

Peptide-mediated shape- and size-tunable synthesis of gold nanostructures

While several biological processes have been shown to be useful for the production of well-designed, inorganic nanostructures, the mechanism(s) controlling the size and shape of nano and micron size particles remains elusive. Here we report on the controlled size- and shape-specific production of gold nanostructures under ambient reaction conditions using a dodecapeptide, Midas-2, originally selected from a phage-displayed combinatorial peptide library. Single amino acid changes in Midas-2 greatly influence the size (a few nanometers to ～100 μm) and shape (nanoparticles, nanoribbons, nanowires and nanoplatelets) of the gold nanostructures produced, and these are controllable by adjusting the solution pH and gold ion concentration. The ability to control the shape and size of the gold nanostructures by changing the peptide structure and reaction conditions will lead to many potential applications, including nanoelectronics, sensors and optoelectronics, because of their unique size- and shape-dependent optical and electrical properties.     

Immobilization of aminothiols on poly(oxyalkylene phosphates). Formation of poly(oxyethylene phosphates)/cysteamine complexes and their radioprotective efficiency

The necessity to apply near-toxic amounts of radioprotective drugs to achieve adequate protection during radiation treatments represents a major problem in human medicine. One of the promising strategies to suppress the toxicity of these drugs involves their incorporation into biocompatible polymers. In this study cysteamine (Cy) was attached to poly(oxyethylene phosphate), POEP, via an ionic bond. Radioprotection of E. coli B cells by this substance and its acute toxicity on male C57 BL mice were measured. The toxicity of Cy immobilized within the poly(oxyethylene phosphate) was significantly lower in comparison to pure Cy while its radioprotective efficiency remained high at half the maximum tolerable dose. The high radioprotective efficiency of the Cy/POEP complexes was further confirmed on mice at different polymer molecular weight characteristics, drug immobilization degrees, application times, and doses. It was found that POEP with molecular weight 4700 Da and containing 24% repeating units with attached Cy has the highest protection potential combined with a depot effect.     

Comparative experimental study of 10% and 15% medical gelatin in the anterior chamber and in the posterior eye segment as a viscosubstance in the viscosurgery

This article discusses the possibility of application of 15% medical gelatin solution compared to 10% medical gelatin solution in the anterior chamber and in the posterior eye segment as a viscosubstance in the viscosurgery. The experimental investigations were performed on 24 Chinchilla rabbits, divided in two groups consisting of 12 each. 0.5 ml of 10% and 15% of medical gelatin were injected in the anterior chamber and 2 ml of 10% and 15% medical gelatin were injected in the vitreous body of the tested eyes. 2% methyl cellulose and 0.89% Sodium Chloride were injected in the vitreous body of the control eyes. Clinical, biomicroscopical, ophthalmoscopical, tonometrical, histological and electron-microscopical examinations were performed. It was established that when the eyes were injected with 10% and 15% medical gelatin, as well as with 0.89% Sodium Chloride, the intraocular pressure was not increased but when the eyes were injected with methyl cellulose the intraocular pressure was increased. We also found that 15% of medical gelatin has longer effect than 10% medical gelatin. Toxoallergic and inflammatory changes were not observed in the eyes injected with 10% and 15% medical gelatin. In the same eyes, histologically and by electron microscopy, were not found any changes in the layers of the cornea and retina. These substances could be used as viscosubstances and as instruments in surgical interventions of the anterior eye segment and in the posterior eye segment (vitrectomy).     

Three-dimensional endoluminal ultrasound

PURPOSE: This study was designed to evaluate the application of three-dimensional (3D) transrectal ultrasound (TRUS) in diagnostics, staging, and treatment planning of rectal cancer. METHOD: Transversal images, generated during conventional TRUS examination, are recorded by means of a specially designed computer-based system to obtain a 3D array of slices, covering the whole region of interest. Different structures (normal or pathologically affected) are segmented, isolated, and rendered using the tools of the system to produce a realistic spatial view of investigated organs. Dynamic movies are also generated and replayed for better realization of spatial interrelations of studied objects. RESULTS: Nineteen patients (18 with rectal cancer and 1 who was healthy) have been examined. In 15 patients, full 3D TRUS reconstruction was performed. Results are illustrated with several examples from the studied group. CONCLUSION: We consider 3D TRUS a useful add-on to conventional TRUS. It may significantly improve understanding of the interrelation between normal and pathologic structures and help to exact preoperative staging and treatment planning of rectal carcinoma patients.     

Lipid-modifying and pleiotropic effects of gemfibrozil, simvastatin and pravastatin in patients with dyslipidemia

AIM: To assess the lipid-modifying and pleiotropic effects of drugs of the statin group (simvastatin and pravastatin) and the fibrate group (gemfibrozil) in dyslipidemia patients. PATIENTS AND METHODS: Fifty eight patients with primary dysli pidemia were recruited for a 12-week treatment. Forty two patients were allocated to be treated with statins (20 mg): 24 with simvastatin and 18 with pravastatin. Sixteen patients received gemfibrozil in a dose of 900 mg daily. Using enzyme, colorimetric, turbidimetric, immunoenzyme and chromogenic substrate methods, we studied the following laboratory parameters: 1) lipid parameters - total cholesterol, LDL and HDL cholesterol, triglycerides, apoli poprotein A-I, apoli poprotein B, anticardioli pin antibodies and lipid indices; 2) hemostasis, fibrinolysis and blood rheology parameters - platelet count, ADP-induced platelet aggregation, fibrinogen, platelet factor 4,antithrombin III activity, alpha2-anti plasmin concentrations, alpha2-macroglobulin, alpha1-antitripsin, plasma viscosity and hematocrit. RESULTS: Gemfibrozil elevated significantly apolipoprotein A-I, but decreased the total cholesterol, LDL cholesterol, triglycerides, the lipid indices, the ADP-induced platelet aggregation, plasminogen, alpha2-antiplasmin and hematocrit. Simvastatin treatment of patients reduced the total cholesterol, LDL cholesterol, triglycerides, two of the lipid indices, plasma viscosity and hematocrit. Pravastatin produced the same changes in the lipid parameters, but decreased apolipoprotein A-I. Plasminogen, alpha2-antiplasmin and rheological parameters decreased while antithrombin III increased. CONCLUSION: The lipid-modifying treatment with statins and fibrates, in addition to the effect on lipid metabolism, exerts a pleiotropic effect on hemostasis, fibrinolysis and blood rheology parameters.     

Reverse mapping of normal tissue complication probabilities onto dose volume histogram space: the problem of randomness of the dose volume histogram sampling

A very important issue in contemporary inverse treatment radiotherapy planning is the specification of proper dose-volume constraints limiting the treatment planning algorithm from delivering high doses to the normal tissue surrounding the tumor. Recently we have proposed a method called reverse mapping of normal tissue complication probabilities (NTCP) onto dose-volume histogram (DVH) space, which allows the calculation of appropriate biologically based dose-volume constraints to be used in the inverse treatment planning. The method of reverse mapping requires random sampling from the functional space of all monotonically decreasing functions in the unit square. We develop, in this paper, a random function generator for the purpose of the reverse mapping. Since the proposed generator is based on the theory of random walk, it is therefore designated in this work, as a random walk DVH generator. It is theoretically determined that the distribution of the number of monotonically decreasing functions passing through a point in the dose volume histogram space follows the hypergeometric distribution. The proposed random walk DVH generator thus simulates, in a random fashion, trajectories of monotonically decreasing functions (finite series) that are situated in the unit square [0, 1] X [1,0] using the hypergeometric distribution. The DVH generator is an important tool in the study of reverse NTCP mapping for the calculation of biologically based dose-volume constraints for inverse treatment planning.     

Non-interventional study comparing treatment satisfaction in patients treated with antihistamines

BACKGROUND AND OBJECTIVE: Allergic rhinitis and urticaria are common allergic disorders that may affect approximately 15% of people at some time in their lives. Antihistamines are the most widely used therapeutic interventions for these disorders but the newer generation agents have differing pharmacokinetic characteristics that may result in different patient satisfaction and preferences. The objective of this study was to investigate patients' and physicians' satisfaction with their current antihistamine treatment for allergic disease. METHODS: In an observational study, physicians in nine European countries completed questionnaires evaluating 7,274 patients treated with an oral antihistamine. The satisfaction of patients and physicians with the efficacy and tolerability of treatment was rated on a visual analogue scale. In addition, the proportion of patients satisfied with treatment (overall satisfaction) and willing to continue treatment with the same antihistamine were assessed. Safety and tolerability data were also gathered. RESULTS: The results of this study indicate that modern antihistamines are generally considered effective and well tolerated by patients. In general, levocetirizine scored significantly higher in terms of perception of efficacy, tolerability and overall satisfaction. In terms of tolerability, three-quarters of patients were 'very satisfied' and a further fifth were moderately satisfied with levocetirizine and almost all (95%) were happy to continue treatment. Overall, the most commonly reported adverse event in this study was somnolence, a well known effect of antihistamines. The rate of somnolence in the levocetirizine group (3.8%) was similar to that for fexofenadine (both doses) and desloratadine, two products which are considered to be nonsedating antihistamines, and significantly less than half the rate for cetirizine. CONCLUSION: Levocetirizine is considered an effective and well tolerated option for treating allergic disease by patients and physicians alike, particularly when the best available effectiveness and tolerability are required.     

Differentiation of core gene products of the hepatitis B virus in infected liver tissue using monoclonal antibodies

Hepatitis B virus (HBV) core gene translational products were localised previously in the cytoplasm and/or in the nuclei of infected cells. We investigated in naturally infected human hepatocytes whether this variation in the subcellular expression is due to differences in the presence of assembled core particles and other core gene derived proteins, the expression of HBeAg and the processing of liver tissue. By immunostaining of liver specimens infected with HBeAg-positive and HBeAg-minus variants of HBV, using monoclonal antibodies specific for assembled core particles and for various epitopes on denatured core protein, it was shown that virtually all immunoreactive core gene products are assembled into core particles. The latter are present both in the nuclei and in the cytoplasm of hepatocytes, independent of the infecting virus strain. A marked reduction or absence of immunoreactivity, observed with some monoclonal antibodies, was shown to result from nucleotide sequence variations within or close to the corresponding epitope. These results demonstrate that immunoreactive products, derived from the HBV core gene, in the nuclei and cytoplasm of human hepatocytes represent assembled core particles and that monoclonal antibodies with known recognition sites can reveal region-specific core gene variation of the infecting HBV population. J. Med. Virol. 53:127–138, 1997. © 1997 Wiley-Liss, Inc.