Alterations in Thyroid Hormones and Thyrotropin (TSH) in Morbidly Obese Patients before and after Vertical Gastroplasty

Background: Published results of studies of thyroid function in obesity and after weight loss have differed. Methods: The circulating concentrations of thyroid hormones and TSH were studied in 30 consecutive, euthyroid morbidly obese patients before and after weight loss from vertical gastroplasty, with the aim to determine the relation between body weight loss and pituitarythyroid axis function. Serum TSH, free T3 (FT3) and free T4 (FT4) were measured before operation and repeated 6 and 18 months postoperatively. Results: A significant increase, but within normal levels, in FT3 value at 6 and, mainly, at 18 months after gastroplasty was observed (p = 0.002). The FT4 value was slightly increased at the same time and serum TSH was found to be significantly decreased (p = 0.03 and p = 0.01 respectively). The relative increase in FT4 was negatively correlated with excess body weight and Body Mass Index reduction. This correlation was only moderate with values ranging from r = 0.34 to r = 0.47. Conclusions: Although there were statistically significant differences in thyroid function tests before and after loss of weight, these were not biologically significant. The hypophyseal/thyroid axis remains always active and contributes to body weight homeostasis and its regulation.     

Prediction of food effects on the absorption of celecoxib based on biorelevant dissolution testing coupled with physiologically based pharmacokinetic modeling

Since the rate-determining step to the intestinal absorption of poorly soluble drugs is the dissolution in the gastrointestinal (GI) tract, postprandial changes in GI physiology, in addition to any specific interactions between drug and food, are expected to affect the pharmacokinetics and bioavailability of such drugs. In this study, in vitro dissolution testing using biorelevant media coupled with in silico physiologically based pharmacokinetic (PBPK) modeling was applied to the prediction of food effects on the absorption of a poorly soluble drug, celecoxib, from 200 mg capsules. A PBPK model was developed based on STELLA^® software using dissolution kinetics, solubility, standard GI parameters and post-absorptive disposition parameters. Solubility, dissolution profiles and initial dissolution rate from celecoxib 200 mg capsules were measured in biorelevant and compendial media. Standard GI parameters (gastric emptying rate and fluid volume) were varied according to the dosing conditions. Disposition parameters were estimated by fitting compartmental models to the oral PK data, since intravenous data are not available for celecoxib. Predictions of food effects and average plasma profiles were evaluated using the AUC and C_max and the difference factor (f₁). An approximately 7-fold difference in the maximum percentage dissolved was observed in in vitro dissolution tests designed to represent the fed and fasted states. By contrast, the food effect estimated by simulating the plasma profiles with the PBPK model predicted only a slight delay in the peak plasma level (1 h), and modest increases in the C_max and AUC of 1.9-fold and 1.3-fold in the fed state, respectively. The PBPK approach, combining in silico simulation coupled with biorelevant dissolution test results, thus corresponds much better to the food effect observed for celecoxib in vivo. Additionally, point estimates of AUC and C_max as well as f₁ calculations demonstrated clear advantages of using results in biorelevant rather than compendial media in the PBPK model.     

Epikutane Testung mit Natriumlaurylsulfat Nutzen und Grenzen in Forschung und Praxis

Patch testing with sodium lauryl sulfate (SLS) has been frequently used in the last decade. The evaluation of the SLS test can be performed visually, or with bioengineering methods. Among these, the transepidermal water loss is the most appropriate method, but measurements by laser Doppler flowmetry, colorimetry or corneometry may yield additional relevant data. Various factors such as age, area of testing or climatic conditions may also influence the SLS test, so such factors should be considered when different studies are compared. If correctly used, the SLS test can provide valuable information regarding the skin susceptibility to irritation. An overestimation of the test, just based on objective measurements with bioengineering methods, should be avoided, as the bioengineering data are capable of great precision and reproducibility, but can only define phenomena and not the causal event.     

Liposomal Formulations of Inflammatory Bowel Disease Drugs: Local <Emphasis Type="BoldItalic">versus</Emphasis> Systemic Drug Delivery in a Rat Model

Purpose Based on adherence to intestinal mucosa, intralumenally administered liposomal formulations of 5-aminosalicylate (5-ASA) and 6-mercaptopurine (6-MP) were studied for their potential to enhance local drug delivery to intestinal tissue for the treatment of inflammatory bowel disease.Methods 5-ASA was encapsulated in standard phospholipid liposomes while 6-MP required encapsulation in nonphospholipid liposomes to obtain equivalent drug loading. Encapsulation efficiency was measured by size-exclusion chromatography/high-performance liquid chromatogtaphy (HPLC). Liposomal formulations or solution of the drugs were injected into unligated jejunum to compare pharmacokinetics and into ligated loops of rat ileum and colon to evaluate local delivery. Dextran sulfate and acetic acid induced colitis were used as models of lower intestinal inflammation. Plasma, tissue and luminal drug and metabolite levels were measured by liquid scintillation counting or HPLC.Results Encapsulation efficiency of 6-MP was dependent on lipid content and composition. While liposomal encapsulation significantly reduced systemic absorption of 5-ASA this was not the case for 6-MP. Liposomal adherence to intestinal tissue resulted in increased tissue levels for 5-ASA; however, 6-MP local tissue levels were not improved compared to solution drug.Conclusions Nonphospholipid liposomes optimize encapsulation of 6-MP. While liposomal formulations show potential for local drug delivery to diseased bowel, drug physicochemical properties, absorption, and metabolic profiles dictate tissue-targeting potential. Liposomes reduce systemic availability from paracellular absorption of hydrophilic 5-ASA, but fail to improve local tissue delivery of 6-MP, a molecule absorbed by passive membrane permeation that undergoes extensive first- pass metabolism.     

Skin changes in geriatric nurses prior to training heralding a particular risk of hand dermatitis

Irritant skin changes are a well known problem in nursing services. Especially geriatric nurses often complain of hand dermatitis, most likely induced by frequent washing and hand disinfections. In this cohort study, demographic data and skin changes from 521 nurse trainees were recorded. The data of geriatric nurse trainees (n = 149) were compared to that of other nurse trainees (n = 372), mostly of surgery, internal medicine, pediatric and obstetrics. Geriatric nurse trainees were significantly older and had noticeably severer irritant skin changes at the start of the training. Geriatric nurse trainees were more often undergoing retraining, because they had other jobs before. Interestingly, some nurses performed the retraining because they had problems with hand dermatitis in their previous job. More education concerning the risk of irritant dermatitis in health care occupations is desirable, not only for the starting nurse but also for the employment offices.     

The course of Hymenolepis nana infections in thymus-deficient mice.

The kinetics of infection with Hymenolepis nana was examined in normal thymus-deficient mice. Following inoculation with 5 cyticercoids, the number of adult lumen-dwelling H. nana in congenitally thymus-deficient (nude) mice ultimately was at least 75 times the maximum infection intensity of normal thymus-bearing mice or thymus-reconstituted nude mice. Similar results were obtained following inoculation of H. nana eggs into nude mice; although thymus-bearing mice eliminated their infections, nude mice harbored more than 1,000 adult worms throughout the 7 weeks of the experiments. These data show that in mice, immunity is not generated against H. nana in the absence of thymus function. The data also confirm and establish the requirement of cysticercoid development in the intestinal mucosa for stimulation of a protective immune response against H. nana.