Altered insula response to taste stimuli in individuals recovered from restricting-type anorexia nervosa.

Anorexia nervosa (AN) is an illness characterized by aversion to ingestion of normally palatable foods. We examined whether there is a primary disturbance of taste processing and experience of pleasure using a sucrose/water task in conjunction with functional magnetic resonance imaging (fMRI). To avoid confounding effects of illness, 16 women recovered from restricting-type AN were compared to 16 control women (CW). We used a region of interest-based fMRI approach to test the idea that individuals with AN have differential neural activation in primary and secondary taste cortical regions after sucrose and water administration. Compared to CW, individuals recovered from AN showed a significantly lower neural activation of the insula, including the primary cortical taste region, and ventral and dorsal striatum to both sucrose and water. In addition, insular neural activity correlated with pleasantness ratings for sucrose in CW, but not in AN subjects. Altered taste processing may occur in AN, based on differences in activity in insular-striatal circuits. These data provide the first evidence that individuals with AN process taste stimuli differently than controls, based on differences in neural activation patterns.     

Emil Alvin Pfitzer.

We deeply regret that toxicology has lost a scientist dedicatedto elevating the standards of science in our profession. DrEmil A. Pfitzer, Past President of the Society of Toxicology,passed away on 20 July 2007 at his home in New River, AZ, aftera long illness with a chronic lung disease. Emil was a veryactive participant in and strong advocate for our Society, andas President, he presided over the Society during its 25th anniversaryyear (1985–1986) and was a member of the 40th AnniversaryTask Force.     

Validated HPTLC methods for the determination of salicin in Salix sp. and of harpagoside in Harpogophytum procumbens

Preparations of Harpagophytum procumbens and of Salix species are successfully used for the treatment of degenerative rheumatism and painful arthrosis. For the quality control of both drugs, rapid methods of quantification are desirable. Here we report the development of two HPTLC methods enabling the determination of harpagoside in Harpagophyti radix and of salicin in Salicis cortex. We focused on a standardized methodology and thorough validation including two laboratories. The methods allow the analyses of up to 16 samples in parallel demonstrating the proposed methods as very rapid and cost efficient.     

Amine-reactive pyridylhydrazone-based PEG reagents for pH-reversible PEI polyplex shielding

PEGylation which is reversed after the therapeutic agent reaches the target cell presents an attractive feature for drug, protein or nucleic acid delivery. Amine-reactive, endosomal pH cleavable polyethylene glycol aldehyde-carboxypyridylhydrazone, N-hydroxysuccinimide esters (PEG-HZN-NHS) were synthesized and applied for bioreversible surface shielding of DNA polyplexes. Monofunctional mPEG-HZN-NHS was synthesized by reacting succinimidyl hydraziniumnicotinate with mPEG-butyraldehyde (20 kDa). Bifunctional OPSS-PEG-HZN-NHS was synthesized analogously via a omega-2-pyridyldithio-PEG (10 kDa) propionaldehyde intermediate. Polyethylenimine (PEI) polyplexes were reacted with the pH-sensitive (mPEG-HZN-NHS) or the corresponding stable (mPEG-NHS) reagent. Both types of polyplexes remained shielded at pH 7.4 as demonstrated by particle size and zeta potential measurements after 4h of incubation at 37 degrees C. Polyplex deshielding at endosomal pH 5 was observed only with the mPEG-HZN-NHS shielded particles. This was confirmed by fluorescence correlation spectroscopy using the analogous Alexa-488 fluorescently labeled bifunctional PEGylation reagents. Luciferase gene transfections with epidermal growth factor (EGF) containing polyplexes using EGF-receptor overexpressing hepatoma HUH7 cells showed an up to 16-fold enhancement in gene expression with the reversibly shielded polyplexes as compared to stably shielded polyplexes. Consistently, the reversibly shielded polyplexes mediated also an enhanced tumor specific in vivo transgene expression after intravenous administration in a subcutaneous HUH7 tumor model in SCID mice.     

Response rates for providing a blood specimen for HIV testing in a population-based survey of young adults in Zimbabwe

Background  

To determine differences among persons who provided blood specimens for HIV testing compared with those who did not among those interviewed for the population-based Zimbabwe Young Adult Survey (YAS).     

Möglichkeiten der systemischen Therapie in metastasierten Stadien des Magenkarzinoms

Recently published results from several phase III trials have significantly increased the therapeutic options in the treatment of metastatic stomach cancer: The continuous infusion of 5-FU can be replaced by capecitabine, and cisplatin can be replaced by oxaliplatin in both cases without impairing efficacy. According to the results of the REAL-2 trial, the combination of epirubicin, oxaliplatin and capecitabine (EOX) achieved superior results for overall survival compared to epirubicin, cisplatin und 5-FU (ECF) (9.9 versus 11.2 months, HR 0.8). However, the question of whether an optimal first line therapy should include a triplet regimen or the sequential use of doublets is a matter of debate. The combination of irinotecan and 5-FU may serve as an alternative to platinum-containing regimens in patients where, due to co-morbidity, a platinum-free regimen is preferred. The 3-drug combination of docetaxel, 5-FU and cisplatin (DCF) demonstrated a statistically significant survival benefit compared to the 2-drug combination of 5-FU and cisplatin in a randomized phase III trial, although results were limited by a particularly significant hematological toxicity, which prevents its application in the large group of elderly patients with gastric cancer. Direct randomized phase III comparisons of DCF with other 3-drug combinations, such as EOX are still missing.     

Brustkrebs-Früherkennung in Deutschland

The guideline Early Detection of Breast Cancer in Germany aims to assist physicians, healthy women, and patients in decision making with recommendations based on evidence and formal consensus regarding the diagnostic chain of health care for early detection of breast cancer. This guideline updates the previous version of 2003. The guideline is a precondition to establishing an effective and efficient national early breast cancer detection program in accordance with the requirements of the European Council and the World Health Organization for cancer control programs. The core imaging technique of an early detection program is mammography, whether used for screening or diagnosis. Breast health care outcomes can be improved by embedding this imaging technology in a quality-assured diagnostic chain. The guideline comprises areas of present scientific and medical knowledge, based on evidence and consensus and covering all multidisciplinary aspects of the diagnostic chain, including clinical history taking, risk consultation and communication, breast health awareness, physical breast examination, breast imaging, interventional guided biopsy, excision biopsy, and breast pathology. The guideline provides formal measures as quality indicators to ensure resource availability, process quality, and outcome of the diagnostic chain. Early detection of breast cancer is presently the most promising chance for optimizing diagnosis and treatment of breast cancer in order to reduce mortality and morbidity while improving survivors’ quality of life. The aim is to detect breast cancer as a noninvasive disease or an invasive disease at an early stage, with a 5-year survival rate of more than 90% with adequate treatment. Detecting more noninvasive breast cancer might even help reduce the incidence. Within the scope of secondary prevention, early detection offers the chance of cure at an early disease stage by less intensive treatment.     

Diffusive resistance to O2 transport in muscle

Although it has been generally well-accepted since the work of August Krogh at the start of the 20th century that O2 travels between muscle microvascular red cells and muscle mitochondria by diffusion, the importance of this process to maximal O2 flux remains in question. This review presents data that suggest maximal rates of diffusion of O2 in muscle are limited by both the amount of capillary structure and the haemoglobin concentration in the blood. On the other hand, diffusional conductance appears unrelated to muscle fibre size and thus to distance. Functional data further suggest that the limited rate of diffusion acts to constrain O2 unloading from muscle capillaries and thus also maximal Vo2, at least in the trained state. In fact, the calculated sensitivity of VO2max to muscle diffusional conductance is about as great as that for muscle blood flow. While additional impairment of O2 unloading from perfusion/metabolism heterogeneity cannot yet be excluded (for lack of methodology), it seems evident that the process of O2 transport between the muscle microvasculature and the mitochondria is subject to significant limits, even in health, that have substantial effects on maximal Vo2.     

Randomized trial of sertraline in patients with unexplained chest pain of noncardiac origin

BACKGROUND: Between 10% and 30% of patients with symptoms similar to angina and sufficient to justify cardiac catheterization are found to have normal coronary angiograms. Treatment of patients with chest pain with no apparent cardiac cause is a major clinical problem. Our hypothesis was that sertraline would reduce the severity of pain in patients with chest pain of noncardiac origin. METHODS AND RESULTS: This was a single-site, double-blind, placebo-controlled study of the efficacy, tolerability, and safety of sertraline in the treatment of noncardiac chest pain in outpatients. Thirty patients were enrolled in the study. After 1 week of single-blind placebo washout, patients were randomly assigned in a double-blind fashion either to drug or placebo. The Beck Depression Inventory was administered at baseline and at completion of study. Daily pain diaries (visual analogue scale, rating pain on a scale of 1 to 10) were selfadministered and evaluated at baseline and at follow-up visits. Statistical measures were performed with an intention-to-treat approach. Patients who received sertraline over the course of the study showed a statistically significant reduction in pain compared with those who were receiving placebo. CONCLUSIONS: The use of sertraline in patients with noncardiac chest pain produced clinically significant reduction of daily pain. These results suggest the need for further studies of the efficacy and tolerability of sertraline and other selective serotonin reuptake inhibitors in the long-term management of noncardiac chest pain.