Crossing-over-Theorie oder Reduplikationshypothese?

Ohne ZusammenfassungMit 4 Figuren.     

Influence of acetaminophen and ibuprofen on in vivo patellar tendon adaptations to knee extensor resistance exercise in older adults

Millions of older individuals consume acetaminophen or ibuprofen daily and these same individuals are encouraged to participate in resistance training. Several in vitro studies suggest that cyclooxygenase-inhibiting drugs can alter tendon metabolism and may influence adaptations to resistance training. Thirty-six individuals were randomly assigned to a placebo (67 ± 2 yr old), acetaminophen (64 ± 1 yr old; 4,000 mg/day), or ibuprofen (64 ± 1 yr old; 1,200 mg/day) group in a double-blind manner and completed 12 wk of knee extensor resistance training. Before and after training in vivo patellar tendon properties were assessed with MRI [cross-sectional area (CSA) and signal intensity] and ultrasonography of patellar tendon deformation coupled with force measurements to obtain stiffness, modulus, stress, and strain. Mean patellar tendon CSA was unchanged (P > 0.05) with training in the placebo group, and this response was not influenced with ibuprofen consumption. Mean tendon CSA increased with training in the acetaminophen group (3%, P < 0.05), primarily due to increases in the mid (7%, P < 0.05) and distal (8%, P < 0.05) tendon regions. Correspondingly, tendon signal intensity increased with training in the acetaminophen group at the mid (13%, P < 0.05) and distal (15%, P = 0.07) regions. When normalized to pretraining force levels, patellar tendon deformation and strain decreased 11% (P < 0.05) and stiffness, modulus, and stress were unchanged (P > 0.05) with training in the placebo group. These responses were generally uninfluenced by ibuprofen consumption. In the acetaminophen group, tendon deformation and strain increased 20% (P < 0.05) and stiffness (-17%, P < 0.05) and modulus (-20%, P < 0.05) decreased with training. These data suggest that 3 mo of knee extensor resistance training in older adults induces modest changes in the mechanical properties of the patellar tendon. Over-the-counter doses of acetaminophen, but not ibuprofen, have a strong influence on tendon mechanical and material property adaptations to resistance training. These findings add to a growing body of evidence that acetaminophen has profound effects on peripheral tissues in humans.     

Pericarditis in the course of acute leukemia

Among 140 patients with acute leukemia (AL) diagnosed according to FAB criteria, pericarditis was diagnosed clinically in 5 of them. They were 2 women and 3 men with different types of AL (L2-in one, M2-in one, M3-in one and M4-in two persons). It occurred in one patient at the onset of the disease and was associated with hyperuricemia, in another one--in complete remission, in the third--during partial remission, and in remaining two patients--during induction therapy. In all patients pericarditis was manifested by fever up to 38-40 degrees C, tachycardia and pericardial friction, in 3-heart silhouettes were enlarged. The ECG revealed mainly depression of ST segments. In 1 case only ECG pattern was typical of pericarditis. Clinically the symptoms of right ventricle failure predominated in 3 and of septic shock--in 2 patients. The etiologic factors were: Pseudomonas aeruginosa 2 X, Enterobacter cloacae 1 X, tuberculosis infection 1 X and hyperuricemia and Enterobacter sepsis 1 X. Pericarditis was favourably influenced by treatment with antibiotics, cardiaca and diuretics in 4 patients. One patient died of a sepsis. In no case the patient's death was attributable to pericarditis. The results of postmortem examinations in 79 cases of AL has revealed three additional cases of pericarditis due to tuberculosis infection, Staphylococcus aureus sepsis and aspergillosis.     

Short-term exercise reduces markers of hepatocyte apoptosis in nonalcoholic fatty liver disease

Increased hepatocyte apoptosis is a hallmark of nonalcoholic fatty liver disease (NAFLD) and contributes to the profibrogenic state responsible for the progression to nonalcoholic steatohepatitis (NASH). Strategies aimed at reducing apoptosis may result in better outcomes for individuals with NAFLD. We therefore examined the effect of a short-term exercise program on markers of apoptosis-plasma cytokeratin 18 (CK18) fragments, alanine aminotransferase (ALT), aspartate aminotransferase (AST), soluble Fas (sFas), and sFas ligand (sFasL)-in 13 obese individuals with NAFLD [body mass index 35.2 ± 1.2 kg/m(2), >5% intrahepatic lipid (IHL) assessed by (1)H-MR spectroscopy]. Exercise consisted of treadmill walking for 60 min/day on 7 consecutive days at ～85% of maximal heart rate. Additionally, subjects underwent an oral glucose tolerance test and a maximal oxygen consumption (Vo(2max)) test before and after the exercise intervention. The Matsuda index was used to assess insulin sensitivity. We observed significant decreases in CK18 fragments (558.4 ± 106.8 vs. 323.4 ± 72.5 U/l, P < 0.01) and ALT (30.2 ± 5.1 vs. 24.3 ± 4.8 U/l, P < 0.05), and an increase in whole body fat oxidation (49.3 ± 6.1 vs. 69.4 ± 7.1 mg/min, P < 0.05), while decreases in circulating sFasL approached statistical significance (66.5 ± 6.0 vs. 63.0 ± 5.7 pg/ml, P = 0.06), as did the relationship between percent change in circulating CK18 fragments and ALT (r = 0.55, P = 0.05). We also observed a significant correlation between changes in fat oxidation and circulating sFasL (rho = -0.65, P < 0.05). There was no change in IHL following the intervention (18.2 ± 2.5 vs. 17.5 ± 2.1%, NS). We conclude that short-term exercise reduces a circulatory marker of hepatocyte apoptosis in obese individuals with NAFLD and propose that changes in the proapoptotic environment may be mediated through improved insulin sensitivity and increased oxidative capacity.     

Modulatory role of food, feeding regime and physical exercise on body weight and insulin resistance

Energy intake and expenditure is a highly conserved and well-controlled system with a bias toward energy intake. In times of abundant food supply, individuals tend to overeat and in consequence to increase body weight, sometimes to the point of clinical obesity. Obesity is a disease that is not only characterized by enormous body weight but also by rising morbidity for diabetes type II and cardiovascular complications. To better understand the critical factors contributing to obesity we performed the present study in which the effects of energy expenditure and energy intake were examined with respect to body weight, localization of fat and insulin resistance in normal Wistar rats. It was found that a diet rich in fat and carbohydrates similar to "fast food" (cafeteria diet) has pronounced implication in the development of obesity, leading to significant body weight gain, fat deposition and also insulin resistance. Furthermore, an irregularly presented cafeteria diet (yoyo diet) has similar effects on body weight and fat deposition. However, these rats were not resistant to insulin, but showed an increased insulin secretion in response to glucose. When rats were fed with a specified high fat/carbohydrate diet (10% fat, 56.7% carbohydrate) ad lib or at the beginning of their activity phase they were able to detect the energy content of the food and compensate this by a lower intake. They, however, failed to compensate when food was given in the resting phase and gained more body weight as controls. Exercise, even of short duration, was able to keep rats on lower body weight and reduced fat deposition. Thus, inappropriate food intake with different levels of energy content is able to induce obesity in normal rats with additional metabolic changes that can be also observed in humans.     

Chronobiology of the mammalian response to ionizing radiation. Potential applications in oncology

Ionizing radiation from all sources under appropriate conditions leads to cell death and tissue damage. It is used in cancer treatment under the assumption of a higher radiosensitivity of the fast dividing tumor cells as compared with adjacent host tissues. The radiosensitivities of proliferating host tissues like bone marrow and gastrointestinal lining epithelium are dose limiting. Since these host tissues and many tumors show circadian and other periodicities in their cell proliferation, the timing of radiation treatment according to host and/or tumor rhythms is expected to improve the toxic/therapeutic ratio of the treatment. The experimental data on the chronobiology of radiation exposure show circadian rhythmicity in radiation response after whole body irradiation in mice and rats with highest toxicity in light-dark 12h:12h synchronized animals during their daily activity span. Bone marrow toxicity as well as gastrointestinal epithelial damage show circadian rhythms in part due to radiation damage to the stem cells involved and especially in the intestine also due to damage to the microvasculature. Chronoradiotherapy of malignant tumors seems promising, alone or in combination with response modifiers, provided the host and potential tumor rhythms can be monitored.     

Clinical relevance of about-yearly changes in blood pressure and the environment

Changes identified by inferential statistics from summer to winter of high to low arterial blood pressures (BP) have been quantified as a large predictable about-yearly BP swing. This condition of a large annualBP amplitude (LABPA) raises concern about hypotension as well as hypertension and raises new questions regarding appropriate guidelines for diagnosis and treatment. Recommendations made in the fall on the basis of data collected in the summer may be totally inadequate in dealing with the patient's condition in the winter. In order to avoid such mistakes, it is imperative to implement a systematic surveillance of BP in the light of current chronobiological limits. Patients with a large circannual BP amplitude are particularly suited for a study of the underlying hormonal mechanisms. The longitudinal monitoring of their BP is also amenable to the study of environmental influences from near and far.Dedicated to the memory of Agostino Carandente, MD, who until his death on 26 August 1996 used the resources available to him as manager of a major pharmaceutical company in a nearly fulltime endeavor to foster chronobiology, and published the journalChronobiologia, which for 21 years was a leading medium for the dissemination of chronobiologic research worldwide. Agostino Carandente also inspired his children to follow the trail he helped blaze and contributed his familial, intellectual and financial means to the science of the body's time structure. Agostino's love for Latin prompts the following motto of this paper: Quæcumque vera sunt — tam physicalia, emotionalia, ac intellectualia, quam diagnostica, præventiva, curativaque — cognoscunt ante et supra ceteros chronobiologi et chronobiologæ (whatever truths there are — whether physical, emotional and intellectual, or diagnostic, preventive and curative — before and above all others, chronobiologist understand them).     

Non-isotopic dual parameter competition assay suitable for high-throughput screening of histone deacetylases

Histone deacetylases reside among the most important and novel target classes in oncology. Selective lead structures are intensively developed to improve efficacy and reduce adverse effects. The common assays used so far to identify new lead structures suffer from many false positive hits due to auto-fluorescence of compounds or triggering undesired signal transduction pathways. These drawbacks are eliminated by the dual parameter competition assay reported in this study. The assay involves a new fluorescent inhibitor probe that shows an increase in both, fluorescence anisotropy and fluorescence lifetime upon binding to the enzyme. The assay is well suited for high-throughput screening.     

Turning snails into slugs: induced body plan changes and formation of an internal shell

The archetypal body plan of conchiferan molluscs is characterized by an external calcareous shell, though internalization of shells has evolved independently in a number of molluscan clades, including gastropod families. In gastropods, the developmental process of torsion is regarded as a hallmark that is associated with a new anatomical configuration. This configuration is present in extant prosobranch gastropod species, which predominantly bear external shells. Here, we show that short-term exposure to platinum during development uncouples at least two of the processes associated with torsion of the freshwater snail Marisa cornuarietis. That is, the anus of the treated snails is located anteriorly, but the gill and the designated mantle tissue remains in a posterior location, thus preventing the formation of an external shell. In contrast to the prosobranchian archetype, platinum treatment results in the formation of a posterior gill and a cone-shaped internal shell, which persists across the lifetime. This first finding of artificially induced snail-slug conversion was also seen in the pulmonate snail Planorbarius corneus and demonstrates that selective alteration of embryonic key processes can result in fundamental changes of an existing body plan and-if altered regulation is inherited-may give rise to a new one.