[Experimental models of human skin aging]. / Experimentelle Modelle humaner Hautalterung.

The skin is a representative model for the study of human aging. Despite the high regenerative capacity of the skin, skin physiology changes over the course of life. Medical and cosmetic research is trying to prevent aging, to slow, to stop, or to reverse it. Effects of age-related DNA damage and of changing skin structure on pharmacological parameters are largely unknown. This review article summarizes the state of scientific knowledge in the field of experimental models of human skin aging and shows approaches to improve organotypic skin models, to develop predictive models of aging, and improve aging research.

Role of host feeding niches and host refuges in habitat-related behaviour of Hyssopus pallidus (Hymenoptera: Eulophidae), a larval parasitoid of the codling moth.

Parasitoid fitness depends largely on the capability to locate a host in an ecosystem. A parasitoid of a polyphagous host might not be able to find or to access the host in all its feeding niches. This study evaluated the niche selection of Hyssopus pallidus (Askew), a larval parasitoid of Cydia pomonella (Linnaeus), at the plant level with the goal of assessing its potential for biological control on different fruit crops throughout the plant cycle. Parasitoid behaviour during host location and reproduction rate were investigated on host caterpillars actively feeding on apple, pear, apricot or plum, and on caterpillars diapausing under the bark. Under laboratory conditions, the host searching behaviour of H. pallidus varied depending on the fruit species offered and the infestation of the fruits. Parasitoid females searched longer on apples than on other fruit species, and they searched longer on infested than on uninfested apples. Female wasps were able to locate and parasitize host caterpillars under the tree bark, and their behaviour did not vary with host accessibility. The numbers of caterpillars attacked by H. pallidus depended on the fruit species. The highest numbers of caterpillars were parasitized in apples and apricots. Their accessibility (i.e. position) within the fruit or on the branch did not influence parasitism success. Although hosts were parasitized throughout the season, the best results were achieved with early and late releases. Therefore, the host niche selection behaviour of H. pallidus most likely co-evolved with the host C. pomonella on apples, which renders H. pallidus a valuable biocontrol agent for successful release at different times of the season into apple orchards.

[Patients as partners. Tumor patients and their participation in medical decisions]. / Patienten als Partner in der letzten Lebensphase. Erste Ergebnisse und Perspektiven eines Modellvorhabens.

Between March 2002 and August 2003 as part of the research project "Patients as partners -- tumour patients and their participation in medical decisions" tumour patients undergoing palliative therapy (n=272) were interviewed and asked about their level of information, their desired place to die and whether they had prepared an advance directive. Furthermore, 72 relatives of deceased patients who had been looked after by the project's palliative care team were given a similar questionnaire including questions concerning their knowledge about disease and prognosis, the actual place of death and the relevance of advance directives. According to patients and relatives, information particularly about prognosis is unsatisfactory. Of the inter-viewed patients, 75% said they wanted to die at home and 15% in a hospital. According to their relatives, 36% of the patients looked after by the palliative care team had an advance directive. The survey of the relatives showed a significant relation between the preparation of an advance directive and dying at the desired place. According to the relatives, medical and health reasons, hope for an improvement up to the very end,acute worsening of the condition and deficits in medical care were important reasons for dying in hospital against the patient'swish. In future, advance directives should be used as an aid for communication and the planning of care. Therefore, cooperation between doctors and patients based on a partnership is necessary. The required competence in communication should be improved.

Formation of interferon-gamma and tumor necrosis factor in mice during Salmonella typhimurium infection.

Formation of interferon-gamma (IFN-gamma) and tumor necrosis factor (TNF) during Salmonella typhimurium infection was investigated in lipopolysaccharide (LPS)-sensitive C3H/HeN and C57BL/10ScSn(B10ScSn), and LPS-resistant (lpsd mutant) C3H/HeJ and C57BL/10ScCr(B10ScCr) mice. When infected with 50 colony-forming units (CFU) of S. typhimurium C5, C3H/HeN and B10ScSn mice became hypersensitive to the lethal effect of LPS. In the case of lpsd mutants, only C3H/HeJ mice became hypersensitive to LPS, while B10ScCr mice remained resistant. C3H/HeJ as well as B10ScSn mice produced significant amounts of plasma IFN-gamma on day 3 after infection. By this time bacterial CFU in the liver of B10ScSn and C3H/HeJ mice were 10(6.7) and 10(7.1), respectively. In B10ScCr mice, however, IFN-gamma was not detectable although bacteria present in the liver exceeded 10(8) CFU. On the other hand, plasma TNF was not detectable in any of the mouse strains during S. typhimurium infection. When S. typhimurium-infected mice were challenged with LPS on day 3, significant amounts of plasma TNF were measured in C3H/HeN and B10ScSn mice, while in the lpsd mutant C3H/HeJ and B10ScCr mice plasma TNF was undetectable.

Natriuretic factors and lithium clearance in patients with the syndrome of inappropriate antidiuretic hormone (SIADH)

Because the syndrome of inappropriate antidiuretic hormone (SIADH) is a state of disturbed body fluid volume regulation and altered sodium balance we sought to determine if recently described volume regulatory factors were stimulated in SIADH. We measured atrial natriuretic peptide (ANP), endogenous digitalis-like natriuretic factor (EDNF) and urinary free dopamine in SIADH (n = 27). We also determined fractional clearance of lithium (FCLi). The data obtained in SIADH were compared with similar measurements performed in sodium retaining hyponatremias, such as those of heart failure (n = 26), liver cirrhosis (n = 19) and volume contraction (n = 28). We observed: ANP was 19.5 +/- 2.7 fM/ml in SIADH; it was significantly lower than ANP in cardiac failure, but no different from ANP in volume contraction. Urinary free dopamine was 2.2 +/- 0.8 microM/24 h in SIADH; this was significantly higher than in volume contraction and liver cirrhosis. EDNF (259 +/- 42 nM/24 h) and FCLi (21.4 +/- 2%) were both numerically higher in SIADH than in other hyponatremic disorders; however, the differences did not achieve significance. In conclusion, our observations did not establish a specific role of ANP in chronic stable SIADH. As to the importance of EDNF, dopamine and proximal tubular fluid reabsorption (FCLi) additional work using acute volume changes may demonstrate their participation in the renal sodium handling of SIADH more clearly than our study did.

Role of diuretics, hormonal derangements, and clinical setting of hyponatremia in medical patients.

Because hyponatremia is frequently associated with preceding diuretic treatment and unrestricted fluid intake--conditions which have not been addressed sufficiently in published literature--we studied the pathophysiology and the clinical setting of such hyponatremia in a large group of internal medicine patients. We observed: a) Of an initial 310 patients with chemical hyponatremia only 204 (64%) had an associated plasma hypoosmolality. Since a normal plasma osmolality excludes a disturbance of water metabolism only the 204 patients with hypoosmolar hyponatremia were included in the study. This data shows that plasma osmolality is an essential measurement in any evaluation of hyponatremia. b) In 204 consecutive patients with hypoosmolar hyponatremia the electrolyte disturbance was related to advanced congestive cardiac failure in 25%, decompensated liver cirrhosis in 18%, volume contraction in 28%, syndrome of inappropriate antidiuretic hormone secretion in 19% and renal insufficiency in 4%. c) Plasma vasopressin was measurable in 90% of the 204 patients. It is known that radioimmunoassays to measure vasopressin fail to reliably detect low concentrations of circulating vasopressin (less than 0.5 pg/ml). It may therefore be stated that hypoosmolar hyponatremia was generally characterized by a failure of antidiuretic hormone suppression. d) Mean daily fluid intake of hyponatremic patients was 2.35 +/- 0.15 l. In the presence of stimulated vasopressin this large a fluid intake is bound to worsen the severity of hyponatremia. e) Of 204 patients 126 were treated with diuretics at the time of study. In these patients hyponatremia worsened during such treatments and was associated with evidence of prerenal azotemia. However there were no significant differences between diuretic-treated and -untreated patients with respect to plasma vasopressin stimulation and amount of fluid intake.(ABSTRACT TRUNCATED AT 250 WORDS)

A BrdU-requiring fragile site on chromosome 12.

A BrdU-requiring fragile site, fra(12)(q24.2), on human chromosome 12 of some individuals is reported. This fragile site is inherited in a Mendelian codominant fashion and does not seem to be associated with any physical or mental abnormality in carriers. It was mostly observed as a chromatid gap: no acentric fragments, triradials or deleted chromosomes were found. The fra(12)(q24.2) was expressed in 34%-48% of metaphases in lymphocyte cultures from carriers when BrdU and FdU were added 6.5 h before harvest, while the expression ranged between 5% and 20% when the cultures were treated with BrdU alone. The fra(12)(q24.2) represents the second BrdU-requiring rare fragile site described on human chromosomes.

[The Aubaniac subclavian catheter in surgical intensive care]. / Der Subklavia-Katheter nach Aubaniac in der chirurgischen Intensivtherapie.

The subclavian catheter according to Aubaniac has worked extremely well in surgical intensive therapy through a four-year period of prospective studies. The complication rate was as 13.2 per cent, which was found to be acceptable, provided stringent observance of indications.

The charted and the uncharted waters of hyponatremia.

It was observed that hyponatremia has been evaluated by many studies of patients and laboratory animals. In virtually all of these the presence of nonosmotic ADH has been shown, but several details of this relationship remain controversial at this time. The role of specific receptor areas for ADH stimulation requires further study, particularly in the hyponatremia of a decreased effective arterial blood volume. In addition, it will be important to define the suspected vascular effects of nonosmotic ADH more specifically. Other areas of uncertainty include: the degree to which the tubular effect of ADH in hyponatremia may be modified by a decreased delivery of fluid to the loops of Henle; the potential stimulation of ADH by stress in clinical hyponatremia; and the meaning of very low or non-measurable concentrations of ADH in hyponatremia. New experimental tools such as vasopressin antagonists and agonists, measurements of baroreceptor input, and tests of proximal fluid reabsorption can be expected to clarify some of these questions in the near future.

ColB2-K77, a fertility-repressed F-like factor.

The colicinogenic B factor, transferred from Escherichia coli strain K77 (and termed ColB2-K77 or ColB2) to an E. coli K12 F(-) strain, is capable of promoting its own transfer to other K12 F(-) strains at a low rate (from LFC cultures) which can be increased under special conditions (HFC cultures). LFC cultures of K12 (ColB2)(+) F(-) strains show a low level of adsorption of F-specific phage particles which also increases under HFC conditions. The ColB2 factor is thus inferred to be an F-like sex factor which is repressed in its fertility. This repression is concluded to be due to a cytoplasmic repressor since, when ColB2 is present in cells containing an F factor (either autonomous or integrated), F fertility is also repressed as shown by the inability of such (ColB2)(+)F(+) [or (ColB2)(+)Hfr] strains to plaque F-specific phages, and by a reduction in the level of chromosomal transfer from such strains, compared to the corresponding F(+) (or Hfr) control strains. Mutants of the ColB2 factor in which fertility is no longer repressed (fertility derepressed or Fdr mutants) have been isolated. The ColB2Fdr mutant strains do not appear to be able to mobilize chromosomal transfer, although they have acquired F-specific phage sensitivity demonstrable by plaque formation and they transfer their colicin factor at high frequency and are well piliated. The Fdr mutation is presumed to result in the inability to synthesize the cytoplasmic fertility repressor since the ColB2Fdr factor does not repress the fertility of an F factor when present in the same host strain. A fertility-repressed drug resistance factor of the R(f) type is not stable in the presence of a ColB2 factor in the same cell and is eliminated in about 10% of the cells per generation. In contrast, another factor characteristic of the R(i) type is fully compatible with ColB2. Under conditions artificially stabilizing (ColB2Fdr)(+) (Rf)(+) strains, the enhanced fertility of ColB2Fdr is not repressed by the presence of the R factor, nor does the presence of R(f) in the intermediate strain of an HFC (for ColB2) system inhibit the normal increase in ColB2 transmissibility. It is concluded that the repressors of R(f) and ColB2, although both active on F fertility, are different; this may indicate that at least two independently repressible cistrons are involved in the expression of fertility characteristics.

Mitomycin C and temperature induction of colicin B in the absence of deoxyribonucleic acid synthesis.

An Escherichia coli K-12 strain and its mutant, temperature-sensitive in deoxyribonucleic acid (DNA) synthesis, were used as hosts for two different ColB factors (ColB3-K166 and ColB4-K98). Induction of either colicin occurred in both hosts in the presence of mitomycin C at 42 C. Induction of the temperature-sensitive colicinogenic hosts also occurred without mitomycin C at 42 C at which temperature no DNA synthesis was observed. Colicin synthesis was a nonlethal event in ColB4-K98(+) cultures, whereas in cultures of ColB3-K166(+) induction led to death of a large fraction of the population.