Percutaneous Absorption Enhancement by Nonionic Surfactants

The influence of nonionic surfactants (polysorbates) on hydrocortisone penetration through hairless mouse skin in vitro has been determined. Permeation was quite slow from purely aqueous media containing surfactants following finite dose application. However, if the vehicle contained high propylene glycol concentrations (40% or more), inclusion of a surfactant increased permeation rate significantly. Similar effects were noted following application of a large donor volume (infinite dose). Synergism was attributed to enhancement of surfactant absorption by the stratum corneum leading to changes in skin barrier resistance. With vehicles containing a surfactant, penetration was higher after finite dose application due to compositional changes within the vehicle.     

Experimental study on the application of acoustic emission during the hydraulic pressurization of a reactor pressure vessel

The investigations were aimed at demonstrating the state of the art of acoustic emission testing (AET) of reactor pressure vessels. The object under investigation was the large reactor pressure vessel of the MPA in Stuttgart, a boiling-water reactor pressure vessel, which was provided with a multitude of flaws in weld seams and in the base material. Six hydrostatic tests approximately up to the working pressure of a boiling-water reactor (71 bar) were carried out. In addition to the global multichannel locating technique, also local monitoring techniques were applied. Global location permitted a large number of different indications to be detected simultaneously. Not all of the known flaws did, however, show the expected number of AE events. On the other hand, it was possible to detect flaws previously unknown to the AE staff in some weld seams; these indications were confirmed by nondestructive testing. It was demonstrated that the locating accuracy of local monitoring using signal analysis was improved by a factor of 20 to 30 compared to global monitoring.     

Monitoring, removal and risk assessment of cytostatic drugs in hospital wastewater.

Cytostatic agents are applied in cancer therapy and subsequently excreted into hospital wastewater. As these substances are known to be carcinogenic, mutagenic and toxic for reproduction, they should be removed from wastewater at their source of origin.In this study the fate and effects of the cancerostatic platinum compounds (CPC) cisplatin, carboplatin, oxaliplatin, 5-fluorouracil (5-FU) and the anthracyclines doxorubicin, daunorubicin and epirubicin were investigated in hospital wastewater. Wastewater from the in-patient treatment ward of a hospital in Vienna was collected and monitored for the occurrence of the selected drugs. A calculation model was established to spot the correlation between administered dosage and measured concentrations. To investigate the fate of the selected substances during wastewater treatment, the oncologic wastewater was treated in a pilot membrane bioreactor system (MBR) and in downstream advanced wastewater treatment processes (adsorption to activated carbon and UV-treatment). Genotoxic effects of the oncologic wastewater were assessed before and after wastewater treatment followed by a risk assessment.Monitoring concentrations of the selected cytostatics in the oncologic wastewater were in line with calculated concentrations. Due to different mechanisms (adsorption, biodegradation) in the MBR-system 5 - FU and the anthracyclines were removed < LOD, whereas CPC were removed by 60%. In parallel, genotoxic effects could be reduced significantly by the MBR-system. The risk for humans, the aquatic and terrestrial environment by hospital wastewater containing cytostatic drugs was classified as small in a preliminary risk assessment.     

Expression of p21(waf1/cip1) protein in transitional cell bladder tumours and its prognostic value

Selective antagonists to the Type 3 serotonin receptor (5HT3) in combination with corticosteroids are now considered the standard of care for the prevention of emesis from moderately to highly emetogenic chemotherapy. Here we address issues of optimal dose, schedule and route of administration of four currently available selectable 5HT3 antagonists. This paper utilizes an evidence based medicine approach to the literature regarding this class of drugs, emphasizing the results large, randomized, controlled trials to make formal recommendations concerning optimal use of this important new class of anti-emetic agents. We conclude that for each drug there is a plateau in therapeutic efficacy at a definable dose level above which further dose escalation does not improve outcome. Furthermore, a single dose is as effective as multiple doses or continuous infusion, and finally, emerging data demonstrate that the oral route is equally efficacious as the intravenous route of administration, even with highly emetogenic chemotherapy.     

Differential osteoporosis diagnosis in the woman

Bone mineral density of a woman in the second half of her life depends on the amount of bone made during growth and its subsequent rate of loss. Although the rate of bone loss did receive more attention in the study of pathogenesis of osteoporosis, it is becoming increasingly clear that insufficient accumulation of skeletal mass by young adulthood predisposes a person to low bone mass and subsequently to fractures later in life as age related and menopause-related bone loss ensue. In this article we 1) explain the role of inadequate peak bone mass as a major risk factor for osteoporosis and 2) give an overview of factors leading to osteoporosis by decreasing bone mass. Special emphasis has been put on iatrogenic osteoporosis which is frequently neglected because of the fact that the responsible agents often are not known as to be deleterious to the skeleton: among others, glucocorticoids, thyroid hormones and antiepileptics adversely affect bone.     

Dominant negative alleles of SEC10 reveal distinct domains involved in secretion and morphogenesis in yeast

The accurate targeting of secretory vesicles to distinct sites on the plasma membrane is necessary to achieve polarized growth and to establish specialized domains at the surface of eukaryotic cells. Members of a protein complex required for exocytosis, the exocyst, have been localized to regions of active secretion in the budding yeast Saccharomyces cerevisiae where they may function to specify sites on the plasma membrane for vesicle docking and fusion. In this study we have addressed the function of one member of the exocyst complex, Sec10p. We have identified two functional domains of Sec10p that act in a dominant-negative manner to inhibit cell growth upon overexpression. Phenotypic and biochemical analysis of the dominant-negative mutants points to a bifunctional role for Sec10p. One domain, consisting of the amino-terminal two-thirds of Sec10p directly interacts with Sec15p, another exocyst component. Overexpression of this domain displaces the full-length Sec10 from the exocyst complex, resulting in a block in exocytosis and an accumulation of secretory vesicles. The carboxy-terminal domain of Sec10p does not interact with other members of the exocyst complex and expression of this domain does not cause a secretory defect. Rather, this mutant results in the formation of elongated cells, suggesting that the second domain of Sec10p is required for morphogenesis, perhaps regulating the reorientation of the secretory pathway from the tip of the emerging daughter cell toward the mother-daughter connection during cell cycle progression.     

Unusual gunshot injuries

Ectopic meningioma outside the skull and spinal column is uncommon. We report a cutaneous meningioma of the scalp in a 77-year-old man. A review of types and their management options are discussed. We also highlight that in certain carefully selected cases, these lesions can be treated conservatively.     

Metastatic pulmonary artery sarcoma. Report of a case with diagnosis by fine needle aspiration

Spontaneously hypertensive rats (SHR) of 3 to 12 months of age learned and retrieved less information than normotensive Wistar-Kyoto rats (WKY), although no difference was found with animals from 18 and 24 months of age. The combined influence of hypertension and aging had an additive detrimental effect on cognitive functions. Notwithstanding these deficiencies in learning and memory, SHR have seldom been used as a model in the screening of drugs with therapeutic potential for treatment of disorders of cognitive processes. Moreover, the calcium channel blocker nimodipine has beneficial effects on learning in both aged and hypertensive animals and humans. However, no attempt has been made to investigate whether nimodipine can reverse the additive deleterious effects of aging and hypertension in the same subject. We recently reported that deteriorated animals (middle-aged and/or hypertensive) chronically treated with nimodipine (via osmotic minipumps) exhibit higher learning scores. This information indicates that nimodipine can reverse the impairing effects of either aging or hypertension on learning; the presence of the two conditions, however, produces a severe impairment that can be partially reversed by this drug. Therefore, we propose that mature and middle-aged SHR represent a model for the screening of potentially useful drugs in the treatment of learning disorders, probably associated with hypertension and/or aging. Nevertheless, it must be remembered that the SHR is a genetic model and the appearance of neural disturbances could be a parallel genetic phenomenon and not necessarily or exclusively related to hypertension per se.