Sp?tsch?den nach Behandlung des Hodgkin-Lymphoms

Im Hinblick auf die eindrucksvollen Remissionsraten, die in den letzten Jahren in der Therapie des Hodgkin-Lymphoms erzielt wurden, gewinnen die therapieinduzierten Spätkomplikationen einen immer größeren Stellenwert. In Abhängigkeit von Stadium und Risikofaktoren können nach der Primärtherapie mittlerweile Langzeitremissionen von über 80% erzielt werden. Demzufolge hat gerade das Überleben junger Patienten im reproduktiven Alter zugenommen, weshalb genaue Analysen therapieinduzierter Spätfolgen immer mehr in den Vordergrund treten. Zu den wichtigsten therapieinduzierten Akut- und Spättoxizitäten zählen Infertilität, kardiale, pulmonale oder thyroidale Funktionsstörungen und insbesondere Sekundärneoplasien, die zu einer signifikanten Mortalität beitragen. Außerdem kann ein noch lange Zeit nach der Therapie anhaltendes Fatiguesyndrom auftreten. Die Therapiestrategien aktueller klinischer Studien zielen daher insbesondere auf eine Reduktion von therapiebedingten Spätfolgen bei gleichzeitiger Beibehaltung der guten Tumorkontrolle.     

Voltammetric Quality Control of Bioactive Additives: Determination of B<Subscript>1</Subscript>, B<Subscript>2</Subscript>, C,E Vitamins and Quercetin

Rapid voltammetric procedures for the determination of water-soluble vitamins C, B₁, and B₂, fat-soluble vitamin E (α-tocopherol acetate), and quercetin in bioactive food additives have been developed. The systematic error (i.e., correctness) of the proposed procedures was evaluated using certified reference materials and the additive recovery tests, which gave the following limiting metrological characteristics: relative error, 25 %; reproducibility, 28 %; convergence, 22 %. The full analysis time (with sample preparation) did not exceed 2 hours. Voltammetric determinations under optimum conditions can be performed in the automated regime controlled by a computer according to the specially developed software.__________Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 39, No. 3, pp. 54 – 56, March, 2005.     

Alkaline Hydrolysis Kinetics and No-Donor Activity of Tenonitrozole

The kinetics of alkaline hydrolysis of N-(5-nitro-2-thiazolyl)-2-thiophenylcarboxamide (tenonitrozole or atrican) has been studied by photometric and polarographic techniques, and the thermodynamic parameters in the intermediate state of this process were determined. A mechanism explaining the nitric oxide (NO) production during the hydrolytic decomposition of tenonitrozole is proposed. It is suggested that the antiprotozoal and antimicrobial activity of this drug under anaerobic conditions is related to the formation of nitro radical anions and NO. Under aerobic and microaerophilic conditions, the hydrolysis of tenonitrozole may lead to the formation of a peroxynitrite anion, which is a strong cytotoxic agent. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 39, No. 6, pp. 15 – 18, June, 2005.     

Asthma inhalers and subsurface enamel demineralisation: an in situ pilot study.

AIM: The purpose of this pilot study was to identify the subsurface enamel demineralising potential of two possible acidogenic lactose-based powders and their corresponding generic pump inhalers. METHODS: Ten healthy non-asthmatic adults participated in a 5- leg randomised crossover study including a 10% sucrose control. A twice-daily 400 microg dose of inhaler was applied in vitro to a demineralised enamel slab on the buccal flange of a mandibular removable appliance before in situ placement for 14 days each. Lesion parameters were determined using transverse microradiography and digitised image analysis. RESULTS: Minimal demineralisation occurred with sucrose, both pump and one powder inhaler. The remaining powder was associated with remineralisation (p = 0.29). Overall, mean lesion depth increased (p = 0.12). CONCLUSION: Asthma inhalers failed to demonstrate a significant acidogenic/cariogenic effect.     

Toll-like receptor signaling inhibits structural development of the distal fetal mouse lung.

We tested the hypothesis that innate immune signaling in utero could disrupt the structural development of the fetal lung, contributing to the pathogenesis of bronchopulmonary dysplasia. Injection of Escherichia coli lipopolysaccharide (LPS) into the amniotic fluid of E15 BALB/cJ mice increased the luminal volume density of fetal mouse lungs at embryonic day (E) 17 and E18. LPS also increased luminal volume and decreased distal lung branching in fetal mouse lung explants. This effect required NF-kappaB activation and functional Toll-Like Receptor 4. Airway branching may require fibronectin-dependent epithelial-mesenchymal interactions, representing a potential target for innate immune signaling. Anti-fibronectin antibodies and LPS both blocked distal lung branching. By immunofluorescence, fibronectin localized to the clefts between newly formed airways but was restricted to peripheral mesenchymal cells in LPS-exposed explants. These data suggest that LPS may alter the expression pattern of mesenchymal fibronectin, potentially disrupting epithelial-mesenchymal interactions and inhibiting distal airway branching and alveolarization. This mechanism may link innate immune signaling with defects in structural development of the fetal lung.     

Olfactory neuroblastoma mimicking primary intracranial neoplasm

A case of esthesioneuroblastoma with an unusual clinical and radiographic presentation is reported. The presenting symptoms as well as the computed tomographic examination were compatible with a primary intracranial mass.     

Junctional epidermolysis bullosa keratinocytes in culture display adhesive, structural, and functional abnormalities.

An unusual, elongated, refractile cell morphology was observed in keratinocytes cultured from three patients with non-lethalis forms of junctional epidermolysis bullosa (JEB). To determine whether these changes might be related to altered cell adhesion, keratinocyte strains established from one patient were examined for adhesive, structural, and functional characteristics. JEB keratinocytes expressed keratin tonofilaments, as determined by staining with AE1 monoclonal antibodies and direct observation of tonofilaments by electron microscopy. JEB keratinocytes showed diminished cell-substratum adhesions, judged by interference reflection microscopy. Areas of diminished cell-substratum adhesion corresponded to F-actin-rich cell adhesions (focal adhesions) and not to cellular areas that abundantly express hemidesmosomal antigens. Analysis of cell-substratum adhesion by electron microscopy revealed extensive areas of cell-substratum separation in JEB keratinocytes that were not present in normal keratinocytes maintained in serum-free medium. Normal keratinocytes displayed numerous regions of focal contact between the ventral plasma membrane and the culture substratum, but these structures were not seen in JEB keratinocytes. Bundled actin filaments (stress fibers) were greatly diminished in expected regions of cell-substratum adhesion in JEB keratinocytes and, instead, displayed disorganized individual filaments. The growth rate of JEB keratinocytes was quite slow in culture, with a population doubling time of 2.7 d versus 1.5 d for normal keratinocytes under identical conditions. JEB keratinocytes also displayed a reduced ability to aggregate into colonies upon exposure to medium with increased extracellular calcium. JEB keratinocytes thus display adhesive, structural, and functional abnormalities that suggest this cell type may be central to the pathogenesis of junctional epidermolysis bullosa. Study of affected keratinocytes could be important to characterize associated molecular pathologies.     

Susceptibility of upper-genital tract isolates from women with pelvic inflammatory disease to ampicillin, cefpodoxime, metronidazole, and doxycycline

The antibiotics that are recommended for treatment of pelvic inflammatory disease (PID) in the outpatient setting are efficacious against Neisseria gonorrhoeae and Chlamydia trachomatis. The susceptibility of non-sexually transmitted pathogens to these agents has not been well studied. The mean inhibitory concentrations of ampicillin, cefpodoxime, metronidazole, and doxycycline were determined for 137 upper-genital tract isolates from 84 women with confirmed PID. Antibiotic resistance was noted in 16%, 9%, 93%, and 72% of the facultative and 0%, 11%, 10%, and 56% of the anaerobic bacteria when tested against ampicillin, cefpodoxime, metronidazole, and doxycycline, respectively. The authors conclude that doxycycline is limited to coverage of Chlamydia and that a single dose of another antibiotic may not be adequate to eradicate the non-sexually transmitted disease pathogens from the upper-genital tract. Additional clinical and microbiologic studies are needed to determine whether the current outpatient antibiotic regimens provide optimal coverage for the non-sexually transmitted pathogens that are associated with PID.