The developmental neurotoxicity of fipronil: notochord degeneration and locomotor defects in zebrafish embryos and larvae.

Fipronil is a phenylpyrazole insecticide designed to selectively inhibit insect gamma-aminobutyric acid (GABA) receptors. Although fipronil is often used in or near aquatic environments, few studies have assessed the effects of this neurotoxicant on aquatic vertebrates at sensitive life stages. We explored the toxicological effects of fipronil on embryos and larvae using the zebrafish (Danio rerio) experimental model system. Embryos exposed to fipronil at nominal concentrations at or above 0.7 microM (333 mug/l) displayed notochord degeneration, shortening along the rostral-caudal body axis, and ineffective tail flips and uncoordinated muscle contractions along the body axis in response to touch. This phenotype closely resembles zebrafish locomotor mutants of the accordion class and is consistent with loss of reciprocal inhibitory neurotransmission by glycinergic commissural interneurons in the spinal cord. Consistent with the hypothesis that notochord degeneration may be due to abnormal mechanical stress from muscle tetany, the expression patterns of gene and protein markers specific to notochord development were unaffected by fipronil. Moreover, the degenerative effects of fipronil (1.1 microM) were reversed by coexposure to the sodium channel blocker MS-222 (0.6mM). The notochord effects of fipronil were phenocopied by exposure to 70 microM strychnine, a glycinergic receptor antagonist. In contrast, exposure to gabazine, a potent vertebrate GABA(A) antagonist, resulted in a hyperactive touch response but did not cause notochord degeneration. Although specifically developed to target insect GABA receptors with low vertebrate toxicity, our results suggest that fipronil impairs the development of spinal locomotor pathways in fish by inhibiting a structurally related glycine receptor subtype. This represents an unanticipated and potentially novel mechanism for fipronil toxicity in vertebrates.     

Der Einfluß von N1-n-Butylbiguanid auf das Verhalten der Unveresterten Fettsäuren (UFS) bei Normalpersonen und bei Diabetikern und am epididymalen Fettgewebe der Ratte

Zusammenfassung Das Verhalten der Unveresterten Fettsäuren an Gesunden und Diabetikern und am epididymalen Fettgewebe der Ratte unter N₁-n-Butylbiguanid wurde untersucht. Normalpersonen mit und ohne Biguanid reagieren bei Blutzuckerabfall mit einem Anstieg der UFS, der unter Biguanid signifikant höher ist. Diabetiker zeigen einen geringfügigen Abfall der UFS nach Biguanid. Unter Biguanidkonzentrationen, die der therapeutischen Serumkonzentration entsprechen (5/ml), werden vom Fettgewebe in Gegenwart von Glucose vermehrt UFS utilisiert. Bei hohen Konzentrationen (100 bis 1000/ml) tritt ein Wirkungsumschlag ein, die Fettsäureutilisation wird gehemmt.Teile dieser Arbeit sind in den Dissertationen vonM. L'age undJ. Stehr enthalten.     

Formation of Artemisinin in Artemisia annua During One Vegetation Period*,1

In order to investigate the possibility of isolating greater amounts of the antimalarial compound artemisinin (quinghaosu), plants of ARTEMISIA ANNUA were cultivated and analysed at different stages of development. We found the highest content just before flowering. It was also possible to correlate development of the plants with the maximum content of artemisinin. ARTEMISIA ANNUA plants cultivated from various other sources were also examine for artemisinin content. According to our results, none of these plants contained sufficient amounts of artemisinin to justify an isolation on a technical scale. Furthermore other Artemisia species were tested. We found artemisinin in only one other species. To possibly increase the amount of artemisinin during the growth period of the plant, we tested two hormone-type growth regulators on A. ANNUA strain 811. The results showed that one of them, chlormequat, was able to increase the artemisinin content by 30% over untreated plants. We also found some slight effects of the growth regulators on morphological criteria of glandular trichomes.     

Gesundheitsinformationsverhalten 65+: Erreichbarkeit älterer Zielgruppen

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Der Anteil älterer Personen in der Bevölkerung wächst stetig. Gleichzeitig steigen im Alter die Risiken für...     

Leiomyom der Glans Penis

Glans penis leiomyomas are uncommon as primary nonepithelial tumors of the urogenital tract. Only 4 cases are described until today. We saw an other case of an 12 years old boy with a leiomyoma of the glans penis. Clinically the lesion presented as a yellow induration with no symptoms as pain, pruritus or bleeding. The biopsy revealed histological a leiomyoma in the subcutis of the glans penis with no symptoms of malignancy. Because of suspected functional and cosmetic deficiency a total resection was not performed. None of the cases described in the literature showed in the follow up malignancy or recurrency. 18 months postoperatively our patient is furthermore well and without symptoms. Nevertheless the leiomyoma of that localization is rare, this tumor should be included in the differential diagnosis of the neoplasms of the glans penis.     

Surgical strategy in aortoesophageal fistulae: endovascular stentgrafts and in situ repair of the aorta with cryopreserved homografts

OBJECTIVE: The surgical treatment of aortoesophageal fistulae (AEF) has a high morbidity and mortality rate. We report our experience with the sequential use of endovascular thoracic stentgrafts and cryopreserved aortic homografts for in situ repair of the descending thoracic aorta. METHODS: In a 7-year period, 6 patients with AEF were treated at our center. After primary endovascular repair in all cases, 4 patients subsequently underwent in situ repair of the descending thoracic aorta with cryopreserved homografts. Long-term antibiotic therapy was given in all cases. Recent clinical status and radiologic findings on follow-up studies of each patient were analyzed. The mean follow-up time was 35 months (range, 2-76). RESULTS: Endovascular stentgraft repair was technically successful in all cases. Two patients were not candidates for open surgical repair because of their medical condition; they both died within 8 weeks after discharge from the hospital, 1 from recurrent septic episodes, and the other from upper gastrointestinal bleeding. One of 4 patients who had undergone open surgical repair died 1 year later from upper gastrointestinal bleeding that occurred presumably due to an infectious degeneration of the homograft after secondary infection with a methacillin-resistant Staphyloccocus aureus. In 1 case persistent paraplegia and in another case persistent renal failure occurred. CONCLUSION: The use of cryopreserved homografts is a valuable alternative to in situ repair with prosthetic vascular grafts or extra-anatomic reconstructions in the surgical treatment of AEF. Endovascular stentgraft placement plays a role as a bridging procedure in emergency situations.     

Pertussis--an illness with typical clinical symptoms?]

There has been a noticeable increase in the incidence of pertussis in West Germany over the last decade. Since the availability of adequate bacteriological diagnosis a much broader clinical spectrum can be attributed to infections with B. pertussis. Three patients with an unusual clinical presentation of pertussis are presented. A three month old infant presented with severe apneic spells without cough as the sole clinical symptoms of the infection. B. pertussis was isolated in the nasopharyngeal swab. A nine month old premature infant with bronchopulmonary dysplasia after long time intubation and artificial ventilation presented with apneic spells, pulmonary and cardiac decompensation and required ventilatory support. The diagnosis was suggested by a massive leucocytosis with lymphocytosis. The diagnosis on the patient was established by serologic methods. Adult contacts of this patient developed longstanding cough and clinical signs of pertussis. The diagnosis of pertussis in these persons was established by nasopharyngeal culture. The third patient with trisomy 21 and a corrected AV canal suffered from nonspecific cough and gradually developed signs of congestive heart failure with pneumonia. B. pertussis was isolated from the nasopharynx. This patient showed neither the typical paroxysmal coughing spells nor disclosed the typical lymphocytosis in his white blood count. Microbiological investigations of patients with symptoms of respiratory tract infections should include the isolation of B. pertussis. Thus, additional cases of pertussis not suspected on the basis of their initial clinical presentation will be detected.