6-Nitrochrysene has previously been shown to be a potent lung and liver carcinogen following i.p. administration to newborn mice and to be metabolically activated to DNA-binding derivatives by nitro-reduction or a combination of nitro-reduction and ring oxidation. In this study, we have examined fecal metabolites and DNA-carcinogen adducts in 5-week-old conventional and germfree Balb/c mice treated with [3H]6-nitrochrysene in order to determine if the metabolic activation pathway(s) for this compound in these mice differs from that observed in preweanling mice. We further evaluated the role of the intestinal microflora on the metabolism and generation of DNA-reactive metabolites in this system. The amount of 6-aminochrysene excreted in the feces of germfree mice within 48 h after treatment with a single i.p. dose of [3H]6-nitrochrysene (0.03 mumol/5 microliters/g body wt) was approximately 25% of that excreted in identically treated conventional mice. However, the levels of carcinogen-DNA adducts in the lungs and livers of conventional and germfree Balb/c mice were similar at the 24 and 48 h time points examined. HPLC analysis of hydrolysates of liver and lung DNA indicated that adducts derived from both N-hydroxy-6-aminochrysene and trans-1,2-dihydroxy-1,2-dihydro-6-aminochrysene metabolites were formed in the liver whereas only the latter adduct was detected in the lung. This contrasts with previous findings in preweanling mice where the adduct derived from the trans-1,2-dihydroxy-1,2-dihydro-6-aminochrysene metabolite was the single major adduct detected in both liver and lung DNA. The proportion of adducts derived from N-hydroxy-6-aminochrysene was significantly greater in the liver DNA of germfree mice than in the liver DNA of conventional mice.

Animals↗

PubMedDate not supplied

Severe asthma due to household pets: a form of child abuse or neglect.

Children may suffer severe asthma as a result of exposure to household pets. Failure of parents or other caretakers to remove pets from the home environment may be considered child abuse or neglect. Physicians caring for such children may be required to report those cases to the state government.

Adolescent↗

PubMedDate not supplied

Duration of response following cessation of pollen immunotherapy.

Following successful immunotherapy estimates of relapse rate ranged from 22% to 42%, depending on method of follow-up. The time to relapse varied with the method of follow-up, indicating that recall may play a major role in the perception of a relapse. How much of the continued well-being of most patients (58% of contacted patients) is due to immunotherapy or the natural history of the illness cannot be ascertained from this study.

Humans↗

PubMedDate not supplied

Sponsor/contract laboratory communication: a team approach to quality.

The true measure of any successful quality endeavor is the final product. The final product generated at contract facilities conducting nonclinical studies is the final report. This should be accurate, complete, and consistent with regard to the raw data, and in compliance itself. The final report resulting from studies conducted at contract laboratories should be reflective of the collaborative efforts of sponsor and laboratory staffs. The dual interaction of the respective Quality Assurance Units (QAUs) in ensuring that optimal study performance is maintained from initiation through final report submission is of paramount importance. Key to any productive sponsor/contract laboratory relationship is communication. The multidirectional flow of information inherent in the conduct of nonclinical studies must be managed to maximize the strengths of the principals involved, while at the same time assuring that consistent emphasis is placed on team focus. Although the role of the QAUs representing the contract facilities and the sponsor both ensure the quality of study conduct, and ultimately the final product, their respective approaches may be from different perspectives. The contract QAU's primary focus is the specific study conduct, including appropriate inspections of ongoing critical phases and audits of raw data and reports, along with compliance to site Standard Operating Procedures (SOPs), protocols and sponsor requirements. On the other hand, sponsor QAUs focus mainly on overall study conduct, assurance that contract QAUs are operating effectively, and ensuring that sponsor monitors are communicating adequately with contract facility personnel. Open communication between the respective QAUs is the most productive and useful way of ensuring that all quality criteria are met.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Protocols↗