Stimulation of the LH release by naloxone in anaesthetized cats after ovariectomy

The effect of intravenous injections or infusions of the opioid receptor antagonist naloxone on the secretion of luteinizing hormone (LH) was studied in 18 spayed cats anaesthetized with Althesin. Effective injections significantly increased the LH concentration of plasma samples (taken every 10-15 min and measured by radio-immunoassay) to a peak 20-30 min after injection. The concentration thereafter declined exponentially (ke = 0.42), and, in 4/8 trials rose again significantly and declined again without further injection. The threshold dose was between 0.4 and 0.5 mg/kg. There did not appear to be a dose dependence of the effect above threshold. Infusion of naloxone at levels up to 5 mg/kg/h was effective in producing a pulsatile release of LH and repeated injections of threshold doses (0.5 mg/kg) could produce a maintained plateau and pulsatile release at frequencies comparable to pulse frequencies in vivo.     

The effect of secondhand smoke exposure on the association between active cigarette smoking and colorectal cancer

Background  

Studies published prior to 1980 failed to find an association between smoking and colorectal cancer, while subsequent studies reported an association after accounting for a three to four decade initiation period. The aims of this study were to determine the effect of accounting for secondhand smoke (SHS) exposure on the association between smoking and colorectal cancer and to determine the association between SHS and colorectal cancer.     

Mitochondrial DNA damage in lymphocytes: a role in immunosenescence?

An age-related increase of DNA damage/mutation has been previously reported in human lymphocytes. The high copy number and mutation rate make the mtDNA genome an ideal candidate for assessing damage and to act as a potential biomarker of ageing. In the present study, two assays were developed to evaluate the level of mtDNA(4977) and the accumulation of point mutations with age. A competitive polymerase chain reaction (PCR) methodology incorporating three primers was used to detect and quantify the levels of mtDNA(4977) and a novel heteroduplex reference strand conformational analysis (RSCA) technique was used to analyse the accumulation of point mutations. The assays were applied to an in vitro model of T cell ageing and ex vivo DNA samples from an elderly cohort of subjects and a younger control group. The mtDNA(4977) was detected in all the DNA samples examined but only a very low concentration was observed and no age-related increase or accumulation was observed. No accumulation of point mutations was identified using RSCA within the T cell clones as they were aged or the ex vivo lymphocytes from the elderly cohort. A higher level of variation was observed within the ex vivo DNA samples, verifying the high resolution of RSCA and its ability to identify different mtDNA species, although no correlation with age was observed. The low level of mtDNA damage observed with respect to the ex vivo lymphocyte DNA samples within this study may be due in part to the high turnover of blood cells/mtDNA, which may inhibit the accumulation of genetically abnormal mtDNA that may play a role in immunosenescence. A similar explanation may also apply to the in vitro model of T cell ageing if the vast majority of the cells are replicating rather than entering senescence.     

Can decreasing smoking prevalence reduce leukemia mortality?

Previous studies have demonstrated a modest association between smoking and leukemia particularly for myeloid disorders. Our objective was to examine whether changing trends in cigarette smoking prevalence nationally and within selected states parallel similar trends in mortality from leukemia. Trends in national smoking rates were correlated with trends in leukemia mortality rates obtained from the Centers for Disease Control and Prevention and the Surveillance Epidemiology and End Results registry, respectively. State-specific correlations were assessed from 1984 to 2004 using smoking prevalence data from the Behavioral Risk Factor Surveillance System and leukemia mortality data from National Vital Statistics System. Correlations were computed using the Spearman rank correlation coefficient. Leukemia mortality decreased overall in the United States in parallel with decreased smoking. Analyzed on a state-specific basis, leukemia mortality decreased in states where smoking rates declined markedly but remained unchanged where smoking prevalences were relatively stable. The findings suggest that declining rates of leukemia mortality are associated with changing patterns of smoking behavior.     

Mutation detection in DNA isolated from cerebrospinal fluid and urine: Clinical utility and pitfalls of multiple displacement amplification

This study describes the use of cerebral spinal fluid (CSF) and/or urine as source of DNA for mutation analysis combined with multiple displacement amplification. The findings illustrate the opportunities and pitfalls of these methods in the search for identification of the pathogenic mutations in the case that only scarce material is available such as CSF.     

In vivo regulation of phenylalanine hydroxylase in the genetic mutant hph-1 mouse model

The hph-1 mouse has low liver activity of GTP cyclohydrolase 1, the rate limiting enzyme in the biosynthesis of tetrahydrobiopterin (BH₄). BH₄ is the cofactor for phenylalanine hydroxylase (PAH) and in the early stages of life the hph-1 mouse is hyperphenylalaninemic. At approximately 15 days after birth the blood phenylalanine levels normalize. During this period the animals provide an in vivo model which can be used to study the regulatory effects of phenylalanine on PAH, and for related pediatric metabolic disease in humans; from birth to youth. We therefore, examined; liver PAH activity using BH₄ and 6-methyltetrahydropterin (6MPH₄) as cofactor; PAH total enzyme concentration by Western blotting using the PH8 antibody, and PAH state of phosphorylation using the PH7 antibody from 4 to 18 days after birth. The findings were compared to the wild type animals that are not hyperphenylalaninemic during this period. PAH (6MPH₄) activity and total protein (PH8 antibody) rose steadily in the hph-1 mice. In control mice, both activity and total protein fluctuated. The degree of phosphorylation of PAH in the mutants and the state of activation (as measured by the 6MPH₄/BH₄ activity ratio) increased as phenylalanine levels rose, and decreased when they fell. Similar patterns were not seen in the control animals. These studies provide in vivo evidence that phenylalanine concentration regulates the activity of PAH in the hph-1 mouse and that this acts via a mechanism that includes phosphorylation of the PAH molecule. The kinetic values (K_m and V_max) for mouse PAH are also reported.     

Dispositional predictors of placebo responding: a motivational interpretation of flower essence and gratitude therapy

OBJECTIVES: The aim of this study was to test a motivational interpretation of placebo responding using two different types of placebo therapy, one using flower essences and the other a nonspecific psychological therapy. The motivational concordance interpretation is that therapeutic rituals that are consistent with self-defining or self-actualizing goals have a nonspecific therapeutic benefit independently of expectancy. METHODS: Study 1 was a replication of an earlier flower essence outcome study but with additional outcome and predictor variables: 167 people completed questionnaires in return for free flower essence treatment. Predictor variables consisted of two measures of spirituality, optimism, expectancy, and attitudes and beliefs to complementary medicine. Outcome was assessed after 3 weeks. In Study 2, 90 people took part in "gratitude therapy" for improved sleep quality over one night in return for questionnaire completion (trait gratitude, spirituality, and expectancy). RESULTS: Study 1 confirmed previous research: Trait spirituality predicted perceived improvement. This improvement was independent of optimism (P<.001), cannot be explained by acquiescence or social desirability, and was independent of a highly conservative test of expectancy (P=.02). In Study 2, trait gratitude predicted perceived sleep improvement independently of expectancy (P=.01): Spirituality did not correlate with improvement. CONCLUSIONS: These data suggest that in addition to expectations, degree of engagement in a positive, therapeutic ritual determines the extent of the placebo response. The placebo response depends in part on the interaction (i.e., the degree of concordance) between the type of therapy and the participant's personality: Dispositional predictors vary with the type of placebo therapy.