The clinical indications for identical pathogenesis of isolated and non-isolated testicular relapses in acute lymphoblastic leukaemia

In the present population-based study, we compared the clinical data of testicular relapses with and without concurrent bone marrow relapse and clinical data of the relapses in other locations among boys with acute lymphoblastic leukaemia (ALL), in order to study the possible evidence of early sequestration and local regulation of leukaemic lymphoblast in the testis of humans. The results suggest that the pathogenesis of isolated testicular relapse (T) and testicular relapse with a concurrent bone marrow relapse (T+BM) is likely to be similar. Isolated and non-isolated testicular relapses appeared late after the achievement of remission (T 34±16 months, T+BM 32±15 months) in ALL compared to relapses in other locations (CNS 23±11 months, BM 25±19 months). The better prognosis after testicular relapses (estimated second event free survival probability, 2-EFS: T 0.63, T+BM 0.32) compared to bone marrow relapse (2-EFS: BM 0.13) further suggests that testicular relapse with a concurrent bone marrow relapse possibly originates from the isolated testicular relapse, and that the isolated testicular relapse is a separate entity and not a manifestation of systemic recurrence. Higher frequencies of isolated and non-isolated testicular relapses (T 9%, T+BM 5%) were observed among boys with onset of ALL in early puberty (10-12y) compared to those among younger (T 4%, T+BM 2%) and older (T 0%, T+BM 0%) boys. The late occurrence, the possible association with hormonal maturation and the good prognosis after testicular relapses suggest a possible local regulation of the residual leukaemic lymphoblast in human testis.     

Evaluation of the effects of a specific α2-adrenoceptor antagonist, atipamezole, on α1- and α2-adrenoceptor subtype binding, brain neurochemistry and behaviour in comparison with yohimbine

In the present study we evaluated the α₁- and α₂-adrenoceptor subtype binding, central α₂-adrenoceptor antagonist potency, as well as effects on brain neurochemistry and behavioural pharmacology of two α₂-adrenoceptor antagonists, atipamezole and yohimbine. Atipamezole had higher selectivity for α₂- vs. α₁-adrenoceptors than yohimbine regardless of the subtypes studied. Both compounds had comparable affinity for the α_2A-, α_2C- and α_2B-adrenoceptors, but yohimbine had significantly lower affinity for the α_2D-subtype. This may account for the fact that significantly higher doses of yohimbine than atipamezole were needed for reversal of α₂-agonist (medetomidine) -induced effects in rats (mydriasis) and mice (sedation and hypothermia). The effect on central monoaminergic activity was estimated by measuring the concentrations of transmitters and their main metabolites in whole brain homogenate. At equally effective α₂-antagonising doses in the rat mydriasis model, both drugs stimulated central noradrenaline turnover (as reflected by increase in metabolite levels) to the same extent. Atipamezole increased dopaminergic activity only slightly, whereas yohimbine elevated central dopamine but decreased central 5-hydroxytryptamine turnover rates. In behavioural tests, atipamezole (0.1–10 mg/kg) did not affect motor activity but stimulated food rewarded operant (FR-10) responding (0.03–3 mg/kg) whereas yohimbine both stimulated (1 mg/kg) and decreased (≥ 3 mg/kg) behaviour in a narrow dose range in these tests. In the staircase test, both antagonists increased neophobia, but in the two compartment test only yohimbine (≥ 3 mg/kg) decreased exploratory behaviour. The dissimilar effects of the antagonists on neurochemistry and behaviour are thought to be caused by non α₂-adrenoceptor properties of yohimbine. In conclusion, the α₂-antagonist atipamezole blocked all α₂-adrenoceptor subtypes at low doses, stimulated central noradrenergic activity and had only slight effects on behaviour under familiar conditions, but increased neophobia. The low affinity for the α_2D-adrenoceptor combined with its unspecific effects complicates the use of yohimbine as pharmacological tool to study α₂-adrenoceptor physiology and pharmacology. Received: 20 May 1997 / Accepted: 29 July 1997     

Portocaval shunt,an H3-antagonist and plasma hormone levels

Inflammation Research -     

Delayed ontogenesis of histamine in the hypothalamus of the homozygous Brattleboro rat

The ontogenetic development of histamine was studied in the diabetes insipidus rat to clarify the possible interference between the lack of vasopressin and the development of histaminergic systems in the hypothalamus. Rat pups were decapitated at different ages between the 2nd and 38th postnatal days. In addition to homozygous Brattleboro (diabetes insipidus) rats, Long Evans controls and heterozygous animals were studied. In all three genotypes hypothalamic histamine was almost equal during the first 6 postnatal days. In homozygous Brattleboro rats the period of most rapid increase occurred between days 14 to 26, which was significantly later than in Long Evans rats. In the remainder of the brain no such difference was seen. On the contrary, histamine values were highest in the youngest animals. It remains to be elucidated whether the delayed ontogenesis is causally related to vasopressin deficiency and what is the underlying mechanism.     

Telomere length in relation to insulin resistance,inflammation and obesity among Arab youth

Aim: The aim of this study was to determine the associations of telomere length to markers of obesity, insulin resistance and inflammation in Saudi children. Methods: A total of 69 boys and 79 girls, aged 5–12 years, participated in this cross‐sectional study. Anthropometrics were measured. Serum glucose and lipid profile were measured using routine laboratory methods. Serum insulin, leptin, adiponectin, resistin, tumour necrosis factor‐alpha and active plasminogen activator inhibitor 1 were quantified using customized multiplex assay kits. C‐reactive protein and angiotensin II were quantified using ELISA. Leucocyte telomere length was examined by quantitative real time PCR utilizing IQ cycler. Results: Mean telomere length was significantly shorter in obese boys compared with their lean counterparts (p = 0.049), not in girls. It was not associated to insulin resistance, adipocytokines and markers of inflammation. In girls, the significant predictor of telomere length was waist circumference, explaining 24% of variance (p = 0.041) while in boys, systolic blood pressure explained 84% of the variance (p = 0.01). Conclusion: Childhood obesity in boys corresponds to shorter leucocyte telomere length which is not evident in girls. The association of leucocyte telomere length to blood pressure and waist circumference in children suggests clinical implications as to the contribution of these parameters in premature ageing.     

Height, health and growth hormone

The principal objective of this paper is to provide health practitioners with information on the positive aspects of shorter stature for use in counseling short children with poor self-images. Another objective is to provide information on the physical capabilities, health potential and psychosocial characteristics of shorter stature as a baseline for deciding whether a healthy short child should receive growth hormone therapy. The information presented here was obtained from review of publications covering medical and nutritional research, gerontological studies, athletic performance and environmental, biological and engineering aspects of the human body. It was found that the popular belief in the superiority of tall stature is based primarily on social bias rather than on a scientific foundation. Studies indicating that taller people are healthier or more productive than shorter ones have ignored a wide range of evidence that shorter people are highly creative, productive, long-lived, athletic and better for the environment. The authors urge medical and scientific professionals to consider the many advantages of shorter stature in terms of health, social and environmental benefits.     

Is histamine involved in milk ejection in goats?

Inflammation Research -