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Abstract Cyproheptadine is a cheap, widely available anti-allergy drug with a broad receptor binding profile which resembles that of clozapine. In rats discriminating clozapine from vehicle cyproheptadine mimicked clozapine very [...]

Background and objectives Humans co-evolved with pathogens, especially helminths, that educate the immune system during development and lower inflammatory responses. The absence of such stimuli in industrialized countries is associated with higher baseline levels of C-reactive protein (CRP) among adults who appear at greater risk for inflammatory disorders. This cross-sectional study examined effects of early life development on salivary CRP levels in 452 British-Bangladeshis who spent varying periods growing up in Bangladesh or UK. We also analyzed how gender and central obesity modulate effects on CRP. We hypothesized that: (i) first-generation Bangladeshis with higher childhood exposure to pathogens would have chronically lower CRP levels than second-generation British-Bangladeshis; (ii) effects would be greater with early childhoods in Bangladesh; (iii) effects by gender would differ; and (iv) increasing obesity would mitigate early life effects. Methodology Saliva samples were assayed for CRP using ELISAs, and anthropometric data collected. Participants completed questionnaires about demographic, socioeconomic, lifestyle and health histories. Data were analyzed using multiple linear regression. Results First-generation migrants who spent early childhoods in mostly rural, unhygienic areas, and moved to UK after age 8, had lower salivary CRP compared to the second-generation. Effects differed by gender, while waist circumference predicted higher CRP levels. CRP increased with years in UK, alongside growing obesity. Conclusions and implications Our study supports the hypothesis that pathogen exposure in early life lowers inflammatory responses in adults. However, protective effects differed by gender and can be eroded by growing obesity across the life course which elevates risks for other inflammatory disorders. Lay Summary: Migrants to the UK who spent early childhoods in less hygienic environments in Bangladesh that help to educate their immune systems had lower levels of the inflammatory marker, C-reactive protein (CRP) compared to migrants who grew up in UK. Both gender and increasing obesity were associated with increased levels of CRP. [ABSTRACT FROM AUTHOR]

Background: Adrenarche involves maturation of the hypothalamic‐pituitary‐adrenal axis and increased production of dehydroepiandrosterone and its sulfate ester, dehydroepiandrosterone‐sulfate (DHEA‐S). It occurs at ages 6 to 8 in industrialized populations, marking the transition from childhood to juvenility and cognitive development at middle childhood. Studies in subsistence level populations indicate a later age (8‐9) for adrenarche, but only two such studies currently exist for comparison. Aims: To investigate adrenarcheal age among Maya girls and its association with body composition and dietary variables. We hypothesized adrenarche would occur earlier given the current dual burden of nutrition in Mexico. Materials and Methods: 25 Maya girls aged 7 to 9 from Merida, Mexico using ELISAs to measure salivary DHEA‐S, standard anthropometry for height, weight, and skinfolds, bioelectrical impedance for body composition variables, as well as a food frequency questionnaire for dietary information. Results: Our hypothesis was rejected—adrenarche occurred close to 9 years. While no measures of body composition were significantly associated with adrenarcheal status, girls eating meat and dairy products more frequently had significantly higher DHEA‐S levels. Discussion: Like other populations living in ecologically challenging environments, adrenarche occurred relatively late among Maya girls. Adrenarche has been linked to measures of body composition, particularly, the adiposity or body mass index rebound, but no relevant anthropometric measures were associated, possibly because of the small sample. Conclusion: Further studies are required to illuminate how adrenarcheal variation relates to developmental plasticity, body composition, pubertal progression, and animal product consumption in other transitional populations. [ABSTRACT FROM AUTHOR]

Cyproheptadine is a cheap, widely available anti-allergy drug with a broad receptor binding profile which resembles that of clozapine. In rats discriminating clozapine from vehicle cyproheptadine mimicked clozapine very closely. Acutely it induced full generalization in the absence of response suppression, as observed with clozapine. Chronic administration of clozapine and cyproheptadine induced tolerance and cross-tolerance respectively to the clozapine stimulus. This was characterized by circa 3.5-fold parallel shifts to the right in the clozapine generalization curves. Such tolerance and cross-tolerance was spontaneously reversible, suggesting that it was pharmacodynamic, and that clozapine and cyproheptadine induce similar neuroadaptations when administered chronically. Administration of chtordiazepoxide at a very high dose induced no cross-tolerance to the clozapine stimulus showing the pharmacological specificity of tolerance. The clozapine stimulus is a compound cue involving actions at various receptors, and various clozapine-like antipsychotic (APD) drugs generalize fully to it. These data demonstrate that in vivo cyproheptadine resembles clozapine both acutely and chronically. Our findings, in conjunction with other actions of cyproheptadine -- induction of weight gain, alleviation of clozapine withdrawal, anxiolytic actions, alleviation of 'typical' APD-induced motoric side effects, and some preliminary clinical findings -- suggest that further study of cyproheptadine in conjunction with a 'typical' APD for the possible treatment of schizophrenia is merited at both pre-clinical and clinical levels. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "H1-histamine Receptor Affinity Predicts Short-Term Weight Gain for Typical and Atypical Antipsychotic Drugs," in the 2003 issue.