Effect of Elastic Liquid-State Vesicle on Apomorphine Iontophoresis Transport Through Human Skin In Vitro

Pharmaceutical Research -     

Pediatrics (79)

Pain children: a common experience. (Erasmus University Rotterdam, Rotterdam, The Netherlands) Pain 2000;87:51–57. This study analyzed the prevalence of pain in Dutch children from 0 to 18 years of age. A random sample of 1300 children 0–3 years of age was taken from the register of population in Rotterdam, The Netherlands. In the Rotterdam area, 27 primary schools and 14 secondary schools were selected to obtain a representative sample of 5336 children from 4–18 years of age. Depending on the age of the child, a questionnaire was either mailed to the parents (0–3 years) or distributed at school (4–18 years). Of 6636 children surveyed, 5424 (82%) responded; response rates ranged from 64% to 92%, depending on the subject age and who completed the questionnaire. Of the respondents, 54% had experienced pain within the previous 3 months. Overall, a quarter of the respondents reported chronic pain (recurrent or continuous pain for more than 3 months). The prevalence of chronic pain increased with age, and was significantly higher in girls (P < 0.001). In girls, a marked increase occurred in reporting chronic pain between 12 and 14 years of age. The most common types of pain in children were limb pain, headache, and abdominal pain. Half of the respondents who had reported pain reported to have multiple pain, and one‐third of the chronic pain sufferers experienced frequent and intense pain. These multiple pains and severe pains were more often reported by girls (P < 0.001). The intensity of pain was higher in the case of chronic pain (P < 0.001) and multiple pains (P < 0.001), and for chronic pain the intensity was higher for girls (P < 0.001). These findings indicate that chronic pain is a common complaint in childhood and adolescence. In particular, the high prevalence of severe chronic pain and multiple pain in girls aged 12 years and over calls for follow‐up investigations documenting the various bio‐psycho‐social factors related to this pain.     

Detection of human papillomavirus DNA in urine. A review of the literature

The detection of human papillomavirus (HPV) DNA in urine, a specimen easily obtained by a non-invasive self-sampling method, has been the subject of a considerable number of studies. This review provides an overview of 41 published studies; assesses how different methods and settings may contribute to the sometimes contradictory outcomes; and discusses the potential relevance of using urine samples in vaccine trials, disease surveillance, epidemiological studies, and specific settings of cervical cancer screening. Urine sampling, storage conditions, sample preparation, DNA extraction, and DNA amplification may all have an important impact on HPV DNA detection and the form of viral DNA that is detected. Possible trends in HPV DNA prevalence in urine could be inferred from the presence of risk factors or the diagnosis of cervical lesions. HPV DNA detection in urine is feasible and may become a useful tool but necessitates further improvement and standardization.     

Effects of chemical chaperones on partially retarded NaCl cotransporter mutants associated with Gitelman's syndrome in a mouse cortical collecting duct cell line.

BACKGROUND: Epithelial cells lining the distal convoluted tubule express the thiazide-sensitive Na-Cl cotransporter (NCC) that is responsible for the reabsorption of 5-10% of the filtered load of Na(+) and Cl(-). Mutations in NCC cause the autosomal recessive renal disorder Gitelman's syndrome (GS). GS mutations give rise to mutant transporters that are either fully (class I) or partially (class II) retarded. Recent evidence indicates that class II mutations do not alter the intrinsic transport activity of NCC. These findings suggest that in GS caused by class II NCC mutations, pharmacological chaperones may be useful in treatment. METHODS: Initial attempts using 4-phenylbutyrate and glycerol to increase Na(+) uptake in Xenopus laevis oocytes expressing the class II mutant L215P were unsuccessful. To study the effect of the chaperones in a more physiological setting, we next expressed hNCC in the polarized epithelial cell line of distal tubular origin, mpkCCD. RESULTS: mpkCCD cells readily expressed the class II mutant R955Q, but not the class I mutant G741R. Wild-type hNCC was predominantly present in the approximately 120-1403 kD complex glycosylated form. In contrast, the R955Q mutant was predominantly present in a lower molecular weight form of approximately 100 kD. Pretreatment of R955Q expressing cells with 4-phenylbutyrate (5 mM, 16 h), but not thapsigargin (1 microM, 90 min), dimethyl sulfoxide (1%, 16 h) or glycerol (4%, 16 h), increased the expression of the complex glycosylated form and in parallel the number of hNCC positive cells. CONCLUSIONS: Taken together, the data indicate that 4-phenylbutyrate is a promising candidate for rescuing partially retarded but otherwise functional class II GS mutants.