RESUMO
Specific carbohydrates, i.e. prebiotics such as fructo-oligosaccharide (FOS), are not digested in the small intestine but fermented in the colon. Besides beneficial health effects of an enhanced bifidobacteria population, intestinal gas production resulting from fermentation can induce abdominal symptoms. Partial replacement with slowly fermented acacia gum may attenuate side effects. The aim was to compare the effects of FOS with those of a prebiotic mixture (50 % FOS and 50 % acacia gum; BLEND) and a rapidly absorbed carbohydrate (maltodextrin) on general intestinal wellbeing, abdominal comfort and anorectal sensory function. Twenty volunteers (eight male and twelve female; age 20-37 years) completed this double-blind, randomised study with two cycles of a 2-week run-in phase (10 g maltodextrin) followed by 5 weeks of 10 g FOS or BLEND once daily, separated by a 4-week wash-out interval. Abdominal symptoms and general wellbeing were documented by telephone interview or Internet twice weekly. Rectal sensations were assessed by a visual analogue scale during a rectal barostat test after FOS and BLEND treatment. Both FOS and BLEND induced more side effects than maltodextrin. Belching was more pronounced under FOS compared with BLEND (P = 0.09 for females; P = 0.01 for males), and for self-reported general wellbeing strong sex differences were reported (P = 0.002). Urgency scores during rectal barostat were higher with FOS than BLEND (P = 0.01). Faced with a growing range of supplemented food products, consumers may benefit from prebiotic mixtures which cause fewer abdominal side effects. Sex differences must be taken in consideration when food supplements are used.
Assuntos
Carboidratos da Dieta/administração & dosagem , Goma Arábica/administração & dosagem , Saúde , Intestinos/microbiologia , Oligossacarídeos/administração & dosagem , Polissacarídeos/administração & dosagem , Adulto , Bifidobacterium/metabolismo , Colo/microbiologia , Estudos Cross-Over , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Fermentação , Flatulência , Humanos , Masculino , Probióticos/metabolismo , Fatores Sexuais , Inquéritos e Questionários , Telemedicina/métodosRESUMO
In this study we show that E6 of human papillomavirus has the ability to deregulate the cell cycle G1/S transition. In rodent immortalized fibroblasts (NIH3T3) serum deprivation or over-expression of the cyclin-dependent kinase inhibitors, p16(INK4a) or p27(KIP1), leads to G1 cell cycle arrest. HPV16 E6 overcomes the antiproliferative signals, gaining the ability to drive serum-deprived and p16(INK4a) or p27(KIP1) over-expressing cells into S phase. E6 protein from the benign HPV type 1 displays a similar activity to HPV16 E6 to deregulate the G1/S transition. Thus, this activity appears to be conserved between E6 proteins from non-oncogenic and oncogenic HPV types. Furthermore, we show that HPV16 E6 is not able to circumvent a G1 arrest imposed by pRb mutant in which all CDK phosphorylation sites have been mutated. These data indicate that the viral protein acts upstream of pRb and its mechanism in promoting cell cycle progression is dependent on pRb phosphorylation. In summary, this study describes a novel biological function of HPV E6 and shows that the S phase entry, required for viral DNA replication, is not exclusively controlled by E7, but that E6 also is involved in this event.
Assuntos
Inibidor p16 de Quinase Dependente de Ciclina/fisiologia , Fase G1 , Proteínas dos Microfilamentos/fisiologia , Proteínas Musculares , Proteínas Oncogênicas Virais/fisiologia , Proteínas Repressoras , Fase S , Células 3T3 , Animais , Ciclina A/genética , Ciclina E/genética , Camundongos , Proteína do Retinoblastoma/fisiologiaRESUMO
Importin-alpha proteins do not only mediate the nuclear import of karyophilic proteins but also regulate spindle assembly during mitosis and the assembly of ring canals during Drosophila oogenesis. Three importin-alpha genes are present in the genome of Drosophila. To gain further insights into their function we analysed their expression during spermatogenesis by using antibodies raised against each of the three Importin-alpha proteins identified in Drosophila, namely, Imp-alpha1, -alpha2, and -alpha3. We found that each Imp-alpha is expressed during a specific and limited period of spermatogenesis. Strong expression of Imp-alpha2 takes place in spermatogonial cells, persists in spermatocytes, and lasts up to the completion of meiosis. In growing spermatocytes, the intracellular localisation of Imp-alpha2 appears to be dependent upon the rate of cell growth. In pupal testes Imp-alpha2 is essentially present in the spermatocyte nucleus but is localised in the cytoplasm of spermatocytes from adult testes. Both Imp-alpha1 and -alpha3 expression initiates at the beginning of meiosis and ends during spermatid differentiation. Imp-alpha1 expression extends up to the onset of the elongation phase, whereas that of Imp-alpha3 persists up to the completion of nuclear condensation when the spermatids become individualised. During meiosis Imp-alpha1 and -alpha3 are dispersed in the karyoplasm where they are partially associated with the nuclear spindle, albeit not with the asters. At telophase they aggregate around the chromatin. During sperm head differentiation, both Imp-alpha1 and -alpha3 are nuclear. These data indicate that each Imp-alpha protein carries during Drosophila spermatogenesis distinct, albeit overlapping, functions that may involve nuclear import of proteins, microtubule organisation, and other yet unknown processes.
Assuntos
Drosophila/metabolismo , Espermatogênese , Testículo/metabolismo , alfa Carioferinas/biossíntese , Animais , Diferenciação Celular , Divisão Celular , Núcleo Celular/metabolismo , Clonagem Molecular , Feminino , Fertilidade/genética , Imuno-Histoquímica , Masculino , Meiose , Microscopia Confocal , Mitose , Modelos Moleculares , Mutação , Fenótipo , Espermatócitos/metabolismo , Fatores de Tempo , Distribuição TecidualRESUMO
Several studies have suggested the involvement of cutaneous human papillomaviruses (HPVs) in the development of nonmelanoma skin cancers. Here we have characterized the in vitro properties of E7 proteins of three cutaneous HPV types, 10, 20, and 38, which are frequently detected in skin specimens. We show that HPV38 E7 is able to inactivate the tumor suppressor pRb and induces loss of G(1)/S transition control, a key event in carcinogenesis. In contrast, HPV10 and HPV20 E7 proteins do not display these in vitro transforming activities. We also show that the two early proteins E6 and E7 of HPV38 are sufficient to corrupt the cell cycle and senescence programs in primary cells, inducing active and long-lasting proliferation of primary human keratinocytes, the natural host cells. Our study shows that E6 and E7 of this cutaneous HPV type have transforming activity in primary human cells, suggesting a role for HPV38 infection in skin carcinogenesis. In further support of such a role, we detected HPV38 DNA in approximately 50% of nonmelanoma skin cancers, but only in 10% of healthy skin specimens (P < 0.001).