The influence of lycopene on the proliferation of human breast cell line (MCF-7).

Lycopene, a non-provitaminic carotenoid, present in many fruit and vegetables, such as tomatoes and their processed products, has been associated with decreased risk of chronic diseases including cancer. The influence of lycopene on the proliferation of the breast tumour cell line (MCF-7) was tested using MTT and BrdU assays at different time intervals (from 24 to 72h) and dose-response (from 0.125 to 100muM). The induction of Gap Junction Intercellular Communication (GJIC) was evaluated by dye-transfer assay using Lucifer Yellow on monolayer cells treated with different lycopene concentrations (from 0.125 to 5muM) for 6 to 48h. The Minimal Inhibitory Concentration (MIC) of lycopene was of 5muM, after a 24h exposure. A prolonged exposure time (72h) induced a similar inhibitory effect. Lycopene stimulated the functionality of GJIC at concentrations of 1muM after 24h and this effect was dose-dependent. The induction of GJIC by lycopene was confirmed by an increased expression of connexin 43. Collectively, the above data confirm the inhibitor effects of lycopene on MCF-7 cell growth and suggest that lycopene is involved in the modulation of the gap junction intercellular communication in this cell line, as observed for other cancer cell lines.     

Hydrogen breath test for diagnosis of lactose malabsorption: the importance of timing and the number of breath samples.

BACKGROUND: The hydrogen breath test (H(2)BT) is the most widely used procedure in the diagnostic workup of lactose malabsorption and lactose intolerance. AIM: To establish whether a simplified two- or three-sample test may reduce time, costs and staff resources without reducing the sensitivity of the procedure. PATIENTS AND METHODS: Data from 1,112 patients (292 men, 820 women) with a positive 4 h, nine-sample H(2)BT were retrospectively analyzed. Patients were stratified according to the degree of lactose malabsorption, the occurrence and type of symptoms. Loss of sensitivity in the procedure was evaluated taking into account two-sample tests (0 min and 120 min or 0 min and 210 min) or three-sample tests (0 min, 120 min and 180 min or 0 min, 120 min and 210 min). RESULTS: Using a two-sample test (0 min and 120 min or 0 min and 210 min) the false-negative rate was 33.4% and 22.7%, respectively. With a three-sample test (0 min, 120 min and 180 min or 0 min, 120 min or 210 min), lactose malabsorption was diagnosed in 91.2% (1,014 of 1,112) patients and in 96.1% (1,068 of 1,112) patients, respectively. Of 594 patients with abdominal symptoms, 158 (26.6%) and 73 (12.2%) would have false-negative results with 0 min and 120 min or 0 min and 210 min two-sample tests, respectively. The three-sample tests, 0 min, 120 min and 180 min or 0 min, 120 min and 210 min, have a false-negative rate of 5.9% and 2.1%, respectively. CONCLUSIONS: A three-sample H(2)BT is time- and cost-sparing without significant loss of sensitivity for the diagnosis both of lactose malabsorption and lactose intolerance.     

Erwiderung an Saul

Ohne Zusammenfassung     

Metallothionein (I+II) confers, via c-myc, immune plasticity in oldest mice: model of partial hepatectomy/liver regeneration

Because of its similarity to ageing in impaired immune efficiency 48 h after surgical procedures on young partially hepatectomised mice, partial hepatectomy/liver regeneration (pHx) provides a good model for the study of inflammation in ageing. In old age, high metallothionein (I+II) (MT) sequesters a substantial number of intracellular zinc ions consequently leading to low zinc ion bioavailability for an adequate immune response. Corticosterone and IL-6 affect MTmRNA induction in inflammation and after pHx against oxidative damage. The aim of this study was to investigate the role played by MT in conferring immune plasticity in ageing and in very old age using the pHx model. 48 h after their partial hepatectomy, the crude zinc balance was negative in young, old and very old mice coupled with increased MT, corticosterone, sIL-6R and IL-6. Concomitantly, Natural Killer (NK) cell activity and IL-2 production decreased. Complete restoration of the nutritional-endocrine-immune parameters occurred 15 days from the surgical procedures in young and very old mice, but not in old or transgenic mice overexpressing MT. A significant positive or inverse correlation among nutritional-endocrine-immune parameters exists in young and very old mice, but not in old mice during liver regeneration. Since MT also affects c-myc, the gene expression of c-myc declines from 48 h to days 7 and 15 after pHx in young and very old mice, but remains constantly high in old pHx mice for the same days. This circumstance leads to the appearance of tumours in the long run in old pHx mice and survival times that are shorter than old sham controls. Because complete remodelling also occurs in IL-6 and in sIL-6R in very old mice during liver regeneration, the pre-existing inflammation is not detrimental in very old age. As such, very old mice are still responsive to large inflammation, such as pHx, thanks to correct MT homeostasis. Correct MT homeostasis, via c-myc, is therefore pivotal in both suitable liver regeneration and in conferring immune plasticity with subsequent successful ageing. High MT plays an extremely harmful role in ageing: on one hand it lowers zinc ion bioavailability levels required for immune efficiency and on the other hand it increases c-myc expression. The combination of immune depression and enhanced c-myc, via high MT, may trigger the appearance of age-related degenerative diseases.     

Trisomy 8 in myelodysplasia and acute leukemia is constitutional in 15-20% of cases.

The trisomy 8 found in malignancies may derive from a constitutional trisomy 8 mosaicism (CT8M), and in these cases the trisomy itself may be regarded as the first mutation in a multistep carcinogenetic process. To assess the frequency of CT8M in hematological dysplastic and neoplastic disorders with trisomy 8, an informative sample of 14 patients was collected. The data ascertained included chromosome analyses of fibroblast cultures and of PHA-stimulated blood cultures in patients with normal blood differential count, as well as possible CT8M clinical signs. One patient showed trisomy 8 in all cell types analyzed and undoubtedly has a CT8M; a second patient consistently showed trisomy 8 in PHA-stimulated blood cultures when no immature myeloid cells were present in blood and should be considered as having CT8M; a third patient, with Philadelphia-positive chronic myelocytic leukemia, was more difficult to interpret, but the possibility that she had CT8M is likely. A few clinical signs of CT8M were also present in these three patients. Our data indicate that the frequency of CT8M in hematological dysplastic and neoplastic disorders with trisomy 8 is approximately 15-20%.     

Extensible endoprostheses of the humerus after resection of bone tumours

We carried out extensible endoprosthetic replacement of the proximal or total humerus in 18 children aged between six and 12 years, after resection of primary bone tumours mainly for osteosarcoma and Ewing's sarcoma. In 11 patients we performed 44 lengthening procedures, with an average of two per child annually and a mean total extension of 29.9 mm per patient. We were able to achieve lengthening of the operated limb with few complications and a mean functional rating of 79.3% according to the Enneking system. Progressive lengthening of these prostheses does not adversely affect the overall function of the arm, and superior subluxation of the head of the prosthesis has not been a problem.     

Assessment of volume preservation performed before or after partial nephrectomy accurately predicts postoperative renal function: Results from a prospective multicenter study

Purpose

Partial nephrectomy (PN) is standard for small renal masses, improving renal function by preserving renal parenchyma compared with radical nephrectomy. Recent work demonstrated that postoperative surgeon assessment of volume preservation (SAVP) and 3D imaging measurements agree and correlate with postoperative function. We hypothesize preoperative assessment of volume preservation (PAVP) with PN based on preoperative imaging will reliably indicate postoperative renal function.

The relation of rhinitis to recurrent cough and wheezing: a longitudinal study

BACKGROUND: Recurrent cough can be a clinical manifestation of rhinitis. However, it remains unclear if the association between rhinitis and recurrent cough among children is independent of asthma. OBJECTIVE: The aim of the present study was to determine, in a large longitudinal cohort, whether rhinitis is significantly associated with recurrent cough alone, wheezing alone, or the combination of both symptoms during childhood. METHODS: We investigated determinants of recurrent cough, with or without wheezing, using longitudinal data from the Tucson Children's Respiratory Study. Among the 1246 subjects originally enrolled, 1024 children completed at least one questionnaire between the ages of 6 and 18 years and were included in the present study. In any survey, wheezing was defined as at least one wheezing episode during the past year and recurrent cough as two or more coughing episodes lasting at least 1 week without a cold during the past year. Generalized estimating equations were used to determine significant risk factors. RESULTS: After adjusting for sex, skin test reactivity and parental asthma, both rhinitis (OR = 2.47 CI = 1.84, 3.30) and sinusitis (OR = 1.54 CI = 1.11, 2.14) were associated with an increased risk of recurrent cough plus wheezing. The OR associated with rhinitis were significantly reduced for subjects reporting only recurrent cough or only wheezing (OR = 1.43, CI = 1.03, 1.99; and OR = 1.30, CI = 1.07, 1.58, respectively). Recurrent cough and wheezing, when examined independently, showed different patterns of risk factors. CONCLUSION: We found rhinitis to be an independent risk factor for both recurrent cough and wheezing during childhood. Different pathways may be involved in the association of rhinitis with recurrent cough and wheezing.     

Sensitivity to inhibition by β-chemokines correlates with biological phenotypes of primary HIV-1 isolates

Primary HIV-1 isolates were evaluated for their sensitivity to inhibition by β-chemokines RANTES (regulated upon activation, normal T-cell expressed and secreted), macrophage inflammatory protein 1α (MIP-1α), and MIP-1β. Virus isolates of both nonsyncytium-inducing (NSI) and syncytium-inducing (SI) biological phenotypes recovered from patients at various stages of HIV-1 infection were assessed, and the results indicated that only the isolates with the NSI phenotype were substantially inhibited by the β-chemokines. More important to note, these data demonstrate that resistance to inhibition by β-chemokines RANTES, MIP-1α, and MIP-1β is not restricted to T cell line-adapted SI isolates but is also a consistent property among primary SI isolates. Analysis of isolates obtained sequentially from infected individuals in whom viruses shifted from NSI to SI phenotype during clinical progression exhibited a parallel loss of sensitivity to β-chemokines. Loss of virus sensitivity to inhibition by β-chemokines RANTES, MIP-1α, and MIP-1β was furthermore associated with changes in the third variable (V3) region amino acid residues previously described to correlate with a shift of virus phenotype from NSI to SI. Of interest, an intermediate V3 genotype correlated with a partial inhibition by the β-chemokines. In addition, we also identified viruses sensitive to RANTES, MIP-1α, and MIP-1β of NSI phenotype that were isolated from individuals with AIDS manifestations, indicating that loss of sensitivity to β-chemokine inhibition and shift in viral phenotype are not necessarily prerequisites for the pathogenesis of HIV-1 infection.