Individual astringency responsiveness affects the acceptance of phenol-rich foods

Sensory responses greatly vary between individuals, and individual sensory experiences influence eating behaviour. Three groups responding differently to phenolic astringent stimuli (Low Responding, LR, n=20, Medium Responding, MR, n=37 and High Responding, HR, n=20) were identified from a population of 77 subjects, based on the maintenance vs fluctuation of salivary characteristics after repeated stimulation of the masticatory and taste/somatosensory systems. The effect of LR, MR and HR status on perceived astringency and liking for phenol-containing apple, grape and carrot juices spiked with increasing tannic acid (TA) concentrations was examined. TA induced a greater increase of perceived astringency in HR, compared to MR and LR subjects. A decrease in liking for spiked juices was found in HR and to a lesser extent in MR and LR subjects. No significant differences were found comparing MR and LR groups for both astringency intensity and liking data. Liking for and familiarity with 37 food items, as well as preference for 14 phenol-rich foods and beverages, each paired with a less astringent counter-product, were also examined. An internal preference map was computed on liking scores and product subgroups were identified. An effect of LR/HR status was found for two food subgroups consisting of coffee without sugar, tea without sugar, raw chicory and milk chocolate, tea with sugar, coffee with sugar. LR subjects rated the products with the most astringency higher and those with the least astringency lower than did HR subjects. LR subjects also rated their familiarity with highly astringent products higher than did HR subjects. Thus, individual differences related to the physiological salivatory response to oral stimulations affect responses to astringent stimuli and can influence the overall acceptability of phenol-rich food items.     

The efficacy and safety of bortezomib and dexamethasone as a maintenance therapy in patients with advanced multiple myeloma who are responsive to salvage bortezomib-containing regimens

BACKGROUND:

Although treatment for multiple myeloma (MM) has considerably improved in the past decade, MM continues to be an incurable hematological malignancy that causes most patients to eventually relapse and die from their illness. Thus, the identification of effective salvage strategies remains a priority.

METHODS:

In this trial, the authors evaluated the safety and efficacy of bortezomib and dexamethasone [V: on days 1 and 15 (1.3 mg/mq); D: on days 1‐2 and 15‐16, every 28‐day cycle until progression (20 mg/d)] as maintenance therapy (MT) in patients with advanced MM who responded to salvage therapy that used a bortezomib‐containing regimen.

RESULTS:

Forty‐nine MM patients were enrolled in this study between October of 2004 and April of 2008. All patients who were included in this study were responsive to a prior salvage therapy with bortezomib and had a measurable disease. The bortezomib and dexamethasone MT improved the quality of responses to complete remission in 4 patients and very good partial response in 3 patients. In addition, 10 patients experienced at least a 50% improvement in their symptoms. The median time to progression (TTP) was 16 months with a progression‐free survival of 61% after 1 year. The overall response after 1 year was 76%, and the cumulative incidence of death due to disease progression, which was adjusted for competitive risk events, was 14%. Non‐dose‐limiting toxicities included neuropathy (predominantly grade 1), herpes zoster reactivation, pneumonia, and gastrointestinal affections (constipation and diarrhea). Three patients developed grade 2 neuropathy, which required a bortezomib dose reduction to 1.0 mg/mq. No grade 3 or 4 toxicities were recorded.

CONCLUSIONS:

The use of bortezomib and dexamethasone as MT in advanced MM was effective and well tolerated. The twice‐monthly bortezomib infusion appeared to reduce the incidence of grade 3 and 4 neuropathies in comparison to similar experiences in other settings. Cancer 2011. © 2010 American Cancer Society.     

Urinary excretion of 1-pyrenol in automotive repair workers

Summary The urinary excretion of a pyrene metabolite was evaluated in 65 automotive repair workers whose skin was exposed to used mineral oils, and in 41 controls. Pyrene contents were determined in oily material taken from cloths used to clean various types of engines (n = 8) and were found to vary (mean ± SD) from 2.8 ± 0.4 ppm for dirty matter obtained from diesel truck engines to 9.3 ± 8.2 ppm for that from petrol car engines. Tobacco smoking and polycyclic aromatic hydrocarbon (PAH)-rich diets were considered as confounding factors. At both the beginning and the end of the working week, the values of urinary 1-pyrenol were slightly higher in exposed subjects (0.178 ± 0.150 and 0.194 ± 0.135 mol/mol creatinine on Monday and Friday, respectively) than in controls (0.124 ± 0.090 mol/mol creatinine) (Mann-Whitney test, z = 2.741, P < 0.01). The urinary 1-pyrenol values were higher in both smoking and non-smoking subjects than in controls. The highest values were found in urinary samples of smokers exposed to used mineral oils (0.259 ±0.201 mol/mol creatinine). In non-smoking workers (n = 40), post-shift 1-pyrenol values were 0.154 ± 0.105 ol/mol creatinine, as against 0.083 ± 0.042 mol/mol creatinine for the 19 non-smoking controls (Mann-Whitney test, z = 2.765, P < 0.01). In automobile repair workers, urinary 1-pyrenol values before the beginning of the weekly workshift did not differ substantially from those measured at the end of the week, not being related to the subjective degree of dirty skin as stated by workers. Multiple regression analysis between urinary metabolite levels and the three independent variables turned out to be statistically significant (r ² = 0.295, 0.246; F-test = 14.2, 11.1; P both < 0.01) for Monday and Friday urinary metabolite values and revealed that tobacco smoking had a greater influence (contribution to r ² = 16.1% and 18.3% on Monday and Friday, respectively) than occupational exposure (3.8% and 6.6%, respectively) on urinary levels of 1-pyrenol; the influence of PAH-rich foods on urinary pyrene metabolite levels was only detectable when subjects returned to work after the weekend (5.5%).Comparison between urinary excretion of 1-pyrenol in this group of workers and that found in professionally exposed subjects indicates that exposure to PAHs through contamination of the skin with used engine oil during automotive repair work is very low.     

Implications of gender differences for human health risk assessment and toxicology

This paper from The Human Health working group of SGOMSEC 16 examines a broad range of issues on gender effects in toxicology. Gender differences in toxicology begin at the gamete and embryo stage, continuing through development and maturation and into old age. Sex influences exposure, toxicokinetics, and toxicodynamics. The effects of sex have often been overlooked in both epidemiology and toxicology. In addition to the obvious modifying effects of the sex hormones and conditions affecting the male and female reproductive organs and sex roles, both genetic and hormonal effects influence many aspects of life and toxic responses. All aspects of toxicology should consider gender-balanced designs so that a more comprehensive understanding of differences and similarities can be obtained. Differential gene expression is a new frontier in toxicology. Risk assessment should account for gender and life cycle differences. The biological basis for altered sex ratios observed in several populations should be sought in animal models, and expanded to other compounds that might exert sex-selective effects. Wherever possible and feasible, toxicologic and environmental epidemiological studies should be designed and have sufficient statistical power to quantify differential gender-based exposures and outcomes.     

A phase 2 trial of fludarabine and mitoxantrone chemotherapy followed by yttrium-90 ibritumomab tiuxetan for patients with previously untreated, indolent, nonfollicular, non-Hodgkin lymphoma

BACKGROUND: A prospective, single-arm, open-label, nonrandomized Phase 2 study of combined fludarabine and mitoxantrone (FM) plus radioimmunotherapy was conducted to evaluate efficacy and safety in patients with untreated, indolent, nonfollicular non-Hodgkin lymphoma (NHL). METHODS: Between February 2005 and June 2006, at their institute, the authors treated 26 eligible patients with previously untreated, indolent, nonfollicular NHL (10 marginal zone lymphomas, 8 lymphoplasmacytic lymphomas, and 8 small lymphocytic lymphomas) using a novel regimen that consisted of 6 cycles of FM chemotherapy followed 6 to 10 weeks later by yttrium-90 (90Y) ibritumomab tiuxetan. RESULTS: After FM chemotherapy, the overall response rate was 80.5% and included a 50% complete remission (CR) rate (13 patients) and a 30.5% partial remission (PR) rate (8 patients). Of the 20 patients (13 with CR and 7 with PR) who were evaluable (at least a PR with normal platelet counts and bone marrow infiltration <25%) for subsequent 90Y ibritumomab tiuxetan, 100% obtained a CR at the end of the entire treatment regimen. At a median follow-up of 20 months, the estimated 3-year progression-free survival rate was 89.5%, and the estimated 3-year overall survival rate was 100%. The 90Y ibritumomab tiuxetan toxicity included grade >or=3 hematologic toxicity in 16 of 20 patients; the most common grade >or=3 toxicities were neutropenia (11 patients) and thrombocytopenia (16 patients) (adverse events were graded according to the World Health Organization criteria for toxicity). Transfusions of erythrocytes and/or platelets were given to 5 patients. CONCLUSIONS: The current study established the feasibility, tolerability, and efficacy of the FM plus 90Y ibritumomab tiuxetan regimen for the treatment of patients with untreated, indolent, nonfollicular NHL.     

Primary mediastinal large B-cell lymphoma (PMLBCL): long-term results from a retrospective multicentre Italian experience in 138 patients treated with CHOP or MACOP-B/VACOP-B

The optimal treatment of primary mediastinal large B-cell lymphoma (PMLBCL) is still undefined. In the absence of randomised studies, we retrospectively analysed: (a) the effectiveness of two chemotherapy regimens (CHOP vs MACOP-B/VACOP-B) in complete remission (CR) achievement and event-free survival (EFS) and (b) the role of mediastinal involved-field radiotherapy (IF-RT) as consolidation. From 1982 to 1999, 138 consecutive patients affected by PMLBCL were treated in 13 Italian institutions with CHOP (43) or MACOP-B/VACOP-B (95). The two groups of patients were similar as regard to age, gender, presence of bulky mediastinal mass, pleural effusion, stage and international prognostic indexes category of risk. Overall, 75.5% of patients in CR received IF-RT as consolidation. Complete remission was 51.1% in the CHOP group and 80% in MACOP-B/VACOP-B (P<0.001). Relapse occurred in 22.7% of CHOP- and in 9.2% of MACOP-B/VACOP-B-treated patients (n.s.). Event-free patients were 39.5% in CHOP and 75.7% in the MACOP-B/VACOP-B group (P<0.001). The addition of IF-RT as consolidation improved the outcome, irrespectively of the type of chemotherapy (P=0.04). At a multivariate analysis, achievement of CR (P<0.0001) and type of CT (MACOP-B/VACOP-B) retained the significance for OS (P=0.008) and EFS (P=0.03). In our experience, MACOP-B/VACOP-B appears to positively influence OS and EFS in patients affected by PMLBCL, as compared to CHOP. Consolidation IF-RT on mediastinum further improves the outcome of CR patients.     

Immunologic effector cells in head and neck cancer.

Freshly isolated tumor-infiltrating lymphocytes (TIL) and lymph node lymphocytes (LNL) in patients with head and neck cancer (HNC) often have low or undetectable functional responses. Because impaired ability of these cells to produce cytokines could be responsible for their functional incompetence, spontaneous and in vitro-induced production of interleukin-2 (IL2), interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and interferon gamma (IFN-gamma) by TIL, LNL from tumor-free as well as tumor-involved lymph nodes (LN), and peripheral blood lymphocytes (PBL) were measured. Although TIL or PBL of patients with HNC produced IL-1 beta and TNF-alpha spontaneously or after in vitro activation, LNL did not produce measurable levels of these cytokines. LNL also produced lower levels of IFN-gamma than PBL. In situ hybridization for cytokine mRNA performed with tumor tissues, and LN of patients with HNC showed that TIL as well as LNL localized in the immediate proximity of the tumor were activated, as evidenced by the expression of mRNA for IL2, IFN-gamma, IL-1 beta, TNF-alpha, and both alpha- and beta-chains of the IL2 receptor. In addition, many LNL located next to the tumor expressed mRNA for transforming growth factor-beta (TGF-beta). In contrast, LNL not adjacent to the tumor in involved LN, as well as those in tumor-uninvolved LN, did not express mRNA for cytokines or IL2 receptor.(ABSTRACT TRUNCATED AT 250 WORDS)     

Expression of mRNA for cytokines in tumor-infiltrating mononuclear cells in ovarian adenocarcinoma and invasive breast cancer.

Cytokine gene expression in tumor-infiltrating lymphocytes (TIL) in frozen-tissue sections of 2 types of human solid tumor--ovarian adenocarcinoma and invasive breast cancer--was examined by in situ hybridization with 35S-labeled cDNA probes for human cytokines. The proportion of cells containing mRNA able to hybridize to the antisense c-DNA probes for interleukin 2 (IL-2), tumor necrosis factor alpha (TNF alpha), interferon gamma (IFN gamma) or receptors for IL-2 (either p55 or p70) was also determined in human normal peripheral lymphoid tissues and inflammatory tissues. Few cells were positive for IL2 and TNF alpha mRNA in reactive human lymph nodes and tonsils. Inflammatory lesions, such as salpingitis or chronic active hepatitis, contained 10-20 times more cells positive for cytokine mRNA than reactive lymphoid tissue. In contrast, tumor-infiltrating lymphocytes (TIL) in the stroma of ovarian carcinomas or most ductal breast tumors only rarely expressed mRNA for TNF alpha, IL2 or IFN gamma. The intensity of mononuclear cell infiltration in these tumors correlated positively with the percentage of cells which expressed mRNA for IL-2, TNF alpha and IL-2R. In those ductal breast carcinomas which contained intracellular or intraductal mucins, up to 30% of lymphoid cells in the tumor stroma were positive for IL-2, TNF alpha, IFN gamma and IL-2R. Thus, strong evidence for local activation of mononuclear cells in situ, exemplified by the expression of genes for cytokines, was obtained only in inflammatory lesions and in mucin-producing breast carcinomas. In most carcinomas studied, few TIL expressed genes for cytokines as measured by in situ hybridization. Thus, human solid tumors appear to differ in their ability to induce gene expression for cytokines in TIL.