Clinical risk scores do not accurately identify a very high risk population with diffuse large B cell lymphoma-an analysis of 386 Portuguese patients.

The identification of high-risk patients deserving alternative first-line treatments to R-CHOP is a research priority in diffuse large B cell lymphoma (DLBCL). Despite the increasing recognition of biological features underlying aggressive behavior, clinical scores remain the basis for prognostic evaluation and treatment stratification in DLBCL. We performed a retrospective analysis of patients with DLBCL uniformly treated with immunochemotherapy with the aim of assessing the discriminative power of the NCCN international prognostic index (IPI) and the GELTAMO-IPI scores in risk group stratification and compared them with the IPI. Additionally, we investigated if bulky disease, gender, beta-2 microglobulin (ß2m), body mass index, and B-symptoms have independent prognostic impact. We confirmed the discriminative ability of the three prognostic scores in terms of progression-free survival and overall survival and found that the NCCN-IPI performs better in the identification of a high-risk population compared to the IPI and the GELTAMO scores. In an attempt to improve the prognostic power of the NCCN-IPI we analyzed additional clinical variables. Bulky disease and elevated ß2m were found to be independent predictors of prognosis when controlling for the NCCN-IPI risk groups. However, they seem to bring no incremental power to the latter in the identification of poor outcome patients. We support the use of the NCCN-IPI for the clinical identification of high-risk patients in DLBCL. Future studies to unravel the biological heterogeneity within NCCN-IPI groups are needed to improve risk prediction and design targeted therapies for poor prognosis patients.

Hypoadiponectinaemia in nonalcoholic fatty liver disease obese women is associated with infrequent intake of dietary sucrose and fatty foods.

BACKGROUND: The present study aimed to investigate the relationship between adiponectinaemia and food intake among obese women with nonalcoholic fatty liver disease (NAFLD). METHODS: In total, 60 obese women were examined by abdominal ultrasound for liver steatosis and subcutaneous and visceral adiposity. A standard interview (including questions about alcohol intake, medical history and physical activity), a physical examination (including height, weight, body mass index, waist and hip circumferences, waist-to-hip ratio, and body composition) and biochemical and clinical parameters (including serum glucose and insulin, homeostatic model assessment insulin resistance, lipid profile, aminotransferases, C-reactive protein, adiponectin, leptin, resistin, tumour necrosis factor-α, interleukin-6 levels and blood pressure) were performed. Food intake was evaluated by a qualitative food frequency questionnaire. RESULTS: Twenty-four NAFLD patients and thirty-six controls were analysed. The Mann-Whitney test showed lower adiponectin levels in the liver disease group compared to controls (P < 0.05). The Pearson correlation coefficient indicated that adiponectinaemia was negatively correlated with lipid profile and serum tumour necrosis factor-α (P = 0.05) and was positively associated with adiposity measures and serum leptin (P < 0.05). By simple linear regression, all of these variables predicted serum adiponectin levels. Chi-squared and Fisher's exact tests indicated that, in both groups, food intake showed no differences, although sucrose and fatty foods were associated with lower adiponectin levels in the liver disease group (P < 0.05 and P < 0.05, respectively), as well as in the control group (P = 0.05 and P < 0.05, respectively). CONCLUSIONS: Hypoadiponectinaemia in NAFLD was associated with dietary sucrose and fatty food intake, emphasising the important role of diet in the occurrence of this disease.

New chiral imidazolium ionic liquids from isomannide.

New chiral bis and mono-imidazolium ionic liquids derived from isomannide were synthesized. The structural features of the chiral organic cations impart a special arrangement of the chiral cavity. The new chiral chloride salts of isomannide derivatives are pivotal compounds for the synthesis of different organic ionic liquids. After metathesis different anions were associated to the chiral cations providing a new class of chiral ionic liquids.

Characterization of the volatile fraction emitted by Pinus spp. by one- and two-dimensional chromatographic techniques with mass spectrometric detection.

The chemical composition of the needles of P. pinea, P. pinaster, P. halepensis, P. nigra, P. brutia, P. patula, P. radiata, P. taeda, P. elliotti, P. kesiya, P. sylvestris and P. eldarica was investigated. Headspace solid-phase microextraction and steam distillation extraction were used to collect the volatile fractions. Samples were analyzed using one-dimensional gas chromatography (1D-GC) and comprehensive two-dimensional gas chromatography (GCxGC) associated with a quadrupole and a time-of-flight mass detectors. Results showed that the analytical capabilities of 1D-GC are partially limited by the separation power of the columns. The higher sensibility and the absence of peak skewing of the time-of-flight mass analyzer, with the use of automated peak finding and deconvolution algorithms, allowed for the detection of trace components with qualitative full spectra and the extraction of true mass spectra from coeluting compounds, promoting their reliable identification and thus significantly improving results obtained by 1D-GC/MS, when using a quadrupole mass analyzer. The use of GC x GC resulted in enhanced separation efficiency and increased signal to noise ratio (sensitivity) of the analytes, maximizing mass spectra quality and improving compound detection and identification. This work shows the use of 1D-GC/ToFMS for the analysis of pine needles volatiles, achieving the detection of 177 compounds, that is more than twice the number previously identified by standard 1D-GC/MS. The analysis by GC x GC for the same sample allowed the detection of 212 compounds. The enantioselective GC x GC analysis performed for all the Pinus spp. under study achieved the detection of 422 different compounds. Cross-over phenomena according to operational conditions are highlighted and discussed.

Correlation of serum leptin and insulin levels of pregnant protein-restricted rats with predictive obesity variables.

During pregnancy and protein restriction, changes in serum insulin and leptin levels, food intake and several metabolic parameters normally result in enhanced adiposity. We evaluated serum leptin and insulin levels and their correlations with some predictive obesity variables in Wistar rats (90 days), up to the 14th day of pregnancy: control non-pregnant (N = 5) and pregnant (N = 7) groups (control diet: 17% protein), and low-protein non-pregnant (N = 5) and pregnant (N = 6) groups (low-protein diet: 6%). Independent of the protein content of the diet, pregnancy increased total (F1,19 = 22.28, P < 0.001) and relative (F1,19 = 5.57, P < 0.03) food intake, the variation of weight (F1,19 = 49.79, P < 0.000) and final body weight (F1,19 = 19.52, P < 0.001), but glycemia (F1,19 = 9.02, P = 0.01) and the relative weight of gonadal adipose tissue (F1,19 = 17.11, P < 0.001) were decreased. Pregnancy (F1,19 = 18.13, P < 0.001) and low-protein diet (F1,19 = 20.35, P < 0.001) increased the absolute weight of brown adipose tissue. However, the relative weight of this tissue was increased only by protein restriction (F1,19 = 15.20, P < 0.001) and the relative lipid in carcass was decreased in low-protein groups (F1,19 = 4.34, P = 0.05). Serum insulin and leptin levels were similar among groups and did not correlate with food intake. However, there was a positive relationship between serum insulin levels and carcass fat depots in low-protein groups (r = 0.37, P < 0.05), while in pregnancy serum leptin correlated with weight of gonadal (r = 0.39, P < 0.02) and retroperitoneal (r = 0.41, P < 0.01) adipose tissues. Unexpectedly, protein restriction during 14 days of pregnancy did not alter the serum profile of adiposity signals and their effects on food intake and adiposity, probably due to the short term of exposure to low-protein diet.

Correlation of serum leptin and insulin levels of pregnant protein-restricted rats with predictive obesity variables

During pregnancy and protein restriction, changes in serum insulin and leptin levels, food intake and several metabolic parameters normally result in enhanced adiposity. We evaluated serum leptin and insulin levels and their correlations with some predictive obesity variables in Wistar rats (90 days), up to the 14th day of pregnancy: control non-pregnant (N = 5) and pregnant (N = 7) groups (control diet: 17 percent protein), and low-protein non-pregnant (N = 5) and pregnant (N = 6) groups (low-protein diet: 6 percent). Independent of the protein content of the diet, pregnancy increased total (F1,19 = 22.28, P < 0.001) and relative (F1,19 = 5.57, P < 0.03) food intake, the variation of weight (F1,19 = 49.79, P < 0.000) and final body weight (F1,19 = 19.52, P < 0.001), but glycemia (F1,19 = 9.02, P = 0.01) and the relative weight of gonadal adipose tissue (F1,19 = 17.11, P < 0.001) were decreased. Pregnancy (F1,19 = 18.13, P < 0.001) and low-protein diet (F1,19 = 20.35, P < 0.001) increased the absolute weight of brown adipose tissue. However, the relative weight of this tissue was increased only by protein restriction (F1,19 = 15.20, P < 0.001) and the relative lipid in carcass was decreased in low-protein groups (F1,19 = 4.34, P = 0.05). Serum insulin and leptin levels were similar among groups and did not correlate with food intake. However, there was a positive relationship between serum insulin levels and carcass fat depots in low-protein groups (r = 0.37, P < 0.05), while in pregnancy serum leptin correlated with weight of gonadal (r = 0.39, P < 0.02) and retroperitoneal (r = 0.41, P < 0.01) adipose tissues. Unexpectedly, protein restriction during 14 days of pregnancy did not alter the serum profile of adiposity signals and their effects on food intake and adiposity, probably due to the short term of exposure to low-protein diet.

Rice bran supplementation during nutritional recovery period of malnourished rats improves colon development.

OBJECTIVE: To investigate the colon's development in rats subjected to protein energy malnutrition followed by supplementation with rice bran. MATERIALS AND METHODS: Weaned Wistar male rats (21 days old), weight (40-50 g) were divided into two groups: diet with 17% protein (C; control group) or an aproteic diet (A; aproteic group), for 12 days. After this, 50% of the rats from each group were sacrificed. The remaining rats were further distributed in the three groups for a recovery (21 days): control (C) continued to receive the control diet whereas the aproteic group (A) received either a control diet (AC) or a control diet supplemented with 5% of rice bran (ARB). RESULTS: The A group showed alterations in the colon and cecum, excreted dry feces mass and fecal nitrogen, compared with C rats. In the proximal colon of A rats, the external muscularis and the width of the colon wall were higher whereas in the distal colon they were lower than C. After the recovery period, the relative cecum mass, colon mass and colon length of the recovered groups (AC and ARB) were higher than in the C group. Dry feces and fecal nitrogen excreted of the rats from recovered groups were lower than C group. Colon length of the AC group was lower than in the C group. Only the crypt's depth from ARB group was higher than in the C group. CONCLUSION: Control diet supplemented with 5% rice bran, reestablished the large intestine of aproteic rats. The recovery in the ARB group was even better than in the AC rats.

Comprehensive two-dimensional gas chromatography/mass spectrometric analysis of pepper volatiles.

The headspace compositions of 13 pepper and peppercorn samples of different species, colloquially also referred to as pepper, were analyzed, and more than 300 compounds were tentatively characterized by means of comprehensive two-dimensional gas chromatography in tandem with flame ionization detection, quadrupole mass spectrometric detection and time-of-flight mass spectrometric detection (GC x GC-FID, GC x GC/qMS and GC x GC/TOFMS, respectively). The analysis of volatile organic compounds (VOCs) was performed after solid-phase microextraction (SPME) using a 75-microm PDMS/DVB fibre. Fingerprint comparison between the three techniques permitted peaks to be assigned in the GC x GC-FID experiment based on the analogous MS analysis, taking into account retention shifts arising from method variations. When using GC x GC/TOFMS, about five times more peaks were identified than in GC x GC/qMS. Retention indices for all peaks were calculated in the bi-dimensional column set comprising of a 5% phenyl polysilphenylene-siloxane primary column and a polyethylene glycol second column. The spectra obtained by both mass detection techniques (qMS and TOFMS) give very similar results when spectral library searching was performed. The majority of the identified compounds eluted as pure components as a result of high-resolution GC x GC separations, which significantly reduces co-elution, and therefore increases the likelihood that pure spectra can be obtained. The differences between TOFMS and qMS (in fast scanning mode) spectra were generally small. Whilst spectral quality and relative ion ratios across a narrow peak (e.g. w(b) approximately 100-150 ms) do vary more for the fast peaks obtained in GC x GC/qMS operation, than with TOFMS, in general adequate spectral matching with the library can be achieved.

Characterization of the volatile fraction emitted by phloems of four pinus species by solid-phase microextraction and gas chromatography-mass spectrometry.

Pine forests constitute some of the most important renewable resources supplying timber, paper and chemical industries, among other functions. Characterization of the volatiles emitted by different Pinus species has proven to be an important tool to decode the process of host tree selection by herbivore insects, some of which cause serious economic damage to pines. Variations in the relative composition of the bouquet of semiochemicals are responsible for the outcome of different biological processes, such as mate finding, egg-laying site recognition and host selection. The volatiles present in phloem samples of four pine species, P. halepensis, P. sylvestris, P. pinaster and P. pinea, were identified and characterized with the aim of finding possible host-plant attractants for native pests, such as the bark beetle Tomicus piniperda. The volatile compounds emitted by phloem samples of pines were extracted by headspace solid-phase micro extraction, using a 2cm 50/30mm divinylbenzene/carboxen/polydimethylsiloxane table flex solid-phase microextraction fiber and its contents analyzed by high-resolution gas chromatography, using flame ionization and a non polar and chiral column phases. The components of the volatile fraction emitted by the phloem samples were identified by mass spectrometry using time-of-flight and quadrupole mass analyzers. The estimated relative composition was used to perform a discriminant analysis among pine species, by means of cluster and principal component analysis. It can be concluded that it is possible to discriminate pine species based on the monoterpenes emissions of phloem samples.

Colorectal cancer: lifestyle and dietary factors.

INTRODUCTION: Colorectal cancer is the most common tumor in the developed countries, and the number of new cases annualy is aproximately equal for men and women. Several environmental factors can interact in all steps of carcinogenesis. Lately the balance between genetic predisposition and these factors, including nutritional components and lifestyle behaviors, determines individual susceptibility to develop colorectal cancer. The aim of this study is to revise the references about lifestyle include diet, physical exercise, tobacco smoking and use of alcohol, and the risk of colorectal cancer in databases published during 1994-2004. DIETARY FACTORS: According to the reports high intake of red meat, and particularly of processed meat and positive energetic balance (high intake of total fat and carbohydrate) was associated with a moderate but significant increase in colorectal cancer risk. Convincing preventive factors include increase consumption of a wide variety of fruit and vegetable, particularly, dark-green leafy, cruciferous, a deep-yellow on tones, and fibre. LIFESTYLE: Physical activity as a means for the primary prevention of colorectal cancer. There is a probable synergic effect among physical inactivity, high energy intake and obesity and incidence of colorectal cancer. A growing body of evidence supports that avoidance overweight and the use of tobacco and alcohol is recommended to prevent colorectal cancer. CONCLUSION: Current data suggest that lifestyle modification including proper diet such as the ones rich in vegetable and poor in red meat and fat, regular physical activity and maintaining an appropriate body weight and avoiding the use of tobacco and alcohol may lead to reduce colorectal cancer risk.

Multiple sclerosis: long-term remission after a high dose of cyclophosphamide.

The objective of this case report is to document the possibility that immunoablative doses of cyclophosphamide may provide a long-term remission of multiple sclerosis (MS). We report the case of a 48-year-old woman with definite MS diagnosed in 1994 who has been in complete remission since a dose of 3800 mg of cyclophosphamide was accidentally given intravenously in early 1997. For 7 years there have been no signs of disease activity on history, physical examination, or on high-quality magnetic resonance imaging (MRI) with appropriate contrast-enhancement methodology. This case includes information on the possibility that less aggressive chemotherapy than that used with stem cell transplantation may be effective in the long-term control of MS.

Complementary use of hyphenated purge-and-trap gas chromatography techniques and sensory analysis in the aroma profiling of strawberries (Fragaria ananassa).

The aroma compositions of Fragaria ananassa varieties are assessed by purge-and-trap high-resolution gas chromatography. Gas chromatography/mass spectrometry and gas chromatography/Fourier transform infrared spectroscopy allow the identification of 93 components from which 21 are for the first time described as constituents of strawberry aroma. Despite the complexity of the aroma, sensory properties are assigned to 40 components as perceived by three independent testers by application of a sniffing technique to the chromatographic effluent. The data are used for comparative sensory characterization of strawberry varieties by means of principal component analysis.

Enhanced mucosal re-epithelialization induced by short chain fatty acids in experimental colitis.

The short chain fatty acids (SCFA) are the best nutrients for the colonocytes. Glucose is poorly used as a fuel but may be transformed into SCFA by colonic bacteria. The aim of this study was to investigate the effect of SCFA or glucose on experimental colitis. Colitis was induced in 30 Wistar rats by colonic instillation of 4% acetic acid. Five days later they were randomized to receive twice a day colonic lavage containing saline (controls, N = 10), 10% hypertonic glucose (N = 10) or SCFA (N = 10) until day 8 when they were killed. At autopsy, the colon was removed and weighed and the mucosa was evaluated macro- and microscopically and stripped out for DNA assay. Data are reported as mean +/- SD or median [range] as appropriate. All animals lost weight but there was no difference between groups. Colon weight was significantly lower in the SCFA group (3.8 +/- 0.5 g) than in the control (5.3 +/- 2.1 g) and glucose (5.2 +/- 1.3 g) groups (P<0.05). Macroscopically, the severity of inflammation was less in SCFA (grade 2 [1-5]) than in control (grade 9 [4-10]) and glucose-treated (grade 9 [2-10]) animals (P<0.01). Microscopically, ulceration of the mucosa was more severe in the glucose and control groups than in the SCFA group. The DNA content of the mucosa of SCFA-treated animals (8.2 [5.0-20.2] mg/g of tissue) was higher than in glucose-treated (5.1 [4.2-8.5] mg/g of tissue; P<0.01) and control (6.2 [4.5-8.9] mg/g of tissue; P<0.05) animals. We conclude that SCFA may enhance mucosal re-epithelialization in experimental colitis, whereas hypertonic glucose is of no benefit.

Enhanced mucosal re-epithelialization induced by short chain fatty acids in experimental colitis

The short chain fatty acids (SCFA) are the best nutrients for the colonocytes. Glucose is poorly used as a fuel but may be transformed into SCFA by colonic bacteria. The aim of this study was to investigate the effect of SCFA or glucose on experimental colitis. Colitis was induced in 30 Wistar rats by colonic instillation of 4 percent acetic acid. Five days later they were randomized to receive twice a day colonic lavage containing saline (controls, N = 10), 10 percent hypertonic glucose (N = 10) or SCFA (N = 10) until day 8 when they were killed. At autopsy, the colon was removed and weighed and the mucosa was evaluated macro- and microscopically and stripped out for DNA assay. Data are reported as mean + or -SD or median [range] as appropriate. All animals lost weight but there was no difference between groups. Colon weight was significantly lower in the SCFA group (3.8 + or - 0.5 g) than in the control (5.3 + or - 2.1 g) and glucose (5.2 + or - 1.3 g) groups (PP<0.05). Macroscopically, the severity of inflammation was less in SCFA (grade 2 [1-5]) than in control (grade 9 [4-10]) and glucose-treated (grade 9 [2-10]) animals (P<0.01). Microscopically, ulceration of the mucosa was more severe in the glucose and control groups than in the SCFA group. The DNA content of the mucosa of SCFA-treated animals (8.2 [5.0-20.2] mg/g of tissue) was higher than in glucose-treated (5.1 [4.2-8.5] mg/g of tissue; P<0.01) and control (6.2 [4.5-8.9] mg/g of tissue; P<0.05) animals. We conclude that SCFA may enhance mucosal re-epithelialization in experimental colitis, whereas hypertonic glucose is of no benefit

Bioequivalence assessment of diltiazem preparations by means of discriminant analysis of data from solid-phase extraction and liquid chromatography.

A solid-phase extraction technique for sample clean-up coupled with a new LC procedure is reported for the assay of diltiazem in plasma. The use of disposable cartridges provides selective extraction and easy automation. A new LC system based on LiChrospher RP 60 Select B columns is described. For routine analysis, the procedure provides a rapid simultaneous clean-up of several samples prior to chromatography and reproducible recoveries over a concentration range of 10-800 ng. The procedure was used to analyse the plasma samples from a bioequivalence study of three commercial diltiazem preparations. The pharmacokinetic parameters in 12 healthy male volunteers were determined and the assessment of bioequivalence was conducted by discriminant analysis.