Apolipoprotein B48 metabolism in chylomicrons and very low-density lipoproteins and its role in triglyceride transport in normo- and hypertriglyceridemic human subjects.

BACKGROUND: Renewed interest in triglyceride-rich lipoproteins as causative agents in cardiovascular disease mandates further exploration of the integrated metabolism of chylomicrons and very low-density lipoproteins (VLDL). METHODS: Novel tracer techniques and an integrated multi-compartmental model were used to determine the kinetics of apoB48- and apoB100-containing particles in the chylomicron and VLDL density intervals in 15 subjects with a wide range of plasma triglyceride levels. RESULTS: Following a fat-rich meal, apoB48 appeared in the chylomicron, VLDL1 and VLDL2 fractions in all subjects. Chylomicrons cleared rapidly from the circulation but apoB48-containing VLDL accumulated, and over the day were 3-fold higher in those with high versus low plasma triglyceride. ApoB48-containing particles were secreted directly into both the chylomicron and VLDL fractions at rates that were similar across the plasma triglyceride range studied. During fat absorption, whilst most triglyceride entered the circulation in chylomicrons, the majority of apoB48 particles were secreted into the VLDL density range. CONCLUSION: The intestine secretes apoB48-containing particles not only as chylomicrons but also directly into the VLDL1 and VLDL2 density ranges both in the basal state and during dietary lipid absorption. Over the day, apoB48-containing particles appear to comprise about 20-25% of circulating VLDL and, especially in those with elevated triglycerides, form part of a slowly cleared 'remnant' particle population, thereby potentially increasing CHD risk. These findings provide a metabolic understanding of the potential consequences for increased CHD risk when slowed lipolysis leads to the accumulation of remnants, especially in individuals with hypertriglyceridemia.

Investigation of human apoB48 metabolism using a new, integrated non-steady-state model of apoB48 and apoB100 kinetics.

BACKGROUND: Triglyceride-rich lipoproteins and their remnants have emerged as major risk factors for cardiovascular disease. New experimental approaches are required that permit simultaneous investigation of the dynamics of chylomicrons (CM) and apoB48 metabolism and of apoB100 in very low-density lipoproteins (VLDL). METHODS: Mass spectrometric techniques were used to determine the masses and tracer enrichments of apoB48 in the CM, VLDL1 and VLDL2 density intervals. An integrated non-steady-state multicompartmental model was constructed to describe the metabolism of apoB48- and apoB100-containing lipoproteins following a fat-rich meal, as well as during prolonged fasting. RESULTS: The kinetic model described the metabolism of apoB48 in CM, VLDL1 and VLDL2 . It predicted a low level of basal apoB48 secretion and, during fat absorption, an increment in apoB48 release into not only CM but also directly into VLDL1 and VLDL2 . ApoB48 particles with a long residence time were present in VLDL, and in subjects with high plasma triglycerides, these lipoproteins contributed to apoB48 measured during fasting conditions. Basal apoB48 secretion was about 50 mg day-1 , and the increment during absorption was about 230 mg day-1 . The fractional catabolic rates for apoB48 in VLDL1 and VLDL2 were substantially lower than for apoB48 in CM. DISCUSSION: This novel non-steady-state model integrates the metabolic properties of both apoB100 and apoB48 and the kinetics of triglyceride. The model is physiologically relevant and provides insight not only into apoB48 release in the basal and postabsorptive states but also into the contribution of the intestine to VLDL pool size and kinetics.

Adverse effects of fructose on cardiometabolic risk factors and hepatic lipid metabolism in subjects with abdominal obesity.

BACKGROUND: Overconsumption of dietary sugars, fructose in particular, is linked to cardiovascular risk factors such as type 2 diabetes, obesity, dyslipidemia and nonalcoholic fatty liver disease. However, clinical studies have to date not clarified whether these adverse cardiometabolic effects are induced directly by dietary sugars, or whether they are secondary to weight gain. OBJECTIVES: To assess the effects of fructose (75 g day-1 ), served with their habitual diet over 12 weeks, on liver fat content and other cardiometabolic risk factors in a large cohort (n = 71) of abdominally obese men. METHODS: We analysed changes in body composition, dietary intake, an extensive panel of cardiometabolic risk markers, hepatic de novo lipogenesis (DNL), liver fat content and postprandial lipid responses after a standardized oral fat tolerance test (OFTT). RESULTS: Fructose consumption had modest adverse effects on cardiometabolic risk factors. However, fructose consumption significantly increased liver fat content and hepatic DNL and decreased ß-hydroxybutyrate (a measure of ß-oxidation). The individual changes in liver fat were highly variable in subjects matched for the same level of weight change. The increase in liver fat content was significantly more pronounced than the weight gain. The increase in DNL correlated positively with triglyceride area under the curve responses after an OFTT. CONCLUSION: Our data demonstrated adverse effects of moderate fructose consumption for 12 weeks on multiple cardiometabolic risk factors in particular on liver fat content despite only relative low increases in weight and waist circumference. Our study also indicates that there are remarkable individual differences in susceptibility to visceral adiposity/liver fat after real-world daily consumption of fructose-sweetened beverages over 12 weeks.

Fructose intervention for 12 weeks does not impair glycemic control or incretin hormone responses during oral glucose or mixed meal tests in obese men.

BACKGROUND AND AIMS: Incretin hormones glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP) are affected early on in the pathogenesis of metabolic syndrome and type 2 diabetes. Epidemiologic studies consistently link high fructose consumption to insulin resistance but whether fructose consumption impairs the incretin response remains unknown. METHODS AND RESULTS: As many as 66 obese (BMI 26-40 kg/m2) male subjects consumed fructose-sweetened beverages containing 75 g fructose/day for 12 weeks while continuing their usual lifestyle. Glucose, insulin, GLP-1 and GIP were measured during oral glucose tolerance test (OGTT) and triglycerides (TG), GLP-1, GIP and PYY during a mixed meal test before and after fructose intervention. Fructose intervention did not worsen glucose and insulin responses during OGTT, and GLP-1 and GIP responses during OGTT and fat-rich meal were unchanged. Postprandial TG response increased significantly, p = 0.004, and we observed small but significant increases in weight and liver fat content, but not in visceral or subcutaneous fat depots. However, even the subgroups who gained weight or liver fat during fructose intervention did not worsen their glucose, insulin, GLP-1 or PYY responses. A minor increase in GIP response during OGTT occurred in subjects who gained liver fat (p = 0.049). CONCLUSION: In obese males with features of metabolic syndrome, 12 weeks fructose intervention 75 g/day did not change glucose, insulin, GLP-1 or GIP responses during OGTT or GLP-1, GIP or PYY responses during a mixed meal. Therefore, fructose intake, even accompanied with mild weight gain, increases in liver fat and worsening of postprandial TG profile, does not impair glucose tolerance or gut incretin response to oral glucose or mixed meal challenge.

Increased proportion of mature NK cells is associated with successful imatinib discontinuation in chronic myeloid leukemia.

Recent studies suggest that a proportion of chronic myeloid leukemia (CML) patients in deep molecular remission can discontinue the tyrosine kinase inhibitor (TKI) treatment without disease relapse. In this multi-center, prospective clinical trial (EURO-SKI, NCT01596114) we analyzed the function and phenotype of T and NK cells and their relation to successful TKI cessation. Lymphocyte subclasses were measured from 100 imatinib-treated patients at baseline and 1 month after the discontinuation, and functional characterization of NK and T cells was done from 45 patients. The proportion of NK cells was associated with the molecular relapse-free survival as patients with higher than median NK-cell percentage at the time of drug discontinuation had better probability to stay in remission. Similar association was not found with T or B cells or their subsets. In non-relapsing patients the NK-cell phenotype was mature, whereas patients with more naïve CD56bright NK cells had decreased relapse-free survival. In addition, the TNF-α/IFN-γ cytokine secretion by NK cells correlated with the successful drug discontinuation. Our results highlight the role of NK cells in sustaining remission and strengthen the status of CML as an immunogenic tumor warranting novel clinical trials with immunomodulating agents.

Forages and Pastures Symposium: development of and field experience with drought-tolerant maize.

Drought-tolerant maize hybrids currently are being marketed by several seed suppliers. Such hybrids were developed by phenotypic and marker-assisted selection or through genetic modification and tested by exposing these hybrids to various degrees of water restriction. As drought intensifies, crop yields and survival progressively decline. Water need differs among plants due to differences in root structure, evaporative loss, capacity to store water or enter temporary dormancy, and plant genetics. Availability of water differs widely not only with rainfall and irrigation but also with numerous soil and agronomic factors (e.g., soil type, slope, seeding rates, tillage practices). Reduced weed competition, enhanced pollen shed and silk production, and deep, robust root growth help to reduce the negative impacts of drought. Selected drought-tolerant maize hybrids have consistently yielded more grain even when drought conditions are not apparent either due to reduced use of soil water reserves before water restriction or due to greater tolerance of intermittent water shortages. In DuPont Pioneer trials, whole plant NDF digestibility of maize increased with water restriction, perhaps due to an increased leaf to stem ratio. Efficiency of water use, measured as dry matter or potential milk yield from silage per unit of available water, responded quadratically to water restriction, first increasing slightly but then decreasing as water restriction increased. For grain production, water restriction has its greatest negative impact during or after silking through reducing the number of kernels and reducing kernel filling. For silage production, water restriction during the vegetative growth stage negatively impacts plant height and biomass yield. Earlier planting and shorter season maize hybrids help to avoid midsummer heat stress during pollination and can reduce the number of irrigation events needed. Although drought tolerance of maize hybrids has been improved due to genetic selection or biotech approaches, selecting locally adapted hybrids or crops, adjusting seeding rates, and modifying tillage and irrigation practices are important factors that can improve efficiency of use of available water by grain and forage crops.

Colorectal cancer in colonic Crohn's disease--high frequency of DNA-aneuploidy.

BACKGROUND: The risk of colorectal cancer (CRC) in colonic Crohn's disease (CCD) seems to be of the same magnitude as in extensive, longstanding ulcerative colitis (UC) and colonoscopic surveillance has been advocated. Mucosal dysplasia and DNA-aneuploidy are early warning markers of malignant transformation in UC. Data concerning the occurrence of such premalignant lesions in CCD are scarce. AIMS: The objective of this study was to investigate the DNA ploidy pattern in CCD-patients with manifest CRC, both in the tumour, as well as in the adjacent and distant colorectal mucosa. The results from DNA-flow cytometry analyses (FCM) prior to the development of a CRC in CCD were also investigated. MATERIALS AND METHODS: Biopsies obtained at colonoscopy and surgical specimens from 43 patients with colonic or ileocolonic CD developing CRC between 1988 and 1998 were reviewed. The CRC histological phenotype, and the occurrence of dysplasia were registered. CRC-tissue and tissue from areas with dysplasia adjacent to and/or distant from the tumour were obtained from paraffin-embedded blocks and were analysed by FCM after preparation. RESULTS: Twenty-four CRCs in 21 patients (14 men) were suitable for FCM-analyses. The median age at CRC-diagnosis was 53 years (21-73) and the median CCD-duration was 14.5 years (1-50). A predominance of CRC was found either in the cecum (9124) or in the rectum (7/24). DNA-aneuploidy was found in 62.5% (15/24) of the tumours, in 25% (2/8) in adjacent and/or distant mucosa, and in 50% (2/4) of the patients that had been subjected to colonoscopic surveillance prior to the CRC-diagnosis. In 7patients (29%), definite dysplasia was detected adjacent to andlor distant from the tumour. Of the 6 patients undergoing colonoscopic surveillance, 3 (50%) displayed definite dysplasia prior to the colectomy. CONCLUSION: Since DNA- aneuploidy is a' common feature in CRCs in CCD and precede the development of invasive carcinoma, inclusion of FCM-analyses of colorectal biopsies may enhance the sensitivity of identifying high-risk CCD-patients prone to develop CRC within the frame of colonoscopic surveillance programs.

Effect of high-oil corn on growth performance, diet digestibility, and energy content of finishing diets fed to beef cattle.

Sixty crossbred beef steers (initial BW = 412 kg) were used in a 83-d finishing study to determine the effect of feeding dry rolled high-oil corn on performance and total-tract digestibility of finishing diets. Steers were allotted by weight to the following dietary treatments: 1) control corn (C; 82% normal corn, 12% triticale silage), 2) high-oil corn (HO; 82% high-oil corn, 12% silage), and 3) high-oil corn formulated to be isocaloric to C (ISO; 74% high-oil corn, 20% silage). Total lipid content was 4.9% (DM basis) for normal corn and 7.0% for high-oil corn. Steers were individually fed using electronic gates. Quantity of feed offered and refused was recorded daily. Fecal samples were collected on d 63 to 66 of the trial to determine digestibility. Chromic oxide was fed as an indigestible marker for 7 d before fecal collection began. Planned contrasts of HO vs C and ISO vs C were used to assess treatment differences. Dry matter intake was greater for steers fed C vs HO (P < 0.01) or C vs ISO (P < 0.01), but daily gain and feed efficiency were not affected (P > 0.05) by treatments. Digestibility of DM, OM, starch, and GE was greater (P < 0.05) for the HO diet than the C diet, but lipid digestibility did not differ among treatments (P > 0.05). The combined effect of greater GE content and digestibility resulted in greater (P < 0.01) DE content for the HO than for the C diet. Calculated DE of the corn was 8.3% greater (3.74 Mcal/kg; P < 0.01) for the HO diet and 6.5% greater (3.67 Mcal/kg; P < 0.01) for the ISO diet than the corn in the C diet (3.25 Mcal/kg). Dry matter and GE digestibility did not differ (P > 0.05) between the C and ISO diets. Steers consuming ISO had greater (P < 0.05) starch digestibility than steers fed the C diet. Although HO had higher DE, DE intake was similar (P > 0.05) for HO and C due to lower DMI for HO. These results indicate that available energy is greater from high-oil corn than from typical corn, but depressed voluntary feed intake prevented performance improvements and resulted in equal energy intakes between high-oil corn and typical corn diets.

Airway flow dynamics and voice acoustics after autologous fascia augmentation of paralyzed vocal fold.

The aim of this study was to assess the effect of vocal fold medialization, accomplished by injection of autologous fascia, on airflow dynamics and voice acoustics. Ten patients with unilateral vocal fold paralysis were included. Flow-volume spirometry, body plethysmography, and acoustic analysis of voice were performed within 1 week before injection of autologous fascia and 4 to 14 months after operation. Medialization of the paralyzed vocal fold decreased the mean peak inspiratory flow (PIF) from 4.63 L to 4.10 L (p = .012). The acoustic characteristics of the voice improved: the values of jitter, shimmer, and mean noise-to-harmonics ratio decreased significantly (p = .006, p = .017, and p = .047, respectively), and the mean maximal phonation time almost doubled (p = .002). Changes in PIF and shimmer showed a negative correlation (r = -.857, p = .007). In conclusion, injection of autologous fascia improves voice acoustics, but induces a slight abnormal limitation on PIF. The results also suggest that improvement in voice acoustics is most prominent in subjects with the least deterioration in inspiratory airflow.

Voice acoustics after autologous fascia injection for vocal fold paralysis.

OBJECTIVES: The present study was carried out to assess the impact of fascial injection on voice acoustics Preliminary results had suggested that voice, as rated by a panel of listeners, was significantly improved after autologous fascia augmentation of a paralyzed vocal fold. STUDY DESIGN: A prospective study among patients with unilateral vocal fold paralysis was carried out. Eighteen subjects were analyzed 9 months (mean) after the procedure. METHODS: The preoperative and postoperative samples of vowel /a/ were analyzed by Key Elemetrics (Lincoln Park, NJ). Computerized Speech Lab. RESULTS: There was a significant improvement (P<.05) in all parameters measured, including jitter, shimmer, noise-to-harmonic ratio, and maximum phonation time. No laryngeal complications were seen. CONCLUSIONS: According to these preliminary results, vocal fold augmentation by an injection of autologous fascia seems a simple, inexpensive, reliable and safe method to restore voice quality after unilateral vocal fold paralysis.

Effect of inoculation rate of selected strains of lactic acid bacteria on fermentation and in vitro digestibility of grass-legume forage.

Grass-legume forage was used to evaluate the effect of inoculation rate of selected strains of lactic acid bacteria on fermentation and in vitro digestibility during 57 d of ensiling. Chopped forage (DM = 28%) was ensiled in 4 to 6-kg quantities and treated as: 1) control, 10(3) epiphytic lactic acid bacteria; 2) 10(5) added lactic acid bacteria; and 3) 10(6) added lactic bacteria/g of wet forage. Samples were obtained for analyses on d 0, 1, 2, 3, 6, 10, 14, 29, and 57 of fermentation. Treated silages were observed to have: 1) greater quantities of lactic acid bacteria, 2) a greater proportion of homofermentative lactic acid bacteria, and 3) lactic acid bacteria with greater biological activity. Addition of each amount of lactic acid bacteria: 1) increased the rate of utilization of water-soluble carbohydrate and decline in pH, 2) limited the formation of NH3 N, and 3) increased the in vitro digestibility of DM and ADF. No differences were observed in the lactic acid content of the silages after 57 d of fermentation.

Concentrations of cadmium and other metals in Fucus vesiculosus L. and Fontinalis dalecarlica Br. Eur. from the northern Baltic Sea and the southern Bothnian Sea.

Concentrations of Cd and ten other metals (Al, Co, Cr, Cu, Fe, Mn, Ni, Pb, V and Zn) were determined in the brown seaweed Fucus vesiculosus L. and the aquatic moss, Fontinalis dalecarlica Br. Eur. from the northern Baltic Sea and the southern Bothnian Sea. Elevated concentrations of metals were found in samples taken close to densely populated areas, such as Stockholm and Nynäshamn. Very high concentrations of especially Zn were found in both Fucus and Fontinalis samples taken from the area south of the Gulf of Gävle. The results indicate that mining and industrial activities along the river Dalälven are the main sources of Zn and several other metals. Cd concentrations in Fucus plants reached maximum values (24.5 mg kg(-1)) at the northern site. The gradual increase of Cd concentrations in Fucus plants northward could not be totally explained by the salinity gradient in the Baltic Sea; reasons for this are discussed in this paper.

Studies on metal content in the brown seaweed, Fucus vesiculosus, from the Archipelago of Stockholm.

Concentrations of eleven metals (Al, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, V and Zn) were determined in the brown seaweed Fucus vesiculosus collected from the Archipelago of Stockholm. Several factors which influence the metal content in the seaweed have been studied, including errors caused by epiphytes, sea exposure and differences depending on which part of the seaweed is analysed. It is concluded that, if all these factors are considered, Fucus vesiculosus plants are excellent bio-indicators of metal pollution. This is also demonstrated by a significant increase in metal content in transplanted Fucus vesiculosus near the city of Stockholm. The results from this investigation also indicate increasing metal concentrations, especially Cd, in samples from the northern parts of the Archipelago and the reason for this is discussed.

Results of surgical treatment of lung metastases in children.

Between 1970 and 1979, 14 patients were operated on for pulmonary metastases. In 9 of these the primary tumour was a Wilms' nephroblastoma. Five out of the 14 patients are presently alive and free from disease (3 to 10 years after pulmonary resection). Primary tumours of the survivors were Wilms' tumour in 3 cases, an ovarian teratoma in one patient and a Ewing's sarcoma in one patient. Two of survivors had bilateral involvement and one had multiple metastases of one lung with pleural exudation. The disease-free interval was the same among the survivors and the non-survivors. It is apparent from the present material that some patients with a very poor prognosis as predicted from different prognostic factors can be cured after surgical excision of the metastases. The surgical procedure in children involves a very small risk and only moderate discomfort. An active surgical approach is therefore recommended.

Blood oxygen tension and oxyhemoglobin saturation in hypoxemia due to right to left shunt or low inspired oxygen concentration. An experimental study of the effects of changes in blood oxygen affinity.

Oxygen tension, oxyhemoglobin saturation, and pH were measured in arterial and in venous blood from heart, brain, kidney, liver, gut and pulmonary artery in anesthetized hypoxemic dogs during a reduction of blood oxygen affinity due to increasing acidosis caused by the administration of CO2 and NH4Cl (pH range 7.40-6.80). In dogs with hypoxemia due to right to left shunt (anastomosis between inferior vena cava and left atrium), a reduction in blood oxygen affinity was followed by increasing Pao2 and Pvo2 at unchanged Sao2. In dogs with hypoxemia caused by alveolar hypoxia, or a combination of alveolar hypoxia and right to left shunt, a reduction of blood oxygen affinity was followed by arterial and venous desaturation at unchanged Pao2 values. Infusions of sodium bicarbonate or blood transfusions with reduced 2,3-diphosphoglycerate (2,3-DPG)-concentrations, if given to patients suffering from hypoxemia due to right to left shunt, may reduce the Pao2. Such therapy should be prescribed with caution.

Paravertebral widening in a case of recurrent Wilms' tumour.

In infants and children the association of paravertebral widening and abdominal tumour has been regarded as typical of neuroblastoma. However, a paraspinal mass may develop in other malignant tumours too, but seems to be extremely rare in nephroblastoma. The fourth case so far on record is reported. Microscopically the tumour was of the sarcomatous clear cell variant.