Consequences of dietary calcium and phosphorus depletion and repletion feeding sequences on growth performance and body composition of growing pigs.

The effect of a calcium (Ca) and phosphorus (P) depletion and repletion strategy was studied in four consecutive feeding phases of 28 days each. In all, 60 castrated male pigs (14±1.6 kg initial BW) received 60% (low (L) diet; depletion) or 100% (control (C) diet; repletion) of their Ca and digestible P requirements according to six feeding sequences (CCCC, CCCL, CLCC, CCLC, LCLC and LLLL; subsequent letters indicate the diet received in phases 1, 2, 3 and 4, respectively). Pigs bone mineral content in whole-body (BMCb) and lumbar vertebrae L2 to L4 (BMCv) was measured in every feeding phase by dual-energy X-ray absorptiometry. Growth performance was slightly (<10%) affected by depletion, however, dietary treatments did not affect overall growth. Compared with control pigs, depletion reduced BMCb (34%, 38%, 33% and 22%) and BMCv (46%, 54%, 38% and 26%) in phases 1 to 4, respectively. Depletion increased however digestible P retention efficiency from the second to the fourth phases allowing LLLL pigs to present no differences in BMCb and BMCv gain compared with CCCC pigs in phase 4. Growth performance in repleted compared with control pigs was lower in phase 2, was no different in phase 3 and was lower in CLCC pigs in phase 4. Repletion increased body P and Ca retention efficiency when compared with control pigs (respectively, 8% and 10% for LC v. CC, P<0.01; 8% and 10% for CLC v. CCC, P<0.10; 18% and 25% for CLCC, CCLC, LCLC v. CCCC, P<0.001). Moreover, BMCv gain was higher in CLC pigs (P<0.001) and gains of body P, Ca, BMCb and BMCv in phase 4 were also higher in repleted than in CCCC pigs (respectively, 14%, 20%, 20% and 52%; P⩽0.02). Repletion reduced body P, Ca, BMCb and BMCv masses in phase 2 but no differences were found in phase 4 compared with control pigs. Lumbar vertebrae L2 to L4 bone mineral content was more sensitive to depletion and repletion sequences than BMCb especially in the first phase probably due to a higher proportion of metabolically active trabecular bone in vertebrae than in the whole skeleton. Dietary Ca was, however, oversupply in L compared with C diets (3.1 v. 2.5 Ca:digestible P ratio, respectively) suggesting that P has probably driven the regulations. Phosphorus and Ca depletion and repletion increases dietary P utilization efficiency and can help to reduce dietary P supply, but the underlying mechanisms need elucidation before its practical application.

Down-regulation of IL-8 by high-dose vitamin D is specific to hyperinflammatory macrophages and involves mechanisms beyond up-regulation of DUSP1.

BACKGROUND AND PURPOSE: There is current interest in vitamin D as a potential anti-inflammatory treatment for chronic inflammatory lung disease, including cystic fibrosis (CF). Vitamin D transcriptionally up-regulates the anti-inflammatory gene DUSP1, which partly controls production of the inflammatory chemokine IL-8. IL-8 is overabundant in CF airways, potentially due to hyperinflammatory responses of CF macrophages. We tested the ability of vitamin D metabolites to down-regulate IL-8 production in CF macrophages. EXPERIMENTAL APPROACH: CF and healthy monocyte-derived macrophages (MDM) were treated with two vitamin D metabolites, 25-hydroxyvitamin D3 (25OHD3 ) and 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3 ), or paricalcitol, synthetic analogue of 1,25(OH)2 D3 . 25OHD3 was tested at doses of 25-150 nM, whereas 1,25(OH)2 D3 and paricalcitol at doses of up to 100 nM. IL-8 was stimulated by bacterial virulence factors. As potential anti-inflammatory mechanism of vitamin D metabolites, we assessed up-regulation of DUSP1. KEY RESULTS: MDM from patients with CF and some healthy donors showed excessive production of stimulated IL-8, highlighting their hyperinflammatory phenotype. Vitamin D metabolites down-regulated stimulated IL-8 only in those hyperinflammatory MDM, and only when used at high doses (>100 nM for 25OHD3 , or >1 nM for 1,25(OH)2 D3 and paricalcitol). The magnitude of IL-8 down-regulation by vitamin D metabolites or paricalcitol was moderate (∼30% vs. >70% by low-dose dexamethasone). Transcriptional up-regulation of DUSP1 by vitamin D metabolites was seen in all tested MDM, regardless of IL-8 down-regulation. CONCLUSIONS AND IMPLICATIONS: Vitamin D metabolites and their analogues moderately down-regulate IL-8 in hyperinflammatory macrophages, including those from CF. This down-regulation appears to go through DUSP1-independent mechanisms.

Effect of reduced dietary calcium concentration and phytase supplementation on calcium and phosphorus utilization in weanling pigs with modified mineral status.

The present study was conducted to assess the effect of 2 dietary Ca concentrations on P and Ca digestive and metabolic utilization in weanling pigs fed diets providing practical concentrations of P, with or without phytase. The responses of pigs fed diets adequate or moderately deficient in Ca and P postweaning were compared. A total of 60 pigs weaned at 28 d of age were used. Two groups of 30 pigs with differing mineral status resulted from a 10-d depletion period, during which the animals received depletion diets (DD) that consisted of corn-soybean meal with either 1.42% Ca and 0.80% P (DD+) or 0.67% Ca and 0.43% P (DD-), designed to achieve the same Ca:digestible P ratio. At the end of the depletion period, a plasma sample was taken from each pig and 12 pigs (6 from each group) were slaughtered for bone assessment to establish the baseline mineral status. The animals fed the DD- diet had signs of P deficiency with reduced plasma P (13%; P < 0.01) and femur ash concentration (8%; P < 0.05), and increased plasma Ca (9%; P < 0.05) and alkaline phosphatase activity (31%; P < 0.01). For the subsequent 25-d period, the remaining 24 pigs from each group were fed 1 of 4 repletion diets: 1) 0.56% P, 1.06% Ca; 2) 0.56% P, 0.67% Ca; 3) diet 1 + 1,000 phytase units (FTU) of Natuphos phytase/kg; and 4) diet 2 + 1,000 FTU of Natuphos phytase/kg. Total feces and urine were collected from d 5 to 11, and a blood sample was taken from each pig at d 11 and 25. The initial moderate P deficiency (DD-) stimulated Ca absorption (5%; P < 0.01), irrespective of the repletion diet, and stimulated P absorption (5%; DD x phytase, P < 0.05), only when the diets contained phytase. At the end of the repletion period, because of these compensatory phenomena, the depleted pigs achieved full recovery of femur DM and ash weight when they received phytase, whereas ash concentration tended to remain reduced by 3% (P = 0.08). Phosphorus digestibility was improved in the diets supplemented with phytase (73.0 vs. 56.0%; P < 0.001), whereas an increase in dietary Ca decreased P digestibility (65.6 vs. 63.4%; P < 0.05). Those 2 effects were independent, indicating that dietary Ca reduced equally P digestibility with and without phytase and did not influence the efficiency of phytase in releasing P in the digestive tract. In pigs fed diets with phytase, however, the reduction of Ca (Ca:P from 1.9 to 1.3) increased urinary P losses 5-fold. Those extra losses were due to a lack of Ca for skeleton ash deposition, resulting in a 4% reduction in femur ash concentration. In the end, reducing the dietary Ca:P from 1.9 to 1.3 in a practical diet containing 0.56% P did not improve the efficiency of phytase in releasing P. Moreover, the reduction in dietary Ca (Ca:P) caused an imbalance between Ca and P that impaired bone mineralization.

Phase 3 randomized trial on larynx preservation comparing sequential vs alternating chemotherapy and radiotherapy.

BACKGROUND: Both induction chemotherapy followed by irradiation and concurrent chemotherapy and radiotherapy have been reported as valuable alternatives to total laryngectomy in patients with advanced larynx or hypopharynx cancer. We report results of the randomized phase 3 trial 24954 from the European Organization for Research and Treatment of Cancer. METHODS: Patients with resectable advanced squamous cell carcinoma of the larynx (tumor stage T3-T4) or hypopharynx (T2-T4), with regional lymph nodes in the neck staged as N0-N2 and with no metastasis, were randomly assigned to treatment in the sequential (or control) or the alternating (or experimental) arm. In the sequential arm, patients with a 50% or more reduction in primary tumor size after two cycles of cisplatin and 5-fluorouracil received another two cycles, followed by radiotherapy (70 Gy total). In the alternating arm, a total of four cycles of cisplatin and 5-fluorouracil (in weeks 1, 4, 7, and 10) were alternated with radiotherapy with 20 Gy during the three 2-week intervals between chemotherapy cycles (60 Gy total). All nonresponders underwent salvage surgery and postoperative radiotherapy. The Kaplan-Meier method was used to obtain time-to-event data. RESULTS: The 450 patients were randomly assigned to treatment (224 to the sequential arm and 226 to the alternating arm). Median follow-up was 6.5 years. Survival with a functional larynx was similar in sequential and alternating arms (hazard ratio of death and/or event = 0.85, 95% confidence interval = 0.68 to 1.06), as were median overall survival (4.4 and 5.1 years, respectively) and median progression-free interval (3.0 and 3.1 years, respectively). Grade 3 or 4 mucositis occurred in 64 (32%) of the 200 patients in the sequential arm who received radiotherapy and in 47 (21%) of the 220 patients in the alternating arm. Late severe edema and/or fibrosis was observed in 32 (16%) patients in the sequential arm and in 25 (11%) in the alternating arm. CONCLUSIONS: Larynx preservation, progression-free interval, and overall survival were similar in both arms, as were acute and late toxic effects.

Effects of reduced dietary calcium and phytase supplementation on calcium and phosphorus utilisation in broilers with modified mineral status.

1. The impact of modified mineral status and dietary Ca:P ratio on Ca and P utilisation was measured in chicks with or without phytase supplementation. 2. In a preliminary study, 4 diets were given to chicks from 3 to 15 d of age: D1 (6.5 g P/kg and Ca:P = 1.5) and D2, D3 and D4 (6.0, 5.4 and 5.0 g P/kg, respectively, and Ca:P = 1.2). Growth performance was similar across diets. Tibia ash was similar in chicks given D1 and D2, but was gradually depressed from D2 to D4 (-22%). 3. In the depletion period, two groups of chicks, with similar performance, but with different mineral status were achieved by feeding them, from 5 to 15 d of age, diets with a similar Ca:P ratio of 1.2, but containing 6.3 or 5.2 g P/kg. 4. During the subsequent 11 d of the repletion period, chicks from each of the two previous groups were given one of the 4 diets containing 5.7 g P/kg, but differing in their Ca (8.3 and 5.3 g Ca/kg) and microbial phytase (0 or 1000 FTU, Natuphos levels in a 2 x 2 x 2 factorial arrangement. 5. At the end of the repletion period, the initially depleted chicks could not be differentiated from the non-depleted chicks, indicating the capacity of chicks to compensate for their initial depleted mineral status. 6. Interaction between dietary Ca and phytase levels was not significant. Phytase improved growth performance and bone characteristics. Reduced dietary Ca enhanced feed intake and growth rate, but depressed bone dry matter and ash weight. 7. At the end, diets supplemented with phytase maximised bone ash weight when chicks were fed with a Ca:P ratio of 1.5 but elicited the highest growth rate when chicks were fed with a Ca:P ratio of 0.9.

Effect of glutamine supplementation on splanchnic metabolism in lactating dairy cows.

The suggestion that glutamine (Gln) might become conditionally essential postpartum in dairy cows has been examined through increased postruminal supply of Gln. Net nutrient flux through the splanchnic tissues and mammary gland was measured in 7 multiparous Holstein cows receiving abomasal infusions of water or 300 g/d of Gln for 21 d in a crossover design. Milk yield increased significantly (by 3%) in response to Gln supplementation, but the 2.4% increase in milk protein yield was not statistically significant. Glutamine treatment had no effect on portal or hepatic venous blood flows. Net portal appearance of Gln and Glu was increased by Gln supplementation, accounting for 83% of the infused dose with, therefore, only limited amounts available to provide additional energy to fuel metabolism of the portal-drained viscera. The extra net portal appearance of Gln was offset, however, by a corresponding increase in hepatic removal such that net Gln splanchnic release was not different between treatments. Nonetheless, the Gln treatment resulted in a 43% increase in plasma Gln concentration. Infusions of Gln did not affect splanchnic flux of other nonessential amino acids or of essential amino acids. Glutamine supplementation increased plasma urea-N concentration and tended to increase net hepatic urea flux, with a numerical increase in liver hepatic O2 consumption. There were no effects on glucose in terms of plasma concentration, net portal appearance, net liver release, or postliver supply, suggesting that Gln supplementation had no sparing effect on glucose metabolism. Furthermore, mammary uptake of glucose and amino acids, including Gln, was not affected by Gln supplementation. In conclusion, this study did not support the hypothesis that supplemental Gln would reduce glucose utilization across the gut or increase liver gluconeogenesis or mammary glutamine uptake to increase milk protein synthesis.

Effect of postruminal glutamine supplementation on immune response and milk production in dairy cows.

Seventeen multiparous Holstein cows were used to examine the effect of an increased duodenal supply of Gln on immune function and production. Cows received continuous abomasal infusions of water (control: n = 8) or 300 g/d of Gln (n = 9) for 21 d starting within 48 h of calving. There were nonsignificant increases in milk and milk protein yields in response to Gln supplementation. Glutamine treatment had no effect on plasma glucose, nonesterified fatty acids (NEFA), or beta-hydroxybutyrate (BHBA) concentrations but did tend to increase plasma urea N concentration. The Gln treatment resulted in an increase of 108 microM in the plasma Gln concentration. Total essential AA concentrations decreased with the Gln treatment, whereas total nonessential AA concentrations were unaffected. T Lymphocyte proliferation did not differ between the control and Gln-treated cows. Treatment had no effect on the relative abundance of CD8 T cells but did increase the abundance of CD4 T cells. Cytokine production, as measured by IFN-gamma concentration determined in vitro in concanavalin-A-stimulated peripheral blood mononuclear cells, was similar between the treatments. Over the first 3 wk following calving, Gln supplementation had limited effects on milk production, metabolic parameters, and immune function.

Central pain in a hemispherectomized patient.

We have examined a hemispherectomized patient who complained of touch-evoked pricking and burning pain in her paretic hand, especially when the hand was cold. Psychophysical examination showed that for the paretic side she confused cool and warm temperatures, and confirmed that she had a robust allodynia to brush stroking that was enhanced at a cold ambient temperature. Functional magnetic resonance imaging (fMRI) showed that during brush-evoked allodynia, brain structures implicated in normal pain processing (viz. posterior part of the anterior cingulate cortex, secondary somatosensory cortex, and prefrontal cortices) were activated. The fMRI findings thus indicate that the central pain in this patient was served by brain structures implicated in normal pain processing. Possible pathophysiological mechanisms include plasticity as well as thalamic disinhibition.

Improved immune functions with administration of a low-fat diet in a burn animal model.

The purpose of this study was to characterize the impact of a low-fat (LF; 1% fat) diet, a high-fat (HF; 25% fat) diet, and a standard (SD; 5% fat) diet on immune and oxidative parameters in a 20% body surface area burn animal model fed ad libitum for 10 days postinjury. Although the mechanisms are poorly understood, the amount of dietary lipid in nutritional support has been shown to have immunomodulatory effects after burn injury. Burned mice fed the LF diet showed a normal response in activated splenocyte proliferation compared to burned animals that received the SD or HF diet. Animals fed the SD and HF diets presented increased production of nitric oxide and prostaglandin E2 response after burn injury, which is associated with inhibited splenocyte proliferation. The total thiol concentration in spleen cells from burned animals kept on the HF diet was significantly higher than that in unburned animals, while no increase in these oxidative parameters was observed in LF-fed burned animals. Moreover, the LF diet significantly reduced hepatic lipid peroxidation, as measured by malonaldehyde concentration, compared to the other two diets. These results suggest that the administration of a LF diet in mice after a burn injury prevents inhibition of in vitro splenocyte proliferation and reduces the intensity of oxidative stress.

Primary mediastinal large B-cell lymphoma: the need for prospective controlled clinical trials.

Primary mediastinal large-B cell lymphomas (PMLCL) are considered to be a distinct clinicopathologic entity among the diffuse large B-cell lymphomas. This study evaluated the prognostic factors and therapeutic outcome of PMLCL in a single-institution series. Twenty seven patients were reviewed. Nineteen of the 27 had Stage I-II and 8 had Stage III-IV disease. B-symptoms were found in 11 (41%) and bulky disease in 10 (37%) patients. All were initially given combination chemotherapy (CT): doxorubicin-containing regimens to 23 patients (11 patients had CHOP, 12 received more intensive third-generation regimens) and 4 elderly (>70 years) patients received CVP. Eleven responders were consolidated with irradiation (RT) as part of their initial treatment, with a median total dose of 39 Gy. Nineteen patients (70%) achieved clinical remission (15 CR and 4 PR) with their initial therapy. Forty-four percent of patients remained progression-free and 59% are alive at 3 years. The actuarial 10-year time to progression (TTP) and overall survival (OS) were 44% and 50%, respectively. Age >60 years, performance status >1 and IPI intermediate-high to high risk were significantly associated with poorer OS and TTP by univariate analysis (log-rank test). A better outcome was associated with the use of more aggressive chemotherapy regimens or with the inclusion of RT in the first-line treatment. Our analyses suggest that the application of radiotherapy in combination regimens and the use of more aggressive chemotherapy in the treatment of this particular type of lymphoma should now be evaluated in prospective randomized trials.

Immunomodulatory and protective effects of N-acetylcysteine in mitogen-activated murine splenocytes in vitro.

N-Acetylcysteine (NAC) is a pro-glutathione drug used to treat chronic lung disorders and because of its anti-AIDS virus activity in vitro, has been proposed for AIDS therapy. The effect of NAC on mitogen-activated-lymphocyte blastogenesis in C57B1/6 mouse splenocytes and ability of NAC to protect lymphocytes against mitogen-induced cytotoxicity was examined in vitro. NAC increased splenocyte proliferation in the presence of optimal and suboptimal concentrations of concanavalin A (Con A) and lipopolysaccharide (LPS). Stimulatory and costimulatory effects of NAC on mitogen-induced responses were also evident. The dose-response relationship describing the effects of NAC on lymphocyte proliferation with Con A-induced responses were enhanced in a dose-dependent manner, whereas the corresponding LPS-induced responses increased to a maximum level followed by decline in responses at higher concentrations of NAC. When splenocytes were incubated with inhibitory supraoptimal concentrations of Con A (10 microg/ml) or LPS (150 microg/ml), NAC partially enhanced the Con A-induced response but completely prevented the inhibitory effect of supraoptimal concentrations of LPS on splenocyte blastogenesis. Optimal and supraoptimal concentrations of Con A caused activation-induced cell death in the splenocytes whereas comparable concentrations of LPS did not produce a similar effect. Splenocyte cell death produced by the optimal mitogenic concentrations of Con A was completely blocked by the addition of NAC to cultures. Immunomodulation and protective effects of NAC were observed in mitogen-activated lymphocytes in vitro.

Dietary addition of cellular metabolic intermediates and carcass fat deposition in broilers.

Ninety-six 1-day-old male broilers were fed a diet containing 0, 2, 4, 6, 8, or 10% of a 1:1 mixture of pyruvic acid (PY) and dihydroxyacetone (DH) for ad libitum consumption for 42 days. Feed intake, body weight gain, and feed efficiency decreased linearly (P < .001) with increasing levels of PY and DH. There were no significant differences among treatments for abdominal fat percentage. Carcass chemical analysis revealed small but significant (P < .05) differences among dietary treatments for protein and fat percentages. In a second experiment, 192 1-day-old male broilers were fed diets containing 5% of PY, lactic acid (LA), citric acid (CI), DH, or glycerol (GY) or mixtures (1:1) of DH or GY in combination with each organic acid. Bird performance was impaired (P < .05) by PY or CI but not by DH or GY. Lactic acid reduced (P < .05) feed intake by 9% without affecting weight gain. Lactic acid plus DH, CI plus DH, and CI plus GY mixtures decreased (P < .05) bird performance but other combinations had no effect. Pyruvic acid or CI decreased abdominal fat and carcass lipid percentages. Dihydroxyacetone increased (P < .05) carcass lipid percentage and GY increased (P < .05) abdominal fat percentage. Lactic acid plus DH increased (P < .05) carcass lipid percentage. Only PY and CI decreased carcass fat deposition, but they also impaired broiler performance.

Evaluation of the immunomodulatory potential of diethyl dithiocarbamate derivatives.

The cytotoxicity, immunotoxicity and immunomodulatory potential of four dithiocarbamate derivatives were assessed and compared with the effects of Immuthiol (diethyl dithiocarbamate, DE-DTC) in mice. Cellular stimulation and cell viability were examined after in vitro exposure of spleen lymphocytes to selected DTC analogues: N-methyl-D-glucamine dithiocarbamate (NMG-DTC), dimethyl dithiocarbamate (DM-DTC), dibuthyl dithiocarbamate (DB-DTC) and diisobuthyl dithiocarbamate (DIB-DTC). Lymphocyte activation by plant and bacterial mitogens: concanavalin A (Con A), phytohaemagglutinin (PHA), lipopolysaccharide (LPS) and allogeneic stimulation of cells in mixed lymphocyte reaction (MLR) were examined in vitro in the presence of 10(-4)-10(-9) g/ml DE-DTC and other selected DTC derivatives. No direct in vitro lymphoproliferative activity of DTC derivatives was observed, although a relatively stronger cytotoxicity with DE-DTC and DM-DTC was noted. In addition, the in vivo effects of DTC derivatives were examined by cytofluorometric profile of splenic and bone marrow cells as well as in mitogenic and allogenic responses, after i.v. exposures of animals to two subsequent (25 mg/kg b.w.) doses of the chemical. Less cytotoxic DIB-DTC, NMG-DTC and DB-DTC expressed weak in vivo immunostimulatory potential when compared with the effect of DE-DTC, whereas the effects of DM-DTC on alloantigenic and mitogenic lymphocyte stimulation were comparable with the known effects of DE-DTC. Cytofluorometric studies showed that the number of cytotoxic/suppressor T-cells (Ts) and helper T-cells (Th) in the cell was increased by DE-DTC and NMG-DTC only. In addition, DM-DTC appeared to affect the Ts/Th ratio. DE-DTC did not affect the B-cell subpopulation, whereas other derivatives induced marked modifications of the pre-B-cell subpopulations in bone marrow. Our data suggest that in vivo the immunostimulatory effect of DM-DTC could be accompanied with major changes in bone marrow B-cell frequency and alteration of spleen Ts/Th ratio.

[Plasma insulin and glucagon after ingestion of meal enriched with increased doses of pectin in healthy man]. / Insulin et glucagon plasmatiques après ingestion d'un repas enrichi par des doses croissantes de pectine chez l'homme sain.

The effects of three doses of pectin (5, 10 and 15 g) included in a solid-liquid meal on the postprandial plasma insulin and glucagon responses were studied in 12 healthy men. The mean plasma glucagon level was significantly smaller with 5 g of pectin than the control values at 150 min (p less than 0.05) whereas plasma insulin values did not vary. No change in mean plasma glucagon and insulin levels was noted with 10 g and 15 g of pectin although the mean blood glucose levels were significantly higher than the control values at 180 min (p less than 0.05). Addition of pectin to a meal, even if the doses were relatively important, had little or no effect on the postprandial hormonal responses in healthy men. However, pectin could be of renewed interest because of the possibility of its action of satiety by means of sustained late blood glucose levels.

Antibiotic-lock technique: a new approach to optimal therapy for catheter-related sepsis in home-parenteral nutrition patients.

During a cumulated survey of 286 months, covering 11 gastroenterological patients under nocturnal-cyclic home parenteral nutrition, 24 cases of catheter-related sepsis were observed (one/11.9 months). None of these were associated with focus of infection at the cutaneous entry point or at the subcutaneous tunnel of the catheters. In this study attempt was made to control sepsis without removal of the surgically implanted siliconed lines (Vygon code 180-20 with an internal filling volume of 1 ml). The first two catheter-sepsis were conventionally treated with systemic antibiotics for 3 weeks which meant a 1-month hospital admission each time. Consequently, we used a new antibiotic therapy consisting of locking 12 hr/day 2 ml of highly concentrated antibiotic solution within the catheter. After identification of bacterial strains by blood cultures, the antibiotic lock-technique was daily applied either alone for 16 days (group I, n = 11) or for 12 days following a 3-day course of systemic antibiotics (group II, n = 11). After starting antibiotics via the infected line, the time taken for fever abatement and for obtaining negative in-line blood cultures were 2 and 4 days, respectively, and identical in group I and II. Failure of antibiotic treatment leading to catheter withdrawal was observed once in each group (9%) and was due to secondary candida catheter-sepsis. The time for hospital stay was shorter p less than 0.02 in group I (4 days) than in group II (7 days). Antibiotic-lock technique was then applied by trained patients at home.(ABSTRACT TRUNCATED AT 250 WORDS)

An evaluation of total parenteral nutrition in the management of steroid-dependent and steroid-resistant patients with Crohn's disease.

This study is an evaluation of short- and long-term benefits of total parenteral nutrition (TPN) in 20 patients with active Crohn's disease but without fistulae. TPN was done during 42 (14-80) days (median-range) after failure of medical therapy including patients with steroid-resistant (11 SR) or steroid-dependent (9 SD) active Crohn's disease. Efficacy of short-term TPN was demonstrated by nutritional repair and achievement of clinical remission in all but one patients. Follow-up was 28 (8-78) months in the 19 patients (10 SR, 9 SD) discharged improved after the end of TPN. At 1 yr, the cumulative recurrence rate was 26% (5/19). During the follow-up, three patients (2 SR, 1 SD) remained symptom-free, 13 (6 SR, 7 SD) had a partial remission defined as relapse controlled by medication, and only three patients (2 SR, 1 SD) had a relapse uncontrolled by medical therapy leading to surgery. Therefore in our selected population without fistula or abscess, after failure of medical therapy TPN was obviously an effective therapy which avoided surgery. Furthermore follow-up indicated that SD and SR were only transient events in the course of Crohn's disease patients.

Effect of increased amounts of pectin on a solid-liquid meal digestion in healthy man.

The effect of three concentrations of high-methoxy apple pectin (5, 10, and 15 g), on solid-liquid meal digestion was studied in 12 healthy men by the gastrointestinal intubation technique. The gastric emptying of water and carbohydrates is significantly reduced only after 10 and 15 g pectin. The changes in gastric pH are similar for pectin-free and pectin-containing meals. Cumulative lipase and trypsin outputs are not significantly different with and without pectin. When gastric uronic acid concentration is above 6 g/l, the duodenal absorption of carbohydrates is significantly reduced (p less than 0.001). The mean blood glucose levels with 10 and 15 g pectin are significantly higher than the control values at 180 min (p less than 0.05). Pectin does not modify serum concentrations of secretin, cholecystokinin (CCK), vasoactive intestinal polypeptide (VIP), gastric inhibitory polypeptide (GIP), and somatostatin but serum motilin and gastrin levels are below the control values after high fiber meal.

Opiate receptor interaction of a new analgesic drug 2-piperidinoethyl dibenzylglycolate.

The pharmacological properties of a new analgesic drug, 2-piperidinoethyl dibenzylglycolate (PDG), have been demonstrated by classical tests. The technique of iontophoresis was used in order to compare the effects of PDG with those of Tyr-D-Ser-Gly-Phe-Leu-Thr (DSTLE), syndyphalin, morphine and naloxone (NAL) on hypothalamic neurones. PDG as other four substances evoked only inhibitory responses. Some neurones, on which were tested three substances, were sensitive to one, two or three of these substances. The differential responses so obtained suggested that PDG does not act on mu- and delta-receptors but on an unidentified receptor for which morphine and NAL have a high affinity as agonist. Structural requirements for activity on different receptors were also proposed on the basis of crystallographic data and the above results.

Dietary fibers and supplementary iron in a milk replacer for veal calves.

Thirty 1-wk-old male Holstein calves were allotted randomly to six groups into a 3 X 2 factorial design. The control diet was skim milk, whey, tallow, vitamins, and minerals. Either Alpha-Floc or pectin was added at 5% dry matter. Supplementary iron was added at 30 and 50 ppm (dry basis). The six diets were fed for 14 wk. Calves without supplementary iron were mildly anemic at 6 wk and severely at 14 wk (7 and 5 g/dl hemoglobin). At 14 wk, both fibers had decreased blood hemoglobin in calves given supplementary iron. Feed refusal began at 8 wk with the appearance of anemia for calves unsupplemented with iron, but both Alpha-Floc and pectin decreased feed refusal. Supplementary iron practically eliminated feed refusal. Supplementary iron improved average daily gain and feed conversion, but dietary fibers had no effect. Adding Alpha-Floc and pectin to the diets reduced frequency of diarrheic feces. Mean carcass weight of calves fed supplementary iron was 11.6% higher than that of unsupplemented calves. Supplementary iron decreased liver lipids and increased glutamic oxaloacetic transaminase activity in blood plasma.

Preferential binding to delta-receptors of the enkephalin-like tetrapeptide Tyr-Ile-Phe-Val. Electrophysiological and conformation studies.

The technique of microiontophoresis was used to study the effects of leucine-enkephalin [( Leu]enkephalin) and the tetrapeptide Tyr-Ile-Phe-Val on spontaneous and evoked activity of guinea-pig hypothalamic neurons. The inhibitory effects of the tetrapeptide were similar to those of [Leu]enkephalin on some neurons. However, in other cases, [Leu]enkephalin was inhibitory whereas Tyr-Ile-Phe-Val was without effect. These data and the fact that naloxone caused a different antagonism of inhibitory effects by these two peptides suggest the existence of two types of opiate receptors on some hypothalamic neurons and that Tyr-Ile-Phe-Val preferentially binds to delta-receptors. Conformational features of Tyr-Ile-Phe-Val have been established by 1H-NMR spectroscopy and were found to be in accordance with the above considerations. The peptide has a peculiar folded conformation called gamma-turn. Due to the restricted flexibility of this structure, the aromatic moieties (Tyr and Phe) and the hydrophobic (Val) or hydrophilic (terminal NH2 and CO2H) parts are positioned in a specific spatial relationship which can be related to an optimal binding to delta-receptors.