Evaluating internal and external markers versus fecal sampling procedure interactions when estimating intake in dairy cows consuming a corn silage-based diet.

Feed intake assessment is a valuable tool for herd management decisions. The use of markers, either internal or external, is currently the most used technique for estimating feed intake in production animals. The experiment used 10 multiparous Holstein cows fed a corn silage-based diet, with 55:45 forage-to-concentrate ratio, the average fecal recovery (FR) of TiO2 was higher than FR of Cr2O3, and both FR were more than unity. With internal markers, acetyl bromide lignin and cutin FR were lower than unity, and average FR for indigestible neutral detergent fiber (iNDF) and indigestible acid detergent fiber (iADF) was 1.5. The FR was unaffected by the fecal sampling procedure and appears to be an intrinsic property of each molecule and how it interacts with digesta. Of the 2 external markers, only Cr2O3 produced accurate fecal output (FO) estimates and the same happened to dry matter digestibility (DMD) when iNDF and iADF were used. Estimates for DMD and FO were affected by sampling procedure; 72-h bulk [sub-sample from total feces collection (TFC)] sampling consistently produced accurate results. The grab (sub-samples taken at specific times during the day) sampling procedures were accurate when using either of the indigestible fibers (iNDF or iADF) to estimate DMD. However, grab sampling procedures can only be recommended when concomitant TFC is performed on at least one animal per treatment to determine FR. Under these conditions, Cr2O3 is a suitable marker for estimating FO, and iNDF and iADF are adequate for estimating DMD. Moreover, the Cr2O3+iADF marker pair produces accurate dry matter intake estimates and deserves further attention in ruminant nutrition studies. The method of dosing the external markers is extremely important and greatly affects and determines results. Whichever the method, it must allow the animals to display normal feeding behavior and not affect performance. The grab sampling procedures can replace TFC (once FR is established), which may open new possibilities for pasture-based or collectively housed animals.

Randomized clinical trial of 24 versus 72 h antimicrobial prophylaxis in patients undergoing open total gastrectomy for gastric cancer.

BACKGROUND: Open total gastrectomy carries a high risk of surgical-site infection (SSI). This study evaluated the non-inferiority of antimicrobial prophylaxis for 24 compared with 72 h after open total gastrectomy. METHODS: An open-label, randomized, non-inferiority study was conducted at 57 institutions in Japan. Eligible patients were those who underwent open total gastrectomy for gastric cancer. Patients were assigned randomly to continued use of ß-lactamase inhibitor for either 24 or 72 h after surgery. The primary endpoint was the incidence of SSI, with non-inferiority based on a margin of 9 percentage points and a 90 per cent c.i. The secondary endpoint was the incidence of remote infection. RESULTS: A total of 464 patients (24 h prophylaxis, 228; 72 h prophylaxis, 236) were analysed. SSI occurred in 20 patients (8·8 per cent) in the 24-h prophylaxis group and 26 (11·0 per cent) in the 72-h group (absolute difference -2·2 (90 per cent c.i. -6·8 to 2·4) per cent; P < 0·001 for non-inferiority). However, the incidence of remote infection was significantly higher in the 24-h prophylaxis group. CONCLUSION: Antimicrobial prophylaxis for 24 h after total gastrectomy is not inferior to 72 h prophylaxis for prevention of SSI. Shortened antimicrobial prophylaxis might increase the incidence of remote infection. Registration number: UMIN000001062 ( http://www.umin.ac.jp).

Accurate and rapid novel genetic diagnosis for detection of sentinel lymph node metastasis in breast cancer patients.

BACKGROUND: The transcription-reverse transcription concerted reaction (TRC) test is a novel molecular-based procedure, which can assess nodal metastasis accurately and quickly. We examined the usefulness of the TRC test with a double marker, cytokeratin 19 (CK19) and carcinoembryonic antigen (CEA) mRNA, to detect sentinel lymph nodes (SLN) metastasis in breast cancer patients. METHODS: A total of 264 SLNs from 131 breast cancer patients were assigned to a training set (109 SLNs from 50 patients) and validation set (155 SLNs from 81 patients). Cytokeratin 19 and CEA mRNA were detected by TRC tests, and the sensitivity and specificity of the SLN metastasis between the TRC and histology cohorts were compared. RESULTS: Mean copy numbers of CK19 and CEA by TRC tests were increased according to the metastatic size. In the training set, TRC test showed 100% sensitivity, specificity and concordance rates against the permanent histopathology test. In the validation set, sensitivity was 97.1%, specificity was 99.2% and the concordance rate was 99.4%. CONCLUSION: Our results showed that the detection of CK19 and CEA mRNA using the TRC test is, an accurate and rapid method for detection of SLN metastasis and can be applied as an intraoperative molecular diagnosis in breast cancer patients.

Validation of fingernail fluoride concentration as a predictor of risk for dental fluorosis.

The aim of this study was to validate the use of fingernail fluoride concentrations at ages 2-7 years as predictors of the risk for developing dental fluorosis in the permanent dentition. Fifty-six children of both genders (10-15 years of age) had their incisors and premolars examined for dental fluorosis using the Thylstrup-Fejerskov index. Fingernail fluoride concentrations were obtained from previous studies when children were 2-7 years of age. Data were analyzed by unpaired t test, ANOVA, and Fisher's exact test when the fingernail fluoride concentrations were dichotomized (≤ 2 or >2 µg/g). Children with dental fluorosis had significantly higher fingernail fluoride concentrations than those without the condition, and the concentrations tended to increase with the severity of fluorosis (r(2) = 0.47, p < 0.0001). Using a fingernail fluoride concentration of 2 µg/g at ages 2-7 years as a threshold, this biomarker had high sensitivity (0.84) and moderate specificity (0.53) as a predictor for dental fluorosis. The high positive predictive value indicates that fingernail fluoride concentrations should be useful in public health research, since it has the potential to identify around 80% of children at risk of developing dental fluorosis.

Cryoprecipitate transfusion: assessing appropriateness and dosing in trauma.

BACKGROUND: Originally developed for patients with congenital factor VIII deficiency, cryoprecipitate is currently largely used for acquired hypofibrinogenemia in the context of bleeding. However, scant evidence supports this indication and cryoprecipitate is commonly used outside guidelines. In trauma, the appropriate cryoprecipitate dose and its impact on plasma fibrinogen levels are unclear. OBJECTIVES: The aims were to evaluate (i) the appropriateness of cryoprecipitate transfusion in trauma and (ii) the plasma fibrinogen response to cryoprecipitate transfusion during massive transfusion in trauma. METHODS: Retrospective review (January 1998-June 2008) of indications, dose and plasma fibrinogen response to cryoprecipitate transfusion at a large teaching hospital. A fibrinogen of <1.0 g L(-1) within 2 and 6 h of transfusion was used for evaluating appropriateness. RESULTS: Ten thousand five hundred and forty cryoprecipitate units were transfused in 1004 patients. Thirty-seven percent and 31% were used in cardiac surgery and trauma, respectively. In 394 events in trauma, 238 (60%) and 259 (66%) were considered appropriate using the 2- and 6-h cut-off criteria, respectively. In patients who did not receive plasma components 2 h prior to cryoprecipitate, a dose of 8.7 (± 1.7) units caused a mean increase in fibrinogen levels of 0.55 (± 0.24) g L(-1), or 0.06 g L(-1) per unit. CONCLUSIONS: In our hospital, where transfusion guidelines are overseen by transfusion medicine specialists and technologists, and policies for rapid blood component and laboratory turnaround times exist, it is possible to achieve high rates of appropriateness for cryoprecipitate transfusion in trauma. The current recommended dose causes a modest increase in fibrinogen levels (0.55 g L(-1) ).

Factors associated with fluoride concentrations in whole and parotid ductal saliva.

BACKGROUND/AIMS: There are still uncertainties regarding the use of whole and parotid ductal saliva as indicators of chronic exposure to fluoride. This study evaluated the effect of water fluoride concentration, age, gender, geographical area and localization (urban/rural) on fluoride concentrations in whole and ductal saliva. METHODS: Subjects (n = 300) aged 3-7, 14-20, 30-40 and 50-60 years, from five communities (A-E) with different fluoride concentrations in the drinking water, participated in the study. Two samples of drinking water and parotid and whole saliva were collected for each subject and were analyzed for fluoride using appropriate electrode techniques. RESULTS: Mean water F concentrations (±SE, mg/l, n = 60) were 0.09 ± 0.01, 0.15 ± 0.01, 0.66 ± 0.01, 0.72 ± 0.02, and 1.68 ± 0.08 for A-E, respectively. Mean F concentrations (±SE, mg/l, n = 15) ranged between 0.014 ± 0.002 (A, 3-7 years) and 0.297 ± 0.057 (D, 14-20 years) for whole saliva and 0.009 ± 0.001 (C, 30-40 years) and 0.284 ± 0.038 (E, 50-60 years) for parotid saliva. Results of multivariate linear regression analysis showed that geographical area and water fluoride concentration exerted the strongest influence in whole and ductal saliva F concentrations, respectively. CONCLUSION: Therefore, parotid ductal saliva seems to be a more appropriate biomarker of fluoride exposure, and factors like age and localization should also be considered when using this biomarker.

Nutrition education in medical schools (NEMS) project: Joining ESPEN and university point of view.

BACKGROUND & AIMS: Nutrition education is not well represented in the medical curriculum. The aim of this original paper was to describe the Nutrition Education in Medical Schools (NEMS) Project of the European Society for Clinical Nutrition and Metabolism (ESPEN). METHODS: On 19 January 2020, a meeting was held on this topic that was attended by 51 delegates (27 council members) from 34 countries, and 13 European University representatives. RESULTS: This article includes the contents of the meeting that concluded with the signing of the Manifesto for the Implementation of Nutrition Education in the Undergraduate Medical Curriculum. CONCLUSION: The meeting represented a significant step forward, moved towards implementation of nutrition education in medical education in general and in clinical practice in particular, in compliance with the aims of the ESPEN Nutrition Education Study Group (NESG).

The effect of angiotensin-converting enzyme inhibitors of left atrial pressure in dogs with mitral valve regurgitation.

BACKGROUND: Despite many epidemiological reports concerning the efficacy of angiotensin-converting enzyme (ACE) inhibitors in dogs with mitral regurgitation (MR), the hemodynamic effects of ACE inhibitor administration have not been fully evaluated. OBJECTIVES: To document left atrial pressure (LAP) in dogs with MR administered ACE inhibitors, in order to obtain interesting information about daily LAP changes with administration of ACE inhibitors. ANIMALS: Five healthy Beagle dogs weighing 9.8 to 14.2 kg (2 males and 3 females; aged 2 years). METHODS: Experimental, crossover, and interventional study. Chordae tendineae rupture was induced, and a radiotelemetry transmitter catheter was inserted into the left atrium. LAP was recorded for 72 consecutive hours during which each of 3 ACE inhibitors--nalapril (0.5 mg/kg/d), temocapril (0.1 mg/kg/d), and alacepril (3.0 mg/kg/d)--were administered in a crossover study. RESULTS: Averaged diurnal LAP was significantly, but slightly reduced by alacepril (P = .03, 19.03 +/- 3.01-18.24 +/- 3.07 mmHg). The nightly drops in LAP caused by alacepril and enalapril were significantly higher than the daily drops (P = .03, -0.98 +/- 0.19 to -0.07 +/- 0.25 mmHg, and P = .03, -0.54 +/- 0.21-0.02 +/- 0.17 mmHg, respectively), despite the fact that the oral administrations were given in the morning. Systolic blood pressure (122.7 +/- 14.4-117.4 +/- 13.1 mmHg, P = .04) and systemic vascular resistance (5800 +/- 2685-5144 +/- 2077 dyne x s/cm5, P = .03) were decreased by ACE inhibitors. CONCLUSIONS AND CLINICAL IMPORTANCE: ACE inhibitors decrease LAP minimally, despite reductions in left ventricular afterload. ACE inhibitors should not be used to decrease LAP.

A case of feline gastrointestinal eosinophilic sclerosing fibroplasia limited to the mesentery.

An entire, female, mixed-breed cat of unknown age was presented with a 6-week history of lethargy, anorexia and vomiting. There was an increase in the number of white blood cells in the blood, including neutrophils and eosinophils; moderate anaemia; ascites; and possible mesenteric peritonitis. Exploratory laparotomy revealed firm, multifocal small nodules in the mesentery. As the nodules were surgically unresectable, they were biopsied. Histologically, the nodules were composed of thin trabeculae of dense collagen fibres mixed with plump fibroblasts and numerous eosinophils, consistent with feline gastrointestinal eosinophilic sclerosing fibroplasia. Bacteria were not detected on histological examination of the nodules and cytology of the ascites. Remission of disease occurred following treatment with prednisolone and ciclosporin A for 22 days and antibiotics for 40 days. After remission, ciclosporin A was administered for 236 days and then discontinued. Eosinophilia also resolved after treatment with ciclosporin A. The cat is still alive and in good condition on day 689. This report describes what may be an atypical case of feline gastrointestinal eosinophilic sclerosing fibroplasia, lacking involvement of the gastrointestinal tract, and was apparently cured by treatment that involved ciclosporin A.

Environmental and individual factors associated with nail fluoride concentration.

Nails have been suggested as suitable biomarkers of exposure to F, with the advantage of being easily obtained. The effect of water F concentration, age, gender, nail growth rate and geographical area on the F concentration in the fingernail and toenail clippings were evaluated. Volunteers (n = 300) aged 3-7, 14-20, 30-40 and 50-60 years from five Brazilian communities (A-E) participated. Drinking water and nail samples were collected and F concentration was analyzed with the electrode. A reference mark was made on each nail and growth rates were calculated. Data were analyzed by ANOVA and linear regression (alpha = 0.05). Mean water F concentrations (+/- SE, mg/l) were 0.09 +/- 0.01, 0.15 +/- 0.01, 0.66 +/- 0.01, 0.72 +/- 0.02, and 1.68 +/- 0.08 for A-E, respectively. Mean F concentrations (+/- SE, mg/kg) ranged between 1.38 +/- 0.14 (A, 50-60 years) and 10.20 +/- 2.35 (D, 50-60 years) for fingernails, and between 0.92 +/- 0.08 (A, 14-20 years) and 7.35 +/- 0.80 (E, 50-60 years) for toenails. Among the tested factors, geographical area and water F concentration exerted the most influence on finger- and toenail F concentrations. Subjects of older age groups (30-40 and 50-60 years) from D and E showed higher nail F concentrations than the others. Females presented higher nail F concentration than males. Water F concentration, age, gender and geographical area influenced the F concentration of finger- and toenails, and hence should be taken into account when using this biomarker of exposure to predict risk for dental fluorosis.

Daily rhythms of left atrial pressure in beagle dogs with mitral valve regurgitation.

BACKGROUND: Mitral valve regurgitation (MR) causes increased left atrial pressure (LAP) and is associated with occurrence of clinical signs. It will be useful to understand diurnal variations of LAP for the management of MR. HYPOTHESIS: Circulatory parameters and diurnal rhythm are linked to clinical signs in cardiac diseases. LAP also exhibits a diurnal rhythm in dogs with MR. ANIMALS: Five healthy Beagle dogs weighing 9.8-12.8 kg (3 males and 2 females; aged 2 years) were used. METHODS: A radiotelemetry system for continuous measurement of LAP was used in this study. Rupture of the chordae tendineae was experimentally induced via left atriotomy, and a transmitter catheter was inserted into the left atrium. The body of the transmitter was implanted SC. After clinical condition was stabilized, the severity of MR was evaluated by echocardiography, and LAP was recorded for 72 consecutive hours for the analysis of diurnal variation. RESULTS: Abrupt increases in LAP, which averaged 16.7 mmHg, were observed at feeding periods. In contrast, strong diurnal LAP variations were found, with a significant but slight increase in daytime LAP compared with nighttime LAP. CONCLUSIONS AND CLINICAL IMPORTANCE: Diurnal LAP is characterized by a slight but significant nocturnal decrease and abrupt increases in response to excitation. The latter seemed to be more important considering the relationship with clinical manifestations. The clinical relevance of exercise restriction in the management of MR was acknowledged.

GLIM criteria for the diagnosis of malnutrition - A consensus report from the global clinical nutrition community.

RATIONALE: This initiative is focused on building a global consensus around core diagnostic criteria for malnutrition in adults in clinical settings. METHODS: In January 2016, the Global Leadership Initiative on Malnutrition (GLIM) was convened by several of the major global clinical nutrition societies. GLIM appointed a core leadership committee and a supporting working group with representatives bringing additional global diversity and expertise. Empirical consensus was reached through a series of face-to-face meetings, telephone conferences, and e-mail communications. RESULTS: A two-step approach for the malnutrition diagnosis was selected, i.e., first screening to identify "at risk" status by the use of any validated screening tool, and second, assessment for diagnosis and grading the severity of malnutrition. The malnutrition criteria for consideration were retrieved from existing approaches for screening and assessment. Potential criteria were subjected to a ballot among the GLIM core and supporting working group members. The top five ranked criteria included three phenotypic criteria (non-volitional weight loss, low body mass index, and reduced muscle mass) and two etiologic criteria (reduced food intake or assimilation, and inflammation or disease burden). To diagnose malnutrition at least one phenotypic criterion and one etiologic criterion should be present. Phenotypic metrics for grading severity as Stage 1 (moderate) and Stage 2 (severe) malnutrition are proposed. It is recommended that the etiologic criteria be used to guide intervention and anticipated outcomes. The recommended approach supports classification of malnutrition into four etiology-related diagnosis categories. CONCLUSION: A consensus scheme for diagnosing malnutrition in adults in clinical settings on a global scale is proposed. Next steps are to secure further collaboration and endorsements from leading nutrition professional societies, to identify overlaps with syndromes like cachexia and sarcopenia, and to promote dissemination, validation studies, and feedback. The diagnostic construct should be re-considered every 3-5 years.

GLIM criteria for the diagnosis of malnutrition - A consensus report from the global clinical nutrition community.

RATIONALE: This initiative is focused on building a global consensus around core diagnostic criteria for malnutrition in adults in clinical settings. METHODS: In January 2016, the Global Leadership Initiative on Malnutrition (GLIM) was convened by several of the major global clinical nutrition societies. GLIM appointed a core leadership committee and a supporting working group with representatives bringing additional global diversity and expertise. Empirical consensus was reached through a series of face-to-face meetings, telephone conferences, and e-mail communications. RESULTS: A two-step approach for the malnutrition diagnosis was selected, i.e., first screening to identify "at risk" status by the use of any validated screening tool, and second, assessment for diagnosis and grading the severity of malnutrition. The malnutrition criteria for consideration were retrieved from existing approaches for screening and assessment. Potential criteria were subjected to a ballot among the GLIM core and supporting working group members. The top five ranked criteria included three phenotypic criteria (weight loss, low body mass index, and reduced muscle mass) and two etiologic criteria (reduced food intake or assimilation, and inflammation or disease burden). To diagnose malnutrition at least one phenotypic criterion and one etiologic criterion should be present. Phenotypic metrics for grading severity as Stage 1 (moderate) and Stage 2 (severe) malnutrition are proposed. It is recommended that the etiologic criteria be used to guide intervention and anticipated outcomes. The recommended approach supports classification of malnutrition into four etiology-related diagnosis categories. CONCLUSION: A consensus scheme for diagnosing malnutrition in adults in clinical settings on a global scale is proposed. Next steps are to secure further collaboration and endorsements from leading nutrition professional societies, to identify overlaps with syndromes like cachexia and sarcopenia, and to promote dissemination, validation studies, and feedback. The diagnostic construct should be re-considered every 3-5 years.

Effect of immunotherapy and spleen preservation on immunological function in patients with gastric cancer.

Splenectomy is often performed in patients who undergo total gastrectomy for cancer of the upper stomach. Although splenectomy facilitates lymph node dissection of the splenic hilum and recent reports advocate spleen preservation, the role of the spleen is not fully elucidated in gastric cancer treatment. This prospective randomized study was performed to evaluate the role of the spleen in immunological function in gastric cancer patients who underwent total gastrectomy and received postoperative immunochemotherapy. Forty-five patients with gastric cancer were randomly allocated to four groups: 1. splenectomy without immunotherapy (OK-432 administration), 2. splenectomy with immunotherapy, 3. spleen preservation without immunotherapy, 4. spleen preservation with immunotherapy. Postoperative immunological function of these patients was compared among the four groups. NK cell activity of the peripheral blood lymphocytes (PBL) in spleen-preserved patients who received immunotherapy was significantly higher for 24 weeks after surgery than that of the splenectomized patients with and without OK-432 administration. IL-2 production of PBL in spleen-preserved patients with immunotherapy was significantly higher between 4 and 24 weeks after surgery compared with that of the splenectomized patients without immunotherapy. The results suggest that spleen preservation might be beneficial in patients with less advanced gastric cancer who receive postoperative immunochemotherapy after total gastrectomy.

Echocardiographic evaluation of myocardial changes observed after closure of patent ductus arteriosus in dogs.

BACKGROUND: Closure of PDA can be associated with echocardiographic changes including deterioration of LV systolic function. Although PDA is commonly encountered in dogs, few comprehensive reports of echocardiographic changes in dogs with PDA closure are available. OBJECTIVES: To evaluate the short-term echocardiographic changes observed after PDA closure in dogs using strain analysis. ANIMALS: Seventeen client-owned dogs with left-to-right PDA. METHODS: Echocardiographic evaluations, including standard echocardiography and two-dimensional tissue tracking (2DTT), were performed before and within 3 days of PDA closure. RESULTS: Preclosure examination showed LV and left atrial dilatation indicating volume overload as a result of PDA. Closure of PDA resulted in significant reduction of LVIDd (<.0001) and LA/Ao (0.01) without change in LVIDs, suggestive of decreased preload. Postclosure LV systolic dysfunction was observed with significant decreased in FS (<.0001) and strain values (P = .0039 for radial strains, P = .0005 for circumferential strains). Additionally, significant LV dyssynchrony (P = .0162) was observed after closure of PDA. CONCLUSIONS AND CLINICAL IMPORTANCE: Closure of PDA resulted in decreased preload as a result of alleviation of LV volume overload, which in turn caused transient deterioration of LV systolic function. Additionally, this study demonstrated that strain analysis is load dependent. Therefore, care should be taken when interpreting strain measurements as an indicator of LV systolic function.

Genomic structure and expression analyses of serine acetyltransferase gene in Citrullus vulgaris (watermelon).

The genomic clones of Sat gene encoding serine acetyltransferase (SATase), a key enzyme in cysteine biosynthesis in plants, were isolated from the genomic library of Citrullus vulgaris (watermelon). The determination of nucleotide sequence of 5.7 kilobase pair (kbp) length revealed the presence of two introns of 1939 basepair (bp) and 515 bp length in the gene. The transcription start point was determined by primer extension experiments. Southern blot analysis indicated the presence of a single copy of the Sat gene and a couple of additional related sequences in the genome of C. vulgaris. The expression of Sat was analyzed in watermelon plants growth under sulfur- and/or nitrogen-starved conditions and in the presence of pyrazole, O-acetylserine and N-acetylserine. Only slight increment (ca. 1.5-2-fold) of Sat gene expression was observed upon sulfur starvation for 48 h. Interestingly, the addition of pyrazole, which is a precursor of beta-pyrazolealanine (beta-PA) synthesized by SATase and cysteine/beta-PA synthase, enhanced the expression of Sat by ca. 2-fold.

Bacterial translocation-related mortality may be associated with neutrophil-mediated organ damage.

Balb/c mice were transfused with .2 mL of C3H/HeJ mouse blood. 5 days later, the mice were gavaged with 10(10) 14C-labeled Escherichia coli, and a 20% full thickness flame burn was inflicted. Additional animals were treated with enisoprost (prostaglandin E1 (PGE1) analog) 200 micrograms/kg/day orally for 3 days before burn. Bacterial translocation was determined by both radionuclide counts (dpm) and viable colony counts 24 h post burn. Neutrophil accumulation was evaluated by the measurement of myeloperoxidase (MPO) in the liver. In addition, splenic macrophages were separated and cultured for 24 h with or without 10 micrograms/mL of LPS. Tumor necrosis factor, interleukin-1 (IL-1), IL-6, and PGE2 were measured in the cell culture supernatants. Consistent with previous work, enisoprost significantly reduced translocation. MPO in the liver was significantly greater in the control group compared to the enisoprost group. There was a significant correlation between MPO content and the degree of bacterial translocation (p < .05). Lipopolysaccharide-stimulated macrophage production of IL-1, IL-6, and PGE2 were significantly greater in the enisoprost group.

Interleukin-1 and tumor necrosis factor alter plasma concentration and interorgan fluxes of taurine in dogs.

We examined the effects of interleukin-1 beta (IL-1), tumor necrosis factor (TNF), and alanylglutamine (Ala-Gln) infusion on the plasma concentrations and interorgan fluxes of taurine and taurine precursors, including methionine and serine, using chronically catheterized awake dogs. In the first study, the dogs received 5 micrograms/kg/h of either human recombinant IL-1 or TNF intravenously for 2 h. Taurine fluxes in the liver and gut were calculated by blood flows and arteriovenous differences during infusion and for 2 h after discontinuation of the cytokine infusions. The 2 h continuous infusions of TNF and IL-1 resulted in 60 and 90% increases, respectively, in the arterial plasma taurine concentration. Hepatic taurine flux changed from uptake to release after 2 h of continuous IL-1 infusion. In the second study, we investigated whether Ala-Gln infusion affects taurine metabolism under normal and stress conditions. The dogs were given a constant 2 h intravenous infusion of IL-1 or saline. Ala-Gln (6 mumol/kg/min) was infused simultaneously during the second hour. Plasma concentrations and fluxes, across the liver, gut, and lung, of taurine and taurine precursors were studied. IL-1 administration increased the plasma concentration, hepatic release, and lung uptake of taurine. Ala-Gln infusion did not affect either plasma concentrations or organ fluxes of taurine. These data suggest that cytokines play a role in taurine metabolism under stress conditions.

The primary site of bacterial translocation.

OBJECTIVE: To establish the primary anatomic site of bacterial translocation in the intestinal tract. DESIGN: Prospective randomized experimental trials. SETTING: Laboratory. MATERIALS: Hartley guinea pigs. INTERVENTIONS: In guinea pigs, 10-cm closed loops of upper jejunum, distal ileum, or proximal colon were created. The animals then received intraluminal injections of Escherichia coli labeled with radioactive carbon (14C) before a 50% full-thickness burn was inflicted. Four hours after the burn injury, the animals were killed, and the intestinal loops, mesenteric lymph nodes, spleen, liver, and lung were harvested. Intestinal loops were irrigated and then treated with ethylenedinitroilotetraacetic acid to separate the enterocytes and colonocytes from the lamina propria. Radionuclide counts were determined in the effluents, the enterocytes (or colonocytes), lamina propria, and other organs. Colony-forming units of E coli were also determined in mesenteric lymph nodes, spleen, liver, and lung. MEASUREMENTS AND MAIN RESULTS: No significant differences were noted in the radionuclide counts in the lamina propria and epithelial cell fraction related to the type of loop. In addition, no significant differences were noted in the radionuclide counts in the mesenteric lymph nodes, liver, spleen, and lung related to the type of loop, but more viable bacteria were recovered when bacteria were injected into the jejunal loop. CONCLUSIONS: Translocation of bacteria occurred with similar intensity throughout the gut, but more bacteria were killed in the process of translocation across the lower part of the intestinal tract.

Detrimental effects of a nitric oxide synthase inhibitor (N-omega-nitro-L-arginine-methyl-ester) in a murine sepsis model.

OBJECTIVE: To examine the effects of a nitric oxide synthase inhibitor on host elimination of bacteria, tumor necrosis factor (TNF) production, and survival in a murine sepsis model. DESIGN: Prospective randomized experimental trials. SETTING: Laboratory. MATERIALS: Female Balb/c mice. INTERVENTIONS: Balb/c mice were injected with Escherichia coli (10(8) colony-forming units per body) into the peritoneal cavity. N-omega-Nitro-L-arginine-methyl-ester (L-NAME), an inhibitor of nitric oxide synthase, was given intraperitoneally at 10 mg/kg (N10 group) or 100 mg/kg (N100 group) 1 hour before bacterial challenge. MAIN OUTCOME MEASURES: Thirty animals were observed for survival. Samples of peritoneal lavaged fluid (PLF), blood, liver, and lungs were obtained at 4 and 6 hours after bacterial challenge (n = 60). The peritoneal exudative cells were counted. Viable bacterial counts were determined in PLF, blood, and organs. The TNF levels also were determined in plasma, PLF, and supernatant samples of cultured peritoneal exudative cells. RESULTS: Survival times after E coli challenge were significantly reduced by pretreatment with L-NAME (100 mg/kg intraperitoneally). Numbers of viable bacteria in the peritoneal cavity and plasma TNF level 4 hours after E coli challenge were higher in both L-NAME-treated groups than in the control group. The number of bacteria in the blood and the plasma TNF level 6 hours after E coli challenge were higher in the L-NAME-treated group (N100 group) than in the control group. Conversely, the number of hepatic bacteria in the control group was significantly higher than in the L-NAME-treated groups. Plasma TNF level showed significant positive correlations with numbers of bacteria in the PLF and in the blood 4 hours after challenge. No significant differences were noted in TNF levels in PLF and peritoneal exudative cell cultured supernatants. CONCLUSION: Inhibition of nitric oxide production is detrimental in this gram-negative sepsis model.