Effect of glycoelectrolytic supplement on post-weaning piglet performance and intestinal integrity.

This study evaluated the effects of glycoelectrolytic supplements on the performance, blood parameters, and intestinal morphology of piglets during the post-weaning period. In the study, a total of 240 piglets weaned aged 17 22.60 + 1.10 days were used. The control group (n = 120) received only water, and the treatment group (n = 120) received an oral glycoelectrolytic supplement diluted in water (0.75%) during the first three days after weaning. Feed intake, daily weight gain, final weight, feed conversion ratio, and post-weaning mortality were evaluated. On the third day after weaning, the blood glucose levels of all piglets were analyzed. Blood was collected from 12 piglets from each treatment group on day 3 after weaning for blood count analysis, and intestinal fragments were collected for anatomopathological and morphometric evaluation. Better feed conversion ratio (1.29) and higher consumption of liquids (0.639 L/day) were observed in the piglet group supplemented with glycoelectrolytes on day 3 after weaning (P < 0.05). The supplemented group presented a higher glycemic index (80.78 mg/dL), average corpuscular volume (67.35 fL), and average corpuscular hemoglobin (20.46 pg) than the control group (P < 0.05). The evaluation of intestinal integrity and the probability of diarrhea occurrence were similar between the groups (P > 0.05). Oral glycoelectrolytic supplementation can be an option for piglets immediately after weaning as it improves feed conversion and consumption of liquids, in addition to increasing blood glucose without the occurrence of diarrhea, thus reducing dehydration and energy deficit.

CDX2 prognostic value in stage II/III resected colon cancer is related to CMS classification.

BACKGROUND: Caudal-type homeobox transcription factor 2 (CDX2) is involved in colon cancer (CC) oncogenesis and has been proposed as a prognostic biomarker in patients with stage II or III CC. PATIENTS AND METHODS: We analyzed CDX2 expression in a series of 469 CC typed for the new international consensus molecular subtype (CMS) classification, and we confirmed results in a series of 90 CC. RESULTS: Here, we show that lack of CDX2 expression is only present in the mesenchymal subgroup (CMS4) and in MSI-immune tumors (CMS1) and not in CMS2 and CMS3 colon cancer. Although CDX2 expression was a globally independent prognostic factor, loss of CDX2 expression is not associated with a worse prognosis in the CMS1 group, but is highly prognostic in CMS4 patients for both relapse free and overall survival. Similarly, lack of CDX2 expression was a bad prognostic factor in MSS patients, but not in MSI. CONCLUSIONS: Our work suggests that combination of the consensual CMS classification and lack of CDX2 expression could be a useful marker to identify CMS4/CDX2-negative patients with a very poor prognosis.

Expression of pEGFR and pAKT as response-predictive biomarkers for RAS wild-type patients to anti-EGFR monoclonal antibodies in metastatic colorectal cancers.

BACKGROUND: RAS wild-type (RASw/t) tumours have been associated with better outcomes in patients with metastatic colorectal cancer (mCRC) treated with anti-EGFR monoclonal antibodies (mAb). We investigated the expression of EGFR downstream proteins under their active phosphorylated forms as potential markers in response to these patients. METHODS: One-hundred tumour samples were collected from patients with mCRC refractory to FOLFOX and/or FOLFIRI and treated by a combination of chemotherapy with anti-EGFR mAb. The outcomes were measured on response evaluation criteria in solid tumour (RECIST), progression-free survival (PFS) and overall survival (OS). All samples were assessed for RAS and BRAF mutations, and the key phosphorylated proteins of EGFR downstream signalling were quantitatively analysed using the BioPlex Protein array. RESULTS: Among the 60 RASw/t patients, 45.0% achieved a complete or partial response when treated with anti-EGFR mAb. Expression of pAKT, pERK1/2 and pMEK1 was significantly lower in RASw/t patients (P=0.0246; P=0.004; P=0.0110, respectively). The response rate was significantly higher for RASw/t patients who express pEGFR and pAKT (P=0.0258; P=0.0277, respectively). CONCLUSIONS: Overexpression of pEGFR and pAKT may predict the response rate in RASw/t patients treated with anti-EGFR mAb. On the basis of our results, we hypothesise that the association of anti-EGFR mAb and anti-AKT therapies could be of interest.

Timpanismo ruminal crônico secundário à hipoplasia de pregas de omaso em dois bovinos / Chronic ruminal bloat secondary to omasal laminae hypoplasia in two cattle

Um novilho normando e outro charolês apresentando distensão abdominal, diarreia intermitente e timpanismo ruminal crônico, que iniciaram após desmame, foram enviados para necropsia. Observou-se ausência de pregas omasais associada à hipoplasia do órgão, assim como redução de tamanho das papilas ruminais e reticulares. Com base nas lesões e histórico, conclui-se que o timpanismo ruminal foi ocasionado pela falha no desenvolvimento do omaso...

Two emaciated juvenile steers, one Normande and one Charolaise breed with abdominal distension, intermittent diarrhea and chronic ruminal bloat that had begun at weaning were necropsied. Absence of the omasal laminae with omasal hypoplasia were found together with loss of ruminal papillae and reticular folds. Based on the lesions and history we concluded that the ruminal bloat was due to a development failure of the omasum...

Doença granulomatosa sistêmica em bovinos no estado de Santa Catarina associada ao pastoreio de ervilhaca peluda (Vicia villosa) / Systemic granulomatous disease in cattle in Santa Catarina, Brazil, associated with grazing of vetch (Vicia villosa)

Spontaneous intoxication in three dairy cows grazing pasture contaminated with Vicia villosa in two different farms was reported. Hyperthermia, skin alopecia and pruritus were the main clinical signs. Macroscopically, gray to white up to 5cm nodules were detected, especially in kidney and lymph nodes, which correspond to mild to severe multifocal granulomatous infiltrate. This is the first report of systemic granulomatous disease due to consumption of hairy vetch in the State of Santa Catarina, Brazil.

Treatment of neurogenic bowel dysfunction using transanal irrigation: a multicenter Italian study.

STUDY DESIGN: Thirty-six patients with unsatisfactory treatment of neurogenic bowel dysfunctions (NBD) were enrolled from Spinal Units and Rehabilitation Centers in Italy. Treatment was for 3 weeks using a newly developed integrated system with an enema continence catheter for transanal irrigation (Peristeen, Coloplast A/S Kokkedal Denmark). OBJECTIVES: To evaluate the effects of Peristeen Anal Irrigation on NBD and patient quality of life (QoL). SETTING: Italy. METHODS: Lesion level, ambulatory status and hand functionality were determined in all patients. NBD symptoms and QoL were evaluated before and after treatment, using a specific questionnaire. Statistical analysis was performed using McNemar Test and Sign Test. RESULTS: Thirty-six patients were enrolled, and 32 patients completed the study. At the end of the treatment, 28.6% of patients reduced or eliminated their use of pharmaceuticals. Twenty-four patients became less dependent on their caregiver. There was a significant increase in patients' opinion of their intestinal functionality (P=0.001), QoL score (P=0.001) and their answers regarding their degree of satisfaction (P=0.001). A successful outcome was recorded for 68% of patients with fecal incontinence, and for 63% of patients with constipation. CONCLUSION: Peristeen Anal Irrigation is a simple therapeutic method for managing NBD and improving QoL. It should be considered as the treatment of choice for NBD, playing a role in the neurogenic bowel analogous to that of intermittent clean catheterization in bladder treatment.

Mammomonogamus laryngeus (Railliet, 1899) infection in buffaloes in Rio Grande do Sul, Brazil.

Parasites of the genus Mammomonogamus affect the respiratory tract of domestic animals. The present study was carried out to determine the presence of Mammomonogamus laryngeus infection and to analyze its lesions in infected buffaloes in Rio Grande do Sul, Brazil, between April and November 1999. The infection rate was 30.5%. In 32 infected buffaloes, the worm pairs collected per animal did not exceed 20. The microscopic diagnosis showed intense polypoid to intramucosal proliferation at the entrance to the pharynx, to which the parasites had adhered, with foci of multifocal hydropic degeneration of the epithelium or individual degeneration of epithelial cells with mild intraepithelial inflammatory infiltrate. The submucosa revealed intense lymphocyte infiltrate extending into the salivary glands. The submucosa also showed formation of structures that resemble lymphoid follicles.

Clinical, pathological and antigenic aspects of bovine viral diarrhea virus (BVDV) type 2 isolates identified in Brazil.

Nucleotide sequencing and phylogenetic analysis of Brazilian bovine viral diarrhea virus (BVDV) field isolates identified four viruses belonging to the genotype 2. Comparison of 5' UTR sequences from these isolates to those of North American BVDV type 2 revealed genomic variations that correlated with the geographic origins of the isolates. Two of the Brazilian type 2 viruses were isolated from clinical cases of gastroenteric/respiratory disease and two were isolated from healthy bovine fetuses. The clinical cases affected young animals (8- and 18-months-old) and were characterized by diarrhea, respiratory signs, extensive oral and digestive tract erosions, conjunctival and vulvar congestion, occasional digestive bleeding and vulvar and heart petechial hemorrhage. Antigenic analysis of these isolates with a panel of 10 monoclonal antibodies revealed marked antigenic differences in the major envelope glycoprotein, gp53/E2, compared to standard laboratory and vaccine BVDV strains. In addition, virus-specific antisera raised to Brazilian BVDV type 2 viruses displayed very low serological cross-reactivity with standard BVDV type 1 strains. Differences up to 64-fold in cross-neutralization titers were observed between BVDV type 1 and Brazilian BVDV type 2 isolates. The identification of BVDV type 2 among Brazilian cattle may have important implications for epidemiological studies, diagnostic and immunization strategies. Furthermore, the low neutralizing activity of BVDV type 1 antisera against the recently identified Brazilian BVDV type 2 isolates raises the question about the degree of protection conferred by BVDV vaccines, most of them based on a single type 1 strain.

Role of angiotensin II in sympathetic nervous system induced left ventricular dysfunction.

Experiments were undertaken to determine whether angiotensin (Ang) II concentration increases during massive sympathetic nervous system (SNS) activation and whether such an increase plays a role in the pathogenesis of SNS-induced left ventricular (LV) dysfunction. We also sought to determine whether excessive Ca2+ uptake through L-type channels due to intense adrenoceptor activation is responsible for the LV dysfunction. AngII concentration was measured in the plasma and myocardium before and after massively activating the SNS with an intracisternal injection of veratrine. In separate experiments, rabbits were given losartan, enalaprilat, enalaprilat plus HOE-140, nifedipine, -Bay K 4866, or saline before massively activating the SNS. LV function was evaluated 2.5 h later. The intense SNS activity caused plasma and myocardial AngII to increase by 400 and 437%, respectively. AngII receptor blockade did not prevent LV dysfunction. In contrast, enalaprilat reduced the degree of dysfunction, but its cardioprotection was abolished by HOE-140. Although nifedipine prevented SNS-induced LV dysfunction, administration of the Ca2+ channel opener, -Bay K 4866, did not increase its severity. Our results indicate that AngII is not involved in the pathogenesis of SNS-induced LV dysfunction and that the cardioprotection provided by angiotensin converting enzyme (ACE) inhibition is due to activation of a bradykinin pathway. Furthermore, the finding that the magnitude of the LV dysfunction was reduced by enalaprilat, and not increased by -Bay K 4866, suggests that intense adrenoceptor activation of L-type Ca2+ channels is not the primary pathogenetic mechanism.

Time-dependent changes in norepinephrine-induced left ventricular dysfunction and histopathologic condition.

BACKGROUND: Intense activation of the sympathetic nervous system or administration of high concentrations of catecholamines diminishes myocardial contractility and produces infarct-like lesions throughout the heart. This study was conducted to determine whether norepinephrine-induced left ventricular (LV) dysfunction reverses with time and whether the histopathologic condition and the cardiac dysfunction produced by high doses of norepinephrine are causally related. METHODS: Norepinephrine, 10 microg bolus followed by 2.5 microg/kg/min for 90 minutes, was administered to conscious New Zealand white rabbits. Control rabbits (n=8) received saline solution. LV function was evaluated either immediately (n=7), on day 4 (n=8), or on day 10 (n=7) after norepinephrine treatment. Transverse sections from the left ventricle were then prepared for light microscopic study. RESULTS: Animals studied immediately after norepinephrine treatment demonstrated severe LV dysfunction and a decrease in global LV compliance. In contrast, LV function and compliance were normal in rabbits studied on day 4, but tissue sections from the left ventricle showed diffuse areas of inflammation. By day 10 the inflammatory process had progressed, and substantial collagen deposition had occurred. LV systolic function was normal, but a decrease in LV compliance was evident at this time. CONCLUSIONS: The normal LV systolic function on days 4 and 10 in spite of multiple foci of inflammation suggests (1) that norepinephrine-induced LV systolic dysfunction is reversible and (2) that the histologic derangements and the LV dysfunction are not causally related.

Role of EDRF in the cardiopulmonary dysfunction produced by massive sympathetic activation.

This study was undertaken to determine whether endothelium-derived relaxing factor (EDRF) modulates the pulmonary and systemic hemodynamic responses to massive sympathetic nervous system (SNS) activation and, in so doing, also modulates the degree of SNS-induced left ventricular (LV) dysfunction and the likelihood for pulmonary edema formation. The SNS of 13 anesthetized untreated rabbits and 14 anesthetized rabbits pretreated with the EDRF inhibitor, N omega-nitro-L-arginine (L-NNA, 20 mg/kg), was massively activated with an intracisternal injection of veratrine. Pulmonary and systemic arterial pressures increased to the same extent in both groups, but LV end-diastolic pressure was significantly lower in untreated rabbits. During this time, cardiac output decreased by 37% in L-NNA pretreated rabbits compared with 8% in untreated animals. Peak systemic and pulmonary vascular resistances increased significantly in L-NNA rabbits, whereas only systemic vascular resistance increased significantly in untreated rabbits. However, this increase in systemic vascular resistance was threefold less than that observed for L-NNA-treated animals. Although the degree of LV dysfunction was greater in the L-NNA rabbits, pulmonary edema developed less frequently in this group. We suggest that when EDRF release is inhibited during massive SNS activity, pulmonary vascular resistance increases markedly, which causes the right ventricle to fail. We further suggest that the reduced right ventricular output maintains pulmonary microvascular pressure below levels required for edema development.

Temporal changes in left ventricular function after massive sympathetic nervous system activation.

Intense activation of the sympathetic nervous system (SNS) decreases the contractile state of the rabbit left ventricle (LV). In this study, we determined the time course of LV dysfunction after massive central activation of the SNS in dogs. Veratrine (40-80 micrograms/kg) was injected intracisternally to activate the SNS in six chloralose-anesthetized dogs, and LV end-diastolic pressure (LVEDP), cardiac output, heart rate, and aortic pressure (Pa) were measured at 30-min intervals for 3 h. Pa increased from 147 +/- 8 (SE) to 272 +/- 7 mmHg (1 mmHg = 133.3 Pa) within 15 min, then declined to 148 +/- 16 mmHg by 1 h LV function curves (stroke work versus LVEDP or stroke work verus LV transmural pressure) showed a marked decrease in slope and a shift to the right within minutes after activating the SNS, which persisted for the duration of the experiment. These data indicate that LV contractility was diminished in these animals. No changes in LV function were observed in three dogs serving as time-matched controls. In three additional dogs, LV pressure was raised to a degree similar to that observed after SNS activation by constricting the ascending aorta for 1 h. These animals exhibited only modest shifts in the LV function curve during and after aortic constriction. Mean plasma catecholamine concentration increased by one to two orders of magnitude in animals after SNS activation, but only minor changes were observed in the other two groups. We conclude that myocardial contractility declines markedly soon after massive SNS activation and is not solely a function of the initial hypertensive period.

Myocardial work load is a major determinant of norepinephrine-induced left ventricular dysfunction.

This study was conducted to determine whether increased myocardial energy demand plays a role in norepinephrine (NE)-induced left ventricular (LV) dysfunction. A range of arterial pressure-heart rate (P-R) products (myocardial energy demand) was produced in both conscious and pentobarbital sodium-anesthetized rabbits with the same dose of NE (10 micrograms priming bolus plus 2.5 micrograms.kg-1 x min-1 for 2.5 h). After NE treatment, LV function was evaluated in vitro and found to be markedly diminished in the rabbits that had an elevated P-R product. In contrast, LV function was not significantly affected when the P-R product was maintained near control levels during NE treatment. In separate experiments, rabbit hearts were isolated and exposed to NE (10,000 or 50,000 pg/ml) for 2.5 h under low P-R product conditions. These hearts exhibited a dose-dependent decrease in LV function that was modest compared with that observed in rabbits that had elevated P-R products during in vivo NE treatment. Our results suggest that high concentrations of NE may cause modest degrees of LV dysfunction independently of increases in myocardial energy demand, but the LV dysfunction is exacerbated when myocardial energy demand is elevated.

Persistent left ventricular dysfunction after cocaine treatment in rabbits.

The present study was undertaken to determine whether the diminished cardiac performance associated with cocaine administration persists after the drug has been eliminated from the body. Cocaine (5 or 10 mg/kg iv) was administered to conscious (n = 7) or pentobarbital-anesthetized (n = 7) rabbits, respectively. Seven conscious and seven anesthetized control rabbits received the saline vehicle. Two and one-half hours later, the hearts were removed from the animals and perfused under cocaine-free conditions. Left ventricular (LV) contractility was evaluated by plotting steady-state LV systolic and diastolic pressures as a function of LV end-diastolic volume (preload). LV systolic performance was diminished in a dose-related manner in hearts isolated from cocaine-treated rabbits, but was statistically different from control only at the higher cocaine dose (P < 0.05). In a second set of experiments, hearts (n = 6) were isolated, and their LV function was evaluated before, during, and after cocaine exposure. In these experiments, cocaine was added to the perfusate in increments to produce concentrations of 5, 10, and 15 mg/liter. After LV function was evaluated at the highest cocaine dose, cocaine-free perfusion conditions were restored, and LV function was reevaluated. In these experiments, cocaine produced a dose-dependent decrease in LV function that readily reversed when cocaine-free perfusion was reinstated. We conclude that cocaine diminishes LV contractility, and that the diminished cardiac performance may not readily reverse after in vivo exposure. Moreover, the rapid restoration of cardiac performance after exposure to cocaine in vitro suggests that the mechanism operating in vivo involves more than a simple direct action on the myocyte. Catecholamine cardiotoxicity does not appear to be a primary factor.

Factors involved in left ventricular dysfunction after massive sympathetic activation.

We sought to determine whether catecholamines are responsible for the depressed left ventricular (LV) function that follows massive sympathetic nervous system (SNS) activation and whether the additional myocardial energy demands of SNS-induced hypertension contribute to this disorder. An intracisternal injection of veratrine was used to intensely activate the SNS of anesthetized rabbits, and 150 min later, LV function was evaluated in vitro using established techniques. To assess catecholamine involvement, rabbits were pretreated with phentolamine, propranolol, or saline prior to SNS activation. Control animals received veratrine intravenously. In separate experiments, angiotensin II (ANG II) was administered to rabbits to produce hemodynamic and plasma catecholamine profiles comparable to that produced by intense SNS activity. LV function of hearts after either massive SNS activation or ANG II administration was significantly diminished compared with control (P less than 0.01) and could be prevented by pretreatment with the catecholamine antagonists. LV function was also not diminished in another group of animals in which arterial pressure was maintained near baseline throughout the SNS discharge, thus suggesting that the increased myocardial energy demand associated with the development of arterial hypertension contributes to the LV dysfunction. We conclude that toxic concentrations of catecholamines are responsible for SNS-induced LV dysfunction and that hypertension, most likely because of its ability to increase myocardial energy demand, is one of the important events that leads to depressed cardiac function.

Circulating neuropeptide Y does not produce pulmonary hypertension during massive sympathetic activation.

We tested the possibility that neuropeptide Y (NPY) may contribute to the pulmonary hypertension that occurs after massive sympathetic activation produced by intracisternal veratrine administration in the chloralose-anesthetized dog. In six dogs, veratrine caused arterial NPY-like immunoreactivity (NPY-LI) to rise from 873 +/- 150 (SE) pg/ml to peak values of 3,780 +/- 666 pg/ml by 60-120 min. (In 3 animals, adrenalectomy significantly reduced the increases in NPY-LI.) In five additional dogs, we infused porcine NPY for 30 min in doses that increased arterial NPY-LI to 8,354 +/- 1,514 pg/ml and observed only minor changes in pulmonary hemodynamics. In three isolated perfused canine left lower lung lobe (LLL) preparations, increasing doses of NPY were administered, producing levels of plasma NPY-LI, at the highest dose, that exceeded those observed after veratrine administration by three orders of magnitude. No changes in LLL arterial or double-occlusion capillary pressures were observed at any dose. Similarly, no changes in LLL hemodynamics were observed in three additional lobes when NPY was administered while norepinephrine was being infused. We conclude that it is unlikely that NPY plays a role as a circulating vasoactive agent in producing the pulmonary hypertension and edema that occur in this model.

Pulmonary vascular protein sieving capability after exposure to high vascular pressures.

We evaluated the ability of the canine in situ left lower lobe (LLL) vasculature to sieve endogenous plasma proteins of various molecular radii (34-124 A) after LLL arterial pressure had been transiently elevated to 23.8 +/- 0.9 (control group, n = 5) or 92.3 +/- 1.4 (SE) Torr (high-pressure group, n = 9) by restricting LLL venous outflow under conditions of constant flow. After LLL flow was returned to natural perfusion, left atrial pressure was elevated in step increments, and LLL lymph and blood samples were collected until filtration-independent lymph-to-plasma protein concentration ratios (CL/CP) were obtained. The osmotic reflection coefficients (sigma d) for total proteins and seven protein fractions (separated by gradient gel electrophoresis) were calculated. The average total protein sigma d of the high-pressure group [0.51 +/- 0.06 (SE)] was significantly lower than that of the control group (0.68 +/- 0.03). Several LLLs of the high-pressure group, however, exhibited normal sigma d's. Protein fraction CL/CP's decreased with increasing molecular radius in both groups, but the CL/CP-molecular radius relationship was displaced upward in the high-pressure group. Pore analysis suggested that the decreases in sigma d could be explained by increases in the fractional flow through a large-pore system.

Senecio spp poisoning in cattle in southern Brazil.

Epidemiological, clinical, necropsy and histopathological data were accumulated during the study of 15 outbreaks of Senecio spp poisoning in cattle occurring during the last 3 y in the State of Rio Grande do Sul, Brazil. Morbidity averaged 17% and mortality was virtually 100%. The peak mortality occurred during spring and early summer. The most constant clinical signs included anorexia, depression, tenesmus often followed by rectal prolapse, and rough hair coat. Affected animals remained apart from the rest of the herd, lost weight, presented ascites, and had signs of digestive and neurological disturbances. Icterus, photodermatitis, polydipsia, and dependent subcutaneous edema were occasionally noticed. Two main clinical courses could be distinguished. In the protracted form, progressive weight loss terminated with death within many weeks or months. Alternatively, an acute or subacute course led to death in a few days. In both forms, necropsy and histopathological findings included diffuse fibrosis of the liver, hepatomegalocytosis, and biliary hyperplasia. Extrahepatic lesions included gastrointestinal and mesenteric edema, distension, edema and adenomatoid hyperplasia of the gallbladder, and spongy degeneration of the cerebral white matter. S brasiliensis and S oxyphyllus were the species involved in the field outbreaks.

Effect of intracoronary infusion of histamine or compound 48/80 on coronary vascular permeability and myocardial fluid balance.

This study was undertaken to determine if coronary vascular permeability (CVP) increases and if myocardial edema develops in the canine heart after local exposure to histamine. Histamine (50 or 15 micrograms/min) or compound 48/80 (0.1-0.2 mg/kg) was infused into the left anterior descending coronary artery (LAD) of open-chest dogs, and changes in CVP were determined by comparing prenodal cardiac lymph flow (Q1) and lymph-to-plasma protein concentration ratio (C1/Cp) before and during histamine or compound 48/80 treatment. CVP increased in most, but not all, experiments with both doses of histamine as indicated by simultaneous increases in both Q1 and C1/Cp. The injection of compound 48/80 into the LAD of four dogs caused unequivocal increases in CVP in only one experiment. Compared with the effect of histamine on the forelimb, the average increases in Q1 and C1/Cp were not large with either histamine or compound 48/80, which suggests that the increases in CVP were relatively small. Moreover, edema did not develop. These results indicate that the coronary microvasculature of the intact dog heart is relatively insensitive to increases in permeability produced by histamine. Furthermore, the release of histamine from myocardial mast cells would not be expected to play a major role in the myocardial edema that develops under various pathological conditions.