Vasopressin dilates the rat carotid artery by stimulating V1 receptors.

The acute effects of various vasopressor agents on the diameter of the common carotid artery were studied in halothane-anesthetized normotensive rats. The animals were infused intravenously for 60 min with equipressor doses of angiotensin II (10 ng/min), the alpha1-stimulant methoxamine (5 microg/min), lysine vasopressin (5 mU/min), or vehicle. The arterial diameter was measured by using a high-resolution ultrasonic echo-tracking device. The three vasoconstrictors increased the carotid artery diameter, but this effect was significantly more pronounced with lysine vasopressin. Even a nonpressor dose of lysine vasopressin (1 mU/min) caused a significant increase in the arterial diameter. The lysine vasopressin-induced vasodilatation could be prevented by the administration of d(CH2)5Tyr(Me)AVP (10 microg, i.v.), a selective V1-vasopressinergic receptor antagonist. These data therefore suggest that a short-term increase in blood pressure induces in rats a distention of the carotid artery. The increase in arterial diameter seems to involve an active mechanism with lysine vasopressin caused by the stimulation of V1-vasopressinergic receptors.

Systematic review: Terlipressin in acute oesophageal variceal haemorrhage

Background: Controversy exists surrounding pharmacological therapy in acute variceal bleeding. Methods: To determine the efficacy and safety of terlipressin. Methods: Randomized trials were identified and duplicate, independent, review identified 20 randomized trials involving 1609 patients that compared terlipressin with placebo, balloon tamponade, endoscopic treatment, octreotide, somatostatin or vasopressin for treatment of acute oesophageal variceal haemorrhage. Results: Meta-analysis showed that compared to placebo, terlipressin reduced mortality (relative risk 0.66, 95% CI 0.49-0.88), failure of haemostasis (relative risk 0.63, 95% CI 0.45-0.89) and the number of emergency procedures per patient required for uncontrolled bleeding or rebleeding (relative risk 0.72, 95% CI 0.55-0.93). When used as an adjuvant to endoscopic sclerotherapy, terlipressin reduced failure of haemostasis (relative risk 0.75, 95% CI 0.58-0.96), and had an effect on reducing mortality that approached statistical significance (relative risk 0.74, 95% CI 0.53-1.04). No significant difference was demonstrated between terlipressin and endoscopic sclerotherapy, balloon tamponade, somatostatin or vasopressin. Haemostasis was achieved more frequently with octreotide compared to terlipressin (relative risk 1.62, 95% CI 1.05-2.50), but this result was based on unblinded studies. Adverse events were similar between terlipressin and the other comparison groups except for vasopressin, which caused more withdrawals due to adverse events. Conclusions: Terlipressin is a safe and effective treatment for acute oesophageal variceal bleeding, with or without adjuvant endoscopic sclerotherapy. Terlipressin appears to reduce mortality in acute oesophageal variceal bleeding compared to placebo, and is the only pharmacological agent shown to do so. Future studies will be required to detect potential mortality differences between terlipressin and other therapeutic approaches.

Apparent digestibility of diets with different concentrations of lysine and energy in piglets with different body weights and post-weaning age

The effects of body weight or age and dietary digestible lysine and metabolizable energy on apparent digestibility of energy and dry matter were evaluated in piglets after weaning. The animals were weaned at 21 days of age and distributed in two groups: 8.68 ± 0.76 kg at 28 days of age (weaned 7 days earlier); and 12.73 ± 0.99 kg at 35 days of age (weaned 14 days earlier). The pigs were allotted in digestibility cages in a completely randomized block design with the following factorial arrangements: 2 × 4 composed of two weight categories and four levels of digestible lysine (1.222; 1.305; 1.390 and 1.497%); and 2 × 3 composed of two weight categories and three levels of metabolizable energy (3,510; 3,700 and 3,830 kcal/kg rations). Digestible lysine was evaluated in six replications and metabolizable energy in eight replications and each animal constituted an experimental unit. Piglets with higher body weight and age were more efficient in nitrogen retention and energetic balance, compared to lighter and younger piglets, particularly those given lower concentration of lysine in the diet. The energy increase favored nitrogen retention by the heavier and older piglets. However, coefficients of dry matter and energy apparent digestibility did not differ among weight categories. Older and heavier piglets were more efficient in nitrogen retention, although this efficacy depended on concentration of the energy in the diet. This better use of protein and energy suggest differences on nutritional requirements.

Dietary levels of lysine for male broilers from 23 to 36 days of age: performance and body composition

One thousand and fifty (1,050) Ross male broilers from 23 to 36 days of age were used to evaluate the dietary effects of levels of lysine. It was used a random block design with 5 levels of digestible lysine (0.95; 1.00; 1.05; 1.10 and 1.15%). Each level was applied to seven replicates and the experimental unit was composed of 30 birds. Diets were offered in seven replicates and the experimental unit was represented by 30 birds. Weight gain, feed intake, feed conversion, carcass traits, cut yields, composition and deposition of body nutrients were evaluated. The concentration of 1.09% of digestible lysine optimized performance without significant effects on feed intake. Carcass traits and cut yields had no significant differences among levels of lysine. On the other hand, there was a quadratic effect on carcass weight, which was the best at the level of 1.07% of digestible lysine. On crude protein content of the empty body, the best response was observed at the level of 1.10% of dietary lysine. This same level corresponded to a quadratic response in the deposition of water from carcass and empty body. The level of digestible lysine for better performance, chemical composition and body nutrient deposition in broilers from 23 to 36 days of age is between 1.07 and 1.10%.

Digestible lysine and organic zinc for male broiler from 1 to 11 days of age: performance and body composition

This study evaluated levels of digestible lysine and organic zinc for male Ross strain broilers from 1 to 11 days of age. It was used 1,050 chicks distributed in randomized block design, in 5 × 2 factorial scheme, with seven repetitions of 15 birds per experimental unit. The dietary concentrations of digestible lysine were 0.90; 1.00; 1.10; 1.20; and 1.40% combined with 43 and 253 ppm zinc chelate. The diets contained 2,965 ± 18 kcal/kg of apparent metabolizable energy (AME) and 21.48 ± 0.18% of CP. It was determined chemical composition, protein, lipid, mineral and water depositions on carcass and empty body. There was no interaction among the factors digestible lysine and organic zinc. Effect of zinc concentration increase was observed on greatest deposition of body fat, indicating that there is interference in lipid metabolism of the birds in the studied phase. The most pronounced effects resulted from the dietary inclusion of lysine. There was a linear effect on reconstituted body weight as a response to the increase of dietary lysine, which suggests equal or superior requirement to the greatest studied level. However, the deposition of water and protein on the carcass had a quadratic increase, characterizing higher muscle mass accumulation up to the levels 1.25 and 1.27 of this amino acid in the diet. Considering the studied strain, broiler chickens from the first to the 11th days of age require 1.28 ± 0.01% of digestible lysine, according to the deposition of muscle mass.

Lysine and zinc chelate in diets for brown laying hens: effects on egg production and composition

It was evaluated the effects of levels of digestible lysine and chelate zinc combined in the diet for laying on the egg quality. It was used 720 birds, from 48 to 60 weeks of age, distributed in a completely randomized design in a 3 × 5 factorial scheme with three levels of zinc and five levels of lysine, applied into six replicates in the experimental units of eight birds per plot. The levels were: 137, 309 and 655 ppm zinc and 0.482, 0.527, 0.582, 0.644 and 0.732% digestible lysine. It was not observed any interaction among digestible lysine and zinc for the primary variables of fractions and egg composition. Levels of zinc reduced egg weight, suggesting the lowest efficiency in nutrient intake. At the highest dietary concentration of zinc, the addition of digestible lysine coincided with a linear increase in shell weight. However, zinc addition, regardless of lysine level in the diet, resulted in the reduction of egg weight and of the percentage of mineral matter in the yolk, limiting the efficiency of mineral deposition in this fraction of the egg. Concentration of zinc that produced the best results was 137 ppm inasmuch as higher quantities limit the use of digestible lysine, with effects harming composition and egg quality. The study indicates the following requirement for digestible lysine: 0.639% from the 48th to the 52nd week, 0.679% from the 52nd to 56th week, and 0.635% from the 56th to the 60th week. Considering the total period from 48th to the 60th week, the level 0.638% of lysine or the daily intake of 707 mg of the amino acid met the requirement for egg quality of semi-heavy layers used in this study.

An upflow fixed-bed anaerobic-aerobic reactor for removal of organic matter and nitrogen from L-lysine plant wastewater

This paper reports on the design of a new reactor configuration - an upflow fixed-bed combined anaerobic-aerobic reactor - can operate as a single treatment unit for the removal of nitrogen (approximate to 150 mg N/L) and organic matter (approximate to 1300 mg COD/L) from Lysine plant wastewater. L-Lysine, an essential amino acid for animal nutrition, is produced by fermentation from natural raw materials of agricultural origin, thus generating wastewater with high contents of organic matter and nitrogen. The best operational condition of the reactor was obtained with a hydraulic retention time of 35 h (21 h in the anaerobic zone and 14 h in the aerobic zone) and a recycling ratio (R) of 3.5. In this condition, the COD, total Kjeldahl nitrogen (TKN), and total nitrogen (TN) removal efficiencies were 97%, 96%, and 77%, respectively, with average effluent concentrations of 10 +/- 36 mg COD/L, 2 +/- 1 mg NH(4)(+)-N/L, 8 +/- 3 mg Org-N/L, 1 +/- 1 mg NH(2)(-)-N/L, and 26 +/- 23 mg NH(3)(-)-N/L.

Lysine biosynthesis and nitrogen metabolism in quinoa (Chenopodium quinoa): Study of enzymes and nitrogen-containing compounds

Aspartate kinase (AK, EC 2.7.2.4), homoserine dehydrogenase (HSDH, EC 1.1.1.3) and dihydrodipicolinate synthase (DHDPS, EC 4.2.1.52) were isolated and partially purified from immature Chenopodium quinoa Willd seeds. Enzyme activities were studied in the presence of the aspartate-derived amino acids lysine, threonine and methionine and also the lysine analogue S-2-aminoethyl-L-cysteine (AEC), at 1 mM and 5 mM. The results confirmed the existence of, at least, two AK isoenzymes, one inhibited by lysine and the other inhibited by threonine, the latter being predominant in quinoa seeds. HSDH activity was also shown to be partially inhibited by threonine, whereas some of the activity was resistant to the inhibitory effect, indicating the presence of two isoenzymes, one resistant and another sensitive to threonine inhibition. Only one DHDPS isoenzyme highly sensitive to lysine inhibition was detected. The results suggest that the high concentration of lysine observed in quinoa seeds is possibly due to a combined effect of increased lysine, synthesis and accumulation in the soluble form and/or as protein lysine. Nitrogen assimilation was also investigated and based on nitrate content, nitrate reductase activity, amino acid distribution and ureide content, the leaves were identified as the predominant site of nitrate reduction in this plant species. The amino acid profile analysis in leaves and roots also indicated an important role of soluble glutamine as a nitrogen transporting compound. (c) 2007 Elsevier Masson SAS. All rights reserved.

Dietary lysine requirement of juvenile pacu Piaractus mesopotamicus (Holmberg, 1887)

Lysine is the reference essential amino acid in fish feeds and usually the most limiting amino acid in feedstuffs. The dietary lysine requirement of juvenile pacu Piaractus mesopotamicus (4.3 g) was determined using five isonitrogenous (32% CP) test diets containing graded levels of lysine (0.9, 1.17, 1.44, 1.69 and 1.96% of dry diet) fed three times a day to four groups of 18 fish for 74 days. Growth, body composition, nutrient retention and hematological parameters of pacu were analyzed. Analysis of variance showed that all growth performance parameters were significantly affected by dietary treatments. The lysine requirements estimated using regression analysis for maximum weight gain and feed efficiency were 1.45 and 1.51% of dry diet, respectively. Nitrogen retention efficiency increased with increasing levels of dietary lysine up to 1.43% (p<0.05). Whole-body protein increased (p<0.05) and whole-body lipid decreased (p<0.05) with increasing dietary lysine level. Thus, the lysine requirement of juvenile pacu was estimated as being 1.4-1.5% of dry diet or 4.4-4.7% of dietary protein. (c) 2009 Elsevier B.V. All rights reserved.

BLOCKING CENTRAL LEUKOTRIENES SYNTHESIS AFFECTS VASOPRESSIN RELEASE DURING SEPSIS

Recent studies revealed that vasopressinergic neurons have a high content of cys-leukotriene C(4) (LTC(4)) synthase, a critical enzyme in cys-leukotriene synthesis that may play a role in regulating vasopressin secretion. This study investigates the role of this enzyme in arginine vasopressin (AVP) release during experimentally induced sepsis. Male Wistar rats received an i.c.v. injection of 3-[1-(p-chlorobenzyl)-5-(isopropyl)-3-tert-butylthioindol-2-yl]-2, 2-dimethylpropanoic acid (MK-886) (1.0 mu g/kg), a leukotrienes (LTs) synthesis inhibitor, or vehicle, 1 h before cecal ligation and puncture (CLP) or sham operation. In one group of animals the survival rate was monitored for 3 days. In another group, the animals were decapitated at 0, 4, 6, 18 and 24 h after CLP or sham operation, and blood was collected for hematocrit, serum sodium and nitrate, plasma osmolality, protein and AVP determination. A third group was used for blood pressure measurements. The neurohypophysis was removed for quantification of AVP content, and the hypothalamus was dissected for LTC4 synthase analysis by Western blot. Mortality after CLP was reduced by the central administration of MK-886. The increase in plasma AVP levels and hypothalamus LTC4 synthase content in the initial phase of sepsis was blocked, whereas the decrease in neurohypophyseal AVP content was partially reversed. Also the blood pressure drop was abolished in this phase. The increase of serum nitric oxide and hematocrit was reduced, and the decrease in plasma protein and osmolality was not affected by the LTs blocker. In the final phase of sepsis, the plasma AVID level and the hypothalamic LTC4 synthase content were at basal levels. The central administration of MK-886 increased the hypothalamic LTC4 synthase content but did not alter the plasma and neurohypophysis AVID levels observed, or the blood pressure during this phase. These results suggest that the central LTs are involved in the vasopressin release observed during sepsis. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.

Effects of an oral vasopressin receptor antagonist (OPC-31260) in a dog with syndrome of inappropriate secretion of antidiuretic hormone

Objective The syndrome of inappropriate secretion of antidiuretic hormone is a rare disorder in dogs characterised by hypo-osmolality and persistent arginine vasopressin production in the absence of hypovolaemia and/or hypotension. The study describes the efficacy and safety of the nonpeptide selective arginine vasopressin V-2 receptor antagonist OPC-31260 in a dog with the naturally occurring syndrome. Design The detailed case history of a dog with spontaneous syndrome of inappropriate secretion of antidiuretic hormone that received long-term therapy with oral OPC-31260 is presented. Effects of the first dose of OPC-31260 and of a dose administered after a continuous dosing period of 12 days are reported. Procedure Packed cell volume, plasma sodium, total protein, arginine vasopressin, renin activity, atrial natriuretic peptide, urine specific gravity, urine output, heart rate and body weight were monitored for 2 h before, and for 4 h after, the first dose of OPC-31260. The same parameters plus plasma osmolality and urine osmolality were monitored when an identical dose was administered after 12 days of therapy. Results Oral administration of OPC-31260 at 3 mg/kg body weight resulted in marked aquaresis with increased urine output and decline in urine specific gravity within 1 h. Corresponding increases in concentrations of plasma sodium, plasma osmolality and plasma renin activity were recorded over a 4 h period. Arginine vasopressin concentration remained inappropriately elevated throughout the study. Results were similar when the trial procedure was repeated after a stabilisation period of 12 days. Long-term therapy with OPC-31260 at a dose of 3 mg/kg body weight orally every 12 h resulted in good control of clinical signs with no deleterious effects detected during a 3-year follow-up period. Despite sustained clinical benefits observed in this case, plasma sodium did not normalise with continued administration of the drug. Conclusions Treatment of a dog with naturally occurring syndrome of inappropriate secretion of antidiuretic hormone with OPC-31260 at 3 mg/kg body weight orally every 12 h resulted in marked aquaresis and significant palliation of clinical signs with no discernible side-effects detected over a 3-year period. Thus, OPC-31260 appears to offer a feasible medical alternative to water restriction for treatment of dogs with syndrome of inappropriate secretion of antidiuretic hormone. Higher doses of OPC-31260 may be required to achieve and maintain normal plasma sodium in dogs with this syndrome.

Multiple recurrent genetic events converge on control of histone lysine methylation in medulloblastoma

We used high-resolution SNP genotyping to identify regions of genomic gain and loss in the genomes of 212 medulloblastomas, malignant pediatric brain tumors. We found focal amplifications of 15 known oncogenes and focal deletions of 20 known tumor suppressor genes (TSG), most not previously implicated in medulloblastoma. Notably, we identified previously unknown amplifications and homozygous deletions, including recurrent, mutually exclusive, highly focal genetic events in genes targeting histone lysine methylation, particularly that of histone 3, lysine 9 (H3K9). Post-translational modification of histone proteins is critical for regulation of gene expression, can participate in determination of stem cell fates and has been implicated in carcinogenesis. Consistent with our genetic data, restoration of expression of genes controlling H3K9 methylation greatly diminishes proliferation of medulloblastoma in vitro. Copy number aberrations of genes with critical roles in writing, reading, removing and blocking the state of histone lysine methylation, particularly at H3K9, suggest that defective control of the histone code contributes to the pathogenesis of medulloblastoma.

Cardiovascular responses to microinjection of noradrenaline into the medial amygdaloid nucleus of conscious rats result from alpha(2)-receptor activation and vasopressin release

The medial amygdaloid nucleus (MeA) is involved in the modulation of physiological and behavioral processes, as well as regulation of the autonomic nervous system. Moreover, MeA electrical stimulation evokes cardiovascular responses. Thus, as noradrenergic receptors are present in this structure, the present study tested the effects of local noradrenaline (NA) microinjection into the MeA on cardiovascular responses in conscious rats. Moreover, we describe the types of adrenoceptor involved and the peripheral mechanisms involved in the cardiovascular responses. Increasing doses of NA (3, 9, 27 or 45 nmol/100 nL) microinjected into the MeA of conscious rats caused dose-related pressor and bradycardic responses. The NA cardiovascular effects were abolished by local pretreatment of the MeA with 10 nmol/100 nL of the specific alpha(2)-receptor antagonist RX821002, but were not affected by local pretreatment with 10 nmol/100 nL of the specific alpha(1)-receptor antagonist WB4101. The magnitude of pressor response evoked by NA microinjected into the MeA was potentiated by intravenous pretreatment with the ganglion blocker pentolinium (5 mg/kg), and blocked by intravenous pretreatment with the selective V(1)-vasopressin antagonist dTyr(CH(2))(5)(Me)AVP (50 mu g/kg). In conclusion, our results show that microinjection of NA into the MeA of conscious rats activates local alpha(2)-adrenoceptors, evoking pressor and bradycardic responses, which are mediated by vasopressin release.