Administration Of Lysine Research Articles

Abstract 042: Therapeutic Administration Of L-lysine Leads To The Attenuation Of Salt-sensitive Hypertension

Our previous studies using a multilayered omics approach showed a deficiency of lysine metabolites in Dahl Salt-sensitive (SS) rats fed a high-salt (HS) diet. Consequent studies attempted to rewire these metabolic changes by treating the SS rats with lysine in drinking water while on an HS diet. Rats treated with lysine revealed that the treatment significantly attenuated the development of SS hypertension (HTN) and decreased kidney damage via increased diuresis, accelerated lysine metabolism, and inhibited tubular albumin uptake. Our current study hypothesizes that lysine administration will also be beneficial when blood pressure is already elevated. For this purpose, we used a therapeutic approach where we fed 8-week-old male rats with an HS diet for 10 days (at which point they develop moderate kidney damage (by historic data) and a mean arterial pressure (MAP) of ~140 mmHg, N=13) and consequently put on either L-lysine (17 mg/ml drinking water supplement) or vehicle treatment for 11 more days. MAP was continuously measured using radiotelemetry. At the end of the protocol, the L-lysine-treated group showed a significant decrease in MAP compared to the vehicle group (endpoint 145±5 vs. 176±8 mmHg, N=6-7). Next, using targeted metabolomics, we measured 42 amino acids and their derivatives in the kidney, plasma, and urine at the endpoint of these rats to determine the influence of the treatment on amino acid metabolism. Lysine was upregulated in the treatment group in the kidney, plasma, and urinary excretion compared to the control (log 2 FC & p-value: 0.24, 0.01; 1.22, 3.37E-06; 6.6, 0.04; N=4-5 per group). Lysine degradation product, alpha-Aminoadipic-acid was also increased by 1.56-fold and 1.86-fold in the kidney and plasma, respectively (p-value:0.03 & 0.006). Additionally, 13 other amino acids or derivatives significantly changed in the kidney, plasma, or urine. Our current data suggest that L-lysine administration in hypertensive subjects can have therapeutic effects on the progression and magnitude of SS HTN. As shown by our previous study, it is likely the mechanisms behind this beneficial effect lie in the increased lysine metabolism, which can affect critical downstream metabolic pathways such as the TCA cycle and Fatty Acid metabolism.

Accelerated lysine metabolism conveys kidney protection in salt-sensitive hypertension

Hypertension and kidney disease have been repeatedly associated with genomic variants and alterations of lysine metabolism. Here, we combined stable isotope labeling with untargeted metabolomics to investigate lysine’s metabolic fate in vivo. Dietary 13C6 labeled lysine was tracked to lysine metabolites across various organs. Globally, lysine reacts rapidly with molecules of the central carbon metabolism, but incorporates slowly into proteins and acylcarnitines. Lysine metabolism is accelerated in a rat model of hypertension and kidney damage, chiefly through N-alpha-mediated degradation. Lysine administration diminished development of hypertension and kidney injury. Protective mechanisms include diuresis, further acceleration of lysine conjugate formation, and inhibition of tubular albumin uptake. Lysine also conjugates with malonyl-CoA to form a novel metabolite Nε-malonyl-lysine to deplete malonyl-CoA from fatty acid synthesis. Through conjugate formation and excretion as fructoselysine, saccharopine, and Nε-acetyllysine, lysine lead to depletion of central carbon metabolites from the organism and kidney. Consistently, lysine administration to patients at risk for hypertension and kidney disease inhibited tubular albumin uptake, increased lysine conjugate formation, and reduced tricarboxylic acid (TCA) cycle metabolites, compared to kidney-healthy volunteers. In conclusion, lysine isotope tracing mapped an accelerated metabolism in hypertension, and lysine administration could protect kidneys in hypertensive kidney disease.

The Effects of KKRRPGP (Lys-Lys-Arg-Arg-Pro-Gly-Pro) and KRRKPGP (Lys-Arg-Arg-Lys-Pro-Gly-Pro) Peptides on Hemostasis Parameters, Lipid Profile, Blood Glucose Level, and Body Weight Changes in Rats with Metabolic Syndrome and Endothelial Dysfunction

Intranasal administration of lysine- and arginine-containing peptides Lys-Lys-Arg-Arg-Pro-Gly-Pro and Lys-Arg-Arg-Lys-Pro-Gly-Pro was performed daily at a single dose of 100 µg/kg for 7 days on laboratory rats with experimental metabolic syndrome and endothelial dysfunction. Metabolic syndrome was modeled by a high-calorie diet maintained throughout the experimental period, while endothelial dysfunction was simulated by daily intraperitoneal injection of L–NAME at a single dose of 10 mg/kg for 5 days. It was found that these peptides had anticlotting, hypoglycemic, and lipid-lowering effects and reduced body weight gain in experimental rats. They affected both primary (vascular-platelet) hemostasis, decreasing platelet aggregation, and all elements of plasma hemostasis by increasing anticoagulant, fibrin-depolymerizing, and enzymatic fibrinolytic activities as well as anti-fibrin-stabilizing properties of plasma and reducing the concentration of fibrinogen in it. At the same time, the studied peptides diminished the content of total cholesterol, low-density lipoprotein cholesterol, and triglycerides, while increasing the concentration of high-density lipoprotein cholesterol. These effects were observed 20 h after the last administration of peptides and persisted, although to a lesser extent, 7 days (168 h) after treatment withdrawal. In this regard, the prolonged action can be considered for both glyproline peptides containing lysine and arginine aminoacid residues in their structure and their ability to protect the body from the development of metabolic diseases and endothelial dysfunction. The maximum effects were provided by the Lys-Arg-Arg-Lys-Pro-Gly-Pro peptide, which may be associated with its structural features.

Abstract P026: The Accumulation Of Lysine In The Kidney Cortex Protects From Proximal Tubule Damage And Salt-Sensitive Hypertension.

The kidneys are highly sensitive to metabolic changes. Metabolic phenotyping uncovered a number of pathways associated with high blood pressure and kidney diseases, which sheds light on the complex pathophysiology of hypertension and associated kidney injury. However, the mechanisms underlying the effects of dietary interventions on kidney function and associated changes in cellular metabolic intermediates remain incompletely understood. L-lysine, one of the essential amino acids, is necessary for many physiological functions. Among all organs, the kidney is a key organ in lysine turnover and metabolism, in particular for modified lysines. Our recent metabolomics study revealed that intrarenal levels of L-Lysine are reduced in Dahl salt-sensitive (SS) rats fed an HS diet. This finding provided further evidence that L-Lysine is critical for metabolic states in the kidney. Using a well-established SS rat model of hypertension and kidney injury, we found that administration of lysine at a concentration of 17mg/ml in drinking water counteracted the lysine deficit in kidneys, restored albumin balance, triggered diuresis, and diminished the development of salt-sensitive hypertension (133±2 vs. 165±4 (136±4 vs. 166±7), mmHg in L-Lysine treated rats vs. control rats male (female) after 14 (21) days of an 8 (4) % NaCl diet). HPLC analysis revealed a significant elevation of lysine in the renal cortex of treated rats. In contrast, the concentration of other amino acids, such as glycine and arginine, did not change with increasing blood pressure. Overall, dietary lysine supplementation of SS rats on the HS diet leads to significant protection of proximal tubule damage, shown by Kim-1 immunostaining. Also, it restores kidney function by the rapid excretion of the pathologically accumulated renal albumin and rebalancing megalin abundance. Moreover, the analyses of glomerular damage showed improvement for the lysine treated group. In conclusion, dietary L-Lysine supplementation significantly enhanced cardiorenal protection via acute inhibition of metabolic load and oxidative stress triggered by hypertension.

The Effect of Adding Lysine in Commercial Feed on Growth Rate, Feed Efficiency, and Feed Convertion Ratio to Tambaqui (Colossoma Macropomum)

Tambaqui (Colossoma macropomum) is one of the freshwater fishery commodities of high economic value. Its delicious taste like that of carp makes it popular and the demand for this commodity increases every year both for domestic and export market (Samardyanto, 2011). Tambaqui needs amino acids to improve its growth process, one essential amino acids can only be obtained through lysine foods. Lysine is one of the ten essential amino acids. The purpose of this research is to find out how the administration of lysine on commercial feed increases tambaqui’s growth rate, feed efficiency, and feed conversion ratio. This is experimental research, using Completely Random Design (RAL) with 4 treatment and 5 repeats on each treatment. The dosage of lysine added in commercial diet were P0 (0%), P1 (0.6%), P2 (1.2%), and P3 (2%). The observed parameters include growth rate, feed efficiency, and feed conversion ratio. The data analysis used was Variant Analysis (ANOVA) followed by Double Distance Test Duncan. The results showed the addition of lysine on commercial feed during a 30- day maintenance had the same effect (P > 0.05 ) on the growth rate of tambaqui, the same effect (P > 0.05 ) on the feed efficiency, and quite similar (P > 0.05 ) on the feed conversion ratio of tambaqui. When we increased the amount of lysine in the administration of commercial feed to the fish, we observed an increase in the growth rate, specific growth rate, feed efficiency, and feed conversion of ratio in tambaqui. The best treatment was found in P1 treatment with lysine dosage 0.6%, and the highest growth rate of 1.726 grams/day, specific growth rate was 2.326%/day, feed efficiency 68.70%, and the feed conversion ratio of 1.472. We observed that the P0 treatment i.e. treatment without lysine had a value growth rate, specific growth rate, feed efficiency, and feed conversion ratio of respectively 1.243 grams/day, 1.796%/day, 53.25%, and the feed conversion ratio 1.924.

Regulation of Skeletal Muscle Protein Degradation and Synthesis by Oral Administration of Lysine in Rats

Several catabolic diseases and unloading induce muscle mass wasting, which causes severe pathological progression in various diseases and aging. Leucine is known to attenuate muscle loss via stimulation of protein synthesis and suppression of protein degradation in skeletal muscle. The aim of this study was to investigate the effects of lysine intake on protein degradation and synthesis in skeletal muscle. Fasted rats were administered 22.8-570 mg Lys/100 g body weight and the rates of myofibrillar protein degradation were assessed for 0-6 h after Lys administration. The rates of myofibrillar protein degradation evaluated by MeHis release from the isolated muscles were markedly suppressed after administration of 114 mg Lys/100 g body weight and of 570 mg Lys/100 g body weight. LC3-II, a marker of the autophagic-lysosomal pathway, tended to decrease (p=0.05, 0.08) after Lys intake (114 mg/100 g body weight). However, expression of ubiquitin ligase E3 atrogin-1 mRNA and levels of ubiquitinated proteins were not suppressed by Lys intake. Phosphorylation levels of mTOR, S6K1 and 4E-BP1 in the gastrocnemius muscle were not altered after Lys intake. These results suggest that Lys is able to suppress myofibrillar protein degradation at least partially through the autophagic-lysosomal pathway, not the ubiquitin-proteasomal pathway, whereas Lys might be unable to stimulate protein synthesis within this time frame.

Oral administration of lysine restores food intake and ventromedial hypothalamic dopamine in chicken on a lysine-free diet

1. This study was conducted to examine whether oral administration of lysine solution affect food intake and the ventromedial hypothalamic (VMH) monoamines in chickens fed on a lysine-free diet. 2. Chickens were assigned to four treatment groups. Two groups of chickens were given two different doses of lysine solution (0·1 g and 0·07 g in 1 ml of saline) exogenously (orally) while being fed on a lysine-free diet, and these results were compared with a control diet plus saline group. Another group of chickens was fed on a lysine-free diet without lysine supplementation, and their results were compared with the lysine treated groups. The extracellular dopamine (DA), norepinephrine (NE) and serotonin (5-HT) in the VMH of freely moving chicken were measured by in vivo microdialysis. 3. There was no significant difference in food intake between the control diet and the lysine supplemented groups during the time-course of the experiments. Food intake significantly decreased at 4, 5 and 6 h in the lysine-free diet plus saline group compared with the lysine supplemented groups. Of the VMH monoamines, the DA concentration remained close to the baseline in the lysine supplemented groups. This DA concentration was significantly lower than the baseline in the lysine-free diet plus saline group at 3·5 h and thereafter. 4. No significant difference from the baseline was observed for NE in the lysine-free diet plus saline group. The 5-HT concentrations were close to the baseline for all groups throughout the experiments. 5. The findings suggest that oral administration of lysine solution to chickens fed on a lysine-free diet restored food intake which was associated with the variations of VMH DA concentration.

Marked reduction of Na+, K+-ATPase and creatine kinase activities induced by acute lysine administration in glutaryl-CoA dehydrogenase deficient mice

Glutaric acidemia type I (GA I) is an inherited neurometabolic disorder caused by a severe deficiency of the mitochondrial glutaryl-CoA dehydrogenase activity leading to accumulation of predominantly glutaric (GA) and 3-hydroxyglutaric (3HGA) acids in the brain and other tissues. Affected patients usually present with hypotonia and brain damage and acute encephalopathic episodes whose pathophysiology is not yet fully established. In this study we investigated important parameters of cellular bioenergetics in brain, heart and skeletal muscle from 15-day-old glutaryl-CoA dehydrogenase deficient mice (Gcdh−/−) submitted to a single intra-peritoneal injection of saline (Sal) or lysine (Lys — 8μmol/g) as compared to wild type (WT) mice. We evaluated the activities of the respiratory chain complexes II, II-III and IV, α-ketoglutarate dehydrogenase (α-KGDH), creatine kinase (CK) and synaptic Na+, K+-ATPase. No differences of all evaluated parameters were detected in the Gcdh−/− relatively to the WT mice injected at baseline (Sal). Furthermore, mild increases of the activities of some respiratory chain complexes (II-III and IV) were observed in heart and skeletal muscle of Gcdh−/− and WT mice after Lys administration. However, the most marked effects provoked by Lys administration were marked decreases of the activities of Na+, K+-ATPase in brain and CK in brain and skeletal muscle of Gcdh−/− mice. In contrast, brain α-KGDH activity was not altered in WT and Gcdh−/− injected with Sal or Lys. Our results demonstrate that reduction of Na+, K+-ATPase and CK activities may play an important role in the pathogenesis of the neurodegenerative changes in GA I.

Induction of oxidative stress in brain of glutaryl-CoA dehydrogenase deficient mice by acute lysine administration

In the present work we evaluated a variety of indicators of oxidative stress in distinct brain regions (striatum, cerebral cortex and hippocampus), the liver, and heart of 30-day-old glutaryl-CoA dehydrogenase deficient (Gcdh−/−) mice. The parameters evaluated included thiobarbituric acid-reactive substances (TBA-RS), 2-7-dihydrodichlorofluorescein (DCFH) oxidation, sulfhydryl content, and reduced glutathione (GSH) concentrations. We also measured the activities of the antioxidant enzymes glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), superoxide dismutase (SOD) and glucose-6-phosphate dehydrogenase (G6PD). Under basal conditions glutaric (GA) and 3-OH-glutaric (3OHGA) acids were elevated in all tissues of the Gcdh−/− mice, but were essentially absent in WT animals. In contrast there were no differences between WT and Gcdh−/− mice in any of the indicators or oxidative stress under basal conditions. Following a single intra-peritoneal (IP) injection of lysine (Lys) there was a moderate increase of brain GA concentration in Gcdh−/− mice, but no change in WT. Lys injection had no effect on brain 3OHGA in either WT or Gcdh−/− mice. The levels of GA and 3OHGA were approximately 40% higher in striatum compared to cerebral cortex in Lys-treated mice. In the striatum, Lys administration provoked a marked increase of lipid peroxidation, DCFH oxidation, SOD and GR activities, as well as significant reductions of GSH levels and GPx activity, with no alteration of sulfhydryl content, CAT and G6PD activities. There was also evidence of increased lipid peroxidation and SOD activity in the cerebral cortex, along with a decrease of GSH levels, but to a lesser extent than in the striatum. In the hippocampus only mild increases of SOD activity and DCFH oxidation were observed. In contrast, Lys injection had no effect on any of the parameters of oxidative stress in the liver or heart of Gcdh−/− or WT animals. These results indicate that in Gcdh−/− mice cerebral tissue, particularly the striatum, is at greater risk for oxidative stress than peripheral tissues following Lys administration.

Localization, mechanism and reduction of renal retention of technetium‐99m labeled epidermal growth factor receptor‐specific nanobody in mice

Nanobodies are single-domain antigen binding fragments derived from functional heavy-chain antibodies elicited in Camelidae. They are powerful probes for radioimmunoimaging, but their renal uptake is relatively high. In this study we have evaluated the role of megalin on the renal uptake of anti-EGFR (99m)Tc-7C12 nanobody and the potency of gelofusine and/or lysine to reduce renal uptake of (99m)Tc-7C12. First we compared the renal uptake of (99m)Tc-7C12 in megalin-deficient and megalin-wild-type mice using pinhole SPECT/microCT and ex vivo analysis. The effect of gelofusine and lysine administration on renal accumulation of (99m)Tc-7C12 was analyzed in CD-1 mice divided into lysine preload at 30 min before tracer injection (LysPreload), LysPreload + gelofusine coadministration (LysPreload + GeloCoad), lysine coadministration (LysCoad), gelofusine coadministration (GeloCoad) and LysCoad + GeloCoad. The combined effect of gelofusine and lysine on tumor uptake was tested in mice xenografts. Renal uptake of (99m)Tc-7C12 was 44.22 ± 3.46% lower in megalin-deficient compared with megalin-wild-type mice. In CD-1 mice, lysine preload had no effect on the renal retention whereas coinjection of lysine or gelofusine with the tracer resulted in 25.12 ± 2.99 and 36.22 ± 3.07% reduction, respectively. The combined effect of gelofusine and lysine was the most effective, namely a reduction of renal retention of 45.24 ± 2.09%. Gelofusine and lysine coadministration improved tumor uptake. Megalin contributes to the renal accumulation of (99m)Tc-7C12. Gelofusine and lysine coinjection with the tracer reduces the renal uptake while tumor uptake is improved. Although this methodology allows for optimization of imaging protocol using nanobodies, further improvements are needed before using these molecules for radionuclide therapy.

Lysine and arginine reduce the effects of cerebral ischemic insults and inhibit glutamate-induced neuronal activity in rats

Intravenous administration of arginine was shown to be protective against cerebral ischemic insults via nitric oxide production and possibly via additional mechanisms. The present study aimed at evaluating the neuroprotective effects of oral administration of lysine (a basic amino acid), arginine, and their combination on ischemic insults (cerebral edema and infarction) and hemispheric brain swelling induced by transient middle cerebral artery occlusion/reperfusion in rats. Magnetic resonance imaging and 2,3,5-triphenyltetrazolium chloride staining were performed 2 days after ischemia induction. In control animals, the major edematous areas were observed in the cerebral cortex and striatum. The volumes associated with cortical edema were significantly reduced by lysine (2.0 g/kg), arginine (0.6 g/kg), or their combined administration (0.6 g/kg each). Protective effects of these amino acids on infarction were comparable to the inhibitory effects on edema formation. Interestingly, these amino acids, even at low dose (0.6 g/kg), were effective to reduce hemispheric brain swelling. Additionally, the effects of in vivo microiontophoretic (juxtaneuronal) applications of these amino acids on glutamate-evoked neuronal activity in the ventromedial hypothalamus were investigated in awake rats. Glutamate-induced neuronal activity was robustly inhibited by microiontophoretic applications of lysine or arginine onto neuronal membranes. Taken together, our results demonstrate the neuroprotective effects of oral ingestion of lysine and arginine against ischemic insults (cerebral edema and infarction), especially in the cerebral cortex, and suggest that suppression of glutamate-induced neuronal activity might be the primary mechanism associated with these neuroprotective effects.

Ibuprofen lysine administration to neonates with a patent ductus arteriosus: effect on platelet plug formation assessed by in vivo and in vitro measurements

Ibuprofen might have advantages over indomethacin, when used to effectuate closure of a neonate's patent ductus arteriosus (PDA). Several previous studies indicate that platelet plug formation is impaired after administration of indomethacin, but it is not clear whether a similar impairment occurs following ibuprofen dosing. We performed template bleeding times and PFA-100 tests (platelet function analyzer) on 20 neonates who had a PDA, before and again at various preset intervals following ibuprofen dosing. Patients ranged from 23 to 40 weeks gestation and weighed 511 to 2566 g. Their first dose of ibuprofen was administered at 72 h (18 to 363 h) after birth (median, range). None of the subjects had clinical bleeding problems noted during the days they received ibuprofen dosing. The template bleeding times before dosing ranged from 135 to 450 s. Repeat tests were performed in groups of four, at 2 h, 4 to 6 h, 12 to 18 h, 24 h after the first dose, and at 2 h after the third dose of ibuprofen. No changes in bleeding times were detected. (P=0.299) A PFA-100 time was performed on all 20 patients before and again after the ibuprofen administration. However, 3 of the 40 tests were unsuccessful, because of microclots in the blood sample (n=1) or failure of the analyzer for an unspecified reason (n=2). Before the dosing the PFA-100 time ranged from 52 to 300 s. A paired t-test showed a slight but statistically significant lengthening in PFA-100 time after the ibuprofen administration (P=0.019). The correlation between the bleeding time and the PFA-100 was poor (R(2)=0.212, P=0.576). On the basis of our present studies, we speculate that ibuprofen lysine administration to neonates with a PDA, when used according to the manufacturer's recommendations, has little adverse effect on platelet plug formation. This information might be a factor to consider when deciding whether to select indomethacin or ibuprofen for PDA closure.

Effects of oral L‐carnitine, L‐lysine administration and exercise on body composition and histological and biochemical parameters in pigeons

The purpose of this study was to examine whether L-carnitine and its precursor L-lysine could have any beneficial effect in racing pigeons, and if so, whether this effect is influenced by the extent of exercise (short-distance flight: 135 km vs. long-distance flight: 580 km). Birds were divided into seven groups of animals. Group 1: negative control, no flight, no treatment, Group 2: positive control, placebo treatment before the short-distance flight, Group 3: 200 mg/day L-carnitine treatment before the short-distance flight, Group 4: 400 mg/day L-lysine treatment before the short-distance flight, Group 5: positive control, placebo treatment before the long-distance flight, Group 6: 200 mg/day L-carnitine treatment before the long-distance flight, Group 7: 400 mg/day L-lysine treatment before the long-distance flight. L-carnitine, L-lysine and distilled water (placebo) were orally administered (tube feeding) for 7 days before flight. Just after returning home, blood samples were collected and analyzed for glucose, fructosamine, cholesterol, triglycerides and thiobarbituric acid reactive substances. Pigeons were euthanized using carbon dioxide as an inhalation agent, and the whole body was subjected to proximate analysis. The status at arrival was referred to as a basis for comparison. Sex did not affect the measured parameters. As a result of the L-carnitine and L-lysine administrations, the body fat mobilization was higher during the 580 km flight, whereas no changes were noted during the 135 km flight. The main changes in the measured blood parameters were caused by the extent of exercise. This experiment considered the extent of exercise as a factor potentially modulating L-carnitine supplementation effects. In conclusion, flight distance affected several parameters but the supplements of L-carnitine and L-lysine were not effective in the tested situations.

Effect of oral administration of L-lysine on conjunctivitis caused by feline herpesvirus in cats

To determine whether oral administration of L-lysine to cats would lessen the severity of conjunctivitis caused by feline herpesvirus (FHV-1). 8 healthy young adult cats. Cats received oral administration of lysine monohydrochloride (500 mg, q 12 h) or placebo (lactose) beginning 6 hours prior to inoculation of virus. The left conjunctival sac received a 50-microl suspension of FHV-1 grown in cell culture (1.8 X 10(8) tissue culture infective dose50) on day 1. Cats were evaluated and scores given for clinical signs each day for 21 days. Samples for virus isolation were collected from the eye and throat every third day. Plasma lysine and arginine concentrations were measured prior to the study and on days 3, 14, and 22. Cats that received lysine had less severe conjunctivitis than cats that received placebo. Virus isolation results did not differ between the groups. Plasma lysine concentration was significantly higher in cats that received lysine, compared with control cats, whereas plasma arginine concentrations did not differ between groups. Oral administration of 500 mg of lysine to cats was well tolerated and resulted in less severe manifestations of conjunctivitis caused by FHV-1, compared with cats that received placebo. Oral administration of lysine may be helpful in early treatment for FHV-1 infection by lessening the severity of disease.

Effects of L-lysine and L-arginine on in vitro replication of feline herpesvirus type-1.

To determine the effects of various concentrations of L-lysine and L-arginine on in vitro replication of feline herpesvirus type-1 (FHV-1). Cultured Crandell-Reese feline kidney (CRFK) cells and FHV-1 strain 727. Uninfected CRFK cells or CRFK cells infected with FHV-1 were cultured in Dulbecco's modified Eagle's medium or in 1 of 7 test media containing various concentrations of lysine and arginine. Viral titer and CRFK growth rate were assessed in each medium. Media depleted of arginine almost completely inhibited viral replication, whereas 2.5 or 5.0 microg of arginine/ml of media was associated with a significant increase in FHV-1 replication. In media with 2.5 microg of arginine/ml, supplementation with 200 or 300 microg of lysine/ml reduced viral replication by 34.2 and 53.9%, respectively. This effect was not seen in media containing 5.0 microg of arginine/ml. Growth rates of CRFK cells also were suppressed in media containing these concentrations of amino acids, but they were not significantly different from each other. Arginine exerts a substantial growth-promoting effect on FHV-1. Supplementation of viral culture medium with lysine attenuates this growth-promoting effect in media containing low concentrations of arginine. Analysis of data from this study indicates that high concentrations of lysine reduce in vitro replication of FHV-1 but only in media containing low concentrations of arginine. Clinical trials will be necessary to determine whether supplemental administration of lysine, with or without arginine restriction, will be useful in the management of cats with FHV-1 infections.

Influence of L-lysine and zinc administration during exposure to lead or lead and ethanol in rats.

Influence of lysine and zinc administration on the lead-sensitive biochemical parameters and the accumulation of lead during exposure to lead or lead and ethanol was investigated in rats. The lead exposure inhibited blood delta-aminolevulinic acid dehydratase (ALAD) activity, increased blood zinc protoporphyrin (ZPP), urinary delta-aminolevulinic acid (ALA), serum glutamic oxalacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), blood and tissue lead levels, and decreased blood and hepatic glutathione (GSH) contents. Some of these effects were enhanced on coexposure to ethanol. The simultaneous administration of lysine and zinc reduced tissue accumulation of lead and most of the lead-induced biochemical alterations irrespective of exposure to lead alone or lead and ethanol. The depletion of endogenous calcium and magnesium owing to lead or ethanol exposure was also prevented by co-administration of lysine and zinc.

Lysine deficiency in postweaned calves fed corn and corn gluten meal diets.

Holstein bull calves (n = 36) weaned at 6 wk of age were used in six trials to examine the response of N balance to postruminal administration of lysine with or without methionine in postweaned calves receiving diets based on corn and corn gluten meal. Calves were younger than 3 mo of age in Trials 1 and 2 but older than 3 mo in Trials 4 to 6. L-Lysine monohydrochloride was supplemented with or without DL-methionine twice daily through the reticular groove, except in Trial 4, in which N supplements were infused through duodenal cannulas. L-Glutamine was used as a nonspecific N source in every trial, and casein was a positive control in Trials 4 and 5. When daily CP intake from the diet was 3.9 g/kg BW, lysine was limiting for calves less than 11 wk of age (Trials 1 and 2) but not limiting for calves greater than 12 wk of age (Trial 3). No amino acid seemed to be limiting for calves greater than 20 wk of age (Trial 4) when daily CP intake was 4.1 g/kg BW, but lysine was limiting when CP intake was restricted to 3.0 g/kg BW when calves were more than 17 wk of age (Trial 5). However, lysine was not limiting above 18 wk of age (Trial 6) when CP intake was increased to 3.8 g/kg BW by adding urea to the diet. Results suggest that lysine may be limiting for corn and corn gluten meal diets only when ruminal microbial protein synthesis is restricted.

Evaluation in vitro and in rats of 161Tb-DTPA-octreotide, a somatostatin analogue with potential for intraoperative scanning and radiotherapy.

The characteristics of terbium-161 diethylene triamine penta-acetic acid (DTPA) labelled octreotide with respect to specific binding to somatostatin (octreotide) receptors on rat brain cortex membranes, biological activity, uptake and excretion by isolated perfused rat livers and metabolism in vivo in normal and tumour-bearing rats were determined and compared to those of indium-111 DTPA-octreotide. The results of the binding studies demonstrate that 161Tb-DTPA-octreotide is a high-affinity radioligand for somatostatin receptors, with an affinity comparable to that of 111In-DTPA-octreotide. Rat growth hormone secretion inhibition experiments showed that 161Tb-DTPA-octreotide has a similar potency to 111In-DTPA-octreotide. 161Tb-DTPA-octreotide appeared to be taken up even less by the isolated perfused rat liver than 111In-DTPA-octreotide, as almost no tracer disappeared from the perfusion medium. Furthermore, hardly any radioactivity was found in the liver, and excretion into the bile was negligible. The biodistribution studies showed that for octreotide receptor-positive organs, such as pancreas and adrenals, uptake of 161Tb-DTPA-octreotide is lower then that of 111In-DTPA-octreotide. However, as the clearance from the blood of the former compound is faster than that of the latter, the tissue/blood ratio is higher in the case of 161Tb-DTPA-octreotide than with 111In-DTPA-octreotide. Furthermore, these studies demonstrated that the uptake of 161Tb-DTPA-octreotide by the renal tubular cells after glomerular filtration can be reduced by administration of lysine or sodium maleate. Increase in urine production before and during the experiment had no effect on the kidney uptake of 161Tb-DTPA-octreotide.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevention of renal tubule re-absorption of radiometal (indium-111) labelled Fab fragment of a monoclonal antibody in mice by systemic administration of lysine

Systemic administration of lysine to mice injected with indium-111-labelled Fab fragment of a monoclonal antibody has been shown to reduce renal uptake/retention of the radiometal. This treatment should be applicable to clinical immunoscintigraphy and radioimmunotherapy with radiometal-labelled antibody fragments.

Effects of lysine or ruminally protected lysine administration on nitrogen utilization in goat fed a diet supplemented with ruminally protected methionine

Effects of lysine or ruminally protected lysine administration on nitrogen utilization in goat fed a diet supplemented with ruminally protected methionine