Serum interleukin-17 levels are associated with nephritis in childhood-onset systemic lupus erythematosus

OBJECTIVES: To determine the serum interleukin-17 (IL-17) levels in childhood-onset systemic lupus erythematosus patients and to evaluate the association between IL-17 and clinical manifestations, disease activity, laboratory findings and treatment. METHODS: We included 67 consecutive childhood-onset systemic lupus erythematosus patients [61 women; median age 18 years (range 11-31)], 55 first-degree relatives [50 women; median age 40 years (range 29-52)] and 47 age- and sex-matched healthy controls [42 women; median age 19 years (range 6-30)]. The childhood-onset systemic lupus erythematosus patients were assessed for clinical and laboratory systemic lupus erythematosus manifestations, disease activity [Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)], cumulative damage [Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) Damage Index] and current drug use. Serum IL-17 levels were measured by an enzyme-linked immunosorbent assay using commercial kits. RESULTS: The median serum IL-17 level was 36.3 (range 17.36-105.92) pg/mL in childhood-onset systemic lupus erythematosus patients and 29.47 (15.16-62.17) pg/mL in healthy controls (p=0.009). We observed an association between serum IL-17 levels and active nephritis (p=0.01) and migraines (p=0.03). Serum IL-17 levels were not associated with disease activity (p=0.32), cumulative damage (p=0.34), or medication use (p=0.63). CONCLUSION: IL-17 is increased in childhood-onset systemic lupus erythematosus and may play a role in the pathogenesis of neuropsychiatric and renal manifestations. Longitudinal studies are necessary to determine the role of IL-17 in childhood-onset systemic lupus erythematosus. .

Autistic children exhibit distinct plasma amino acid profile.

In order to ascertain whether autistic children display characteristic metabolic signatures that are of diagnostic value, plasma amino acid analyses were carried out on a cohort of 138 autistic children and 138 normal controls using reverse-phase HPLC. Pre-column derivatization of amino acids with phenyl isothiocyanate forms phenyl thio-carbamate derivates that have a λmax of 254 nm, enabling their detection using photodiode array. Autistic children showed elevated levels of glutamic acid (120 ± 89 vs. 83 ± 35 mmol/L) and asparagine (85 ± 37 vs. 47 ± 19 mmol/L); lower levels of phenylalanine (45 ± 20 vs. 59 ± 18 mmol/L), tryptophan (24 ± 11 vs. 41 ± 16 mmol/L), methionine (22 ± 9 vs. 28 ± 9 mmol/L) and histidine (45 ± 21 vs. 58 ± 15 mmol/L). A low molar ratio of (tryptophan/large neutral amino acids) × 100 was observed in autism (5.4 vs 9.2), indicating lesser availability of tryptophan for neurotransmitter serotonin synthesis. To conclude, elevated levels of excitatory amino acids (glutamate and asparagine), decreased essential amino acids (phenylalanine, tryptophan and methionine) and decreased precursors of neurotransmitters (tyrosine and tryptophan) are the distinct characteristics of plasma amino acid profile of autistic children. Thus, such metabolic signatures might be useful tools for early diagnosis of autism.

Peripheral serotoninergic response to physical exercise in athletic horses

The purpose of this study was to evaluate the influence of exercise on plasma tryptophan (TRP) and free serotonin (f5-HT), whole blood-5-HT (WB-5-HT) and f5-HT/WB-5-HT ratio in Italian Saddle horses. Six clinically healthy Italian Saddle horses were subjected to a 450 meters obstacles course. Blood samples were collected from each horse by jugular venipuncture using vacutainer tubes with K3-EDTA at rest, immediately after exercise, and after 30 min. TRP, f5-HT and WB-5-HT were analyzed by HPLC. Immediately after exercise, statistically significant increases of f5-HT (p<0.001) and WB-5-HT (p<0.001) were observed. After 30 min, f5-HT and WB-5-HT decreased compared to immediately after exercise, but were still significantly higher than rest values (p<0.01 and p<0.05, respectively). A significant linear regression between f5-HT and WB-5-HT was observed during experimental conditions. f5-HT and WB-5-HT modifications after exercise suggest an important role of peripheral serotoninergic markers in response to physical activity. The possible source of extra serotonin detected after show jumping should be clarified by further investigation.

Gender based response to fluoxetine hydrochloride medication in endogenous depression

To determine the gender based response to fluoxetine HCl medication in relation to tryptophan metabolism in depressed patients. Design: A comparative, analytical study. Place and Duration of Study: Clinical Biochemistry and Psychopharmacology Research Unit, Department of Biochemistry, University of Karachi during the year 2002 to 2003. Subjects and Sixteen adults depressed patients who were not having any other major comorbidity were selected from the outpatients department of local psychiatric clinic for the study. They were subjected to a semi-structured interview for associated clinical characteristics and diagnosis of depression according to ICD-10 criteria. A control group of normal health male and female individuals was identified for comparison with the depressed group.All the depressed patients were treated with fluoxetine hydrochloride [Prozac 20 mg/day] for four weeks. Healthy individual's data was compared with the depressed group and evaluated for gender based response to fluoxetine HCl medication. Significant decreases were found in total tryptophan concentrations [33%, p<0.01,56%, p<0.01] in depressed male and female patients respectively, in contrast, serum cortisol levels were increased by 68% and 98% in male and female depressed patients respectively as compared to healthy controls. Significant increases [23%, p<0.05] in albumin levels were found in females only. Four weeks treatment of male and female depressed group by Fluoxetine HCL [Prozac] 20 mg/kg/day, increased serum total tryptophan concentrations significantly by 32% [p<0.05] in males and by 83% [p<0.01] in females. Serum-free tryptophan concentrations were increased by 22% [p<0.05] in males only. In contrast serum cortisol concentrations were decreased by 31% [p<0.01] and 45.35% [p<0.01] in males and females respectively. Increases in tryptophan and decreases in cortisol concentrations were greater in females which may contribute to better response of the drug in females

Tryptophan and tyrosine catabolic pattern in neuropsychiatric disorders.

Catabolism of tryptophan and tyrosine in relation to the isoprenoid pathway was studied in neurological and psychiatric disorders. The concentration of trytophan, quinolinic acid, kynurenic acid, serotonin and 5-hydroxyindoleacetic acid was found to be higher in the plasma of patients with all these disorders; while that of tyrosine, dopamine, epinephrine and norepinephrine was lower. There was increase in free fatty acids and decrease in albumin (factors modulating tryptophan transport) in the plasma of these patients. Concentration of digoxin, a modulator of amino acid transport, and the activity of HMG CoA reductase, which synthesizes digoxin, were higher in these patients; while RBC membrane Na+-K+ ATPase activity showed a decrease. Concentration of plasma ubiquinone (part of which is synthesised from tyrosine) and magnesium was also lower in these patients. No morphine could be detected in the plasma of these patients except in MS. On the other hand, strychnine and nicotine were detectable. These results indicate hypercatabolism of tryptophan and hypocatabolism of tyrosine in these disorders, which could be a consequence of the modulating effect of hypothalamic digoxin on amino acid transport.

Endogenous strychnine, nicotine, and morphine--description of hypo and hyper-strychninergic, nicotinergic and morphinergic state in relation to neuropsychiatric diseases.

Previous work from this laboratory had demonstrated the presence of endogenous morphine, strychnine and nicotine in the mammalian brain and human serum samples. Morphine is synthesised from tyrosine and strychnine and nicotine from tryptophan. This study examines the role of strychnine, nicotine and morphine in neuropsychiatric disorders. The blood levels of tyrosine, tryptophan, strychnine, nicotine and morphine were studied as also RBC membrane Na(+)-K+ ATPase activity. It was found that serum tyrosine levels were reduced and tryptophan levels elevated in all neuropsychiatric disorders studied with a reduction in RBC Na(+)-K+ ATPase activity. Nicotine was present in significant amounts in serum of patients with schizophrenia, CNS glioma and syndrome X with multiple lacunar state. Morphine was present in significant amounts only in the serum of patients with multiple sclerosis and MDP. Strychnine was present in significant amounts in the serum of patients with epilepsy, Parkinson's disease and MDP. The presence of nicotine and strychnine in significant amounts could be related to elevated tryptophan levels suggesting the synthesis of these alkaloids from tryptophan. Morphine was not detected in most of the disorders owing to low tyrosine levels noted in them. Na(+)-K+ ATPase inhibition noticed in most of the disorders could be related to decreased hyperpolarising morphinergic transmission and increased depolarising nicotinergic and strychinergic transmission. The role of morphine, strychnine and nicotine in the pathogenesis of these disorders in the setting of membrane Na(+)-K+ ATPase inhibition is discussed.

Effects of tryptophan depletion on anxiety induced by simulated public speaking

Several lines of evidence point to the participation of serotonin (5HT) in anxiety. Its specific role, however, remains obscure. The objective of the present study was to evaluate the effect of reducing 5HT-neurotransmission through an acute tryptophan depletion on anxiety induced by a simulated public speaking (SPS) test. Two groups of 14-15 subjects were submitted to a 24-h diet with a low or normal content of tryptophan and received an amino acid mixture without (TRY-) or with (TRY+) tryptophan under double-blind conditions. Five hours later they were submitted to the SPS test. The state-trait anxiety inventory (STAI) and the visual analogue mood scale (VAMS) were used to measure subjective anxiety. Both scales showed that SPS induced a significant increase in anxiety. Although no overall difference between groups was found, there was a trend (P = 0.078) to an interaction of group x gender x phases of the SPS, and a separate analysis of each gender showed an increase in anxiety measured by the STAI in females of the TRY- group. The results for the female TRY- group also suggested a greater arousing effect of the SPS test. In conclusion, the tryptophan depletion procedure employed in the present study did not induce a significant general change in subjective anxiety, but tended to induce anxiety in females. This suggests a greater sensitivity of the 5HT system to the effects of the procedure in this gender.

Rat brain serotonin metabolism following single and repeated administration of sodium salicylate

Single administration of sodium salicylate at dose of 400 mg/kg increased plasma total and free trytophan levels as well as brain levels of tryptophan, 5-hydroxytryptamine [5-HT] and 5-bydroxyindoleacetic acid [5-HIAA]. Administration of sodium salicylate at dose of 100 mg/kg daily for 5 days also increased plasma total, free tryptophan, brain tryptophan, 5-HT and 5-HIAA concentration 24th after the last administration. Administration of sodium salicylate at doses of 400 mg/kg to rats already injected 100mg/kg sodium salicylate for five days potentiated the effects of sodium salicylate on the enhancement of plasma tryptophan, brain tryptophan and 5-HIAA concentrations. These findings together with our previous reports show that repeated administration of analgesia drugs may increase the availability of tryptophan to the brain for the synthesis of 5-HT

Separación de aminoácidos mediante cromatografía líquida de alta resolución / Amino acid analysis by high-performance liquid chromatography

Se presenta una compilación de la aplicación de la cromatografía líquida de alta resolución en el análisis de aminoácidos. Se analizan las formas de derivatización, se comparan los distintos derivados según sus alcances y limitaciones, la forma de detección y los distintos modos cromatográficos: cromatografía de intercambio iónico, cromatografía en fase normal, cromatografía en fase reversa y cromatografía en fase quiral. También se presentan los métodos automatizados comerciales más recientes para este tipo de análisis. Se dan ejemplos de aplicación de interés en el campo clínico-bioquímico, con el análisis de muestras de líquido cafalorraquídeo, de orina y de plasma/sangre o manchas de sangre seca. El análisis de los aminoácidos de hidrolizados de proteínas y de péptidos resulta más complejo y las condiciones de hidrólisis juegan un rol muy importante en los resultados, que son tratados en esta compilación. Se incluyen, además, aspectos referidos al análisis de los aminoácidos lábiles en proteínas, la preparación de las muestras, las recomendaciones prácticas al hacer HPLC y la influencia de los buffers

Effects of a competitive triathlon on plasma concentrations of tryptophan and branched-chain amino acids

The aim of this work was to determine the acute responses of tryptophan and branched chain amino acids to a triathlon competition. Fourteen male triathletes were studied. All took part in a international triathlon race consisting of 1,5 Km swimming, 40 Km biking and 10 km running. Venous blood samples were drawn before (-24h) and after (15 min) the triathlon. Plasma concentration of branched chain amino acids and total and free tryptophan were determined. Branched chain amino acids decreased from 465 ñ 108.3 to 364 ñ 98.9 mol/L (p < 0.03). Free tryptophan increases from 9.2 to 16.3 mol/L (p < 0.006). Furthermore the ratio of free trytophan to branched chain amino acids increased from 2.07 ñ 0.48 5 to 4.24 ñ 0.79 (p < 0.001). This increases the rate of transport of tryptophan accross the blood-brain barrier and also increases the rate of synthesis of 5-hydroxytryptamine in the central nervous system. A high presence of 5-hydroxytryptamine in the brain develops physical and mental fatigue during the triathlon. This data support the participation of amino acids in fatigue process during triathlon

Desnutrición intrauterina: I. L-triptófano, serotonina y aminoácidos plasmáticos en humanos / Intrauterine malnutrition: I. L-tryptophan, serotonin and plasma amino acids in humans

La desnutrición temprana induce cambios metabólicos específicos sobre el sistema serotoninergico cerebral, en animales de experimentación. La síntesis de serotonina cerebral se encuentra elevada, lo que depende del incremento de su precursor que es el triptófano plasmático libre; la relación del triptófano unido a albúmina con la fracción libre, determina la disponibilidad del precursor para su paso a través de la barrera hematoencefálica. En el presente estudio reportamos los resultados del metabolismo de la serotonina periférica, en dos grupos de recién nacidos humanos con desnutrición intrauterina y sus controles normales. La fracción libre del L-triptófano fue significativamente elevada, los aminoácidos neutros apresentaron modificaciones substanciales y la fracción unida a albúmina del triptófano y las proteínas del plasma fueron significativamente menores al compararse con los recién nacidos con peso adecuado para la edad gestacional. La elevación de la fracción libre del triptófano plasmático en recién nacidos con desnutrición temprana sugiere un incremento del transporte de esta aminoácido al cerebro con un aumento de la síntesis del neurotransmisor