Serum Phenylalanine Concentrations Research Articles

Experimental facility had a greater effect on growth performance, gut microbiome, and metabolome in weaned pigs than feeding diets containing subtherapeutic levels of antibiotics: A case study.

The objective of this study was to define changes in the intestinal metabolome and microbiome associated with growth performance of weaned pigs fed subtherapeutic concentrations of antibiotics. Three experiments with the same antibiotic treatments were conducted on the same research farm but in two different facilities (nursery and wean-finish) using pigs weaned at 20-days of age from the same source herd and genotype, and fed the same diets formulated without antibiotics (NC) or with 0.01% chlortetracycline and 0.01% sulfamethazine (AB). Pigs were weighed and feed disappearance was determined on days (d) 10, 21, and 42 post-weaning to calculate average daily gain (ADG), average daily feed intake (ADFI), and gain:feed (G:F). On d 42, one pig/pen was selected for blood and ileal and cecal content collection. Targeted and untargeted metabolomic profiles were determined in serum and cecal contents using liquid chromatography-mass spectrometry, and composition of bacterial communities in intestinal content samples was determined by sequencing the V4 region of the 16s rRNA gene. Metabolomics and microbiome data were analyzed using diverse multivariate and machine learning methods. Pigs fed AB had significantly greater (P < 0.05) overall ADG and ADFI compared with those fed NC, and pig body weight, ADG, and G:F were also significantly different (P < 0.05) between experiments. Differences (P < 0.05) in serum metabolome along with ileal and cecal microbiome beta diversity were observed between experiments, but there were no differences in microbiome alpha diversity between experiments or treatments. Bacteria from the families Clostridiaceae, Streptomycetaceae, Peptostreptomycetaceae, and Leuconostocaceae were significant biomarkers for the AB treatment. In addition, pigs fed AB had increased serum arginine, histidine, lysine, and phenylalanine concentrations compared with NC. Percentage error from a random forest analysis indicated that most of the variation (8% error) in the microbiome was explained by the facility where the experiments were conducted. These results indicate that facility had a greater effect on growth performance, metabolome, and microbiome responses than feeding diets containing subtherapeutic levels of antibiotics.

High frequency repetitive transcranial magnetic stimulation improves cognitive performance parameters in patients with Alzheimer's disease - an exploratory pilot study.

Currently available medication for Alzheimer's disease (AD) may slows cognitive decline only transitory, but has failed to bring about long term positive effects. For this slowly progressive neurodegenerative disease so far no disease modifying therapy exists. To find out if non-pharmacologic non-ivasive neuromodulatory repetitive transcranial magnetic stimulation (rTMS) may offer a new alternative or an add on therapeutic strategy against loss of cognitive functions. In this exploratory intervention study safety and symptom development before and after frontopolar cortex stimulation (FPC) using intermittent theta burst stimulation (iTBS) at 10 subsequent working days was monitored as add-on treatment in 28 consecutive patients with AD. Out of these, 10 randomly selected patients received sham stimulation as a control. In addition, ​serum concentrations of neurotransmitter precursor amino acids, of immune activation and inflammation markers, of brain derived neurotrophic factor (BDNF) as well as of nitrite were measured. Treatment was well tolerated, no serious adverse effects were observed. Improvement of cognition was detected by an increase of Mini Mental State Examination score (MMSE; p<0.01, paired rank test) and also by an increase in a modified repeat address phrase test, part of the 6-item cognitive ​impairment test (p < 0.01). A trend to an increase in the clock drawing test (CDT; p = 0.08) was also found in the verum treated group. Furtheron, in 10 of the AD patients with additional symptoms of depression treated with iTBS, a significant decrease in the HAMD-7 scale (p <0.01) and a trend to lower serum phenylalanine concentrations (p = 0.08) was seen. No changes of the parameters tested were found in the sham treated patients. Our preliminary results may indicate that iTBS is effective in the treatment of AD. Also a slight influence of iTBS on the metabolism of phenylalanine was found after 10 iTBS sessions. An impact of iTBS to influence the enzyme phenylalanine hydroxylase (PAH), as found in previous series of treatment resistant depression, could not be seen in this our first observational trial in 10 AD patients with comorbidity of depression. Longer treatment periods for several weeks in a higher number of AD patients with depression could cause more intense and disease modifying effects visible in different neurotransmitter concentrations important in the pathogenesis of AD.

222 Corn-expressed Phytase Modulates Serum Amino Acids and Proteomics Profiles in Nursery Pigs Fed with Low-protein, -calcium, and -phosphorous Diets

Abstract Feeding pigs with very low-protein (VLP) and low-phosphorous (P) diets may be useful for decreasing the nutrients excretion to the environment; however, this practice negatively impacts the animals’ growth performance. A beneficial effect of corn-expressed phytase (CEP) on growth performance of pigs fed with VLP diets was shown by our group recently. Little is known whether this improvement is related with alterations in profile of blood proteins and amino acids (AA). The objective of this study was to investigate whether supplementation of VLP, low-calcium (Ca) and low-P diets with a CEP can influence the serum AA and proteomics profiles in pigs. Forty-eight weaned barrows were subjected into one of the following groups (n = 8/group) for 4 weeks: positive control (PC), negative control-reduced protein (NC), NC+low-dose CEP, i.e 2,000 FTU/kg (LD), NC+high-dose CEP, i.e. 4,000 FTU/kg (HD), LD with reduced Ca/P (LDR), and HD with reduced Ca/P (HDR). At week 4, blood samples were collected from all pigs. Compared to PC, NC reduced the serum leucine and phenylalanine concentrations; however, LD recovered their levels. Using trypsinolysis and mass spectrometry, 703 serum proteins were identified and quantified, wherein 25 were found to be differentially expressed among groups. Hierarchical clustering showed a clear separation in proteins identified among dietary groups. Compared to NC, 23 and 24 proteins were found to be differentially expressed in serum of LD and HD groups, respectively, with some important proteins in growth regulation such as SELENOP being upregulated and the IGFBP family being downregulated in these groups. A positive correlation was detected between growth and abundance of BGN, TLN1, PDLIM1 and COL1A2 that are involved in bone mineralization and muscle structure development. Thus, CEP improved the serum profile of some essential AA and affected the expression of proteins involved in regulation of growth in pigs fed with VLP diets.

Metabolomic Profile of ARDS by Nuclear Magnetic Resonance Spectroscopy in Patients With H1N1 Influenza Virus Pneumonia

The integrated analysis of changes in the metabolic profile could be critical for the discovery of biomarkers of lung injury, and also for generating new pathophysiological hypotheses and designing novel therapeutic targets for the acute respiratory distress syndrome (ARDS). This study aimed at developing a nuclear magnetic resonance (NMR)-based approach for the identification of the metabolomic profile of ARDS in patients with H1N1 influenza virus pneumonia. Serum samples from 30 patients (derivation set) diagnosed of H1N1 influenza virus pneumonia were analyzed by unsupervised principal component analysis to identify metabolic differences between patients with and without ARDS by NMR spectroscopy. A predictive model of partial least squares discriminant analysis (PLS-DA) was developed for the identification of ARDS. PLS-DA was trained with the derivation set and tested in another set of samples from 26 patients also diagnosed of H1N1 influenza virus pneumonia (validation set). Decreased serum glucose, alanine, glutamine, methylhistidine and fatty acids concentrations, and elevated serum phenylalanine and methylguanidine concentrations, discriminated patients with ARDS versus patients without ARDS. PLS-DA model successfully identified the presence of ARDS in the validation set with a success rate of 92% (sensitivity 100% and specificity 91%). The classification functions showed a good correlation with the Sequential Organ Failure Assessment score (R = 0.74, P < 0.0001) and the PaO2/FiO2 ratio (R = 0.41, P = 0.03). The serum metabolomic profile is sensitive and specific to identify ARDS in patients with H1N1 influenza A pneumonia. Future studies are needed to determine the role of NMR spectroscopy as a biomarker of ARDS.

Higher serum phenylalanine concentration is associated with more rapid telomere shortening in men

Background: Telomere length and telomere shortening are associated with age-related health outcomes. Only a few studies have been able to longitudinally report on factors that are associated with changes in telomere length in an aging population.Objective: We studied the longitudinal relation between telomere length, the change in telomere length, and circulating amino acids.Design: A total of 812 subjects from the Helsinki Birth Cohort Study (born from 1934 to 1944), who underwent 3 clinical visits during a 10-y interval that included measurements of cardiometabolic risk factors, were included in the study. Leukocyte telomere length (LTL) was measured with the use of quantitative real-time polymerase chain reaction. Circulating branched-chain and aromatic amino acids (alanine, glycine, histidine, phenylalanine, leucine, isoleucine, valine, and tyrosine) were assessed with the use of high-throughput nuclear magnetic resonance spectroscopy.Results: The relative ± SD LTL at a mean age of 71 y was 0.79 ± 0.27 in men and 0.89 ± 0.35 in women (P < 0.001). Of the studied amino acids, the strongest inverse association was observed between the phenylalanine concentration that was measured 5 y earlier and the LTL. This finding was significant in men (P = 0.021) and remained significant after adjustment for multiple comparisons, but it was not significant in women (P = 0.39). Longitudinally, the change in LTL over 10 y was inversely associated with the phenylalanine concentration in men (P = 0.007) but not in women (P = 0.58) after adjustment for baseline LTL, age, smoking, and percentage of body fat.Conclusions: The serum phenylalanine concentration is associated with telomere length and, therefore, potentially with the aging process. Because the associations reported are observational, no conclusions can be made regarding causality. Our findings support the hypothesis that cellular pathways that regulate aging are sex specific.

Adult phenylketonuria presenting with subacute severe neurologic symptoms

We report a 48-year-old Japanese woman with phenylketonuria (PKU) who presented with severe neurological symptoms more than 30years after discontinuation of dietary treatment. She was diagnosed with PKU at 6-years-old and was treated with a phenylalanine restricted diet until she was 15years old. When she was 48-years-old she started having difficulty walking. After several months, she presented with severe disturbance of consciousness and was admitted. She was diagnosed as having neurological complications associated with PKU. We observed temporal changes in her laboratory data, brain MRI and single-photon emission computed tomography (SPECT) scan findings. Brain MRI on T2-weighted, fluid-attenuated inversion recovery and diffusion-weighted images revealed high intensity lesions in her bilateral frontal lobes and 123I-IMP SPECT showed marked and diffuse hypoperfusion in the bilateral cerebrum and cerebellum. After the resumption of dietary treatment, serum phenylalanine concentrations immediately decreased to the normal range. However, her neurological symptoms took longer to improve. We also found no clear temporal association between MRI findings and clinical severity. SPECT abnormalities showed marked improvement after treatment. It is well known that PKU patients who discontinue the dietary restriction from their childhood develop minor neurological impairments. However, PKU patients with late-onset severe neurological symptoms are very rare. To our knowledge, this is the first report regarding SPECT findings of PKU patients with late-onset severe neurological deterioration.

Serum tryptophan, kynurenine, phenylalanine, tyrosine and neopterin concentrations in 100 healthy blood donors

Abstract Formation of neopterin, a biomarker of the activated human immune system, is linked with tryptophan (TRP) and phenylalanine (PHE) metabolism. To obtain normal values, in this study, serum concentrations of neopterin as well as of TRP, PHE and their respective metabolites kynurenine (KYN) and tyrosine (TYR) were investigated in 100 successive blood donor serum specimens from the University Clinics of Innsbruck, Austria. In addition, nitrite concentrations were determined. Donors had passed anamnestic examination at entry and were therefore considered as healthy. The mean age of participants was 49±11.4 (mean±SD) years; 18% were older than 60 years. Both genders were included in the analysis. Neopterin concentrations measured by enzyme-linked immunosorbent assay were 5.9±1.6 nmol/L (mean±SD). Levels of amino acids and metabolites were determined by HPLC. Mean KYN and TRP concentrations were 1.78±0.42 μmol/L and 67.4±10.2 μmol/L, respectively. KYN to TRP ratio (KYN/TRP), an estimate for the activity of tryptophan-degrading enzyme indoleamine 2,3-dioxygenase, was 26.7±6.2 μmol/mmol. Mean PHE and TYR concentrations were 65.2±11.1 μmol/L and 90.6±22.9 μmol/L. PHE to TYR ratio (PHE/TYR), an estimate for the activity of PHE-converting enzyme phenylalanine hydroxylase, was 0.75±0.14 μmol/μmol. Nitrite concentrations, estimated by Griess-Ilosvay reagent, were 44.9±32.0 μmol/L. Males were taller and heavier than females (both p&lt;0.01), but body mass index did not differ. Males presented with significantly higher TRP and TYR concentrations than females (both p&lt;0.05). There existed significant correlations between neopterin and KYN (rs=0.368), KYN/TRP (rs=0.453), TYR (rs=–0.267; all p&lt;0.01) and PHE/TYR (rs=0.236; p&lt;0.05) concentrations. Data indicate that also in a population of healthy individuals an association exists between “low-grade” immune activation as is indicated by slightly higher neopterin concentrations and biochemical alterations in the amino acid metabolism. Although minor, such changes may interfere with psychoneuroimmunological regulatory networks and thus be of clinical relevance.

HPLC for confirmatory diagnosis and biochemical monitoring of Cuban patients with hyperphenylalaninemias.

Hyperphenylalaninemias are inborn errors of phenylalanine metabolism caused by deficiency of L-phenylalanine hydroxylase (the enzyme that converts phenylalanine to tyrosine), resulting in increased serum phenylalanine (>4 mg/dL or 240 µmol/L). Phenylketonuria, or PKU, is the most common form. Untreated PKU is associated with progressive neurodevelopmental delay, evolving towards intellectual impairment. Cuba introduced a national newborn screening program for PKU in 1986. It has enabled early diagnosis and initiation of dietary treatment, reducing appearance of intellectual impairment in these patients. Originally, confirmatory diagnosis was done only by quantifying serum phenylalanine. In 2010, however, an HPLC method for quantifying serum phenylalanine and tyrosine simultaneously was validated at the National Medical Genetics Center, to perform confirmatory and differential diagnosis of hyperphenylalaninemias, as well as biochemical monitoring of patients diagnosed. Describe experience using HPLC confirmatory diagnosis for positive cases from the National Neonatal Screening Program for Phenylketonuria and in biochemical monitoring of diagnosed patients after initiation of dietary treatment. A descriptive retrospective case-series study was conducted from June 2010 through June 2012. The study population comprised 531 infants who tested positive in the National Neonatal Screening Program for Phenylketonuria. Variables used were serum phenylalanine concentration (first criterion of positivity) and tyrosine, phenylalanine/tyrosine ratio (second criterion, both detected by reverse-phase HPLC with direct fluorescence), hyperphenylalaninemia classification, year of diagnosis, sex, and province of origin. Of the samples, 97.7% (519/531) were confirmed as false positives, and 10.4% (55/531) had transient neonatal tyrosinemia. Hyperphenylalaninemia was diagnosed in 12 infants (2.2%): 1.3% (7/531) presented classical PKU, with 34.7 ± 14.7 mg/dL phenylalanine in serum and phenylalanine/tyrosine ratio of 18.9 ± 12.7; and 0.9% (5/531) had persistent hyperphenylalaninemia, with 8.9 ± 3.4 mg/dL of phenylalanine and phenylalanine/tyrosine ratio of 4.5 ± 1.6. Matanzas Province contributed more cases than any of Cuba's 14 other provinces (3/12, 25%) and there was a slight predominance of male sex (7/12, 58.3%). During biochemical monitoring, 83.3% of patients (10/12) reduced their levels of phenylalanine (≤5 mg/dL or 300 µmol/L): 5 with classical PKU and all 5 with persistent hyperphenylalaninemia. The incidence of neonatal hyperphenylalaninemias was 1/22,503 live births and 1/38,577 for classical PKU. HPLC for simultaneous quantification of phenylalanine and tyrosine in serum meets the needs of a confirmatory test for patients testing positive in Cuba's National Neonatal Screening Program for Phenylketonuria (which has high false positive rates). It has enabled introduction in Cuba of a second PKU diagnostic criterion of positivity for both the classification of hyperphenylalaninemias and the biochemical monitoring of diagnosed patients.

Immune activation in patients with Alzheimer's disease is associated with high serum phenylalanine concentrations

BackgroundImmune activation and inflammation represent critical factors in the pathogenesis of Alzheimer's disease (AD) and are associated with increased blood concentrations of markers like neopterin and the kynurenine to tryptophan ratio (Kyn/Trp). In chronic inflammatory conditions, also increased serum phenylalanine concentrations and phenylalanine to tyrosine ratios (Phe/Tyr) were reported and could relate to neuropsychiatric symptoms. ObjectiveTo examine serum phenylalanine and tyrosine concentrations in patients with AD and to compare results to neopterin and Kyn/Trp levels. Materials and methodsSerum was collected from 43 patients with AD and concentrations of phenylalanine and tyrosine as well as neopterin, tryptophan and kynurenine were measured and Phe/Tyr and Kyn/Trp were calculated. ResultsA subgroup of AD patients presented with increased phenylalanine and Phe/Tyr concentrations, phenylalanine levels correlated with neopterin (rs=0.329), kynurenine (rs=0.352) and Kyn/Trp levels (rs=0.288; all p<0.05). There was no significant relationship between phenylalanine metabolism and cognitive ability test scores mini-mental state examination and clock drawing test. ConclusionsHigher serum phenylalanine concentrations related to immune activation are detectable in a subgroup of AD patients. The impaired conversion of phenylalanine may affect not only the production of tyrosine but also the biosynthesis of the neurotransmitters dopamine, norepinephrine and epinephrine. Further studies are justified in patients with AD to investigate a possible role of phenylalanine biochemistry in the development of neurovegetative and behavioral abnormalities.

Association of Eeg Abnormality and Developmental Delay in Phenylketonuria (PKU): An Analytic Historical Case Control Study

Objectivegram (EEG) is an easy and non invasive evaluation method for diagnosis and early prognosis in children. Our aim was to assess the association between EEG and the patients’ Developmental Quotient (DQ) level in phenylketonuria. Materials & Methods In this study, 94 PKU patients (45 boys, 49 girls; mean age: 8.5 6.2 years) who were diagnosed through newborn screening tests or later were followed. PKU was confirmed with a serum phenylalanine concentration above 6 mg/ dl in untreated newborns. The patients were matched in gender, age and phenylalanine level. The ASQ (Age and Stage Questionnaire) was used for evaluation of the developmental stage of the case (abnormal EEG) and control (normal EEG) groups and the Wechsler Intelligence Scale was used to assess cognitive and intellectual abilities. Finally, one way ANOVA and chi square tests were used for analysis and P< 0.05 was considered significant. Results case group consisted of 63 patients (67%) with abnormal EEGs and the control group consisted of 31 patients (33%) with normal EEGs. In patients with abnormal EEGs, 34 (53%) had mild, nine (14%) had moderate and 20 (33%) had severe EEG changes. Distribution of high and low DQ levels in these three groups show significant difference (p=0.001). Distribution of DQ level in the abnormal and normal EEG patients showed a significant difference (p=0.001). Conclusionwas no significant difference between phenylalanine level in case and

Association of EEG Abnormality and Developmental Delay in Phenylketonuria (PKU): an Analytic Historical Case on Phenylketonuria (PKU): An Analytic Historical Case-Control

Objective Electroencephalogram (EEG) is an easy and non invasive evaluation method for diagnosis and early prognosis in children. Our aim was to assess the association between EEG and the patients' Developmental Quotient (DQ) level in phenylketonuria. Materials & Methods In this study, 94 PKU patients (45 boys, 49 girls; mean age: 8.5 6.2 years) who were diagnosed through newborn screening tests or later were followed. PKU was confirmed with a serum phenylalanine concentration above 6 mg/ dl in untreated newborns. The patients were matched in gender, age and phenylalanine level. The ASQ (Age and Stage Questionnaire) was used for evaluation of the developmental stage of the case (abnormal EEG) and control (normal EEG) groups and the Wechsler Intelligence Scale was used to assess cognitive and intellectual abilities. Finally, one way ANOVA and chi square tests were used for analysis and P< 0.05 was considered significant. Results The case group consisted of 63 patients (67%) with abnormal EEGs and the control group consisted of 31 patients (33%) with normal EEGs. In patients with abnormal EEGs, 34 (53%) had mild, nine (14%) had moderate and 20 (33%) had severe EEG changes. Distribution of high and low DQ levels in these three groups show significant difference (p=0.001). Distribution of DQ level in the abnormal and normal EEG patients showed a significant difference (p=0.001). Conclusion There was no significant difference between phenylalanine level in case and control groups; therefore, EEG findings may affect patients' developmental scores despite a normal phenylalanine level in PKU patients.

Sapropterin: A New Therapeutic Agent for Phenylketonuria

To summarize the role of pharmacotherapy in the management of phenylketonuria (PKU) and to review the pharmacology, pharmacokinetics, pharmacodynamics, efficacy data, and safety profile of sapropterin for this indication. A literature search was conducted using MEDLINE (1966-May 2009), International Pharmaceutical Abstracts (1970-May 2009), and Cochrane database (2008) for the following key words: sapropterin, tetrahydrobiopterin, phenylketonurias, and phenylalanine. English-language studies involving humans examining the role of tetrahydrobiopterin (BH4) in the management of PKU were reviewed to evaluate the pharmacology, pharmacokinetics, pharmacodynamics, efficacy data, and safety profile for sapropterin. All Phase 2 and 3 randomized controlled trials assessing the safety and efficacy of sapropterin were included in this literature evaluation. Sapropterin represents the only Food and Drug Administration-approved medication for BH4-responsive PKU, marking an important advance in the treatment of this condition. Among individuals with hyperphenylalaninemia and some residual phenylalanine hydroxylase function, sapropterin can enhance activity of this enzyme to decrease serum phenylalanine concentrations. Sapropterin has been compared with placebo in one Phase 2 and one Phase 3 clinical trial, demonstrating significantly better response rates. Based on available studies, this agent appears to be safe and well tolerated, with adverse event rates similar to those of placebo. However, additional studies are warranted to assess the long-term safety and efficacy of sapropterin therapy. Sapropterin offers a promising therapeutic option for select individuals with BH4-responsive PKU, although long-term data are limited evaluating its safety and efficacy in traditional clinical practice settings. When considering sapropterin therapy, clinicians must consider factors such as cost and patient adherence to drug therapy and/or diet.

Serum phenylalanine concentrations in patients post trauma and burn correlate to neopterin concentrations

Serum phenylalanine concentrations in patients post trauma and burn correlate to neopterin concentrations

A limited spectrum of phenylalanine hydroxylase mutations is observed in phenylketonuria patients in western Poland and implications for treatment with 6R tetrahydrobiopterin

Phenylketonuria (PKU) is an autosomal recessive defect in hepatic metabolism of phenylalanine, which is secondary to mutations in the phenylalanine hydroxylase (PAH) gene. Sixty-seven ethnically Polish PKU patients, followed at the Outpatient Department of Pediatrics and Developmental Medicine in Poznan, Poland, were assessed for mutations in the PAH gene. Two mutations were identified in 61 of 67 patients and a single mutation was identified in the remaining six patients. The four most prevalent mutations (p.R408W, 68%; c.1066-11G>A, 6%; c.1315+1G>A, 5.2%; c.822-832delGCCCATGTATA, 3.7%) accounted for 83% of the mutant alleles. Fifteen additional mutations were identified of which most (13/15) were observed in an individual patient. Before knowledge of PAH genotypes, 19 patients were challenged with a 20 mg kg(-1) dose of 6R tetrahydrobiopterin (BH(4)) and serum phenylalanine concentration was monitored in hospital over 24 h. Two patients responded to the BH(4) challenge with a reduction of serum phenylalanine concentration >30% from baseline. PAH genotypes of the two responsive patients would have been predicted, as they contained mutations recognized as BH(4) responsive, whereas the 17 patients who were unresponsive would have been predicted as their mutations were either recognized as non-responsive or were highly deleterious frame-shift mutations. Overall, only 7.5% (5/ 67) of patients had PAH mutations recognized as responsive to co-factor therapy. Among the PKU patients from western Poland, PAH mutations responsive to BH(4) therapy are poorly represented; therefore, genotyping may be useful for identifying candidate patients likely to respond to BH(4) before physiological challenge.

The rehabilitation programme of an adult phenylketonuria with upper motor neuron involvement

Phenylketonuria (PKU) is a disorder characterized by several biochemical mechanisms which may impair the brain functions in PKU, leading to neurological problems. Our case report concerns a 19 year-old man with phenylketonuria who was evaluated with the onset of stiffness following the abandonment of the phenylalanine-restricted diet. He was assessed with grade-4 spasticity according to Modified Aschworth scale. The deep tendon reflexes had increased and the plantar reflexes were positive. Knee extensions were limited due to the shortening of the hamstring muscles. Serum phenylalanine concentration was elevated and plasma vitamin B12 level was low. Cranial magnetic resonance imaging scan revealed demyelinization area in periventricular deep white matter. We administered a phenylalanine-restricted diet and a rehabilitation program. Following the treatment, spasticity was reduced to grade-1 and patient could walk without aid. This case shows that, the combination of diet, medication and a rehabilitation program is an effective treatment model on adult PKU with upper motor neuron involvement.

Knowledge, compliance and serum phenylalanine concentrations in adolescents and adults with phenylketonuria and the effect of a patient‐focused educational resource

There is a lack of dedicated resources for adolescent and adult patients with phenylketonuria (PKU) and few studies have examined dietary practices within this group. One hundred and seventy-seven PKU patients were sent questionnaires to assess dietary compliance and the preferred format for an educational resource. Seventy-one patients responded; 32 following diet were recruited to assess the resource's impact on test variables. The results were compared for the intervention group (n = 22) and control group (n = 10) at baseline, and 1 and 6 months after resource intervention. Most patients were aware of dietary recommendations, although this did not always result in compliance. The preferred resource format was a filofax-style folder with inserts (P < 0.05). There was a significant difference in the extent of change in knowledge score between baseline and 1 month in favour of the intervention group (P < 0.05). The improvement in knowledge was not accompanied by a significant improvement in measures of compliance. These findings add to the knowledge base about this patient group and support the use of patient involvement in resource development. It is likely that the test parameters used were not sensitive enough to pick up subtle and longer-term effects on compliance.

Serum phenylalanine concentrations in patients with ovarian carcinoma correlate with concentrations of immune activation markers and of isoprostane-8

Increased blood concentrations of essential amino acid phenylalanine are common in patients with HIV infection, in trauma and sepsis and in patients with cancer. The reason for this phenomenon is still unclear. However, all these clinical conditions are known to be linked with inflammation and immune activation. Oxidative stress resulting from chronic immune activation and inflammation could impair activity of phenylalanine (4)-hydroxylase (PAH) and thus give rise to increased phenylalanine concentrations. We therefore examined in 20 patients with ovarian cancer a possible association of serum concentrations of phenylalanine and tyrosine with immune activation markers 75kDa soluble tumor necrosis factor-α receptor (sTNF-R75) and neopterin, and of oxidative stress marker isoprostane-8.Phenylalanine concentrations were higher in patients with higher FIGO stage and correlated with concentrations of sTNF-R75 (rs=0.441) and neopterin (rs=0.346; both p<0.05). No such correlations existed for tyrosine levels. The phenylalanine to tyrosine ratio (phe/tyr), an estimate of PAH activity, correlated somewhat stronger with sTNF-R75 (rs=0.549; p<0.01) and neopterin (rs=0.497; p=0.01). Finally, phenylalanine concentrations correlated with isoprostane-8 concentrations (rs=0.450, p=0.02).Correlations of phenylalanine and phe/tyr with immune activation markers point to a potential role of inflammation and immune activation in the accumulation of phenylalanine. The relationship between oxidative stress marker isoprostane-8 and phenylalanine as well as sTNF-R75 concentrations suggests a link between reactive oxygen species formed during chronic immune activation and inflammation and the decline of PAH activity, which might underlie the increase of phe/tyr (248 words).

Serum Phenylalanine Concentration as a Marker of Liver Function in Obese Patients Before and After Bariatric Surgery

Human obesity is associated with increased serum phenylalanine concentration, which is probably caused by liver dysfunction related to liver steatosis. This study examines whether improvements of liver function after bariatric surgery is associated with a decrease of serum phenylalanine concentration caused by an increase of phenylalanine metabolism. Serum phenylalanine and alanine aminotransferase (an independent predictor of liver steatosis) concentrations as well as several parameters related to obesity were measured in 16 obese patients (seven men and nine women) before and 6 months after vertical banded gastroplasty. Ten (six men and four women) lean, healthy subjects served as controls. Obese patients before surgery had approximately twofold higher serum phenylalanine concentration than control subjects. The serum phenylalanine concentration decreased 6 months after bariatric surgery. Serum alanine aminotransferase (ALT) concentration was higher in obese patients before surgery, and decreased 6 months after bariatric surgery. Changes in serum phenylalanine concentration correlated positively with changes of ALT concentration (r = 0.75; p < 0.001). The body weight, BMI, HOMA-IR, serum triacylglycerol, LDL-cholesterol/HLD-cholesterol ratio, leptin, insulin, and glucose concentrations were higher in obese patients, and decreased 6 months after bariatric surgery. Serum HDL-cholesterol concentration was lower in obese patients before surgery than in control subjects and increased 6 months after surgery. Results obtained indicate that bariatric surgery-induced weight loss had beneficial effects on several laboratory parameters including serum phenylalanine, ALT, lipid concentrations and insulin resistance. A strong positive correlation between serum phenylalanine and serum ALT concentrations suggests that deterioration of liver function in obese patients is contributing to a decrease in phenylalanine metabolism and consequently to the increase of serum phenylalanine concentration. One can suppose that serum phenylalanine concentration could be noninvasive marker of liver dysfunction associated with liver steatosis in obese patients.

Nutritional factors affecting serum phenylalanine concentration during pregnancy for identical twin mothers with phenylketonuria

The effect of energy, protein, fat, and phenylalanine on serum phenylalanine concentrations during pregnancy for a set of identical twins with phenylketonuria (PKU) was examined. Blood samples were collected one to two times per week. The subjects completed a 3-d food record prior to each blood collection. The effect of the factors on serum phenylalanine levels was evaluated statistically using time-series analysis. Dietary intakes of the nutrients evaluated were similar for the subjects. For one subject, there were highly significant effects of energy, protein, and fat on serum phenylalanine levels. In contrast, these nutrients had no significant effect on serum phenylalanine for the other subject. Dietary phenylalanine had no significant effect on serum phenylalanine for either twin. Conclusions: There was no effect of phenylalanine intake and no consistent effect of energy, protein, or fat on serum phenylalanine. Other dietary or environmental factors or a combination of factors may impact serum phenylalanine levels of pregnant women with PKU.

Detection of new amino acid markers of liver trauma by proton nuclear magnetic resonance spectroscopy

We examined serum in patients of liver injury to explore the possible clinical application of abnormal micrometabolites as a marker of liver injury and severity in cases of traumatic liver damage. Serum were screened by proton nuclear magnetic resonance spectroscopy in 96 patients with varying degree of liver injury and compared with concentrations in healthy control volunteers. Large quantities of phenylalanine and tyrosine were detected by spectroscopic analysis in patients with liver injury but not in those without liver injury (P < 0.001). Proton nuclear magnetic resonance spectroscopy revealed two unique amino acids, phenylalanine and tyrosine, in the sera of the subjects with liver injury, irrespective of the extent and type of injury gauged by radiology or laparotomy. Phenylalanine spectrum was obtained in all 84 patients with liver injury (100% sensitivity) whereas tyrosine spectrum was present in 83 out of 84 patients (98.8% sensitivity) suggesting that these amino acids were specifically released in the patients of liver injury. Significant correlations were observed between phenylalanine and tyrosine concentrations and total bilirubin levels and albumin levels. Serum phenylalanine and tyrosine concentrations correlated well with imaging and laparotomy findings of liver injury. Phenylanaline and tyrosine appear to be specific and new markers of liver injury.