Phenylalanine hydroxylation across the kidney in humans rapid communication

Phenylalanine hydroxylation across the kidney in humans. BACKGROUND: Although phenylalanine hydroxylase activity is detectable in in vitro renal tissue preparations, no data on in vivo phenylalanine hydroxylation across the human kidney, as well as on its possible contribution to whole-body hydroxylation, currently exist. METHODS: To this aim, we have measured whole-body, renal, and splanchnic phenylalanine hydroxylation to tyrosine, as well as phenylalanine and tyrosine rates of appearance (Ra) and disposal (Rd), in postabsorptive subjects by means of renal and splanchnic arteriovenous catheterization combined with phenylalanine and tyrosine isotope infusions. RESULTS: In the kidney, a relevant phenylalanine hydroxylation activity was detected (3.51 +/- 0.97 micromol/min x 1.73 m2 of body surface), whereas it was 2.48 +/- 1. 35 micromol/min x 1.73 m2 across the splanchnic area. These two sites together accounted for virtually the entire whole-body phenylalanine hydroxylation. Renal production of tyrosine from phenylalanine hydroxylation accounted for approximately 13% of whole-body tyrosine Ra, whereas renal total tyrosine Ra accounted for approximately 34% of whole-body tyrosine Ra. In the splanchnic area, these figures were approximately 9 and 40%, respectively. Hydroxylation accounted for approximately 70% of phenylalanine Rd in the kidney, as opposed to approximately 8% in the splanchnic area. CONCLUSIONS: These data indicate that hydroxylation represents the major route of phenylalanine disposal within the kidney. The kidney and the splanchnic bed together account for all of the whole-body phenylalanine hydroxylation. These data also provide a further explanation for the reduced tyrosine pools occurring in uremia.     

Effects of peritoneal dialysis on protein metabolism

Protein-energy wasting is relatively common in renal patients treated with haemodialysis or peritoneal dialysis (PD) and is associated with worse outcome. In this article, we review the current state of our knowledge regarding the effects of PD on protein metabolism and the possible interactions between PD-induced changes in protein turnover and the uraemia-induced alterations in protein metabolism. Available evidence shows that PD induces a new state in muscle protein dynamics, which is characterized by decreased turnover rates and a reduced efficiency of protein turnover, a condition which may be harmful in stress conditions, when nutrient intake is diminished or during superimposed catabolic illnesses. There is a need to develop more effective treatments to enhance the nutritional status of PD patients. New approaches include the use of amino acid/keto acids-containing supplements combined with physical exercise, incremental doses of intraperitoneal amino acids, vitamin D and myostatin antagonism for malnourished patients refractory to standard nutritional therapy.     

Incremental value of amyloid-PET versus CSF in the diagnosis of Alzheimer’s disease

European Journal of Nuclear Medicine and Molecular Imaging - To compare the incremental diagnostic value of amyloid-PET and CSF (Aβ42, tau, and phospho-tau) in AD diagnosis in patients with...     

Nicotinic Acetylcholine Receptor Density in the “Higher-Order” Thalamus Projecting to the Prefrontal Cortex in Humans: a PET Study

Molecular Imaging and Biology - The parcellation of the thalamus into different nuclei involved in different corticothalamocortical loops reflects its functional diversity. The connections between...     

First imaging results of an intraindividual comparison of 11C-acetate and 18F-fluorocholine PET/CT in patients with prostate cancer at early biochemical first or second relapse after prostatectomy or radiotherapy

Purpose

¹⁸F-Fluorocholine (FCH) and ¹¹C-acetate (ACE) PET are widely used for detection of recurrent prostate cancer (PC). We present the first results of a comparative, prospective PET/CT study of both tracers evaluated in the same patients presenting with recurrence and low PSA to compare the diagnostic information provided by the two tracers.

Methods

The study group comprised 23 patients studied for a rising PSA level after radical prostatectomy (RP, 7 patients, PSA ≤3 ng/ml), curative radiotherapy (RT, 7 patients, PSA ≤5 ng/ml) or RP and salvage RT (9 patients, PSA ≤5 ng/ml). Both FCH and ACE PET/CT scans were performed in a random sequence a median of 4 days (range 0 to 11 days) apart. FCH PET/CT was started at injection (307?±?16 MBq) with a 10-min dynamic acquisition of the prostate bed, followed by a whole-body PET scan and late (45 min) imaging of the pelvis. ACE PET/CT was performed as a double whole-body PET scan starting 5 and 22 min after injection (994?±?72 MBq), and a late view (45 min) of the prostate bed. PET/CT scans were blindly reviewed by two independent pairs of two experienced nuclear medicine physicians, discordant subgroup results being discussed to reach a consensus for positive, negative end equivocal results.

Results

PET results were concordant in 88 out of 92 local, regional and distant findings (Cohen’s kappa 0.929). In particular, results were concordant in all patients concerning local status, bone metastases and distant findings. Lymph-node results were concordant in 19 patients and different in 4 patients. On a per-patient basis results were concordant in 22 of 23 patients (14 positive, 5 negative and 3 equivocal). In only one patient was ACE PET/CT positive for nodal metastases while FCH PET/CT was overall negative; interestingly, the ACE-positive and FCH-negative lymph nodes became positive in a second FCH PET/CT scan performed a few months later.

Conclusion

Overall, ACE and FCH PET/CT showed excellent concordance, on both a per-lesion and a per-patient basis, suggesting that both tracers perform equally for recurrent prostate cancer staging.     

Pre–clinical diagnosis of Alzheimer disease combining platelet amyloid precursor protein ratio and rCBF spect analysis

Platelet Amyloid Precursor Protein ratio of different abnormal forms and 99mTc–ECD SPECT perfusion analysis were evaluated in Mild Cognitive Impairment (MCI) subjects who progressed to Alzheimer Disease (AD) and in stable MCI. We report that their combined evaluation increases the discriminative power of the analysis in identifying presymptomatic AD. The positive predictive value of these combined markers in identifying progressive MCI was 0.87, and the negative predictive value was 0.90. This observation suggests that the interplay of different markers should be considered for enhancing diagnostic accuracy of pre–clinical AD. Drs. Di Luca and Padovani contributed equally to this work.     

Leptin as a uremic toxin interferes with neutrophil chemotaxis

Leptin is a pleiotropic molecule involved in energy homeostasis, hematopoiesis, inflammation, and immunity. Hypoleptinemia characterizing starvation has been strictly related to increased susceptibility to infection secondary to malnutrition. Nevertheless, ESRD is characterized by high susceptibility to bacterial infection despite hyperleptinemia. Defects in neutrophils play a crucial role in the infectious morbidity, and several uremic toxins that are capable of depressing neutrophil functions have been identified. Only a few and contrasting reports about leptin and neutrophils are available. This study provides evidence that leptin inhibits neutrophil migration in response to classical chemoattractants. Moreover, serum from patients with ESRD inhibits migration of normal neutrophils in response to N-formyl-methionyl-leucyl-phenylalanine with a strict correlation between serum leptin levels and serum ability to suppress neutrophil locomotion. Finally, the serum inhibitory activity can be effectively prevented by immune depletion of leptin. The results also show, however, that leptin by itself is endowed with chemotactic activity toward neutrophils. The two activities-inhibition of the cell response to chemokines and stimulation of neutrophil migration-could be detected at similar concentrations. On the contrary, neutrophils exposed to leptin did not display detectable [Ca(2+)](i) mobilization, oxidant production, or beta(2)-integrin upregulation. The results demonstrate that leptin is a pure chemoattractant devoid of secretagogue properties that are capable of inhibiting neutrophil chemotaxis to classical neutrophilic chemoattractants. Taking into account the crucial role of neutrophils in host defense, the leptin-mediated ability of ERSD serum to inhibit neutrophil chemotaxis appears as a potential mechanism that contributes to the establishment of infections in ERSD.