Importance of amino acid composition to improve skin collagen protein synthesis rates in UV-irradiated mice

Skin collagen metabolism abnormalities induced by ultraviolet (UV) radiation are the major causes of skin photoaging. It has been shown that the one-time exposure of UV irradiation decreases procollagen mRNA expression in dermis and that chronic UV irradiation decreases collagen amounts and induces wrinkle formation. Amino acids are generally known to regulate protein metabolism. Therefore, we investigated the effects of UV irradiation and various orally administered amino acids on skin collagen synthesis rates. Groups of 4–5 male, 8-week-old HR-1 hairless mice were irradiated with UVB (66 mJ/cm2) twice every other day, then fasted for 16 h. The fractional synthesis rate (FSR; %/h) of skin tropocollagen was evaluated by incorporating l-[ring-2H5]-phenylalanine. We confirmed that the FSR of dermal tropocollagen decreased after UVB irradiation. The FSR of dermal tropocollagen was measured 30 min after a single oral administration of amino acids (1 g/kg) to groups of 5–16 UVB-irradiated mice. Branched-chain amino acids (BCAA, 1.34 ± 0.32), arginine (Arg, 1.66 ± 0.39), glutamine (Gln, 1.75 ± 0.60), and proline (Pro, 1.48 ± 0.26) did not increase the FSR of skin tropocollagen compared with distilled water, which was used as a control (1.56 ± 0.30). However, essential amino acids mixtures (BCAA + Arg + Gln, BCAA + Gln, and BCAA + Pro) significantly increased the FSR (2.07 ± 0.58, 2.04 ± 0.54, 2.01 ± 0.50 and 2.07 ± 0.59, respectively). This result suggests that combinations of BCAA and glutamine or proline are important for restoring dermal collagen protein synthesis impaired by UV irradiation

CT Characteristics of Pheochromocytoma: Relevance for the Evaluation of Adrenal Incidentaloma.

BACKGROUND: Up to 7% of all adrenal incidentalomas (AIs) are pheochromocytomas (PCCs). In the evaluation of AI, it is generally recommended that PCC be excluded by measurement of plasma-free or 24-hour urinary fractionated metanephrines. However, recent studies suggest that biochemical exclusion of PCC not be performed for lesions with CT characteristics of an adrenocortical adenoma (ACA). AIM: To determine the proportion of PCCs with ACA-like attenuation or contrast washout on CT. METHODS: For this multicenter retrospective study, two central investigators independently analyzed the CT reports of 533 patients with 548 histologically confirmed PCCs. Data on tumor size, unenhanced Hounsfield units (HU), absolute percentage washout (APW), and relative percentage washout (RPW) were collected in addition to clinical parameters. RESULTS: Among the 376 PCCs for which unenhanced attenuation data were available, 374 had an attenuation of >10 HU (99.5%). In the two exceptions (0.5%), unenhanced attenuation was exactly 10 HU, which lies just within the range of ≤10 HU that would suggest a diagnosis of ACA. Of 76 PCCs with unenhanced HU > 10 and available washout data, 22 (28.9%) had a high APW and/or RPW, suggestive of ACA. CONCLUSION: Based on the lack of PCCs with an unenhanced attenuation of <10 HU and the low proportion (0.5%) of PCCs with an attenuation of 10 HU, it seems reasonable to abstain from biochemical testing for PCC in AIs with an unenhanced attenuation of ≤10 HU. The assessment of contrast washout, however, is unreliable for ruling out PCC

Long-Term Outcomes with Subcutaneous C1-Inhibitor Replacement Therapy for Prevention of Hereditary Angioedema Attacks

Background For the prevention of attacks of hereditary angioedema (HAE), the efficacy and safety of subcutaneous human C1-esterase inhibitor (C1-INH[SC]; HAEGARDA, CSL Behring) was established in the 16-week Clinical Study for Optimal Management of Preventing Angioedema with Low-Volume Subcutaneous C1-Inhibitor Replacement Therapy (COMPACT). Objective To assess the long-term safety, occurrence of angioedema attacks, and use of rescue medication with C1-INH(SC). Methods Open-label, randomized, parallel-arm extension of COMPACT across 11 countries. Patients with frequent angioedema attacks, either study treatment-naive or who had completed COMPACT, were randomly assigned (1:1) to 40 IU/kg or 60 IU/kg C1-INH(SC) twice per week, with conditional uptitration to optimize prophylaxis (ClinicalTrials.gov registration no. NCT02316353). Results A total of 126 patients with a monthly attack rate of 4.3 in 3 months before entry in COMPACT were enrolled and treated for a mean of 1.5 years; 44 patients (34.9%) had more than 2 years of exposure. Mean steady-state C1-INH functional activity increased to 66.6% with 60 IU/kg. Incidence of adverse events was low and similar in both dose groups (11.3 and 8.5 events per patient-year for 40 IU/kg and 60 IU/kg, respectively). For 40 IU/kg and 60 IU/kg, median annualized attack rates were 1.3 and 1.0, respectively, and median rescue medication use was 0.2 and 0.0 times per year, respectively. Of 23 patients receiving 60 IU/kg for more than 2 years, 19 (83%) were attack-free during months 25 to 30 of treatment. Conclusions In patients with frequent HAE attacks, long-term replacement therapy with C1-INH(SC) is safe and exhibits a substantial and sustained prophylactic effect, with the vast majority of patients becoming free from debilitating disease symptoms

Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course