Tryptophan Metabolism, Inflammation, and Oxidative Stress in Patients with Neurovascular Disease.

Atherosclerosis is a leading cause of major vascular events, myocardial infarction, and ischemic stroke. Tryptophan (TRP) catabolism was recognized as an important player in inflammation and immune response having together with oxidative stress (OS) significant effects on each phase of atherosclerosis. The aim of the study is to analyze the relationship of plasma levels of TRP metabolites, inflammation, and OS in patients with neurovascular diseases (acute ischemic stroke (AIS), significant carotid artery stenosis (SCAS)) and in healthy controls. Blood samples were collected from 43 patients (25 with SCAS, 18 with AIS) and from 25 healthy controls. The concentrations of twelve TRP metabolites, riboflavin, neopterin (NEO, marker of inflammation), and malondialdehyde (MDA, marker of OS) were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Concentrations of seven TRP metabolites (TRP, kynurenine (KYN), 3-hydroxykynurenine (3-HK), 3-hydroxyanthranilic acid (3-HAA), anthranilic acid (AA), melatonin (MEL), tryptamine (TA)), NEO, and MDA were significantly different in the studied groups. Significantly lower concentrations of TRP, KYN, 3-HAA, MEL, TA, and higher MDA concentrations were found in AIS compared to SCAS patients. MDA concentration was higher in both AIS and SCAS group (p < 0.001, p = 0.004, respectively) compared to controls, NEO concentration was enhanced (p < 0.003) in AIS. MDA did not directly correlate with TRP metabolites in the study groups, except for 1) a negative correlation with kynurenine acid and 2) the activity of kynurenine aminotransferase in AIS patients (r = -0.552, p = 0.018; r = -0.504, p = 0.033, respectively). In summary, TRP metabolism is clearly more deregulated in AIS compared to SCAS patients; the effect of TRP metabolites on OS should be further elucidated.

Detection of carotid artery stenosis using histological specimens: a comparison of CT angiography, magnetic resonance angiography, digital subtraction angiography and Doppler ultrasonography.

BACKGROUND: Carotid endarterectomy (CEA) is accepted as a primary modality to treat carotid stenosis. The accuracy of measuring carotid stenosis is important for indication of the CEA procedure. Different diagnostic tools have been developed and used in the past 2 decades for the diagnosis of carotid stenosis. Only a few studies, however, have focused on the comparison of different diagnostic tools to histological findings of carotid plaque. METHOD: Patients with internal carotid artery (ICA) stenosis were investigated primarily by computed tomography angiography (CTA). Digital subtraction angiography (DSA), Doppler ultrasonography (DUS) and magnetic resonance angiography (MRA) were performed as well. Atherosclerotic plaque specimens were transversally cut into smaller segments and histologically processed. The slides were scanned and specimens showing maximal stenosis were determined; the minimal diameter and the diameter of the whole plaque were measured. High quality histological specimen and histological measurement was considered to be the prerequisite for inclusion into the analysis. The preoperative findings were compared with histological measurement. CTA and histological measurements were obtained from 152 patients. DSA measurements were available in 138 of these cases, MRA in 107 and DUS in 88. A comparison between preoperative and histological findings was performed. In addition, correlation coefficients were computed and tested. RESULTS: A significant correlation was found for each of the diagnostic procedures. The strongest correlation coefficient and the best allocation of stenosis into clinical significant groups (<50 %, 50-69 %, ≥70 %) was observed for CTA. Mean differences in the whole cohort between preoperative and histological measurements were as follows: CTA underestimated histological measurement by 2.4 % (based on European Carotid Surgery Trial [ECST] methodology) and 11.9 % (based on North American Symptomatic Carotid Endarterectomy Trial [NASCET] methodology). DSA underestimated the histological measurement by 7 % (ECST) and 12.2 % (NASCET). MRA overestimated the histological measurement by 2.6 % (ECST) and underestimated by 0.6 % (NASCET). DUS overestimated the stenosis by 1.8 %. CONCLUSIONS: CTA yields the best accuracy in detection of carotid stenosis, provided that all axial slices of the stenosis are checked and carefully analysed. DSA underestimates moderate and mild ICA stenosis, whereas DUS overestimates high-grade ICA stenosis. For MRA, a relatively low correlation coefficient was observed with histological findings. We conclude that CTA-ecst technique is the most reliable technique for carotid stenosis measurement.

Prolonged overdose of all-trans retinoic acid enhances bone sensitivity in castrated mice.

OBJECTIVES: Intake of multivitamin preparations is very common in developed countries. However, excessive intake of vitamin A was associated with increased bone fragility. The aim of this study was to determine if chronic administration of the active metabolite of vitamin A all-trans-retinoic acid (ATRA) in slight excess is associated with changes of bone turnover and density in intact and castrated mice. METHOD: Three mo old male mice (C57B1/6) intact and castrated were injected intraperitonealy with 10 mg/kg/d of the ATRA or vehicle (control) once daily for 3 wk. The bone density, ash weights, calcium, and phosphorus content of the femur were measured. Plasma tartrate-resistant acid phosphatase (Tr-ACP) and serum bone alkaline phosphatase (B-ALP) were determined. RESULTS: ATRA decreased bone density in both groups; however, this effect was more pronounced in castrated animals (1.487 ± 0.04 to 1,360 ± 0.05 g/cm(3)) than in intact mice (1.570 ± 0.03 to 1.510 ± 0.03 g/cm(3)). Bone density correlated with decreased B-ALP and increased Tr-ACP in ATRA-treated mice. ATRA treatment led to significantly lower thickness of cortical bone both in the intact and castrated animals. CONCLUSION: Our results indicate that repeated administration of ATRA in slight excess leads to significant bone loss both in intact and castrated mice. This effect was more pronounced in testosterone-deficient animals. Testosterone deficiency as occurs following castration may sensitize the bone to resorption mediated by ATRA. Therefore, chronic vitamin A administration may be a risk factor for osteoporosis, especially in older and testosterone-depleted subjects.