Background Testosterone supplementation has been shown to increase muscle mass and strength in healthy older men. The safety and efficacy of testosterone treatment in older men who have limitations in mobility have not been studied. Methods Community-dwelling men, 65 years of age or older, with limitations in mobility and a total serum testosterone level of 100 to 350 ng per deciliter (3.5 to 12.1 nmol per liter) or a free serum testosterone level of less than 50 pg per milliliter (173 pmol per liter) were randomly assigned to receive placebo gel or testosterone gel, to be applied daily for 6 months. Adverse events were categorized with the use of the Medical Dictionary for Regulatory Activities classification. The data and safety monitoring board recommended that the trial be discontinued early because there was a significantly higher rate of adverse cardiovascular events in the testosterone group than in the placebo group. Results A total of 209 men (mean age, 74 years) were enrolled at the time the trial was terminated. At baseline, there was a high prevalence of hypertension, diabetes, hyperlipidemia, and obesity among the participants. During the course of the study, the testosterone group had higher rates of cardiac, respiratory, and dermatologic events than did the placebo group. A total of 23 subjects in the testosterone group, as compared with 5 in the placebo group, had cardiovascular-related adverse events. The relative risk of a cardiovascular-related adverse event remained constant throughout the 6-month treatment period. As compared with the placebo group, the testosterone group had significantly greater improvements in leg-press and chest-press strength and in stair climbing while carrying a load. Conclusions In this population of older men with limitations in mobility and a high prevalence of chronic disease, the application of a testosterone gel was associated with an increased risk of cardiovascular adverse events. The small size of the trial and the unique population prevent broader inferences from being made about the safety of testosterone therapy.

The major sources of vitamin D for most humans are casual exposure of the skin to solar ultraviolet B (UVB;290-315 nm) radiation and from dietary intake. The cutaneous synthesis of vitamin D is a function of skin pigmentation and of the solar zenith angle which depends on latitude, season, and time of day. In order to mimic the natural environment of skin to sunlight exposure, we therefore measured serum 25-hydroxyvitamin D levels in volunteers with different skin types following repeated UV irradiation. Because melanin pigment in human skin competes for and absorbs the UVB photons responsible for the photolysis of 7-dehydrocholesterol to previtamin D 3 , we also studied the effect of skin pigmentation on previtamin D 3 production in a human skin by exposing type II and type V skin samples to noon sunlight in June when the solar zenith angle is most acute. Vitamin D is rare in food. Among the vitamin D-rich food, oily fish are considered to be one of the best sources. Therefore, we analyzed the vitamin D content in several commonly consumed oily and non-oily fish. The data showed that farmed salmon had a mean content of vitamin D that was ~25% of the mean content found in wild caught salmon from Alaska, and that vitamin D 2 was found in farmed salmon, but not in wild caught salmon. The results provide useful global guidelines for obtaining sufficient vitamin D 3 by cutaneous synthesis and from dietary intake to prevent vitamin D deficiency and its health consequences.ensuing illness, especially, bone fractures in the elderly.

Green tea catechins (GTCs), which include (-)-epicatechin (EC), (-)-epicatechin gallate (ECG), (-)epigallocatechin (EGC) and (-)-epigallocatechin gallate (EGCG), possess a variety of biological activities. We have previously studied the effect of dietary GTCs as a mixture on membrane oxidation of red blood cells and found that GTCs were partially absorbed and detected in the blood of rats given an oral ingestion of 100 mg of GTCs. To explain the partial absorption of GTCs and their varying free-radical scavenging capacity at different pH, the present paper was to study further the pH stability of these GTC isomers because there is a sharp increase in pH from the acidic stomach to the slightly alkaline intestine. Longjing GTCs as a mixture in alkaline solutions (pH > 8) were extremely unstable and degraded almost completely in a few minutes, whereas in acidic solutions (pH < 4) they were very stable. For the pH between 4 and 8, the stability of GTCs was pH-dependent, i.e., the lower the pH, the greater the stability. Four epicatechin isomers examined demonstrated varying stability in alkaline solutions with EGCG and EGC being equally instable, and EC and ECG being relatively stable. The present results suggest that part of the mechanism by which GTCs were partially absorbed may be attributed to instability of EGCG and EGC in the intestine where the pH is neutral or alkaline.

Optical coherence tomography (OCT)-based angiography is increasingly becoming a clinically useful and important imaging technique due to its ability to provide volumetric microvascular networks innervating tissue beds in vivo without a need for exogenous contrast agent. Numerous OCT angiography algorithms have recently been proposed for the purpose of contrasting microvascular networks. A general literature review is provided on the recent progress of OCT angiography methods and algorithms. The basic physics and mathematics behind each method together with its contrast mechanism are described. Potential directions for future technical development of OCT based angiography is then briefly discussed. Finally, by the use of clinical data captured from normal and pathological subjects, the imaging performance of vascular networks delivered by the most recently reported algorithms is evaluated and compared, including optical microangiography, speckle variance,phase variance, split-spectrum amplitude decorrelation angiography, and correlation mapping. It is found that the method that utilizes complex OCT signal to contrast retinal blood flow delivers the best performance among all the algorithms in terms of image contrast and vessel connectivity. The purpose of this review is to help readers understand and select appropriate OCT angiography algorithm for use in specific applications.

Reference ranges generated in a community-based sample of men provide a rational basis for categorizing testosterone levels as low or normal. Men with low TT or FT by these criteria had higher prevalence of physical dysfunction, sexual dysfunction, and diabetes. These reference limits should be validated prospectively in relation to incident outcomes and in randomized trials.

Objective To correlate images from swept source optical coherence tomography microangiography (SS-OMAG) with images from fluorescein angiography (FA) and indocyanine green angiography (ICGA) performed on asymptomatic eyes with intermediate age-related macular degeneration. Study Design and Methods A retrospective, observational, consecutive case series of patients with asymptomatic, intermediate AMD in one eye and neovascular AMD in their fellow eye. The patients underwent SS-OMAG, FA, and ICGA, and the images obtained from these three angiographic techniques were compared. Results Three patients were identified with intermediate AMD in one eye and symptomatic, neovascular AMD in their fellow eye. The three asymptomatic eyes had drusen and pigmentary abnormalities in the central macula and no evidence of macular fluid on OCT imaging. One patient presented with minimal leakage on FA from the asymptomatic eye. ICGA revealed the presence of central macular plaques, and SS-OMAG revealed type 1 neovascularization corresponding to the plaques. The type 1 neovascularization was visualized using en face slabs that extended from the border of the outer retina to the choriocapillaris (CC), 8 μm beneath Bruch’s membrane. Conclusions SS-OMAG identified type 1 neovascularization within ICGA plaques. The ability of OCTA to provide non-invasive, fast, detailed, depth-resolved identification of non-exudative neovascular lesions in eyes with intermediate AMD suggests the need for new terminology that distinguishes between non-exudative intermediate AMD and non-exudative, neovascular intermediate AMD. This distinction should prove useful for managing AMD patients at risk for conversion to late, exudative AMD once natural history studies are performed to better understand disease progression.

Retinoids, particularly all-trans-retinoic acid (RA), are potent regulators of cell differentiation, cell proliferation, and apoptosis. The role of all-trans-RA during development and in the maintenance of adult tissues has been well established. The control of all-trans-RA levels in cells and tissues is regulated by the balance between its biosynthesis and its catabolism to inactive metabolites. The cytochrome P450 enzyme P450RAI (herein renamed P450RAI-1) is partially responsible for this inactivation of all-trans-RA. In this report, we describe the identification, molecular cloning, and characterization of a second related enzyme, P450RAI-2, which is also involved in the specific inactivation of all-trans-RA. Transiently transfected P450RAI-2 can convert all-trans-RA to more polar metabolites including 4-oxo-, 4-OH-, and 18-OH-all-trans-RA. Competition experiments with other retinoids suggest that all-trans-RA is the preferred substrate. The high level of expression of P450RAI-2, particularly in the cerebellum and pons of human adult brain, suggests a unique role for this enzyme in the protection of specific tissues from exposure to retinoids.

Patients with CKD suffer high rates of thrombosis, particularly after endovascular interventions, yet few options are available to improve management and reduce thrombotic risk. We recently demonstrated that indoxyl sulfate (IS) is a potent CKD-specific prothrombotic metabolite that induces tissue factor (TF) in vascular smooth muscle cells (vSMCs), although the precise mechanism and treatment implications remain unclear. Because IS is an agonist of the aryl hydrocarbon receptor (AHR), we first examined the relationship between IS levels and AHR-inducing activity in sera of patients with ESRD. IS levels correlated significantly with both vSMC AHR activity and TF activity. Mechanistically, we demonstrated that IS activates the AHR pathway in primary human aortic vSMCs, and further, that AHR interacts directly with and stabilizes functional TF. Antagonists directly targeting AHR enhanced TF ubiquitination and degradation and suppressed thrombosis in a postinterventional model of CKD and endovascular injury. Furthermore, AHR antagonists inhibited TF in a manner dependent on circulating IS levels. In conclusion, we demonstrated that IS regulates TF stability through AHR signaling and uncovered AHR as an antithrombotic target and AHR antagonists as a novel class of antithrombotics. Together, IS and AHR have potential as uremia-specific biomarkers and targets that may be leveraged as a promising theranostic platform to better manage the elevated thrombosis rates in patients with CKD.