The role of ubiquitin-proteasome system in the accelerated atherosclerotic progression of diabetic patients is unclear. We evaluated ubiquitin-proteasome activity in carotid plaques of asymptomatic diabetic and nondiabetic patients, as well as the effect of rosiglitazone, a peroxisome proliferator-activated receptor (

Ubiquitin-proteasome overactivity is associated with enhanced inflammatory reaction in symptomatic plaques. The inhibition of ubiquitin-proteasome activity in lesions of symptomatic patients by rosiglitazone is associated with plaque stabilization, possibly by down-regulating NFkB-mediated inflammatory pathways.

Abstract-Whether morning blood pressure surge influences the molecular mechanisms of plaque progression toward instability is not known. Recently, we have demonstrated enhanced activity of the ubiquitin-proteasome system in human plaques and evidenced that it is associated with inflammatory-induced plaque rupture. We evaluated the inflammatory infiltration and ubiquitin-proteasome activity in asymptomatic carotid plaques of hypertensive patients with different patterns of morning blood pressure surge. Plaques were obtained from 32 hypertensive patients without morning blood pressure surge and 28 with morning blood pressure surge enlisted to undergo carotid endarterectomy for extracranial high-grade (Ͼ70%) internal carotid artery stenosis. Plaques were analyzed for macrophages, T-lymphocytes, human leukocyte antigen-DRϩcells, ubiquitin-proteasome activity, nuclear factor-B, inhibitor kB-␤, tumor necrosis factor-␣, nitrotyrosine, matrix metalloproteinase-9, and collagen content (immunohistochemistry and ELISA). Compared with plaques obtained from hypertensive patients without morning blood pressure surge, plaques from with morning blood pressure surge had more macrophages, T-lymphocytes, human leukocyte antigen-DRϩcells (PϽ0.001), ubiquitin-proteasome activity, tumor necrosis factor-␣, nuclear factor-kB (PϽ0.001), nitrotyrosine, and matrix metalloproteinase-9 (PϽ0.01), along with a lesser collagen content and IkB-␤ levels (PϽ0.001). Enhanced ubiquitin-proteasome activity in atherosclerotic lesions of patients with morning blood pressure surge is associated with inflammatory-dependent unstable plaque phenotype. These data suggest a potential interplay between morning blood pressure surge and ubiquitin-proteasome activity in atherosclerosis pathophysiology. (Hypertension. 2007;49:784-791.)Key Words: morning blood pressure Ⅲ atherosclerotic plaque Ⅲ inflammation Ⅲ ubiquitin-proteasome activity M any studies in the past decade have demonstrated diurnal variation in the onset of acute cardiovascular disorders in hypertensive patients, such as acute coronary syndrome, and ischemic and hemorrhagic stroke occurring in the morning (6:00 AM to noon), after a nadir in these events during the night. 1 Blood pressure (BP) falls during the night because of the reduction of sympathetic activity that is brought about by sleep and then increases steeply when in the morning the subject awakes and resumes his/her daily activities. 2 This increase occurs together with a peak incidence of cerebral and cardiac events in the morning hours. 3 Moreover, a recent prospective study suggests that higher morning BP surge (MBPS) might be an independent risk factor of atherosclerotic events beyond ambulatory BP and nocturnal BP falls. 4 The molecular mechanisms associating MBPS peak and vulnerable atherosclerotic plaque are not clear, although inflammation, which plays a central role in the cascade of events that result in plaque erosion and fissuring, also were related to MBPS. 5 There is emerging evidence that the ubiquitin-proteasome syste...

Introduction: Vitamin D inadequacy or deficiency (VDID) has been reported in a high percentage of otherwise healthy individuals. Factors that may contribute to the high prevalence of VDID in people with mental disorders include diet low in vitamin D, poor sunlight exposure, decrease in cutaneous vitamin D synthesis, intake of certain medications, poor mobility, excessive alcohol intake, and tobacco smoking. VDID has been correlated to a host of adverse conditions, including rickets, osteoporosis, osteomalacia, muscle diseases, depression, cognitive dysfunction, and even certain cancers. Objectives: The purpose of this study was to report the prevalence and correlates of vitamin D inadequacy in a sample of 290 psychiatric patients admitted to inpatient or day hospital treatment at the University of Siena Medical Center. Methods: We retrospectively evaluated the prevalence of VDID in 290 psychiatric inpatients' medical records during the year 2017 and evaluated the correlates of VDID in patients with mental illness. Results: Two hundred and seventy two out of two hundred and ninety patients (94%) showed VDID. Physical activity and regular diet were positively correlated with vitamin D levels whereas age, tobacco smoking, PTH, alkaline phosphatase levels were negatively correlated. Statistically significant differences were found among smokers and non-smokers in all study groups. Conclusions: VDID was highly prevalent in our sample. In addition to vitamin D supplementation, psychosocial intervention able to promote and help sustain physical activity, appropriate diet, quitting smoking and sensible sun exposure to prevent and treat VDID in patients with mental health should be implemented, tested, and introduced in our clinical practice.

Background: Major depressive disorder (MDD) is a recurrent illness with high rates of chronicity, treatmentresistance, and significant economic impact. S-Adenosylmethionine (SAMe), a molecule that is formed naturally in the human body, has shown antidepressant effects and may expand the available options for treating MDD. This systematic review examines the evidence concerning the efficacy of SAMe as monotherapy or in combination with antidepressants. Methods: A systematic search in Medline, Psychinfo, AMED, and Cochrane Controlled Trials Register was conducted for any reference recorded up to March 2020. Double-blind, randomised controlled trials, comparing the antidepressant efficacy of SAMe to placebo or/and to other antidepressants, were selected. Two authors evaluated each study independently and then, reconciled findings. Results: Eight trials, with a total of 11 arms and 1011 subjects, evaluating the efficacy of SAMe used as monotherapy or as adjunctive therapy (512 individuals), were included in this review. The study duration ranged between 2 and 12 weeks and the daily dose of SAMe varied from 200 to 3200 mg. Five comparisons evaluated the differences between SAMe and placebo and SAMe resulted significantly better than placebo in three of these studies. Four comparisons evaluated the differences between SAMe and other antidepressants (imipramine or escitalopram) and showed no significant difference. One study showed that SAMe was significantly better than placebo in accelerating the response to imipramine from day 4 to day 12, but the mean scores were not statistically different at the day 14 endpoint. One study showed that SAMe combined with serotonin reuptake inhibitors (SSRI) was better than PBO combined with SSRI. The studies reported only mild, transient or non-clinically relevant side effects. Conclusions: The existing trials of SAMe, used as monotherapy or add on to another antidepressants, have shown encouraging and generally positive results. However, more evidence is necessary before definitive conclusions can be drawn. Larger, double-blind randomised controlled studies are warranted to confirm the antidepressant effectiveness of SAMe.