The effect of bariatric surgery on serum 25-OH vitamin D levels: a systematic review and meta-analysis.

BACKGROUND: Concerns have emerged about post-operative decreases in calcium and vitamin D following bariatric surgery. This review explores changes in metabolic bone health in persons with obesity undergoing gastric bypass surgery compared to non-surgical controls, providing an updated and comprehensive perspective on the literature. METHODS: An electronic search was conducted in MEDLINE, Pubmed, EMBASE and Cochrane databases to 8 November 2016. Eligible trials included randomized controlled trials or controlled observational studies of patients who have undergone laparoscopic gastric bypass surgery. Statistical analysis was carried out using the Cochrane Collaboration Review Manager (RevMan 5.0), and a random effects model was implemented. Outcomes were expressed as weighted mean difference (WMD). The primary outcome examined was change in 25-OH-D levels at 12 months post surgery, and secondary outcomes included change in bone mineral density (BMD) measurements at 12 months post surgery at the lumbar spine (LS) and total hip (TH). RESULTS: At 12 months, there was no significant difference in 25-OH vitamin D in the surgical group compared to controls (WMD = 6.79%; 95% CI: -9.01, 22.59; p = 0.40; I2 = 68%). There was no statistically significant difference between fracture risk in the surgical population compared to controls (RR = 1.24; 95% CI: 0.99, 1.56; p = 0.06; I2 = 0%). A significant BMD reduction was however shown at the TH (WMD, -7.33%, 95% CI = -8.70 to -5.97, p < .001, I2 = 0%), and a trend towards decline was observed at the LS (WMD, -1.73%, 95% CI = -3.56 to 0.11, p = 0.06, I2 = 0%). Changes at 24 months for applicable outcomes were similar to the results at 12 months. CONCLUSIONS: Bariatric surgery may compromise metabolic bone health, but the paucity of high-quality literature limits conclusions.

Homocysteine Induced Cerebrovascular Dysfunction: A Link to Alzheimer's Disease Etiology.

A high serum level of homocysteine, known as hyperhomocystenemia (HHcy) is associated with vascular dysfunction such as altered angiogenesis and increased membrane permeability. Epidemiological studies have found associations between HHcy and Alzheimer's disease (AD) progression that eventually leads to vascular dementia (VaD). VaD is the second most common cause of dementia in people older than 65, the first being AD. VaD affects the quality of life for those suffering by drastically decreasing their cognitive function. VaD, a cerebrovascular disease, generally occurs due to cerebral ischemic events from either decreased perfusion or hemorrhagic lesions. HHcy is associated with the hallmarks of dementia such as tau phosphorylation, Aß aggregation, neurofibrillary tangle (NFT) formation, neuroinflammation, and neurodegeneration. Previous reports also suggest HHcy may promote AD like pathology by more than one mechanism, including cerebral microangiopathy, endothelial dysfunction, oxidative stress, neurotoxicity and apoptosis. Despite the corelations presented above, the question still exists - does homocysteine have a causal connection to AD? In this review, we highlight the role of HHcy in relation to AD by discussing its neurovascular effects and amelioration with dietary supplements. Moreover, we consider the studies using animal models to unravel the connection of Hcy to AD.

Analysis of the stent expansion in a stenosed artery using finite element method: application to stent versus stent study.

In this article, finite element method is used to investigate the mechanical behavior of a stent and to determine the biomechanical interaction between the stent and the artery in a stenting procedure. The main objective of this study is to reach to a model close to a real condition of coronary stent placement. Unlike most of the models proposed in the literature, all the steps of the deployment of a stent in the stenotic vessel (i.e. pressure increasing, constant load pressure and pressure decreasing) are simulated in this article to show the behavior of the stent in different stages of implantation. The results indicate that the first step of deployment, that is, pressure increasing, plays a main role in the success of stent implantation. So that, in order to compare the behavior of different types of stents, it is sufficient to compare their behavior at the end of pressure increasing step. In order to show the application of the findings in stent versus stent studies, three commercially available stents (the Palmaz-Schatz, Multi-Link and NIR stents) are modeled and their behavior is compared at the end of pressure increasing step. The effect of stent design on the restenosis rate is investigated. According to the findings, the possibility of restenosis is lower for Multi-Link and NIR stents in comparison with Palmaz-Schatz stent which is in good agreement with clinical results. Therefore, the testing methodology outlined here is proposed as a simple and economical alternative for "stent versus stent" complicated clinical trials.

Curcumin-primed exosomes mitigate endothelial cell dysfunction during hyperhomocysteinemia.

AIM: Exosomes, the nano-units (<200 nm), released from diverse cell types in the extracellular body fluid, possess non-immunogenic property and ability to cross the blood-brain barrier (BBB). Since exosomes carry biological information from their cells of origin, we hypothesize that priming cells with potential therapeutic agents release improved cellular contents through exosomes. Curcumin possesses anti-oxidative and anti-inflammatory properties and provides a promising treatment for cerebral diseases and therefore, the aim of the study is to establish that mouse brain endothelial cells (MBECs) when primed with curcumin (7.5 µM), release an alleviated exosome population that can help recover the endothelial cell (EC) layer permeability. MAIN METHODS: Homocysteine is a well-known causative factor of BBB disruption; therefore, homocysteine-treated ECs were used as a model of BBB disruption and curcumin-primed exosomes were utilized to check their potential for mitigating EC disruption. MBECs were treated with curcumin and exosomes were isolated by using ultracentrifugation and immunoprecipitation. Expression levels of junction proteins were detected by Western blot and immunocytochemistry assays. Endothelial cell permeability was analyzed with Fluorescein isothiocyanate-Bovine serum albumin (FITC-BSA) leakage assay using transwell permeable supports. KEY FINDINGS: Exosomes derived from curcumin-treated (primed) cells (CUR-EXO) alleviated oxidative stress, tight junctions (ZO-1, claudin-5, occludin), adherent junction (VE-cadherin) proteins and EC layer permeability induced during EC damage due to high homocysteine levels (hyperhomocysteinemia). SIGNIFICANCE: In conclusion, the study potentiates the use of CUR-EXO for cerebral diseases where drug delivery is still a challenge. The results also pave the way to novel translational therapies for cerebral diseases by maintaining and establishing therapeutic conservatories via primed exosomes.

Hydrogen sulfide attenuates neurodegeneration and neurovascular dysfunction induced by intracerebral-administered homocysteine in mice.

High levels of homocysteine (Hcy), known as hyperhomocysteinemia are associated with neurovascular diseases. H2S, a metabolite of Hcy, has potent anti-oxidant and anti-inflammatory activities; however, the effect of H2S has not been explored in Hcy (IC)-induced neurodegeneration and neurovascular dysfunction in mice. Therefore, the present study was designed to explore the neuroprotective role of H2S on Hcy-induced neurodegeneration and neurovascular dysfunction. To test this hypothesis we employed wild-type (WT) males ages 8-10 weeks, WT+artificial cerebrospinal fluid (aCSF), WT+Hcy (0.5 µmol/µl) intracerebral injection (IC, one time only prior to NaHS treatment), WT+Hcy+NaHS (sodium hydrogen sulfide, precursor of H2S, 30 µmol/kg, body weight). NaHS was injected i.p. once daily for the period of 7 days after the Hcy (IC) injection. Hcy treatment significantly increased malondialdehyde, nitrite level, acetylcholinestrase activity, tumor necrosis factor-alpha, interleukin-1 beta, glial fibrillary acidic protein, inducible nitric oxide synthase, endothelial nitric oxide synthase and decreased glutathione level indicating oxidative-nitrosative stress and neuroinflammation as compared to control and aCSF-treated groups. Further, increased expression of neuron-specific enolase, S100B and decreased expression of (post-synaptic density-95, synaptosome-associated protein-97) synaptic protein indicated neurodegeneration. Brain sections of Hcy-treated mice showed damage in the cortical area and periventricular cells. Terminal deoxynucleotidyl transferase-mediated, dUTP nick-end labeling-positive cells and Fluro Jade-C staining indicated apoptosis and neurodegeneration. The increased expression of matrix metalloproteinase (MMP) MMP9, MMP2 and decreased expression of tissue inhibitor of metalloproteinase (TIMP) TIMP-1, TIMP-2, tight junction proteins (zonula occulden 1) in Hcy-treated group indicate neurovascular remodeling. Interestingly, NaHS treatment significantly attenuated Hcy-induced oxidative stress, memory deficit, neurodegeneration, neuroinflammation and cerebrovascular remodeling. The results indicate that H2S is effective in providing protection against neurodegeneration and neurovascular dysfunction.

Immunotherapy as an adjuvant therapy in the management of advanced, surgically resected, melanoma.

Metastatic melanoma continues to be one of the most devastating of all cancers. It is a heterogeneous solid tumor whose treatment is challenging and difficult. It afflicts thousands of otherwise healthy patients annually, and clinicians have yet to discover an effective treatment for locally advanced disease. Over the years, much attention has been devoted to the development of an effective adjuvant treatment for patients with resected melanoma who remain at high risk for recurrence. The new advances in the understanding of melanoma's microenvironment and the complexity of its disease process, makes it clear that the treatment approach to this disease needs to be multi-directional. Numerous studies have tested various immunotherapeutic strategies in the treatment of advanced melanoma, in particular. These strategies include melanoma vaccines, interferon-alpha, interleukin-2 (IL-2), and dendritic cell vaccines. The Dr. Wallack's Surgery Research Laboratory has been studying melanoma vaccines for the past three decades. The first generation melanoma vaccine proposed by the Laboratory showed promising results in a subset of patients. Recently, the same Laboratory has produced a second generation melanoma vaccine (DC-Melvac) that consists of five human melanoma cell lines, a recombinant vaccinia virus that encodes for IL-2, as well as dendritic cells that have been programmed to recognize certain melanoma associated antigens. DC-MelVac was recently approved by the Food and Drug Administration for its use in Phase I clinical trials. These trials are expected to be underway in the near future. The ensuing review discusses many of the immunotherapeutic strategies that have been studied in the treatment of melanoma, including DC-MelVac.