Somatomedin receptor of human placenta: solubilization, photolabeling, partial purification, and comparison with insulin receptor

Using a recently isolated human basic somatomedin (basic SM) similar to insulin-like growth factor I (IGF-I), we studied both the photoaffinity-labeled and unlabeled basic-SM receptor solubilized from human placental cell membranes. Unlike the result with the insulin receptor, high yields of soluble basic-SM-binding activity are obtained with Triton X-100. The soluble basic-SM receptor retains high-affinity (Kd approximately 0.3 nM) peptide-specific binding of basic SM, similar to the binding present in particulate placenta membranes; the receptor exhibits a comparatively low affinity for insulin (Kd approximately 3 microM). On Sepharose 6B, like the crude soluble insulin receptor, the basic-SM receptor migrates as a species with an apparent Stokes radius of 7.2 nm; unlike the insulin receptor, the basic-SM receptor does not, under similar conditions, yield a smaller binding species (apparent Stokes radius 3.8 nm). Upon photoaffinity labeling with 125I-labeled basic SM, one principal specifically labeled constituent is detected. Upon gel electrophoresis in the presence of 2-mercaptoethanol, the photolabeled constituent, like the insulin receptor, migrates as a species with an apparent molecular weight of about 140,000; in the absence of reducing agent, a molecular weight greater than 240,000 is observed. Lectin-agarose affinity chromatography yields a 30-fold purification both of the basic-SM-binding activity and the photolabeled constituent. Anti-insulin receptor antibody does not appear to precipitate the basic-SM receptor. We conclude that the basic-SM receptor of human placenta is a glycoprotein, remarkably similar to (an isoreceptor) but distinct from the insulin receptor previously characterized in this tissue.     

Supraventricular arrhythmias limit effective cardiac resynchronization therapy: Diagnosis using intracardiac electrograms and device based pacing maneuvers

Cardiac resynchronization therapy is an effective tool for the treatment of drug-refractory heart failure in patients with left ventricular dysfunction and inter/intra ventricular conduction delay. Supraventricular tachycardias may prevent effect delivery of this therapy. We report three cases in which effective therapy was limited by asymptomatic supraventricular tachycardia. Diagnostic pacing maneuvers were performed via the implanted device to determine the underlying arrhythmia mechanism. These cases highlight the importance of (1) treating supraventricular tachycardias before and after implantation of cardiac devices and (2) using device based programmed stimulation to diagnose the mechanism of supraventricular tachycardias. Dr. Gerstenfeld is supported by a Scientist Development Grant from the American Heart Association.     

Recent Advances in Visualizing Vulnerable Plaque: Focus on Noninvasive Molecular Imaging

Traditional imaging methods in atherosclerosis have focused primarily on anatomic information. Imaging approaches that visualize molecular targets rather than anatomic structures may emphasize biologic aspects of atherosclerosis. Molecular imaging of atherosclerotic lesions has become a crucial experimental tool and is now emerging in the clinical arena. In this review, we briefly highlight the rationale and fundamental principles of molecular imaging. We then discuss the promising imaging modalities, along with their potential limitations, and the molecular targets being investigated in experimental research. Finally, we summarize the most important clinical studies recently performed in humans.     

Anti-inflammatory and anti-arthritic effects of 3-hydroxy, 2-methoxy sodium butanoate from the leaves of Clerodendrum phlomidis L.f.

Introduction

The leaves of Clerodendrum phlomidis L.f. have been used in the Indian traditional system of medicine to treat several inflammatory diseases and arthritis. The aim of the present study was to assess the anti-inflammatory and anti-arthritic activities of the leaves of C. phlomidis and to isolate the active principle by bioactivity guided fractionation.

Materials and methods

To find the anti-inflammatory constituents from this plant, fractionations were performed with concurrent bioassays. Carrageenan-induced inflammation and Freund complete adjuvant (FCA)-induced arthritic rat models were used. The anti-inflammatory and anti-arthritic activities of the isolated compound were studied by assessing the histology of the joints, levels of lysosomal enzymes, protein-bound carbohydrates, acute phase protein, etc., in plasma, as well as by estimating the levels and expression of pro-inflammatory cytokines in the joints.

Results

Repeated fractionations and bioassays yielded a novel bioactive compound: 3-hydroxy, 2-methoxy-sodium butanoate. Treatment with this compound reduced the paw edema induced by carrageenan and FCA dose dependently. The levels of lysosomal enzymes and protein-bound carbohydrates decreased significantly upon treatment with the compound. The level of plasma acute phase protein was also decreased compared with control animals. Protein levels and mRNA expression of pro-inflammatory cytokines TNF, IL-1 and IL-6 in the joints were decreased significantly in a dose-dependent manner and the histopathological data also added evidence of the anti-arthritic property of the compound.

Conclusion

The 3-hydroxy,2-methoxy sodium butanoate isolated from plant leaves displays considerable potency in anti-inflammatory action and has a prominent anti-arthritic effect. This is the first report of this natural compound with bioactivity.     

Interaction of KSHV with Host Cell Surface Receptors and Cell Entry

Virus entry is a complex process characterized by a sequence of events. Since the discovery of KSHV in 1994, tremendous progress has been made in our understanding of KSHV entry into its in vitro target cells. KSHV entry is a complex multistep process involving viral envelope glycoproteins and several cell surface molecules that is utilized by KSHV for its attachment and entry. KSHV has a broad cell tropism and the attachment and receptor engagement on target cells have an important role in determining the cell type-specific mode of entry. KSHV utilizes heparan sulfate, integrins and EphrinA2 molecules as receptors which results in the activation of host cell pre-existing signal pathways that facilitate the subsequent cascade of events resulting in the rapid entry of virus particles, trafficking towards the nucleus followed by viral and host gene expression. KSHV enters human fibroblast cells by dynamin dependant clathrin mediated endocytosis and by dynamin independent macropinocytosis in dermal endothelial cells. Once internalized into endosomes, fusion of the viral envelope with the endosomal membranes in an acidification dependent manner results in the release of capsids which subsequently reaches the nuclear pore vicinity leading to the delivery of viral DNA into the nucleus. In this review, we discuss the principal mechanisms that enable KSHV to interact with the host cell surface receptors as well as the mechanisms that are required to modulate cell signaling machinery for a successful entry.     

The quality of systematic reviews/meta‐analyses published in the field of bariatrics: A cross‐sectional systematic survey using AMSTAR 2 and ROBIS

High‐quality systematic reviews (SR) and meta‐analyses (MA) are considered to be reliable sources of information. This study aims to assess the quality of studies published as SR or MA in the field of bariatrics in 2016 and 2017. We identified SR and MA in the field of bariatrics by searching electronic databases (MEDLINE, Embase, and Cochrane Database of Systematic Reviews). Eligible studies were those identified as SR/MA in the title/abstract, which aimed to assess any outcome in patients with morbid obesity undergoing or scheduled to undergo bariatric surgery. Two authors independently reviewed all titles and abstracts, assessed full texts of potentially eligible studies, and assessed the quality of included studies. Any discrepancies were resolved by the third reviewer. We evaluated the quality and risk of bias of each SR/MA using AMSTAR 2 checklist and ROBIS tool, respectively. Seventy‐eight of 4236 references met inclusion criteria and were assessed for their quality/risk of bias. The methodological quality of 99% of all papers was classified as “critically low.” A total of 6% of the studies were at low risk of bias, and 78% were assessed as being at high risk of bias. The methodological quality of studies published in 2016 and 2017 as SR/MA is highly unsatisfactory.     

Visual disorders,the prosopometamorphopsia and prosopagnosia type in the early days after the onset of brain hemorrhagic stroke – a case report

Presented case report illustrates symptoms of prosopometamorphopsia (PM) and prosopagnosia, observed in the early days after the onset of a hemorrhagic stroke resulting from a complication of endovascular treatment of intracranial aneurysms and the use of anticoagulation therapy. PM is a visual disorder in which faces are perceived as distorted. The female patient described in the present study reported that faces she looked at seemed younger or older than in reality or as if they were dirty, swollen, or with a grimace. She also experienced symptoms of prosopagnosia, which is difficulty of recognizing familiar faces of people (e.g., of her husband and daughter). In the interview 6 months after the first examination, the patient reported spontaneous withdrawal of the visual disturbances.     

Oral Ibandronate in Postmenopausal Osteoporotic Women Alters Micromechanical Properties Independently of Changes in Mineralization

Postmenopausal osteoporotic (PMOP) women treated with ibandronate had higher bone mineral density, lower bone turnover, and decreased incidence of new vertebral fractures. The aim of this study was to investigate the effect of daily or intermittent oral ibandronate on the degree of mineralization (DMB) of bone and microhardness (Hv) at the bone tissue and bone structural unit (BSU) levels. A total of 110 iliac biopsies were taken from patients treated for 22 or 34 months with an oral placebo (n = 36), 2.5 mg daily oral ibandronate (n = 40), or 20 mg intermittent oral ibandronate (n = 34). These regimens provide annual cumulative exposures (ACEs) that are about half of the therapeutic doses currently licensed for PMOP women. DMB and Hv were measured at the global level (i.e., cortical or cancellous) and the focal level (i.e., BSU). At the global level, DMB and its distribution were not significantly different from placebo after 22 and 34 months of treatment. Hv was significantly higher in the cortical, cancellous, and total bone after 22 and 34 months of ibandronate versus placebo for both regimens. At the focal level, DMB and Hv, measured simultaneously in 3,760 BSUs, were significantly and positively correlated in all groups (r = 0.59–0.65, p < 0.0001). However, analysis of covariance highlighted the differences in the y intercepts of the linear regressions of the placebo- and ibandronate-treated groups. We infer that a low ACE of oral ibandronate altered the bone micromechanical properties irrespective of changes in secondary mineralization.