The somatomedin-C receptor of human placenta

The binding and physical characteristics of the human placenta somatomedin-C (Sm-C) receptor were investigated and compared with those of the placental insulin receptor. These receptors were found to have many similar properties, but several distinctions exist between them. The two receptors have similar binding properties. Although distinct receptors, as evidenced by specificity studies, the Sm-C and insulin receptors possess similar affinities (10 X 10(9) L/mol and 3 X 10(9) L/mol, respectively) and receptor concentrations (0.4 pm/mg and 0.2 pm/mg) in placental membranes. There is also a low-affinity, high-capacity receptor for each hormone. The intact receptors are indistinguishable in size by three methods. The Stokes radius is 7.2 nm by gel filtration, the sedimentation coefficient is 11S, and the SDS polyacrylamide gel apparent molecular weight is approximately 350,000 daltons. The two receptors differ in their pH optimum for ligand binding, their isoelectric points, and their subunit size. The pH optimum for Sm-C binding is 8.2, and for insulin binding the optimum is 7.9. The isoelectric point for the Sm-C receptor is 4.6, whereas the isoelectric point for the insulin receptor is 4.2. Although the whole receptor and the half receptors for Sm-C and insulin cannot be distinguished by size on SDS gels, the binding subunit for the Sm-C receptor appears to be 8000 daltons smaller than that of the insulin receptor (134,000 v 142,000 daltons). We conclude from these studies that the insulin and Sm-C receptors of human placenta are similar in structure but are distinct entities.     

How oral environment simulation affects ceramic failure behavior

Statement of problem

Investigating the mechanical behavior of ceramics in a clinically simulated scenario contributes to the development of new and tougher materials, improving the clinical performance of restorations. The optimal in vitro environment for testing is unclear.

CKD‐501, a novel selective PPARγ agonist,shows no carcinogenic potential in ICR mice following oral administration for 104 weeks

CKD‐501 is a peroxisome proliferator‐activated receptor gamma (PPARγ) agonist that is effective for the treatment of diabetes. However, its carcinogenic potential remains controversial. The current carcinogenicity study was conducted over a period of 104 weeks in ICR mice. Three groups, each consisting of 60 male and 60 female mice, received oral CKD‐501 dosages of 0.2, 1.0 or 6.0 mg kg^?1day^–1. The mortality rates of the male control, 0.2, 1.0 and 6.0 mg kg^–1 day^–1 treated groups were 60%, 68%, 58% and 67%, respectively and 57%, 68% and 67% in the female control, 0.2 and 1.0 mg kg^?1 day^–1 treated groups. It was 67% in the female 6.0 mg kg^?1 day^–1 treated group, which was terminated at week 98 due to its increased mortality rate. No significant treatment‐related effects were observed on the survival rates, with the exception of females in the 6.0 mg kg^?1 day^–1 group. Body weights increased in females receiving 1.0 and 6.0 mg kg^?1 day^–1 due to the class effects of the PPARγ agonist. Differences were not found in hematology parameters between the CKD‐501‐treated groups and their corresponding controls, but the histopathological evidence did not reveal any findings attributed to CKD‐501. Treated animals exhibited non‐neoplastic findings (adipocyte proliferation, bone marrow hypoplasia cardiomyopathy), but all of these were expected changes for this class of compound. There were no treatment‐related neoplastic changes in this study. The results of this study therefore demonstrate a lack of carcinogenicity following oral administration of CKD‐501 to ICR mice for 104 weeks. Copyright © 2013 John Wiley & Sons, Ltd.     

Getting to the Heart of the Matter: A Review of Drug Interactions Between HIV Antiretrovirals and Cardiology Medications

The past 20 years have seen remarkable advances in the treatment of HIV such that most people diagnosed with HIV today can live long, healthy lives by taking antiretrovirals which are usually life-long. Advancements in antiretroviral therapy include the availability of well tolerated, single tablet regimens that are associated with a lower risk of drug-drug interactions. Despite this, many people living with HIV infection might be taking antiretroviral agents that are associated with significant drug-drug interactions. Because HIV infection itself is associated with cardiovascular complications and this population is living longer, concomitant use of antiretrovirals and medications to treat cardiovascular-related diseases is often required. For this reason, it is imperative that clinicians are aware of the potential for clinically significant drug-drug interactions between antiretroviral agents and cardiac medications as well as the useful HIV drug interaction resources that might provide guidance. Available data on significant interactions are summarized and suggested guidance regarding management is discussed.     

Effects of standardized extracts GK501, from Ginkgo biloba L., G115 from Panax ginseng C. A. Meyer,and their combination,gincosan® (PHL-00701), on the brain levels of biogenic monoamines and on the serum content of prolactin,growth hormone and ACTH

In experiments on old (26 months old) rats, we found that the extracts of Panax ginseng (G115), Ginkgo biloba (GK501) and their combination Gincosan® (PHL-00701) administered orally at two doses for 7 days induced changes in the levels of biogenic monoamines in some brain regions (frontal cerebral cortex, hippocampus, striatum, hypothalamus and pons). The most characteristic change was the increase produced by the two extracts and their combination in the serotonin level in all brain structures except for pons compared with controls. In the hippocampus G115, GK501 and their combination decreased the noradrenaline level. The same doses of G115, GK501 and their combination applied for 7 days to young (3 months old) and old (26 months old) rats caused significant changes in the blood level of prolactin (PRL), growth hormone (GH) and ACTH compared with age-matched controls: both G115 and GK501 decreased the serum level of PRL compared with age-matched controls; the hormone level being high in old controls, in extract-treated rats it became equal to that in young controls; G115 and PHL-00701 greatly increased the serum level of ACTH in both age groups compared with age-matched controls. Under conditions of induced immobilization and cold stress in young rats, the 7-day pretreatment with G115, GK501 and their combination led to significant changes in the blood levels of PRL, GH and ACTH compared with control untreated stressed and unstressed rats.     

The Effectiveness of Surgical Treatment of Acute Aortic Dissection

Ten consecutive patients have undergone operative repair of acute aortic dissection at St. Thomas Hospital in the last three years. Two died. To assess the status of the residual aorta, all 8 survivors were evaluated by postoperative aortography. Only the patient with a clotted dissection on preoperative study showed no residual dissection of the distal aorta. Analysis of postoperative aortograms suggests that the original dissection reentry points become sites of inflow following removal of the original intimal tear. No death resulted from these residual abnormalities. Retrograde dissection and aortic insufficiency were obliterated. The major sites of aortic rupture were removed. It is concluded that surgical therapy for acute aortic dissection is effective in that it avoids the major sources of mortality. The resultant surviving population must be carefully observed in view of the high frequency of residual aortic abnormality.     

Accumulation of amantadine by isolated chromaffin granules

The accumulation of amantadine and the effect of this pharmacologic amine upon the magnitude of the transmembrane proton gradient (ΔpH) and of the transmembrane potential gradient (ΔΨ) were investigated in bovine adrenal chromaffin granules isolated in isotonic sucrose. Freshly isolated chromaffin granules have an intragranular pH of 5.5, as measured by [^14C]methylamine distribution [R. G. Johnson and A. Scarpa, J. gen. Physiol.68, 601 (1976)]. The addition of amantadine (1–50 mM) to well-buffered suspensions of granules at pH 7.0 resulted in a dose-related alkalinization of the granule interior. Similar results were obtained with equivalent external concentrations of ammonia. When the time-resolved influx of labeled amines into the granules was studied radiochemically, using low external amine concentrations, the accumulation of [³H]amantadine was quite similar to that of [¹⁴C]methylamine with regard to rate and extent over a wide range of magnitudes of the transmembrane proton gradient. However, unlike biogenic amine accumulation into the chromaffin granule, which is driven by both transmembrane proton and potential gradients, the accumulation of [³H] amantadine was not stimulated by the existence of a transmembrane potential, nor was it inhibited by reserpine. Moreover, low concentrations of amantadine did not competitively inhibit biogenic amine accumulation in the isolated granules. These results indicate that amantadine can distribute across the membrane of chromaffin granules according to the magnitude of the endogenous ΔpH, and suggest that in vivo amantadine may be concentrated and stored as a pharmacologic agent in amine containing granules.