Clinical evaluation of indoramin as the sole agent for the treatment of hypertension

An open-ended clinical trial of Indoramin (WY-21901), a new antihypertensive agent with both a-adrenergic blocking and cardio-inhibitory properties, was conducted on a group of 27 patients with mild or moderate essential hypertension. Blood pressures, erect and supine, were effectively lowered. In 70% of the patients the mean standing diastolic pressures were well controlled. Heart rate was not significantly lowe.red. Side-effects occurred in 80% of patients, but did not persist in most of them. Severe side-effects, necessitating withdrawal of Indoramin, were experienced by one-third of the patients. Proteinuria was observed in 3 patients and a slightly elevated serum urea in 1. No other biochemical tests were abnormal.S. Afr. Med. J., 48, 1569 (1974

Blood Pressure in Relation to Concentrations of PCB Congeners and Chlorinated Pesticides

BackgroundResidents of Anniston, Alabama, live near a Monsanto plant that manufactured polychlorinated biphenyls (PCBs) from 1929 to 1971 and are relatively heavily exposed.ObjectivesThe goal of this study was to determine the relationship, if any, between blood pressure and levels of total serum PCBs, several PCB groups with common actions or structure, 35 individual PCB congeners, and nine chlorinated pesticides.MethodsLinear regression analysis was used to determine the relationships between blood pressure and serum levels of the various contaminants after adjustment for age, body mass index, sex, race, smoking, and exercise in 394 Anniston residents who were not taking antihypertensive medication.ResultsOther than age, total serum PCB concentration was the strongest determinant of blood pressure of the covariates studied. We found the strongest associations for those PCB congeners that had multiple ortho chlorines. We found the associations over the full range of blood pressure as well as in those subjects whose blood pressure was in the normal range. The chlorinated pesticides showed no consistent relationship to blood pressure.ConclusionsIn this cross-sectional study, serum concentrations of PCBs, especially those congeners with multiple ortho chlorines, were strongly associated with both systolic and diastolic blood pressure

Nuclear Polarizabilities and Logarithmic Sum Rules

The electric polarizability and logarithmic mean-excitation energy are calculated for the deuteron using techniques introduced in atomic physics. These results are then used to improve limits on the atomic-deuterium frequency shift due to nuclear polarization in the unretarded dipole limit, as well as confirming previous results.Comment: 7 pages, latex -- To appear in Phys. Rev. C -

Managed trade: The US–Mexico sugar suspension agreements

Under the 1994 North American Free Trade Agreement, Mexican sugar producers were ultimately granted free access to the US sugar market, while all other suppliers, including US refiners, were subject to supply quotas. Following a surge in imports of Mexican sugar, the American Sugar Coalition initiated anti‐dumping and countervailing duty (ADCVD) proceedings against Mexico in early 2014. In December 2014, the ADCVD cases were halted as a result of two suspension agreements negotiated between the US and Mexico. This paper contributes to a small number of empirical studies that have estimated the impact of suspension agreements. We measure the impacts of the ADCVD filings and the suspension agreements on US domestic raw and refined prices, the raw‐to‐refined margin and the quantity and composition of sugar imports from Mexico. Results suggest US raw sugar prices increased by 3¢ per lb. (14%) under ADCVD proceedings, equivalent to an ad valorem tariff between 40% and 50%, while the suspension agreements increased US raw sugar prices by 5¢ (70% tariff equivalent). US refined sugar prices increased by similar amounts under the ADCVD proceedings and the suspension agreements (4.5¢ per lb.). Ultimately, both the ADCVD proceedings and the suspension agreements significantly reduced sugar imports from Mexico. US sugar refiner economic welfare hinges critically on the quantity and composition of raw sugar imports. As such, refiner revenue, following the ADCVD filings and suspension agreements, is estimated to have declined by 16%, relative to a free trade environment

Higher-Order Nuclear-Polarizability Corrections in Atomic Hydrogen

Nuclear-polarizability corrections that go beyond unretarded-dipole approximation are calculated analytically for hydrogenic (atomic) S-states. These retardation corrections are evaluated numerically for deuterium and contribute -0.68 kHz, for a total polarization correction of 18.58(7) kHz. Our results are in agreement with one previous numerical calculation, and the retardation corrections completely account for the difference between two previous calculations. The uncertainty in the deuterium polarizability correction is substantially reduced. At the level of 0.01 kHz for deuterium, only three primary nuclear observables contribute: the electric polarizability, $\alpha_E$, the paramagnetic susceptibility, $\beta_M$, and the third Zemach moment, $_{(2)}$. Cartesian multipole decomposition of the virtual Compton amplitude and its concomitant gauge sum rules are used in the analysis.Comment: 26 pages, latex, 1 figure -- Submitted to Phys. Rev. C -- epsfig.sty require

Lancet commission on hypertension group position statement on the global improvement of accuracy standards for devices that measure blood pressure

The Lancet Commission on Hypertension identified that a key action to address the worldwide burden of high blood pressure (BP) was to improve the quality of BP measurements by using BP devices that have been validated for accuracy. Currently, there are over 3000 commercially available BP devices, but many do not have published data on accuracy testing according to established scientific standards. This problem is enabled through weak or absent regulations that allow clearance of devices for commercial use without formal validation. In addition, new BP technologies have emerged (e.g. cuffless sensors) for which there is no scientific consensus regarding BP measurement accuracy standards. Altogether, these issues contribute to the widespread availability of clinic and home BP devices with limited or uncertain accuracy, leading to inappropriate hypertension diagnosis, management and drug treatment on a global scale. The most significant problems relating to the accuracy of BP devices can be resolved by the regulatory requirement for mandatory independent validation of BP devices according to the universally-accepted International Organisation for Standardization Standard. This is a primary recommendation for which there is an urgent international need. Other key recommendations are development of validation standards specifically for new BP technologies and online lists of accurate devices that are accessible to consumers and health professionals. Recommendations are aligned with WHO policies on medical devices and universal healthcare. Adherence to recommendations would increase the global availability of accurate BP devices and result in better diagnosis and treatment of hypertension, thus decreasing the worldwide burden from high BP

The Optimal Design of Trade Policy Flexibility in the WTO

This paper is a contribution to the literature on rational design of trade agreements. The World Trade Organization (WTO) is an incomplete contract among sovereign states. Incomplete contracts contain gaps. Ex post, contractual gaps may leave gains from trade unrealized; they may create 'regret' in signatories once unanticipated contingencies or sudden protectionist backlashes have occurred. Trade policy flexibility mechanisms, such as the 'safeguards clause' under Art. XIX GATT, are geared towards seizing ex post regret by allowing parties affected by a protectionist shock to partially and temporarily withdraw from previously made trade liberalization concessions - given that they compensate the victim(s) of such backtracking behavior. This paper examines the somewhat understudied issue of optimal trade policy flexibility design in the WTO: In particular, we analyze whether ex post escape should be organized by means of a unilateral opt-out clause (a 'liability rule' of escape), or a bilateral renegotiation provision (a 'property rule' of escape). Modeling the WTO as a fully non-contingent tariff liberalization contract with contingencies (or 'states of nature') asymmetrically revealed, we find that a liability rule backed by expectation remedies payable to the affected victim Pareto-dominates both a renegotiation clause, as well as any other remedy arrangement connected to a liability rule. Only the remedial design of liability-cum-expectation damages yields the desirable incentives to liberalize ex ante, and to default ex post and therewith is able to replicate the outcomes of the hypothetical contracting ideal of the complete contingent contract

Windei, the Drosophila Homolog of mAM/MCAF1, Is an Essential Cofactor of the H3K9 Methyl Transferase dSETDB1/Eggless in Germ Line Development

The epigenetic regulation of gene expression by the covalent modification of histones is a fundamental mechanism required for the proper differentiation of germ line cells during development. Trimethylation of histone 3 lysine 9 (H3K9me3) leads to chromatin silencing and the formation of heterochromatin by recruitment of heterochromatin protein 1 (HP1). dSETDB1/Eggless (Egg), the ortholog of the human methyltransferase SETDB1, is the only essential H3K9 methyltransferase in Drosophila and is required for H3K9 trimethylation in the female germ line. Here we show that Windei (Wde), the Drosophila homolog of mouse mAM and human MCAF1, is an essential cofactor of Egg required for its nuclear localization and function in female germ line cells. By deletion analysis combined with coimmunoprecipitation, we have identified the protein regions in Wde and Egg that are necessary and sufficient for the interaction between the two proteins. We furthermore identified a region of Egg that gets covalently modified by SUMOylation, which may facilitate the formation of higher order chromatin-modifying complexes. Together with Egg, Wde localizes to euchromatin, is enriched on chromosome 4, and binds to the Painting of fourth (POF) protein. Our data provide the first genetic and phenotypic analysis of a mAM/MCAF1 homolog in a model organism and demonstrate its essential function in the survival of germ line cells

E2F1 Mediated Apoptosis Induced by the DNA Damage Response Is Blocked by EBV Nuclear Antigen 3C in Lymphoblastoid Cells

EBV latent antigen EBNA3C is indispensible for in vitro B-cell immortalization resulting in continuously proliferating lymphoblastoid cell lines (LCLs). EBNA3C was previously shown to target pRb for ubiquitin-proteasome mediated degradation, which facilitates G1 to S transition controlled by the major transcriptional activator E2F1. E2F1 also plays a pivotal role in regulating DNA damage induced apoptosis through both p53-dependent and -independent pathways. In this study, we demonstrate that in response to DNA damage LCLs knocked down for EBNA3C undergo a drastic induction of apoptosis, as a possible consequence of both p53- and E2F1-mediated activities. Importantly, EBNA3C was previously shown to suppress p53-induced apoptosis. Now, we also show that EBNA3C efficiently blocks E2F1-mediated apoptosis, as well as its anti-proliferative effects in a p53-independent manner, in response to DNA damage. The N- and C-terminal domains of EBNA3C form a stable pRb independent complex with the N-terminal DNA-binding region of E2F1 responsible for inducing apoptosis. Mechanistically, we show that EBNA3C represses E2F1 transcriptional activity via blocking its DNA-binding activity at the responsive promoters of p73 and Apaf-1 apoptosis induced genes, and also facilitates E2F1 degradation in an ubiquitin-proteasome dependent fashion. Moreover, in response to DNA damage, E2F1 knockdown LCLs exhibited a significant reduction in apoptosis with higher cell-viability. In the presence of normal mitogenic stimuli the growth rate of LCLs knockdown for E2F1 was markedly impaired; indicating that E2F1 plays a dual role in EBV positive cells and that active engagement of the EBNA3C-E2F1 complex is crucial for inhibition of DNA damage induced E2F1-mediated apoptosis. This study offers novel insights into our current understanding of EBV biology and enhances the potential for development of effective therapies against EBV associated B-cell lymphomas