mRNA vaccines were highly effective in response to the COVID-19 pandemic, making them an attractive platform to address cancers and other infectious diseases. Many new mRNA vaccines in development are multivalent, which represents a difficulty for the standard assays commonly used to characterize the critical quality attributes of monovalent formulations. Here, we present a multiplexed analytical tool with nucleic acid microarray technology using the VaxArray platform that measures the identity and quantity of mono- and multivalent mixtures of naked mRNA and mRNA encapsulated in lipid nanoparticle formulations in under 2 h without any additional preparation steps, such as extraction or RT-PCR.
View Article and Find Full Text PDFThe COVID-19 pandemic highlighted mRNA as a promising platform for vaccines and therapeutics. Many of the analytical tools used to characterize the critical quality attributes of mRNA are inherently singleplex and are not necessarily optimal from a labor and cost perspective. Here, we demonstrate the feasibility of a multiplexed platform (VaxArray) for efficient identity verification and concentration determination for both monovalent and multivalent mRNA formulations.
View Article and Find Full Text PDFIn general, persistence of the left superior vena cava (LSVC), the most common anomaly of the venous circulation, is asymptomatic. Diagnosis of a catheter in a persistent LSVC is not straight forward, and a LSVC can create difficulties during central venous and pulmonary artery catheterization. We discuss the differential diagnosis of left-sided central venous catheters (CVC).
View Article and Find Full Text PDFHodgkin's disease (HD) is not currently included within the Centers for Disease Control (CDC) classification system for AIDS. Upon HD diagnosis, HIV(human immunosuppressive virus)-positive patients are generally found within Stages III or IV of the Ann Arbor HD classification system, already exacerbating the problem of treatment. In contrast, HIV-negative patients diagnosed with HD are generally found within Stages I or II.
View Article and Find Full Text PDFBiochem Biophys Res Commun
August 1992
Recent studies indicate that galactoside-binding proteins may bind the poly-N-acetyllactosamine sequences of laminin. We questioned whether human galactoside-binding protein (hL-31) binds to laminin and whether cells that express hL-31 on their surface use it as a laminin receptor to promote cellular attachment. The data show that both lectin and cells bind to immobilized laminin.
View Article and Find Full Text PDFPediatric Acquired Immunodeficiency Syndrome (AIDS) is expected to increase by greater than 75% by 1993. Most of these infants will become infected with the Human Immunodeficiency Virus (HIV) through the mother. It is unclear exactly how the virus is passed from mother to child.
View Article and Find Full Text PDF[Sar1,Phe(Br5)8] angiotensin II (Br5Ang II) is a specific, quasi-irreversible antagonist of angiotensin II (Ang II) in vitro. In vivo, this compound is a very potent, Ang II-specific antagonist with a very long duration of action against Ang II-induced blood pressure (BP) increases. In the "low-sodium" dog, this compound induces a prolonged BP reduction during and after intravenous infusion at doses comparable to cilazapril, a potent ACE inhibitor.
View Article and Find Full Text PDFArzneimittelforschung
September 1987
The cardiovascular effects of N-(3,4-dimethoxyphenethyl)-2-(3,4-dimethoxyphenyl-N-methyl-m-dithiane-2- propylamine-1,1,3,3-tetraoxide HCl (tiapamil, Ro 11-1781, Larocord), a new calcium entry blocker, were investigated in chronically-instrumented conscious dogs and compared with those of verapamil and nifedipine. Oral administration of tiapamil to normotensive dogs dilated preferentially the arterial vascular bed as evidenced by marked increases in the coronary and abdominal aortic blood flow in the absence of a depression of the myocardial contractile force. The vasodilator effects induced a reflex increase in heart rate and cardiac output, which prevented a decrease in blood pressure in normotensive, but not in renal hypertensive dogs.
View Article and Find Full Text PDFJ Cardiovasc Pharmacol
July 1986
Chronic daily administration of cilazapril (1 X 10 mg/kg/day p.o., from age 4 to 14 weeks) to young spontaneously hypertensive rats (SHR) prevented the development of hypertension.
View Article and Find Full Text PDFCilazapril is a new angiotensin-converting-enzyme inhibitor. In conscious renal-hypertensive dogs, cilazapril (2 X 10 mg/kg/day p.o.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
July 1985
Stimulation of the sympathetic outflow (spinal cord segments T 7-9) in pithed rats resulted in an increase in mean arterial pressure, heart rate, total peripheral vascular resistance and cardiac output. The increase in blood pressure and peripheral resistance was markedly depressed by prazosin and to a lesser extent by yohimbine, suggesting that these responses were mediated primarily by postjunctional alpha 1-adrenoceptors. The calcium entry blockers nifedipine, tiapamil and verapamil also depressed pressor responses and the increase in total peripheral resistance to electrical stimulation of the sympathetic outflow in these rats.
View Article and Find Full Text PDFDaily oral administration of tiapamil (2 X 50-2 X 150 mg/kg, for 13 weeks) to spontaneously hypertensive rats (SHR) resulted in a dose-dependent inhibition of hypertension development, with complete prevention occurring at the highest dose. Tiapamil (2 X 100 mg/kg/day, p.o.
View Article and Find Full Text PDFJ Cardiovasc Pharmacol
July 1984
The cardiovascular properties of Ro 13-6438 (R-6-chloro-1,5-dihydro-3- methylimidazo -[2,1-b] quinazolin -2[ 3H]-one), a novel nonglycoside , noncatechol cardiotonic agent, were investigated in vitro and in vivo by both intravenous and oral administration. Ro 13-6438 increased tension development of isolated guinea pig left atria in a concentration-dependent manner with an EC50 of 30 microM, but had no stimulant effect on the spontaneous rate of right atria. The positive inotropic effect of Ro 13-6438 was additive to that of ouabain (0.
View Article and Find Full Text PDFThe effects of bufuralol and its carbinol metabolite have been compared with those of propranolol in the anaesthetised and conscious cat and dog. Bufuralol and its carbinol metabolite are nonselective beta-adrenoceptor antagonists; the former has equivalent potency to propranolol, whereas the latter is six times more potent. In anaesthetised animals both bufuralol and its metabolite exhibited partial agonistic activity, resulting in tachycardia and vasodilation.
View Article and Find Full Text PDFIn pithed rats increases in blood pressure were induced by i.v. injections of the alpha 1-agonist methoxamine and the alpha 2-agonists clonidine, oxymetazoline and B-HT 920.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
December 1982
The inhibitor of phenylethanolamine-N-methyl transferase (PNMT), SK&F 64139 (7, 8-dichloro-1, 2, 3, 4-tetrahydroisoquinoline), when given i.v. (5 mg/kg), did not prevent the decrease of blood pressure induced in conscious spontaneously hypertensive rats (SHR) by alpha-methyldopa (50 mg/kg i.
View Article and Find Full Text PDFJ Cardiovasc Pharmacol
August 1982
We studied the hemodynamic effects of the new calcium antagonist tiapamil (Ro 11-1781) in anesthetized open-chest dogs and compared them with those of verapamil. Increasing doses of tiapamil injected intravenously caused the following hemodynamic effects: increase in coronary flow and decrease in coronary vascular resistance, followed by decreases in heart rate, blood pressure, and total peripheral resistance. Tiapamil did not depress myocardial contractility over a rather wide dose range, while verapamil did.
View Article and Find Full Text PDFJ Pharmacol Exp Ther
March 1981
Ro 12-4713, an oxadiazolopyrimidine derivative, lowered blood pressure of conscious spontaneously hypertensive rats and renal hypertensive dogs in a dose-dependent manner from 10 to 100 mg/kg p.o. The antihypertensive effect was slow in onset, had a long duration of action and was not subject to the development of tachyphylaxis.
View Article and Find Full Text PDFBiotelem Patient Monit
January 1982
A fully implantable telemetric system for the measurement of cardiac left ventricular pressure and derived parameters in conscious dogs is presented. It provides the following advantages: ethical acceptability, scientific relevance, economical experimentation, avoidance of stress-induced situations for the animal, experiments without anaesthesia or sedation. The system has an operation time which allows the sequential pharmacological evaluation of a great number of drugs in individual dogs as has been shown by testing the effect of the positive inotropic agent, dobutamine, and the calcium antagonists, verapamil and nifedipine.
View Article and Find Full Text PDF8-Chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a][1,4]benzodiazepine (midazolam, Ro 21-3981, Dormicum) is an imidazobenzodiazepine whose salts are soluble and stable in aqueous solution. It has a quick onset and, due to rapid metabolic inactivation, a rather short duration of action in all species studied. Midazolam has a similar pharmacologic potency and broad therapeutic range as diazepam.
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