Demonstration of in vivo bioequivalence of a generic albuterol metered-dose inhaler to Ventolin.

Study Objective: To use histamine bronchoprovocation and bioassay statistical procedures to evaluate the in vivo bioequivalence of a generic albuterol metered-dose inhaler (MDI).

Design: A randomized, double-blind, balanced, crossover design was used to determine the potency of each generic albuterol MDI actuation relative to Ventolin (Glaxo Wellcome; Research Triangle Park, NC) administration. One treatment was administered on each of 4 study days.

Efficacy of acrivastine plus pseudoephedrine for symptomatic relief of seasonal allergic rhinitis due to mountain cedar.

Background: Acrivastine is a second-generation H1-antagonist chemically related to triprolidine, but more polar and with less central nervous system penetration than triprolidine.

Objective: The efficacy of the antihistamine-decongestant combination product (Semprex-D capsules) containing acrivastine 8 mg plus pseudoephedrine HCl 60 mg was evaluated for the treatment of seasonal allergic rhinitis symptoms.

Methods: A total of 676 patients sensitive to mountain cedar pollen was enrolled into a 6-center, randomized, double-blind, placebo-controlled, parallel, 4-group study designed to compare acrivastine + pseudoephedrine, acrivastine, pseudoephedrine, and placebo.

Polymerase chain reaction for diagnosis of enterohemorrhagic Escherichia coli infection and hemolytic-uremic syndrome.

Two pairs of oligonucleotide primers were designed to amplify fragments of the genes for Shiga-like toxin I (SLT-I) and SLT-II in a single reaction. A 370-bp segment and a 283-bp segment were amplified for SLT-I and SLT-II, respectively. The specificities of the polymerase chain reaction (PCR) amplification products were confirmed by using radioactively labeled oligonucleotide probes.

Intrahospital spread of a single gentamicin-resistant, beta-lactamase-producing strain of Enterococcus faecalis in Argentina.

Six beta-lactamase-producing (Bla+) isolates of Enterococcus faecalis recovered over a 17-month period from an Argentinian pediatric hospital were found to have identical or almost identical chromosomal restriction patterns by pulsed-field gel electrophoresis, although the plasmid patterns were different. These isolates, like Bla+ enterococci in the United States, hybridized to a staphylococcal Bla gene probe. The presence of a single strain was somewhat surprising, since all isolates transferred Bla by conjugation.

Lack of homology of enterococci which have high-level resistance to trimethoprim with the dfrA gene of Staphylococcus aureus.

Multiresistant enterococci were tested for susceptibility to trimethoprim (TMP). Although most enterococci are inhibited by less than or equal to 1.0 microgram/ml, the MICs for 7 of 29 selected multiresistant isolates were greater than or equal to 8 micrograms/ml, including for two beta-lactamase positive (Bla+) strains, for which the MICs of TMP were greater than 1,000 micrograms/ml, and for another Bla+ strain, for which the MIC was 128 micrograms/ml.

Pharmacokinetics of oral and transdermal triprolidine.

In this open, nonrandomized, three-way crossover study, six healthy male volunteers received single doses of triprolidine (TPL) hydrochloride syrup orally (2.5 mg) and wore transdermal TPL patches (5 mg and 10 mg doses) to compare the pharmacokinetic profiles and dose tolerance of the two formulations. A washout period of at least 1 week was scheduled between the three dosing periods.

Pharmacokinetics of acrivastine after oral and colonic administration.

Six healthy male volunteers participated in this randomized, crossover open-label pharmacokinetic study consisting of two dosing segments separated by a washout period of at least 5 days. During each dosing segment, each volunteer received 12 mg of acrivastine, an investigational histamine H1-receptor antagonist, in a syrup form either orally or by colonic administration in random order. After oral and colonic administration, respectively, the following mean +/- SD pharmacokinetic parameters were obtained: Cmax 179 +/- 11 and 13.

Pulmonary alterations in rats due to acute phosgene inhalation.

This study evaluated the relationship between low-level phosgene (COCl2) exposure and pulmonary change or damage. Male Sprague-Dawley rats were exposed to phosgene for 4 hr at concentrations of 0.125 to 1.

Changes in lung ATP concentration in the rat after low-level phosgene exposure.

Inhibition of mitochondrial respiratory activity and decreased lung adenosine triphosphate (ATP) concentration occur following exposure to 240 ppm.min phosgene. To determine the relationship between energy stores and the onset of phosgene-induced pulmonary edema, we measured the ATP concentration in rapidly frozen rat lung tissue before and during pulmonary edema.

A comparison of the acute hemodynamic effects of prostacyclin and hydralazine in primary pulmonary hypertension.

In patients with primary pulmonary hypertension the administration of a vasodilating drug is often used to test pulmonary vasoreactivity. Hydralazine has been employed as a test drug, but because of its long duration of action there is a risk of sustained systemic arterial hypotension in patients with a fixed pulmonary vascular resistance. In this study we compared the acute hemodynamic effects of intravenous prostacyclin, a potent, short-acting vasodilator, with the effects of oral or intravenous hydralazine.

Response of the pulmonary surfactant system to phosgene.

Rats were exposed to 240 ppm X min phosgene (1.0 ppm for 4 hrs) in a Rochester-type chamber. At intervals thereafter over a 4 day period, lungs were removed for determination of wet weight; total, microsomal and surfactant protein concentrations; surfactant phospholipid concentrations; and 1-acyl-2-lyso-phosphatidylcholine: palmitoyl-CoA acyl transferase activity.

Prophylactic and antidotal effects of hexamethylenetetramine against phosgene poisoning in rabbits.

New Zealand white rabbits were exposed to phosgene doses, expressed as Ct factors, of 125-3120 ppm X min. Hexamethylenetetramine (HMT), 0.3 gm/kg as a 40% aqueous solution, was injected via an ear vein into separate groups of animals at 5-10 min pre-exposure or at 15 min post-exposure to the gas.

Response of pulmonary energy metabolism to phosgene.

Rats were exposed to phosgene at a concentration of 1.0 ppm for 4 hours in a Rochester-type chamber. At intervals thereafter over a 4 day period, lungs were obtained for histological and biochemical assessments.

Relation of arachidonate metabolites to abnormal control of the pulmonary circulation in a child.

To evaluate the role of arachidonate metabolites in regulating pulmonary vascular tone, we performed multiple studies on a 17-month-old girl with idiopathic pulmonary hypertension, systemic arterial hypoxemia (due to ventilation-perfusion mismatching), and an elevated thromboxane A2 (TXA2) to prostacyclin (PGI2) ratio due to increased TXA2 (measured as their stable metabolites, TXB2 and 6-keto-PGF1 alpha, respectively). Intravenous infusions of PGI2 reduced mean pulmonary arterial pressure (from 80 to 47 mmHg), increased cardiac output (from 3.43 to 3.

Comparison of pseudoephedrine and triprolidine, alone and in combination in preventing nasal congestion in subjects with allergic rhinitis using nasal histamine challenge.

The abilities of triprolidine 2.5 mg and pseudoephedrine 60 mg, alone and in combination, to protect against an increase in nasal airway resistance (NAR) after histamine challenge were determined in eighteen individuals with grass pollen allergy. The study was conducted outside the pollen season using a double-blind, placebo controlled crossover design.

The role of acyl transferase in the biosynthesis of pulmonary microsomal phosphatidylglycerol.

Dog lung microsome contain an enzymatic system capable of catalyzing the transfer of radiolabel from [14C]-acyl CoA, palmitoyl or oleoyl, to 1-acyl-2-lysophosphatidylglycerol thereby forming phosphatidylglycerol. This synthetic activity is consistent with a 1-acyl-2-lyso-phosphatidylglycerol:acyl-CoA acyl transferase. Kinetic analysis suggests the enzyme is preferentially, but not exclusively, orientated to the production of 1-acyl-2-oleoyl-phosphatidylglycerol.

Prostacyclin-induced acute pulmonary vasodilation in primary pulmonary hypertension.

To evaluate the effects of prostacyclin (prostaglandin I2) on pulmonary vascular tone in primary pulmonary hypertension (PPH), we performed right-heart catheterization on seven patients with PPH and made hemodynamic measurements before and after infusing incremental doses of prostacyclin. In maximal doses of 2-12 mg/kg/min (mean 5.7 +/0 3.

1-Acyl-2-lysophosphatidylcholine: phosphatidylglycerol-2-acyltransacylase in lung microsomes and type II pneumocyte-derived cultures.

The formation of [3H]phosphatidylcholine from 1-acyl-2-lysophosphatidylcholine and 1-acyl-2-[9,10-3H]palmitoylphosphatidylglycerol, presumably by 1-acyl-2-lysophosphatidylcholine : phosphatidylglycerol-2-acyltransacylase (phosphatidylglycerol transacylase), was detected in lung microsomes and Set 4 type II pneumocyte-derived cultured cells but not in A549 adenocarcinoma-derived type II cell analogs. There was greater phosphatidylglycerol transacylase activity in Set 4 cells at confluence than at the mid-log stage. Since the phosphatidylglycerol transacylase activity was always markedly less than that observed for 1-acyl-2-lysophosphatidylcholine : acyl-CoA acyltransferase, the former does not appear to represent a major pathway for synthesis of pulmonary dipalmitoylphosphatidylcholine.

Surface-active material in human amniotic fluid.

Surface-active fractions similar to the biochemical constituents of the pulmonary surfactant system can be isolated from human amniotic fluid and lung tissue from week 10 of gestation through term. Amniotic fluid yielded 10 mg. per 100 ml.

Effect of phosgene on rat lungs after single high-level exposure.

Rats were exposed under static conditions to phosgene at concentrations within the LCt50 range and above. Lungs were removed at various postexposure intervals. Degrees of pulmonary edema were estimated by increases in percentage of water in the lungs of exposed groups as opposed to control animals.

Culture characteristics of cells derived from type II pneumocyte enriched fractions from rabbit and rat.

Type II cell enriched fractions were isolated from rabbit and rat lungs using density gradient centrifugation. Cultures established from these fractions contained predominantly cells similar in most morphological respects to type II pneumocytes. These were in continuous replicating culture for 1 year and still exhibited contact inhibition.