The Africanized honey bee.

The Africanized honey bee (AHB), "the bee with an attitude problem," is described as more defensive, more likely to defend its nest in large numbers, and therefore cause multiple stings compared with the European honey bee (EHB) with which we are familiar. We can expect a greater number of toxic reactions related to multiple stings in addition to the more familiar allergic (IgE-mediated) reactions. The title "Killer Bees" is largely media derived. The first identified colony arriving by natural northward migration arrived in the Lower Rio Grande Valley in October 1990. Additional colonies have been trapped, identified, and destroyed by now. Because of extensive media coverage, the facts become very important because patients and possibly media may be contacting you as specialists in stinging insect allergy. Those living in the Southern United States are most likely to be involved. State and federal government agencies as well as certain industries have recognized this situation as important with a potentially very serious impact on agricultural interest. Some of these impacts will be discussed as well as local involvement in the Lower Rio Grande Valley of the Texas AHB Management Plan and medical plans.

Accuracy of tobramycin delivery by four i.v. infusion methods.

The accuracy of tobramycin delivery by four methods of intermittent intravenous infusion was studied in 11 healthy male volunteers. Subjects received intravenous tobramycin (as the sulfate salt) 1.5 mg/kg by each of four infusion methods in a nonblinded, randomized, four-way crossover design. The methods used for intravenous infusion were (1) minibag via gravity flow (MG), (2) minibag with the secondary infusion tubing inserted below a volumetric infusion pump (MP), (3) metered chamber via volumetric infusion pump (MC), and (4) syringe pump (SP). Doses were diluted to a volume of 50 mL, except for the two minibag methods, for which the dilution was necessarily greater because of manufacturer overfill. Intravenous flow rates for both primary fluid and drug administration were set at 100 mL/hr, and the duration of drug infusion was documented by observation for each administered dose. The fluid volume of 12 minibags was measured to assess manufacturer overfill. Fluid remaining in the secondary i.v. tubing for the minibag methods was collected after the infusion. Seventeen blood samples were obtained before and at various time intervals after each dose and analyzed in duplicate for tobramycin content by fluorescence polarization immunoassay. A mean of 10% of each dose remained in the secondary i.v. tubing at the completion of the infusion for the minibag methods, whereas less than 1% of each dose remained in the secondary tubing for the SP method.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of four intravenous infusion methods on tobramycin pharmacokinetics.

The influence of four intermittent intravenous infusion methods on the determination of tobramycin pharmacokinetic values and predicted doses was evaluated in 11 healthy adult volunteers. Each subject received tobramycin (as the sulfate salt) 1.5 mg/kg by each of four i.v. infusion methods: (1) minibag via gravity flow (MG), (2) minibag with the secondary infusion tubing inserted below a volumetric pump (MP), (3) metered chamber via volumetric pump (MC), and (4) syringe pump (SP). Infusion rates were initially set to administer each dose over a 30-minute period. Sixteen blood samples were obtained over an eight-hour period before and at various time intervals after each dose and were analyzed for tobramycin content by fluorescence polarization immunoassay. Area under the serum concentration-time curve from time zero to infinity (AUC0-infinity) was calculated by the trapezoidal rule. Serum tobramycin concentration data for each subject were fitted to a biexponential decay model with zero-order input. beta and V beta were calculated from fitted data. One-compartment pharmacokinetic values, elimination rate constant (kappa), apparent volume of distribution (V), and predicted doses to achieve steady-state peak concentrations of 6 micrograms/mL were calculated by the method of Sawchuk and Zaske. There were no significant differences in either beta or kappa among the infusion methods. V beta values (mean +/- S.D.) for the methods were 0.240 +/- 0.025 (MG), 0.257 +/- 0.025 (MP), 0.221 +/- 0.027 (MC), and 0.231 +/- 0.032 (SP) L/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Iron uptake from lactoferrin and transferrin by Neisseria gonorrhoeae.

The major iron (Fe) sources available to Neisseria gonorrhoeae in the human host are probably transferrin (TF) and lactoferrin (LF). Although a number of studies have examined Fe uptake by Neisseria meningitidis, no comparable studies have been done on Fe uptake by the gonococcus from TF and LF. We found that, like meningococci, gonococci removed Fe from TF and LF in an energy-dependent manner; uptake was repressed by Fe and did not proceed by a siderophore-mediated uptake system. Unlike published studies examining meningococcal Fe uptake from TF, our study showed that gonococcal Fe uptake from both TF and LF was highly efficient; uptake saturated at 1 microM protein, and growth with 5% saturated TF and LF occurred at maximal rates when the protein was present in appreciable concentrations. We conclude that the availability of protein-bound Fe probably does not limit growth of N. gonorrhoeae in the human body.

Antigens of alternaria. I. Isolation and partial characterization of a basic peptide allergen.

A basic peptide allergen has been isolated from Alternaria extracts. Flat-bed gel preparative isoelectric focusing followed by dialysis and lyophilization allowed for concentration of substantial quantities of this heretofore unrecognized allergen. Rocket immunoelectrophoresis and autoradiography (using a 2 X concentrated, IgE serum fraction from Alternaria patient sera and 125I-anti human IgE), a RAST inhibition assay, and skin testing of Alternaria-sensitive patients were used to demonstrate the allergenicity of this fraction. The allergenicity of this protein was sufficient to give 50% RAST inhibition at a concentration of 100 micrograms/ml using standard RAST procedures. The immunoelectrophoresis autoradiography also indicated allergenicity. Skin tests indicated that over 90% of patients hypersensitive to Alternaria crude extracts were also hypersensitive to the basic allergen fraction.

Efficacy of phenylephrine-phenylpropanolamine in the treatment of rhinitis.

A double-blind placebo-controlled crossover study was done to evaluate the efficacy of an oral decongestant preparation in the treatment of rhinitis. The preparation consisted of 5 mg of phenylephrine hydrochloride, 45 mg of phenylpropanolamine hydrochloride, and 200 mg of guaifenesin (Rymed). Subjects were selected for participation in the study on the basis of history, physical examination, and immediate hypersensitivity skin testing. Fourteen of 20 subjects (P less than .05) observed a reduction in the severity of nasal symptoms while taking the drug. The mean symptom score of the 20 subjects while taking the drug was 31.344 and while taking placebo, 42.979. This is a statistically significant difference (P = .009717). Side effects were minimal. We concluded that the oral decongestant preparation used in this study is effective in controlling symptoms of rhinitis.

Common mechanism for the adaptive increase in hepatic ethanol and acetaldehyde metabolism due to chronic pretreatment with ethanol.

Perfused livers from ethanol pretreated rats utilized ethanol and acetaldehyde at higher rates than appropriate controls. This adaptive increase in hepatic ethanol and acetaldehyde uptake was associated with a marked (greater than 60%) increase in hepatic oxygen uptake. Ethanol uptake in both ethanol-treated and control livers was similarly sensitive to inhibition by 4-methylpyrazole, rotenone, and antimycin A. The adaptive increase in ethanol uptake was apparently specifically abolished by ouabain, an inhibitor of the sodium-plus potassium-activated ATPase. The data are consistent with the hypothesis that chronic treatment with ethanol increases ATPase activity. The ADP produced from these initiating events enters the mitochondrial space and stimulates electron transport and oxygen uptake. As a consequence of these events, a greater rate of NADH reoxidation occurs, resulting in a greater rate of production of NAD+ which stimulates ethanol oxidation via alcohol dehydrogenase and acetaldehyde oxidation via aldehyde dehydrogenase(s).

Significant pathways of hepatic ethanol metabolism.

Rat liver microsomes oxidized ethanol two to three times faster than propanol when incubated with either an NADPH- or an H2O2-generating system. In addition, solubilized, purified microsomal subfractions were found to contain protein with an electrophoretic mobility identical to rat liver catalase on SDS polyacrylamide gels, suggesting that the separation of catalase from cytochrome P-450 and other microsomal components may not be feasible. These data support the postulate that catalase is responsible for NADPH-dependent microsomal ethanol oxidation. Direct read-out techniques for pyridine nucleotides, the catalase-H2O2 complex, and cytochrome P-450 were utilized to evaluate the specificity of inhibitors of alcohol dehydrogenase (4-methylpyrazole; 4 mM) and catalase (aminotriazole; 1.0 g/kg) qualitatively in perfused rat livers. 4-Methylpyrazole and aminotriazole are specific inhibitors for alcohol dehydrogenase and catalase, respectively, under these conditions. Neither inhibitor nor a combination of them altered the mixed function oxygen of p-nitroanisole to p-nitrophenol as observed by oxygen uptake and product formation. When ethanol utilization was measured over the concentration range 20-80 mM in perfused liver, a concentration dependence was observed. At low concentrations of ethanol, ethanol oxidation was almost totally abolished by 4-methylpyrazole; however, the contribution of 4-methylpyrazole-insensitive ethanol uptake increased as a function of ethanol concentration. At 80 mM ethanol, ethanol utilization was nearly 50% methylpyrazole-insensitive. This portion of ethanol oxidation, however, was abolished by aminotriazole. The data indicate that alcohol dehydrogenase and catalase-H2O2 are responsible for hepatic ethanol oxidation. At low ethanol concentrations (less than 20 mM), alcohol dehydrogenase is predominant; however, at higher ethanol concentrations (up to 80 mM), the contribution of catalase-H2O2 to overall ethanol utilization is significant. No evidence that the endoplasmic reticulum is involved in ethanol metabolism in the perfused liver emerged from these studies.

Pathways of ethanol metabolism in perfused rat liver.

The primary pathway of hepatic ethanol metabolism involves alcohol dehydrogenase. Hydrogen generated from ethanol metabolism enters the mitochondrial space most likely as malate over a substrate shuttle mechanism, and is subsequently oxidized by the mitochondrial respiratory chain. The rate-limiting step in this overall multicompartmental process is the rate of reduced cofactor (NADH) reoxidation by the respiratory chain. Since the electron flux in the respiratory chain is controlled by the ADP supply, alcohol dehydrogenase-dependent ethanol metabolism can be activated by perturbations which circumvent the rate-limiting step, such as artificial electron acceptors, gluconeogenic precursors, and uncoupling agents. Moreover, an ATP utilizing process is responsible for the stimulation of ethanol metabilism observed following chronic pretreatment with ethanol. In perfused rat liver catalase also participates in ethanol metabolism to a lesser extent than alcohol dehydrogenase. Quantitative assessments indicate that the predominant ethanol oxidase at low ethanol concentrations (less than 20 mM) is a alcohol dehydrogenase; however, at higher ethanol concentrations, a significant portion of total ethanol metabolism (up to 50%) is mediated by catalase-hydrogen peroxide complex. This pathway is limited by the rate of generation of hydrogen peroxide in the hepatocyte, and can be stimulated with substrates for intraperoxisomal hydrogen peroxide generation such as glycolate, urate and D-amino acids. Considerable evidence implicates catalase-hydrogen peroxide complex in the mechanism of NADPH-dependent microsomal ethanol oxidation.