Role of alpha adrenoceptor activation in modulating the murine primary antibody response in vitro

The present study shows that positive and negative modulation of the immunoglobulin M antibody response in mouse spleen cells immunized with sheep erythrocytes can be achieved by selective activation of alpha adrenoceptor subtypes. Alpha-1 adrenoceptor activation by methoxamine produced a number of spleen cells secreting immunoglobulin M antibody which was enhanced 63% above control on day 4 after immunization and which returned to control levels on days 5 (peak day of control antibody response), 6 and 7. This response mimicked the previously reported response produced by norepinephrine in the presence of propranolol, but not by norepinephrine alone. Alpha-2 adrenoceptor activation by clonidine produced no change when compared to control on days 4, 6 or 7, but produced a 50% suppression on day 5. Activation of both adrenoceptor subtypes by phenylephrine produced a control response on day 4, a depressed response on day 5 and an elevated response on days 6 and 7 by 50 and 64% above control, respectively. All drug responses were concentration-dependent and the methoxamine and clonidine responses were antagonized by phentolamine. These results suggest that antibody responses can be modulated by alpha-1 adrenoceptor activation to produce an enhanced response 1 day sooner than the peak control response and by alpha-2 adrenoceptor activation to produce a depressed response at the time of the peak control response.     

Incomplete Relaxation between Beats after Myocardial Hypoxia and Ischemia

Recovery from hypoxia has been shown to prolong cardiac muscle contraction, particularly the relaxation phase. The present studies were designed to examine whether incomplete relaxation between beats can result from this prolongation of contraction and relaxation in isolated muscle after hypoxia and in the canine heart after both hypoxia and acute ischemia. The relationship between heart rate and the extent of incomplete relaxation is emphasized in view of the known enhancement of the velocity of contraction caused by increasing heart rate.The extent of incomplete relaxation during 10-s periods of pacing at increasing rates was examined before and after hypoxia in isometric cat right ventricular papillary muscle (12-120 beats/min) and in the canine isovolumic left ventricle (120-180 beats/min). Incomplete relaxation was quantified by measuring the difference between the lowest diastolic tension or pressure during pacing and the true resting tension or pressure determined by interruption of pacing at each rate. In eight cat papillary muscles (29 degrees C), there was significantly greater incomplete relaxation 5 min after hypoxia at rates of 96 and 120 beats/min (P < 0.02 vs. before hypoxia). In seven canine isovolumic left ventricles, recovery from hypoxia and higher heart rates also resulted in incomplete relaxation. Incomplete relaxation before hypoxia at a rate of 180 beats/min was 0.8+/-0.5 cm H(2)O and at 5 min of recovery from hypoxia was 12.6+/-3.5 cm H(2)O (P < 0.01). 12 hearts were subjected to a 1.5-3-min period of acute ischemia and fibrillation. There was significant incomplete relaxation at a rate of 140 beats/min for 5 min after defibrillation and reperfusion.These data indicate that incomplete relaxation is an important determinant of diastolic hemodynamics during recovery from ischemia or hypoxia. The extent of incomplete relaxation appears to be a function of the rate of normalization of the velocity of relaxation and tension development after ischemia or hypoxia, the heart rate, and the magnitude of developed tension or pressure.     

In Vitro Studies with Cefaclor, a New Oral Cephalosporin

In vitro studies were performed to evaluate the activity of cefaclor in comparison with cephalexin against 180 clinical isolates. Broth dilution susceptibility tests showed cefaclor to be 4- to 16-fold more active than cephalexin against Streptococcus pneumoniae, Haemophilus influenzae, and cephalothin-susceptible Enterobacteriaceae. Neither drug was highly active against cephalothin-resistant Enterobacteriaceae or methicillin-resistant Staphylococcus aureus. Cefaclor zones with 30-μg disks were generally larger than cephalexin zones, 4 mm larger than cephalothin zones against Enterobacteriaceae, and 6 mm smaller than cephalothin zones against S. aureus. Quantitative kill curves indicated that killing by both cefaclor and cephalexin was slow and often incomplete over a 24-h period. Cefaclor-induced filamentation of gram-negative bacilli was not as extensive as that produced by cephalexin, and some spherule formation did occur. However, cefaclor was significantly more unstable in solution than cephalexin, with a half-life of less than 6 h at 37°C. Thus, results obtained in tests after prolonged incubation may not provide an accurate measure of cefaclor's activity.     

Development of test panel of beta-lactamases expressed in a common Escherichia coli host background for evaluation of new beta-lactam antibiotics.

A test panel of 35 different beta-lactamases expressed in a common Escherichia coli host was created to compare the effect that each beta-lactamase had on susceptibility to various beta-lactam antibiotics. A comparison of the MICs obtained with this panel generally reflected differences in the substrate profiles of the various beta-lactamases examined. In addition, several strains of the panel were subjected to selection with porin-specific bacteriophages to obtain mutants lacking either the OmpC or OmpF porin protein. A mutation in either OmpC or OmpF did change the susceptibilities of certain strains expressing beta-lactamase to certain beta-lactam antibiotics. However, the loss of a single porin did not predictably alter susceptibility to any given beta-lactam drug. This panel of strains producing various beta-lactamases was found to be a useful tool for comparing the effects of different beta-lactamases and outer membrane permeability upon susceptibility to beta-lactam drugs.     

Sisomicin: Evaluation In Vitro and Comparison with Gentamicin and Tobramycin

Sisomicin is a new antibiotic produced by Micromonospora inyoensis. The in vitro activities of sisomicin, gentamicin, and tobramycin, three similar aminoglycosides, were determined against 228 clinical isolates representing 10 genera of common pathogens. No difference was noted in the activities of these antimicrobial agents when assayed by a standard broth dilution technique against Klebsiella, Enterobacter, Escherichia, Salmonella, Citrobacter, enterococci, or Staphylococcus aureus. Sisomicin was significantly more active than tobramycin against Serratia and indole-positive Proteus strains. Sisomicin was significantly more active than gentamicin against indole-negative Proteus strains and slightly more active against indole-positive Proteus strains. Tobramycin was more active than sisomicin or gentamicin against Pseudomonas and indole-negative Proteus strains. Gram-negative bacilli resistant to one of the three antimicrobial agents were not necessarily resistant to either of the other two. Activity of sisomicin was independent of the susceptibility or resistance of these isolates to nine other antimicrobial agents as assayed by the Bauer-Kirby technique. The presence of 50% human serum did not antagonize the in vitro activity of sisomicin against gram-negative isolates. Because sisomicin showed certain advantages over gentamicin or tobramycin in vitro, further investigation of this new antimicrobial agent is warranted.     

Surface EMG measurements during fMRI at 3T: accurate EMG recordings after artifact correction

In this experiment, we have measured surface EMG of the first dorsal interosseus during predefined submaximal isometric contractions (5, 15, 30, 50, and 70% of maximal force) of the index finger simultaneously with fMRI measurements. Since we have used sparse sampling fMRI (3-s scanning; 2-s non-scanning), we were able to compare the mean amplitude of the undisturbed EMG (non-scanning) intervals with the mean amplitude of the EMG intervals during scanning, after MRI artifact correction. The agreement between the mean amplitudes of the corrected and the undisturbed EMG was excellent and the mean difference between the two amplitudes was not significantly different. Furthermore, there was no significant difference between the corrected and undisturbed amplitude at different force levels. In conclusion, we have shown that it is feasible to record surface EMG during scanning and that, after MRI artifact correction, the EMG recordings can be used to quantify isometric muscle activity, even at very low activation intensities.     

Saturday-morning television: do sponsors promote high-risk behavior for burn injury?

Television has become an important tool for learning and socialization in children. Although television violence has been associated with adverse effects, data on depiction of fire and burn injury are lacking. We sought to determine whether Saturday-morning television programming, viewed primarily by children, depicts fire and burn injury as safe or without consequence, thus potentially increasing the incidence of burn injury in children. This was a prospective observational study. Saturday-morning children's television programs were videotaped from 7 AM to 11 AM for eight different television networks during a 6-month period. Tapes were scored for scenes depicting fire or smoke by independent observers. Recorded items included show category, scene type, gender target, context of fire, and outcome after exposure to flame. Fire events were documented during programs and their associated commercials. A total of 108 hours of children's programs, 16 hours per network, were recorded. Scenes depicting fire or smoke were identified 1960 times, with 39% of events occurring during the program itself and 61% in commercials. Fire was depicted as either safe or without consequence in 64% of incidents. Action adventure stories accounted for 56% of flame depictions. Overall, one incident involving flame and fire was portrayed for each 3 minutes of television programming. Saturday-morning television programming frequently depicts fire as safe, empowering, or exciting. The incidence of flame use in programming varies between stations but is most prevalent in action/adventure stories. Television commercials, although brief, provide the majority of the misinformation regarding fire. Medical professional societies should alert the public to this potential hazard and recommend responsible portrayal of fire in children's television programming.     

Effects of polyaspartic acid on pharmacokinetics of tobramycin in two strains of rat.

To provide insight into polyaspartic acid nephroprotection and differences in aminoglycoside renal toxicity between two rat strains, the single-dose pharmacokinetics of tobramycin was examined in the presence and absence of polyaspartic acid. Following a single subcutaneous 6.5-mg/kg dose of tobramycin alone, higher aminoglycoside concentrations were measured in Sprague-Dawley rats than in Fischer rats (P < 0.05). Simultaneous administration of polyaspartic acid (50 mg/kg) and tobramycin did not alter the concentrations of tobramycin in serum. The amount of tobramycin in renal tissue and the amount recovered in urine over a 24-h period were greater in both rat strains when tobramycin and polyaspartic acid were given concomitantly. In summary, polyaspartic acid did not alter the concentrations in serum achieved after a single dose of tobramycin in two different rat strains but did result in higher renal concentrations and greater urinary excretion of tobramycin.