Bacteriological, pharmacokinetic, and clinical studies of cefixime (CFIX), a newly developed oral cephalosporin, was conducted in our pediatric department as outlined below. Bacteriology The prevalent MICs of CFIX by microbiological species, compared with those of the reference drugs, were detailed below. Against 16 strains of S. aureus, the MICs averaged 6.25 micrograms/ml, and were found to be nearly the same as the MICs of amoxicillin (AMPC) but higher than those of cephalexin (CEX) and cefaclor (CCL). For 4 strains of S. pyogenes, the MICs averaged 0.05 microgram/ml, and were higher than the MICs of AMPC but lower than those of CEX and CCL. Mean MICs of CFIX against other clinical isolates were lower than those of CEX, CCL, or AMPC; E. coli (20 strains), 3.13 micrograms/ml; K. pneumoniae (9), 0.10 microgram/ml; P. mirabilis (16), 0.025 microgram/ml; P. vulgaris (5), 0.10 microgram/ml; H. influenzae (11), 0.05 microgram/ml; and S. typhimurium (4), 0.10 microgram/ml. The MICs of CFIX against 10 strains of P. aeruginosa were distributed at and above 25 micrograms/ml, a range much lower than greater than or equal to 100 micrograms/ml for CEX, CCL, or AMPC. Pharmacokinetics The serum concentrations and urinary recovery were studied in 3 children ranging from age 7 to 13. They were given CFIX on empty stomach in 2 different single doses of 3 and 6 mg/kg in a cross-over design. Average serum CFIX concentrations were dose-dependent, as evidenced by the respective peak concentrations of 1.70 microgram/ml for a 3 mg/kg dosage and 2.72 micrograms/ml for 6 mg/kg, which were attained 4 hours after the administration of the drug. The average half-lives of CFIX in the serum were 3.09 hours and 3.11 hours, respectively, and the 12-hour serum concentrations were 0.32 microgram/ml and 0.77 microgram/ml, respectively, for the 2 different dose levels. The average 12-hour urinary recovery was 25.2% and 22.3%, respectively. Clinical study Clinical effectiveness, bacteriological effectiveness, and side effects were studied in 27 children with infection including 4 patients with acute pharyngitis, 13 with acute purulent tonsillitis, 5 with acute pneumonia, 3 with urinary tract infection, and 1 each with acute rhinitis and acute bronchitis. One child with acute pneumonia (Mycoplasma pneumonia) was excluded from the study. The therapeutic effectiveness was "excellent" in 21, "good" in 3, "fair" in 1, and "poor" in 1, with an effectiveness rate of 92.3%.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacteria↗

PubMed1986

[List of standard body weight].

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Adolescent↗

PubMed1985

Dication and trication which can increase the permeability of Escherichia coli outer membrane.

Recent success in the preparation of the monomer, dimer and trimer in compound 48/80 prompted us to investigate the action of these compounds on Escherichia coli cells. It was found that compound 48/80 inhibited growth of E. coli cells, while the monomer, dimer and trimer in 48/80 did not. However, the following experiments showed that the dimer and trimer disrupted the permeability barrier of the outer membrane of E. coli. First, addition of the dimer or trimer in cell suspension stimulated the uptake of tetraphenylphosphonium cation. Second, the synergistic effect of the dimer on the action of gramicidin caused the efflux of K+. In experiments using isolated cytoplasmic membrane vesicles, addition of gramicidin alone caused the efflux of K+. Thus, it was speculated that, with whole cells, the dimer formed some defect structure in the outer membrane, through which gramicidin reached the cytoplasmic membrane and increased the K+ permeability. The temperature dependence of efflux K+ showed that the dimer in 48/80 rendered the outer membrane permeable to gramicidin at temperatures above the phase transition of the outer membrane.

Cell Membrane Permeability↗

PubMed1985

Naloxone prevents the analgesic action of alpha-MSH in mice.

alpha-MSH (0.1, 1, 10 micrograms) was administered intracerebroventricularly and its action on pain sensitivity was investigated by the hot-plate method in mice. alpha-MSH produced dose-dependent analgesia and this analgesic effect was prevented by naloxone (1 mg/kg, s.c.). It is possible that alpha-MSH may play a role in the mechanism of pain through endogeneous opioid systems.

Analgesics↗

PubMed1985

Potential-derived point-charge model study of electrostatic interaction energies in some hydrogen-bonded systems.

Mulliken's atomic changes (MC) and potential derived (PD) point charges obtained from STO-3G wave functions are used to study the electrostatic interaction energies for a series of representative hydrogen-bonded complexes. The results of the above-mentioned models are compared with the more accurate results of segmental multipole moment (SMM) expansion, and it is shown that the PD model is superior to the MC model. The results of PD model are shown to be well correlated with the results of SMM expansion technique. Results of our calculations using 6-31G and 6-31G** PD charges are also reported here. Electrostatic interaction energies obtained using 6-31G** PD charges are compared with the 6-31G** SCF interaction energies available for the nine hydrogen-bonded dimers of ammonia, water, and hydrogen fluoride and a good correlation between the two is shown. The interrelationship between the results of different basis sets are also examined for the PD point-charge model. The electrostatic interaction energies obtained using STO-3G PD model are shown to be well correlated to the results of 6-31G and 6-31G** PD models.

Ammonia↗

PubMed1985

Effects of intermittent capillary flow on oxygen transport in skeletal muscle studied by dynamic computer simulation.

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Animals↗

PubMed1985

Osmosensitivity of preoptic thermosensitive neurons in hypothalamic slices in vitro.

The effects of local osmotic changes on the activity of preoptic thermosensitive neurons were investigated in rat hypothalamic slices in vitro. Thirty-seven (53%) of 70 neurons recorded from the medial preoptic nucleus (MPO) (66% of thermosensitive neurons and 12% of thermally insensitive neurons) changed their firing rates in response to alterations in local osmolality of less than 15 mOsm/kg. The minimum change in osmolality to produce the neuronal response for six neurons tested was found to be less than 5 mOsm/kg. Statistical analysis revealed that there was a higher incidence of warm-sensitive neurons inhibited by hyperosmolality (50% of warm-units) and of thermally insensitive neurons which were osmotically insensitive (88%). None of the four warm-sensitive neurons tested lost either their osmosensitivity or thermosensitivity during synaptic blockade, and were taken to possess an inherent sensitivity to both temperature and osmolality. The phenomenon of reduced evaporative heat loss in dehydrated mammals may be explained, at least in part, by the reduced activity of MPO warm-sensitive neurons in a hyperosmotic environment.

Animals↗

PubMed1985

Suppression of the polyclonal B-cell responses by concanavalin A-treated bone marrow B cells in vitro.

A suppressor cell that inhibits the development of a polyclonal antibody response of splenic B cells to lipopolysaccharide is generated in the bone marrow cell culture in response to a mitotic dose (10 micrograms/ml) of concanavalin A (Con A). The Con A-responding suppressor cell is radioresistant and found in a bone marrow B (BM-B) cell population of normal as well as athymic mice. The suppressor activity of Con A-treated BM-B cells was consistently higher (P less than 0.01-0.0001) than those of untreated BM-B and fresh BM cells. The BM-B cell population recovered from short-term (3-day) cultures with Con A contained about 65% surface immunoglobulin (Ig)-positive cells, about 6% T cells, and less than 0.5% plastic-adherent cells, the latter two of which did not contribute to the suppressive activity. Thus, cytolytic treatment with various anti-T-cell antibodies could not eliminate the suppressive activity of the Con A-treated BM-B cells, and the Con A-treated macrophage population provided no significant suppression. The Con A-treated BM-B cells adherent to anti-Ig or anti-Con A dishes exhibited highly enriched suppressive activity. It was therefore concluded that an immature B-cell population of bone marrow could develop in response to stimulation with Con A into surface Ig-positive suppressor cells, contributing to the regulation of nonspecific B-cell responses.

Animals↗

PubMed1985

Microcirculatory responses to carotid sinus nerve stimulation at various ambient O2 tension in the rabbit tenuissimus muscle.

To quantify the integrated effects of local and central control mechanisms through tissue metabolites and the autonomic nervous system on the peripheral vascular beds, microcirculatory responses to the carotid sinus nerve stimulation at various levels of ambient oxygen tension (PO2) were measured in the rabbit tenuissimus muscle suffused with oxygenated Tyrode solution, using a microscope-TV system. The statistical analysis of the experimental data exhibited that both capillary red cell velocity and perfused capillary density at the control state were significantly decreased as PO2 was elevated (P less than 0.01) and that the stimulation also significantly augmented their values (P less than 0.01) except for the peak velocity data. Regression analysis indicated that both the velocity and density responses to PO2 changes during stimulation were less sensitive than those at the control state. For instance, the vasodilating effect of stimulation on density at PO2 20 mm Hg was enhanced by about four-fold at 80 mm Hg, although the effect on velocity was increased only by 16% with the same PO2 change. From these results, it was concluded that the microcirculatory changes due to the arteriolar smooth muscle contraction evoked by unit sympathetic discharge was significantly influenced by the ambient PO2 level. Such synergistic interaction of the local and central control mechanisms like a series-coupled gain control system was suspected to play an important role in the overall regulation of the microcirculation.

Animals↗

PubMed1985

Effects of single cortical spreading depression on metabolic heat production in the rat.

The effect of a single cortical spreading depression (CSD), elicited unilaterally by 10% KCI injection at the occipital cortex, was observed on the metabolic heat production in the rat with unilateral lesions in the preoptic and anterior hypothalamus (PO/AH). The metabolic rate increased by maximally 20% above its pre-CSD level for 7 min with a rise in rectal temperature when CSD entered the frontal cortex contralateral to the PO/AH lesion. By contrast, with the same onset, the increase in metabolic rate was lower (maximum 12%) and of shorter duration (3 min) in the ipsilateral CSD trial. Non-CSD trial with 0.9% NaCl injection had no effect on metabolic rate. The results provide further evidence to support the view that the frontal cortex of the rat is involved in the central thermoregulation.

Animals↗

PubMed1985

Effects of endotoxin and sodium salicylate on the preoptic thermosensitive neurons in tissue slices.

Effects of E. coli endotoxin and sodium salicylate (Sal) on single-unit activity of thermosensitive neurons recorded in slices of preoptic and anterior hypothalamic area (PO/AH) were studied in vitro. Perfusion of endotoxin-containing Krebs-Ringer's solution or local application of endotoxin in the immediate vicinity of recording neurons decreased and increased the firing rate of 31 of 34 warm-sensitive neurons and a cold-sensitive neuron, but had no effect on the majority of thermally insensitive neurons. In about half of warm-sensitive neurons the inhibitory response to endotoxin was preceded by a transient increase in firing rate. The pyrogen-induced decrease in firing rate in warm-sensitive neurons was reversibly blocked or attenuated by local application of Sal in a dose-dependent manner. The results are consistent with the view that pyrogen and Sal act in the PO/AH to produce fever and antipyresis, respectively, by appropriately offsetting the activity of thermosensitive neurons.

Animals↗

PubMed1985

Subchronic toxicity study of sodium o-phenylphenate in mice.

A 13-week subchronic oral toxicity study of sodium o-phenylphenate (SOPP) was conducted in B6C3F1 mice. Body weight gain was significantly depressed in 1.0 and 2.0% SOPP-treated males and in both sexes treated with 4.0%. Urinalysis showed an increase in pH and a decrease of specific gravity in the 4.0% group of both sexes. Relative liver weights of both sexes receiving 1.0, 2.0 and 4.0% SOPP were significantly greater than those of the controls. No treatment-related histopathologic findings were noted. On scanning electron microscopic (SEM) examination, the bladder epithelium of mice given 2.0% SOPP appeared normal at any time periods investigated. This study showed that while 4.0% SOPP was very toxic to both sexes, 2.0% SOPP did not cause statistically significant changes in organ weights.

Animals↗

PubMed1985

Absence of age effect on plasma haloperidol neuroleptic levels in psychiatric patients.

Plasma neuroleptic levels in 41 patients (21 men, 20 women, aged 18 to 74) on haloperidol therapy were examined in relation to their age by means of radioreceptor assay. There was no significant difference among three age groups (below 45 years, 46 to 60 years, over 60 years) in the ratio of the plasma neuroleptic level to daily dose (nM/mg/kg), but a significant difference in the plasma neuroleptic level was found between the average values in parkinsonian (19.1 +/- 8.5 nM, M +/- SD) and nonparkinsonian (5.5 +/- 3.0 nM, M +/- SD) patients. There was, however, no significant difference in the incidence of parkinsonian symptoms between the young (below 60 years) and the old (over 60 years) age groups. These results suggest that in contrast to the previously reported study with chlorpromazine, the plasma neuroleptic level of haloperidol is not altered with aging and that parkinsonian symptoms induced by haloperidol occur simply in a plasma-neuroleptic-level-dependent manner.

Administration, Oral↗