Previously, it was shown that some environmental substances (ES) which were taken into the body daily suppressed or enhanced the replication of herpes symplex virus, type 2 (HSV-2). This time, those substances were evaluated in various latent infection systems in vitro, whether those ES affect also the onset and cure of recurrent herpes infection.The latent infection systems were prepared, (i) using UV-irradiated HSV-2 at a nonpermissive temperature (NPT), and viruses were reactivated by lowering the temperature to a permissive one (PT), (ii) using Ara C treated human embryo cells at NPT and viruses were reactivated by superinfection with human cytomegalovirus, (iii) using trigeminal ganglions in latent infection state of mice which were infected in vivo. It was found that food dyes (amaranth, erythrosine), aromatic (safrole), antipyretic (phenacetin), materials of dyestuff (2-acetylaminofluorene: 2-AAF) and heavy metals (SbCl₃, HgCl₂) inhibited the reactivation of HSV-2 from some latent infection systems.Nicotine enhanced the reactivation of UV-irradiated HSV-2 at PT, however it did not enhanced the reactivation in Ara C treated cell system.None were shown to reactivate HSV-2 from the latent state at NPT without any reactivant.Clear results could not be obtained in the trigeminal ganglion system because of a large variation of virus yield reactivated.
These results suggest that some ES may influence the onset and cure of recurrent HSV infection.

View full abstract

With 50 strains of methicillin-and cephem-resistant S.aureus (MRSA) isolated from clinical materials as test organism, the MIC and bactericidal effect of β-lactam antibiotics against MRSA cultured at varying temperature were determined.The results were as follows:
1.The MIC values of various β-lactam antibiotics were measured under the following conditions: 1) inoculum size 10⁶/ml, incubation temperature at 30°C, 2) inoculum size 10⁶/ml, incubation temperature at 30°C. inoculum size 10⁶/ml.incubation temperature at 37°C, 4) inoculum size 10⁶/ml, incubation temperature at 37°C. The experiment revealed that MICs greatly varied with change of the incubation temperature, even if the inoculum size of MRSA was constant. Namely, compared with MICs at 30°C, MICs at 37°C generally shifted towards at a lower concentration range with 8-to 32-fold increase in sensitivity.
2.The bactericidal effect of each β-lactam antibiotic against MRSA was determined under the same conditions of culture as in the measurement of MICs.Some concentrations of antibiotics which showed no bactericidal effect at 30°C clearly recognized bactericidal effect at 37°C.
3.The fact that the bactericidal effect varied with change of incubation temperature was confirmed by the observation of morphological changes of MRSA through a phase-contrast microscope.When the organisms were exposed to the antibiotic, swollen cells inhibiting septal wall synthesis began to be observed at low concentrations.Whereas cell lysis was almost not detected even when the antibiotic concentration was increased considerably high in organisms cultured at 30°C. the cell lysis were observed together with swollen cells while the antibiotic concentration was still at a relatively low level in organisms cultured at 37°C.
4.The discrepancy of MICs and bactericidal effect through change of incubation temperature was observed in derivative strain eliminated PCase plasmid but retaining resistance to methicillin and cephem too.
5.It was investigated that the above phenomenon occurred because penicillin-binding protein-2' itself is temperature sensitive, so the optimal temperature for its production was at 30°C than at 37°C.

View full abstract

In vitro and in vivo stabilities of cefbuperazone (CBPZ) to various β-lactamages were compared with cefmetazole (CMZ), cefotaxime (CTX) and cefazolin (CEZ).
The stabilities of CBPZ were superior to CTX and CEZ against penicillinase derived from K.pneumoniae Y-4 and cefuroximase derived from P.vulgaris T-178. Furthermore, CBPZ was also more stable to cephalosporinases produced by E.cloacae H-27 and C.freundii GN 346 than CMZ, CTX and CEZ.These results were well reflected by the stabilities of each drug in crude β-lactamase solution. When single doses of 100mg/kg of CBPZ, CMZ, CTX and CEZ were intravenously administered to rats with granuloma pouch infected by E.cloacae H-27, P.vulgaris T-178 or K. pneumonia. Y-4, the serum levels of each drug were not largely affected by the three infectious organisms, except those of CTX for P.vulgaris T-178.Although CBPZ in granuloma pouch were hardly affected by the three infectious organisms CTX for P.vulgaris T-178 and E.cloacae 11-27 were apparently lowered, and CMZ for E.cloacae H-27 and CEZ for three infectious organisms were not detected at any measured points, presumably as a result of hydrolysis by the bacterial β-lactamase at the site of infection.

View full abstract

Sensitivity to co-trimoxazole as well as to sulfamethoxazole (SMX) and to trimethoprim (TMP) was studied for 905 gram-negative rod bacteria isolated at our university hospital from 1977 to 1981.The results were as follows.
1) In most of the isolates the sensitivity to co-trimoxazole was equal to or less than 3.13μg/ml at MIC₅₀ and 12.5μg/ml at MIC₈₀.
2) No remarkable annual change of MIC values was observed expect for Citrobacter strains isolated in 1980 most of which were resistant to all three drugs.
3) The reports of disc sensitivity test performed in the clinical pathology laboratory of the hospital tended to show that many strains belonging to Enterobacteriaceae were apparently more resistant to drugs than their MIC values.On the other hand, Pseudomonas aeruginosa strains which were rather sensitive to co-trimoxazole by paper disc test were entirely resistant in MIC study.
4) Synergistic activity of TMP was clearly demonstrated when added to SMX in 77.5% of the strains (373/481) with MIC of SMX equal to or less than 50μg/ml. On the other hand, the synergistics activity of SMX when added to TMP was observed only in 51.4% of the strains (384/743) with MIC of TMP equal to or less than 50μg/ml. Synergistic combination was rarely demonstrated in strains highly resistant to TMP.

View full abstract

The pharmacokinetics of aspoxicillin (ASPC), a new semi-synthesized penicillin, was studied in 6 healthy volunteers and 24 patients with impaired renal function after a single 1g intravenous injection.Concentrations of ASPC in serum and urine were assayed by the thin-layer paper disc method using E.coli ATCC 27166 as a test organism.
The pharmacokinetic parameters of ASPC were obtained by analysing the serum concentrations of ASPC based on a two-compartment open model.
The following results were obtained.
1. Serum concentrations of ASPC after a single 1g intravenous injection were higher in proportion to lowering of Ccr.
2. Cumulative urinary recovery rate within 24 hours after administration of 1 g dose was 67.3% in normal volunteers and 6.1% in patients with severe impairment of renal function (Ccr≤10ml/min).
3. Mean serum half-life Was 1.5±0.2 hr in normal volunteers and 7.2±4.0 hr in patients with severe impairment of renal function.
4.There were significant correlations of Ccr to β, t_1/2β, renal and total body clearance.
5. Ratio of body clearance/Ccr was 1.7 in normal volunteers and 11.4 in patients with severe impairment of renal function.
6.There was removal of ASPC from dialyzer membrane.
These results showed that extrarenal excretion increased in patients with severe impairment of renal function, because unchanged ASPC was mainly excreted by the kidney.
Lower dose or longer intervals of administration should be employed according to Ccr in patients with renal failure (Ccr≤30ml/min).

View full abstract