Topical vitamin D3 analogues induce thymic stromal lymphopoietin and cathelicidin in psoriatic skin lesions.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease of unknown aetiology, and an active form of vitamin D(3) (1α,25-dihydroxyvitamin D(3)) and its analogues (VD3As) are widely used topical reagents for psoriasis treatment. Besides their well-known calcium homeostasis functions, VD3As have been shown to have various immune-modulating effects including the induction of thymic stromal lymphopoietin (TSLP), a master cytokine for inducing Th2 inflammation, in mouse models, but not yet in human psoriasis. VD3As also have been shown to induce cathelicidin, an antimicrobial peptide and strong inducer of innate immunity. Cathelicidin is overexpressed in psoriatic skin lesions; however, its role in this disease seems as yet inconclusive. OBJECTIVES: To clarify whether topical VD3As induce TSLP and cathelicidin, and to examine the modulation of expression patterns of related cytokines in human psoriatic lesions. METHODS: Skin biopsy samples from psoriatic lesions with or without VD3A treatment were subjected to immunohistochemical staining and quantitative reverse transcription-polymerase chain reaction analyses to measure the expression levels of various cytokines. RESULTS: Significantly higher levels of TSLP, thymus and activation-related chemokine and CCR4 expression were observed in VD3A+ skin samples than in VD3A- samples. In contrast, significantly lower levels of interleukin (IL)-12/23 p40, IL-1α, IL-1ß and tumour necrosis factor (TNF)-α expression were observed in the VD3A+ samples than in the VD3A- samples. Expression of cathelicidin was elevated in VD3A+ samples. CONCLUSIONS: Topical VD3As induce TSLP and cathelicidin in psoriatic lesions, resulting in suppression of IL-12/23 p40, IL-1α, IL-1ß and TNF-α, thereby ameliorating psoriatic plaques.

A protective role of gamma/delta T cells in primary infection with Listeria monocytogenes in mice.

We have previously reported that T cells bearing T cell receptors (TCRs) of gamma/delta type appear at a relatively early stage of primary infection with Listeria monocytogenes in mice. To characterize the early-appearing gamma/delta T cells during listeriosis, we analyzed the specificity and cytokine production of the gamma/delta T cells in the peritoneal cavity in mice inoculated intraperitoneally with a sublethal dose of L. monocytogenes. The early-appearing gamma/delta T cells, most of which were of CD4-CD8- phenotype, proliferated and secreted IFN-gamma and macrophage chemotactic factor in response to purified protein derivative from Mycobacterium tuberculosis, or recombinant 65-kD heat-shock protein derived from M. bovis but not to heat-killed Listeria. To further elucidate the potential role of the gamma/delta T cells in the host-defense mechanism against primary infection with Listeria, we examined the effects of in vivo administration of monoclonal antibodies (mAbs) against TCR-gamma/delta or TCR-alpha/beta on the bacterial eradication in mice infected with Listeria. Most of alpha/beta T cells or gamma/delta T cells were depleted in the peripheral lymphoid organs at least for 12 d after an intraperitoneal injection of 200 micrograms TCR-alpha/beta mAb or 200 micrograms TCR-gamma/delta mAb, respectively. An exaggerated bacterial multiplication was evident at the early stage of listerial infection in the gamma/delta T cells-depleted mice, whereas the alpha/beta T cell-depleted mice exhibited much the same resistance level as the control mice at this stage although the resistance was severely impaired at the late stage after listerial infection.(ABSTRACT TRUNCATED AT 250 WORDS)

A sustained increase of cytosolic Ca2+ in gammadelta T cells triggered by co-stimulation via TCR/CD3 and LFA-1.

We previously reported that co-stimulation with LFA-1 triggered apoptosis in gammadelta T cells but not in alphabeta T cells after TCR engagement. We extended our earlier study on TCR/LFA-1 triggered apoptosis to two autoreactive TCR gammadelta and TCR alphabeta T cell clones, which were derived from syngeneic mixed lymphocyte culture of BALB/c mice. A gammadelta T cell clone, KM1, expressed the Vgamma4 and Vdelta5 genes and CD4-CD8-CD45RB+ phenotype; and an alphabeta T cell clone, BASL1.1, expressed Vbeta6 and CD4+CD8-CD45RB+. Both clones produced Th-1-type cytokines in response to syngeneic BALB/c stimulator cells. KM1 underwent apoptosis upon stimulation with immobilized anti-CD3/LFA-1 mAbs, whereas BASL1.1 could proliferate successfully in response to stimulation with the immobilized mAbs. BASL1.1 was able to down-regulate the increased cytosolic Ca2+ after the simultaneous stimulation, but KM1 exhibited a sustained increase of cytosolic Ca2+ after stimulation via CD3 and LFA-1. Similar results with respect to the kinetics of cytosolic Ca2+ were obtained with normal heterogeneous gammadelta and alphabeta T cell populations after co-stimulation via CD3 and LFA-1. Our results suggested that persistently high levels of cytosolic Ca2+ might be related to apoptosis in gammadelta T cell clone triggered by co-stimulation via CD3 and LFA-1.

CD4 expression is important but not essential for infection with exogenous mouse mammary tumor virus.

We studied local events in the popliteal lymph nodes of CD4-deficient mice following foot pad injection with an MMTV strain which carries the gene for a V beta 14-specific superantigen. Injection of the V beta 14-specific MMTV induced vigorous expansion of V beta 14+ CD4+ T cells and B cells in their lymph nodes of CD4+/- heterozygous control mice. On the other hand, CD4-/- mice injected with the MMTV showed a proliferation of V beta 14+ T cells among the population of TCR alpha beta + CD4-CD8- T cells, although to a lesser extent. This phenomenon was not accompanied by vigorous B cell expansion. A PCR assay revelated that the MMTV definitely infected the lymph nodes cells of the CD4-/- mouse. However, the infectivity of the MMTV in CD4-/- mice was approximately 20 times lower than that in CD4+/- mice. These findings indicate that, in MMTV infection of CD4-deficient mice, the superantigen-reactive T cells among the population of TCR alpha beta +CD4-CD8- T cells substitute for the superantigen-reactive CD4- T cells of normal mice, and that the absence of CD4 molecules decreased the infectivity of MMTV because of insufficient expansion of the superantigen-reactive T cells.

The induction of skin xenograft tolerance in rat-to-mouse combination could be affected by DFR mediating cells and antibodies against rat bone marrow cells as well as NK cells in the cyclophosphamide-induced tolerance system.

We investigated whether the prolongation of skin xenograft survival was obtained by a tolerance-inducing method using cyclophosphamide (CY), by which long-lasting skin allograft tolerance could be induced. The long-lasting skin allograft survival could be obtained in the recipient C3H/HeN (C3H) mice which were given 100 micrograms of anti-CD4 mAb on day -3, 1 x 10(8) spleen cells (SC) plus 3 x 10(7) bone marrow cells (BMC) derived from C57BL/6 (B6) mice on day -2,200 mg/kg CY on day 0, and which were grafted with allogeneic B6 skin on day 14. When the C3H mice were treated with anti-CD4 mAb, 1 x 10(8) s.c. plus 5 x 10(7) BMC derived from F344 rat and CY, the F344 skin grafts survived slightly longer (about 15 days) than those in untreated recipients (about 8.4 days). Such a prolongation of skin xenograft survival was considered donor-specific because rejection of 3rd party skin grafts from BN rats occurred significantly earlier than that of F344 skin grafts. In the recipient C3H mice treated with anti-CD4 mAb, F344 s.c. plus BMC and CY, mixed chimerism in the periphery was detected for a few days after CY administration, although intrathymic chimerism was not detected throughout this study. In these recipient C3H mice, cytotoxic T lymphocytes (CTL) against F344 antigens were completely abrogated through the delayed footpad reaction (DFR) remained at a low but significant level. Moreover, though antibody (Ab) activity against F344 s.c. was completely abrogated, neither Ab activity against F344 BMC, which seemed to have a background common to natural Ab activity, nor NK activity were abrogated by this treatment. These results suggested that DFR mediating cells directly mediated skin xenograft rejection in the recipient mice treated with anti-CD4 mAb, F344 cells, and CY. Such cells may interfere with establishment of mixed chimerism and long-lasting skin xenograft tolerance, presumably in cooperation with CY-resistant Ab activity and NK cells.

Hypernatremic myopathy.

We describe a 21-year-old man presenting with proximal muscle weakness associated with hypernatremia. His manifestations other than muscle weakness included dry skin, loss of axillary and pubic hair, decreased libido and loss of thirst sensation. His serum sodium level was elevated to 169-171 mEq./l but all other electrolytes were normal. In addition, serum CK was elevated and an EMG study showed myogenic changes. Endocrinological studies revealed hypothalamic hypopituitarism, while MRI revealed a suprasellar mass. A partial correction of hypernatremia led to an immediate recovery of the muscle weakness as well as a normalization of both the serum CK level and EMG findings, suggesting a direct association between the muscle weakness and hypernatremia. The phosphocreatine/inorganic phosphorus (PCr/Pi) ratios in the resting calf muscle, obtained using 31P magnetic resonance spectroscopy (MRS), were very low during the state of muscle weakness, while they returned to nearly normal values after clinical improvement, suggesting that the muscle weakness in hypernatremic state was caused by a depletion of the intramuscular energy stores, probably due to an overworking Na-K pump to correct the intracellular electrolyte imbalance.

Prediction for biodegradability of chemicals by an empirical flowchart.

A method for predicting aerobic biodegradability of chemicals was developed based on empirical knowledge. A flowchart was derived from rule of thumb relationships between the biodegradability and the number of the functional groups and substructures in a certain skeletal structure of chemicals. The flowchart classified chemicals into readily biodegradable, not readily biodegradable and not predictable. It was validated by using MITI data of 177 mono benzene derivatives and 168 acyclic compounds, resulting in correct prediction at 94% and 88% levels, respectively.

[Studies on the pharmacokinetics of cefotaxime in neonates].

The pharmacokinetics of cefotaxime was investigated in neonates. The following results were obtained. 1. The peak serum concentration of cefotaxime, seen 15-minutes after a single intravenous of 20 mg/kg, was 51.6 +/- 9.3 mcg/ml by bioassay. After 6 hours the mean serum concentration decreased to 5.6 +/- 3.1 mcg/ml. Concentrations obtained by HPLC paralleled those determined by bioassay. The peak serum concentration of the desacetyl metabolite was attained 30 minutes to 2 hours after injection. The mean serum desacetyl metabolite concentration was about 1/2.5 times higher than the cefotaxime concentration. The half-life was inversely related to the age of the neonates, decreasing to 1.64 hours on day 11 postpartum. 2. Serum concentrations determined by bioassay and HPLC after administering a dose of 10 mg/kg of cefotaxime by 30-minute intravenous drip infusion were comparable. The peak serum concentration at the completion of intravenous drip infusion was 21.0 mcg/ml by bioassay. The half-life of cefotaxime was 2.85 hours. The peak serum concentration of the desacetyl metabolite, seen at the completion of intravenous drip infusion, was about 1/2 times that of the peak cefotaxime concentration. 3. The peak serum concentration at the completion of a 30-minute intravenous drip infusion of 20 mg/kg displayed a mean value of 33.5 +/- 10.3 mcg/ml by bioassay. After 6 hours the mean serum concentration was 4.0 +/- 1.0 mcg/ml. The peak serum concentration of the desacetyl metabolite, seen at the completion of infusion to 2 hours thereafter, was equivalent to about 1/2.2 the peak cefotaxime concentration. 4. Mean urinary excretion rate of cefotaxime in 2-day-old neonates was 23.4% by bioassay 6 hours after a 30-minute intravenous drip infusion of 10 mg/kg. The mean urinary excretion rate of the desacetyl metabolite was 8.7%. Mean 6-hour excretion rates in 2-day-old and 4-day-old neonates administered 20 mg/kg of cefotaxime by 30-minute intravenous drip infusion were 6.2% and mean 37.7%, respectively. The corresponding values for the desacetyl metabolite were 2.4% and 12.4%, respectively.

[Experimental and clinical evaluation of cefsulodin in the pediatric field].

Antimicrobial, pharmacokinetic and clinical evaluation of cefsulodin (CFS) was made and the following results were obtained. 1. Antimicrobial activity of CFS against P. aeruginosa was similar to a little lower than that of GM. Antimicrobial activity of CFS against S. aureus was similar to that of SBPC and against E. coli CFS showed lower antimicrobial activity. 2. Twenty or 50 mg/kg CFS was administered by 1 hour intravenous drip infusion. Average serum levels at the completion of the infusion were 35.1 +/- 8.0, 114.5 +/- 36.1 micrograms/ml and 1.6 +/- 0.7, 4.5 +/- 3.2 micrograms/ml at 6 hours afterward with the half life times of 1.50, 1.29 hours respectively. In case of 12.1 mg/kg 1 hour intravenous drip infusion, peak serum level was 13.4 micrograms/ml at the completion of infusion, and the concentration in the sputum was 1.0 micrograms/ml at 5 hours after completion of infusion. Average serum levels of CFS by one shot infusion of 20 mg/kg were 58.4 +/- 6.8 micrograms/ml, 2.7 +/- 2.5 micrograms/ml at 15 minutes and 6 hours after injection respectively. Half-life time was 1.54 hours. Average urinary excretion rates of CFS were 64.4%, 64.2% and 48.9% up to 6 hours after 1 hour intravenous drip infusion of 20 mg/kg, 50 mg/kg CFS and one shot intravenous of 20 mg/kg CFS respectively. 3. CFS was administered to 2 pneumonia cases caused by P. aeruginosa, i.e. one was 15 years and 11 months old male accompanying bronchial asthma and the another 4 years old male with LENNOX syndrome. Neither bacteriological nor clinical efficacy was, however, observed. Side effect as well as bacterial superinfection were not observed.

[Laboratory and clinical studies of cefoxitin in pediatric field (author's transl)].

The authors have carried out the laboratory and clinical studies of cefoxitin. The results were as follows: The sensitivity was estimated by plate dilution method on 26 strains of S. aureus, 25 strains of E. coli, 24 strains of K. pneumoniae, 27 strains of Serratia and 17 strains of Salmonella isolated from patients. The distribution of sensitivity of S. aureus was 1.56-3.13 microgram/ml and the peak of distribution was 3.13 microgram/ml. The strains of 76.0% of E. coli was inhibited at concentration of less than 3.13 microgram/ml. The strains of 91.7% of K. pneumoniae was inhibited at concentration of less than 3.13 microgram/ml. The distribution of sensitivity of Serratia was 6.25-more than 100 microgram/ml and the peak of distribution was 100 microgram/ml. The all strains of Salmonella were inhibited at concentration of less than 3.13 microgram/ml. Cefoxitin was given by intravenous administration for 5 minutes at a single dose of 25 mg/kg of cefoxitin to 2 children, and by drip infusion for 60 minutes at a single dose of 25 mg/kg of cefoxitin to 4 children. After intravenous administration of cefoxitin, the mean peak of serum level was 67.3 +/- 6.3 microgram/ml at 15 minutes, and at 4 and 6 hours after administration was not detected. Half-life time was 22 minutes. And after drip infusion of cefoxitin for 60 minutes, the mean peak of serum level was 35.7 +/- 5.3 microgram/ml at 1 hour, and at 4 and 6 hours after administration was not detected. Half-life time was 20 minutes. The mean urinary recovery rate was 82.4 +/- 3.0% and 90.2 +/- 6.8% up to 6 hours after intravenous administration and drip infusion respectively. Cefoxitin was effective in all of 15 cases with bacterial infections. No side effects was observed.

[Pharmacokinetics and clinical studies on CS-1170 (author's transl)].

The authors have carried out the pharmacokinetics and clinical studies of CS-1170. The results were as follows; CS-1170 was given by drip infusion for 1 hour dose of 20 mg per kg body weight to 3 children. The maximum blood level was reached at one hour after drip infusion. This blood levels were 38 micrograms/ml, 68 micrograms/ml and 86 micrograms/ml, respectively, (mean 64 micrograms/ml), and level at 2 hours, 11.5 micrograms/ml, 9.4 micrograms/ml, 16 micrograms/ml respectively, (mean 12.3 micrograms/ml), the blood level at 6 hours was not determined. The urinary excretion rates were 94.8 approximately 96.8% up to 6 hours after drip infusion dose of 20 mg per kg body weight. CS-1170 was effective in 7 of 8 cases with pediatric bacterial infections. An ineffective case was a pneumonia due to Serratia marcescens. No side effect was observed except for 2 cases with diarrhea and one case with elevation of GOT and GPT.

[Experimental and clinical evaluation of cefpiramide in pediatrics].

The authors have carried out the laboratory and clinical studies of cefpiramide (CPM). The results were as follows; The sensitivity was estimated by plate dilution method on 27 strains of S. aureus and P. aeruginosa, 26 strains of E. coli, 25 strains of K. pneumoniae and 13 strains of Proteus sp. isolated from patients. The distribution of S. aureus was 0.78 approximately 6.25 micrograms/ml and the peak of distribution was 1.56 micrograms/ml. The distribution of E. coli was 0.78 approximately 50 micrograms/ml and the peak of distribution was 0.78 and 25 micrograms/ml. The growth of 24% of K. pneumoniae was not inhibited at concentration of more than 50 micrograms/ml. The distribution of Proteus sp. was 6.25 approximately 100 micrograms/ml. The growth of 77.8% of P. aeruginosa was inhibited at concentration of less than 3.13 micrograms/ml. CPM was given by intravenous administration for 5 minutes and drip infusion for 30 minutes at a single dose of 20 mg/kg of CPM to each 2 children respectively. After intravenous administration of CPM, the mean peak serum level was 200.5 +/- 37.5 micrograms/ml at 15 minutes, 44.3 +/- 0.9 micrograms/ml at 6 hours, 19.9 +/- 0.3 micrograms/ml at 12 hours respectively. Half-life time was 4.2 hours. After drip infusion of CPM, the mean peak serum level was 150.5 +/- 14.5 micrograms/ml at end of infusion, 23.6 +/- 3.3 micrograms/ml at 6 hours and 8.2 +/- 2.0 micrograms/ml at 12 hours respectively. Half-life time was 3.8 hours. The mean urinary excretion rate was 23.15%, 28.2% up to 12 hours after intravenous administration and drip infusion respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

[Experimental and clinical evaluation of cefotetan in pediatrics].

The authors have carried out the laboratory and clinical studies of cefotetan (CTT), and obtained the following results. The antibacterial activities of CTT were measured by the plate dilution method against the clinical isolates of S. aureus, E. coli, K. pneumoniae, S. marcescens and Salmonella sp. The susceptibility distribution of S. aureus to CTT was at concentration of 6.25-12.5 micrograms/ml and the peak of that was obtained at 6.25 micrograms/ml with an inoculum size of 10(6) cells/ml. And the peaks of susceptibility distribution of E. coli and K. pneumoniae to CTT were obtained at less than 0.1 microgram/ml respectively, and that of S. marcescens was obtained at 6.25-12.5 micrograms/ml with an inoculum size of 10(6) cells/ml. The growth of all strains of Salmonella sp. was inhibited at concentration of less than 0.1 microgram/ml. As for pharmacokinetic study, CTT was given by intravenous bolus injection and drip infusion for 30 minutes at a single dose of 20 mg/kg. After intravenous bolus injection of 20 mg/kg of CTT, the mean peak serum level was 175.0 +/- 7.0 micrograms/ml at 15 minutes after injection, and half-life time was 3.53 hours. After 30 minutes drip infusion of 20 mg/kg of CTT, the mean serum concentration was 106.0 +/- 6.0 micrograms/ml at end of infusion, half-life time was 2.41 hours. The mean urinary excretion rates were 49.4% and 64.2% up to 8 hours after drip and bolus injection of 20 mg/kg of CTT, respectively. CTT was given 15 cases with bacterial infection. Daily doses of CTT were from 15.0 to 107.0 mg/kg. Clinical results obtained were excellent and good responses in 12 of 15 cases (80.0%). No side effects were obtained except for 2 cases with elevation of GOT and GPT, and 1 case with eosinophilia.

[Laboratory and clinical studies on cefamandole (author's transl)].

The authors have carried out the laboratory and clinical studies of cefamandole (CMD). The results are as follows: The sensitivity was measured by plate dilution method on 26 strains of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and 14 strains of Salmonella typhimurium isolated from patients. The distribution of sensitivity of S. aureus was 0.39 approximately 3.13 micrograms/ml and the peak of distribution was 1.56 micrograms/ml. The distribution of sensitivity of E. coli was 0.78 approximately greater than 100 micrograms/ml, and K. pneumoniae, 1.56 approximately greater than 100 micrograms/ml. The distribution of sensitivity of Salmonella typhimurium was 6.25 approximately greater than 100 micrograms/ml and its peak was 6.25 micrograms/ml. CMD were given intravenously for 30 and 60 minutes at a single dose of 25 mg/kg body weight to 6 children. The serum mean levels of CMD were 105.3 micrograms/ml at 30 minutes, 15.1 micrograms/ml at 1.5 hours, 1.6 micrograms/ml at 2.5 hours after drip infusion for 30 minutes, respectively, and 34.7, 5.2, 0.6 micrograms/ml at 1, 2, 3 hours after drip infusion for 60 minutes, respectively. And the serum level at 4 hours after administration was not detected. The mean urinary excretion rates were 73.3% in the drip infusion for 30 minutes and 60.7% in its for 60 minutes, up to 8 hours after administration. Half life was 26 minutes. CMD was effective in 18 of 21 cases of bacterial infections. No side effects were observed except for 2 cases with elevation of serum transaminase.

[Laboratory and clinical studies on cefuroxime (author's transl)].

The authors have carried out the laboratory and clinical studies of cefuroxime (CXM). The results were as follows: The sensitivity was measured by plate dilution method on 26 strains of S. aureus, 22 strains of E. coli and 24 strains of K. pneumoniae isolated from patients. The distribution of sensitivity of S. aureus was 0.78 approximately 3.13 micrograms/ml and the peak of distribution was 1.56 micrograms/ml. The distribution of sensitivity of E. coli was 1.56 approximately 50 micrograms/ml and the peak was 6.25 micrograms/ml. The growth of 79.2% K. pneumoniae was inhibited in concentration of less than 3.13 micrograms/ml. CXM was given intravenously for 30 minutes at a single dose of 20 mg/kg to 3 children. The serum mean levels of CXM were 99.0 +/- 10.6 micrograms/ml at 30 minutes, 18.0 +/- 10.7 micrograms/ml at 1 hour, 7.0 +/- 2.0, 2.2 +/- 0.6, 0.79 +/- 0.2 microgram/ml at 2, 4 and 6 hours after drip infusion for 30 minutes, respectively. Mean half life was 48 minutes. The mean urinary recovery rate was 96.2% up to 8 hours after administration. CXM was effective in 9 of 10 cases of bacterial infections. No side effect was observed except for 1 case with elevation of serum transaminase.

[Clinical studies of S-6437 in pediatrics (author's transl)].

Peak blood level of cephalexin was obtained at 4 hours after the administration of S-6437 as opposed to 2 hours after regular cephalexin. Peak blood level with regular cephalexin was higher than that with S-6437. Blood levels with S-6437, however, stayed for longer period than those with regular cephalexin. Mean urinary recovery within 12 hours after the administration of S-6437 after meal and during meal were 57.1 and 69.3%, respectively. S-6437 was studied in 23 pediatric patients, 7 with acute tonsillitis, 15 with acute cystitis and 1 with cellulitis. They were orally given 400 to 1,200 mg/day of S-6437 in two divided doses at 30 minutes after meal for 4 approximately 12 days. Of the 23 patients, 18 responded to the drug but 5 did not respond. As for side effects, eruption and diarrhea were observed in 1 and 2 patients, respectively. No other side effects were found.

[Laboratory and clinical studies of cefroxadine (author's transl)].

The authors have carried out the laboratory and clinical studies of cefroxadine (CXD), and obtained the following results. The antibacterial activities of CXD were measured by plate dilution method on 26 clinical isolates of S. aureus, E. coli and K. pneumoniae. CXD inhibited the growth of all strains of S. aureus at concentrations less than 6.25 microgram/ml, the peak of activity distribution was obtained at 3.13 microgram/ml with an inoculum size of 10(6) cells/ml. And the p eak sensitivity distribution of E. coli was obtained at 6.25 microgram/ml. The growth of all strains of K. pneumoniae was inhibited at concentrations of less than 25 microgram/ml. Phagocytosis was determined by QUIE'S method. In the presence of CXD, phagocytosis of human PMNs was not enhanced to E. coli and K. pneumoniae. For pharmacokinetic study, CXD was given orally at a single dose of 10 mg/kg to 3 children before and after meals. The serum levels of CXD on fasting were 14.2 microgram/ml, 11.0 microgram/ml, 4.0 microgram/ml and 0.57 microgram/ml at 0.5, 1, 2. 4 hours after administration respectively, and the level at 6 hours was not detectable. Half-life was 0.65 hours. The serum levels of CXD after meals were 3.9 microgram/ml, 5.3 microgram/ml, 5.3 microgram/ml, 2.4 microgram/ml and 0.42 microgram/ml at 0.5, 1, 2, 4, 6 hours after administration respectively, but at 8 hours it was not detectable. Half-life was 0.95 hours. The 8-hour urinary excretion rates on fasting and non fasting were 89.4%, 89.0% respectively. CXD was given to 31 cases with tonsillitis, 4 with bronchitis, 1 with impetigo, 3 with cervical lymphadenitis, 7 with U.T.I, totalling 46. A daily dose of CXD 400 approximately 1,500 mg was given for 4 approximately 14 days. Clinical results obtained were good and excellent responses in 43/46 (93.5%) cases. No side effects were observed except for 1 case with elevation of GOT, 2 cases with elevation of GOT and GPT and 1 case with eosinophilia.

[Laboratory and clinical studies of cefoperazone in pediatric field (author's transl)].

The authors have carried out the laboratory and clinical studies of cefoperazone (CPZ). The results were as follows: The sensitivity was estimated by plate dilution method on 26 strains of S. aureus, E. coli and K. pneumoniae, 25 strains of P. aeruginosa, 14 strains of Salmonella sp. and 9 strains of GM resistant P. aeruginosa isolated from patients. The distribution of sensitivity of S. aureus was 1.56 approximately 25 mcg/ml and the peak of distribution was 3.13 mcg/ml. The growth of 96.2% of E. coli was inhibited at concentration of less than 12.5 mcg/ml. The growth of 50.0% of K. pneumoniae was inhibited at concentration of less than 6.25 mcg/ml. The peak of distribution of P. aeruginosa was 12.5 approximately 25 mcg/ml (GM sensitive) and 12.5 mcg/ml (GM resistant). CPZ was given by drip infusion for 30 minutes at a single dose of 25 mg/kg to 2 children, and by drip infusion for 60 minutes at a single dose of 46.9 mg/kg to a child. The serum mean level of CPZ was 127.5 +/- 8.5 mcg/ml at 30 minutes, 30.5 +/- 7.5 mcg/ml at 1 hour, 23.5 +/- 3.5 mcg/ml at 2 hours, 10.5 +/- 1.5 mcg/ml at 4 hours and 6.8 +/- 2.4 mcg/ml at 6 hours after administration at a single dose of 25 mg/kg, respectively. The serum level was 102.0 mcg/ml at 1 hour, 32 mcg/ml at 2 hours, 14.5 mcg/ml at 5 hours and 12.5 mcg/ml at 7 hours after administration at a single dose of 46.9 mg/kg. Half-life time was 92 minutes. The mean urinary excretion rate was 32.0 +/- 7.3% in the drip infusion for 30 minutes up to 8 hours after administration. CPZ was effective in 6 of 8 cases with pediatric bacterial infections. No side effects were observed except for 1 case with elevation of GOT.

[Basic and clinical studies of cefotiam in pediatric field (author's transl)].

The basic and clinical studies of cefotiam (CTM) in pediatric infections were carried out, and the following results were obtained: 1. The antibacterial activity of CTM against S. aureus was equal or slightly less than that of cefazolin (CEZ). Those of CTM against E. coli and K. pneumoniae were eight times more active than those of CEZ. 2. CTM 20 mg/kg was administered wither by 30 minutes or 1 hour intravenous drip infusion. The peak serum levels were obtained at the end of each drip infusion, with the mean peak levels being 44.8 and 41.4 mcg/ml respectively. The serum levels at 1.5 and 2 hours after drip infusion were 2.8 and 2.2 mcg/ml respectively, and at 3.5 and 4 hours after drip and 4 hours after drip infusion were 0.3 and 0.7 mcg/ml respectively. The half lives were 0.62 and 1.15 hours, respectively. The mean urinary excretion over 6 hours were 52.8% in ;the 30 minutes drip infusion group and 42.6% in the 1 hour drip infusion group. 3. Clinical efficacy was evaluated in sixteen cases suffering from tonsillitis (4 cases), pneumonia (4), bronchitis (2), cervical lymphadenitis (2), purulent meningitis (2), suppurative arthritis (1) and suspected sepsis (1). Good and excellent responses were obtained in 15 of 16 cases (93.8%). Bacteriological response in the form of eradication was noted in 4 of 6 cases. Side effect observed was rash in 1 case, and laboratory abnormalities were elevation of BUN in 1 case and elevation of GPT in 2 cases.

[Laboratory and clinical studies of 6059-S in pediatric field (author's transl)].

The authors have carried out the laboratory and clinical studies of 6059-S. The results were as follows: The sensitivity was estimated by the plate dilution method on 27 strains of S. aureus, 26 strains of E. coli, K. pneumoniae and P. aeruginosa, 21 strains of Salmonella sp. and 9 strains of GM resistant P. aeruginosa isolated from patients. The distribution of sensitivity of S. aureus was 6.25-12.5 micrograms/ml and the peak of distribution was 6.25 micrograms/ml. The growth of 80.8% of E. coli was inhibited at concentration of less than 0.1 microgram/ml. The growth of 88.5% of K. pneumoniae was inhibited at concentration of less than 0.2 microgram/ml. The growth of 81.0% of Salmonella sp. was inhibited at concentration of less than 1.56 microgram/ml. The distribution of sensitivity of P. aeruginosa was 12.5- greater than 100 micrograms/ml and the peak of distribution was 25.0 micrograms/ml. The distribution of sensitivity of GM-resistance P. aeruginosa (greater than or equal to 25 micrograms/ml) was 12.5-50 microgram/ml and 5 of 8 strains were inhibited at concentration of less than 25 micrograms/ml. Phagocytosis was determined by Quie's method. Phagocytosis of E. coli, K. pneumoniae, Proteus vulgaris and Enterobacter cloacae by human polymorphonuclear neutrophil was more enhanced in the presence of 1 MIC and 1/2 MIC for 6059-S than for cefazolin at 4 and 6 hours after incubation. But phagocytosis of S. aureus did not enhanced in the presence of 6059-S. 6059-S was given by intravenous administration for 5 minutes and drip infusion for one hour at a single dose of 10 mg/kg of 6059-S to 3 and 4 children respectively. After intravenous administration of 6059-S, the mean peak serum level was 76.0 +/- 2.0 micrograms/ml at 15 minutes, 36.0 +/- 2.8 micrograms/ml at one hour, 1.5 +/- 0.4 micrograms/ml at 6 hours respectively. Half-life time was 1.3 hours. And after drip infusion of 6059-S was 39.9 +/- 9.7 micrograms/ml at one hour, 11.7 +/- 4.8 micrograms/ml at 3 hours and 1.8 +/- 1.4 micrograms/ml at 7 hours respectively. Half-life time was 1.4 hours. The mean urinary excretion rate was 90.4 +/- 6.1%, 76.5 +/- 16.0% up to 6 hours after intravenous administration and drip infusion respectively. 6059-S was effective in 17 cases out of 18 cases with bacterial infections. No side effects were observed except for 4 cases with elevation of serum transaminase, each on case of eosinophilia and of anemia.