Search PubMed⌕ Search

Biomedical subjects

M Haraoka

Publications and source records attributed to M Haraoka.

28 records · Page 2Linked to original sources

Enhancement of superoxide production of polymorphonuclear neutrophils by ofloxacin and the effects of the inhibitors of protein kinase C.

Polymorphonuclear neutrophils (PMN) represent an important defense mechanism against bacterial infection. Superoxide is one of the most important factors released by PMN following various stimulations including bacteria. Augmentation of chemiluminescence response of PMN stimulated by phorbol myristate acetate was observed following the addition of 25-200 micrograms/ml of ofloxacin, a new quinolone antimicrobial agent. In addition, the effects of two inhibitors of protein kinase C, staurosporine and H-7, were examined. The augmented superoxide production was inhibited by 1 or 2 microM of staurosporine or 50 or 100 microM of H-7. These results suggest that ofloxacin augments superoxide production of PMN and that this augmentation is probably due to the enhancement of leukocyte protein kinase C.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Suppression of chemotactic activity of neutrophils in hyperosmotic conditions comparable to the renal medulla: partial preservation by phosphoenolpyruvate.

Chemotaxis is one of the most important functions of the polymorphonuclear leukocyte (PMN). In the host defense against pyelonephritis, the renal medulla is a site of interaction between bacteria and PMNs. At this site the osmotic pressure is elevated due to a high concentration of NaCl and urea. We evaluated the in vitro chemotactic activity of PMNs under the hyperosmolar conditions created by high concentrations of NaCl and urea. This activity was suppressed by the stimulation of opsonized zymosan and formyl-methionyl-leucyl-phenylalanine. The inhibition of chemotaxis was partially preserved by phosphoenolpyruvic acid (PEP), a precursor of adenosine triphosphate (ATP), in hyperosmolar NaCl but not in urea. The intracellular content of ATP was increased by supplementing the hyperosmolar NaCl with PEP. These observations suggest that inhibition of the chemotactic activity of PMNs is due to differing mechanisms for each NaCl and urea, and that PEP may protect the PMNs against hyperosmolar NaCl by maintaining ATP content.

Adenosine Triphosphate↗

Effect of recombinant human granulocyte-colony-stimulating factor on renal scarring following infection with MS-piliated bacteria.

Renal scars have been thought to occur only in later stages of chronic pyelonephritis. In our experimental pyelonephritis model, bacteria with mannose-sensitive (MS) pili on its surface promoted renal scarring when inoculated into renal parenchyma. Pretreatment with recombinant human granulocyte-colony-stimulating factor (rhGCSF) inhibited the renal scarring which followed inoculation with MS-piliated bacteria, whereas posttreatment at an early stage of infection had no effect on renal scarring. These findings suggest that rhGCSF may be useful for the prevention of infection without increasing the tissue damage to the renal parenchyma which leads to the renal scarring. Even when rhGCSF is used for treatment of kidney infection, it does not promote increased renal scarring through the increased invasion of leukocytes at the inflammatory site.

Animals↗

Suppressive effect of sera from patients undergoing chronic hemodialysis on neutrophil chemiluminescence response.

To determine the mechanism of easy infectability of uremic patients, we studied the effect of sera from uremic patients who were undergoing chronic hemodialysis on the chemiluminescence (CL) response of polymorphonuclear leukocytes (PMN). The luminol-dependent CL response was examined following stimulation with phorbol myristate acetate (PMA) and N-formyl-methionyl-leucyl-phenylalanine (FMLP). The patient's sera suppressed the CL response following stimulation by PMA, but not by FMLP. These findings suggest that sera from uremic patients undergoing hemodialysis contain a suppressive substance that suppresses the activation of PMNs by PMA.

Female↗

Effect of prednisolone on renal scarring in rats following infection with Serratia marcescens.

Renal scarring is considered a criterion of reflux nephropathy and the end stage of pyelonephritis. Prednisolone, a strong anti-inflammatory drug, at doses of 1 or 2 mg/kg prevented renal scarring in rats following infection with Serratia marcescens. Four or 8 mg/kg of prednisolone, however, did not inhibit renal scar formation. In a time course experiment, renal scarring was prevented when 4-day treatment with prednisolone was initiated 2, 5, or 13 days after infection. These results show that prednisolone is effective in preventing such scarring and suggest the clinical use of this drug for preventing renal scar formation after pyelonephritis and reflux nephropathy.

Animals↗

[The value of an aseptic intermittent catheterization program in the early management of spinal cord injury patients].

From 1979 to 1989, 269 patients with spinal cord injury were managed by an aseptic intermittent catheterization program during the acute phase of their injuries at the Spinal Injuries Center. One hundred fifty one patients with incomplete cord lesion and 36 males with complete tetraplegia were managed by program I, which protects the shocked bladder from overdistention. In contrast, 82 patients with complete cord lesion excluding male tetraplegia were managed by program II, which allows overdistention of the bladder. Of the 187 patients managed by program I, 137 (73.3%) achieved trigger voiding function, 61.3% of whom were completely dry. Of the 82 patients managed by program II, 62 (75.6%) were put to self- or assisted catheterization, 67.7% of whom were dry. The incidence of a grade I, which means normal bladder configuration, was 88.0% for program I and 87.3% for program II during the follow up course. Upper urinary tract deterioration occurred in only one case. Surgical treatment for urinary tract complications was performed in 14 cases (5.2%). These results suggest that the patients with incomplete cord lesion managed by non-distension regimen of the bladder (program I) and those, especially female, with complete cord lesion managed by overdistention regimen of the bladder (program II) achieve urinary continence with excellent urinary prognosis.

Humans↗

Enhanced chemiluminescence response of polymorphonuclear leukocytes by new quinolone antimicrobials.

Some of the many antimicrobial agents (beta-lactams, macrolides, aminoglycosides, tetracyclines, new quinolones; NQs) were reported to have a bactericidal or bacteriostatic effect cooperating with host defense mechanisms including polymorphonuclear neutrophils (PMNs). We investigated the effect of new quinolone antimicrobials on chemiluminescence (CL) response of human PMNs. Among many NQs, we chose ofloxacin, lomefloxacin, fleroxacin, sparfloxacin, AM-1155, NM-394, Q-35, Y-26611 and T-3761. Twenty-five or 100 micrograms/ml of fleroxacin and ofloxacin enhanced luminol-dependent CL response of PMNs up to 1.5-2.0 times compared to the drug free condition. Other antimicrobial agents, however, inhibited CL response. This suggested that fleroxacin and ofloxacin were more efficient in the treatment of bacterial infections with respect to the interaction between antimicrobials and PMNs.

Anti-Infective Agents↗

Effect of ebselen on renal scarring in rats following renal infection.

Renal scarring, which occurs following refluxing pyelonephritis, is considered to be involved in the development of reflux nephropathy. Prevention of renal scar formation requires immediate initiation of antimicrobial treatment; treatment delay results in renal scarring. We demonstrate that Ebselen, an antioxidant agent, given at a dose of 15 mg/kg twice a day prevents renal scarring in rats following direct renal parenchymal bacterial inoculation. In addition, using an ascending pyelonephritis model, which clinically resembles refluxing pyelonephritis in humans, we show that when initiation of antimicrobial treatment was delayed, coadministration of Ebselen prevents renal scar formation. These results show that Ebselen is effective in preventing renal scarring and suggest that the clinical use of this drug may prevent renal scar formation following pyelonephritis and progression to reflux nephropathy.

Animals↗

Combination chemotherapy for infections due to methicillin-resistant Staphylococcus aureus with combination therapy by cefuzonam and fosfomycin or minocycline in the urologic field.

To determine the bacterial and clinical effects of methicillin-resistant Staphylococcus aureus (MRSA) on urinary tract infection (UTI), postoperative wound infection, and bacteremia, 22 strains of MRSA from infected patients were examined; minimal inhibitory concentration (MIC), fractional inhibitory concentration (FIC) index, coagulase typing, and change in MIC in the combination of cefuzonam (CZON) and fosfomycin (FOM) or minocycline (MINO), and the clinical effects of the combination therapy of CZON+FOM or CZON+MINO were investigated in 23 patients. MIC distribution was assessed for 11 drugs: methicillin (DMPPC), cefazolin (CEZ), cefotiam (CTM), cefuzonam (CZON), minocycline (MINO), vancomycin (VCM), arbekacin (ABK), imipenem (IPM), fosfomycin (FOM), ofloxacin (OFLX), and clarithromycin (CAM). For VCM and ABK, MICs ranged from 0.2 to 12.5 micrograms/ml. MINO showed a wide range of MIC, from 0.05 to 25 micrograms/ml. All strains were less sensitive to other antimicrobials. This MIC distribution was assessed in categories by coagulase typing. For CAM, type II strains revealed > or = 100 micrograms/ml of MIC50 and MIC90 compared with 0.2 and 3.13 micrograms/ml in type VII strains. For mixed combinations of CZON and MINO at ratios of 10 to 1 and 40 to 1, the rates of blood concentration for drugs 10 and 120 min after the intravenous injection, MIC distribution was observed between MINO and CZON. For mixed combinations of CZON and FOM at ratios of 1 to 1 and 1 to 4, MIC distribution was more sensitive than for FOM or CZON alone. With respect to the clinical effects of combination therapy by CZON+MINO and CZON+FOM, of seven cases of UTI with CZON+MINO, MRSA was eliminated completely in 4 patients (57.1%). In all patients who received CZON+FOM, MRSA was completely eliminated by this treatment regimen. In 4 of 7 (57.1%) patients with would infection and bacteremia, MRSA was eliminated by the combination of CZON+FOM or CZON+MINO. These results suggest that CZON+FOM is an effective combination in treating UTI and other MRSA infections in urology.

Adult↗