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PubMed2005

Protective effect of a protein kinase inhibitor on cellular injury induced by cephaloridine in the porcine kidney cell line LLC-PK(1).

We investigated the effects of a protein kinase C inhibitor and a tyrosine kinase inhibitor on the cellular injury induced by cephaloridine in an established renal epithelial cell line, LLC-PK(1). Cephaloridine increased the leakage of lactate dehydrogenase (LDH) from LLC-PK(1) cells into the medium and also caused an increase in the level of lipid peroxide (index of oxidative stress) in the cells. Treatment of the cells with a hydroxyl radical scavenger, dimethylthiourea (DMTU), inhibited the increases in LDH leakage and lipid peroxidation in LLC-PK(1) cells exposed to cephaloridine. A protein kinase C inhibitor, H-7, and tyrosine kinase inhibitors, genistein and lavendustinA, inhibited the increases in LDH leakage and lipid peroxidation in LLC-PK(1) cells exposed to cephaloridine. These results suggest that a signaling pathway which involves protein kinase C and tyrosine kinase plays a role in the generation of reactive oxygen species in LLC-PK(1) cells damaged by cephaloridine.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1975

[Penetration of cephaloridine and cephalothin into the cerebrospinal fluid-clinical study (author's transl)].

There were 35 cases, treated with Cephaloridine or Cephalothin after neurosurgical operation. Neurological surgeon always troubled with passage of blood-brain barrier when drug was given. Antibiotics was not exceptionally, therefore we, neurological surgeon, must select the effective drug to bacterium, that which penetrated enough to the intracranial organ through the blood-brain barrier. In this paper, we measured the concentration of Cephaloridine and Cephalothin into cerebrospinal fluid in the cases with non inflammatory meninges. We collected the cerebrospinal fluid from continued ventricle tap and serum, then measured the concentration of the drug with bioassay. Cephaloridie treated cases. 22 cases. 1) 1 g intramuscular injection. 4 cases. Serum level got to highest value, 64 mug/ml (mean value) 1 hour after injection. CSF level got to maximum concentration 46.8 mug/ml. (mean value) serum mean level 21.5 mug/ml. CSF mean level 0.73 mug/ml. 2) 1 g 3 minutes-intravenous injection 5 cases. Serum level got to highest value 67.5 mug/ml. CSF maximum level was 5.25 mug/ml. Serum mean level 19.74 mug/ml. CSF mean level 0.61 mug/ml. 3) 1 g 1 hour-intravenous drip. 9 cases. Serum maximum level 121.0 mug/ml. CSF maximum level 2.30 mug/ml. Serum mean level 20.08 mug/ml. CSF mean level 0.67 mug/ml. 4) 1 g 8 hours-intravenous drip. 3 cases. Serum maximum level 61.0 mug/ml. CSF maximum level 1.36 mug/ml. Serum mean level 14.78 mug/ml. CSF mean level 0.47 mug/ml. Cephalothin treated cases, 12 cases. 1) 1 g 8 hours-intravenous drip, 4 cases. In fact we could detect the drug only in one case, in CSF, and we could not in other three cases. In KF - 4 case, serum maximum concentration was 26.0 mug/ml, CSF maximum concentration was 0.07 mug/ml. Serum mean level 16.97 mug/ml. CSF mean level 0.01 mug/ml 2) 2 g 1 hour-intravenous drip, 9 cases. Serum maximum level 690.0 mug/ml. CSF maximum level 2.03 mug/ml. Serum mean level 29.59 mug/ml. CSF mean level 0.06 mug/ml. In cephaloridine cases, the tendency was observed, that which, as concentration of the drug in CSF increased, cell count and protein decreased, and, as concentration of the drug decreased, cell count and protein increased. CSF/serum concentration ratio of Cephaloridine increased, when time passed, in intramuscular, 3 minutes intravenous, and 1 hour-intravenous drip group. Then only in 8-hours-intravenous prip group. Then only in 8-hours-intravenous drip group, concentration ratio decreased. In Cephaloridine group, mean value of CSF/serum ratio showed. 1 g i.m. 0.084 1 g 3 minutes-i.v. 0.098 1 g 1 hour-i.v. 0.194 1 g 8 hours-i.v. 0.044.

Adolescent↗
PubMed1979

Effect of cephaloridine on respiration by renal cortical mitochondria.

The effects of the nephrotoxic antibiotic, cephaloridine, were studied in rabbit renal cortical mitochondria. Mitochondria from animals which received a toxic dose of 200 mg/kg of the drug 2 hr before sacrifice (in vivo exposure) had significantly decreased rates of respiration compared with those of mitochondria from untreated control animals. In vitro exposure of normal mitochondria to cephaloridine resulted in a qualitatively similar decrease of respiration. With both in vivo and in vitro exposure, inhibition was greatest with ADP-dependent respiration using succinate as substrate. The severity of in vitro inhibition of respiration showed some correlation to the degree of in situ cytotoxicity at different cephaloridine concentrations. The results are in agreement with the finding of a reduction of rates of respiration in renal tubule suspensions after similar in vivo and in vitro exposure to cephaloridine. These studies provide preliminary evidence that cephaloridine nephrotoxicity may be mediated through an inhibitory effect on mitochondrial respiration.

Adenosine Diphosphate↗
PubMed1983

Effects of piperonyl butoxide on cephalosporin nephrotoxicity in the rabbit. An effect on cephaloridine transport.

To evaluate the hypothesis that cytochrome P-450 mixed-function oxidase (MFO) activity may have a causal role in the production of cephalosporin nephrotoxicity, the effects of the MFO inhibitors cobaltous chloride and piperonyl butoxide on the nephrotoxicity of cephaloridine in the rabbit were examined. Although cobaltous chloride had no effect on cephaloridine nephrotoxicity, piperonyl butoxide had a significant protective effect. However, in correlated studies of the effects on the renal cortical uptake and disappearance of cephaloridine, it was found that piperonyl butoxide significantly reduces (by 50%) the cortical concentrations of the cephalosporin, both decreasing its uptake by and increasing its disappearance from tubular cells. Finally, we evaluated the effect of piperonyl butoxide on the nephrotoxicity of cephaloglycin, a more toxic cephalosporin that lacks the thiophene side-ring proposed as the target of MFO activation in earlier studies with cephaloridine. No protection against cephaloglycin was found. It is concluded that these inhibitors of MFO activity do not reduce cephalosporin nephrotoxicity in general, and that the reduction of cephaloridine toxicity by piperonyl butoxide can be explained by an effect on the intracellular concentrations of that particular cephalosporin.

Acute Kidney Injury↗
PubMed1977

Nephrotoxicity of cephaloridine in newborn rabbits: role of the renal anionic transport system.

The nephrotoxicity of cephaloridine, cefazolin and mercuric chloride was studied in rabbits of various ages. Cephaloridine produced dose-related elevations in serum urea nitrogen, creatinine and renal tubular necrosis in adult and 30-day-old rabbits, only slight changes at 15 days of age and no effect in 5-day-old rabbits. Cefazolin also produced dose-related nephrotoxicity in adult rabbits but no effect in 15-day-old rabbits. Mercuric chloride administration resulted in similar nephrotoxicity in 5-, 15- and 30-day-old rabbits and adults. The development of susceptibility to cephaloridine nephrotoxicity paralleled the maturation of the renal anionic transport system as determined by the accumulation of p-aminohippurate by renal cortical slices in vitro. Substrate stimulation of the anionic transport system by p-aminohippurate or penicillin increased the nephrotoxicity of cephaloridine in between rabbits. The authors concluded that the lack of cephaloridine nephrotoxicity in newborn rabbits is due to the incomplete development of the renal anionic transport system.

Animals↗
PubMed1978

Primary appendectomy. The effect of prophylatic cephaloridine on postoperative wound infection.

A prospective, randomized, double-blind study on the effect of cephaloridine prophylaxis in the surgical management of appendicitis was performed. Of the 139 patients studied, 70 received cephaloridine and 69 received placebo prophylaxis. Both groups of patients were well matched with regard to age, sex, operative findings, and bacteria isolated at operation. Postoperative wound infections were detected in 11.6% of placebo-treated patients and in 1.4% of cephaloridine-treated patients (P less than .02). Prophylactic treatment with cephaloridine of patients undergoing surgery for uncomplicated appendicitis resulted in a perceptible reduction in the rate of postoperative wound infection.

Acute Disease↗
PubMed1979

The interaction of cephaloridine with model membrane systems and rat kidney lysosomes.

The antibiotic cephaloridine has been shown to interact with phospholipid structures, using the techniques of ultraviolet difference spectroscopy, surface pressure measurements and liposome models. The results indicate that this interaction is at least partly hydrophobic in nature and help explain the disruptive effects of high concentrations of cephaloridine on both artificial and natural phospholipid structures (lysosomes). Low concentrations of cephaloridine were shown to inhibit a lysosomal membrane-bound phospholipase 2 and it is suggested that such an inhibition may explain the cephaloridine-induced stabilization of rat-kidney lysosomes.

Animals↗
PubMedDate not supplied

Therapy of staphylococcal infections: (a comparative study of cephaloridine and gentamicin).

Two groups of 38 patients have been treated for staphylococcal infection with either cephaloridine (4 gm daily) or gentamicin (320 mg daily) by the intramuscular route. The rate of favorable clinical response was higher among the patients who received cephaloridine (78.8 per cent) than among those who were treated with gentamicin (60.5 per cent). No death related to the infection occurred in the cephaloridine-treated patients. The mean peak and trough antibacterial activity reached in the serum of the patients after injection of the antibiotics was higher in patients receiving cephaloridine (1/64 and 1/16) than in those treated with gentamicin (1/16 and 1/4). Patients who failed to respond to therapy had often a low antibacterial activity of the serum. These studies suggest that the 1/8 level of bactericidal activity should be attained in the serum one hour after the administration of the antibiotics to allow optimal results in staphylococcal infections.

Adult↗
PubMed1974

Biliary tract excretion of cefazolin, cephalothin, and cephaloridine in the presence of biliary tract disease.

The biliary tract excretion of three cephalosporins, cefazolin, cephaloridine, and cephalothin, was compared in patients with biliary tract disease. In the absence of obstruction, mean antibiotic levels in bile from gall bladder and common duct in patients undergoing cholecystectomy were highest for cefazolin (17 and 31 mug/ml, respectively) than either cephaloridine (7 and 9 mug/ml) or cephalothin (1 and 4 mug/ml). Biliary tract levels generally paralleled serum levels. In no patient with cystic duct obstruction were any of the cephalosporins detectable in appreciable amounts in gall bladder bile. In patients with T-tube drainage given each of the three different cephalosporins on separate days, concentrations of cefazolin in bile were many-fold higher than either cephaloridine or cephalothin. Peak levels of cefazolin in T-tube bile averaged 51 mug/ml after intravenous and 26 mug/ml after intramuscular administration, whereas mean peak levels of cephalothin and cephaloridine were only 6 and 16 mug/ml, respectively. Here, too, T-tube levels reflected serum concentrations and obstruction to biliary flow impaired excretion of each of the drugs.

Biliary Tract↗
PubMed1970

Cephaloridine serum levels in patients on maintenance haemodialysis.

Cephaloridine serum half-life was determined in 11 patients undergoing maintenance haemodialysis. Three of them were anephric. The mean cephaloridine half-life was 10.4 hours. There was an inverse correlation between cephaloridine half-life and the duration of maintenance haemodialysis treatment. Reasons for this are discussed.The effect of haemodialysis with the Kiil dialyser on cephaloridine half-life was studied in three patients.Dosage recommendations for patients on maintenance haemodialysis are suggested.

Adolescent↗
PubMed1968

Sensitivity of penicillinase-forming strains of Staphylococcus aureus and of their penicillinase-negative variants to cephaloridine, cephalothin, methicillin, and benzylpenicillin.

Twenty-eight penicillinase-forming cultures of Staphylococcus aureus and their penicillinase-negative variants were examined for resistance to benzylpenicillin, methicillin, cephalothin, and cephaloridine. The results supported the view that cephaloridine was more easily destroyed by staphylococcal penicillinase than was cephalothin. In our tube-dilution tests, the minimum inhibitory concentration (M.I.C.) of cephaloridine for methicillin-sensitive cultures was never as high as some of the values reported by other workers who used apparently comparable methods. This was probably due to small differences in technique. The M.I.C. is an unsatisfactory measure of the antibiotic sensitivity of an organism which produces an enzyme which destroys the antibiotic.Methicillin-resistant strains of Staph. aureus have an intrinsic resistance of ;heterogenous' type also to benzylpenicillin, cephalothin, and cephaloridine.

Cephaloridine↗
PubMed1980

Controlled clinical trial comparing intra-incisional cephaloridine and Polybactrin Spray.

300 patients undergoing various operations were randomly allocated to receive, intra-incisionally, just before skin suture, either a solution of 1 g cephaloridine or Polybactrin aerosol. An equal number of patients were allocated to each group, and various factors likely to influence the incidence of wound infections were evenly distributed. 13 wound infections (9.8%) developed in the cephaloridine group and 28 (20.1%) in the Polybactrin group (p less than 0.02). In the former group, the infections were milder and there were 44 fewer patient-days of hospitalisation. The difference in infection rates for 'potentially contaminated and contaminated' operations was greater (p less than 0.01), in favour of cephaloridine. Other differences are discussed and some reasons for the superiority of cephaloridine over other agents (e.g., povidone-iodine, ampicillin) are advanced.

Adolescent↗
PubMed1995

Glucocorticoid amelioration of nephrotoxicity: a study of cephaloridine-methylprednisolone interaction in the rat.

Groups of ten male rats were treated with a high challenge dose of cephaloridine (CPH, 3750 mg kg-1), with methylprednisolone (MP, 100 mg kg-1) or with cephaloridine and methylprednisolone (CPH + MP) by single subcutaneous injection. A control group received the injection vehicles only. Urine was collected from all animals daily over 18-h collection periods, up to 96 h after treatment. Blood was collected at 24, 48, 72 and 96 h after treatment. At necropsy, kidneys were weighed, processed and examined histopathologically. Results show that methylprednisolone significantly ameliorated the nephrotoxicity of the challenge dose of cephaloridine. CPH-only treated rats had severe toxic nephrosis characterised by acute tubular necrosis, and elevated blood urea and creatinine. By contrast, the majority of CPH + MP treated rats had only a slight or moderate toxic nephrosis, and had lower blood urea and creatinine levels compared with rats treated with CPH only, indicating preservation of kidney function. Interestingly, rats treated with CPH + MP had higher urinary enzymes (alkaline phosphatase, lactate dehydrogenase, gamma glutamyltransferase and N-acetyl-beta-glucosaminidase) as well as protein and glucose, compared with rats treated with CPH only. This is taken to indicate that rats treated with CPH only had such marked kidney damage and necrosis that the population of cells able to produce these marker enzymes was significantly and rapidly depleted, but the protection afforded by methylprednisolone allowed CPH + MP treated rats to sustain urinary enzyme output. Effects on urinary glucose and other parameters such as body weight and kidney weight demonstrate interactions between glucocorticoid pharmacology and cephaloridine nephrotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

The effects of diethyldithiocarbamate and carbon disulfide on acute nephrotoxicity induced by furan, bromobenzene and cephaloridine in mice.

In previous studies (Masuda and Nakayama, 1983), diethyldithiocarbamate (DTC) and carbon disulfide (CS2) have been found to be protective against acute nephrotoxicity induced by CHCl3 and 1,1-dichloroethylene in normal and CCl4-poisoned mice, and it has been suggested that the protective action of DTC and CS2 might be mediated through inhibition of bioactivation of these nephrotoxicants in the kidney. As an extension of these studies, similar experiments were undertaken with furan, bromobenzene and cephaloridine, other nephrotoxic agents that are also thought to require metabolic activation. DTC or CS2 prevented mice from suffering renal injury induced by furan and bromobenzene, as evidenced by suppression of elevations in plasma urea nitrogen concentration and kidney calcium content and of morphologic alterations. Cephaloridine nephrotoxicity, however, was not prevented. In CCl4-poisoned mice, furan nephrotoxicity was augmented, whereas bromobenzene and cephaloridine nephrotoxicity was suppressed. The augumented furan nephrotoxicity was also prevented by DTC or CS2. These observations suggest that furan, like CHCl3 and 1,1-dichloroethylene, may exert nephrotoxicity through active metabolites formed in the kidney. For bromobenzene and cephaloridine nephrotoxicity, a renal bioactivation mechanism is suspected. DTC and CS2 also protected against hepatotoxicity induced by furan and thiophene.

Animals↗
PubMed1985

Separation of cephaloridine from the rat urine contaminated by feces and diet pellets in high-performance liquid chromatography. Pretreatment with strongly basic anion exchange resin following deproteinization.

In this study, a high-performance liquid chromatographic method including a treatment with ion exchange resin following a deproteinization treatment, was studied for determination of cephaloridine in the rat urine which was contaminated by pieces of feces and diet pellets. The solvent system used was 10% acetonitrile (v/v) in 0.1 M K2 HPO4-H3 PO4 buffer, pH 7.5, and this was isocratically eluted on a reversed-phase column of NOVA-PAK C18. The urine sample containing cephaloridine was deproteinized, treated with a strongly basic anion exchange resin of Dowex-1-Chloride, and then chromatographed. In comparison to the sample treated by the simple deproteinization, the residual substances after the deproteinization, which interfered the cephaloridine peak, were removed by the following treatment with Dowex-1-Chloride, as was confirmed using a three-dimensional computing spectrophotometric monitor. Thus, the present method is considered to be useful in determination of cephaloridine in such body fluids as urine in which many interfering substances are contained.

Animal Feed↗
PubMed1975

Cephalothin and cephaloridine therapy for bacterial meningitis.

The efficacy of cephalothin and cephaloridine in the treatment of bacterial meningitis was evaluated from a review of 106 cases reported in the literature. Fifty-nine percent of 34 patients treated with intravenous cephalothin responded suboptimally; those receiving daily doses of 12 g or more fared significantly better (P less than 0.025). In contrast, 74% of 72 patients treated with cephaloridine responded favorably; those who received concomitant intrathecal cephaloridine responded significantly better (P less than 0.005). These findings indicate that cephalosporin therapy for bacterial meningitis, without concomitant intrathecal medication, is unreliable and that this is probably due to inadequate penetration of the antibiotics into cerebrospinal fluid. In penicillin-allergic patients with pneumococcal, meningococcal, and hemophilus meningitis, chloramphenicol is the agent of choice. For staphylococcal meningitis, intravenous cephalothin at doses of 12 g/day with additional intrathecal cephaloridine at doses of 12.5 to 50 mg/day should be administered concomitantly.

Bacterial Infections↗
PubMed1975

Evaluation of antibacterial activities of cephalosporin antibiotics: cefazolin, cephaloridine, cephalothin, and cephalexin.

The antibacterial activities of 4 cephalosporin antibiotics, cefazolin, cephaloridine, cephalothin and cephalexin, against 330 isolates of bacteria from patients at National Taiwan University Hospital, were determined by an agar plate dilution technique. Cephalosporins possess strong antibacterial activity against gram-positive bacteria except Enterococci. Staphylococcus aureus is the most susceptible among the organisms tested. More than 90% of Staphylococcus aureus strains are suppressed by cefazolin, cephaloridine and cephalothin at the concentrations of 3.13 mug/ml or less, except that 49.1% are suppressed by cephalexin. The relative potency of cephalosporins against Staphylococcus aureus in decreasing order is cephaloridine, cephalothin, cefazolin, and cephalexin. The gram-negative bacilli, Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis are less susceptible to cephalosporins than the gram-positive cocci. Among the cephalosporins, cefazolin is the most active against the gram-negative pathogens tested. The relative potency of antibacterial activity of cephalosporins against E. coli in decreasing order is cefazolin, cephaloridine, cephalexin, and cephalothin. One hour after the intramuscular injection of 500 mg of cefazolin, the maximum concentration of 33.3 mug/ml is reached in the serum. The sufficient high levels are sustained for 8 hours. Very high concentrations of cefazolin are also found in the urine.

Adult↗
PubMed1977

[State of the blood coagulating system in the treatment of puerperal infections using semisynthetic penicillins and cephaloridine].

The effect of some semi-synthetic penicillins, such as methicillin and oxacillin and cephalosporings, such as cephaloridin on the condition of the blood coagulation system in 85 patients with postnatal mastitis and endomyometritis was studied. It was shown that the above antibiotics had no significant effect on the parameters of the blood coagulating system. A decrease in the fibrinogen level was found in the mastitis patients treated with semi-synthetic penicillins and cephaloridin. An increase in the prothrombins index in the patients treated with methicillin oxacillin was shown. The use of the semi-synthetic penicillins and cephaloridin for the therapy of the puerpera with endomyometritis resulted in prolongation of the recalcification period. A decrease in the fibrinolytic activity most pronounced in therapy with cephaloridin was also found. Therefore, the above changes in the blood coagulating system of the puerpera with postnatal infections subjected to short-term treatment courses were insignificant and required no special correction.

Adolescent↗