Showing papers in "Chemotherapy in 2002"

Acrylamide: Increased Concentrations in Homemade Food and First Evidence of Its Variable Absorption from Food, Variable Metabolism and Placental and Breast Milk Transfer in Humans

Abstract: We have developed a liquid chromatography/mass spectrometry (LC-MS/MS) assay to determine acrylamide in various body fluids. The assay also allows the reliable quantitation of acrylamide in food. In a total of 11 healthy male and female subjects, we were able to show that acrylamide from food given to humans is in fact absorbed from the gut. The half-lives determined in two male subjects were 2.2 and 7 h. Acrylamide was found in human breast milk and penetrated the human placenta (n = 3). The variability of acrylamide concentrations found in this investigation is most likely caused by variable intersubject bioavailability and metabolism. This may be an important indication that the assessment of the risk from acrylamide for the individual may be very difficult without knowing the concentrations of acrylamide in the body. This should be considered in the design of any risk assessment study or post hoc analysis of earlier studies. At this time, we suggest that pregnant women and breast-feeding mothers avoid acrylamide-containing food.

Protection effects of Taurine supplementation against cisplatin-induced nephrotoxicity in rats.

Abstract: Backgound: Taurine, which is the major intracellular free β-amino acid, is known to be an antioxidant and a membrane-stabilizing agent. This study was designed to investigate the protective role of taurine supplementation against cisplatin-induced nephrotoxicity. Methods: Male Wistar rats were divided into six groups and treated as follows: (1) saline-treated control drinking tap water, (2) saline-treated plus taurine-supplemented (1.5% taurine in the drinking water), (3) saline-treated plus taurine-depleted (3% β-alanine in the drinking water), (4) cisplatin-treated, CDDP 6 mg/kg intraperitoneally, (5) taurine-supplemented plus CDDP-treated and (6) taurine-depleted plus CDDP-treated. Rats were sacrificed 7 days after CDDP treatment, and serum as well as kidneys were isolated and analyzed. Results: CDDP-treated rats showed increased kidney weight as a percentage of total body weight, serum creatinine and BUN levels and decreased serum albumin and calcium levels. Also, CDDP treatment resulted in a depletion of kidney GSH content, a reduction in the kidney glutathione peroxidase (GSH-Px) activity and increased kidney MDA production level. Taurine supplementation attenuated CDDP-induced nephrotoxicity which was manifested by jeopardizing the elevation in serum creatinine and BUN levels and the reduction in serum albumin and calcium levels. Moreover, taurine supplementation restored kidney GSH content and GSH-Px activity and reduced platinum accumulation and MDA production levels in the kidney tissue following CDDP treatment. Histopathological examination of the kidney of CDDP-treated rats revealed tubular atrophy, tubular necrosis and desquamation of renal tubular cells. However, taurine supplementation protected against CDDP-induced histopathological changes. Conclusions: The data suggest that taurine supplementation effectively attenuates the accumulation of platinum within kidney tissue and counteracts the deleterious effect of CDDP on the renal tubular function.

In vitro activity of FK463, a novel lipopeptide antifungal agent, against a variety of clinically important molds.

Abstract: The in vitro antifungal activity of FK463 against a variety of clinically important opportunistic molds was compared with amphotericin B, itraconazole and fluconazole by using the broth microdilution method M27-A specified by the National Committee for Clinical Laboratory Standards. FK463 exhibited potent activity against Aspergillus species, which was superior to those of all other compounds tested. FK463 was also active against the dematiaceous fungi Cladosporium trichoides, Exophiala spinifera, Fonsecaea pedrosoi, and Exophiala dermatitidis except for certain clinical isolates. However, FK463 had no activity against Fusarium solani, Pseudallesheria boydii, and the zygomycetes Absidia corymbifera, Cunninghamella elegans, Rhizopus oryzae, and Rhizopus microsporus var. rhizopodiformis. These results suggest that FK463 has potential utility for the treatment for infections caused by Aspergillus species and dematiaceous fungi.

Efficacy and Tolerability of Once-Daily Therapy with Telithromycin for 5 or 10 Days for the Treatment of Acute Maxillary Sinusitis

Abstract: Background: The efficacy and tolerability of oral telithromycin 800 mg once daily for 5 vs. 10 days were assessed in patients with acute maxillary sinusitis (AMS). Methods: Adults (n = 341) with confirmed AMS diagnosed on clinical signs and symptoms and sinus X-ray showing total opacity or air-fluid level were randomized to receive oral telithromycin for 5 days (followed by placebo for 5 days; n = 170) or 10 days (n = 171). Causative pathogens were isolated by pretreatment sinus puncture (day 1). Clinical and bacteriologic outcomes, and safety and tolerability endpoints were assessed. Results: Clinical cure rates post-therapy (per-protocol; days 17–21) were comparable (91.1% in the 5-day group, n = 123; 91.0% in the 10-day group, n = 133). Bacteriologic eradication rates (per-protocol) were also similar (90.7 vs. 91.3%). Both regimens were well tolerated. Conclusions: A 5-day course of telithromycin 800 mg once daily is an effective, well-tolerated treatment for adults with AMS, comparable to a 10-day regimen.

Inhibition of Nitric Oxide Synthase Aggravates Cisplatin-Induced Nephrotoxicity: Effect of 2-Amino-4-Methylpyridine

Abstract: Background: Nitric oxide (NO) has been shown to play a role in maintaining normal renal function. However, the role of NO in cisplatin (CDDP)-induced nephrotoxicity is still unclear. The aim of the present work was to examine the effect of the NO synthase (NOS) inhibitor, 2-amino-4-methylpyridine, on the severity of CDDP-induced nephrotoxicity. Methods: Male Wistar rats were divided into six groups. Three control groups received plain drinking water or water containing 1.5% L-arginine. One of the two groups receiving plain water was treated with an intraperitoneal injection of 2-amino-4-methylpyridine (1 mg/kg in normal saline), and the other two control groups were injected intraperitoneally with normal saline. Another three groups were treated in the same manner and injected with CDDP (6 mg/kg, i.p.). CDDP was injected 1 h after 2-amino-4-methylpyridine treatment. Rats were sacrificed 7 days after CDDP treatment, and serum as well as kidneys were isolated and analysed. Results: CDDP-treated rats showed increases in the kidney weight as a percentage of the total body weight and serum creatinine and urea levels and decreases in serum albumin and calcium levels. Also, CDDP treatment induced reductions in the kidney total nitrate/nitrite (NOx), reduced glutathione (GSH) and glutathione peroxidase activity (GSH-Px) levels and an increase in the kidney malondialdehyde (MDA) production level. In contrast, 2-amino-4-methylpyridine treatment 1 h prior to CDDP injection induced marked exacerbation of CDDP-induced nephrotoxicity, as manifested by severe aggravation of the indices of nephrotoxicity. Also, 2-amino-4-methylpyridine plus CDDP-treated rats showed exaggeration of the reduction in the kidney total NOx content and GSH-Px activity and elevation of the kidney platinum accumulation level with normalization of the kidney MDA production level and rebound in the kidney GSH content. Histopathologically, CDDP-treated rats showed marked interstitial nephritis, tubular atrophy and tubular necrosis. However, treatment with 2-amino-4-methylpyridine 1 h prior to CDDP injection revealed marked exacerbation of CDDP-induced histopathological changes. Conclusions: The present findings suggest that NO plays a role in CDDP-induced nephrotoxicity. Administration of 2-amino-4-methylpyridine, an NOS inhibitor, exacerbates CDDP-induced nephrotoxicity.

Combination treatment of influenza A virus infections in cell culture and in mice with the cyclopentane neuraminidase inhibitor RWJ-270201 and ribavirin.

Abstract: Treatment of virus infections with compounds acting by different mechanisms may lead to more potent effects when these agents are used in combination. Under this premise, two known active influenza virus inhibitors, ribavirin and the novel cyclopentane influenza virus neuraminidase inhibitor (1S,2S,3R,4R)-3-[(1S)-(acetylamino)-2-ethylbutyl]-4-[(aminoiminomethyl)amino]-2-hydroxy-cyclopentanecarboxylic acid (RWJ-270201, BCX-1812) were studied. Experiments in cell culture demonstrated that RWJ-270201 plus ribavirin synergistically reduced extracellular influenza A/NWS/33 (H1N1) virus yields at low concentrations of each inhibitor. Mice were treated with ribavirin at 20 and 6.25 mg/kg/day combined with RWJ-270201 at 1, 0.32, or 0.1 mg/kg/day, or used alone. Treatments were twice daily for 5 days starting 4 h before exposure to influenza A/NWS virus. Only RWJ-270201 alone at 1 mg/kg/day significantly prevented mortality. In contrast, most drug combinations increased survival significantly compared to the placebo group. Doses of the two compounds used in combination delayed the mean day of death, and improved arterial oxygen saturation levels, as measured on day 11 of the infection. The combination of the two inhibitors produced additive to synergistic interactions in these mouse experiments with no enhancement of host toxicity. Treatment of influenza infections in the clinical setting may benefit by these two agents in combination.

Pharmacokinetics and absolute oral bioavailability of an 800-mg oral dose of telithromycin in healthy young and elderly volunteers.

Abstract: Background: This two-way, randomized, single-dose, crossover study determined the pharmacokinetics and absolute oral bioavailability of telithromycin in young and elderly healthy subjects. Methods: Twelve young (18–40 years) and 12 elderly (>65 years and ≤85 years) subjects received a single 800-mg oral dose of telithromycin or an intravenous infusion of 400 mg (young subjects) or 480 mg (elderly subjects) of telithromycin over 2.5 h in two treatment periods, separated by a 1-week washout period. The plasma concentrations and pharmacokinetic parameters of telithromycin and its major metabolite, RU 76363, were determined. Absolute oral bioavailability was calculated using the area under the plasma concentration-time curve (AUC) from zero hours to infinity. Results: The absolute oral bioavailability of telithromycin was 57% in both young and elderly subjects. The AUC for the metabolite was lower after intravenous infusion of telithromycin, indicating first-pass loss following oral administration. Telithromycin was well tolerated in both groups of subjects. Conclusions: Telithromycin has an absolute oral bioavailability of 57% in young and elderly subjects and is well tolerated.

Investigation of the anti-HIV properties of oxihumate.

Abstract: A unique process has been developed to convert bituminous coal by controlled wet oxidation followed by base treatment to a water-soluble humate called oxihumate. Oxihumate inhibited HIV-1 infection of MT-2 cells with an IC(50) of 12.5 microg/ml. Treatment of free and cell-attached HIV with oxihumate irreversibly reduced infectivity, while the susceptibility of target cells to the virus was not impaired by treatment prior to infection. The infectivity of the HIV particles was inhibited by interference with CD4 binding and the V3 loop-mediated step of virus entry. No viral resistance to oxihumate developed over a 12-week period in vitro. Oxihumate therefore holds promise for the treatment of HIV-infected patients.

Actions of farnesol and xylitol against Staphylococcus aureus.

Abstract: Background: Heavy colonization of atopic dermatitis (AD) with Staphylococcus aureus is well documented. The isolation rate of methicillin-resistant S. au

Biliary Excretion of Antimicrobial Drugs

Abstract: The development of drugs able to prevent and cure bacterial infections is one of the 20th century's major contributions to human longevity and quality of life Antibacterial agents are among the most commonly prescribed drugs of any kind worldwide Used appropriately, these drugs are lifesaving To eliminate an infection as rapidly as possible, a sufficient concentration of the drug(s) chosen must reach the site of infection Serum/tissue concentration is a result of various parameters such as absorption, excretion, protein binding and metabolic inactivation Biliary excretion is an important route for the elimination of some drugs and drug metabolites in humans Thus, drugs with a high bile concentration are indicated for the treatment of gallbladder infectious diseases We present a review of a large number of antimicrobial agents most commonly used in daily clinical practice, with regard to their biliary excretion

Bcl-xL antisense oligonucleotides chemosensitize human glioblastoma cells.

Abstract: Background: Resistance to chemotherapy in glioblastoma has been linked to the expression of antiapoptotic Bcl-2 family members including Bcl-xL. Methods: Bcl-xL expression was specifically reduced in M059K glioblastoma cells with antisense oligonucleotides (ISIS 16009, ISIS 16967) as assessed by Western blotting. Induction of apoptosis by treatment with antisense oligonucleotides in combination with paclitaxel in cell culture was monitored by WST-1 assays and flow cytometric analysis. Results: Antisense oligonucleotide-mediated reduction of Bcl-xL levels led to enhanced cytotoxicity in M059K cells when compared to the use of a mismatch control oligonucleotide (p < 0.001). A decreased threshold for the induction of apoptosis led to significantly enhanced cytotoxic responses to paclitaxel treatment in WST-1 assays (p < 0.001) and flow cytometric analyses. Conclusion: Combination treatment using Bcl-xL antisense oligonucleotides and paclitaxel may qualify as a promising strategy to ultimately improve the clinical outcome of glioblastoma.

Penetration of ravuconazole, a new triazole antifungal, into rat tissues.

Abstract: Ravuconazole (BMS 207147, ER-30346) is a long-lasting triazole antifungal agent active against a broad spectrum of fungal pathogens including non-albicans Candida, Aspergillus, Cryptococcus and key dermatophytic fungi. The penetration of ravuconazole into rat tissues was examined. Fifty-five 7-week-old specific pathogen free female rats were used in this study. Plasma, lung and uterus tissue of rats were taken at 1, 2, 4, 8, 12, 16, 24, 32, 48, 60, and 72 h (n = 5) after oral administration of 10 mg/kg of ravuconazole. The quantitative assays of ravuconazole by HPLC after the extraction with diethylether were conducted for each tissue sample homogenate. tmax, t 1/2, and Cmax of ravuconazole is 8 h, 16.9 h and 1.68 µg/ml, respectively. The concentrations of ravuconazole in rat uterus and lung tissues were 2–to 6 times higher than the corresponding blood concentrations. The ratio of plasma to lung levels of ravuconazole was superior to the published data of other azoles. Considering its antifungal spectrum, ravuconazole would thus be a good candidate for treatment of deep-seated fungal infections caused by Candida, Aspergillus and Cryptococcus.

Antiproliferative activity of the extract of Gleditsia sinensis fruit on human solid tumour cell lines

Abstract: Background The fruit extract of Gleditsia sinensis Lam. (GSE) is a traditional herbal medicine that is saponin-rich. However, its activity on solid tumour cell lines has never been demonstrated. Methods The activity of GSE was demonstrated in four cancer cell lines (breast cancer MCF-7, MDA-MB231, hepatoblastoma HepG2 and oesophageal squamous carcinoma cell line SLMT-1) using MTT assay, anchorage-independent clonogenicity assay, DNA laddering and in situ cell death detection. Results The mean MTT(50) (the mean concentration of GSE to reduce MTT activity by 50%) ranged from 16 to 20 microg/ml of GSE. An anchorage-independent clonogenicity assay showed that all of the four solid tumour cell lines gradually lost their regeneration potential after treatment with GSE, DNA fragmentation and TUNEL analysis demonstrated that the action of GSE is both dose- and time course-dependent. Conclusions Our results suggest that GSE has a cytotoxic activity and can induce apoptosis in human solid tumour cell lines.

Bactericidal Effect of Combinations of Antibiotic and Antineoplastic Agents against Staphylococcus aureus and Escherichia coli.

Abstract: Background: The bactericidal effect of some antibiotic and antineoplastic agents commonly used in clinical practice was investigated to analyse whether the combinations act synergistically, have indifferent or antagonistic antibacterial effects compared to the effect of the antibiotics alone. Methods: The rate of killing of meropenem, ceftazidime and tobramycin was studied against six different strains of Staphylococcus aureus and Escherichia coli, and the results were compared to the rate of killing of the antibiotics in combination with the cytostatic drugs doxorubicin, etoposide and 5-fluorouracil (5-FU). Results: Tobramycin showed synergy against two strains of S. aureus after 3 h in the presence of 5-FU and against one strain of S. aureus in the presence of doxorubicin. Meropenem induced an antagonistic bactericidal effect against one isolate of S. aureus after 24 h. Ceftazidime expressed an indifferent bactericidal effect together with the cytostatic agents. The antineoplastic agents had no impact on the bacterial killing of any of the antibiotics against E. coli. Conclusions: Tobramycin expressed a significantly better bactericidal effect against S. aureus after 3 h in the presence of doxorubicin and 5-FU than tobramycin alone. Meropenem expressed antagonism against one clinical strain of S. aureus, but the cytostatic drugs did not affect the killing of other strains tested. Ceftazidime expressed indifferent bactericidal activity together with the antineoplastic agents.

Central venous catheter infections in patients with acute leukemia.

Abstract: Background: Central venous catheters (CVCs) have become an essential tool for an appropriate management of patients with acute leukemia. Infectious complications are a major concern

Ceftriaxone versus Other Cephalosporins for Perioperative Antibiotic Prophylaxis: A Meta-Analysis of 43 Randomized Controlled Trials

Abstract: The efficacy of ceftriaxone versus other cephalosporins in the perioperative prophylaxis of surgical wound, urinary tract and respiratory tract infections was compared in a meta-analysis of randomized

A Pilot Trial of Combination Cisplatin, 5-Fluorouracil and Interferon-α in the Treatment of Advanced Esophageal Carcinoma

Abstract: Background/Objectives: Based on the synergistic effect between cisplatin and 5-fluorouracil (5-FU), and between 5-FU and interferon-α, we conducted a trial to assess the response ra

Multiple-dose pharmacokinetics and excretion balance of gatifloxacin, a new fluoroquinolone antibiotic, following oral administration to healthy Caucasian volunteers.

Abstract: The multiple-dose pharmacokinetics and excretion balance of gatifloxacin were evaluated in 42 healthy Caucasian volunteers. Following multiple oral doses of 400 and 600 mg, the pharmacokinetics of gatifloxacin were similar on days 1 and 15, suggesting no therapeutically relevant time-dependent changes in the pharmacokinetics of gatifloxacin at the doses and duration of dosing studied. Gatifloxacin was rapidly absorbed and a favourable elimination half-life of 7-8 h was evaluated. Saliva concentrations were similar to plasma concentrations. The main route of excretion is the urine. After a single dose of 400 mg of gatifloxacin, the recovery in urine was 83% and 5.2% in faeces. Following multiple doses of 400 or 600 mg, the renal excretion was 80 and 77%, respectively. The drug was well tolerated.

Carboplatin Induces Less Apoptosis in the Cochlea of Guinea Pigs than Cisplatin

Abstract: Background: Cisplatin (CDDP) is known to cause inner ear damage while carboplatin (CBDCA) induces less ototoxicity than CDDP. We examined apoptotic changes in the cochlea of guinea pigs after injection of CDDP or CBDCA using immunohistochemical and electrophysiological techniques. Methods: Three days after the injection of each solution, the cochleas were immunohistochemically examined for the presence of fragments of single-stranded DNA (ssDNA). The auditory brain stem response was recorded before and three days after the injection. Results: We detected fragments of ssDNA in the stria vascularis and the spiral ligament of the CDDP-treated cochlea. In this group, the threshold of the auditory brainstem response was significantly elevated, however, in the CBDCA group, no apparent change of the threshold was detected. In the CBDCA group, fragments of ssDNA were detected in the stria vascularis and the spiral ligament. The number of cells that stained positive for ssDNA, was less than that in the CDDP group. Conclusions: Our findings indicate that CBDCA induces less apoptosis than CDDP and that this phenomenon contributes to the ototoxicity of CDDP.

The activity of levofloxacin and comparator agents against clinical isolates of Streptococcus pneumoniae collected worldwide during 1999 and 2000.

Abstract: Background: Increases in penicillin-resistant Streptococcus pneumoniae have been documented worldwide. Methods: During 1999 and 2000, 5,015 S. pneumoniae isolates were collected from 13 countries on five continents and tested for antimicrobial susceptibility. Results: Penicillin resistance rates were as follows: South Korea, 70.1%; Hong Kong, 50.3%; Thailand, 39.3%; France, 28.7%; Spain, 24.8%; Mexico, 18.1%; Ireland, 11.8%; South Africa, 11.1%; Italy, 9.4%; United Kingdom, 3.1%; Brazil, 2.9%; China, 2.3%, and Germany, 0.7%. Resistance to azithromycin, clarithromycin and trimethoprim-sulfamethoxazole was commonly associated with penicillin resistance. Levofloxacin-resistant isolates were detected in 8 of 13 countries: Germany (0.2%), France (0.4%), Thailand (0.5%), South Korea (0.9%), Mexico (1.5%), Spain (1.6%), China (3.3%) and Hong Kong (8.0%). Multidrug resistance (resistance to ≧3 antimicrobial classes) occurred in 626/5,015 isolates (12.5%). Levofloxacin was active against 96.0% (601/626) of the multidrug-resistant (MDR) isolates and 99.7% (4,374/4,389) of the non-MDR isolates. Conclusion: Although relatively high levels of levofloxacin resistance were detected in China and Hong Kong, overall, levofloxacin remained active against >99% of clinical isolates of S. pneumoniae despite their resistance to other agents. Continued surveillance of S. pneumoniae will track any changes in levofloxacin activity, should they occur.

Report of a case with polymicrobial endocarditis related to multiresistant strains.

Abstract: We present a patient with polymicrobial endocarditis who had been operated on previously for a mycotic aneurysm and was seen at the cardiology clinic because of palpitations related to effort. A transesophageal echocardiogram revealed a 15-mm vegetation on his aortic valve. Staphylococcus epidermidis and Corynebacterium striatum were isolated from the blood cultures. Both strains were multiresistant (susceptible to 3 antibiotics at most) against chemotherapy in vitro. Microbiological eradication was not achieved from blood cultures even after applying antimicrobial therapy with effective antibiotics as determined with an antibiotic susceptibility test. For this reason, the patient underwent valve replacement. He was discharged from hospital in fairly good health.

Comparative pharmacokinetic and pharmacodynamic profile of piperacillin/tazobactam 3.375G Q4H and 4.5G Q6H.

Abstract: When piperacillin/tazobactam has been used to treat hospitalized patients with serious infections, including nosocomial pneumonia caused by Pseudomonas aeruginosa , it has usually be

Effect of Micafungin (FK463) on Candida albicans adherence to epithelial cells.

Abstract: Background: Adherence is considered a major virulence trait of Candida albicans . FK463 is a new investigational intravenous antifungal of the ‘candin family’ with

Esberitox® N as Supportive Therapy when Providing Standard Antibiotic Treatment in Subjects with a Severe Bacterial Infection (Acute Exacerbation of Chronic Bronchitis)

Abstract: 53 patients with planned antibiotic therapy for the treatment of acute exacerbation of chronic bronchitis as an example of a severe bacterial infection requiring antibiotics were included in a prospec

Antiviral activity of Petiveria alliacea against the bovine viral diarrhea virus.

Abstract: Background: Natural products are a relevant source of antiviral drugs. Five medicinal plants used in Argentina have been assayed to detect inhibition of viral growth. Metho

Influence of Mucin on the Activity of the Antiseptic Lavasept® against Staphylococcus aureus

Abstract: Background: Lavasept®, containing the polymeric biguanide polyhexanide, may be effective against Staphylococcus aureus colonizing the nasal mucosa. To

Irinotecan (CPT-11) in patients with advanced colon carcinoma relapsing after 5-fluorouracil-leucovorin combination.

Abstract: The purpose of the present study was to investigate the association between performance status (PS) and mean dose of irinotecan (CPT-11) in patients with recurrent advanced colorectal cancer relapsing after 5-fluorouracil and leucovorin chemotherapy. Patients who had completed their last chemotherapy course with 5-fluorouracil and leucovorin for at least 6 weeks and progressed were included. Based on PS, we administered a starting dose of 250 mg/m2 in patients with a PS 70–80 (group A), and 350 mg/m2 for those with a PS > 80 (group B). Of a total of 90 treated patients, all were evaluable, 18 had a partial response (PR) (20%), 39 stable disease (43%), and 15 progressed (37%). No significant difference was noticed between patients with PS ≧ 90 or ≤ 80 (p = 0.925), or between those who received a mean dose of CPT-11 ≧300 or ≤300 (p = 0.602), for response, survival and time to progression. Toxicity was increased in group B as expected, with significant differences for acute cholinergic syndrome (p = 0.02), diarrhea after the first 24 h (p = 0.03) and severe diarrhea (p = 0.03). According to these results, we conclude that response to CPT-11 is independent of its dose, and that a dose of 250 mg/m2 every 3 weeks might be a cost-effective and less toxic alternative in this setting. However, further adequately powered phase II or III randomized studies might be required in order to confirm this observation.

Infectious endocarditis due to Yersinia enterocolitica.

Abstract: Yersinia enterocolitica is a gram-negative coccobacillus. Y. enterocolitica infection is acquired by humans via the oral route. Infection due to Y. enterocolitica was first observed in 1933 in New York. Y. enterocolitica septicemia has been increasingly recognized in recent years, whereas endocarditis due to Y. enterocolitica is a rare manifestation. We herein describe a patient who developed Y. enterocolitica endocarditis and was successfully treated with a combination of drugs consisting of a quinolone (ofloxacin) and an aminoglycoside (netilmicin).

Modified ESHAP as Salvage Chemotherapy for Recurrent or Refractory Non-Hodgkin’s Lymphoma: Results of a Single-Center Study of 32 Patients

Abstract: Background: We have evaluated the clinical efficacy and toxicity of a modified etoposide, methylprednisolone, cytarabine and cisplatin (ESHAP) chemotherapy regimen that has been use

Cytotoxic effects of diazenes on tumor cells in vitro.

Abstract: Background: We have shown previously that diazenecarboxamides (diazenes) were cytotoxic for several tumor cell lines. Their target seems to be the intracellular glutathione (GSH). To improve the solubility and biological activity of these drugs, new compounds have been synthesized. In the present study we examined the cytotoxic effect of six new diazenes: BR-25, UP-39, UP-11, JK-1024, RL-514 and RL-625. Methods: The cytotoxicity of diazenes was tested on nine human tumor cell lines: laryngeal carcinoma HEp2 cells, cervical carcinoma HeLa cells, mammary carcinoma MCF-7 cells, breast adenocarcinoma SK-BR-3 cells, and glioblastoma A1235 cells and their four drug-resistant cell lines. Cytotoxicity was determined using the colorimetric MTT assay. The intracellular GSH content (following the treatment with diazenes) was examined spectrophotometrically in human cervical carcinoma cells by the procedure developed by Tietze. Results: Results show that diazene UP-39 was mostly efficient, significantly reducing the cell survival of all nine cell lines examined, including four drug-resistant cell lines. Diazenes UP-11, RL-514 and BR-25 given in the highest concentrations decreased the survival of some examined cell lines, but to less than 50%. Diazenes RL-625 and JK-1024 had no influence on the cell survival. None of the examined diazenes significantly influenced the intracellular level of GSH. Conclusion: Our results suggest that diazene UP-39 may be a promising new drug for the treatment of tumors and encourage further research on this compound.