Potential of ceragenin CSA-13 and its mixture with pluronic F-127 as treatment of topical bacterial infections.

AIMS: Ceragenin CSA-13 is a synthetic mimic of cationic antibacterial peptides, with facial amphiphilic morphology reproduced using a cholic acid scaffold. Previous data have shown that this molecule displays broad-spectrum antibacterial activity, which decreases in the presence of blood plasma. However, at higher concentrations, CSA-13 can cause lysis of erythrocytes. This study was designed to assess in vitro antibacterial and haemolytic activity of CSA-13 in the presence of pluronic F-127. METHODS AND RESULTS: CSA-13 bactericidal activity against clinical strains of bacteria associated with topical infections and in an experimental setting relevant to their pathophysiological environment, such as various epithelial tissue fluids and the airway sputum of patients suffering from cystic fibrosis (CF), was evaluated using minimum inhibitory and minimum bactericidal concentration (MIC/MBC) measurements and bacterial killing assays. We found that in the presence of pluronic F-127, CSA-13 antibacterial activity was only slightly decreased, but CSA-13 haemolytic activity was significantly inhibited. CSA-13 exhibits bacterial killing activity against clinical isolates of Staphylococcus aureus, including methicillin-resistant strains, Pseudomonas aeruginosa present in CF sputa, and biofilms formed by different Gram (+) and Gram (-) bacteria. CSA-13 bactericidal action is partially compromised in the presence of plasma, but is maintained in ascites, cerebrospinal fluid, saliva, and bronchoalveolar lavage fluid. The synergistic action of CSA-13, determined by the use of a standard checkerboard assay, reveals an increase in CSA-13 antibacterial activity in the presence of host defence molecules such as the cathelicidin LL-37 peptide, lysozyme, lactoferrin and secretory phospholipase A (sPLA). CONCLUSION: These results suggest that CSA-13 may be useful to prevent and treat topical infection. SIGNIFICANCE AND IMPACT OF THE STUDY: Combined application of CSA-13 with pluronic F-127 may be beneficial by reducing CSA-13 toxicity.

Association of arylamine N-acetyltransferase (NAT1 and NAT2) genotypes with urinary bladder cancer risk.

Arylamines are known bladder carcinogens deriving from tobacco smoke and environmental pollution. Arylamines are metabolised by NAT1 and NAT2 polymorphic enzymes in reactions of carcinogen activation and detoxification. We analysed genetic polymorphisms in both NAT1 and NAT2 genes in 56 bladder cancer patients and 320 healthy patients. Peripheral blood lymphocytes were collected from each subject and genotyped for NAT1 (six alleles) and NAT2 (four alleles) by PCR-RFLP. A weak association between NAT1 and NAT2 genotypes and bladder cancer risk was found when the genotypes were estimated separately (odds ratio OR 1.2, 95%CI 0.7-2.0, and OR 1.3, 95%CI 0.7-1.9, respectively). Almost all NAT1 genotypes possessing at least one "risk" *10 allele were more frequent in the bladder cancer group than in the control group. There was also an increased frequency of "risk" genotypes along with increased cigarette smoking in bladder cancer patients. The coincidence of NAT1-fast/NAT2-slow appears as a potential risk factor for urinary bladder cancer (OR 1.5, 0.8-3.0), as compared with the other genotype combinations.

Case report. Histoplasmosis in an AIDS paediatric patient.

Histoplasmosis has been little reported among HIV-infected children. We report a case of a 4-year old boy with AIDS who presented with disseminated histoplasmosis diagnosed by lung biopsy. The patient had a good clinical response to amphotericin B followed by itraconazole oral solution.

[The value of computer tomography for diagnosis of seminal vesicle cysts]. / Wartosc tomografii komputerowej w rozpoznawaniu torbieli pecherzyków nasiennych.

Presented report deals with the case of a giant cyst of the left seminal vesicle with major diagnostic difficulties. After urography, cystoscopy, and computer tomography all symptoms in patient with cyst disappeared, and the tumor was not stated during physical examination. Six months later all symptoms in the patient exaggerated. Among diagnostic procedures used only computer tomography visualized giant cyst of the seminal vesicle which occupied the whole pelvis. After surgical excision of the cyst the patient had and erectile dysfunction.

Ceftriaxona em meningites na infância: possibilidade de tratamento ambulatorial / Ceftriaxone in miningitis childhood

Devido ao amplo espectro antimicrobiano e seu esquema de dose única diária, a ceftriaxona tem sido largamente usada para o tratamento de infecçöes graves, incluindo meningite bacteriana. Entre os importantes problemas enfrentados por médicos e pacientes em países desenvolvidos, estäo a falta de leitos hospitalares e a alta incidência de hospitalares. Por estas razöes e baseados em nossa experiência prévia com o uso de ceftriaxona, decidimos estudar a possibilidade de um regime terapêutico que permitisse tratamento ambulatorial de pacientes com meningite bacteriana. Vinte crianças com idades variando entre 3 e 75 meses e com diagnóstico de meningite bacteriana causada por N. meningitidis, S. pneumoniae ou H. influenzae, foram tratadas com dose única...

[Gentamicin level in the prostate and its pharmacokinetics in patients with benign prostatic hypertrophy]. / Stezenie w gruczole krokowym i farmakokinetyka gentamycyny u chorych z lagodnym przerostem gruczolu krokowego.

The study involved 15 male patients with periurethral prostatic adenoma without complete anuresis. The patients were given 80 mg of gentamicin intramuscularly one day before surgery and 80 mg in a one-hour infusion immediately before an operation. Gentamicin blood concentrations were measured. Pharmacokinetic parameters were calculated and dosage schemes for each patient basing on the antibiotic blood levels. Gentamicin levels in removed adenomas were also determined. Adenomas weighed between 18.0 and 45.8 grams while gentamicin concentration ranged from 1.31 to 3.8 micrograms/mL. It was found that gentamicin concentration in adenomas depend upon their weight. Moreover, pharmacokinetic parameters of this antibiotic exert negligible effect on its levels in adenoma.

HMG-CoA reductase activity in the microsomal fraction from human placenta in early and term pregnancy.

The activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) mevalonate: NADP oxidoreductase (CoA acylating; EC 1.1.1.34) in microsomes from early- and term-pregnancy placenta has been found to be 24 +/- 2 and 6 +/- 3 pmol/min per mg protein, respectively. Inactivation of the enzyme required the addition of ATP and Mg2+ and was dependent on the time of preincubation. Reactivation of the enzyme was also dependent on the incubation time and prevented by the presence of fluoride--a phosphoprotein phosphatase inhibitor. These data suggest that (despite a low activity) placental HMG-CoA reductase is covalently modulated via the phosphorylation-dephosphorylation system. The conversion of [14C]acetate and [3H]mevalonate into digitonin precipitable placental sterols indicates that the lower reductase activity in term, than in early, placental microsomes is accompanied by a less active conversion of [14C]acetate in this tissue.