The role of RANKL and FGF23 in Assessing Bone Turnover in Type 2 Diabetic Patients.

CONTEXT: Type 2 diabetes is a chronic metabolic disease which affects bone. There is evidence in the literature about some serum markers that reflect the bone turnover metabolism, such as RANKL (Receptor Activator of Nuclear factor Kappa-b Ligand) and Fibroblast Growth Factor (FGF) 23. OBJECTIVE: We aimed to investigate the correlations between RANKL and FGF23 and other diabetes-related factors possibly influencing early bone turnover changes. SUBJECTS AND METHOD: We conducted a cross-sectional analytical study on a group of 171 patients with type 2 diabetes, without Charcot's arthropathy or a history of amputations, in which a complete history and anthropometric, clinical, biochemical and dietary evaluation were performed. We evaluated the serum level of RANKL and FGF 23. RESULTS: RANKL was significantly lower in patients with macroangiopathy (0.42±0.15 pmol/L vs. 0.47±0.2 pmol/L, p=0.001). The level of FGF23 was lower in patients with neuropathy (0.37±0.36 pmol/L vs. 0.41±0.17 pmol/L, p=0.001). We found that FGF23 increased with age, but decreased with the duration of diabetes. We also found an inverse relationship between FGF23 levels and HbA1c, triglycerides, diastolic blood pressure, total proteins, albuminemia. CONCLUSIONS: RANKL was significantly lower in patients with macroangiopathy, and FGF 23 in patients with neuropathy. Therefore, more studies are needed to elucidate their role in early bone turnover changes.

Biomarkers, lactate, and clinical scores as outcome predictors in systemic poisons exposures.

Acute exposure to systemic poisons represents an important challenge in clinical toxicology. We aimed to analyze the potential role of cardiac biomarkers, routine laboratory tests, and clinical scores as morbidity and in-hospital mortality predictors in patients intoxicated with various systemic poisons. We conducted a prospective study on adults acutely exposed to systemic poisons. We determined the PSS, Glasgow Coma Scale (GCS), and we performed electrocardiogram, laboratory tests, lactate and cardiac biomarkers (which were reassessed 4 h, respectively 6 h later). Of 120 patients included, 45% developed complications, 19.2% had a poor outcome, and 5% died. Multivariate logistic regression sustained lactate (odds ratio (OR) 1.58; confidence interval (CI) 95%: 0.97-2.59; p 0.066), MB isoenzyme of creatine kinase (6h-CKMB; OR 1.08; CI 95%: 1.02-1.16; p 0.018) as predictors for a poor outcome. A GCS < 10 (OR 0.113; CI 95%: 0.019-0.658; p 0.015) and 4h-lactate (OR 4.87; CI 95%: 0.79-29.82; p 0.087) predicted mortality after systemic poisons exposure. Receiver operating characteristic analysis showed that brain natriuretic peptide (area under the curve (AUC), 0.96; CI 95%: 0.92-0.99; p < 0.001), lactate (AUC, 0.91; CI 95%: 0.85-0.97; p < 0.001), and 6h-CKMB have good discriminatory capacity for predicting a poor outcome. In conclusion, these biomarkers, lactate, and GCS can be used to predict morbidity and mortality after systemic poisons exposure.

Antibacterial quaternized gellan gum based particles for controlled release of ciprofloxacin with potential dermal applications.

This paper presents the synthesis and characterization of gellan gum derivatives containing quaternary ammonium groups, with the purpose of obtaining particulate controlled release systems for ciprofloxacin. Quaternized gellan derivatives were synthesized by grafting N-(3-chloro-2-hydroxypropyl)-trimethyl ammonium chloride onto gellan primary hydroxyl groups by nucleophilic substitution, in the presence of alkali, under specific reaction conditions using various gellan/N-(3-chloro-2-hydroxypropyl)-trimethyl ammonium chloride molar ratios. Degree of quaternization was determined by (1)H NMR spectroscopy and AgNO3 conductometric titration. Thermal behavior was investigated for all materials by thermogravimetric analysis. A study of the degree of quaternization and effect of the reaction conditions upon activation energy of quaternized gellan derivatives for the main degradation step by applying the Kissinger method at four heating rates is also reported. The novelty that this work brings refers to obtaining quaternized gellan and chitosan based particles with retention of quaternary ammonium moieties' antibacterial activity. In vitro transdermal release tests of ciprofloxacin from loaded particles were carried out on rat skin in isotonic phosphate buffer solution (pH=7.43). Ciprofloxacin was released up to 24 h, confirming quaternized gellan-chitosan particles' potential as controlled release systems for topical dermal applications.

[Detection of extended-spectrum beta-lactamases production in enterobacteriaceae strains]. / Detectarea producerii de beta-lactamaze cu spectru extins la tulpini de Enterobacteriaceae.

Extended-spectrum beta-lactamases (ESBL) cause resistance to ceftazidime, ceftriaxone, cefotaxime and other cephalosporins. The ESBL enzymes are most often derivatives of beta-lactamases from the TEM or SHV group. The aim of our work was to study ESBL production by 35 ceftazidime-resistant strains. We selected these strains among 335 Enterobacteriaceae, isolated in Eastern Romania from healthy carriers and patients, between january-june 1999. To identify the studied strains we used API 20E and API 32E. The ESBL production was established by using both double disk synergy test (DDT) and EXPERT computer program of miniAPI (Bio Merieux). We revealed ESBL production in 26 strains when EXPERT program was used and only 23 when DDT was used. Our results suggest that miniAPI is a better method to study ESBL production than DDT.

Resistance mechanism for a number of non-typhoidic Salmonella strains isolated in Iasi, Romania.

The aim of this study was to find a possible explanation for the resistance pattern of the selected strains and to evaluate the impact in case of isolating such strains. During the period February-March 1998, in the Pediatric Hospital "Sf. Maria" from Iasi, Romania, 12 non-typhoidic Salmonella strains, non-duplicates were isolated from stools of newborns and, in one case, from mother as well. Identification was done by standard methods, and sensitivity testing by disk diffusion method, against the following antimicrobials: Ampicillin (A), Amoxycilin/Clavulanic Acid (AMC), Tetracycline (T), Streptomycin (S), Cloramphenicol (C), Nalidixic Acid (NA), Ciprofloxacin (CIP), Cephalotin (KF), Cefuroxime (CXM), Ceftriaxone (CRO), Cefotaxime (CTX), Ceftazidime (CAZ), Aztreonam (AZT), Imipenem (IPM), Amikacin (AK). All strains showed resistance to: A, AMC, T, S, C, NA, CRO, CAZ, CXM, CTX, KF except one strain, CTX and CRO sensitive. The possible explanation is the production of an extended-spectrum beta-lactamase (ESbLA), detected by microbiological methods (Masuda and clover-leaf). Resistance transfer was realised by using the previously described method. In conjugation experiments we have obtained only one transconjugant, identified as E. coli, that has acquired all resistance determinants. This report highlights on the isolation of multiresistant non-typhoidic Salmonella strains in hospitalised patients without previous antibiotic treatment and possibility of detecting such strains by being aware of the correlation: resistance phenotype-resistance mechanism.

Sensitivity of Enterobacteriaceae strains to the third generation cephalosporins.

The aim of this study was to evaluate the in vitro activity of cefotaxime, ceftriaxone, ceftazidime, ceftibuten and aztreonam against the clinical isolates of Enterobacteriaceae. MICROORGANISMS: A total of 973 enterobacteria isolated from clinical material (urine and faeces) were tested. Strains were collected during 1996-1998 period, in some centers of Eastern Romania. SENSITIVITY STUDY: MICs were performed using the agar dilution method following standardized techniques (NCCLS, 1994). Stock solutions of antibacterial agents were prepared from their respective powder forms, in concentrations ranging from 0.03 to 128 mg/ml. Our results show a good activity of the tested antimicrobials on Escherichia coli, Shigella spp and Klebsiella spp tested, and reveal a particular behaviour for Salmonella spp, characterized by a heterogenous susceptibility. In conclusion, cefotaxime, ceftriaxone, ceftazidime, ceftibuten and aztreonam were active at low concentrations against tested isolates. Against Salmonella spp, these agents were less active: percent of resistant strains by beta-lactamase production was significant.

[New isatin-derived hydrazones and Mannich bases with possible biological activity]. / Noi hidrazone si baze Mannich derivate de la isatina, cu eventuala activitate biologica.

The paper presents a synthesis of six new Mannich bases, five hydrazones derived from 1-piperidino-methyl-5-R-isatin and three copper complex compounds of 3-(3'-R-phenyl-pyridazinil-hydrazone)-indoline-2-ones (R=H, CH3, OCH3). The structure of the new compounds was confirmed by the results of the elementary and spectral analysis. Pharmacodynamic studies indicated that copper complex compounds present effective biological properties. Thus, it can be seen that the experimental carrageenan-induced inflammatory oedema was 58.3% inhibited by the complex V (R=CH3) after oral administration. Antimicrobial tests revealed that only compound V (R=OCH3) shows a moderate antimicrobial activity against the gram-positive and gram-negative bacteria, used in the test.

The antimicrobial susceptibility of Escherichia coli isolated in eastern area of Romania. A surveillance study.

To evaluate the resistance trends for Escherichia coli isolates during 1993-1999 period in Eastern Romania to: ampicillin (A), ampicillin-sulbactam (A/S), ceftazidime (CAZ), cefotaxime (CTA), ceftriaxone (CRO), aztreonam (AZT), ofloxacin (OF), ciprofloxacin (CIP), tetracycline (T) and chloramphenicol (C). We tested 2012 clinical isolates obtained from faeces and urine. MICs were determined by a dilution method in Mueller-Hinton agar (NCCLS guidelines). Resistance rates were analyzed using the NCCLS breakpoints for the fully susceptible category (moderately susceptible strains were classified as resistant). No significant differences were observed in susceptibility of E. coli to ampicillin and ampicillin/sulbactam in the last years. The high percentage of resistant isolates was observed in 1995 for ampicillin (89.7%). Higher incidences of resistance were detected for A, A/S, T; the addition of sulbactam restored A susceptibility only for a small percent. CAZ, CTA, CRO, AZT, OF and CIP resistance among E. coli isolates was progressively increased in the last period.