"In-vitro" corrosion behaviour of the magnesium alloy with Al and Zn (AZ31) protected with a biodegradable polycaprolactone coating loaded with hydroxyapatite and cephalexin

Mg alloys are very susceptible to corrosion in physiological media. This behaviour limits its widespread use in biomedical applications as bioresorbable implants, but it can be controlled by applying protective coatings. On one hand, coatings must delay and control the degradation process of the bare alloy and, on the other hand, they must be functional and biocompatible. In this study a biocompatible polycaprolactone (PCL) coating was functionalised with nano hydroxyapatite (HA) particles for enhanced biocompatibility and with an antibiotic, cephalexin, for anti-bacterial purposes and applied on the AZ31 alloy. The chemical composition and the surface morphology of the coated samples, before and after the corrosion tests, were studied by scanning electron microscopy (SEM) coupled with energy dispersive x-ray analysis (EDX) and Raman. The results showed that the presence of additives induced the formation of agglomerates and defects in the coating that resulted in the formation of pores during immersion in Hanks' solution. The corrosion resistance of the coated samples was studied in Hank's solution by electrochemical impedance spectroscopy (EIS). The results evidenced that all the coatings can provide corrosion protection of the bare alloy. However, in the presence of the additives, corrosion protection decreased. The wetting behaviour of the coating was evaluated by the static contact angle method and it was found that the presence of both hydroxyapatite and cephalexin increased the hydrophilic behaviour of the surface. The results showed that it is possible to tailor a composite coating that can store an antibiotic and nano hydroxyapatite particles, while allowing to control the in-vitro corrosion degradation of the bioresorbable Mg alloy AZ31. (C) 2015 Elsevier Ltd. All rights reserved.

Bioequivalence study of two oral formulations of cefadroxil in healthy volunteers

Two different cefadroxil (CAS 50370-12-2) formulations were evaluated for their relative bioavailability in 24 healthy volunteers who received a single 500 mg oral dose of each preparation. An open, randomized clinical trial designed as a two-period crossover study with a 7-day washout period between doses was employed. Plasma samples for assessments of their cefadroxil concentration by HPLC-UV were obtained over 8 h after administration. Values of 48.94 +/- 10.18 mu g . h/ml for test, and 48.51 +/- 9.02 mu g . h/ml for the reference preparation AUC(0-t) demonstrate a nearly identical extend of drug absorption. Maximum plasma concentration C-max of 16.04 +/- 4.94 mu g/ml and 16.01 +/- 4.02 mu g/ml achieved for the test and reference preparations did not differ significantly. The parametric 90% confidence intervals (CI) of the mean of the difference (test-reference) between log-transformed values of the two formulations were 96.80% to 104.51% and 92.01% to 107.00% for AUC(0-t) and C-max, respectively. Since for both AUC(0-t) or C-max the 90% CI values are within the interval proposed by the Food and Drug Administration, the test product is bioequivalent to the reference product for both the rate and extent of absorption after single dose administration.

Outcomes and safety of drug provocation tests

Drug provocation tests (DPTs) are considered the gold standard for identifying adverse drug reactions (ADRs). The aim of this study was to analyze DPT results and discuss severe systemic reactions associated with them. This was a retrospective analysis of 500 patients with ADRs who sought treatment and were submitted to DPTs when indicated between 2006 and 2010. We performed DPTs according to the European Network for Drug Allergy recommendations. Single-blind, placebo-controlled DPTs were performed with antibiotics, local anesthetics, and nonsteroidal anti-inflammatory drugs, as well as with other drugs. Patient characteristics, DPT results, and reactions were analyzed. The sample comprised 198 patients (80.8% of whom were female patients) submitted to 243 DPTs. Ages ranged from 9 to 84 years (mean, 39.9 years). The 243 DPTs were performed with local anesthetics (n = 93), antibiotics (n = 19), acetaminophen (n = 44), benzydamine (n = 33), COX-2 inhibitors (n = 26), dipyrone (n = 7), aspirin (n = 4), or other drugs (n = 17). The results of 4 tests (1.6%) were inconclusive, whereas those of 10 (4.1%) revealed positive reactions to antibiotics (2/19), COX-2 inhibitors (2/26), acetaminophen (3/44), and local anesthetics (3/93). Two severe reactions were observed: cephalexin-induced anaphylactic shock and bupivacaine-induced anaphylaxis without shock. Four patients (2.0%) reacted to the placebo before administration of the drug. Drug provocation tests are safe for use in clinical practice but they should be placebo-controlled and should be performed under the supervision of an allergist. To confirm a presumptive diagnosis and to manage allergies appropriately, it is crucial to perform DPTs. (Allergy Asthma Proc 32:301-306, 2011; doi: 10.2500/aap.2011.32.3450)

MOLECULAR IDENTIFICATION AND ANTIMICROBIAL RESISTANCE PATTERN OF SEVEN CLINICAL ISOLATES OF Nocardia spp. IN BRAZIL

Nocardia is a ubiquitous microorganism related to pyogranulomatous infection, which is difficult to treat in humans and animals. The occurrence of the disease is on the rise in many countries due to an increase in immunosuppressive diseases and treatments. This report of cases from Brazil presents the genotypic characterization and the antimicrobial susceptibility pattern using the disk-diffusion method and inhibitory minimal concentration with E-test® strips. In summary, this report focuses on infections in young adult men, of which three cases were cutaneous, two pulmonary, one neurological and one systemic. The pulmonary, neurological and systemic cases were attributed to immunosuppressive diseases or treatments. Sequencing analysis of the 16S rRNA segments (1491 bp) identified four isolates of Nocardia farcinica, two isolates of Nocardia nova and one isolate of Nocardia asiatica. N. farcinica was involved in two cutaneous, one systemic and other pulmonary cases; N. nova was involved in one neurological and one pulmonary case; and Nocardia asiatica in one cutaneous case. The disk-diffusion antimicrobial susceptibility test showed that the most effective antimicrobials were amikacin (100%), amoxicillin/clavulanate (100%), cephalexin (100%) and ceftiofur (100%), while isolates had presented most resistance to gentamicin (43%), sulfamethoxazole/trimethoprim (43%) and ampicillin (29%). However, on the inhibitory minimal concentration test (MIC test), only one of the four isolates of Nocardia farcinica was resistant to sulfamethoxazole/trimethoprim.

Preliminary study of community-acquired Staphylococcus aureus infection in Manaus Hospital, Amazonia Region, Brazil

Methicillin resistant Staphylococcus aureus is considered a public health problem with a strong potential for dissemination and high rates of morbidity and mortality. In this study we describe bacteriological and epidemiological characteristics of Staphylococcus aureus in Manaus (Amazon region). During the one-year study period (2000-2001), sixteen cases of acute pyogenic multiple abscess were evaluated. Community-acquired S. aureus was identified as causative agent in 10 (62.5%) patients. The strains tested with antimicrobials by discs diffusion method, exhibited a high rate of sensitivity to cephalexin (100%), erythromycin (90%). Oxacillin-susceptible Staphylococcus aureus was 90%. No isolate was resistant to Vancomycin. To our knowledge, no series of community-acquired Staphylococcus aureus in Manaus hospital has been published. Our partial results showed a high rate of antimicrobial sensitivity among community-acquired Staphylococcus aureus in the hospital of Tropical Medicine Institute of Manaus, Amazon Region.

Agar dilution method for susceptibility testing of Neisseria gonorrhoeae

The antibiotic susceptibilities of Neisseria gonorrhoeae isolates obtained from patients attending a clinic for sexually transmitted diseases in Tucumán, Argentina, were determined by the agar dilution method (MIC). 3.5% of the isolates produced ²-lactamase. A total of 96.5% of ²-lactamase negative isolates tested were susceptible to penicillin (MIC < 2 µgml-1); 14.03% of the tested isolates were resistant to tetracycline (MIC < 2 µgml-1), and 98% of the tested isolates were susceptible to spectinomycin (MIC < 64 µgml-1). The MICs for 95% of the isolates, tested for other drugs were: < 2 µgml-1 for cefoxitin, < 0.06 µgml-1 for cefotaxime, < 0.25 µgml-1 for norfloxacin, < 10 µgml-1 for cephaloridine, < 10 µgml-1 for cephalexin, and < 50 µgml-1 for kanamycin. Antibiotic resistance among N. gonorrhoeae isolates from Tucumán, Argentina, appeared to be primarily limited to penicillin and tetracycline, which has been a general use against gonorrhoeae in Tucumán since 1960. Periodic monitoring of the underlying susceptibility profiles of the N. gonorrhoeae strains prevalent in areas of frequent transmission may provide clues regarding treatment options and emerging of drug resistance.

In vitro Comparison of Disk Diffusion and Agar Dilution Antibiotic Susceptibility Test Methods for Neisseria gonorrhoeae

At present, most Neisseria gonorrhoeae testing is done with ß-lactamase and agar dilution tests with common therapeutic agents. Generally, in bacteriological diagnosis laboratories in Argentina, study of antibiotic susceptibility of N.gonorrhoeae is based on ß-lactamase determination and agar dilution method with common therapeutic agents. The National Committee for Clinical Laboratory Standards (NCCLS) has recently described a disk diffusion test that produces results comparable to the reference agar dilution method for antibiotic susceptibility of N.gonorrhoeae, using a dispersion diagram for analyzing the correlation between both techniques. We obtained 57 gonococcal isolates from patients attending a clinic for sexually transmitted diseases in Tucumán, Argentina. Antibiotic susceptibility tests using agar dilution and disk diffusion techniques were compared. The established NCCLS interpretive criteria for both susceptibility methods appeared to be applicable to domestic gonococcal strains. The correlation between the MIC's and the zones of inhibition was studied for penicillin, ampicillin, cefoxitin, spectinomycin, cefotaxime, cephaloridine, cephalexin, tetracycline, norfloxacin and kanamycin. Dispersion diagrams showed a high correlation between both methods.

Determinação espectrofotométrica de cefalexina em formulações farmacêuticas explorando a sua reação de transferência de carga com a quinalizarina

This work proposes a new simple and fast spectrophotometric method for cephalexin determination in pharmaceutical formulations. The method is based on the charge transfer reaction between cephalexin and quinalizarin in dimethylsulfoxide medium. Several analytical parameters related to the system were optimized and the reaction was characterized in terms of stoichiometry. Also, association constant and apparent molar absorptivity of the product were determined. The method presented a limit of detection of 0.46 mg L-1 and a quantification limit of 1.5 mg L-1. It was successfully applied in the determination of cephalexin in two samples of commercial pharmaceutical formulations.

Avaliação de métodos de extração para a determinação de cromo e níquel em formulações farmacêuticas e em matérias-primas usadas na fabricação de medicamentos à base de cefalexina e ciprofloxacino

This paper reports the evaluation of extraction strategies for the treatment of medicine samples to determine chromium and nickel by GFAAS. Different approaches for extraction were evaluated and the most efficient involved magnetic stirring. The metals were quantitatively extracted by stirring 0.20 g samples with 25 mL of 2.0 mol L-1 HCl solution for 60 min. The developed method was successfully applied for the determination of Cr and Ni in tablets containing antibiotics and raw materials, with cephalexin and ciprofloxacin as active ingredients.

A Semi-Selective agar medium to detect the presence of Xanthomonas axonopodis pv. malvacearum in naturally infected cotton seed

A semi-selective agar medium was developed for detection of Xanthomonas axonopodis pv. malvacearum (Xam) in cotton (Gossypium hirsutum) seed. The basic medium was peptone-sucrose-agar (PSA). Criteria for the semi-selective medium were the typical colony characters of Xam and its pathogenicity on cotton. Several systemic fungicides and antibiotics in different concentrations were tested alone or in combination with others. The final composition of the semi-selective agar medium was established after several attempts in order to inhibit most of the fungal and bacterial saprophytes and favour the development of Xam. It contained PSA + cyclohexamide, cephalexin, pencycuron, triadimenol and tolylfluanid. The bacteria were recovered from naturally infected seeds by the direct plating of 2,000 surface disinfected seeds on the semi-selective medium. The recovery of the pathogen from naturally infected leaf tissues and in dilution plating, on semi-selective medium and on nutrient agar, were comparable. Among the three detection methods tested, the semi-selective medium was found to be the most reliable and quantifiable. Degree of severity of angular leaf spot in the field was not always correlated with the level of infection in the seed. This is the first report of a semi-selective agar medium to detect the presence of Xam in naturally infected cotton seed.

A simple method for the spectrophotometric determination of cephalosporins in pharmaceuticals using variamine blue

A simple spectrophotometric method for the determination of cefotaxime, ceftriaxone, cefadroxil and cephalexin with variamine blue is presented. The determination is based on the hydrolysis of β-lactam ring of cephalosporins with sodium hydroxide which subsequently reacts with iodate to liberate iodine in acidic medium. The liberated iodine oxidizes variamine blue to violet colored species of maximum absorption at 556 nm. The absorbance is measured within the pH range of 4.0-4.2. Beer's law is obeyed in the range of 0.5-5.8 µg mL-1, 0.2-7.0 µg mL-1, 0.2-5.0 µg mL-1 and 0.5-8.5 µg mL-1 for cefotaxime, ceftriaxone, cefadroxil and cephalexin respectively. The analytical parameters were optimized and the method is successfully applied for the determination of cefotaxime, ceftriaxone, cefadroxil and cephalexin in pharmaceuticals.

Voltammetric Sensors for the Determination of Pharmaceuticals

Electrochemical sensors are increasingly being investigated to perform measurements for single or multiple analytes. Demanded by modern medical diagnosis, advances in microfabrication technology have led to the development of fast, sensitive and selective electrochemical sensors for drug analysis. Electrochemical sensors for the measurement of analytes of interest in clinical chemistry are ideally suited for these applications, due to their high sensitivity and selectivity, simple-to-operate, rapid response time and low-cost. As part of the present investigations eight voltammetric sensors have been fabricated for six drugs such as PAM Chloride, Tamsulosin Hydrochloride, Hesperidin Methyl Chalcone, Guaiphenesin, Cephalexin and Amoxicillin trihydrate. The modification techniques adopted as part of the present work include multiwalled carbon nanotube (MWNT) based modifications, electropolymerization, gold nanoparticle (AuNP) based modifications and platinum nanoparticle (PtNP) based modifications. The thesis is divided into nine chapters

Effect of cationic micelles on the decomposition of alpha-aminophenyl cephalosporins

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Isolation of Staphylococcus epidermidis from inflamed upper respiratory tract of an orange-spined hairy dwarf porcupine (Sphiggurus villosus)

The orange-spined hairy dwarf porcupine (Sphiggurus villosus) is a rodent species common in most parts of South America, and little is known about the pathologies that can afflict it. A specimen was delivered at the Wildlife Research and Medical Center (CEMPAS), School of Veterinary Medicine and Animal Husbandry, UNESP, Botucatu, SP, Brazil. The animal showed intense apathy, with purulent secretion in the nasal cavity and fracture of the lumbar spine. Due to the unfavorable prognosis, the porcupine was euthanized and microbiological culture of nasal discharge showed Staphylococcus epidermidis. The antimicrobial resistance test revealed sensitivity to all tested antimicrobials (ampicillin, oxacillin, tetracycline, penicillin G, neomycin, cephalexin, gentamicin, enrofloxacin, ciprofloxacin, cotrimoxazol, cefoxitin and cephalothin). This bacterium is part of the nasal flora of humans and other animals, and may cause infection under certain conditions. In the present study, the infection and colonization by S. epidermidis was the probable cause of the inflammatory process. The sensitivity to all tested antimicrobials suggests that this strain has not been previously exposed to such drugs.

Etiologia, perfil de sensibilidade aos antimicrobianos e aspectos epidemiológicos na otite canina: estudo retrospectivo de 616 casos

A retrospective study of etiology, antimicrobial susceptibility profile and multiple drug resistance, and major epidemiological aspects were investigated in 616 cases of canine otitis. Staphylococcus beta hemolitic (26.27%), Malassezia pachydermatis (12.35%), and Pseudomonas aeruginosa (8.8%) were the most common microorganisms identified. The isolates were susceptible mainly to norfloxacin (89.62%), gentamicin (83.25%), and ofloxacin (80.16%). High occurrence of resistance of isolates was observed to neomicin (30.84%) and cephalexin (27.63%). Multiple drug resistance to three or more and five or more of antimicrobials tested was observed in 34.9% and 15.5% of isolates, respectively. The cases of canine otitis occurred predominantly in first years of age, in mixed breeds animals, at autumn season. The presence of itch, bad smell, and secretion in ear conduct were the major signs observed at clinical examination.