2,3,4,6-Tetra-O-(3-nitropropanoyl)-O-β-D-glucopyranoside, a new antimicrobial from the roots of Heteropteris aphrodisiaca

A new 2,3,4,6-tetra-O-(3-nitropropanoyl)-O-β-D-glucopyranoside anomer was isolated from the roots of Heteropteris aphrodisiaca and characterized by spectroscopic methods. Activity against Staphylococcus aureus, Bacillus subtilis, Candida albicans, C. parapsilosis, C. krusei, and C. tropicalis was demonstrated.

Análise térmica de esparfloxacino

Sparfloxacin, a third-generation fluoroquinolone, is a potent antibacterial agent against a wide range of Gram-positive and Gram-negative organisms, for example Streptococcus pneumonias, Staphylococcus aureus (including methicillin-resistant strains), Legionella spp., Mycoplasma spp., Chlamydia spp. and Mycobacterium spp. This compound has been submitted to thermal analysis and the results are presented here. The DSC curve of sparfloxacin has an endothermic peak that indicates a melting point at 276.5 °C. The DTA curve of the sample in synthetic air shows two exothermic peaks, at 341.6 and 579.2 °C, attributed to compound decomposition. In the TG curve, the loss of mass can be seen to occur in two steps between 285.5 and 645.3 °C. The DTA curve obtained in a nitrogen atmosphere shows an exothermic peak, with decomposition of sparfloxacin at 340.0 °C; from the corresponding TG plot, the loss of mass starts at 254.4 °C.

Effect of rotary instrumentation and of the association of calcium hydroxide and chlorhexidine on the antisepsis of the root canal system in dogs

This study aimed at evaluating the antisepsis of the root canal system (RCS) and periapical region (PR) provided by rotary instrumentation associated with chlorhexidine + calcium hydroxide as intracanal medicament. Chronic periapical lesions were induced in 26 pre-molar roots in two dogs. After microbiological sampling, automatic instrumentation using the Profile system and irrigation with 5.25% sodium hypochlorite solution, with a final rinse of 14.3% EDTA followed by profuse irrigation with physiological saline were carried out in 18 root canals. After drying the canals, a paste based on calcium hydroxide associated with a 2% chlorhexidine digluconate solution was placed inside them. After 21 days, the medication was removed, leaving the root canals empty and coronally sealed. After 96 hours, a final microbiological sample was obtained, followed by histomicrobiological processing by the Brown & Brenn method. Eight untreated root canals represented the control group (C-G). Based on the Mann-Whitney test at a confidence level of 5% (p < 0.05), the procedures of antisepsis used offered significant efficacy (p < 0.05) resulting in 100.0% of the canals free of microorganisms. In the C-G, an elevated incidence of various microbial morphotypes was confirmed in all sites of the RCS, with the presence of microbial colonies in the periapical region. In contrast, the experimental group showed a similar pattern of infection in the RCS, although less intense and a reduced level of periapical infection (p < 0.05). It was concluded that adequate instrumentation followed by the application of calcium hydroxide + chlorhexidine offered significant elimination of microorganisms.

Clinical evaluation of an ointment with 10% metronidazole and 2% lidocaine in the treatment of alveolitis.

AIM: In this study, the authors evaluate the use of a 10% metronidazole and 2% lidocaine ointment, using a lanolin base and mint as flavoring, to treat alveolitis in humans. METHODS: Twenty-five patients, with a diagnosis of alveolitis, were treated in the following way: locoregional anesthesia; surgical cleaning of the socket with alveolar curettes; saline solution irrigation with a 20 ml disposable syringe; and complete filling of the socket with the ointment. RESULTS: The analysis of the results showed that the painful symptoms were severe before and on the day of the treatment in 17 (68%) of the 25 patients treated. Post-treatment analysis presented 2 patients (18%) with severe painful symptoms after 24 h of the treatment and complete remission of painful symptoms after 48 h of the treatment with the ointment. CONCLUSIONS: Based on the results, it is possible to conclude that the 10% metronidazole and 2% lidocaine ointment, with mint flavoring and lanolin as a base, can be used to treat alveolitis.

Clinical and radiographic evaluation of pulpotomies employing calcium hydroxide and trioxide mineral aggregate

This study utilized clinical and radiographic examinations to compare the effectiveness of calcium hydroxide paste and mineral trioxide aggregate (MTA) for pulpotomies of primary molars in children. Ninety primary molars that showed clinical and radiographic indications for pulpotomy treatment were selected. The pulpotomies were performed in two sessions, using a corticosteroid/ antibiotic solution as therapeutic dressing. The sample was divided into two groups of 45 teeth, in which the pulpal remains were protected with either calcium hydroxide paste (Group 1) or MTA (Group 2). Radiographs were taken immediately and at 3-, 6-, and 12-month follow-up appointments. Three teeth in Group 1 failed after three months, while two cases failed after six months and one more failed at one year. Two failures were found in Group 2 at the 12-month follow-up. These results indicate that both materials may be utilized for pulpotomies in primary teeth.

Antimicrobial endodontic compounds do not modulate alkylation-induced genotoxicity and oxidative stress in vitro

Objective: To investigate if formocresol, paramonochlorophenol, or calcium hydroxide modulate the genotoxic effects induced by the oxidatively damaging agent hydrogen peroxide (H 2O 2) or the alkylating agent methyl methanesulfonate (MMS) in vitro by using single cell gel (comet) assay. Study design: Chinese hamster ovary (CHO) cells in culture were exposed directly to formocresol, paramonochlorophenol, or calcium hydroxide (adjusted to 100 μg/mL) for 1 hour at 37°C. Subsequently the cultures were incubated with increasing concentrations (0-10 μmol/L) of MMS in phosphate-buffered solution (PBS) for 15 minutes at 37°C or of H 2O 2 at increasing concentrations (0-100 μmol/L) in distilled water for 5 minutes on ice. The negative control cells were treated with PBS for 1 hour at 37°C. The parameter from the comet assay (tail moment) was assessed by the Kruskal-Wallis nonparametric test followed by a post hoc analysis (Dunn test). Results: Clear concentration-related effects were observed for the genotoxin-exposed CHO cells. Increase of MMS-induced DNA damage was not significantly altered by the presence of the compounds tested. Similarly, no significant changes were observed when hydrogen peroxide was used with the endodontic compounds evaluated. Conclusion: Formocresol, paramonochlorophenol, and calcium hydroxide are not able to modulate alkylation-induced genotoxicity or oxidative DNA damage as depicted by the single cell gel (comet) assay. © 2006 Mosby, Inc. All rights reserved.

Excipientes de medicamentos e as informações da bula

Aim: To evaluate the presence of preservatives, dyes, sweeteners and flavouring substances in 73 pharmaceutical preparations of 35 medicines for oral administration, according to drug labeling information about the excipients. Methods: 35 medications were selected, both over-the-counter and prescription durgs, marketed in Brazil. The sample included: analgesic/antipyretic, antimicrobial, mucoregulatory, cough and cold, decongestant, antihistamine, bronchodilator, corticosteroid, antiinflammatory and vitamin medications. We collected data on 73 preparations of these drugs, according to drug labeling information regarding preservatives, dyes, sweeteners and flavourings. Results: Methylparaben and propylparaben were the most common preservatives found (43% and 35.6% respectively). The most common sweeteners were: sucrose (sugar) (53.4%), sodium saccharin (38.3%) and sorbitol (36.9%). Twenty-one medicines (28,7%) contained two sweeteners. Colourless medicines predominated (43.8%), followed by those with sunset yellow dye (FD&C yellow no. 6) (15%). Five products (6.8%) contained more than one colour agent. Tartrazine (FD&C yellow no. 5) was present in seven preparations (9.5%). Fruit was the most common flavouring found (83%). Labelings of drugs which contained sugar frequently omitted its exact concentration (77%). Of the four labelings of medicines which contained aspartame, two did not warn patients regarding phenylketonuria. Conclusions: Omission and inacuracy of drug labeling information on pharmaceutical excipients may expose susceptible individuals to adverse reactions caused by preservatives and dyes. Complications of inadvertent intake of sugar-containing medicines by diabetics, or aspartame intake by patients with phenylketonuria may also occur.

In vitro antimicrobial activity of different gutta-percha points and calcium hydroxide pastes

The aim of this study was to evaluate the antimicrobial activity of different trademarks and compositions of gutta-percha points and calcium hydroxide pastes used in endodontic therapy. The evaluated material consisted of gutta-percha points containing calcium hydroxide (Roeko™), gutta-percha points containing chlorhexidine (Roeko™), two convencional gutta-percha points (Endo Points™ and Roeko™) and two calcium hydroxide pastes (Calen™ and Calen/PMCC™). Antimicrobial tests included five species of microorganisms: Escherichia coli (ATCC10538), Staphylococcus epidermidis (ATCC12228), Staphylococcus aureus (ATCC6538), Pseudomonas aeruginosa (ATCC27853), and Micrococcus luteus (ATCC9341). The Agar difusion method was employed. The plates were kept at room temperature for 2 h for prediffusion and then incubated at 37°C for 24 h. The triphenyltetrazolium chloride gel was added for optimization and the zones of inhibition were measured. Statistical evaluation was carried out using analysis of variance and Tukey Test. The obtained results showed that all microbial species used in the study were inhibited by the gutta-percha points containing chlorhexidine and by the calcium hydroxide pastes (Calen™ and Calen/ PMCC™), with similar results (p > 0.05). No antimicrobial activity was observed for the other groups. It was concluded that the gutta-percha points containing chlorhexidine presented antimicrobial activity, whereas the gutta-percha points containing calcium hydroxide did not.

Antimicrobial activity of Uncaria tomentosa against oral human pathogens

Uncaria tomentosa is considered a medicinal plant used over centuries by the peruvian population as an alternative treatment for several diseases. Many microorganisms usually inhabit the human oral cavity and under certain conditions can become etiologic agents of diseases. The aim of the present study was to evaluate the antimicrobial activity of different concentrations of Uncaria tomentosa on different strains of microorganisms isolated from the human oral cavity. Micropulverized Uncaria tomentosa was tested in vitro to determine the minimum inhibitory concentration (MIC) on selected microbial strains. The tested strains were oral clinical isolates of Streptococcus mutans, Staphylococcus spp., Candida albicans, Enterobacteriaceae and Pseudomonas aeruginosa. The tested concentrations of Uncaria tomentosa ranged from 0.25-5% in Müeller-Hinton agat. Three percent Uncaria tomentosa inhibited 8% of Enterobacteriaceae isolates, 52% of S. mutans and 96% of Staphylococcus spp. The tested concentrations did not present inhibitory effect on P. aeruginosa and C. albicans. It could be concluded that micropulverized Uncaria tomentosa presented antimicrobial activity on Enterobacteriaceae, S. mutans and Staphylococcus spp. isolates.

Chorismate synthase: An attractive target for drug development against orphan diseases

The increase in incidence of infectious diseases worldwide, particularly in developing countries, is worrying. Each year, 14 million people are killed by infectious diseases, mainly HIV/AIDS, respiratory infections, malaria and tuberculosis. Despite the great burden in the poor countries, drug discovery to treat tropical diseases has come to a standstill. There is no interest by the pharmaceutical industry in drug development against the major diseases of the poor countries, since the financial return cannot be guaranteed. This has created an urgent need for new therapeutics to neglected diseases. A possible approach has been the exploitation of the inhibition of unique targets, vital to the pathogen such as the shikimate pathway enzymes, which are present in bacteria, fungi and apicomplexan parasites but are absent in mammals. The chorismate synthase (CS) catalyses the seventh step in this pathway, the conversion of 5-enolpyruvylshikimate-3-phosphate to chorismate. The strict requirement for a reduced flavin mononucleotide and the anti 1,4 elimination are both unusual aspects which make CS reaction unique among flavin-dependent enzymes, representing an important target for the chemotherapeutic agents development. In this review we present the main biochemical features of CS from bacterial and fungal sources and their difference from the apicomplexan CS. The CS mechanisms proposed are discussed and compared with structural data. The CS structures of some organisms are compared and their distinct features analyzed. Some known CS inhibitors are presented and the main characteristics are discussed. The structural and kinetics data reviewed here can be useful for the design of inhibitors. © 2007 Bentham Science Publishers Ltd.

The inhibition of 5-enolpyruvylshikimate-3-phosphate synthase as a model for development of novel antimicrobials

EPSP synthase (EPSPS) is an essential enzyme in the shikimate pathway, transferring the enolpyruvyl group of phosphoenolpyruvate to shikimate-3-phosphate to form 5-enolpyruvyl-3-shikimate phosphate and inorganic phosphate. This enzyme is composed of two domains, which are formed by three copies of βαβαββ-folding units; in between there are two crossover chain segments hinging the nearly topologically symmetrical domains together and allowing conformational changes necessary for substrate conversion. The reaction is ordered with shikimate-3-phosphate binding first, followed by phosphoenolpyruvate, and then by the subsequent release of phosphate and EPSP. N-[phosphomethyl]glycine (glyphosate) is the commercial inhibitor of this enzyme. Apparently, the binding of shikimate-3-phosphate is necessary for glyphosate binding, since it induces the closure of the two domains to form the active site in the interdomain cleft. However, it is somehow controversial whether binding of shikimate-3-phosphate alone is enough to induce the complete conversion to the closed state. The phosphoenolpyruvate binding site seems to be located mainly on the C-terminal domain, while the binding site of shikimate-3-phosphate is located primarily in the N-terminal domain residues. However, recent results demonstrate that the active site of the enzyme undergoes structural changes upon inhibitor binding on a scale that cannot be predicted by conventional computational methods. Studies of molecular docking based on the interaction of known EPSPS structures with (R)- phosphonate TI analogue reveal that more experimental data on the structure and dynamics of various EPSPS-ligand complexes are needed to more effectively apply structure-based drug design of this enzyme in the future. © 2007 Bentham Science Publishers Ltd.

Estudo morfológico comparativo das cascas e folhas de Stryphnodendron adstringens, S. polyphyllum e S. obovatum - Leguminosae

The genus Stryphnodendron (S.) belongs to the family Leguminosae, subfamily Mimosoideae, which includes mostly trees of tropical and subtropical South America. Extracts of the stem bark are used traditionally by the local population to treat leucorrhoea and diarrhoea, as anti-inflammatory and antiseptic agents (antimicrobial) and to promote blood clotting and wound healing, and in a few cases of gastric ulcers. A review of the literature presented a previous morpho-anatomical study only for S. adstringens (Mart.) Coville. The aim of the present work is to compare morpho-anatomically the stem bark and leaves of three species of Stryphnodendron, known popularly as barbatimão: S. adstringens, S. polyphyllum and S. obovatum, in order to help botanical identification and contribute to quality control. Macro- and microscopical evaluation of the stem barks revealed no significant differences among the species. Morphological analyses of the leaves revealed differences in size, coloration, and pubescence. The leaves of S. adstringens are the largest, glabrous, and concolor. The leaves of S. polyphyllum are smaller, pubescent, and discolor; whereas the leaves of S. obovatum are the same size as those of S. polyphyllum, however, they are glabrous, and discolor.

Molecular hybridization: A useful tool in the design of new drug prototypes

Molecular hybridization is a new concept in drug design and development based on the combination of pharmacophoric moieties of different bioactive substances to produce a new hyrid compound with improved affinity and efficacy, when compared to the parent drugs. Additionally, this strategy can results in compounds presenting modified selectivity profile, different and/or dual modes of action and reduced undesired side effects. So, in this described several example of different strategies for drug design, discovery and pharmacomodulation focused on new innovative hybrid compounds presenting analgesic, anti-inflammatory, platelet anti-aggregating, anti-infections, anticancer, cardio- and neuroactive properties.

Detecção da produção de slime por estafilococos coagulase-negativa isolados de cateter venoso central

Slime production is an important virulence factor of coagulase-negative Staphylococcus spp., allowing them to attach to smooth surfaces of biomaterials, and it has been associated with infections of implanted medical devices. In the present study the production of slime capsules in 27 strains of coagulase-negative Staphylococcus was investigated by culture in Congo Red agar (77.7% positivity), spectrophotometric or microplate method (81.4% positivity) and scanning electron microscopy (88.9% positivity). The resistance of coagulase-negative strains of Staphylococcus to various antimicrobial agents was also determined by agar disk diffusion. The proportion of strains resistant to penicillin G, oxacillin, erythromycin, clindamycin and gentamicin among the slime-producing staphylococci was 88.9%, 70.4%, 81.5%, 66.7% and 59.2%, respectively; all of the coagulase-negative staphylococci were susceptible to vancomycin. The strains isolated from central venous catheters were identified by a conventional method and the API Staph system. The 27 coagulase-negative Staphylococcus strains were identified as: S. saprophyticus (3.7%), S. xylosus (7.4%), S. haemolyticus (14.8%), S. epidermidis (37.0%), S. warneri (14.8%), S. lugdunensis (7.4%), S. hominis (7.4%), S. schleiferi (3.7%) and S. chromogenes (3.7%). It can be concluded that in the most of the coagulase-negative Staphylococcus species there was an association between slime production, the nosocomial origin of the strains and reduced sensitivity to the antibiotics, suggesting a pathogenic potential in the hospital environment.