Tigecycline: A Review of Properties, Applications, and Analytical Methods

Tigecycline is a new glycylcycline with an expanded broad-spectrum antibiotic, including inhibition of Gram-positive, Gram-negative, atypical, anaerobic, and antibiotic-resistant organisms. Trials have demonstrated that tigecycline is noninferior to the comparators for the treatment of complicated skin and skin structure infections as well as complicated intra-abdominal infections. Tigecycline is only available as an intravenous preparation and analytical methods to its quantitation in pharmaceutical products has not been published to date. This review examined tigecycline characteristics, the spectrum and mechanism of action, pharmacokinetics, applications, and, mainly, the instrumental conditions of published chromatographic methods used to measure tigecycline, its metabolites, and some analogs in clinical and biologic research.

Stpahylococcus aureus biofilms on central venous haemodialysis catheters

As infecções devido a biofilmes bacterianos são comuns em pacientes sob tratamento em hemodiálise. Neste estudo, 16 pacientes (7 homens, 9 mulheres, de 22 a 81 anos, média 50 anos de idade), com um total de 25 cateteres de hemodiálise (3 de triplo-lúmen e 22 de duplo-lúmen) de poliuretano inseridos em veia subclávia foram estudados. Os cateteres permaneceram no local de 3 a 91 dias (média de 47 dias). Os cateteres foram removidos devido ao: mau funcionamento (44%), suspeita de infecção relacionada ao cateter (20%), viabilidade de um acesso permanente (16%), remoção acidental (12%), sinais e sintomas de infecção no local da inserção do cateter (4%) e contaminação exógena (4%). Culturas positivas de ponta foram observadas em sete cateteres (28%), concomitantemente com três culturas positivas de sangue. Das culturas de sangue foram identificados Staphylococcus aureus (12%) e de uma das conexões foi isolado S. aureus. Biofilmes foram observados sobre todas as pontas de cateteres. Os S. aureus isolados do sangue e cateter (ponta e conexão) eram resistentes a pencilina e sensíveis a azitromicina, ciprofloxacina, clindamicina, cloranfenicol, gentamicina, oxacilina, rifampicina, sulfametoxazole, tetraciclina e vancomicina. As cepas de S. aureus isoladas de sangue, ponta de cateter e conexão foram consideradas idênticas devido à coincidência do perfil de sensibilidade. E similaridade genética, avaliada por meio de ribotipagem.

Cytokines released from blood monocytes and expressed in mucocutaneous lesions of patients with paracoccidioidomycosis evaluated before and during trimethoprim-sulfamethoxazole treatment

Background Mucocutaneous lesions in paracoccidioidomycosis are granulomatous and result from tissue responses to Paracoccidioides brasiliensis, the aetiological agent.Objectives and methods In this study we investigate the expression of tumour necrosis factor (TNF)-alpha, interleukin (IL)-10 and transforming growth factor (TGF)-beta 1 by immunohistochemistry in skin and mucosa lesions from patients with the chronic form of paracoccidioidomycosis, evaluated before and at day 20 of trimethoprim-sulfamethoxazole treatment. Cytokine production by peripheral blood monocytes was also studied by enzyme immunoassay.Results Intense immunostaining for TNF-alpha was detected in mononuclear cells that infiltrated granulomas in all skin and mucosa lesions before treatment simultaneously with low IL-10 granular deposits in these cells. At day 20 of treatment, there was reduced TNF-alpha and IL-10 deposition. Immunoreactive TGF-beta 1 was observed diffusely in the dermis and generally in the cytoplasm of macrophages and giant cells, before treatment, and as increased TGF-beta 1 deposits in the fibrosis area at day 20 of treatment. Peripheral blood monocytes from patients with paracoccidioidomycosis, evaluated before treatment, produced high endogenous levels of TNF-alpha, TGF-beta 1 and IL-10 in relation to healthy controls. Lipopolysaccharide-stimulated monocytes from patients secreted lower levels of TNF-alpha in both periods of evaluation while no impairment in capacity of IL-10 and TGF-beta production was observed.Conclusions Trimethoprim-sulfamethoxazole therapy was effective in decreasing fungal load in the lesions, allowing patient immune response to control the infection leading to the healing of the lesions.

Cytokines and acute-phase serum proteins as markers of inflammatory regression during pulmonary tuberculosis treatment

Tuberculosis is still increasing and was declared a worldwide sanitary emergency by the World Health Organization (WHO) in 1995. Its control is difficult due to long treatment duration and lack of markers of treatment success or failure. Cytokines such as IFN-gamma and TNF-alpha, a central factor in immune response against Mycobacterium tuberculosis, are responsible for the interaction between T lymphocytes and the infected macrophage and are also produced during this interaction. As proinflammatory cytokines have a close relationship with mycobacteria clearance, in fact even preceding it, they could be used as markers for inflammatory activity and response to treatment. Proinflammatory cytokines act in the liver and stimulate a strong local and systemic acute-phase response as a result of homeostatic and physiological responses also induced by them. Acute-phase proteins produced by cytokine activity are useful diagnostic markers that could also be used to monitor treatment response as they can be serially quantified. The objective of this study was to evaluate IFN-gamma, TNF-alpha, IL-10 and TGF-beta production in supernatant of peripheral blood mononuclear cell (PBMC) and monocyte (MO) cultures, as well as serum acute-phase response through total protein, albumin, globulin, C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP), and erythrocyte sedimentation rate (ESR) as regression markers of inflammatory response during pulmonary tuberculosis treatment. Twenty blood donors (G1) from the Blood Bank at Botucatu School of Medicine's University Hospital (BSM-UH) were evaluated once and 28 pulmonary tuberculosis patients (G2): 13 from BSM-UH and 15 from the Bauru State Health Secretariat. Patients were evaluated at three moments of treatment: before (M1), at three months (M2), and at the end (M3). Cytokines were determined in 20ml of peripheral blood (ELISA), with or without activation: lipopolysaccharide (LPS) for MO culture and phytohemagglutinin (PHA) for PBMC culture. Acute-phase protein behavior in G2 throughout treatment was: Globulins: M1> M2, M1> M3 (rho < 0.001); CRP: M1> M2> M3 (.< 0.001); AGP for men: M1> M2, M1> M3 (rho < 0.001); ESR for men: M1> M2, M1> M3 (rho < 0.0016) and for women: M1> M2 (.< 0.025). Comparison between cytokine levels found in supernatant of MO and PBMC cultures, with and without stimulus, in G1 and G2 during treatment showed: TNF-alpha (with/ without LPS) at M1: G2> G1; at M2: G2> G1 (rho < 0.001); (without LPS) at M3: G2> G1 (rho < 0.001), (with LPS) at M3: G2> G1 (rho < 0.028); IFN-. (with and without PHA) at M1: G2> G1; at M2: G2> G1 (rho < 0.001); IL-10 (with and without LPS) at M1: G2> G1; at M2: G2> G1; at M3: G2> G1 (rho < 0.001); TGF-beta (with and without LPS) at M1: G2> G1; at M2: G2> G1 (rho < 0.001), (without LPS) at M3: G2> G1 (rho < 0.001). In G2, all cytokines in supernatant of MO and PBMC cultures, with and without stimulus, showed: M1> M2> M3 (rho < 0.01). Levels of globulins, CRP, AGP, and ESR in patients with pulmonary tuberculosis before treatment (M1) were significantly higher than reference values, suggesting their use as diagnostic markers and indicators of treatment. The CRP decreasing values along treatment could be taken as a marker of the regression of inflammatory process and of response to treatment in patients with pulmonary tuberculosis.Regarding cytokines, there was significant increase in TNF-alpha, IFN-gamma, IL-10, and TGF-alpha levels before and at three months treatment, with and without stimulus; in TNF-a and IL-10 lvels, with and without stimulus, as well as in TGF-alpha levels without stimulus at six months. Patients had higher levels of all studied cytokines than controls before treatment, and these values decreased along treatment. In this study, pulmonary tuberculosis patients showed a Th0 cytokine profile before treatment, with the production of both Th1 (IFN-gamma) and Th2 (IL-10) cytokines, in addition to TNF-alpha inflammatory and TGF-alpha regulatory and fibrosis-inducer cytokines. At the end of treatment, all had evolved to Th2 profile, probably in an attempt to reduce the harmful effects of the proinflammatory activity of the Th1 cytokine profile and of the still above-normal levels of TNF-alpha. The high levels of TGF-alpha, also found in these patients, are related to its important role in the extracellular matrix deposition and fibrosis induction that characterize tuberculosis healing process. IFN-gamma was the only cytokine reaching normal levels at the end of treatment, which suggests its use as a marker of response to treatment.

Mucosal Bridge of the Vocal Fold: Difficulties in the Diagnosis and Treatment

Mucosal bridges are rare laryngeal lesions probably of genetic origin. They may cause dysphonia of varying degrees, especially when associated with other laryngeal lesions such as vocal sulci and cysts. Reports on mucosal bridges are rare, and the better treatment is inconclusive.Aim. To report the authors' experience in 14 cases of mucosal bridge showing details on endoscopic examinations and treatment.Study Design. Retrospective study.Methods. We reviewed the medical records of 14 patients with a diagnosis of mucosal bridge confirmed by video-laryngostroboscopy and direct laryngoscopy who attended the Outpatient Clinic of Voice Disorders of the Discipline of Otorhinolaryngology, Botucatu Medical School, São Paulo State University, São Paulo. Data collected included information on gender, age, symptoms, time of onset, history of intubation, smoking status, alcohol intake, associated laryngeal lesions, treatment, and GRBAS (grade of hoarseness, roughness, breathiness, asthenia, and stress) scale ratings.Results. of 14 patients, 10 were females and four were males. There was a prevalence of adults (n = 12), with only two of the patients being younger than 13 years (10 and 13 years). Mucosal bridges showed no correlations with smoking, alcohol intake, or gastroesophageal and sinonasal symptoms. Voice abuse was reported in 50% of the cases that consisted of patients who had high-voice demand occupations. In seven cases, mucosal bridges were associated with other laryngeal lesions, particularly vocal cysts and sulci. All patients who underwent surgery and phonotherapy showed improved vocal quality.Conclusions. We documented 14 patients with dysphonia caused by mucosal bridge. Promising results were obtained with surgery.

Serum Levels of Interleukins 6, 10, and 13 Before and After Treatment of Classic Hodgkin Lymphoma

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

Occurrence of Odontogenic Infections in Patients Treated in a Postgraduation Program on Maxillofacial Surgery and Traumatology

This study assessed the occurrence and characteristics of oral and maxillofacial infections in patients treated at a Brazilian oral and maxillofacial emergency service during a 7-year period. The clinical files of all patients treated at the Oral and Maxillofacial Surgery and Traumatology Service of the Aracatuba Dental School, São Paulo State University, Brazil, between 2002 and 2008 were reviewed. From a population of 3645 patients treated in this period, the study sample consisted of 93 subjects who presented odontogenic infections. Data referring to the patients' sex, age, medical history, and the etiology, diagnosis, complications, drug therapy/treatment, and evolution of the pathologic diseases were collected and analyzed using the Epi Info 2000 software. of these patients, 54 were men (58.1%) and 39 were women (41.9%). Most patients were in the 31- to 40-year-old (20.7%) and 21- to 30-year-old (19.6%) age groups. The most frequent etiology was pulp necrosis due to caries (80.6%). Regarding the treatment, antibiotics were administered to all patients, surgical drainage was done in 75 patients (82.4%), and 44 patients (47.3%) needed hospital admission. First-generation cephalosporin alone or combined with other drugs was the most prescribed antibiotic (n = 26) followed by penicillin G (n = 25). Most patients (n = 85, 91.4%) responded well to the treatment. Five cases had complications: 3 patients needed hospital readmission, 1 case progressed to descending mediastinitis, and 1 patient died. Odontogenic infections can be life-threatening and require hospital admission for adequate patient care. Complications from odontogenic infections, although rare, may be fatal if not properly managed.

Influence of apical patency and filling material on healing process of dogs' teeth with vital pulp after root canal therapy

Foi propósito deste trabalho observar o processo de reparo de dentes de cães após obturação dos canais com dois cimentos diferentes, fazendo ou não a patência apical. Após uma sobreinstrumentação, os canais receberam um curativo de uma solução de corticosteróide-antibiótico por 7 dias, com o objetivo de obter invaginação de tecido conjuntivo para dentro dos canais. Após esse período, esse tecido foi totalmente removido em metade dos casos (grupos com patência apical) e preservados no restante dos casos (grupos sem patência apical). Os canais foram obturados pela técnica da condensação lateral empregando um cimento a base de hidróxido de cálcio (Sealer Plus) ou um cimento de Grossman (Fill Canal). Os animais foram sacrificados por overdose anestésica 60 dias após o tratamento endodôntico e as peças anatômicas foram obtidas e preparadas para análise histológica. Os dados obtidos foram analisados com base em diversos parâmetros histomorfológicos. Os resultados foram melhores nos grupos sem patência apical (p=0,01) do que nos grupos com patência. Dentre os cimentos estudados, os melhores resultados foram observados com o cimento Sealer Plus (p=0,01). em conclusão, tanto a patência apical (presença ou ausência) quanto o tipo de material obturador de canal influíram no processo de reparo apical de dentes de cães com polpas vitais após tratamento endodôntico. O emprego de um cimento a base de hidróxido de cálcio em dentes sem patência apical promoveu os melhores resultados, dentre as condições experimentais propostas.

The Short-Term Effectiveness of Non-Surgical Treatment in Reducing Levels of Interleukin-1 beta and Proteases in Gingival Crevicular Fluid From Patients With Type 2 Diabetes Mellitus and Chronic Periodontitis

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Accurate Approach in the Treatment of Oral Bisphosphonate-Related Jaw Osteonecrosis

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is not completely understood and difficult to treat. Even though the occurrence of BRONJ is mainly related to the therapy with intravenous bisphosphonates (BPs), this article reports a case of long-term oral BP use and BRONJ occurrence. In addition, a literature review provides some additional information about BPs, BRONJ, and also a guideline for the prevention and treatment of BRONJ stages. A 79-year-old patient presented intense and persistent pain, purulent secretion, and exposed bone at the right side of the lower jaw. Thus, she was submitted to anamnesis, radiologic and tomographic examinations, and bacterial culture and sensitivity tests. These procedures were followed by surgical debridement of the bone and surrounding tissues/cyst and antibiotic prescription and histopathologic analysis of the fragments. Together, the examinations performed showed the occurrence of stage 2 BRONJ. Moreover, the antibiotic prescription, discontinuation of oral BP, and surgical procedures ensure that the patient had no more symptoms. Therefore, considering the presented case, we believe that an accurate approach is promising to diagnose and treat stage 2 BRONJ and other associated pathologic findings.

Finasteride treatment alters MMP-2 and-9 gene expression and activity in the rat ventral prostate

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

An immunocytochemical and in situ hybridization analysis of annexin 1 expression in rat mast cells: Modulation by inflammation and dexamethasone

The presence and localization of the anti-inflammatory protein annexin 1 (also known as lipocortin 1) in perivenular rat mast cells was investigated here. Using the rat mesenteric microvascular bed and a combination of morphologic techniques ranging from immunofluorescence to electron microscopy analyses, we detected the presence of annexin 1 in discrete intracellular sites, both in the nucleus and in the cytoplasm. In resting mast cells, most of the protein pool (approximately 80% of the cytosolic portion) was localized to cytoplasmic granules. In agreement with other cell types, treatment of rats with dexamethasone (0.2 mg/kg, ip) increased annexin 1 expression in mast cells, inducing a remarkable appearance of dusters of protein immunoreactivity. This effect was most likely the result of de novo protein synthesis as determined by an increase in mRNA seen by in situ hybridization. Triggering an ongoing experimental inflammatory response (0.3 mg of carrageenin, ip) increased annexin 1 mRNA and protein levels. In conclusion, we report for the first time the localization of annexin 1 in connective tissue mast cells, and its susceptibility not only to glucocorticoid hormone treatment, but also to an experimental acute inflammatory response.

Quasispecies of hepatitis C virus genotype 1 and treatment outcome with Peginterferon and Ribavirin

The majority of patients with chronic hepatitis C fail to respond to antiviral therapy. The genetic basis of this resistance is unknown. The quasispecies nature of HCV may have an important implication concerning viral persistence and response to therapy. The HCV nonstructural 5A (NS5A) protein has been controversially implicated in the inherent resistance of HCV to interferon (IFN) antiviral therapy. To evaluate whether the NS5A quasispecies pre-treatment composition of HCV 1a/1b is related to responsiveness to combined pegylated interferon (PEG-IFN) and Ribavirin therapy, detailed analyses of the complete NS5A were performed. Fifteen full-length NS5A clones were sequenced from 11 pretreatment samples of patients infected with genotype 1 HCV (3 virological sustained responders, 4 non-responders, and 4 end-of-treatment responders). Our study could not show a significant correlation between the mean number of mutations in HCV NS5A before treatment and treatment outcome, and the phylogenetic construction of complete NS5A sequences obtained from all patients failed to show any clustering associated with a specific response pattern. No single amino acid position was associated with different responses to therapy in any of the NS5A regions analyzed, and mutations were clustered downstream the ISDR, primarily in the V3 region. We observed that the CRS and NLS regions of the NS5A protein were conflicting for some variables analyzed, although no significant differences were found. If these two regions can have antagonistic functions, it seems viable that they present different mutation profiles when compared with treatment response. The patient sample that presented the lowest genetic distance values also presented the smallest number of variants, and the most heterogeneous pattern was seen in the end-of-treatment patients. These results suggest that a detailed molecular analysis of the NS5A region on a larger sample size may be necessary for understanding its role in the therapy outcome of HCV 1a/1b infection. (C) 2008 Elsevier B.V. All rights reserved.

Knowledge of general dentists in the current guidelines for emergency treatment of avulsed teeth and dental trauma prevention

A high prevalence of dental trauma exists and its effects on function and esthetics deserve the attention of general dentists. The aim of this study was to assess the level of general dental practitioners' (GDPs) knowledge about guidelines for dental avulsion and its prevention using a questionnaire. The 21-item questionnaire was distributed among 264 GDPs and the survey was realized between August-November 2006. The data obtained were statistically analyzed using descriptive analysis and Pearson's Chi-square test to determine associations between knowledge regarding emergency treatment and dentists from public or private dental schools and years of experience. The results showed that the participants exhibited appropriate knowledge concerning procedures in cases of tooth avulsion and its prevention. The number of correct answers was low in relation to recommended treatment at the site of injury. Storage medium, preparation of the alveolus and splint time for receiving the avulsed tooth received a high number of correct answers. One statistically significant association between years of experience and recommended treatment at the site of the injury in the case an avulsed tooth (KH2 = 9.384, P = 0.009). In conclusion, this survey showed appropriate knowledge of dental avulsion management and its prevention among the surveyed dentists. The findings also showed that communication between dentists and the population is deficient, especially concerning practitioners of high risk and contact sports.

Relationship between temporomandibular disorders and orthodontic treatment: a literature review

OBJETIVO: revisar a literatura mais atual, dos últimos 15 anos, em busca de estudos clínicos que relatem a relação entre a disfunção temporomandibular (DTM) e o tratamento ortodôntico e/ou a má oclusão. A intenção foi verificar se o tratamento ortodôntico aumentaria o aparecimento de sinais e sintomas de DTM, e se o tratamento ortodôntico seria um recurso para o tratamento ou prevenção dos sinais e sintomas de DTM. MÉTODOS: artigos dos tipos revisão de literatura, editorial, carta, estudo experimental em animais e comunicação foram excluídos dessa revisão. Foram incluídos artigos prospectivos, longitudinais, caso-controle ou retrospectivo com amostra maior, com relevante análise estatística. Estudos que abordassem deformidades e síndromes craniofaciais e tratamento por cirurgia ortognática também foram excluídos, bem como aqueles que relatassem apenas a associação entre má oclusão e DTM. RESULTADOS: foram encontrados 20 artigos relacionando Ortodontia à DTM, segundo os critérios adotados. Os estudos, então, associando sinais e sintomas de DTM ao tratamento ortodôntico apresentaram resultados heterogêneos. Alguns encontraram efeitos positivos do tratamento ortodôntico para os sinais e sintomas de DTM; entretanto, nenhum deles apresentou diferença estatisticamente significativa. CONCLUSÕES: todos os estudos citados nessa revisão de literatura relataram que o tratamento ortodôntico não forneceu risco ao desenvolvimento de sinais e sintomas de DTM, independentemente da técnica utilizada para tratamento, da exodontia ou não de pré-molares e do tipo de má oclusão previamente apresentada pelo paciente. Alguns estudos realizados com acompanhamento em longo prazo concluíram que o tratamento ortodôntico não seria preventivo ou uma modalidade de tratamento para DTM.