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.

Root trunk height as a risk factor for periodontal furcation involvement in maxillary first molars: an in vitro study.

The aim of this study was to correlate the root trunk height from the furcation openings on the buccal, mesial and distal surfaces to the cemento-enamel junction in upper first permanent molars in human beings with risk for periodontal disease progression. One hundred extracted maxillary first molars were used. Reference points and demarcations were determined from the entrance of the buccal (F1), mesial (F2) and distal (F3) furcations to the cemento-enamel junction in millimeters. The mean distances found were 3.50 mm, 4.44 mm and 4.26 mm for the buccal, mesial and distal furcations, respectively, in relation to the cemento-enamel junction. The statistical analyses were Student's t-test and Chi-square (X2). With periodontal disease progression, the buccal furcation presents a greater compromising risk due to its proximity to the cemento-enamel junction, while the mesial furcation is the most distant, comprising a lesser risk.

Exclusion of known gene for enamel development in two Brazilian families with amelogenesis imperfecta

Amelogenesis imperfecta (AI) is a genetically heterogeneous group of diseases that result in defective development of tooth enamel. Mutations in several enamel proteins and proteinases have been associated with AI. The object of this study was to evaluate evidence of etiology for the six major candidate gene loci in two Brazilian families with AI. Genomic DMA was obtained from family members and all exons and exon-intron boundaries of the ENAM, AMBN, AMELX, MMP20, KLK4 and Amelotin gene were amplified and sequenced. Each family was also evaluated for linkage to chromosome regions known to contain genes important in enamel development. The present study indicates that the AI in these two families is not caused by any of the known loci for AI or any of the major candidate genes proposed in the literature. These findings indicate extensive genetic heterogeneity for non-syndromic AI.

Evaluation of clinical periodontal conditions in smokers and non-smokers

Given that tobacco smoking habit is a risk factor for periodontal diseases, the aim of this study was to compare clinical periodontal aspects between smokers and non-smokers. The clinical status were assessed in 55 patients, 29 smokers and 26 non-smokers, aged 30 to 50 years, with mean age of 40. The clinical parameters used were: probing depth (PD), plaque index (PI), gingival index (GI), clinical attachment level (CAL), gingival recession (GR) and gingival bleeding index (GBI) for arches (upper and lower ) and teeth (anterior and posterior). Tooth loss was also evaluated in both groups. Multiple regression analysis showed: tendency of greater probing depth and clinical attachment level means for smokers; greater amount of plaque in smokers in all regions; greater gingival index means for non-smokers with clinical significance (p<0.05) in all regions. Although, without statistical significance, the analysis showed greater gingival bleeding index means almost always for nonsmokers; similar gingival recession means in both groups and tendency of upper tooth loss in smokers and lower tooth loss in non-smokers. The findings of this study showed that clinical periodontal parameters may be different in smokers when compared to non-smokers and that masking of some periodontal signs can be a result of nicotine's vasoconstrictor effect.

Transmission of Aggregatibacter actinomycetemcomitans between Brazilian women with severe chronic periodontitis and their children

This study evaluated the transmission of Aggregatibacter actinomycetemcomitans (Aa) in women with severe chronic periodontitis and their children. Thirty women (mean age = 36.1±6.0 years) who were mothers of at least one child aged 7 to 16 years were enrolled. In order to investigate mother-child transmission of Aa, the children were also evaluated when their mothers were colonized by the bacterium. Subgingival plaque samples of each woman were collected from 3 sites (mean probing depth of 7.3±1.2 mm and mean clinical attachment level of 7.9±1.5 mm) and pooled in reduced transport fluid (RTF). These samples were processed, inoculated onto TSBVagar selective medium and incubated at 37°C in microaerophilic atmosphere for 5 days. Aa was identified on the basis of colony morphology, Gram staining, catalase and oxidase reactions. Aa was found in 8 out of 30 women. Therefore, 8 children from these women (mean age= 12 ± 3.7 years) were evaluated, but Aa was found only in 2 of them. Aa strains of the two mother-child pairs were evaluated by arbitrarily-primed polymerase chain reaction (AP-PCR), although it was not found similarity between the amplitypes of each pair. No Aa transmission was found between Brazilian women with severe chronic periodontitis and their children.

The effects of up to 240 days of tacrolimus therapy on the gingival tissues of rats - A morphological evaluation

Background: Tacrolimus, an immunosuppressive drug used in organ transplantation, has been reported not to induce gingival overgrowth. However, prevalence studies are limited, and the methods used for assessing gingival overgrowth varies among studies. Objective: The purpose of this study was to evaluate the effects of up to 240 days of tacrolimus therapy on gingival tissues of rats. Materials and methods: Rats were treated for 60, 120, 180 and 240 days with daily subcutaneous injections of 1 mg/kg body weight of tacrolimus. After histological processing, the oral and connective tissue, volume densities of fibroblasts (Vf), collagen fibers (Vcf) and other structures (Vo) were assessed in the region of the lower first molar. Results: After 60 and 120 days of treatment with tacrolimus, gingival overgrowth was not observed. The gingival epithelium, connective tissue, as well as the values for Vf, Vcf, and Vo were similar to those of the control rats (P > 0.05). After 180 and 240 days of the treatment, gingival overgrowth was associated with a significant increase in the gingival epithelium and connective tissue as well as an increase in the V f and Vcf (P < 0.05). Conclusions: Within the limits of the experimental study, it may be concluded that the deleterious side effects of tacrolimus on the gingival tissues of rats may be time-related. © 2007 Blackwell Munksgaard All rights reserved.

Information for the diagnosis and treatment of root resorption due to tooth replantation.

A favorable prognosis after tooth avulsion depends on some variables, such as the extra-alveolar period and storage medium. Vitality of the periodontal ligament cells is considered a critical factor for a successful outcome without root resorption. The dental surgeon is provided with clinical information and radiographic findings to establish a diagnosis and may rely on current available guidelines. Once trauma has occurred, treatment must be quick and effective, and periodic follow-up must be performed. Clinical, radiographic, and histologic characteristics for each type of root resorption due to tooth replantation are presented, with the aim to provide information for the diagnosis and treatment of healing complications.

Root surface treatment with vitamin C in tooth replantation: microscopic study in rats

AIM: Late tooth replantation is a worthy procedure, especially in growing patients, being the best option for tooth avulsion. This study evaluated the effects of root surface treatment with 2% acidulated phosphate sodium fluoride and effervescent vitamin C (Redoxon) in late replantation. METHODS: Twenty rat teeth (Rattus norvegicus, albinus, Wistar) were extracted and left on a table for 6 h. Then, the dental papilla and enamel organ were sectioned and the pulp was removed through the apex. After removal of the periodontal ligament with a blade, the animals were divided into 2 groups: Group I teeth were immersed in 2% acidulated phosphate sodium fluoride solution for 10 min and obturated with Ca(OH)(2) paste. Group II teeth were immersed in effervescent vitamin C solution (Redoxon 2 g) for 10 min and obturated as for Group I. After these procedures, teeth were replanted and animals were killed after 60 days. RESULTS: The study revealed a larger amount of replacement resorption in Group I and larger amount of ankylosis in Group II, with statistically significant difference and absence of inflammatory resorption. CONCLUSION: The substances used for root surface treatment were unable to prevent replacement resorption and ankylosis, which are expected when the periodontal ligament has been lost.

A clinical decision support system for cancer diseases

The second main cause of death in Brazil is cancer, and according to statistics disclosed by National Cancer Institute from Brazil (INCA) 466,730 new cases of cancer are forecast for 2008. The analysis of tumour tissues of various types and patients' clinical data, genetic profiles, characteristics of diseases and epidemiological data may lead to more precise diagnoses, providing more effective treatments. In this work we present a clinical decision support system for cancer diseases, which manages a relational database containing information relating to the tumour tissue and their location in freezers, patients and medical forms. Furthermore, it is also discussed some problems encountered, as database integration and the adoption of a standard to describe topography and morphology. It is also discussed the dynamic report generation functionality, that shows data in table and graph format, according to the user's configuration. © ACM 2008.

Dental trauma involving root fracture and periodontal ligament injury: A 10-year retrospective study

The purpose of this retrospective study was to analyze the cases of traumatic dental injuries involving root fracture and/or periodontal ligament injury (except avulsion) treated at the Discipline of Integrated Clinic, School of Dentistry of Araçatuba, São Paulo State University (UNESP), Brazil, from January 1992 to December 2002. Clinical and radiographic records from 161 patients with 287 traumatized teeth that had sustained root fracture and/or injuries to the periodontal ligament were examined. The results of this survey revealed that subluxation (25.09%) was the most common type of periodontal ligament injury, followed by extrusive luxation (19.86%). There was a predominance of young male patients and most of them did not present systemic alterations. Among the etiologic factors, the most frequent causes were falls and bicycle accidents. Injuries on extraoral soft tissues were mostly laceration and abrasion, while gingival and lip mucosa lacerations prevailed on intraoral soft tissues injuries. Radiographically, the most common finding was an increase of the periodontal ligament space. The most commonly performed treatment was root canal therapy. Within the limits of this study, it can be concluded that traumatic dental injuries occur more frequently in young male individuals, due to falls and bicycle accidents. Subluxation was the most common type of periodontal ligament injury. Root canal therapy was the type of treatment most commonly planned and performed.

Conservative management of severe intrusion in a primary tooth: A 4-year follow-up

The purpose of this report was to describe the case of an 18-month-old boy who was referred to the pediatric clinic of the School of Dentistry of Araçatuba, São Paulo State University, Araçatuba, São Paulo, Brazil, 3 days after sustaining severe trauma that led to the complete intrusion of the primary maxillary right lateral incisor, a crown fracture of the primary maxillary right central incisor without pulp involvement, and disruption of the superior labial frenum. Four months later, spontaneous re-eruption was observed in the intruded tooth and no endodontic intervention was necessary in either traumatized teeth. Four years after the trauma, a morphological change in the germ of the permanent successor was noted. Clinical follow-up and periodic radiographies are necessary after traumatic intrusion of primary teeth to monitor possible sequelae in the permanent successors.

Severe fracture of the maxillary alveolar process associated with extrusive luxation and tooth avulsion: A case report

Aim: The aim of this report is to present a case of severe fracture of the maxillary anterior alveolar process with substantial bone dislodgement associated with extrusive tooth luxation and avulsion. Background: Dentoalveolar trauma is a challenge to dentistry, especially in young patients, for it can lead to early tooth loss which compromises oral function, esthetics, self-esteem, and alter the long-term plan of care for the victim. Case Report: A 12-year-old girl with severe dentoalveolar trauma to the maxillary anterior region presented for emergency care for her injury. Treatment consisted of fracture reduction of the alveolar process, repositioning of the teeth that had suffered extrusive luxation, placement of a semi-rigid splint, and suturing of soft tissue lacerations. The traumatized teeth presented with pulpal necrosis and were treated endodontically. After 24 months of follow up, the fracture of the alveolar process was completely healed and the displaced teeth presented no signs of ankylosis or root resorption. Summary: First-aid care contributed remarkably to this case allowing the re-establishment of esthetics, function, and patient's self-esteem. In spite of trauma extension the treatment outcomes were favorable. Clinical Significance: Cases of dentoalveolar trauma should be evaluated on an individual basis. However, early emergency management and adequate follow-up can prevent further complications and contribute to treatment success.

Effect of induced diabetes mellitus on alveolar bone loss after 30 days of ligature-induced periodontal disease

Several studies have shown that diabetics are more susceptible to the development of severe periodontal disease. Currently, the use of animal models can be considered a feasible alternative in radiographic assessments of these two pathologies. The purpose of this radiographic study was to evaluate the effect of induced diabetes mellitus on alveolar bone loss after 30 days of ligature-induced periodontal disease. Sixty-four Wistar rats were randomly distributed into four experimental groups. Diabetes was induced in Groups II and IV, while periodontal disease was induced in Groups III and IV; Group I was used as control. In order to perform the radiographic assessment of the specimens, the rats were killed on the 3rd and 30th days of the study. Radiographic measurements were assessed with ANOVA and Tukey's test to determine statistically significant differences (p < 0.05). It was observed that Groups III and IV featured greater bone loss when compared to Groups I and II. Only the diabetic group with periodontal disease (Group IV) featured statistically significant greater bone loss when compared to the other groups. These results suggested that the alveolar bone loss resulting from the periodontal disease installation is greater when associated to the diabetes mellitus.