Sensitization and cross-sensitization after chronic treatment with methylphenidate in adolescent Wistar rats

An increasing debate exists about the potential of early exposure to methylphenidate to increase the risk for drug abuse. In addition, little is known about the neurobiological effects of early exposure to methylphenidate. This study was designed to investigate whether chronic treatment with methylphenidate induces behavioral sensitization to subsequent methylphenidate and D-amphetamine challenge in adolescent Wistar rats. Young Wistar rats (P25) were treated with either methylphenidate (1, 2, or 10 mg/kg, intraperitoneally) or saline for 28 days. After 14 days of washout, animals were challenged with methylphenidate 2.5 mg/kg intraperitoneally or D-amphetamine 2 mg/kg intraperitoneally (P67). Locomotor behavior was assessed using the open field test. Rats chronically treated with methylphenidate in the adolescent period showed augmented locomotor sensitization to D-amphetamine but not to methylphenidate in the adult phase. These findings suggest that early exposure do methylphenidate might increase the risk for subsequent D-amphetamine abuse. Further studies focusing on the neurobiological effects of early exposure to methylphenidate are warranted.     

Comparative study of the expression of cellular cycle proteins in cervical intraepithelial lesions

Interaction of human papilloma virus oncoproteins E6 and E7 with cell cycle proteins leads to disturbances of the cell cycle mechanism and subsequent alteration in the expression of some proteins, such as p16^INK4a, cyclin D1, p53 and KI67. In this study, we compared alterations in the expression of these proteins during several stages of intra-epitelial cervical carcinogenesis. Accordingly, an immunohistochemical study was performed on 50 cervical biopsies, including negative cases and intraepithelial neoplasias. The expression patterns of these markers were correlated with the histopathological diagnosis and infection with HPV. The p16^INK4a, followed by Ki67, showed better correlation with cancer progression than p53 and cyclin D1, which recommends their use in the evaluation of cervical carcinogenesis. These monoclonal antibodies can be applied to cervical biopsy specimens to identify lesions transformed by oncogenic HPV, separating CIN 1 (p16^INK4a positive) and identifying high-grade lesions by an increase in the cellular proliferation index (Ki67). In this way, we propose immunomarkers that can be applied in clinical practice to separate patients who need a conservative therapeutic approach from those who require a more aggressive treatment.     

Microtensile bond strengths of composite to dentin treated with desensitizer products

PURPOSE: This study was designed to analyze the influence of desensitizing procedures on dentin bond strength. MATERIALS AND METHODS: Forty bovine incisors were used, divided into four groups (n = 10): G1: control; G2: Gluma Desensitizer (Heraeus Kulzer); G3: Oxa-Gel (Art-Dent); G4: low-intensity laser (MMOptics). The buccal surface was wet ground flat with 180-, 400- and 600-grit silicon carbide abrasive paper to expose midcoronal dentin and create a uniform surface. After the application of the desensitizing agents to the exposed dentin, the specimens were etched with 35% phosphoric acid for 30 s, and an adhesive (Single Bond) was applied and light cured. A 4-mm high crown of composite resin (Filtek Z250) was then built up. Specimens were trimmed to an hourglass shape with cross sections of 1 mm2. Each specimen was individually fractured by a microtensile testing machine at a crosshead speed of 0.5 mm/min. The data, recorded in MPa, were analyzed with one-way ANOVA and the Duncan test (p = 0.05). RESULTS: Specimens treated with dentin desensitizers (except Gluma) yielded significantly lower mean bond strengths than nontreated control specimens. The mean values in MPa (+/- SD) were: G1: 13.4 (6.2); G2: 13.2 (4.8); G3: 7.15 (4.3); G4: 7.21 (4.6). CONCLUSIONS: Among the desensitizing agents studied, only Gluma Desensitizer did not detrimentally influence the bond strength values. It is a useful material for dentin desensitization.     

How may stressful experiences contribute to the development of temporomandibular disorders?

Temporomandibular disorders (TMD) comprise the most common cause of chronic facial pain conditions, and they are often associated with somatic and psychological complaints including fatigue, sleep disturbances, anxiety, and depression. For many health professionals, the subjectivity of pain experience is frequently neglected even when the clinic does not find any plausible biologic explanation for the pain. This strictly biomedical vision of pain cannot be justified scientifically. The purpose of this study is to demonstrate, by original articles from the literature and recent studies conducted in our own laboratory, the biological processes by which psychological stress can be translated into the sensation of pain and contribute to the development of TMD. The role of the hypothalamic–pituitary–adrenal axis, the serotoninergic and opioid systems in the pathogenesis of facial pain is exposed, including possible future therapeutic approaches. It is hoped that knowledge from apparently disparate fields of dentistry, integrated into a multidisciplinary clinical approach to TMD, will improve diagnosis and treatment for this condition through a clinical practice supported by scientific knowledge.     

The pediatric patient at a maxillofacial service: Eye prosthesis

Congenital absence or loss of the ocular globe during childhood causes psycho-social and cosmetic disorders and compromise the normal development of the orbital region. The literature relating to congenital or acquired etiology, due to trauma or disease, demonstrates the necessity of prevention and early detection in order to minimize the sequelae and disturbances in orbital growth. Installation of an eye prosthesis is essential to the rehabilitation process, so as to produce satisfactory development of the region. In order to characterize a profile of the child patient with this condition, a survey was carried out at the Prosthetic Eye sector, Out-patient Clinic, Discipline of Maxillofacial Prosthodontics, School of Dentistry, University of S?o Paulo (FOUSP), during the period from 1988 to 2003. The 124 (14.02%) patients within the age group of 0-13 years registered for ocular prosthesis were divided into a first group of 64 patients (51.62%) with 0-7 years, and a second group of 60 patients (48.38%) with 8-13 years. Fifty nine were girls and 65 were boys. No statistical significance was observed regarding the distribution of genders in the two analyzed age groups (p = 0.069). However, there was statistical significance at the level of 0.01 in relation to etiology, with higher prevalence of congenital and pathological disturbances in the younger group and traumatic occurrences in the older group. The etiology also presented variation according to the gender, at the significance level of 0.05, where girls presented three times less trauma than boys in the older age group. The necessity of prosthetic ocular repair was evenly distributed along the childhood period and the eye losses that required prosthetic treatment equally affected both genders. However, the etiology of eye loss varied according to the considered gender and age bracket.     

Pharmacological assessment of the freezing, antinociception, and exploratory behavior organized in the ventrolateral periaqueductal gray

Opioid and serotonergic mechanisms of the ventrolateral periaqueductal gray (vlPAG) are recruited by conditioned freezing and antinociception. However, it is unclear whether freezing and antinociception induced by stimulation of the vlPAG are interrelated. To address this issue we looked at the effects of the opioid antagonist naltrexone, the 5-HT2 antagonist ketanserin, and the benzodiazepine agonist midazolam injected into the vlPAG on the freezing and antinociception induced by electrical stimulation of this region. This antinociception was evaluated by the tail-flick and formalin tests. To further characterize the involvement of the vlPAG in unconditioned fear, the effects of intra-vlPAG injections of midazolam on the exploratory behavior were also assessed in independent groups of rats submitted to the elevated plus-maze test (EPM). The data obtained showed that: (i) electrical stimulation of the vlPAG causes freezing blocked by midazolam but not by naltrexone and ketanserin; (ii) antinociception generated at the level of the vlPAG is inhibited by naltrexone, ketanserin, and midazolam; (iii) activation of benzodiazepine-mediated mechanisms in the vlPAG increased the exploratory behavior of rats in the closed arms but not the avoidance behavior of open arms of the EPM. Thus, freezing and antinociception generated in the vlPAG are dissociated pharmacologically. Whereas antinociception is a multimediated process sensitive to naltrexone, ketanserin, and midazolam, the freezing induced by vlPAG stimulation was reversed only by the benzodiazepine compound. As injections of midazolam into the vlPAG do not cause anxiolytic effects in the EPM, the aversive stimuli inherent of this test seem to bypass the vlPAG.     

Study of dimensional alterations of the orbit following loss of the eye

PURPOSE: This study aimed to assess the dimensional alterations in the anterior region of the orbit after enucleation or evisceration. MATERIALS AND METHODS: Analysis of orbital areas and perimeters of 17 patients with unilateral removal of the ocular bulb was performed, and posteroanterior radiographic examination was carried out by a single specialist, who had been previously calibrated. RESULTS: Data obtained from measurements confirmed the clinically observed facial asymmetry. CONCLUSION: The observation of asymmetry in the anterior orbital area, confirmed by our results, indicates early treatment to prevent orbital disturbances and will aid in the planning of prosthetic rehabilitation.     

Heparin-induced thrombocytopenia and warfarin-induced skin necrosis: case report

This paper describes a case of heparin-induced thrombocytopenia complicated by warfarin-induced skin necrosis in a 74-year old female patient hospitalized with diagnoses of a hip fracture, deep vein thrombosis and pulmonary thromboembolism. Warfarin-induced skin necrosis is a rare complication of anticoagulant therapy, with high morbidity and mortality that may be associated with heparin-induced thrombocytopenia.     

Selection of patients for percutaneous balloon mitral valvotomy: Is there a definitive limit for the Wilkins score?

AimThe aim of this study was to determine the early and long-term results of percutaneous balloon mitral valvotomy (PBMV) in patients with Wilkins score (WS) between 9 and 11.MethodsWe performed a retrospective review of clinical records of patients with rheumatic mitral stenosis who underwent PBMV between November 1991 and March 2008. Follow-up was obtained by telephone interview and/or clinical records. The procedure was considered unsuccessful when post-procedure mitral valve area was <1.5 cm².ResultsWe analyzed 124 patients, 108 (87.1%) of them women. Mean age at the time of repair was 46±11 years and mean follow-up time was 10±4 years. Before the procedure, 100 patients (80.6%) had WS ≤8 and 24 (19.4%) were in the “gray zone” (>8 and <11). Patients with WS ≤8 and patients in the gray zone had similar ages at first intervention (45±11 vs. 49±11 years; p=0.095) and follow-up time (10±4 vs. 11±5 years; p=0.55). There were no differences between groups in gender (women: 86% vs. 92%; p=0.735), or in baseline echocardiographic measurements (mitral valve area by planimetry 1.0 cm² [P25-P75: 0.9-1.1] vs. 0.9 [P25-P75: 0.8-1.2], p=0.514; pulmonary artery systolic pressure 53 mmHg [P25-P75: 45-63] vs. 50 [P25-P75: 44-54], p=0.823]; left atrial diameter >55 mm [16.5% vs. 13.6%, p=1.00]; mitral regurgitation [46.5% vs. 37.5%, p=0.428]) or baseline transmitral gradient (13 mmHg [P25-P75: 10-19] vs. 13 mmHg [P25-P75: 7-20]). Improvements in mitral valve area by planimetry and in hemodynamic gradient were similar in the two groups (0.91±0.39 cm² vs. 0.84±0.44 cm², p=0.55; 8.8±5.3 mmHg vs. 7.3±5.9 mmHg, p=0.275, respectively). There were no significant differences in major complications or success rates (4.0 vs. 12.5 p=0.131; 89.9% vs. 95.8%, p=0.69) or in need for urgent surgery or future reintervention (2.0 vs. 8.3%, p=0.168; 22% vs. 27.3%, p=0.594). In-hospital mortality occurred only in patients in the WS gray zone (2 [8.3%] vs. 0%, p=0.04), one death (4.2% vs. 0%, p=0.194) possibly being related to a higher WS (secondary to stroke) and the other as a consequence of peripheral vascular complication. Improvements in NYHA functional class soon after the procedure and during follow-up were similar in the two groups. Total mortality was similar in the two groups (3.1 vs. 8.7%, p=0.244).ConclusionsPBMV was a safe and effective procedure in patients in the WS gray zone. Optimal results can be achieved in these patients if they are carefully selected and operated at experienced centers.