Cementoblastoma related to a primary tooth: a case report

Cementoblastomas are benign lesions of the odontogenic ectomesenchyme that rarely occur related to the primary dentition, especially on the left side of the mandible. This study describes a case of a true cementoblastoma related to the left second primary mandibular molar in a 7-year-old child (the largest one seen in the left side of the mandible). Additionally, the radiographic and histologic findings of the lesion are described in details.     

Early-onset gastric carcinomas display molecular characteristics distinct from gastric carcinomas occurring at a later age

Gastric cancer is thought to result from a combination of environmental factors and accumulation of specific genetic alterations, and consequently mainly affects older patients (>50 years of age). Fewer than 10% of patients present with the disease before 45 years of age and these young patients are thought to develop carcinomas with a different molecular genetic profile from that of sporadic carcinomas occurring at a later age. Forty early-onset gastric carcinoma resection specimens were characterized for microsatellite instability (MSI) and loss of heterozygosity status using 22 polymorphic microsatellite markers. Twenty-four biopsies were additionally evaluated for the presence of MSI. No MSI was observed in any of the cases analysed. Losses were infrequent, but were most common for the D1S234 (26.1%) and D1S1676 (17.4%) markers, flanking the RUNX3 gene; for the p53ALU (23.1%) and TP53 (15.4%) markers, near the TP53 gene; and for the D16S2624 (17.2%) marker, near the E-cadherin (CDH1) gene. All cases with loss of CDH1, as well as 6/7 cases with loss of TP53, displayed aberrant staining of the corresponding proteins, pointing to a functional role for these proteins in early-onset gastric carcinogenesis. No germline CDH1, TP53 or RUNX3 mutations were detected in any of the cases analysed. No correlation was observed between non-functional E-cadherin and the histological type of the tumours analysed. Finally, Epstein-Barr virus was not detected in any of the cases analysed. On the basis of these results, early-onset gastric carcinomas appear to have characteristics distinct from gastric carcinomas occurring at a later age.     

Histopathology of familial and early-onset gastric cancer

Early-onset gastric cancer (EOGC) is defined as gastric cancer presenting at the age of 45 or younger. Approximately 10% of gastric cancer patients fall into the EOGC category. Furthermore, 10% of young gastric cancer patients have a positive family history, some of which are accounted for by inherited gastric cancer predisposition syndromes. Although the underlying genetic events are not always known, it can involve CDH1 germline mutations, encoding an aberrant form of E-cadherin, resulting in Hereditary diffuse gastric cancer (HDGC) and this occurs in 25–40% of tested families. Management options for asymptomatic mutation carriers are fraught, since endoscopic surveillance can miss cancer foci and prophylactic gastrectomy has profound clinical sequelae. This review serves to bring us up-to-date with the latest findings in EOGC and HDGC including implications for the clinician, geneticist and pathologist.     

Zidovudine-induced diaphragmatic contractile dysfunction: impact of an antioxidant diet

OBJECTIVE: Zidovudine (AZT) is a primary drug therapy used to treat HIV-infected individuals. While AZT inhibits replication of HIV, it also induces a drug-specific myopathy resulting in altered muscle mitochondria, increased oxidative stress and muscle contractile dysfunction. The purpose of this study was to assess the impact of an antioxidant diet (high in vitamins C and E) on AZT-mediated diaphragmatic contractile dysfunction in rodents. METHODOLOGY: Adult, Sprague-Dawley rats were assigned to feeding groups: control (CON, n = 9), AZT-treatment (AZT, n = 8), antioxidant diet only (Anti-Ox, n = 6), and AZT + antioxidant diet (AZT + Anti, n = 9). Two costal diaphragm strips were removed from each animal (under surgical anaesthesia) and evaluated for force-frequency relationship, maximal specific tension, and fatigue resistance using an in vitro preparation. RESULTS: Results indicate significant reductions in normalized force production (20-200 Hz), including maximal specific tension, between AZT animals and all other groups. While AZT reduced diaphragm contractility, the addition of an antioxidant diet eliminated this decrease. CONCLUSION: These data suggest that an increase in oxidative stress mediated by AZT may contribute to AZT-induced muscle contractile dysfunction, and that antioxidant vitamin supplementation may help ameliorate this effect.     

Quantitative Measurement of the Target-Mediated Internalization Kinetics of Biopharmaceuticals

Pharmaceutical Research - Measurement of internalization of biopharmaceuticals targeting cell surface proteins can greatly facilitate drug development. The objective of this study was to develop a...     

Methamphetamine Exposure Combined with HIV-1 Disease or gp120 Expression: Comparison of Learning and Executive Functions in Humans and Mice

Methamphetamine dependence is a common comorbid condition among people living with HIV, and may exacerbate HIV-associated neurocognitive disorders. Animal models of neuroAIDS suggest that the gp120 protein may also cause cognitive impairment. The present work evaluated the separate and combined effects of HIV/gp120 and methamphetamine on learning and executive functions in both humans and transgenic mice. Human participants were grouped by HIV serostatus (HIV+ or HIV−) and lifetime methamphetamine dependence (METH+ or METH−). A neurocognitive test battery included domain-specific assessments of learning and executive functions. Mice (gp120+ and gp120−) were exposed to either a methamphetamine binge (METH+) or saline (METH−), then tested in the attentional-set-shifting task to assess learning and executive functions. In humans, HIV status was associated with significant impairments in learning, but less so for executive functions. The frequency of learning impairments varied between groups, with the greatest impairment observed in the HIV+/METH+ group. In mice, gp120 expression was associated with impairments in learning but not reversal learning (executive component). The greatest proportion of mice that failed to complete the task was observed in the gp120+/METH+ group, suggesting greater learning impairments. Our cross-species study demonstrated that HIV in humans and gp120 in mice impaired learning, and that a history of methamphetamine exposure increased the susceptibility to HIV-associated neurocognitive deficits in both species. Finally, the similar pattern of results in both species suggest that the gp120 protein may contribute to HIV-associated learning deficits in humans.