Chlorine, chromium, proteins of oxidative stress and DNA repair pathways are related to prognosis in oral cancer.

The comparison of chemical and histopathological data obtained from the analysis of excised tumor fragments oral squamous cell carcinoma (OSCC) with the demographic and clinical evolution data is an effective strategy scarcely explored in OSCC studies. The aim was to analyze OSCC tissues for protein expression of enzymes related to oxidative stress and DNA repair and trace elements as candidates as markers of tumor aggressiveness and prognosis. Tumor fragments from 78 OSCC patients that had undergone ablative surgery were qualitatively analyzed by synchrotron micro-X-ray fluorescence for trace elements. Protein expression of SOD-1, Trx, Ref-1 and OGG1/2 was performed by immunohistochemistry. Sociodemographic, clinical, and histopathological data were obtained from 4-year follow-up records. Disease relapse was highest in patients with the presence of chlorine and chromium and lowest in those with tumors with high OGG1/2 expression. High expression of SOD-1, Trx, and Ref-1 was determinant of the larger tumor. Presence of trace elements can be markers of disease prognosis. High expression of enzymes related to oxidative stress or to DNA repair can be either harmful by stimulating tumor growth or beneficial by diminishing relapse rates. Interference on these players may bring novel strategies for the therapeutic management of OSCC patients.

Effects of prenatal immune activation on amphetamine-induced addictive behaviors: Contributions from animal models.

BACKGROUND: Prenatal environmental adversities may affect brain development and are associated with increased risk for schizophrenia, an illness with 50% comorbidity with addiction. Maternal immune activation by poly-inosinic-citidilic acid (Poly(I:C)) exposure can promote behavioral alterations consistent with schizophrenia symptoms in rodents. OBJECTIVES: Considering the vulnerability to addiction in patients with schizophrenia, we evaluated the interactions between prenatal Poly(I:C) administration and addiction in two animal models (behavioral sensitization and conditioned place preference - CPP) in mice repeatedly treated with amphetamine (AMP). Additionally, stereotyped behavior and cross-sensitization with cocaine (COC) were also investigated. METHODS: Swiss male mice offspring were submitted to prenatal administration of 5mg/kg Poly(I:C) in the 9(th) day of pregnancy. At the age of 90days, mice were treated with 2.5mg/kg AMP for 9days to evaluate behavioral sensitization or stereotyped behavior. Cross-sensitization with 10mg/kg COC was evaluated 24h after the last treatment day. For AMP-induced CPP evaluation, mice were treated during 8 consecutive days. RESULTS: Prenatal Poly(I:C) administration potentiated both AMP-induced behavioral sensitization and CPP. Furthermore, Poly(I:C) increased cross-sensitization with COC. CONCLUSIONS: Prenatal administration of Poly(I:C) is able to potentiate vulnerability to addiction in two animal models, without however modulating stereotyped behavior.

Short-term social isolation induces depressive-like behaviour and reinstates the retrieval of an aversive task: mood-congruent memory in male mice?

BACKGROUND: Although mood-congruent memory (MCM), or the tendency to recall information consistent with one's mood, is a robust phenomenon in human depression, to our knowledge, it has never been demonstrated in animals. METHODS: Mice were subjected to social isolation (SI) or crowding for 12 hours and had their depressive-like behaviour (evaluated by the forced swim, tail suspension, sucrose preference and splash tests) or their serum corticosterone concentrations evaluated. In addition, we determined the temporal forgetting curve of the plus-maze discriminative avoidance task (PM-DAT) and examined the effects of SI or crowding on memory retrieval in the PM-DAT. Finally, we verified the effects of metyrapone pretreatment on reinstatement of memory retrieval or on the increase of corticosterone levels induced by SI. RESULTS: Twelve hours of SI produced depressive-like behaviour, enhanced corticosterone concentration and reinstated retrieval of a forgotten discriminative aversive (i.e., negatively valenced) task. Depressive-like behaviour was critical for this facilitative effect of SI because 12 hours of crowding neither induced depressive-like behaviour nor enhanced retrieval, although it increased corticosterone levels at the same magnitude as SI. However, corticosterone increase was a necessary condition for MCM in mice, in that the corticosterone synthesis inhibitor metyrapone abolished SI-induced retrieval reinstatement. LIMITATIONS: Our study did not investigate the effects of the social manipulations proposed here in a positively valenced task. CONCLUSION: To our knowledge, the present paper provides the first evidence of MCM in animal models.

Addictive potential of modafinil and cross-sensitization with cocaine: a pre-clinical study.

Repeated or even a single exposure to drugs of abuse can lead to persistent locomotor sensitization, which is the result of an abundance of neuroplastic changes occurring within the circuitry involved in motivational behavior and is thought to play a key role in certain aspects of drug addiction. There is substantial controversy about the addictive potential of modafinil, a wake-promoting drug used to treat narcolepsy that is increasingly being used as a cognitive enhancer and has been proposed as a pharmacotherapy for cocaine dependence. Male mice were used to investigate the ability of modafinil to induce locomotor sensitization after repeated or single administration in mice. Bidirectional cross-sensitization with cocaine and modafinil-induced conditioned place preference were also evaluated. Both repeated and single exposure to moderate and high doses of modafinil produced a pronounced locomotor sensitization that cross-sensitized in a bidirectional way with cocaine. Remarkably, when cocaine and modafinil were repeatedly administered sequentially, their behavioral sensitization was additive. Supporting these behavioral sensitization data, modafinil produced a pronounced conditioned place preference in the mouse. Taken together, the present findings provide pre-clinical evidence for the addictive potential of modafinil. Our data also strongly suggest that similar neural substrates are involved in the psychomotor/rewarding effects of modafinil and cocaine.