Annals of the New York Academy of Sciences
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Ann. N. Y. Acad. Sci. · Dec 2008
Endocrine factors in stress and psychiatric disorders: focus on anxiety and salivary steroids.
Glucocorticoids and other steroids produced in the adrenal cortex are altered in chronic stress situations associated with enhanced anxiety. A useful tool to evaluate changes in adrenal steroids during stress and anxiety under both laboratory and real-life stress situations is determination of steroids in saliva. The main advantages of this technique are its noninvasiveness and its measurement of biologically active free hormone levels. ⋯ We have provided the first data on the relationship between aldosterone and trait anxiety. Obtained results show a significant negative correlation between morning salivary aldosterone concentrations and trait anxiety scores in women (luteal phase), but not in men. A more proper elucidation of the association between aldosterone and anxiety seems to be an important target of further research.
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Ann. N. Y. Acad. Sci. · Dec 2008
Persistence of residual beta cells and islet autoimmunity during increasing duration of diabetes in NOD mice and experimental approaches toward reversing new-onset disease with bioactive peptides.
The precise fate of beta cells and the presence of islet infiltrates after onset of type 1 diabetes have not yet been fully characterized. Recently we showed that in newly diabetic NOD mice an appreciable number of beta cells remain. This was also observed during the first 2 weeks of diabetes in NOD mice without treatment with insulin. ⋯ We speculate that the residual beta cells present soon after onset of diabetes may respond to experimental regeneration. Treatment of newly diabetic NOD mice with the bioactive peptides EGF and gastrin resulted in partial and temporary reversal of diabetes. We propose that peptide therapies combined with other benign immunomodulatory approaches to rescue and preserve beta cells in the long term and to prevent recurring autoimmunity may be more effective than peptide therapy alone in reversing diabetes in NOD mice.
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Ann. N. Y. Acad. Sci. · Nov 2008
ReviewExperimental therapeutic strategies for severe sepsis: mediators and mechanisms.
Severe sepsis is the leading cause of mortality in intensive care units. The limited ability of current therapies to reduce sepsis mortality rates has fueled research efforts for the development of novel treatment strategies. Through the close collaboration between clinicians and scientists, progress can be seen in the struggle to develop effective therapeutic approaches for the treatment of sepsis and other immune and inflammatory disorders. ⋯ Nonetheless, specific strategies that target the pathophysiological disorders in sepsis patients are essential to further improve clinical outcomes. This article reviews current clinical management approaches and experimental interventions that target pleiotropic or late-acting inflammatory mediators like caspases, C5a, MIF, and HMGB1, or the body's endogenous inflammatory control mechanisms such as the cholinergic anti-inflammatory pathway. These inflammatory mediators and anti-inflammatory mechanisms, respectively, show significant potential for the development of new experimental therapies for the treatment of severe sepsis and other infectious and inflammatory disorders.
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Ann. N. Y. Acad. Sci. · Oct 2008
ReviewAn update on substance use and treatment following traumatic brain injury.
Traumatic brain injury (TBI) is a leading cause of mortality and morbidity among young adults. Substance abusers constitute a disproportionate percentage of these patients. A history of substance abuse predicts increased disability, poorer prognosis, and delayed recovery. ⋯ While this comorbidity presents a challenge for the successful treatment and rehabilitation of both disorders, there is sparse evidence to recommend any specific treatment strategy for these individuals. Mild TBI and substance abuse are bidirectionally related both for risks and treatment. Further understanding the neuropsychiatric pathology and different effects of different types of injuries will likely improve the implementation of effective treatments for each of these two conditions.
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Ann. N. Y. Acad. Sci. · Oct 2008
Role of the NMDA receptor and nitric oxide in memory reconsolidation of cocaine-induced conditioned place preference in mice.
Classical pavlovian conditioning has a major role in the development and persistence of drug addiction. Appetitive conditioning by drug reward, as measured by the conditioned place preference (CPP) paradigm, is an exemplar of classical pavlovian conditioning. Aversive conditioning by footshock involves learning and memory processes similar to those involved in appetitive conditioning. ⋯ Male nNOS knockout (KO) mice acquired short-lived cocaine CPP compared to wild-type (WT) mice. A single acute administration of the NO-donor molsidomine to nNOS KO mice immediately after retrieval of CPP prolonged the expression of place preference compared to controls that received saline, suggesting partial strengthening of memory reconsolidation. Taken together, these findings support the role of the NMDAR/NO signaling pathway in memory reconsolidation of cocaine CPP, and suggest that disruption of this pathway during memory reconsolidation may afford resistance to drug-seeking behavior.