Acute renal and hepatic toxicity of 2-haloanilines in Fischer 344 rats.

Aniline and its halogenated derivatives are widely used as chemical intermediates. The purpose of this study was to determine the hepatotoxic and nephrotoxic potential of the 2-haloanilines. Male Fischer 344 rats (n > or = 4) were injected (i.p.) with 1.0 or 1.25 mmol/kg of: aniline (A), 2-fluoroaniline (2-FA), 2-chloroaniline (2-ClA), 2-bromoaniline (2-BrA), 2-iodoaniline (2-IA) or vehicle (0.9% saline, 2.5 ml/kg). All compounds were injected as hydrochloride salts. Renal and hepatic function was monitored 24 h after treatment. All of the 2-haloanilines induced oliguria, diminished kidney weight, tubular casts and decreased renal cortical slice accumulation of organic anions. Blood urea nitrogen (BUN) levels were increased (P < 0.05) by treatment with 1.0 or 1.25 mmol/kg of 2-FA, 2-ClA or 2-BrA. Hepatic alterations were also observed and characterized by elevated plasma ALT/GPT activity and altered morphology in the centrilobular region. The nephrotoxic and hepatotoxic potentials were similar among the 2-haloanilines but aniline was less toxic than its 2-halo derivatives. These results demonstrated that halogen substitution at the 2-position of aniline increased hepatic and renal toxicity. However, the severity of toxicity was not influenced by the nature of the halogen substituent.     

Do theories of suicide play well together? Integrating components of the hopelessness and interpersonal psychological theories of suicide

Given that suicide is a leading cause of death worldwide, there has been considerable research on theories of suicide risk. Despite the volume of such research, each theory is largely investigated in isolation and there has been little attempt to integrate them. Thus, the goal of the present study is to integrate two theories of suicide risk, Alloy and Abramson’s hopelessness theory of suicide (HT) and Joiner’s interpersonal psychological theory of suicide (IPTS), into one mediational model where the effects of the risk associated with the HT variables (i.e., a negative cognitive style) on suicidal ideation are transmitted by the IPTS (i.e., perceived burdensomeness and thwarted belonging) variables. Participants were 245 young adults with elevated levels of depressive symptoms who completed self-report measures of suicide risk at baseline and a measure of suicidal ideation eight weeks later. The results of a mediated model supported our hypothesis. The effects of the HT variables on suicidal ideation were mediated by the IPTS variables. Furthermore, results did not support the reverse model, suggesting specificity of the direction of our hypotheses. These findings imply that there may be merit in attempting to integrate theories of suicide risk rather than studying them in isolation.     

Conservative Beliefs,Male Gender,and Beliefs About Means Safety Among Firearm Owners

Cognitive Therapy and Research - Reducing access to highly lethal methods for suicide (i.e., means safety) has been promoted as a way to reduce suicide risk. Research by Anestis et al. (J Affect...     

Effect of three n-acetylamino acids on N-(3,5-dichlorophenyl)succinimide (NDPS) and ndps metabolite nephrotoxicity in Fischer 344 rats

The agricultural fungicide N-(3,5-dichlorophenyl)succinimide (NDPS) induces nephrotoxicity in mammals characterized as polyuric renal failure and proximal tubular necrosis. Recent studies have suggested that NDPS-induced nephrotoxicity may be mediated by metabolites arising from the nephrotoxic NDPS metabolites N-(3,5-dichlorophenyl)-2-hydroxysuccinimide (NDHS) and/or N-(3,5-dichlorophenyl)-2-succinamic acid (2-NDHSA). The purpose of this study was to examine the effects of N-acetylcysteine (NAC), a nucleophilic agent, and two nonnucleophilic N-acetylamino acids, N-acetylserine (NAS) and N-acetylalanine (NAA), on NDPS and NDPS metabolite-induced nephrotoxicity. Male Fischer 344 rats (4-8/group) were administered intraperitoneally (ip) an N-acetylamino acid (1 mmol/kg) 2 h before an ip injection of NDPS (0.4 mmol/kg), NDHS (0.1 mmol/kg), 2-NDHSA (0.1 mmol/kg), or vehicle. Renal function was then monitored at 24 and 48 h. NAC pretreatment markedly attenuated NDPS-, NDHS-, and 2-NDHSA-mediated nephrotoxicity. The nonnucleophilic N-acetylamino acids (NAS, NAA) only partly reduced NDPS and NDHS nephrotoxicity, and they had little effect on 2-NDHSA nephrotoxicity. These results suggest that reactive NDPS metabolites may be formed from NDHS and 2-NDHSA and that nucleophilic substrates (e.g., NAC) may offer protection from NDPS-induced nephrotoxicity. However, mechanisms other than chemical neutralization of reactive NDPS metabolites may also be contributing to the attenuation of NDPS nephrotoxicity, since nonnucleophilic N-acetylamino acids (e.g., NAA) also provided some protection against NDPS and NDHS nephrotoxicity.     

Effect of sulfation substrates/inhibitors on N-(3,5-dichlorophenyl)succinimide nephrotoxocity in Fischer 344 rats.

The agricultural fungicide N-(3,5-dichlorophenyl)succinimide (NDPS) is an acute nephrotoxicant in rats. Our previous studies suggested that sulfate conjugation of NDPS metabolites might be a bioactivation step mediating NDPS nephrotoxicity. In this study, effects of substrates and/or inhibitors of sulfation on NDPS nephrotoxicity were examined to explore further the role of sulfation in NDPS nephrotoxicity. Male Fischer rats (4-8/group) were administered one of the following intraperitoneal (ip) pretreatment (dose, pretreatment time) prior to NDPS (0.6 mmol/kg) or NDPS vehicle (sesame oil, 2.5 ml/kg): (1) no pretreatment, (2) dehydroepiandrosterone (DHEA) (0.5 mmol/kg, 1 h), or (3) 2,6-dichloro-4-nitrophenol (DCNP) (0.04 mmol/kg, 1 h). Following NDPS or NDPS vehicle administration, renal function was monitored at 24 and 48 h. Pretreatment with DHEA, a typical substrate for and an inhibitor of hydroxysteroid (alcohol) sulfotransferase, resulted in marked protection against NDPS nephrotoxicity. A selective inhibitor of phenol sulfotransferase, DCNP, afforded little attenuation in NDPS nephrotoxicity. These results suggest that alcohol sulfate conjugates of NDPS metabolites, rather than phenolic sulfate conjugates, may be a penultimate or ultimate nephrotoxicant species mediating NDPS nephrotoxicity. The marked, but not complete, protection by DHEA also suggests that there are other metabolites or mechanisms responsible for NDPS nephrotoxicity.     

Overcoming the fear of lethal injury: Evaluating suicidal behavior in the military through the lens of the Interpersonal–Psychological Theory of Suicide

Suicide rates have been increasing in military personnel since the start of Operation Enduring Freedom and Operation Iraqi Freedom, and it is vital that efforts be made to advance suicide risk assessment techniques and treatment for members of the military who may be experiencing suicidal symptoms. One potential way to advance the understanding of suicide in the military is through the use of the Interpersonal–Psychological Theory of Suicide. This theory proposes that three necessary factors are needed to complete suicide: feelings that one does not belong with other people, feelings that one is a burden on others or society, and an acquired capability to overcome the fear and pain associated with suicide. This review analyzes the various ways that military service may influence suicidal behavior and integrates these findings into an overall framework with relevant practical implications. Findings suggest that although there are many important factors in military suicide, the acquired capability may be the most impacted by military experience because combat exposure and training may cause habituation to fear of painful experiences, including suicide. Future research directions, ways to enhance risk assessment, and treatment implications are also discussed.     

Discomfort Intolerance and the Acquired Capability for Suicide

Research has yet to examine the potential relationship between discomfort intolerance and the acquired capability for suicide. However, a link between numerous constructs related to discomfort intolerance (e.g., DT, pain tolerance) and the acquired capability has been established. Although these constructs are similar to the concept of discomfort intolerance, the operational definitions associated with these variables are divergent enough to merit an investigation pertaining to the relationship between discomfort intolerance and acts of lethal self-harm. Specifically, we chose to determine whether low discomfort intolerance would be associated with elevated levels of the acquired capability for suicide. Results were consistent with the our hypothesis, revealing a significant association between discomfort intolerance and the acquired capability above and beyond the effects of sex, self-reported and behaviorally-indexed DT, pain tolerance, and prior exposure to painful and/or provocative experiences. These findings serve to clarify the role of discomfort intolerance in the acquisition of the capability required to engage in acts of lethal self-harm. Furthermore, these results emphasize the importance of enduring aversive physiological sensations in the development of the acquired capability for suicide.     

Dysregulated Eating and Distress: Examining the Specific Role of Negative Urgency in a Clinical Sample

Many theories exist regarding dysregulated eating behaviors such as bingeing and purging. Recent research has provided consistent and compelling evidence supportive of theories that favor an emotion regulatory model (Smyth et al. J Consult Clin Psychol 75:629–638, 2007). Specifically, these theories posit that individuals engage in dysregulated eating behaviors in a maladaptive attempt to alleviate negative affect. Along these lines, several studies have reported that negative urgency, the tendency to act rashly in an attempt to immediately reduce feelings of negative affect (Whiteside and Lynam Pers Individ Dif 30:669–689, 2001), is a particularly important variable in this process (Anestis et al. Behav Res Ther 45:3018–3029, 2007; Fischer et al. Int J Eat Disord 33:406–411, 2003). In this study, we sought to expand upon prior research by testing the relationship between negative urgency and EDI-Bulimia in a clinical sample (N = 130) when controlling for an extensive list of relevant covariates, including additional components of impulsivity. Results supported our hypotheses. These findings indicate that the previously reported relationship between negative urgency and dysregulated eating behaviors remains significant in a clinical setting, even when controlling a more extensive list of impulsivity related variables than has been utilized in prior research. As such, this study has potentially important clinical implications.