- Effects of Δ9-THC and cannabidiol vapor inhalation in male and female rats. [Journal Article]
- PPsychopharmacology (Berl) 2018 Jun 16
- CONCLUSIONS: In summary, the inhalation of THC or CBD, alone and in combination, produces approximately equivalent effects in male and female rats. This confirms the efficacy of the e-cigarette-based method of THC delivery in female rats.
- Ketamine administration during a critical period after forced ethanol abstinence inhibits the development of time-dependent affective disturbances. [Journal Article]
- NNeuropsychopharmacology 2018 May 24
- Forced abstinence from chronic two bottle-choice ethanol drinking produces the development of negative affective states in female C57BL/6J mice. We previously reported that this disrupted behavior is...
Forced abstinence from chronic two bottle-choice ethanol drinking produces the development of negative affective states in female C57BL/6J mice. We previously reported that this disrupted behavior is acutely reversed by administration of ketamine 30 min-prior to testing. Here we assessed whether ketamine can be used as an inoculant against the development of abstinence- dependent affective disturbances. In parallel, we examined the impact of ketamine administration on long-term potentiation (LTP) in the bed nucleus of the stria terminalis (BNST), a region implicated in affective disturbances. We administered ketamine (3 mg/kg i.p.) to female C57BL/6J mice with a history of chronic ethanol drinking at either the onset, two, or 6 days- post-abstinence and observed its impact on affective behavior in the elevated plus maze (EPM), the Novelty Suppressed Feeding Test (NSFT), and the Forced Swim Test (FST). In addition, we assessed BNST synaptic plasticity with field potential electrophysiology two to 3 weeks into abstinence. We found that early abstinence was associated with disrupted behavior on the EPM. Ketamine administered at the onset of forced abstinence prevented both the deficit in early EPM behavior, and the delayed deficits in NSFT and FST. However, ketamine administered either two or 6 days post-abstinence failed to prevent the abstinence-induced affective disturbances. To begin to explore potential alterations in neural circuit activity that accompanies these actions of ketamine, we assessed the impact of ketamine administration at the onset of forced abstinence and measured LTP induction in the BNST. We find that early ketamine administration persistently increased the capacity for LTP within the BNST. These findings suggest a critical period at the onset of forced abstinence in which ketamine inoculation can prevent the development of affective disturbances, in part by enhancing plasticity within the BNST.
- Proximal and Distal Effects of Sensation Seeking and Parenting Environments on Alcohol Use Trajectories from Early Adolescence to Early Adulthood. [Journal Article]
- JYJ Youth Adolesc 2018 Jun 15
- Adolescent alcohol use is related to disinhibition traits and family environments. However, research is scarce on whether these factors predict alcohol use trajectories distally, from early adolescen...
Adolescent alcohol use is related to disinhibition traits and family environments. However, research is scarce on whether these factors predict alcohol use trajectories distally, from early adolescence into early adulthood. We examined whether sensation seeking and parenting environments in early adolescence predicted adolescents' alcohol use trajectories proximally (middle-adolescence) and distally (early adulthood). Using four waves of data from 345 adolescents (51.3% female; 80% white) and their primary caregivers, we estimated adolescents' alcohol use trajectories and examined variability in these by sensation seeking and parental control. The findings revealed distal, positive associations between sensation seeking and alcohol use; and negative, proximal associations between parental control and alcohol use. Also proximally, there was a significant interaction between sensation seeking and parental control. We discuss implications for theory and practice.
- Disulfiram/copper causes ROS levels alteration, cell cycle inhibition, and apoptosis in acute myeloid leukaemia cell lines with modulation in the expression of related genes. [Journal Article]
- BPBiomed Pharmacother 2018; 99:561-569
- The majority of acute myeloid leukaemia (AML) patients will die from their disease or therapy-related complications. There is an inevitable need to improve the survival of AML patients. Previous stud...
The majority of acute myeloid leukaemia (AML) patients will die from their disease or therapy-related complications. There is an inevitable need to improve the survival of AML patients. Previous studies show that disulfiram (DSF), an anti-alcoholism drug with a low toxicity profile, demonstrates anticancer behaviors. Here, we evaluated the cytotoxicity and mechanistic action of DSF on the AML cell lines KG-1, NB4, and U937. The microculture tetrazolium test revealed that DSF alone or in combination with copper (Cu) is highly toxic to the AML cells at concentrations lower than those achievable in the clinical setting, with Cu increasing the DSF-induced inhibition of metabolic activity. Flow cytometric analysis and QRT-PCR indicated that in the two cell lines, NB4 and U-937, DSF/Cu increased reactive oxygen species (ROS) levels in association with the induction of superoxide dismutase 2 (SOD2) expression and suppression of catalase (CAT). In the KG-1 cell line, DSF/Cu reduced the ROS levels in agreement with the induction of CAT expression. The cell cycle and apoptosis assessment by flow cytometry demonstrated that DSF/Cu induced G0/G1 cell cycle arrest and apoptosis. These were associated with the increased expression of FOXO tumor suppressors, decreased expression of the MYC oncogene and the modulation of their known target genes related to the cell cycle and apoptosis. Therefore, DSF/Cu caused the disturbance of the ROS balance, cell cycle arrest and apoptosis in AML cells in coordination with the modulation in expression of their related genes. These results propose the possible use of DSF in AML therapies.
- Vibrio vulnificus infection: a persistent threat to public health. [Journal Article]
- KJKorean J Intern Med 2018 Jun 15
- Vibrio vulnificus is a gram-negative bacterium that can cause serious, potentially fatal infections. V. vulnificus causes three distinct syndromes: an overwhelming primary septicemia caused by consum...
Vibrio vulnificus is a gram-negative bacterium that can cause serious, potentially fatal infections. V. vulnificus causes three distinct syndromes: an overwhelming primary septicemia caused by consuming contaminated seafood, wound infections acquired when an open wound is exposed to contaminated warm seawater, and gastrointestinal tract-limited infections. Case-fatality rates are higher than 50% for primary septicemia, and death typically occurs within 72 hours of hospitalization. Risk factors for V. vulnificus infection include chronic liver disease, alcoholism, and hematological disorders. When V. vulnificus infection is suspected, appropriate antibiotic treatment and surgical interventions should be performed immediately. Third-generation cephalosporin with doxycycline, or quinolone with or without third-generation cephalosporin, may be potential treatment options for patients with V. vulnificus infection.
- Orbital frontal cortex updates state-induced value change for decision-making. [Journal Article]
- EElife 2018 Jun 13; 7
- Recent hypotheses have posited that orbital frontal cortex (OFC) is important for using inferred consequences to guide behavior. Less clear is OFC's contribution to goal-directed or model-based behav...
Recent hypotheses have posited that orbital frontal cortex (OFC) is important for using inferred consequences to guide behavior. Less clear is OFC's contribution to goal-directed or model-based behavior, where the decision to act is controlled by previous experience with the consequence or outcome. Investigating OFC's role in learning about changed outcomes separate from decision-making is not trivial and often the two are confounded. Here we adapted an incentive learning task to mice, where we investigated processes controlling experience-based outcome updating independent from inferred action control. We found chemogenetic OFC attenuation did not alter the ability to perceive motivational state-induced changes in outcome value but did prevent the experience-based updating of this change. Optogenetic inhibition of OFC excitatory neuron activity selectively when experiencing an outcome change disrupted the ability to update, leaving mice unable to infer the appropriate behavior. Our findings support a role for OFC in learning that controls decision-making.
- Isoniazid-induced neuropathy in a pre-pubertal child. [Journal Article]
- PIPaediatr Int Child Health 2018 Jun 13; :1-3
- Isoniazid (INH)-induced peripheral neuritis is not uncommonly reported in adults, especially those with malnutrition and alcoholism, but it is very rare in children. INH leads to peripheral neuritis ...
Isoniazid (INH)-induced peripheral neuritis is not uncommonly reported in adults, especially those with malnutrition and alcoholism, but it is very rare in children. INH leads to peripheral neuritis by causing a deficiency in the serum level of pyridoxine which depends on the dose of INH, duration of treatment and the patient's nutritional and acetylator status. A 12-year-old girl developed tingling and numbness of the lower limbs after commencing anti-tuberculous therapy which included INH 10 mg/kg/day. The symptoms continued despite the dose being reduced to 5 mg/kg/day. Nerve conduction velocity was normal. Her diet was poor: she consumed little or no fruit and vegetables and ate mostly dal and rice. Discontinuation of INH was advised and her therapy was changed to ofloxacin, rifampicin, ethambutol and pyrazinamide along with a high dose of pyridoxine and multi-vitamins. The tingling and numbness subsided within 15 days, after which INH was prescribed at the dose of 10 mg/kg/day. Although INH-induced neuropathy is rare in children, the World Health Organization recommends pyridoxine prophylaxis for children on INH who are malnourished or have HIV infection.
- "Immune Gate" of Psychopathology-The Role of Gut Derived Immune Activation in Major Psychiatric Disorders. [Review]
- FPFront Psychiatry 2018; 9:205
- Interaction between the gastrointestinal tract (GI) and brain functions has recently become a topic of growing interest in psychiatric research. These multidirectional interactions take place in the ...
Interaction between the gastrointestinal tract (GI) and brain functions has recently become a topic of growing interest in psychiatric research. These multidirectional interactions take place in the so-called gut-brain axis or more precisely, the microbiota-gut-brain axis. The GI tract is the largest immune organ in the human body and is also the largest surface of contact with the external environment. Its functions and permeability are highly influenced by psychological stress, which are often a precipitating factor in the first episode, reoccurrence and/or deterioration of symptoms of psychiatric disorders. In recent literature there is growing evidence that increased intestinal permeability with subsequent immune activation has a major role in the pathophysiology of various psychiatric disorders. Numerous parameters measured in this context seem to be aftermaths of those mechanisms, yet at the same time they may be contributing factors for immune mediated psychopathology. For example, immune activation related to gut-derived bacterial lipopolysaccharides (LPS) or various food antigens and exorphins were reported in major depression, schizophrenia, bipolar disorder, alcoholism and autism. In this review the authors will summarize the evidence and roles of such parameters and their assessment in major psychiatric disorders.
- Occult Hepatitis B and Other Unexplored Risk Factors for Hepatocellular Carcinoma in Latin America. [Journal Article]
- AHAnn Hepatol 2018 Jun 20; 17(4):541-543
- Occult hepatitis B infection (OBI) is the presence of hepatitis B virus (HBV) DNA in the liver and/or serum (< 200 IU/mL) in HBsAgnegative patients with or without serologic markers of previous vi...
Occult hepatitis B infection (OBI) is the presence of hepatitis B virus (HBV) DNA in the liver and/or serum (< 200 IU/mL) in HBsAgnegative patients with or without serologic markers of previous viral exposure. The clinical significance of OBI is of concern in posttransfusional hepatitis B infection, hepatitis B reactivation, chronic liver disease and hepatocellular carcinoma (HCC). The diagnosis of OBI relays on the use of highly sensitive and specific laboratory techniques. Herein, comments derived from a study analyzing the frequency and characteristics of OBI in HCC Japanese patients are stated. While OBI and other causes of HCC have been highly studied in Asia and Europe, research in Latin America in these topics is limited. Several findings such as population risk groups with high prevalence of overt and OBI infection, HBV genotype F in Argentinean HCC patients, and the clinical impact of the foreign A-D genotypes suggest the need of further investigation. Additionally, alcoholism, obesity, NASH and type 2 diabetes may override the presence of OBI. Therefore, OBI diagnosis is essential. It is known that anti-HBc alone is a predictive signal of potential OBI and given the fluctuations of the HBV infection markers, testing for HBsAg and anti-HBc at baseline and follow-up is recommended. In conclusion, OBI and other causes involved in the epidemiology of HCC in Latin America are unexplored risk factors. Genome-based research is required to decipher the role of gene-environmental interactions associated with chronic liver disease. Novel algorithms to detect OBI supported by basic/applied/clinical research are also needed.
New Search Next
- Intensity of Daily Drinking and its Relation to Alcohol Use Disorders. [Journal Article]
- ACAlcohol Clin Exp Res 2018 Jun 12
- CONCLUSIONS: Daily drinkers represents a highly heterogeneous group, and the correlates of daily drinking depend on the usual quantity of daily drinks and the frequency of alcohol-related problems in a given sample. Moreover, AUD, defined both according to DSM-IV and DSM-5, did not capture more than 68% of daily binge drinkers. Given that daily binge drinking is an extremely high threshold for use, this finding may present a challenge for our current classification system. This article is protected by copyright. All rights reserved.