Finding changes induced by the drug of abuse is one of the most important approaches to design new drugs for the treatment of substance use disorders (SUD). Postmortem study is the most reliable method for detecting alteration in the brain of SUD patients. Recently, the role of orexinergic system in SUD is in consideration. In the current study, we evaluated the level of orexin-A in the CSF and protein kinase C alpha (PKC alpha) in the brain of pureopioid (POA) and multi-drug abusers (MDA). A total of 56 POA, 45 MDA, and 13 matched control brains were collected from the legal medicine center, Tehran, Iran. The CSF was gathered from the third ventricle immediately after opening the skull and kept at - 80 degrees C. The medial prefrontal cortex (mPFC), lateral prefrontal cortex (lPFC), orbitofrontal cortex (OFC), nucleus accumbens (NAc), and amygdala were dissected from fresh brain, frozen with liquid nitrogen and kept at - 80 degrees C. The level of orexin-A evaluated in the CSF. Using western blotting, the level of PKC alpha assessed in the brain. Obtained data revealed that the level of orexin-A increased in POA and MDA compared with the control group (p < 0.05). In addition, the level of PKC alpha increased in the prefrontal cortex and amygdala of the abusers compared with the control group, although we did not detect changes in the level of PKC alpha in the NAc. Along with animal studies, the current results showed that the level of orexin increased in the CSF of drug abusers, which might be related to increases in the activation of lateral hypothalamic orexinergic neurons faced with the drug of abuse. Enhancement in the level of PKC alpha in the drug reward circuits might be adaptational changes induced by orexin and drugs of abuse.

Background The pathogenic spectrum of bloodstream infections (BSIs) varies across regions. Monitoring the pathogenic profile and antimicrobial resistance is a prerequisite for effective therapy, infection control and for strategies aimed to counter antimicrobial resistance. The pathogenic spectrum of BSIs in blood cultures was analysed, focusing on the resistance patterns of Acinetobacter baumannii, Escherichia coli, and Klebsiella pneumoniae, in Aljouf region. Methods This descriptive cross-sectional study analysed the culture reports of all non-duplicate blood samples collected from January 1 to December 31, 2019. Antibiograms of A. baumannii, E. coli, and K. pneumoniae were analysed for antibiotic resistance. The frequency and percentages of multi-drug, extensively-drug, pan-drug and carbapenem resistance were calculated. Results Of the 222 bloodstream infections, 62.2% and 36.4% were caused by gram-negative and gram-positive bacteria, respectively. Most BSIs occurred in patients aged >= 60 years (59.5%). Among the 103 isolates of the studied Gram-negative bacteria (GNB), 47.6%, 38.8%, and 2.9% were multi-drug, extensively drug and pan-drug resistant respectively. 46% of K. pneumoniae isolates were carbapenemase producers. Resistance to gentamycin, 1(st)-4(th) generation cephalosporins, and carbapenems was observed for A. baumannii. More than 70% of E. coli isolates were resistant to 3(rd)- and 4(th)-generation cephalosporins. Klebsiella pneumoniae presented a resistance rate of >60% to imipenems. Conclusions Gram-negative bacteria dominate BSIs, with carbapenem-resistant K. pneumoniae most frequently detected in this region. Resistant GNB infections make it challenging to treat geriatric patients. Regional variations in antimicrobial resistance should be continually monitored.