Acid sphingomyelinase mediates the noise‐induced liver disorder in mice

Noise‐induced structural and functional disorder of the liver has been realized, but the underlying mechanism remains to be characterized, which has limited the introduction of precautious measures. Over‐activation of acid sphingomyelinase (ASM)/ceramide (Cer) pathway takes centre stage in hepatocyte injury entailed by various stimulus. We aimed to investigate whether it mediated the noise elicited liver disorder on infrastructure, lipid metabolism, apoptosis, and oxidative stress. Mice were exposed to broad band noise (20–20k Hz, 90–110 dB) for 1, 3, 5 or 7 days by 3 hr/d. Doxepin hydrochloride (DOX), an ASM inhibitor was given by 5 mg/kg/d gavage. We showed that 5 or 7 days intense, broad band noise exposure caused significant infrastructure derangement and lipid droplets storage in hepatocytes. The content of cholesterol, free fatty acids or triglyceride was increased significantly in liver tissue upon noise stimulation. Moreover, the noise promoted apoptosis and superoxide generation in hepatocytes significantly, enhancing activity of aspartate aminotransferase (AST) or alanine amino transferase (ALT) in serum. Acid sphingomyelinase activity and Cer generation in liver tissue were elevated by noise exposure, which was normalized with DOX administrated. Accordingly, DOX alleviated steatosis, apoptosis, oxidative stress and enzymatic change in hepatocytes or serum of noise exposed mice substantially. In summary, our results suggest the ASM/Cer pathway contributes to the broad band noise elicited liver damage in mice.     

High‐dose buprenorphine for treatment of high potency opioid use disorder

A 29‐year‐old woman presented to detox for treatment of an opioid use disorder with illicit fentanyl. While in detox, she was started on opioid agonist treatment with buprenorphine/naloxone. Unfortunately, she continued to have withdrawal symptoms despite being optimised to a dose of 32 mg. She was given additional PRNs of buprenorphine/naloxone to a total daily dose of 40 mg, which helped to alleviate her symptoms of withdrawal and cravings. She was stabilised on buprenorphine/naloxone 40 mg daily without any side effects and was discharged to a rehabilitation centre.     

Panic disorder. A long‐term treatment study: fluoxetine vs imipramine

This double‐blind study evaluates the efficacy and tolerability of fluoxetine and imipramine in the acute and long‐term treatment of panic disorder in 38 patients meeting DSM‐IV criteria for panic disorder with or without agoraphobia. On the basis of HRSA mean scores evaluation, fluoxetine was found to be quicker than imipramine in reducing generalized anxiety at the end of the first week of treatment. However, through PASS and CGI mean scores evaluation, no statistically significant differences were found at any time in the efficacy of fluoxetine and imipramine on the total number of panic attacks, anticipatory anxiety or phobia severity. Fluoxetine has also turned out to be better tolerated than imipramine and to be effective at dosages low enough to avoid the event of an activation syndrome. Long‐term evaluation has shown high rates of persistent remission with both drugs. Copyright © 1999 John Wiley & Sons, Ltd.     

Aberrant expression of miR‐451a contributes to 1,2‐dichloroethane‐induced hepatic glycerol gluconeogenesis disorder by inhibiting glycerol kinase expression in NIH Swiss mice

The identification of aberrant microRNA (miRNA) expression during chemical‐induced hepatic dysfunction will lead to a better understanding of the substantial role of miRNAs in liver diseases. 1,2‐Dichloroethane (1,2‐DCE), a chlorinated organic toxicant, can lead to hepatic abnormalities in occupationally exposed populations. To explore whether aberrant miRNA expression is involved in liver abnormalities mediated by 1,2‐DCE exposure, we examined alterations in miRNA expression patterns in the livers of NIH Swiss mice after dynamic inhalation exposure to 350 or 700 mg m^–3 1,2‐DCE for 28 days. Using a microarray chip, we discovered that only mmumiR‐451a was significantly upregulated in the liver tissue of mice exposed to 700 mg m^–3 1,2‐DCE; this finding was validated by quantitative real‐time polymerase chain reaction. In vitro study revealed that it was metabolite 2‐chloroacetic acid, not 1,2‐DCE that resulted in the upregulation of mmu‐miR‐451a in the mouse AML12 cell line. Furthermore, our data showed that the upregulation of mmu‐miR‐451a induced by 2‐chloroacetic acid could suppress the expression of glycerol kinase and lead to the inhibition of glycerol gluconeogenesis in mouse liver tissue and AML12 cells. These observations provide evidence that hepatic mmu‐miR‐451a responds to 1,2‐DCE exposure and might induce glucose metabolism disorders by suppressing the glycerol gluconeogenesis process.     

Short‐term and long‐term evaluation of selective serotonin reuptake inhibitors in the treatment of panic disorder: fluoxetine vs citalopram

This double‐blind study evaluates the efficacy and tolerability of fluoxetine and citalopram in the acute and long‐term treatment of panic disorder in 42 patients meeting DSM‐IV criteria for panic disorder with or without agoraphobia. Fluoxetine and citalopram showed similar efficacy in the treatment of panic disorder patients. On the basis of HRSA and PASS mean score evaluation, fluoxetine was more rapid than citalopram in reducing generalized anxiety symptoms, spontaneous panic attacks and anticipatory anxiety. Fluoxetine appeared to be effective at a dosage of 10 mg/day, while citalopram reached the same efficacy at a dosage of 30 mg/day. Long‐term evaluation has demonstrated high rates of persistent full remission with both drugs. Copyright © 1999 John Wiley & Sons, Ltd.     

Using the Severity of Dependence Scale to screen for DSM‐5 khat use disorder

Objective

This study aimed to determine the efficacy of the Severity of Dependence Scale (SDS) as a screening tool for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition‐defined khat use disorder.

Methods

Cross‐sectional, purposive sample of past‐year khat consumers aged 16 and above were recruited from khat markets and cafes from university and general community in Adama, Ethiopia. Participants self‐completed a survey comprising current substance use disorder.

Results

The SDS formed a unifactorial structure, consistent with the dependence construct. Almost three quarters (73%) of the sample were identified as experiencing Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition khat use disorder. The SDS demonstrated excellent discrimination (area under the curve = 0.92) and an optimal cut‐off as a score of 3 or greater, with sensitivity of 81% and specificity of 96%. This classification validly identified a group with more frequent and higher dose khat use than participants that did not screen positive.

Conclusion

Although khat is a mild stimulant, there is clear evidence that some consumers are both concerned with their use and experience problems associated with their use. Consistent with its application for other drugs, the SDS is a brief and simple screening tool that appears to validly identify individuals experiencing a khat use disorder syndrome and experiencing high rates of adverse consequences in association with use.     

Synthesis and Antifungal Activity of 1‐Aryl‐3‐phenethylamino‐1‐propanone Hydrochlorides and 3‐Aroyl‐4‐aryl‐1‐phenethyl‐4‐piperidinols

Mono‐Mannich bases, 1‐aryl‐3‐phenethylamino‐1‐propanone hydrochlorides, 1a, 2a , 3a , 4a , 5a , 6a , 7a , 8a , 9a , and semi‐cyclic mono‐Mannich bases, 3‐aroyl‐4‐aryl‐1‐phenethyl‐4‐piperidinols, 1b , 2b , 3b , 4b , 5b , 6b , 7b , 8b , 9b , were synthesized by a non‐classical Mannich reaction. The aryl part was: C₆H₅ for 1a , 1b ; 4‐CH₃C₆H₄ for 2a , 2b ; 4‐CH₃OC₆H₄ for 3a , 3b ; 4‐ClC₆H₄ for 4a , 4b ; 4‐FC₆H₄ for 5a , 5b ; 4‐BrC₆H₄ for 6a , 6b ; 2,4‐(Cl)₂C₆H₃ for 7a , 7b ; 4‐NO₂C₆H₄ for 8a , 8b ; and C₄H₃S(2‐yl) i. e., 2‐thienyl for 9a , 9b . Piperidinol compounds 2b , 3b , 4b , 5b , 7b , 8b , and 9b are reported here for the first time. The synthesized compounds were tested against seven types of plant pathogenic fungi and three types of human pathogenic fungi using the agar dilution assay. Itraconazole was tested against Candida parapsilosis as the reference compound, while Nystatin was tested as the reference compound against the other fungi. Compounds 1a , 1b , 2a , 4a , 4b , 5a , 5b , 6a , 7a , 8a , 9a , and 9b can be selected as model compounds to develop new antifungal agents against the human pathogen Microsporum canis. Compounds 8a and 8b , which had a similar antifungal activity compared with the reference compound Nystatin against the plant pathogen Aspergillus flavus, can serve as model compounds to develop new antifungal agents to solve agricultural problems.