OBJECTIVES: To assess the regulatory effect of cannabidiol (CBD) on circadian rhythm sleep disorders following general anesthesia and explore its potential mechanism in a rat model of propofol-induced rhythm sleep disorder. METHODS: An electrode was embedded in the skull for cortical EEG recording in 24 male SD rats, which were randomized into control, propofol, CBD treatment, and diazepam treatment groups (n=6). Eight days later, a single dose of propofol (10 mg/kg) was injected via the tail vein with anesthesia maintenance for 3 h in the latter 3 groups, and daily treatment with saline, CBD or diazepam was administered via gavage; the control rats received only saline injection. A wireless system was used for collecting EEG, EMG, and body temperature data within 72 h after propofol injection. After data collection, blood samples and hypothalamic tissue samples were collected for determining serum levels of oxidative stress markers and hypothalamic expressions of the key clock proteins. RESULTS: Compared with the control rats, the rats with CBD treatment showed significantly increased sleep time at night (20:00-6:00), especially during the time period of 4:00-6:00 am. Compared with the rats in propofol group, which had prolonged SWS time and increased sleep episodes during 18:00-24:00 and sleep-wake transitions, the CBD-treated rats exhibited a significant reduction of SWS time and fewer SWS-to-active-awake transitions with increased SWS aspects and sleep-wake transitions at night (24:00-08:00). Diazepam treatment produced similar effect to CBD but with a weaker effect on sleep-wake transitions. Propofol caused significant changes in protein expressions and redox state, which were effectively reversed by CBD treatment. CONCLUSIONS CBD can improve sleep structure and circadian rhythm in rats with propofol-induced sleep disorder possibly by regulating hypothalamic expressions of the key circadian clock proteins, suggesting a new treatment option for perioperative sleep disorders.
Animals ; Rats, Sprague-Dawley ; Male ; Cannabidiol/therapeutic use* ; Rats ; Circadian Rhythm/drug effects* ; Propofol/adverse effects* ; Anesthesia, General/adverse effects* ; Sleep Wake Disorders/chemically induced* ; Hypothalamus/metabolism* ; Electroencephalography

OBJECTIVETo observe the effective mechanism and side effects of thalidomide to multiple myeloma (MM).

METHODSTen cases of MM were studied, of which 3 were previously untreated and 7 refractory or relapsed. Bone marrow microvascular density (MVD) was detected by factor-VIII related antigen and CD(34) immunohistological staining and serum concentration of vascular endothelial growth factor (VEGF) before and after treatment was determined by ELISA. The initial dosage of thalidomide was 100 approximately 200 mg/d with a weekly escalation of 50 mg/d to 450 approximately 650 mg/d. The therapeutic effectiveness is classified into partial remission, improvement and uneffective according to the decrease of serum M protein and bone marrow myeloma cells. Anemia, renal function and blood electrolytes were also observed.

RESULTSBefore treatment, MVD was 73.32 +/- 28.80 and 32.30 +/- 12.50 in MM and control group, respectively, (P < 0.01). MVD in MM group decreased to 56.12 +/- 19.34 after treatment, and was of significant difference (P < 0.05) as compared to the pretreatment value. However, there was still a significant difference as compared to control (56.12 +/- 19.34 vs 32.30 +/- 12.50, P < 0.01). The concentration of VEGF significantly decreased after treatment [from (178.23 +/- 26.56) ng/L to (78.48 +/- 19.98) ng/L, P < 0.01)]. The total effective rate was 70%. There were no serious side effects.

CONCLUSIONMVD and VEGF concentration were decreased obviously by thalidomide treatment. The dosage of 450 approximately 650 mg/d might be effective in refractory or initial MM.

Aged ; Angiogenesis Inhibitors ; adverse effects ; therapeutic use ; Antigens, CD34 ; analysis ; Bone Marrow ; blood supply ; drug effects ; Constipation ; chemically induced ; Endothelial Growth Factors ; blood ; Fatigue ; chemically induced ; Female ; Humans ; Immunohistochemistry ; Intercellular Signaling Peptides and Proteins ; blood ; Lymphokines ; blood ; drug effects ; Male ; Middle Aged ; Multiple Myeloma ; blood ; drug therapy ; pathology ; Nausea ; chemically induced ; Sleep Wake Disorders ; chemically induced ; Thalidomide ; adverse effects ; therapeutic use ; Treatment Outcome ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors ; von Willebrand Factor ; analysis