亚麻醉剂量氯胺酮对抑郁小鼠肠道菌群的影响

目的：　探究亚麻醉剂量氯胺酮对雄性和雌性抑郁样小鼠肠道菌群的影响。方法：　SPF级健康雄性和雌性C57BL/6小鼠各20只,随机分为8组（n=5）：雌性对照组（FC组）,雌性氯胺酮组（FCK组）,雌性抑郁组（FD组）和雌性抑郁+氯胺酮组（FDK组）;雄性对照组（MC组）,雄性氯胺酮组（MCK组）,雄性抑郁组（MD组）和雄性抑郁+氯胺酮组（MDK组）。FCK组和MCK组经尾静脉注射质量分数为10 mg/kg的氯胺酮,FC组和MC组经尾静脉注射等量生理盐水;FD组、FDK组、MD组和MDK组采用慢性不可预知温和应激（chronic unpredictable mild stress,CUMS）造模,造模后FDK组和MDK组分别经尾静脉注射10 mg/kg氯胺酮,FD组和MD组注射等量生理盐水。采用强迫游泳实验、糖水偏好实验和旷场试验评价小鼠抑郁行为变化,接着采集不同组别小鼠粪便进行粪便微生物16S rDNA序列定性分析及功能预测分析。采用单因素方差分析（one-way ANOVA）不考虑性别时各组肠道菌群的变化,采用双因素方差分析（two-way ANOVA）性别因素和氯胺酮处理对肠道菌群的影响,必要时进一步采用Tukey校正的多重比较对实验结果进行后检验。P<0.05为差异有统计学意义。结果：　分别与不同性别的对照组比较,使用CUMS方法处理小鼠后,强迫游泳不动时间明显延长（P<0.05）,糖水偏好度明显下降（P<0.05）,旷场试验水平运动得分和垂直运动得分明显减少（P<0.05）。经亚麻醉剂量氯胺酮处理后,行为学检测结果表明小鼠均有不同程度的改善（P<0.05）。物种组成分析结果显示,在经过CUMS造模处理后,各组小鼠肠道菌群多样性和丰度未发生明显改变。物种差异分析发现,亚麻醉剂量氯胺酮可以改善抑郁小鼠放线菌的降低程度,使肠道菌群的组成发生变化,并使雌性抑郁小鼠Bacteroidaceae相对丰度降低程度得到缓解,而雄性抑郁小鼠Alistipes相对丰度增加。结论：　不同性别小鼠对CUMS刺激和亚麻醉剂量氯胺酮处理表现出不同的肠道菌群变化。亚麻醉剂量氯胺酮可以改善抑郁小鼠放线菌的降低程度,并缓解雌性抑郁小鼠Bacteroidaceae相对丰度降低程度,增加雄性抑郁小鼠Alistipes相对丰度,进而改善小鼠的抑郁样行为。     

Intravenous anaesthetic agents

This article gives an overview of drugs frequently used for intravenous anaesthetic induction, as well as a brief overview of total intravenous anaesthesia. Physicochemical properties of intravenous anaesthetic drugs and their clinical and adverse effects are summarized. The article also discusses the historical context on the introduction of intravenous anaesthetic agents and highlights developments of novel agents.     

Dexmedetomidine and ketamine show distinct patterns of cell degeneration and apoptosis in the developing rat neonatal brain

Objective: Early exposure to common anesthetic and sedative agents causes widespread brain cell degeneration and apoptosis in the developing rat brain, associated with persistent learning deficits in rats. This study was designed to determine whether the α₂ adrenergic receptor agonist, dexmedetomidine, produces brain cell degeneration and apoptosis in postnatal day-7 rats in the same brain areas when compared to ketamine.

Methods: Systemic saline, ketamine 20?mg/kg, or dexmedetomidine at 30 or 45?μg/kg were given six times to postnatal day 7 rats (n = 6/group) every 90?min. Twenty-four hours after the initial injection, brain regions were processed and analyzed for cell degeneration using the silver stain and for apoptosis using activated caspase-3 immunohistochemistry.

Results: Exposure to ketamine resulted in significant cellular degeneration and apoptosis in limbic brain regions, but nonsignificant changes in primary sensory brain regions. In contrast, dexmedetomidine produced significant cellular degeneration and apoptosis in primary sensory brain regions, but nonsignificant changes in limbic regions.

Conclusions: These data show that ketamine and dexmedetomidine result in anatomically distinct patterns of cell degeneration and apoptosis in the brains of 7-day-old rat pups. The meaning and the clinical significance of these findings remain to be established.     

Delayed Urinary Symptoms Induced by Ketamine

One of the side-effects of ketamine abuse is genito-urinary damage. This report describes a case of a former ketamine user who presented with urinary symptoms associated with ketamine years after stopping consumption. This was a 26-year-old male with a history of ketamine abuse. He started treatment for alcohol dependence at age 19. He smoked marijuana daily and denied any other drug use. During the follow-up, urinary symptoms were evidenced (dysuria, frequency, urgency, incontinence, nocturia, hematuria, and suprapubic pain). Urinary symptoms started two years ago and worsened over time. The patient was referred to a urologist. A cystoscopy revealed lesions compatible with interstitial cystitis like the ones that appear in some ketamine abusers. Given the medical history, the urologist asked him about ketamine consumption and the patient declared a daily use of 50 milligrams intranasally from age 15 to age 17. Given these findings, not reported previously in the medical literature, future research should follow up patients who at some point in their life made an abusive consumption of ketamine in order to understand the pathogenesis and to be able to intervene before clinical disease manifests itself.