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BACKGROUND: Sclareol (SCL), a labdane diterpene compound found in Salvia sclarea L., exhibited therapeutic effects. This study investigated the potential interaction between SCL and diazepam (DZP) in modulating sedation in the thiopental sodium-induced sleeping animal model, supported by in-silico molecular docking analysis.
METHODS: The control, sclareol (5, 10 and 20 mg/kg), and the reference drugs [diazepam: 3 mg/kg and Caffeine (CAF): 10 mg/kg] were used in male albino mice. Then, sodium thiopental (40 mg/kg, i.p.) was administrated to induce sleep. The latent period, percentage of sleep incidence and modulation of latency were measured. Further, homology modeling of human γ-aminobutyric acid (GABA) was conducted examine the binding mode of GABA interaction with SCL, DZP, and CAF compounds RESULTS: SCL (low dose) slightly increased the sleep latency, while the higher dose significantly prolonged sleep latency. DZP, a GABAA receptor agonist, exhibited strong sleep-inducing properties, reducing sleep latency, and increasing sleeping time. Caffeine (CAF) administration prolonged sleep latency and reduced sleeping time, consistent with its stimulant effects. The combination treatments involving SCL, DZP, and CAF showed mixed effects on sleep parameters. The molecular docking revealed good binding affinities of SCL, DZP, and CAF for GABAA receptor subunits A2 and A5.
CONCLUSIONS: Our findings highlighted the complex interplay between SCL, DZP, and CAF in regulating sleep behaviors and provided insights into potential combination therapies for sleep disorders.

UNASSIGNED: Standard dosages of analgesic and sedative drugs are given to intensive care patients. The resulting range of blood concentrations and corresponding clinical responses need to be better examined. The purpose of this study was to describe daily dosages, measured blood concentrations, and clinical responses in critically ill patients. The purpose was also to contribute to establishing whole blood concentration reference values of the drugs investigated.
UNASSIGNED: A descriptive study of prospectively collected data from 302 admissions to a general intensive care unit (ICU) at a university hospital. Ten drugs (clonidine, fentanyl, morphine, dexmedetomidine, ketamine, ketobemidone, midazolam, paracetamol, propofol, and thiopental) were investigated, and daily dosages recorded. Blood samples were collected twice daily, and drug concentrations were measured. Clinical responses were registered using Richmond agitation-sedation scale (RASS) and Numeric rating scale (NRS).
UNASSIGNED: Drug dosages were within recommended dose ranges. Blood concentrations for all 10 drugs showed a wide variation within the cohort, but only 3% were above therapeutic interval where clonidine (57 of 122) and midazolam (38 of 122) dominated. RASS and NRS were not correlated to drug concentrations.
UNASSIGNED: Using recommended dose intervals for analgesic and sedative drugs in the ICU setting combined with regular monitoring of clinical responses such as RASS and NRS leads to 97% of concentrations being below the upper limit in the therapeutic interval. This study contributes to whole blood drug concentration reference values regarding these 10 drugs.

Quercetin is the most common polyphenolic flavonoid present in fruits and vegetables demonstrating versatile health-promoting effects. This study aimed to examine the effects of quercetin (QR) and sclareol (SCL) on the thiopental sodium (TS)-induced sleeping and forced swimming test (FST) mouse models. SCL (1, 5, and 10 mg/kg, p.o.) or QR (50 mg/kg, p.o.) and/or diazepam (DZP) (3 mg/kg, i.p.) were employed. After 30 min of TS induction, individual or combined effects on the animals were checked. In the FST test, the animals were subjected to forced swimming after 30 min of administration of the test and/or controls for 5 min. In this case, immobility time was measured. In silico studies were conducted to evaluate the involvement of GABA receptors. SCL (5 and 10 mg/kg) significantly increased the latency and decreased sleeping time compared to the control in the TS-induced sleeping time study. DZP (3 mg/kg) showed a sedative-like effect in animals in both sleeping and FST studies. QR (50 mg/kg) exhibited a similar pattern of activity as SCL. However, its effects were more prominent than those of SCL groups. SCL (10 mg/kg) altered the DZP-3-mediated effects. SCL-10 co-treated with QR-50 significantly (p < 0.05) increased the latency and decreased sleep time and immobility time, suggesting possible synergistic antidepressant-like effects. In silico studies revealed that SCL and QR demonstrated better binding affinities with GABAA receptor, especially α2, α3, and α5 subunits. Both compounds also exhibited good ADMET and drug-like properties. In animal studies, the both compounds worked synergistically to provide antidepressant-like effects in a slightly different fashion. As a conclusion, the combined administration of SCL and QR may be used in upcoming neurological clinical trials, according to in vivo and in silico findings. However, additional investigation is necessary to verify this behavior and clarify the potential mechanism of action.

Thiopental has been used as a pharmacological cerebral protection strategy during carotid endarterectomy surgeries. However, the optimal dosage required to induce burst suppression on the electroencephalogram (EEG) remains unknown. This retrospective study aimed to determine the optimal dosage of thiopental required to induce burst suppression during non-shunt carotid endarterectomy.
The Neurological Institute of Thailand Review Board approved the study. Data were collected from 2009 to 2019 for all non-shunt carotid endarterectomy patients who received thiopental for pharmacological cerebral protection and had intraoperative EEG monitoring. Demographic information, carotid stenosis severity, intraoperative EEG parameters, thiopental dosage, carotid clamp time, intraoperative events, and patient outcomes were abstracted.
The study included 57 patients. Among them, 24 patients (42%) achieved EEG burst suppression pattern with a thiopental dosage of 26.3±10.1 mg/kg/hr. There were no significant differences in perioperative events between patients who achieved burst suppression and those who did not. After surgery, 33.3% of patients who achieved burst suppression were extubated and awakened. One patient in the non-burst suppression group experienced mild neurological deficits. No deaths occurred within one month postoperative.
The optimal dosage of thiopental required to achieve burst suppression on intraoperative EEG during non-shunt carotid endarterectomy was 26.3±10.1 mg/kg/hr.

Selecting a method of euthanasia is an important step in designing research studies that use animals; euthanasia methods must be humane, cause minimal pain and suffering to the animal, and preserve the tissue architecture of the organs of interest. In this study, we evaluated the histomorphology of the internal organs (lung, spleen, heart, kidney, liver, brain, and adrenal gland) of rats submitted to five different methods of euthanasia, with the goal of determining which protocol caused the least alteration of histomorphology. Twenty adult Wistar Han rats (Rattus norvegicus) were divided into 5 groups of 4 rats each (2 females and 2 males) and were euthanized by CO₂ or isoflurane inhalation, sodium thiopental or xylazine plus ketamine overdose, or decapitation. All euthanasia was performed in accordance with published guidelines and local legal require- ments. Necropsy was performed immediately after euthanasia. Specific internal organs were removed and placed in formalin and submitted for routine histologic processing. Histomorphological examination of hematoxylin and eosin-stained tissues revealed circulatory alterations in multiple organs, predominantly congestion in multiple tissues, pulmonary hemorrhage, and hepatic degeneration. The euthanasia methods that induced the most severe alterations were exposure to CO₂ and anesthetic overdose with xylazine plus ketamine or sodium thiopental. Euthanasia by overexposure to isoflurane caused less damage, and the alterations were of minimal severity. Decapitation resulted in the lowest incidence of lesions in multiple organs but due its traumatic nature, it caused the highest incidence of pulmonary hemorrhage. In selecting a method of euthanasia, factors to consider are the species of animal, the purpose of the research, and the practical ability to perform the procedure to achieve maximal animal welfare without iatrogenic changes that could compromise the outcome and reproducibility of the study.

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OBJECTIVE: The aim: To determine the peculiarities of the antioxidant-prooxidant balance in the kidney of rats of different ages under conditions of experimental cranioskeletal trauma (CST).
METHODS: Materials and methods: The experiments involved 147 male white Wistar rats of different age groups. The first experimental group included immature animals aged 100-120 days. The second group included sexually mature animals aged 6-8 months. The third group included old animals aged 19-23 months. In all experimental groups, CST was modelled under thiopental-sodium anaesthesia. The control groups of rats was only injected with thiopental-sodium anaesthesia. The animals were withdrawn from the experiments under anaesthesia after 1, 3, 7, 14, 21 and 28 days by total bleeding from the heart. The content of reagents to thiobarbituric acid and catalase activity was determined in a 10 % kidney homogenate extract, and the antioxidant-prooxidant index (API) was calculated from the ratio of these two parameters.
RESULTS: Results: As a result of the application of CST in rats of different age groups, a decrease in the value of renal API was observed with a maximum in immature rats - after 7 days, in mature and old rats - after 14 days. By day 28, the index increased in all experimental groups, but did not reach the control level. The degree of decrease in renal API in old rats under the influence of CCT was significantly higher than in other experimental groups. In immature rats, the impairment of renal API after the application of CST was less, indicating higher reserve capacity of the renal antioxidant defence system in this age group of rats.
CONCLUSIONS: Conclusions: Simulation of CST in rats of different age groups is accompanied by a decrease in the value of API, which by day 28 does not reach the control level in any of the experimental groups. The degree of decrease in renal API value statistically significantly increases with increasing age of rats at all times of the post-traumatic period.

BACKGROUND: Neuroprotective agents are needed to reduce cerebral damage during surgical or neurointerventional procedures including stroke patients.
OBJECTIVE: To evaluate if thiopental can be used as a neuroprotective agent when injected intra-arterially in a transient ischemia model.
METHODS: In total, 24 rabbits were studied as four groups of six animals. Group 1 served as the control group. In group 2, transient ischemia was obtained by intracarotid administration of degradable starch microspheres (DSM). Group 3 was administered thiopental intra-arterially via the carotid artery. Group 4 (experimental group) received both thiopental and DSM intra-arterially. DSM and thiopental were administered through a microcatheter placed into the common carotid artery via the central ear artery access. After sacrifice, apoptotic cells in the cerebral tissues of the animals were evaluated in H&E and TUNEL stained slides.
RESULTS: There was a significant increase in the number of apoptotic glial or neuronal cells in group 2 compared to the control group and group 3. The mean number of both the apoptotic neuronal cells (6.8 ± 2.1 vs. 2.5 ± 1.3, P < 0.001) and the apoptotic glial cells (9.4 ± 3.1 vs. 4.6 ± 1.6, P < 0.001) were higher in group 2 compared to group 4. In addition, a higher level of neurological improvement was observed in group 4 compared to group 2 based on neurological assessment score.
CONCLUSIONS: The intra-arterial administration of thiopental has a protective effect on both glial and neuronal cells during temporary cerebral ischemia in low doses.

Date-rape drugs given to victims through drinks without their knowledge in drug-facilitated sexual assaults and thefts (money, property and body organs), are important threats for the public. Detection in beverage residues gains importance, since some of them can be quickly eliminated from the body, till the victim understands what he/she has experienced, goes to the hospital and gives a urine sample for analysis. Here, date-rape drugs; ketamine, thiopental, phenobarbital, zolpidem, phenytoin and zopiclone were analyzed simultaneously in 1.00mL caffeine-based carbonated beverage residue, through direct injection, using a modified, economical emergency first-step screening method with high performance liquid chromatography-diode array detector (elution time: 11 minutes). Screening power of the method was qualitatively observed in sour cherry juice, sweet soda and beer with some additional experiments. Caffeine in caffeine-based carbonated beverage could also be detected simultaneously. LODs and LOQs were between 0.02-1.79 and 0.08-5.60µgmL-1. Repeatability and reproducibility values were <9.91%. HorRat values were between 0.184-0.500. As the first screening and quantitative study on the simultaneous analysis of these drugs in a beverage, it\'s important for solving the crimes committed using drugs in caffeine-based carbonated beverage residues found at the crime scene, when the use of these drugs is suspected after anamnesis and inspection.