Assessment of delta-9-tetrahydrocannabinol (THC) in saliva and blood after oral administration of medical cannabis with respect to its effect on driving abilities.

Medical cannabis has recently been legalized in many countries, and it is currently prescribed with increasing frequency, particularly for treatment of chronic pain resistant to conventional therapy. The psychoactive substance delta-9-tetrahydro-cannabinol (THC) contained in cannabis may affect driving abilities. Therefore, the aims of this study (open-label, monocentric, nonrandomized) were to evaluate blood and saliva concentrations of THC after oral administration of medical cannabis and to assess the time needed for THC levels to decline below a value ensuring legal driving. The study involved 20 patients with documented chronic pain using long-term medical cannabis therapy. They were divided into two groups and treated with two different doses of cannabis in the form of gelatin capsules (62.5 mg or 125 mg). In all patients, the amount of THC was assessed in saliva and in blood at pre-defined time intervals before and after administration. THC levels in saliva were detected at zero in all subjects following administration of both doses at all-time intervals after administration. Assessment of THC levels in blood, however, showed positive findings in one subject 9 h after administration of the lower dose and in one patient who had been given a higher dose 7 h after administration. Our finding suggested that for an unaffected ability to drive, at least 9-10 h should elapse from the last cannabis use.

Can changes in skin impedance be used to monitor sedation after midazolam and during recovery from anesthesia?

It has been suggested that sympathetic activity, measured as changes in electrical skin impedance (SI), can be used to assess the adequacy of general anesthesia. Our prospective study investigated if measurements of skin impedance can determine levels of sedation induced by midazolam. Twenty-seven patients scheduled for arthroscopy requiring general anesthesia were served as their own control. These were blinded to the order of injections by telling them that they will be randomly administered a placebo (saline) orsedative agent. A DM 3900 multimeter was used for SI measurements. The degree of sedation was measured using the modified Observer's Assessment of Alertness and Sedation (mOAAS) scale. Resting SI values were noted, and all participants were then administered the placebo followed 5 min later by midazolam 2 mg i.v. Five min after that, patients were administered standard general anesthesia with propofol, oxygen, nitrous oxide 60 %, and isoflurane 1 MAC via a laryngeal mask, and sufentanil 5 - 10 µg. SI significantly increased after administration of midazolam and induction of anesthesia. There were no significant differences between pre-administration (baseline) and placebo and end of surgery and end of anesthesia with closed eyes. There were highly significant differences (p<0.001) between pre-administration vs. midazolam, placebo vs. midazolam, pre-administration vs. induction of anesthesia. We found slight correlation between mOAAS and SI. There were no significant changes between the end of surgery and the end of anesthesia with closed eyes, but SI significantly decreased (p<0.01) after eyes opened.

VEGF: A KEY PLAYER NOT ONLY IN MACULAR DEGENERATION. A REVIEW.

The issue of macular retinal degeneration is one of the key areas of ophthalmology. Recent advances in the targeted delivery of vascular endothelial growth factor (VEGF) suppressants have significantly impacted the patient's prognosis in the form of a significant deceleration in disease progression. Some of the drugs have gradually found their use in other indications (central retinal vein occlusion or diabetic macular edema). The following text gives a brief look at the physiology of VEGF, but not only in the eye, but throughout the human body, particularly in the context of adverse effects resulting from systemic inhibition of its effects.

A new strategy for the treatment of atherothrombosis - inhibition of inflammation.

Improvement in the prognosis of patients at risk of atherothrombotic events is based on three pillars - slowing down the process of atherogenesis (i.e. the development of atherosclerotic plaque), stabilizing the current atherosclerotic plaque, and reducing the risk of thrombotic occlusion in cases with unstable atherosclerotic plaque. The current prophylaxis has so far taken into consideration the adjustment of several risk factors, including dyslipidemia, arterial hypertension, smoking, and diabetes through lifestyle changes or pharmacological therapies. An essential part of prophylaxis is the anti-thrombotic strategy, especially anti-platelet therapy. Recently, a new pathway has been developed, based on reducing the activity of the inflammatory process with NLRP3 inflammasome, specifically a monoclonal antibody against interleukin 1beta (canakinumab). The efficacy and safety of this treatment, in secondary prevention, were documented in the CANTOS study. Other therapeutic procedures, including suppression of the inflammatory component of atherogenesis, are at the stage of clinical assessment.

Efficacy and tolerability of injectable collagen-containing products in comparison to trimecaine in patients with acute lumbar spine pain (Study FUTURE-MD-Back Pain).

Low back pain (LBP) represents an important subgroup of vertebrogenic pain with estimated prevalence around 80 %. Locally acting injectable collagen for topical application has recently extended the limited range of treatment options. The aim of the study was to evaluate the efficacy and safety of injectable collagen in patients with LBP. Patients suffering from LBP (< three months) were enrolled. They were administered either collagen 4 ml or trimecaine 1 % 4 ml in the form of subcutaneous paravertebral injections into eight pre-specified points (0.5 ml per each point) in the following schedule: two administrations in the first and second week, one in the third week. The pain intensity, Thomayer distance, Oswestry disability index, Lasseque test, quality of life, consumption of rescue medication and safety were evaluated. Exertional and rest pain, evaluated by a visual analogue scale, gradually decreased in both groups. Both treatments showed a statistically significant improvement in mobility and quality of life. The consumption of paracetamol as a rescue medication was significantly lower in patients treated with collagen than in the group treated with trimecaine (p=0.048). The analgesic efficacy of locally acting injectable collagen, as well as an analgesic sparing effect when compared to local anesthetics were demonstrated.

Non-traditional administration of remifentanil in an experimental setting.

Remifentanil is ultrashort-acting opioid with a unique pharmacokinetic profile. It is used exclusively intravenously. While considering its rapid onset of action and other pharmacokinetic properties, we decided to assess its effects following administration via non-traditional routes. Rabbits (n=10 per each group) were randomized into six groups: remifentanil 1 microg/kg and 3 microg/kg IM, 5.0 and 10.0 microg/kg conjunctivally, and 10 microg/kg and 25.0 microg/kg intranasally. Sedating effects were assessed via a loss of the righting reflex. Secondary, mean arterial blood pressure, arterial oxygen saturation of hemoglobin, and pulse rate was monitored in all rabbits. Non-traditional routes of administration were shown to provide a rapid onset of action as well as fast recovery. Importantly, the administration of remifentanil did not result in any deterioration of cardiovascular functions.

Chronic Low Back Pain: Current Pharmacotherapeutic Therapies and a New Biological Approach.

Chronic low back pain (CLBP) syndrome represents one of the leading causes of long-term disability worldwide. The prevalence of CLBP has been rising significantly in relation to increasing average life expectancy. CLBP results from chronification of acute low back pain. There are many factors contributing to the CLBP crisis; common etiopathogenetic factors include e.g., functional blockage of intervertebral joints. The treatment of CLBP is complex. An important part of treatment consists of pain pharmacotherapy, for which several groups of drugs are used. The problem lies in the side effects of many of these traditionally used medications. Therefore, new and safer treatment methods are being sought. Innovative options for CLBP pharmacology include injections containing collagen, which can be combined with other traditionally used drugs, which helps reduce dosages and increase the overall safety of CLBP therapy.

Sedative effects of intranasal oxytocin in rabbits and rhesus monkeys.

Oxytocin is a hormone therapeutically used mainly for its peripheral effects during pregnancy in the uterus and breasts. However, additional central effects, i.e. anxiolytic effect, decreased level of social stress and increased empathy have been also observed. Hence, the aim of our study was to evaluate if nasal oxytocin can be used as anxiolytic substance in rhesus monkeys (n=20) and rabbits (n=20). Simultaneously, mean arterial blood pressure, arterial oxygen saturation of hemoglobin and pulse rate were monitored in all the evaluated animals. While rabbits lost righting reflex, monkeys developed a dose-dependent loss of aggressiveness and/or anxiety as evaluated by behavioral methods (aggressive behavior was classified as non-sedated - sedated - strongly sedated).

[A fixed dose combination of telmisartan, and a thiazide diuretic in the treatment of hypertension]. / Fixní kombinace telmisartanu a thiazidového diuretika v lécbe hypertenze.

The article gives an overview of the risk factors for hypertension and the appropriate indication for using a fixed combination of telmisartan and hydrochlorothiazide. It cites large, multicentre clinical trials that demonstrate the efficacy and safety of telmisartan in patients with hypertension and also a metaanalysis of treatment with either telmisartan alone (TELMI) or in combination with hydrochlorothiazide (HCTZ) which shows that it is a very well tolerated and safe treatment for patients across a wide age range.

Ephedrine accelerates psychomotor recovery from anesthesia in macaque monkeys.

BACKGROUND: Ephedrine is used in treatment of hypotension during anesthesia. We investigated its effects on the psychomotor recovery and its potential adverse reactions on cardiorespiratory functions in rhesus monkeys. METHODS: The monkeys received 50 µg/kg medetomidine, 2.0 mg/kg S-ketamine with 150 IU hyaluronidase i.m. Pulse rate, blood pressure and saturation of haemoglobin were monitored for 20 minutes. Thereafter, 1 mg/kg of ephedrine or a placebo was administered i.m. and behavioural changes, pulse rate, blood pressure and saturation of haemoglobin were monitored every 5 minutes. RESULTS: Ephedrine shortened recovery from anaesthesia from 80.4 ± 25.8 to 14.83 ± 13.70 minutes. Ephedrine also increased oxygen saturation of haemoglobin and systolic blood pressure and caused significant decrease in pulse rate 5 minutes after its administration. CONCLUSIONS: Ephedrine can be successfully used to accelerate psychomotor recovery after the use of common anesthetic protocols combining dissociative anesthetic agent and alpha 2-adrenoceptor agonist in primates.

[The role of cyclooxygenase in pain processing in CNS]. / Role cyklooxygenázy pri prenosu bolesti v CNS.

Enzyme cyclooxygenase plays an important role in many cellular processes. It is necessary for a synthesis prostaglandines, which belong to the most important mediators of inflammatory and pain processes. Many studies show an importance of this enzyme not only in periphery but in central nervous system as well. The main unsolved question is, if the cyclooxygenase-1 or cyclooxygenase-2 play the main role in synaptic transmission. In this review we try to summarise the current overview in relation to this topic.