Ioanna Vasileiou

Propofol: A review of its non-anaesthetic effects

Propofol, a short-acting intravenous anaesthetic agent has gained wide acceptance since its introduction in the late 80s, not only in operating rooms but also in other departments, due to its several advantages. Apart from its multiple anaesthetic advantages, it has been reported recently that propofol exerts a number of non-anaesthetic effects. The drug stimulates constitutive nitric oxide (NO) production and inhibits inducible NO production. Propofol has also anxiolytic properties, which may be related to several neuromediator systems. Moreover, it has antioxidant, immunomodulatory, analgesic, antiemetic and neuroprotective effects. Furthermore, propofol inhibits both platelet aggregation and intracellular calcium increases in response to thrombin or ADP and it also exerts direct inhibitory effects on recombinant cardiac sarcolemmal KATP channels. All these beneficial properties may expand propofols clinical use.

The role of endocannabinoids in pain modulation

The endocannabinoid system (ES) is comprised of cannabinoid (CB) receptors, their endogenous ligands (endocannabinoids), and proteins responsible for their metabolism. Endocannabinoids serve as retrograde signaling messengers in GABAergic and glutamatergic synapses, as well as modulators of postsynaptic transmission, that interact with other neurotransmitters. Physiological stimuli and pathological conditions lead to differential increases in brain endocannabinoids that regulate distinct biological functions. Furthermore, endocannabinoids modulate neuronal, glial, and endothelial cell function and exert neuromodulatory, anti‐excitotoxic, anti‐inflammatory, and vasodilatory effects. Analgesia is one of the principal therapeutic targets of cannabinoids. Cannabinoid analgesia is based on the suppression of spinal and thalamic nociceptive neurons, but peripheral sites of action have also been identified. The chronic pain that occasionally follows peripheral nerve injury differs fundamentally from inflammatory pain and is an area of considerable unmet therapeutic need. Over the last years, considerable progress has been made in understanding the role of the ES in the modulation of pain. Endocannabinoids have been shown to behave as analgesics in models of both acute nociception and clinical pain such as inflammation and painful neuropathy. The framework for such analgesic effects exists in the CB receptors, which are found in areas of the nervous system important for pain processing and in immune cells that regulate the neuro‐immune interactions that mediate the inflammatory hyperalgesia. The purpose of this review is to present the available research and clinical data, up to date, regarding the ES and its role in pain modulation, as well as its possible therapeutic perspectives.

Current clinical status on the preventive effects of cranberry consumption against urinary tract infections.

Urinary tract infections (UTIs) represent a common and quite costly medical problem, primarily affecting the female population which may be due to a shorter urethra. The bacterium Escherichia coli are mainly responsible for most uncomplicated UTIs. Cranberry antibacterial effects have widely been studied in vitro, and laboratory and clinical studies have also been performed to elucidate the mechanisms of cranberry actions and the clinical benefits of cranberry consumption against UTIs. The present review aimed to summarize the proposed mechanisms of cranberry actions against UTIs and the clinical trials that evaluated the efficacy of supplementing cranberry products in different subpopulations. Taking into consideration the existing data, cranberry consumption may prevent bacterial adherence to uroepithelial cells which reduces the development of UTI. Cranberry consumption could also decreasing UTI related symptoms by suppressing inflammatory cascades as an immunologic response to bacteria invasion. The existing clinical trials suggest that the beneficial effects of cranberry against UTIs seem to be prophylactic by preventing the development of infections; however, they exert low effectiveness in populations at increased risk for contracting UTIs. Additional well-designed, double-blind, placebo-controlled clinical trials that use standardized cranberry products are strongly justified in order to determine the efficiency of cranberry on the prevention of UTIs in susceptible populations.

Propofol prevents lung injury following intestinal ischemia-reperfusion.

BACKGROUND The antioxidant properties of propofol have been shown to improve ischemia/reperfusion injury. We investigated whether anesthesia with propofol can ameliorate remote lung injury induced by intestinal ischemia-reperfusion (IIR). MATERIALS AND METHODS Thirty male Wistar rats were randomly allocated in three groups (n = 10 each): animals in group Sham were anesthetized with ketamine and xylazine and then laparotomy and sham IIR followed. Animals in group IIR received ketamine and xylazine and were then subjected to clamping of the superior mesenteric artery for 45 min and reperfusion for 4 h. Group IIR+P received anesthesia with propofol and then IIR was induced, as in group IIR. Blood samples for blood gases and malondialdehyde measurements were drawn at the end of reperfusion. Bronchoalveolar lavage fluid (BALF) was obtained to measure cell counts, total protein, and phospholipids levels. RESULTS Induction of IIR resulted in deteriorated oxygenation, acidemia, and inflammatory cells sequestration, along with increased BALF protein content and increased proportions of small surfactant aggregates. Anesthesia with propofol alleviated intestinal injury and efficiently prevented lipid oxidation. In group IIR+P inflammatory cell infiltration and pulmonary histologic changes were significantly limited. The increase in BALF total protein and the changes in surfactant aggregates were prevented, leading to normal systemic oxygenation. CONCLUSION Using propofol to induce and maintain anesthesia efficiently prevented IIR-induced lung injury. Systemic antioxidant protection, improvement of intestinal injury, inhibition of the inflammatory response, and preservation of the alveolar-capillary permeability seem to be crucial mediating mechanisms for this simple and clinically relevant intervention.

Toll like receptors in liver ischemia reperfusion injury: A novel target for therapeutic modulation?

Background: There is increasing evidence that Toll-like receptors (TLRs) sense host tissue damage by engaging with endogenous ligands. TLRs are considered to be involved in many primarily non-immune-related diseases. Hepatic ischemia reperfusion injury (IRI) represents one of these disorders. Objective: To present the latest findings supporting the involvement of TLRs in liver IRI and to explore their role as potential targets for therapeutic intervention. Methods: A review of the literature summarizing the latest advances in TLR signaling, the role of TLRs in each hepatic cell population and the involvement of TLRs in the pathophysiology of hepatic IRI. The potential role of TLR-targeting treatment strategies in liver IRI is discussed. Conclusions: Recent experimental evidence suggests that TLR activation on Kupffer cells provides the triggering signal for pro-inflammatory responses that lead to liver IRI. Modulating TLR signaling could have a beneficial effect in patients with liver IRI.

The neuroprotective role of endocannabinoids against chemical-induced injury and other adverse effects.

Considerable progress has been made, recently, in understanding the role of the endocannabinoid system in regard to neuroprotection. Endogenous cannabinoids have received increasing attention as potential protective agents in several cases of neuronal injury. The endocannabinoid system is comprised of cannabinoid receptors (CB1 and CB2), their endogenous ligands (endocannabinoids) and proteins responsible for their metabolism. Endocannabinoids serve as retrograde signalling messengers in GABAergic and glutamatergic synapses, as well as modulators of post‐synaptic transmission, interacting with other neurotransmitters, including norepinephrine and dopamine. Furthermore, endocannabinoids modulate neuronal, glial and endothelial cell function and exert neuromodulatory, anti‐excitotoxic, anti‐inflammatory and vasodilatory effects. Physiological stimuli and pathological conditions lead to differential increases in brain endocannabinoids that regulate distinct biological functions. The purpose of this review is to present the available in vivo and in vitro experimental data, up to date, regarding the endocannabinoid system and its role in neuroprotection, as well as its possible therapeutic perspectives. Copyright

Management of the airway without the use of neuromuscular blocking agents: the use of remifentanil

Remifentanil belongs to opioid drugs, and its pharmacokinetic characteristics make it unique in this class of drugs and appropriate for use during intubation without neuromuscular blockage. This up‐to‐date review aims to summarize the findings of recent studies regarding remifentanil and intubation. Remifentanil combined either with propofol or with inhaled anesthetic agents has been proved to provide acceptable intubating conditions. Regarding children patients, remifentanil can be used safely, and as far as intubating conditions are concerned, its effectiveness is as excellent as with neuromuscular blockage. Strong evidence exists that illuminates the usefulness of the drug in cases of difficult airway as well as in neuromuscular diseases. Beyond all these favorable characteristics, anesthesiologists must be conscious with the use of remifentanil.

Toll-Like Receptor 4 Immunohistochemical Expression Is Enhanced in Macrophages of Symptomatic Carotid Atherosclerotic Plaques

Background: A growing body of evidence supports a role for Toll-like receptor 4 (TLR4), a primary receptor of the innate immune system, in atherosclerosis initiation and progression. Carotid atheroma macrophages (MACs) and smooth muscle cells (SMCs) express TLR4; nevertheless, correlations with epidemiological and clinical variables and especially cerebrovascular symptomatology remain unsettled. Methods: Carotid atherosclerotic plaques were obtained by standard carotid endarterectomy on 157 patients with carotid artery disease (84 asymptomatic – 73 symptomatic). TLR4 expression in MACs and SMCs of carotid atheroma was detected by immunohistochemistry techniques. TLR4 positivity, overexpression and intensity of immunostaining in MACs and SMCs were correlated with cerebrovascular symptomatology, epidemiological and clinical variables. Results: MAC TLR4 positivity was noted in 129 (82.2%) patients. Patients receiving statins had significantly lower TLR4 expression. Rates of MAC TLR4 positivity were higher among symptomatic patients (odds ratio, OR = 5.1; 95% confidence interval, CI = 1.8–14.3; p < 0.001); the association was stronger for transient ischemic attacks. TLR4 overexpression was also significantly enhanced among symptomatic patients (OR = 2.3; 95% CI = 1.02–5.03; p < 0.05). No correlations were detected between SMC TLR4 expression and cerebrovascular symptoms. In multivariate models adjusting for age, gender, body mass index, hyperlipidemia and smoking, MAC TLR4 positivity was associated with a cerebrovascular event during the last 6 months (OR = 4; 95% CI = 1.2–13.3; p = 0.02). Conclusions: Symptomatic carotid artery plaques are characterized by increased expression of TLR4 in macrophages supporting a potential role for TLR4 in the pathophysiology and clinical presentation of cerebrovascular disease. Further investigation is warranted.

Ephrins and pain

Introduction: The ephrin receptor family is the largest family of receptor tyrosine kinases, which comprises 14 members that are divided into A and B subclasses. The ephrin receptor (Eph-receptor) ligands are named ephrins. Ephrins/Eph receptors interact with a variety of membrane receptors that respond to chemokines, neurotransmitters or growth factors. A growing body of evidence indicates that ephrins/Eph receptors are involved in the modulation of different types of pain. Areas covered: A literature review summarizing the most recent data in terms of ephrins and their ligands and their association with different types of pain. Moreover, the latest knowledge regarding the involvement of ephrins/Eph receptors in pain modulation as well as its possible therapeutic perspectives are presented. Expert opinion: The ephrins/Eph receptors system seems to be an emerging target for pain drug discovery, because it is involved in the pathophysiology of many types of pain. The modulation of different types of pain by selective agonists or antagonists may hold tremendous therapeutic potential in various pain conditions mentioned in this review. However, the current limited but promising data, merit consideration and further investigation.

Spinal versus General Anaesthesia in Postoperative Pain Management during Transurethral Procedures

We compared the analgesic efficacy of spinal and general anaesthesia following transurethral procedures. 97 and 47 patients underwent transurethral bladder tumour resection (TUR-B) and transurethral prostatectomy (TUR-P), respectively. Postoperative pain was recorded using an 11-point visual analogue scale (VAS). VAS score was greatest at discharge from recovery room for general anaesthesia (P = 0.027). The pattern changed significantly at 8 h and 12 h for general anaesthesias efficacy (P = 0.017 and P = 0.007, resp.). A higher VAS score was observed in pT2 patients. Patients with resected tumour volume >10 cm3 exhibited a VAS score >3 at 8 h and 24 h (P = 0.050, P = 0.036, resp.). Multifocality of bladder tumours induced more pain overall. It seems that spinal anaesthesia is more effective during the first 2 postoperative hours, while general prevails at later stages and at larger traumatic surfaces. Finally, we incidentally found that tumour stage plays a significant role in postoperative pain, a point that requires further verification.