Ghrelin and toxicity: recent findings and future challenges.

Ghrelin is a novel brain-gut peptide that plays various roles in mammals, including control of food intake and growth hormone release, as well as gastric motility and acid secretion in the gastrointestinal tract. It is mainly secreted by the gastric mucosa, but is also expressed in various other tissues. Different studies confirm the multiple biological roles of and possible protective effects of ghrelin. Multiple in vitro and in vivo studies support the powerful protective action of ghrelin against heart, gastric and liver injury. Moreover, ghrelin has been reported to be beneficial in renal tissue injury and excretory function after ischemia-reperfusion and to exert neuroprotective effects in cerebral ischemic regions. The aim of this review is to summarize and evaluate all the currently available in vivo and in vitro studies regarding the effects of ghrelin on tissue injury induced in different organs and tissues.

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.

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 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.

Hybrid repair of ruptured infected anastomotic femoral pseudoaneurysms: Emergent stent-graft implantation and secondary surgical debridement.

BACKGROUND: Rupture of infected anastomotic femoral artery pseudoaneurysms (AFAPs) represents a limb and life-threatening condition requiring emergency intervention. This study aimed to evaluate the feasibility, safety, and efficacy of a hybrid repair for ruptured infected AFAPs consisted of percutaneous stent-graft deployment and second-stage surgical debridement. METHODS: Between October 2004 and January 2008, 6 patients (3 female, mean age 65.8 +/- 11.4 years) with ruptured infected AFAPs were treated with emergent percutaneous stent-graft implantation and secondary surgical debridement. Three patients had undergone a femoro-popliteal and 1 a femoro-tibial bypass for peripheral arterial disease, while 2 patients had a femoral arteriovenous graft (AVG) for hemodialysis access due to chronic renal failure. Four pseudoaneurysms were located at the common femoral artery (CFA) and 2 involved the superficial femoral artery (SFA). Mean pseudoaneurysm diameter was 6.8 +/- 0.9 mm (range, 5.4-7.8 mm). The mean interval between the initial operation and presentation to our department was 26.7 +/- 14.5 months (range, 7-50 months). All patients suffered from severe comorbidities and were judged unfit for major surgery under general anesthesia. RESULTS: All patients were successfully managed by urgent percutaneous deployment of covered stents at the site of the arterial deficit. Extensive surgical debridement along with pseudoaneurysm excision was accomplished successfully in all 6 patients 1-3 days after stent-graft placement under local anesthesia, without the need for extended vessel exposure for proximal and distal control. No death occurred within 30 days after stent-graft implantation. During follow-up, (mean 14.1 +/- 8.2 months, range, 6 to 25 months) all stent-grafts remained patent without endoleak, while no signs of recurrent local or systemic infection were noticed. Two patients died at 8 and 10 months after the procedure due to heart failure complications and acute myocardial infarction, respectively. CONCLUSION: Emergency stent-graft deployment, followed by secondary surgical debridement and long-term antimicrobial therapy is a viable alternative for ruptured infected AFAPs. Especially for patients unfit for major surgery, it may be the most favorable treatment option.

The potential role of primary care in the management of common ear, nose or throat disorders presenting to the emergency department in Greece.

BACKGROUND: The aim of this study was to assess the prevalence of common ear, nose or throat (ENT) conditions presenting to emergency departments that could be managed by a primary healthcare system Method: Between January 2001 and January 2006 a total of 33 792 patients attended the ENT emergency department of one hospital. All cases were included in this retrospective study. The registry of ENT emergency department was analysed; age, sex and clinical diagnosis were tabulated. All patients were evaluated by a specialist. Classification of the cases was based on the main symptom seeking care. RESULTS: A total of 33 792 patients visited the otorhinolaryngology emergency department. Of these, 17 775 patients (52.6%) were men and 16 017 (47.4%) were women. Over 40% of the cases were classified in eight major groups of diagnosis. Acute tonsillitis (12.5%) and acute pharyngitis (11.4%) followed by acute otitis externa (5.9%) were the most common causes of all ENT emergency department visits. The admission rate was 1.2 % and only 0.6% (84) of patients were referred to other specialties. CONCLUSION: Most common ENT disorders presenting to the emergency department in Greece could be managed at the level of primary health care. Incorporating ENT expertise into educational and training programmes of general practitioners may be successful in managing ENT problems in primary care in future.

Management of minor medical problems and trauma: the role of general practice.

INTRODUCTION: It has been established that patients prefer receiving health information from primary care physicians. In Greece, recent reforms supporting urban primary healthcare have not been enacted, and long waiting times in Athens' emergency departments are common. AIM: To evaluate cases treated in the emergency department of a Greek general hospital and explore the potential role of primary care in managing these cases. METHODS: A total of 53,926 patients visited the emergency department studied during on-call days from February 2005 to February 2006. The cases were classified into 6 groups according to their main complaint: (1) internal medicine; (2) surgical; (3) orthopedic; (4) otorhinolaryngology (ENT); (5) eye disorders (ophthalmology); and (6) gynecology-obstetric. RESULTS: Of the 53,926 patients studied, 9167 (17%) came from a rural area. The internal medicine department was most commonly attended (15,373; 28.5%), followed by orthopedics (16.9%). In the surgical, ENT, ophthalmology and gynecology groups, almost one in three patients could have been managed by a GP, as could 40% of orthopedic cases. Orthopedic and ENT patients had the highest rate of X-rays performed. CONCLUSION: Many emergency patients visiting hospitals can be managed at the primary care level. The development of a 'practice-based curriculum' for GPs would be an excellent method to obtain higher professional standards.

Avian flu: how informed are children in Greece?

OBJECTIVES: The current cluster of avian influenza outbreaks in birds has occurred in areas where humans live in proximity to poultry. Dissemination of accurate information may be the cornerstone for proper community preparation. In the herein presented study, we attempted to asses the information level among Greek children regarding avian flu. METHODS: A descriptive study was carried out in 2006 in ten Greek prefectures to determine the information level among students about transmission ways, symptoms and prevention measures of avian flu. RESULTS: A total of 1400 Greek students participated in the study. Approximately 75% of the students reported to know what bird flu is and 53% reported to know that there has been at least one case of avian flu in Greece. More than half (55.6%) reported that an effective vaccine against avian flu does exist; of the students asked, 47% reported that avian flu can be transmitted from human to human whereas 21.4% believed that humans can suffer from avian flu. Media contribution in providing information was very high among students. CONCLUSION: The level of information about avian flu among Greek students was found inadequate especially in some questions regarding serious aspects of avian flu. This study highlights the need for adaptation of health programs in Greek schools, which should include the provision of accurate information.

Primary care in the management of common orthopaedic problems.

BACKGROUND: Improving national healthcare services through the enhancement of primary care, is a major challenge in many countries. AIM: To assess the prevalence of those orthopaedic cases that could be managed by a primary healthcare system. METHOD: Between January 2001 and January 2006 a total of 39 172 patients attended the orthopaedic emergency department (ED) of Laikon University Hospital. All cases were included in this retrospective study. The registry of the orthopaedic ED was analysed by age, sex and clinical diagnosis. All patients were evaluated by a specialist. Classification of the cases was based on the main symptom of those seeking care. RESULTS: A total of 39 172 patients visited the orthopaedic ED; 17 040 (43.5%) of these patients were stratified in six major groups of diagnosis. Back pain (17.1%) was the most common reason for seeking care in the orthopaedic ED, followed by ankle injuries (10.3%). The admission rate was 1.2%, and X-ray examination was necessary for 93.4% (15 220) of patients. CONCLUSION: This study confirms the widely held view that most cases attending the orthopaedic ED could have been managed by appropriately equipped primary care settings. In this context, the role of general practitioners should be re-appraised and strengthened.

Lower gastrointestinal bleeding treated with transcatheter arterial embolization. Case report and review of the literature.

Acute lower gastrointestinal bleeding, is often a dramatic situation, associated with mortality rate up to 28%. Currently transcatheter alternatives have found their place in the therapeutic spectrum of this situation. An interesting question is when should this procedure be performed and which are the difficulties when performing it. We present the case of a 75-year old woman with acute massive lower gastrointestinal bleeding on the tenth post-operative day of a colic and partial ileal resection. Superselective angiography of the superior mesenteric artery was obtained that disclosed marked contrast extravasation of distal branches of the left colic artery as well as from a small branch feeding the distal enteric anastomoses. Clinical success was achieved after superselective embolization which was accomplished by using polyvinyl alcohol particles. The patient was discharged 5 days later and there were no procedure-related complications during 6-month follow-up period. So, especially in post-operative patients who are considered to be poor candidates for surgical treatment, arterial embolotherapy should be established not only as treatment option, but also as first line therapy for LGI bleeding.

Assessing the level of awareness of avian influenza among Greek students.

INTRODUCTION: Current concern regarding avian influenza, the so-called 'bird flu', concerns H5N1, a highly pathogenic avian influenza form that has spread across Asia, into Western Europe and Africa. The wide spread of bird flu makes it a serious threat to humans. A key factor in reducing the risk of an influenza pandemic is adequate preparedness, including providing prospective, accurate information to the public. In our study, we attempted to assess the level of information among Greek students aged 8 to 15 years, regarding avian influenza. METHODS: A descriptive study was carried out in 6 Greek prefectures to determine the information level regarding avian influenza among students, concerning methods of transmission, symptoms and prevention measures. RESULTS: In total, 2805 Greek students participated in the study (47% male and 53% female). Approximately 90% of the students reported knowing what 'bird flu' is, and 25% wrongly answered that there had been at least one human infection from avian influenza in Greece. Nearly half the students (46.2%) reported that an effective vaccine exists against avian influenza, and almost all the study participants (95.7%) believed that they should not touch an ill or dead bird. Forty-two per cent of the students reported that avian influenza can be transmitted from human to human, and only 11.9% believed that humans can present symptoms after being infected. The media was their main source of information. CONCLUSION: The level of information about avian influenza among Greek students was found to be satisfactory, if not ideal. These findings, along with the potential for a future avian influenza pandemic, highlight the need for intensified health education programs in Greek schools, in order to deal with this serious public health problem.

FAK/Src family of kinases: protective or aggravating factor for ischemia reperfusion injury in nervous system?

INTRODUCTION: The focal adhesion kinase (FAK) and the Src families of kinases are subfamilies of the non-receptor protein tyrosine kinases. FAK activity is regulated by gene amplification, alternative splicing and phosporylation/dephosphorylation. FAK/Src complex has been found to participate through various pathways in neuronal models of ischemia-reperfusion injury (IRI) with conflicting results. The aim of the present review is to summarize the currently available data on this subject. AREAS COVERED: The MEDLINE/PubMed database was searched for publications with the medical subject heading IRI and FAK and/or Src, nervous system. We restricted our search till 2014. We identified 93 articles that were available in English as abstracts or/and full-text articles that were deemed appropriate for our review. EXPERT OPINION: FAK has been found to have a beneficial preconditioning effect on IRI through activation via the protein kinase C (PKC) pathway by anesthetic agents. Of great importance are the interactions between FAK/Src and VEGF that has been already detected as a protective mean for IRI. The effect of VEGF administration might depend on dose as well as on time of administration. A Ca(2+)/calmodulin-dependent protein kinase II or PKC inhibitors seem to have protective effects on IRI by inhibiting ion channels activation.

Proteasome inhibitors: possible novel therapeutic strategy for ischemia-reperfusion injury?

INTRODUCTION: The ubiquitin-proteasome system (UPS) is responsible for the degradation of misfolded or damaged proteins, regulating inflammatory processes and cell cycle progression. The aim of this article is to summarize the currently available data regarding the possible utility of proteasome inhibitors (PIs) in the treatment of ischemia-reperfusion injury (IRI). AREAS COVERED: Data were reviewed from the published literature using the Medline database. The effect of PIs on IRI is dependent on the dosage, time of administration (prior to or post IRI induction), the affected organ, and the experimental model used. Undoubtedly, in most cases PIs' application resulted in attenuated IRI, although it was uniformly shown that inhibition of the UPS prior to ischemic preconditioning (IPC) abolished the protective effect of IPC in IRI. Mechanism of action involves several pathways, including nuclear factor kappa-B (NF-κB) inactivation, antineutrophil action, decreased intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression, and the cytoprotective proteins eNOS, heme oxigenase 1 and hsp70 up-regulation. EXPERT OPINION: Current data are limited, but appear promising with regard to PI consideration as an effective future therapeutic strategy for IRI. Nevertheless, further investigation is required in terms of safety and validation of the appropriate for each agent dosage, in order to establish their possible contribution in human IRI.

The treatment of iatrogenic male incontinence: latest results and future perspectives.

Male Stress Urinary Incontinence (SUI) is an increasingly recognized problem particularly after the treatment of prostate cancer. Postprostatectomy incontinence is a major problem that needs to be solved, since it has great impact on quality of life affecting the patient's physical activity and social well-being. The initial treatment for SUI that persists after 12 months consists of conservative measures such as pelvic floor muscle exercises and behavioral therapy. Properly selected and informed patients can also be treated efficiently with minimally invasive procedures such as the implantation of a male suburethral sling, although the experience with such devices is not extensive. However, the implantation of artificial urinary sphincter is the gold standard therapy.

Evidence for the involvement of cannabinoid receptors' polymorphisms in the pathophysiology of human diseases.

INTRODUCTION: Considerable progress has been made, over the last years, in understanding the role of the endocannabinoid system (ES) in regard to its role in a variety of physiological processes including nociception (pain-sensation), appetite, lipid metabolism, gastrointestinal motility, cardiovascular modulation, motor activity, and memory. Furthermore, ES is strongly associated with human behavior and the skeletal ES is of major importance. ES is comprised of cannabinoid receptors (CB1 and CB2), their endogenous ligands (endocannabinoids) and proteins responsible for their metabolism. AREAS COVERED: To summarize and present all the existing literature that associate CB receptors' polymorphisms with behavior and disease in different populations, as well as its possible therapeutic perspectives. A literature review presenting the most recent data in terms of ES and the latest knowledge regarding the involvement of genetic polymorphisms of cannabinoid receptors in a variety of human diseases and psychiatric and neurological disorders. EXPERT OPINION: The ES is an emerging target for drug discovery, because it is involved in the regulation of many cellular and physiological functions. The modulation of the ES by selective agonists or antagonists may hold tremendous therapeutic potential in various conditions mentioned in this review. However, further information is still required before the ES is completely comprehended.

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.

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.

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.

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.

Recurrent urethrovesical anastomotic strictures following artificial urinary sphincter implantation: a case report.

INTRODUCTION: The management of an anastomotic stricture after a radical prostatectomy can become a complex and difficult situation when an artificial urinary sphincter precedes the formation of the stricture. The urethral narrowing does not allow the passage of the routinely used urological instruments and no previous reports have suggested alternate approaches. CASE PRESENTATION: We present the case of a 68-year-old Greek man diagnosed as having a recurrent anastomotic stricture approximately two years after a radical prostatectomy and three years after the implantation of an artificial urinary sphincter, and propose novel alternate methods of treatment. Our patient was first subjected to stricture incision with the use of a rigid ureteroscope with a holmium:yttrium-aluminium-garnet laser fiber, which was followed by a second successful attempt with the use of a pediatric resectoscope. After a one-year follow-up, our patient is doing well, with no evidence of recurrence. CONCLUSIONS: To the best of our knowledge, this is the first report of the management of recurrent urethral strictures following an artificial urinary sphincter implantation. Minimal invasive techniques with the use of small caliber instruments may offer efficient treatment options, diminishing the danger of urethral corrosion.