Potentiating glymphatic drainage minimizes post-traumatic cerebral oedema.

Cerebral oedema is associated with morbidity and mortality after traumatic brain injury (TBI)1. Noradrenaline levels are increased after TBI2-4, and the amplitude of the increase in noradrenaline predicts both the extent of injury5 and the likelihood of mortality6. Glymphatic impairment is both a feature of and a contributor to brain injury7,8, but its relationship with the injury-associated surge in noradrenaline is unclear. Here we report that acute post-traumatic oedema results from a suppression of glymphatic and lymphatic fluid flow that occurs in response to excessive systemic release of noradrenaline. This post-TBI adrenergic storm was associated with reduced contractility of cervical lymphatic vessels, consistent with diminished return of glymphatic and lymphatic fluid to the systemic circulation. Accordingly, pan-adrenergic receptor inhibition normalized central venous pressure and partly restored glymphatic and cervical lymphatic flow in a mouse model of TBI, and these actions led to substantially reduced brain oedema and improved functional outcomes. Furthermore, post-traumatic inhibition of adrenergic signalling boosted lymphatic export of cellular debris from the traumatic lesion, substantially reducing secondary inflammation and accumulation of phosphorylated tau. These observations suggest that targeting the noradrenergic control of central glymphatic flow may offer a therapeutic approach for treating acute TBI.

Loss of p53 drives neuron reprogramming in head and neck cancer.

The solid tumour microenvironment includes nerve fibres that arise from the peripheral nervous system1,2. Recent work indicates that newly formed adrenergic nerve fibres promote tumour growth, but the origin of these nerves and the mechanism of their inception are unknown1,3. Here, by comparing the transcriptomes of cancer-associated trigeminal sensory neurons with those of endogenous neurons in mouse models of oral cancer, we identified an adrenergic differentiation signature. We show that loss of TP53 leads to adrenergic transdifferentiation of tumour-associated sensory nerves through loss of the microRNA miR-34a. Tumour growth was inhibited by sensory denervation or pharmacological blockade of adrenergic receptors, but not by chemical sympathectomy of pre-existing adrenergic nerves. A retrospective analysis of samples from oral cancer revealed that p53 status was associated with nerve density, which was in turn associated with poor clinical outcomes. This crosstalk between cancer cells and neurons represents mechanism by which tumour-associated neurons are reprogrammed towards an adrenergic phenotype that can stimulate tumour progression, and is a potential target for anticancer therapy.

Clinical Use of Adrenergic Receptor Ligands in Acute Care Settings.

In this chapter, we review how ligands, both agonists and antagonists, for the major classes of adrenoreceptors, are utilized in acute care clinical settings. Adrenergic ligands exert their effects by interacting with the three major classes of adrenoceptors. Adrenoceptor agonists and antagonists have important applications, ranging from treatment of hypotension to asthma, and have proven to be extremely useful in a variety of clinical settings of acute care from the operating room to the critical care environment. Continued research interpreting the mechanisms of adrenoreceptors may help the discovery of new drugs with more desirable clinical profiles.

Beta adrenergic receptor antagonist can modify Pseudomonas aeruginosa biofilm formation in vitro: Implications for chronic wounds.

Non-healing wounds are a major medical challenge, affecting over 6.5 million people in the US alone, with associated healthcare costs of about $16 billion annually. They can result in prolonged hospitalizations, work loss, disability, poor quality of life, and in diabetic patients with foot ulcers, amputation of the affected limb in 25% of patients. Though chronic ulcers may arise from different underlying diseases, the unifying feature is chronic infection, driving persistent inflammation that prolongs the healing process. One of the most frequently cultured or genetically identified pathogens in skin wounds is Pseudomonas aeruginosa. This species avidly forms biofilms in the wound that impede bacterial eradication by the host's immune mechanisms and limit efficacy of systemic antibiotics. Thus, non-antibiotic approaches to limit the growth and biofilm formation of this wound pathogen would be an advance in the treatment of chronic wounds. Prior work has demonstrated that the growth of other microbial species can be modulated by catecholamine agonists and antagonists of the adrenergic receptors (ARs). Here, we demonstrate that not only can the growth of this common wound pathogen be modulated by catecholamines, but also that the beta-AR antagonists can significantly decrease their growth, and importantly, limit their ability to form biofilms. These findings suggest that beta adrenergic antagonists may have a therapeutic role in the treatment of chronic skin wounds.

Dexmedetomidine Ameliorated Cognitive Dysfunction Induced by Intestinal Ischemia Reperfusion in Mice with Possible Relation to the Anti-inflammatory Effect Through the Locus Coeruleus Norepinephrine System.

Cognitive impairment is a common central nervous system complication that occurs following surgery or organs damage outside the nervous system. Neuroinflammation plays a key role in the molecular mechanisms of cognitive impairment. Dexmedetomidine alleviates neuroinflammation and reduces cognitive dysfunction incidence; however, the mechanism by which dexmedetomidine alleviates cognitive dysfunction remains unclear. This study evaluated the effect of dexmedetomidine on attenuation of early cognitive impairment induced by intestinal ischemia-reperfusion in mice and examined whether the locus coeruleus norepinephrine (LCNE) system participates in the anti-inflammatory effect of dexmedetomidine. The superior mesenteric artery was clamped for 45 min to induce intestinal ischemia reperfusion injury. Dexmedetomidine alone or combined with DSP-4, a selective locus coeruleus noradrenergic neurotoxin, was used for pretreatment. Postoperative cognition was assessed using the Morris water maze. Serum and hippocampal levels of IL-1ß, TNF-α, norepinephrine (NE), and malondialdehyde (MDA) were assessed by enzyme-linked immunosorbent assay. Immunofluorescence, immunohistochemistry, and hematoxylin and eosin staining were used to evaluate the expression of tyrosine hydroxylase (TH) in the locus coeruleus, hippocampal microglia, and intestinal injury. Pretreatment with dexmedetomidine alleviated intestinal injury and decreased the serum and hippocampal levels of NE, IL-1ß, TNF-α, and MDA at 24 h after intestinal ischemia reperfusion, decreased TH-positive neurons in the locus coeruleus, and ameliorated cognitive impairment. Similarly, DSP-4 pre-treatment alleviated neuroinflammation and improved cognitive function. Furthermore, α2-adrenergic receptor antagonist atipamezole or yohimbine administration diminished the neuroprotective effects and improved cognitive function with dexmedetomidine. Therefore, dexmedetomidine attenuated early cognitive dysfunction induced by intestinal ischemia-reperfusion injury in mice, which may be related to its anti-inflammatory effects through the LCNE system.

[CYP2D6 gene polymorphic markers role in determining the optimal treatment tactics for portal hypertension in patients with liver cirrhosis].

AIM: To study the polymorphic markers CYP2D6*4 (G1846A, rs3892097), CYP2D6*6 (T1707del, rs5030655), CYP2D6*10 (C100T, rs1065852), CYP2D6*41 (G2988A, rs28371725) and CYP2D6*3 (A2549del, rs4986774) role in treatment optimization of portal hypertension with propranolol in patients with liver cirrhosis (LC). MATERIALS AND METHODS: The study included 60 patients with LC who received propranolol therapy at a daily dose of 30 mg for 14 days. The efficacy of treatment was assessed by ultrasonography measuring the linear blood flow velocity of portal vein. Genotyping of CYP2D6*4, CYP2D6*6, CYP2D6*10, CYP2D6*41 and CYP2D6*3 was carried out by real-time polymerase chain reaction. Evaluation of the CYP2D6 activity was carried out by determining the ratio of pinoline and its metabolite concentration in morning urine using high performance liquid chromatography with mass spectrometry. RESULTS: Positive hemodynamics in the form of any increase in the mean linear blood flow velocity of the portal vein compared to baseline was observed in 41 patients. Portal vein mean linear blood flow rate increased from 10.43.9 to 14.74.3 cm/s (p0.001). Of these, 29 patients showed an increase in this indicator by 20% from the initial one with a dynamic of 5.5 cm/s (p0.001). The regression analysis constructed by us revealed the presence of a statistically significant effect of the CYP2D6 gene polymorphic marker G1846A carriage on the propranolol therapeutic effect (p0.05). There was no statistically significant effect of polymorphic markers T1707del, C100T, G2988A, and A2549del of the CYP2D6 gene (p0.05). No convincing reliable dependence of CYP2D6 activity on the severity of LC was revealed (p0.05). CONCLUSION: An association was found between CYP2D6 gene polymorphic marker G1846A carriage and the hemodynamic effect of propranolol in patients with LC of the Russian population. There is a more significant positive dynamics of manifestations of portal hypertension on the background of propranolol therapy in carriers of the homozygous GG CYP2D6*4 genotype, in contrast to patients with the heterozygous GA genotype. Based on the results of the study, an algorithm has been developed for personalizing the treatment of patients with LC with nonselective b-adrenergic blockers using the method of CYP2D6 genotyping. Carriage of polymorphic markers T1707del, C100T, G2988A and A2549del gene CYP2D6 does not affect the effectiveness of propranolol therapy in patients with LC.

[Retrospective analysis of clinical outcomes of patients with COVID-19 depending on receiving antihypertensive, lipid-lowering and antihypertensive therapy].

BACKGROUND: The main factors that increase the risk of cardiovascular accidents and mortality among patients with COVID-19 include hyperglycemia, arterial hypertension and dyslipidemia. Therefore, all patients with COVID-19 and metabolic syndrome should receive antihypertensive (AHT), hypolipidemic (GLT) and hypoglycemic therapy (GGT). Currently, there is a limited number of studies regarding the effectiveness and safety of this therapy in patients with COVID-19. AIM: Evaluate the clinical outcomes of patients with COVID-19, depending on the recipient of AHT, GLT and GGT. MATERIALS AND METHODS: A retrospective analysis of the clinical outcomes "discharged/died" of 1753 patients with COVID-19 was carried out depending on the received AHT, GLT and GGT. RESULTS: A significant reduction in the risk of mortality among patients with COVID-19 was observed during therapy with angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers ACE inhibitors/ARBs (OR 0.39, 95% CI 0.210.72; p0.05) and b-adrenergic blockers b-AB (OR 0.53, 95% CI 0.281; p0.05). At the same time, against the background of therapy with ACE inhibitors/ARBs and b-ABs, the chance of mortality decreased more significantly among patients with type 2 diabetes mellitus (T2DM) compared with patients without T2DM. Diuretic therapy was associated with a 3-fold increase in the chances of death: OR 3.33, 95% CI 1.884.79; p0.05. Statin therapy did not affect clinical outcomes in COVID-19 patients. On the background of therapy with oral hypoglycemic drugs, the risk of mortality decreased 5-fold (OR 0.19, 95% CI 0.070.54; p0.05). Against the background of insulin therapy, there was an increase in mortality risk by 2.8 times (OR 2.81, 95% CI 1.55.29; p0.05). CONCLUSION: A significant reduction in mortality among patients with COVID-19 was observed during therapy with ACEI/ARB, b-AB, and oral hypoglycemic therapy. Increased risk of death was associated with insulin therapy and diuretic therapy.

Risk factors, pathophysiology, and treatment of hot flashes in cancer.

Hot flashes are prevalent and severe symptoms that can interfere with mood, sleep, and quality of life for women and men with cancer. The purpose of this article is to review existing literature on the risk factors, pathophysiology, and treatment of hot flashes in individuals with cancer. Electronic searches were conducted to identify relevant English-language literature published through June 15, 2012. Results indicated that risk factors for hot flashes in cancer include patient-related factors (eg, age, race/ethnicity, educational level, smoking history, cardiovascular risk including body mass index, and genetics) and disease-related factors (eg, cancer diagnosis and dose/type of treatment). In addition, although the pathophysiology of hot flashes has remained elusive, these symptoms are likely attributable to disruptions in thermoregulation and neurochemicals. Therapies that have been offered or tested fall into 4 broad categories: pharmacological, nutraceutical, surgical, and complementary/behavioral strategies. The evidence base for this broad range of therapies varies, with some treatments not yet having been fully tested or showing equivocal results. The evidence base surrounding all therapies is evaluated to enhance hot flash treatment decision-making by clinicians and patients.

Effect of Secondary Prevention Medication on the Prognosis in Patients With Myocardial Infarction With Nonobstructive Coronary Artery Disease.

Myocardial infarction with nonobstructive coronary arteries (MINOCA) has been and remained a puzzling clinical entity. The role of secondary prevention therapy in patients with MINOCA remains unclear. This study aimed to evaluate the associations between secondary prevention medications and outcomes in patients with MINOCA. A total of 259 patients with MINOCA were consecutively enrolled. Basic information and medication of patients were assessed. We defined major adverse cardiovascular events as the primary end point and angina rehospitalization as the secondary end point. Logistic regression models were used to assess the correlation between treatment and outcomes. The proportion of statins, aspirin, clopidogrel, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEI/ARB), and ß-blocker used at admission was 88.8%, 86.9%, 84.6%, 51.7%, and 61.4%, respectively. At discharge, patients with MINOCA were less likely to be released on statins, aspirin, clopidogrel, ACEI/ARB, and ß-blocker. The use of secondary prevention medications was significantly lower at 2 years of follow-up with the most significant reductions being clopidogrel 29.4%, ACEI/ARB 39.0%, and aspirin 42.3%. About 19.1% of patients with MINOCA suffered adverse events during the follow-up period. Adverse events risk decreased when statins and ACEI/ARB were used, whereas the risk of adverse events was not lower in patients with aspirin, clopidogrel, and ß-blocker. In conclusion, patients with MINOCA were less likely to receive secondary prevention medications at the time of discharge and early discontinuation of medications at the time of follow-up. Statins and ACEI/ARB were the only medications substantially associated with lower adverse events; by comparison, aspirin, clopidogrel, and ß-blocker seem to have no impact on prognosis.

Case report of a suspected pheochromocytoma co-presenting with a glioblastoma multiforme: case report and review of the literature.

The combination of a pheochromocytoma with any brain neoplasm is a rare occurrence, to our knowledge, this is the first reported case of a glioblastoma multiforme co-presenting with undiagnosed pheochromocytoma.

Are patients with hormonally functional phaeochromocytoma and paraganglioma initially receiving a proper adrenoceptor blockade? A retrospective cohort study.

OBJECTIVE: Pharmacological treatment is mandatory in patients with hormonally functional phaeochromocytoma and paraganglioma (PHAEO/PGL). We evaluated if patients initially diagnosed with hormonally functional PHAEO/PGL by various medical subspecialties received proper adrenoceptor blockade, and analysed factors predicting the prescription of adequate treatment. METHODS: In a retrospective cohort study, we reviewed data from patients initially diagnosed with hormonally functional PHAEO/PGL outside the National Institutes of Health and Cedars-Sinai Medical Center, who were referred to these institutions between January 2001 and April 2015. Logistic regression was used to assess factors associated with proper adrenoceptor blockade. RESULTS: A total of 381 patients were included. Adequate pharmacological treatment was prescribed to 69·3%, of which 93·1% received α-adrenoceptor blockers. Regarding patients who were inappropriately treated, 53% did not receive any medication. Independent predictors of the prescription of a proper blockade were the diagnosis by endocrinologists [odds ratio (OR) 4·14; 95% confidence interval (CI), 2·51-6·85; P < 0·001], the presence of high blood pressure (OR 5·94; 95% CI, 3·11-11·33; P < 0·001) and the evidence of metastasis (OR 5·96; 95% CI, 1·93-18·46; P = 0·002). CONCLUSIONS: Although most patients received adequate pharmacological treatment, almost one-third were either not treated or received inappropriate medications. The diagnosis by endocrinologists, the presence of high blood pressure and the evidence of metastatic disease were identified as independent predictors of a proper blockade. These results highlight the need to educate physicians about the importance of starting adequate adrenoceptor blockade in all patients with hormonally functional PHAEO/PGL.

Analgesic Effects of 1st Generation Anti-histamines in Mice.

Pain is sensed, transmitted, and modified by a variety of mediators and receptors. Histamine is a well-known mediator of pain. In addition to their anti-histaminic effects, the classical, or 1st generation, anti-histamines (1st AHs) possess, to various degrees, anti-muscarinic, anti-serotonergic, anti-adrenergic, and other pharmacologic effects. Although there have been attempts to use 1st AHs as analgesics and/or analgesic adjuvants, the advent of non-steroidal anti-inflammatory drugs (NSAIDs) discouraged such trials. We previously reported that in patients with temporomandibular disorders, osteoporosis, and/or osteoarthritis, the analgesic effects of certain 1st AHs (chlorpheniramine and diphenhydramine) are superior to those of the NSAIDs flurbiprofen and indomethacin. Here, we compared analgesic effects among 1st AHs and NSAIDs against responses shown by mice to intraperitoneally injected 0.7% acetic acid. Since 1st AHs are water soluble, we selected water-soluble NSAIDs. For direct comparison, drugs were intravenously injected 30 min before the above tests. Histamine-H1-receptor-deficient (H1R-KO) mice were used for evaluating H1-receptor-independent effects. The tested 1st AHs (especially cyproheptadine) displayed or tended to display analgesic effects comparable to those of NSAIDs in normal and H1R-KO mice. Our data suggest that the anti-serotonergic and/or anti-adrenergic effects of 1st AHs make important contributions to their analgesic effects. Moreover, combination of a 1st AH with an NSAID (cyclooxygenase-1 inhibitor) produced remarkably potent analgesic effects. We propose that a 1st AH, by itself or in combination with a cyclooxygenase-1 inhibitor, should undergo testing to evaluate its usefulness in analgesia.

Stress-induced cardiomyopathy.

OBJECTIVES: Reversible stress-induced cardiac dysfunction is frequently seen as a complication of a multitude of acute stress states, in particular neurologic injuries. This dysfunction may be difficult to distinguish between that caused by myocardial ischemia and may impact both the treatment strategies and prognosis of the underlying condition. Critical care practitioners should have an understanding of the epidemiology, pathophysiology, clinical characteristics, precipitating conditions, differential diagnosis, and proposed treatments for stress-induced cardiomyopathy. DATA SOURCES: MEDLINE database search conducted from inception to August 2014, including the search terms "tako-tsubo," "stress-induced cardiomyopathy," "neurogenic cardiomyopathy," "neurogenic stress cardiomyopathy," and "transient left ventricular apical ballooning syndrome". In addition, references from pertinent articles were used for a secondary search. STUDY SELECTION AND DATA EXTRACTION: After review of peer-reviewed original scientific articles, guidelines, and reviews resulting from the literature search described above, we made final selections for included references and data based on relevance and author consensus. DATA SYNTHESIS: Stress-induced cardiomyopathy occurs most commonly in postmenopausal women. It can be precipitated by emotional stress, neurologic injury, and numerous other stress states. Patients may present with symptoms indistinguishable from acute coronary syndrome or with electrocardiogram changes and wall motion abnormalities on echocardiogram following neurologic injury. Nearly all patients will have an elevated cardiac troponin. The underlying etiology is likely related to release of catecholamines, both locally in the myocardium and in the circulation. Differential diagnosis includes myocardial infarction, myocarditis, neurogenic pulmonary edema, and nonischemic cardiomyopathy. Although the natural course of stress-induced cardiomyopathy is resolution, treatment strategies include sympathetic blockade and supportive care. CONCLUSIONS: Stress-induced cardiomyopathy may mimic myocardial infarction and is an important condition to recognize in patients with underlying stress states, particularly neurologic injuries.

Adrenergic nervous system in heart failure: pathophysiology and therapy.

Heart failure (HF), the leading cause of death in the western world, develops when a cardiac injury or insult impairs the ability of the heart to pump blood and maintain tissue perfusion. It is characterized by a complex interplay of several neurohormonal mechanisms that become activated in the syndrome to try and sustain cardiac output in the face of decompensating function. Perhaps the most prominent among these neurohormonal mechanisms is the adrenergic (or sympathetic) nervous system (ANS), whose activity and outflow are enormously elevated in HF. Acutely, and if the heart works properly, this activation of the ANS will promptly restore cardiac function. However, if the cardiac insult persists over time, chances are the ANS will not be able to maintain cardiac function, the heart will progress into a state of chronic decompensated HF, and the hyperactive ANS will continue to push the heart to work at a level much higher than the cardiac muscle can handle. From that point on, ANS hyperactivity becomes a major problem in HF, conferring significant toxicity to the failing heart and markedly increasing its morbidity and mortality. The present review discusses the role of the ANS in cardiac physiology and in HF pathophysiology, the mechanisms of regulation of ANS activity and how they go awry in chronic HF, methods of measuring ANS activity in HF, the molecular alterations in heart physiology that occur in HF, along with their pharmacological and therapeutic implications, and, finally, drugs and other therapeutic modalities used in HF treatment that target or affect the ANS and its effects on the failing heart.

Pheochromocytomas in Multiple Endocrine Neoplasia Type 2.

Pheochromocytoma (PC) is a neuroendocrine tumor that originates from chromaffin cells of the adrenal medulla. The production of catecholamines, including epinephrine, norepinephrine and dopamine, may lead to haemodynamic instability. Over 30% of PCs are associated with germline mutations, including re-arranged in transfection (RET) mutations seen in multiple endocrine neoplasia type 2 (MEN2) syndromes. Around 40% of individuals with MEN2 develop PC, though it is rarely the presenting feature. Compared to sporadic PC, MEN2-associated PC is more likely to be epinephine secreting and demonstrate bilateral adrenal involvement, and is less likely to be malignant. The diagnosis of PC requires clinical suspicion and biochemical testing, followed by imaging studies. Novel nuclear medicine modalities, including FDG positron emission tomography (PET) and 68Ga DOTATATE PET have added to the conventional techniques of 123I-metaiodobenzylguanindine (MIBG) scintigraphy, computer tomography and magnetic resonance imaging. Treatment of PC is surgical and requires peri-operative alpha and, frequently, beta blockade. Novel surgical techniques, such as adrenal sparing surgery and a laparoscopic approach, have decreased peri-operative morbidity. Surveillance for PC is life long, due to the risk of metastatic disease.

Does age modify the relationship between adherence to secondary prevention medications and mortality after acute myocardial infarction? A nested case-control study.

PURPOSE: Clinical trials have shown that evidence-based secondary prevention medications reduce mortality after acute myocardial infarction (AMI). Yet, these medications are generally underused in daily practice, and older people are often excluded from drug trials. The purpose of this study was to examine whether the relationship between adherence to evidence-based drugs and post-AMI mortality varies with increasing age. METHODS: The study population was defined as all residents in the Local Health Authority of Bologna (Italy) hospitalized for AMI between January 1, 2008 and June 30, 2011, and followed up until December 31, 2012. Medication adherence was calculated as the proportion of days covered (PDC) for filled prescriptions of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, ß-blockers, antiplatelet drugs, and statins; patients were classified as adherent (PDC ≥75 %) or nonadherent (PDC <75 %). We used incidence density sampling, and the moderating effect of age on the relationship between adherence and mortality was investigated through conditional multiple logistic regression analysis. RESULTS: The study population comprised 3963 patients. During the 5-year study period, 1085 deaths (27.4 %) were observed. For both younger and older patients, adherence to polytherapy (three or four medications) was associated with lower mortality (adj. rate ratio = 0.41; P < 0.001). A significant inverse relationship was found between adherence to each of the four medications and mortality, although the risk reduction associated with antiplatelet therapy declined after the age of 70-75. CONCLUSIONS: The beneficial effect of evidence-based polytherapy on mortality following AMI is observed also in older populations. Nevertheless, the risk-benefit ratio associated with antiplatelet therapy is less favorable with increasing age.

Outcomes of medical and surgical treatment for lower urinary tract symptoms (benign prostatic obstruction)--a population-based cohort study.

OBJECTIVE: To compare outcome of lower urinary tract symptoms (LUTS) between men with medical and surgical treatment. MATERIALS AND METHODS: A questionnaire was mailed to men aged 55, 65 and 75 years living in Tampere region, Finland in 1999 and the survey was repeated in 2004. LUTS were evaluated using DAN-PSS-1 questionnaire. A total of 1679 men (68% of the eligible) responded to both questionnaires. Of them, 114 men reported LUTS at baseline and medical treatment in the repeat survey and 47 men with LUTS had received surgical treatment. Seventy-two men with prostate cancer were excluded. Men with no medical treatment or surgery for LUTS in either questionnaire were included to no-treatment group. RESULTS: The men after surgical treatment showed a reduction in all LUTS symptom groups. However, among the medically treated and untreated men, all the symptoms worsened during the follow up. The proportion of symptomatic men after surgery was lower than among the medically treated men. In men with medical treatment, the prevalence of all 12 LUTS increased. Dysuria and postmicturition dribble were the only symptoms that had slightly better results in medical than in surgical treatment group. CONCLUSIONS: In this population-based study, operative treatment seemed to relieve LUTS, whereas medical treatment only slowed down their progression. These findings suggest that men with surgical treatment experience a more favourable outcome in LUTS than those receiving medical treatment.

Analgesic and anti-inflammatory effects of honey: the involvement of autonomic receptors.

The use of honey for therapeutic purposes is on the increase and many studies have shown that honey has the ability to influence biological systems including pain transmission. Therefore, this study was designed to investigate the analgesic and anti-inflammatory effects of honey and the effects of concurrent administration of autonomic nervous system blocking drugs. Studies on analgesic activities was carried out using hotplate and formalin-induced paw licking models while the anti-inflammatory activity was by the carrageenan paw oedema method. Animals were distributed into six groups consisting of five animals each. They were administered saline, honey (600 mg/kg), indomethacin (5 mg/kg), autonomic blockers (3 µg/kg of tamsulosin, 20 mg/kg (intraperitoneally) of propranolol, 2 ml/kg of atropine or 10 mg/kg (intra muscularly) of hexamethonium) or honey (200 and 600 mg/kg) with one of the blockers. The results showed that honey reduced pain perception especially inflammatory pain and the administration of tamsulosin and propranolol spared the effect of honey. Hexamethonium also spared the effects of honey at the early and late phases of the test while atropine only inhibited the early phase of the test. However, atropine and hexamethonium spared the anti-inflammatory effects of honey but tamsulosin abolished the effects while propranolol only abolished the anti-inflammatory effects at the peak of the inflammation. The results suggest the involvement of autonomic receptors in the anti-nociceptive and anti-inflammatory effects of honey although the level of involvement depends on the different types of the receptors.

Assessment of therapeutic biomarkers in the treatment of children with postural tachycardia syndrome and vasovagal syncope.

BACKGROUND: Postural tachycardia syndrome and vasovagal syncope are common causes of orthostatic intolerance in children. The supplementation with water, or salt, or midodrine, or ß-blocker was applied to children with postural tachycardia syndrome or vasovagal syncope. However, the efficacy of such medication varied and was not satisfied. This review aimed to summarise the current biomarkers in the treatment of the diseases. DATA SOURCES: Studies were collected from online electronic databases, including OVID Medline, PubMed, ISI Web of Science, and associated references. The main areas assessed in the included studies were clinical improvement, the cure rate, and the individualised treatment for postural tachycardia syndrome and vasovagal syncope in children. RESULTS: Haemodynamic change during head-up tilt test, and detection of 24-hour urinary sodium excretion, flow-mediated vasodilation, erythrocytic H2S, and plasma pro-adrenomedullin as biological markers were the new ways that were inexpensive, non-invasive, and easy to test for finding those who would be suitable for a specific drug and treatment. CONCLUSION: With the help of biomarkers, the therapeutic efficacy was greatly increased for children with postural tachycardia syndrome and vasovagal syncope.

Comparison of efficacy of labetalol and fentanyl for attenuating reflex responses to laryngoscopy and intubation.

Stress response due to laryngoscopy and intubation has been universally recognized phenomenon resulting in increase in heart rate, arterial, intracranial, and intraocular pressure. Various pharmacological approaches have been used to blunt or attenuate such pressure responses. This prospective, randomized, placebo controlled, double blinded study was designed to compare the efficacy of bolus dose of Labetalol and Fentanyl for attenuating reflex responses to laryngoscopy and intubation. Ninety patients with physical status of ASA I and II were scheduled for elective surgery under standard protocol of general anaesthesia, randomly allocated into three groups, consisting of 30 patients in each group, assigned as C (Control), L (Labetalol), and F (Fentanyl). In control group 10ml of 0.9% saline, in Labetalol group 0.25 mg/kg Labetalol and in Fentanyl group 2µgm/kg of Fentanyl were given intravenously at 3 minutes prior to laryngoscopy and intubation. Pulse rate, systolic, diastolic, mean arterial pressure and rate pressure products (RPP) were recorded before and after premedication, after administration of study drugs and at 1, 3, 5, 10 and 15 minutes after intubation. For statistical analysis of data, ANOVA tests were performed for comparison between groups. There were an increase in heart rate, systolic, diastolic, mean arterial pressures and rate pressure product in all the three groups after intubation in comparison to base line value. But the rise was minimum in L and F group as compared to C group which is statistically significant and also minimum in L group as compared to F group. So Labetalol is better agent for attenuation of laryngoscopic and intubation reflex.