Self-expandable metal stents in the treatment of acute esophageal variceal bleeding.

Acute variceal bleeding (AVB) is a life-threatening complication in patients with cirrhosis. Hemostatic therapy of AVB includes early administration of vasoactive drugs that should be combined with endoscopic therapy, preferably banding ligation. However, failure to control bleeding or early rebleed within 5 days still occurs in 15-20% of patients with AVB. In these cases, a second endoscopic therapy may be attempted (mild bleeding in a hemodynamically stable patient) or we can use a balloon tamponade as a bridge to definitive derivative treatment (i.e., a transjugular intrahepatic portosystemic shunt). Esophageal balloon tamponade provides initial control in up to 80% of AVB, but it carries a high risk of major complications, especially in cases of long duration of tamponade (>24 h) and when tubes are inserted by inexperienced staff. Preliminary reports suggest that self-expandable covered esophageal metallic stents effectively control refractory AVB (i.e., ongoing bleeding despite pharmacological and endoscopic therapy or massive bleeding precluding endoscopic therapy) with a low incidence of complications. Thus, covered self-expanding metal stents may represent an alternative to the Sengstaken-Blakemore balloon for the temporary control of bleeding in treatment failures. Further studies are required to determine the role of this new device in AVB.

Outcome of patients admitted with acute coronary syndrome on palliative treatment: insights from the nationwide AMIS Plus Registry 1997-2014.

OBJECTIVE: Compliance with guidelines is increasingly used to benchmark the quality of hospital care, however, very little is known on patients admitted with acute coronary syndromes (ACS) and treated palliatively. This study aimed to evaluate the baseline characteristics and outcomes of these patients. DESIGN: Prospective cohort study. SETTING: Eighty-two Swiss hospitals enrolled patients from 1997 to 2014. PARTICIPANTS: All patients with ACS enrolled in the AMIS Plus registry (n=45,091) were analysed according to three treatment groups: palliative treatment, defined as use of aspirin and analgesics only and no reperfusion; conservative treatment, defined as any treatment including antithrombotics or anticoagulants, heparins, P2Y12 inhibitors, GPIIb/IIIa but no pharmacological or mechanical reperfusion; and reperfusion treatment (thrombolysis and/or percutaneous coronary intervention during initial hospitalisation). The primary outcome measure was in-hospital mortality and the secondary measure was 1-year mortality. RESULTS: Of the patients, 1485 (3.3%) were palliatively treated, 11,119 (24.7%) were conservatively treated and 32,487 (72.0%) underwent reperfusion therapy. In 1997, 6% of all patients were treated palliatively and this continuously decreased to 2% in 2013. Baseline characteristics of palliative patients differed in comparison with conservatively treated and reperfusion patients in age, gender and comorbidities (all p<0.001). These patients had more in-hospital complications such as postadmission onset of cardiogenic shock (15.6% vs 5.2%; p<0.001), stroke (1.8% vs 0.8%; p=0.001) and a higher in-hospital mortality (25.8% vs 5.6%; p<0.001).The subgroup of patients followed 1 year after discharge (n=8316) had a higher rate of reinfarction (9.2% vs 3.4%; p=0.003) and mortality (14.0% vs 3.5%; p<0.001). CONCLUSIONS: Patients with ACS treated palliatively were older, sicker, with more heart failure at admission and very high in-hospital mortality. While refraining from more active therapy may often constitute the most humane and appropriate approach, we think it is important to also evaluate these patients and include them in registries and outcome evaluations. CLINICAL TRIAL NUMBER: ClinicalTrials.gov Identifier: NCT01 305 785.

Calcium-Mediated Induction of Paradoxical Growth following Caspofungin Treatment Is Associated with Calcineurin Activation and Phosphorylation in Aspergillus fumigatus.

The echinocandin antifungal drug caspofungin at high concentrations reverses the growth inhibition of Aspergillus fumigatus, a phenomenon known as the "paradoxical effect," which is not consistently observed with other echinocandins (micafungin and anidulafungin). Previous studies of A. fumigatus revealed the loss of the paradoxical effect following pharmacological or genetic inhibition of calcineurin, yet the underlying mechanism is poorly understood. Here, we utilized a codon-optimized bioluminescent Ca(2+) reporter aequorin expression system in A. fumigatus and showed that caspofungin elicits a transient increase in cytosolic free Ca(2+) ([Ca(2+)]c) in the fungus that acts as the initial trigger of the paradoxical effect by activating calmodulin-calcineurin signaling. While the increase in [Ca(2+)]c was also observed upon treatment with micafungin, another echinocandin without the paradoxical effect, a higher [Ca(2+)]c increase was noted with the paradoxical-growth concentration of caspofungin. Treatments with a Ca(2+)-selective chelator, BAPTA [1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid], or the L-type Ca(2+) channel blocker verapamil abolished caspofungin-mediated paradoxical growth in both the wild-type and the echinocandin-resistant (EMFR-S678P) strains. Concomitant with increased [Ca(2+)]c levels at higher concentrations of caspofungin, calmodulin and calcineurin gene expression was enhanced. Phosphoproteomic analysis revealed that calcineurin is activated through phosphorylation at its serine-proline-rich region (SPRR), a domain previously shown to be essential for regulation of hyphal growth, only at a paradoxical-growth concentration of caspofungin. Our results indicate that as opposed to micafungin, the increased [Ca(2+)]c at high concentrations of caspofungin activates calmodulin-calcineurin signaling at both a transcriptional and a posttranslational level and ultimately leads to paradoxical fungal growth.

Is altitude training an efficient treatment for obesity?

Worldwide, about half the adult population is considered overweight as defined by a body mass index (BMI - calculated by body weight divided by height squared) ratio in excess of 25 kg.m-2. Of these individuals, half are clinically obese (with a BMI in excess of 30) and these numbers are still increasing, notably in developing countries such as those of the Middle East region. Obesity is a disorder characterised by increased mass of adipose tissue (excessive fat accumulation) that is the result of a systemic imbalance between food intake and energy expenditure. Although factors such as family history, sedentary lifestyle, urbanisation, income and family diet patterns determine obesity prevalence, the main underlying causes are poor knowledge about food choice and lack of physical activity3. Current obesity treatments include dietary restriction, pharmacological interventions and ultimately, bariatric surgery. The beneficial effects of physical activity on weight loss through increased energy expenditure and appetite modulation are also firmly established. Another viable option to induce a negative energy balance, is to incorporate hypoxia per se or combine it with exercise in an individual's daily schedule. This article will present recent evidence suggesting that combining hypoxic exposure and exercise training might provide a cost-effective strategy for reducing body weight and improving cardio-metabolic health in obese individuals. The efficacy of this approach is further reinforced by epidemiological studies using large-scale databases, which evidence a negative relationship between altitude of habitation and obesity. In the United States, for instance, obesity prevalence is inversely associated with altitude of residence and urbanisation, after adjusting for temperature, diet, physical activity, smoking and demographic factors.

Recommandations pour le traitement et la prévention du zona et des douleurs associées chez la personne âgée [Recommendations for treatment and prevention of herpes zoster and associated pain in aged adults].

Initiated within the first 72hours of the rash, prescribing antiviral drugs reduces both acute neuralgia (AN) and later complications and especially postherpetic neuralgia (PHN). But their analgesic as well as preventative effect on AN and PHN is modest. Combination with analgesic drugs is more often needed for pain management. However, the pharmacological management of pain, in the context of old patients' frailty, co-morbidities and often polypharmacy, must be carefully considered. Based on analyses of the evidences from the literature, this review presents the therapeutic options we have at one's disposal and proposes a stepwise management for both AN and PHN specifically designed for aged population.

Treatment of cancer with oral drugs: a position statement by the Spanish Society of Medical Oncology

Cancer treatment involves the participation of multiple medical specialties and, as our knowledge of the disease increases, this fact becomes even more apparent. The degree of multidisciplinarity is determined by several factors, which include the severity and type of disease, the increasing diversity in the available pharmacological and non-pharmacological therapies, and the range of specialists involved in cancer therapy, such as medical oncologists, radiotherapists, gynecologists, gastroenterologists, urologists, surgeons, and pneumologists, among others. Across Europe, the situation of cancer care can be variable due to the diversity of health systems, differences in drug reimbursement, and the degree of establishment of Medical Oncology as a medical specialty in the European Union states.

Oncobiguanides: Paracelsus" law and nonconventional routes for administering diabetobiguanides for cancer treatment

The dose makes the poison, the common motto of toxicology first expressed by Paracelsus more than 400 years ago, may effectively serve to guide potential applications for metformin and related biguanides in oncology. While Paracelsus' law for the dose-response effect has been commonly exploited for the use of some anti-cancer drugs at lower doses in non-neoplastic diseases (e.g., methotrexate), the opposite scenario also holds true; in other words, higher doses of non-oncology drugs, such as anti-diabetic biguanides, might exert direct anti-neoplastic effects. Here, we propose that, as for any drug, there is a dose range for biguanides that is without any effect, one corresponding to"diabetobiguanides" with a pharmacological effect (e.g., insulin sensitization in type 2 diabetes, prevention of insulin-dependent carcinogenesis, indirect inhibition of insulin and growth factor-dependent cancer growth) but with minimal toxicity and another corresponding to 'oncobiguanides' with pharmacological (i.e., direct and strong anticancer activity against cancer cells) as well as toxic effects. Considering that biguanides demonstrate a better safety profile than most oncology drugs in current use, we should contemplate the possibility of administering biguanides through non-conventional routes (e.g., inhaled for carcinomas of the lung, topical for skin cancers, intravenous as an adjunctive therapy, rectal suppositories for rectal cancer) to unambiguously investigate the therapeutic value of high-dose transient biguanide exposure in cancer. Perhaps then, the oncobiguanides, as we call them here, could be viewed as a mechanistically different type of anti-cancer drugs employed at doses notably higher than those used chronically when functioning as diabetobiguanides

Hyperalgesic effect induced by barbiturates, midazolam and ethanol: pharmacological evidence for GABA-A receptor involvement

The involvement of GABA-A receptors in the control of nociception was studied using the tail-flick test in rats. Non-hypnotic doses of the barbiturates phenobarbital (5-50 mg/kg), pentobarbital (17-33 mg/kg), and thiopental (7.5-30 mg/kg), of the benzodiazepine midazolam (10 mg/kg) or of ethanol (0.4-1.6 g/kg) administered by the systemic route reduced the latency for the tail-flick response, thus inducing a 'hyperalgesic' state in the animals. In contrast, non-convulsant doses of the GABA-A antagonist picrotoxin (0.12-1.0 mg/kg) administered systemically induced an increase in the latency for the tail-flick response, therefore characterizing an 'antinociceptive' state. Previous picrotoxin (0.12 mg/kg) treatment abolished the hyperalgesic state induced by effective doses of the barbiturates, midazolam or ethanol. Since phenobarbital, midazolam and ethanol reproduced the described hyperalgesic effect of GABA-A-specific agonists (muscimol, THIP), which is specifically antagonized by the GABA-A antagonist picrotoxin, our results suggest that GABA-A receptors are tonically involved in the modulation of nociception in the rat central nervous system

Pharmacological and histopathological study of cyclophosphamide-induced hemorrhagic cystitis - comparison of the effects of dexamethasone and Mesna

Chemotherapy with oxazaphosphorines, such as cyclophosphamide (CYP), is often limited by unacceptable urotoxicity. Without uroprotection, hemorrhagic cystitis (HC) becomes dose-limiting. To compare the uroprotective efficacy of classical 2-mercaptoethanesulfonic acid (Mesna) treatment with dexamethasone in CYP-induced HC, male Wistar rats (150-200 g; N = 6 in each group) were treated with saline or Mesna (40 mg/kg, ip) immediately and 4 and 8 h after ip administration of CYP (200 mg/kg). One, 2 or 3 doses of Mesna were replaced with dexamethasone (1 mg/kg, ip). The animals were sacrificed 24 h later. Cystitis was evaluated by determining the changes in bladder wet weight (BWW) and by macroscopic and microscopic analysis. CYP treatment induced a marked increased in BWW (162%, P<0.05), which was significantly inhibited by treatment with 3 doses of Mesna (P<0.05; 80%). The replacement of 1 or 2 doses of Mesna with dexamethasone reduced the increase in BWW by 83.3 and 95%, respectively. Macroscopic analysis of the bladder of rats with CYP-induced HC showed severe edema and hemorrhage, confirmed by microscopic analysis, that also showed mucosal erosion, inflammatory cell infiltration and ulcerations. The replacement of 1 or 2 doses of Mesna with dexamethasone inhibited the CYP-induced increase in BWW and almost abolished the macroscopic and microscopic alterations, with no significant difference between the effects of Mesna and dexamethasone, indicating that both drugs were efficient in blocking HC. However, although the replacement of all Mesna doses with dexamethasone reduced the edema, it did not prevent HC, suggesting that Mesna is necessary for the initial uroprotection.

Pharmacological study of anti-allergic activity of Syzygium cumini (L.) Skeels

Myrtaceae is a plant family widely used in folk medicine and Syzygium and Eugenia are among the most important genera. We investigated the anti-allergic properties of an aqueous leaf extract of Syzygium cumini (L.) Skeels (SC). HPLC analysis revealed that hydrolyzable tannins and flavonoids are the major components of the extract. Oral administration of SC (25-100 mg/kg) in Swiss mice (20-25 g; N = 7/group) inhibited paw edema induced by compound 48/80 (50% inhibition, 100 mg/kg; P <= 0.05) and, to a lesser extent, the allergic paw edema (23% inhibition, 100 mg/kg; P <= 0.05). SC treatment also inhibited the edema induced by histamine (58% inhibition; P <= 0.05) and 5-HT (52% inhibition; P <= 0.05) but had no effect on platelet-aggregating factor-induced paw edema. SC prevented mast cell degranulation and the consequent histamine release in Wistar rat (180-200 g; N = 7/group) peritoneal mast cells (50% inhibition, 1 µg/mL; P <= 0.05) induced by compound 48/80. Pre-treatment of BALB/c mice (18-20 g; N = 7/group) with 100 mg/kg of the extract significantly inhibited eosinophil accumulation in allergic pleurisy (from 7.662 ± 1.524 to 1.89 ± 0.336 x 10(6)/cavity; P <= 0.001). This effect was related to the inhibition of IL-5 (from 70.9 ± 25.2 to 12.05 ± 7.165 pg/mL) and CCL11/eotaxin levels (from 60.4 ± 8.54 to 32.8 ± 8.4 ng/mL) in pleural lavage fluid, using ELISA. These findings demonstrate an anti-allergic effect of SC, and indicate that its anti-edematogenic effect is due to the inhibition of mast cell degranulation and of histamine and serotonin effects, whereas the inhibition of eosinophil accumulation in the allergic pleurisy model is probably due to an impairment of CCL11/eotaxin and IL-5 production.

Stress-induced neuroinflammation: mechanisms and new pharmacological targets

Stress is triggered by numerous unexpected environmental, social or pathological stimuli occurring during the life of animals, including humans, which determine changes in all of their systems. Although acute stress is essential for survival, chronic, long-lasting stress can be detrimental. In this review, we present data supporting the hypothesis that stress-related events are characterized by modifications of oxidative/nitrosative pathways in the brain in response to the activation of inflammatory mediators. Recent findings indicate a key role for nitric oxide (NO) and an excess of pro-oxidants in various brain areas as responsible for both neuronal functional impairment and structural damage. Similarly, cyclooxygenase-2 (COX-2), another known source of oxidants, may account for stress-induced brain damage. Interestingly, some of the COX-2-derived mediators, such as the prostaglandin 15d-PGJ2 and its peroxisome proliferator-activated nuclear receptor PPARγ, are activated in the brain in response to stress, constituting a possible endogenous anti-inflammatory mechanism of defense against excessive inflammation. The stress-induced activation of both biochemical pathways depends on the activation of the N-methyl-D-aspartate (NMDA) glutamate receptor and on the activation of the transcription factor nuclear factor kappa B (NFκB). In the case of inducible NO synthase (iNOS), release of the cytokine TNF-α also accounts for its expression. Different pharmacological strategies directed towards different sites in iNOS or COX-2 pathways have been shown to be neuroprotective in stress-induced brain damage: NMDA receptor blockers, inhibitors of TNF-α activation and release, inhibitors of NFκB, specific inhibitors of iNOS and COX-2 activities and PPARγ agonists. This article reviews recent contributions to this area addressing possible new pharmacological targets for the treatment of stress-induced neuropsychiatric disorders.

Cholinergic enhancement of perceptual learning : behavioral, physiological, and neuro-pharmacological study in the rat primary visual cortex

Les cortices sensoriels sont des régions cérébrales essentielles pour la perception. En particulier, le cortex visuel traite l’information visuelle en provenance de la rétine qui transite par le thalamus. Les neurones sont les unités fonctionnelles qui transforment l'information sensorielle en signaux électriques, la transfèrent vers le cortex et l'intègrent. Les neurones du cortex visuel sont spécialisés et analysent différents aspects des stimuli visuels. La force des connections entre les neurones peut être modulée par la persistance de l'activité pré-synaptique et induit une augmentation ou une diminution du signal post-synaptique à long terme. Ces modifications de la connectivité synaptique peuvent induire la réorganisation de la carte corticale, c’est à dire la représentation de ce stimulus et la puissance de son traitement cortical. Cette réorganisation est connue sous le nom de plasticité corticale. Elle est particulièrement active durant la période de développement, mais elle s’observe aussi chez l’adulte, par exemple durant l’apprentissage. Le neurotransmetteur acétylcholine (ACh) est impliqué dans de nombreuses fonctions cognitives telles que l’apprentissage ou l’attention et il est important pour la plasticité corticale. En particulier, les récepteurs nicotiniques et muscariniques du sous-type M1 et M2 sont les récepteurs cholinergiques impliqués dans l’induction de la plasticité corticale. L’objectif principal de la présente thèse est de déterminer les mécanismes de plasticité corticale induits par la stimulation du système cholinergique au niveau du télencéphale basal et de définir les effets sur l’amélioration de la perception sensorielle. Afin d’induire la plasticité corticale, j’ai jumelé des stimulations visuelles à des injections intracorticales d’agoniste cholinergique (carbachol) ou à une stimulation du télencéphale basal (neurones cholinergiques qui innervent le cortex visuel primaire). J'ai analysé les potentiels évoqués visuels (PEVs) dans le cortex visuel primaire des rats pendant 4 à 8 heures après le couplage. Afin de préciser l’action de l’ACh sur l’activité des PEVs dans V1, j’ai injecté individuellement l’antagoniste des récepteurs muscariniques, nicotiniques, α7 ou NMDA avant l’infusion de carbachol. La stimulation du système cholinergique jumelée avec une stimulation visuelle augmente l’amplitude des PEVs durant plus de 8h. Le blocage des récepteurs muscarinique, nicotinique et NMDA abolit complètement cette amélioration, tandis que l’inhibition des récepteurs α7 a induit une augmentation instantanée des PEVs. Ces résultats suggèrent que l'ACh facilite à long terme la réponse aux stimuli visuels et que cette facilitation implique les récepteurs nicotiniques, muscariniques et une interaction avec les récepteur NMDA dans le cortex visuel. Ces mécanismes sont semblables à la potentiation à long-terme, évènement physiologique lié à l’apprentissage. L’étape suivante était d’évaluer si l’effet de l’amplification cholinergique de l’entrée de l’information visuelle résultait non seulement en une modification de l’activité corticale mais aussi de la perception visuelle. J’ai donc mesuré l’amélioration de l’acuité visuelle de rats adultes éveillés exposés durant 10 minutes par jour pendant deux semaines à un stimulus visuel de type «réseau sinusoïdal» couplé à une stimulation électrique du télencéphale basal. L’acuité visuelle a été mesurée avant et après le couplage des stimulations visuelle et cholinergique à l’aide d’une tâche de discrimination visuelle. L’acuité visuelle du rat pour le stimulus d’entrainement a été augmentée après la période d’entrainement. L’augmentation de l’acuité visuelle n’a pas été observée lorsque la stimulation visuelle seule ou celle du télencéphale basal seul, ni lorsque les fibres cholinergiques ont été lésées avant la stimulation visuelle. Une augmentation à long terme de la réactivité corticale du cortex visuel primaire des neurones pyramidaux et des interneurones GABAergiques a été montrée par l’immunoréactivité au c-Fos. Ainsi, lorsque couplé à un entrainement visuel, le système cholinergique améliore les performances visuelles pour l’orientation et ce probablement par l’optimisation du processus d’attention et de plasticité corticale dans l’aire V1. Afin d’étudier les mécanismes pharmacologiques impliqués dans l’amélioration de la perception visuelle, j’ai comparé les PEVs avant et après le couplage de la stimulation visuelle/cholinergique en présence d’agonistes/antagonistes sélectifs. Les injections intracorticales des différents agents pharmacologiques pendant le couplage ont montré que les récepteurs nicotiniques et M1 muscariniques amplifient la réponse corticale tandis que les récepteurs M2 muscariniques inhibent les neurones GABAergiques induisant un effet excitateur. L’infusion d’antagoniste du GABA corrobore l’hypothèse que le système inhibiteur est essentiel pour induire la plasticité corticale. Ces résultats démontrent que l’entrainement visuel jumelé avec la stimulation cholinergique améliore la plasticité corticale et qu’elle est contrôlée par les récepteurs nicotinique et muscariniques M1 et M2. Mes résultats suggèrent que le système cholinergique est un système neuromodulateur qui peut améliorer la perception sensorielle lors d’un apprentissage perceptuel. Les mécanismes d’amélioration perceptuelle induits par l’acétylcholine sont liés aux processus d’attention, de potentialisation à long-terme et de modulation de la balance d’influx excitateur/inhibiteur. En particulier, le couplage de l’activité cholinergique avec une stimulation visuelle augmente le ratio de signal / bruit et ainsi la détection de cibles. L’augmentation de la concentration cholinergique corticale potentialise l’afférence thalamocorticale, ce qui facilite le traitement d’un nouveau stimulus et diminue la signalisation cortico-corticale minimisant ainsi la modulation latérale. Ceci est contrôlé par différents sous-types de récepteurs cholinergiques situés sur les neurones GABAergiques ou glutamatergiques des différentes couches corticales. La présente thèse montre qu’une stimulation électrique dans le télencéphale basal a un effet similaire à l’infusion d’agoniste cholinergique et qu’un couplage de stimulations visuelle et cholinergique induit la plasticité corticale. Ce jumelage répété de stimulations visuelle/cholinergique augmente la capacité de discrimination visuelle et améliore la perception. Cette amélioration est corrélée à une amplification de l’activité neuronale démontrée par immunocytochimie du c-Fos. L’immunocytochimie montre aussi une différence entre l’activité des neurones glutamatergiques et GABAergiques dans les différentes couches corticales. L’injection pharmacologique pendant la stimulation visuelle/cholinergique suggère que les récepteurs nicotiniques, muscariniques M1 peuvent amplifier la réponse excitatrice tandis que les récepteurs M2 contrôlent l’activation GABAergique. Ainsi, le système cholinergique activé au cours du processus visuel induit des mécanismes de plasticité corticale et peut ainsi améliorer la capacité perceptive. De meilleures connaissances sur ces actions ouvrent la possibilité d’accélérer la restauration des fonctions visuelles lors d’un déficit ou d’amplifier la fonction cognitive.

Biochemical & Pharmacological evaluation of liver oils of selected deep sea sharks and chimaeras of the Indian EEZ

With a seacoast of 8,1 18 km, an exclusive economic zone (EEZ) of 2 million square km, and with an area of about 30,000 square km under aquaculture, lndia produces close to six million tonnes of fish, over 4 per cent of the world fish production. While the marine waters upto 50m depth have been fully exploited, those beyond, remain unexplored. There is an ever increasing demand for fishery resources as food. The coastal fishery resources of the country are dwindling at a rapid pace and it becomes highly imperative that we search for alternate fishery resources for food. The option we have is to hunt for marine fishery resources. Studies pertaining to proximate composition, amino acid and fatty acid composition are essential to understand the nutraceutical values of these deep sea fishery resources. The present study was aimed to carry out proximate composition of deep sea fishery resources obtained during cruises onboard the FORV Sarise Sampada, to identify fishery resources which have appreciable lipid content and thereby analyse the bioactive potentials of marine lipids, to study the amino acid profile of these fishery resources, to understand the contents of SPA, MUFA and PUFA and to calculate the n3/n6 fatty acid contents. Though the presence of nutraceuticals was identified in the marine fishery resources their use as potential food resources deserve further investigation. So the study were carried out to calculate the hepatosomatic indices of sharks & chimaeras and conduct biochemical characterisation of liver oils of Apristurus indicus, Cenlrophorus scalprams, Centroselachus crepidater, Neoharriotta raleighana, and Harriotta pinnata obtained during cruises onboard the FORV Sugar Sampada.Therapeutic use of shark liver oil is evident from its use for centuries as a remedy to heal wounds and fight flu (Neil er al. 2006). Japanese seamen called it 'samedava' or "cure all". Shark liver oil is being promoted worldwide as a dietary supplement to boost the immune system, fight infections, to treat cancer and to lessen the side effects of conventional cancer treatment. These days more emphasis is laid on the nutritive benefits of shark liver oils especially on the omega 3 polyunsaturated fatty acids ( PUFAs) (Anandan er al. 2007) and alkylglycerols (AKGs) (Pugliese er al. I998) contained in them due to the high rise of inflammatory disorders such as arthritis, asthma and neurodegenerative diseases like Alzheimer’s, Parkinson’s and Schizophrenia. So the present study also evaluate the pharmacological properties with respect to analgesic, anti-inflammatory, anti pyretic and anti-ulcer effects of four different liver oils of sharks belonging to the Indian EEZ and to identify the components of oil responsible for these activities.The analgesic and anti-inflammatory activities of liver oils from Neoharriotra raleighana (NR), Centrosymnus crepidater (CC), Apristurus indicus (AI), and Centrophorus sculpratus (CS) sharks caught from the Arabian Sea and the Indian Ocean were compared. The main objectives also include determination of the cholesterol lowering effects of liver oils of Neoharriotra raleighana (NR) and Centrophorus sculpratus (CS) on the high fat diet induced dyslipidemia and to compare the impact of four isolipidemic diets, on levels of serum diagnostic marker enzymes, on lipid profile of blood and liver and antioxidant status of heart in male Albino rats. And also to study the efficacy of Centrophorus sculpratus (CS) liver oil against Complete Freund’s Adjuvant-induced arthritis and to compare the anti-inflammatory activity of this oil with a traditionally used anti-inflammatory substance gingerol (oleoresin extracted from ginger.). The results of the present study indicated that both (Centrophorus sculpratus liver oils as well as gingerol extracts proved to be effective natural remedies against CFA-induced arthritis in Albino rats.

Obsessive Compulsive Treatment Efficacy Trial (OCTET) comparing the clinical and cost effectiveness of self-managed therapies: study protocol for a randomised controlled trial

Background: UK National Institute of Health and Clinical Excellence guidelines for obsessive compulsive disorder (OCD) specify recommendations for the treatment and management of OCD using a stepped care approach. Steps three to six of this model recommend treatment options for people with OCD that range from low-intensity guided self-help (GSH) to more intensive psychological and pharmacological interventions. Cognitive behavioural therapy (CBT), including exposure and response prevention, is the recommended psychological treatment. However, whilst there is some preliminary evidence that self-managed therapy packages for OCD can be effective, a more robust evidence base of their clinical and cost effectiveness and acceptability is required. Methods/Design: Our proposed study will test two different self-help treatments for OCD: 1) computerised CBT (cCBT) using OCFighter, an internet-delivered OCD treatment package; and 2) GSH using a book. Both treatments will be accompanied by email or telephone support from a mental health professional. We will evaluate the effectiveness, cost and patient and health professional acceptability of the treatments. Discussion: This study will provide more robust evidence of efficacy, cost effectiveness and acceptability of self-help treatments for OCD. If cCBT and/or GSH prove effective, it will provide additional, more accessible treatment options for people with OCD.

Pharmacological and local toxicity studies of a liposomal formulation for the novel local anaesthetic ropivacaine

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)