1,721,102 research outputs found
INTERAZIONE TRA FARMACI IN OSTETRICIA E GINECOLOGIA
No full textC’è ormai piena consapevolezza che le interazioni tra i farmaci costituiscono uno dei problemi più importanti della terapia medica. E’ infatti del tutto eccezionale che un paziente venga trattato con un singolo farmaco. Nella stragrande maggioranza dei casi ai pazienti vengono somministrati due o più farmaci contemporaneamente. Ed è sempre più frequente il caso di pazienti trattati cronicamente con certi farmaci (antiipertensivi, anticoagulanti, antiepilettici, contraccettivi, ansiolitici, antidepressivi, antipsicotici, antireumatici/analgesici, ecc.) ai quali, per patologie acute intercorrenti, devono essere somministrati altri farmaci, che non raramente vanno ad alterare la metabolizzazione, l’eliminazione e/o gli effetti dei primi, con la comparsa di reazioni avverse, di riduzione o viceversa di potenziamento della loro attività. L’incidenza di reazioni avverse aumenta in maniera quasi esponenziale con l’aumentare del numero di farmaci che vengono assunti contemporaneamente. Ed in effetti una percentuale significativa e crescente di ricoveri ospedalieri è la conseguenza di effetti avversi gravi da interazioni tra farmaci. La sempre migliore conoscenza dei meccanismi d’azione e dei processi di metabolizzazione dei farmaci consente ormai, nella maggior parte dei casi, di dare una spiegazione delle interazioni osservate, o di poterle addirittura prevedere. Gli effetti di un farmaco possono venire modificati dalla contemporanea somministrazione di altri farmaci, o anche da certi alimenti, o da inquinanti ambientali (compreso il fumo di tabacco). Le interazioni tra farmaci (interazioni farmacologiche) possono avere conseguenze positive, e infatti molto spesso farmaci diversi vengono somministrati in associazione proprio per ottenere un effetto terapeutico più intenso, o di maggiore durata; o per ridurre le dosi e quindi la tossicità dei singoli componenti l’associazione; o per ritardare lo sviluppo di resistenza, nel caso di chemioterapici antiinfettivi o antitumorali. Oppure, le interazioni tra farmaci possono avere conseguenze negative: riduzione dell’intensità e della durata dell’effetto, sommazione di effetti tossici sugli stessi organi o apparati, comparsa di effetti tossici del tutto nuovi. Nel caso dei contraccettivi ormonali, l’assunzione contemporanea di alcuni antibiotici o di antidepressivi triciclici possono riduce l’efficacia contraccettiva e l'effetto antidepressivo rispettivamente. L’interazione dei due farmaci somministrati contemporaneamente può essere di tipo farmacocinetico, farmacodinamico, o chimico-fisico (farmaceutico; incompatibilità farmaceutica). Nel caso dell’interazione di tipo farmacocinetico un farmaco può interferire con un altro a livello di assorbimento, di distribuzione nell’organismo (es: legame con le proteine plasmatiche), di metabolizzazione (induzione e inibizione enzimatica), di eliminazione. Nel caso dell’interazione di tipo farmacodinamico si possono verificare sommazione di effetti; sinergismo, antagonismo recettoriale; antagonismo funzionale. Verranno prese in considerazione le conseguenze negative delle interazioni farmacologiche, perché di gran lunga più importanti per i loro riflessi sul paziente e sul decorso della malattia, e perché sono quelle che maggiormente preoccupano chi prescrive i farmaci. E anche perché sempre più spesso è il paziente stesso a preoccuparsi e ad informarsi delle possibili conseguenze negative dell’assunzione contemporanea di farmaci diversi.
obiettivi di apprendimento: L’obiettivo sarà quello di fornire ai medici le basi per poter comprendere e prevenire eventuali reazioni avversa da farmaci
Saffron (Crocus Sativus L.) and its potential applications in sexual dysfunction
No full textSaffron (Crocus Sativus L.) has long been known for its medical, aromatic and coloring qualities. Due to its taste and yellow-orange colour, it was used as a dye in Persian, Arab, European and Indian cuisine; moreover it is also a component of liquors, candies and food supplements. It is considered the most expensive and prestigious spice in the world, therefore nicknamed “Red Gold”. It is estimated more than 90% worldwide production of saffron come from Iran and that about 5-6 tons of saffron is being produced annually in the Herat region of Afghanistan. The chemical elements which confer to saffron its organoleptic qualities are: crocin, crocetin, picrocrocin and safranal. The main saffron constituents, such as crocin and safranal are known for their many biological functions. It is well documented its potential therapeutic role in cancer, diabetes, atherosclerosis and depression. Saffron has long considered an aphrodisiac drugs (Madan, 1966). Preclinical and clinical studies support saffron as a treatment for male and female sexual disorders, particularly if related to major depression (Hosseinzadeh et al., 2008). On the other hand, administration of antidepressants such as serotonin reuptake inhibitors (SSRI) is associated with sexual disorders and it has been observed that the use of saffron improves sexual disorders induced by fluoxetine and other SSRI (Modabbernia et al., 2012; Kashani et al., 2013). Hosseinzadeh and collaborators (2008) reported that crocin improves sexual behavior in rodents; in addition, crocetin has been shown to induce endothelium-dependent relaxation by increasing eNOS activity. Other studies show that crocin could inhibit extracellular Ca2+ influx, and intracellular Ca2+, release from deposits of endoplasmic reticulum, which contributes to relaxation of the corpus cavernosum smooth muscle with consequent erection
Dual acting anti-inflammatory drugs
No full textDrugs able to inhibit both cyclooxygenases (COX-1 and COX-2) and 5-lipoxygenase (5-LOX) (dual acting anti-inflammatory drugs) have been designed in order to obtain compounds that retain the activity of classical nonsteroidal anti-inflammatory drugs (NSAIDs) while avoiding their main drawbacks. The classical NSAIDs display their anti-inflammatory action mainly through inhibition of COX and one of their main drawbacks is the curtailed production of gastroprotective prostaglandins (PGs) being associated with the concurrent increased production of the gastro-damaging and bronchoconstrictive leukotrienes (LTs). Leukotrienes and cysteinyl-leukotrienes are moreover pro-inflammatory and increase microvascular permeability. One of the leukotrienes (LTB4) is the most potent chemotactic agent and it induces chemotaxis of eosinophils, neutrophils and monocytes in the inflamed tissue, increases superoxide generation and proinflammatory cytokines production. It is further advantageous for a drug to have both COX and 5-LOX inhibiting activities because prostaglandins enhance leukotriene-mediated inflammation. Various structural families of dual inhibitors have been designed and several compounds are currently undergoing clinical development. In the post-COX-2 selective inhibitors era, these dual acting inhibitors may turn out to be promising new drugs to treat inflammatory diseases and possibly other diseases. Indeed, both COX-2 and 5-LOX are also involved in the development and progression of several types of cancer; in these conditions, selective inhibition of COX-2 alone may lead to a shunt of arachidonic acid metabolism towards the leukotriene pathway, and therefore the blockade of both COX-2 and 5-LOX may produce a better anticancer response. In addition, the dual inhibition of both COX and 5-LOX is neuroprotective by suppressing toxic actions of reactive microglia and macrophages, that are increased in aging brain and in age-related degenerative conditions, particularly Alzheimer's and Parkinson's diseases. Finally, the blockade of 5-LOX does not impair the synthesis of lipoxins (LXs), which are mainly produced by further lipoxygenation of 15-HPETE, and which have potent anti-inflammatory properties and can be considered as stop-signal mediators. Leukocyte 15-LOX and platelet 12-LOX by intercellular mechanism via leukocyte/platelet cell-cell interaction convert 15-HPETE into lipoxins
Developments and new vistas in the field of melanocortins
No full textMelanocortins play a fundamental role in several basic functions of the organism (sexual activity, feeding, inflammation and immune responses, pain sensitivity, response to stressful situations, motivation, attention, learning, and memory). Moreover, a large body of animal data, some of which were also confirmed in humans, unequivocally show that melanocortins also have impressive therapeutic effects in several pathological conditions that are the leading cause of mortality and disability worldwide (hemorrhagic, or anyway hypovolemic, shock; septic shock; respiratory arrest; cardiac arrest; ischemia- and ischemia/reperfusion-induced damage of the brain, heart, intestine, and other organs; traumatic injury of brain, spinal cord, and peripheral nerves; neuropathic pain; toxic neuropathies; gouty arthritis; etc.). Recent data obtained in animal models seem to moreover confirm previous hypotheses and preliminary data concerning the neurotrophic activity of melanocortins in neurodegenerative diseases, in particular Alzheimer's disease. Our aim was (i) to critically reconsider the established extrahormonal effects of melanocortins (on sexual activity, feeding, inflammation, tissue hypoperfusion, and traumatic damage of central and peripheral nervous system) at the light of recent findings, (ii) to review the most recent advancements, particularly on the effects of melanocortins in models of neurodegenerative diseases, (iii) to discuss the reasons that support the introduction into clinical practice of melanocortins as life-saving agents in shock conditions and that suggest to verify in clinical setting the impressive results steadily obtained with melanocortins in different animal models of tissue ischemia and ischemia/reperfusion, and finally, (iv) to mention the advisable developments, particularly in terms of selectivity of action and of effects
Melanocortins As Innovative Drugs for Ischemic Diseases and Neurodegenerative Disorders: Established Data and Perspectives
No full textIschemic insults and neurodegenerative diseases are by far the leading cause of mortality and disability. Whole-body hypoperfusion, as it occurs in polytraumatic and hemorrhagic shock, is alike an increasingly frequent condition, especially due to traffic accidents, wars and acts of terrorism. It is now clearly established that inflammatory processes play a fundamental role in the pathophysiology of both hypoperfusion/ischemia damage (be it generalized to the whole body, as in the case of shock, or limited to individual organs) and neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis). On the other hand, concurrent animal and human data show that melanocortin peptides with agonist activity at melanocortin MC3/MC4 receptors are highly effective in different shock conditions as well as in conditions of ischemia/ischemia-reperfusion of individual organs (heart, brain, intestine, kidney, etc.), and accumulating evidence indicates that such effects of melanocortins are mostly due to quite peculiar antiinflammatory mechanisms. Melanocortins have also long been known (i) to exert important neurotrophic effects, not only during fetal development but also in adulthood, in different animal models of brain lesions; (ii) to reduce the morphological correlates of brain aging; (iii) to retard the behavioral deficits that develop during the aging process. Moreover, recent data from different laboratories show that after brain ischemic episodes melanocortins activate the transcription of neurotrophins and their receptors in the cerebral cortex and in the hippocampus, and increase the proliferation of progenitor neuron cells. The above arguments support the view that pharmacokinetically suitable agonists at MC3/MC4 melanocortin receptors may represent a completely innovative class of drugs for an effective treatment of both ischemic and neurodegenerative diseases
DUAL ACTING ANTI-INFLAMATORY DRUGS
No full textDrugs able to inhibit both cyclooxygenases (COX-1 and COX-2) and 5-lipoxygenase (5-LOX) (dual acting
anti-inflammatory drugs) have been designed in order to obtain compounds that retain the activity of classical nonsteroidal
anti-inflammatory drugs (NSAIDs) while avoiding their main drawbacks. The classical NSAIDs display their anti-
inflammatory action mainly through inhibition of COX and one of their main drawbacks is the curtailed production of
gastroprotective prostaglandins (PGs) being associated with the concurrent increased production of the gastro-damaging
and bronchoconstrictive leukotrienes (LTs). Leukotrienes and cysteinyl-leukotrienes are moreover pro-inflammatory and
increase microvascular permeability. One of the leukotrienes (LTB4) is the most potent chemotactic agent and it induces
chemotaxis of eosinophils, neutrophils and monocytes in the inflamed tissue, increases superoxide generation and
proinflammatory cytokines production. It is further advantageous for a drug to have both COX and 5-LOX inhibiting
activities because prostaglandins enhance leukotriene-mediated inflammation. Various structural families of dual
inhibitors have been designed and several compounds are currently undergoing clinical development. In the post-COX-2
selective inhibitors era, these dual acting inhibitors may turn out to be promising new drugs to treat inflammatory diseases
and possibly other diseases. Indeed, both COX-2 and 5-LOX are also involved in the development and progression of
several types of cancer; in these conditions, selective inhibition of COX-2 alone may lead to a shunt of arachidonic acid
metabolism towards the leukotriene pathway, and therefore the blockade of both COX-2 and 5-LOX may produce a better
anticancer response. In addition, the dual inhibition of both COX and 5-LOX is neuroprotective by suppressing toxic
actions of reactive microglia and macrophages, that are increased in aging brain and in age-related degenerative
conditions, particularly Alzheimer’s and Parkinson’s diseases. Finally, the blockade of 5-LOX does not impair the
synthesis of lipoxins (LXs), which are mainly produced by further lipoxygenation of 15-HPETE, and which have potent
anti-inflammatory properties and can be considered as stop-signal mediators. Leukocyte 15-LOX and platelet 12-LOX by
intercellular mechanism via leukocyte/platelet cell-cell interaction convert 15-HPETE into lipoxins
THE ANALGESIC ACTIVITY OF PARACETAMOL IS PREVENTED BY THE BLOCKADE OF CANNABINOID CB1 RECEPTORS
No full textThe mechanism of the analgesic activity of paracetamol (acetaminophen), one of the most widely used drugs for the treatment of pain, is still
not clear. Here we show that in rats, using the hot plate test, the analgesic effect of paracetamol is prevented by two antagonists at cannabinoid CB1
receptors (AM281 and SR141716A) at doses that prevent the analgesic activity of the cannabinoid CB1 agonist HU210. Our present results
suggest that paracetamol-induced antinociception involves the cannabinoid system
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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