Dengue Virus Type 2 Infections of Aedes aegypti Are Modulated by the Mosquito's RNA Interference Pathway

A number of studies have shown that both innate and adaptive immune defense mechanisms greatly influence the course of human dengue virus (DENV) infections, but little is known about the innate immune response of the mosquito vector Aedes aegypti to arbovirus infection. We present evidence here that a major component of the mosquito innate immune response, RNA interference (RNAi), is an important modulator of mosquito infections. The RNAi response is triggered by double-stranded RNA (dsRNA), which occurs in the cytoplasm as a result of positive-sense RNA virus infection, leading to production of small interfering RNAs (siRNAs). These siRNAs are instrumental in degradation of viral mRNA with sequence homology to the dsRNA trigger and thereby inhibition of virus replication. We show that although dengue virus type 2 (DENV2) infection of Ae. aegypti cultured cells and oral infection of adult mosquitoes generated dsRNA and production of DENV2-specific siRNAs, virus replication and release of infectious virus persisted, suggesting viral circumvention of RNAi. We also show that DENV2 does not completely evade RNAi, since impairing the pathway by silencing expression of dcr2, r2d2, or ago2, genes encoding important sensor and effector proteins in the RNAi pathway, increased virus replication in the vector and decreased the extrinsic incubation period required for virus transmission. Our findings indicate a major role for RNAi as a determinant of DENV transmission by Ae. aegypti

Patent characteristics and patent ownership change in agricultural biotechnology

We examine the effect of various patent characteristics on changes in patent ownership that occurred due to mergers, acquisitions, and spin-offs in the agricultural biotechnology industry in the 1980s and 1990s. Our goal is to shed light on the role that certain patent qualities may play in the transfer of knowledge and technology that takes place through merger and acquisition activity. Specifically, we empirically measure the effect of patent value, scope/breadth, strength, and the nationality of the patent owner on the occurrence and frequency of patent ownership change in the agricultural biotechnology sector during the 1980s and 1990s. We find that the greater is the patent breadth and the less valuable and 'weaker' is the patent, the greater is the likelihood and the frequency of patent ownership change. Also, the nature of patent ownership affects patent ownership change, with patents owned by multiple owners of different nationalities most likely to change hands

Italian guidelines for primary headaches: 2012 revised version

The first edition of the Italian diagnostic and therapeutic guidelines for primary headaches in adults was published in J Headache Pain 2(Suppl. 1):105–190 (2001). Ten years later, the guideline committee of the Italian Society for the Study of Headaches (SISC) decided it was time to update therapeutic guidelines. A literature search was carried out on Medline database, and all articles on primary headache treatments in English, German, French and Italian published from February 2001 to December 2011 were taken into account. Only randomized controlled trials (RCT) and meta-analyses were analysed for each drug. If RCT were lacking, open studies and case series were also examined. According to the previous edition, four levels of recommendation were defined on the basis of levels of evidence, scientific strength of evidence and clinical effectiveness. Recommendations for symptomatic and prophylactic treatment of migraine and cluster headache were therefore revised with respect to previous 2001 guidelines and a section was dedicated to non-pharmacological treatment. This article reports a summary of the revised version published in extenso in an Italian version

The triptan formulations: a critical evaluation Formulações dos triptanos: avaliacão crítica

The migraine-specific triptans have revolutionized the treatment of migraine and are usually the drugs of choice to treat a migraine attack in progress. Different triptans are available in different strengths and formulations including oral tablets, orally disintegrating tablets, nasal sprays and subcutaneous injections. In Europe, sumatriptan is also available as a suppository. Specific differences among the triptans exist as evidenced by different pharmacological profiles includingT&frac12;, Tmax, Cmax, AUC, metabolism, drug-drug interaction profiles, amongst other parameters. How or whether these differences translate to clinical efficacy and tolerability differences is not well differentiated. Clinical distinctions among these agents are subtle and proper choice of triptan requires attention to the specific characteristics of each individual patient, knowledge of patient preference, accurate history of the efficacy of previous acute care medications as well as individual features of the drug being considered. Delivery systems may play an important role in the onset of action of triptans. The selection of an acute antimigraine drug for a patient depends upon the stratification of the patient's migraine attack by peak intensity, time to peak intensity, level of associated symptoms such as nausea and vomiting, time to associated symptoms, comorbid diseases, and concomitant treatments that might cause drug-drug interactions. The clinician has in his armamentarium an ever-expanding variety of medications, available in multiple formulations and dosages, with good safety and tolerability profiles. Continued clinical use will yield familiarity with the various triptans, and it should become possible for the interested physician to match individual patient needs with the specific characteristics of a triptan to optimize therapeutic benefit.<br>Os triptanos, drogas anti-migranosas específicas, revolucionaram o tratamento da migrânea e são considerados as drogas de escolha para o tratamento da crise migranosa. Diferentes triptanos são disponíveis em diferentes formulações, incluindo comprimidos, tabletes de dispersão oral, sprays para administração nasal e injeções subcutâneas. Na Europa, sumatriptan também é disponível como supositório. Diferenças específicas entre os triptanos são evidenciadas por seu diferente perfil farmacológico, incluindo T&frac12;, Tmax, Cmax, AUC, metabolismo, perfil de interação entre drogas, entre outros parâmetros. Controvérsias existem sobre se, ou como, essas variáveis traduzem-se em eficácia clínica e tolerabilidade. A distinção clínica entre esses agentes é sutil e a escolha adequada de um triptano requer consideração sobre as características específicas de cada paciente, conhecimento da preferência dos mesmos, obtenção de história acurada sobre a eficácia de medicações previamente utilizadas, assim como consideração sobre as características individuais das diversas drogas. A via posológica parece desempenhar importante papel no modo de ação dos triptanos. A seleção de droga antimigranosa adequada para o tratamento da crise migranosa depende da estratificação do ataque de acordo como a intensidade da dor, tempo para que a máxima intensidade da dor seja atingida, sintomas associados, tempo para que os sintomas associados se manifestem, doenças concomitantes e tratamentos adjuvantes que possam causar interações medicamentosas. O clínico dispõe em seu armamentário uma variedade de medicamentos em constante expansão, em múltiplas formulações e dosagens, seguras e com bom perfil de tolerabilidade. O uso continuado dos triptanos perimitirá familiaridade com essa classe de medicação e possibilitará ao clínico a prescrição de drogas com características específicas para atender as necessidades clínicas de diferentes pacientes, de modo a otimizar o benefício terapêutico