Planejamento e desenvolvimento de novos compostos com atividade frente a Leishmania spp: Síntese, avaliação da atividade e toxicidade de derivados 5-nitro-2-furfurilidênicos e estudos de relações estrutura-atividade / Design of new compounds against Leishmania spp: synthesis, biological evaluation and toxicity of 5-nitro-2-furfurylidene derivates and structure-activity relationship studies

A leishmaniose é uma zoonose de ampla distribuição mundial, causada pelos parasitas tripanossomatídeos do gênero Leishmania. Infelizmente, o arsenal terapêutico disponível é precário, mas vê-se crescente o interesse científico pela busca do potencial de derivados nitroheterocíclicos como alternativas terapêuticas. Nesse contexto, este trabalho analisou o potencial de derivados 5-nitro-2-furfurilidênicos contra diferentes cepas de Leishmania, assim como investigou um possível modo de ação para esta classe de nitrocompostos. Para tal, a quimioteca foi sintetizada de acordo com publicações prévias do grupo. O potencial de inibição de crescimento das culturas de promastigotas de L. (L.) infantum (Linf) e L. (L.) major (Lmaj) foi determinado, utilizando miltefosina (MILT) (Linf - IC50: 8,28±0,33 µM), anfotericina B (AMB) (Linf - IC50: 0,02±0,002 µM) e nifurtimox (NFX) (Lmaj - IC50: 3,5±0,09 µM) como referência. A maioria dos compostos apresentaram maior potencial que as referênias, destacando o composto 40 (Linf - IC50: 0,2±0,019 µM/ Lmaj - IC50: 0,087 ± 0,001 µM) como mais eficaz. Contra as formas amastigotas intracelulares, para Linf os compostos 40, 13 e 15 foram mais eficazes em reduzir a carga parasitária dos macrófagos infectados que fármacos de referência. Para Lmajor, o composto 40 (IC50: 0,006 ± 0,0003 µM) foi mais ativo que o NFX (IC50: 2,15 ± 0,01 µM). Também foi determinada a atividade da quimioteca frente a enzima nitrorredutase (NTR1), utilizando cepas de T. brucei superexpressantes de NTR1, e os compostos analisados foram até 18 vezes mais eficazes que à cepa wild-type. Ademais, a partir da análise exploratória de dados por análise de componentes principais (PCA) e de grupamentos hierárquicos (HCA), foi reconhecida a influência das propriedades relacionadas com o equilíbrio hidrófilo-lipófilo e da natureza estérica/geométrica das moléculas para atividade anti-Leishmania

Leishmaniasis is a worldwide zoonosis caused by trypanosomatid parasites of the genus Leishmania. Unfortunately, the available therapeutic arsenal is precarious, but there is growing scientific interest in searching the potential of nitroheterocyclic derivatives as therapeutic alternatives. In this context, this work analyzed the potential of 5-nitro-2-furfurylidene derivatives against different Leishmania strains, as well as investigated the potential mode of action for this nitro compounds class. To this end, the chemolibrary was synthesized according to our group's previous publications. The growth inhibitory potential potential for promastigote cultures of L. (L.) infantum (Linf) and L. (L.) major (Lmaj) was determined using miltefosine (MILT) (Linf - IC50: 8.28±0.33 µM), amphotericin B (AMB) (Linf - IC50: 0.02±0.002 µM) and nifurtimox (NFX) (Lmaj - IC50: 3.5±0.09 µM) as reference. Most of the compounds were more potent than the references, highlighting compound 40 (Linf - IC50: 0.2±0.019 µM/ Lmaj - IC50: 0.087 ± 0.001 µM) as the most effective. Against intracellular amastigote, for Linf, compounds 40, 13 and 15 were more effective in reducing the parasite load of infected macrophages than reference drugs. For Lmajor, compound 40 (IC50: 0.006 ± 0.0003 µM) was more active than NFX (IC50: 2.15 ± 0.01 µM). The activity against nitroreductase (NTR1) enzyme was determined using overexpressing NTR1 mutant T. brucei strains, and the analyzed compounds were up to 18 times more effective than wild-type. Furthermore, exploratory data analysis using principal component analysis (PCA) and hierarchical clustering (HCA) methods were used. The influence of properties related to the hydrophiliclipophilic balance and the steric/geometric nature of the molecules was associated with the anti-Leishmanial activity

Antiparasitic and immunomodulating effects of nitazoxanide, ivermectin and selenium on Cryptosporidium infection in diabetic mice / Efeitos antiparasitários e imunomodulantes da nitazoxanida, ivermectina e selênio sobre a infecção por Cryptosporidium em camundongos diabéticos

Abstract The present work aims to investigate the antiparasitic and the immunomodulating effects of nitazoxanide (NTZ) and ivermectin (IVC) alone or combined together or combined with selenium (Se), on Cryptosporidium infection in diabetic mice. The results revealed that the combined NTZ and IVC therapy achieved the highest reduction of fecal oocysts (92%), whereas single NTZ showed the lowest reduction (63%). Also, adding Se to either NTZ or IVC resulted in elevation of oocyst reduction from 63% to 71% and from 82% to 84% respectively. All treatment regimens, with the exception of NTZ monotherapy, showed a significant improvement in the intestinal histopathology, the highest score was in combined NTZ and IVC therapy. The unique results of immunohistochemistry in this study showed reversal of the normal CD4/CD8 T cell ratio in the infected untreated mice, however, following therapy it reverts back to a normal balanced ratio. The combined (NTZ+ IVC) treatment demonstrated the highest level of CD4 T cell expression. Taken together, NTZ and IVC combined therapy showed remarkable anti-parasitic and immunostimulatory effects, specifically towards the CD4 population that seem to be promising in controlling cryptosporidiosis in diabetic individuals. Further research is required to explore other effective treatment strategies for those comorbid patients.

Resumo O presente trabalho tem como objetivo investigar os efeitos anti-parasitários e imunomodulantes da nitazoxanida (NTZ) e ivermectina (IVC), isoladas ou em associação, e do selênio (SE), associado à NTZ ou à IVC, sobre a infecção por Cryptosporidium em camundongos diabéticos. Os resultados revelaram que a terapia combinada com NTZ e IVC resultou em maior redução de oocistos fecais, enquanto a NTZ isolada mostrou a menor redução de oocistos fecais (63%). Além disso, a associação do SE com a NTZ ou IVC resultou em redução do número de oocistos fecais de 63% para 71% e de 82% para 84%, respectivamente. Todos os tratamentos, com exceção da monoterapia com NTZ, mostraram uma melhora significativa nos índices relacionados à histopatologia intestinal. Os resultados da imuno-histoquímica mostraram reversão da razão celular CD4/CD8 T normal nos camundongos infectados não tratados, no entanto, após a terapia, houve retorno à razão celular CD4/CD8 T normal. O tratamento combinado (NTZ+ IVC) demonstrou o mais alto nível de expressão celular CD4 T. Em conclusão, a terapia combinada com NTZ e IVC mostrou efeitos anti-parasitários e imunoestimuladores notáveis, especificamente para a população CD4, que parecem ser promissores para o controle da criptosporidiose em indivíduos diabéticos.

Inhibition of Brazilian ZIKV strain replication in primary human placental chorionic cells and cervical cells treated with nitazoxanide

ABSTRACT Zika virus (ZIKV) infection during pregnancy is associated with a congenital syndrome. Although the virus can be detected in human placental tissue and sexual transmission has been verified, it is not clear how the virus reaches the fetus. Despite the emerging severity caused by ZIKV infection, no specific prophylactic and/or therapeutic treatment is available. The aim of the present study was to evaluate the effectiveness antiviral of nitazoxanide (NTZ) in two important congenital transmission targets: (i) a primary culture of human placental chorionic cells, and (ii) human cervical epithelial cells (C33-A) infected with Brazilian ZIKV strain. Initially, NTZ activity was screened in ZIKV infected Vero cells under different treatment regimens with non-toxic drug concentrations for 48 h. Antiviral effect was found only when the treatment was carried out after the viral inoculum. A strong effect against the dengue virus serotype 2 (DENV-2) was also observed suggesting the possibility of treating other Flaviviruses. Additionally, it was shown that the treatment did not reduce the production of infectious viruses in insect cells (C6/36) infected with ZIKV, indicating that the activity of this drug is also related to host factors. Importantly, we demonstrated that NTZ treatment in chorionic and cervical cells caused a reduction of infected cells in a dose-dependent manner and decreased viral loads in up to 2 logs. Pre-clinical in vitro testing evidenced excellent therapeutic response of infected chorionic and cervical cells and point to future NTZ activity investigation in ZIKV congenital transmission models with the perspective of possible repurposing of NTZ to treat Zika fever, especially in pregnant women.

Toxicity and motor changes in Africanized honey bees (Apis mellifera L) exposed to fipronil and imidacloprid

ABSTRACT This study evaluated the in vitro toxicity and motor activity changes in African-derived adult honey bees (Apis mellifera L.) exposed to lethal or sublethal doses of the insecticides fipronil and imidacloprid. Mortality of bees was assessed to determine the ingestion and contact lethal dose for 24 h using probit analysis. Motor activities in bees exposed to lethal (LD50) and sublethal doses (1/500th of the lethal dose) of both insecticides were evaluated in a behavioral observation box at 1 and 4 h. Ingestion and contact lethal doses of fipronil were 0.2316 ? 0.0626 and 0.0080 ? 0.0021 μg/bee, respectively. Ingestion and contact lethal doses of imidacloprid were 0.1079 ? 0.0375 and 0.0308 ? 0.0218 μg/bee, respectively. Motor function of bees exposed to lethal doses of fipronil and imidacloprid was impaired; exposure to sublethal doses of fipronil but not imidacloprid impaired motor function. The insecticides evaluated in this study were highly toxic to African-derived A. mellifera and caused impaired motor function in these pollinators.

Efecto letal agudo de los insecticidas en formulación comercial Imidacloprid, Spinosad y Thiocyclam hidrogenoxalato en obreras de Bombus atratus (Hymenoptera: Apidae) / Acute lethal effect of the commercial formulation of the insecticides Imidacloprid, Spinosad y Thiocyclam hidrogenoxalate in Bombus atratus (Hymenoptera: Apidae) workers

Resumen:Los efectos de los insecticidas sobre las abejas han cobrado gran atención a nivel mundial, sin embargo, son pocos los estudios sobre el efecto de estos agroquímicos en abejas Neotropicales. Bombus atratus es una especie neotropical, distribuida ampliamente en los Andes y es considerado un polinizador importante de ecosistemas y agroecosistemas altoandinos. Sin embargo, al igual que muchas especies silvestres, se desconoce el efecto de los insecticidas en B. atratus. Teniendo en cuenta lo anterior, el presente trabajo determinó la dosis letal media aguda (DL50) por exposición tópica y oral de las formulaciones comerciales de los insecticidas con los ingredientes activos Imidacloprid, Spinosad y Thiocyclam hidrogenoxalato, ampliamente utilizados para el control de plagas de cultivos importantes en Colombia. Las pruebas DL50 se realizaron a partir de modificaciones de los lineamientos establecidos por la EPPO y OEDE para estas pruebas en Apis mellifera. Se evaluaron 5 dosis para cada insecticida y exposición. Se evaluaron 25 obreras de tamaño medio en cada dosis por duplicado. La mortalidad se registró a las 24, 48 y 72 horas después del experimento. Los datos fueron analizados con el modelo de regresión Probit. Para el Imidacloprid la DL50 tópica y oral fue de 0.048 µg/abeja y 0.010 µg/abeja respectivamente. Para el Thiocyclam hidrogenoxalato la DL50 tópica y oral fue de 0.244 µg/abeja y de 0.056 µg/abeja respectivamente. Para el Spinosad, la DL50 por exposición oral correspondió a 0.28 µg/abeja. No fue posible establecer la DL50 por exposición tópica. A partir del cálculo del Cociente de Riesgo (HQ) e Índice de Toxicidad Relativa, los tres ingredientes activos son altamente tóxicos. Se analiza y discute el riesgo debido al uso de los productos evaluados a partir de la naturaleza química de los insecticidas.

Abstract:The effect of insecticides on bees has gained great attention, however, there are few studies that explore this issue on Neotropical bees. Bombus atratus is a neotropical species broadly distributed in Colombia and is considered an important pollinator of both Andean ecosystems and agroecosystems. However, as for many wild bees species, the effect of insecticides on B. atratus is unknow. In this study we determined the acute median lethal dose (LD50) of commercial formulations of insecticides Imidacloprid, Spinosad and Thiocyclam hydrogen oxalate, widely used in Colombia to control several pests of important crops. The LD50 was carried out by oral and contact routes, following and modifying the EPPO and OECD guidelines to perform LD50 on A. mellifera. We evaluated five doses for each route and insecticide, in a total of 25 medium-size workers for each dose by duplicate. Mortality was registered at 24, 48 and 72 hours after the experiment; and data were analyzed with the Probit regression model. For Imidacloprid, contacts and oral LD50 were 0.048 µg/bee and 0.010 µg/bee, respectively. For Thiocyclam hydrogen oxalate, topical and oral LD50 were 0.244 µg/bee and 0.056 µg/bee, respectively. For Spinosad, the oral LD50 corresponded to 0.28 µg/bee; it was not possible to establish the LD50 for the contact route. The Hazard Quotient (HQ) and Index of Relative Toxicity indicated that all three active ingredients are highly toxic. We discussed the risk of the insecticides use on B. atratus, considering their chemical nature. Rev. Biol. Trop. 64 (4): 1737-1745. Epub 2016 December 01.

Study of teratogenicity of 2, 2-dinitroethene-1, 1-diamine in sprague dawley rats / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To detect the toxicity and teratogenicity of 2, 2-dinitroethene-1, 1-diamine (FOX-7) in rats.</p><p><b>METHODS</b>125 adult SD rats were randomly divided into five groups, which are negative control (0 mg/kg) , positive control (280 mg/kg aspirin) , and three dose groups (5, 15, and 45 mg/kg) . They were administrated by gavage once a day from the 5th days to 19th days after pregnancy. The weight changes and toxicity of pregnant rats are recorded within the study, and the skeleton and internal organs malformations are detected by the recommended methods.</p><p><b>RESULTS</b>After 5 or 6 days being poisoned, the pregnant rats appear significantly toxicity symptoms, such as exciting, irritability, and so on. The net weight raise in high dose group is less than the negative group, while the numbers of dead foetus in median and high dose groups are both more than that of negative group. Comparing with the negative group, the body weight and body lenghth of foetus rats in median and high dose groups, and the tail lenghth in high dose group are lower significantly. There are no external malformations in negative group and three dose groups. However, the foetus of high dose group appear significant skeleton and internal organs malformation prevalences that are significant more than negative group, including lateral cerebral ventricles enlarged, which accounts for 9.17%, occipital bone lost, which accounts for 2.59%.</p><p><b>CONCLUSION</b>FOX-7 can induced maternal reproductive toxicity, foetus toxicity and teratogenicity hazards to rats.</p>

Protective effect of broccoli and ferulic acid on imidacloprid-induced hepatotoxicity in rat

Imidacloprid may induce oxidative stress leading to generate free radicals and alternate oxygen free radical scavenging enzyme system. This study aims to investigate the hepatoprotective effect of broccoli water extract and ferulic acid on imidacloprid induced oxidative stress and DNA damage in male albino rats. Rats were co-treated with broccoli water extract [200 mg/kg] or ferulic acid [20 mg/kg] with imidacloprid [80 mg/kg] orally for 28 days. The results revealed that imidacloprid induced high serum levels of aspartate aminotransferase [AST], alanine aminotransferase [ALT] and alkaline phosphatase [ALP]. However, administration of broccoli and ferulic acid reduced these parameters. Broccoli and ferulic acid significantly [Pbroccoli and ferulic acid treated groups. The possible mechanism of broccoli and ferulic acid extract on imidacloprid might be due to decreasing oxidative stress [LPO, NO and DNA damage] and increasing GSH content. Thus, broccoli and ferulic acid was suggested to protected rat's liver against imidacloprid-induced oxidative stress and DNA damage in liver

Study on standard of safe application of thiamethoxam on GAP of Lonicera japonica / 中国中药杂志

The paper is aimed to establish a method of residue analysis for thiamethoxam and to study its degradation dynamic and final residue and its standard of safe application of thiamethoxam on Lonicera japonica. Samples extracted with methanol by ultrasonication were purified with dichloromethane by liquid-liquid extraction and SPE column and analysed by HPLC-UV. The results showed that average rate was 84.91%-94.44% and RSD 1.74%-4.96% with addition of thiamethoxam in respectively diverse concentration, which meets inspection requirement of pesticide residue. Two kinds of dosages of thiamethoxam were treated- varying from recommended dosage (90 g x hm(-2)) to high dosage (135 g x hm(-2)), Results of two years test showed that thiamethoxam was degraded more than 90% seven days after application and the half - life period of thiamethoxam was 1.54-1.66 d. The digestion rate of thiamethoxam was fast in the L. japonica. The recommended MRL of thiamethoxam in the L. japonica is 0.1 mg x kg(-1), the dosage of 25% thiamethoxam WDG from 90-135 g x hm(-2) is sprayed less than three times a year on L. japonica and 14 days is proposed for the safety interval of the last pesticide application's and harvest's date.

Is imidacloprid an effective alternative for controlling pyrethroid-resistant populations of Triatoma infestans (Hemiptera: Reduviidae) in the Gran Chaco ecoregion?

The prevention of Chagas disease is based primarily on the chemical control of Triatoma infestans (Klug) using pyrethroid insecticides. However, high resistance levels, correlated with control failures, have been detected in Argentina and Bolivia. A previous study at our laboratory found that imidacloprid could serve as an alternative to pyrethroid insecticides. We studied the delayed toxicity of imidacloprid and the influence of the blood feeding condition of the insect on the toxicity of this insecticide; we also studied the effectiveness of various commercial imidacloprid formulations against a pyrethroid-resistant T. infestans population from the Gran Chaco ecoregion. Variations in the toxic effects of imidacloprid were not observed up to 72 h after exposure and were not found to depend on the blood feeding condition of susceptible and resistant individuals. Of the three different studied formulations of imidacloprid on glass and filter paper, only the spot-on formulation was effective. This formulation was applied to pigeons at doses of 1, 5, 20 and 40 mg/bird. The nymphs that fed on pigeons treated with 20 mg or 40 mg of the formulation showed a higher mortality rate than the control group one day and seven days post-treatment (p < 0.01). A spot-on formulation of imidacloprid was effective against pyrethroid-resistant T. infestans populations at the laboratory level.

Analysis of the literature on acute aromatic amino or nitro-compounds poisoning / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To review the clinical features of acute toxicity of aromatic amino and nitro compounds.</p><p><b>METHODS</b>A total of 110 papers reporting 1240 cases of acute toxicity induced by aromatic amino and nitro compounds from 1979 to 2013 were collected from CNKI, VIP, and Wanfang database, and were analyzed in this study.</p><p><b>RESULTS</b>Of all included cases, 939 were caused by occupational exposure, and 301 were caused by exposure in daily life. A total of 1044 cases were male, and 196 were female. Age ranged from 9 days to 75 years. There were 13 cases of contact reaction. The numbers of mild, moderate, and severe toxicities were 358, 348, and 139, respectively, and the other 382 cases were not graded for severity. The average incubation period was 4.50±5.71 h (M = 3 h). The average incubation period of aniline toxicity was significantly shorter than that of nitrobenzene toxicity. Methemoglobinemia was found in 1146 cases, while cases of poisonings with 5-nitro-o-toluidine, 2-methyl-4-nitroaniline, and 3-chloro-2-methyl aniline were not found to have methemoglobinemia. The detection rates of MHb and HzB were 83.73% (674/805) and 40.19% (129/321), respectively. Sixty-two (19.31%) out of 321 cases were complicated by intravascular hemolysis, 270 (30.93%) out of 873 cases suffered hepatic impairment, 50 (12.25%) out of 408 cases were accompanied by renal damage. Consciousness disorders were found in 66 cases, and chemical cystitis was found in 36 cases. Oral poisoning could immediately induce severe symptoms including cyanosis, unconsciousness, and hemolysis. In prognosis analysis, it was found that the cure rate was 98.71% (1224/1240), and 14 cases of death were caused by multiple organ dysfunction syndrome, renal failure, uncontrolled hemorrhagic shock, myocardial infarction, and sudden death. Two cases were left with neurological sequelae.</p><p><b>CONCLUSION</b>The clinical manifestations of poisoning with aromatic amino and nitro compounds are methemoglobinemia, intravascular hemolysis, liver damage, and renal damage. Treatment with specific medicine methylene blue can produce ideal clinical prognosis, but severe poisoning may cause death from multiple organ failure.</p>

Nitro-fatty acids: novel anti-inflammatory lipid mediators

Nitro-fatty acids are formed and detected in human plasma, cell membranes, and tissue, modulating metabolic as well as inflammatory signaling pathways. Here we discuss the mechanisms of nitro-fatty acid formation as well as their key chemical and biochemical properties. The electrophilic properties of nitro-fatty acids to activate anti-inflammatory signaling pathways are discussed in detail. A critical issue is the influence of nitroarachidonic acid on prostaglandin endoperoxide H synthases, redirecting arachidonic acid metabolism and signaling. We also analyze in vivo data supporting nitro-fatty acids as promising pharmacological tools to prevent inflammatory diseases.

US Findings of Extensor Hood Injury in Metacarpophalangeal Joint after Acute Trauma and Corresponding MRI Findings

Extensor hood is a structure that stabilizes the extensor tendon at the dorsal side of the metacarpophalangeal joints and keeps the tendon in place during extension and flexion of the joint. Diagnosis of Extensor hood injury of a metacarpophalangeal joint is difficult to diagnose because its clinical symptoms are nonspecific such as pain and swelling. And swelling can interfere with the accurate physical examination. So the imaging findings are important for diagnosis of extensor hood injury. Magnetic resonance image (MRI) and ultrasonography (US) are both good imaging tools. An advantage of ultrasonography is dynamic assessment of extensor tendon and extensor hood. Here, we describe a case of US findings of extensor hood injury with dynamic approach and corresponding MRI findings.

The Usefulness of Ultrasonography in Painful Hip

The causes of hip pain are variable, and, due to its size and deep position, complete physical examination is often difficult. In the past, ultrasonography (US) for the hip was mainly performed in order to rule out developmental hip dysplasia in infants or for evaluation of joint effusion. Now, however, US of the hip has been widely accepted as a useful modality in patients with hip pain and is commonly used in both adults and children. Joint effusion, bursitis, tendinosis or tendon tear, and acetabular labral tear can be main targets. Dynamic study for snapping hip is another unique advantage of US. In addition, US is very useful for guided procedures - aspiration, biopsy, or injection. In this review, the authors will discuss US findings of these common lesions with a brief review of anatomy.

Hybrid Operation (Balloon, Stent Covered Stent and/with Bypass, Excise It!): When and How? / 대한혈관외과학회지

The final goal of vascular surgery is to prevent amputation and maintain walking ability. Many surgical techniques for peripheral arterial disease (PAD) have been reported. The combined use of endovascular and open techniques (hybrid) in the same surgical setting has been reported since the mid-1990s, and has gained popularity over time as vascular surgeons have acquired increasing experience with endovascular interventions. The hybrid operation offers adequate access for the treatment of both inflow and outflow lesions, while dealing with the common femoral artery lesion in the most appropriate way. The main advantage of hybrid procedures is the ability to treat more complex anatomy by less invasive procedures in patients who are considered as high medical risk. Extensive revascularizations can be accomplished without significant hemodynamic changes, minimal blood loss, and limited risk of preoperative complications. Therefore, the hybrid procedure was thought to be an acceptable strategy in PAD patients with severe lower extremity arterial disease and may provide less invasive therapeutic options tailored to the needs of high risk patients with multiple lesions.

Total Laparoscopic Abdominal Aortic Aneurysm Repair: A Case Report / 대한혈관외과학회지

Open surgical repair has long been considered a mainstream treatment for abdominal aortic aneurysm (AAA). Although endovascular aneurysm repair is minimally invasive and yields satisfying short-term results, there has been concerns about it's the long-term durability. Recent studies showed that laparoscopic AAA repair is a feasible technique and that the benefits of laparoscopy can be consistent with open repair. In particular, total laparoscopic AAA repair has the advantage of reducing postoperative problems in abdominal wall and intestine, and increasing the patient's respiratory recovery and general comfort. In this paper, we report a successful case of total laparoscopic AAA repair. To our knowledge, this is the first report of total laparoscopic AAA repair in Korea.

Indirect Radionuclide Coronary Angiography to Evaluate Gradients of Myocardial Blood Flow and Flow Reserve Through Coronary Stenosis Using N-13 Ammonia PET/CT / 전남의대학술지

Although quantitative evaluation of myocardial blood flow (MBF) and myocardial flow reserve (MFR) has been perceived as an attractive advantage of positron emission tomography (PET) over other cardiac imaging technologies, application of the information to specific coronary lesions is a difficult task for nuclear cardiologists. We hypothesized that changes in MBF and MFR over a coronary lesion could be identified by use of a hybrid technology of CT coronary angiography (CTCA) and N-13 ammonia PET. To evaluate this hypothesis, we measured the gradient of MBF and MFR through coronary stenosis in seven patients (M:F=3:4, median age 56 years) with coronary artery disease who underwent N-13 ammonia PET, CTCA, and interventional coronary angiography. Two patients had proximal left anterior descending (LAD) coronary artery disease and five patients had mid to distal LAD disease. Mean global stress and rest MBF were 2.62+/-0.58 and 1.03+/-0.19 ml/min/g, respectively. Mean global MFR was 2.6+/-0.73. Regional stress and rest MBF in the LAD territory were 2.36+/-0.75 and 0.96+/-0.21 ml/min/g, respectively. Regional MFR in the LAD territory was 2.55+/-0.83 ml/min/g. Stress MBF changed dramatically according to the location of coronary stenosis. It dropped acutely in proximal lesions, whereas it diminished gradually in mid to distal lesions. In conclusion, by use of a hybrid technology of CTCA and PET, it was feasible to make a direct correlation of coronary lesions with the gradient of MFR and CFR through coronary stenosis, which indicated the severity of the coronary lesion. We named this technique indirect radionuclide coronary angiography.

Respiratory Syncytial Virus (RSV) Modulation at the Virus-Host Interface Affects Immune Outcome and Disease Pathogenesis

The dynamics of the virus-host interface in the response to respiratory virus infection is not well-understood; however, it is at this juncture that host immunity to infection evolves. Respiratory viruses have been shown to modulate the host response to gain a replication advantage through a variety of mechanisms. Viruses are parasites and must co-opt host genes for replication, and must interface with host cellular machinery to achieve an optimal balance between viral and cellular gene expression. Host cells have numerous strategies to resist infection, replication and virus spread, and only recently are we beginning to understand the network and pathways affected. The following is a short review article covering some of the studies associated with the Tripp laboratory that have addressed how respiratory syncytial virus (RSV) operates at the virus-host interface to affects immune outcome and disease pathogenesis.

Current Status and Future Perspectives on Minimally Invasive Esophagectomy

Esophageal cancer has one of the highest malignant potentials of any type of tumor. The 3-field lymph node dissection is the standard procedure in Japan for surgically curable esophageal cancer in the middle or upper thoracic esophagus. Minimally invasive esophagectomy is being increasingly performed in many countries, and several studies report its feasibility and curability; further, the magnifying effect of the thoracoscope is another distinct advantage. However, few studies have reported that minimally invasive esophagectomy is more beneficial than open esophagectomy. A recent meta-analysis revealed that minimally invasive esophagectomy reduces blood loss, respiratory complications, the total morbidity rate, and hospitalization duration. A randomized study reported that the pulmonary infection rate, pain score, intraoperative blood loss, hospitalization duration, and postoperative 6-week quality of life were significantly better with the minimally invasive procedure than with other procedures. In the future, sentinel lymph node mapping might play a significant role by obtaining individualized information to customize the surgical procedure for individual patients' specific needs.

First Feline Case of Otodectosis in the Republic of Korea and Successful Treatment with Imidacloprid/Moxidectin Topical Solution

In April 2010, pruritic symptoms were recognized in 3 privately-owned Siamese cats raised in Gwangju, Korea. Examination of ear canals revealed dark brown, ceruminous otic exudates that contain numerous live mites at various developmental stages. Based on morphological characteristics of adult mites in which caruncles were present on legs 1 and 2 in adult females and on legs 1, 2, 3, and 4 in adult males while the tarsus of leg 3 in both sexes was equipped with 2 long setae, the mite was identified as Otodectes cynotis. Ten ear mite-free domestic shorthaired cats were experimentally infected with O. cynotis to evaluate the efficacy of 10% imidacloprid/1% moxidectin spot-on. Live mites were recovered from 1 of 10 treated cats on day 9 post-treatment (PT) while no live mites were observed from the ear canals of treated cats on days 16 and 30 PT. The efficacy of 10% imidacloprid/1% moxidectin spot-on on O. cynotis in cats was, therefore, 90% on day 9 and 100% on days 16 and 30 PT. This is the first report of otodectosis in 3 cats naturally infested with O. cynotis in Gwang-ju, Korea. Both natural and experimental infestations were successfully treated with 10% imidacloprid/1% moxidectin spot-on.

Surgical Management of Bisphosphonate Related Osteonecrosis of the Jaw Using Pedicled Buccal Fat Pad Flap