Biallelic BIRC3 inactivation in chronic lymphocytic leukaemia patients with 11q deletion identifies a subgroup with very aggressive disease.

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Эпидемически и эпизоотически опасные виды рыб в отношении описторхидозов в Новосибирской области

The purpose of the research is identifcation of epidemically and epizootically dangerous fsh species for opisthorchosis in the Novosibirsk Region.Materials and methods. Helminthological studies were carried out from 2002 to 2020. We studied a total of 2994 fsh specimens belonging to 8 species of Cyprinidae, carps and allies, namely, ide, Leuciscus idus (L.); dace, L. leuciscus (L.); bream, Abramis brama (L.); roach, Rutilus rutilus (L.); verkhovka, Leucaspius delineatus (Heckel); crucian carp, Carassius carassius (L.); gudgeon, Gobio gobio (L.); and minnow, Phoxinus phoxinus (L.). The fsh were identifed to species according to the fsh guide. To identify Opisthorchidae metacercariae in fsh muscles, the compressor method generally accepted in helminthology was used. The Opisthorchidae metacercariae were identifed using the freshwater fsh parasite guide.Results and discussion. Of 8 studied fsh species of the family Cyprinidae in the Novosibirsk region, the Opisthorchidae metacercariae infection was noted in 7 species (ide, dace, roach, bream, verkhovka, gudgeon, and crucian carp). The following Opisthorchidae species were recorded in the studied fsh: O. felineus, M. bilis, M. xanthosomus, and Metorchis spp. The O. felineus metacercariae were most often found in the supplementary host, in 12.9 % of cases, and M. bilis, M. xanthosomus and Metorchis spp. larvae were found much less often. In terms of epidemy, the ide and bream having large commercial sizes are the most dangerous: the ide as the most heavily infected species, and the bream as the most often caught and eaten by humans. Small non-commercial fsh (the dace, roach, verkhovka, as well as the small ide and bream) are of great epizootological importance, since they are used for food for domestic and wild animals most often. Infected fsh were only found at unregulated marketplaces; the infection prevalence in the roach was 35.5%, of which 22.6% were affected by O. felineus metacercariae, and 12.9% by M. xanthosomus metacercariae.Цель исследований: выявление эпидемически и эпизоотически опасных видов рыб в отношении описторхидозов в Новосибирской области.Материалы и методы. Гельминтологические исследования проводили в период с 2002 по 2020 гг. Всего исследовано 2994 экз. рыб 8 видов сем. Cyprinidae – карповые: язь – Leuciscus idus (L.), елец – L. leuciscus (L.), лещ – Abramis brama (L.), плотва – Rutilus rutilus (L.), верховка – Leucaspius delineatus (Heckel), карась – Carassius carassius (L.), пескарь – Gobio gobio (L.), гольян – Phoxinus phoxinus (L.). Идентификацию рыб до вида проводили по определителям рыб. Для выявления метацеркарий описторхид в мышцах рыбы использовали общепринятый в гельминтологии компрессорный метод. Идентификацию метацеркарий описторхид проводили по определителю паразитов пресноводных рыб.Результаты и обсуждение. Из 8 исследуемых видов рыб сем. Cyprinidae в Новосибирской области зараженность метацеркариями описторхид отмечена у 7 (язь, елец, плотва, лещ, верховка, пескарь и карась). В исследуемой рыбе зарегистрированы следующие виды описторхид: O. felineus, M. bilis, M. xanthosomus и Metorchis spp. Чаще всего в дополнительном хозяине встречаются метацеркарии O. felineus – 12,9%, намного реже – личинки M. bilis, M. Xanthosomus и Metorchis spp. В эпидемическом отношении наиболее опасными являются язь и лещ крупных промысловых размеров: язь как наиболее сильно инвазированный вид, а лещ – как наиболее часто вылавливаемый и употребляемый в пищу человеком. Мелкая непромысловая рыба (елец, плотва, верховка, а также мелкие язи и лещи) имеет большое эпизоотологическое значение, так как чаще всего служит кормом домашним и диким животным. Зараженная рыба выявлена только на стихийных рынках; экстенсивность инвазии плотвы составила 35,5 %, из них 22,6 % были поражены метацеркариями O. felineus, а 12,9% – M. xanthosomus

Effects of nanosuspension and inclusion complex techniques on the in vitro protease inhibitory activity of naproxen

This study investigated the effects of nanosuspension and inclusion complex techniques on in vitro trypsin inhibitory activity of naproxen—a member of the propionic acid derivatives, which are a group of antipyretic, analgesic, and non-steroidal anti-inflammatory drugs. Nanosuspension and inclusion complex techniques were used to increase the solubility and anti-inflammatory efficacy of naproxen. The evaporative precipitation into aqueous solution (EPAS) technique and the kneading methods were used to prepare the nanosuspension and inclusion complex of naproxen, respectively. We also used an in vitro protease inhibitory assay to investigate the anti-inflammatory effect of modified naproxen formulations. Physiochemical properties of modified naproxen formulations were analyzed using UV, IR spectra, and solubility studies. Beta-cyclodextrin inclusion complex of naproxen was found to have a lower percentage of antitryptic activity than a pure nanosuspension of naproxen did. In conclusion, nanosuspension of naproxen has a greater anti-inflammatory effect than the other two tested formulations. This is because the nanosuspension formulation reduces the particle size of naproxen. Based on these results, the antitryptic activity of naproxen nanosuspension was noteworthy; therefore, this formulation can be used for the management of inflammatory disorders

Novel Sulfated Polysaccharides Disrupt Cathelicidins, Inhibit RAGE and Reduce Cutaneous Inflammation in a Mouse Model of Rosacea

Rosacea is a common disfiguring skin disease of primarily Caucasians characterized by central erythema of the face, with telangiectatic blood vessels, papules and pustules, and can produce skin thickening, especially on the nose of men, creating rhinophyma. Rosacea can also produce dry, itchy eyes with irritation of the lids, keratitis and corneal scarring. The cause of rosacea has been proposed as over-production of the cationic cathelicidin peptide LL-37.We tested a new class of non-anticoagulant sulfated anionic polysaccharides, semi-synthetic glycosaminoglycan ethers (SAGEs) on key elements of the pathogenic pathway leading to rosacea. SAGEs were anti-inflammatory at ng/ml, including inhibition of polymorphonuclear leukocyte (PMN) proteases, P-selectin, and interaction of the receptor for advanced glycation end-products (RAGE) with four representative ligands. SAGEs bound LL-37 and inhibited interleukin-8 production induced by LL-37 in cultured human keratinocytes. When mixed with LL-37 before injection, SAGEs prevented the erythema and PMN infiltration produced by direct intradermal injection of LL-37 into mouse skin. Topical application of a 1% (w/w) SAGE emollient to overlying injected skin also reduced erythema and PMN infiltration from intradermal LL-37.Anionic polysaccharides, exemplified by SAGEs, offer potential as novel mechanism-based therapies for rosacea and by extension other LL-37-mediated and RAGE-ligand driven skin diseases

Influence of Various Polymorphic Variants of Cytochrome P450 Oxidoreductase (POR) on Drug Metabolic Activity of CYP3A4 and CYP2B6

Cytochrome P450 oxidoreductase (POR) is known as the sole electron donor in the metabolism of drugs by cytochrome P450 (CYP) enzymes in human. However, little is known about the effect of polymorphic variants of POR on drug metabolic activities of CYP3A4 and CYP2B6. In order to better understand the mechanism of the activity of CYPs affected by polymorphic variants of POR, six full-length mutants of POR (e.g., Y181D, A287P, K49N, A115V, S244C and G413S) were designed and then co-expressed with CYP3A4 and CYP2B6 in the baculovirus-Sf9 insect cells to determine their kinetic parameters. Surprisingly, both mutants, Y181D and A287P in POR completely inhibited the CYP3A4 activity with testosterone, while the catalytic activity of CYP2B6 with bupropion was reduced to approximately ∼70% of wild-type activity by Y181D and A287P mutations. In addition, the mutant K49N of POR increased the CLint (Vmax/Km) of CYP3A4 up to more than 31% of wild-type, while it reduced the catalytic efficiency of CYP2B6 to 74% of wild-type. Moreover, CLint values of CYP3A4-POR (A115V, G413S) were increased up to 36% and 65% of wild-type respectively. However, there were no appreciable effects observed by the remaining two mutants of POR (i.e., A115V and G413S) on activities of CYP2B6. In conclusion, the extent to which the catalytic activities of CYP were altered did not only depend on the specific POR mutations but also on the isoforms of different CYP redox partners. Thereby, we proposed that the POR-mutant patients should be carefully monitored for the activity of CYP3A4 and CYP2B6 on the prescribed medication

Pediatric Hospitalizations Associated with 2009 Pandemic Influenza A (H1N1) in Argentina

Fil: Libster, Romina. Fundación Infant, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Bugna, Jimena. Fundación Infant, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Coviello, Silvina. Fundación Infant, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Hijano, Diego R. Hospital De Niños Sor María Ludovica, La Plata; Argentina.Fil: Dunaiewsky, Mariana. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Reynoso, Natalia. Hospital Municipal Materno Infantil de San Isidro; Argentina.Fil: Cavalieri, Maria L. Hospital Eva Perón, Benito Juárez, Buenos Aires; ArgentinaFil: Guglielmo, Maria C. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Areso, M. Soledad. Hospital Eva Perón, Benito Juárez, Buenos Aires; ArgentinaFil: Gilligan, Tomas. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Santucho, Fernanda. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Cabral, Graciela. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Gregorio, Gabriela L. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Moreno, Rina. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Lutz, Maria I. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Panigasi, Alicia L. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Saligari, Liliana. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Caballero, Mauricio T. Hospital De Niños Sor María Ludovica, La Plata; Argentina.Fil: Egües Almeida, Rodrigo M. Hospital De Niños Sor María Ludovica, La Plata; Argentina.Fil: Gutierrez Meyer, Maria E. Hospital De Niños Sor María Ludovica, La Plata; Argentina.Fil: Neder, Maria D. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Davenport, Maria C. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Del Valle, Maria P. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Santidrian, Valeria S. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Mosca, Guillermina. Ministerio de Ciencia, Técnica e Innovación. Fundación Infant, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Alvarez, Liliana. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Landa, Patricia. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Pota, Ana. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Boloñati, Norma. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Dalamon, Ricardo. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Sanchez Mercol, Victoria I. Hospital Eva Perón, Benito Juárez, Buenos Aires; Argentina.Fil: Espinoza, Marco. Fundación Infant, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Peuchot, Juan Carlos. Hospital Eva Perón, Benito Juárez, Buenos Aires; Argentina.Fil: Karolinski, Ariel. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Bruno, Miriam. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Borsa, Ana. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Ferrero, Fernando. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Bonina, Angel. Hospital De Niños Sor María Ludovica, La Plata; Argentina.Fil: Ramonet, Margarita. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Albano, Lidia C. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Luedicke, Nora. Ministerio de Ciencia, Técnica e Innovación. Fundación Infant, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Alterman, Elias. Fundación Infant, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Savy, Vilma L. ANLIS Dr.C.G.Malbrán. Instituto de Enfermedades Infecciosas; Argentina.Fil: Baumeister, Elsa. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Virología. Servicio de Virosis Respiratoria; Argentina.Fil: Chappell, James D. Vanderbilt University. Pathology, Nashville, Tennessee; Estados Unidos.Fil: Edwards, Kathryn M. Vanderbilt University. Departments of Pediatrics, Nashville, Tennessee; Estados Unidos.Fil: Melendi, Guillermina A. Vanderbilt University. Departments of Pediatrics, Nashville, Tennessee; Estados Unidos.Fil: Polack, Fernando P. Vanderbilt University. Departments of Pediatrics, Nashville, Tennessee; Estados Unidos.Background: While the Northern Hemisphere experiences the effects of the 2009 pandemic influenza A (H1N1) virus, data from the recent influenza season in the Southern Hemisphere can provide important information on the burden of disease in children. Methods: We conducted a retrospective case series involving children with acute infection of the lower respiratory tract or fever in whom 2009 H1N1 influenza was diagnosed on reverse-transcriptase polymerase-chain-reaction assay and who were admitted to one of six pediatric hospitals serving a catchment area of 1.2 million children. We compared rates of admission and death with those among age-matched children who had been infected with seasonal influenza strains in previous years. Results: Between May and July 2009, a total of 251 children were hospitalized with 2009 H1N1 influenza. Rates of hospitalization were double those for seasonal influenza in 2008. Of the children who were hospitalized, 47 (19%) were admitted to an intensive care unit, 42 (17%) required mechanical ventilation, and 13 (5%) died. The overall rate of death was 1.1 per 100,000 children, as compared with 0.1 per 100,000 children for seasonal influenza in 2007. (No pediatric deaths associated with seasonal influenza were reported in 2008.) Most deaths were caused by refractory hypoxemia in infants under 1 year of age (death rate, 7.6 per 100,000). Conclusions: Pandemic 2009 H1N1 influenza was associated with pediatric death rates that were 10 times the rates for seasonal influenza in previous years

Epidemically and epizootically dangerous fsh species for opisthorchosis in the Novosibirsk Region

The purpose of the research is identifcation of epidemically and epizootically dangerous fsh species for opisthorchosis in the Novosibirsk Region.Materials and methods. Helminthological studies were carried out from 2002 to 2020. We studied a total of 2994 fsh specimens belonging to 8 species of Cyprinidae, carps and allies, namely, ide, Leuciscus idus (L.); dace, L. leuciscus (L.); bream, Abramis brama (L.); roach, Rutilus rutilus (L.); verkhovka, Leucaspius delineatus (Heckel); crucian carp, Carassius carassius (L.); gudgeon, Gobio gobio (L.); and minnow, Phoxinus phoxinus (L.). The fsh were identifed to species according to the fsh guide. To identify Opisthorchidae metacercariae in fsh muscles, the compressor method generally accepted in helminthology was used. The Opisthorchidae metacercariae were identifed using the freshwater fsh parasite guide.Results and discussion. Of 8 studied fsh species of the family Cyprinidae in the Novosibirsk region, the Opisthorchidae metacercariae infection was noted in 7 species (ide, dace, roach, bream, verkhovka, gudgeon, and crucian carp). The following Opisthorchidae species were recorded in the studied fsh: O. felineus, M. bilis, M. xanthosomus, and Metorchis spp. The O. felineus metacercariae were most often found in the supplementary host, in 12.9 % of cases, and M. bilis, M. xanthosomus and Metorchis spp. larvae were found much less often. In terms of epidemy, the ide and bream having large commercial sizes are the most dangerous: the ide as the most heavily infected species, and the bream as the most often caught and eaten by humans. Small non-commercial fsh (the dace, roach, verkhovka, as well as the small ide and bream) are of great epizootological importance, since they are used for food for domestic and wild animals most often. Infected fsh were only found at unregulated marketplaces; the infection prevalence in the roach was 35.5%, of which 22.6% were affected by O. felineus metacercariae, and 12.9% by M. xanthosomus metacercariae