TNF-α mediated upregulation of Na1.7 currents in rat dorsal root ganglion neurons is independent of CRMP2 SUMOylation

Clinical and preclinical studies have shown that patients with Diabetic Neuropathy Pain (DNP) present with increased tumor necrosis factor alpha (TNF-α) serum concentration, whereas studies with diabetic animals have shown that TNF-α induces an increase in NaV1.7 sodium channel expression. This is expected to result in sensitization of nociceptor neuron terminals, and therefore the development of DNP. For further study of this mechanism, dissociated dorsal root ganglion (DRG) neurons were exposed to TNF-α for 6 h, at a concentration equivalent to that measured in STZ-induced diabetic rats that developed hyperalgesia. Tetrodotoxin sensitive (TTXs), resistant (TTXr) and total sodium current was studied in these DRG neurons. Total sodium current was also studied in DRG neurons expressing the collapsin response mediator protein 2 (CRMP2) SUMO-incompetent mutant protein (CRMP2-K374A), which causes a significant reduction in NaV1.7 membrane cell expression levels. Our results show that TNF-α exposure increased the density of the total, TTXs and TTXr sodium current in DRG neurons. Furthermore, TNF-α shifted the steady state activation and inactivation curves of the total and TTXs sodium current. DRG neurons expressing the CRMP2-K374A mutant also exhibited total sodium current increases after exposure to TNF-α, indicating that these effects were independent of SUMOylation of CRMP2. In conclusion, TNF-α sensitizes DRG neurons via augmentation of whole cell sodium current. This may underlie the pronociceptive effects of TNF-α and suggests a molecular mechanism responsible for pain hypersensitivity in diabetic neuropathy patients.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Síndrome de Chiari e Hidrossiringomielia com comprometimento neurológico: um relato de caso

A Malformação de Chiari (MC) pertence a um amplo grupo de raras deformidades estruturais da junção craniocerebelomedular. O tipo I da doença caracteriza-se pela herniação tonsilar ou amigdaliana cerebelar devido à anomalia da base do crânio e da parte superior da coluna cervical, além de a porção medial do lobo inferior do cerebelo pelo canal cervical também se protuberar através do forame magno, impedindo que o líquor flua normalmente através do canal. A real prevalência da doença é desconhecida, pois muitos pacientes com herniação cerebelar são assintomáticos e o problema agrava-se na fase adulta, com queixas de cefaleia intensa e, por vezes, parestesia. O objetivo deste estudo é relatar um caso de síndrome de Chiari (SC) em uma paciente de 53 anos, ao abordar sua apresentação clínica, diagnóstico e tratamento. Paciente do sexo feminino, 53 anos, foi admitida em um hospital da rede pública de referência se queixando de cefaleia occipital intensa e cervicalgia com irradiação da dor para os membros superiores, acompanhada de parestesia nos quatro segmentos. Relatou já sentir dor há 2 anos, mas apresentou piora do quadro clínico há 8 meses. Foi, também, observada incontinência urinária devido à dissinergia detrusora-esfincteriana por provável bexiga neurogênica. Foi, então, realizado exame de imagem de ressonância magnética (RNM) do crânio e da coluna cervical, com obtenção de sequências ponderadas em T1, T2 e STIR, nos planos sagital e transverso com contraste, o qual evidenciou leve alargamento medular, além de sinais de hidrossiringomielia difusa, com hipossinal na sequência T2 intramedular na altura de D1-D2 (coluna dorsal). Foi notada discreta herniação das tonsilas cerebelares junta ao forame magno, típica da SC, sendo, por fim, confirmado o diagnóstico. A paciente, no entanto, não apresentava hidrocefalia, mesmo com a interrupção do fluxo do líquido cefalorraquidiano (LCR) para o canal vertebral. Ela encaixou- se nos parâmetros de indicação cirúrgica, sendo realizada craniotomia occipital, com acesso ao plexo coroide do quarto ventrículo do tronco encefálico com o intuito de elevar as tonsilas cerebelares baixas, herniadas no canal espinhal cervical e bloqueando o fluxo do LCR. Após a descompressão craniocervical, o curso do líquor foi restaurado e a paciente foi, por fim, encaminhada à sala de recuperação pós-operatória. A SC é uma rara doença que apresenta quadro clínico e alterações radiológicas complexas e extensas e, por vezes, o diagnóstico é retardado devido à inespecificidade dos sintomas confundidos com cervicalgias e cefaleias comuns. A hipótese diagnóstica deve ser embasada nas queixas do paciente, na anamnese minuciosa, exame clínico e nos exames de imagens, sendo a prevalência desta patologia de difícil definição e com faixas etárias distintas

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Propriedades mecânicas de meniscos frescos de coelhos e preservados em glicerina 98%

O presente estudo avaliou a resistência à compressão de meniscos mediais de coelhos da raça Nova Zelândia, por meio de teste mecânico de compressão. Trinta meniscos foram distribuídos em três grupos: grupo MF, composto por dez meniscos frescos; grupo MG, dez meniscos preservados em glicerina 98%, por 30 dias, e grupo MR, dez meniscos preservados em glicerina 98%, por 30 dias e reidratados em NaCl 0,9%, por 12 horas. Os meniscos de cada grupo foram submetidos ao teste de compressão no sentido perpendicular ao seu plano anatômico regular e foram avaliados o limite de elasticidade, a deformação elástica, a tensão ao ponto de ruptura e ao limite de elasticidade e ainda, o índice de rigidez. Os meniscos dos grupos preservados, MG e MR, tiveram o limite elástico semelhante ao grupo de meniscos frescos (MF). O grupo de meniscos em glicerina (MG) apresentou menor capacidade de deformação elástica (P<0,05) que os grupos MF e MR, e maior capacidade de sofrer tensão ao limite elástico. Os meniscos do grupo (MG) apresentaram maior rigidez (P<0,05) que os meniscos dos grupos MF e MR. Conclui-se que o grupo de meniscos preservados em glicerina 98%, seguido de reidratação em NaCl 0,9% (MR), não apresentou alterações significativas na capacidade de resistência ao limite elástico dos meniscos.The present study evaluated the compressive strength of medial menisci of New Zealand rabbits, through mechanical compression test. Thirty menisci were distributed in three groups: group MF, composed by ten fresh menisci; MG group, composed by ten menisci preserved in 98% glycerin for 30 days; and, group MR, ten menisci preserved in 98% glycerin for 30 days and rehydrated in NaCl 0.9% for 12 hours. The menisci in each group were submitted to compression test in the perpendicular direction to the anatomical plane and had the elasticity limit, the elastic deformity, the rupture stress point and the stiffness index evaluated. The menisci from the preserved groups MG and MR had the elastic limit similar to the fresh menisci group (MF). The group of menisci preserved in glycerin (MG) presented lower elastic deformity capacity (P<0.05) if compared to the other groups, MF and MR, and a higher tension capacity at elastic limit. The menisci from group (MG) presented higher stiffness (P<0.05) than the ones in the MF and MR groups. It can be concluded that the group menisci preserved in glycerin 98% followed by rehydration in Nacl 0,9% (MR), did not showed any significant alterations in the capacity of the menisci elastic limit

A new surgical technique to treat corneal perforations using amniotic membrane and surgical adhesive

The objectives of this study were to compare surgical techniques and the effects of using n-butyl 2-cyanoacrylate and bovine amniotic membrane to repair perforated lesions in corneas. Penetrating keratoplasty was performed in sixty New Zealand White rabbits under general anesthesia. Group 1 (G1) was treated with n-butyl 2-cyanoacrylate, group 2 (G2) received a fragment of amniotic membrane through the anterior chamber and application of n-butyl 2-cyanoacrylate over the lesion, group 3 (G3) was treated with the same technique as G2 with the addition of an amniotic membrane bandage covering the cornea and sutured in the limbus region, and group 4 (G4) was treated with an amniotic membrane sutured to the lesion and an amniotic membrane bandage sutured in the limbus region. Clinical, histological and histomorphometric examinations of the corneas were performed. The membrane acted as a barrier for aqueous humor in G2 and G3, thereby keeping the surface dry for adhesive application; it also prevented the adhesive from contacting intraocular structures. The groups treated with amniotic membrane and surgical adhesive showed better results than the groups treated with either material alone. Thus, the combination of the membrane with the adhesive is recommended for this type of lesion.Os objetivos deste estudo foram comparar técnicas cirúrgicas e efeitos do n-butil 2-cianoacrilato e da membrana amniótica bovina na reparação de lesões perfuradas em córneas. Sessenta coelhos da raça Nova Zelândia Branca foram submetidos à ceratoplastia penetrante sob anestesia geral. O grupo 1 (G1) foi tratado com n-butil 2-cianoacrilato; o grupo 2 (G2) recebeu um fragmento de membrana amniótica pela câmara anterior e aplicação de n-butil 2-cianoacrilato sobre a lesão; o grupo 3 (G3) foi tratado com a mesma técnica aplicada ao G2, adicionando-se uma bandagem de membrana amniótica cobrindo a córnea e suturada à região do limbo; e o grupo 4 (G4) foi tratado com membrana amniótica suturada nas bordas da lesão e bandagem de membrana amniótica suturada na região do limbo. Foram realizados exames clínico, histológico e histomorfométrico. A membrana atuou como barreira contra o extravasamento do humor aquoso nos grupos 2 e 3, manteve a superfície seca para posterior aplicação do adesivo e impediu o contato do adesivo com as estruturas intraoculares. Os grupos tratados com o adesivo associado à membrana amniótica demonstraram melhores resultados do que aqueles tratados com cada material isoladamente. Assim, a combinação da membrana com o adesivo é indicada neste tipo de lesão.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES