O destino dos rins transplantados tratados com OKT3 para rejeição córtico-resistente

OBJECTIVE: To evaluate the long-term effects of the monoclonal antibody anti-CD3 (OKT3), used to treat steroid-resistant acute renal allograft rejection, on allograft function and long-term allograft and patient survival. MATERIALS AND METHODS: We studied 231 kidney transplants from living and cadaver donors and with prednisone, azathioprine and cyclosporin used for baseline immunosuppression. Diagnosis of acute rejection was based on clinical and laboratory criteria. Sixty-three (27.2%) patients did not present acute rejection, 135 (58.4%) presented steroid-sensitive rejection, and 33 (14.2%) received OKT3 as a rescue therapy for steroid-resistant rejection. We evaluated demographic data, serum creatinine, and allograft and patient survival up to the 5th posttransplant year, as well as causes of graft loss and patient death. RESULTS: Vascular anastomosis time and prevalence of  acute tubular necrosis were significantly higher in OKT3- reated patients. Average serum creatinine was not different between steroid-sensitive and steroid-resistant patients. Graft survival in the first year was poorer in the OKT3 group as compared to the non-rejection (P = 0.001) and steroidsensitive rejection (P = 0.04) groups; there was no difference, however, in the survival up to the 5th posttransplant year. In transplants from cadaver donors, graft survival was statistically different only between OKT3 and non-rejection patients. Patient survival did not differ between the 3 groups up to the end of the follow-up. There were no differences in causes of graft loss, but the proportion of deaths associated with infection was greater in patients treated with OKT3. CONCLUSIONS: OKT3 used for rescue therapy in steroid--resistant acute rejection was not associated with poorer renal graft function or survival over the 5-year follow-up period. However, graft survival in the first year was significantly poorer in patients that needed OKT3. The use of a more potent immunosuppression did not result in higher mortality rates up to the 5th year of posttransplant, but OKT3-treated recipients presented a higher incidence of deaths related to infection. OBJETIVO: Avaliar o efeito do anticorpo monoclonal anti-CD3 (OKT3), utilizado para tratamento de rejeição aguda córtico-resistente em pacientes transplantados renais, em relação à função do rim transplantado e à sobrevida do enxerto e do paciente a longo prazo.PACIENTES E MÉTODOS: Foram estudados 231 pacientes transplantados renais de doador vivo e cadavérico, tendo como imunossupressão de base prednisona, azatioprina e ciclosporina. O diagnóstico de rejeição aguda baseou-se em critérios clínicos e laboratoriais. Sessenta e três (27,2%) pacientes não apresentaram rejeição aguda, 135 (58,4%) tiveram rejeição córtico-sensível e 33 (14,2%) receberam OKT3 para rejeição córtico-resistente. Foram avaliados dados demográficos, função do enxerto, sobrevida do enxerto e do paciente até o quinto ano de transplante, bem como as causas de perda do rim transplantado e de óbito.RESULTADOS: O tempo de anastomose vascular e a prevalência de necrose tubular aguda foram significativamente maiores nos pacientes que receberam OKT3. A média da creatinina sérica do grupo OKT3 não diferiu do grupo com rejeição córtico-sensível. A sobrevida do enxerto no primeiro ano foi significativamente pior no grupo tratado com OKT3 em relação ao pacientes sem rejeição (P = 0,001) e com rejeição córticoresponsiva (P = 0,04), mas a sobrevida ao final do seguimento não diferiu. Nos transplantes cadavéricos, a diferença ocorreu apenas entre o grupo OKT3 e os pacientes sem rejeição. A sobrevida do paciente em 5 anos foi semelhante entre os 3 grupos. Não houve diferença nas causas de perda do enxerto, mas a proporção de óbitos associados à infecção foi maior nos pacientes que utilizaram OKT3.CONCLUSÕES: O uso de OKT3 como terapia de resgate não esteve associado a uma pior função ou pior sobrevida do enxerto renal em 5 anos, mas no primeiro ano a sobrevida do enxerto foi significativamente menor nos pacientes tratados com OKT3. O emprego de uma imunossupressão mais potente não se refletiu em maior mortalidade até o 5º ano do transplante, mas o grupo que utilizou OKT3 apresentou uma maior incidência de óbitos associados à infecção

Edema and nociception induced by Philodryas patagoniensis venom in mice: a pharmacological evaluation with implications for the accident treatment

histamine-serotonin inhibitor (cyproheptadine) failed in inhibiting both effects. In groups pretreated with captopril (angiotensin-converting enzyme inhibitor) the edema was unaltered, but nociception was clearly increased, suggesting the participation of kinins in the pathophysiology of the nociception but not of the edema-forming effect of PpV. When PpV was treated with EDTA, the nociception was similar to the one induced by untreated venom, but edema was markedly reduced. We concluded that PpV-induced edema and nociception have cyclooxygenase eicosanoids as main mediators and no participation of vasoactive amines. Kinins seem to participate in nociception but not in edema induced by PpV. Results also suggest that metalloproteinases are the main compounds responsible for the edema, but not for the nociception induced by this venom

Edema and Nociception Induced by Philodryas patagoniensis Venom in Mice: A Pharmacological Evaluation with Implications for the Accident Treatment

ABSTRACT We have investigated the mechanisms involved in the genesis of edema and nociception induced by Philodryas patagoniensis venom (PpV) injected into the footpad of mice. PpV induced dose-related edema and nociceptive effects. Pretreatment of mice with cyclooxygenase inhibitor (indomethacin), but not with cyclooxygenase 2 inhibitor (celecoxib) markedly inhibited both effects. Pretreatments with H 1 receptor antagonist (promethazine) or with dual histamine-serotonin inhibitor (cyproheptadine) failed in inhibiting both effects. In groups pretreated with captopril (angiotensin-converting enzyme inhibitor) the edema was unaltered, but nociception was clearly increased, suggesting the participation of kinins in the pathophysiology of the nociception but not of the edema-forming effect of PpV. When PpV was treated with EDTA, the nociception was similar to the one induced by untreated venom, but edema was markedly reduced. We concluded that PpV-induced edema and nociception have cyclooxygenase eicosanoids as the main mediators and no participation of vasoactive amines. Kinins seem to participate in nociception but not in edema induced by PpV. The results also suggest that metalloproteinases are the main compounds responsible for the edema, but not for the nociception induced by this venom

Chronic wasting disease risk assessment in Portugal: analysis of variability and genetic structure of the Portuguese roe deer population

Among the Transmissible Spongiform Encephalopathies, Chronic Wasting Disease (CWD) in cervids is now the rising concern in wildlife within Europe after the first case detected in Norway in 2016. CWD shows a notable horizontal transmission, affecting both free-ranging and captive cervids. Furthermore, several genetic variants in the Prion Protein (PRNP) gene coding sequence of the cervid were identified, which increase the susceptibility to the disease.This work was supported by the project WastingPrionRisk [POCI-01-0145-FEDER-029,947/ PTDC/CVT-CVT/29947/2017] funded by the Portuguese Foundation for Science and Technology (FCT). FCT PhD grant [SFRH/BD/146961/2019] financed by FCT through FSE (Fundo Social Europeu). This work was also supported by national funds [UIDB/CVT/00772/2020], [LA/P/0059/2020] and [UIDB/04033/2020] by FCT.info:eu-repo/semantics/publishedVersio

Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & Nemésio 2007; Donegan 2008, 2009; Nemésio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016

Temperature Effects Explain Continental Scale Distribution of Cyanobacterial Toxins

Insight into how environmental change determines the production and distribution of cyanobacterial toxins is necessary for risk assessment. Management guidelines currently focus on hepatotoxins (microcystins). Increasing attention is given to other classes, such as neurotoxins (e.g., anatoxin-a) and cytotoxins (e.g., cylindrospermopsin) due to their potency. Most studies examine the relationship between individual toxin variants and environmental factors, such as nutrients, temperature and light. In summer 2015, we collected samples across Europe to investigate the effect of nutrient and temperature gradients on the variability of toxin production at a continental scale. Direct and indirect effects of temperature were the main drivers of the spatial distribution in the toxins produced by the cyanobacterial community, the toxin concentrations and toxin quota. Generalized linear models showed that a Toxin Diversity Index (TDI) increased with latitude, while it decreased with water stability. Increases in TDI were explained through a significant increase in toxin variants such as MC-YR, anatoxin and cylindrospermopsin, accompanied by a decreasing presence of MC-LR. While global warming continues, the direct and indirect effects of increased lake temperatures will drive changes in the distribution of cyanobacterial toxins in Europe, potentially promoting selection of a few highly toxic species or strains.Peer reviewe