998 resultados para Rins - Doenças - Estudos experimentais


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Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

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Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

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The development of complex diseases such as preeclampsia are determined by both environmental and genetic factors, but there is also interaction among these factors. Preeclampsia is a pregnancy-specific disorder characterized by de-novo hypertension and proteinuria after 20th week of gestation. There is a broad spectrum of clinical presentations related to hypertensive disorders of pregnancy (HDP) that can range from mild preeclampsia to eclampsia (seizures) or HELLP syndrome (Hemolysis, Elevation of Liver enzymes, Low Platelets). Those clinical outcomes might be linked to different pathological mechanisms. Our work aims to identify factors (i.e. genes and environmental) associated with the HDP’s clinical spectrum. Using a case-control approach, we selected a total of 1498 pregnant women for epidemiological and genetic studies, encompassing 755 normotensive (control); 518 preeclampsia; 84 eclampsia; and 141 HELLP. Women were genotyped for 18 SNPs across 5 candidate genes (FLT1, ACVR2A, ERAP1, ERAP2 and LNPEP). For the environmental factors, we found maternal age, parity status and pre-gestational body mass index as important risk factors associated with disease. Genes were associated in a phenotype-specific manner: ACVR2A with early preeclampsia (rs1424954, p=0.002); FLT1 with HELLP syndrome (rs9513095, p=0.003); and ERAP1 with eclampsia (rs30187, p=0.03). Our results suggest that different genetic mechanisms along with specific environmental factors might determine the clinical spectrum of HDP. In addition, phenotype refinement seems to be an essential step in the search for complex disease genes

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Camu-camu (Myrciaria dubia H.B.K. (McVaugh)) is a native Amazon fruit, recognized worldwide as one of the main natural sources of ascorbic acid. Due to its great acidity, this fruit is generally consumed after processing into juice or as ingredient in food preparations. As a co-product of the camu-camu processing, a significant amount of agroindustrial residue is generated. Despite the studies showing the bioactive value and biological potential of the fruit, few studies have approached the possible processing techniques, transformation and preservation of camu-camu fruits and its agroindustrial pomace. Therefore, the present work has the objective of evaluating two different drying processes applied to camu-camu pomace (peel and seeds with residual pulp), freeze drying and hot air drying, in order to obtain a functional fruit product. This thesis was divided into three stages: the first one shows the studies related to the freeze drying and hot air drying, where we demonstrated the impact of the selected drying techniques on the bioactive components of camu-camu, taking the fresh pomace as the control group. Among the investigated conditions, the groups obtained at 50ºC and 4 m/s (SC50) and 80ºC and 6 m/s (SC80) were selected as for further studies, based on their ascorbic acid final content and Folin-Ciocalteau reducing capacity. In addition to SC50 and SC80, the fresh pomace (RF) and freeze dried (RL) samples were also evaluated in these further stages of the research. Overall, the results show higher bioactive concentration in the RF samples, followed by RL, SC50 and SC80. On the second step of the research, the antioxidant, antimicrobial and antienzymatic activities were evaluated and the same tendency was observed. It was also reported, for the first time in the literature, the presence of syringic acid in dried camu-camu pomace. In the third and final stage of the research, it was investigated the effect of dried camu-camu on aging and neuroprotective disorders, using the in vivo model C.elegans. It was observed that camu-camu extracts were able to modulate important signaling genes relevant to thermal and oxidative stresses (p < 0.05). The polar acid, polar basic and polar neutral fractions obtained from the low molecular extracts of SC50 were able to extend the lifespan of wild type N2 C. elegans in 20% and 13% (p < 0.001). Results also showed that the paralysis induced by the β1-42 amyloid was significantly (p < 0.0001) retarded in CL4176 worms. Similarly, the camu-camu extracts attenuated the dopaminergic induction associated to Parkinson’s disease. Finally, a global analysis of the data presented here reveal that the camu-camu pomace, a co-product obtained from the industrial processing of a native Brazilian fruit, is a relevant natural source of health relevant compounds. This thesis, shows for the first time, the multifunctionality of camu-camu pomace, a natural resource still underexploited for scientific, commercial and technological purposes.

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Population aging is a global demographic trend. This process is a reality that merits attention and importance in recent years, and cause considerable impact in terms of greater demands on the health sector, social security and special care and attention from families and society as a whole. Thus, in the context of addressing the consequences of demographic transition, population aging is characterized as a major challenge for Brazilian society. Therefore, this study was conducted in two main objectives. In the first article, variables of socioeconomic and demographic contexts were employed to identify multidimensional profiles of elderly residents in the Northeast capitals, from specific indicators from the 2010 Census information Therefore, we used the Grade of Membership Method (GoM), whose design profiles admits that an individual belongs to different degrees of relevance to multiple profiles in order to identify socioeconomic and demographic factors associated with living conditions of the elderly in the Northeastern capitals. The second article examined the possible relationship between mortality from chronic diseases and socio-economic indicators in the elderly population, of the 137 districts in Natal, broken down by ten-year age groups (60 to 69 years, 70-79 years and 80 and over. The microdata from the Mortality Information System (SIM), was used, provided by the Health Secretariat of Christmas, and population information came from the Population Census 2010. The method refers to the Global and Local Index neighborhood logic (LISA) Moran, whose spatial distribution from the choropleth maps allowed us to analyze the mortality of the elderly by neighborhoods, according to socioeconomic and demographic indicators, according to the presence of special significance. In the first article, the results show the identification of three extreme profiles. The Profile 1 which is characterized by median socioeconomic status and contributes 35.5% of elderly residents in the area considered. The profile 2 which brings together seniors with low socioeconomic status characteristics, with a percentage of 24.8% of cases. And the Profile 3 composing elderly with features that reveal better socioeconomic conditions, about 29.7% of the elderly. Overall, the results point to poor living conditions represented by the definition of these profiles, mainly expressed by the results observed in more than half of the northeastern elderly experience a situation of social vulnerability given the large percentage that makes up the Profile 1 and Profile 2, adding 60% of the elderly. In the second article, the results show a higher proportion of elderly concentrated in the neighborhoods of higher socioeconomic status, such as Petrópolis and LagoaSeca. Mortality rates, according to the causes of death and standardized by the empirical Bayesian method were distributed locally as follows: Neoplasms (Reis Santos, New Discovery, New Town, Grass Soft and Ponta Negra); Hypertensive diseases (Blue Lagoon, Potengi, Redinha, Reis Santos, Riverside, Lagoa Nova, Grass Soft, Neópolis and Ponta Negra); Acute Myocardial Infarction (Northeast, Guarapes and grass Soft); Cerebrovascular diseases (Petrópolis and Mother Luiza); Pneumonia (Ribeira, Praia do Meio, New Discovery, Grass Soft and Ponta Negra); Chronic Diseases of the Lower Way Airlines (Igapó, Northeast and Thursdays). The present findings at work may contribute to other studies on the subject and development of specific policies for the elderly.

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Population aging is a global demographic trend. This process is a reality that merits attention and importance in recent years, and cause considerable impact in terms of greater demands on the health sector, social security and special care and attention from families and society as a whole. Thus, in the context of addressing the consequences of demographic transition, population aging is characterized as a major challenge for Brazilian society. Therefore, this study was conducted in two main objectives. In the first article, variables of socioeconomic and demographic contexts were employed to identify multidimensional profiles of elderly residents in the Northeast capitals, from specific indicators from the 2010 Census information Therefore, we used the Grade of Membership Method (GoM), whose design profiles admits that an individual belongs to different degrees of relevance to multiple profiles in order to identify socioeconomic and demographic factors associated with living conditions of the elderly in the Northeastern capitals. The second article examined the possible relationship between mortality from chronic diseases and socio-economic indicators in the elderly population, of the 137 districts in Natal, broken down by ten-year age groups (60 to 69 years, 70-79 years and 80 and over. The microdata from the Mortality Information System (SIM), was used, provided by the Health Secretariat of Christmas, and population information came from the Population Census 2010. The method refers to the Global and Local Index neighborhood logic (LISA) Moran, whose spatial distribution from the choropleth maps allowed us to analyze the mortality of the elderly by neighborhoods, according to socioeconomic and demographic indicators, according to the presence of special significance. In the first article, the results show the identification of three extreme profiles. The Profile 1 which is characterized by median socioeconomic status and contributes 35.5% of elderly residents in the area considered. The profile 2 which brings together seniors with low socioeconomic status characteristics, with a percentage of 24.8% of cases. And the Profile 3 composing elderly with features that reveal better socioeconomic conditions, about 29.7% of the elderly. Overall, the results point to poor living conditions represented by the definition of these profiles, mainly expressed by the results observed in more than half of the northeastern elderly experience a situation of social vulnerability given the large percentage that makes up the Profile 1 and Profile 2, adding 60% of the elderly. In the second article, the results show a higher proportion of elderly concentrated in the neighborhoods of higher socioeconomic status, such as Petrópolis and LagoaSeca. Mortality rates, according to the causes of death and standardized by the empirical Bayesian method were distributed locally as follows: Neoplasms (Reis Santos, New Discovery, New Town, Grass Soft and Ponta Negra); Hypertensive diseases (Blue Lagoon, Potengi, Redinha, Reis Santos, Riverside, Lagoa Nova, Grass Soft, Neópolis and Ponta Negra); Acute Myocardial Infarction (Northeast, Guarapes and grass Soft); Cerebrovascular diseases (Petrópolis and Mother Luiza); Pneumonia (Ribeira, Praia do Meio, New Discovery, Grass Soft and Ponta Negra); Chronic Diseases of the Lower Way Airlines (Igapó, Northeast and Thursdays). The present findings at work may contribute to other studies on the subject and development of specific policies for the elderly.

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The theoretical and experimental developments in the biomaterials area have been directly applied to different fields of Medicine (odontology, regenerative medicine and radiotherapy). These advances have focused both for diagnosing diseases such as for quantifying degrees of progression. From the perspective of these studies, biomaterials are being designed and manufactured for application in various areas of science, provided advances in diagnostic radiology, radiotherapy dosimetry and calibration of radiotherapy equipment. Develop a phantom from a biomaterial has become a great ally of medicine in the treat patients with oncological diseases, allowing better performance of the equipment in order to reduce damage to healthy tissue due to excessive exposure to radiation. This work used polymers: chitosan and gelatin, for making the polymeric structures and controlled for different types of production and processing, characterizing and evaluating the biopolymer by physical techniques (STL, SEM and DEI) and therefore analyze applicability as phantom mouse lung. It was possible to evaluate the morphology of biomaterials quantitatively by scanning electron microscopy associated with imaging technique. The relevance of this work focuses on developing a phantom from polymeric biomaterials that can act as phantom providing high image contrast when subjected to analysis. Thus, the choice of DEI technique is satisfactory since it is an imaging technique of X-ray high resolution. The images obtained by DEI have shown the details of the internal microstructure of the biomaterial produced which have ≈ 10 μm dimension. The phantoms had made density ranging from 0.08 a 0.13 g/cm3.

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Introdução: O aumento da gordura abdominal e o sedentarismo contribuem para o risco de doença cardiovascular. A utilização de corrente elétrica de baixa intensidade (microcorrente) na região abdominal, associado ao exercício físico, parece ser um método inovador no aumento da taxa lipolítica dos adipócitos abdominais. Objetivos: Analisar os efeitos da utilização da microcorrente associada a um programa de exercícios em indivíduos saudáveis e com doença arterial coronária na gordura abdominal, e ainda, analisar os efeitos de um programa de exercício físico específico realizado no domicílio em indivíduos com doença arterial coronária, na fase de manutenção da reabilitação cardiovascular, na capacidade cardiorrespiratória. Métodos: Foram conduzidos três estudos: Estudo 1, em indivíduos saudáveis, durante 5 semanas (n=42), distribuídos aleatoriamente por quatro grupos experimentais (realizavam microcorrente e exercício físico: grupo 1- frequência 25 a 10Hz, elétrodos transcutâneos, exercício físico após; grupo 2- frequência 25 a 50Hz, elétrodos trancutâneos, exercício físico após; grupo 3- frequência 25 a 10Hz, elétrodos percutâneos e exercício físico após; grupo 4- frequência 25 a 10Hz, elétrodos transcutâneos e exercício físico realizado em simultâneo) e placebo (realizavam apenas exercício físico), onde foram avaliadas medidas de gordura abdominal; Estudo 2, em indivíduos saudáveis, durante uma sessão de microcorrente e exercício físico (n=83), distribuídos aleatoriamente por grupo experimental (realizavam microcorrente e exercício físico) e grupo placebo (realizavam exercício físico), onde foram avaliadas a atividade lipolítica (níveis de glicerol) e a oxidação de ácidos gordos (estimada pelo VO2 e VCO2); Estudo 3, em indivíduos após um ano de evento de síndrome coronária aguda (n=44), distribuídos aleatoriamente em dois grupos experimentais (grupo 1- exercício físico no domicílio; grupo 2- microcorrente e exercício físico no domicílio) e um grupo controlo (cuidados habituais), durante 8 semanas, sendo avaliados a gordura abdominal, o colesterol, a capacidade cardiorrespiratória, os hábitos de atividade física e alimentares e a qualidade de vida. Resultados: No estudo 1, após 5 semanas de intervenção de microcorrente e exercício físico, verificou-se uma redução das medidas de gordura abdominal (p<0,05); No estudo 2 observou-se que uma sessão de microcorrente associada ao exercício físico aumentou a taxa lipolítica, através da medição de glicerol (p<0,05), sem alterações significativas na oxidação de ácidos gordos, durante o exercício. No estudo 3, após as 8 semanas de aplicação de microcorrente associada a um programa de exercícios específicos no domicílio ocorreu uma diminuição significativa na gordura subcutânea (p<0,05). O programa de exercício físico de reabilitação cardiovascular no domicílio, per se, aumentou a capacidade cardiorrespiratória, na fase de manutenção (p<0,05). Não se verificaram alterações do colesterol total, dos hábitos alimentares, da atividade física e da qualidade de vida entre os três grupos. Conclusão: A utilização da microcorrente associada ao exercício físico parece ser um meio coadjuvante ao programa de exercícios, na redução do tecido adiposo abdominal em indivíduos saudáveis e em indivíduos após 1 ano de enfarte agudo do miocárdio. O programa de Reabilitação Cardiovascular no domicílio, em fase de manutenção, demonstrou melhoria da capacidade cardiorrespiratória.

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The immune system is able to produce antibodies, which have the capacity to recognize and to bind to foreign molecules or pathogenic organisms. Currently, there are a diversity of diseases that can be treated with antibodies, like immunoglobulins G (IgG). Thereby, the development of cost-efficient processes for their extraction and purification is an area of main interest in biotechnology. Aqueous biphasic systems (ABS) have been investigated for this purpose, once they allow the reduction of costs and the number of steps involved in the process, when compared with conventional methods. Nevertheless, typical ABS have not showed to be selective, resulting in low purification factors and yields. In this context, the addition of ionic liquids (ILs) as adjuvants can be a viable and potential alternative to tailor the selectivity of these systems. In this work, ABS composed of polyethylene glycol (PEG) of different molecular weight, and a biodegradable salt (potassium citrate) using ILs as adjuvants (5 wt%), were studied for the extraction and purification of IgG from a rabbit source. Initially, it was tested the extraction time, the effect on the molecular weight of PEG in a buffer solution of K3C6H5O7/C6H8O7 at pH≈7, and the effect of pH (59) on the yield (YIgG) and extraction efficiency (EEIgG%) of IgG. The best results regarding EEIgG% were achieved with a centrifugation step at 1000 rpm, during 10 min, in order to promote the separation of phases followed by 120 min of equilibrium. This procedure was then applied to the remaining experiments. The results obtained in the study of PEGs with different molecular weights, revealed a high affinity of IgG for the PEG-rich phase, and particularly for PEGs of lower molecular weight (EEIgG% of 96 % with PEG 400). On the other hand, the variation of pH in the buffer solution did not show a significant effect on the EEIgG%. Finally, it was evaluated the influence of the addition of different ILs (5% wt) on the IgG extraction in ABS composed of PEG 400 at pH≈7. In these studies, it was possible to obtain EEIgG% of 100% with the ILs composed of the anions [TOS]-, [CH3CO2]-and Cl-, although the obtained YIgG% were lower than 40%. On the other hand, the ILs composed of the anions Br-, as well as of the cation [C10mim]+, although not leading to EEIgG% of 100%, provide an increase in the YIgG%. ABS composed of PEG, a biodegradable organic salt and ILs as adjuvants, revealed to be an alternative and promising method to purify IgG. However, additional studies are still required in order to reduce the loss of IgG.

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Tese de dout. em Ciências Agrárias, especialidade Protecção de Plantas, Faculdade de Engenharia e Recursos Naturais, Univ. do Algarve, 2001

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A doença de Alzheimer constitui uma ameaça significativa a nível mundial. Estima-se que, mundialmente existam cerca de 35 milhões de pessoas afetadas por este tipo de demência. Os compostos contendo um esqueleto benzocicloalcanol (que incluem benzofuranos e di-hidrobenzofuranóis) mostram atividades biológicas significativas e possuem muito potencial no tratamento das doenças neurodegenerativas. Nos últimos anos têm havido avanços significativos no campo das reações catalisadas por metais. As reações de adição nucleófila intramolecular e a de Heck intramolecular constituem metodologias importantes para a síntese de benzocicloalcanóis. No âmbito deste trabalho, pretendia-se sintetizar uma biblioteca de compostos contendo um esqueleto benzocicloalcanol. A estratégia adotada para a síntese de dihidrobenzofuranóis envolveu um método de ciclização catalítica de cetonas aril-éteres e para a síntese de benzofuranos, um método de ciclização catalítico de enoatos e enamidas (amidas de Weinreb). Várias condições foram estudadas; Abstract: Studies on Synthetic Catalytic Pathways to Benzocycloalkanols and Derivatives – Potential Drugs for Alzheimer’s Disease Alzheimer's disease constitutes a significant threat worldwide. It is estimated that are about 35 million people worldwide suffering from this type of dementia. The compounds containing a benzocycloalkanol scaffold (including benzofurans and dihydrobenzofurans) show significant biological activity and have great potential in the treatment of neurodegenerative diseases. In recent years there have been many advances in the field of catalyzed reactions by transition-metals. The intramolecular nucleophilic addition and the intramolecular Heck reactions constitute important methods for the synthesis of benzocycloalkanols. Within this work, the main goal was to synthesize a library of compounds containing a benzocycloalkanol scaffold. The adopted strategy for the synthesis of dihydrobenzofurans was the catalytic cyclization of aryl ether ketones and for the synthesis of benzofurans, the catalytic cyclization of enoates and enamides (Weinreb amides). Several conditions were studied

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Os diversos compostos químicos liberados no ambiente oriundos do uso indiscriminado na agricultura, pecuária e na indústria são responsáveis por efeitos ecológicos adversos, causando a contaminação do solo e corpos d´água e acumulando-se em organismos não alvo. O tratamento dos esgotos resulta na produção do lodo de esgoto, o qual muitas vezes é utilizado como fonte alternativa de nutrientes para as plantas devido ao seu alto teor de matéria orgânica. Contudo, o lodo pode conter metais pesados em sua composição advindos principalmente do setor industrial, os quais podem expressar seu potencial poluente diretamente nos organismos do solo, além da possibilidade de transferência para outros organismos via cadeia alimentar ou pela contaminação das águas (CHANG et al., 1987). Embora o controle químico de pragas tenha reduzido o índice de doenças para homens e animais e incrementado a produção agrícola, agentes poluentes podem permanecer ativos no ambiente por longos períodos, afetando os ecossistemas. Os efeitos desses agentes ao longo do tempo representam um grande risco para a saúde pública, tornando-se necessário o monitoramento em águas, solos, alimentos e ar. Nesse contexto, as alterações ao nível bioquímico são as primeiras respostas detectáveis e quantificáveis em uma mudança do meio ambiente, sendo indicadores mais sensíveis que os de maiores níveis de organização biológica porque exibem um tempo de exposição mais curto. A partir do processo de bioacumulação, os agentes poluentes podem se concentrar em diferentes tecidos e promover a ativação ou inibição de sistemas enzimáticos, tais como o das fosfatases ácidas (JONSSON, 2005; JONSSON, AOYAMA, 2007). As fosfatases ácidas ou ortofosfato monoéster fosfohidrolases (E.C.3.1.3.2.) são enzimas que catalisam a hidrólise de uma grande variedade de ésteres de ortofosfato e reações de transfosforilação. Inibições in vitro de fosfatases de vários organismos causadas por pesticidas, têm sido relatadas na literatura (SEKEROGLU et al., 1980; EL DEMERDASH et al., 2001). O ensaio enzimático in vitro representa uma ferramenta útil para o screening de poluentes, elucidação de mecanismos de toxicidade e monitoramento de áreas contaminadas. Entretanto, os testes de toxicidade em organismos aquáticos podem complementar as análises in vitro. O objetivo deste estudo foi avaliar o efeito in vitro de agentes agroquímicos e metais pesados contaminantes de lodo de esgoto sobre a fosfatase ácida total de Daphnia similis, comparando-se com os resultados obtidos em testes de toxicidade aguda.

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Trabalhos relacionados à identificação de Neonectria ditissima, agente causador do cancro europeu das pomáceas, e de fungos causadores de doenças do tronco da videira, Phaeomoniella chlamydospora, Phaeoacremonium spp. e Botryosphaeria spp., foram conduzidos no Laboratório 2 de Fitopatologia, entre julho 2015 e junho de 2016.

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O ?Mal de Pierce? (Pierce?s disease) é uma doença de importância quarentenária A1, ou seja, ainda não encontrada no Brasil. Economicamente representa uma grande ameaça para a vitivinicultura por ser altamente destrutiva e de difícil controle, devido a sua disseminação natural por vetores aéreos (cigarrinhas) e por dispor de inúmeras hospedeiras alternativas nativas. Esta doença foi primeiramente constatada em 1884, próximo a Pomona e Anaheim na California. Foi chamada inicialmente de Anaheim disease, doença misteriosa, doença da California, praga da videira, entre outros. Em 1892 foi pela primeira vez descrita por Newton B. Pierce, de quem posteriormente herdou o nome e passou a chamar-se ?Pierce?s disease?. Algumas decadas depois a doença foi identificada em outras regiões vitícolas, incluindo o Sul da California até a Florida. O Mal de Pierce foi por muito tempo considerado uma doença causada por vírus. Entretanto investigações conduzidas a partir da década de 70 do século passado, mostraram que em plantas doentes tratadas com antibióticos os sintomas desapareciam e que a imersão de material vegetativo dormente em água quente eliminava o agente causal. Estudos posteriores com microscopia eletrônica demonstraram a presença de bactéria do tipo ricketisia nos tecidos xilemáticos de plantas doentes. Em 1978 a bactéria foi isolada e cultivada em meio de cultura artificial e completado o postulado de Koch?s comprovando-se ser o agente causal da doença. Em 1987 foi definitivamente classificada por Wells e colaboradores como Xylella fastidiosa, bactéria sistêmica do tipo bastonete, gram-negativa, fastidiosa, aflagelada, aeróbica e limitada aos vasos xilemáticos da planta. Esta bactéria apresenta várias estirpes (raças) que causam doenças em outras culturas além da videira, como a queimadura das folhas da amendoeira, nanismo da alfafa, ?phony peach? em pessegueiro, clorose variegada dos citros, escaldadura das folhas da ameixeira e requeima do cafezeiro. Há evidências experimentais que as doenças da videira, amendoeira e alfafa são causadas pela mesma estirpe da bactéria.