Os desafios na conduta terapêutica em pacientes acometidos com feridas crônicas / Challenges in the therapeutic conduct in patients affected with chronic wounds / Retos en la conducta terapéutica en pacientes afectados de heridas crónicas

Considerado um grave problema em saúde pública, as feridas crônicas são patologias que desafiam o manejo terapêutico e infelizmente acometem milhares de pessoas em todo o mundo. Essa doença apresenta altos índices de morbidade impactando negativamente na qualidade de vida dos seus portadores, além de influenciar negativamente no domínio "bem-estar", principalmente quando associado aos fatores clínicos podendo estar relacionado há anos de tratamento sem cura da ferida. As feridas crônicas são caracterizadas por demora ou dificuldade nos processos de cicatrização e reparação ordenada da integridade anatômica e funcional da pele durante um período de no mínimo três meses. Porém, algumas lesões permanecem por anos e até décadas sem cicatrizar. Objetivo: O escopo dessa revisão é mostrar o limitado arsenal terapêutico bem como a dificuldade no manejo clínico e dessa forma proporcionar uma reflexão sobre sua fisiopatologia e a urgente necessidade de novas opções e condutas terapêuticas que possam auxiliar no tratamento desses pacientes. Metodologia: Trata-se de uma revisão integrativa da literatura sobre feridas crônicas, cujo critérios de inclusão foram artigos publicados no período de janeiro de 2005 a fevereiro de 2023. Conclusão: A problemática acerca dessa patologia é vasta, tratando de uma doença de difícil cura, com uma gama de fatores associados que dificultam a cura da lesão, estendendo essa doença a altos índices de morbidade. Novas condutas terapêuticas e novos fármacos, precisam ser desenvolvidos urgentemente. Destaca-se que o uso de probióticos e o emprego da nanotecnologia tem mostrado um grande potencial inovador no tratamento de pacientes portadores de feridas crônicas.

Considered a serious public health problem, chronic wounds are pathologies that defy therapeutic management and unfortunately affect thousands of people around the world. This disease has high morbidity rates, negatively impacting the quality of life of its patients, in addition to negatively influencing the "well-being" domain, especially when associated with clinical factors, which may be related to years of treatment without healing of the wound. Chronic wounds are characterized by delay or difficulty in healing processes and orderly repair of the anatomical and functional integrity of the skin over a period of at least three months. However, some injuries remain for years and even decades without healing. Objective: The scope of this review is to show the limited therapeutic arsenal as well as the difficulty in clinical management and thus provide a reflection on its pathophysiology and the urgent need for new options and therapeutic approaches that can help in the treatment of these patients. Methodology: This is an integrative review of the literature on chronic wounds, whose inclusion criteria were articles published from January 2005 to February 2023. Conclusion: The problem surrounding this pathology is vast, dealing with a difficult-to-cure disease, with a range of associated factors that make healing of the lesion difficult, extending this disease to high morbidity rates. New therapeutic approaches and new drugs need to be developed urgently. It is noteworthy that the use of probiotics and the use of nanotechnology have shown great innovative potential in the treatment of patients with chronic wounds.

Consideradas un grave problema de salud pública, las heridas crónicas son patologías que desafían el manejo terapéutico y que, lamentablemente, afectan a miles de personas en todo el mundo. Esta enfermedad presenta altas tasas de morbilidad, impactando negativamente en la calidad de vida de sus pacientes, además de influir negativamente en el dominio "bienestar", especialmente cuando se asocia a factores clínicos, que pueden estar relacionados con años de tratamiento sin curación de la herida. Las heridas crónicas se caracterizan por un retraso o dificultad en los procesos de cicatrización y reparación ordenada de la integridad anatómica y funcional de la piel durante un periodo de al menos tres meses. Sin embargo, algunas heridas permanecen durante años e incluso décadas sin cicatrizar. Objetivo: El alcance de esta revisión es mostrar el limitado arsenal terapéutico así como la dificultad en el manejo clínico y así aportar una reflexión sobre su fisiopatología y la urgente necesidad de nuevas opciones y enfoques terapéuticos que puedan ayudar en el tratamiento de estos pacientes. Metodología: Se trata de una revisión integradora de la literatura sobre heridas crónicas, cuyos criterios de inclusión fueron artículos publicados desde enero de 2005 hasta febrero de 2023. Conclusiones: La problemática que rodea a esta patología es amplia, tratándose de una enfermedad de difícil curación, con una serie de factores asociados que dificultan la cicatrización de la lesión, extendiendo esta enfermedad a altas tasas de morbilidad. Es urgente desarrollar nuevos enfoques terapéuticos y nuevos fármacos. Cabe destacar que el uso de probióticos y el empleo de nanotecnología han mostrado un gran potencial innovador en el tratamiento de pacientes con heridas crónicas.

Efeito do probiótico lactobacilus casei adjunto a terapia periodontal em modelo experimental de periodontite: uma relação entre periodonto e intestino / Effect of the probiotic lactobacilus casei as an adjunct to periodontal therapy in an experimental model of periodontitis: a relationship between periodontium and intestine

A periodontite é uma condição crônica inflamatória que pode influenciar a microbiota intestinal. O tratamento padrão ouro para a periodontite inclui a raspagem e o alisamento corono-radicular (RACR), porém em casos complexos pode-se utilizar terapias adjuvantes, como os probióticos. A utilização deste tratamento adjuvante poderá contribuir para a melhoria da condição periodontal e a simbiose intestinal. O objetivo deste estudo foi avaliar o efeito na inflamação periodontal e intestinal da utilização do Lactobacillus casei (LC) adjunto a RACR em camundongos Balb/c com periodontite, induzida por ligadura. Este estudo é um ensaio pré-clínico, in vivo, randomizado, cego e controlado por placebo, constituído por 36 camundongos Balb/c machos. Os animais foram submetidos a indução da periodontite por colocação de ligadura com fio de seda 4.0 ao redor do segundo molar superior direito, sendo divididos em 4 grupos,o grupo controle: Sem Periodontite e sem RACR (n=8); Grupo Ligadura: Com Periodondite e sem RACR (n=10); Grupo raspagem: Com Periodontite e com RACR (n=10) ; Grupo raspagem + L.casei (n=8): Com Periodontite e com RACR + administração de LC, por gavagem, durante 30 dias. Foram realizadas análises de citocinas pelo método ELISA no tecido gengival (IL-6), intestinal (IL-1ß, IL-6 e IL-10) e sanguíneo (IL-1ß e IL-6), além de análises bioquímicas (TGO, TGP, ureia e creatinina) e contagem diferencial de leucócitos do sangue. Foram coletados fragmentos do intestino grosso desses animais e analisados quanto a biomarcadores do estresse oxidativo (SOD, GSH e MDA), atividade da acetilcolinesterase (AChE) e foi realizada contagem da população de Bactérias Produtoras de Ácido Láctico das fezes dos animais. A utilização do LC adjunto a RACR resultou em uma redução na expressão da IL-6 no tecido gengival de camundogos com Periodontite (p < 0,05). Para as inteleucinas séricas (IL-1ß e IL-6), não houve diferenças entre os grupos (p > 0,05). Já para as citocinas intestinais houve uma redução na expressão de IL-10 (p < 0,05), para os grupos em que foi induzida a Periodontite. Com relação ao estresse oxidativo intestinal os animais do Grupo raspagem e raspagem + LC tiveram uma redução dos níveis de MDA (p < 0,05), para a SOD e o GSH, não houve diferenças significativas entre os 4 grupos pesquisados (p < 0,05). Conclui-se que o uso de LC adjunto a RACR em camungongos com periodontite induzida por ligadura pode reduzir a liberação de IL-6 no tecido gengival. Com relação aos efeitos intestinais foi observada a modulação da resposta inflamatória, com a redução de MDA, nos animais que receberam o tratamento periodontal. E a redução da expressão da IL-10, nos animais com Periodontite (AU).

Periodontitis is a chronic inflammatory condition that can influence the gut microbiota. The gold standard treatment for periodontitis includes scaling and crown-root planing, but in complex cases adjuvant therapies such as probiotics can be used. The use of this adjuvant treatment may contribute to the improvement of periodontal condition and intestinal symbiosis. The aim of this study was to evaluate the effect on periodontal and intestinal inflammation of the use of Lactobacillus casei (LC) adjunct to scaling and root planing (RACR) in Balb/c mice with ligature-induced periodontitis. This study is a preclinical, in vivo, randomized, blinded, placebo-controlled trial consisting of 40 male Balb/c mice. The animals were submitted to periodontitis induction by placing a 4.0 silk suture ligature around the upper right second molar. The sample was divided into 4 groups, each with 10 animals: Group I: Without Periodontitis and without RACR; Group II: With Periodontitis and without RACR; Group III: With Periodontitis and with RACR; Group IV: With Periodontitis and with RACR + gavage of LC, for 30 days. Cytokine analyzes were performed by the ELISA method in gingival tissue (IL-6), intestinal tissue (IL-1ß, IL-6 and IL-10) and blood (IL-1ß and IL-6), the blood was also subjected to analysis biochemical (TGO, TGP, urea and creatinine) and differential leukocyte count. Fragments of the large intestine of these animals were collected and analyzed for biomarkers of oxidative stress (SOD, GSH and MDA), acetylcholinesterase (AChE) activity, and the population of Lactic Acid-Producing Bacteria in the animals' feces was counted. The use of LC adjunct to RACR resulted in a reduction in the expression of IL-6 in the gingival tissue of mice with Periodontitis (p < 0.05), for the blood inteleukins (IL-1ß and IL-6), there were no differences between the groups (p > 0.05). As for intestinal cytokines, there was a reduction in the expression of IL-10 (p < 0.05), for the groups that presented Periodontitis. Regarding intestinal oxidative stress, the animals in Groups III and IV had a reduction in MDA levels (p < 0.05), for SOD and GSH, there were no significant differences between the 4 groups studied (p < 0.05 ). It is concluded that the use of LC adjunct to RACR in mice with ligation-induced periodontitis can reduce the release of IL-6 in the gingival tissue. Regarding the intestinal effects, two effects were found: The first related to the modulation of the inflammatory response, with the reduction of MDA, in the animals that received periodontal treatment. And the second related to a pro-inflammatory effect, with the reduction of IL-10 expression (AU).

Inmunomodulación con bióticos y alergia alimentaria en pediatría / Immunomodulation properties of biotics and food allergy in pediatrics

El parto prematuro, la cesárea, el uso de antibióticos y la lactancia materna limitada son señalados como responsables en parte del aumento de enfermedades crónicas no transmisibles en niños, como las alergias, principalmente la alergia a la proteína de la leche de vaca (APLV). Quienes desarrollan enfermedades alérgicas muestran diferencias en la composición de su microbiota intestinal durante los primeros meses de vida, en comparación con los que no lo hacen. Las intervenciones tempranas para modular la microbiota intestinal y el sistema inmunológico pueden ser herramientas claves para el abordaje y tratamiento de la APLV. El criterio clínico y el trabajo interdisciplinario de alergólogos, gastroenterólogos, inmunólogos, microbiólogos y nutricionistas le permitirá al pediatra lograr un adecuado diagnóstico y un tratamiento oportuno. En este contexto, el empleo de bióticos (prebióticos, probióticos, sinbióticos y posbióticos) como herramientas nutricionales complementarias tiene un presente con sustento científico y un futuro promisorio para la prevención y tratamiento de estas patologías.

Preterm birth, C-section, antibiotic use, and limited breastfeeding are blamed in part for the increasing incidence of chronic noncommunicable diseases among children, such as allergies, mainly cow's milk protein allergy (CMPA). Those who develop allergic diseases, against those who do not, show differences in the composition of their gut microbiota during the first months of life. Early interventions to modulate the intestinal microbiota and the immune system may be the key tools for the management of CMPA. Clinical judgment and the interdisciplinary work of allergists, gastroenterologists, immunologists, microbiologists, and nutritionists will allow pediatricians to achieve an adequate diagnosis and a timely treatment. In this setting, the use of biotics (prebiotics, probiotics, synbiotics, and postbiotics) as supplementary dietary tools is scientifically supported at present and seems to be very promising for the prevention and treatment of these conditions.

Abordaje de los probióticos en pediatría: el rol de Lactobacillus rhamnosus GG / Approach to probiotics in pediatrics: the role of Lactobacillus rhamnosus GG

El parto prematuro, las cesáreas, los antibióticos y la lactancia materna limitada contribuyen al aumento de enfermedades crónicas no transmisibles. El objetivo fue realizar una revisión descriptiva del uso de probióticos en pediatría, con foco en la cepa Lactobacillus rhamnosus GG. Ciertos probióticos han demostrado ser eficaces en la diarrea aguda y en la diarrea asociada a antibióticos. L. rhamnosus GG y Saccharomyces boulardii pueden acortar la duración y los síntomas. L. reuteri DSM 17938 y L. rhamnosus GG fueron efectivos para el abordaje del cólico del lactante. El uso de esta cepa en fórmulas infantiles para alergia a las proteínas de leche de vaca promovería la adquisición más temprana de tolerancia. En la prevención de dermatitis atópica, la administración de L. rhamnosus GG durante el embarazo redujo su manifestación en el bebé. El empleo de probióticos como coadyuvantes es una posibilidad para considerar en la práctica pediátrica actual.

Preterm birth, C-sections, antibiotics, and limited breastfeeding contribute to the increase in noncommunicable diseases. Our objective was to perform a descriptive review of probiotic use in pediatrics, focused on Lactobacillus rhamnosus GG. Certain probiotics have demonstrated to be effective in acute diarrhea and antibiotic-associated diarrhea. L. rhamnosus GG and Saccharomyces boulardii may shorten their duration and symptoms. L. reuteri DSM 17938 and L. rhamnosus GG were effective to manage infant colic. The use of this strain in infant formulas for cow's milk protein allergy may promote an earlier tolerance acquisition. In relation to the prevention of atopic dermatitis, the administration of L. rhamnosus GG during pregnancy reduced its development in the infant. The use of probiotics as adjuvants is a possibility to consider in current pediatric practice.

Alternativas aos antibióticos na profilaxia das infecções urinárias recorrentes não complicadas na mulher / Alternatives to antibiotics in the prophylaxis of recurrent uncomplicated infections in women

A infecção do trato urinário (ITU) é a doença bacteriana mais comum no sexo feminino, e cerca de 25% a 30% das mulheres apresentam ITUs recorrentes ao longo da vida. Os antibióticos são muito utilizados para o tratamento e prevenção dessas infecções. Entretanto, o uso excessivo e indevido desses medicamentos, além dos efeitos adversos, está relacionado ao surgimento de uropatógenos multirresistentes. Há um interesse crescente na comunidade científica para encontrar alternativas ao uso de antibióticos para tratamento e/ou prevenção das infecções bacterianas. Esta revisão tem por objetivo discutir algumas dessas alternativas.(AU)

Urinary tract infection (UTI) is the most common bacterial disease in females, and about 25% to 30% of women experience recurrent UTIs throughout their lives. Antibiotics are widely used standard for treating and preventing these infections. However, the excessive and improper use of these drugs, in addition to the adverse effects, is related to the emergence of multidrug-resistant uropathogens. There is a growing interest in the scientific community to find alternatives to the use of antibiotics for the treatment and/or prevention of bacterial infections. This review aims to discuss some of these alternatives.(AU)

The effect of kefir consumption on the lipid profile for individuals with normal and dyslipidemic properties: a randomized controlled trial / O efeito do consumo de kefir no perfil lipídico em indivíduos com propriedades normais e dislipidêmicas: um ensaio clínico randomizado

ABSTRACT Objective This research was conducted as a prospective, self-controlled, eight-week clinical trial to investigate the effect of kefir consumption on the lipid profile of individuals with normal and dyslipidemic properties. Methods Kefir microorganisms given to volunteer subjects were determined using classical microbial count methods and qReal-Time Polymerase Chain Reaction. The study was carried out with 23 volunteer hospital health personnel between the ages of 20 and 55 who met the research criteria and did not have any health problems. The volunteers regularly consumed kefir on an empty stomach for four weeks. In the last stage, the eight-week study was completed by making blood and anthropometric measurements of the subjects, who continued to be studied without kefir consumption for four more weeks. Results Considering the changes in the serum lipid profiles of 13 individuals with dyslipidemic symptoms during the 4-week period they consumed kefir, Total Cholesterol values decreased by 9.15% compared to initial values, LDL-Cholesterol values decreased by 10.64%, HDL-Cholesterol values decreased by 6.9%, and triglyceride values decreased by 2.46%. The changes in the serum lipid profiles of 13 individuals with dyslipidemic findings at the end of an eight-week study were a 5.71% decrease in total cholesterol values (p<0.018) considered statistically significant, as well as a 5.31% decrease in LDL-Cholesterol values (p<0.021); the HDL-Cholesterol results were found to be significant with an 8.58% decrease in the values (p<0.035) and insignificant with a 17.21% increase in the triglyceride values (p<0.926). We concluded that regular kefir consumption was effective in both women and men in lowering total cholesterol and LDL-Cholesterol from blood lipid profiles, especially in individuals with dyslipidemic symptoms, while this effect was not observed in normal individuals. Conclusion Kefir can positively affect the total cholesterol and LDL-Cholesterol blood parameters of dyslipidemic individuals with high serum lipid values.

RESUMO Objetivo Esta pesquisa foi conduzida como um ensaio clínico prospectivo e autocontrolado de oito semanas para investigar o efeito do consumo de kefir no perfil lipídico de indivíduos com propriedades normais e dislipidêmicas. Métodos Microrganismos kefir dados a voluntários foram determinados usando métodos clássicos de contagem microbiana e de reação em cadeia da polimerase em tempo real. O estudo foi conduzido em 23 profissionais de saúde de hospitais voluntários, com idades entre 20 e 55 anos, que atendiam aos critérios da pesquisa e não apresentavam problemas de saúde. Os voluntários consumiram kefir com o estômago vazio regularmente durante quatro semanas. No último estágio, o estudo de oito semanas foi concluído com medidas de sangue e antropométricas dos indivíduos, que continuaram a ser avaliados sem consumo de kefir por mais quatro semanas. Resultados Considerando as mudanças nos perfis lipídicos séricos de 13 indivíduos com sintomas dislipidêmicos durante o período de quatro semanas em que consumiram kefir, os valores de colesterol total diminuíram em 9,15% em comparação com os valores iniciais; os valores de LDL-Colesterol diminuíram em 10,64%, os valores de HDL-Colesterol diminuíram em 6,9% e os valores de triglicerídeos diminuíram em 2,46%. Ao final de um estudo de oito semanas, o resultado foi considerado estatisticamente significativo, com queda de 5,71% nos valores de colesterol total (p<0,018); de 5,31% nos valores de Colesterol-LDL (p<0,021) e de 8,58% nos valores de HDL-Colesterol (p <0,035), e insignificantes com aumento de 17,21% nos valores de triglicerídeos (p<0,926). Como resultado do estudo, concluiu-se que o consumo regular de kefir foi eficaz em mulheres e homens na redução do colesterol total e do LDL-Colesterol dos perfis de lipídios no sangue, especialmente em indivíduos com sintomas dislipidêmicos, enquanto esse efeito não foi observado em indivíduos normais. Conclusão O kefir pode afetar positivamente os parâmetros sanguíneos do colesterol total e do LDL-Colesterol de indivíduos dislipidêmicos com altos valores de lipídios séricos.

Impact of probiotics on the lung development of Bama minipig after premature birth / 中华儿科杂志

Objectives: To examine the impact of probiotics on the lung development of preterm birth of Bama pig. Methods: From April 2020 to October 2021, this animal experimental research was performed by setting up preterm (birth at gestation 104 d), full-term (birth at gestation 113 d), preterm with probiotics (birth at gestation 104 d treated with probiotics given at 3 d after birth), and full-term with probiotics (birth at gestation 113 d treated with probiotics given at 3 d after birth) groups and using the preterm Bama minipig model, the body weights were recorded and lung, ileum, and intestinal content samples were collected at birth, 4 days, 9 days, and 21 days after births of the piglets in preterm and full-term groups, the same samples were collected on 9 days after births of the piglets in preterm with probiotics and full-term with probiotics groups. The body weight and radial alveolar counts (RAC) were compared to evaluate the lung development of the piglets. The lengths of ileal villus were compared to evaluate the development of ileum. The composition structures of bacteria in ileum were analyzed by 16 S rRNA sequencing. The statistical analyses between different groups were performed by t test. Results: There were totally 30 piglets (16 female piglets and 14 male piglets) involving 12 piglets in preterm and full-term groups respectively and 3 piglets in preterm with probiotics and full-term with probiotics groups respectively. The body weights of the piglets in preterm group were lower than those in full-term group at 4, 9 and 21 d after birth ((507±27) vs. (694±56) g, (620±35) vs. (1 092±154) g, (1 660±210) vs. (2 960±418) g,t=2.96, 2.99, 2.78, all P<0.05). The alveolarization of the preterm piglets at 9 days after birth was significantly lower than that of the full-term piglets at the equivalent time point (4.00±0.29 vs. 6.11±0.35, t=4.64, P<0.01). The bacteria genus with the highest abundance in ileum were all different between the preterm and the full-term groups at 4, 9 and 21 d after birth (4 d Escherichia-Shigella (26.63%) and Enterococcus (30.48%) respectively;9 d Turicibacter (35.94%) and Lactobacillus (27.33%) respectively;21 d Escherichia-Shigella (28.02%) and Lactobacillus (46.29%) respectively). The heights of ileal villus of the preterm piglets at 9 d after birth were significantly lower than those of the full-term minipigs at the equivalent time point ((297±21) vs. (411±32) μm, t=3.01, P=0.007).There were both no differences in the body weight and alveolarization ((692±36) vs. (767±67) g, 5.44±0.34 vs. 5.89±0.26, t=0.74, 1.04, both P>0.05) between the piglets in preterm with probiotics group and those in full-term with probiotics group. Turicibacter was the dominant genus in the piglets of both preterm with probiotics and the full-term with probiotics groups. The heights of ileal villus of the piglets in preterm with probiotics group were significantly longer that those of the piglets in preterm group ((371±13) vs. (297±21) μm, t=3.04, P=0.006), and were both not significantly different from those of the piglets in full-term with probiotics group and full-term group ((371±13) vs. (338±12) and (411±32) μm, t=1.90, 1.15, both P>0.05). Conclusions: Premature birth could impact the lung alveolarization of piglets. The probiotics could improve the lung alveolarization of preterm minipigs by promoting the development of ileum.

Probiotics improves abnormal behavior and hippocampal injury in pregnant-stressed offspring rats / 中南大学学报(医学版)

OBJECTIVES@#During pregnancy, pregnant women are prone to stress reactions due to external stimuli, affecting their own health and fetal development. At present, there is no good treatment for the stress reactions from pregnant women during pregnancy. This study aims to explore the effect of probiotics on abnormal behavior and hippocampal injury in pregnant stressed offspring.@*METHODS@#SD pregnant rats were divided into a control group, a stress group, and a probiotics group, with 6 rats in each group. The control group was untreated; the stress group was given restraint stress on the 15th-20th day of pregnancy; the probiotics group was given both bifidobacterium trisporus capsules and restraint stress on the 15th-20th day of pregnancy, and the offspring continued to be fed with probiotics until 60 days after birth (P60). The offspring rats completed behavioral tests such as the open field test, the elevated plus maze test, the new object recognition test, and the barnes maze test at 60-70 d postnatally. Nissl's staining was used to reflect the injury of hippocampal neurons; immunohistochemical staining was used to detect the expression of microglia marker ionized calcium binding adapter molecule 1 (IBA-1) which can reflect microglia activation; ELISA was used to detect the content of plasma TNF-α and IL-1β; Western blotting was used to detect the expression of Bax, Bcl-2, and caspase-3.@*RESULTS@#The retention time of offspring rats in the stress group in the central area of the open field was significantly less than that in the control group (P<0.01), and the retention time of offspring rats in the probiotic group in the central area of the open field was significantly more than that in the stress group (P<0.05). The offspring rats in the stress group stayed in the open arm for a shorter time than the control group (P<0.05) and entered the open arm less often than the control group (P<0.01); the offspring rats in the probiotic group stayed in the open arm for a longer time than the stress group and entered the open arm more often than the stress group (both P<0.05). The discrimination ratio for new to old objects in the offspring rats of the stress group was significantly lower than that of the control group (P<0.01), and the discrimination ratio for new to old objects in the offspring rats of the probiotic group was significantly higher than that of the stress group (P<0.05). The offspring rats in the stress group made significantly more mistakes than the control group (P<0.05), and the offspring rats in the probiotic group made significantly fewer mistakes than the stress group (P<0.05). Compared with the control group, the numbers of Nissl bodies in CA1, CA3, and DG area were significantly reduced in the offspring rats of the stress group (all P<0.001), the number of activated microglia in DG area of hippocampus was significantly increased (P<0.01), the contents of TNF-α and IL-1β in peripheral blood were significantly increased (P<0.05 or P<0.01), the protein expression level of Bcl-2 was significantly down-regulated, and the protein expression levels of Bax and caspase-3 were significantly up-regulated (all P<0.001). Compared with the stress group, the numbers of Nissl bodies in CA1, CA3, and DG area were significantly increased in the probiotic group offspring rats (P<0.001, P<0.01, P<0.05), the number of activated microglia in the DG area of hippocampus was significantly reduced (P<0.05), and the TNF-α and IL-1β levels in peripheral blood were significantly decreased (both P<0.05), the protein expression level of Bcl-2 was significantly up-regulated, and the protein expression levels of Bax and caspase-3 were significantly down-regulated (all P<0.001).@*CONCLUSIONS@#Probiotic intervention partially ameliorated anxiety and cognitive impairment in rats offspring of pregnancy stress, and the mechanism may be related to increasing the number of neurons, inhibiting the activation of hippocampal microglia, and reducing inflammation and apoptosis.

Is Regular Probiotic Practice Safe for Management of Sepsis? / 中国结合医学杂志

For decades, the gut has been thought to play an important role in sepsis pathogenesis. Sepsis is a serious life-threatening, chronic condition of an infection caused by dysregulated host immune response in most of the intensive care unit patients. Probiotics have dual roles in polymicrobial sepsis i.e. probiotics may induce sepsis in many cases and may prevent its prognosis in many cases. Experimental evidence from both pre-clinical and clinical studies have demonstrated that probiotic therapy ameliorates various inflammatory mediators such as tumor necrosis factor, interleukin-10 (IL-10), IL-6, etc., in septicemia. In addition, probiotic use was also found to reduce the severity of pathological conditions associated with irritable bowel disorder and prevent development of endocarditis in septicemia. On contrary, probiotic therapy in neonatal and athymic adult mice fail to provide any beneficial effects on mortality and sepsis-induced inflammation. Importantly, in few clinical trials probiotic use was found to aggravate sepsis by promoting inflammatory cascade rather than suppressing it. This review discusses various studies regarding the beneficial or harmful effects associated with probiotic therapy in sepsis.

O que as revisões sistemáticas Cochrane dizem sobre as intervenções com probióticos em crianças? / What are systematic reviews Cochrane say about interventions with probiotics in children?

Contextualização: Os probióticos constituem microrganismos vivos que, em quantidades adequadas, podem ser benéficos à saúde. Foram incorporados a produtos industrializados e suplementos e, atualmente, são amplamente utilizados. Entretanto, os efeitos podem ser diferentes em crianças e adultos, o que demanda cautela quanto à generalização de seus efeitos e a utilização exagerada. Objetivo: O presente estudo teve como objetivo avaliar as revisões sistemáticas desenvolvidas pela Cochrane no que concerne às intervenções com probióticos para crianças. Metodologia: Trata-se de overview de revisões sistemáticas Cochrane. Procedeu-se à busca por revisões sistemáticas na Cochrane Library. Foi utilizado o termo MeSH "probióticos". Os critérios de inclusão envolveram intervenções quaisquer com probióticos para crianças. Resultados: A estratégia de busca recuperou 56 revisões sistemáticas e, destas, 11 foram incluídas, diante dos critérios de inclusão e exclusão estabelecidos, totalizando 50.647 participantes avaliados a partir de 277 ensaios clínicos randomizados. Discussão: A maior evidência, em nível moderado, para o uso de probióticos em crianças encontra respaldo nas revisões sistemáticas Cochrane no que tange à prevenção da diarreia concomitante ao uso de antibióticos e na prevenção da diarreia causada por Clostridium. Para análise e qualificação de melhor nível de evidência de outros desfechos, é necessária a realização de novos ensaios clínicos de qualidade. Conclusão: A utilização de probióticos, amplamente recomendada atualmente, não tem efetividade tão promissora encontrada nas revisões sistemáticas Cochrane realizadas até esse momento.

Probiotic Saccharomyces boulardii Alleviates Lung Injury by Reduction of Oxidative Stress and Cytokine Response Induced by Supraceliac Aortic Ischemia-Reperfusion Injury in Rats

Abstract Objectives: Ischemia-reperfusion injury is an important cause of multiple organ failure in cardiovascular surgery. Our aim is to investigate the effect of the probiotic Saccharomyces boulardii on oxidative stress, inflammatory response, and lung injury in an experimental model of aortic clamping. Methods: Twenty-one Wistar rats were randomized into three groups (n=7). Control group animals received saline gavage for a week before undergoing median laparotomy. In other groups, supraceliac aorta was clamped for 45 minutes to induce ischemia followed by reperfusion for 60 minutes. In the ischemia-reperfusion group, saline gavage was given preoperatively for one week. Ischemia-reperfusion+probiotic group rats received probiotic gavage for seven days before aortic clamping. The levels of oxidative stress markers and pro-inflammatory cytokines were determined in both serum and lung tissue samples. Ileum and lung tissues were harvested for histological examination. Results: Ischemia-reperfusion caused severe oxidative damage and inflammation evident by significant increases in malondialdehyde and cytokine levels (tumor necrosis factor alpha and interleukin-1 beta) and decreased glutathione levels in both serum and lung tissues. There was severe histological tissue damage to the lung and ileum in the ischemia-reperfusion group. Probiotic pretreatment before aortic clamping caused significant suppression of increases in serum and lung tissue malondialdehyde and tumor necrosis factor alpha levels. Histological damage scores in tissue samples decreased in the ischemia-reperfusion+probiotic group (P<0,005). Conclusions: Oral supplementation of probiotic S. boulardii before supraceliac aortic ischemia-reperfusion in rats alleviates lung injury by reducing oxidative stress, intestinal cellular damage, and modulation of inflammatory processes.

Intervención con probióticos para la prevención de enterocolitis necrotizante en prematuros extremos menores de 1500 gramos o de 32 semanas / Probiotic intervention to prevent necrotizing enterocolitis in extremely preterm infants born before 32 weeks of gestation or with a birth weight of less than 1500 g

Introducción. Existe evidencia del beneficio de los probióticos en prevenir enterocolitis necrotizante en prematuros extremos. Desde 2015, se usa probiótico preventivo en el Servicio de Neonatología, Hospital Hernán Henríquez Aravena, Temuco, Chile.Objetivo. Evaluar el impacto de este probiótico en la incidencia, gravedad, necesidad de terapia quirúrgica y letalidad por enterocolitis necrotizante en prematuros extremos. Pacientes y método. Estudio retrospectivo de cohortes. Datos analizados con Stata. Se aplicó la prueba exacta de Fisher para comparar porcentajes y, para los promedios, la prueba t para varianzas distintas. Los egresados entre 2015 y 2017 recibieron Lactobacillus reuteri Protectis (LRP), dosis única (1 x 108 unidades formadora de colonias) desde los primeros días de vida hasta cumplir las 36 semanas de edad gestacional corregida. Los controles egresados entre 2012 y 2014 no recibieron LRP.Resultados. El 3,45 % de los casos tuvo algún grado de enterocolitis: grado i (el 64 %), ii (el 18 %), iii (el 18 %); requirió cirugía el 18 % y no hubo letalidad. El 3,75 % de los controles históricos presentaron enterocolitis: grado i (el 12 %), ii (el 35 %), iii (el 53 %); el 64,7 % requirió cirugía, y el 47 % falleció. El grupo intervenido presentó grado ii o iii en un 36 %; en el grupo control, la sumatoria de estos estadios fue del 88 %.Conclusión.LRP administrado en dosis única diaria al prematuro extremo no modificó la incidencia de enterocolitis, pero disminuyó su gravedad, la letalidad y necesidad de tratamiento quirúrgico.

Introduction. There is evidence of the beneficial effects of probiotics to prevent necrotizing enterocolitis in extremely preterm infants. Probiotic prevention has been used since 2015 in the Division of Neonatology of Hospital Hernán Henríquez Aravena, Temuco, Chile.Objective. To assess the impact of this probiotic on the incidence, severity, surgical treatment requirement, and fatality rate of necrotizing enterocolitis in extremely preterm infants.Patients and methods. Retrospective, cohort study. Data were analyzed using Stata. Fisher's exact test was used to compare percentages, and the unequal variances t-test, for averages. Infants discharged between 2015 and 2017 received Lactobacillus reuteri Protectis (LRP), in a single dose (1 x 108 colony forming units), since the first days of life until 36 weeks of corrected gestational age. Controls discharged between 2012 and 2014 did not receive LRP.Results. Some degree of enterocolitis was observed in 3.45 % of cases: stage I (64 %), stage II (18 %), stage III (18 %); 18 % required surgery, and there were no deaths. Among historical controls, 3.75 % had enterocolitis: stage I (12 %), stage II (35 %), stage III (53 %); 64.7 % required surgery, and 47 % died. In the intervention group, stage II or III accounted for 36 % of cases, whereas in the control group, for 88 %.Conclusion. Administering a single daily dose of LRP to extremely preterm infants did not affect the incidence of enterocolitis, but reduced its severity, fatality rate, and surgical treatment requiremen

Evaluation of mean gray values of a cat with chronic renal failure: case report / [Avaliação dos valores médios de cinza em um gato com insuficiência renal crônica: relato de caso]

In this case, a 12-year-old female domestic cat with chronic renal failure (CRF), which had lived longer than the mean survival time for cats with that condition, was monitored to evaluate the effects of treatment and mean gray value (MGV) changes. The cat has lived for nearly four years since the diagnosis. Probiotics have been used as an additional, classical supportive therapy since the beginning of treatment. The temporal changes in renal MGV were statistically evaluated in the last year of the four-year period. The cat had a comfortable existence and good body condition all her life and probiotic therapy may have had a positive influence post-CRF diagnosis. Ultrasonography (US) examination is a commonly used tool for monitoring the CRF situation, but it is not particularly sensitive. Therefore, MGV may be more useful for the quantitative evaluation of the extent of renal failure. Also, to the best of our knowledge, this is the first report for a long-term clinical evaluation of MGV in a cat with CRF. The aim of this case report was the evaluation of the relationship between MGV and clinical and biochemical changes in a cat with chronic renal failure.(AU)

No presente caso, uma gata doméstica de 12 anos com insuficiência renal crônica (IRC), que viveu mais do que o tempo médio de sobrevivência para gatos nessa condição, foi monitorada para avaliar os efeitos do tratamento e as alterações do valor cinza médio (MGV). A gata viveu quase quatro anos desde o diagnóstico. Os probióticos têm sido usados como uma terapia de suporte clássica adicional desde o início do tratamento. As alterações temporais do MGV renal foram avaliadas estatisticamente no último ano do período de quatro anos. A gata teve uma existência confortável e boas condições corporais durante toda a vida e a terapia com probióticos pode ter tido uma influência positiva após o diagnóstico de IRC. O exame de ultrassonografia (US) é uma ferramenta comumente usada para monitorar a situação da IRC, mas não é particularmente sensível. Portanto, o MGV pode ser mais útil para a avaliação quantitativa da extensão da insuficiência renal. Além disso, até onde se sabe, este é o primeiro relatório de uma avaliação clínica de longo prazo de MGV em um gato com IRC. O objetivo deste relato de caso foi avaliar a relação entre o MGV e as alterações clínicas e bioquímicas em um gato com insuficiência renal crônica.(AU)

Efficacy of probiotics in preventing late-onset sepsis in very low birth weight infants: a Meta analysis / 中国当代儿科杂志

OBJECTIVE@#To study the efficacy of probiotics in preventing late-onset sepsis (LOS) in very low birth weight (VLBW) infants.@*METHODS@#Databases including PubMed, Web of Science, Cochrane Library, Wanfang Data, China National Knowledge Infrastructure, and Chinese Biomedical Literature Database were searched for randomized controlled trials (RCTs) of probiotics in preventing LOS in VLBW infants. LOS was classified as clinical LOS and confirmed LOS. RevMan 5.4 was used to perform the Meta analysis.@*RESULTS@#A total of 31 RCTs were included, with 3 490 VLBW infants in the probiotics group and 3 376 VLBW infants in the control group. The Meta analysis showed that compared with the control group, the probiotics group had significantly lower risks of clinical LOS (@*CONCLUSIONS@#Current evidence indicates that probiotics may reduce the risk of clinical LOS and clinical/confirmed LOS in VLBW infants, and the risk of confirmed LOS in VLBW infants who are exclusively breastfed.

Aportes de la biotecnología al diagnóstico y tratamiento de la enfermedad renal crónica y comorbilidades frecuentes / Biotechnology contribution to the diagnosis and treatment of chronic kidney disease and frequent comorbidities

Este trabajo tiene como objetivo revisar las contribuciones de la biotecnología, en relación con el tratamiento, diagnóstico y la monitorización de la enfermedad renal crónica (ERC) y sus comorbilidades más frecuentes, especialmente la anemia. En relación con los tratamientos, enfocamos el desarrollo de productos biofarmacéuticos como los agentes estimulantes de la eritropoyesis (ESA), que fueron los primeros biofármacos utilizados para el tratamiento de la anemia asociada a la ERC; analizamos sus características y utilización actual después de varios años de experiencia clínica, así como también otras alternativas en desarrollo. Revisamos distintos tipos de bioterapias, la utilización de las células estromales mesenquimales de médula ósea (MSC) y tratamientos alternativos con modificaciones dietarias, que se basan en la asociación entre la microbiota intestinal de los pacientes renales crónicos y sus condiciones fisiopatológicas. Finalmente, en relación con el diagnóstico y monitorización, nos referimos al estudio y validación de biomarcadores diagnósticos, predictivos y terapéuticos que han permitido optimizar los resultados clínicos en este tipo de pacientes. (AU)

The aim of this work is to review the contributions of biotechnology, in relation to the treatment, diagnosis and monitoring of chronic kidney disease (CKD) and its most frequent comorbidities, especially anemia. Regarding the treatment, we focus on the development of biopharmaceutical products such as erythropoiesis stimulating agents (ESA), which were the first biopharmaceuticals used to treat anemia associated with chronic kidney disease (CKD). We analyzed their characteristics and their current use after several years of clinical experience, as well as other alternatives in development. We also review different types of biotherapies, the use of bone marrow mesenchymal stromal cells (MSC) and alternative treatments with dietary modifications, which are based on the association between the intestinal microbiota of chronic kidney patients and their pathophysiological conditions. Finally, in relation to diagnosis and monitoring, we refer to the study and validation of diagnostic, predictive and therapeutic biomarkers that have made clinical results possible to be optimized in this type of patient. (AU)

Potencialidades de los probióticos en el escenario de pandemia COVID-19 / Potential of probiotics in the Covid-19 pandemic scenario

La pandemia COVID-19 iniciada en diciembre de 2019 en Wuhan, China, ha captado la atención de la comunidad científica internacional debido a su alta propagación en el mundo, causada por el virus SARS-CoV-2 que se transmite por vías respiratorias y gastrointestinal, y ante la situación de no tenerse identificada una terapia farmacológica efectiva de carácter preventivo o curativo.En vista de ello, cada país se ha visto en la necesidad de implementar terapias alternativas que muestren algún grado de efectividad contra la enfermedad COVID-19. Entre las alternativas que se han reportado, múltiples estudios demuestran el potencial de los probióticos para prevenir la infección con este virus y combatir la enfermedad, al reflejar que existen relaciones entre los microbiomas de las vías respiratorias y gastrointestinales, y con el consumo de probióticos se modula el sistema inmunológico al reestablecer el balance gastrointestinal, lo cual implica la respuesta del sistema inmune para combatir la enfermedad y próximas pandemias, ya que el tracto digestivo es un punto focal de las defensas del cuerpo,y por ende, en la prevención de la infección viral. Ante estos potenciales, más gobiernos deberían financiar los ensayos con probióticos como parte de la estrategia general para aplanar la curva de propagación de la pandemia de la COVID-19(AU)

Saccharomyces cerevisiae as a probiotic agent and a possible aflatoxin B1 adsorbent in simulated fish intestinal tract conditions / Saccharomyces cerevisiae como agente probiótico e possível adsorvente de aflatoxina B1 em condições simuladas do trato intestinal de peixes

The aim of this study was to evaluate in vitro the probiotic potential and absorption of Saccharomyces cerevisiae for the aflatoxin B1 in simulated fish intestinal tract conditions. Three yeast strains were used, two from brewery: S. cerevisiae RC1 and S. cerevisiae RC3 and one from a fish farming environment: S. cerevisiae A8L2. The selected yeasts were subjected to the following in vitro tests: homologous inhibition, self-aggregation, co-aggregation, antibacterial activity, gastrointestinal conditions tolerance and adsorption of AFB1. All S. cerevisiae strains showed good capability of self-aggregation and co-aggregation with pathogenic bacteria. All yeast strains were able to survive the gastrointestinal conditions. In acidic conditions, the factors (strain vs. time) had interaction (P=0.0317), resulting in significant variation among the strains tested in the time periods analyzed. It was observed that there was also interaction (P=0.0062) in intestinal conditions, with an increased number of cells in the 12-hour period for all strains tested. In the adsorption test, the A8L2 strain was statistically more effective (P<0.005) for both AFB1 concentrations evaluated in this study (10 and 25ng/mL). Thus, it was observed that the strains of S. cerevisiae have potential probiotic and adsorbent of AFB1.(AU)

Objetivou-se, com esta pesquisa, avaliar in vitro o potencial probiótico e adsorvente de Saccharomyces cerevisiae para aflatoxina B1 em condições simuladas do trato intestinal de peixes. Foram utilizadas três cepas de leveduras, sendo duas provenientes de cervejaria: S. cerevisiae RC1 e S. cerevisiae RC3, e uma de ambiente de piscicultura: S. cerevisiae A8L2. As leveduras selecionadas foram submetidas aos seguintes testes in vitro: inibição homóloga, autoagregação, coagregação, atividade antibacteriana, viabilidade às condições gastrointestinais e adsorção de AFB1. Todas as estirpes de S. cerevisiae mostraram boa capacidade de autoagregação e coagregação com bactérias patogênicas. Todas as estirpes de levedura foram capazes de sobreviver às condições gastrointestinais. Em condições ácidas, os fatores (cepa x tempo) tiveram interação (P=0,0317), resultando em variações significativas entre as cepas testadas nos períodos de tempo analisados. Observou-se que também houve interação (P=0,0062) em condições intestinais, havendo um aumento do número de células no período de 12h para todas as cepas avaliadas. No ensaio de adsorção, a estirpe A8L2 foi a mais eficaz estatisticamente (P<0,005), para as duas concentrações de AFB1 avaliadas neste estudo (10 e 25ng. mL-1). Dessa forma, conclui-se que as cepas de Saccharomyces cerevisiae possuem potencial probiótico e adsorvente de AFB1.(AU)