Litografie-gebaseerde keramiekvervaardiging (LCM) is 'n laagvervaardigingstegnologie (LV) wat pasgemaakte, driedimensionele keramiekonderdele laag vir laag bou. Die vlak van akkuraatheid van die proses maak voorsiening vir die druk van pasgemaakte intern-aaneenlopende roosterstrukture en ontwerpe wat geskik is vir beenimplantate. Hierdie studie het die LCM-veraardigbaarheid van verskeie roosterstrukture ondersoek met die hidroksieapatiet (HA480) verskaf deur Lithoz. Verskillende roosterstrukture is gekarakteriseer. Die mikroskopiese struktuur, die samestelling en die oppervlakrofheid van die toetsmonsters is bepaal. Om die meganiese eienskappe van die strukture te verkry, is druktoetse uitgevoer. Die waargenome mikroporieë van ±3 µm en die makroporieë van ±320 µm was geskik vir beenselgroei. Die gemete mikrohardheid van HA480 was 556±25 HV in die bourigting en 559±27 HV loodreg op die bourigting. Die druksterkte van die rombiese dodekaëderroosterstruktuur was 4±0.5 MPa, en was beter as ander getoetste roosters. Uit die resultate is tot die gevolgtrekking gekom dat roosterstrukture wat deur LCM vervaardig word, die potensiaal het om gebruik te word vir vervaardiging van pasgemaakte beenregenererende steiers.

Lithography-based ceramic manufacturing (LCM) is an additive manufacturing (AM) technology that builds custom-designed, three-dimensional ceramic parts layer by layer. The level of precision of the process allows for the printing of custom-made interconnected lattices and designs suitable for bone implants. This study investigated the LCM printability of various lattice structures with the hydroxyapatite (HA480) supplied by Lithoz. Different lattice structures were characterised. The microscopic structure, the composition, and the surface roughness of the test specimens were determined. To obtain the mechanical properties of the structures, compression tests were performed. The observed micropores of ±3 µm and the macropores of ±320 µm were suitable for bone cell growth. The measured microhardness of HA480 was 556±25 HV in the built direction and 559±27 HV perpendicular to the built direction. The compressive strength of the rhombic dodecahedron lattice structure was 4±0.5 MPa, and was superior to other tested lattices. From the results it was concluded that lattice structures produced through LCM have the potential to be used to produce customised bone-regenerating scaffolds.

Introdução: Metástase óssea é a neoplasia maligna mais comum do esqueleto, e a tomada de decisão cirúrgica depende de múltiplos fatores, incluindo as complicações pós-operatórias e a expectativa de vida. A identificação de novos fatores prognósticos pode auxiliar na tomada de decisão. Objetivo: Analisar em metástases de ossos longos, a incidência de complicações e sobrevida pós-operatórias até 1 ano correlacionando-as com NLR e PLR. Método: Revisão de 160 prontuários de operados por metástase óssea no esqueleto apendicular. Além de características epidemiológicas, foram determinados os valores de NLR e PLR correlacionando-os com sobrevida e complicações. Resultado: Mulheres representaram 64,5% com tumor primário na mama em 62,6%; o fêmur proximal foi o mais acometido; sobrevida média foi 13,2 meses e a de 1 ano 34,7%; ressecção tumoral com endoprótese foi mais comum. A taxa de complicação pós-cirúrgicas foi de 10% e o tempo médio para a ocorrência de complicações pós-operatórias foi de 27,9 dias (0-140). Foi encontrada associação da variável neutrófilos com a complicação pós-operatória (p=0,04). A cada 100 unidades a mais de neutrófilos houve aumento de 1% nas chances de complicações pós-cirúrgicas. Valores médios do NLR e PLR foram, respectivamente, 5,3 (0,2-30,7) e 199,7 (32,1-676,7).  Os pacientes com NLR ≥ 2 (p<0,001) apresentaram diminuição na sobrevida de 92,3% para 62,5% no 3° mês e de 61,5% para 31,3% em 1 ano. Aqueles com PLR ≥209 (p<0,001) apresentaram diminuição na sobrevida de 69% para 59,3% no 3° mês, e de 40,2% para 25,9% em 1 ano. Conclusão: Não foi verificada associação positiva entre o NLR e o PLR com complicações pós-operatórias, mas com sobrevida fortemente sim, a partir do 3° mês de pós-operatório.

Introduction: Bone metastasis is the most common malignant neoplasm of the skeleton, and surgical decision-making depends on multiple factors, including postoperative complications and life expectancy. The identification of new prognostic factors can assist in decision making. Objective: In long bones metastases, to analyze the incidence of complications and postoperative survival up to 1 year, correlating them with NLR and PLR. Method: Review of 160 medical records of patients who underwent surgery for bone metastasis in the appendicular skeleton. In addition to epidemiological characteristics, NLR and PLR values were determined, correlating them with survival and complications. Result: Women represented 64.5% with a primary breast tumor in 62.6%; the proximal femur was the most affected; median survival was 13.2 months and in 1 year 34.7%. Tumor resection with endoprosthesis was more common. The post-surgical complication rate was 10% and the average time for post-operative complications to occur was 27.9 days (0-140). An association between the neutrophil variable and postoperative complications was found (p=0.04). For every 100 more units of neutrophils there was a 1% increase in the chances of post-surgical complications. Mean NLR and PLR values were, respectively, 5.3 (0.2-30.7) and 199.7 (32.1-676.7). Patients with NLR NLR ≥ 2 (p<0,001) showed a decrease in survival from 92,3% to 62,5% at the 3rd month, and from 61,5% to 31,3% at 1 year. Those with PLR ≥209 (p<0.001) showed a decrease in survival from 69% to 59.3% at the 3rd month, and from 40.2% to 25.9% at 1 year. Conclusion: There was no positive association between NLR and PLR with postoperative complications, but strongly yes with survival from the 3rd month after surgery.

Introduction: In general, inflammation stimulates the production and release of neutrophils and, at the same time, decreases the production of lymphocytes. Lymphopenia reflects that cell-mediated immunity is impaired, while neutrophilia represents a response to systemic inflammation in these cancers. Objective: To review the incidence of complications and postoperative survival rates in patients with bone metastases in long bones, correlating them with markers NLR and PLR. Method: Narrative review carried out collecting information published on virtual platforms in Portuguese and English, initially carried out by searching for descriptors related to the topic, which were: “lower extremity, surgery, metastasis, epidemiology, postoperative complications, neutrophils, lymphocytes, platelets”. The extension incorporated AND or OR, by title and/or summary, and full reading of the texts most related to the topic. Result: 21 articles were included. Conclusion: The higher both the NLR and PLR are associated with lower survival in patients with bone metastases when undergoing surgical treatment, especially after 3 months postoperatively. However, there is still no confirmation that they signal any outcome, favorable or not, in relation to postoperative complications.

Introdução : De um modo geral, a inflamação estimula a produção e liberação de neutrófilos e, ao mesmo tempo, diminui a produção de linfócitos. A linfopenia reflete que a imunidade mediada pelas células é prejudicada, enquanto a neutrofilia representa resposta à inflamação sistêmica nesses cânceres. Objetivo : Revisar nos pacientes com metástase óssea em ossos ao longo da incidência de complicações e taxas de sobrevida pós-operatória correlacionando-as com os marcadores NLR e PLR. Método : Revisão narrativa feita colhendo informações publicadas em plataformas virtuais em português e inglês inicialmente realizada por busca dos descritores relacionados ao tema que foram: “extremidade inferior, cirurgia, metástase, epidemiologia, complicações pós-operatórias, neutrófilos, linfócitos, plaquetas” e seus equivalentes em inglês “ extremidade inferior, cirurgia, metástase, epidemiologia, sobrevivência, complicações, neutrófilos, linfócitos, plaquetas sanguíneas ”. A extensão incorporou AND ou OR, pelo título e/ou resumo, e leitura na íntegra dos textos mais relacionados ao tema.  Resultado : Foram incluídos 21 artigos. Conclusão : Quanto maiores, tanto o NLR quanto o PLR estão associados à menor sobrevida em pacientes com MO quando submetidos ao tratamento cirúrgico, especialmente após 3 meses de pós-operatório. Contudo, ainda não há confirmação de que eles sinalizam algum estágio, positivo ou não, em relação às complicações pós-operatórias.

Introdução: O L-PRF é concentrado de plaquetas e leucócitos em rede de fibrina, obtido pela centrifugação autóloga coletada no momento da cirurgia. Faz parte da segunda geração de concentrados plaquetários, sendo de baixo custo, fácil preparo, simples obtenção e tem a capacidade de acelerar a cicatrização de tecidos moles e duros. Objetivo: Revisar o reparo ósseo de defeitos não críticos em calvária utilizando o L-PRF isoladamente e em associação com osso autógeno particulado. Método: Revisão integrativa da literatura retirada das plataformas SciELO, Pubmed e Scopus em inglês e português utilizando os seguintes descritores: “L-PRF, cicatrização óssea, defeitos em calvária. Coelhos” em AND ou OR pelo título ou resumo. Após a seleção apenas os artigos cosiderados pertinentes foram lidos na íntegra. Resultados: Foram incluídos 39 artigos. Conclusão: O L-PRF isoladamente teve efeito positivo na formação óssea no decorrer das semanas.

Introduction: L-PRF is a concentrate of platelets and leukocytes in a fibrin network, obtained by autologous centrifugation collected at the time of surgery. It is part of the second generation of platelet concentrates, being low cost, easy to prepare, simple to obtain and has the ability to accelerate the healing of soft and hard tissues. Objective: To review bone repair of non-critical calvarial defects using L-PRF alone and in association with particulated autogenous bone. Method: Integrative review of literature taken from the SciELO, Pubmed and Scopus platforms in English and Portuguese using the following descriptors: “L-PRF, bone healing, calvarial defects, rabbit” in AND or OR by the title or summary. After selection, only articles considered relevant were read in full. Results: 39 articles were included. Conclusion: L-PRF alone had a positive effect on bone formation over the weeks.

RESUMEN Introducción: La herida es una pérdida de continuidad de la piel o mucosa producida por algún agente físico o químico. Una herida es “compleja” cuando por su extensión, localización, profundidad o exposición de elementos nobles, necesita para su curación una terapéutica especial. Este es el caso de heridas con compromiso tisular que afecta a estructuras como músculos, fascias, tendones, huesos, vasos sanguíneos, nervios o las lesiones de lenta evolución como úlceras o escaras. Objetivos: Determinar el método de reconstrucción más utilizado en el manejo terapéutico de las heridas complejas del tercio distal de la pierna en los pacientes atendidos en el Hospital de Trauma y en la Unidad de Cirugía Plástica de la FCM - UNA. Materiales y métodos: Estudio de diseño observacional, tipo de estudio descriptivo y retrospectivo. Fueron incluidos pacientes de ambos sexos, mayores de edad, con heridas complejas en el tercio distal de la pierna, atendidos en el Hospital de Trauma y en la Unidad de Cirugía Plástica de la FCM - UNA, durante el periodo 2010 al 2019. Resultados: Se incluyó a 112 pacientes de los cuales el 80,36 % fue hombres y el 19,64 % mujeres. Las edades estaban comprendidas entre los 18 y los 73 años y una media de 33,8 ± 14 años. La edad más frecuente fue 18 años. La mediana de edad es de 30 años, lo que implica que la mitad de la muestra tuvo por lo menos dicha edad. En cuanto a la procedencia, el 41,07 % era del interior, el 30,36 % del departamento Central y el 28,57 % restante de Asunción. En cuanto al mecanismo de la lesión, se puede observar que el mecanismo más frecuente fue el accidente de tráfico, seguido por caída de altura, en un gran porcentaje. En cuanto a la evolución y complicaciones se puede ver que 92 individuos, o sea 82 % de los pacientes no tuvo ninguna evolución negativa o complicaciones. Lo más común fue la infección con 1,9% de prevalencia, la pérdida parcial del colgajo o piel representan el 2,4%, dehiscencia de la sutura el 0,9 %, hematoma 0,6 % y pérdida total del colgajo 0,54 %. En cuanto al tratamiento aplicado, se debe tener en cuenta que los pacientes pudieron haber recibido más de un tratamiento por lo que el tamaño de la muestra se refiere a las visitas. El tratamiento más frecuente fue el colgajo sural con 28,57%, tutor externo con el 20,19%, injerto de piel 16,46%, toillete 12,73% y colgajo fascio - cutáneo en 6,21%. Conclusión: La gran mayoría de los casos tratados corresponde a algún tipo de accidente de tránsito. Se necesita de un equipo multidisciplinario: ortopedistas, cirujanos plásticos, cirujanos vasculares, fisioterapeutas, etc. en trabajo coordinado para tratar estas graves lesiones de forma a obtener resultados favorables. Para la cobertura de la pierna traumatizada, con exposición ósea, recurrimos a los colgajos musculares, en el 1/3 proximal el gemelo, en el 1/3 medio el sóleo. Para la cobertura del 1/3 distal de la pierna utilizamos el colgajo neuro-veno-fascio-cutáneo (sural) a pedículo distal.

ABSTRACT Introduction: The wound is a loss of continuity of the skin or mucosa produced by some physical or chemical agent. A wound is “complex” when due to its extension, location, depth, exposure of noble elements, it requires special therapy to heal. This is the case of wounds with tissue involvement that affects structures such as muscles, fascia, tendons, bones, blood vessels, nerves, or slowly evolving lesions such as ulcers or bedsores. Objectives: Determine the reconstruction method most used in the therapeutic management of complex wounds of the distal third of the leg in patients treated at the Trauma Hospital and the Plastic Surgery Unit of the FCM - UNA. Materials and methods: Observational, descriptive, and temporally retrospective study. Patients of both sexes, of legal age, with complex wounds in the distal third of the leg, treated at the Trauma Hospital and in the Plastic Surgery Unit of the FCM - UNA, during the period 2010 to 2019, were included. Results: 112 patients were included, of which 80.36% are men and 19.64% are women. The ages range from 18 to 73 years and an average of 33.8 ± 14 years. The most common age was 18 years. The median age is 30 years, which implies that half of the sample is at least that age. Regarding origin, 41.07% are from the interior, 30.36% from the Central department and the remaining 28.57% from Asunción. Regarding the mechanism of injury, the most frequent mechanism was a traffic accident, followed by a fall from a height, in a large percentage. Regarding the evolution and complications, 92, that is, 82% of the patients do not have any negative evolution or complications. The most common was infection with 1.9%, partial loss of the flap or skin represented 2.4%, suture dehiscence with 0.9%, hematoma 0.6%, and total loss of the flap 0.54. %. Regarding the treatment applied, it must be considered that patients may have received more than one treatment, so the sample size refers to visits. The most frequent treatment was the sural flap with 28.57%, external tutor with 20.19%, skin graft 16.46%, toilette 12.73% and fasciocutaneous flap in 6.21%. Conclusion: Most cases treated correspond to some type of traffic accident. A multidisciplinary team is needed: orthopedists, plastic surgeons, vascular surgeons, physiotherapists, etc. in coordinated work to treat these serious injuries to obtain favorable results. To cover the traumatized leg, with bone exposure, we resort to muscle flaps. In the proximal 1/3, the gastrocnemius. In the middle 1/3, the soleus. To cover the distal 1/3 of the leg we used the neuro-veno-fascio-cutaneous (sural) flap to the distal pedicle.

Flouride contamination of water is recognised as a serious challenge facing humanity. Consumption of water that contains excessive amounts of fluoride can result in fluorosis. Consequently, concerted efforts have been made to develop cheap, effective and green techniques/materials to remove fluoride from water, particularly potable water. Bone char prepared from bovine, swine, and equine bones has been used extensively in this regard, and is the most promising, cheap and green material for treating drinking water with high fluoride concentration, particularly in developing countries. However, research on bone char prepared from bones of animals in the wild, as well as those from domestic and semi-wild animals treated with antibiotics to enhance growth, has been scanty. Such research is important as the use of antibiotics may alter the composition of bones, and thus their potential as a green adsorbent to remove fluoride may be impaired. Furthermore, little attempt has been made so far to package char bones for easy application domestically, particularly in rural communities. SIGNIFICANCE: • Contamination of water by fluoride is a major problem globally. • Various techniques and materials have been employed for water defluoridation, including the use of bone char, which has several advantages. • Bone char prepared from bones of animals in the wild and those from domestic and semi-wild animals treated with antibiotics to enhance growth should be further investigated. • Cheaper and less elaborate processes and packaging are required to scale down the use of bone char at domestic level.

ABSTRACT In sheep, there is a relationship between the mass of the crural muscles and the greater or lesser ability to walk in turn perhaps related to body proportions, so there could be functional differences between breeds, based on different motor skills. The calcaneal bone represents the base of insertion of the crural muscles responsible in part for walking. To corroborate this hypothesis, it was obtained digital images of 28 calcanei of domestic sheep of four breeds from the Iberian Peninsula: Churra, Merina, Merino preto and Merino branca. The images were analysed using geometric morphometry techniques from 20 anatomical landmarks (bone points). There appeared significant differences between breeds, both for shape and size, being greater in merinos. It can be deduced that the conformation of the calcaneus reflects an area of enthesis which varies according to the greater or lesser development of the crural muscles. It is considered that these differences between breeds are mainly explained by the body conformation rather than dynamogenic capacity.

RESUMEN En el ovino, hay una relación de la masa de los músculos crurales con la mayor o menor aptitud a la marcha, a su vez quizás relacionada con las proporciones corporales, por lo que podrían darse diferencias funcionales entre razas, a tenor de aptitudes motoras diferentes. El hueso calcáneo representa la base de inserción de los músculos crurales responsables en parte de la marcha. Para corroborar esta hipótesis, se obtuvieron imágenes digitales de 28 calcáneos de ovejas domésticas de cuatro razas de la Península Ibérica: Churra, Merina, Merino preto y Merino branca. Las imágenes se analizaron mediante técnicas de morfometría geométrica a partir de 20 hitos anatómicos (puntos óseos). Se obtuvieron diferencias significativas entre razas, tanto para la forma como para el tamaño, siendo mayor en los merinos. Se deduce que la conformación del calcáneo refleja un área entésica que es variable según el mayor o menor desarrollo de los músculos crurales. Se considera que estas diferencias entre razas son debidas mayor-mente a una cuestión de conformación corporal más que de capacidad dinamógena.

Abstract Undifferentiated pleomorphic sarcoma (UPS) is a very aggressive malignant tumor that originates in bone or soft tissues, being its most frequent location in the extremities. We present the case of a 71-year-old man who, two years of follow-up after a lower right limb UPS excision surgery, presented a single metastasis of sarcomatoid origin in the pancreas that was treated by cephalic pancreaticoduodenectomy. Sarcomatoid metastases to the pancreas are extremely rare. Resection of the metastasis is the only therapeutic alternative that has reported benefit in terms of the survival of these patients.

Resumen El sarcoma pleomórfico indiferenciado (SPI) es un tumor maligno muy agresivo que se origina en el hueso o tejidos blandos, siendo su localización más frecuente en las extremidades. Presentamos el caso de un varón de 71 años que a los dos años de seguimiento tras cirugía de exéresis de un SPI presenta una metástasis única de origen sarcomatoide a nivel del páncreas que se trató mediante duodenopancreatectomía cefálica. Las metástasis sarcomatoides a nivel de páncreas son extremadamente raras. La cirugía de exéresis de la metástasis es la única alternativa terapéutica que ha reportado beneficio en cuanto la supervivencia de estos pacientes.

ABSTRACT Proton pump inhibitors (PPIs) are the most potent drugs to inhibit gastric acid secretion, being used in the treatment of most inflammatory conditions of the gastric mucosa. They are among the most prescribed and overprescribed medications worldwide; for example, in the United States, according to the National Health and Nutrition Examination Survey, they almost doubled their use in adults aged 40 years and older from 4.9 % to 8.3 % between 1999 and 2012. Although they are generally considered well tolerated, some epidemiological studies extracting information from large databases have reported a number of adverse effects associated with their prolonged use, including cognitive impairment, chronic kidney disease, myocardial infarction, stroke, bone fractures and even death, among others. The objective was to conduct a narrative review of the literature on the effects of chronic use of PPIs on cognitive impairment in older adults. Articles were reviewed based on a search in the PubMed, Scopus and SciELO databases using both English and Spanish keywords and related MeSH/DeCS terms. Neurological side effects induced by chronic PPI use may be indirectly related to secondary systemic disorders (magnesium and vitamin B12 deficiency) or to direct effects on neuronal functioning after passing through the blood-brain barrier. Although several neurobiological mechanisms by which PPIs could favor the development of dementia-which involve Tau protein function, beta-amyloid [βA] accumulation and cobalamin deficiency, among others-have been described, most of the available clinical evidence has not shown a significant association between PPI use and the risk of dementia or cognitive impairment. To establish the adverse clinical effects of chronic PPI use more clearly, especially on brain functioning, well-designed cohort studies with large sample sizes and long follow-up periods, with a reliable method to adjust for standardized confounders, as well as subgroup analyses are needed.

RESUMEN Los inhibidores de la bomba de protones (IBP) son los medicamentos más potentes para inhibir la secreción gástrica ácida, y se utilizan en el tratamiento de la mayor parte de las afecciones inflamatorias de la mucosa gástrica. Forman parte de los fármacos más recetados y sobreprescritos en todo el mundo; por ejemplo, en los Estados Unidos, según la Encuesta nacional de salud y nutrición, casi duplicaron su uso en los adultos de 40 años de un 4,9 % hasta un 8,3 %, entre los años 1999 a 2012. Aunque, en general, se consideran bien tolerados, algunos estudios epidemiológicos ―que extraen información a partir de grandes bases de datos― han reportado una serie de efectos adversos asociados con su uso prolongado, entre los cuales están el deterioro cognitivo, la enfermedad renal crónica, el infarto de miocardio, el accidente cerebrovascular, las fracturas óseas e incluso la muerte, entre otros. El objetivo fue realizar una revisión narrativa de la literatura acerca de los efectos del uso crónico de los IBP sobre el deterioro cognitivo en los adultos mayores. Se revisaron artículos a partir de una búsqueda en las bases de datos Pudmed, Scopus y Scielo con las palabras clave y términos Mesh/DeCS relacionados tanto en inglés como en español. Los efectos secundarios a nivel neurológico inducidos por el uso crónico de los IBP pueden estar relacionados indirectamente con la presencia de alteraciones sistémicas secundarias (deficiencia de magnesio y vitamina B12) o con efectos directos sobre el funcionamiento neuronal después de pasar a través de la barrera hematoencefálica. Si bien se han descrito varios mecanismos neurobiológicos por medio de los cuales los IBP podrían favorecer el desarrollo de la demencia ―que comprenden el funcionamiento de la proteína tau, la acumulación de beta amiloide (βA) y la deficiencia de cobalamina, entre otros―, la mayor parte de la evidencia clínica disponible no ha encontrado una asociación significativa entre el uso de los IBP y el riesgo de demencia o el deterioro cognitivo. Para establecer de una manera más clara los efectos clínicos adversos del uso crónico de los IBP, en especial, en el funcionamiento cerebral, se necesitan estudios de cohorte bien diseñados, con tamaños de muestra grandes y periodos de seguimiento prolongados, con un método confiable para ajustar los factores de confusión estandarizados y, además, realizar análisis por subgrupos.

Resumo Nanopartículas são consideradas opções viáveis no tratamento do câncer. Este estudo foi conduzido para investigar o efeito de nanopartículas de magnetita (MNPs) e núcleo de folato de magnetita (MFCS) em culturas de células leucêmicas e de hepatocarcinoma, bem como seu efeito no modelo animal de leucemia mielocítica aguda (LMA). Através do atual estudo, nanopartículas foram sintetizadas, caracterizadas por várias técnicas, e suas propriedades foram estudadas para confirmar sua nanoestrutura. No estudo in vivo, as nanopartículas foram avaliadas para inspecionar sua atividade citotóxica contra células SNU-182 (carcinoma hepatocelular humano), K562 (leucemia humana) e THLE2 (fígado epitelial humano normal) por meio do teste MTT. A expressão das proteínas sinalizadoras apoptóticas Bcl-2 e Caspase-3 foram inspecionadas através do método RT-PCR. Um efeito citotóxico de MNPs e MFCS foi detectado em culturas de células anteriores. Além disso, a apoptose foi identificada por meio de regulação positiva significativa da Caspase-3, com regulação negativa de Bcl-2. No estudo in vitro, a AML foi induzida em ratos por N-metil-N-nitrosoureia seguida por tratamento oral com MNPS e MFCS. Índices bioquímicos como aspartato e alanina aminotransferases e atividades de lactato desidrogenase, ácido úrico, hemograma completo e Beta-2-microglubulina foram avaliados no soro. A imunofenotipagem para detecção de CD34 e CD38 foi realizada. Fígado, rim e medula óssea foram examinados microscopicamente. A metilação do promotor Bcl-2 e os níveis de mRNA foram examinados. Embora tanto os MNPs quanto os MFCS representem uma melhora nos parâmetros bioquímicos, o MFCS os aliviou em direção ao controle normal. A atividade anticâncer de MNPs e MFCS foi aprovada especialmente para AML. Sempre, a administração de MFCS foi mais eficaz do que MNPs. O presente trabalho é um dos poucos estudos que utilizou o MFCS como agente anticâncer.

Abstract Nanoparticles are considered viable options in the treatment of cancer. This study was conducted to investigate the effect of magnetite nanoparticles (MNPs) and magnetite folate core shell (MFCS) on leukemic and hepatocarcinoma cell cultures as well as their effect on the animal model of acute myelocytic leukemia (AML). Through current study nanoparticles were synthesized, characterized by various techniques, and their properties were studied to confirm their nanostructure. Invivo study, nanoparticles were evaluated to inspect their cytotoxic activity against SNU-182 (human hepatocellular carcinoma), K562 (human leukemia), and THLE2 (human normal epithelial liver) cells via MTT test. Apoptotic signaling proteins Bcl-2 and Caspase-3 expression were inspected through RT-PCR method. A cytotoxic effect of MNPs and MFCS was detected in previous cell cultures. Moreover, the apoptosis was identified through significant up-regulation of caspase-3, with Bcl-2 down-regulation. Invitro study, AML was induced in rats by N-methyl-N-nitrosourea followed by oral treatment with MNPS and MFCS. Biochemical indices such as aspartate and alanine amino transferases, and lactate dehydrogenase activities, uric acid, complete blood count, and Beta -2-microglubulin were assessed in serum. Immunophenotyping for CD34 and CD38 detection was performed. Liver, kidney, and bone marrow were microscopically examined. Bcl-2 promoter methylation, and mRNA levels were examined. Although, both MNPs and MFCS depict amelioration in biochemical parameters, MFCS alleviated them toward normal control. Anticancer activity of MNPs and MFCS was approved especially for AML. Whenever, administration of MFCS was more effective than MNPs. The present work is one of few studies used MFCS as anticancer agent.

Resumo A fibrose hepática é a fase inicial de qualquer doença hepática crônica, e em sua fase final desenvolve-se para cirrose. As doenças hepáticas crônicas são uma questão de saúde global crucial e a causa de aproximadamente 2 milhões de mortes por ano em todo o mundo. A cirrose, hoje em dia, é a 11ª causa mais comum de morte globalmente. O tratamento da célula-tronco mesenquimal (MSCs) é uma maneira eletiva de tratar a doença hepática aguda e crônica. O objetivo deste estudo é melhorar o potencial terapêutico dos MSCs combinados com a melatonina (MLT) para superar a fibrose hepática induzida por CCl4 e também investigar o impacto individual da melatonina e MSCs contra o comprometimento do fígado induzido por CCl4 no modelo animal. Os ratos BALB / C fêmeas foram usados como modelo de animal fibrótico de fígado induzido por CCl4. Cinco grupos de modelo animal foram feitos: Controle Negativo, Controle Positivo, CCl4 + MSCs Tratados Grupo, Grupo Tratado CCl4 + MLT e Grupo Tratado CCl4 + MSCs + MLT. MSCs cultivados da medula óssea dos ratos foram transplantados para o modelo de camundongos de fígado induzido por CCl4, individualmente, bem como em conjunto com a melatonina. Duas semanas após a administração MSCs e MLT, todos os grupos de camundongos foram sacrificados para o exame. Os resultados morfológicos e histopatológicos mostraram que a terapia combinada do MSCs + MLT mostrou impacto benéfico substancial no modelo ferido no fígado induzido pelo CCl4, em comparação com o MSCs e o MLT individualmente. A redução bioquimicamente considerável foi observada em bilirrubina sérica e níveis ALT de ratinhos tratados com MLT + MSCs, em comparação com outros grupos. Os resultados de PCR mostraram regulação negativa do BAX e regulação positiva do BCL-XL e da albumina, confirmando um efeito terapêutico significativo do MSCs + MLT na fibrose hepática induzida por CCl4. Dos resultados, conclui-se que a terapia combinada de MSCs e MLT mostram um forte efeito terapêutico na fibrose hepática induzida por CCl4, em comparação com MSCs e MLT individualmente.

Abstract Liver fibrosis is initial stage of any chronic liver disease and its end stage is develops into cirrhosis. Chronic liver diseases are a crucial global health issue and the cause of approximately 2 million deaths per year worldwide. Cirrhosis is currently the 11th most common cause of death globally. Mesenchymal stem cell (MSCs) treatment is the best way to treat acute and chronic liver disease. The aim of this study is to improve the therapeutic potential of MSCs combined with melatonin (MLT) to overcome CCl4-induced liver fibrosis and also investigate the individual impact of melatonin and MSCs against CCl4-induced liver impairment in animal model. Female BALB/c mice were used as CCL4-induced liver fibrotic animal model. Five groups of animal model were made; negative control, Positive control, CCl4+MSCs treated group, CCl4+MLT treated group and CCl4+MSCs+MLT treated group. Cultured MSCs from mice bone marrow were transplanted to CCl4-induced liver injured mice model, individually as well as together with melatonin. Two weeks after MSCs and MLT administration, all groups of mice were sacrificed for examination. Morphological and Histopathological results showed that combined therapy of MSCs+MLT showed substantial beneficial impact on CCl4-induced liver injured model, compared with MSCs and MLT individually. Biochemically, considerable reduction was observed in serum bilirubin and ALT levels of MLT+MSC treated mice, compared to other groups. PCR results shown down-regulation of Bax and up-regulation of Bcl-xl and Albumin, confirm a significant therapeutic effect of MSCs+MLT on CCI4-induced liver fibrosis. From the results, it is concluded that combined therapy of MSCs and MLT show strong therapeutic effect on CCL4-induced liver fibrosis, compared with MSCs and MLT individually.

Resumo Mutações de ocorrência natural na proteína morfogenética 15 (BMP15) estão associadas à diminuição da taxa de ovulação (TO), tamanho da ninhada (TN) e esterilidade. Estudar a BMP15 na raça Cholistani para elevar o status socioeconômico e o conhecimento da criação de ovinos Cholistani no sul de Punjab, Paquistão. Em nosso estudo, 50 ovelhas Cholistani inférteis sem parentesco sanguíneo foram rastreadas para mutações BMP15. Para tanto, um DNA de alta qualidade foi extraído do sangue dessas ovelhas, seguido de concepção do primer, amplificação da reação em cadeia da polimerase (PCR), sequenciamento de DNA e análises in silico. Do total de 50 amostras, 9, incluindo caso 1 (T3), caso 2 (T8), caso 3 (T17), caso 4 (T22), caso 5 (T25), caso 6 (T33), caso 7 (T40), caso 8 (T44) e caso 9 (T47), foram consideradas positivas para uma variedade de mutações BMP15 novas e já relatadas. Mais análises in silico das mutações observadas mostraram o impacto funcional dessas mutações em diferentes características (peso molecular, PI teórico, meia-vida estimada, índice de instabilidade, localização subcelular e confirmação 3D) das proteínas codificadas, possivelmente alterando a funcionalidade normal. Nossos achados confirmaram o possível papel essencial das mutações BMP15 na infertilidade de ovelhas Cholistani.

Abstract Naturally occurring mutations in morphogenetic protein 15 (BMP15) are associated with decreased ovulation rate (OR), litter size (LS), and sterility. It is of a great interest to elucidate BMP15 gene in Cholistani sheep breed to uplift socio-economic status and the knowledge of Cholistani sheep breeding in Southern Punjab, Pakistan. In our study, a total of 50 infertile Cholistani sheep aged between 2-6 years and having no blood relation were screened for BMP15 mutations. For this purpose, a high-quality DNA was extracted from the blood of sheep followed by primer designing, Polymerase Chain Reaction (PCR) amplification, DNA sequencing, and in silico analyses. Out of total 50 samples, 9 samples including case 1 (T3), case 2 (T8), case 3 (T17), case 4 (T22), case 5 (T25), case 6 (T33), case 7 (T40), case 8 (T44), and case 9 (T47) were found positive for a variety of already reported and novel BMP15 mutations. Further in silico analyses of the observed mutations have shown the functional impact of these mutations on different characteristics (molecular weight, theoretical PI, estimated half-life, instability index, sub-cellular localization, and 3D confirmation) of the encoded proteins, possibly altering the normal functionality. In a nutshell, findings of this study have confirmed the possible essential role of the BMP15 mutations in the infertility of the Cholistani sheep.

Resumo Frangos de corte Hubbard com 320 dias de idade foram alocados aleatoriamente em quatro tratamentos (8 repetições, 10 aves/curral) e foram criados em condições de manejo padrão. As aves do primeiro grupo serviram como controle e foram alimentadas com uma dieta à base de milho, enquanto as aves dos três grupos restantes, ou seja, A, B e C, foram alimentadas com dieta basal suplementada com nanopartículas de cobre (CuNP) a 5, 10 e 15 mg/kg de dieta, respectivamente, por 35 dias. A suplementação de CuNP aumentou linearmente (P ≤ 0,05) o peso corporal (PC), o ganho de peso médio diário (GPDA) e o consumo de ração (FI) em frangos de corte. O ácido úrico, os níveis de glicose no sangue e a conversão alimentar (TCF) reduziram linearmente (P ≤ 0,05) com a suplementação de CuNP na dieta. A suplementação de CuNP na dieta também aumentou linearmente (P ≤ 0,05) peso, comprimento, diâmetro, índice peso/comprimento (P/L) e índice tibiotársico (índice TT) da tíbia. A inclusão de CuNP na dieta de frangos de corte aumentou linearmente os parâmetros medidos de músculo, ou seja; pH, diâmetro da fibra, área da seção transversal da fibra, diâmetro do fascículo, área da seção transversal do fascículo (P ≤ 0,05). A concentração de cobre, ferro, cálcio e fósforo no sangue também aumentou linearmente (P ≤ 0,05) com a suplementação de CuNP. No geral, CuNP afetou positivamente o desempenho de crescimento, características histológicas dos músculos, resistência óssea e metabólitos séricos em frangos de corte.

Abstract Three hundred and twenty day old Hubbard broilers were randomly allocated to four treatments (8 replicates, 10 birds/pen) and were raised under standard management conditions. Birds in the first group served as control and were fed a corn based diet, while birds in the remaining three groups i.e.; A, B and C were fed with a basal diet supplemented with copper nanoparticles (CuNP) at 5, 10 and 15 mg /kg of diet respectively for 35 days. Supplementation of CuNP linearly increased (P≤0.05) body weight (BW), average daily weight gain (ADWG) and feed intake (FI) in broilers. Uric acid, glucose levels in blood and feed conversion ratio (FCR) reduced linearly (P≤0.05) with CuNP supplementation in diet. Supplementation of CuNP in the diet also linearly increased (P≤0.05) tibia weight, length, diameter, weight/length index (W/L) and Tibiotarsal index (TT index). Inclusion of CuNP in broilers diet linearly increased the measured parameters of muscle i.e.; pH, fiber diameter, fiber cross-sectional area, fascicle diameter, fascicle cross-sectional area (P≤0.05). Concentration of copper, iron, calcium and phosphorous in blood also increased line-arly (P ≤ 0.05) with CuNP supplementation. Overall, CuNP positively affected the growth performance, histological characteristics of muscles, bone strength and serum metabolites in broilers.

Resumo Trata-se de um estudo de caso controle e coorte, realizado no Departamento de Bioquímica da FUAST, comprimindo 24 ratos albinos Wistar. A especiaria natural Illicium verum (anis estrelado) e o brócolis vegetal verde geralmente são utilizados para o tratamento fitoterápico quimiopreventivo por conta da atividade antioxidante da vitamina C. A hepatotoxicidade foi induzida no fígado dos ratos modelo por injeção única interperitoneal de 200 mg/kg de peso corporal (PC) de N-nitrosodietilamina e administração oral de 1 mg/kg de peso corporal de fenobarbital por 14 dias durante o período de prolongamento da doença. A análise da vitamina C de Illicium verum (anis estrelado), brócolis verde, suco de laranja, casca de laranja e polpa de laranja foi realizada pelo método de titulação quantitativa e qualitativa iodométrica. Os ratos receberam composto de acordo com seu peso corporal como 1 mg/kg B.W. Após 14 dias (Período de Promoção e Propagação da Doença) e 28 dias (Período de Cura da Doença) de tratamento a atividade comportamental foi monitorada por atividade locomotora em experimento de campo aberto, atividade estimulatória em gaiola e efeitos ansiolíticos observados em aparelhos claros e escuros e também em T Labirinto. A atividade comportamental foi significativamente aumentada em ratos tratados com Illicium verum e brócolis verde. O estudo hematológico incluindo hemoglobina (Hb), glóbulos brancos (WBC), glóbulos vermelhos (RBC), volume corpuscular médio (MCV), hemoglobina corpuscular média (MCH), concentração média de hemoglobina corpuscular (MCHC), largura de distribuição de glóbulos vermelhos (RDW) e Plaquetas foi feito pela célula do analisador de laboratório Ababot. O valor de Hb e RBC também foi significativamente aumentado em ratos tratados com anis estrelado e brócolis, mostraram função adequada de RBC na microcirculação. WBC também estava na faixa normal revelando que nenhuma doença relaciona-se à medula óssea e leucemia. A atividade bioquímica de ratos, incluindo uréia, creatinina, proteína total, albumina, globulina, razão A/G, amilase e cálcio no soro sanguíneo foram analisadas, enquanto a saúde ou desempenho do fígado também foi determinada por LFT (teste de função hepática). As variáveis comportamentais e laboratoriais foram analisadas pelo SPSS v. 20 e valor de p < 0,05 foi considerado estatisticamente significativo. O estudo relata efeito significativo perceptível de Illicium verum e brócolis na hepatotoxicidade do modelo experimental. Resultados estatísticos de estudos experimentais recentes mostram relação recíproca entre o consumo de dieta vegetal e tempero natural com o risco de hepatotoxicidade. Assim, o objetivo do estudo foi potencializar a função do anis estrelado ou da especiaria natural Illicium verum e do brócolis vegetal verde como agente anticancerígeno ou quimioprofilático.

Abstract This is a case control and cohort study, conducted at Department of Biochemistry in FUAST, compressing 24 number of albino Wistar rats. Illicium verum (star anise) natural spice and green vegetable broccoli are used for chemo-preventive herbal treatment in relation with vitamin C antioxidant activity. Hepatotoxicity was induced in liver of model rats by giving interperitoneally single injection of 200 mg/kg bod weight (B.W) of N-nitrosodiethylamine and orally giving 1 mg/kg BW phenobarbital for 14 days during disease prorogation period. The vitamin C analysis from Illicium verum (star anise), green broccoli, orange juice, orange peel and orange pulp was done by iodometric quantitative and qualitative titration method. Rats were given compound according to their bodyweight as 1 mg/kg B.W. After 14 days (Disease Promotion and Propagation Period) and 28 days (Disease cure period) of treatment behavioral activity was monitored by locomotors activity in open field experiment, stimulatory activity in home cage and anxiolytic effects observed in light and dark apparatus and also in T maze. Behavioral activity were significantly increased in Illicium verum and green broccoli treated rats. Hematological study including hemoglobin (Hb), white blood cells (WBC), red blood cells (RBC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW) and Platelets was done by abbot laboratory analyzer cell. The value of Hb and RBC was also significantly increased in star anise and broccoli treated rats, showed proper function of RBC in microcirculation. WBC was also in normal range revealed that no disease regards to bone marrow and leukemia’s. The biochemical activity of rats including urea, creatinine, total protein, albumin, globulin, A/G ratio, amylase and calcium in blood serum were analyzed while, liver health or performance was also determined by LFT (liver function test). Behavioral and laboratorial variables were analyzed by using SPSS v. 20 and p-value < 0.05 was considered statistically significant. The study report noticeable significant effect of Illicium verum and broccoli on hepatotoxicity of experimental model. Recent experimental study statistical outcomes show reciprocal relationship between the consumption of vegetable diet and natural spice with the risk of Hepatotoxicity. Thus, the aim of the study is to enhance the function of star anise or illicium verum natural spice and green vegetable broccoli as an anticancer or chemoprophylaxis agent.