Genetic analysis of a child with D bifunctional protein deficiency born to a consanguineous pedigree / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic etiology of a child with D bifunctional protein deficiency (DBPD) born to a consanguineous pedigree.@*METHODS@#A child with DBPD who was admitted to the First Affiliated Hospital of Hainan Medical College on January 6, 2022 due to hypotonia and global developmental delay was selected as the study subject. Clinical data of her pedigree members were collected. Peripheral blood samples of the child, her parents and elder sisters were collected and subjected to whole exome sequencing. Candidate variant was validated by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The child, a 2-year-and-9-month-old female, had featured hypotonia, growth retardation, unstable head lift, and sensorineural deafness. Serum long-chain fatty acids were elevated, and auditory brainstem evoked potentials had failed to elicit V waves in both ears with 90 dBnHL stimulation. Brain MRI revealed thinning of corpus callosum and white matter hypoplasia. The child's parents were secondary cousins. Their elder daughter had a normal phenotype and no clinical symptoms related to DBPD. Elder son had frequent convulsions, hypotonia and feeding difficulties after birth, and had died one and a half month later. Genetic testing revealed that the child had harbored homozygous c.483G>T (p.Gln161His) variants of the HSD17B4 gene, for which both of her parents and elder sisters were carriers. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.483G>T (p.Gln161His) was rated as a pathogenic variant (PM1+PM2_Supporting+PP1+PP3+PP4).@*CONCLUSION@#The homozygous c.483G>T (p.Gln161His) variants of the HSD17B4 gene caused by the consanguineous marriage probably underlay the DBPD in this child.

Analysis of SLC25A13 gene variants in 16 infants with intrahepatic cholestasis caused by citrin protein deficiency / 中华医学遗传学杂志

OBJECTIVE@#To explore the characteristics of SLC25A13 gene variants in 16 infants with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD).@*METHODS@#The infants were subjected to high-throughput DNA sequencing for coding exons and flanking regions of the target genes. Suspected variants were verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#Among the 16 NICCD cases, 15 were found to harbor pathogenic variants. Among these, IVS14-9A>G, c.1640G>A, c.762T>A, c.736delG, c.1098Tdel and c.851G>A were previously unreported.@*CONCLUSION@#Six novel SLC25A13 variants were found by high-throughput sequencing, which has enriched the spectrum of SLC25A13 gene variants and provided a basis for genetic counseling and prenatal diagnosis.

Proteinemia as a Prognostic Factor in Colorectal Cancers beyond Surgery and Chemotherapy

Background: Globally, 1,096,601, 704,376, and 48,541 new colon, rectum, and anus cancer cases were recorded in 2018, respectively. Besides, 551,269, 310,394 and 19,129 cases of colon, rectum, and anus cancer deaths occurred in the same year. As a result, these cancers ranked in the third level of cancer incidence, and in the second level of cancer mortality. As it is known, all cancer patients are subjected to cancerinduced and therapy-induced nutritional deficiencies (mainly of proteins and calories). The present study aimed to assess proteins level in colorectal cancer (CRC) patients who underwent surgery and chemotherapy. Methods: A combined retrospective and prospective study was performed. The present study enrolled 100 CRC patients with their data on surgical procedures and chemotherapy management. Assessments of the studied samples were conducted as a baseline before receiving chemotherapy and preoperatively as P0, while the period after that was termed as P1. The serum samples were collected to measure protein concentration. Total Protein Kit, Micro was used. Results: The mean age of the patients was 50.7±12.88 years old. Only 8% had a positive CRC family history. Rectosigmoid cancer represented the most frequent site, figured in 41% of the cases, followed by rectum cancer. Multiple sites of CRC metastasis were recorded in 15% of the patients. All patients received chemoradiation. Folinic acid (leucovorin), 5-FU, and oxaliplatin (FOLFOX) was the most used regimen, administered in 40% of the patients. Oxaliplatin and capecitabine (also called Xeloda) (XELOX) were administered in 14% of the patients. Folinic acid (leucovorin), 5-FU, oxaliplatin, and irinotecan (FOLFOXIRI) were administered in 16% of the patients. Single-agent oxaliplatin or carboplatin were administered in 6% of the patients, each. 5-FU plus leucovorin was administered to 12% of the patients. Three patients received irinotecan, and oxaliplatin (IROX). One patient received folinic acid (leucovorin), 5-FU and irinotecan (FOLFIRI). Also, Gemzar was administered to two patients only. A total of 80% of the patients underwent several surgical procedures. Anterior perineal resection (APR) and total mesorectal excision (TME) were the most common two surgeries, performed in 20 and in 30% of the patients, respectively. In P0 status, 44% of the patients suffered from low protein levels, and 13% of the patients were within the normal level. These findings were statistically different (p=0.03). After CRC management (i.e., P1 status), 70% of the patients had protein deficiency. These results have strong significant differences (p=0.000). The mean of protein concentration declined gradually after management, from 8.82±0.9 μg/L to 6.210.78 μg/L, with a strong association between a reduction in proteins levels towards deficiency and surgical procedures and chemotherapy protocols (p=0.000). Conclusion: The incidence of CRC is increasing annually, and the chance of being diagnosed with this type of cancer has risen in recent years. In the present study, the male to female ratio was 1:1.5, and the 5th decade of life was themost common age for the diagnosis of CRC. A negative family history and bowel inflammatory diseases (IBD) history did not exclude people from exposure to the incidence of CRC. Colorectal cancer with localized and moderately differentiated adenocarcinoma were the most common types in the present work. Tumor distance from the anal verge seems to be very important and plays a significant role in the choosing of surgical intervention types and chemoradiation protocols. Colorectal cancer acts as a complex condition and, in addition to its management, nutritional state influences it in different mechanisms. Most patients suffered from hypoproteinemia after surgery and chemoradiation. As a result, alteration in the treatment outcomes, delaying in wound healing, and an increase in postoperative complications may occur. (AU)

D-bifunctional protein deficiency caused by / 中国当代儿科杂志

A 15-day-old boy was admitted to the hospital due to repeated convulsions for 14 days. The main clinical manifestations were uncontrolled seizures, hypoergia, feeding difficulties, limb hypotonia, and bilateral hearing impairment. Clinical neurophysiology showed reduced brainstem auditory evoked potential on both sides and burst-suppression pattern on electroencephalogram. Measurement of very-long-chain fatty acids in serum showed that C26:0 was significantly increased. Genetic testing showed a pathogenic compound heterozygous mutation, c.101C>T(p.Ala34Val) and c.1448_1460del(p.Ala483Aspfs*37), in the

Desgaste proteico energético en pacientes con enfermedad renal crónica en estadios III a IV en Caldas, Colombia / Protein Energy Wasting in Patients with Chronic Renal Disease in Stage III to IV Caldas (Colombia)

Resumen Introducción: la enfermedad renal crónica (ERC) es un problema de salud mundial con una prevalencia aproximada del 7,2 % en países desarrollados y del 10 % en todo el mundo; además, es un factor independiente de morbilidad y riesgo cardiovascular que se caracteriza por la pérdida progresiva de la función renal. Objetivo: evaluar la frecuencia de desgaste proteico energético (DPE) en pacientes con ERC en estadios III a IV. Materiales y métodos: estudio descriptivo y de corte transversal. Se realizó una evaluación de los registros de las base de datos de la Sociedad Internacional de Nutrición y Metabolismo Renal sobre pacientes con ERC que contaran con variables sociodemográficas, bioquímicas, valoración global subjetiva (VGS) y medidas antropométricas para el diagnóstico de DPE. Resultados: de 200 pacientes revisados en consulta externa de Nefrología, 60 cumplieron con los criterios de inclusión. El promedio de edad fue de 68,4 años, con una media de tasa de filtración glomerular (TFG) de 47,1 mL/min. Respecto a la ERC, el 61,66 % (n=37) de los participantes fue clasificado en estadio IIIa; el 31,6 % (n=19), en estadio IIIb, y el 6,66 % (n=4), en estadio IV. Ninguno de los pacientes cumplió con los criterios para el DPE. La evaluación de la VGS mostró que el 53,33 % (n=32) de los pacientes estaba en categoría VGS-A (bien nutridos), el 45 % (n=27) en VGS-B (malnutrición moderada) y solo un paciente en VGS-C (malnutrición grave). La mayor proporción de pacientes con bajos niveles de albúmina y colesterol estuvo en pacientes con ERC en estadio IIIb, y los pacientes con índice de masa corporal <23, en estadios IIIb y IV. Conclusión: según los criterios de la Sociedad Internacional de Nutrición y Metabolismo Renal, ningún paciente presentó DPE.

Abstract Introduction: Chronic kidney disease (CKD) is a condition that is recognized as a global health problem and has an approximate prevalence of 7.2% in developed countries, and 10% in the world population, it is also an independent factor of cardiovascular morbidity and risk characterized by progressive loss of kidney function. Objective: To evaluate the frequency of DPE in patients with CKD stages III to IV. Methods: Descriptive, cross-sectional study. Evaluation of a database of patients with CKD, which will have sociodemographic, biochemical variables, Subjective Global Assessment (VGS), and anthropometric measures, for the diagnosis of DPE of the International Society for Nutrition and Renal Metabolism. Results: Of 200 reviewed patients from the Nephrology outpatient clinic, 60 met the inclusion criteria. The average age was 68.4 years, with a mean glomerular filtration rate (GFR) of 47.1ml / min. Regarding CKD, 61.66% (37) of the patients classified in stage IIIa, 31.6% (19) in stage IIIb, and 6.66% (4) in stage IV. None of the patients met the criteria for DPE. The VGS evaluation showed that 53.33% (32) of the patients were in the VGS A category (well nourished), 45% (27) VGS B (moderate malnutrition) and only one patient was classified as VGS C (severe malnutrition). The highest proportion of patients with low levels of albumin and cholesterol was in patients with CKD stage IIIb, and patients with BMI less than 23 in stages IIIb and IV. Conclusion: According to the criteria of the International Society for Renal Nutrition and Metabolism, no patient had DPE. outpatient clinic in Caldas, with CKD stages III to IV-. METHODS: Descriptive, cross-sectional study. Evaluation of a database of patients with CKD, which will have sociodemographic, biochemical variables, Subjective Global Assessment (SGA), and anthropometric measures, for the diagnosis of PEW of the International Society for Nutrition and Renal Metabolism. RESULTS: Of200 reviewed patients from the Nephrology outpatient clinic, 60 met the inclusion criteria. The average age was 68.4 years, with a mean glomerular filtration rate (GFR) of 47.1ml / min. Regarding CKD, 61.66% (37) of the patients were classified in stage IIIa, 31.6% (19) in stage IIIb, and 6.66% (4) in stage IV. None of the patients met the criteria for PEW. The SGA evaluation showed that 53.33% (32) of the patients were in SGAA category (well nourished), 45% (27) SGA B (moderate malnutrition) and only one patient was classified as SGA C (severe malnutrition). The highest proportion of patients with low albumin and cholesterol levels was in patients with CKD in stage IIIb, and patients with BMI less than 23 in stages IIIb and IV. Conclusion: According to the criteria of the International Society for Nutrition and Renal Metabolism, no patient had PEW.

Spinal anesthesia for c-section in patients with protein S deficiency: case report and literature review / Anestesia espinal para cesárea en paciente con deficiencia de proteína S: informe de caso y revisión de la literatura

Abstract Introduction: Congenital protein S deficiency is a very rare disease in the population. In pregnant women it is associated with spontaneous abortion and fetal death, among other complications. Case presentation: We present the case of a 32-year-old multigravida with a 36-week pregnancy, with thromboprophylaxis with enoxaparin from the 4th week of gestation and with a diagnosis of thrombophilia-due to functional protein S deficiency-which was intervened with elective c-section under spinal anesthesia. In addition, a review of the relevant literature was conducted. Discussion: The risk of venous thromboembolism is approximately 4 to 5 times greater during gestation, and the recommendation of thromboprophylaxis in low-risk thrombophilia is based on the presence of associated risk factors. In patients receiving low molecular weight heparin (LMWH) as thromboprophylaxis, an interval of at least 12 hours after the last dose of LMWH before neuropsy and restarting the next dose after at least 4hours of spinal technique use is recommended. Conclusion: Neuroaxial techniques should be individualized and receive pre and postpartum thromboprophylaxis. In addition, non-pharmacological thromboprophylaxis measures in the perioperative period should be considered. Spinal anesthesia was effective and safe in this patient.

Resumen Introducción: La deficiencia congénita de proteína S es una enfermedad muy rara en la población. En gestantes está asociada a aborto espontáneo y muerte fetal, entre otras complicaciones. Presentación del caso: Presentamos el caso de una multigesta de 32 años con embarazo de 36 semanas, con tromboprofilaxis con enoxaparina desde la semana cuarta de gestación y con diagnóstico de trombofilia -por deficiencia de proteína S funcional-, la cual fue intervenida con cesárea electiva bajo anestesia espinal. Además, se realizó revisión de la literatura al respecto. Discusión: El riesgo de tromboembolismo venoso es aproximadamente 4 a 5 veces mayor durante la gestación, y la recomendación de tromboprofilaxis en trombofilias de bajo riesgo se basa en la presencia de factores de riesgo asociados. En pacientes que reciben Heparinas de Bajo Peso Molecular (HBPM) como tromboprofilaxis, se recomienda un intervalo de al menos 12 horas después de la última dosis de HBPM antes de la punción del neuroeje, y reiniciar la siguiente dosis después de al menos 4 horas de uso de la técnica espinal. Conclusión: Las técnicas neuroaxiales deben ser individualizadas y recibir tromboprofilaxis pre y posparto. Además, se deben tener en cuenta las medidas de tromboprofilaxis no farmacológicas en el periodo perioperatorio. La anestesia espinal fue efectiva y segura en esta paciente.

Protein C and S deficiency as a cause of mesenteric thrombosis: Differential diagnosis of systemic vasculitis / Deficiencia de proteínas C y S como causa de trombosis mesentérica: diagnóstico diferencial de las vasculitis sistémicas

ABSTRACT Acute mesenteric ischemia is a medical emergency that accounts for less than 1/1000 hospital admissions. The disease affects adults older than 50 years predominantly with cardiac compromise, in whom the presence of acute abdominal pain is the cardinal manifestation, and should make the clinician suspect this entity. Its presentation in adolescents is unusual; therefore, in these cases, the possibility of an underlying thrombophilia should be part of the differential diagnosis. The case is presented here of a young female with a protein C and S deficiency as the cause of mesenteric thrombosis.

RESUMEN La isquemia mesentérica aguda es una urgencia médica que se presenta en menos de 1/1.000 ingresos hospitalarios. Es una entidad clínica infrecuente, predominante en adultos mayores de 50 arios con afectación cardíaca, en quienes la presencia de dolor abdominal agudo es la manifestación cardinal y debería hacer sospechar dicho diagnóstico. La presentación en adolescentes es inusual, por lo que, en estos casos, la posibilidad de una trombofilia subyacente debe formar parte del diagnóstico diferencial. Presentamos el caso de una paciente joven con deficiencia de proteínas C y S como agente causal de trombosis mesentérica.

Centros de recuperación nutricional: 1984-2011 / Nutritional Recovery Centers: 1984-2011

Los centros de recuperación nutricional (CRN) fueron creados por el Dr. José María Bengoa en Venezuela. En el presente estudio se realizó una revisión sistemática cualitativa, de 1984 al 2011, que permitió analizar las modalidades de funcionamiento de los diferentes CRN en el mundo, mediante indicadores de: criterios de admisión, parámetros utilizados en estos centros, así como las modalidades de tratamiento, tiempo de estancia y criterios de alta. Se encontraron diecisiete artículos que describen algunos o todos estos indicadores. El uso de los CRN se encontró en cuatro países de África (Etiopía, Kenia, Malawi y Nigeria), cuatro de América (Bolivia, Brasil, Chile y Nicaragua) y dos en Asia (India y Nepal). Los resultados reflejan la importancia de los CRN en el tratamiento de la desnutrición, sobre todo si se acompaña con la educación de las madres sobre la alimentación, prácticas higiénicas, etc., para un mejor cuidado en el hogar. Nuevas evidencias en el tratamiento de la desnutrición han motivado la evolución de los centros, pero aún así, sus limitaciones persisten. No obstante, las ventajas de su uso son excepcionales. Se propone, de acuerdo con los diferentes tipos de centros, y en base a las deficiencias o limitaciones observadas en su conceptualización y designación, redefinir las NRC bajo el concepto de Centros Globales de Nutrición (GloNuCen) basados en la comunidad y la personalización nutricional, los cuales podrían ser centros fijos en el caso de hospitales y servicios ambulatorios, e instalaciones móviles para situaciones de emergencia que, si duran con el tiempo, puedan convertirse en centros fijos(AU)

The Nutritional Recovery Centers (NRC) were created by Dr. Jose María Bengoa in Venezuela. In the present study a qualitative systematic review was carried out, from 1984 to 2011, allowing us to analyze the operating modalities of the different CRNs in the world, by means of indicators of: admission criteria, parameters used in these centers, as well as their treatment modalities, time of stay and discharge criteria. Seventeen articles have been found that describe some or all of these indicators. The use of NRCs was found in four African countries (Ethiopia, Kenya, Malawi and Nigeria), four in America (Bolivia, Brazil, Chile and Nicaragua) and two in Asia (India and Nepal). The results reflect the importance of NRC in the treatment of malnutrition, especially if it is reinforced with mothers' education about food, hygiene practices, etc., for better home care. New evidence in the treatment of malnutrition has motivated the evolution of the centers, but still, their limitations persist. Nonetheless, the advantages of their use are exceptional. It is proposed, according to the different types of centers, and based on the deficiencies or limitations observed in their conceptualization and designation, to redefine the NRCs under the concept of Global Nutrition Centers (GloNuCen) based on the community and nutritional customization, which could be fixed centers in the case of hospitals and outpatient services, and mobile facilities for emergency situations that, if they last over time, could turn into fixed centers(AU)

Protein malnutrition effects of perivascular bone marrow microenvironment on the regulation of hematopoiesis / Efeitos da desnutrição proteica sobre o microambiente perivascular medular na regulação da hematopoese

Protein malnutrition (PM) causes anemia and leukopenia by reduction of hematopoietic precursors and impaired production of mediators that induce hematopoiesis, as well as structural and ultrastructural changes in the bone marrow (BM) extracellular matrix. Hematopoiesis occurs in the bone marrow (BM) in distinct regions called niches, which modulate the processes of differentiation, proliferation and self-renewal of the hematopoietic stem cell (HSC). The perivascular niche, composed mainly by mesenchymal stem cells (MSC) and endothelial cells (EC), is the major modulator of HSC and its function extends to the migration of mature hematopoietic cells into the peripheral blood through the production of cytokines and growth factors. Thus, our hypothesis is that PM changes the perivascular niche and our objective is to evaluate whether PM affects the modulatory capacity of MSC and EC on hematopoiesis. C57BL/6 male mice were divided into Control and Malnourished groups, which received for 5 weeks, respectively, a normal protein diet (12% casein) and a low protein diet (2% casein). After this period, animals were euthanized, nutritional and hematological evaluations were performed, featuring the PM. We performed leukemic myelo-monoblasts cells transplantation and observed that these cells have a lower proliferation rate and are rather in the cell cycle G0/G1 phases in malnourished mice, indicating that the BM microenvironment is compromised in PM. MSC were isolated, characterized and differentiated in vitro into EC cells, which were evidenced by CD31 and CD144 markers. We performed the quantification of HSC and hematopoietic progenitors, as well as some regulators of proliferation and differentiation, ex vivo and after cultures with MSC or EC. We observed that PM reduces HSC and hematopoietic progenitors ex vivo. In PM, MSC promote increase in HSC and suppress hematopoietic differentiation, whereas ECs induce cell cycle arrest. Additionally, we verified that PM affects granulopoesis by decreasing the expression of G-CSFr in granule-monocytic progenitors. Thus, we conclude that PD compromises hematopoiesis due to intrinsic alterations in HSC, as well as alterations in the medullary perivascular niche

A desnutrição proteica (DP) provoca anemia e leucopenia decorrente da redução de precursores hematopoéticos e comprometimento da produção de mediadores indutores da hematopoese. A hematopoese ocorre na medula óssea (MO) em regiões distintas chamadas de nichos, que modulam os processos de diferenciação, proliferação e auto renovação da célula tronco hematopoiética (CTH). O microambiente perivascular, composto principalmente por células tronco mesenquimais (CTM) e células endoteliais (CE), é o principal modulador das CTH e sua função se estende até a migração das células hematopoiéticas maduras para o sangue periférico, através da produção de citocinas e fatores de crescimento. Dessa forma, nossa hipótese é que a DP altera o microambiente perivascular e objetivamos avaliar se a DP afeta a capacidade modulatória das CTM e CE sobre a hematopoese. Utilizamos camundongos C57BL/6 machos, divididos em grupos Controle e Desnutrido, sendo que o grupo Controle recebeu ração normoproteica (12% caseína) e o grupo Desnutrido recebeu ração hipoproteica (2% caseína), ambos durante 5 semanas. Após este período, os animais foram eutanasiados, foi realizada a avaliação nutricional e hematológica, caracterizando a DP. Realizamos transplantes de mielomonoblastos leucêmicos e observamos que estas células apresentam menor taxa de proliferação e se encontram em maior quantidade nas fases G0/G1 do ciclo celular em camundongos desnutridos, indicando que o microambiente medular está comprometido. Isolamos CTM, que foram caracterizadas e diferenciadas in vitro em CE, o que foi evidenciado pelos marcadores CD31 e CD144. Quantificamos CTH e progenitores hematopoéticos, bem como reguladores de proliferação e diferenciação, ex vivo e após culturas com CTM ou CE. Observamos que a DP reduz CTH e progenitores hematopoéticos ex vivo. Na DP, as CTM promovem incremento de CTH e suprimem a diferenciação hematopoética, enquanto que as CE induzem parada no ciclo celular. Adicionalmente, observamos que a DP afeta a granulopoese por diminuição da expressão de G-CSFr nos progenitores grânulo-monocíticos. Dessa forma, concluímos que a DP compromete a hematopoese por alterações intrínsecas na CTH, como também por alterações ocasionadas no microambiente perivascular medular

Difference of Low Skeletal Muscle Index According to Recommended Protein Intake in Korean

BACKGROUND: Sarcopenia has become a major concern owing to its association with a high risk of fall or fracture and metabolic impairments. There is insufficient evidence to support the role of dietary protein intake in reducing the prevalence of sarcopenia. This study was conducted to investigate the variation in low skeletal muscle index (SMI) with the dietary levels of protein intake.METHODS: This study analyzed data of 3,482 male and 4,838 female aged 50 years or older from the Korean National Health and Nutrition Examination Survey (KNHNES) database (2008–2011). Low SMI was indicated by a value <0.789 in male and <0.512 in female. Multiple logistic regression was performed to analyze the association of SMI with protein intake, whereby it was tested whether the dietary intake of proteins met the estimated average requirement (EAR) or the reference nutrient intake (RNI) as stated in the dietary reference intake (DRI) for Koreans, 2015.RESULTS: Irrespective of sex, the prevalence of low SMI was significantly high when the protein intake did not meet the EAR or RNI. Following adjustment for covariates, the odds ratio (OR) for low SMI in subjects with unmet EARs was 1.63 (1.28–2.09) in male and 1.35 (1.10–1.66) in female. The OR for low SMI in subjects with unmet RNI was 1.74 (1.38–2.18) in male and 1.39 (1.14–1.69) in female.CONCLUSION: The prevalence of low SMI was significantly higher when the protein intake did not meet the EAR or RNI as stated in the DRI for Koreans.

Influence of protein malnutrition on cutaneous wound healing in rats / Impacto da desnutrição proteica na cicatrização de feridas cutâneas em ratos

ABSTRACT Objective Investigate histological changes related to inflammatory response and collagen expression during wound healing in rats with protein malnutrition. Methods Twenty male Wistar rats underwent cutaneous surgery and were divided into two experimental groups: Malnourished (8% casein diet); Nourished (17% casein diet). Animals were euthanized after 5th and 10th days, descriptive and quantitative analyses were performed on sections stained with hematoxylin-eosin and sirius red, respectively. Statistical analysis of data using nonparametric Fisher's exact test with p<0.05 was carried out. Results At five days, increased fibroblast proliferation (p<0.01) and collagen expression (p<0.05) was observed in N5 group. After ten days, N10 and MN10 animals showed higher amount of granulation tissue and edema/inflammatory infiltrate independent of nutritional status (p>0.05), only N10 group showed fibroblast proliferation (p<0.01) and increased collagen expression (p<0.01). Conclusion Protein malnutrition seems not to influence inflammatory phase of healing, whereas it negatively effects fibroblast proliferation and collagen synthesis.

RESUMO Objetivo Investigar as alterações histológicas relacionadas à resposta inflamatória e à expressão de colágeno durante a cicatrização em ratos com desnutrição protéica. Métodos Vinte ratos Wistar machos foram submetidos à cirurgia cutânea e divididos em dois grupos experimentais: Desnutridos (dieta com caseína a 8%); Nutridos (17% de dieta com caseína). Animais foram eutanasiados após 5 e 10 dias, análises descritivas e quantitativas foram realizadas em cortes corados com hematoxilina-eosina e sirius vermelho, respectivamente. Análise estatística dos dados utilizando teste exato não paramétrico de Fisher com p<0,05 foi realizada. Resultados Aos cinco dias, observou-se aumento da proliferação fibroblástica (p<0,01) e expressão de colágeno (p<0,05) no grupo N5. Após 10 dias, animais N10 e MN10 apresentaram maior quantidade de tecido de granulação e edema/infiltrado inflamatório independente do estado nutricional (p>0,05), apenas grupo N10 apresentou proliferação fibroblástica (p<0,01) e aumento da expressão de colágeno (p<0,01). Conclusão A desnutrição protéica parece não influenciar na fase inflamatória da cicatrização, porém afeta negativamente a proliferação de fibroblastos e a síntese de colágeno.

Comportamento social em ratos recuperados após desnutrição proteica: análise comparativa entre machos e fêmeas / Social behavior in rats recovered from protein malnutrition: comparative analysis between males and females

A maturação do sistema nervoso central depende, entre outros fatores, da ingestão adequada de nutrientes. Períodos de desnutrição podem afetar seu desenvolvimento, comprometendo a capacidade cognitiva. O objetivo do trabalho foi avaliar o comportamento social de ratos e ratas Wistar alimentados com dieta hipoproteica e posteriormente recuperados com dieta normoproteica. Foram utilizados ratos Wistar (machos e fêmeas) divididos em dois grupos: Controle (C), alimentado com dieta normoproteica (AIN 14% de proteína) durante 12 semanas e Recuperado (R), desnutrido com dieta hipoproteica (AIN 6% de proteína) por 6 semanas e posteriormente alimentado com dieta normoproteica da 7ª a 12ª semanas. A massa corporal foi verificada semanalmente e após o período experimental os animais foram submetidos aos testes de labirinto em cruz elevado e reconhecimento social. Foram avaliados os parâmetros sensoriais utilizados pelos ratos no reconhecimento de seus pares no lócus de convívio. Utilizou-se o paradigma intruso-residente na análise, sendo observado que a dieta hipoproteica comprometeu o ganho de massa corporal em machos e fêmeas, como também foi verificado redução na capacidade de reconhecer seus pares, após exposição consecutiva de curta duração, e ainda, houve uma intensa manifestação de agressividade nos machos do grupo recuperado, fato que não foi observado pelas fêmeas indicando que a intensidade de comprometimento no sistema nervoso central, gerado pela desnutrição pode ter relação com o dimorfismo sexual. (AU)

The maturation of the central nervous system depends, among other factors, proper intake of nutrients. Periods of malnutrition can affect your development, undermining the cognitive ability. The objective of this work was to evaluate the social behavior of mice and Wistar rats fed with hipoproteica diet and later recovered with present diet. Wistar rats were used (males and females) divided into two groups: control (C), fed up with the present diet (AIN 14% protein) for 12 weeks and recovered (R), malnourished with diet hipoproteica (AIN 6% protein) for 6 weeks and subsequently fed with the present diet of 7th to 12th weeks. Body mass was checked weekly and after the trial period the animals were subjected to the tests of high cross maze and social recognition. We evaluated the sensory parameters used by rats in the recognition of his peers in locus. The intruder-resident paradigm in the analysis, being observed that diet hipoproteica undertook the weight gain in males and females and verified reduction in ability to recognize their peers, after successive exposure of short duration, and yet, there was an intense manifestation of aggression in males of the group recovered, a fact that was not observed for females, indicating that the intensity of commitment in the central nervous system, generated by malnutrition may be related to sexual dimorphism. (AU)

Hemopoese em desnutrição proteica: caracterização do estroma medular e avaliação da participação do cálcio / Hematopoiesis in protein malnutrition: characterization of bone marrow stroma and evaluation of calcium participation

A desnutrição proteica continua sendo um dos principais problemas nutricionais do mundo. Trabalhos de nosso laboratório e de outros autores evidenciam que entre as alterações presentes na desnutrição proteica, está a alteração do tecido hemopoético, com modificações em componentes da matriz extracelular, alterações no ciclo celular da célula tronco/progenitora hemopoética, redução da produção de precursores hemopoéticos, tanto na série eritrocitária como na série leucocitária, levando a anemia e leucopenia. Os mecanismos de participação do Ca2+ nas células da medula óssea são pouco conhecidos, porém, sabe-se que ele atua no processo de hemopoese. Têm sido descrito que elevações da concentração de Ca2+ citoplasmático induzem a proliferação e diferenciação de células mielóides. A ação dessa via em indivíduos desnutridos também é pouco conhecida. Este estudo tem como objetivo avaliar o estabelecimento da celularidade medular in vitro, bem como investigar mecanismos moleculares envolvidos na proliferação e diferenciação dessa celularidade, além de avaliar a ação do cálcio na presença da interleucina-3 em células-tronco hemopoéticas murinas e sua modulação para avaliar alterações na via das MAPKs. Camundongos C57BL/6, machos e adultos foram submetidos à desnutrição proteica e, após a perda de aproximadamente 20% de seu peso corporal, as células da medula óssea foram colhidas. Essas células foram imunofenotipadas, além de reagirem com anticorpos específicos para caracterização da célula-tronco hemopoética e proteínas da via de sinalização de cálcio intracelular. Observamos que a celularidade do estroma medular em cultura de longa duração de animais desnutridos é alterada, principalmente em células de origem mesenquimal, que aparecem em maior número em desnutridos ao longo dos dias de cultura. Além disso, as ondas de cálcio intracelular estavam diminuídas em animais desnutridos, bem como as proteínas p-PKC, p-PLCy, CAMKII, p-AKT e p-STAT5 não respondem ao estímulo de IL-3, levando a uma deficiência da expressão das MAPK: ERK 1/2, JNK e p38. A desnutrição proteica pode causar alterações na celularidade estromal da medula óssea e na diferenciação das células tronco hemopoéticas pela via das MAPKs estimulada por IL-3

Protein malnutrition remains one of the world's major nutritional problems. Studies from our laboratory and others shown that alterations in protein malnutrition include hemopoietic tissue alterations, changes in extracellular matrix components, changes in the hemopoietic stem/progenitor cell tissue, reduction in the production of hemopoietic precursors, in the erythroid series as in the mieloyd series, leading to anemia and leukopenia. Mechanisms of Ca2+ participation in bone marrow cells are poorly understood, but no hemopoiesis has been developed. Elevations of cytoplasmic Ca2+ concentration in proliferation and differentiation of myeloid cells were included. Such an action through malnourished animals is also a little known. This study aims to evaluate the establishment of cellularity in vitro as well as investigate the molecular involvement in cell proliferation and differentiation, as well as to evaluate the action of calcium in the presence of IL-3 in hemopoietic stem cells and its modulation by analytical evaluations in the MAPKs pathway. C57BL/6, male adult mices were subjected to protein restriction and, after loss of approximately 20% of their body weight, bone marrow cells were harvested. These were immunophenotyped in addition to specific activation terms for the hemopoietic stem cell and intracellular signaling pathway proteins. We observed that the bone marrow cells in long-term culture of malnourished animals is altered, mainly in cells of mesenchymal origin, which appears in greater numbers in undernourished throughout the days of culture. In addition, as intracellular calcium waves decreased in malnourished animals, as well as the p-PKC, p-PLC, CAMKII, p-AKT and p-STAT5 proteins did not respond to IL-3, sugesting expression of the expression of MAPK: ERK 1/2, JNK and p38. Protein malnutrition may have changes in bone marrow capacity and differentiation of hemopoietic stem cells through IL-3-stimulated MAPKs

A participação da autofagia na regulação da célula-tronco hemopoética em camundongos knockouts para Atg7 e transglutaminase 2 / The participation of autophagy in hemopoietic stem cell regulation in mice Knockouts for Atg7 and transglutaminase 2

A desnutrição é um dos principais problemas de saúde pública do mundo, que contribui significativamente para o aumento da morbidade e mortalidade. Estima-se um total de 815 milhões de pessoas subnutridas no mundo, e apesar da melhoria dos recursos alimentares o número de pessoas desnutridas ainda é alarmante. Estudos de nosso laboratório tem demonstrado, em modelo murino de desnutrição proteica, hipoplasia medular com evidências histológicas de alterações na matriz extracelular (MEC) e permanência da célula-tronco hemopoética (CTH) na fase G0/G1 do ciclo celular em camundongos desnutridos. Dados deste trabalho evidenciaram alterações nas proteínas Akt /mTOR, que podem contribuir para o aumento da expressão autofágica nas CTHs e CTPHs (célula-tronco progenitora). A literatura demonstra que desequilíbrios nutricionais e metabólicos podem induzir ativação autofágica. Autofagia é um processo catabólico que participa da manutenção da homeostase celular, da MEC e na regulação das CTHs, dados deste trabalho demonstram diminuição da quantidade de CTH e CTPH em camundongos desnutridos sem a presença do gene Atg7, proteína participativa no processo autofágico. Já camundongos com deleção da transglutaminase 2 (TG2) e submetidos a privação de nutrientes por 24 horas , apresentou diminuição da quantidade de CTH e aumento da diferenciação da CTPH. A TG2 tem participação na impulsão e formação do fagóforo (processo inicial autofágico). Considerando que a desnutrição proteica leva a comprometimento da hemopoese, alterações no ciclo celular das CTHs e hipoplasia medular com pancitopenia periférica e que privação e ou jejum prolongado de nutrientes pode aumentar a atividade autofágica, concluímos nesse projeto que autofagia é importante para regulação da CTH e diferenciação da CTPH, entretanto a desnutrição proteica e privação de nutrientes estimula de maneira diversa o mecanismo de diferenciação da CTH

Malnutrition is one of the world's major public health problems, which contributes significantly to increased morbidity and mortality. An estimated 815 million people are undernourished in the world, and despite the improvement in food resources the number of undernourished people is still alarming. Studies of our laboratory have demonstrated in murine model of protein malnutrition, medullary hypoplasia with histological evidence of extracellular matrix (ECM) changes and hemopoietic stem cell (HSC) stay in the G0/ G1 phase of the cell cycle in malnourished mice. Data from this work showed alterations in Akt / mTOR proteins, which may contribute to the increase of autophagic expression in HSC and HPC (progenitor stem cell). The literature demonstrates that nutritional and metabolic imbalances can induce autophagic activation. Autophagy is a catabolic process that participates in the maintenance of cellular homeostasis, ECM and in the regulation of HSC, data from this work demonstrate a decrease in the amount of HSC and HPC in malnourished mice without the presence of the Atg7 gene, a participatory protein in the autophagic process. Mice with transglutaminase 2 deletion (TG2) and submitted to nutrient deprivation for 24 hours showed a decrease in the amount of HSC and an increase in the differentiation of HPC. TG2 plays a role in the uptake and formation of phagophore (autophagic initial process). Considering that protein malnutrition leads to hemopoiesis, alterations in the cell cycle of HSC and spinal cord hypoplasia with peripheral pancytopenia, and that prolonged nutrient starvation or fasting may increase the autophagic activity, we conclude in this project that autophagy is important for regulation of HSC and differentiation of HPC, however, protein malnutrition and nutrient deprivation stimulate in a different way the mechanism of differentiation of HSC

Nutrition and growth: assessing the impact of regional nutritional intake on childhood development and metacarpal parameters / 대한해부학회지

Measuring skeletal development throughout juvenile growth can provide a greater understanding into the health, hormonal function and genetics of children. The metacarpals have been of interest for their potential to provide insights into healthy juvenile skeletal development. This study investigated the growth patterns of developing females from isolated communities who had varied diets. Anthropometrical measurements and hand-wrist X-rays were taken of 353 juvenile females from three populations: Pari Coastal Village and Bundi Highlands Village, Papua New Guinea (PNG); and Brisbane, Australia between 1968 to 1983. Radiographs were digitized, and the length and width of the second and third metacarpals compared to each subject's height and weight. As subject heights increased, metacarpal length and width increased. However, stature and second metacarpal length indicated the strongest correlation (P < 0.01), compared to third metacarpal length (P < 0.01) or width. From 11 to 13 years of age, Brisbane subjects were significantly heavier and taller in comparison to subjects from PNG, and coastal females were heavier and taller than the highland females. A prominent difference between the two PNG populations was the regional intake of protein in their diets. The second metacarpal presents particularly accurate measurements when determining the height or development of a child. Nutritional intake appears to have a major influence normal childhood growth, with a potential for protein deficiency to strongly inhibit growth. Any delayed growth is particularly evident in the child's stature, as well as in the development of the metacarpal long bones of the hand.

Evaluación de la ingesta dietética en estudiantes de cuarto año de medicina / Dietary intake evaluation in students of fourth year of medicine

La malnutrición, ya sea por déficit o exceso de nutrientes, constituye un problema creciente a nivel mundial, siendo los jóvenes universitarios uno de los grupos más vulnera- bles. Objetivo: Evaluar la ingesta dietética de los estudiantes de Farmacología II y/o Fisiopatología II de medicina de la Universi- dad Nacional Autónoma de Honduras en el Valle de Sula (UNAH-VS) en mayo del 2017. Pacientes y métodos: Se realizó un estudio cuantitativo, descriptivo, transversal, en el mes de mayo del 2017, en estudiantes del cuarto año de medicina. Mediante muestreo probabilístico aleatorio estratificado se obtuvo una muestra de 65 estudiantes. La información fue recolectada mediante dos encuestas de recordatorio de 24 horas reali- zadas en dos días diferentes. Dicha informa- ción fue procesada mediante el software NutrINCAP y Microsoft Excel. Resultados: Se encontró que los participantes tenían una ingesta energética media de 3892.88 kcal/día y de 2245.16 kcal/día y una ingesta de proteí- nas de 136.06 y 82.79 gramos al día para hombres y mujeres, respectivamente. La ingesta media de colesterol en hombres fue de 490.04 mg/día, mientras que en las muje- res fue de 268.31 mg/día. En promedio, el consumo de calcio que se encontró para ambos sexos fue 640.56 mg/día y 946.59 mg/día, mientras que de hierro fue 27.32 mg y 38.63 mg/día, para mujeres y hombres, respectivamente. Conclusiones: Los hom- bres evaluados presentaron una dieta hiper- calórica, con exceso de colesterol y déficit de calcio y hierro. Por su parte, las mujeres man- tienen una dieta hipocalórica, hiperproteica y con déficit de calcio y hierro...(AU)

Hambre oculta / Hidden Hunger

El hambre oculta es un problema a nivel mun-dial que ocasiona altas tasas de mortalidad si se compara con algunas de las enfermedades infectocontagiosas como malaria y tuberculo-sis. Cuando existe la desnutrición aumenta el deterioro en la capacidad de producción, trabajo y por ende en la producción de alimen-tos. Hambre oculta se de ne como la de cien-cia crónica de micronutrientes. Afecta la salud de forma silenciosa y grave, llegando a ocasio-nar en muchos casos la muerte. El problema engloba a los niños con desnutrición y también a aquellos con sobrepeso que esconden la escasez de nutrientes, por lo que debemos educar a la población sobre como recibir una alimentación balanceada y equilibrada.En Centroamérica y el Caribe existe un dé cit importante de micronutrientes. Debemos de ser proactivos en mejorar la alimentación para disminuir la desnutrición y obesidad. Para ello debemos mejorar la producción de alimentos. La forti cación de granos y cereales es la opción más rentable y sostenible en las mejo-ras del estado nutricional, aumentando su biodisponibilidad de los nutrientes.Erradicar el hambre y la desnutrición debe ser nuestra meta concreta, por lo que el objetivo de esta revisión es resaltar la importancia de administrar una cantidad y composición adecuada de micronutrientes desde el primer día de la gestación para hacer que disminuyaeste agelo. Es nuestra responsabilidad, y debe ser parte de la política pública, ya que a los problemas éticos ligados a la desnutrición, se añaden consecuencias negativas que afecta-ran a todos los niños...(AU)

A unified pathogenesis for kidney diseases, including genetic diseases and cancers, by the protein-homeostasis-system hypothesis

Every cell of an organism is separated and protected by a cell membrane. It is proposed that harmony between intercellular communication and the health of an organism is controlled by a system, designated the protein-homeostasis-system (PHS). Kidneys consist of a variety of types of renal cells, each with its own characteristic cell-receptor interactions and producing characteristic proteins. A functional union of these renal cells can be determined by various renal function tests, and harmonious intercellular communication is essential for the healthy state of the host. Injury to a kind of renal cells can impair renal function and induce an imbalance in total body health. Every acute or chronic renal disease has unknown etiologic substances that are responsible for renal cell injury at the molecular level. The immune/repair system of the host should control the etiologic substances acting against renal cells; if this system fails, the disease progresses to end stage renal disease. Each renal disease has its characteristic pathologic lesions where immune cells and immune proteins, such as immunoglobulins and complements, are infiltrated. These immune cells and immune proteins may control the etiologic substances involved in renal pathologic lesions. Also, genetic renal diseases and cancers may originate from a protein deficiency or malfunctioning protein under the PHS. A unified pathogenesis for renal diseases, including acute glomerulonephritis, idiopathic nephrotic syndrome, immunoglobulin A nephropathy, genetic renal diseases such as Alport syndrome, and malignancies such as Wilms tumor and renal cell carcinoma, is proposed using the PHS hypothesis.

Efectos histomorfológicos en la mandíbula de ratas albinas sometidas a dieta deficiente en proteína y diferentes concentraciones de hierro / Histo-morphological effects on the jaw of albino rats subjected to diet deficient in protein and different concentrations of iron

La nutrición es un fenómeno peculiar y activo de los seres vivientes en su constante proceso de intercambio con el medio ambiente. Objetivo: Se evaluó el efecto histomorfológico en la mandíbula de ratas albinas sometidas a dieta deficiente en proteína con diferentes concentraciones de hierro. Metodología: La muestra fue de 24 ratas albinas Holzman machos; de 21 días de nacidas, agrupadas en 4 grupos experimentales, alimentadas liad libitum" durante 46 días; grupo A (control) recibió proteína 10g hierro 29 mg/100g, grupo B recibió proteína 10g, hierro 46 mg/100g; grupo C proteína 5g Hierro 29 mg/100g); grupo D proteína 5g, hierro 46 mg/100mg. Se controló el peso corporal y consumo del alimento. La medición anatómica de la mandíbula (longitudinal vertical, grosor del cuerpo, longitud vertical rama) y primera molar inferior (longitud coronal y mesiodistal), análisis y conteo celular de los elementos estructurales del complejo dentino-pulpar, del periodonto de inserción y del cóndilo. Resultados: Existen cambios histomorfológicos en el complejo dentino-pulpar, periodonto de inserción y cóndilo, traducidos en disminución de los elementos celulares, capa dentinaria disminuida, zona acelular de Weil evidente; presencia de grupos isogénicos nodulares, e hipertróficos en el grupo C, y grupos isogénicos columnares alternando con zonas nodulares hipertróficas en el grupo D del cóndilo. En ratas albinas sometidas a dieta proteína 5g, hierro 26mg /100g y 46 mg/100g) grupos C y D. Conclusiones: Las dietas deficientes en proteína y diferentes concentraciones de hierro (proteína 5g, hierro 29,46 mg/100g) producen cambios histomorfológicos de la mandíbula, disminuyendo la capa dentinaria, los odontoblastos y fibroblastos pulpares, las fibras colágenas, disminución del número de fibroblastos, cementoblastos, osteoblastos, osteocitos y osteoclastos; disminución del número de condroblastos, condrocitos. Disminución en el peso corporal, longitud y grosor de la de la mandíbula...

Nutrition is a phenomenon peculiar and active living beings in their ongoing process of exchange with the environment. Objective: Histomorphological effect the jaw albino rats subjected to protein-deficient diet with different iron concentrations assessed. Methodology: The sample consisted of 24 male albino rats Holzman; 21 days old, grouped into 4 experimental groups fed ôad libitum" for 46 days; Group A (control) received 29 mg protein 10g hierro / 100g, group B received 10g protein, 46 mg iron / 100g; 5g protein C group lron 29 mg / 100g); Group D protein 5g, 46 mg iron / 100mg, The anatomical jaw (vertical longitudinal body thickness, vertical branch length) and lower first molar (coronal and mesiodistal length) cell count analysis and structural elements of the dentin-pulp complex periodontal insertion and the condyle. Results: There histomorphological changes in the dentin-pulp, periodontal insertion and condyle translated in decreased cellular elements, earmark layer decreased, acellular obvious area Wiel complex; periodontal membrane stage, presence of nodular isogenic groups, and hypertrophic in group C, columnar and nodular isogenic groups alternating with hypertrophic zones in group C condyle. In rats subjected to diet 5g protein, iron 26mg /100g y 46 mg / 100g) groups C and D. Conclusions: Diets deficient in protein (5g protein, iron 29.46 mg / 100g), and different iron concentration, produces histomorphological effect the jaw rats; reducing dentin layer, pulp odontoblasts and fibroblasts, collagen fibers, reducing the number of fibroblasts, cementoblasts, osteoblasts, osteocytes and osteoclasts; fewer chondroblasts, chondrocytes. Decrease in body weight, length and thickness of the jaw; coronal mesiodistal length and diameter of the first molar of the rats.