Model of nutritional supplementation with hepatotrophic factors increases cell proliferation in the liver of healthy rats

Foram avaliados dois protocolos de administração, em ratos sadios, de uma solução de fatores hepatotróficos (FH), composta por aminoácidos, vitaminas, sais minerais, glicose, insulina, glucagon e triiodotironina (T3). A solução foi administrada durante 10 dias, 40mg/kg/dia, i.p., em duas, grupo 2xFH (n=15), ou três doses, grupo 3xFH (n=15), diárias. Foram observados os efeitos na proliferação celular dos hepatócitos, na angiogênese e na matriz extracelular hepática, assim como as possíveis reações adversas. Os animais dos grupos 2xFH e 3xFH apresentaram aumento da massa hepática de 30,1% e 22,5%, respectivamente, em relação ao grupo-controle (CT; n=15). O índice de proliferação hepatocelular foi maior nos grupos 2xFH (1,4%) e 3xFH (1,2%) em relação ao grupo CT (0,53%), e a densitometria relativa do fator de crescimento do endotélio vascular pelo imunoblot não revelou diferença estatística entre os três grupos. Nos grupos 2xFH e 3xFH, houve redução do colágeno intersticial em relação ao grupo CT. A solução de FH estimulou o crescimento hepático e reduziu o volume de colágeno perissinusoidal. A administração em três doses diárias resultou em mortalidade de 26,7%, possivelmente pelo excessivo estresse da manipulação e pela menor adaptação fisiológica dos ratos, o que não ocorreu nos grupos 2xFH e CT. Para esse tipo de abordagem em ratos, o procedimento experimental mais apropriado, seguro, com melhor chance de adaptação dos animais e com resultados significativos é a aplicação dos FH em duas doses diárias.Two protocols of hepatotrophic factors (HF) administration, in solution composed by aminoacids, vitamins, mineral salts, glucose, insulin, glucagon, and triiodothyronine were evaluated in healthy rats. This solution was administered for 10 days, (40mg/kg/day) i.p., in two (group 2xFH; n=15) or three daily doses (group 3xFH n=15). The effects on hepatocytes cell proliferation, angiogenesis, and hepatic extracellular matrix, and also possible adverse reactions were analyzed. Animals of groups 2xFH and 3xFH presented an increase in hepatic mass of 30.1% and 22.5%, respectively, when compared rats of control group (CT; n=15). Hepatocellular proliferation index was higher in rats of groups 2xFH (1.4%) and 3xFH (1.2%) when compared to CT group animals (0.53%), and the relative densitometry of the vascular endothelial growth factor analyzed with immunoblot did not show a significant difference among the three groups. Rats of groups 2xFH and 3xFH showed a reduction of interstitial collagen when compared to CT rats. HF solution stimulated hepatic growth and reduced the volume of perisinusoidal collagen. Administration in three daily doses resulted in 26.7% mortality, possibly due to excessive stress from manipulation and lower physiological adaptation of rats, which did not occur in rats of groups 2xFH and CT. The more appropriate and safer experimental procedure for this approach in rats with higher chance of animal adaptation and significant results is the application of HF in two daily doses

Modulation of extracellular matrix by nutritional hepatotrophic factors in thioacetamide-induced liver cirrhosis in the rat

Nutritional substances associated to some hormones enhance liver regeneration when injected intraperitoneally, being denominated hepatotrophic factors (HF). Here we verified if a solution of HF (glucose, vitamins, salts, amino acids, glucagon, insulin, and triiodothyronine) can revert liver cirrhosis and how some extracellular matrices are affected. Cirrhosis was induced for 14 weeks in 45 female Wistar rats (200 mg) by intraperitoneal injections of thioacetamide (200 mg/kg). Twenty-five rats received intraperitoneal HF twice a day for 10 days (40 mL·kg-1·day-1) and 20 rats received physiological saline. Fifteen rats were used as control. The HF applied to cirrhotic rats significantly: a) reduced the relative mRNA expression of the genes: Col-α1 (-53%), TIMP-1 (-31.7%), TGF-β1 (-57.7%), and MMP-2 (-41.6%), whereas Plau mRNA remained unchanged; b) reduced GGT (-43.1%), ALT (-17.6%), and AST (-12.2%) serum levels; c) increased liver weight (11.3%), and reduced liver collagen (-37.1%), regenerative nodules size (-22.1%), and fibrous septum thickness. Progranulin protein (immunohistochemistry) and mRNA (in situ hybridization) were found in fibrous septa and areas of bile duct proliferation in cirrhotic livers. Concluding, HF improved the histology and serum biochemistry of liver cirrhosis, with an important reduction of interstitial collagen and increased extracelullar matrix degradation by reducing profibrotic gene expression

Productive aspects of pigs fed forage cactus silage associated with feed restriction

This study aimed to evaluate the use of silage of forage cactus (Opuntia ficus-indica Mill) in diets for finishing pigs. Two experiments were conducted: the first for digestibility and the second for performance. In the performance trial, the quantitative levels of feed restriction (0%, 10%, 20%, and 30%) were evaluated, which were associated with the supply of forage cactus silage. Forage cactus silage presented 2463.59 and 2456 kcal/kg of digestible and metabolizable energy, respectively. The feed restriction levels associated with the supply of forage cactus silage influenced feed intake, weight gain and final weight negatively, but did not affect feed conversion. Carcass absolute weight was influenced negatively. However, the yield of carcass and cuts and the amount of meat in the carcass were not influenced. With the increase in feed restriction, there was a decrease in duodenal mucosa thickness, intestinal glands, liver glycogen storage and the occurrence of inflammation in the submucosa and intestinal mucosa. Forage cactus silage is not accepted well by animals. The restriction up to 30% of balanced feed did not affect feed conversion, yield of carcass and cuts and economic viability. However, levels over 10% affected intestinal health.Keywords: Alternative feed, feed preservation, intestinal health, Opuntia ficus-indica Mill, pig nutritio

Supplementation of diets for piglets with L-Arginine and powdered whole milk

The objective of this study was to evaluate the supplementation of L-Arginine in diets with and without dairy products for piglets weaned at 21 days old. Thirty-two animals with initial mean weight of 5.16 ± 1.92 kg and from the same commercial lineage were allocated in a randomized block design to four diets. The experimental diets consisted of a corn and soybean meal-based diet (NDD), the same diet supplemented with 0.6% L-Arginine (NDDA), the diet supplemented with powdered whole milk (DD), and the diet supplemented with powdered whole milk and 0.6% of L-Arginine (DDA). At 43 days old, 16 animals were slaughtered. The productive performance, incidence of diarrhoea, serum parameters, relative organ weight, morphometry and intestinal health were evaluated. Supplementation with 0.6% of L-Arginine increased (P <0.05) the daily and final weight gain of the piglets at 32 days old and reduced the incidence of diarrhoea. DDA promoted a higher villi to crypt ratio (P <0.05). There was a lower rate of mitosis and apoptosis in the jejunum of animals fed DD and DDA. The non-dairy diet supplemented with 0.6% arginine (NDDA) increased serum immunoglobulin A (IgA) and Immunoglobulin G (IgG) concentrations compared with NDD (P <0.05). Thus, supplementation with 0.6% L-Arginine increased immunological activity, improved intestinal integrity, and reduced the incidence of diarrhoea

Comparison Of Bone Quantity By Ultrasound Measurements Of Phalanges Between White And Black Children Living In Paraná,brazil, With Europeans

The objective of this study was to determine bone quantity by ultrasound measurements of the proximal fnger phalanges (AD-SoS = amplitude-dependent speed of sound) of healthy Brazilian schoolchildren living in Paraná, Brazil, and to compare these values with European populations. The sample was composed of 1356 Brazilian schoolchildren of both genders (660 males, 696 females), aged 6 to 11 years, divided into white (840) and black (516) groups and compared to age- and gender-matched Europeans. AD-SoS of the schoolchildren increased significantly with age for both genders. Significantly higher AD-SoS values were observed for the white children (1916 ± 58) compared to their black counterparts (1898 ± 72) and for the female gender (1920 ± 61) compared to the male gender (1898 ± 66). Overall, the AD-SoS outcomes for females were similar to those of European studies. However, the AD-SoS of the Brazilian schoolchildren of both genders and skin colors was lower than that reported for children in Poland. AD-SoS outcomes for Brazilian schoolboys were similar to those obtained in Italian studies and were lower than those of the Spanish children. In conclusion, Brazilian schoolchildren of both genders and skin colors showed lower bone quantities than Polish children and Spanish males, and levels similar to Italian children and Spanish females.4310976981Mora, S., Gilsanz, V., Establishment of peak bone mass (2003) En-docrinol Metab Clin North Am, 32, pp. 39-63Silva, C.C., Goldberg, T.B., Teixeira, A.S., Dalmas, J.C., Bone mineralization among male adolescents: Critical years for bone mass gain (2004) J Pediatr, 80, pp. 461-467Habicht, J.P., Martorell, R., Yarbrough, C., Malina, R.M., Klein, R.E., Height and weight standards for preschool children. How relevant are ethnic differences in growth potential? (1974) Lancet, 1, pp. 611-614WHO Working Group (1986) Bull World Health Organ, 64, pp. 929-941. , Use and interpretation of anthropometric indicators of nutri-tional statusCauley, J.A., Lui, L.Y., Stone, K.L., Hillier, T.A., Zmuda, J.M., Hochberg, M., Longitudinal study of changes in hip bone mineral density in Caucasian and African-American women (2005) J Am Geriatr Soc, 53, pp. 183-189Neuner, J.M., Zhang, X., Sparapani, R., Laud, P.W., Nattinger, A.B., Racial and socioeconomic disparities in bone density testing before and after hip fracture (2007) J Gen Intern Med, 22, pp. 1239-1245Leder, B.Z., Araujo, A.B., Travison, T.G., McKinlay, J.B., Racial and ethnic differences in bone turnover markers in men (2007) J Clin Endocrinol Metab, 92, pp. 3453-3457Travison, T.G., Araujo, A.B., Esche, G.R., McKinlay, J.B., The relationship between body composition and bone mineral content: Threshold effects in a racially and ethnically diverse group of men (2008) Osteoporos Int, 19, pp. 29-38Travison, T.G., Beck, T.J., Esche, G.R., Araujo, A.B., McKinlay, J.B., Age trends in proximal femur geometry in men: Variation by race and ethnicity (2008) Osteoporos Int, 19, pp. 277-287Hill, D.D., Cauley, J.A., Sheu, Y., Bunker, C.H., Patrick, A.L., Baker, C.E., Correlates of bone mineral density in men of African ancestry: The Tobago bone health study (2008) Osteoporos Int, 19, pp. 227-234INEP (Instituto Nacional de Estudos e Pesquisas Edu-cacionais Anísio Teixeira) Mostre Sua Raça, , http://inep.gov.br/imprensa/noticias/censo/escolar/news05_05.htm, declare sua cor, Accessed July 26, 2010Ribeiro, R.R., Guerra-Junior, G., de Barros-Filho, A., Bone mass in schoolchildren in Brazil: The effect of racial miscegenation, pubertal stage, and socioeconomic differences (2009) J Bone Miner Metab, 27, pp. 494-501Baroncelli, G.I., Federico, G., Bertelloni, S., de Terlizzi, F., Cadossi, R., Saggese, G., Bone quality assessment by quantitative ultrasound of proximal phalanxes of the hand in healthy subjects aged 3-21 years (2001) Pediatr Res, 49, pp. 713-718Gimeno, B.J., Azcona San Julián, C., Sierrasesúmaga Ariznabarreta, L., Bone mineral density determination by os-teosonography in healthy children and adolescents: Normal values (2001) An Esp Pediatr, 54, pp. 540-546Vignolo, M., Brignone, A., Mascagni, A., Ravera, G., Biasotti, B., Aicardi, G., Infuence of age, sex, and growth variables on phalangeal quantitative ultrasound measures: A study in healthy children and adolescents (2003) Calcif Tissue Int, 72, pp. 681-688Vignolo, M., Parodi, A., Mascagni, A., Torrisi, C., de Terlizzi, F., Aicardi, G., Longitudinal assessment of bone quality by quantitative ultrasonography in children and adolescents (2006) Ultrasound Med Biol, 32, pp. 1003-1010Halaba, Z.P., Quantitative ultrasound measurements at hand phalanges in children and adolescents: A longitudinal study (2008) Ultrasound Med Biol, 34, pp. 1547-1553Pena, S.D.J., Bortolini, M.C., Pode a genética defnir quem deve se benefciar das cotas universitárias e demais ações afr- mativas? (2004) Estud Av, 18, pp. 31-50Pena, S.D.J., Bastos-Rodrigues, L., Pimenta, J.R., Bydlowski, S.P., DNA tests probe the genomic ancestry of Brazilians (2009) Braz J Med Biol Res, 42, pp. 870-876Telles, E., (2003) Racismo À Brasileira: Uma Nova Perspectiva Soci-ológica, , Rio De Janeiro: Relume Dumará, Fundação FordOliveira, F., Ser negro no Brasil: Alcances e limites (2004) Estud Av, 18, pp. 57-60Gilsanz, V., Skaggs, D.L., Kovanlikaya, A., Sayre, J., Loro, M.L., Kaufman, F., Differential effect of race on the axial and appendicular skeletons of children (1998) J Clin Endocrinol Metab, 83, pp. 1420-1427Nelson, D.A., Simpson, P.M., Johnson, C.C., Barondess, D.A., Kleerekoper, M., The accumulation of whole body skeletal mass in third- and fourth-grade children: Effects of age, gender, ethnicity, and body composition (1997) Bone, 20, pp. 73-78Bell, N.H., Shary, J., Stevens, J., Garza, M., Gordon, L., Edwards, J., Demonstration that bone mass is greater in black than in white children (1991) J Bone Miner Res, 6, pp. 719-723Rupich, R.C., Specker, B.L., Lieuw, A.F., Ho, M., Gender and race differences in bone mass during infancy (1996) Calcif Tissue Int, 58, pp. 395-397Abrams, S.A., O'Brien, K.O., Liang, L.K., Stuff, J.E., Differences in calcium absorption and kinetics between black and white girls aged 5-16 years (1995) J Bone Miner Res, 10, pp. 829-833Bryant, R.J., Wastney, M.E., Martin, B.R., Wood, O., McCabe, G.P., Morshidi, M., Racial differences in bone turnover and calcium metabolism in adolescent females (2003) J Clin Endocrinol Metab, 88, pp. 1043-1047Jaime, P.C., Latorre, M.R., Florindo, A.A., Tanaka, T., Zerbini, C.A., Dietary intake of Brazilian black and white men and its relationship to the bone mineral density of the femoral neck (2006) São Paulo Med J, 124, pp. 267-270Bhattoa, H.P., Bettembuk, P., Ganacharya, S., Balogh, A., Prevalence and seasonal variation of hypovitaminosis D and its relationship to bone metabolism in community dwelling postmenopausal Hungarian women (2004) Osteoporos Int, 15, pp. 447-451Wuster, C., Albanese, C., de Aloysio, D., Duboeuf, F., Gambac-Ciani, M., Gonnelli, S., Phalangeal osteosonogrammetry study: Age-related changes, diagnostic sensitivity, and discrimination power (2000) J Bone Miner Res, 15, pp. 1603-1614. , The Phalangeal Osteosonogrammetry Study Grou

Observational Constraints on Chaplygin Quartessence: Background Results

We derive the constraints set by several experiments on the quartessence Chaplygin model (QCM). In this scenario, a single fluid component drives the Universe from a nonrelativistic matter-dominated phase to an accelerated expansion phase behaving, first, like dark matter and in a more recent epoch like dark energy. We consider current data from SNIa experiments, statistics of gravitational lensing, FR IIb radio galaxies, and x-ray gas mass fraction in galaxy clusters. We investigate the constraints from this data set on flat Chaplygin quartessence cosmologies. The observables considered here are dependent essentially on the background geometry, and not on the specific form of the QCM fluctuations. We obtain the confidence region on the two parameters of the model from a combined analysis of all the above tests. We find that the best-fit occurs close to the $\Lambda$CDM limit ($\alpha=0$). The standard Chaplygin quartessence ($\alpha=1$) is also allowed by the data, but only at the $\sim2\sigma$ level.Comment: Replaced to match the published version, references update

The nuclear energy density functional formalism

The present document focuses on the theoretical foundations of the nuclear energy density functional (EDF) method. As such, it does not aim at reviewing the status of the field, at covering all possible ramifications of the approach or at presenting recent achievements and applications. The objective is to provide a modern account of the nuclear EDF formalism that is at variance with traditional presentations that rely, at one point or another, on a {\it Hamiltonian-based} picture. The latter is not general enough to encompass what the nuclear EDF method represents as of today. Specifically, the traditional Hamiltonian-based picture does not allow one to grasp the difficulties associated with the fact that currently available parametrizations of the energy kernel $E[g',g]$ at play in the method do not derive from a genuine Hamilton operator, would the latter be effective. The method is formulated from the outset through the most general multi-reference, i.e. beyond mean-field, implementation such that the single-reference, i.e. "mean-field", derives as a particular case. As such, a key point of the presentation provided here is to demonstrate that the multi-reference EDF method can indeed be formulated in a {\it mathematically} meaningful fashion even if $E[g',g]$ does {\it not} derive from a genuine Hamilton operator. In particular, the restoration of symmetries can be entirely formulated without making {\it any} reference to a projected state, i.e. within a genuine EDF framework. However, and as is illustrated in the present document, a mathematically meaningful formulation does not guarantee that the formalism is sound from a {\it physical} standpoint. The price at which the latter can be enforced as well in the future is eventually alluded to.Comment: 64 pages, 8 figures, submitted to Euroschool Lecture Notes in Physics Vol.IV, Christoph Scheidenberger and Marek Pfutzner editor

Continuous population-level monitoring of SARS-CoV-2 seroprevalence in a large European metropolitan region.

Effective public health measures against SARS-CoV-2 require granular knowledge of population-level immune responses. We developed a Tripartite Automated Blood Immunoassay (TRABI) to assess the IgG response against three SARS-CoV-2 proteins. We used TRABI for continuous seromonitoring of hospital patients and blood donors (n = 72'250) in the canton of Zurich from December 2019 to December 2020 (pre-vaccine period). We found that antibodies waned with a half-life of 75 days, whereas the cumulative incidence rose from 2.3% in June 2020 to 12.2% in mid-December 2020. A follow-up health survey indicated that about 10% of patients infected with wildtype SARS-CoV-2 sustained some symptoms at least twelve months post COVID-19. Crucially, we found no evidence of a difference in long-term complications between those whose infection was symptomatic and those with asymptomatic acute infection. The cohort of asymptomatic SARS-CoV-2-infected subjects represents a resource for the study of chronic and possibly unexpected sequelae