Utilização de hormônios e antibióticos em produtos alimentícios de origem animal: aspectos gerais e toxicológicos / Use of hormones and antibiotics in animal food products: general and toxicological aspects

OBJECTIVE: To approach the use of hormones and antibiotics in the production of animal origin food, mechanisms of action, toxicity, regulations in Brazil and worldwide and methods for residues detection in food. Data source: For this review, articles were searched using databases indexed in MEDLINE, LILACS, PUBMED and SciELO, using the key words: residues, antibiotics, hormones, meat, milk, eggs, in addition to their translations in Portuguese and Spanish. Data synthesis: We considered publications in the last 10 years, including 28 articles. CONCLUSIONS: The consumption of foods containing antibiotics and hormones residues is a problem to be considered, therefore, it is necessary to develop better methods of compounds detection and invest in food inspection

OBJETIVO: Abordar o uso de hormônios e antibióticos na produção de alimentos de origem animal, mecanismos de ação, toxicidade, regulamentação no Brasil e no mundo e os métodos para detecção dos resíduos nos alimentos. FONTE DE DADOS: Para essa revisão, artigos foram pesquisados usando bancos de dados indexados no MEDLINE, LILACS, PubMed e SciELO, utilizando as palavras-chave: resíduos, antibióticos, hormônios, carne, leite, ovos, além das respectivas traduções em inglês e espanhol. SÍNTESE DOS DADOS: Foram consideradas publicações dos últimos 10 anos, sendo incluídos 28 artigos. CONCLUSÕES: O consumo de alimentos contendo resíduos de hormônios e antibióticos constitui um problema a ser considerado, entretanto há necessidade de desenvolver melhores metodologias de detecção dos compostos e investir em fiscalização de alimentos

Qual o valor do efeito placebo no tratamento da sintomatologia do climatério?: revisão farmacológica do mecanismo de ação das drogas: [revisão] / What is the importance of the placebo effect on the treatment of the climacteric symptoms?: a pharmacological review of drugs' mechanism of action: [review]

Com o objetivo de revelar o valor do efeito placebo no tratamento dos sintomas climatéricos, foi realizada uma busca, na literatura médica, por trabalhos que pudessem mostrar a dimensão desse efeito. O método usado foi tentar fazer o inverso do que é feito em trabalhos controlados por placebo, em que o placebo é o modelo de comparação, ou seja, procurou-se usar o efeito dos hormônios como modelo para avaliar o efeito do placebo. Também foi feita uma revisão da farmacologia concernente ao mecanismo de ação das drogas e dos placebos. Os resultados não são animadores, tendo em vista uma divergência grande nos valores obtidos, o que em parte é explicado pelas diferenças pessoais nas respostas e nos achados científicos; entretanto, o efeito placebo está presente em todo o tratamento com drogas ativas ou não.

In order to show the placebo effect on the treatment of the climacteric symptoms, a search in the literature on this subject was carried out intending to do the opposite that is usually done, that is, to take the active drug as a comparative model for the placebo, and to look for the differences between them in regard to the relief of menopausal transition symptoms. A review of the pharmacology regarding drugs mechanism and placebo effects was also conducted. The results are not encouraging because of the data differences, mainly in respect to the personal variability in the responses to active and inactive drugs that was observed in scientific presentations. However, the placebo effect is present in any kind of treatment, either with active or inactive drugs.

Regulação endócrina de curto prazo de hormônios relacionados à fome em mulheres obesas que apresentam episódios de compulsão alimentar / Short-term endocrine regulation of hunger related hormones in obese women with binge eating episodes

A compulsão alimentar está associada a diversas doenças, entre elas, a obesidade. Com o intuito de pesquisar a diferença hormonal ligada ao controle da fome e da saciedade associada ao episódio de compulsão alimentar (ECA), avaliou-se a concentração sérica dos hormônios que regulam, este processo em mulheres adultas. Métodos: O estudo experimental foi composto de 3 grupos (n=23), sendo: grupo Eutrófico (GE;n=8), grupo obeso sem ECA (GO;n=7) e obesas com ECA (ECA;n=8). Todas as mulheres que participaram do estudo freqüentavam os serviços de saúde da Policlínica Piquet Carneiro. Foram dosados os hormônios: Grelina Total, Glucagon, Adiponectina, Amilina, Peptídeo C, GLP-1, Insulina e Leptina séricos nos tempos: jejum, 15 e 60 minutos após a ingestão da refeição fornecida. As refeições ingeridas foram controladas em energia, 55% carboidratos, 15% proteínas, 30% lipídios. Os dados foram analisados como valores médios por grupo em software SAS, considerando p<0,05. Resultados: A idade das mulheres estudadas variou de 32 a 50 anos. A concentração de adipon ectina encontrada, que é inversamente proporcional a adiposidade, foi significativamente menor no grupo ECA em relação aos demais grupos (P=0,01). Em relação à leptina, o grupo GO apresentou concentração maior em relação aos demais grupos (P<0,0001). Já, a concentração de grelina encontrada foi significativamente menor no grupo ECA em relação aos demais grupos (p=0,02). Foram encontradas concentrações significativamente maiores de insulina no grupo GO em relação aos demais grupos (p=0,04). A concentração de amilina encontrada foi significativamente maior no grupo GO em relação aos outros grupos (p=0,01). A concentração de GLP-1 encontrada no grupo GO foi maior em média, porém esta diferença não foi estatisticamente significativa entre os grupos (p=0,25). A concentração de Peptídeo C encontrada no grupo GO foi maior em relação aos outros grupos (p=0,003). Apesar da concentração de Glucagon no grupo ECA...

Binge eating is associated to several diseases, including obesity. In order to study the hormonal control of hunger and satiety that is commonly involved in binge-eating process: we evaluated the serum concentration of these hormones in adult women. Methods: The experimenal study was composed of 3 groups, n=23: Lean (GE, n=8), Obese without binge (GO, n=7) and obese with binge (BEE, n=8). All women who participated in the study attended the health services of the Polyclinic Piquet Carneiro. Serum hormones were assayed: total ghrelin, glucagon, adiponectin, Amylin, c-Peptide, glucagon like peptide (GLP-1), insulin and Leptin in fasting, 15 and 60 minutes after food intake. Meals were controlled in energy, 55% carbohidrates, 15% protein, 30% lipids. Data were analyzed as average values per group in SAS software, considering p<0.05. Results: Women's age ranged from 32 to 50 years. The adiponectin concentration, which is inversely proportional to adiposity, was significantly lower in BEE group than the other groups (p=0.01). Leptin of the GO group presented higher concentration than the others (p<0.0001). Ghrelin concentration was significantly lower in BEE group than the other groups (p=0.02). We found a significantly higher concentration of insulin in GO group in comparison to the others (p=0.04). Amylin concentration was significantly higher in GO group in comparison to the other groups (p=0.01). GLP-1 concentration of GO group was higher on average, but not statistically significant between groups (p=0.25). C-peptide concentration found in GO group was higher than the others (p=0.003). Despita glucagon concentration in the BEE group was greater than the other groups, these values were not statistically different (p=0.13). Conclusion: Our findings shown that BEE group have different hormonal profile than GO and GE. The lowest concentration of ghrelin found in BEE group and the hithest concentration of insulin, C-peptide and amylin found in both obese...

In vitro action of leukemia inhibitory factor (LIF) on mid-secretory stage endometrial stromal cells collected from hormone-simulated, ovariectomized monkey and maintained in three-dimensional primary culture.

Leukemia inhibitory factor (LIF) is a pleiotropic cytokine that is known to play an important role in blastocyst implantation. The putative action of LIF in the regulation of uterine function has been examined using mid-secretory stage monkey endometrial stromal cells cultured on rat-tail collagen type I and treated with recombinant human LIF (rhLIF) or immunoneutralized LIF (in LIF) under serum-free condition. Long-term ovariectomized rhesus monkeys (n=8) underwent simulation of their menstrual cycles with steroid hormones and endometrial tissue samples were collected on cycle day 18; stromal cells were isolated and grown in primary culture on three-dimensional collagen matrix. Significant decline in cellular protein synthesis (P < 0.01) and cell proliferation index (P < 0.05) was observed in cells with increasing doses (0-1000 ng/ml) of rhLIF under serum-free in vitro condition. JAK1 expression in cultured cells increased (P < 0.01) in response to rhLIF as revealed from Western blot and confocal laser scanning microscopic examination, STAT1 and STAT2 expressions were unchanged, while pSTAT3 expression increased (P < 0.01) with increased concentration of rhLIF in culture medium. Autophosphorylation of JAK1 in endometrial stromal cells showed no change with increasing concentration (0.01 to 100 ng/ml) of rhLIF in vitro, but significant (P < 0.05) increase was observed with the time of exposure to rhLIF. Immunoneutralization of LIF or no addition of rhLIF to cultured cells led to significant (P < 0.01) increase in stromal cell proliferation index and significant (P < 0.01) decrease in the level of JAK1 and its autophosphorylation as compared to cells exposed to rhLIF alone. From the present set of experiments we conclude that rhLIF affects the physiological behaviour of monkey mid secretory stage endometrial stromal cells in vitro via the JAK-STAT signaling pathway.

Gap junction modulation by extracellular signaling molecules: the thymus model

Gap junctions are intercellular channels which connect adjacent cells and allow direct exchange of molecules of low molecular weight between them. Such a communication has been described as fundamental in many systems due to its importance in coordination, proliferation and differentiation. Recently, it has been shown that gap junctional intercellular communication (GJIC) can be modulated by several extracellular soluble factors such as classical hormones, neurotransmitters, interleukins, growth factors and some paracrine substances. Herein, we discuss some aspects of the general modulation of GJIC by extracellular messenger molecules and more particularly the regulation of such communication in the thymus gland. Additionally, we discuss recent data concerning the study of different neuropeptides and hormones in the modulation of GJIC in thymic epithelial cells. We also suggest that the thymus may be viewed as a model to study the modulation of gap junction communication by different extracellular messengers involved in non-classical circuits, since this organ is under bidirectional neuroimmunoendocrine control

Effects of GABA on pancreatic exocrine secretion of rats

Since GABA and its related enzymes had been determined in beta-cells of pancreas islets, effects of GABA on pancreatic exocrine secretion were investigated in the isolated perfused rat pancreas. GABA, given intra-arterially at concentrations of 3, 10, 30 and 100 microM, did not exert any influence on spontaneous or secretin (12 pM)-induced pancreatic exocrine secretion. However, GABA further elevated cholecystokinin (10 pM)-, gastrin-releasing peptide (100 pM)- or electrical field stimulation-induced pancreatic secretions of fluid and amylase, dose-dependently. The GABA-enhanced CCK-induced pancreatic secretions were completely blocked by bicuculline (10 microM), a GABAA receptor antagonist but not affected by saclofen (10 microM), a GABA(B) receptor antagonist. The enhancing effects of GABA (30 microM) on CCK-induced pancreatic secretions were not changed by tetrodotoxin (1 microM) but partially reduced by cyclo-(7-aminoheptanonyl-Phe-D-Trp-Lys-Thr[BZL]) (10 microM), a somatostatin antagonist. In conclusion, GABA enhances pancreatic exocrine secretion induced by secretagogues, which stimulate enzyme secretion predominantly, via GABA(A) receptors in the rat pancreas. The enhancing effect of GABA is partially mediated by inhibition of islet somatostatin release. GABA does not modify the activity of intrapancreatic neurons.

Exogenous cysteamine increases basal pancreatic exocrine secretion in the rat

To determine whether exocrine pancreatic secretion is regulated by endogenous somatostatin, somatostatin deficiency was induced by cysteamine. Rats were subcutaneously administered a single dose of cysteamine (30 mg/100 g body weight) 12 hr before experiment. Anesthetized rats were prepared with cannulation into bile duct, pancreatic duct, duodenum, and jugular vein and pancreatic juice was collected. For in vitro study, isolated pancreata of rats, pretreated with cysteamine, were perfused with an intraarterial infusion of Krebs-Henseleit solution (37 degrees C) at 1.2 mL/min, and pancreatic juice was collected in 15-min samples. In vivo experiment of the rat, the mean basal pancreatic secretions, including volume, bicarbonate, and protein output were significantly increased from 18.4+/-0.5 microL/30 min, 0.58+/-0.05 microEq/30 min, and 214.0+/-26.1 microg/30 min to 51.6+/-3.7 microL/30 min, 1.52+/-0.11 microEq/30 min, and 569.8+/-128.9 microg/30 min, respectively (p<0.05). In the isolated perfused pancreas, cysteamine also resulted in a significant increase in basal pancreatic secretion (p<0.05). Simultaneous intraarterial infusion of octreotide (10 pmol/hr) to isolated pancreata partially reversed the effect of cysteamine on basal pancreatic secretion. These findings suggest that endogenous somatostatin play an important role on the regulation of basal pancreatic exocrine secretion.

The hyperinsulinemia produced by concanavalian A in rats is opioid-dependent and hormonally regulated

The present study examines the effect of concanavalin A (Con A) on the blood insulin and glucose levels of rats. Male and female rats treated with Con A (62.5-500 mug/kg) for three days showed a dose-and time-dependent hyperinsulinemia that lasted more than 48 h. Male rats were more sensitive to Con A. Thus, 6 h after treatment with Con A the circulating insulin levels in male rats had increased by 85 percent (control: 10.2 + 0.9 mU/l and Con A-treated: 18.8 + 1 mU/l) compared to only 38 percent (control: 7.5 + 0.2 mU/l; Con A-treated: 10.3 + mU/l) in females. An identical response was seen after 12 h. Con A (250 mug/kg) produced time-dependent hypoglycemia in both sexes but more pronounced in males. There was no correlation between the hypoglycemia and hyperinsulinemia described above. The Con A-induced hyperinsulinemia in rats of both sexes was abolished in gonadectomized animals (intact males: +101 + 17 percent vs orchiectomized males: -5 + 3 percent; intact females: +86 + 23 percent vs ovariectomized females: -18 + 7.2 percent). Pretreating intact male and female rats with human chorionic gonadotropin also significantly inhibited the Con A-induced hyperinsulinemia. Estradiol (10 mug/kg, im) significantly blocked the Con A-induced increase in circulating insulin in male rats (101 + 17 percent for controls vs 32 + 5.3 percent for estradiol-treated animals, P<0.05) while testosterone (10 mg/kg, im) had no similar effect on intact female rats. Pretreating Con A-injected rats with opioid antagonists such as naloxone (1 mg/kg, sc) and naltrexone (5 mg/kg, sc) blocked the hyperinsulinemia produced by the lectin in males (control: +101 + 17 percent vs naloxone-treated: +5 + 14 percent, or naltrexone-treated: -23 + 45 percent) and females (control: +86 + 23 por cent vs naloxone-treated: +21 + 20 percent, or naltrexone-treated: -18 + 11 percent). These results demonstrate that Con A increases the levels of circulating insulin in rats and that this response is opioid-dependent and hormonally regulated.

Hormone-mediated positive and negative regulation of a silencer region containing laminin B2 promoter in astrocytes.

Primary astrocytes synthesize only B2 chain (200 Kda) of laminin, which is one of the major components of basement membranes in the central nervous system (CNS). In CNS, B2 laminin functions as a potent neurite growth factor. Laminin B2 promoter contain no TATA or CAAT boxes but is GC rich. By deletion analysis and transient transfection assays of B2 laminin promoter, we have identified a silencer-like activity in the upstream region of the promoter. Thyroid hormone, insulin and phorbol ester mediated the induction of the promoter activity. Induction was repressed by the treatment of astrocytes with synthetic glucocorticoid hormone, dexamethasone. Hormone-mediated regulation through specific positive and negative responsive elements in transactivation of this silencer-containing TATA-less laminin B2 gene has been postulated.

Effect of (d-Ala6) LHRH on hypophyseal gonadotrophs and ovary of adult frog, Rana tigrina (Daud.) during post-breeding regression phase.

Effects of synthetic luteinizing hormone-releasing hormone (LHRH, 1.5 micrograms) agonist on pituitary and ovary were studied in R. tigrina during November, the post-breeding regression phase. Injections (ip) were given 6 days a week for 30 days and frogs were sacrificed on day 31. Pituitary sections were stained with AB-PAS-OG. The staining intensity, cytoplasmic granulation and cell, nuclear and cytoplasmic areas of hypophyseal gonadotrophs (B2 cells) increased (P < 0.05) following LHRH administration. In controls, the B2 cells were small and faintly stained. LHRH treatment significantly increased ovarian weight over controls due to recruitment of medium sized second growth phase oocytes (MSGP) from the first growth phase (FGP) oocytes. Nearly 50% of oocytes from the FGP oocyte pool were recruited to SGP. Control frog ovaries lacked SGP oocytes. The results demonstrate that both ovary and pituitary of R. tigrina remain responsive to gonadotrophic and GnRH stimulation respectively during the post breeding regression phase.

In vitro influence of hormones on transport of glucose and glycogen in liver and muscle of pinealectomised pigeons, Columba livia Gmellin.

To substantiate the increased peripheral utilization of blood glucose by pineal in wild pigeons, an in vitro study on the ability of liver and muscle slices of intact and pinealectomised wild pigeons (C. livia) in terms of uptake and release of glucose, and deposition and depletion of glycogen, in presence of insulin, acetylcholine, glucagon and adrenaline has been undertaken. A total insensitivity of liver and muscle of pinealectomised birds for glycogen deposition and insensitivity of liver for glucose uptake has been observed. Increased glucose release from liver in response to adrenalin has been observed. The results are discussed in terms of involvement of pineal in metabolic regulation associated with breeding activities.

Hormonal modulation of biosynthesis of prostatic specific antigen, prostate specific acid phosphatase and prostatic inhibin peptide.

Hormonal modulation of in vitro biosynthesis of three prostatic secretory proteins, prostate specific acid phosphatase (PSAP), prostate specific antigen (PSA) and prostatic inhibin peptide (PIP) by human benign hyperplasia (BPH) tissue was studied. LH and inhibins caused increase in the synthesis of all three proteins whereas FSH enhanced the synthesis of PIP and PSA only but decreased PSAP synthesis. Prolactin and thyroid releasing hormone decreased synthesis of PIP and PSAP. However, PSA synthesis was enhanced by TRH and was decreased by prolactin. Estradiol caused significant increase in PSA and PSAP but no discernible changes in PIP synthesis were noticed. Testosterone caused an increase in PIP, PSA and PSAP. These data indicate that biosynthesis of PIP, PSA and PSAP by BPH tissue is under multihormonal regulation.

Hormônios anabolizantes em alimentos: aspectos analíticos / Anabolic hormones in foods: analytical aspects

Desde a década dos setenta o uso de hormônios como promotores de crescimento em animais de criaçäo tem sido proibido em vários países, inclusive no Brasil. Para o controle destes anabolizantes foi desenvolvida uma enorme variedade de métodos, tanto como propósitos de triagem como de confirmaçäo. Os métodos mais usados säo os físico-químicos, tais como cromatografia em camada delgada, cromatografia a gás acoplada a espectrômetro de massa, cromatografia líquida de alto desempenho com detector UV, ou ensaios imunoquímicos, tais como radioimunoensaio ou enzimaimunoensaio. Este artigo tem por finalidade revisar os métodos analíticos mais usados internacionalmente no controle de substâncias anabolizantes em tecidos e urina de animais criados para consumo humano. Atençäo especial é dada ao anabolizante potencialmente carcinogênico Dietilstibestrol (DES) em relaçäo à sua toxicocinética, dinámica, seu possível uso no Brasil e às dificuldades envolvidas em sua determinaçäo

Kinetic characteristics of soluble and brush border alkaline phosphatase and sucrase activities in developing rat intestine: effect of hormones.

Suckling rat intestine contains 35 and 65% of the cytosolic and membrane-bound alkaline phosphatase (AP) activities. The corresponding values for sucrase were 20 and 80% respectively. The amount of the soluble enzymes was reduced to 7-11% in adult rat intestine. Administration of cortisone, thyroxine or insulin to suckling animals induced adult type distribution of the enzymes. There were apparent differences in kinetic characteristics of soluble and brush border enzymes, but the kinetic properties of the normally developed and hormone-induced AP and sucrase were essentially similar. This suggested identical nature of these enzymes under these conditions. A biphasic Arrhenius plot was obtained for AP in weaned and hormone injected pups with a break point around 18 degrees C, while the soluble enzyme yielded a monophasic curve (Ea = 8-11 kcal/mole). Arrhenius plot for sucrase was monophasic in the suckling, hormone-injected and adult rat intestine (Ea = 8.3-15.1 kcal/mole). Membrane-bound enzymes were generally labile, while soluble enzyme activities were stable to heat treatment (sucrase at 50 degrees C and AP at 60 degrees C) in various experimental groups.

Kinetic properties of gamma-glutamyltranspeptidase and leucine-amino-peptidase in developing rat intestine: effect of hormones.

Administration of cortisone and thyroxine produced adult-type increase in the activities of soluble and membrane-bound gamma-glutamyltranspeptidase (gamma-GTP) in suckling rat intestine. Membrane-bound enzyme activity remained unaltered while the soluble enzyme activity was reduced (27%) in insulin-injected pups. Kinetic analysis revealed that the observed changes in the enzyme levels were a consequence of altered Vmax with no change in apparent Km. A 2-fold increase in the Km value was observed in adult gamma-GTP activity compared to that of suckling animals. Membrane-bound and soluble gamma-GTP yielded similar values of the Ea (9.7-13.1 kcal/mole) but exhibited apparent differences in heat stability in the control and hormone-injected groups. Leucine-amino peptidase(LAP) activity was reduced to adult levels in insulin-treated suckling animals. Thyroxine- and cortisone-treatment did not affect soluble activity but significantly (P less than 0.001) augmented the membrane-bound LAP levels. This increase was due to enhanced (54-82%) Vmax with no change in Km. The observed decrease in LAP activity in response to insulin was due to reduced Vmax. There was no change in Ea (8-11.6 kcal/mole) except the value was raised to 19.1 kcal/mole in cortisone-injected pups. Both the soluble and membrane-bound LAP activities were quite resistant to heat inactivation upto 30 min at 60 degrees C except in weanling rats. Thus, the kinetic behaviour of normally developed and precociously induced gamma-GTP and LAP is essentially similar but there are apparent differences in the mode of action of insulin, cortisone and thyroxine in affecting the development of these enzymes.