The use of genes for performance enhancement: doping or therapy?

Recent biotechnological advances have permitted the manipulation of genetic sequences to treat several diseases in a process called gene therapy. However, the advance of gene therapy has opened the door to the possibility of using genetic manipulation (GM) to enhance athletic performance. In such ‘gene doping’, exogenous genetic sequences are inserted into a specific tissue, altering cellular gene activity or leading to the expression of a protein product. The exogenous genes most likely to be utilized for gene doping include erythropoietin (EPO), vascular endothelial growth factor (VEGF), insulin-like growth factor type 1 (IGF-1), myostatin antagonists, and endorphin. However, many other genes could also be used, such as those involved in glucose metabolic pathways. Because gene doping would be very difficult to detect, it is inherently very attractive for those involved in sports who are prepared to cheat. Moreover, the field of gene therapy is constantly and rapidly progressing, and this is likely to generate many new possibilities for gene doping. Thus, as part of the general fight against all forms of doping, it will be necessary to develop and continually improve means of detecting exogenous gene sequences (or their products) in athletes. Nevertheless, some bioethicists have argued for a liberal approach to gene doping

Effect of selective β-adrenoceptor blockade and surgical resection of the celiac-superior mesenteric ganglion complex on delayed liquid gastric emptying induced by dipyrone, 4-aminoantipyrine, and antipyrine in rats

There is evidence for participation of peripheral β-adrenoceptors in delayed liquid gastric emptying (GE) induced in rats by dipyrone (Dp), 4-aminoantipyrine (AA), and antipyrine (At). The present study aimed to determine whether β-adrenoceptors are involved in delayed GE induced by phenylpyrazole derivatives and the role of the prevertebral sympathetic nervous system in this condition. Male Wistar rats weighing 220-280 g were used in the study. In the first experiment rats were intravenously pretreated with vehicle (V), atenolol 30 mg/kg (ATE, β1-adrenergic antagonist), or butoxamine 25 mg/kg (BUT, β2-adrenergic antagonist). In the second experiment, rats were pretreated with V or SR59230A 2 mg/kg (SRA, β3-adrenergic antagonist). In the third experiment, rats were subjected to surgical resection of the celiac-superior mesenteric ganglion complex or to sham surgery. The groups were intravenously treated with saline (S), 240 µmol/kg Dp, AA, or At, 15 min after pretreatment with the antagonists or V and nine days after surgery. GE was determined 10 min later by measuring the percentage of gastric retention (%GR) of saline labeled with phenol red 10 min after gavage. The %GR (means±SE, n=6) values indicated that BUT abolished the effect of Dp (BUT+Dp vs V+Dp: 35.0%±5.1% vs 56.4%±2.7%) and At (BUT+At vs V+At: 33.5%±4.7% vs 52.9%±2.6%) on GE, and significantly reduced (P<0.05) the effect of AA (BUT+AA vs V+AA: 48.0%±5.0% vs 65.2%±3.8%). ATE, SRA, and sympathectomy did not modify the effects of treatments. These results suggest that β2-adrenoceptor activation occurred in delayed liquid gastric emptying induced by the phenylpyrazole derivatives dipyrone, 4-aminoantipyrine, and antipyrine. Additionally, the released neurotransmitter did not originate in the celiac-superior mesenteric ganglion complex4931

Effect Of The Gabab Agonist Baclofen On Dipyrone-induced Delayed Gastric Emptying In Rats.

Dipyrone administered intravenously (iv) or intracerebroventricularly (icv) delays gastric emptying (GE) in rats. Gamma-aminobutyric acid (GABA) is the most potent inhibitory neurotransmitter of the central nervous system. The objective of the present study was to determine the effect of icv baclofen, a GABAB receptor agonist, on delayed GE induced by dipyrone. Adult male Wistar rats received a saline test meal containing phenol red as a marker. GE was indirectly evaluated by determining the percent of gastric retention (%GR) of the meal 10 min after orogastric administration. In the first experiment, the animals were injected iv with vehicle (Civ) or 80 mg/kg (240 micromol/kg) dipyrone (Dpiv), followed by icv injection of 10 microl vehicle (bac0), or 0.5 (bac0.5), 1 (bac1) or 2 microg (bac2) baclofen. In the second experiment, the animals were injected icv with 5 microl vehicle (Cicv) or an equal volume of a solution containing 4 micromol (1333.2 microg) dipyrone (Dpicv), followed by 5 microl vehicle (bac0) or 1 microg baclofen (bac1). GE was determined 10 min after icv injection. There was no significant difference between control animals from one experiment to another concerning GR values. Baclofen at the doses of 1 and 2 microg significantly reduced mean %GR induced by iv dipyrone (Dpivbac1 = 35.9% and Dpivbac2 = 26.9% vs Dpivbac0 = 51.8%). Similarly, baclofen significantly reduced the effect of dipyrone injected icv (mean %GR: Dpicvbac1 = 30.4% vs Dpicvbac0 = 54.2%). The present results suggest that dipyrone induces delayed GE through a route in the central nervous system that is blocked by the activation of GABAB receptors.3899-10

The Effect Of Bacterial Lipopolysaccharide On Gastric Emptying In Rats Suffering From Moderate Renal Insufficiency.

The objective of the present study was to evaluate the response of rats suffering from moderate renal insufficiency to bacterial lipopolysaccharide (LPS, or endotoxin). The study involved 48 eight-week-old male SPF Wistar rats (175-220 g) divided into two groups of 24 animals each. One group underwent 5/6 nephrectomy while the other was sham-operated. Two weeks after surgery, the animals were further divided into two subgroups of 12 animals each and were fasted for 20 h but with access to water ad libitum. One nephrectomized and one sham-treated subgroup received E. coli LPS (25 micrograms/kg, i.v.) while the other received a sterile, pyrogen-free saline solution. Gastric retention (GR) was determined 10 min after the orogastric infusion of a standard saline test meal labeled with phenol red (6 mg/dl). The gastric emptying of the saline test meal was studied after 2 h. Renal function was evaluated by measuring the plasma levels of urea and creatinine. The levels of urea and creatinine in 5/6 nephrectomized animals were two-fold higher than those observed in the sham-operated rats. Although renal insufficiency did not change gastric emptying (median %GR = 26.6 for the nephrectomized subgroup and 29.3 for the sham subgroup), LPS significantly retarded the gastric emptying of the sham and nephretomized groups (median %GR = 42.0 and 61.0, respectively), and was significantly greater (p < 0.01) in the nephrectomized rats. We conclude that gastric emptying in animals suffering from moderate renal insufficiency is more sensitive to the action of LPS than in sham animals.31515-

Effect Of 4-aminoantipyrine On Gastric Compliance And Liquid Emptying In Rats.

Dipyrone (Dp) delays gastric emptying (GE) in rats. There is no information about whether 4-aminoantipyrine (AA), one of its metabolites, has the same effect. The objectives of the present study were to assess the effects of AA and Dp on GE when administered intravenously (iv) and intracerebroventricularly (icv) (240 micromol/kg and 4 micromol/animal, respectively) and on gastric compliance when administered iv (240 micromol/kg). GE was determined in male Wistar rats weighing 250-300 g (5-10 per group) after icv or iv injection of the drug by measuring percent gastric retention (GR) of a saline meal labeled with phenol red 10 min after administration by gavage. Gastric compliance was estimated in anesthetized rats (10-11 per group), with the construction of volume-pressure curves during intragastric infusion of a saline meal. Compliance was significantly greater in animals receiving Dp (mean +/- SEM = 0.26 +/- 0.009 mL/mmHg) and AA (0.24 +/- 0.012 mL/mmHg) than in controls (0.19 +/- 0.009 mL/mmHg). AA and Dp administered iv significantly increased GR (64.4 +/- 2.5 and 54.3 +/- 3.8%, respectively) compared to control (34 +/- 2.2%), a phenomenon observed only with Dp after icv administration. Subdiaphragmatic vagotomy reduced the effect of AA (GR = 31.4 +/- 1.5%) compared to sham-treated animals. Baclofen, a GABAB receptor agonist, administered icv significantly reduced the effect of AA (GR = 28.1 +/- 1.3%). We conclude that Dp and AA increased gastric compliance and AA delayed GE, with the participation of the vagus nerve, through a pathway that does not involve a direct action of the drug on the central nervous system.40903-

Effect Of Antipyrine On The Gastric Emptying Of Liquid In Rats.

Antipyrine (At) and dipyrone (Dp) delay gastric emptying (GE) in rats. The objective of the present study was to assess the effects of intravenous (iv) and intracerebroventricular (icv) administration of At and Dp on the GE of liquid by rats. GE was assessed in male Wistar rats (5-10 in each group) 10 min after the icv or iv drug injection by measuring percent gastric retention (%GR) of a saline test meal labeled with phenol red 10 min after administration by gavage. The At iv group was significantly higher (64.4 +/- 2.6%) compared to control (33.4 +/- 1.5%) but did not differ from the Dp group (54.3 +/- 3.8%). After icv administration of At, %GR (34.2 +/- 2%) did not differ from control (32.6 +/- 1.9%), but was significantly higher after Dp (54.5 +/- 2.3%). Subdiaphragmatic vagotomy significantly reduced %GR in the At group (30.2 +/- 0.7%) compared to the sham group, but was significantly higher than in the controls (23.0 +/- 0.5%). In the animals treated with At iv, baclofen significantly reduced %GR (28.3 +/- 2.4%) compared to vehicle-treated animals (55.2 +/- 3.2%). The same occurred in the animals treated iv with vehicle and icv with baclofen. Although vagotomy and baclofen reduced %GR per se, the reduction was twice more marked in the animals treated with At. The results suggest that At administered iv, but not icv, delays GE of liquid in rats with the participation, at least in part, of the vagus nerve and that this phenomenon is blocked by the activation of GABA B receptors in the central nervous system.391507-1

Suplementação com soro sanguíneo de vacas leiteiras em diferentes períodos da lactação na produção in vitro de embriões bovinos.

Dissertação (Mestrado em Ciências) - Programa de Pós-Graduação em Veterinária, Faculdade de Veterinária, Universidade Federal de Pelotas, Pelotas, 2017. Orientador: Márcio Nunes Corrêa, Co-orientadora: Lígia Margareth Cantarelli Pegoraro

Opening the black box of selection

Peer reviewedPublisher PD

Tecnologias para a produção de sementes de feijão-caupi na comunidade ribeirinha do Cujubim Grande, em Rondônia.

A comunidade do Cujubim é formada por cerca de 100 famílias, que residem em cinco localidades, no entorno do lago do Cujubim Grande, situado à margem direita do Rio Madeira, a 35 km de Porto Velho, em Rondônia. A população local constitui-se principalmente de ribeirinhos, os quais têm na pesca, na produção de farinha e no extrativismo a sua principal fonte de renda. A agricultura de subsistência é praticada como atividade complementar pela maioria dos moradores da comunidade, sendo o feijão-caupi (Vigna unguiculata L.) e a melancia [Citrullus lanatus) algumas das principais culturas. Durante seis meses do ano, o nível das águas do rio Madeira baixa, trazendo à tona uma grande extensão de terras, as quais têm por característica a alta fertilidade, umidade constantemente próxima à capacidade de campo e isenção de propágulos de plantas daninhas. O uso agrícola dessas áreas dispensa o uso de adubação, irrigação e aplicação de herbicidas, o que favorece o cultivo agroecológico do feijão-caupi, a um custo de produção consideravelmente baixo. No entanto, a falta de conhecimentos adequados ou mesmo as dificuldades financeiras inviabilizavam a produção local e a manutenção de sementes para o plantio da safra seguinte, o que fazia com que os produtores ficassem sempre na dependência de adquiri-las no mercado local. Nesse contexto, a partir dos resultados de um projeto de pesquisa participativa executado pela Embrapa Rondônia entre 2005 e 2006 foram selecionadas quatro variedades de feijão-caupi, além de pequenos ajustes no sistema de produção utilizado pelos produtores. A partir daí, aprovou-se um projeto de transferência de tecnologias, executado entre 2007 e 2008, que possibilitou multiplicar as sementes dessas variedades e construir um banco para armazenagem das sementes. Foram realizadas ainda ações de capacitação dos produtores e um curso de organização social, visando promover uma melhor interação entre a equipe do projeto e os ribeirinhos. Com a realização das ações constantes no projeto conseguiu-se contribuir para o incremento quantitativo e qualitativo do cultivo de feijão-caupi junto à comunidade de Cujubim Grande, além do efeito multiplicador junto a outras regiões do baixo Madeira, que resultou inclusive em outro projeto, ora em execução, em duas comunidades do Distrito de Calama, em Porto Velho-RO

Substituted diaryl diselenides: Cytotoxic and apoptotic effect in human colon adenocarcinoma cells

AbstractAimsTo investigate the effects and study the underlying cell death mechanisms of diaryl diselenides, including: diphenyl diselenide (C6H5Se)2; 4-chlorodiphenyl diselenide (4-ClC6H4Se)2; 3-(trifluoromethyl)-diphenyl diselenide (3-CF3C6H4Se)2 and 4-methoxydiphenyl diselenide (4-MeOC6H4Se)2, on the human colon adenocarcinoma cell line HT-29.Main methodsThe viability of HT-29 cells after exposure to the diaryl diselenides and its substituted structures was based on the MTT assay. To verify if cell death was mediated throughout apoptosis mechanisms, flow cytometry and real-time PCR (qPCR) analyses were conducted.Key findingsThe MTT assay and flow cytometry analyses showed that (3-CF3C6H4Se)2 and (4-MeOC6H4Se)2 induced cytotoxicity through apoptosis mechanisms in HT-29 cells. qPCR revealed there was an up-regulation of pro-apoptotic (Bax, casapase-9, caspase-8, apoptosis-inducing factor (AIF) and Endonuclease G (EndoG)) and cell-cycle arrest genes (p53 and p21) and down-regulation of anti-apoptotic (Bcl-2 and survivin) and Myc genes.SignificanceThese results demonstrate that (3-CF3C6H4Se)₂ and (4-MeOC6H4Se)2 have the potential to induce apoptosis in HT-29 cells through the activation of caspase-dependent and independent pathways and through cell-cycle arrest