Efeitos hemodinâmicos e renais da injeção de doses elevadas de clonidina no espaço peridural do cão

JUSTIFICATIVA E OBJETIVOS: Não existem estudos que relatem as repercussões renais determinadas pela injeção de doses elevadas de clonidina no espaço peridural. O objetivo do estudo foi avaliar os efeitos hemodinâmicos e renais determinados pela injeção de doses elevadas de clonidina no espaço peridural do cão. MÉTODO: Vinte animais anestesiados com tiopental sódico e fentanil foram distribuídos aleatoriamente e de forma duplamente encoberta em dois grupos: Grupo 1 ou placebo (n = 10), que recebeu 0,2 mL.kg-1 de solução fisiológica, e Grupo 2 ou clonidina (n = 10), que recebeu 0,2 mL.kg-1 de uma solução contendo 50 µg.mL-1 de clonidina, no espaço peridural. Foram avaliados os seguintes parâmetros hemodinâmicos: freqüência cardíaca (FC): bat.min-1; pressão arterial média (PAM): mmHg; pressão da artéria pulmonar ocluida (PAOP): mmHg; débito cardíaco (DC): L.min-1; volume sistólico (VS): mL; também, os seguintes parâmetros da função renal foram avaliados: fluxo sangüíneo renal (FSR): mL.min-1; resistência vascular renal (RVR): mmHg.mL-1.min; volume urinário minuto (VUM): mL.min-1; depuração de creatinina (D Cr): mL.min-1; depuração de para-aminohipurato (D PAH): mL.min-1; fração de filtração (FF); depuração de sódio (D Na): mL.min-1; depuração de potássio (D K): mL.min-1; excreção fracionária de sódio (EF Na): %; excreção urinária de sódio (U NaV): µEq.min-1; excreção urinária de potássio (U K V): µEq.min-1. O experimento consistiu em três momentos de 20 minutos cada. Os dados foram coletados aos 10 minutos de cada momento e a diurese, no início e no final de cada momento. Ao término de M1, a clonidina ou a solução fisiológica foi administrada no espaço peridural. Após período de 20 minutos iniciou-se M2 e, em seguida, M3. RESULTADOS: A clonidina na dose de 10 µg.kg-1 no espaço peridural do cão promoveu alterações significativas, com diminuições da freqüência cardíaca e do débito cardíaco e aumento da relação depuração de para-aminohipurato de sódio/débito cardíaco. CONCLUSÕES: Nas condições realizadas e nas doses empregadas, pode-se concluir que a clonidina não promoveu alteração da função renal, mas diminuiu valores hemodinâmicos (freqüência e débito cardíaco).

Determinação das doses letal 50 e 100 do propofol em nanoemulsão ou em emulsão lipídica pela via intraperitoneal em camundongos

The formulation of a drug can interfere with its absorption into the circulatory system and may result in changes in the dose required to achieve that particular effect. The aim of this study was to determine the lethal dose 50 (LD 50) and 100 (LD100) of a nanoemulsion of propofol and the lipid emulsion in mice intraperitoneally. One hundred sixty animals weighing 36.47 +/- 4.6g, which were distributed randomly into two groups: NANO and EMU who received propofol 1% in the nanoemulsion and lipid emulsion, respectively, intraperitoneally. Began with a dose of 250mg/kg (n=10) and from this isdecreased or increased the dose until achieving 0 and 100% of deaths in each group thus formed were seven subgroups in NANO (each subgroup n = 10) at doses 200, 250, 325, 350, 400, 425 and 475 mg/kg and in EMU eight subgroups (n= 10 each subset) 250, 325, 350, 400, 425, 475, 525 and 575 mg/kg. In the CONTROL group (n= 10) animals received saline in the largest volume used in the other groups to rule out death by the volume injected. Analysis of LD 50 and LD 100 were obtained by linear regression. The LD 50 was 320, 95 mg / kg and 4243, 51mg / kg and the LD 100 was445.99 mg / kg and 595.31 mg / kg to groups NANO and EMU, respectively. It follows that nanoemulsion is propofol in 25% more potent compared to the lipid emulsionintraperitoneally.

Combinations of low doses of unfractionated heparin and of low-molecular-weight heparin prevent experimental venous thrombosis

Synergism between low-molecular-weight heparin and low doses of unfractionated heparin (UH) enhancing anti-factor Xa activity and the release of tissue factor pathway inhibitor was observed. The aim of this study was to verify whether this association is effective in preventing experimental venous thrombosis. Seventy rats were allocated into 7 groups: the control group treated with distilled water, the H-350 group treated with UH 350 IU/kg, the E-2 group treated with enoxaparin 2 mg/kg, the H-175 group treated with UH 175 IU/kg, the E-1 group treated with enoxaparin 1 mg/kg, the H-175 + E-1 group treated with UH 175 IU/kg plus enoxaparin 1 mg/kg, and the H-100 + E-0.5 group treated with UH 100 IU/kg plus enoxaparin 0.5 mg/kg. Forty minutes after subcutaneous injection, thrombosis was induced in vena cava. Three hours later, if present, thrombi were withdrawn and weighed. Bleeding time, activated partial thromboplastin time, thrombin time (TT), and anti-factor Xa were measured at the beginning and end of the experiment. Fortyeight other animals were treated, but without inducing thrombus, and tests were performed 40 min after injection. Thrombus developed in 90.9% of control animals, 20% of the H-350 group, 22.2% of the E-2 group, 10% of the H-175 + E-1 group, and 30% of the H-100 + E-0.5 group; there was a difference between group C and the other groups. Only in the H-350 and H-175 + E-1 groups were TT and activated partial thromboplastin time prolonged in relation to control at the end of the experiment. Forty minutes after injection, TT was prolonged in the H-350 and H-175 + E-1 groups. In conclusion, combinations of low doses of low-molecular-weight heparin and low doses of UH were as effective as high doses of each one used alone in preventing thrombus development in rat vena cava. Copyright (c) 2005 S. Karger AG, Basel.

Efeito de diferentes doses de ácido retinoico sobre a resistência óssea de ratos jovens

OBJETIVO: Avaliar os efeitos da suplementação de diferentes doses de todo-trans ácido retinóico sobre a resistência óssea, por meio de ensaio biomecânico de flexão, em tíbia de ratos jovens. MÉTODOS: Foram estudados 58 ratos jovens, com quatro diferentes doses de vitamina A em suas dietas, sendo divididos em 4 grupos: grupo-controle (n=15), sem acréscimo de todo-trans ácido retinoico; grupo com acréscimo de 0,3mg de todo-trans ácido retinoico por kg de ração (n=13); grupo com 10mg de todo-trans ácido retinoico por kg de ração (n=15); e grupo com 50mg de todo-trans ácido retinoico por kg de ração (n=15). O estudo durou 30 dias. Após o sacrifício dos animais, suas patas esquerdas foram congeladas, dissecadas e as tíbias submetidas ao ensaio de flexão. Foram avaliados a carga máxima e o coeficiente de rigidez. Foi aplicada análise de variância one-way. O nível de significância estatístico adotado foi p<0,05. RESULTADOS: Os valores médios de carga máxima (em Newton) foram: grupo-controle =37,94, DP=4,76; grupo todo-trans ácido retinoico 0,3=36,49, DP= 4,38; grupo todo-trans ácido retinoico 10=40,12, DP=6,03; grupo todo-trans ácido retinoico 50=35,68, DP=5,22 (p=0,107). Os valores médios de coeficiente de rigidez (em Newton/milímetros) foram: grupo-controle =31,84 DP=6,75; grupo todo-trans ácido retinoico 0,3=29,18, DP=4,35; grupo todo-trans ácido retinoico 10=35,48, DP=8,14; grupo todo-trans ácido retinoico 50=30,31, DP=7,14 (p=0,85). CONCLUSÃO: Conclui-se que a exposição a diferentes doses de todo-trans ácido retinoico, em ratos, durante 30 dias, não exerce efeito sobre a resistência óssea, quando avaliada por ensaios biomecânicos.

Supraphysiological Triiodothyronine Doses Diminish Leptin and Adiponectin Gene Expression, but do not Alter Resistin Expression in Calorie Restricted Obese Rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Influence of aqueous extract of Agaricus blazei on rat liver toxicity induced by different doses of diethylnitrosamine

The modifying potential of prior administration of an aqueous extract of the mushroom Agaricus blazei Murrill (Agaricaceae) (Ab) on hepatotoxicity induced by different doses of diethylnitrosamine (DEN) in male Wistar rats was evaluated. During 2 weeks, animals of groups G3 (Ab+DEN50), G5 (Ab+DEN100), G7 (Ab+DEN200), and G8 (Ab-treated) were treated with the A. blazei through drinking water. After this period, groups G2 (DEN50), G3 (Ab+DEN50), G4 (DEN100) G5 (Ab+DEN100), G6 (DEN200), and G7 (Ab+DEN200) were given a single i.p. injection of 50, 100 and 200 mg/kg of DEN, respectively, while groups G1 (nontreated) and G8 (Ab-treated) were treated with 0.9% NaCl only. All animals were killed 48 h after DEN or NaCl treatments. The hepatocyte replication rate was estimated by the index of the proliferating cell nuclear antigen (PCNA) positive hepatocytes and the appearance of putative preneoplastic hepatocytes through expression of the enzyme glutathione S-transferase placental form (GSTP). After DEN-treatment, ALT levels, PCNA labeling index, and the number of GST-P positive hepatocytes were lower in rats that received A. blazei treatment and were exposed to 100 mg/kg of DEN. Our findings suggest that previous treatment with A. blazei exerts a hepatoprotective effect on both liver toxicity and hepatocarcinogenesis process induced by a moderately toxic dose of DEN. (C) 2002 Elsevier B.V. Ireland Ltd. All rights reserved.

Comparação de diferentes doses de colagenase em modelo de indução de tendinite para eqüinos: estudo clínico e ultra-sonográfico

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Estudo comparativo entre a acepromazina, clorpromazina e levomepromazina em diferentes doses, através do exame bispectral, termo e pressoalgimetria, em cães

The study's objective was to realize comparisons among different acepromazine, chlorpromazine and methotrimeprazine doses, evaluate parametric changes, test analgesia using press and term algimetry, and evaluate bispectral condition. 90 mongrel dogs were used, male and female, adult, weighting 10 to 15 Kg as a rule, distributed in 9 groups with 10 animals each. At first, second and third groups acepromazine was used at 0,1; 0,05 e 0,025 mg/Kg, respectively. At forth, fifth and sixth groups, chlorpromazine was used at 1,0; 0,5 and 0,25 mg/Kg, respectively. At seventh, eighth and ninth groups, methotrimeprazine at 1,0; 0,5 and 0,25 mg/Kg was used, respectively. All drugs were administered intravenously. objects of study: heart rate (HR), non invasive blood pressure (SAP, MAP, DAP), respiratory rate (f), capnography (ETCO(2)), pulse oxymetry (SatO(2)), mouth and rectal temperature, bispectral index (BIS), electromyography (EMG%), press and term algimetry. Somatic analgesia was evaluated by animal's response to nociceptives stimulus. We concluded that chlorpromazine had more bypotension. Dogs showed higher hypnosis level at: chlorpromazine group, with evident myorelaxation. All groups showed analgesia to thermic and mechanic stimulus. Acepromazine group showed high duration to both pain stimuli. Bispectral index was shorten at chlorpromazine group at 1,0 mg/kg doses, showing higher hypnosis index, and acepromazine was the less depressing considering the bispectral index.

Alternative low doses and routes of administering a prostaglandin F2 alpha analogue to induce luteolysis in Nelore cows

The present study was conducted in order to verify the efficacy of lower doses and alternative routes of a prostaglandin F2 alpha analogue, luprostiol (PGF), for the induction of luteolysis and the precipitation of estrus in nonlactating Nelore cows (Bos taurus indicus). A conventional dose (15 mg) of PGF was compared to doses lower than the conventional dose, which ranges from 10 to 50%, that were administered intramuscularly (IM), intravulvosubmucosally (IVSM), or in the Bai-hui acupuncture site located within the lumbosacral area. The cows were administered PGF 8 day after estrus in the presence of a corpus luteum, and randomly assigned to the following groups: G1 (positive control), 15 mg, IM (n = 23); G2, 7.5 mg, IM (n = 23); G3, 3.75 mg, I M (n = 24); G4, 7.5 mg, IVSM (n = 25); G5, 3.75 mg, Bai-hui acupoint (n = 24); and G6, 1.5 mg, Bai-hui acupoint (n = 25). The results indicated that 50% of a conventional dose of PGF (7.5 mg) resulted in a complete luteal regression (plasma progesterone < 1 ng/ml) at Hour 48, and hastened estrus, regardless of whether or not PGF was administered IM or IVSM. Comparatively, 10 or 25% of the conventional dose, even when administered to the Bai-hui acupoint, resulted in an initial reduction in the concentration of progesterone at Hour 24, followed by an increase observed at Hour 48. In conclusion, 25% of a conventional PGF dose administered via the Bai-hui acupoint proved inadequate to induce a complete luteal regression, whereas 50% of a conventional dose administered IM or IVSM was found to be the minimal dose required to induce effectively a complete luteal regression, and to precipitate the onset of estrus in nonlactating Nelore cows.

Improvement of embryo production by the replacement of the last two doses of porcine follicle-stimulating hormone with equine chorionic gonadotropin in Sindhi donors

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Patterns of Gene Expression in the Bovine Corpus Luteum Following Repeated Intrauterine Infusions of Low Doses of Prostaglandin F2alpha

Natural luteolysis involves multiple pulses of prostaglandin F2alpha (PGF) released by the nonpregnant uterus. This study investigated expression of 18 genes from five distinct pathways, following multiple low-dose pulses of PGF. Cows on Day 9 of the estrous cycle received four intrauterine infusions of 0.25 ml of phosphate-buffered saline (PBS) or PGF (0.5 mg of PGF in 0.25 ml of PBS) at 6-h intervals. A luteal biopsy sample was collected 30 min after each PBS or PGF infusion. There were four treatment groups: Control (n = 5; 4 PBS infusions), 4XPGF (4 PGF infusions; n = 5), 2XPGF-non-regressed (2 PGF infusions; n = 5; PGF-PBS-PGF-PBS; no regression after treatments), and 2XPGF-regressed (PGF-PBS-PGF-PBS; regression after treatments; n = 5). As expected, the first PGF pulse increased mRNA for the immediate early genes JUN, FOS, NR4A1, and EGR1 but unexpectedly also increased mRNA for steroidogenic (STAR) and angiogenic (VEGFA) pathways. The second PGF pulse induced immediate early genes and genes related to immune system activation (IL1B, FAS, FASLG, IL8). However, mRNA for VEGFA and STAR were decreased by the second PGF infusion. After the third and fourth PGF pulses, a distinctly luteolytic pattern of gene expression was evident, with inhibition of steroidogenic and angiogenic pathways, whereas, there was induction of pathways for immune system activation and production of PGF. The pattern of PGF-induced gene expression was similar in corpus luteum not destined for luteolysis (2X-non-regressed) after the first PGF pulse but was very distinct after the second PGF pulse. Thus, although the initial PGF pulse induced mRNA for many pathways, the second and later pulses of PGF appear to have set the distinct pattern of gene expression that result in luteolysis.

Efficiency of Matricaria chamomilla CH12 and number of doses of rabies vaccine on the humoral immune response in cattle

This study evaluated the effect of Matricaria chamomilla and vaccination frequency on cattle immunization against rabies. Four groups (n = 15/group) were treated with or without Matricaria chamomilla CH12 and vaccinated with one or two doses of rabies vaccine (30 day interval). No effect of chamomile was found on cattle immunization against rabies; however, antibody titers were protective in cattle vaccinated twice, while 93.3% of cattle vaccinated only once had titers under 0.5 UI/ml after 60 days. In conclusion, the use of chamomile did not alter the Immoral immune response in cattle, and two vaccine doses are suggested for achieving protective antibody titers.

Effects of low-level laser therapy (685 nm) at different doses in osteogenic cell cultures

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)