Polyethylene Catheter Research Articles

EFFECT OF STRESS ON CARDIOVASCULAR ACTIVITY AND SERUM CHOLESTEROL IN NORMOTENSIVE AND HYPERTENSIVE RATS: PP.29.174

Aims: We examined the effect of immobilization stress (60 min) on cardiovascular stress-responses and serum cholesterol levels in normotensive and hypertensive rats. Methods: The experiments were carried out on mongrel male rats. To induce high levels of blood pressure (BP) rats were been clipped at the renal artery with a silver clip (Goldblatt hypertension, 2K, 1C). Rats were instrumented with polyethylene catheters in artery for measuring of mean arterial pressure (MAP) and heart rate (HR). The hemodynamic parameters were measured using PowerLab system for direct recorder of blood pressure signals. Serum total cholesterol was determined with automated methods by a spectrophotometric assay. Results: Results showed that ischemia of kidney was accompanied by development of hypertension. Stress induced greater increase in HR and more prolongation of increase in MAP in hypertensive males vs. normotensive males. The basal cholesterol levels were significant lower in hypertensive males than in normotensive males. Stress resulted to increase in total cholesterol concentration in both groups of rats. Interestingly notice that stressed levels of cholesterol were higher in hypertensive males vs. normotensive males. Conclusion: Thus our data suggest that development of renal hypertension is characterized by decreased basal serum cholesterol. But despite this fact in hypertensive rats vs. normotensive group stress induces more pronounced increase in cardiovascular stress-reactivity which accompanied by more significant increase in serum cholesterol levels.

Urodynamic Effects of Propiverine on Detrusor Overactivity and Abdominal Straining during Voiding in Awake Rats with Intravesical Prostaglandin E2Instillation

PurposeWe investigated the effect of propiverine on cystometric parameters based on intraabdominal pressure (IAP) in awake rats in an overactive bladder (OAB) model induced by intravesical instillation of prostaglandin E2 (PGE2).Materials and MethodsTwenty-two female Sprague-Dawley rats were used. Polyethylene catheters were implanted into the bladder to record the intravesical pressure (IVP) and into the femoral artery to administer medication. A balloon-fitted catheter was positioned in the abdominal cavity to record the IAP. Awake cystometries were performed before and after intraarterial administration of propiverine 1 mg/kg (n=6), intravesical administration of 50µM PGE2 only (n=6), or intravesical PGE2 plus 1 mg/kg (n=4) or 3 mg/kg (n=6) of intraarterial propiverine. Cystometric pressure and volume parameters and variables related to detrusor overactivity (DO) were investigated.ResultsRats administered intravesical PGE2 showed increased pressure parameters and decreased volume parameters comparable to the DO model, which was effectively prevented by propiverine (1 or 3 mg/kg). Typical DO shown during the filling phase was decreased by intraarterial propiverine (3 mg/kg) injection. After propiverine (3 mg/kg) injection, IAP was increased at the time of micturition pressure with or without threshold pressure (p<0.05, p<0.01) depending on the dose administered.ConclusionsPropiverine improved pressure- and volume-related parameters in an OAB model. Furthermore, it also decreased the frequency of DO. However, higher concentrations of propiverine induced straining voiding.

Temporal analysis of the spontaneous baroreceptor reflex during mild emotional stress in the rat

The effect of emotional stress on the spontaneous baroreceptor reflex (sBRR) in freely moving rats was investigated. Six male Wistar rats equipped with an intra-arterial polyethylene catheter were exposed to a 2-min air-jet stress. For time course analysis of the sBRR response to stress, the records of systolic blood pressure (SBP) and pulse interval (PI) were divided into five regions: baseline (BASELINE), acute exposure to air-jet stress (STRESS), immediate recovery (IMMED. RECOVERY), remaining recovery (RECOVERY), and delayed response (DELAYED RESPONSE). In addition to sBRR sensitivity and effectiveness, we introduce the sequence coverage area and its median for evaluation of the sBRR operating range and set point. During exposure to STRESS and IMMED. RECOVERY, sBRR sensitivity was preserved, its effectiveness was decreased, its operating range was enlarged, and the set point was shifted towards higher SBP and lower PI values. According to the joint symbolic dynamics analysis, the SBP and PI relationship became less predictable hence more prone to respond to stress. In RECOVERY the parameters regained baseline values and DELAYED RESPONSE occurred during which re-setting of sBRR was noted. It follows that emotional stress modulates sBRR differentially during the time course of stress and recovery, affecting both linearity and unpredictability of the BP and PI relationship.

LOX-1 augments oxLDL uptake by lysoPC-stimulated murine macrophages but is not required for oxLDL clearance from plasma

Oxidized LDL (oxLDL) promotes lipid accumulation as well as growth and survival signaling in macrophages. OxLDL uptake is mainly due to scavenger receptors SR-AI/II and CD36. However, other scavenger receptors such as lectin-like oxLDL receptor-1 (LOX-1) may also play a role. We used mice with targeted inactivation of the LOX-1 gene to define the role of this receptor in the uptake of oxLDL and in activation of survival pathways. There was no difference in uptake or degradation of 125I-oxLDL in unstimulated macrophages from wild-type and LOX-1 knockout mice and no difference in the rate of clearance of oxLDL from plasma in vivo. However, when expression of LOX-1 was induced with lysophosphatidylcholine, oxLDL uptake and degradation increased 2-fold in wild-type macrophages but did not change in LOX-1 knockout macrophages. Macrophages lacking LOX-1 showed the same stimulation of PKB phosphorylation and enhancement of survival by oxLDL as wild-type cells. These data show that LOX-1 does not alter the uptake of oxLDL in unstimulated macrophages and is not essential for the pro-survival effect of oxLDL in these cells. However, LOX-1 expression is highly inducible by lysophosphatidylcholine and pro-inflammatory cytokines, and if that occurred in macrophages within atheromas, LOX-1 could substantially increase oxLDL uptake by lesion macrophages.

Comparison of voiding function and nociceptive behavior in two rat models of cystitis induced by cyclophosphamide or acetone

Nociceptive behavior and its relationship with bladder dysfunction were investigated in two cystitis models, which were induced by intraperitoneal (i.p.) injection of cyclophosphamide (CYP) or intravesical instillation of acetone, using freely moving, non-catheterized conscious rats. Female Sprague-Dawley rats were used. Cystitis was induced by i.p. injection of CYP (100 and 200 mg/kg) or intravesical instillation of acetone (10%, 30%, and 50%) via a polyethylene catheter temporarily inserted into the bladder through the urethra. Then the incidence of nociceptive behavior (immobility with decreased breathing rates) was scored. Voided urine was collected simultaneously and continuously to measure bladder capacity. The plasma extravasation in the bladder was quantified by an Evans blue (EB) dye leakage technique. CYP (100 mg/kg, i.p.) induced nociceptive behavior without affecting bladder capacity or EB concentration in the bladder. A higher dose of CYP (200 mg/kg, i.p.) decreased bladder capacity and increased EB levels as well as nociceptive behavior. In contrast, intravesical instillation of acetone (30%) decreased bladder capacity and increased EB levels, but evoked nociceptive behavior less frequently compared with CYP-treated animals. In capsaicin-pretreated rats, nociceptive behavior induced by CYP or acetone was reduced; however, the overall effects of CYP or acetone on bladder capacity and bladder EB levels were unaffected. These results suggest that there is a difference in the induction process of nociceptive behavior and small bladder capacity after two different types of bladder irritation, and that C-fiber sensitization is more directly involved in pain sensation than reduced bladder capacity.

CARDIOVASCULAR EFFECTS OF ACETYLCHOLINE MICROINJECTED INTO THE LATERAL PERIAQUEDUCTAL GRAY AREA OF RATS.

INTRODUCTIONThe periaqueductal gray area (PAG) is a mesencephalic region that is involved in the modulation of cardiovascular changes associated with behavioural responses. Among the neurotransmitters present in the PAG, acetylcholine (Ach) is also known to be involved in central cardiovascular control. In the present study, we attempted the cardiovascular effects of the microinjection of Ach into the lateral portion of the PAG (lPAG) of rats.METHODSMale Wistar rats were used. Guide cannulas were implanted in the lPAG for drug injection and a polyethylene catheter was implanted in the femoral artery for arterial pressure (AP) and heart rate (HR) recording using a computerized acquisition system.RESULTSThe injection of different doses of Ach (27 and 81nmol/ 50nl) into the lPAG of unanaesthetized rats caused dose‐related depressor responses accompanied by bradycardia. However, the injection of different doses of Ach (27 and 81nmol/50nl) into the lPAG of anaesthetized rats caused dose‐related depressor responses accompanied by tachycardia.CONCLUSIONThe present results indicate that activation of cholinergic receptors within the lPAG can evoke cardiovascular responses of rats.FINANCIAL SUPPORTFapesp (07/50166‐1) and Fapesp (05/57227‐0)

Effect of Elevated Intra-Abdominal Pressure on Portal Vein and Superior Mesenteric Artery Blood Flow in a Rat

Recent clinical experience suggests that minimal access portoenterostomy (the Kasai procedure) for biliary atresia leads to transplantation sooner, compared to the traditional open approach. It should be emphasized that elevated intra-abdominal pressure (IAP) may reduce hepatic and portal blood flow and thus may cause histologic liver damage. The aim of the present study was to evaluate the effects of IAP on blood flow in the portal vein (PV), compared to the superior mesenteric artery (SMA), and on the systemic mean arterial blood pressure (MABP). Male Sprague-Dawley rats were anesthetized with intraperitoneal ketamine (90 mg per kg) and xylasine (13 mg per kg). Polyethylene catheters (PE-50) were introduced into the right carotid artery for the measurement of MABP. After a midline laparotomy, the SMA and PV were isolated. Ultrasonic blood-flow probes were placed on the vessels for the continuous measurement of regional blood flow. Two large-caliber percutaneous peripheral intravenous catheters were introduced into the peritoneal cavity for inflation of air and for the measurement of IAP. The time course of MABP and SMA and PV flow as well as the relationship between IAP and SMA and PV flow were determined. Although all three hemodynamic parameters decreased with the increase in the IAP, the most significant changes were observed in PV blood flow. IAP at 3 mm Hg resulted in a 26% decrease in PV flow (P < 0.05), a 19% decrease in SMA flow (P < 0.05), and an 11% decrease in MABP (P < 0.05). IAP at 6 mm Hg caused a two-fold decrease in PV flow (P < 0.05), a 30% decrease in SMA flow (P < 0.05), and a 19% decrease in MABP (P < 0.05). There were no changes in the time course of MABP and PV and SMA flow. PV and SMA flow returned to normal values immediately after abdominal deflation. Persistent IAP decreased MABP, SMA, and, especially, PV flow by 50%. We speculate that in biliary atresia patients with already present liver dysfunction, decrease in SMA flow and even a greater decrease in PV flow from increased IAP, which occurs during a laparoscopic Kasai procedure, may further compromise liver function. This may be one of the explanations for the progression to earlier transplantation in infants undergoing a laparoscopic Kasai procedure.

Whole-body synthesis-secretion rates of long-chain n-3 PUFAs from circulating unesterified α-linolenic acid in unanesthetized rats

Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), long-chain n-3 PUFAs important for brain and heart function, can be obtained from dietary fish products or by liver synthesis from alpha-linolenic acid (alpha-LNA). Their daily human dietary requirements are not clear, and their liver synthesis rates in humans and nonhumans are unknown. We estimated whole-body (presumably liver) synthesis rates in unanesthetized rats by infusing [U-(13)C]alpha-LNA intravenously for 2 h and measuring labeled and unlabeled n-3 PUFA in arterial plasma using negative chemical ionization GC-MS. Newly synthesized esterified [(13)C]DHA, [(13)C]EPA, and [(13)C]docosapentaenoic acid (DPA) appeared in arterial plasma after 60 min of infusion, then their concentrations rose in an S-shaped manner. Esterified concentration x plasma volume data were fit with a sigmoidal equation, whose peak first derivatives provided synthesis rates of unlabeled EPA, DPA, and DHA equal to 8.40, 6.27, and 9.84 mumol/day, respectively. The DHA synthesis rate exceeded the published daily rat brain DHA consumption rate by 30-fold, suggesting that liver synthesis from alpha-LNA could maintain brain DHA homeostasis were DHA absent from the diet. This stable isotope infusion method could be used to quantify whole-body DHA synthesis rates in human subjects.

Sphingosine 1-Phosphate Modulates Spinal Nociceptive Processing

Sphingosine 1-Phosphate (S1P) modulates various cellular functions such as apoptosis, cell differentiation, and migration. Although S1P is an abundant signaling molecule in the central nervous system, very little is known about its influence on neuronal functions. We found that S1P concentrations were selectively decreased in the cerebrospinal fluid of adult rats in an acute and an inflammatory pain model. Pharmacological inhibition of sphingosine kinases (SPHK) decreased basal pain thresholds and SphK2 knock-out mice, but not SphK1 knock-out mice, had a significant decrease in withdrawal latency. Intrathecal application of S1P or sphinganine 1-phosphate (dihydro-S1P) reduced the pain-related (nociceptive) behavior in the formalin assay. S1P and dihydro-S1P inhibited cyclic AMP (cAMP) synthesis, a key second messenger of spinal nociceptive processing, in spinal cord neurons. By combining fluorescence resonance energy transfer (FRET)-based cAMP measurements with Multi Epitope Ligand Cartography (MELC), we showed that S1P decreased cAMP synthesis in excitatory dorsal horn neurons. Accordingly, intrathecal application of dihydro-S1P abolished the cAMP-dependent phosphorylation of NMDA receptors in the outer laminae of the spinal cord. Taken together, the data show that S1P modulates spinal nociceptive processing through inhibition of neuronal cAMP synthesis.

The enhanced hyperglycemic response to hemorrhage hypotension in obese rats is related to an impaired baroreflex

The aim of the present study was to assess the metabolic adjustments in adult rats with autonomic imbalance induced by hypercaloric diet. Male Wistar rats (4 weeks of age) were fed a chow diet (CD, n = 12) or hypercaloric diet (HD, n = 13) for 19 weeks. Body weight and dietary intake were measured every week and the basal metabolic rate was assessed. After 19 weeks of diet, six animals from each group were anesthetized with a lethal dose of barbital sodium (100 mg/Kg body weight, intraperitoneal; i.p.). Lee index was evaluated and adipose pads weighted. The remaining animals had a silastic cannula placed into the jugular vein for drug administration, blood collecting, and hemorrhage (1.2 mL/100 g bw/2 min). A polyethylene catheter (PE50) was inserted into the abdominal artery through the femoral artery for cardiovascular monitoring. The assessment of autonomic balance was done by evaluation of baroreflex sensitivity (intravenous (IV) injection of phenylephrine and sodium nitroprusside) and hemorrhage (1.2 mL/100 g bw/2 min). As expected, the HD induced obesity; increased weight gain (28%), adipose pads weight, and baroreflex dysfunction. The plasma level of free fatty acids and triacylglycerols were increased in HD rats by about 124% and 424%, respectively, as well as the basal metabolic rate measured at 19th weeks of diet (p < 0.01). We observed that baroreflex sensitivity to phenylephrine was reduced by about 50%, and the hyperglycemic response to hemorrhage hypotension was increased by 128% in HD rats. We found also a negative correlation between the alteration in baroreflex sensitivity and the increase in hyperglycemic response to hemorrhage in the obese rats (r = 0.72, p < 0.01) and a strong positive correlation between the increased Lee index and the hemorrhagic hyperglycemia (r = 0.93, p < 0.01). Our data demonstrate that obesity induced by hypercaloric diet in Wistar rats promotes an autonomic imbalance, which interferes with metabolic responses dependent on baroreflex sensitivity. In addition, we showed the existence of close correlation between the loss of baroreflex sensitivity and the degree of obesity.

Colfibrate attenuates blood pressure and sodium retention in DOCA-salt hypertension

Clofibrate, a peroxisome proliferator-activated receptor-alpha (PPAR alpha) agonist, increases renal tubular cytochrome P450 4a (Cyp4a) expression thereby increasing 20-hydroxyeicosatetraenoic acid (20-HETE) production. To determine if clofibrate affects blood pressure regulation we studied mice with DOCA-salt induced hypertension in wild-type and PPAR alpha knockout mice. Wild-type mice treated with DOCA-salt had higher mean arterial pressures and higher cumulative sodium balance, but lower renal 20-HETE production than did vehicle-treated mice. Treating DOCA-salt mice with clofibrate attenuated the increase in mean arterial pressure and cumulative sodium balance while increasing 20-HETE production and renal Cyp4a expression. In contrast the PPAR alpha knockout mice treated with clofibrate and DOCA-salt showed no attenuation in the increase of blood pressure, cumulative sodium balance, renal 20-HETE production or Cyp4a protein expression. Expression of the PPAR alpha protein was greater in proximal tubules than in renal microvessels. Our results show that PPAR alpha pathway induces renal tubular 20-HETE production which affects sodium retention and blood pressure regulation in DOCA-salt-treated mice.

Long-lasting breaches in the bladder epithelium lead to storage dysfunction with increase in bladder PGE2 levels in the rat

Increase in bladder mucosal permeability can be reproduced by intravesical administration of protamine sulfate (PS); however, the influence of PS once administered into the bladder disappears within several days. We developed a chronic animal model of urothelial injury using PS. Insertion of a polyethylene catheter through the bladder dome was performed in female Wistar rats. The other end of the catheter was connected to an osmotic pump for continuous delivery of PS or vehicle for 2 wk. Urinary frequency (UF) and voided volume (VV) were measured in the metabolic cage. The fifth group of rats received a high dose of PS (10 mg/ml) for 2 wk and were followed for a further 2 wk without PS. The sixth group received a high dose of PS for 2 wk and loxoprofen (0.1 mg.kg(-1).day(-1)) for 4 wk. UF was increased, and VV was reduced in rats treated with a high dose of PS but not changed in rats treated with a vehicle or a low dose of PS (1 mg/ml). UF was further increased in the fifth group, while unchanged in the sixth group. Histological sections in rats treated with a high dose of PS demonstrated a loss of the upper layer of urothelial cells and an increased number of mast cells. PGE2 level in the bladder was significantly elevated in the fifth group. These results indicate that chronic urotherial injury leads to an increase in UF and a decrease in VV. Increased PGE2 level in the bladder is likely to be associated with long-lasting storage dysfunction.

The enhanced hyperglycemic response to hemorrhage hypotension in obese rats is related to an impaired baroreflex.

We assessed the hyperglycemic response to hemorrhage in rats fed with hypercaloric diet. Male wistar rats (4 weeks) were fed a chow (CD, n=6) or hypercaloric diet (HD, n=7) for 19 weeks. After 19 weeks, the animals were submitted to implantation of silastic cannula into jugular vein for drugs administration, blood collecting and hemorrhage (1.2 mL/100g body wt/2 min). A polyethylene catheter was inserted into abdominal aorta for cardiovascular monitoring. An utonomic balance was evaluated by testing baroreflex sensitivity (with phenylephrine and sodium nitroprusside). Our data showed that hypercaloric diet induced obesity. We observed a reduction in baroreflex sensitivity (50%) and an increase in hemorrhagic hyperglycemia response (35%) in HD compared to CD group (p&lt;0.01). We found a negative correlation between the change in baroreflex sensitivity and the increase in hyperglycemic response to hemorrhage (r=0.72, p&lt;0.01) and in the Lee index (r=0.72, p&lt;0.01). A positive correlation between the increased Lee index and hemorrhage hyperglycemia (r=0.90, p&lt;0.01) was also observed. Our data showed that obesity induced by hypercaloric diet promotes an autonomic imbalance characterized by enhanced hemorrhagic hyperglycemia response, which is related to impaired baroreflex sensitivity. Supported by: CNPq and FAPEMIG.

CARDIOVASCULAR EFFECTS OF ACETYLCHOLINE MICROINJECTED INTO THE VENTROLATERAL PERIAQUEDUCTAL GRAY AREA OF RATS.

INTRODUCTIONThe periaqueductal gray area (PAG) is a mesencephalic region that is involved in the modulation of cardiovascular changes associated with behavioural responses. Among the neurotransmitters present in the PAG, acetylcholine (Ach) is also known to be involved in central cardiovascular control. In the present study, we attempted to study the cardiovascular effects of the microinjection of Ach into the ventrolateral portion of the PAG (vlPAG) of rats.METHODS: Male Wistar rats were used. Guide cannulas were implanted in the vlPAG for drug injection and a polyethylene catheter was implanted into the femoral artery for arterial pressure (AP) and heart rate (HR) recording using a computerized acquisition system. RESULTS: The injection of different doses of Ach (27 and 81nmol/50nL) into the vlPAG of unanaesthetized rats caused dose‐related depressor responses accompanied by bradycardia. However, the injection of different doses of Ach (27 and 81nmol/50nL) into the vlPAG of anaesthetized rats caused dose‐related depressor responses accompanied by tachycardia.CONCLUSION: The present results indicate that activation of cholinergic receptors within the vlPAG can evoke cardiovascular responses in rats.FINANCIAL SUPPORT: CNPq and Fapesp (05/57227‐0)

Aspirado traqueal de cavalos clinicamente sadios da raça Quarto de Milha após prova de três tambores

O objetivo do presente estudo foi avaliar,com o auxílio de endoscopia, a citologia do aspiradotraqueal em vinte sete cavalos da raça Quartode Milha, provenientes de Curitiba e Região Metropolitana,após prova de Três Tambores. Foi obtidasecreção das vias aéreas por aspirado traquealcom cateter de polietileno introduzido no canal detrabalho do endoscópio, na altura da bifurcação traqueal.As lâminas citológicas foram preparadas poresfregaço e coradas pela técnica de panótico rápidoe a contagem diferencial foi realizada em 500células através de microscopia óptica com aumentode 1000 vezes. Nenhum dos cavalos apresentouanormalidade, incluindo epistaxe, ao exame clínico.Entretanto, à citologia detectou-se hemossiderófagosem três animais, sugerindo que alguns delespoderiam estar sofrendo de hemorragia pulmonarsubclínica. A contagem diferencial de células do aspiradotraqueal foi em média de: 44,09 ± 35,68% decélulas epiteliais; 1,10 ± 2,18% de células caliciformes;23,10 ± 35,93% de neutrófilos; 0,13 ± 0,37%de linfócitos; 0,91 ± 2,81% de eosinófilos; 30,57 ±23,62% de macrófagos e 0,13 ± 0,93% de hemossiderófagos.Em conclusão, baseado no presentetrabalho, a avaliação das populações celularescom o aspirado traqueal pode fornecer ao clínicoimportantes informações adicionais, especialmenteacerca de processos inflamatórios das vias aéreasinferiores e hemorragia pulmonar.

Abstract 526: Oral And Intravenous Anti-thrombotic Activities Of F 16618, A New Selective Par1 Antagonist With Minor Risk Of Bleeding

F 16618 is a new phenyl-pentadienoyl derivative which competitively antagonizes PAR1 giving a prevention in vitro against human platelet aggregation. The main goal of the present study was to investigate the anti-thrombotic effects of F 16618 in two models of platelet aggregation-induced arterial thrombosis: an arteriovenous shunt in anesthetized rats and a photochemical-induced carotid artery thrombosis in anesthetized guinea-pigs. Firstly, a shunt was placed between the right jugular vein and the left carotid artery using polyethylene catheters. The kinetics of thrombus formation were assessed by a thermic probe fixed in the middle of the shunt. F 16618 was administered by gavage 15 min before anesthesia. F 16618 dose-dependently increased the occlusion time from 10 to 80 mg/kg, p.o. The first effective dose was 20 mg/kg and the maximal response was found at 40 mg/kg (54 ± 14 %, P &lt; 0.001 vs. vehicle). In addition, 29 % of the shunts remained open 20 min after unclamping in presence of F 16618 (40 mg/kg, n = 7). Similarly, a high dose of F 16618 administered i.v. significantly delayed the occlusion time (29 ± 8 %, P &lt; 0.05) without any significant effect on the tail bleeding time (358 ± 26 sec in the presence of F 16618 vs 397 ± 38 sec in the presence of vehicle). Secondly, the intravenous activity of F 16618 (from 40 μg/kg to 630 μg/kg) was investigated in a model based on the photochemical reaction between Rose Bengal and trans-illuminated green light to induce a transluminal thrombus in a guinea-pig carotid artery. F 16618 was administered as bolus over 2 min before Rose Bengal administration, followed by a constant infusion over 15 min immediately after the source of light was turned on. F 16618 at 80 μg/kg only tended to increase the occlusion time (29 ± 36 % vs. vehicle). From the dose of 160 μg/kg, F 16618 significantly prolonged this occlusion time and the maximal effect was obtained with 320 μg/kg (bolus and infusion, 112 ± 36 %, P &lt; 0.001 vs. vehicle). Collectively, the results demonstrate that F 16618, a new PAR1 antagonist, dose-dependently prevents platelet-induced arterial thrombosis with minor risk of bleeding by both single intravenous or oral administration.

Linfadenocromatografia perigástrica com carbono ativado (CH40): estudo experimental

RACIONAL: Procedimento cirúrgico bem instituído e planejado constitui ainda a única terapêutica efetiva para o câncer gástrico. Entretanto, os resultados de cura não têm melhorado significativamente nas últimas décadas, principalmente no ocidente. O principal benefício de introdução endoscópica de corantes na submucosa gástrica está na facilitação de linfadenectomias regradas, podendo facilitar a localização acurada dos linfonodos. Além disso, a linfadenocromatografia possibilita futuras pesquisas para a detecção do linfonodo sentinela e sua aplicabilidade racional e seletiva na indicação precisa da linfadenectomia, principalmente dos grupos de linfonodos de ressecção mais trabalhosa e com maiores possibilidades de complicações. A linfadenocromatografia com carbono ativado (CH40) foi analisada neste estudo experimental (fase 1). OBJETIVOS: Testar a efetividade e inocuidade da linfadenocromatografia com CH40, em três espécies animais diferentes. MÉTODOS: Como preconizado pela Associação Brasileira de Pesquisas Clínicas (Resoluções nº 196/96 e 251/97, CNS/MS), foram utilizados três espécies diferentes de animais: 3 cães, 10 coelhos e 20 ratos. Em todos os cães, a introdução de CH40 na camada submucosa de estômago foi realizada através da endoscopia gástrica e utilizando, cateter de polietileno agulhado, usualmente empregado na esclerose de varizes esofageanas. O período de observação variou de 43 a 125 dias, quando o procedimento cirúrgico foi realizado. Em todos os coelhos e ratos a introdução de CH40 foi realizada através de agulha hipodérmica e seringa insulínica, na região subcutânea inguinal. O período de observação foi de 102 a 105 dias e 110 a 122 dias, respectivamente. RESULTADOS: Nos períodos de observação, desde a injeção até a eutanásia, não se detectou em nenhum animal efeito colateral ou óbito. Nos cães, linfonodos perigástricos foram corados pelo CH40. Em todos os coelhos e ratos, o tecido celular subcutâneo da região inguinal foi fortemente corado de preto. Também, em todos ratos, linfonodos da região aórtica abdominal foram tingidos pelo CH40. CONCLUSÃO: A linfadenocromatografia com CH40 não mostrou toxicidade nas três espécies de animais estudadas. O carbono ativado foi efetivo no tingimento de linfonodos neste estudo.

Distribution of Spermatozoa and Embryos in the Female Reproductive Tract after Unilateral Deep Intra Uterine Insemination in the Pig

Distribution of Spermatozoa and Embryos in the Female Reproductive Tract after Unilateral Deep Intra Uterine Insemination in the Pig

The Interaction between Intrathecal NMDA Receptor Antagonist and 5-HT3Receptor Agonist in the Rat Formalin Test

Background: A single agent administered is not effective enough to block nociception. Combination of agents acting through different mechanisms may be one of the best ways for better analgesic methods. The purpose of this study was to investigate the spinally mediated analgesic interaction between 5-HT3 receptor agonist (m-CPBG) and NMDA receptor antagonist (MK801) in the rat formalin test. Methods: A polyethylene catheter was inserted in the atlanto-occipital membrane to the thoracolumbar level of the spinal cord. On postoperative 7 day, the normal saline (n = 6), m-CPBG (10, 30, 100μg: n = 18) and MK801 (0.1, 1, 10μg: n = 18) were injected intrathecally before subcutaneous injection of 5% formalin. The combinations of each 1/2ED50 + 1/2ED50, 1/4ED50 + 1/4ED50, 1/8ED50 + 1/8ED50 were tested and the ED50 of the combination was determined. The experimental ED50 values were compared with the theoretical additive values. Results: m-CPBG dose-dependently decreased the number of flinches in both phase 1 and 2. MK801 dose-dependently reduced the number of flinches in phase 2, but not in phase 1. The combination of m-CPBG and MK801 produced dose-dependent decreases of flinches on both phase 1 and 2. ED50 values (2.75μg for m-CPBG and 0.076μg for MK801) of phase 2 in the combination were significantly less than the calculated additive values (20.0μg for m-CPBG and 0.55μg for MK801)(P ＜ 0.01). Conclusions: Intrathecally administered m-CPBG and MK801 had synergistic analgesic effects on formalin-induced hyperalgesia as well as antinociceptive effects in phase 1 on the rat formalin test.

Upregulated liver conversion of α-linolenic acid to docosahexaenoic acid in rats on a 15 week n-3 PUFA-deficient diet

We quantified incorporation rates of plasma-derived alpha-linolenic acid (alpha-LNA, 18:3n-3) into "stable" liver lipids and the conversion rate of alpha-LNA to docosahexaenoic acid (DHA, 22:6n-3) in male rats fed, after weaning, an n-3 PUFA-adequate diet (4.6% alpha-LNA, no DHA) or an n-3 PUFA-deficient diet (0.2% alpha-LNA, no DHA) for 15 weeks. Unanesthetized rats were infused intravenously with [1-14C]alpha-LNA, and arterial plasma was sampled until the liver was microwaved at 5 min. Unlabeled alpha-LNA and DHA concentrations in arterial plasma and liver were reduced >90% by deprivation, whereas unlabeled arachidonic acid (20:4n-6) and docosapentaenoic acid (22:5n-6) concentrations were increased. Deprivation did not change alpha-LNA incorporation coefficients into stable liver lipids but increased synthesis-incorporation coefficients of DHA from alpha-LNA by 6.6-, 8.4-, and 2.3-fold in triacylglycerol, phospholipid, and cholesteryl ester, respectively. Assuming that synthesized-incorporated DHA eventually would be secreted within lipoproteins, calculated liver DHA secretion rates equaled 2.19 and 0.82 micromol/day in the n-3 PUFA-adequate and -deprived rats, respectively. These rates exceed the published rates of brain DHA consumption by 6- and 10-fold, respectively, and should be sufficient to maintain normal and reduced brain DHA concentrations, respectively, in the two dietary conditions.