Effect of ibotenate lesions of the ventromedial hypothalamus on the water and salt intake induced by activation of the median preoptic nucleus in sodium-depleted rats

In this study we investigated the influence of a ventromedial hypothalamus (VMH) lesion with ibotenic acid on water and sodium intake and presser responses induced by combined treatment of the median preoptic nucleus (MnPO) with angiotensin Il (ANG II) and adrenergic agonists (phenylephrine, norepinephrine, isoproterenol and clonidine). Male Holtzman rats with a stainless steel cannula implanted into the MnPO and bilateral sham (vehicle) or VMH lesions with ibotenic acid were used. The ingestion of water and sodium and mean arterial pressure (MAP) were determined in separate groups submitted to sodium depletion with the diuretic furosemide (20 mg/rat). ANG II (10 pmol) injection into the MnPO of sham-lesioned rats induced water and sodium intake and presser responses. VMH-lesion reduced ANG II-induced water intake and increased saline intake, In sham rats phenylephrine (80 nmol) into MnPO increased, whereas norepinephrine (80 nmol) and clonidine (40 nmol) reduced ANG II-induced water intake while sodium intake was reduced only by clonidine into MnPO. In VMH-lesioned rats, phenylephrine reduced, noradrenaline increased and clonidine produced no effect on ANG II-induced water intake. In lesioned rats ANG II-induced sodium intake was reduced by phenylephrine and noradrenaline, whereas clonidine produced no change. ANG II-induced presser response was reduced in VMH-lesioned rats, but the presser response combining ANG II and phenylephrine or noradrenaline in VMH-lesioned rats was bigger than sham rats. These results show that the VMH is important for the changes in water and sodium intake and cardiovascular responses induced by angiotensinergic and adrenergic activation of the MnPO. (C) 1997 Elsevier B.V. B.V.

LESION OF THE ANTEROVENTRAL 3RD VENTRICLE REGION IMPAIRS THE RECOVERY OF ARTERIAL-PRESSURE INDUCED BY HYPERTONIC SALINE IN RATS SUBMITTED TO HEMORRHAGIC-SHOCK

The effect of intravenous infusion of hypertonic saline (HS, 7.5% NaCl) on the recovery of mean arteria pressure (MAP) after hemorrhage was studied in sham-operated rats and in rats with electrolytic lesion of the anteroventral third ventricle (AV3V) region (4 h, 4 and 20 days). Rats anesthetized with thiopental sodium were bled (about 2.8 ml/100 g) until the MAP was stabilized at the level of 60 mmHg for 30 min. In sham-lesioned rats, MAP increased to 90 mmHg and became stable near this level after intravenous infusion of 7.5% NaCl (4 ml/kg b.wt.). In AV3V-lesioned rats, the same infusion induced a smaller increase in MAP (80 mmHg) and the MAP returned to pre-infusion levels within 30 min. These results show that the AV3V region plays an important role in the recovery of arterial pressure induced by hypertonic saline in rats submitted to hemorrhagic shock.

Losartan (DUP-753) blocks the natriuretic, kaliuretic and antidiuretic effect of intracerebroventricular injection of carbachol in water-loaded rats

We determined the effect of intracerebroventricular (icv) administration of losartan, an angiotensin II (ANG II) subtype 1 receptor (AT1) antagonist, on icv carbachol-induced natriuresis, kaliuresis and antidiuresis in water-loaded male Holtzman rats (250-300 g) with a cannula implanted into the lateral ventricle (LV). The rats were water loaded with 5% of their body weight by gavage twice, with the second gavage one hour after the first. Carbachol (2 nmol in 1 mu l) was injected icv immediately after the second load. When losartan (DUP-753, 50 nmol in 1 mu l) was administered icv, it was given 3 min before carbachol. Previous icv treatment with losartan significantly reduced the icv carbachol-induced natriuresis (324 +/- 17 mu Eq/120 min), kaliuresis (103 +/- 15 mu Eq/120 min) and antidiuresis (13.5 +/- 2.1 ml/120 min) compared to the effects of previous icv injection of saline (Nai excretion = 498 +/- 22 mu Eq/120 min; K+ excretion = 167 +/- 20 mu Eq/120 min; urine volume = 5.2 +/- 1.2 ml/120 min). These results, reported as means +/- SEM for 12 rats in each group, are consistent with the hypothesis that AT1 subtype receptors participate in the regulation of body electrolyte balance.

Repeated administration intensifies the reinforcing effect of fencamfamine in rats

1. In the present study, we evaluated the role of repeated administration on conditioning place preference (CPP) induced by fencamfamine (FCF) in male rats.2. Repeated FCF (3.5 mg/kg) or saline once or daily for ten consecutive days enhanced sniffing du ration and decreased locomotion and rearing duration.3. At the 3.5 mg/kg dose, FCF produced a significant place-preference effect.4. Repeated exposures to FCF intensified its reinforcing properties.5. These results suggest that repeated FCF administration sensitizes its rewarding effects, as with other addictive substances. GEN PHARMAC 29;2:265-261, 1997. (C) 1997 Elsevier B.V.

The effect of hetero- and homosexual experience and long-term treatment with fluoxetine on homosexual behavior in male rats

Introduction the selective serotonin reuptake inhibitors have become the most frequently prescribed drugs for the treatment of depression. Sexual side effects have been noted to occur with this treatment on heterosexual behavior in rats. Heterosexual experience facilitates sexual orientation of male rats and decreases the latencies to first mount and first intromission. on the other hand, homosexual behavior in male rats induced by female hormones has not been evaluated.Aim the objective of this work is to evaluate the effects of heterosexual and homosexual experience in male rats long-term treated with fluoxetine (FLX) on homosexual hormone-induced behavior.Materials and Methods Male rats were treated with FLX or saline solution (10 mg/kg for 65 days). At days 36, 50, and 65 of the treatment, the rats were evaluated for homosexual behavior. Other rats treated with FLX or saline solution for 60 consecutive days were submitted to heterosexual behavior at 14, 21, and 28 days of the treatment. After this, they were orquiectomized and homosexual hormone-induced behavior was observed at 45 and 60 days of the treatment.Results (1) Only treatment with FLX did not affect the homosexual behavior. (2) the homosexual experience facilitated the homosexual behavior mainly on the animals from the control group. (3) the heterosexual experience facilitated the homosexual behavior on both groups.Conclusions Only long-term administration of FLX does not interfere with the homosexual behavior in male rats. The homosexual and the heterosexual experience facilitated the homosexual behavior on the control and experimental groups. We suggested that learning aspects related to sexual behavior are responsible by these results.

EFFECT OF A PERSISTENT INFLAMMATORY PROCESS ON EXPERIMENTAL HETEROTOPIC OSSIFICATION - THE INFLUENCE OF MACROPHAGES

1. We investigated the effect of a persistent carrageenin- or nystatin-induced inflammatory reaction on heterotopic ossification produced by the subcutaneous implant of a demineralized bone matrix in female Swiss mice (25 to 35 g).2. Subcutaneous carrageenin injection (0.3 ml of a 2% solution in saline) into mice induced an inflammatory reaction characterized by a mature granuloma predominantly of macrophages containing particles of the irritant in their cytoplasm and which remained unchanged until the end of the experiment (40th day).3. Subcutaneous nystatin inoculation (30,000 IU in 0.3 ml saline) induced an inflammatory reaction consisting initially of macrophages (4th day) but later turning into an epithelioid granuloma (7th day) consisting predominantly of epithelioid cells and which was present up to the 2 lst day when it was gradually replaced by adipocytes up to the 30th day.4. An intramuscular implant of demineralized bone matrix (DBM, approximately 10 mg) induced the formation of cartilage and bone tissue and of hemopoietic bone marrow (heterotopic ossification) in 100% of the control animals (N = 5). An intramuscular DBM implant in animals that received carrageenin (N = 19) or nystatin (N = 21) induced heterotopic ossification in 100 and 57% (P<0.01)) of the animals, respectively.5. The response to a dorsal subcutaneous DBM implant was essentially negative in control animals (N = 5), whereas implants performed near the site injected with carrageenin (N = 28) or nystatin (N = 31) produced a response in 71 (P <0.01) and 36 % (P<0.01) of the animals, respectively. A DBM implant into the contralateral (control) dorsal subcutaneous tissue of the same animals that received carrageenin (N = 25) or nystatin (N = 29) resulted in heterotopic ossification in 64 (P<0.01) and 7% of the animals, respectively.6. The results suggest that the macrophages present in the mature granuloma induced by carrageenin somehow favored the development of metaplastic plates after subcutaneous DBM implant and that this effect may be systemic since the same response was observed in contralateral subcutaneous tissue.

Inhibitory effect of DUP-753 on the drinking responses of rats to central administration of noradrenaline and angiotensin II and to dehydration

We investigated the effect of losartan (DUP-753) on the dipsogenic responses produced by intracerebroventricular (icv) injection of noradrenaline (40 nmol/mu l) and angiotensin II (ANG II) (2 ng/mu l) in male Holtzman rats weighing 250-300 g. The effect of DUP-753 was also studied in animals submitted to water deprivation for 30 h. After control injections of isotonic saline (0.15 M NaCl, 1 mu l) into the lateral ventricle (LV) the water intake was 0.2 +/- 0.01 ml/h. DUP-753 (50 nmol/mu l) when injected alone into the LV of satiated animals had no significant effect on drinking (0.4 +/- 0.02 ml/h) (N = 8). DUP-753 (50 nmol/mu l) injected into the LV prior to noradrenaline reduced the water intake from 2.4 +/- 0.8 to 0.8 +/- 0.2 ml/h (N = 8). The water intake induced by injection of ANG II and water deprivation was also reduced from 9.2 +/- 1.4 and 12.7 +/- 1.4 ml/h to 0.8 +/- 0.2 and 1.7 +/- 0.3 ml/h (N = 6 and N = 8), respectively. These data indicate a correlation between noradrenergic pathways and angiotensinergic receptors and lead us to conclude that noradrenaline-induced water intake may be due to the release of ANG II by the brain. The finding that water intake was reduced by DUP-753 in water-deprived animals suggests that dehydration releases ANG II, and that AT(1) receptors of the brain play an important role in the regulation of water intake induced by deprivation.

Effect of intracerebroventricular injection of ramipril on the drinking response caused by injection of noradrenaline into the third ventricle

We studied the effect of ramipril injected into the third ventricle (3rdV) on the control of water intake induced by injection of noradrenaline into the 3rdV of adult male Holtzman rats (250-300 g) implanted with a chronic stainless steel cannula into the 3rdV. The injection volume was always 1 mu l and was injected over a period of 30-60 sec. Control animals were injected with 0.15 M NaCl. After the injection of isotonic saline (control, 0.15 M NaCl) into the 3rdV, water ingestion was 0.3 +/- 0.1 ml/h. Ramipril (1 mu g/mu l) injected into the 3rdV prior to isotonic saline produced no changes in water ingestion (0.4 +/- 0.2 ml/h). The injection of noradrenaline (40 nmol/mu l) after isotonic saline induced an increase in water intake (3.0 +/- 1.1 ml/h). The prior injection of ramipril decreased this ingestion to 1.8 +/- 0.3 ml/h. These data show that the inhibition of converting enzyme in the brain reduces the water intake induced by catecholaminergic stimulation. We conclude that the brain is able to transform the prodrug ramipril into the active drug ramiprilat.

Effect of sodium hypochlorite and five intracanal medications on Candida albicans in root canals

The aim of this study was to evaluate the effect of 1% sodium hypochlorite and five intracanals medications on Candida albicans harvested inside root canals. The contaminated canals were irrigated with sterile saline solution and then treated as follows: (i) filled with Calen paste (calcium hydroxide/glycol polyethylene paste); (ii) filled with camphorated paramonochloro phenol (CPMC); (iii) filled with 2% iodine-iodate solution; (iv) filled with tricresol formalin; (v) filled with Calen and CPMC pastes; (vi) irrigation with 1% sodium hypochlorite and filled with no intracanal medication; and (vii) no intracanal medication was used. Canal access and the apical foramen were then sealed with Cavit and the roots were stored in a humid chamber at 37 +/- 1 degreesC for 14 days. The canals were reinstrumented and irrigated with sterile saline solution. Sterile paper points were used to transfer the root canal contents to test tubes containing sterile saline solution. Part of the suspension was harvested in Sabouraud dextrose agar with chloramphenicol and incubated at 37 +/- 1 degreesC for 48 h, CPMC was effective in 100% of the samples followed in decreasing order of effectiveness by calcium hydroxide with CPMC (70% effective), 1% sodium hypochlorite (70% effective) (p < 0.05), tricresol formalin (60% effective), 2% iodine-iodate solution (50% effective), calcium hydroxide paste (30% effective), and saline + no intracanal medication.

EFFECT OF CAFFEINE ON THE METABOLISM OF RATS EXERCISING BY SWIMMING

Several studies have demonstrated that caffeine improves endurance exercise performance but the mechanisms are not fully understood. Possibilities include increased free fatty acid (FFA) oxidation with consequent sparing of muscle glycogen as well as enhancement of neuromuscular function during exercise. The present study was designed to investigate the effects of caffeine on liver and muscle glycogen of 3-month old, male Wistar rats (250-300 g) exercising by swimming. Caffeine (5 mg/kg) dissolved in saline (CAF) or 0.9% sodium chloride (SAL) was administered by oral intubation (1 mu l/g) to fed rats 60 min before exercise. The rats (N = and-IO per group) swam bearing a load corresponding to 5% body weight for 30 or 60 min. FFA levels were significantly elevated to 0.475 +/- 0.10 mEq/l in CAF compared to 0.369 +/- 0.06 mEq/l in SAL rats at the beginning of exercise. During exercise, a significant difference in FFA levels between CAF and SAL rats was observed at 30 min (0.325 +/- 0.06 vs 0.274 +/- 0.05 mEq/l) but not at 60 min (0.424 +/- 0.13 vs 0.385 +/- 0.10 mEq/l). Blood glucose showed an increase due to caffeine only at the end of exercise (CAF = 142.1 +/- 27.4 and SAL = 120.2 +/- 12.9 mg/100 ml). No significant difference in liver or muscle glycogen was observed in CAF as compared to SAL rats, at rest or during exercise. Caffeine increased blood lactate only at the beginning of exercise (CAF = 2.13 +/- 0.2 and SAL = 1.78 +/- 0.2 mmol/l). These data indicate that caffeine (5 mg/kg) has no glycogen-sparing effect on rats exercising by swimming even though the FFA levels of CAF rats were significantly higher at the beginning of exercise.

Effect of maternal obesity on diabetes development in adult rat offspring

This study aimed to evaluate whether maternal obesity leads to the onset of diabetes in adult Wistar rats offspring. MSG solution neonatally administration induced obesity in rats (F(1)MSG group, n = 30); and saline solution was also administrated to control rats (F1CON group, n = 13). In 3rd month of age, both control and MS G groups were mated for offspring (generation FA named as F2CON, n = 28 and F(2)MSG groups, n = 15; and so both generations were studied until 7th month of life. Lee Index was measured for experimental obesity validation from 5th to 7th month. Glycemia was weekly determined during pregnancy and monthly from 3rd to 7th month. In the end of experimental period all rats were submitted to oral glucose tolerance test (OGTT), with estimation of total area under the curve (AUC); and insulin tolerance test (ITT). Rats were then anesthetized and killed. Data were statistically analyzed with significance level of p < 0.05. Lee Index has confirmed obesity in all MSG rats. Glycemic levels comparisons between generations showed significant maternal interference in control and MSG groups. OGTT analysis showed higher glycemia in obese rats (F(1)MSG) and their offspring (F(2)MSG) as compared to their respective controls; and MSG groups increased AUC from OGTT. As regards ITT, F(2)MSG showed higher glycemia at 30 and 120 min, suggesting a delay of insulin action decreasing. Although glucose intolerance and insulin resistance clinical conditions represent as a factors for type 2 Diabetes mellitus development, this experimental model proposal was not efficient to induce type 2 Diabetes mellitus, but for obesity developing, glucose intolerance and insulin resistance in successive generations of rats. (c) 2007 Elsevier B.V. All rights reserved.

Reversal of the anticoagulant and anti-hemostatic effect of low molecular weight heparin by direct prothrombin activation

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

Effect of intraperitoneal or incisional bupivacaine on pain and the analgesic requirement after ovariohysterectomy in dogs

Objective To compare the effect of intraperitoneal (IP) or incisional (INC) bupivacaine on pain and the analgesic requirement after ovariohysterectomy in dogs.Study design Prospective, randomized clinical study.Animals Thirty female dogs undergoing ovariohysterectomy (OHE).Methods Dogs admitted for elective OHE were anesthetized with acepromazine, butorphanol, thiopental and halothane. Animals were randomly assigned to one of three groups (n = 10 per group). The treatments consisted of preincisional infiltration with saline solution (NaCl 0.9%) or bupivacaine with epinephrine and/or IP administration of the same solutions, as follows: INC and IP 0.9% NaCl (control group); INC 0.9% NaCl and IP bupivacaine (5 mg kg(-1), IP group); INC bupivacaine (1 mg kg(-1)) and IP 0.9% NaCl (INC group). Postoperative pain was evaluated by a blinded observer for 24 hours after extubation by means of a visual analog scale (VAS) and a numeric rating scale (NRS). Rescue analgesia (morphine, 0.5 mg kg(-1), IM) was administered if the VAS was > 5/10 or the NRS > 10/29.Results At 1 hour after anesthesia, VAS pain scores were [medians (interquartile range)]: 6.4 (3.1-7.9), 0.3 (0.0-2.6) and 0.0 (0.0-7.0) in control, IP and INC groups, respectively. VAS pain scores were lower in the IP compared to the control group. Over the first 24 hours, rescue analgesia was administered to 7/10, 5/10 and 3/10 dogs of the control, INC and IP groups, respectively. Total number of dogs given rescue analgesia over the first 24 hours did not differ significantly among groups.Conclusions and clinical relevance Intraperitoneal bupivacaine resulted in lower pain scores during the first hour of the postoperative period and there was a trend towards a decreased need for rescue analgesia after OHE in dogs.

Effect of calcium and magnesium silicate on the growth of the castor oil plant subjected to salinity levels

Salt stress decreases the osmotic potential of soil solution causing water stress, causing toxic effects in the plants resulting in injuries on the metabolism and nutritional disorders, thus compromising the plant growth, resulting in lower production. The calcium silicate and magnesium can perform the same function as limestone, besides providing silicon to plants, may also contribute to the resistance of plants to salt stress. Thus, the objective of this study was to evaluate the effect of calcium and magnesium silicate on the growth of the castor oil plant BRS Energia cultivated under saline conditions. This study evaluated plant height, stem diameter, number of leaves, leaf area, dry weight of shoot and root, and soil chemical characteristics. There was no interaction between factors of salinity level and of silicate level regarding the evaluated variables. There was a direct relationship between salinity levels and plant growth in height and stem diameter. The K concentration in soil were affected by salinity levels.

Multifactorial control of water and saline intake: Role of α2-adrenoceptors

Water and saline intake is controlled by several mechanisms activated during dehydration. Some mechanisms, such as the production of angiotensin II and unloading of cardiovascular receptors, activate both behaviors, while others, such as the increase in blood osmolality or sodium concentration, activate water, but inhibit saline intake. Aldosterone probably activates only saline intake. Clonidine, anα2-adrenergic agonist, inhibits water and saline intake induced by these mechanisms. One model to describe the interactions between these multiple mechanisms is a wire-block diagram, where the brain circuit that controls each intake is represented by a summing point of its respective inhibiting and activating factors. The α2-adrenoceptors constitute an inhibitory factor common to both summing points.