Ethanol anapyrexia in rats

In the present series of experiments we tested whether ethanol decreases body temperature by impairing thermal regulation (poikilothermia) or by shifting the set point downwards. The central temperature of rats kept in a thermocline and the selected ambient temperature were recorded by telemetry. After an IP injection of 2 g/kg of ethanol the rats selected an ambient temperature 7 degrees C lower than the one they selected before the ethanol injection and 8 degrees C lower than the one selected by the same rats after saline injection. At the same time the central temperature decreased by 2.5 degrees C. After about 40 min the rats preferred warmer ambient temperatures and 10 min later the central temperature began to rise. When, after ethanol, the rats were kept at 30 degrees C the central temperature remained at the normal level. At 35-36 degrees C the central temperature of normal rats without ethanol rose, in 1 h, from 37 degrees C to 39.75 degrees C. The results suggest that ethanol hypothermia is due to a downward shift of the set point and, in fact, is an anapyrexia, a condition inverse to fever.     

Endothelin-1 does not mediate the endothelium-dependent hypoxic contractions of small pulmonary arteries in rats

Various pulmonary artery preparations in vitro demonstrate sustained endothelium-dependent contractions upon hypoxia. To determine whether endothelin-1 could mediate this phenomenon, we examined the effect of bosentan, a new antagonist of both the ETA and ETB subtypes of the endothelin receptor. Small (300 pm) pulmonary arteries from rats were mounted on a myograph, precontracted with prostaglandin F2 alpha and exposed to hypoxia (PO2, 10 to 15 mm Hg, measured on-line) for 45 min. Endothelium-intact control rings exhibited a biphasic response, with a transient initial vasoconstriction (phase 1) followed by a second slowly developing sustained contraction (phase 2). Expressed in percent of the maximal response to 80 mmol/L KCl, the amplitudes of phase 1 (peak tension) and 2 (tension after 45 min of hypoxia) averaged 37 +/- 12% and 17 +/- 14%, respectively (n = 11). In endothelium-denuded rings, phase 1 persisted while the amplitude of phase 2 was reduced to 2 +/- 12% (p < 0.05, n = 8), showing the endothelium dependence of this contraction. Neither phase was significantly decreased in rings treated with 10(-5) mmol/L bosentan (38 +/- 15% and 17 +/- 12%, respectively, n = 6). The PO2 threshold for onset of hypoxic contraction was not significantly different among these three groups and averaged 32 +/- 24 mm Hg. In a separate experiment, we assessed the inhibitory effect of 10(-5) mol/L bosentan on the response to 10(-8) mol/L endothelin-I. Rings treated for 45 min with 10(-8) mol/L endothelin-1 alone exhibited a maximal contraction of 75 +/- 27% (n = 6). This was reduced to 4 +/- 17% (p < 0.01, n = 6) in rings treated with both 10(-8) mol/L endothelin-1 and 10(-5) mol/L bosentan. We conclude that complete blockade of all endothelin receptor subtypes has no effect on either endothelium-dependent or -independent hypoxic contractions in this preparation. This suggests that endothelial factors other than endothelin-I mediate the acute hypoxic contractions of small pulmonary arteries in the rat.     

NO does not mediate inhibitory neural responses in sheep airway and bronchial vascular smooth muscle

Endogenous nitric oxide (NO) influences acetylcholine-induced bronchovascular dilation in sheep and is a mediator of the airway smooth muscle inhibitory nonadrenergic, noncholinergic neural response in several species. This study was designed to determine the importance of NO as a neurally derived modulator of ovine airway and bronchial vascular smooth muscle. We measured the response of pulmonary resistance (RL) and bronchial blood flow (Qbr) to vagal stimulation in 14 anesthetized, ventilated, open-chest sheep during the following conditions: 1) control; 2) infusion of the alpha-agonist phenylephrine to reduce baseline Qbr by the same amount as would be produced by infusion of Nomega-nitro-L-arginine (L-NNA), a NO synthase inhibitor; 3) infusion of L-NNA (10(-2) M); and 4) after administration of atropine (1.5 mg/kg). The results showed that vagal stimulation produced an increase in RL and Qbr in periods 1, 2, and 3 (P < 0.01) that was not affected by L-NNA. After atropine was administered, there was no increase in Qbr or RL. In vitro experiments on trachealis smooth muscle contracted with carbachol showed no effect of L-NNA on neural relaxation but showed a complete blockade with propranolol (P < 0.01). In conclusion, the vagally induced airway smooth muscle contraction and bronchial vascular dilation are not influenced by NO, and the sheep's trachealis muscle, unlike that in several other species, does not have inhibitory nonadrenergic, noncholinergic innervation.     

Pneumoperitoneum does not potentiate the nephrotoxicity of aminoglycosides in rats

OBJECTIVES: Pneumoperitoneum is associated with transient renal dysfunction. To our knowledge, the safety of administering nephrotoxins such as aminoglycosides during pneumoperitoneum has not been studied. Our hypothesis was that pneumoperitoneum potentiates the nephrotoxicity of aminoglycosides. METHODS: From 29 rats we obtained preprocedure 24-hour urine collections. In the pneumoperitoneum group (n = 7), carbon dioxide was insufflated intra-abdominally at 15 mm Hg pressure for 2 hours. In the gentamicin group (n = 7), 10 mg/kg gentamicin was administered intravenously. In the combined pneumoperitoneum/gentamicin group (n = 8), the same dose of gentamicin was administered 10 minutes before pneumoperitoneum. Sham rats (n = 7) received anesthesia only. Urine was collected for the 24 hours after the procedure, and 1 week later blood for creatinine determination and final 24-hour urine collections were obtained. All urine samples were assayed for creatinine and N-acetyl-beta-glucosaminidase (NAG). RESULTS: Only the gentamicin and combined pneumoperitoneum/gentamicin groups presented day 1 values for NAG excretion that were significantly greater than same day sham or paired preprocedure values; the rest of the urinary creatinine and NAG day 1 levels and all the day 7 levels were not significantly different from same day sham or paired preprocedure levels. Day 7 serum creatinine and creatinine clearance did not differ significantly among the groups. CONCLUSIONS: We found that intravenous gentamicin transiently increased urinary excretion of NAG in rats, which resolved within 1 week. Pneumoperitoneum for 2 hours at 15 mm Hg did not increase urinary NAG, either alone or in gentamicin-treated rats. Moreover, our data are sufficient to refute with 95% certainty the possibility that gentamicin plus pneumoperitoneum decreases creatinine clearance more than approximately 60%. These results do not support the hypothesis that pneumoperitoneum potentiates the nephrotoxicity of aminoglycosides.     

Dietary fish oil does not alter glucose tolerance in conscious rats

We examined the effect of dietary fish oil (MaxEPA) and sunflower seed oil on glucose tolerance in male Wistar rats. Semipurified diets containing 100 g oil/kg diet were administered for 30 d. The fish oil diet contained 26 g (n-3) fatty acids, 16 g eicosapentaenoic acid and 10.4 g docosahexaenoic acid/kg diet. Phospholipids from liver, pancreas, and pancreatic islets were enriched in eicosapentaenoic and docosahexaenoic acids by the fish oil diet. In unfed pentobarbital-anesthetized rats, both basal plasma insulin concentration and insulin responses to intravenous glucose were significantly lower for fish oil-fed rats although glucose responses were similar; however, incremental excursions in plasma insulin over the basal concentrations did not differ. Intravenous glucose tolerance was also examined in conscious unfed rats under minimal restraint. Responses of plasma glucose and insulin were similar for fish oil- and sunflower oil-fed groups. Furthermore, in another experiment, intravenous glucose tolerance tests were similar for conscious rats provided with either 100 g fish oil or corn oil/kg nonpurified diet. Thus, glucose-induced insulin secretion is lower in rats fed fish oil than in rats fed sunflower oil, when tests are conducted in pentobarbital-anesthetized animals but not when tests are performed in conscious rats; there was no effect on plasma glucose in either anesthetized or nonanesthetized rats. Therefore, substitution of (n-3) for (n-6) polyunsaturated fatty acids in tissue phospholipids does not alter plasma glucose or insulin in conscious male Wistar rats.     

Moderate alcohol consumption does not augment bone density in ovariectomized rats

Moderate levels of alcohol consumption have been reported to have a beneficial effect on bone mineral density in postmenopausal women. The objective of this study was to examine the effect of a moderate level of alcohol consumption on bone density in a rigorously controlled animal model of osteoporosis. Ovariectomized and nonovariectomized rats were placed on standard lab pellets with free access to deionized water ad libitum. Alcohol-treated animals were given 0.38 g/kg of alcohol daily by intubation in the mid-afternoon and free access to standard lab pellets for 6 weeks. The amount of the alcohol solution was calculated daily to give the human equivalent of 2 glasses of wine/day. Pair-fed control animals were given, on the following day, an equal volume of the diet consumed by individual ethanol-fed rats. They received daily intubation solutions, with the ethanol replaced by isocaloric and isovolumetric amounts of maltose-dextrin. Chow-fed control animals received no intubations and were given access to standard lab pellets ad libitum. Ovariectomized animals had increased weight and decreased femur density and bone volume per total volume. They also had decreased total trabecular area, trabecular area, and number, as well as increased trabecular separation. Significant differences were found between the ovariectomized and nonovariectomized animals in the parameters under discussion, but there were no differences between diet groups. No beneficial effects were found after daily alcohol treatments.     

Pancreatic cancer in rats and hamsters does not induce IAPP-related hyperglycaemia

The X-ray crystallographic structure of the branched-chain amino acid aminotransferase from Escherichia coli was determined by means of isomorphous replacement using the selenomethionyl enzyme as one of the heavy atom derivatives. The enzyme is a homo hexamer with D3 symmetry, and the polypeptide chain of the subunit is folded into two domains (small and large domains). The coenzyme, pyridoxal 5'-phosphate, resides at the domain interface, its re-face facing toward the protein. The active site structure shows that the following sites can recognize branched-chain amino acids and glutamate as substrates: (1) a hydrophobic core formed by Phe36, Tyr164, Tyr31*, and Val109* for a branched-chain; (2) Arg97 for an acidic side chain of glutamate; and (3) Tyr95 and two main chain NH groups of Thr257 and Ala258 for the alpha-carboxylate of substrates. Although the main chain conformation of the active site is homologous to that of D-amino acid aminotransferase, many of the active site residues are different between them.     

Endogenous angiotensin II does not contribute to sympathetic venoconstriction in dorsal hand veins of healthy humans

Autocrine stimulation of growth factor receptors by autonomously produced ligands regulates different aspects of cellular transformation and progression. In several tumors, including gliomas, multiple autocrine systems are activated and may exert different functions in the malignant transformation process. The c-kit proto-oncogene is widely expressed in human gliomas, and it may be activated by its co-expressed ligand, stem cell factor (SCF). Studies in glioma cell lines as well as different tumor types suggest the possibility of intracellular interactions of c-kit with SCF. Although c-kit and SCF may not play a primary and causal role in the initiation and progression of glial tumors they may still be contributing factors in glioma biology. It can be hypothesized that the parallel activation of several autocrine systems including some of which have found less attention in gliomas, such as c-kit/SCF, could compromise the efficacy of therapies targeting different autocrine loops. A better understanding of the multiplicity and mechanisms of autocrine stimulation has implications for the development of new therapies interfering with autocrine tumor cell growth.     

Zinc status does not affect aluminum deposition in tissues of rats

To examine whether zinc deficiency would increase the toxicity of dietary aluminum, weanling, male Sprague-Dawley rats were fed purified diets containing either 2 or 30 mg Zn/kg diet, with or without 500 mg Al/kg diet for 28 d. Individually pair-fed rats were fed the 30 mg Zn/kg diet with or without added aluminum to control for inanition secondary to zinc deficiency. Rats fed the 2 micrograms Zn/kg diet showed evidence of zinc deficiency, including anorexia, growth retardation, and depressed concentrations of zinc in tibias and livers. Zinc deficiency did not significantly increase the concentrations of aluminum in the tibias, livers, kidneys, or regions of the brain examined (cerebrum, cerebellum, midbrain, and hippocampus). Inclusion of aluminum in the diet did not alter aluminum concentrations in the various tissues. Under the conditions of this study, zinc deficiency did not result in greater sensitivity to dietary aluminum exposure.     

Ipriflavone does not alter bone apatite crystal structure in adult male rats

We have previously found that a short-term treatment with high doses of ipriflavone increased bone density and improved the biomechanical properties of adult male rat bones, without altering their mineral composition. To determine whether this effect can be associated with alterations of bone crystal structure, we have performed X-ray diffraction analysis of bones obtained from rats treated with ipriflavone at doses that were effective in inducing favorable changes on bone density and biomechanics. Eighteen-week-old male Sprague Dawley rats were treated by oral route with either ipriflavone (200 or 400 mg/kg/day), or its vehicle for 12 weeks. The treatment was well tolerated and body weight increased to the same extent in all animals. As a measure of bone crystallinity, we examined the (310) and (002) reflections of the X-ray diffraction patterns, corresponding to the directions perpendicular and parallel to the c-axis of the crystals, respectively. No major differences were observed between ipriflavone-treated and control animals for the broadening parameter beta(1/2) for (310) and (002) peaks, as well as for lattice parameters. Therefore, a 12-week treatment with ipriflavone at high doses does not induce significant modifications of bone "crystallinity." Thus, the positive effect of ipriflavone on bone mineral density appears to be associated with an increased apatite crystal formation rather than an increase of crystal size. These results provide further evidence for the safety and usefulness of ipriflavone in the treatment of osteoporotic syndromes.     

Dextromethorphan potentiates morphine antinociception, but does not reverse tolerance in rats

The N-methyl-D-aspartate (NMDA) and cholecystokinin (CCK)-B receptors may have a role in the development and reversal of tolerance to morphine. In morphine-tolerant rats, addition of the CCK-B receptors antagonist CI 988 or the NMDA receptor blocker dextromethorphan enhanced the antinociceptive effect of morphine on the hot plate test. However, combined administration of CI 988 and dextromethorphan did not further potentiate the antinociceptive effect of morphine in tolerant rats. Dextromethorphan by itself had no effect in tolerant rats. In drug-naive rats, dextromethorphan by itself had no antinociceptive effect, but when combined with morphine or morphine and CI 988, it significantly potentiated the magnitude and duration of the effect of morphine. Thus, unlike the reversal of tolerance with CI 988 at doses that did not potentiate the effect of morphine, the antinociception observed with the NMDA antagonist in the presence of morphine in tolerant rats may not represent the reversal of tolerance, but may instead reflect the potentiation of morphine's analgesic effect by dextromethorphan.     

Increased dietary oxalate does not increase urinary calcium oxalate saturation in hypercalciuric rats

BACKGROUND: Human calcium oxalate (CaOx) nephrolithiasis may occur if urine is supersaturated with respect to the solid-phase CaOx. In these patients, dietary oxalate is often restricted to reduce its absorption and subsequent excretion in an effort to lower supersaturation and to decrease stone formation. However, dietary oxalate also binds intestinal calcium which lowers calcium absorption and excretion. The effect of increasing dietary oxalate on urinary CaOx supersaturation is difficult to predict. METHODS: To determine the effect of dietary oxalate intake on urinary supersaturation with respect to CaOx and brushite (CaHPO4), we fed 36th and 37th generation genetic hypercalciuric rats a normal Ca diet (1.2% Ca) alone or with sodium oxalate added at 0.5%, 1.0%, or 2.0% for a total of 18 weeks. We measured urinary ion excretion and calculated supersaturation with respect to the CaOx and CaHPO4 solid phases and determined the type of stones formed. RESULTS: Increasing dietary oxalate from 0% to 2.0% significantly increased urinary oxalate and decreased urinary calcium excretion, the latter presumably due to increased dietary oxalate-binding intestinal calcium. Increasing dietary oxalate from 0% to 2.0% decreased CaOx supersaturation due to the decrease in urinary calcium offsetting the increase in urinary oxalate and the decreased CaHPO4 supersaturation. Each rat in each group formed stones. Scanning electron microscopy revealed discrete stones and not nephrocalcinosis. X-ray and electron diffraction and x-ray microanalysis revealed that the stones were composed of calcium and phosphate; there were no CaOx stones. CONCLUSION: Thus, increasing dietary oxalate led to a decrease in CaOx and CaHPO4 supersaturation and did not alter the universal stone formation found in these rats, nor the type of stones formed. These results suggest the necessity for human studies aimed at determining the role, if any, of limiting oxalate intake to prevent recurrence of CaOx nephrolithiasis.     

Oral arginine supplementation does not affect lymphocyte proliferation during endotoxin-induced inflammation in rats

Earlier studies from this laboratory were unable to confirm reported immunostimulatory effects of supplemental dietary arginine on healthy, unstressed young or aged rats. The present study was undertaken to determine effects of oral arginine supplementation on in vitro measures of immune function using a stressed rat model. The stressor used was intraperitoneal injection of bacterial lipopolysaccharide (1 mg/kg body wt). Four-month-old male Sprague-Dawley rats were placed in either a control or an arginine-supplemented (7.5 g/L arginine-HCl in drinking water) group for 7 d, after which control and supplemented rats received injections of endotoxin or phosphate-buffered saline. Rats were killed 3 d following injections. Endotoxin treatment resulted in lower food intake, less thymic cellularity and greater splenic weight. Endotoxin injections also enhanced proliferative response of rat splenocytes to pokeweed mitogen (1 mg/L) and lipopolysaccharide (25 and 100 mg/L) and enhanced response of thymocytes to concanavalin A (10 mg/L), phytohemagglutinin (25 and 100 mg/L) and pokeweed mitogen (1 mg/L). Supplemental arginine did not reduce thymic weight loss or influence mononuclear cell proliferation or interleukin-2 production in the presence or absence of endotoxin stress. These data indicate no benefit of arginine supplementation during endotoxin stress in rats.     

Long-term alpha 1 blockade does not reverse cardiac hypertrophy in spontaneously hypertensive rats

Not all antihypertensive drugs induce regression of left ventricular (LV) hypertrophy in hypertension, although they may equally lower blood pressure. The effects of alpha 1-blockers on regression have been inconsistent. In this study, bunazosin, a selective alpha 1-blocker, (15 mg/kg/day in food) was given to male spontaneously hypertensive rats (SHR) from 15 to 35 weeks of age to evaluate its effects on cardiac hypertrophy, hemodynamics, and neurohumoral factors. Age- and sex-matched SHR served as controls. LV function and cardiac output were determined by a micromanometer and thermodilution, respectively. Bunazosin significantly decreased blood pressure in conscious rats (from 209 to 192 mmHg, p < 0.01) but did not reduce LV mass. Heart rate, LV end-diastolic pressure, dp/dtmax, and cardiac output were similar in the 2 groups. Plasma renin activity was unaltered but plasma norepinephrine levels were higher in the treated rats (p < 0.05). Thus, bunazosin produced a significant relative reduction of blood pressure but did not reverse LV hypertrophy in SHR. Inadequate afterload reduction (8%) due to severe hypertension (> 200 mmHg) may explain the absence of regression. The rise of plasma norepinephrine levels may also offset the beneficial effects of bunazosin.     

Endogenous vasopressin increases acute endotoxin shock-provoked gastrointestinal mucosal injury in the rat

Administration of a low dose of endotoxin (from Escherichia coli, 3 mg kg(-1), i.v.), which does not affect vascular permeability or blood pressure over 1 h, leads to the release of endogenous vasopressin and damage to the mucosal microvasculature. Thus, endogenous vasopressin could be involved in septic shock. In the present study, we investigated the role of endogenous vasopressin in gastrointestinal mucosal injury induced by acute endotoxin shock, which was generated in rats by administering a high dose of E. coli endotoxin (50 mg kg(-1), i.v.). Tissues were removed 15 min after endotoxin. The vasopressin V1 receptor antagonist, d[CH2]5Tyr[Me]arginine-vasopressin (0.2-1 microg kg(-1), i.v.), was injected 10 min before endotoxin. Monastral blue (30 mg kg(-1), i.v.), which stains damaged vasculature, was injected 10 min before autopsy. Endotoxin reduced systemic arterial blood pressure (from 115+/-5 to 42+/-4 mmHg), generated macroscopic and microvascular injury, and elevated plasma vasopressin levels (from 3.4+/-0.2 to 178+/-16 pg ml(-1)). The vasopressin V1 receptor antagonist reduced this macroscopic injury, and in the vasopressin-deficient Brattleboro rat a similar reduction of gastrointestinal mucosal damage was found. Substantial decreases in endotoxin-induced microvascular damage were observed in each tissue, e.g., the gastric Monastral blue staining was reduced by 47+/-3% and 96+/-3% (P < 0.01) after vasopressin V1 receptor antagonist treatment and in Brattleboro rats, respectively. Vasopressin, acting through its V1 receptors, thus appears to be involved in acute endotoxin shock-provoked gastrointestinal injury.     

Chronic fluoride exposure does not cause detrimental, extraskeletal effects in nutritionally deficient rats

On the basis of observations that endemic fluorosis occurs more often in malnourished populations, a series of studies tested the hypothesis that deficient dietary intake of calcium, protein or energy affects fluoride metabolism so that the margin of safe fluoride exposure may be reduced. The objective of the investigation was to determine whether changes in fluoride metabolism in nutritionally deficient rats resulted in manifestation of any extraskeletal toxic fluoride effects not observed in healthy animals. This investigation included two studies, one that monitored the effect of calcium deficiency on the effects of chronic fluoride exposure, and a second study that observed fluoride effects in rats that were deficient either in protein or in energy and total nutrient intake. Control and experimental rats received drinking water containing 0, 0.26 (5), 0.79 (15) or 2.63 (50) mmol fluoride/L (mg/L) for 16 or 48 wk. Control rats were fed optimal diets and experimental rats were fed diets deficient in calcium (Study 1) or protein (Study 2). An additional group of experimental rats (Study 2) was provided with a restricted amount of diet; thus these rats were deficient in energy and total nutrient intake. The intake, excretion and retention of fluoride were monitored; after the rats were killed, tissue fluoride levels and biochemical markers of tissue function were analyzed. Bone marrow cells were harvested from some of the rats, after 48 wk of treatment, for determining the frequency of sister chromatid exchange, a marker of genetic damage. Although there were significant differences among fluoride treatment groups in fluoride excretion and retention that resulted in significantly greater fluoride levels in tissues of the experimental rats, we were unable to detect any harmful, extraskeletal biochemical, physiologic or genetic effects of fluoride in the nutritionally deficient rats.     

Prolonged severe hemorrhagic shock and resuscitation in rats does not cause subtle brain damage

OBJECTIVE: Some patients who survived severe hemorrhagic shock (HS) seem to exhibit persistent subtle neurobehavioral deficits. This finding is of concern if limited hypotensive fluid resuscitation is applied in hypotensive victims with penetrating trauma. This study was designed to determine whether subtle brain damage would occur in rats after severe prolonged HS. We hypothesized that rats surviving HS with mean arterial pressure (MAP) controlled at 40 mm Hg for 60 minutes would recover with slight permanent brain damage in terms of cognitive function without morphologic loss of neurons and that rats surviving HS with MAP at 30 mm Hg for 45 minutes (60 minutes were not tolerated) would have grossly abnormal brain function and loss of neurons. METHODS: Under light nitrous oxide-halothane anesthesia, spontaneously breathing rats underwent MAP-controlled HS (HS phase I), volume resuscitation to normotension and invasive monitoring to 60 minutes (resuscitation phase II), and observation to 10 days with detailed assessment of cognitive function (observation phase III). Five conscious rats served as normal controls. Three treatment groups were compared: group 1, shams (11 of 12 rats survived to 10 days); group 2, HS at MAP 40 mm Hg for 60 minutes (10 of 17 rats survived); group 3, HS at 30 mm Hg for 45 minutes (10 of 14 rats survived). RESULTS: On post-HS day 10, all normal controls and all survivors of all three groups were functionally normal with overall performance category = 1 (normal) (overall performance category 1 = normal, 5 = death) and neurologic deficit scores < or = 7% (neurologic deficit scores 0-10% = normal, 100% = brain death). Post-HS beam balance, beam walking, and Morris water maze test results in HS groups 2 and 3 showed latencies not significantly different from those in shams and normal controls. Light microscopic scoring of five selectively vulnerable brain regions and other regions in five coronal sections revealed no ischemic (pyknotic, shrunken, eosinophilic) neurons in any of the survivors to 10 days. There was no statistical difference between normal controls, sham animals, and both HS groups in the number of normal neurons counted in the hippocampal CA-1 region in the 10-day survivors. All nonsurvivors died with intestinal necrosis. CONCLUSION: HS at MAP 40 mm Hg for 60 minutes or MAP 30 mm Hg for 45 minutes does not cause subtle functional or histologic brain damage in surviving rats. Controlling MAP at 30 mm Hg carries a risk of sudden cardiac arrest. These data suggest that limited fluid resuscitation, to maintain MAP at about 40 mm Hg, as recommended for victims of penetrating trauma with uncontrolled HS, is safe for the brain.     

Parathyroidectomy does not prevent the renal PTH/PTHrP receptor down-regulation in uremic rats

In a recent study we demonstrated that the PTH/PTHrP receptor (PTH-R) mRNA was markedly down-regulated in the remnant kidney of uremic rats with severe secondary hyperparathyroidism. Among the factors potentially implicated in this down-regulation, to date only PTH has been demonstrated to modulate PTH-R expression. Here, we examined the effect of thyroparathyroidectomy (TPTX) on the renal expression of PTH-R in rats with normal renal function or with chronic renal failure (CRF) induced by 5/6 nephrectomy. Four groups of rats were studied: control, TPTX, CRF, and CRF + TPTX. Moderate-degree renal failure was documented by mean (+/- SD) creatinine clearances (microliter/min/100 g body wt) of 259 +/- 40 and 212 +/- 45 in CRF and CRF + TPTX rats, compared with 646 +/- 123 and 511 +/- 156 in control and TPTX rats, respectively. Plasma phosphorus, calcitriol, and ionized calcium were significantly lower in CRF and CRF + TPTX than in control animals. Plasma ionized calcium and calcitriol were also lower in TPTX than in control rats. Plasma PTH levels (pg/ml) were increased in CRF rats (41.8 +/- 29.4), and markedly decreased in TPTX (10.1 +/- 7.8) and CRF + TPTX (8.0 +/- 3.8) rats compared with control rats (21.7 +/- 7.5). Northern blot analysis showed that the level of the steady-state PTH-R mRNA in the kidney of CRF and CRF + TPTX rats was markedly decreased compared with that of control rats, the ratios of PTH-R mRNA/beta-actin mRNA being 0.28 +/- 0.04 and 0.27 +/- 0.03 versus 0.54 +/- 0.05, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chronic neonatal nicotine increases anxiety but does not impair cognition in adult rats.

Developmental nicotine exposure has been implicated in the association between maternal smoking and adverse outcomes in offspring. The 3rd trimester of human pregnancy is equivalent to the 1st postnatal week in rodents; both are periods of active brain growth during which nicotinic acetylcholine receptors are transiently upregulated. Chronic neonatal nicotine (CNN; 6 mg/kg/day) from postnatal Days 1 to 7 was given orally to rat pups to evaluate long-term behavioral effects. Males and females were tested as adolescents or as young adults. CNN significantly decreased center time, ambulatory behavior, and rearing in the open-field test and decreased the number of entrances and time spent in the open arm of the elevated plus-maze in both sexes and ages. CNN did not change performance in the T maze or in the water maze in adult males or females. Motor coordination was not altered. In summary, CNN had long-term effects on anxiety-like behavior but did not affect spatial learning and memory functions. This finding is particularly important when evaluating the benefits of nicotine-replacement therapies during human pregnancies, which may improve smoking cessation rates but could result in long-term behavioral consequences. (PsycINFO Database Record (c) 2010 APA, all rights reserved)