In vivo regulation of MAP kinases in Ratus norvegicus renal papilla by water loading and restriction

In cultured renal cells, hypertonicity activates multiple mitogen-activated protein kinases (MAPKs) and enhances the expression of heat shock proteins (HSPs). In rats, 24 h water restriction increased mean urinary osmolality (Uosm) from 2, 179+/-153 mOsm/kg to 2,944+/-294 mOsm/kg (P < 0.001) and was associated with significant (P < 0.05) increases in the papillary activity of c-Jun NH2-terminal protein kinase (JNK) by 22%, extracellular signal-regulated protein kinase (ERK) by 49%, and p38 MAPK by 15%. Conversely, 24 h of water-loading (Uosm 473+/-33 mOsm/kg) caused suppression of JNK activity by 43% (P < 0.001), ERK by 39% (P < 0.05), and p38 MAPK by 26% (P < 0.05). No such modulation was observed in the isotonic cortex. c-Jun phosphorylation was decreased in papilla from water-loaded rats by 45% versus controls. Expression of Hsp 110, inducible Hsp 70, and Hsp 25 was greater in the hyperosmotic papilla than the isosmotic cortex but was not affected by the animal's hydration state. In cultured inner medullary collecting duct cells, HSP expression was maximal at 500 mOsm/kg, while activation of JNK continued to increase. We conclude that under basal conditions of hydration, these HSPs are maximally expressed in the hypertonic inner medulla, while the activation of all three members of the MAPK family approaches but is not maximal.     

Water balance in elderly people: is there a deficiency of vasopressin?

Since elderly people are prone to develop both hypo- and hyper-natraemia, we have investigated the biochemical and hormonal responses to overnight (9 h) abstinence from fluids and subsequent oral water load (20 ml/kg) in a group of healthy elderly (E) (mean age 68 years) and young (Y) (mean age 28 years) volunteers. The elderly subjects had significantly higher baseline plasma osmolality (E 293.5 +/- 0.5, Y 290.5 +/- 0.8 mOsm/kg, p < 0.05) but lower urinary osmolality (E 508 +/- 47, Y 842 +/- 52 mOsm/kg, p < 0.001) and lower plasma vasopressin (E 0.5 +/- 0.1, Y 2.3 +/- 0.6 pmol/l, p < 0.001) than the young. There was a significant difference in the mode of excretion, particularly maximum free water clearance (E 6.0 +/- 0.6, Y 10.1 +/- 0.8 ml/min) but no difference in the overall ability to excrete the water load (at 4 h E 93 +/- 8%, Y 92 +/- 5%, p > 0.05). The biochemical and hormonal results suggest that the elderly subjects were in a state similar to partial cranial diabetes insipidus which may predispose them to dehydration and hypernatraemia. The reduction in maximum free water clearance may predispose them to hyponatraemia if excess fluid is administered.     

Extracellular dextran-induced p-nitrophenyl-alpha-D-glucoside-hydrolyzing enzyme of Bacillus circulans KA-304: a producer of Schizophyllum commune-lytic enzyme

We previously reported that centrally administered neuropeptide FF (NPFF) inhibited arginine vasopressin (AVP) release. In this study, immunoneutralization of central NPFF was performed to evaluate the role of endogenous NPFF in the regulation of AVP release. Intracerebroventricular (ICV) injection of antiserum against NPFF (Anti-NPFF) significantly augmented the plasma AVP increase induced by hyperosmolality [intraperitoneal injection of hypertonic saline (600 mOsm/kg, 2% BW)] at 60 min after ICV injection compared with normal rabbit serum (NRS) (NRS: 4.20+/-0.30 pg/ml, Anti-NPFF: 5.83+/-0.46 pg/ml, p < 0.01). Anti-NPFF did not cause significant change in plasma osmolality, plasma volume or arterial blood pressure. This evidence indicates that endogenous NPFF might be physiologically involved in osmoregulation of the plasma AVP level through its inhibitory action.     

Effects of an isotonic oral rehydration solution, enriched with glutamine, on fluid and sodium absorption in patients with a short-bowel

AIM: To compare the effects of a standard oral rehydration solution with a polymeric glucose isotonic solution enriched with glutamine on water and sodium absorption in the short bowel. METHODS: Six patients with high jejunostomy were tested in a random order on 2 consecutive days with the standard solution (20 g/L glucose, 94 mmol/L sodium, 292 mOsm/kg osmolality) and a solution containing maltodextrins (18 g/L Glucidex 12; hydrolysis of 18 g of Glucidex 12 yields 20 g glucose) enriched with 14.6 g/L of glutamine (94 mmol/L sodium, 282 mOsm/kg osmolality). Solutions were administered via a naso-gastric tube at a rate of 2 mL/min. Jejunal effluent for each solution was collected during an 8-h period, after a 14-h equilibrium period. RESULTS: The net 8-h fluid absorption was not significantly different between the standard solution and the solution with glutamine (333 +/- 195 and 213 +/- 251 mL, respectively (mean +/- S.E.M.)). Net sodium absorption was higher for the standard solution than for the solution with glutamine (15 +/- 15 vs. 2 +/- 20 mmol, P < 0.05). The rate of glucose absorption was not different between the solutions. CONCLUSION: The replacement of glucose by maltodextrins and the addition of glutamine to the standard oral rehydration solution, without changing its sodium content or osmolality, results in a reduction of sodium absorption in the short-bowel syndrome.     

Histamine H3 receptors contribute to drinking elicited by eating in rats

A role for endogenous histamine and its H3 receptor subtype for mediating drinking elicited by eating was examined in adult male Sprague-Dawley rats. The i.p. injection of the H3 agonist R-alpha-methylhistamine (Ramh, 2.5 mg/kg) shortened the latency to initiate drinking and increased 1-h water intake in nondeprived rats freely eating pellets and drinking water. The ICV injection (through a surgically implanted chronic cannula) of 10 micrograms Ramh increased water intake; this Ramh-induced drinking was abolished by previous ICV injection of the H3 antagonist thioperamide (Th, 60 micrograms). For rats drinking and eating after 24-h food deprivation, s.c. Th inhibited drinking behavior: for example, 10 mg/kg Th s.c. delayed the latency to initiate drinking and inhibited 1-h water intake without inhibition of food intake. In contrast, 60 micrograms Th ICV failed to inhibit food-related drinking in rats eating after food deprivation. For nondeprived rats eating a small cracker, 10 mg/kg Th s.c. delayed the latency to initiate drinking and abolished water intake without effect of eating, and 60 micrograms Th ICV had similar effects upon drinking elicited by ingestion of cracker. The IG infusion (through a surgically implanted gastric catheter) of 2 ml 600 or 900 mOsm/kg NaCl, a treatment that is subthreshold for increase in systemic plasma osmolality at the initiation of drinking, elicited drinking that was abolished by 10 mg/kg Th s.c. and attenuated by 60 micrograms Th ICV. The IG infusion of 2 ml 1800 mOsm/kg NaCl, a treatment that is above threshold for increase in systemic plasma osmolality, elicited drinking that was attenuated by 10 mg/kg s.c. or 60 micrograms Th ICV. These results demonstrate that peripheral and central H3 receptors for histamine have a role in drinking elicited by eating and the postprandial gastrointestinal osmotic consequences of eating. These findings extend the evidence demonstrating a histaminergic contribution to food-related drinking in rats.     

Acute and delayed hormonal changes in mitral stenosis treated by balloon valvulotomy

The role of left atrial and aortic pressures on the secretion of the main hormones controlling blood volume is still subject to debate in humans. Because of increased mean left atrial pressure and decreased mean aortic pressure produced by balloon inflation in patients with mitral stenosis treated with balloon valvulotomy, the hormonal changes occurring acutely (group II of patients) were measured. The same studies (group I patients) were also performed 48 hours after this treatment, a period at which left atrial pressure permanently diminished. Inflation of the balloon resulted in a decrease in plasma renin activity and increases in plasma atrial natriuretic factor (ANF) and plasma arginine vasopressin (AVP). Forty-eight hours after balloon valvulotomy, which had produced a decrease in left atrial pressure, plasma ANF was lower (58.9 +/- 7.9 vs 95.3 +/- 11.9 pg/ml; p < 0.001), and plasma renin activity (2,575 +/- 533 vs 960 +/- 113 pg/ml/hour; p < 0.01), plasma angiotensin II (25.0 +/- 4.1 vs 9.3 +/- 1.3 pg/ml; p < 0.001) and plasma aldosterone (181.7 +/- 36.7 vs 139.9 +/- 19.8 pg/ml; p < 0.05) were higher than their respective control levels 24 hours before treatment of the stenosis. In contrast, plasma AVP (3.7 +/- 0.25 vs 4.4 +/- 0.31 pg/ml; p = 0.001) diminished moderately along with plasma osmolality (282.4 +/- 0.1 vs 286.2 +/- 0.6 mOsm/kg; p < 0.001). Urinary sodium excretion was also examined before and after balloon valvulotomy.(ABSTRACT TRUNCATED AT 250 WORDS)     

0.45% saline and 5% dextrose in water, but not 0.9% saline or 5% dextrose in 0.9% saline, worsen brain edema two hours after closed head trauma in rats

In this study, we examined the effect of four i.v. fluids (250 mL/kg) on blood glucose and osmolality and brain tissue specific gravity after closed head trauma (CHT) in rats. CHT was delivered at Time 0; blood was sampled at 60 min; fluid infusion began at 75 min and ended at 105 min. Blood was again sampled at 105 and 120 min, and brain tissue specific gravity was determined at 120 min. Five groups (one control and four fluid-treated groups) received CHT, and five other groups (one control and four fluid-treated) did not (n = 9 in each group). 0.45% saline (1/2 NS) and 5% dextrose in water (D5W) accentuated the decrease of brain tissue specific gravity (1.0366 +/- 0.0025 and 1.0368 +/- 0.0028, respectively; mean +/- SD) caused by CHT (1.0395 +/- 0.0036), but 5% dextrose in 0.9% saline (D5NS) and 0.9% saline (NS) did not (1.0431 +/- 0.0042 and 1.0389 +/- 0.0049, respectively). In addition, 1/2 NS decreased blood osmolality (248 +/- 6 mOsm/L), D5W increased blood glucose (1095 +/- 173 mg/dL), D5NS increased blood osmolality (350 +/- 5 mOsm/L) and glucose (1695 +/- 76 mg/dL), and NS caused no significant change. We conclude that administering hypoosmolar i.v. fluids after CHT causes a significant worsening of cerebral edema 2 h after CHT. Implications: We previously reported worse neurological outcome and/or mortality after closed head trauma in rats when 5% dextrose in water or 0.45% saline was given i.v. compared with 0.9% saline or 5% dextrose in 0.9% saline. The present results and our previous findings indicate that worsening of outcome after closed head trauma in rats may be caused more by edema formation than by hyperglycemia.     

Inorganic fluoride nephrotoxicity: prolonged enflurane and halothane anesthesia in volunteers

The effects of prolonged enflurane and halothane administration on urine-concentrating ability were determined in volunteers by examining their responses to vasopressin before anesthesia and on days 1 and 5 after anesthesia. A significant decrease in maximum urinary osmolality of 264 +/- 34 mOsm/kg (26 per cent of the preanesthetic value) was present on day 1 after enflurane anesthesia, whereas subjects anesthetized with halothane had a significant increase in maximum urinary osmolality of 120 +/- 44 mOsm/kg. Serum inorganic fluoride level peaked at 33.6 muM and remained above 20 muM for approximately 18 hours. Thus, the threshold level for inorganic fluoride nephrotoxicity is lower than previously suspected.     

Anti-inflammatory mystixin peptides inhibit plasma leakage without blocking endothelial gap formation

Mystixins are synthetic peptides that inhibit plasma leakage after tissue injury. We sought to determine the mechanism of the antileakage effect of mystixins, with particular reference to the formation of endothelial gaps in postcapillary venules. Intravenous administration of mystixin-7, a prototype heptapeptide (p-anisoyl-Arg-Lys-Leu-Leu-D-Thi-Ile-D-Leu-NH2), decreased Evans blue leakage induced by substance P (5 microg/kg i.v.) with an ED50 (95% confidence limits) of 130 (76-211) microg/kg in trachea and 52 (27-100) microg/kg in skin of anesthetized F344 rats. Leakage was decreased without a reduction in the number or size of endothelial gaps, visualized by silver deposits after silver nitrate staining. The number of silver deposits per tracheal endothelial cell was 11.4 +/- 0.2 (mean +/- S.E.) after vehicle pretreatment vs. 13.0 +/- 0.8 after mystixin-7 pretreatment (100 microg/kg i.v.). Silver deposit diameter was unchanged at 1.4 +/- 0.1 micron. Mean arterial blood pressure dropped by a maximum of 38% from baseline for approximately 10 min after mystixin-7 (100 microg/kg i.v.), then recovered to a plateau at about 13% below baseline. The antileakage effect of mystixin-7 pretreatment in vivo was also demonstrated in aldehyde-fixed vessels perfused in situ with Evans blue at constant flow (skin, 79% reduction; trachea, 49% reduction), which suggests that mystixin can reduce leakage independent of its hypotensive effect. We conclude that the antileakage effect of mystixin does not depend on reducing the number or size of endothelial gaps, but instead could be caused by residual hypotension, which reduces the negative interstitial fluid pressure toward zero, or clogging of endothelial gaps.     

Hypervolemia in men from fluid ingestion at rest and during exercise

BACKGROUND: Plasma osmolality (Osm) is important for controlling and maintaining plasma volume (PV) and body water. The effect of oral rehydration fluids for ameliorating dehydration is well-established; but optimal composition and Osm of fluids for hyperhydrating normally hydrated subjects is less clear. METHODS: Six treatments were used without and with oral fluids of varying ionic and constituent concentrations for hyperhydrating six previously euhydrated men (30 +/- SD 8 yr, 76.84 +/- 16.19 kg, 73 +/- 12 ml.kg-1 PV, 40 +/- 10 ml.min-1.kg-1 peak VO2) sitting at rest for 90 min (VO2 = 0.39 +/- SE 0.02 L.min-1) and during subsequent 70 min of submaximal exercise (VO2 = 2.08 +/- SE 0.33 L.min-1, 70 +/- 7% peak VO2). The hypothesis was that the fluid composition is more important than plasma Osm for increasing PV in euhydrated subjects at rest and maintaining it during exercise. Drink formulation compositions, given at 10 ml.kg-1 body wt, (mean = 768 ml), for the sitting period were: Performance 1 (P1; 55 mEq Na+, 365 mOsm.kg H2O-1), P2 (97 mEq Na+, 791 mOsm.kg-1), P2G (113 mEq Na+, 4% glycerol, 1382 mOsm.kg-1), AstroAde (AA; 164 mEq Na+, 253 mOsm.kg-1), and 01 and 02 (no drinking). The exercise drink (10 ml.kg-1, 768 ml) was P1 for all treatments except 02 (no drinking); thus, drink designations were: P1/P1, P2/P1, P2G/P1, AA/P1, 0/P1, and 0/0. RESULTS: PV at rest increased (p < 0.05) by 4.7% with P1 and by 7.9% with AA. Percent change in PV during exercise was +1% to +3% (NS) with AA/P1; -6% to 0% (NS) with P1/P1, P2/P1, P2G/P1, and 0/P1; and -8% to -5% (p < 0.05) with 0/0. AA, with the lowest Osm of 253 mOsm.kg-1, increased PV at rest (as did P1) and maintained it during exercise, whereas the other drinks with lower Na+ and higher Osm of 365-1382 mOsm.kg-1 did not. CONCLUSION: Drink composition appears to be more important than its Osm for increasing PV at rest and for maintaining it during exercise in previously euhydrated subjects.     

Contribution of luminal concentration of nutrients and osmolality to postprandial intestinal hyperemia in dogs

Intestinal blood flow is increased during digestion. This study assesses if the concentration of nutrients and/or osmolality of chyme in the intestinal lumen are factors determining the hyperemia. Six digested food mixtures containing different concentrations of nutrients and/or having different osmolalities were placed into the jejunal lumen, and their effects on local venous outflow compared. The 100% (999 mOsm/kg), 33% (291 mOsm/kg), and 20% (183 mOsm/kg) food mixtures all increased flow, but the 10% food mixture (94 mOsm/kg) did not. The hyperemic effect of 33 and 20% food was similar, but 100% food produced a greater increase in flow than did 33 or 20% food. Luminal placement of a 30% solution of a nonabsorbable substance polyethylene glycol (1000 mOsm/kg) did not alter flow. Also, the vascular effects of 20 or 10% food mixtures were not altered when these mixtures were made isotonic by the addition of NaCl. These studies indicate that lumen osmolality, within a range of 180 to 1000 mOsm/kg, is not a significant factor contributing to the local hyperemia occurring when nutrients are in the gut lumen. However, the concentration of nutrients in the lumen is a factor determining the local hyperemia.     

Resistance to vasopressin action on the kidney in patients with Cushing's disease

OBJECTIVE: To assess the plasma levels and action of arginine vasopressin (AVP) in patients with Cushing's disease. There are many reports that patients with Addison's disease have increased AVP levels associated with hyponatraemia and hypoosmolality, but none on the dynamics of secretion of this neurohormone during osmolality-based stimulation in patients with chronic hypercortisolism. DESIGN AND SUBJECTS: The plasma AVP concentration and the urinary and plasma osmolality after a 7.5-h water deprivation test (WDT) were evaluated in 13 patients with Cushing's disease and 15 normal (control) individuals. In patients with Cushing's disease we also assessed the urinary osmolality in response to 10 micrograms i.v. desmopressin (DDAVP) administered at the end of the WDT. RESULTS: At the end of the WDT, urinary osmolality was significantly lower in patients with Cushing's disease (511.5 +/- 148.5 mOsm/l) than in the normal subjects (981.1 +/- 107.1 mOsm/l, P < 0.001), whereas plasma osmolality did not differ between the two groups. Consequently, the urine/plasma osmolality ratio (Uosm/Posm) was lower in patients with Cushing's disease than in normal individuals (1.8 +/- 0.5 compared with 3.4 +/- 0.4, P < 0.001). The AVP concentration also was greater (7.3 +/- 3.1 pmol/l) in those with Cushing's disease than in the controls (3.9 +/- 2.3 pmol/l, P < 0.005). After administration of DDAVP to the hypercortisolaemic patients, the urinary osmolality attained (718.0 +/- 200.0 mOsm/l) was still lower than that in the normal group at the end of WDT (P < 0.005). CONCLUSIONS: Patients with Cushing's disease presented higher AVP levels and smaller Uosm/Posm ratios than normal subjects. After DDAVP, the patients with Cushing's disease were unable to concentrate the urine adequately. These data suggest that the kidney shows resistance to the action of both endogenous and exogenous AVP in patients with Cushing's disease.     

Primary polydipsia. Syndrome of inappropriate thirst

A patient with lifelong severe polyuria and polydipsia had normal serum antidiuretic hormone (ADH) levels and responded to water deprivation with a prompt increase in urine osmolality and maintenance of normal plasma osmolality (less than 290 mOsm/kg), despite extreme thirst. When treated with desmopressin acetate and allowed free access to water, she was able to reduce plasma osmolality below 270 mOsm/kg, and her compelling thirst disappeared. The disorder is interpreted to be the result of excessive fluid intake in response to a thirst stimulus that was not inhibited by normal plasma osmolality. This study indicates that osmoreceptor control of ADH secretion is normal. Continued administration of vasopressin has relieved the symptoms and has not resulted in water intoxication.     

Altered response to histamine in brain tumor vessels: the selective increase of regional cerebral blood flow in transplanted rat brain tumor

The authors studied the effect of intracarotid administration of histamine on the regional cerebral blood flow (rCBF) in transplanted rat C6 glioma by the hydrogen clearance method. Histamine infusion at doses of 1 and 10 micrograms/kg/min produced an increase of rCBF in the tumor (24.6% +/- 16.4%, p < 0.002, and 37.6% +/- 18.2%, p < 0.0001, respectively) and also in brain surrounding the tumor (26.8% +/- 16.2%, p < 0.002, and 34.9% +/- 9.2%, p < 0.0001, respectively) without any significant changes in the ipsilateral hemisphere. Intravenous administration of pyrilamine (H1 antagonist) and cimetidine (H2 antagonist) reduced blood flow responses to histamine; cimetidine was a more effective blocking agent than pyrilamine. Intracarotid infusion of histamine (1 and 10 micrograms/kg/min) with intravenous injection of Evans blue dye disclosed the selective extravasation of dye in the tumor and the brain surrounding the tumor. These results indicated that brain tumor vessels could respond to histamine differently than normal brain capillaries. The mechanism of selective response to histamine could be explained either by increased permeability or by altered characteristics of histamine receptors in the tumor vessels.     

Recombinant or plasma-derived antisecretory factor inhibits cholera toxin-induced increase in Evans blue permeation of rat intestinal capillaries

The effect of cholera toxin on small intestinal capillary function, utilizing the Evans blue dye method, was analyzed. The modulatory influence of plasma-derived or recombinant human antisecretory factor on this variable was also investigated. Male Sprague-Dawley rats were briefly anesthetized with ether, and a jejunal loop was constructed that was challenged for 90 min with phosphate-buffered saline or cholera toxin. Five minutes prior to death, the rats received an intravenous injection of Evans blue. The tissue content of dye in the loop was quantitated spectrophotometrically or demonstrated histochemically. Cholera toxin increased the recovery of Evans blue; extravasation of the dye was prominent in the top of the villi, while the crypts were spared. It is suggested that the toxin caused increased transcapillary permeation of albumin in a heterogenous fashion in the gut wall. This effect of the toxin was prevented by pretreatment with the antisecretory factor.     

Effect of 6-hydroxydopamine injection into the arcuate hypothalamic nucleus on the osmotic release of vasopressin in conscious rats

The aim of the present study was to evaluate a role in vasopressin secretion of the catecholaminergic neurons, including the tuberohypophysial dopaminergic neurons situated in the arcuate hypothalamic nucleus. A neurotoxin, 6-hydroxydopamine (6 g/l), was injected locally into the arcuate nucleus and its effects on catecholamine levels of the hypothalamic tissue and the neurointermediate lobe, and on the plasma vasopressin concentrations before and during i.v. infusion (0.1 ml kg-1 min-1) of isotonic (0.15 mol/l) or hypertonic saline (2.5 mol/l), were examined in conscious rats. The infusion of hypertonic saline produced increases of plasma vasopressin 15 and 30 min later, accompanied by elevations of plasma osmolality, sodium, chloride and arterial pressure. The vasopressin response was potentiated markedly by the 6-hydroxydopamine injection performed 8 days before, which hardly affected the responses of the other variables. Histological examination indicated that the injection sites of 6-hydroxydopamine in those rats had been located in the area ranging from rostral to medial arcuate nucleus. The i.v. infusion of isotonic saline did not change plasma vasopressin, osmolality, sodium, chloride or arterial pressure, regardless of the presence or absence of pretreatment with 6-hydroxydopamine. It was confirmed that when 6-hydroxydopamine was injected into the arcuate nucleus region 8 days before, noradrenaline and adrenaline concentrations of the hypothalamic tissue containing the injection site were decreased remarkably, although we could not detect any significant alteration in the dopamine concentration of the hypothalamic tissue or the neurointermediate lobe. On the basis of these results, we concluded that catecholaminergic neurons in the arcuate nucleus may act to inhibit osmotic vasopressin secretion.     

Urinary indices in llamas fed different diets

Indices of renal function and damage were measured in 12 healthy male adult llamas fed a diet of mixed alfalfa/grass hay (mixed hay) and water ad libitum. Using a collection bag fitted over the preputial area, urine samples were collected at 6, 12, and 24 hours. Serum samples were obtained concurrently to determine endogenous creatinine clearance (CL), total (TE) and fractional excretion (FE) of electrolytes (Na, K, Cl, P), electrolyte CL, urine and serum osmolality, urine enzyme activities (gamma-glutamyltransferase and N-acetyl-beta-D-glucosaminidase), and urine protein concentration. Urine production was quantified. Three months later, 10 of the 12 llamas were fed a grass hay diet and water ad libitum. Similar samples were obtained, and similar measurements were made. Urine production was higher when the llamas were fed the mixed hay diet. Total urine volume for llamas fed mixed hay ranged from 628 to 1,760 ml/24 h, with a median of 1,307.5 ml/24h, compared with a range of 620 to 1,380 ml/24 h and a median of 927.50 ml/24h for llamas fed grass hay. Median urine osmolality was higher in llamas fed mixed hay (1,906 mOsm/kg of body weight, with a range of 1,237 to 2,529 mOsm/kg), compared with llamas fed grass hay (1,666 mOsm/kg with a range of 1,163 to 2,044 mOsm/kg). Creatinine CL did not vary significantly over time for either diet.(ABSTRACT TRUNCATED AT 250 WORDS)     

Experimental basis of cancer combination chemotherapy with retinoids, cytokines, 1,25-dihydroxyvitamin D3, and analogs

The effects of IRFI-048 (2,3-dihydro-5-methoxy-4,6,7-trimethyl-2-benzofuranyl acetic acid), a selective analogue of Vitamin E, on myocardial tissue injury were examined in anaesthetized rats subjected to 60-min occlusion of the left coronary artery followed by 60-min reperfusion. Infarct size (Evan's blue and tetrazolium stain), serum creatinphosphokinase (CPK), plasma malonaldehyde (MAL), cardiac myeloperoxidase (MPO) activity, and ST-segment of electrocardiogram (ECG) and survival rate were evaluated. Postischaemic reperfusion produced severe cardiac necrosis, caused neutrophil (PMNs) infiltration (evaluated by MPO activity) in the jeopardized tissue, increased serum CPK and plasma MAL, raised ST-segment of ECG, and decreased survival rate. IRFI-048, (200 and 400 mg/kg o.s.) given to the rats 6 h before occlusion, caused a reduction of necrotic area expressed as a percentage of either the area at risk or the total left ventricle, decreased MPO activity both in the area at risk (from 3.2 +/- 0.3 U x 10(-3)/g tissue to 1.1 +/- 0.4 U x 10(-3)/g tissue; p < .005) and in the necrotic area (from 5.7 +/- 0.9 U x 10(-3)/g tissue to 1.8 +/- 0.5 U x 10(-3)/g tissue; p < .001), attenuated the rise of ST-segment of ECG (from 0.51 +/- 0.14 mV in the vehicle group to 0.28 +/- 0.11 mV in the treated group; p < .005), reduced the increase of plasma MAL and serum CPK during reperfusion (from 42 +/- 5.3 nmol/ml to 15 +/- 3.1 nmol/ml and 139 +/- 13 IU/100 ml to 58 +/- 7.5 IU/100 ml, respectively; p < .001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Necker cube reversal: sensory or psychological satiation?

Mechanisms determining the natriuresis in ECV-expansion are not yet completely understood. The present study was therefore undertaken to investigate if prostaglandins (PG) are involved in the natriuresis of acute ECV-expansion and by which mechanisms PG may affect renal Na-absorption. In non-expanded rats the PG synthetase inhibitor indomethacin (INDO) had no effect on renal function. In 37 Sprague-Dawley rats ECV-expansion with isotonic saline corresponding to an increase in b.wt. of 10% was induced. Twenty-one animals received an oral dose of 10 mg/kg b.wt. of INDO prior to ECV-expansion. Sixteen animals served as ECV-expanded controls (C). GFR (INDO: 12.5 +/- 1.0; C: 10.5 +/- 0.9 ml/min/kg b.wt.) did not significantly differ in both groups. However, total renal plasma flow (RPF) (INDO: 22.9 +/- 1.8; C: 30.1 +/- 2.7 ml/min/kg b.wt.), urinary flow rate (INDO: 1.11 +/- 0.20; C: 1.93 +/- 0.21 ml/min/kg b.wt.) and urinary excretion of sodium (INDO: 141 +/- 26; C: 267 +/- 46 muEq/min/kg b.wt.) and potassium (INDO: 13.0 +/- 0.9; C: 19.8 +/- 1.7 muEq/min/kg b.wt.) markedly decreased in animals pretreated with INDO. The results indicate that PG are involved in the natriuresis of acute ECV-expansion and suggest, that PG may inhibit the intrinsic capacity for Na-absorption in more proximal parts of the nephron possibly via intrarenal physical factors.     

Osmolality of equine blastocyst fluid from day 11 to day 25 of pregnancy

Horse conceptuses collected between Day 11 and Day 18 of pregnancy float in isotonic media. To investigate this phenomenon, blastocyst fluids from 30 conceptuses from 13 mares were analysed for osmolality and for concentrations of Na+, Cl-, K+, glucose, urea and creatinine. In conceptuses from Group A, samples from Day 11 to Day 16 yielded the following results (mean +/- s.e.m.): osmolality, 121.4 +/- 1.5 mOsm kg-1; Na+, 11.0 +/- 2.2 mM; Cl-, 29.3 +/- 2.5 mM; K+, 26.2 +/- 2.6 mM; glucose, 0.6 +/- 0.1 mM; urea, 6.0 +/- 0.6 mM; creatinine, 9.6 +/- 1.1 microM. Between Day 16 and Day 25, the osmolalities and Na+ concentrations increased gradually with age but the former never exceeded 255 mOsm kg-1. Fluids from Group B were obtained from eight conceptuses exposed to saline solutions of different osmolalities for various periods of time. An increased perivitelline space of 1-3 mm became evident at the lower pole of the floating conceptus after 45 min of exposure to solutions with osmolalities of > or = 300 mOsm kg-1, suggesting that Na+ and Cl- diffuse freely through the capsule but not through the trophoblast. The significance of the hypo-osmolality of equine blastocyst fluid is discussed but remains unclear.