Comparison of a natural heparinoid with sodium and calcium heparin for their effect on the inhibitor of activated factor X.

The reaction between activated factor X (Xa) and its natural inhibitor (XaI) was accelerated in vitro by both sodium heparin and an heparinoid, which was about 3 times less potent than heparin. The s. c. administration in humans of 5,000 units of sodium and calcium heparin was followed by the detection of a plasma activity potentiating XaI. In the majority of subjects, the heparinoid was not effective. These observations indicate that the use of heparinoids should not be considered as an alternative to heparin in the prevention of thromboembolism.     

Experimenteller Beitrag zur Frage der Klärfaktoraktivierung

Summary After intravenous injection of a³⁵S-labelled heparinoid (N-formyl-chitosan-polysulfuric acid ester) into rabbits, a highly purified clearing factor preparation was obtained from the blood plasma. The heparinoid content of this preparation is approximately 40 times higher, weight for weight, than that of the other plasma proteins.      

Förderung der gastrointestinalen Resorption von Heparin durch Calciumbindungsmittel

Summary The gastroenteral absorption of heparin in rats as measured by clearing-factor activation is considerably enhanced by simultaneous administration of a number of calcium-binding substances as ethylendiamine-tetraacetate, sodium citrate, ion-exchangers, soaps and phosphates.Single oral administrations of heparin at the very high dose of 2 g/kg also lead to a maximum activity of the clearing factor.A binding of calcium ions seems to enable the intestinal absorption of heparin in all these cases.     

Sodium deoxycholate promotes the absorption of heparin administered orally, probably by acting on gastrointestinal mucosa, in rats

Sodium deoxycholate (DOC), selected as a promoter of gastrointestinal absorption of heparin, was administered orally to rats, followed, at increasing intervals, by heparin. Maximal plasma clearing activity (PC) was obtained with a 60-min interval, though PC was still elicited after 24 h, suggesting that DOC acts on the gastrointestinal mucosa. Inhibition of blood coagulation was also observed after oral heparin. The suggestion that DOC increases heparin absorption is supported by increased plasma levels of heparin. No signs of several gastrointestinal damage were seen.     

Sodium deoxycholate promotes the absorption of heparin administered orally,probably by acting on gastrointestinal mucosa,in rats

Summary Sodium deoxycholate (DOC), selected as a promoter of gastrointestinal absorption of heparin, was administered orally to rats, followed, at increasing intervals, by heparin. Maximal plasma clearing activity (PC) was obtained with a 60-min interval, though PC was still elicited after 24 h, suggesting that DOC acts on the gastrointestinal mucosa. Inhibition of blood coagulation was also observed after oral heparin. The suggestion that DOC increases heparin absorptions is supported by increased plasma levels of heparin. No signs of several gastrointestinal damage were seen.     

Heparin effects on cultured mammalian cells.

Plasmacytoma cells exposed to heparin exhibited zeiotic blebs in the G1 phase, S phase, and early G2 phase. Zeiosis was not seen in mitotic cells. This heparin effect was reversible. Also fibroblasts were sensitive to heparin. After trypsinization of fibroblasts, heparin produced large non-reversible zeiotic blebs in the cells, except in those in mitosis. The primary target for heparin is apparently to be sought among components of the cellular periphery.     

Direkte Hemmwirkung des Heparins auf die Insulinsekretion

Summary The injection of heparin into the A. pancreaticoduodenalis of anaesthetized dogs produces an immediate decrease of the IRI-concentration in the pancreatic and peripheral venous plasma. This decrease could not be correlated with any alteration of blood sugar or FFA. A direct inhibitory action of heparin on the pancreatic B-cell is suggested.     

Peptide YY enhances NaCl and water absorption in the rat colon in vivo.

Peptide YY (PYY) is thought to possess paracrine and endocrine functions. The highest concentrations of this peptide are in the colonic mucosa. The effect of PYY on electrolyte and water transport in the rat colon was studied in vivo. Under urethane anesthesia, rat colonic loops were perfused at a constant rate with physiological buffer solution containing phenol red as a nonabsorbable volume marker, and net movements of water, sodium, chloride and potassium in the perfused colon were determined every 10 min. Intravenous administration of PYY produced a dose-dependent increase in the net absorption of sodium chloride and water, as well as a decrease in the net secretion of potassium. PYY inhibited the reduction in net absorption of sodium chloride and water evoked by vasoactive intestinal peptide (VIP), but did not affect the VIP-evoked increase in net potassium secretion. These findings suggest that PYY acts as an enhancer of sodium chloride and water absorption and as an antagonist to VIP-induced secretion in the colon.     

Peptide YY enhances NaCl and water absorption in the rat colon in vivo

Peptide YY (PYY) is thought to possess paracrine and endocrine functions. The highest concentrations of this peptide are in the colonic mucosa. The effect of PYY on electrolyte and water transport in the rat colon was studied in vivo. Under urethane anesthesia, rat colonic loops were perfused at a constant rate with physiological buffer solution containing phenol red as a nonabsorbable volume marker, and net movements of water, sodium, chloride and potassium in the perfused colon were determined every 10 min. Intravenous administration of PYY produced a dose-dependent increase in the net absorption of sodium chloride and water, as well as a decrease in the net secretion of potassium. PYY inhibited the reduction in net absorption of sodium chloride and water evoked by vasoactive intestinal peptide (VIP), but did not affect the VIP-evoked increase in net potassium secretion.These findings suggest that PYY acts as an enhancer of sodium chloride and water absorption and as an antagonist to VIP-induced secretion in the colon.     

Über den Einfluss von Natriumsulfit,Natriumtellurit und Natriumselenit auf die Retention von Zink,Kadmium und Quecksilber im Organismus

Summary The influence of sodium sulfite, sodium tellurite and sodium selenite on the retention of zinc, cadmium and mercury in mice was studied. The retention of mercury was increased by sodium selenite and by sodium tellurite. The retention of cadmium was increased only by sodium selenite. Sodium sulfite did not influence the retention of metals studied. The retention of zinc was not influenced by any compounds used.     

Heparin inhibition of the antithrombin activity of alpha-2-macroglobulin]

The interaction between thrombin and alpha-2-macroglobulin was studied on human purified materials, either in the presence or in the absence of heparin, by kinetic analysis of thrombin inhibition and polyacrylamide gel electrophoresis. In the absence of heparin, binding of thrombin to alpha-2-macroglobulin, shown by electrophoresis, leads to the loss of the coagulant property of the enzyme. In the presence of heparin the rate of inhibition of thrombin clotting activity by alpha-2-macroglobulin is strongly decreased. Heparin binds to thrombin, impairing the formation of thrombin-alpha-2-macroglobulin complex. These data show that heparin paradoxically protects thrombin from inhibition by alpha-2-macroglobulin whereas it increases the enzyme inhibition by antithrombin III. Such a phenomenon could be of practical interest for treatment of thrombosis in patients with high plasma level of alpha-2-macroglobulin and low level of antithrombin III, such as occurs in the nephrotic syndrome.     

Nitric oxide-dependent blood-brain barrier permeability alteration in the rat brain

The role of nitric oxide (NO), a well known vasodilator, in the regulation of blood-brain barrier (BBB) permeability is not clear. Therefore, the present study was planned to assess the role of NO-releasing compounds like sodium nitroprusside (SNP) and the active metabolite of molsidomine, SIN-1, as well as a precursor of NO, L-arginine, on this physiological barrier. The permeability was assessed by using several tracers. All three agents increased the permeability of BBB to the tracer. The increase in permeability caused by L-arginine was not blocked by N-nitro-L-arginine methyl ester (L-NAME). L-Arginine-treated brains did not show an elevation of nitrite content, thus ruling out the possibility of NO generation and its involvement in BBB permeability alteration. It is concluded that NO itself causes an increase in the permeability of BBB. However arginine-induced opening is not NO mediated.CDRI Communication Number: 5178.     

Effects of scavengers of superoxide radicals, hydrogen peroxide, singlet oxygen and hydroxyl radicals on malondialdehyde generation from arachidonic acid by bovine seminal vesicle microsomes

Superoxide dismutase, catalase and sodium formate did not inhibit the formation of malondialdehyde (MDA) from arachidonic acid, suggesting that O2-., H2O2 and OH. are not involved in the enzymatical oxidation of arachidonic acid. Sodium azide was found to be an inhibitor of MDA production.     

Renal effects of a high unsaturated fat diet in renal artery stenosis in rats

The renal effects of an unsaturated fat (UNSAT) diet in mild to moderate two-kidney, one-clip (2K1C) renovascular hypertension were evaluated. An UNSAT diet (37% by energy) prevented the development of hypertension compared to 2K1C rats fed a high saturated fat (SAT) (37% by energy) and a normal fat (CONTROL) (11% by energy) diet. Urinary sodium and fractional sodium excretion increased in 2K1C rats as compared to SHAM operated controls, regardless of the diet received. In the early weeks of the experiment (weeks 2–4 post-surgery to induce hypertension), an enhanced natriuresis occurred in the 2K1C UNSAT as compared to the 2K1C CONTROL and SAT diet groups. This resulted from an increase in the glomerular filtration rate (GFR in mls·min^–1) as measured using the single-injection [⁵¹Cr] EDTA method (2K1C UNSAT; 1.99±0.18 versus 2K1C SAT; 1.27±0.09, p<0.02; and versus SHAM CONTROL; 1.45×0.01; p<0.02). The increased GFR was not associated with alterations in effective renal plasma flow (ERPF) as measured using the single-injection [¹²⁵I] Na hippurate method. No differences in sodium excretion; GFR; ERPF or renal blood flow (microsphere technique) were noted between the 2K1C UNSAT and SAT diet groups at weeks 6–8 post-surgery, despite a continued antihypertensive effect of the UNSAT diet. Hence, the antihypertensive effect of an unsaturated fat diet in 2K1C renovascular hypertension in rats is associated with transient glomerular changes leading to an enhanced natriuresis.     

Differential influences of various arsenic compounds on glutathione redox status and antioxidative enzymes in porcine endothelial cells

The cellular response and detoxification mechanisms in porcine endothelial cells (PAECs) to arsenic trioxide (As2O3), sodium arsenite (NaAsO2) and sodium arsenate (Na2HAsO4) were investigated. NaAsO2 at 20 microM for 72 h increased Cu/Zn superoxide dismutase activity resulting in elevated intracellular hydrogen peroxide levels, but As2O3 and Na2HAsO4 did not. Trivalent arsenic compounds increased intracellular oxidized glutathione (GSSG) and total glutathione (GSH) and cellular glutathione peroxidase (cGPX) and glutathione S-transferase (GST) activity, but not glutathione reductase activity. The increased cGPX activity resulted in an elevated cellular GSSG content. Na2HAsO4 increased the cellular GSSG level at 72 h compared to controls. These results imply that the increased GSH content responding to the oxidative stress by trivalent arsenic compounds may be mainly related to the regulation of GSH turnover. The increased GST activity implies that the elevated intracellular GSH level responding to the oxidative stress may be used to conjugate arsenic in PAECs and facilitate arsenic efflux.     

Isolation and characterization of hainantoxin-IV,a novel antagonist of tetrodotoxin-sensitive sodium channels from the Chinese bird spider <Emphasis Type="Italic">Selenocosmia hainana</Emphasis>

A neurotoxin, named hainantoxin-IV, was purified from the venom of the spider Selenocosmia hainana. The amino acid sequence was determined by Edman degradation, revealing it to be a 35-residue polypeptide amidated at its C terminal and including three disulfide bridges: Cys2-Cys17, Cys9-Cys24, and Cys16-Cys31 assigned by partial reduction and sequence analysis. Hainantoxin-IV shares 80% sequence identity with huwentoxin-IV from the spider S. huwena, a potent antagonist that acts at site 1 on tetrodotoxin-sensitive (TTX-S) sodium channels, suggesting that hainantoxin-IV adopts an inhibitor cystine knot structural motif like huwentoin-IV. Under whole-cell voltage-clamp conditions, this toxin has no effect on tetrodotoxin-resistant voltage-gated sodium channels in adult rat dorsal root ganglion neurons, while it blocks TTX-S sodium channels in a manner similar to huwentoxin-IV, and the actions of both toxins on sodium currents are very similar to that of tetrodotoxin. Thus, they define a new family of spider toxins affecting sodium channels.     

Comparative effects of ouabain, natriuretic factor and ammonium chloride in the toad urinary bladder

Electrical changes and direct effects on Na-K ATPase activity induced by an endogenous digitalis-like natriuretic factor (NF), NH4Cl and ouabain were studied in toad bladders. NF inhibited the SCC and the Na-K ATPase activity in a similar manner to ouabain, but induced a greater increase in calculated direct current resistance (R) (p less than 0.05). NH4Cl was a weak inhibitor of Na-K ATPase activity, although it produced steeper SCC inhibition slopes than those observed with ouabain or NF (p less than 0.01). The data suggested the same mechanism of action of NF and ouabain on the sodium pump, with an additional effect of the former on apical sodium permeability of the cells and/or closure of paracellular routes leading to an increased tissue resistance. In contrast, the effects of NH4Cl were mostly compatible with intracellular inhibition of apical sodium entry into the cell.     

Regulation of sodium and body fluid homeostasis during development: Implications for the pathogenesis of hypertension

The spontaneously hypertensive rat (SHR) is an important animal model of human essential hypertension. During the first month of life, increased retention of sodium is present in the SHR which appears to be mediated by the renin-angiotensin system. The present review will discuss the role that increased activity of the renin-angiotensin system plays in sodium/body fluid regulation during early development. It is hypothesized that disordered regulation of sodium/body fluid homeostasis during this stage leads to pathological cardiovascular regulation in adulthood. Through an understanding of the relationship between sodium/body fluid balance in the young and cardiovascular function in the adult insights may be gained into both the pathological state of hypertension and the critical role played by early development in shaping homeostatic mechanisms in adulthood.     

Regulation of sodium and body fluid homeostasis during development: implications for the pathogenesis of hypertension.

The spontaneously hypertensive rat (SHR) is an important animal model of human essential hypertension. During the first month of life, increased retention of sodium is present in the SHR which appears to be mediated by the renin-angiotensin system. The present review will discuss the role that increased activity of the renin-angiotensin system plays in sodium/body fluid regulation during early development. It is hypothesized that disordered regulation of sodium/body fluid homeostasis during this stage leads to pathological cardiovascular regulation in adulthood. Through an understanding of the relationship between sodium/body fluid balance in the young and cardiovascular function in the adult insights may be gained into both the pathological state of hypertension and the critical role played by early development in shaping homeostatic mechanisms in adulthood.     

Die Wirkung von synthetischem Oxytocin (Syntocinon) und Acetazolamid auf die Ausscheidung von Wasser,Natrium und Kalium

Summary Changes in water, sodium, and potassium excretion following administration of synthetic oxytocin (Syntocinon)—alone or in combination with acetazolamide— resemble the changes that occur after an equivalent dose of neurohypophysial extract containing oxytocin. Since the action of Syntocinon on water and sodium excretion is manifest when carbonic anhydrase in kidney tissue is fully inhibited by acetazolamide, it may be assumed that the mechanism whereby Syntocinon increases sodium excretion is independent of carbonic anhydrase. Oxytocin does not affect ultrafiltration in the glomeruli (Krause ⁴) and would therefore appear to modify the reabsorption or excretion process in the tubuli.