Hemorheological alterations in mild essential hypertension.

Blood rheological properties were studied in 21 patients suffering from essential hypertension (EHT), degree I-II according to WHO criteria. These patients were diagnosed "de novo". The whole blood filterability (WBF), blood viscosity (BV) at 230 s-1 and 23 s-1, red cell deformability (FI), erythrocyte aggregation in autologous (MEA) and normal plasma (MEAc), fibrinogen (Fbg) and hematocrit (Ht) have been evaluated. In the hypertensive patients we have found decreased WBF, greater BV and FI in comparison with the control group (p less than 0.001). Likewise, MEA and Fbg were increased, though the differences were less significant (p less than 0.01). The evaluation of Ht did not show any differences between the two groups. The results suggest that in the newly diagnosed EHT, clear hemorheological alterations occur, both in plasma and in the erythrocytes, which could play a role in the pathogenesis of the aforementioned disease.     

High levels of plasma FVIII and vWF in the toxic epidemic syndrome patients

Factor VIII and von Willebrand factor proteins were evaluated in 115 patients having the chronic phase of the Toxic Epidemic Syndrome (TES), a new multisystemic disease probably caused by the ingestion of denatured rapeseed oil, and in 50 control volunteers. Higher circulating levels of factor VIII procoagulant activity (VIII:C) (158 +/- 58.4 U/dl), von Willebrand factor antigen (vWF:Ag) (166.1 +/- 55.5 U/dl) and von Willebrand factor ristocetin cofactor activity (vWF:RCo) (178.7 +/- 55.2 U/dl) were seen in TES patients (p less than 0.001, TES patients versus control subjects, for each parameter). The increased levels of vWF:Ag and vWF:RCo observed in TES patients correlated with the scleroderma like lesion of the skin, with the sicca syndrome and with Raynaud's phenomenon (p less than 0.01), but not with other clinical manifestations. The multimeric analysis of vWF in 92% of the TES patients was similar to that found in normal plasma, but in the remaining 8% a very slight increase of larger vWF multimers in plasma were observed. The raised levels of vWF found in TES patients in the chronic phase may reflect an "in vivo" vascular injury.     

2-Chloro-N6-[3H]cyclopentyladenosine ([3HCCPA) —a high affinity agonist radioligand for A1 adenosine receptors

Summary The tritiated analogue of 2-chloro-N⁶-cyclopentyladenosine (CCPA), an adenosine derivative with subnanomolar affinity and a 10000-fold selectivity for A₁ adenosine receptors, has been examined as a new agonist radioligand. [³H]CCPA was prepared with a specific radioactivity of 1.58 TBq/mmol (43 Ci/mmol) and bound in a reversible manner to A₁ receptors from rat brain membranes with a high affinityK _D-value of 0.2 nmol/l. In the presence of GTP aK _D-value of 13 nmol/l was determined for the low affinity state for agonist binding. Competition of several adenosine receptor agonists and antagonists for [³H]CCPA binding to rat brain membranes confirmed binding to an A₁ receptor. Solubilized A1 receptors bound [³H]CCPA with similar affinity for the high affinity state. At solubilized receptors a reduced association rate was observed in the presence of MgCl₂, as has been shown for the agonist [³H]N⁶-phenylisopropyladenosine ([³H]PIA). [³H]CCPA was also used for detection of A₁ receptors in rat cardio myocyte membranes, a tissue with a very low receptor density. A K_D-value of 0.4 nmol/l and aB _max-value of 16 fmol/ mg protein was determined in these membranes. In human platelet membranes no specific binding of [³H]CCPA was measured at concentrations up to 400 nmol/l, indicating that A2 receptors did not bind [³H]CCPA. Based on the subnanomolar affinity and the high selectivity for A₁ receptors [³H]CCPA proved to be a useful agonist radioligand for characterization of A₁ adenosine receptors also in tissues with very low receptor density.Abbreviations CHA N⁶-cyclopenyadenosine - CPA N⁶-cy-clopentyladen,osine - CCPA 2-chloro-N⁶-cyclopentyladenosine - CCCPA 2-chloro-5-chloro-5-deoxy-N⁶-cyclopentyladenosine; - CHAPS 3-[3-(cholamidopropyl)dimethylammonio]-1-propanesulfonate - DPCPX 8-cyclopentyl-1,3-dipropylxanthine - NECA N-ethylcarboxamidoadenosine - PEI polyethylenimine - PIA N⁶-phenylisopropyladenosine Send offprint requests to K.-N. Klotz at the above address     

Effect of furosemide upon urinary kallikrein excretion

Having in mind the significant decrease of urinary kallikrein in rat with renal hypertension and in humans with essential hypertension, the effects of furosemide on kininogenase activity has been studied in urine of normal and hypertensive rats which received tap water or a 1% NaCl solution for drinking. Administration of 20 mg furosemide which produces maximal diuretic effect in normal rats, induced in these animals a 150–200% increase of the excretion of this enzyme after 8 hours, when compared to the activity measured before giving the drug. This increase which is observed in the normal rats drinking either water or a 1% NaCl solution shows a significant correlation with the excretion of sodium, potassium and water. In hypertensive rats, in 7 or 9 cases, an increase of kallikrein excretion (200–600%) is observed, which does not reach the levels of excretion in normal untreated rats. Furosemide did not produce increase of urinary kallikrein in hypertensive rats drinking 1% NaCl solution.     

Role of fatty acid oxidation in mechanism of action of gastric secretagogues

The role of beta-oxidation in the mechanism of stimulation of acid secretion was examined in toad gastric mucosa in vitro. The incubation with 4-pentenoate selectively inhibited in a dose-dependent manner the rate of 14CO2 formation from [1-14C]octanoate. Pretreatment with 20 mM 4-pentenoate sharply reduced the respiratory and secretory responses to theophylline and histamine. Tracer studies showed a major utilization of exogenous octanoate over glucose and pyruvate by the in vitro toad gastric mucosa. Theophylline and histamine stimulated by 69% the rate of octanoate oxidation. Over 60% of the increments in oxygen uptake produced by theophylline and histamine accounted for the increments in octanoate oxidation, whereas glucose and pyruvate together accounted for less than 25%. Octanoate-dependent respiration was shown to correlate with octanoate oxidation under both inhibition with 4-pentenoate and stimulation with theophylline. Theophylline stimulated by 25% the rate of octanoate oxidation in Cl--free glucuronate-nutrient solutions. The present work provides further evidence for the primary role of fatty acid oxidation in the mechanism of acid secretion in amphibian.     

Architectural organisation of neuronal activity-associated magnetic fields: a hypothesis for memory

Despite intensive investigation into the mechanisms underlying the memory process, the physical bases for this superior cognitive function remain elusive. Neuronal activity-associated magnetic fields (NAAMFs) hypothesis of memory suggests that items of information are stored as three-dimensional bundles of magnetic fields associated to the complex but extremely organised cerebral cortex. The present paper proposes a plausible architectural organisation of neuronal activity-associated magnetic fields that may explain how information could be stored in the human cerebral cortex. Magnetic fields generated as consequence of neuronal minicolumns activation could modify the basal "electromagnetic status" of the closest astrocytes allowing codification and storage of information.     

Lower olfactory threshold during the ovulatory phase of the menstrual cycle

We investigated whether olfactory detection threshold is correlated with phase of the menstrual cycle. Three hundred and thirty-two women 13-49 years old were tested once during either the follicular, ovulatory, luteal or menstrual phase, and 15 women 20-43 years old were tested at each of these phases across one complete cycle. In three non-cycling control groups subjects were each tested once; 83 post-menopausal women 47-86 years old, 60 pre-pubertal girls 5-12 years old, and 183 men 17-30 years old. Odor detection thresholds were determined using sniff bottles containing -log9.5 to -log6.0 concentrations of amyl acetate presented in ascending order. Thresholds differed significantly across the cycle and were lowest during the ovulatory and highest during the menstrual phase. Thresholds for all control groups were higher than for the cycling women during the ovulatory phase. The results confirm that olfactory threshold is related to phase of the menstrual cycle and thus possibly to hormonal state.     

Inhibins are the major activin ligands expressed during early thymocyte development.

Activins are members of the transforming growth factor-beta (TGFbeta) superfamily, which regulate cell differentiation processes. Here we report the first quantitative analysis of the expression of Activin/Inhibin ligands, type I and II receptors, as well as Smad proteins in fetal (E14-E16) and adult thymic subpopulations. Our data showed that Alk4, ActRIIA, ActRIIB, and Smads 2, 3, and 4, are expressed in fetal thymus (E14 > E15 > E16) and in thymocytes from adult mice (mostly in the double negative [DN] subpopulation). Ligand expression analysis showed that betaA, betaB, and alpha subunits were mainly detected in thymic stromal cells. Interestingly, alpha subunits were expressed at much higher levels compared to betaA and betaB subunits, demonstrating for the first time the potential role of Inhibins as important mediators during early T cell development. Our data indicate that Activin/Inhibin signaling could regulate the process of thymus organogenesis and early thymocyte differentiation, as it has been demonstrated for other members of the TGF-beta superfamily.     

Ionotropic glutamate receptor subunits are differentially regulated in the motoneuronal pools of the rat hypoglossal nucleus in response to axotomy

Unilateral hypoglossal nerve axotomy was used as a model to analyse immunohistochemically the expression of the GluR1, GluR2, GluR3, and GluR4 glutamate receptor subunits of the -amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) subtype and the NR1 subunit of the N-methyl-D-aspartate (NMDA) subtype in the different morphofunctional hypoglossal pools from 1 to 45 days postaxotomy. Following hypoglossal nerve axotomy, the percentage of motoneurons that were GluR1-immunopositive and the labeling intensity for this subunit was increased in some hypoglossal pools. Immunolabeling for the GluR2 subunit was undetectable. These results contrast with the unchanged pattern for these two subunits after sciatic nerve axotomy previously described. Image analysis showed a significant decrease in the intensity of immunohistochemical labeling for the GluR2/3 and GluR4 subunits in motoneurons, although most motoneurons were still immunopositive for these 2 subunits after axotomy. The intensity of immunolabeling for the NR1 subunit was slightly decreased postlesion, whereas the percentage of NR1-immunopositive motoneurons increased. Immunoreactivity returned to basal levels 45 days postlesion. These findings show that in axotomized hypoglossal motoneurons, i) AMPA and NMDA receptor subunits are still expressed, ii) the composition of the ionotropic glutamate receptor subunit pool is subjected to continuous changes during the regeneration process, iii) AMPA receptors, if functional, would have physiological properties different to those in intact motoneurons, and iv) the various AMPA receptor subunits are differentially regulated. The present results also suggest a faster recovery of basal levels of immunoreactivity for caudally localised groups of motoneurons which could reflect a caudo-rostral sequential functional revovery in the hypoglossal nucleus.