Brevetoxin depresses synaptic transmission in guinea pig hippocampal slices

Extracellular recordings were obtained from area CA1 of guinea pig hippocampal slices. PbTx-3, a brevetoxin fraction isolated from the red tide dinoflagellate Ptychodiscus brevis. was applied by bath perfusion. The toxin produced a concentration-dependent depression of the orthodromically evoked population spike with an EC50 of 37.5 nM. Brevetoxin concentrations below 10 nM were without effect, and concentrations above 100 nM led to total inhibition of evoked responses. PbTx-3 did not produce spontaneous synchronous discharges but did induce afterdischarges following evoked responses in about 50% of the slices tested, particularly at concentrations between 10 nM and 100 nM. Orthodromically evoked responses were more sensitive to PbTx-3 than were those elicited by antidromic stimulation. High-Ca²⁺ solution, 4-aminopyridine, and tetraethylammonium failed to antagonize either orthodromic or antidromic effects of the toxin. Although the precise mechanism by which PbTx-3 depresses evoked responses is not certain, depolarization of the presynaptic nerve terminals leading to failure of transmitter release could explain the toxin's actions. This is the first report of the effects of brevetoxin applied directly to central nervous system tissue.     

Stratum corneum dynamic function measurements after moisturizer or irritant application

Two simple tests were conducted which allowed the quantification of parameters that characterize the stratum corneum (SC) dynamic functions in vivo under physiological conditions after moisturizer applications for 1 h and after irritation with different concentrations of sodium lauryl sulphate (SLS; 0.5–4%) applied under occlusion for 15 min or 24 h. Both tests, the sorption-desorption test (SDT) and the moisture accumulation test (MAT), were performed with a Nova Dermal Phase Meter 9003. The following parameters were quantified: prehydration state (SDT, MAT), hygroscopicity, water-holding capacity (SDT), water accumulation velocity and water accumulation (MAT). These procedures allowed the demonstration of the water-holding effect of urea contained in moisturizers. Differences between the long and the short application time of SLS were characterized by differences in SC dynamic functions while the hydration state was not changed. An effect on transepidermal water loss (TEWL) was noted only after the long application time, although the MAT clearly showed dynamic parameters to be changed after 15 min of treatment. These tests were simple in practice and allowed the demonstration of functional modifications of the SC while other parameters remained unchanged. They gave insight into possible action mechanisms of urea and SLS in the SC.     

A mechanism for incorporation of carbonate into apatite

Summary Octacalcium phosphate (Ca₈H₂(PO₄)₆·5H₂O) is considered to be a precursor in the formation of apatite in bones and teeth; a crucial step for incorporation of impurities appears to occur during its hydrolysis. The present study examines the role that octacalcium phosphate plays in the process of incorporation of carbonate into apatite. Chemical, X-ray diffraction, and infrared techniques were used. When octacalcium phosphate is hydrolyzed in the presence of sodium and carbonate ions in aqueous media, approximately one sodium and one carbonate ion seem to substitute for a calcium and phosphate ion, respectively, in forming apatite, and thea axis is shortened. The infrared spectrum of the product indicates that the carbonate is in the type B site, which is presumed to be a phosphate site. This mechanism is of particular importance since the presence of carbonate in human enamel appears to be related to caries susceptibility. A structural mechanism for the incorporation of impurities during hydrolysis of octacalcium phosphate is presented.     

Issues in exercise-induced asthma

It is concluded that challenge by exercise and ISH induces asthma by the same mechanism, the protective effect of water vapor is evidence that the events that lead to bronchial smooth muscle contraction begin in the airway lumen, it is the loss of water rather than the loss of heat from the airways that is the primary stimulus to EIA and HIA, the mechanism by which water loss induces asthma is by increasing the osmolarity of the epithelial fluid, in some subjects with asthma, cooling of the airways enhances the response to water loss, the increase in osmolarity stimulates the production and release of bronchoactive substances from mast cells and epithelial cells, vagal afferent pathways are activated by changes in osmolarity and by the released mediators, and vagal efferent activity may be modified by alpha-adrenoceptor antagonists and SCG.     

A microspectrophotometric analysis of the effect of fluoride on immature enamel matrix protein of rat molar teeth

Summary Over a 24-h period, Wistar rats from 4 litters, 6 to 9 days old, were given five intraperitoneal injections of a solution of 0.9% sodium chloride containing sodium fluoride (3 mg F/kg body weight). Within-litter controls were used. All rats were killed by decapitation 2 h after the final injection and the rat heads, cut sagittally, were processed for protein histochemistry. The intensity of staining of the protein in the enamel matrix of the upper jaw molar tooth buds was quantified using the two-wavelength method of microphotometry. A significant increase in the intensity of staining of fluoride-treated tissues over controls was observed with the histochemical methods specific for arginine (P<0.01), tyrosine (P < 0.05), and cysteine (P<0.05). Other histochemical methods specific for amino acid groups failed to show any significant difference between fluoride and non-fluoride-treated enamel matrix.     

Isolation and characterization of the third and fifth components of rabbit complement

Highly purified rabbit C3 and C5 have been obtained from normal rabbit plasma by differential precipitation and column chromatography. Apparent molecular weights of the two proteins as determined by SDS-polyacrylamide gel electrophoresis were 176,500 (C3) and 171,000 (C5), whereas reduction of the samples prior to electrophoresis allowed estimation of the molecular weights of the α and β subunit chains of each protein at 123,000 and 70,100 for C3 and 128,500 and 88,000 for C5. Serum concentrations as determined by rocket immunoelectrophoresis were 1.2 mg/ml for C3 and 0.2 mg/ml for C5, whereas hemolytic activities of C3 and C5 in normal rabbit serum were 2.4 × 10¹⁰ and 3.2 × 10¹⁰ effective molecules per ml, respectively. Amino acid analyses of the C3 and C5 preparations indicated similar but not identical amino acid compositions of the the two rabbit proteins, but there were no unusual amino acids or other features of the composition. Monospecific antisera to each of the two complement components were obtained in goats by immunization with the purified material.     

A 6-month dietary toxicity study of acidic sodium aluminium phosphate in beagle dogs

Sodium aluminium phosphate [NaAl3H14(PO4)8. 4H2O], a leavening acid, was administered to groups of six male and six female beagle dogs at dietary concentrations of 0, 0.3, 1.0 or 3.0% for 6 months. No adverse treatment-related clinical signs were observed. There were no statistically significant differences in mean body weights between test and control groups at any of the weekly determinations. Weekly mean food consumption values of all male treated groups did not differ significantly from those of the control group at any stage of the study. Statistically significant reductions in food consumption occurred sporadically in all treated groups of female dogs. No significant absolute or relative organ-weight differences were found between any of the treated groups and their respective controls. Haematological, blood chemistry and urinalysis data showed no toxicologically significant trends. Histopathological examination revealed no changes considered to be related to treatment. Thus dietary administration of sodium aluminum phosphate for 6 months at concentrations of 3% or lower caused no significant toxicological effects in beagle dogs.     

Electrolytic lesions and knife cuts in the region of the zona incerta impair sodium appetite

Bilateral lesions in the anterior zona incerta of male rats produced reliable impairments of need-related sodium appetite which were more severe than those seen after bilateral lesions in the thalamic gustatory nucleus. Horizontal knife cuts dorsal to the zona incerta, separating it from the ventral thalamus, seemed to reproduce the effects of thalamic lesions on sodium appetite. Horizontal knife cuts ventral to the zona incerta, separating it from the hypothalamus, produced a greater reduction in sodium intake than did the dorsal knife cuts. Neural pathways that might mediate regulatory sodium intake were discussed.     

Hypothalamic Na and Ca ions and temperature set-point: New mechanisms of action of a central or peripheral thermal challenge and intrahypothalamic 5-HT, NE, PGE1, and pyrogen

The effects of changes in ambient and central temperature, amines, PGE₁ and pyrogen were investigated with respect to the mechanism of Na⁺−Ca⁺⁺ ratio in the posterior hypothalamus of the unrestrained cat. Guide tubes were implanted bilaterally above the posterior hypothalamic area of 23 cats so as to accommodate push-pull cannulae. After a Na⁺ or Ca⁺⁺ sensitive site was identified by perfusion at 50 μ1/min of an artificial CSF containing 10.4 mM excess Ca⁺⁺ ions or 13.6 mM excess Na⁺ ions, several types of experiments were undertaken with the results summarized as follows: if the cat was exposed to a cold or warm environmental temperature as the posterior hypothalamus was perfused with excess cation, the typical hypothermia was produced by Ca⁺⁺ and hyperthermia by Na⁺ ions. However, if the cat was exposed to peripheral cooling or warming 30 min prior to the perfusion, the fall or rise produced by Ca⁺⁺ or Na⁺ was attenuated or prevented. In other experiments, 1.0 μCi ^{4 5}Ca⁺⁺ was injected in the ion sensitive site in the posterior hypothalamus to label stores of the cation. Raising of ambient temperature caused a retention of ^{4 5}Ca⁺⁺ in this hypothalamic area, whereas a cold environmental temperature enhanced the efflux of ^{4 5}Ca⁺⁺ at the same perfusion site. The magnitude of change in ^{4 5}Ca⁺⁺ efflux depended upon the intensity of the thermal challenge. Similarly, warming of the anterior hypothalamic, preoptic area by means of implanted thermodes caused an immediate diminution in ^{4 5}Ca⁺⁺ efflux in the posterior hypothalamus, whereas cooling of this anterior region augmented the extrusion of ^{4 5}Ca⁺⁺ ions from the posterior area. When substances which produce a temperature change were applied to the same thermosensitive zone, the direction of shift in ^{4 5}Ca⁺⁺ flux in the posterior area corresponded to the signal for heat production or heat loss. That is, the microinjection of 5-HT, PGE₁, or Salmonella typhosa into the anterior hypothalamus enhanced the efflux of ^{4 5}Ca⁺⁺ in the posterior hypothalamus as hyperthermia developed, whereas a similar microinjection of norepinephrine reduced the ^{4 5}Ca⁺⁺ output from the same sites. Finally, locally anesthetizing the cells of the anterior hypothalamus by the nerve blocker, procaine, prevented the cold and heat-induced ^{4 5}Ca⁺⁺ efflux and retention, respectively. These results suggest that if the Na⁴−Ca⁺⁺ ratio in the posterior hypothalamus establishes and maintains the set-point for body temperature of 37°–38°C, the mechanism of lability of Ca⁺⁺ through changes in binding characteristics, transport, or metabolism of the cation serves two purposes: (1) the active defense of the set-point temperature through gradations in ion shifts; and (2) the upward or downward change in set-point value, pathological or normal, triggered by virtue of impulses relayed from the anterior hypothalamus.     

Sodium cromoglycate in management of vernal and chronic allergic conjunctivitis

This study was planned to find out whether there is any beneficial effect in adding the SCG drops in the treatment of patients with vernal or chronic allergic conjunctivitis. Fifty-eight patients, 12 with vernal and 46 with chronic allergic conjunctivitis, who had used basal solutions, local steroids and peroral antihistamines to manage their symptoms were given SCG drops four times daily in addition to the previous treatment. Fifty-three patients became symptomfree and stayed so when local steroids were tapered off. All but three of these 53 patients have been able to discontinue SCG drops after varying treatment periods, but some 10 to 15 patients probably will need medication during the next pollen season.SCG is not the first choice of local treatment in chronic allergic reactions, because many patients' symptoms can be managed with basal solutions and occasional local steroids if the patients are taught the importance of avoidance of allergens and irritating agents. SCG is indicated whenever the allergic symptoms bother the patient continuously and either the causative factor cannot be identified or it cannot be avoided.In vernal conjunctivitis the effect of SCG drops was so marked in every patient that SCG can be recommended as the basic medication of vernal conjunctivitis.Among ophthalmologists both vernal and chronic allergic conjunctivitis are usually considered to be local problems and the general management of allergic reactions gets too little attention. For permanent results the patient has to learn how to manage both the prevention and the treatment of symptoms and in both these aspects SCG was found helpful.