Evidence for a novel P2X purinoceptor in human placental chorionic surface arteries.

To characterize the P2x purinoceptor of arteries of human term placenta, a non-innervated organ, actions of ATP, alpha, beta-methylene-ATP and UTP on de-endothelialized chorionic surface artery segments were compared. ATP and alpha,beta-methylene-ATP caused reversible concentration-dependent contractions, but UTP elicited little or no contraction up to 517 microM. Concentration-effect curves to ATP and alpha,beta-methylene-ATP were parallel, and alpha,beta-methylene-ATP, EC50 4.2 +/- 1.2 microM, was 28-times as potent as ATP. At a saturating concentration, 103 microM, alpha,beta-methylene-ATP did not desensitize the ATP receptor. Contractions to ATP and alpha,beta-methylene-ATP were antagonized by 300 microM suramin. These findings indicate that P2X purinoceptors are present in placental chorionic surface arteries and that they differ from P2X purinoceptors in arteries of other tissues.

Slit-ventricle syndrome in shunt operated children.

Chronic intracranial hypotension is considered as a frequent complication in shunted hydrocephalus, besides obstruction and shunt-infections. In the last twenty years 32 cases of slit-ventricle were diagnosed among the more than one thousand operations on hydrocephalic children at the Paediatric Department of the National Institute of Neurosurgery, Budapest, Hungary. Most of them have been operated on in infancy. Time from the first operation to the development of slit-ventricle ranged from one to twelve years, the mean was 6.5 years. Seven patients were symptomless (22%), while 25 patients (78%) had more or less severe slit-ventricle syndrome with headache (25 cases), nausea/vomiting (23 cases), altered consciousness (21 cases), brainstem signs (12 cases), and epileptic fits (2 cases). Ten patients with moderate clinical signs improved under conservative treatment. In 15 cases an anti-siphon device (ASD) was implanted. In five of them the clinical result was good, but in the remaining 10 cases typical hypertensive signs were seen. In these cases low flow rate valves were implanted instead of the middle flow rate valve and ASD. In one case the intracranial hypertension persisted, so a middle flow rate shunt system was "reimplanted" and finally the patient improved. In this study the experiences with these 32 cases will be analysed and discussed. The authors stress the primary use of combined valves to avoid the slit-ventricle syndrome.

Pathological and experimental investigations in a case of gigantism.

A pituitary adenoma was transsphenoidally removed from a 4.5-year-old girl suffering from gigantism. Prior to the operation both the growth hormone (GH) and the prolactin (PRL) levels in the serum were elevated. By light microscopy the tumor appeared to be an acidophilic adenoma. Two distinct cell types, the densely granulated and the sparsely granulated cells, could be distinguished by electron microscopy. Double immunolabeling revealed the presence of GH alone in some densely granulated cells and PRL alone in some sparsely granulated cells, as well as GH and PRL co-localized in both of the morphologically distinguished cell types. Both cell types were identified in the monolayer and the suspension cultures by electron microscopy. GH and PRL concentrations in the culture media were measured by radioimmunoassay. The basal secretion of growth hormone was almost uniform during the 3-week cell culture period. GH and PRL release was significantly inhibited by bromocriptine. Our studies revealed a bimorphous and bihormonal mixed adenoma in childhood.

Bombesin-induced pancreatic secretion and growth in rats: effect of proglumide, spantide and ranitidine.

The effect of proglumide (400 mg/kg), spantide (400 g/kg) and ranitidine (20 mg/kg) on pancreatic secretory and trophic response to bombesin (10 micrograms/kg) was studied in the rat. Drugs were administered alone or combined with bombesin three times daily for 5 days. Saline-treated rats were used as controls. At the end of treatment, animals were anaesthetized and pancreatic juice was collected for 1 h after caerulein stimulation (1 microgram/kg intraperitoneally). Afterwards, rats were sacrificed and the weight and composition of pancreatic tissue were determined. As compared with control (saline) values, the volume of pancreatic juice and the output of trypsin and amylase were increased by treatment with bombesin. Neither proglumide nor spantide affected basal and caerulein-stimulated pancreatic exocrine secretion. Ranitidine, although unable to modify protein and enzyme content of pancreatic secretion, significantly reduced the volume of pancreatic juice in both basal conditions and after caerulein stimulation. Bombesin increased pancreatic weight as well as the protein and enzymatic contents of the gland. Neither the weight of the pancreas nor its composition were significantly affected by CCK-antagonist proglumide, the putative bombesin antagonist spantide or the H2-receptor antagonist ranitidine. These results show that bombesin has a trophic effect on rat pancreas and concomitantly increases its secretory capacity. Both effects are likely to be mediated through a direct action of the peptide on the pancreatic gland.

Time-specific development of pancreatic hypersecretory capacity during chronic caerulein treatment in rats.

It is well established that repeated injections of the cholecystokinin (CCK) analogue caerulein induce pancreatic hypersecretion and growth, but so far the time-specific development of hypersecretory capacity has not been studied. Rats were given intraperitoneal injections of caerulein (1 microgram/kg) three times daily for 0-7 days. On the day after the last injection a secretory test was performed with the rats under urethane anaesthesia. Subsequently, pancreatic tissue composition was analysed. Basal and caerulein-stimulated secretion rates of fluid and trypsin were elevated after as little as 1 day of caerulein treatment. These values remained significantly greater than those of the controls after 2-7 days' administration of the peptide. Pancreatic tissue hypertrophy (increases in absolute pancreatic weight, protein and trypsin contents, and also in these values normalized to DNA) appeared after 2 days' pretreatment. Tissue growth turned to hyperplasia (increase in tissue DNA content) after 5 days' caerulein administration. We conclude that chronic administration of the CCK analogue caerulein induces adaptation of the pancreas in a sequential order. First, the hypersecretory state appears, followed by hypertrophy, and, finally, pancreatic growth turns into hyperplasia.

Effect of a new potent CCK antagonist, lorglumide, on caerulein- and bombesin-induced pancreatic secretion and growth in the rat.

1. The effect of lorglumide, a new potent cholecystokinin (CCK) antagonist, on pancreatic secretion and growth induced by caerulein and bombesin was studied in the rat. 2. Pancreatic exocrine secretion was studied both in vitro (isolated and perfused pancreatic segments) and in vivo (anaesthetized animals with cannulation of the common bile duct) whereas the trophic effect was investigated after short-term (5 days) administration of the peptides and/or lorglumide. 3. Both caerulein and bombesin stimulated amylase release from in vitro pancreatic segments in a concentration-dependent manner. Although the efficacy of both peptides was virtually identical, the potency of caerulein was higher than that of bombesin. Lorglumide displaced the concentration-response curves to caerulein to the right without affecting the maximum response, suggesting a competitive antagonism. The Schild plot analysis of data gave a straight line with a slope not significantly different from unity. The calculated pA2 for lorglumide was 7.31 +/- 0.45. The antagonist, however, was completely ineffective when tested against bombesin-induced amylase release. 4. In vivo experiments confirmed results from in vitro studies since lorglumide (5 and 10 mg kg-1) significantly reduced pancreatic exocrine secretion induced by caerulein without affecting the response to bombesin. 5. Administration of either peptide increased the weight of the pancreas, the total pancreatic protein and DNA, trypsin and amylase content. Lorglumide (10 mg kg-1), administered together with caerulein, reduced the peptide-induced increase in pancreatic weight, protein and enzyme content. On the contrary, when lorglumide was given together with bombesin, all the parameters that were examined were not altered by concomitant administration of the antagonist. 6. These results have demonstrated the ability of lorglumide to antagonize the effects on the pancreas of a CCK-analogue, caerulein, and its inability to affect bombesin-induced pancreatic secretion and growth, suggesting that lorglumide is a potent and selective antagonist of CCK-receptors in the pancreas.

Caerulein stimulates pancreatic secretory response in conscious newborn rats.

UNLABELLED: The aim of our study was to measure age-dependent, caerulein-stimulated pancreatic enzyme secretion of conscious CFY suckling rats without pancreatic duct cannulation. Pancreatic secretory response was expressed as the decrease in specific enzyme (trypsin, amylase) activity compared to saline-injected control. The study was performed in three phases. In 10-d-old conscious newborn rats, single 1 and 3 micrograms/kg sc doses of caerulein induced significant decreases in specific trypsin (42 and 47%) and amylase (34 and 33%) activity 15 min after the caerulein injection; the same doses injected at 0 and 30 min evoked a similar decrease 90 min after the first injection. The 0.5 microgram/kg dose was ineffective. In 10-d-old anesthetized rats, the 90-min-decrease in total pancreatic trypsin activity, induced by graded doses (1,3,10, and 30 micrograms/kg) of caerulein, was compared to the 90-min output of trypsin in their bile-pancreatic juice. Each of the applied doses induced significant change in the total trypsin activity both in the pancreas (-33-57%) and juice (+21 +/- 49%) and its decrease in the gland corresponded quantitatively well (r = 0.52; p less than 0.01) to the increase in the simultaneous 90-min trypsin output. The age- and dose-dependent pancreatic response of 3-, 5-, 10-, and 20-d-old conscious rats was investigated under the effect of 1,3,10, and 30 micrograms/kg sc doses of caerulein injected at 0 and 30 min. In 3-d-old rats, the 10 and 30 micrograms/kg and in 20-d-old rats, the 1 and 3 micrograms/kg doses were effective, whereas in 5- and 10-d-old rats each caerulein dose applied evoked a significant decrease in pancreatic-specific trypsin activity. CONCLUSION: The pancreas of newborn rats is in vivo less sensitive to caerulein between postnatal d 3 and 10 than in already weaned rats.

Effect of treatment with submaximal and excessive doses of caerulein on pancreatic growth in newborn rats.

Different groups of CFY female newborn rats were treated with saline, or 1 microgram/kg or 100 micrograms/kg doses of caerulein given s. c. 3 x/day. Application of 100 micrograms/kg dose of caerulein for 3 days stimulated pancreatic growth inducing pancreatic hyperplasia; both (1 and 100 micrograms/kg) doses evoked increase in trypsin/DNA ratio inducing pancreatic hypertrophy in 4-days-old rats. Using the indices as before application of 1 microgram/kg caerulein for 10 days stimulated pancreatic growth and both (1 and 100 micrograms/kg) doses elicited glandular hypertrophy in 11-days-old rats. In 24-old-rats the 1 microgram/kg doses of caerulein given for 3 days stimulated pancreatic growth and induced pancreatic hypertrophy, the 100 micrograms/kg doses of the peptide given for 3 days, however, evoked pancreatic aplasia and atrophy.

Caerulein-induced desensitization of enzyme secretion fails in neonatal rat pancreas.

Pancreatic segments of 1-, 3-, 5-, 10-day-old and adult female OFA (Sprague-Dowley strain) rats were superfused with graded concentrations of caerulein (10(-12)-10(-7) M) to establish concentration-response relation of amylase release. Furthermore, pancreatic segments of 3-, 5-, 10-day-old and adult rats were superfused with 10(-10) or 10(-8) M caerulein and then superfusion was repeated with 10(-10) M concentration of caerulein to show whether the phenomenon of desensitization of amylase release can be induced in the postnatal period. The 1-day-old pancreas was found practically insensitive to caerulein. The 3- and 5-day-old gland was by one order of magnitude less sensitive (EDmax = 10(-8) M) than the adult pancreas (EDmax = 10(-9) M). Repeated superfusion of the 3- and 5-day-old pancreas with 10(-10) M caerulein after the first 10(-8) M caerulein superfusion failed to cause desensitization, while the same (10(-10) M) repeated superfusion of the 10-day-old adult pancreatic segments after the first 10(-8) M caerulein superfusion evoked desensitization of enzyme release. The authors suggest that the failure of desensitization of enzyme secretion for caerulein may be due to the maturation process of newborn rat pancreatic acinar cells at receptorial and postreceptorial level.

Effect of bombesin and its mammalian counterpart, GRP, on exocrine pancreas in the rat.

The effect of equimolar doses (6 nmol/kg) of bombesin and its mammalian counterpart, GRP, on pancreatic growth and secretion was studied in adult rats. Both peptides were administered intraperitoneally three times a day for 5 consecutive days. Saline-treated rats were used as controls. At the end of the treatment, animals were anaesthetized and pancreatic juice was collected in basal conditions and after caerulein (0.75 nmol/kg i.p.) stimulation. Afterwards, the rats were sacrificed and growth and composition of the pancreatic tissue were determined. Compared with the control (saline) values, either basal or stimulated secretion was significantly increased after short-term treatment with both peptides. In addition, both bombesin and GRP increased pancreatic weight, total pancreatic protein, trypsin and amylase content. The DNA content was also increased by both peptides, although only the GRP effect proved to be significant. These results demonstrate that both bombesin and GRP have a growth-promoting effect on rat pancreas and concomitantly increase its secretory capacity. The mechanism of this peculiar biological action is likely to be connected with a direct stimulatory action on the gland.

Excessive doses of cerulein stimulate pancreatic growth in suckling rats but damage the pancreas of weaned rats.

The cerulein-stimulated pancreatic growth response was evaluated in 4- and 11-day-old female suckling CFY rats and compared with the pancreatic response of cerulein-treated 24-day-old weaned rats. Cerulein was given subcutaneously in saline in 1-, 10- and 100-micrograms/kg doses t.i.d. The increase in pancreatic DNA content was regarded as an index for hyperplasia, and the increase in pancreatic weight, protein content and enzyme activity related to milligrams of DNA as an index for hypertrophy. Three-day administration of 1- and 10-micrograms/kg doses of cerulein increased the pancreatic trypsin/DNA ratio, and doses of 100 micrograms/kg cerulein evoked pancreatic hypertrophy and hyperplasia in 4-day-old rats. Ten-day administration of 1- and 10-micrograms/kg doses induced pancreatic hypertrophy and hyperplasia, while the 100-micrograms/kg doses induced pancreatic hypertrophy in 11-day-old rats. In 24-day-old weaned rats, the 3-day administration of 1-microgram/kg doses resulted in hypertrophy of the gland, while the 100-micrograms/kg doses of cerulein evoked pancreatic aplasia and atrophy. It is concluded that the growth-promoting effect of cerulein on the newborn rat pancreas is age- and dose-dependent.

Caerulein stimulates pancreatic growth and somatic growth in suckling rats.

This study deals with the stimulatory effect of caerulein on pancreatic and somatic growth in CFY suckling rats before weaning. After birth, caerulein (0.25, 0.5, 1, 3, 10 and 30 micrograms/kg) was given subcutaneously (s.c.) 3 times daily for 10 days. Saline-treated newborn rats were used as control. Caerulein increased pancreatic weight and total pancreatic trypsin activity reaching the maximum at 1 microgram/kg dose; higher doses did not cause higher values. On this basis 1 microgram/kg caerulein was applied s.c. 3 times daily for 3, 5, 10 and 20 days. At the end of the treatment pancreatic weight, total pancreatic protein, DNA content, trypsin and amylase activity was measured. Increases in body weight due to caerulein treatment were found from 6 days of treatment. Caerulein treatment increased pancreatic weight, total pancreatic DNA and protein content, and trypsin and amylase activity when applied for 5, 10 and 20 days. Treatment for 3, 5, 10 and 20 days with caerulein preferentially increased pancreatic trypsin activity compared to amylase activity. Trypsin activity per mg DNA increased with time in each caerulein-treated group demonstrating that the effect of caerulein increases with duration of treatment. In the saline-treated control group, however, pronounced increase in pancreatic amylase activity compared to that of trypsin activity was found in the age between days 11 and 21. This may be explained by the observation that the plasma corticosterone level increased during this period of postnatal life. The effect of caerulein in promoting pancreatic and somatic growth of suckling rats before weaning may be attributed to a specific enhancing effect of the peptide on proteolytic (e.g. trypsin) enzyme production of the pancreas.

Bombesin promotes pancreatic growth in suckling rats.

UNLABELLED: The pancreatic growth promoting effect of long term administration of bombesin was investigated in suckling rats. The authors showed that bombesin given in 10 micrograms/kg b.wt doses s.c. every 8 h for 10 days from the day of parturition stimulated pancreatic growth: it increased pancreatic weight, protein and DNA content, trypsin and amylase activity and trypsin/DNA ratio. CONCLUSION: Bombesin is an effective stimulator of pancreatic growth in suckling rats.

Immuno-, neuro-, and general toxicologic animal studies on a synthetic pyrethroid: cypermethrin.

The toxicologic properties of the synthetic pyrethroid insecticide cypermethrin have been studied in animal experiments. In the course of acute and subchronic experiments performed by the administration of 1/2 and 1/40, 1/20, and 1/10 proportions of the oral LD50 value, no considerable changes were found in the general toxicologic tests. The compound known to affect the central nervous system, however, induced only a mild enhancement of the central excitation level shown by the EEG investigations in the doses applied. In the immunotoxicologic studies an early and dose-dependent suppression was induced as a result of humoral immune response of rabbits immunised by S. typhi following the administration of cypermethrin. The cell-mediated immune response was also decreased. In rats the immune response determined by anti-sheep erythrocyte and antiovalbumin titer as well as by autologous rosette formation of spleen lymphocytes was hindered. The earliest detectable group of symptoms indicating the effect of a mild cypermethrin exposure is the appearance of the positivity of the immunotoxicologic tests. On the basis of the experimental findings the sensitive immunotoxicologic tests have been regarded as of great importance in the series of toxicologic methods.

A rare case of infantile meningioma.

This paper reports the use of ultrasound and computed tomography in combination to diagnose a case of meningioma in a 3-month-old infant, and also describes the treatment.

Binding of lincomycin to immunoglobulins has no effect on their antigen-binding capacity.

The interaction of lincomycin and immunoglobulins was examined in vitro. While lincomycin bound to the immunoglobulin molecules seemed to decrease the quantity of IgG and IgM detected by radial immunodiffusion and microzone electrophoresis, the level of specific antibodies could not be demonstrated by enzyme-linked immunosorbent assay (ELISA).