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Biomedical subjects

T Ertl

Publications and source records attributed to T Ertl.

At least 19 recordsLinked to original sources

Pulp histology after Er:YAG laser cavity preparation in subhuman primates--a pilot study.

UNLABELLED: The aim of the study was to make a direct comparison of the pulpal effects of laser and turbine preparations in subhuman primates. One female baboon (Papio Ursinus ursinus), weighing 15 kg, was used. General anaesthesia was administered (ketamine 100 mg/ml/kg body weight) and maintained with acepromazine (10 mg/ml/kg body weight). Class V cavities were prepared buccally in a total of 28 teeth (7 in each quadrant). Teeth in the upper right and lower left quadrants were prepared using a conventional 330 carbide bur in a high-speed fibre-optic handpiece with copious water spray. Teeth in the upper left and lower right quadrants were prepared using an Er:YAG laser drill (Fotona Twinlight, Llubljana, Slovenia) delivering 500 mJ at a pulse rate of 10 Hz and a wavelength of 2940 nm. The animal was sacrificed after 25 days. After general anaesthesia as described before, perfusion fixation of the head was accomplished with 10% neutral buffered formalin, pumped through a catheter inserted into the left carotid artery. The jaws were removed and, using a 330 carbide bur in a high speed handpiece, a continuous groove was cut through the bone and the roots at the level of the middle third of all the roots to promote thorough fixation of pulpal tissue. Decalcification and grading of the severity of the pulpal responses were conducted according to standard procedures. RESULTS: Owing to procedural errors seven teeth, FDI numbers 23, 24, 31, 34, 35, 44 and 45, had to be eliminated. The turbine-prepared teeth (N = 11) had a mean remaining dentine thickness (RDT) of 0.77 mm (SD = 0.42) and the laser-prepared teeth (N = 10) had a mean RDT of 0.81 mm (SD = 0.60). All pulps appeared normal except in one turbine-prepared tooth (12 with RDT = 0.20) and one laser-prepared tooth (27 with RDT = 0.30, where irreversible damage was caused. The only other deviations from normal were seen in the laser-treated 41 (RDT = 0.69) and the turbine-treated 36 (RDT = 0.77) where moderate hyperaemia was seen. Within the limitations of this study it can be concluded that there is no significant difference between dental pulp of teeth where Class V cavities were prepared with an Er:YAG laser drill compared with those prepared with a standard turbine drill.

Animals↗

Influence of a partner's HIV serostatus, use of highly active antiretroviral therapy, and viral load on perceptions of sexual risk behavior in a community sample of men who have sex with men.

OBJECTIVE: To assess the perceptions of gay and bisexual men concerning the risk of HIV transmission through various sexual practices with a new sex partner depending on that partner's disclosed HIV status, antiretroviral treatment status, and viral load. METHODS: Study participants read four different scenarios describing sexual situations with a new partner and rated each scenario for risk of HIV transmission. HIV status and antiretroviral treatment status disclosed by the new sex partner were varied across four scenarios: unknown HIV status; HIV-negative; HIV-positive and not taking highly active antiretroviral therapy (HAART); and HIV-positive and taking HAART with an undetectable viral load. RESULTS: Study participants were 472 men attending a gay pride festival who reported that they were HIV-negative. Eighty-nine percent of the men were white, and the mean age of the study participants was 35.8 years. Of the four scenarios, sex with an HIV-positive partner not taking HAART was rated as posing the greatest risk. Sex with an HIV-positive partner taking HAART who had an undetectable viral load was not consistently viewed as riskier than sex with an HIV-negative partner or a man with an unknown HIV status. CONCLUSIONS: The current study provides preliminary evidence for the effect of disclosure of HIV serostatus, use of HAART, and the presence of an undetectable viral load on the perceptions of sexual risk for HIV-negative men. The findings suggest that some gay and bisexual men judge risk based on the perceived HIV status of their sex partners and not on the general assumption that all sex partners entail equal risk, as many prevention campaigns have emphasized.

Adult↗

Sources and behaviour of bismuth active substances (BiAS) in a municipal sewage treatment plant.

Non-ionic surfactants are widely used for household and industrial purposes. For different reasons the metabolites, e.g. 4-nonylphenol, nonylphenol monoethoxylate, nonylphenol diethoxylate and 4-tert-octylphenol, are especially considered to be endocrine disruptive and thus potentially harmful for the environment. In this study, field samples of raw wastewater from different point sources, including industrial effluents, household effluents, the influent and secondary effluent of a wastewater treatment plant that treats this wastewater were monitored simultaneously. Composite samples were taken five times over periods of 1 week at nine sample sites. The results showed that the concentrations and fluxes were varying. In addition industrial, influent and effluent samples were investigated for nonylphenol (NP). The highest concentrations of bismuth active substances (BiAS) were obtained by wastewater samples from a chemical and a cloth washing company ranging from 10,200 to 65,600 microg/l and 14,600 to 33,900 microg/l BiAS, respectively. Although the concentration of BiAS in the wastewater of the paper production was only between 460 and 1200 microg/l BiAS, the NP/BiAS ratio of 0.51% was considerably higher than in other industrial effluents. The BiAS concentration in wastewater samples from households ranged from 2200 to 7900 microg/l BiAS, but the NP concentration was quite low, 0.01% of BiAS. This could be due to the effort within the EU to phase out nonylphenol polyethoxylates in household detergents. Influent concentrations between 700 and 2200 microg/l BiAS with removal rates in the WWTP ranging from 70.7 to 99.4% with an average of 92.2% could be measured.

Bismuth↗

Hyponatremia and sensorineural hearing loss in preterm infants.

In a case-control study the role of hyponatremia in the hearing loss of preterm infants was investigated. One hundred and sixty-four premature infants treated at the neonatal intensive care unit were screened with transient evoked otoacoustic emission (TEAOE). In 32 infants TEAOE results indicated the need for further investigations. Auditory brainstem response was performed and 22 of 32 cases had bilateral hearing impairment (HI). The birth weight and gestational age in the HI group were 1,425 +/- 528 g and 30.4 +/- 3.7 weeks. The matched control group consisted of 25 infants with a mean birth weight and gestational age of 1,410 +/- 280 g and 31.1 +/- 2.1 weeks. Significant differences were found between the HI and control groups: Apgar score (p < 0.05), pH value (p < 0.01) and pO(2) level (p < 0.05) were lower; the total dose of aminoglycosides (p < 0.01), furosemide usage (p < 0.01), the maximum pCO(2) level (p < 0.01), incubator stay (p < 0.05) and hyponatremia (p < 0.01) were higher, and the duration of hyponatremia (p < 0.05) was longer in the HI group. Multivariate logistic regression revealed that aminoglycoside treatment and hyponatremia were the two most significant factors in the development of hearing impairment. These results suggest that hyponatraemia is an additional risk factor for hearing loss in preterm infants.

Aminoglycosides↗

Transfer of research-based HIV prevention interventions to community service providers: fidelity and adaptation.

HIV prevention research interventions usually follow protocols with specific procedures. If a community-delivered intervention uses the same procedures with the same populations as those in the original research, the behavior change effects should be similar. However, community-based providers may not replicate an intervention exactly as it was conducted in the effectiveness study. Adaptation may be needed to better meet the needs of the clients, community, or organization. We propose that interventions can be defined in terms of core elements likely to be responsible for effectiveness. These core elements cannot be changed without fundamentally changing the intervention, whereas other characteristics may be modified without altering effectiveness. HIV prevention researchers and service providers can collaborate to develop interventions that not only are effective but can also be successfully implemented by service organizations. If researchers actively involve service providers and community members in intervention planning, technology transfer goals can be better achieved.

Community Health Services↗

[Neonatal care of premature infants].

Perinatal intensive centers deal with preterm infants of the region. Therefore, the rate of preterm deliveries at the Department of Obstetrics and Gynecology, Medical University of Pécs was high in 1997, about the double of the national rate (18.7%). Among prematures the rate of very low birth weight (VLBW) infants (less than 1500 g) was about 40%, moreover, the rate of extremely low birth weight infants (less than 1000 g) was 39% within the latter group. Related to the new regulation concerning preterm delivery the number of immature infants (weighing less than 750 g) with poor outcome increased. The most characteristic disease of preterm infants is the idiopathic respiratory distress syndrome (IRDS). This could be prevented by maternal steroid treatment, a therapy accepted worldwide, however, not so common in Hungary. Direct fetal steroid therapy may be applied also in selected cases. In the treatment of IRDS surfactant products made a breakthrough. Several factors (maternal tocolytic and fluid therapy, Cesarean section) influence the cardiopulmonary adaptation which may be monitored with impedance cardiography. Late hyponatremia and metabolic acidosis may develop in 1/3 of VLBW infants. Besides the fluid therapy the introduction of enteral feeding must be planned carefully and examination of gastric emptying with ultrasound is useful. The development of osteopenia may be prevented by passive exercise of the preterm infant. Anemia is common and human recombinant erythropoietin is available for treatment. Screening of vision, hearing, and neurodevelopmental follow up are integral parts of neonatal care. As a result of the above mentioned preventive and therapeutic interventions neonatal mortality has decreased significantly in Hungary in the past decades.

Female↗

Calcium dobesilate lowers the blood pressure in mild to moderate midtrimester hypertension: a pilot study.

To test the effects of calcium dobesilate (Doxium) in pregnancies complicated with pregnancy-induced hypertension or mild/moderate pre-eclampsia a double-blind, placebo-controlled pilot study was carried out. Primigravida patients (gestational age </=34 weeks) daily took 2 g Doxium or placebo until delivery. Twelve patients received placebo for 53 days, and 11 patients took the drug for 57 days on average. At the start of the study 2 patients in the placebo group (PG) and 8 in the Doxium group (DG) had pre-eclampsia. The mean arterial pressure (mean +/- SD) significantly decreased from 118 +/- 7 to 99 +/- 9 mm Hg in the DG (p = 0.003), while in the PG it had slightly increased by the end of the study. Proteinuria was higher in the DG at the start but not at the end; however, significant changes of this parameter were detected in neither of the groups throughout the study. Fibronectin decreased significantly in both groups but it was more pronounced in the DG (23.8 vs. 9.4%). Changes of platelet count, plasma and blood viscosity, and erythrocyte deformability were favourable in the DG but in the PG these parameters had deteriorated although the alterations were not significant. No marked differences were found between the two groups regarding fetal well-being, courses of deliveries, and the neonatal period. Neither maternal nor fetal/neonatal side effects were noticed. It seems that Doxium favourably influences the blood pressure and consequently decreases the requirement for medication and hospitalisation in cases of mild to moderate midtrimester hypertension.

Blood Viscosity↗

Postnatal changes of leptin levels in full-term and preterm neonates: their relation to intrauterine growth, gender and testosterone.

The present study was carried out to investigate leptin levels in arterial and venous cord serum and in amniotic fluid in full-term infants at birth and on the 5th postnatal day to define the relationship of leptin to intrauterine growth rate, gender and early postnatal life. The relation of weight gain to serum leptin levels in male preterm infants was determined measuring leptin concentration weekly in the first 5 postnatal weeks. Testosterone levels were determined simultaneously to explore a possible relationship between leptin and testosterone concentrations. Fifty-three term newborn infants with mean birth weight and gestational age of 3,419 g (range 2,150-4,480) and 38.9 weeks (range 36-41) and 19 preterm male infants (mean birth weight and gestational age were 1,416 g (770-1,800) and 30.2 weeks (26-35) were enrolled into the study. Leptin and testosterone levels were determined by radioimmunoassay. It was demonstrated that serum leptin levels were markedly elevated in the cord blood without discernible arteriovenous differences. Cord blood leptin was found to correlate with birth weight (r = 0.40, p < 0.002), weight to length ratio (r = 0.40, p < 0.002) and body mass index (r = 0.35, p < 0.005). It was significantly lower in boys as opposed to girls (p < 0.01) and there was an apparent fall by the 5th postnatal day (p < 0.001). Amniotic fluid contained leptin in much less concentration than cord blood and it proved to be independent of intrauterine growth or gender. Serum leptin concentration in preterm infants at 1 week of age was significantly lower compared with term infants (p < 0.002) and it increased progressively with age (p < 0.01). An inverse relationship was found between leptin and testosterone level (r = -0.358, p < 0.01) and a positive correlation between leptin level and weight/height ratio (r = 0.674, p < 0.01). It is concluded that leptin derived either from placenta or fetal adipose tissue may be involved in regulating fetal growth and development and it may be related to energy intake, storage and expenditure. In preterm male infants serum leptin concentration increases with postnatal weight and testosterone may suppress leptin synthesis.

Adipose Tissue↗

[Effect of the pulsed Er:YSGG and Ho:YAG laser on the organ of Corti of the guinea pig cochlear--a scanning electron microscopy study].

BACKGROUND: Recent experimental studies have demonstrated that, apart from the continuous wave lasers, several pulsed laser systems are also suitable for stapedotomy. The aim of this study was to clarify whether irradiation of the basal convolution of the guinea pig cochlea could cause morphological inner-ear changes using the Er:YSGG and Ho:YAG laser with laser parameters required for stapedotomy. METHODS: After opening the bulla, the basal convolution of the guinea pig cochlea, whose thickness is similar to that of the human stapes footplate, was irradiated with the Er:YSGG and Ho:YAG laser. The laser parameters used were those necessary for an adequate perforation of a human stapes footplate (500-600 microns). The cochleae were removed 90 minutes, 1 day, 2 weeks, or 4 weeks after laser application. The organ of Corti was examined by scanning electron microscopy in all convolutions. RESULTS: Application of Er:YSGG laser parameters effective for stapedotomy (5 pulses, energy: 85 J/pulse, energy density: 36 J/cm2, total energy: 0.425 J) had no adverse effects on the organ of Corti in the guinea pig cochlea. On the other hand, effective Ho:YAG laser parameters (10 pulses, energy: 210 J/pulse, energy density: 90 J/cm2, total energy: 2.1 J) caused damage to the outer hair cells with fusion of stereocilia and formation of giant cilia leading to partial or total cell loss. The inner hair cells and supporting cells were usually normal. CONCLUSION: Our results clearly demonstrate that the Er:YSGG laser has high application safety. It could prove to be a viable alternative to the thermically acting CO2 laser for stapedotomy. The Ho:YAG laser is not well tolerated in animals and has low application safety. Its use in stapedotomy would be unreliable and dangerous for the inner ear.

Animals↗

Changes of maternal serum leptin levels during pregnancy.

Maternal leptin levels in serum and urine, their relations to maternal weight and body mass index, were examined in 9 healthy pregnant women from the 12th week of gestation until term. Serum leptin concentration was found to increase progressively during the first two trimesters followed by a slight decline thereafter. The peak value of 27.6 +/- 15.3 ng/ml (mean +/- SD) concentration was reached at the 28th week. Serum leptin levels during the first two trimesters correlated significantly with maternal weight (p = 0.002) and body mass index (p = 0.002) but such a relationship was absent during the third trimester. Leptin could be detected only in about half of urine samples; its concentrations proved to be independent of serum values. No correlation was found between maternal serum leptin levels and the birth weight of neonates. Maternal leptin levels appear to refer to alterations in maternal fat tissue mass that occur during pregnancy.

Body Mass Index↗

Antagonists of bombesin/gastrin-releasing peptide inhibit growth of SW-1990 human pancreatic adenocarcinoma and production of cyclic AMP.

We investigated the effects of bombesin/GRP antagonists RC-3095 and RC-3940-II on the growth of SW-1990 human pancreatic adenocarcinoma cells xenografted into nude mice or cultured in vitro. Nude mice implanted with SW-1990 tumors received s.c. injections of RC-3095 and RC-3940-II or the vehicle (control) for 28 days. Chronic administration of RC-3940-II inhibited the growth of SW-1990 tumors, as shown by a reduction in tumor volume during the treatment and a significant increase in tumor doubling time. RC-3940-II decreased final tumor volume by 57.7% and tumor growth rate by 65%. Final tumor weights in mice treated with RC-3940-II were 75% lower than in controls. Treatment with RC-3095 induced smaller, and not significant, decreases in tumor volume and weight. In cell cultures, both RC-3095 and RC-3940-II effectively inhibited the proliferation of SW-1990 cells, inducing a dose- and time-dependent decrease in the number of cells. RC-3940-II again suppressed in vitro growth of SW-1990 cells more effectively than RC-3095. After 72 hr of culture, RC-3940-II and RC-3095 at 1 microM concentrations decreased cell numbers by 45.7% and 27.7%, respectively. The estimated EC50 value for RC-3940-II was 1 nM. When SW-1990 cells were cultured in the presence of 1 nM and 10 nM RC-3095 for 72 hr, cAMP levels in the incubation medium were decreased to 77.3% and 26.9% of the control value. Our results indicate that bombesin/GRP antagonist RC-3940-II can inhibit the proliferation of SW-1990 human pancreatic adenocarcinoma cells in vivo and in vitro. Our findings also suggest that this effect may involve the intracellular cAMP pathway.

Adenocarcinoma↗

Somatostatin analog RC-160 inhibits growth of CFPAC-1 human pancreatic cancer cells in vitro and intracellular production of cyclic adenosine monophosphate.

The effect of somatostatin analog RC-160 on the growth of CFPAC-1 human pancreatic cancer cells in vitro was investigated. RC-160 effectively inhibited the proliferation of CFPAC-1 cells in culture, inducing a time- and dose-dependent decrease in the number of treated cells. A significant suppression of cell growth was observed after 48 and 72 hr of the exposure to (1 microM) RC-160, the cell number being decreased by 38% and 46%, respectively. RC-160 was more potent than SS-14 or SMS201-995 in inhibiting the growth of CFPAC-1 cells, and after 48-hr treatment the cell number decreased by 49% for RC-160 compared with 12% for SS-14 and 27% for SMS201-995. Binding experiments demonstrated that specific receptors for somatostatin were present on CFPAC-1 cells. SS-14 showed a high binding affinity for [125I]-Tyr11-SS-14 receptors on CFPAC-1 cells. Scatchard analysis indicated the presence of 2 classes of somatostatin binding sites on the cells, one with high binding affinity and low capacity and the other with low binding affinity and high capacity. RC-160 could bind to somatostatin receptors on these cells with an affinity similar to SS-14 but significantly higher than that of SMS201-995. Radioimmunoassay of intracellular cAMP showed that RC-160 could powerfully inhibit forskolin-stimulated cAMP production in CFPAC-1 cells. Addition of forskolin to the cultures increased cAMP concentrations in the cellular lysate of treated cells. RC-160 attenuated or nullified in a dose-dependent manner the cAMP production stimulated by forskolin. Our observations indicate that somatostatin analog RC-160 inhibits the proliferation of CFPAC-1 human pancreatic cancer cells in vitro and that this effect may involve the intracellular cAMP pathway.

Amino Acid Sequence↗

Flexible waveguides for Er-YAG laser radiation delivery.

Flexible plastic waveguides (FPW) were devised for the delivery of Er-YAG laser radiation. The FPW characteristics were studied under various conditions. In vitro studies were carried out to explore the drilling procedure on extracted teeth and the FPW-tissue mutual effects. The results which were obtained proved that the FPW as a delivery device might be a substitute hand applicator for the pneumatic turbine for drilling in teeth.

Dental Cavity Preparation↗

Inhibition of growth of MKN45 human gastric-carcinoma xenografts in nude mice by treatment with bombesin/gastrin-releasing-peptide antagonist (RC-3095) and somatostatin analogue RC-160.

Nude mice bearing xenografts of the gastrin-responsive human gastric carcinoma MKN45 cell line were treated for 4 to 5 weeks with bombesin/gastrin-releasing-peptide(GRP) antagonist (RC-3095), somatostatin analogues RC-160 and SMS 201-995, or the combination of RC-3095 and RC-160. Tumor volumes and weights were reduced significantly to a similar extent by RC-160 and SMS 201-995, administered by daily s.c. injections at a dose of 100 micrograms/day. Bombesin/GRP antagonist RC-3095, given s.c. at a dose of 20 micrograms/day, had the greatest inhibitory effect on tumor growth. The combination of RC-3095 with RC-160 did not further potentiate the suppression of tumor growth. Histologically, the number of mitotic cels decreased significantly in the groups treated with RC-160 or the combination of RC-3095 with RC-160. Serum gastrin levels were significantly diminished in all treated groups. Therapy with RC-160 or the combination also significantly decreased levels of serum growth hormone. Receptor assays on tumor membranes showed that bombesin was bound to 2 classes of receptor sites, one with high affinity and low capacity, the other with low affinity and high capacity. Binding sites for epidermal growth factor (EGF) were down-regulated in tumor cells after treatment with RC-3095, RC-160 or the combination of RC-3095 with RC-160. In studies in vitro, both RC-160 and RC-3095 significantly inhibited the proliferation of MKN45 cells in culture as measured by cell number. These data demonstrate, for the first time, that the growth of human gastric cancer in nude mice can be inhibited not only by somatostatin analogues, but also by administration of modern bombesin/GRP antagonists, such as RC-3095.

Adenocarcinoma↗

Inhibitory effect of bombesin receptor antagonist RC-3095 on the growth of human pancreatic cancer cells in vivo and in vitro.

In this study, we investigated the effect of bombesin/GRP antagonist RC-3095 on the growth of CFPAC-1 human pancreatic cancer cells transplanted to nude mice or cultured in vitro. Nude mice bearing xenografts of the CFPAC-1 cell line received s.c. injections of RC-3095 (10 micrograms twice a day) or the vehicle (control) for 25 days. Chronic administration of RC-3095 inhibited the growth of CFPAC-1 tumors in nude mice as shown by a significant decrease in tumor volume throughout the period of treatment. Tumor volume doubling time was prolonged by RC-3095 treatment from 7.2 days to 10 days, and the tumor growth rate was decreased by 49%. In mice treated with RC-3095, the tumor growth delay time was 5.8 days. Treatment with RC-3095 decreased the final tumor weight by 37% and reduced DNA and protein contents in tumor tissues by 44 and 39.9%, respectively, compared to the controls. In cultures of the CFPAC-1 cell line, the addition of bombesin(1-14) (1 pM-0.1 microM) to the medium induced a dose-dependent increase in cell number. RC-3095 at 1 nM concentration effectively inhibited the bombesin-stimulated growth of CFPAC-1 cells in cultures. In the presence of 1 microM RC-3095 in the culture medium, the bombesin-induced growth of CFPAC-1 cells was totally suppressed. Bombesin was also shown to stimulate the DNA synthesis in CFPAC-1 cells in vitro as based on [3H]thymidine incorporation assay. When the cells were cultured in the presence of 1-100 nM bombesin, the uptake of [3H]thymidine by the cells was increased by 89-131%. RC-3095 inhibited both the basal and bombesin-stimulated DNA synthesis of CFPAC-1 cells. Addition of RC-3095 (10-100 nM) alone to the cultures caused a 39-40% decrease in the [3H]thymidine incorporation by the cells. Concomitant addition of RC-3095 (1 microM) and bombesin (1-100 nM) to the cultures induced a significant reduction in the uptake of [3H]thymidine by the cells compared to the values obtained with bombesin alone. Receptor binding assays showed the presence of two classes of specific binding sites for bombesin on CFPAC-1 cells, one with high affinity (Kd = 4.25 +/- 0.77 nM) and low capacity (Bmax = 0.268 +/- 0.052 pmol/10(6) cells) and the other with low affinity (Kd = 321.70 +/- 68.46 nM) and high capacity (Bmax = 3.991 +/- 0.374 pmol/10(6) cells).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Bombesin antagonists inhibit in vitro and in vivo growth of human gastric cancer and binding of bombesin to its receptors.

We investigated the effect of bombesin/gastrin-releasing peptide (GRP) antagonist RC-3095 and other analogs on the growth of Hs746T human gastric cancer cells implanted in nude mice or cultured in vitro and on the binding of bombesin to its receptors. Nude mice bearing xenografts of the Hs746T cell line received s.c. injections of RC-3095 (10 micrograms twice daily) or the vehicle (control) for 21 days. Administration of antagonist RC-3095 inhibited the growth of Hs746T tumors. Treatment with RC-3095 produced a significant decrease in tumor volume, prolonged the tumor volume doubling time from 3.6 days to 5.1 days, and decreased the tumor growth rate by 76.9%. The tumor growth delay time in mice treated with RC-3095 was 2.8 days. Treatment with RC-3095 also decreased the final tumor weight by 88.3% and reduced DNA and protein contents in tumors by 91.5% and 89.5%, respectively, as compared to controls. The presence of specific receptors for bombesin/GRP was investigated on the crude membranes of implanted tumors of Hs746T cells. Saturation binding assays showed that the binding of [125I-Tyr4]bombesin to the membranes was saturable and reversible. Scatchard analysis indicated the presence of a single class of binding sites with a high affinity (Kd = 0.24 +/- 0.07 nM) and a low binding capacity (Bmax = 57.0 +/- 0.9 fmol/mg protein). In displacement studies, the binding of [125I-Tyr4]bombesin was inhibited in a dose-dependent manner by unlabelled bombesin(1-14), [Tyr4]-bombesin and GRP (14-27), but not by structurally unrelated peptides. Synthetic bombesin/GRP antagonists RC-3095, RC-3110, and RC-3950-II were all able to inhibit effectively the binding of [125I-Tyr4]bombesin to the membranes of Hs746T cells. RC-3950-II showed a higher binding affinity for bombesin receptors than RC-3095 or RC-3110. Addition of the non-hydrolyzable guanine-nucleotide analog GTP [S] to the binding buffer caused a significant reduction in the amount of [125I-Tyr4]bombesin bound to the cells, indicating that the bombesin receptor is coupled to a G-protein. In cell cultures, bombesin significantly stimulated the growth of Hs746T cells in vitro as shown by an increase in the uptake of [3H]thymidine. Bombesin antagonist RC-3095 could effectively inhibit the bombesin-stimulated growth of Hs746T cells in cultures. These observations suggest that bombesin/GRP may act as growth factors through specific receptors present on the membranes of Hs746T cells. Bombesin/GRP antagonists appear to nullify the effects of bombesin/GRP and may be useful for the treatment of gastric cancers.

Animals↗

Urinary endothelin excretion in the neonate: influence of maturity and perinatal pathology.

The present study was undertaken to establish the developmental pattern of urinary endothelin-1 (ET-1) excretion and to define its possible role in mediating pathophysiological changes related to perinatal asphyxia/infection and dopamine treatment. Urinary ET-1 levels were measured by radioimmunoassay in 7 full-term neonates (mean gestational age 39.3 weeks) on days 1, 3 and 5, and in 9 pre-term neonates (mean gestational age 30.8 weeks) on days 1, 3, 5, 7 and weekly thereafter for 5 consecutive weeks. The results were compared with those of three age-groups of 30 normal children (4-8 years, 9-12 years and 13-18 years); each group consisted of 10 children. The influence of severe cardiopulmonary distress (n = 16, mean gestational age 33.9 weeks, post-natal age 3.3 days) and dopamine administration in a dose of 2 micrograms/min per kg (n = 10, mean gestational and post-natal ages 32.1 weeks and 5.6 days, respectively) were also studied. In full-term infants, ET-1 concentration fell from 34.3 +/- 1.8 pmol/l on day 1 to 21.5 +/- 1.5 pmol/l on day 5 (P < 0.01). In premature infants its absolute value and its post-natal fall were similar in the 1st week and no further change occurred in weeks 2-5; it stabilized at levels between 17.1 +/- 2.2 and 16.7 +/- 1.7 pmol/l. These concentrations tended to be lower than those of 25.5 +/- 1.3, 23.0 +/- 1.0 and 26.2 +/- 0.7 pmol/l measured in three groups of older children.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗