Flash Flood Early Warning System in Colima, Mexico.

This paper presents a system of sensors used in flash flood prediction that offers critical real-time information used to provide early warnings that can provide the minutes needed for persons to evacuate before imminent events. Flooding is one of the most serious natural disasters humans confront in terms of loss of life and results in long-term effects, which often have severely adverse social consequences. However, flash floods are potentially more dangerous to life because there is often little or no forewarning of the impending disaster. The Emergency Water Information Network (EWIN) offers a solution that integrates an early warning system, notifications, and real-time monitoring of flash flood risks. The platform has been implemented in Colima, Mexico covering the Colima and Villa de Alvarez metropolitan area. This platform consists of eight fixed riverside hydrological monitoring stations, eight meteorological stations, nomadic mobile monitoring stations called "drifters" used in the flow, and a sniffer with data muling capability. The results show that this platform effectively compiles and forwards information to decision-makers, government officials, and the general public, potentially providing valuable minutes for people to evacuate dangerous areas.

Foot posture is associated with morphometry of the peroneus longus muscle, tibialis anterior tendon, and Achilles tendon.

The aim of this study was to investigate the association between foot type and the morphometry of selected muscles and tendons of the lower limb. Sixty-one healthy participants (31 male, 30 female; aged 27.1 ± 8.8 years) underwent gray-scale musculoskeletal ultrasound examination to determine the anterior-posterior (AP) thickness of tibialis anterior, tibialis posterior, and peroneus longus muscles and tendons as well as the Achilles tendon. Foot type was classified based on arch height and footprint measurements. Potentially confounding variables (height, weight, hip and waist circumference, rearfoot and ankle joint range of motion, and levels of physical activity) were also measured. Multiple linear regression models were used to determine the association between foot type with muscle and tendon morphometry accounting for potentially confounding variables. Foot type was significantly and independently associated with AP thickness of the tibialis anterior tendon, peroneus longus muscle, and Achilles tendon, accounting for approximately 7% to 16% of the variation. Flat-arched feet were associated with a thicker tibialis anterior tendon, a thicker peroneus longus muscle, and a thinner Achilles tendon. Foot type is associated with morphometry of tendons that control sagittal plane motion of the rearfoot; and the peroneus longus muscle that controls frontal plane motion of the rearfoot. These findings may be related to differences in tendon loading during gait.

Low prevalence and assay discordance of "aspirin resistance" in children.

BACKGROUND: Although "aspirin resistance" (AR-inadequate platelet inhibition as suggested by in vitro testing of aspirin-treated patients) has been widely studied in adults and linked to increased risk of adverse outcomes, its prevalence and clinical significance are largely unknown in children. PROCEDURE: To determine AR prevalence in children and its relationship to assay methodology, we undertook a cross-sectional study of 44 children (1-17 years, 24 male) on aspirin for various indications and considered three published definitions of AR in adults: platelet aggregation >/=70% to 10 microM adenosine diphosphate and >/=20% to 0.5 mg/ml arachidonic acid (AA), normal PFA-100(R) closure time and elevated urinary 11-dehydro thromboxane B(2) (11dhTxB(2)) concentration. RESULTS: Six subjects exhibited AR according to at least one of the criteria (5 by PFA-100(R), 1 by aggregometry and 11dhTxB(2) criteria); nearly all subjects had low levels of 11dhTxB(2) compared with controls. Subjects studied prior to therapy showed pronounced changes in AR parameters after aspirin dosing (e.g., mean aggregation to AA decreased from 82% to 6%, P < 0.001), confirming an aspirin effect. Subjects with AR did not differ from aspirin responsive subjects in terms of age, race, platelet count, or aspirin dose, indication or therapy duration. There was minimal correlation between assays. CONCLUSIONS: In this initial prevalence study of a clinically diverse group of pediatric patients, frequencies of AR were assay-dependent; however, the prevalence of true AR is likely low in children (2.3%; 95% CI 0.1-10.7%), in agreement with adult studies. To better define the clinical relevance of AR in children, multicenter, prospective cohort studies are imperative.

On the effects of straight metallic jewellery on the specific absorption rates resulting from face-illuminating radio communication devices at popular cellular frequencies.

This paper presents simulated and measured phantom results for the possible effects that head worn jewellery may have on the relative levels of energy absorbed in the human head with cellular enabled mobile communication devices. The FDTD electromagnetic code used with simple and complex anatomical mathematical phantoms was used to consider the interactions of metallic jewellery, heads and representative sources at 900 and 1800 MHz. Illuminated metallic pins of different lengths were positioned in front of the face. Initially, a homogenous phantom was used to understand the relative enhancement mechanisms. This geometry allowed the results to be validated with the industry standard DASY4 robot SAR measurement system related to the CENELEC head. Jewellery pins were then added to an anatomically realistic head. The relative increase in the 1 g and 10 g SAR, due to a pin with a length 0.4lambda near the eyebrows of a complex, anatomically realistic head was approximately three times at 1800 MHz. Such pins increased the SAR averaged over a 1 g or 10 g mass by redistributing the energy absorbed inside the head and focusing this energy towards the area of the head nearest to the centre of the pin. Although, the pins increased the SAR, the SAR standards were not breached and the jewellery produced lower values than those of previous studies when the source was positioned close to the ear.

Does a catheter over needle system reduce infusate leak in continuous peripheral nerve blockade: a randomised controlled trial.

Continuous peripheral nerve blockade is a common technique in the analgesic management for many procedures. Leakage of local anaesthetic from around the nerve catheter insertion site can increase the chance of catheter dislodgement, risks infective complications, and could divert anaesthetic away from the nerve causing the block to fail. We conducted a randomised controlled trial to assess whether the type of nerve catheter influenced local anaesthetic leak rate. One hundred and ten patients scheduled for elective unilateral total knee arthroplasty were randomised to receive a perineural catheter with either a catheter over needle (CON) system (Pajunk® E-Cath) (PAJUNK® GmbH, Medizintechnologie, Geisingen, Germany), or catheter through needle (CTN) system (Pajunk® SonoLong) (PAJUNK® GmbH, Medizintechnologie, Geisingen, Germany). There was no statistically significant difference in the rate of leaking catheters between groups (CON 1.8% versus CTN 3.7%; P=0.618), however, the overall leak rate was much lower than anticipated from pilot data. The CON system was on average faster to insert (CON 357 seconds versus CTN 482 seconds; P=0.004), but associated with poorer needle visibility under ultrasound (Likert scale 1-5, mean [SD], CON 3.31 [0.96] versus CTN 3.89 [0.84]; P=0.001). All seven instances of inadvertent catheter dislodgement occurred in the CTN group (P=0.006). There was no statistically significant difference between groups in the proportion of patients who had adequate analgesia on day one (CON 80% versus CTN 86.5%; P=0.294) and day two postoperatively (CON 85.5% versus CTN 91.8%; P=0.369). Our findings show the overall leak rate to be very low with both catheter systems; however, the CON system may have advantages in terms of speed of use and rate of inadvertent catheter dislodgement.

Cellular action of vasopressin in medullary tubules of mice with hereditary nephrogenic diabetes insipidus.

Our previous studies (1974. J. Clin. Invest.54: 753-762.) suggested that impaired metabolism of cyclic AMP (cAMP) may be involved in the renal unresponsiveness to vasopressin (VP) in mice with hereditary nephrogenic diabetes insipidus (NDI). To localize such a defect to specific segments of the nephron, we studied the activities of VP-sensitive adenylate cyclase, cAMP phosphodiesterase (cAMP-PDIE), as well as accumulation of cAMP in medullary collecting tubules (MCT) and in medullary thick ascending limbs of Henle's loop (MAL) microdissected from control mice with normal concentrating ability and from mice with hereditary NDI. Adenylate cyclase activity stimulated by VP or by NaF was only slightly lower (-24%) in MCT from NDI mice, compared with controls. In MAL of NDI mice, basal, VP-sensitive, and NaF-sensitive adenylate cyclase was markedly (> -60%) lower compared with MAL of controls. The specific activity of cAMP-PDIE was markedly higher in MCT of NDI mice compared with controls, but was not different between MAL of control and NDI mice. Under present in vitro conditions, incubation of intact MCT from control mice with VP caused a striking increase in cAMP levels (>10), but VP failed to elicit a change in cAMP levels in MCT from NDI mice. When the cAMP-PDIE inhibitor 1-methyl-3-isobutyl xanthine (MIX) was added to the above incubation, VP caused a significant increase in cAMP levels in MCT from both NDI mice and control mice. Under all tested conditions, cAMP levels in MCT of NDI mice were lower than corresponding values in control MCT. Under the present experimental setting, VP and other stimulating factors (MIX, cholera toxin) did not change cAMP levels in MAL from either control mice or from NDI mice. The results of the present in vitro experiments suggest that the functional unresponsiveness of NDI mice to VP is perhaps mainly the result of the inability of collecting tubules to increase intracellular cAMP levels in response to VP. In turn, this inability to increase cAMP in response to VP is at least partly the result of abnormally high activity of cAMP-PDIE, a somewhat lower activity of VP-sensitive adenylate cyclase in MCT of NDI mice, and perhaps to a deficiency of some other as yet unidentified factors. The possible contribution of low VP-sensitive adenylate cyclase activity in MAL of NDI mice to the renal resistance to VP remains to be defined.

Modulation of cyclic nucleotides in islated rat glomeruli: role of histamine, carbamylcholine, parathyroid hormone, and angiotensin-II.

Because glomerular functions are modulated by numerous humoral agents, probably acting through cyclic nucleotides, the effects of some polypeptide hormones and biogenic amines on cyclic AMP (cAMP) and cyclic 3',5'-guanosine monophosphate (cGMP) were studied in glomeruli isolated from rat renal cortex. Glomeruli and cortical tubules were prepared by a combination of sieving and density-gradient centrifugation. Under basal conditions, the contents of cAMP and cGMP in glomeruli were significantly higher than in tubules and unfractionated renal cortical tissue.Histamine caused a striking increase in cAMP in glomeruli (+Delta% 675+/-87) and, to a lesser degree, increased cAMP in tubules (+Delta% 103+/-25) or in tissue slices. This stimulation was dose-dependent in the range of 1 muM-1 mM histamine. Metiamide (an H(2)-antagonist), but not pyrilamine (an H(1)-antagonist) blocked the effect of histamine on cAMP, which indicates that histamine causes its effect via interaction with H(2) receptors. Histamine caused less extensive increases in cGMP in both glomeruli and tubules. Carbamylcholine caused a marked increase in cGMP in glomeruli (+Delta 295+/-7) and a much lower increase in tubules (+Delta% 70+/-20); these effects were blocked by atropine. Parathyroid hormone (1 mug/ml) increased cAMP and, to a much lesser degree, also cGMP in glomeruli. In tubules, parathyroid hormone caused much more extensive increases in cAMP than in glomeruli; no changes, or rather a small decline in cGMP, was observed. Angiotensin-II (2 muM) markedly lowered cAMP in glomeruli (-Delta% -45+/-8) and in tubules (-Delta% 33+/-7) but had no effect on cGMP. Bradykinin (20 muM) did not consistently influence either cAMP or cGMP in glomeruli or tubules. Present results demonstrate that cAMP and cGMP metabolism in glomeruli are controlled independently by humoral agents known to alter glomerular functions in vivo. Our findings are consistent with the view that histamine and cholinergic agents generated and (or) released locally in glomeruli or in their vicinity may play important roles as mediators of immunopathological injury of glomeruli, and that these effects are mediated by cAMP and (or) cGMP through interaction with H(2) receptors and muscarinic receptors. Likewise, our results suggest that the effects of angiotensin-II and parathyroid hormone on glomerular dynamics may be mediated by cyclic nucleotides.Thus, we surmise that extrarenal as well as intrarenal humoral agents may play an important role in the pathology and physiology of glomeruli through mediation of either cAMP, cGMP, or both.

Diazontized (125I) diiodosulafanilic acid as a label for cell surface membranes. Studies on erythrocytes.

1. Diazotized 2,6-diiodosulfanilic acid (DDISA) appears to have properties suitable to serve as an artificial, non-penetrating label of cell surface membranes. Therefore, the conditions for selective labeling of cell surface membranes as compared to intracellular proteins as well as a method for its chemical determination were explored in the present study. 2. DDISA reacts with alpha-naphthol at neutral pH to produce a compound (1-hydroxy-4-(2,6-diiodo-4-sulfo-1-phenylazo-(naphthylene)), DSPN) with a characteristic spectrum in the visible range (Amax 430 nm). The absorbance of the reaction product, DSPN, is linearly proportional to the concentration of DDISA and can be used as a method for the colorimetric determination of DDISA. Reaction of DDISA with a molar excess of alpha-naphthol was also used as a method for inactivating unreacted DDISA to terminate labeling prior to cell fractionation. 3. [125I]DDISA reacts avidly with a variety of basic, neutral and acidic proteins as well as with cell membranes to form an acid-stable covalent azo linkage. 4. Effectiveness of labeling of the surface membrane of intact erythrocytes after incubation with [125I]DDISA was assessed by th ratio of 125I incorporated into membrane proteins compared to intracellular proteins. When intact erythrocytes were exposed to [125I]DDISA, the optimal labeling of membranes occurred at 37 degrees C after 20 min of incubation time and at a concentration of 10(-4) M [125I]DDISA in the incubation media. Under these conditions the ratio of the specific activity (cpm 125I/mg protein) of the membrane fraction to the specific activity of the soluble protein fraction (membrane/supernatant ratio) was greater than 500. When incubations were conducted at 4 degrees C this ratio was less than 50. However, when osmotically lysed erythrocytes were incubated with [125I]DDISA the majority of the label reacted with the soluble protein fraction resulting in a membrane/supernatant ratio of 0.14. 5. The results thus suggest that [125I]DDISA used under the appropriate incubation conditions, including the inactivation and removal of [125I]DDISA by washing with alpha-naphthol, can serve as a highly selective membrane label with minimal incorporation into intracellular soluble proteins. The general applicability of this method for other cell types remains to be explored.

Auditory brainstem evoked responses in autistic children.

Auditory brainstem evoked responses (ABRs) were studied in 16 autistic children. Three children had severe delays in wave I latency, indicating defective functioning of the peripheral auditory pathway. The remaining subjects also had delayed wave I latency but only for right ear stimulation at the lowest stimulus intensity. Eight autistic children (and no control subjects) had ABR transmission time values 3 SDs beyond the normal mean, suggesting auditory processing defects peripheral to or within the brainstem auditory pathway. These findings (1) may have no causal relationship to the child's autistic handicaps, (2) may represent distortions in auditory input that impair the learning of language, and (3) may reflect an earlier state in which abnormal input directly caused maldevelopment of forebrain systems necessary for language and cognitive function.

Evidence for a major gene for bone mineral density in idiopathic osteoporotic families.

Although there have been a number of studies indicating a heritable component for osteoporosis in middle to late adulthood, the etiology of osteoporosis in young people is uncertain. The present study aims to evaluate the extent to which genetic factors influence familial resemblance for bone mineral density (BMD) in families ascertained on the basis of young osteoporotic probands. The sample comprises eight families (74 total individuals) that were identified through a proband under the age of 35 years with a history of two or more fractures and a spinal bone density of at least 2.5 SDs below the mean for age and sex (Z score). Secondary causes of osteoporosis were excluded in the probands. In total, 27% (18/66) of the probands' relatives had osteoporosis and an additional 30% (20/66) had osteopenia. Classical segregation analysis was performed to evaluate the extent to which a genetic etiology could account for familial resemblance in these families. The results indicate a major gene of codominant inheritance for spinal BMD. Model-fitting comparisons revealed no support for environmental effects or for polygenic inheritance.

Stimulation of phospholipid methylation and thyroid hormone secretion by thyrotropin.

Synthesis of phosphatidylcholine (PC) by S-adenosylmethionine-dependent methylation of phosphatidylethanolamine has previously been associated with receptor-mediated histamine and pituitary hormone secretion. We investigated stimulation of phospholipid methylation by TSH and its possible role in thyroid hormone secretion. Rat hemithyroids were incubated in Krebs-Henseleit-glucose-BSA buffer and the effect of various treatments on the incorporation of [3H-methyl]L-methionine into PC and T4/T3 secretion was studied. TSH treatment elevated thyroid phosphatidylethanolamine methyltransferase activity, the incorporation of [3H-methyl]methionine into PC, and T4/T3 secretion. The increase in PC synthesis was linear up to 6 h in a dose-dependent fashion (half-maximal stimulation at 2.5 micrograms TSH/ml). Stimulation required protein synthesis, because cycloheximide inhibited the increase in PC synthesis by 77%. Inhibitors of phospholipid methylation (100 microM adenosine + 10 microM L-homocysteine thiolactone + 10 microM erythro-9[2-hydroxy-3-nonyl]adenine) significantly decreased TSH-stimulation of phospholipid methylation but not T3/T4 secretion. In conclusion, stimulation of thyroid phospholipid methylation by TSH is not required for stimulated secretion of thyroid hormones.

Lithium-induced polyuria: effect of lithium on adenylate cyclase and adenosine 3',5'-monophosphate phosphodiesterase in medullary ascending limb of Henle's loop and in medullary collecting tubules.

We investigated the effects of hyperosmolality, chronic treatment with lithium chloride (LiCl), and the addition of LiCl in vitro on vasopressin-sensitive (VP) adenylate cyclase (AdC) and cAMP phosphodiesterase (cAMP-PDIE) activities in the medullary thick ascending limb of Henle's loop (MAL) and medullary collecting tubule (MCT) microdissected from the outer medulla of the rat kidney. A hyperosmolar medium (800 mosmol) markedly enhanced AdC activity stimulated by 10(-6) M VP specifically in MCT, while having little effect or slightly decreasing VP-stimulated AdC in MAL, compared to activities under standard isotonic conditions. Hyperosmolality decreased cAMP-PDIE activity to about the same degree in MAL and MCT. Inclusion of LiCl in the incubation medium (15-20 mM) caused a significant dose-dependent inhibition of VP-stimulated AdC activity in both MAL and MCT, but had no effect on CAMP-PDIE in either segment. AdC and cAMP-PDIE activities in MAL and MCT from chronic LiCl-treated polyuric rats did not differ from controls when assayed under standard isotonic conditions. However, when assayed in a hyperosmolar (800 mosmol) medium, VP-sensitive AdC activity was significantly lower (P < 0.01) in MCT from LiCl-treated rats compared to control levels, while VP-sensitive AdC in MAL did not differ in LiCl-treated and control rats. The present results suggest that lowered VP-sensitive AdC activity in MCT of LiCl-treated polyuric rats may contribute to the observed lower concentrating ability and collecting tubule resistance to VP. Inhibition of VP-sensitive AdC in MAL as well as MCT by the acute addition of LiCl in vitro may explain the decreased urinary diluting ability observed with acute infusions of Li salts in vivo in the rat.

Identification of endothelin receptor subtypes in human renal cortex and medulla using subtype-selective ligands.

High affinity and high density endothelin (ET)-binding sites were identified in membranes prepared from human kidney cortex and medulla. Saturation binding experiments performed in membranes prepared from cortex and medulla using [125I]ET-1 and [125I]ET-3 revealed that the proportion of [125I]ET-3-binding sites was 30-35% less than that of [125I]ET-1-binding sites. The apparent dissociation constants and maximum binding for [125I]ET-1 and [125I]ET-3 to membranes from cortex were 91 +/- 5 pM and 165 +/- 10 fmol/mg protein, and 117 +/- 9 pM and 110 +/- 7 fmol/mg protein, respectively, whereas in medulla they were 139 +/- 10 pM and 360 +/- 11 fmol/mg protein, and 142 +/- 11 pM and 245 +/- 15 fmol/mg protein, respectively. In the presence of 10 nM sarafotoxin-6c, which is selective for ETB receptors, [125I]ET-1 binding was decreased by 65-70%, whereas [125I]ET-3 binding was totally abolished, suggesting that 65-70% of [125I]ET-1 binding and 100% of [125I]ET-3 binding was to ETB receptors. This was further confirmed by the use of a cyclic pentapeptide [cyclo(D-Trp,D-Asp,L-Pro, D-Val,L-Leu)] (BQ123), which is selective for ETA receptors. In the presence of 1 microM BQ123, [125I]ET-1 binding was decreased by 25-30%, whereas [125I]ET-3 binding was unaffected, confirming that 30-35% of ET receptors belong to the ETA subtypes, and that [125I]ET-1 bound to both ETA and ETB receptors with the same high affinity, but [125I]ET-3 bound only to ETB receptors with high affinity. These results suggest that human kidney cortex and medulla contain ETA and ETB receptors in a ratio of 30:70, and that sarafotoxin-6c and BQ123 are valuable tools in identifying the subtype of ET receptors in various tissues.

Secretion of human epidermal growth factor from Saccharomyces cerevisiae using synthetic leader sequences.

We have investigated different leader sequences for their ability to direct the efficient secretion of human epidermal growth factor (hEGF) from Saccharomyces cerevisiae. We designed a consensus signal sequence which directs secretion of hEGF from yeast as efficiently as the yeast invertase signal sequence. However, secretion is increased over fivefold by the introduction, after the signal sequence, of a synthetic 19-amino acid (aa) pro-sequence containing a cleavage recognition site for the KEX2 protease. Even in the absence of an Asn-linked glycosylation site, secretion of hEGF using the synthetic prepro-leader was as efficient as that directed by the alpha-factor leader. The role of the KEX2 protease cleavage site was investigated by mutation of the yeast alpha-factor KEX2 site (cleavage after Lys-Arg). Cleavage was obtained with the following order of efficiency, Lys-Arg greater than Pro-Arg greater than Asp-Arg, although the sequence context was also found to affect efficiency.

The Saccharomyces cerevisiae ARO1 gene. An example of the co-ordinate regulation of five enzymes on a single biosynthetic pathway.

The ARO1 gene of Saccharomyces cerevisiae encodes the arom multifunctional enzyme. Specific inhibitors of amino acid biosynthesis have been used to obtain evidence that expression of a cloned ARO1 gene is regulated in response to amino acid limitation. Northern blot analysis and sequence studies indicate that ARO1 is regulated by the well characterised S. cerevisiae 'general control' mechanism. This provides a very economical means of simultaneously tailoring the synthesis of five shikimate pathway enzymes to the needs of the cell.

Structure-function analysis of epidermal growth factor: site directed mutagenesis and nuclear magnetic resonance.

The role of leucine-47 in determining the structure and activity of human epidermal growth factor was examined using site-directed mutagenesis. Wild type protein and four variants in which Leu47 was replaced by valine, glutamate, aspartate and alanine were produced from yeast. 1H NMR experiments demonstrated that substitution of Leu47 had little effect on the protein structure. The observed reduction in receptor binding affinity caused by the substitutions could thus be attributed to perturbation of a residue directly involved in receptor interactions.

Identification of the horse epidermal growth factor (EGF) coding sequence and its use in monitoring EGF gene expression in the endometrium of the pregnant mare.

The PCR technique and highly degenerate oligonucleotide primers were used to amplify a 282 bp fragment of the horse (Equus caballus) epidermal growth factor (EGF) cDNA. The clone corresponded to 94 amino acids of the EGF precursor molecule. The deduced amino acid sequence of the 53 residue EGF mitogenic peptide within the precursor sequence showed 60-70% identity with five other published EGF sequences. The PCR cDNA fragment hybridized to a 4.9 kb transcript in horse kidney and endometrial RNA which was of a similar size to the mature EGF transcript found in other mammalian species. The horse cDNA clone was used in Northern blots to monitor EGF expression in the endometrium of pregnant mares up to day 83 of gestation (term = 330-340 days). The level of expression increased from day 33 and showed a further dramatic increase between days 35 and 45, which coincides with the onset of implantation and placentation in this species. Levels remained elevated up to day 83. The horse DNA sequence was used to design sense and antisense oligonucleotide probes (45-mers) for in situ hybridization studies. The antisense probe showed specific hybridization to the glandular, but not lumenal, epithelial cells of the endometrium and there was no signal in fetal membranes. The in situ hybridization signal increased between days 35 and 45 to a similar degree to that observed in the Northern blot analysis. This dramatic increase in EGF expression in the glandular epithelium of the mare's endometrium during pregnancy may provide a mitogenic stimulus to the endometrium and/or trophoblast to facilitate placental differentiation and attachment. Alternatively, the precursor could be involved in the endometrial gland secretory process which is necessary to produce uterine milk for fetal sustenance. The PCR cloning methods used in this study should be generally applicable to the cloning of EGF cDNAs from other species.

In vivo pharmacological characterization of the non-peptide endothelin receptor antagonist SB 209670.

1. The aim of the present study was to assess the ability of SB 209670, a high affinity non-peptide endothelin receptor antagonist (0.4 and 18 nM Kis at human cloned ETA and ETB receptors, respectively), to inhibit the haemodynamic actions of endothelin-1 in vivo. 2. Systemic administration of (+/-)-SB 209670, given either as a bolus i.v. injection or as a continuous i.v. infusion, did not alter basal haemodynamic parameters in the anaesthetized rat. 3. Infusion of (+/-)-SB 209670 (10 micrograms kg-1 min-1) selectively inhibited the depressor and carotid vasodilator response to exogenous endothelin-1: 100 micrograms kg-1 min-1 was required to inhibit significantly the biphasic haemodynamic actions of endothelin-1. The haemodynamic actions of angiotensin II and calcitonin gene-related peptide were unaltered by 100 micrograms kg-1 min-1 (+/-)-SB 209670. 4. Bolus i.v. administration of (+/-)-SB 209670 (1 mg kg-1) selectively inhibited the depressor and carotid vasodilator actions of endothelin-1: 10 mg kg-1 (+/-)-SB 209670 was required to inhibit the secondary vasoconstrictor actions of endothelin-1. 5. (+/-)-SB 209670 (10 mg kg-1) was also effective at antagonizing the pressor actions of endothelin-1 in the conscious rat for up to 3 h after intraduodenal administration thereby demonstrating that the antagonist was bioavailable upon enteric administration. This dose of (+/-)-SB 209670 did not alter basal haemodynamic parameters in the conscious rat. 6. Thus, ( +/- )-SB 209670 is an effective endothelin receptor antagonist in vivo. Using the doses defined in this study, SB 209670 may, therefore, serve as a useful tool for understanding the role of endogenous endothelin-I in the control of cardiovascular function under both physiological and pathophysiological conditions.

Distribution and characterization of cyclo (His-Pro)-like immunoreactivity in anuran (frog) skins.

The distribution of cyclo (His-Pro)-like immunoreactivity in frog skins from seven frog species was examined. The chromatographic elution profile of cyclo (His-Pro)-like immunoreactivity in amphibian skins measured by radioimmunoassay corresponded precisely to that of [3H-Pro]-cyclo (His-Pro) after DEAE-Cellulose, Sephadex G-25 and high-pressure liquid chromatography. The concentrations of cyclo (His-Pro) in frog skins were much higher than the concentrations of TRH previously observed in skin and the concentrations of cyclo (His-Pro) in both brain and gastrointestinal tract.