PubMed Health⌕ Search

Biomedical subjects

M Costa

Publications and source records attributed to M Costa.

At least 19 recordsLinked to original sources

The relevance of continuity of care: a solution for the chaos in the emergency services.

BACKGROUND: In Brazil, there continues to be an excessive use of emergency services by patients with elective medical problems. Those patients who report having a primary care physician are less likely to utilize the emergency department for non-urgent consultations. OBJECTIVE: The objective of this study was to compare patients who have a primary care physician with those who do not in relation to severity of their chief complaint at presentation in the emergency department. METHODS: The study was carried out as a cross-sectional interview-based survey at the Conceição Hospital Emergency Service in Porto Alegre (Brazil). The sample was 553 patients selected through a systematic random sampling, and the response rate was 88%. The data entry and analysis were performed using the software Epi-info, EGRET and SPSS. The analysis included simple statistics to determine the prevalence of the conditions being investigated and the effect of independent variables (regular doctor) in relation to the dependent variable (severity of disease) through logistic regression. RESULTS: The chief complaints were divided up as follows: 15% emergency cases, 46% urgent cases and 39% elective. The chief complaint was defined as urgent or emergency if it exhibited a significantly statistical association with the following independent variables, after being analysed by a logistic regression model: patients who reported having a primary care physician [odds ratio (OR) = 2.98, 95% confidence interval (CI) = 1.84-4.80] and patients who usually go to the emergency room by car (OR = 2.67, 95% CI = 1.75-4.05). CONCLUSION: One strategy to reduce the number of non-urgent consultations at emergency rooms is to establish a close out-patient relationship between patients and physician. There is a need to optimize the health care of patients who have non-urgent problems but still seek the emergency department through strategies at the primary health care level-especially when continuous care is available-and where a comprehensive approach with an emphasis on prevention would stimulate better quality of care at a lower cost.

Brazil↗

Formation of nitrotyrosine by methylene blue photosensitized oxidation of tyrosine in the presence of nitrite.

Methylene blue photosensitized oxidation of tyrosine in the presence of nitrite produces 3-nitrotyrosine, with maximum yield at pH 6. The formation of 3-nitrotyrosine requires oxygen and increases using deuterium oxide as solvent, suggesting the involvement of singlet oxygen in the reaction. The detection of dityrosine as an additional reaction product suggests that the first step in the interaction of tyrosine with singlet oxygen generates tyrosyl radicals which can dimerize to form dityrosine or react with a nitrite-derived species to produce 3-nitrotyrosine. Although the chemical identity of the nitrating species has not been established, the possible generation of nitrogen dioxide (*NO(2)) by indirect oxidation of nitrite by intermediately produced tyrosyl radical, via electron transfer, is proposed. One important implication of the results of this study is that the oxidation of tyrosine by singlet oxygen in the presence of nitrite may represent an alternative or additional pathway of 3-nitrotyrosine formation of potential importance in oxidative injures such as during inflammatory processes.

Animals↗

Hydrogen peroxide mediates activation of nuclear factor of activated T cells (NFAT) by nickel subsulfide.

Nickel compounds induce cell transformation in cell culture models and tumor formation in experimental animals. However, the molecular mechanisms by which nickel compounds induce tumors are not yet well understood. The present study found that exposure of cells to either Ni(3)S(2) or NiCl(2) could result in specific transactivation of nuclear factor of activated T cells (NFAT), although it did not show any activation of p53 or AP-1. Furthermore, nickel compounds were also able to cause generation of reactive oxygen species (ROS). The scavenging of nickel-induced H(2)O(2) with N-acety-L-cyteine (a general antioxidant) or catalase, or the chelation of nickel with deferoxamine, resulted in inhibition of NFAT activation. In contrast, pretreatment of cells with sodium formate (an .OH radical scavenger) or superoxide dismutase (an O(-.)(2) radical scavenger) did not show any inhibitory effects. These results demonstrate that nickel compounds are able to induce NFAT activation, and that the mechanism of NFAT activation seems to be mediated by the generation of H(2)O(2) by these metal compounds. This study should help us understand the signal transduction pathways involved in carcinogenic effects of these nickel compounds.

Acetylcysteine↗

The histone deacetylase inhibitor trichostatin A reduces nickel-induced gene silencing in yeast and mammalian cells.

We have previously reported that nickel (Ni)-silenced expression of the URA3 gene in yeast (Saccharomyces cerevisiae) and gpt transgene in G12 Chinese hamster cells. In both cases, close proximity to a heterochromatic region was required for gene silencing. Yeast exposed to Ni exhibited reduced acetylation of the lysine residues in the N-terminal tail of histone H4. Ni-induced silencing of the gpt gene in mammalian cells involved hypermethylation of promoter region DNA. Yeast do not employ DNA methylation to silence gene expression. To determine if histone deacetylation participates in Ni-induced silencing of the URA3 and gpt genes, we exposed yeast and G12 hamster cells to the histone deacetylase inhibitor trichostatin A (TSA) prior to and concurrently with Ni. Treatment of yeast cells with 0.2-0.6mM NiCl(2) resulted in reduced expression of the URA3 gene as assessed by increased resistance to 1g/l 5-fluorotic acid (5-FOA). This effect was lessened when yeast were pre-treated with 50 microg TSA/ml. Similarly, treatment of G12 cells with 5 ng/ml TSA during and after exposure to 0.3 microg Ni(3)S(2)/cm(2) reduced silencing of the gpt gene as gauged by resistance to 10 microg/ml 6-thioguanine (6-TG). The ability of TSA alone and in combination with the DNA-demethylating agent (5-AzaC) to reactivate the gpt gene in Ni-silenced variants was also assessed. Although treatment with 100 ng/ml TSA for 48 h was partially effective in reactivating the gpt gene, treatment with 5 microM 5-AzaC was more efficacious. The greatest gpt gene reversion frequencies were observed following a sequential 5-AzaC/TSA treatment. Taken all together, our data from mammalian cells suggests that both DNA methylation and histone deacetylation participate in Ni-induced silencing of the gpt gene with DNA hypermethylation playing the more dominant role in maintaining the silenced state.

Acetylation↗

Plasmid transcriptional repressor CopG oligomerises to render helical superstructures unbound and in complexes with oligonucleotides.

CopG is a 45 amino acid residue transcriptional repressor involved in the copy number control of the streptococcal plasmid pMV158. To do so, it binds to a DNA operator that contains a 13 bp pseudosymmetric DNA element. Binding of CopG to its operator results in repression, at the transcriptional level, of its own synthesis and that of the initiator of replication protein, RepB. Biochemical experiments have shown that CopG co-operatively associates to its target DNA at low protein:DNA ratios, completely protecting four helical turns on the same face of the double helix in both directions from the inverted repeat that constitutes the CopG primary target. This has been correlated with a CopG-mediated DNA bend of about 100 degrees. Here, we show that binding of CopG to DNA fragments containing the inverted repeat just at one end led to nucleation of the protein initiating from the inverted repeat. Nucleation extended to the entire fragment, with CopG-DNA contacts occurring on the same face of the DNA helix. The protein, the prototype for a family of homologous plasmid repressors, displays a homodimeric ribbon-helix-helix arrangement. It polymerises within the unbound crystal to render a continuous right-handed protein superhelix of homodimers, around which a bound double-stranded (ds) DNA could wrap. We have solved the crystal structure of CopG in complex with a 22 bp dsDNA oligonucleotide encompassing the cognate pseudosymmetric element. In the crystal, one protein tetramer binds at one face of the DNA with two parallel beta-ribbons inserted into the major groove. The DNA is bent about 50 degrees under compression of both major and minor grooves. A continuous right-handed complex helix made up mainly by protein-protein and some protein-DNA interactions is observed. The protein-protein interactions involve regions similar to those observed in the oligomerisation of the native crystals and those employed to set up the functional tetramer. A previously solved complex structure of the protein with a 19 bp dsDNA had unveiled a left-handed helical superstructure just made up by DNA interactions.

Bacterial Proteins↗

Synthesis and biological activity of 7-oxo substituted analogues of 5-deaza-5,6,7,8-tetrahydrofolic acid (5-DATHF) and 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF).

We recently described the syntheses of 12a-c, 4-amino-7-oxo substituted analogues of 5-deaza-5,6,7,8-tetrahydrofolic acid (5-DATHF), and 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF), in six steps from commercially available p-substituted methyl benzoates in 20-27% overall yields. Such analogues were tested in vitro against CCRF-CEM leukemia cells and showed that they are completely devoid of any activity, the IC(50) being higher than 20 microg/mL for all cases. To clarify if the presence of the carbonyl group in position C7, the distinctive feature of our synthetic methodology, is the reason for this lack of activity, we have now obtained the 7-oxo substituted analogues of 5-DATHF and DDATHF, 18a-c, in 10-30% overall yield. Testing of 18a-c in vitro against CCRF-CEM leukemia cells revealed that these compounds are totally inactive. A molecular modeling study of 18b inside the active site of the complex E. coliGARTFase-5-DATHF-GAR pointed to an electronic repulsion between the atoms of the 7-oxo group and the carbonyl group of Arg90 as a possible explanation for the inactivity of 18a-c.

Antineoplastic Agents↗

Regulation of DAF-2 receptor signaling by human insulin and ins-1, a member of the unusually large and diverse C. elegans insulin gene family.

The activity of the DAF-2 insulin-like receptor is required for Caenorhabditis elegans reproductive growth and normal adult life span. Informatic analysis identified 37 C. elegans genes predicted to encode insulin-like peptides. Many of these genes are divergent insulin superfamily members, and many are clustered, indicating recent diversification of the family. The ins genes are primarily expressed in neurons, including sensory neurons, a subset of which are required for reproductive development. Structural predictions and likely C-peptide cleavage sites typical of mammalian insulins suggest that ins-1 is most closely related to insulin. Overexpression of ins-1, or expression of human insulin under the control of ins-1 regulatory sequences, causes partially penetrant arrest at the dauer stage and enhances dauer arrest in weak daf-2 mutants, suggesting that INS-1 and human insulin antagonize DAF-2 insulin-like signaling. A deletion of the ins-1 coding region does not enhance or suppress dauer arrest, indicating a functional redundancy among the 37 ins genes. Of five other ins genes tested, the only other one bearing a predicted C peptide also antagonizes daf-2 signaling, whereas four ins genes without a C peptide do not, indicating functional diversity within the ins family.

Amino Acid Sequence↗

A role for Drosophila SMC4 in the resolution of sister chromatids in mitosis.

BACKGROUND: Faithful segregation of the genome during mitosis requires interphase chromatin to be condensed into well-defined chromosomes. Chromosome condensation involves a multiprotein complex known as condensin that associates with chromatin early in prophase. Until now, genetic analysis of SMC subunits of the condensin complex in higher eukaryotic cells has not been performed, and consequently the detailed contribution of different subunits to the formation of mitotic chromosome morphology is poorly understood. RESULTS: We show that the SMC4 subunit of condensin is encoded by the essential gluon locus in Drosophila. DmSMC4 contains all the conserved domains present in other members of the structural-maintenance-of-chromosomes protein family. DmSMC4 is both nuclear and cytoplasmic during interphase, concentrates on chromatin during prophase, and localizes to the axial chromosome core at metaphase and anaphase. During decondensation in telophase, most of the DmSMC4 leaves the chromosomes. An examination of gluon mutations indicates that SMC4 is required for chromosome condensation and segregation during different developmental stages. A detailed analysis of mitotic chromosome structure in mutant cells indicates that although the longitudinal axis can be shortened normally, sister chromatid resolution is strikingly disrupted. This phenotype then leads to severe chromosome segregation defects, chromosome breakage, and apoptosis. CONCLUSIONS: Our results demonstrate that SMC4 is critically important for the resolution of sister chromatids during mitosis prior to anaphase onset.

Alleles↗

The interpersonal context of romantic autonomy in adolescence.

This study explored the interpersonal context of romantic autonomy in mid adolescence by examining within-relationship links with romantic intimacy and affiliation, links across relationships with mothers and friends, and individual differences due to age and gender. Two hundred and thirty adolescents in grades 9, 10 and 11 with a current romantic partner, completed self-report questionnaires assessing their relationships. The results indicated that romantic autonomy was positively linked to romantic intimacy and affiliation, although this link differed according to the duration of the romantic relationship. The results also indicated that romantic autonomy was higher among girls than boys. Finally, romantic autonomy was uniquely linked to intimacy and autonomy in both maternal and friend relationships. Overall, this study highlights the interconnection of intimacy and autonomy in romantic relationships and the interconnections across relationships.

Adolescent↗

Methylmercury and total mercury in estuarine organisms from Rio de Janeiro, Brazil.

Guanabara Bay (GB), located in the Rio de Janeiro State, is still a productive estuary on the south-eastern Brazilian coast. It is an ecosystem heavily impacted by organic matter, oil and a number of other toxic compounds, including Hg. The present study aimed to comparatively evaluate the aquatic total mercury (THg) and MeHg contamination, and the ratios of MeHg to THg (% MeHg), in 3 species of marine organisms, Micropogonias furnieri-carnivorous fish (N = 81), Mugil spp.--detritivorous fish (N = 20) and Perna perna--filter-feeding bivalves (N = 190), which are widely consumed by the population. A total of 291 specimens were collected at the bay in different periods between 1988 and 1998. THg concentrations were determined by cold vapour AAS with stannous chloride as a reducing agent. MeHg was extracted by dithizone-benzene and measured by GC-ECD. Analytical quality was checked through certified standards. All organisms presented both low THg and MeHg concentrations and they were below the maximum limit of 1,000 micrograms Hg.kg-1 wet wt. as established for human intake of predatory fish by the new Brazilian legislation. Carnivorous fish showed higher THg and MeHg concentrations, and also % MeHg in muscle tissues, than organisms with other feeding habits and lower trophic levels. The average of THg concentrations in carnivorous fish was 108.9 +/- 58.6 micrograms.kg-1 wet wt. (N = 61) in 1990 and 199.5 +/- 116.2 micrograms.kg-1 wet wt. (N = 20) in 1998, but they presented different total length and body weights. The average THg content in detritivorous fish was 15.4 +/- 5.8 micrograms.kg-1 wet wt., whereas THg concentrations ranged from 4.1 to 53.5 micrograms.kg-1 wet wt. for the molluscs. The THg and MeHg contents of mussel varied according to the sampling point and water quality. MeHg concentration in detritivorous fish was similar to MeHg concentration in molluscs, but there was a significant difference in the MeHg/THg ratio: the carnivorous fish presented higher MeHg percentages (98%) than the detritivorous fish (54%) and the molluscs (33%). Weight-normalised average concentration of THg in carnivorous fish collected in 1990 (0.18 +/- 0.08 microgram.g-1/0.7 kg wet wt.) and in 1998 (0.16 +/- 0.09 microgram.g-1/0.7 kg wet wt.) presented no significant difference (t = 1.34; P < 0.5). In conclusion, the low THg and MeHg concentrations in the organisms from the GB ecosystem, are related to its eutrophic conditions and elevated amounts of suspended matter. In this situation, Hg could be strongly complexed or adsorbed by the particulate, which would dilute the Hg inputs and reduce its residence time in the water column, with a consequent decrease in its availability to organisms.

Animals↗

Total and methylmercury levels of a coastal human population and of fish from the Brazilian northeast.

A descriptive exposure survey was conduced at Santa Cruz Channel, Pernambuco, Brazil, to assess the possible risk of mercury contamination to which a coastal human population could be exposed through fish consumption. The area was formerly known to be contaminated due to a chlor-alkali plant installed along one of the tributaries of the channel. The values for total and methylmercury were measured in human hair from inhabitants of Itapissuma (1.9 +/- 1.6 ng THg/mg and 1.2 +/- 1.0 ng MHg/mg--mean values), a coastal fishing village, and fish (Mugil sp.) catch in the area (26.9 +/- 26.1 ng THg/g and 19.6 +/- 16.0 ng MHg/g--mean values). Both human hair and fish muscle presented relatively low values for total and methylmercury concentrations. These were found to be well within the average when compared to other Brazilian coastal environments.

Animals↗

Ni(II) and Cu(II) binding with a 14-aminoacid sequence of Cap43 protein, TRSRSHTSEGTRSR.

The tetradecapeptide containing the 10 aminoacid repeated sequence on the C-terminus of the Ni(II)-induced Cap43 protein, was analyzed for Ni(II) and Cu(II) binding. A combined pH-metric and spectroscopic UV-VIS, EPR, CD and NMR study of Ni(II) and Cu(II) binding to the blocked CH3CO-Thr-Arg-Ser-Arg-Ser-His-Thr-Ser-Glu-Gly-Thr-Arg-Ser-Arg-NH2 (Ac-TRSRSHTSEGTRSR-Am) peptide, modeling a part of the C-terminal sequence of the Cap43 protein, revealed the formation of octahedral complexes involving imidazole nitrogen of histidine, at pH 5.5 and pH 7 for Cu(II) and Ni(II), respectively; a major square planar 4N-Ni(II) complex (about 100% at pH 9, log K* = -28.16) involving imidazole nitrogen of histidine and three deprotonated amide nitrogens of the backbone of the peptide was revealed; a 3N-Cu(II) complex (maximum about 70% at pH 7, log K*=-13.91) and a series of 4N-Cu(II) complexes starting at pH 5.5 (maximum about 90% at pH 8.7, log K* = -21.39 for CuH(-3)L), were revealed. This work supports the existence of a metal binding site at the COOH-terminal part of the Cap43 peptide.

Amino Acid Sequence↗

Involvement of Erks activation in cadmium-induced AP-1 transactivation in vitro and in vivo.

Cadmium is a potent and effective carcinogen in rodents and has recently been accepted by IARC (International Agency for Research on Cancer) as a category I carcinogen. Cadmium-induced up-regulation of intracellular signaling pathways leading to increased mitogenesis is thought to be a major mechanism for the carcinogenic activity following chronic cadmium exposure. In the present study, we found that exposure of cells to cadmium induced significant activation of AP-1 and all three members of the MAP kinase family in mouse epidermal JB6 cells. The induction of AP-1 activity by cadmium appears to involve activation of Erks, since the induction of AP-1 activity by cadmium was blocked by pretreatment of cells with PD98058. Interestingly, the induction of AP-1 by cadmium was greatly enhanced by the chemical tumor promoter, TPA and the growth factor EGF, but not by ultraviolet C radiation. In vivo studies demonstrated that cadmium could also induce transactivation of AP-1 in AP-1-luciferase report transgenic mice. Considering the role of AP-1 activation in tumor promotion, the results presented in this study provide a possible molecular mechanism for cadmium-induced carcinogenesis.

Animals↗

Identification of a new HLA-DRB1 allele (DRB1*0318) in three members of a Caucasian Spanish family.

This communication reports the identification of a new allele HLA-DRB1*03 in three members of a Caucasian Spanish family. The new allele has been officially named HLA-DRB1*0318 by the World Health Organization Nomenclature Committee. The exon 2 sequence of this new allele is identical to that of DRB1*03011 except for the first nucleotide of codon 45. The nucleotide change (C replacing G) leads to the amino acid substitution of glycine to arginine (GGG-->CGG) at position 45. This position of the beta1 domain shows very little polymorphism among DRB1* alleles (nucleotide changes at this position have only been reported for DRB1*1436 and DRB1*0105) and locates in the vicinity of the highly polymorphic position 47, which is a constituent of the groove's pocket interacting with the amino acid position 7 of the antigen peptide. The familial study showed that the new allele was maternally transmitted into the HLA-A*3002, -B*1801, -Cw*0501, -DRB1*0318, -DRB3*0202, -DQB1*0201 haplotype. Interestingly, the two siblings of the family, which were HLA identical and suffered of insulin-dependent diabetes mellitus (IDDM), were carriers of the two HLA haplotypes (DRB1*03/DQB1*0201 and DRB1*04/DQB1*0302) reported as susceptibility markers to IDDM in Caucasians.

Alleles↗

The gene mutated in ataxia-ocular apraxia 1 encodes the new HIT/Zn-finger protein aprataxin.

The newly recognized ataxia-ocular apraxia 1 (AOA1; MIM 208920) is the most frequent cause of autosomal recessive ataxia in Japan and is second only to Friedreich ataxia in Portugal. It shares several neurological features with ataxia-telangiectasia, including early onset ataxia, oculomotor apraxia and cerebellar atrophy, but does not share its extraneurological features (immune deficiency, chromosomal instability and hypersensitivity to X-rays). AOA1 is also characterized by axonal motor neuropathy and the later decrease of serum albumin levels and elevation of total cholesterol. We have identified the gene causing AOA1 and the major Portuguese and Japanese mutations. This gene encodes a new, ubiquitously expressed protein that we named aprataxin. This protein is composed of three domains that share distant homology with the amino-terminal domain of polynucleotide kinase 3'- phosphatase (PNKP), with histidine-triad (HIT) proteins and with DNA-binding C2H2 zinc-finger proteins, respectively. PNKP is involved in DNA single-strand break repair (SSBR) following exposure to ionizing radiation and reactive oxygen species. Fragile-HIT proteins (FHIT) cleave diadenosine tetraphosphate, which is potentially produced during activation of the SSBR complex. The results suggest that aprataxin is a nuclear protein with a role in DNA repair reminiscent of the function of the protein defective in ataxia-telangiectasia, but that would cause a phenotype restricted to neurological signs when mutant.

Amino Acid Sequence↗

Neuronal control of the pyloric sphincter of the guinea-pig.

The pyloric sphincter (PS) controls gastric emptying and prevents the reflux of duodenal content into the stomach. Neuronal pathways and reflexes controlling the guinea-pig PS were physiologically investigated in isolated preparations. Simultaneous intracellular or extracellular and tension recordings from PS circular muscle with electrical and stretch stimulation were used. Electrical stimulation evoked an initial small contraction followed by a relaxation with a corresponding inhibitory junction potential (IJP) then a second large contraction with a corresponding excitatory junction potential (EJP). Hyoscine (1 micromol L-1) blocked the first contraction, and reduced the second contraction and EJP by 52.5% and 61%, respectively. These responses were further reduced by the NK2 antagonist, MEN10627 (1 micromol L-1), and the NK1 antagonist, SR140333 (1 micromol L-1). N-nitro-L-arginine (100 micro;mol L-1) and apamin (0.5 micromol L-1) blocked the relaxation and the IJP. Duodenal electrical stimulation evoked an EJP, whereas antral stimulation evoked an IJP followed by a small EJP. All were blocked by hexamethonium (100 micromol L-1). Duodenal stretch evoked tetrodotoxin-sensitive reflex contractions and membrane depolarization with action potentials in the PS. Thus, PS enteric motor neurones receive inputs from the duodenum and the stomach. There are stretch-sensitive ascending excitatory reflex pathways from the duodenum to the PS.

Acetylcholine↗

Analysis of motor patterns in the isolated guinea-pig large intestine by spatio-temporal maps.

We investigated and quantified the spontaneous patterns of motility in the isolated guinea-pig proximal and distal colon taken from adult animals. During spontaneous emptying, profiles of proximal and distal colon were recorded with a video camera, and image analysis was used to construct spatio-temporal maps of the motions of the intestinal wall. Four patterns of motility were recorded. In the proximal colon there were neurally mediated contractions that propagated in the aboral direction at 4.1 mm s(-1), gently pushing the soft contents aborally; these are likely to represent spontaneous peristaltic behaviour. A second pattern, insensitive to tetrodotoxin (TTX; 0.6 microM), consisted, in both oral and aboral propagation, of shallow contractions of the circular muscle (ripples). These contractions propagated aborally at 2.8 +/- 0.45 mm s(-1) and orally at 2.03 +/- 0.31 mm s(-1) (n=10). Of these TTX-resistant contractions, 22.5% propagated both orally and aborally from a common origin. The orally propagated component of these myogenic contractions is likely to correspond to the antiperistalsis widely described in the proximal colon. In the distal colon, two patterns of motor activity were observed. One, induced by natural or artificial pellets, consisted of peristaltic contractions that pushed the pellets aborally at 0.8 mm s(-1) and expelled a pellet every 108 s. In the interval between pellet propulsion and after the distal colon had emptied all of its pellets a second, nerve-mediated pattern of motor activity, consisting of clusters of annular circular muscle contractions separated by short dilated regions, slowly propagated aborally at 0.3 mm s(-1). Both of these motor patterns were abolished by TTX (0.6 microM). A latex balloon, inserted at the oral end of the empty isolated distal colon and inflated to a size similar to faecal pellets, was propelled at 1.4 mm s(-1). Epoxy resin-covered natural pellets were propelled at a similar speed of 1.6 mm s(-1). Our data revealed that myogenic and neurogenic patterns of propagated contractions in the colon occur in isolated preparations and are involved in emptying the colon.

Animals↗

Propagating contractions of the circular muscle evoked by slow stretch in flat sheets of guinea-pig ileum.

Flat sheet preparations of guinea-pig ileum were stretched circumferentially and the propagation of circular muscle contractions along the preparation was investigated. Slow stretch, at 100 microm s-1, of a 50-mm long flat sheet of intestine, evoked circular muscle contraction orally, which propagated, without decrement, for up to 30 mm. This occurred despite circular muscle shortening being prevented, and in the absence of propulsion of contents. Thus, propagation in this flat sheet preparation could not explained on the basis of neuro-mechanical interactions, as previously proposed. Irrespective of the length of preparations, contraction amplitude decreased significantly in the most aboral 10-15 mm of intestine. This was not due to descending inhibitory pathways, but was associated with interruption of ascending excitatory pathways near the aboral end. Slow waves were not detected in circular muscle cells in any preparation (n=8). Smooth muscle action potentials evoked in circular muscle cells, in the presence of tetrodotoxin (TTX, 0.6 micromol L-1), did not propagate for more than 1 mm in the longitudinal axis. Propagation of circular muscle activity, evoked by slow stretch of flat sheet preparations, reveals the presence of a mechanism other than myogenic spread or the neuro-mechanical interactions previously proposed to account for propagation; the nature of this mechanism remains to be determined.

Action Potentials↗