Biomedical subjects

A Romero

Publications and source records attributed to A Romero.

At least 19 recordsLinked to original sources

PubMed1992

Voltage-gated potassium current and resonance in the toadfish saccular hair cell.

Resonance of the membrane potential in response to a perturbing current has been demonstrated in sensory hair cells of many acoustico-lateralis systems and modelled as the result of the interaction of passive membrane properties and the magnitude and kinetics of activation and deactivation of an outward calcium-activated potassium current (IKCa) and an inward calcium current (ICa). However, the majority of the hair cells of the toadfish saccule have, in addition to IKCa, a voltage-gated potassium current (IK) active in the same membrane potential range as IKCa but with considerably slower activation and deactivation kinetics. Additionally, some of these cells have an A current (IA). In the present work, the resonance of cells with these three outward potassium currents were compared with those from cells containing only IKCa. Hair cells with only IKCa produced a high-quality factor (Q) resonance with symmetrical ringing at current onset and termination. In many cells having the IK, resonance could be evoked as a high Q ringing only at the onset of the current pulse. The resonance at command onset was dependent on the presence of IKCa and could be converted into a spike by blocking the IKCa with TEA. Some hair cells with IKCa and IK produced spikes rather than resonance at all holding potentials tested. This spiking was seen in cells with low levels of IKCa or slowly activating IKCa and with cells with IA. The presence of cells with such different response modes implies a difference between hair cells in their role in sensory coding.

Acoustic Maculae↗

PubMed1992

Relationship between fetal weight and litter size in rats: application to reproductive toxicology studies.

The inverse relationship between mammalian fetal weight and litter size has been discussed by many authors, but their opinions reveal no agreement at all. As in toxicity studies of reproduction, both parameters must be correctly evaluated. We investigated the existence of such a relationship in 2466 fetuses from 203 litters of Sprague-Dawley CD control rats. The frequency distribution of fetal weights had a normal adjustment. From the mean weight of fetuses in each litter, the mean fetal weights in each litter size and correlation coefficient were calculated and the regression line was plotted; the correlation coefficient (r = 0.677) was highly significant (P = 0.002), which made evident that there was an inverse relationship between fetal weight and litter size. If fetal weight/litter size inverse relationship is not taken into account when toxicity on the fetal weight is analyzed, wrong conclusions may be reached if the test substance reduces the litter size, provoking embryofoetal mortality. The iatrogenic decrement in fetal weight can be masked by an increment due to the litter size reduction. We suggest that in all three segments of reproductive toxicity studies, litter size must be considered as a covariate to the effect of the test substance on the fetal weight, in order to perform a correct analysis of covariance (ANCOVA), in addition to the dose factor commonly used in common ANOVA.

Animals↗

PubMed1992

Ethinyl estradiol-induced cell proliferation in rat liver. Involvement of specific populations of hepatocytes.

Hepatocyte proliferation was analyzed in vivo during the time course of continuous administration to rats of the liver tumor promoter ethinyl estradiol (EE) at 10 p.p.m. in the diet. EE-induced acute liver hyperplasia was detected in male and female Sprague-Dawley rats as an increased mitotic index of hepatocytes after 2 days of treatment. 5'-Bromodeoxyuridine (BrdU) labeling showed that proliferating hepatocytes were randomly distributed throughout the hepatic lobule. Subsequently, and still during the first few days of continuous EE treatment, hepatocyte proliferation decreased to control levels, and a transient increase in the incidence of apoptosis in the liver was detected. Although consistent with the concept of liver growth regression after mitogen-induced hyperplasia, these results differ from others reported to date in that, in our experiments, the cessation of cell proliferation and the subsequent growth regression occurred without withdrawal of EE in our experiments. After returning to control levels, hepatocellular proliferation again increased between 3 and 6 months of chronic treatment and remained activated during the following months of continuous treatment, as seen by accumulative BrdU labeling. Proliferating hepatocytes were predominantly located in zone 2 of the hepatic lobule at this time, surrounding a periportal zone of vacuolated hepatocytes, which were also induced by the treatment. Moreover, hyperplasia of basophilic hepatocytes was also seen around some portal spaces. In another set of experiments, chronic EE-induced activation was characterized by flow cytometry on hepatocytes isolated from male Fischer rats. Ploidy analysis of hepatocyte cell suspensions showed that the normal polyploid pattern of hepatocytes was altered by EE, the proportion of diploid hepatocytes rising considerably. The results also showed that these diploid cells were the most susceptible hepatocyte population to EE-induced proliferation, as shown by a combination of BrdU labeling and cell sorting methods. In contrast to Sprague-Dawley rats, no vacuolated cells were found histologically in the livers of these animals and the proliferating hepatocytes were located adjacent to the portal areas. These results taken together support the existence of cell target populations in the liver responding to the effects of tumor promoters. The finding that a subpopulation of diploid hepatocytes was the liver cell class most susceptible to proliferation during chronic EE treatment may explain, at least in part, the behavior of EE as a tumor promoter in hepatocarcinogenesis.

Animals↗

PubMed1992

Actinic prurigo.

Explore the source record for details and available documents.

Conjunctival Diseases↗

PubMed1992

The insertion site of the temperate phage HB-746 is located near the phage remnant in the pneumococcal host chromosome.

Combined Southern blot hybridization analyses of DNA digests of several clinical strains of Streptococcus pneumoniae have revealed the presence of a gene (hblR), or part of it, similar to the hbl7 gene coding for the cell wall lytic enzyme of the temperate HB-746 phage. The results confirmed that the genome of HB-746, which contains protein covalently linked to the 5' ends of its DNA, becomes integrated into the host strain 8R1 and showed that both the host and phage attachment sites, attB and attP, lie downstream of the 3' end of the structural region of the hblR and hbl7 genes, respectively. The data reported also highlight some evolutionary relationships between phage and bacteria.

Bacteriophages↗

PubMed1992

Development and validation of prognostic models in metastatic breast cancer: a GOCS study.

The significance of several prognostic factors and the magnitude of their influence on response rate and survival were assessed by means of uni- and multivariate analyses in 362 patients with stage IV (UICC) breast carcinoma receiving combination chemotherapy as first systemic treatment over an 8-year period. Univariate analyses identified performance status and prior adjuvant radiotherapy as predictors of objective regression (OR), whereas the performance status, prior chemotherapy and radiotherapy (adjuvants), white blood cells count, SGOT and SGPT levels, and metastatic pattern were significantly correlated to survival. In multivariate analyses favorable characteristics associated to OR were prior adjuvant radiotherapy, no prior chemotherapy and postmenopausal status. Regarding survival, the performance status and visceral involvement were selected by the Cox model. The predictive accuracy of the logistic and the proportional hazards models was retrospectively tested in the training sample, and prospectively in a new population of 126 patients also receiving combined chemotherapy as first treatment for metastatic breast cancer. A certain overfitting to data in the training sample was observed with the regression model for response. However, the discriminative ability of the Cox model for survival was clearly confirmed.

Analysis of Variance↗

PubMed1992

Acute toxicity studies of sertaconazole.

The acute toxicity of 7-chloro-3-[1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethoxy- methyl]benzo[b]thiophene (sertaconazole, FI-7045, CAS 99592-32-2) was evaluated in mice and rats after single administration by oral, subcutaneous and intraperitoneal routes. The latter intended to ensure maximum blood levels, since intravenous route was unfeasible due to drug insolubility in water. LD50 was indeterminable (greater than 8000 mg/kg) in all routes of dosing. According to these results, and having furthermore proved the absorption of the test substance after oral administration, sertaconazole was concluded to be very safe in the event of overdose or accidental ingestion.

Administration, Oral↗

PubMed1992

Subacute toxicity and maximum tolerable dose of sertaconazole in repeated administration studies.

28-Day oral and dermal subacute toxicity studies of 7-chloro-3-[1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl) ethoxy-methyl] benzo [b] thiophene (sertaconazole, FI-7045, CAS 99592-32-2), were carried out. The oral studies included the evaluation of subacute toxicity in rat (dose levels of 50, 150 and 300 mg/kg) and maximum tolerable dose in repeated administration in ferrets (consecutive dose levels in accordance with a geometric progression of 50, 75, 112.5, 168 and 250 mg/kg), which were the animal species intended for chronic toxicity studies. The dermal studies included the evaluation of subacute toxicity in rats and rabbits (1 ml/kg of a 2% cream). The results, in general, have shown low toxic effects, which can be summarized as a slight non-significant hepatomegalia in the rat with increased gamma-GTP and alkaline phosphatase values and a high urinary pH value; no histopathological changes were observed. These effects are characteristic of azole derivatives and are therefore common to other antifungals with this chemical group.

Administration, Oral↗

PubMed1992

Chronic toxicity studies of sertaconazole after oral administration to rats and ferrets.

Six-month chronic oral toxicity studies of 7-chloro-3-[1-(2, 4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethoxy-methyl] benzo[b]thiophene (sertaconazole, FI-7045, CAS 99592-32-2) were carried out in rats and ferrets. The dose levels used were 50, 150 and 300 mg/kg in rats and 50, 150 and 250 mg/kg in ferrets. There was no mortality associated with the drug in either of the two species. The results obtained show that the toxic effects may be summarized as a smaller body weight increase in rats at 150 and 300 mg/kg and in male ferrets at 250 mg/kg. Food consumption decreased significantly in rats at 300 mg/kg, and was not proportional to the doses of 150 and 50 mg/kg. In serum biochemistry, increases in alkaline phosphatase in rats, ALT in male ferrets at 150 and 250 mg/kg and AST only at 250 mg/kg were observed. BUN increased at 150 and 250 mg/kg in ferrets.

Animals↗

PubMed1992

Reproduction toxicity of sertaconazole. Segment II (teratology) and Segment III (peri-postnatal toxicity).

The reproduction toxicity of 7-chloro-3-[1-(2,4-dichlorophenyl)-2- (1H-imidazol-1-yl)ethoxy-methyl]benzo[b]thiophene (sertaconazole, FI-7045, CAS 99592-32-2) (50, 100 and 150 mg/kg by oral route) has been investigated by performing two studies: the embryotoxicity or teratology study in rats and rabbits, and the peri-postnatal toxicity study in rats. According to the results obtained from the embryotoxicity studies, there was no maternal toxicity in either of the two species studied. The only embryofoetal abnormalities with statistical and toxicological significance were observed at the dose of 150 mg/kg in the teratology study on rabbits: hepatomegalia, pericardial oedema and peritoneal and hepatic haemorrhages. The results of the peri-postnatal study showed that the only maternal effect relating to the drug was an increase, proportional to the dose, in the weight of the ovaries, which was significant at the dose of 150 mg/kg. With reference to the offspring, only a reduction in the viability index at 150 mg/kg was observed. The non observed effects level (NOEL) for all three studies can be estimated at 100 mg/kg.

Aging↗

PubMed1992

Genotoxicity studies on sertaconazole.

A series of 6 studies has been performed to evaluate the potential genotoxic effect of 7-chloro-3-[1-(2,4-dichlorophenyl)-2-(1H- imidazol-1-yl)ethoxy-methyl]benzo[b]thiophene (sertaconazole, FI 7045, CAS 99592-32-2). From these studies, the reverse mutation assay on Salmonella typhimurium, sex-linked recessive lethal mutations on Drosophila and genetic mutations in cultured mammal cells allowed to study the genetic mutations in prokaryotes and eukaryotes. In vitro and in vivo chromosomal aberrations were studied using human lymphocytes cytogenetic test, micronucleus test and sister chromatid exchange test. The results obtained in these studies, which are complemented one another, demonstrated that sertaconazole did not induce any signs of promutagenic, mutagenic or clastogenic activity or interference with the chromosomal segregation process.

Animals↗

PubMed1992

Dermal tolerance and phototoxicity studies of sertaconazole.

The local dermal tolerance of 7-chloro-3-[1-(2,4-dichlorophenyl)-2-(1H- imidazol-1-yl)ethoxy-methyl]benzo[b] thiophene (sertaconazole, FI 7045, CAS 99592-32-2) was evaluated in hairless rats and albino rabbits. Test substance was applied in 2% powder (0.5 g), gel (0.5 ml) and solution (0.5 ml) formulations to rats (this is the concentration intended for the pharmaceutical preparation) and in 6% cream (0.5 ml) to rabbits (this concentration was used to estimate an overdose maximal effect). After 3- and 24-h exposure of the test substance to animals, they were observed for erythema and oedema. Sertaconazole may be considered as non irritant, since its primary irritation index was less than 0.5 in all the tests. A phototoxicity study was also carried out on guinea pigs with 1 ml 2% cream per animal, compared with psoralene as a positive control. Sertaconazole did not present any risk, since the phototoxicity level reached was null, with 2 being the minimum value considered as having toxic significance.

Animals↗

PubMed1991

Initiation of translation at AUC, AUA and AUU codons in Escherichia coli.

A truncated form of the HBL murein hydrolase, encoded by the temperate bacteriophage HB-3, was cloned in a pUC-derivative and translated in Escherichia coli using AUC as start codon, as confirmed by biochemical, immunological, and N-terminal analyses. Using site-directed mutagenesis, we have changed this AUC codon into AUA, AUU and AUG codons. The relative translation efficiencies for these triplets were about 5% for AUC and AUU and 7.5% for AUA compared to that of AUG codon. In the same gene arrangement E. coli beta-galactosidase was also translated at moderate efficiency using AUC as initiator.

Amino Acid Sequence↗

PubMed1991

Presenting features and prognosis of chronic lymphocytic leukemia in younger adults.

We have analyzed 117 younger patients with chronic lymphocytic leukemia (CLL) (mean age, 44.5 years; SD, 4.8; range, 19 to 49; male/female ratio, 2.08) with three main objectives: (1) to see whether these patients have distinctive presenting clinical features; (2) to investigate the impact of the disease on survival; and (3) to analyze whether already well-known prognostic factors are also useful when applied to these patients. As compared with an older age population (greater than or equal to 50 years), there were no major differences in presenting features except for an increased proportion of males (2.08 v 1.21; P less than .025) and a higher hemoglobin level (13.47 +/- 2.70 g/dL v 12.84 +/- 2.77 g/dL; P less than .05) in the younger group. Median survival is 12.3 years (expected median from a control group, 31.2 years). Clinical stages, bone marrow patterns, blood lymphocyte counts, and its doubling time are all useful to separate different risk groups of patients. Whereas patients with favorable prognostic factors have a survival probability of about 80% 14 years after diagnosis, those with poor prognostic features have a median survival of less than 3 years. It is concluded that CLL in younger adults has no major distinctive presenting features and that known prognostic factors are useful to separate different risk groups of patients. These results should be of help in planning therapy for younger persons with CLL.

Adult↗

PubMed1991

Characterization of voltage-gated and calcium-activated potassium currents in toadfish saccular hair cells.

Patch clamp methods were used to study calcium activated (IKCa) and voltage-gated (IK) potassium currents in enzymatically disassociated hair cells from the saccule of the toadfish Opsanus tau. In one population of hair cells, tetraethylammonium bromide (TEA) blocked all outward current, leaving only an inward calcium current (ICa). This current blocked by TEA was also blocked by barium (5 mM) and cadmium (0.2 mM) but only partially blocked by zero external calcium. In the majority of the cells, after TEA (25 mM) was used to block IKCa, a second outward current remained. This current was resistant to block by apamin, barium (5 mM) and cadmium (0.2 mM). Its kinetics of activation and deactivation were considerably slower than those of IKCa. Because of the current/voltage characteristics, its resistance to block by the above agents and voltage-gated activation, this current was termed IK. Study of the rates of activation and deactivation of the two currents in hair cells exhibiting either fast or slow total outward current activation showed that these two kinetic parameters were linked in a cell, i.e., cells with fast IKCa kinetics exhibit faster IKCa kinetics than cells with slower IKCa kinetics. Cell attached and inside out recordings showed a high conductance channel with short open times and a lower conductance channel with longer open times active over the same voltage ranges as those seen in whole cell recordings. Since these two currents with quite different but linked kinetics are active over the same voltage range, their co-existence may be of some importance to sensory coding in the hair cells.

4-Aminopyridine↗

PubMed1991

Cell proliferation and tumour promotion by ethinyl estradiol in rat hepatocarcinogenesis.

A two-stage model of hepatocarcinogenesis is used to study the effect of exposure time to ethinyl estradiol (EE) on promotion of preneoplastic lesions in rat liver induced by diethylnitrosamine (DEN). Young male and female Sprague-Dawley rats initiated by a single dose of DEN (100 mg/kg) were subjected to different times of EE administration incorporated into the diet at 10 p.p.m. (0.5 mg/kg x day). Animals were killed 1 year after initiation. Whereas macroscopic tumours were rarely seen in animals with short exposure (3 or 4 months) or in only-initiated controls, all the animals under a long period of administration (8 months) showed macroscopic tumours. Morphometric studies on glutathione-S-transferase (GST) positive preneoplastic lesions revealed an increase in the mean size of foci and nodules corresponding to 8 months of treatment, whereas no changes were observed between animals with short exposure and only-initiated controls. No differences were seen in the incidence of these lesions between any of the protocols. In addition to an acute hyperplastic effect on non-initiated liver described earlier, our preliminary results suggest cytotoxicity and an enhancement of the liver cell turnover after several months of continuous EE administration. These results taken together suggest that promotion of hepatocarcinogenesis by EE largely depends on the time of exposure to the compound and that chronic effects on the liver cell turnover may play an important role in its ability to promote hepatocarcinogenesis.

Animals↗

PubMed1991

Circadian variations in the superoxide production, enzyme release and neutrophil aggregation in patients with rheumatoid arthritis and controls.

Patients with rheumatoid arthritis (RA) experience fluctuations of symptoms throughout the day. These could be due to mechanical changes or modification of the inflammatory mechanisms. In the present paper we studied fluctuations of superoxide production (O2), enzyme release (beta-glucuronidase and lysozyme) and neutrophil aggregation in the peripheral blood of eight healthy volunteers and eight patients with RA. Although enzyme release was greater in patients with RA, no significant difference was found throughout the day, neither in control nor in patients. Similar results were obtained when studying neutrophil aggregation. On the contrary, the superoxide production, determined at 8:00, 14:00, and 20:00 h, was 6.3 +/- 0.5, 4.40 +/- 0.4 and 6.26 +/- 0.3, respectively, in patients with RA and 6.65 +/- 0.7, 4.7 +/- 0.7 and 7.27 +/- 0.4 in the controls. The values obtained at 14:00 h were significantly lower (alpha = 0.01). There were no differences in the curve form between patients and controls.

Arthritis, Rheumatoid↗

PubMed1991

Assessment of anomalous systemic and pulmonary venous connections by transoesophageal echocardiography in infants and children.

OBJECTIVE: To assess the value of transoesophageal echocardiography in the preoperative definition of systemic and pulmonary venous connections. DESIGN: Transoesophageal echocardiographic studies were performed prospectively under general anaesthesia in 76 consecutive unoperated children. Results were compared with those obtained by earlier transthoracic ultrasound studies (n = 76), cardiac catheterisation (n = 62), and subsequent surgical inspection (n = 58). SETTING: Two tertiary referral centres. PATIENTS: 76 unoperated infants and children (age 0.2-14.8 years, mean age 4.1 years) with congenital heart disease. MAIN OUTCOME MEASURE: Identification of anomalous systemic and pulmonary venous connections. RESULTS: Transoesophageal studies showed anomalous venous connections in 14 patients. Two had both anomalous systemic and pulmonary venous connections. Transoesophageal studies showed 12 anomalous systemic venous connections in nine patients. In eight patients these were confirmed at operation or catheterisation: one patient is awaiting operation. Six anomalous systemic venous connections were missed during earlier transthoracic studies. Anomalous pulmonary venous connections (one mixed total, six partial) were shown in seven patients. These were confirmed at operation in six and by cardiac catheterisation in one. Four of these patients were missed during earlier transthoracic ultrasound studies. No patient defined as having normal venous connections by the transoesophageal study was subsequently shown to have anomalous venous connections at operation or angiography. CONCLUSIONS: Transoesophageal echocardiography is a highly sensitive tool for the preoperative definition of systemic and pulmonary venous connections. In this series it was better than transthoracic ultrasound and complemented cardiac catheterisation and angiocardiography.

Adolescent↗