[Hepatic insufficiency with portal hypertension as the only clinical manifestation of primary amyloidosis].
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Biomedical subjects
Publications and source records attributed to M Vega.
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The aim of the present study was to investigate the action of insulin-like growth factor I (IGF-I) and insulin-like growth factor-binding protein 3 (IGFBP-3) on steroidogenesis and apoptosis in human corpus luteum during the midluteal phase. Slices from corpora lutea were incubated for 4 h with IGF-I or IGFBP-3. Progesterone, oestradiol, androstenedione and testosterone concentrations were determined by radioimmunoassay; caspase 3 expression was assessed by immunohistochemistry; bcl-2, bax and P(450arom) expression were assessed by RT-PCR; and apoptosis was detected by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling. The results showed that addition of IGF-I stimulated progesterone production (150%, P < 0.01), oestradiol production (65%, P < 0.05) and bcl-2 gene expression (approximately 200%, P < 0.05), but decreased apoptosis (P < 0.05). In contrast, IGFBP-3 reduced steroid production and increased bax gene expression and the percentage of apoptotic cells (P < 0.05). Neither IGF-I nor IGFBP-3 had an effect on P(450arom) expression or on the concentrations of its substrates. However, maximum expression of caspase 3 was detected in corpus luteum during the midluteal phase. In conclusion, these results indicate that IGF-I and IGFBP-3 act as regulatory peptides of the function of the human corpus luteum during the midluteal phase. This action may be direct or mediated by steroid production or by bcl-2-bax expression.
In 6-methyl-N-(4-nitrobenzoyl)-5,6-dihydropyridin-2(1H)-one, C(13)H(12)N(2)O(4), (I), the piperidone ring is in a distorted half-chair conformation. In 8-methoxy-3-methyl-N-(4-nitrobenzoyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline-1,6-dione, C(18)H(20)N(2)O(6), (II), the heterocyclic ring is in a slightly distorted half-boat conformation, while the other six-membered ring is in a distorted chair conformation. Compound (II) presents a strong intramolecular C-H...O hydrogen bond. In both (I) and (II), the molecules interact through C-H...O interactions.
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In both 9,10-dimethoxy-11-oxatricyclo[6.2.1.0(2,7)]undeca-4,9-diene-3,6-diol, C(12)H(16)O(5), (I), and 5,6-dimethoxy-3,7-dioxatetracyclo[6.4.0.0(2,6).0(4,12)]dodec-9-en-11-ol, C(12)H(16)O(5), (II), the hetero-oxygen-containing five-membered rings have an envelope conformation. The six-membered rings are in a boat conformation in compound (I), and in (II), one is in a half-boat and the other is in a slightly distorted boat conformation. The molecules in both compounds interact through classical hydrogen bonds and C-H.O contacts.
A reversed-phase liquid chromatographic method was applied to study the stability of thimerosal in Cuban recombinant hepatitis B vaccine samples stored under different temperature conditions. Salicylic acid was used as internal standard, it allowed one to determine the thimerosal in the presence of its degradation products. Good stability of the preservative was demonstrated in vaccine samples for as long as 6 years. The same results were obtained when the vaccine samples were incubated at 37 and 45 degrees C during 30 days. The results were in compliance with the microbiological test for determining the effectiveness of antimicrobial preservative in these samples.
BACKGROUND: After treatment of locally advanced laryngeal carcinomas with induction chemotherapy and radiotherapy, some patients suffer a local or regional failure of the tumor, and salvage surgery is required. The aim of this study was to review the results of such salvage surgery in this group of patients. METHODS: A retrospective study of a cohort of 110 patients diagnosed between 1989 and 1996 with a locally advanced laryngeal carcinoma (T3-T4) treated with induction chemotherapy and radiotherapy was performed. The results of salvage surgery in patients with a local and/or regional failure of the treatment were analyzed. RESULTS: Forty-two patients presented a local and/or a regional recurrence of the tumor: 26 patients in the larynx, eight in the neck, and a further eight in both in the larynx and the neck. Salvage surgery was carried out in 28 patients (67%), consisting of total laryngectomies with neck dissections (24 cases), endoscopic resection of the tumor (one case), and radical neck dissections (three cases). Five-year adjusted survival for the 42 patients was 38%. Five-year survival for the 28 patients treated with salvage surgery was 57%. Five patients had postoperative complications: four had pharyngo-cutaneous fistulas and one had wound infection. CONCLUSIONS: After a local and/or regional recurrence, 67% of patients with advanced laryngeal carcinoma treated with induction chemotherapy and radiotherapy were candidates to salvage surgery. Five-year adjusted survival for this group of patients was 57%.
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The expression of the steroidogenic acute regulatory protein (StAR) in the human corpus luteum (CL) was examined throughout the luteal phase. The primary 1.6-kb StAR transcript was in greater abundance in early (3.1-fold) and mid (2.2-fold) luteal phase CL compared with late luteal phase CL. The larger StAR transcript (4.4 kb) was found in early and midluteal phase CL, but was not detected in late luteal phase specimens. Mature StAR protein (30 kDa) was present in lower amounts within late CL compared with early and midluteal phase CL. The StAR preprotein (37 kDa) was also detected in greater abundance in early and midluteal CL. Immunohistochemistry revealed that StAR staining was most prominent in thecal-lutein cells throughout the luteal phase. The intensity of the signal for StAR exhibited significant changes throughout the luteal phase, being most intense during the midluteal phase and least during the late luteal phase. Plasma progesterone concentrations were highly correlated (r = 0.73 and r = 0.79) with luteal expression of the preprotein and mature StAR isoforms, respectively, throughout the luteal phase. To examine the LH dependency of StAR expression, the GnRH antagonist, Cetrorelix, was administered during the midluteal phase. Cetrorelix caused a decline in serum LH levels within 2 h, which, in turn, caused a pronounced decline in plasma progesterone within 6 h. The StAR 4.4-kb transcript was not detectable, and the 1.6-kb transcript was reduced by approximately 50% within 24 h of Cetrorelix treatment. The mature 30-kDa StAR protein level declined approximately 30% after Cetrorelix treatment. We conclude that 1) StAR mRNA and protein are highly expressed in early and midluteal phase CL; 2) StAR protein is present in both thecal-lutein and granulosa-lutein cells throughout the luteal phase; 3) StAR protein levels in the CL are highly correlated with plasma progesterone levels; 4) declining StAR mRNA and protein levels are characteristic of late luteal phase CL; and 5) suppression of LH levels during the midluteal phase results in a marked decline in plasma progesterone and a diminished abundance of StAR transcripts in the CL without a corresponding significant decline in StAR protein. Collectively, these data are consistent with the idea that StAR gene expression is a key determinant of luteal progesterone during the normal menstrual cycle. However, the pharmacologically induced withdrawal in the midluteal phase of LH support diminishes luteal progesterone output by mechanisms others than reduced StAR protein levels.
The presence of insulin-like growth factors (IGF), IGF binding proteins (IGFBP) and IGF receptor type 1 (IGF-IR) in the human corpus luteum was investigated by examining the expression and production of related proteins throughout the lifespan of the corpus luteum and the action of nitric oxide upon their production. The expression of proteins in corpora lutea from the early, mid-and late luteal phases was assessed by immunohisto-chemistry, evaluated by a semi-quantitative analysis and the functional study was performed in corpus luteum explants incubated with nitric oxide donors. IGF-I and -II and IGFBP-1 and -3 were measured in the culture media by specific immunoassays. The results showed that IGF-I and -II, IGFBP-1 to -6 and IGF-IR were detected in the human corpus luteum throughout the luteal phase. Moreover, the expression and production of IGF-I and IGFBP-1 increased progressively from corpora lutea from the early to late luteal phases (P < 0.05), whereas the expression and production of IGFBP-2, -4 and -5 were significantly higher in corpora lutea from the mid-luteal phase (P < 0.05). No differences were observed in the expression of IGF-II, IGFBP-3 and -6 and IGF-IR throughout the lifespan of the corpus luteum. However, functional studies showed that nitric oxide donors elicited a stimulatory action on production of IGF-I in corpora lutea from the early luteal phase (80%) and on production of IGFBP-1 in corpora lutea from the late luteal phase (50%) (P < 0.05), whereas production of IGF-II and IGFBP-3 was not affected by nitric oxide. In conclusion, the components of the IGF-IGFBP system are expressed in the human corpus luteum throughout its lifespan. Nitric oxide regulates IGF-I and IGFBP-1 production, indicating that the growth factors may serve, at least in part, as mediators of the action of nitric oxide in the human corpus luteum.
A study of the adsorptive stripping voltammetry of cadmium on a mercury drop electrode is reported in which 2-mercapto-5-phenyl-amino-1,3,4-thiadiazole (MPATD), synthesized at home has been used as a chelating agent. The most suitable operating conditions and parameters such as buffer, pH, deposition potential, deposition time, ligand concentration, scan rate and others were selected and the determination of cadmium from aqueous solutions using the standard additions method was possible. As validation criteria, the linearity and range, repeatability of the signal, repeatability of the concentration and accuracy were investigated. A limit of detection of 4.67 x 10(-10) M and a limit of quantification of 1.55 x 10(-9) M were achieved. The interference of other metals and organic substances was studied. Concerning a possible catalytic effect, no one was found. The method was designed in order to determine Cd from biological samples.
Most industrialised countries are currently drawing up their procedures to deal with contaminated land. In the Basque Country generic soil quality values applicable to different land uses have been drawn up for many common soil inorganic and organic pollutants, to assist in the site assessment process. In this paper we present those values aimed at protecting ecosystems as the main target at risk. Ecological risk was defined on the basis of effects on the structure of the soil invertebrate community. Ecotoxicological data from laboratory tests were used in combination with a theoretical extrapolation method. The following groups of compounds were assayed: heavy metals, cyanides, aromatic compounds, polycyclic aromatic hydrocarbons, HCH isomers, chlorinated organic compounds, and mineral oil. A specific toxicity database was created. The reliability of the values obtained as well as the limitations of the derivation process are discussed.
Various studies report an increase in costs when induction chemotherapy is included in the treatment of advanced laryngeal cancer, but to our knowledge no studies have yet compared the economic costs of total laryngectomy versus induction chemotherapy in the treatment of advanced laryngeal cancer. We have conducted a retrospective study comparing the costs of treatment and survival in 96 patients with a T3N0-1 glottic carcinoma. Findings showed that the average cost per patient in the group of patients treated by total laryngectomy with or without postoperative radiotherapy was 5,853 Eur, while that for the group of patients who began treatment with induction chemotherapy was 6,452 Eur. The adjusted 5-year survival for patients treated with total laryngectomy with or without postoperative radiotherapy was 80%, and 72% for patients who began treatment with induction chemotherapy. Sixteen of the 35 patients (46%) receiving induction chemotherapy were spared laryngectomy. The use of induction chemotherapy in the treatment of patients with advanced laryngeal carcinomas involved an increase in cost of 600 Eur in relation to treatment with total laryngectomy and postoperative radiotherapy. However, from an economic point of view, we consider induction chemotherapy to be an important consideration in an organ-preservation strategy.
The purpose of this study was to define the treatment of choice (partial laryngectomy vs radiotherapy) in the early stage of supraglottic squamous cell cancer (ESSC). One hundred and fifteen patients with ESSC were treated with either partial laryngectomy (25 patients) or with radiotherapy(90 patients) between January 1984 and December 1996. All patients had a follow-up of over 29 months. Radiotherapy (RT) had a local control rate of 79%, which increased to 90% with salvage surgery, and a high larynx preservation rate (83%). Partial laryngectomy (PL) offered a better initial local control rate of 84%, which increased to 88% with salvage surgery, and functional results were also good (80%). No statistically significant differences were found between RT and PL. RT was less costly, showed better suitability for treatment, produced moderate morbidity and sequelae, and local recurrence was easier to rescue. However, it is a once-only application technique. PL showed higher immediate postoperative morbidity, higher cost and lower suitability for treatment but had fewer sequelae, offered the best initial local control and is multi-applicable. No clear oncological arguments were found in our series to define whether PL or RT is the treatment of choice for ESSC. Both are effective therapies. Secondary factors such as suitability for treatment, morbidity, cost and applicability should be individually evaluated when choosing the type of treatment. As the laser endoscopic approach decreases morbidity and costs and makes the condition more suitable for treatment, it could be the treatment of choice for ESSC, in cases where local tumoral extent and larynx exposure allow radical excision.
Recombinant adeno-associated viruses (rAAV) are promising candidates as gene vectors, as they transduce non-dividing cells and permit lasting transgene expression in a wide spectrum of tissues. In this paper, we describe a robust procedure for the high throughput production, screening and characterization of rAAV vectors. The technology includes the production of rAAV from rapid small scale plasmid preparations and the analysis of virus productivity (physical and infectious particles) and activity (transgene expression, replication). rAAV are produced by triple transfection (rAAV plasmid and AAV- and adenovirus (Ad)-helper plasmids) on 293 human embryo kidney (HEK) cells. The titers of physical and infectious particles are obtained by dot blot hybridization and by a serial dilution assay, followed by either dot blot hybridization or real-time PCR, respectively. rAAV can be produced and characterized from plasmid mixtures containing as little as 1/100 productive molecules. Experiments on rAAV replication kinetics and Ad helper functions are discussed. All steps are performed in 96-well microtiter plates. The process is reproducible, high throughput, linear and ready for automation.
The present study aimed to investigate the role of nitric oxide (NO) in regression of the human corpus luteum. We therefore examined the effect of both NO and human chorionic gonadotrophin (HCG) on luteal cell apoptosis, and Bcl-2 production. The effect of NO on oestrogen production during corpus luteum regression was also studied. Slices from corpus luteum collected throughout the luteal phase were incubated for 4 h with the nitric oxide synthase (NOS) substrate, L-arginine (L-Arg, 1 mmol/l), the NOS inhibitor N-monomethyl-L-arginine (L-NMMA) (1 mmol/l), or with HCG (10 IU/ml). Oestradiol concentrations were determined by radioimmunoassay; Bcl-2 concentrations were measured by enzyme-linked immunosorbent assay; apoptosis was detected in-situ by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling; and inducible nitric oxide synthase (iNOS) was assessed by immunohistochemistry. Consistent with our previous findings, L-Arg elicited an inhibitory action on the production of oestradiol (P< 0.05). The number of apoptotic cells increased (P<0.05) from early to late corpus luteum, as did the number of cells positive for the expression of iNOS. The percentage of apoptotic cells in mid and late luteal phase was increased by L-Arg (56% and 310% respectively; P <0.05), and decreased by L-NMMA and HCG. Although no changes were observed in Bcl-2 concentration during the corpus luteum life span, L-Arg inhibited, and HCG augmented, Bcl-2 production (P<0.05) from mid and late corpus luteum cells in vitro. In summary, these results suggest that the opposite actions of L-Arg and HCG on human corpus luteum viability may, in part, be mediated by changes in the level of the anti-apoptotic activities caused by oestradiol and Bcl-2 protein.
Human corpora lutea undergo an extremely rapid period of growth, development and regression during the course of non-fertile cycles. The tissue consists of steroidogenic (parenchymal) and non-steroidogenic (stromal) cells. In women and other primates, steroid hormone production by corpora lutea depends on the presence of pituitary-derived LH. Nevertheless, there is also intra-luteal regulation of steroid synthesis. Steroidogenic luteal cells and non-steroidogenic cells interact via endocrine and paracrine pathways, and by contact-dependent pathways (gap junctions). Thus, hormones and locally produced factors including steroids, growth factors, cytokines, reactive oxygen species and nitric oxide may modulate luteal lifespan. The factors regulating regression and rescue of the corpus luteum are not understood completely. This review describes the expression of two representative intragonadal peptides that may influence luteal regression (interleukin 1 beta) and luteal rescue (steroidogenic acute regulatory protein).
From the nutrition al point of view milk is one of the most complete food in the diet of mammals. It contains nearly all the nutrients necessary to sustain life, but milk can deteriorate very easily, either by microbiological contamination or by biochemical reactions during processing and/or storage. The objective of this research study was to design a modified UHT treatment to achieve commercial sterilization and maximize the stabilization of the heat-treated product during storage. To search for a modified UHT process, a mathematical model coupled with an optimization routine (complex method) was developed. The mathematical model considers Kinetics for the inactivation of Bacillus stearothermophilus and several quality factors. To attain the objective function, several commercial UHT milk were analyzed and for the computer search the minimization of hydroxy methyl furfural (HMF) formation was considered and also including constraints for protease and lipase inactivation. The complex optimization procedure was implemented to search for the optimum modified UHT treatment.. One of the optimum modified UHT treatments was the combination of two pre-treatment (3.16 minutes at 62.30 degrees C and 6 minutes at 75 degrees C) in addition with a UHT treatment (0.75 s at 148.8 degrees C). This treatment attains the maximum product stability with a negligible effect on composition and color formation in the treated milk (HMF formation less than 3 mg/mL).