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Biomedical subjects

Carlos Jiménez

Publications and source records attributed to Carlos Jiménez.

At least 19 recordsLinked to original sources

Cell division in the unicellular microalga Dunaliella viridis depends on phosphorylation of extracellular signal-regulated kinases (ERKs).

In mammalian cells, MAPKs are involved in both stress response (JNK and p38 pathways) and cell proliferation and differentiation [extracellular signal-regulated kinase (ERK)] through protein kinase cascades. Exposure of Dunaliella viridis cell cultures to PD98059, a very specific inhibitor of the ERK signalling pathway, resulted in a total arrest of cell proliferation and a complete dephosphorylation of ERK. As shown by flow cytometry analysis of propidium iodide-stained cells, PD98059 stopped mitosis at the G(2) phase after the S phase has been completed. Multiple physiological parameters such as cell motility and reducing power generation (NADPH) clearly indicate that the treated cells are wholly viable. Exposure of D. viridis to environmental stresses that impair cell division, such as hyperosmotic shock, nitrogen starvation, or sublethal UV irradiation, caused a marked decrease in the phospho-ERK levels as detected by western blot. Two 400 bp polynucleotides from D. viridis with high homologies to published sequences of ERK1 and ERK2 were cloned, sequenced, and submitted to GenBank. Northern blot analysis revealed two mRNA bands of approximately 1.9 kb, consistent with the expected size of ERK proteins ( approximately 40 kDa). Sequence analysis showed that they contained several mitogen-activated protein kinase (MAPK) conserved domains, including II, III, VIb, VII, and the double phosphorylation motif. Interestingly, in D. viridis, this motif was T*DY* instead of the canonic T*EY*. Based on this finding, ERK plant sequences can be divided into two groups, one termed the T*DY* branch and the other termed the T*EY* branch. The molecular and functional data presented here suggest that ERK is a very ancient signalling pathway and that it was already present in the last common ancestor of all eukaryotic cells.

Amino Acid Sequence↗

Incidence and risk factors for the development of lung tumors after liver transplantation.

Tobacco and immunosuppression are risk factors for developing upper aerodigestive and lung tumors after transplantation. This study comprises 701 adult recipients who survived more than 2 months after transplant: 276 patients underwent orthotopic liver transplantation (OLT) for alcoholic cirrhosis (AC) and 425 for nonalcoholic disease. The aim is to analyze the incidence, clinical characteristics, risk factors, and outcome of patients who develop lung malignancies after OLT. Incidence of lung cancer was 2.1% (15 patients): 4.3% (12 patients) in the alcoholic group and 0.7% (three patients) in the nonalcoholic group (P < 0.001). Mean time from OLT to tumor diagnosis was 86 months. Thirteen patients were smokers; 12 patients were heavy drinkers; and 11 were drinkers and smokers. Squamous cell carcinoma was diagnosed in nine patients, large cell carcinoma in three, adenocarcinoma in two, and broncoalveolar in one. Tumor staging: 10 patients at stage IV; three at stage IIIB; and two at stage IIB. Tumor resection was performed in one patient, and three also received chemotherapy. Mean survival after tumor diagnosis was 5.4 months. There is a higher risk of lung cancer in smoker patients who have undergone OLT for AC, and have a very poor prognosis because tumors are diagnosed at advanced stages.

Adolescent↗

Coagulation and electrocoagulation of wastes polluted with dyes.

Dyes are common pollutants in a large variety of industrial wastewaters, and the treatment of these wastes by coagulation has been extensively studied in the literature. This work is focused on the comparison of the efficiencies of the chemical and the electrochemical coagulation processes with hydrolyzing aluminum salts, and it tries to determine the similarities or differences that exist between the two coagulation processes. To do this, Eriochrome Black T solutions were used as a model of dye-polluted wastewater, and experiments of both coagulation technologies were planned to meet the same operation conditions. The pH, the aluminum concentration, the type of electrolyte, and the mode of dosing of aluminum were found to influence the process. Moreover, the speciation of aluminum was found to be the key parameter to explain the results, in terms of the mechanisms previously proposed in the literature for dissolved organic matter coagulation.

Aluminum Compounds↗

Isolation and synthesis of (-)-(5S)-2-imino-1-methylpyrrolidine-5- carboxylic acid from Cliona tenuis: structure revision of pyrostatins.

[reaction: see text] (-)-(5S)-2-Imino-1-methylpyrrolidine-5-carboxylic acid (1), previously reported as the N-acetyl-beta-d-glucosaminidase inhibitor pyrostatin B, has been isolated from the organic extracts of the burrowing sponge Cliona tenuis. The structure of 1, including its absolute stereochemistry, was characterized from its spectral data and chemical transformations and confirmed by total synthesis. The synthesis of 1 reveals that the structure of pyrostatin B has been incorrectly assigned. Comparison of NMR spectral data strongly suggests that pyrostatins A and B are identical to 5-hydroxyectoine and ectoine, respectively.

Amino Acids, Diamino↗

The response of nutrient assimilation and biochemical composition of Arctic seaweeds to a nutrient input in summer.

Twenty-one species of macroalgae (four Chlorophyta, eight Rhodophyta, and nine Phaeophyta) from the Kongsfjord (Norwegian Arctic) were examined for their response to nutrient enrichment (nitrate and phosphate) in the summer period. The enzymatic activities related to nutrient assimilation, external carbonic anhydrase (CAext, EC 4.2.1.1), nitrate reductase (NR, EC 1.6.6.1), and alkaline phosphatase (AP, EC 3.1.3.1), as well as the biochemical composition (total C and N, soluble carbohydrates, soluble proteins, and pigments) were measured. CAext activity was present in all species, and showed a general decrease after nutrient enrichment. Inversely, NR activity increased in most of the species examined. Changes in pigment ratios pointed to the implication of light harvesting system in the acclimation strategy. Despite enzymatic and pigmentary response, the Arctic seaweeds can be regarded as not being N-limited even in summer, as shown by the slight effect of nutrient enrichment on biochemical composition. The exception being the nitrophilic species Monostroma arcticum and, to a lesser extent, Acrosiphonia sp. For the rest of the species studied, changes in total internal C and N, soluble proteins, soluble carbohydrates, pigment content, and the internal pool of inorganic N were recorded only for particular species and no general pattern was shown. Acclimation to unexpected nutrient input seemed to ensure the maintenance of a stable biomass composition, rather than an optimized use of the newly available resource (except for the nitrophilic species). This indicates a high degree of resilience of the algal community to a disruption in the natural nutrient availability pattern.

Acclimatization↗

Peritoneal transport in peritoneal dialysis patients is not affected by transitorily successful renal transplantation.

Patients returning to peritoneal dialysis (PD) from failed renal transplantation are recognized to be inflamed, and this situation might produce a high peritoneal solute transport status. We wanted to determine if a period of time with a kidney allograft induces a change in peritoneal function. We studied 19 PD patients who had been living with a graft for a mean of 47 +/- 39 months. We studied their peritoneal function upon starting PD (baseline), immediately before transplantation (pre-Tx), and after returning to PD when the graft failed (post-Tx). We analyzed the peritoneal mass transfer coefficients for urea (U-MTAC) and creatinine (Cr-MTAC), the dialysate-to-plasma ratio of creatinine (D/P-Cr), and net ultrafiltration (UF). We observed no significant differences in the various variables pre-Tx and post-Tx. The U-MTAC post-Tx was significantly lower than at PD baseline (25.9 +/- 8 mL/min vs. 20.2 +/- 5 mL/min, p = 0.03). The U-MTAC and Cr-MTAC post-Tx were not correlated with months on a graft or with MTAC values at baseline. In inherent high transporters (Cr-MTAC > or = 11.5 mL/min at baseline, n = 8), we observed a significant reduction in Cr-MTAC post-Tx (15.2 +/- 2 mL/min vs. 10.2 +/- 4 mL/min, p = 0.03). Three of these patients remained high transporters post-Tx. We conclude that peritoneal function upon reinitiating PD after transplantation is similar to function in the pre-transplantation phase; and that a high peritoneal transport status is more prevalent at first initiation onto PD than at return after transplantation, suggesting that inherently high transport is almost exclusively a feature of an intact, predialysis peritoneum.

Adult↗

Advanced donor age increases the risk of severe recurrent hepatitis C after liver transplantation.

The association between donor age and the severity of recurrent hepatitis C and, whether there is any donor age above which severity of recurrence increases significantly, were analyzed. A total of 131 liver grafts of hepatitis C virus (HCV)-infected recipients were selected for the study. Distribution of donor age was compared between grafts with and without severe recurrence. The risk of developing severe recurrence as well as the hepatitis-free, severe hepatitis-free and HCV-related graft survival was compared between different donor age groups. Mean donor age was higher for grafts with severe recurrence (P = 0.007). The risk of developing severe recurrence within 2 years post-transplant increased with donors aged > or =50 years (RR = 1.34) and donors aged > or =70 years (RR = 1.61). Five-year severe hepatitis-free survival rates decreased progressively when donor age was over 50 years (P < 0.001). The study shows 50 and 70 years as the donor age cut-off points above which the evolution of HCV-infected recipients worsens.

Adolescent↗

Phosphorylation of MAP kinase-like proteins mediate the response of the halotolerant alga Dunaliella viridis to hypertonic shock.

The microalga Dunaliella viridis has the ability to adapt to a variety of environmental stresses including osmotic and thermal shocks, UV irradiation and nitrogen starvation. Lacking a rigid cell wall, Dunaliella provides an excellent model to study stress signaling in eukaryotic unicellular organisms. When exposed to hyperosmotic stress, UV irradiation or high temperature, a 57-kDa protein is recognized by antibodies specific to mammalian p38, to its yeast homologue Hog1, and to the phospho-p38 MAP kinase motif. This 57-kDa protein appears to be both up-regulated and phosphorylated. Three other proteins (50, 45, 43 kDa) were transiently phosphorylated under stress conditions as detected with an antibody specific to the mammalian phospho c-Jun N-terminal kinase (JNK) motif. Treatment with specific inhibitors of p38 MAP kinase (SB203580) and JNK (SP600125) activities markedly impaired the adaptation of Dunaliella to osmotic stress. From an evolutionary standpoint, these data strongly suggest that MAP kinase signaling pathways, other than ERK, were already operating in the common ancestor of plant and animal kingdoms, probably as early as 1400 million years ago.

Adaptation, Physiological↗

New cytotoxic cembranes from the sea pen Gyrophyllum sibogae.

Two new cembrane-type diterpenoids have been isolated from the 2-propanol extract of the sea pen Gyrophyllum sibogae collected in South Africa: 7,8-dihydroflabellatene A (1) and 7,8-dihydroflabellatene B (2). Their structures were determined on the basis of detailed spectroscopic analysis and by single-crystal X-ray analysis of the major metabolite 1, which showed strong in vitro cytotoxicity against a panel of 13 tumor cell lines.

Animals↗

The influence of delayed graft function.

We study the incidence of delayed graft function (DGF) in a group of 3365 renal transplant recipient patients from various Spanish centres, its clinical consequences, and the evolution in time (transplants performed in 1990, 1994 and 1998) of the factors that determine its presence. The incidence of DGF remained constant in the 3 years studied (30.4, 30.8 and 29.2%, respectively) when contrasting the following factors involved in the establishment of DGF were studied: body mass of recipient, donor age, non-heart beating donation, type of replacement treatment in the pre-transplant period, time of vascular anastomosis and time of cold ischaemia. DGF was not associated with graft or patient survival. In the transplants performed with elderly donors, the cold ischaemia time was associated with greater incidence of DGF, and the latter with less survival of the graft when censored for death. The presence of DGF was significantly associated with acute rejection, cytomegalovirus infection, worse renal function and arterial hypertension at 3 months post-transplantation. In conclusion, the incidence of DGF remained stable in our patients over the years studied and, although not directly, it can affect graft survival as it is associated with acute rejection, arterial hypertension and worse renal graft function. A shortening of ischaemia times may reduce the incidence of DGF and improve transplant results.

Adult↗

Evaluation of the effects of several zoanthamine-type alkaloids on the aggregation of human platelets.

Ten zoanthamine-type alkaloids from two marine zoanthids belonging to the Zoanthus genus (Zoanthus nymphaeus and Zoanthus sp.) along with one semisynthetic derivative were evaluated for their antiplatelet activities on human platelet aggregation induced by several stimulating agents. 11-Hydroxyzoanthamine (11) and a synthetic derivative of norzoanthamine (16) showed strong inhibition against thrombin-, collagen- and arachidonic acid-induced aggregation, zoanthenol (15) displayed a selective inhibitory activity induced by collagen, while zoanthaminone (10) behaved as a potent aggregant agent. These evaluations allowed us to deduce several structure-activity relationships and suggest some mechanisms of action for this type of compounds.

Alkaloids↗

Rapid progression from oral leukoplakia to carcinoma in an immunosuppressed liver transplant recipient.

Immunosuppression used to avoid graft rejection in solid organ transplantation recipients leads to a variety of side-effects, and an increased rate of infections and de novo malignancies. Oral conditions usually associated with immunosuppressive drugs include fungal and viral infection, and lip lesions, but intra-oral carcinoma has not been reported as having a high incidence. This report deals with a male liver transplant recipient receiving FK506 (5 mg/day) and prednisone (20 mg/day) who was diagnosed with a homogeneous leukoplakia on the floor of the mouth 4 months after transplantation, and 4 months later with a squamous cell carcinoma growth at the site of this lesion. The rapid transformation of the lesion suggests that in patients who display oral premalignant conditions, immunosuppression must be considered as an important risk factor for oral cancer.

Carcinoma, Squamous Cell↗

A colorimetric assay for determination of cell viability in algal cultures.

In this work, we propose the determination of cell viability in algal cultures by using a colorimetric assay widely used for estimation of cell proliferation in animal cell cultures. The method is based on in vivo reduction by metabolically active cells of a tetrazolium compound (MTS=3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenil)-2H-tetrazolium, inner salt) to a colored formazan, with maximal absorbance at 490 nm, that is released to the culture medium. For this purpose, we have tested two microalgae with high commercial value (Dunaliella and Spirulina) and two seaweeds with different morphology (Ulva and Gracilaria). Color development in this assay is directly proportional to the number of viable cells, to the incubation time in the presence of the assay solution, and to the incubation temperature. A direct significant correlation was found between algal photosynthesis rate and color development in all species used through this work. Moreover, the intensity of absorbance at 490 nm was significantly lower in stressed cells (e.g. in nutrient-limited cultures, in the presence of toxic substances, and in osmotically-stressed cultures). We conclude that cell viability of algal cultures can be rapidly and easily estimated through colorimetric determination of the reduction of MTS to formazan.

Adaptation, Physiological↗

New dammarane triterpenes from the aerial parts of Ibicella lutea grown in Argentina.

Two new dammarane triterpenes have been isolated from the aerial parts of Ibicella lutea, 3-acetyl-24-epi-polacandrin (1) and 1,3-diacetyl-24-epi-polacandrin (2), and were obtained along with the known compounds 20S,24S-epoxy-3beta,12beta,25-trihydroxydammarane (3) and apigenin. The structures of compounds 1 and 2 were deduced by spectroscopic studies and by chemical transformations leading to the preparation of derivatives 4-11. The structure and relative stereochemistry of 1 were verified by single-crystal X-ray analysis. The natural compounds and selected semisynthetic derivatives were evaluated against several tumor cells.

Acetylation↗

Conversion from cyclosporin A to tacrolimus as a non-surgical alternative to reduce gingival enlargement: a preliminary case series.

BACKGROUND: Gingival enlargement (GE) is a frequent side effect that occurs in organ transplant recipients (OTR) after the administration of cyclosporin A (CsA). The availability of new drugs used to suppress graft rejection in OTR offers an opportunity to manage GE non-surgically. This preliminary case series aimed to analyze the effect of CsA withdrawal and its substitution by another immunosuppressant in OTR with severe GE. METHODS: Four organ transplant recipients who had received a liver or renal allograft were recruited for this study. All OTR had developed clinically severe CsA-induced GE. GE scores were assessed for each patient at baseline and at weeks 2, 4, 8, 12, 16, and 54 following conversion to tacrolimus. Scaling and root planing were initially performed and repeated monthly during the first 6 months. Careful polishing of the teeth was carried out once every 2 weeks until month 6 and then monthly until month 12. Hygiene instructions and reinforcement to optimize oral hygiene were maintained throughout the study. RESULTS: The four patients showed a rapid decrease in their gingival symptoms and in the size of the gingivae. This change was clinically evident 8 weeks after conversion to tacrolimus. One year later, all the patients experienced GE regression, although some anatomic irregularities persisted in the interdental papillae of one of the patients. No adverse effects from tacrolimus were observed during the study except in one patient who presented headaches. CONCLUSION: It seems that CsA withdrawal and its conversion to tacrolimus in organ transplant recipients who develop severe gingival enlargement, together with an extensive plaque control program, provide an effective means to control/eliminate gingival hyperplasia, with minimal risk of graft dysfunction.

Adult↗

Cardiovascular risk factors in 116 patients 5 years or more after liver transplantation.

We assessed the cardiovascular risk factors (CVRFs) in 116 stable liver transplant patients surviving for 5 years or more (median: 102 months). The prevalence of smokers was 29.3%, hypertension 49.1%, obesity 22.4%, hypercholesterolemia 34.5%, hypertriglyceridemia 11.2%, and hyperhomocysteinemia 57.8%. Diabetes was found in 21.5% of the patients, being more frequent in patients with hepatitis-C-virus infection (31.8% vs 15.3%; P=0.03). Patients on cyclosporine therapy had a higher prevalence of hypertension, hypercholesterolemia and hyperhomocysteinemia than those treated with tacrolimus. Multivariate analysis showed only an association between cyclosporine therapy and cholesterol concentrations (odds ratio:1.02; 95% confidence interval (CI): 1.00-1.03; P=0.01). The prevalence of hypertension, diabetes, hypercholesterolemia and hypertriglyceridemia was lower at the time of the study than at 1 and 3 years after transplantation ( P<0.05), probably related to steroid withdrawal. Comparing 87 patients' CVRFs with the general Spanish population, we found that the age-gender standardized prevalence ratio was not different: smoking 1.46 (95% CI: 0.88-1.76), obesity 1.16 (95% CI: 0.60-1.44), hypertension 1.55 (95% CI: 0.98-1.81), and hypercholesterolemia 0.64 (95%CI: 0.35-1.90). We conclude that the prevalence of CVRFs in liver transplant patients after 5 years or more is lower that found in the first years after the transplantation, and no different from that found within the Spanish population.

Adult↗

Cyclobutenbriarein A, the first diterpene with a tricyclo[8.4.0.0(3,6)]tetradec-4-ene ring system isolated from the Gorgonian Briareum asbestinum.

Cyclobutenbriarein A (2), a novel class of C20-rearranged diterpene briarane possessing an unprecedented tricyclo[8.4.0.0(3,6)]tetradec-4-ene ring system was isolated, along with five new briarane diterpenoids (1 and 3-6), from the organic extracts of the Bahamian gorgonian Briareum asbestinum. The structures of these secondary metabolites were established on the basis of extensive NMR studies and accurate mass measurements (HRFABMS).

Animals↗