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Biomedical subjects

V Navarro

Publications and source records attributed to V Navarro.

At least 19 recordsLinked to original sources

From the molecular characterization of iodide transporters to the prevention of radioactive iodide exposure.

In the event of a nuclear reactor accident, the major public health risk will likely result from the release and dispersion of volatile radio-iodines. Upon body exposure and food ingestion, these radio-iodines are concentrated in the thyroid, resulting in substantial thyroidal irradiation and accordingly causing thyroid cancers. Stable potassium iodide (KI) effectively blocks thyroid iodine uptake and is thus used in iodide prophylaxis for reactor accidents. The efficiency of KI is directly related to the physiological inhibition of the thyroid function in the presence of high plasma iodide concentrations. This regulation is called the Wolff-Chaikoff effect. However, to be fully effective, KI should be administered shortly before or immediately after radioiodine exposure. If KI is provided only several hours after exposure, it will elicit the opposite effect e.g. lead to an increase in the thyroid irradiation dose. To date, clear evaluation of the benefit and the potential toxicity of KI administration remain difficult, and additional data are needed. We outline in this review the molecular characterization of KI-induced regulation of the thyroid function. Significant advances in the knowledge of the iodide transport mechanisms and thyroid physiology have been made. Recently developed molecular tools should help clarify iodide metabolism and the Wolff-Chaikoff effect. The major goals are clarifying the factors which increase thyroid cancer risk after a reactor accident and improving the KI administration protocol. These will ultimately lead to the development of novel strategies to decrease thyroid irradiation after radio-iodine exposure.

Animals↗

Effects of trans-10,cis-12 conjugated linoleic acid on body fat and serum lipids in young and adult hamsters.

The aim of the present work was to determine whether t-10, c-12 conjugated linoleic acid (CLA) feeding was able to reduce body fat accumulation and improve the serum lipid profile in adult hamsters fed an atherogenic diet, in order to compare these effects with those observed in young growing hamsters. Young and adult hamsters were fed semi-purified atherogenic diets supplemented with 0.5 % linoleic acid or 0.5% t-10, c-12 CLA for 6 weeks. Body weight and food intake were measured every two days. Adipose tissue from different anatomical locations, liver and gastrocnemious muscle were dissected and weighed. Cholesterol, triacylglycerols, non-esterified fatty acids and proteins were determined spectrophotometrically and water content by gravimetry. In young hamsters, no significant differences were found in food intake, final body weight and gastrocnemious muscle weight. White adipose tissue weights were reduced, liver weight was increased and cholesterol and triacyl-glycerols in both serum and liver were reduced. In adult hamsters, CLA feeding decreased food intake and adipose tissue weights. No changes were observed in other parameters. The present study demonstrates that age has an influence in hamster responsiveness to t-10, c-12 CLA because, although when this isomer is added to an atherogenic diet it reduces body fat accumulation in both young and adults hamsters, the lessening of the effects on serum lipids brought about by atherogenic feeding is only observed in young animals. Moreover, it is clear that liver is a target for CLA in young but not in adult hamsters.

Adipose Tissue↗

The body fat-lowering effect of conjugated linoleic acid: a comparison between animal and human studies.

Different reasons which justify differences between rodents and humans in body fat reduction produced by conjugated linoleic acid (CLA) could be proposed. The doses used in humans are lower than those used in rodents. Human experiments have been performed with CLA isomer mixtures instead of isolated isomers. The variable dilution of t-10, c-12, the active isomer, among different preparations might explain the reduced responsiveness in humans. Diet composition may modulate CLA effects on body fat accumulation. As far as human studies are concerned, a specific dietary pattern has not been established. As a result differences among studies and also among subjects in the same study are likely. In rodents, the effects of CLA vary with genotype, suggesting that genetic predisposition to fat accumulation can play an important role in the effectiveness of CLA. Human volunteers with different body mass index have participated in the published studies and even in the same experiment. So, differences in lipid metabolism among subjects could help to explain the discrepancies observed in the literature. Age and maturity may also be crucial. Experiments using rodents have been conducted with growing animals and there is little evidence of CLA effectiveness in adult animals. By contrast, human studies have been performed with adults. Inhibition of lipogenesis in white adipose tissue is one of the mechanisms which have been proposed to explain the body-fat lowering effect of CLA, but lipogenesis in this tissue is very low in humans. Another mechanism suggested is increased fatty acid oxidation in the liver associated with peroxisome proliferation, but humans are relatively insensitive to this effect.

Adipose Tissue↗

[Middle molecules removal. Beyond beta2-microglobulin].

The uremic toxin removal capacity mainly depends on dialyzer and hemodialysis modes. The low-flux hemodialysis only removes solutes having molecular weights less than 5.000 Da. High-flux hemodyalisis represents a form of low-volume hemodiafiltration because of the internal filtration and back-filtration that can take place within a dialyzer. Hemodiafiltration with large volumes of replacement fluid seems to be the best technique for removing all small, medium-sized and large molecules. The objective of our study was to evaluate the large molecules removal bigger than beta2-microglobuline on high flux haemodialysis and on-line hemodiafiltration with postdilutional infusion, in patients with three times a week dialysis and on short daily dialysis. We studied 24 patients, 15 males and 9 females stable on haemodialysis programme, twelve on standard four to five hours three times a week dialysis and twelve on 2 to 2 1/2 hours six times a week dialysis. All patients were dialysed with Fresenius 4008 monitor, three sessions on high flux haemodialysis (HD) and three sessions on on-line hemodiafiltration (OL-HDF). Two sessions with each filter were performed (polisulfone HF80, polyethersulfone Arylane H9 and new polisulfone APS 900). Pre and postdialysis concentrations of urea, creatinine, (beta2-microglobulin (beta2-m), myoglobin, prolactin and alpha1 microglobulin (alpha1-m) were measured. There was no difference in urea and creatinine small molecules removal. beta2m removal was 68% on HD and 81% on OL-HDF. Myoglobin and prolactin present a similar removal pattern, a higher removal with new filters (60% with Arylane and 59% with APS) in comparison with clasical polisulfone (22% with HF80). The mean alpha1-m reduction rate on HD was 6% and on OL-HDF 22%. OL-HDF with APS 900 filter was the most remove technique (35.4%), significatively higher than the other modes and filters. We can conclude that the new filters generation reach a better uremic toxins removal, specially in large molecules higher than beta2-m and on HD modality.

Adult↗

[Monitoring hemodialysis dose with ionic dialisance in on-line hemodiafiltration].

Until now, with the ionic dialysance measurement, it has been possible to determine hemodialysis dose in each session of hemodialysis (HD) and in the conventional hemofiltration (HDF) but not in the modality of on-line HDF. Recently it is possible with a new biosensor that allows to measure the dose in on-line HDF. The aim of this study was to evaluate the value of this biosensor in different dialysis situations comparing the dialysis dose measured in blood in comparison with the values obtained from the sensor. We have analysed 192 hemodialysis sessions performed in 24 patients, 15 male and 9 female, mean age of 70.2 +/- 12 years, included in on-line HDF. All treatments were done using 4008H (Fresenius) monitor equipped with on-line clearance monitoring (OCM), that measure, with non invasive monitoring, the effective ionic dialysance equivalent to urea clearance. Every patient received eight dialysis sessions: one with dialysate flow (Qd) 500 ml/min, two with HD and Qd 800 ml/min and five with on-line HDF. Other habitual haemodialysis parameters were no changed, dialysis time 200 +/- 63 min (135-300) and blood flow 421 +/- 29 ml/min (350-450). Initial and final ionic dialysance values (K), final Kt, Kt/V measured with OCM using V of Watson, and Kt/V determined in blood pre and postdialysis concentrations of urea (Daugirdas second generation), were measured. The mean of initial K was 251 +/- 21 ml/min and the final K was 234 +/- 24 ml/min. The Kt measured with OCM was 50.6 +/- 17 L, 51.2 +/- 17 in men and 49.7 +/- 16 in women. The V (Watson) was 34.5 +/- 6 L. The Kt/V measured with the Kt of OCM and V was 1,499 +/- 0.54 and Kt/V measured in blood samples was 1,742 +/- 0.58. The correlation between both values was 0.956. The Kt was different according to dialysis modality used: in HD and Qd 500 was 44.7 +/- 15 L, in HD and Qd 800 was 50.7 +/- 17 and in on-line HDF (22.1 +/- 7 L of reposition volume), was 51.8 +/- 17 L. The Kt/V from blood samples also shows variation: in HD and QD 500 was 1.60 +/- 0.55, in HD and Qd 800 was 1,726 +/- 0.56 and in on-line HDF was 1,776 +/- 0.59. In this study has been observed a close correlation between the new biosensor OCM with the measures obtained from the blood samples. For this reason this sensor it is useful in all modalities of dialysis treatment, included on-line HDF. The sensor was able to discriminate the efficacy of different dialysis modalities used in this study.

Adult↗

[Improvement of nutritional status in patients with short daily on-line hemodiafiltration].

Daily dialysis have showed excellent results because a higher frequency of dialysis is more physiological and it decreases the fluctuation of liquid, solutes and electrolytes. Improvement of certain causes of anorexia such as postdialysis fatigue, reduction in fluid overload, uremic milieu, medium and large-sized molecule removal could be observed with daily dialysis. The aim of this study was to evaluate nutritional parameters when thrice weekly on-line hemodiafiltration (OL-HDF) were switched to daily OL-HDF. 24 patients have been studied. Eight patients, 6 males and 2 females, mean age of 65.9 +/- 14 years, on thrice weekly 4 to 5 hours OL-HDF were switched to 2 to 2.5 hours six times per week. Dialysis parameters were the same in both periods and only frequency and dialysis time were changed. Other sixteen patients, mean age of 68.4 +/- 14 years, were a control group which dialysis parameters were maintained. Clinical and biochemical outcome were carried out over twelve months. Daily OL-HDF group: Dry weight increased from 67.8 +/- 8 kg at baseline to 68.5 +/- 8 kg after three months, 69.3 +/- 8 kg after six months (NS), 69.5 +/- 8 kg after nine months (p < 0.05) and 70.8 +/- 8 (p < 0.01) after one year. Mean nPCR increased from 0.93 +/- 0.2 g/kg/d on baseline to 1.18 +/- 0.3 after three moths (P < 0.0-5), 1.13 +/- 0.2 after six months (NS), 1.06 +/- 0.2 after nine months (NS) and 1.10 +/- 0.2 after twelve months (NS). There were no significant changes in serum protein, albumin, prealbumin, transferrin, total cholesterol, HDL-c, LDL-c and triglycerides (TG). There were no changes in control group. Mean dry weight was 62.3 +/- 9 kg at baseline and 62.1 +/- 10 kg after one year. Mean nPCR was 0.97 +/- 0.2 g/kg/d on baseline and 1.03 +/- 0.2 g/kg/d after one year. Neither there were changes in serum protein, albumin, transferrin, total cholesterol, HDL-c, LDL-c and TG. Improvement in nutrition status has been observed with the change from thrice weekly OL-HDF to short daily OL-HDF. Increased appetite and protein intake was accompanied by a dry body weight increase of three kg after twelve months.

Adult↗

Residual cognitive impairment in late-life depression after a 12-month period follow-up.

OBJECTIVES: This study investigated cognitive impairment in late-life depression in a follow-up design. The main objective was to assess the most important cognitive domains implicated in late-life depression, in patients who underwent pharmacological treatment, in the acute phase and twelve months after. METHODS: Neuropsychological and clinical data were used from the baseline of patients and controls, to determine the cognitive impairment in the acute phase. Patients repeated the neuropsychological assessment at twelve months. RESULTS: There were significant differences between patients and controls at baseline. But in the patients there was no change over twelve months. There were no differences between remitted and non-remitted patients on neuropsychological scores. CONCLUSIONS: The cognitive impairment seen in the elderly depressed patients seems to be a trait characteristic of this mental disease, even when the depressive episode has remitted.

Aged↗

Effects of conjugated linoleic acid on body fat accumulation and serum lipids in hamsters fed an atherogenic diet.

Conjugated linoleic acid (CLA) refers to a mixture of naturally occurring positional and geometric isomers of linoleic acid that exist in dairy products and meat. The aim of the present work was to study the effects of c-9,t-11 and t-10,c-12 CLA isomers on body fat accumulation and serum lipids in hamsters fed an atherogenic diet. Hamsters were divided in four groups: one group was fed a chow diet (control) and the other three groups were given semi-purified atherogenic diets with 0.5% linoleic acid (LA), c-9,t-11 or t-10,c-12 CLA. Body weight and food intake were measured daily. After 6 weeks, adipose tissues from different anatomical locations and liver were dissected and weighed. Serum glucose, total cholesterol, HDL-c, LDL-c and triacylglycerol levels, as well as total and free cholesterol, triacylglycerol and phospholipid content in liver were determined by enzymatic methods. No differences in either energy intake or final body weight were found. The addition of t-10,c-12 CLA reduced fat accumulation and led to lower serum cholesterol, as compared with LA group. Nevertheless the level remained higher than in the control animals. The reduction in serum cholesterol was limited to LDL-c. This isomer also reduced triacylglycerol content in liver but did not modify serum triacylglycerol level. In summary, the present study demonstrates that t-10,c-12 CLA is the biologically active agent when anti-obesity and hypocholesterolaemic properties of CLA are considered. In contrast, the isomer c-9,t-11 has no effect on lipid metabolism in hamsters.

Adipose Tissue↗

Residual symptoms in elderly major depression remitters.

OBJECTIVE: To assess residual symptoms in severe geriatric major depression in remission, and to determine baseline clinical and sociodemographic predictors of residual symptoms in remitters. METHOD: A total of 108 elderly patients with unipolar major depression were evaluated and treated naturalistically for 9 months so as to record the predictors of residual symptoms in remitters. In order to reduce the likelihood of confusing residual symptoms with normal effects of age, 30 control subjects were also monitored. RESULTS: Seventy-nine patients (73.1%) were considered remitters and 82.3% of remitters showed residual symptoms. Medical burden, chronic stress and subjective social support were the only variables which predicted the severity of residual symptoms in remitters. CONCLUSION: Residual symptoms in elderly patients with major depression in remission should not only be attributed exclusively to intrinsic factors of the illness or the age of the individual patient, but also to external factors.

Aged↗

[Intradialysis hemolysis secondary to hypophosphatemia].

We report a 76-year-old man, stable on a thrice-weekly hemodialysis program over a period of 3 years, who developed acute intradialysis hemolysis secondary to hypophosphatemia, an unusual cause of hemolysis. During the dialysis session we monitored the starting point, the severity and duration of intradialysis hemolysis. Severe hyphosphatemia is a rare cause of intradialysis hemolysis. It is important to think of his possibility to make an adequate diagnosis and treatment. The patient was treated with a phosphorus-enriched acid concentrate, bicarbonate-buffered dialysate, with biochemical and clinical improvement.

Aged↗

Comparison of unidimensional and bidimensional measurements in metastatic non-small cell lung cancer.

Tumour response evaluation after chemotherapy has become crucial in the development of many drugs. In contrast to the standard bidimensional WHO criteria, the recently described Response Evaluation Criteria In Solid Tumors are based on unidimensional measurements. The aim of the present study was to compare both methods in patients with metastatic non-small cell lung cancer. One hundred and sixty-four patients treated with two cisplatin-paclitaxel-based chemotherapy schedules between June 1994 and December 2000 were analysed. The measurements were reviewed by an independent panel of radiologists. Patient characteristics were: median age of 55 years (range 24-77 years) and a male to female ratio of 129 : 35. Adenocarcinoma and squamous carcinoma were the most common histologies. Vinorelbine was the third drug used in 77 patients and gemcitabine in 87. The ratio unidimensional/bidimensional was as follows: response 85 : 85; stable disease 32 : 32; progression 47 : 42 and not assessable 0 : 5. Kappa for agreement between responders was 0.951 (95% CI: 0.795-1.0) (P<0.001). Both WHO criteria and Response Evaluation Criteria In Solid Tumors give similar results in assessing tumour response in patients with non-small cell lung cancer after chemotherapy. The unidimensional measurement could replace the more complex bidimensional one.

Adenocarcinoma↗

Involvement of the neurotensin receptor subtype NTR3 in the growth effect of neurotensin on cancer cell lines.

The expression of the 3 currently known neurotensin receptors was studied in human cancer cells of prostatic, colonic or pancreatic origin by means of RT-PCR analysis and binding experiments. All the cells selected for this work have been shown to exhibit a growth response to neurotensin. We found that the 7 transmembrane domain, levocabastine insensitive receptor (NTR1) is expressed in most but not all of the cells studied whereas the 7 transmembrane domain, levocabastine sensitive receptor (NTR2) is present in none of these cells. The 100 kDa-type I neurotensin receptor (NTR3) is expressed in all the cells assayed. Moreover, we demonstrated that neurotensin can stimulate the growth of CHO cells stably transfected with the NTR3. Taken together, our results strongly suggest that the NTR3 subtype could be involved in the growth response of human cancer cells to neurotensin.

Animals↗

Pharmacological properties of the mouse neurotensin receptor 3. Maintenance of cell surface receptor during internalization of neurotensin.

We recently reported the molecular identification of a new type of receptor for the neuropeptide neurotensin (NT), the neurotensin receptor 3 (NTR3), identical to sortilin, which binds receptor-associated protein. Here, we demonstrate that the cloned mouse NTR3 is expressed on the plasma membrane of transfected COS-7 cells. The mouse NTR3 is detectable by photoaffinity labeling and immunoblotting at the cell surface as a 100 kDa N-glycosylated protein. Biochemical analysis and confocal microscopic imaging clearly indicate that NT is efficiently internalized after binding to NTR3, and that despite this internalization, the amount of receptor present on the cell surface is maintained.

Adaptor Proteins, Vesicular Transport↗

Anticipation of epileptic seizures from standard EEG recordings.

BACKGROUND: New methods derived from non-linear analysis of intracranial recordings permit the anticipation of an epileptic seizure several minutes before the seizure. Nevertheless, anticipation of seizures based on standard scalp electroencephalographical (EEG) signals has not been reported yet. The accessibility to preictal changes from standard EEGs is essential for expanding the clinical applicability of these methods. METHODS: We analysed 26 scalp-EEG/video recordings, from 60 min before a seizure, in 23 patients with temporal-lobe epilepsy. For five patients, simultaneous scalp and intracranial EEG recordings were assessed. Long-term changes before seizure onset were identified by a measure of non-linear similarity, which is very robust in spite of large artifacts and runs in real-time. FINDINGS: In 25 of 26 recordings, measurement of non-linear changes in EEG signals allowed the anticipation of a seizure several minutes before it occurred (mean 7 min). These preictal changes in the scalp EEG correspond well with concurrent changes in depth recordings. INTERPRETATION: Scalp-EEG recordings retain sufficient dynamical information which can be used for the analysis of preictal changes leading to seizures. Seizure anticipation strategies in real-time can now be envisaged for diverse clinical applications, such as devices for patient warning, for efficacy of ictal-single photon emission computed tomography procedures, and eventual treatment interventions for preventing seizures.

Electroencephalography↗

Frontal cerebral perfusion dysfunction in elderly late-onset major depression assessed by 99MTC-HMPAO SPECT.

Baseline regional cerebral blood flow of thirty unmedicated late-onset unipolar major depressed patients over the age of 60 years and 20 sex-, age-, and vascular risk factor-matched healthy controls was imaged with single photon emission computed tomography, using technetium-99m hexamethylpropylene amine oxime as a tracer. To avoid errors of diagnosis--in particular, confusion between major depression and organic cognitive impairment--only treatment responders were included in the final sample. Statistically significant differences were observed in both left and right anterior frontal regions, with reduced uptake in depressed patients; these differences were more pronounced in the left hemisphere. Among patients, there was no correlation between regional cerebral blood flow and the severity of baseline symptoms. Our results support the hypothesis that certain neuroanatomic regions of the central nervous system may be functionally involved in elderly unipolar major depression, particularly in the late-onset subgroup.

Aged↗