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Biomedical subjects

M Cárdenas

Publications and source records attributed to M Cárdenas.

At least 19 recordsLinked to original sources

Protein restriction during fetal and neonatal development in the rat alters reproductive function and accelerates reproductive ageing in female progeny.

Recent studies demonstrate long-term programming of function of specific organ systems resulting from suboptimal environments during fetal life and development up to weaning. Nutrient restriction during pregnancy and lactation impairs overall fetal growth and development. We determined the effects of maternal protein restriction (MPR; 50% normal protein intake) during fetal development and/or lactation in rats on the function and ageing of the reproductive system of female progeny. Rats were fed either a control 20% casein diet (C) or a restricted diet (R) of 10% casein during pregnancy. After delivery mothers received either C or R diet until weaning to provide four groups, CC, RR, CR and RC. We report data on female offspring only. After weaning pups were fed the C diet. MPR increased maternal progesterone, corticosterone, oestradiol and testosterone concentrations at 19 days gestation. Reproductive and somatic phenotype was altered as pup birth weight was decreased, and ano-genital distance was increased by MPR. Pup corticosterone was decreased at 2 days postnatal (PN) life. Vaginal opening and timing of the first oestrus were delayed in RR and CR and these differences were not related to body weight. At 21 days PN oestradiol in RR and CR and progesterone in RR were reduced; at 70 days PN luteinizing hormone (LH) in all restricted groups was reduced in dioestrus while follicle stimulating hormone (FSH) was unchanged. Cycle length increased between 140 days and 1 year in RR and CR but remained unchanged in CC, providing evidence of premature ageing of reproductive function. Fertility rates declined over the same period in the three experimental groups but not CC. MPR in one of the two experimental periods, either pregnancy or lactation, resulted in decreased pup survival compared with CC and RR. These data show that MPR results in delayed sexual maturation and premature ageing of reproductive function.

Adaptation, Physiological↗

Cerebral blood flow during supine rest and the first minute of head-up tilt in patients with orthostatic intolerance.

AIM: To assess the cerebral blood flow velocity during the first minute of head-up tilt in patients with postural tachycardia syndrome (POTS) or neurally-mediated reflex syncope compared with patients with dizziness. METHODS: We evaluated 120 patients selected from 470 patients who underwent head-up tilt testing: 40 with POTS, 40 with typical neurally-mediated reflex syncope and 40 who complained of dizziness with no history of loss of consciousness and a negative head-up tilt test (with and without isosorbide). Transcranial Doppler sonography of the middle cerebral artery, heart rate and brachial blood pressure were recorded during a 70 degrees head-up tilt test. RESULTS: During both baseline in supine position and the first minute of upright tilt, patients with postural tachycardia syndrome showed higher heart rate and cerebral blood flow velocity than patients with dizziness and patients with neurally-mediated reflex syncope (P < 0.05, ANOVA), but no significant difference was observed on the Gosling's pulsatility index. CONCLUSION: Patients with POTS have an autonomic dysfunction that is not triggered by upright posture but is accentuated by it.

Adult↗

Relationship between pharmacokinetic parameters of cyclosporin and the incidence of acute rejection after heart transplantation.

Despite two decades of use, there are limited data on the best way to monitor Cyclosporine (CsA) for heart transplantation. The aim of our study was to determine the relationships between pharmacokinetic parameters and clinical outcomes after heart transplantation and to evaluate the range of CsA trough levels provided the most effective protection against graft rejection. We retrospectively analyzed the clinical outcomes of all adult patients who received a heart transplant between January 1998 and February 2005. All had routine monitoring of CsA trough levels and scheduled endomyocardial biopsies. Rejection was defined as grade > or =3, based on International Society for Heart and Lung Transplantation (ISHLT) criteria. Follow-up period was 1 year. All patients were on CsA, corticosteroids, and azathioprine/mycophenolate mofetil with or without antilymphocyte induction (eight patients with basiliximab). Data were analyzed by unpaired Student t-test, Cox regression model, and ROC curve. Among 70 patients (60 men and 10 women) who entered the study, 34 (48.6%) had at least one acute rejection episode of grade > or =3 during the first posttransplant year. Mean CsA trough level (C(0)) measured at first week posttransplant was significantly lower in the rejection than the no-rejection group (125.17 +/- 56.9 ng/mL versus 169.33 +/- 48.27 ng/mL, P = .001). C(0) was the strongest predictor of acute graft rejection (P = .000, HR = .985.) The risk decreased by 1.5% for each unit increase of the C(0) value. ROC analysis showed that C(0) of 150 ng/mL provided the optimal cutoff. Patients with mean C(0) >150 ng/mL over the first week had less incidence of acute rejection than patients with levels <150 ng/mL (30.3% versus 64.9%) (P = .009, Cochran-Mantel-Haenszel test). In conclusion, our data suggest that in heart transplant patients it may be crucial to target early trough levels above 150 ng/mL during the first days postsurgery to avoid rejection.

Adolescent↗

Induction of a new follicular wave in holstein heifers synchronized with norgestomet.

Treatments with progestin to synchronize the bovine estrous cycle in the absence of the corpus luteum, induces persistence of a dominant follicle and a reduction of fertility at doses commonly utilized. The objective of the present research was to induce a new wave of ovarian follicular development in heifers in which stage of the estrous cycle was synchronized with norgestomet. Holstein heifers (n=30) were used, in which estrus was synchronized using two doses of PGF2alpha i.m. (25 mg each) 11 days apart. Six days after estrus (day 0=day of estrus) heifers received a norgestomet implant (6 mg of norgestomet). On day 12, heifers were injected with 25 mg of PGF2alpha i.m. and assigned to treatments (T1 to T4) as follows: treatment 1, heifers received a second norgestomet implant (T1: N+N, n=6), treatment 2, received 100 microg of GnRH i.m. (T2: N+GnRH, n=6), treatment 3, 200 mg of progesterone i.m. (T3: N+P4, n=6), treatment 4, control treatment with saline solution i.m. (T4: N+SS); in the four treatments (T1 to T4) implants were removed on day 14. For treatment 5, heifers received 100 microg of GnRH i.m. on day 9 and 25 mg of PGF2alpha i.m. (T5: N+GnRH+PGF2alpha) at the time of implant removal (day 16). Ovarian evaluations using ultrasonographic techniques were performed every 48 h from days 3 to 11 and every 24 h from days 11 to 21. Blood samples were collected every 48 h to analyze for progesterone concentration. A new wave of ovarian follicular development was induced in 3/6, 6/6, 3/6, 1/6 and 6/6, and onset of estrus in 6/6, 0/6, 6/6, 6/6 and 6/6 for T1, T2, T3, T4 and T5, respectively. Heifers from T1, T3 and T4 that ovulated from a persistent follicle, showed estrus 37.5 +/- 12.10 h after implant removal and heifers that developed a new wave of ovarian follicular development showed it at 120.28 +/- 22.81 h (P<0.01). Ovulation occurred at 5.92 +/- 1.72 and 2.22 +/- 1.00 days (P<0.01), respectively. Progesterone concentration was <1 ng/ml from days 7 to 15 in T1, T2 and T4; for T3 progesterone concentration was 2.25 +/- 0.50 ng/ml on day 13 and decreased on day 15 to 0.34 +/- 0.12 ng/ml (P<0.01). For T5, progesterone concentration was 1.66 +/- 0.58 ng/ml on day 15. The more desirable results were obtained with T5, in which 100% of heifers had a new wave of ovarian follicular development induced, with onset of estrus and ovulation synchronized in a short time period.

Animals↗

Occurrence and densities of bacteriophages proposed as indicators and bacterial indicators in river waters from Europe and South America.

AIMS: To evaluate the feasibility of bacteriophages as a complementary tool for water quality assessment in surface waters from different parts of the globe. METHODS AND RESULTS: Faecal coliform bacteria, enterococci, spores of sulphite-reducing clostridia, somatic coliphages, F-specific RNA bacteriophages and bacteriophages infecting Bacteroides fragilis were determined by standardized methods in raw sewage and in 392 samples of river water from 22 sampling sites in 10 rivers in Argentina, Colombia, France and Spain, which represent very different climatic and socio-economic conditions. The results showed that the indicators studied maintained the same relative densities in the raw sewage from the different areas. Classifying the river water samples according to the content of faecal coliform bacteria, it can be observed that the relative densities of the different bacterial indicators and bacteriophages changed according to the concentration of faecal coliform bacteria. There was a relative increase in the densities of all groups of bacteriophages and sulphite-reducing clostridia with respect to faecal coliforms and enterococci in the samples with low counts of faecal coliform bacteria. CONCLUSIONS: The numbers of bacterial indicators and bacteriophages were similar in the different geographical areas studied. Once released in rivers, the persistence of the different micro-organisms differed significantly. Bacteriophages and spores of sulphite-reducing clostridia persisted longer than faecal coliforms and enterococci. SIGNIFICANCE AND IMPACT OF THE STUDY: Bacteriophages in river water samples provide additional information to that provided by bacteria about the fate of faecal micro-organisms in river water. The easy, fast and cheap methods for phage determination are feasible both in industrialized and developing countries.

Bacteriophages↗

Removal of bacterial and viral faecal indicator organisms in a waste stabilization pond system in Choconta, Cundinamarca (Colombia).

A major objective for domestic wastewater treatment using waste stabilization pond systems is the removal of pathogenic microorganisms. Traditional evaluation parameters for faecal contamination are the total and faecal coliforms. However, epidemiological studies, environmental resistance and the behaviour in the treatment systems, show that viruses are an important disease agent and even more resistant to disinfection than bacteria. Therefore, it is important to introduce viruses as a faecal indicator and to compare them with the traditional bacterial indicators. A waste stabilization pond system was evaluated in the municipality of Chocontá, Cundinamarca (Colombia), for the removal of faecal indicators (such as Escherichia coli, Streptococcus faecalis, Clostridium perfringens) and viruses like F+, somatic and Bacteroides fragilis phages. The system includes two facultative ponds in series with a flow of 1555 m3/day. Samples were collected at the entrance of the system, in the two ponds and from the final effluent. Results show a decrease between 0.3 and 4.7 logarithmic units in the bacterial indicators and between 1 and 4.6 logarithmic units with viral indicators.

Bacteria↗

Virulence of Pasteurella multocida recA mutants.

In order to determine the role of the RecA protein in the virulence of Pasteurella multocida, a recA mutant was constructed and used in studies of virulence and competition in relation to wild-type strain. To achieve this, firstly, the recA gene was isolated and sequenced, showing an Escherichia coli-like SOS box and encoding a protein of 354 amino acids which has the closest identity with the Haemophilus influenzae RecA protein. Further, the recA mutant was constructed, by inactivating this gene by single recombination of a suicide plasmid containing an internal region of the P. multocida recA gene, and shown to be more sensitive to UV radiation than the parental strain. The P. multocida mutant was slightly attenuated in virulence, as indicated by the LD(50), the time of death of infected animals, and a failure to compete with the wild-type strain in mixed infections. Compared to the parent strain, the mutant had a similar growth rate but a longer lag phase. These data suggest that the diminished virulence of the recA mutant as well as its failure in competition were more a consequence of the long lag phase rather than a direct effect of the inactivation of the recA gene on genes involved in virulence.

Animals↗

In vivo estrogen bioactivities and in vitro estrogen receptor binding and transcriptional activities of anticoagulant synthetic 17beta-aminoestrogens.

Estrogenic activities of the two 17beta-aminoestrogen (AE) derivatives, prolame and butolame, were studied upon coagulation, serum luteinizing hormone (LH) and uterine weight, including endometrial morphology in castrated female rats. We have also investigated the ability of these two compounds, as well as another AE pentolame, to activate transcription through the estrogen receptor alpha (ERalpha) and the estrogen receptor beta (ERbeta). Administration of prolame and butolame to castrated animals increased significantly (P < 0.01) the mean clotting time when compared with that obtained in the group of control animals. Butolame was a more potent anticoagulant than prolame (P < 0.01), as judged by their corresponding IC(50) (5.4 +/- 0.65 and 66.6 +/- 2.57 micro;g/animal, respectively). In contrast, estradiol significantly shortened blood clotting times (P < 0.005). Both prolame and butolame caused a significant inhibition of serum LH levels (EC(50) 8.10 +/- 0.79 and 17 +/- 64 microg/animal, respectively), and restored castration-induced reduction in uterine weight of ovariectomized rats (EC(50) 4.14 +/- 1.57 and 17.0 +/- 1.78 microg/animal, respectively). In terms of the effects of prolame, butolame and pentolame in transient transfection assays, all the three AE activated ER dependent reporter gene expression, however, only at high concentrations. Prolame had the highest activity followed by butolame and pentolame. Induction of transcription by these compounds was preferentially mediated through the ERalpha, especially in the case of pentolame where little, if any, activation occurred through the ERbeta. None of the compounds showed antagonistic activities through either ER subtype. The overall data suggest that modifications in the structure and length of the amino-alcohol side-chain at C-17 might have an impact on the affinity and estrogenic intrinsic properties of AE at the level of diverse target tissues.

Amino Alcohols↗

Reactivity of different LH and FSH standards and preparations in the world health organization matched reagents for enzyme-linked immunoassays of gonadotrophins.

The immunoreactivity of various LH and FSH calibration standards and recombinant preparations in the enzyme-linked immunoassay (EIA) systems for gonadotrophins developed for the Special Programme of Research in Human Reproduction of the World Health Organization (WHO) were compared. The preparations tested included three LH and two FSH pituitary standards (calibrated against LH 80/552 and 68/40 and FSH 78/549 respectively) provided with the EIA or radioimmunoassay WHO matched reagent kits, the pituitary preparation LER-907, and recombinant human LH (rhLH) and FSH (rhFSH). Simultaneous curve fitting of the EIA dose-response curves revealed no significant differences among the slopes generated by the WHO LH standards and LER-907; in contrast, no parallelism was found between the curves of rhLH and the pituitary-derived LH standards. No significant differences were found among the slopes of the curves elicited by the pituitary and recombinant FSH preparations. Each LH preparation exhibited a high degree of charge heterogeneity. Considerable variations in charge isoform distribution among the WHO LH standards, rhLH and LER-907 were also evident. In contrast, the FSH preparations were less heterogeneous and exhibited minor differences in charge distribution. Despite the existing differences in charge isoform distribution, all the pituitary-derived preparations as well as rhFSH seem appropriate for using as calibration standards in this particular EIA system.

Animals↗

Fertility diminution in female rats with experimental chronic nephrosis.

Chronic aminonucleoside nephrosis in rats is an experimental analogue of human focal segmental glomerulosclerosis. This study was undertaken to define the effects of chronic nephrosis on the pituitary-ovarian axis and on fertility. Chronic nephrosis was induced by puromycin aminonucleoside and followed for 112 days. The estrous cycle was evaluated daily in all rats, whereas biochemical parameters, hormonal concentrations, and fertility were measured on Days 7, 14, 28, 56, 84, and 112 (n = 8). Animals were divided in four experimental groups: A, B, C, and D. Group A was used to determine LH, FSH, progesterone, and estradiol concentrations. Group B was used to evaluate fertility, and groups C and D were added to clarify the role of male rats in the fertility of nephrotic female rats. The results showed a persistent proteinuria in nephrotic rats; the estrous cycle of nephrotic animals was disrupted. The LH and estradiol concentrations were significantly low at all time points evaluated, whereas no significant changes were noted in FSH or progesterone values. In addition, fertility and litter size were diminished in nephrotic female rats. Interestingly, the presence of a male rat or its urine resulted in a positive influence on serum estradiol concentrations of nephrotic female rats. These data indicate that experimental chronic nephrosis results in a pituitary-ovarian dysfunction that is characterized by low LH concentration, hypoestrogenism, failure of the hormonal feedback control, and diminution of fertility. In addition, they show the positive effect of a male rat on the fertility of a nephrotic female, which strongly suggests the participation of pheromones.

Animals↗

Transjugular liver biopsy in 52 patients with an automated Trucut-type needle.

A three-year prospective study was conducted to assess the efficacy and safety of transjugular liver biopsy with a Trucut-type needle employing an automated device. Fifty-two consecutive patients (39 women and 13 men), ages 46.3+/-14.6 years, in whom percutaneous liver biopsy was contraindicated were included in the study. An 18-gauge transjugular hepatic needle with a 20-mm throw length, a cutting cannula at the distal end, and an automated trigger device on the proximal end was used. All procedures were performed under fluoroscopic control, and the following variables were assessed: (1) number of passes, (2) size and average number of the obtained fragments, (3) number of portal triads, and (4) adequacy of the specimen for histologic diagnosis. The procedure was successful in 49/52 patients, and all samples obtained were satisfactory for histologic analysis even when cirrhosis or bridging fibrosis were present. Mean biopsy specimen length was 1.7+/-0.88 cm; mean number of passes was 2.42+/-1.01, the mean number of biopsy fragments and portal triads per attempt were 2.5+/-1.01 and 6.24+/-3.18, respectively. No major complications were observed. Transjugular hepatic biopsy with this new cutting system is an effective and safe procedure in patients with contraindication for percutaneous liver biopsy.

Adolescent↗

Positive head-up tilt table test in patients with the long QT syndrome.

AIMS: Syncope in patients with the long QT syndrome is commonly attributed to a ventricular arrhythmia (torsades de pointes). The susceptibility of patients with the long QT syndrome (LQTS) to neurally mediated syncope is currently unknown. METHODS AND RESULTS: Head-up tilt table testing (70 degrees) was performed in six patients with the long QT syndrome and a history of syncope. All patients had syncope with a mixed response. The RR interval was significantly decreased 2 min before the onset of syncope (980 +/- 125 ms vs 630 +/- 91 ms, P=0.003), and significantly increased during syncope (983.17 +/- 224.71; P=0.006). Non-significant changes in QT intervals were observed. Baseline QT was 513 +/- 86 ms and decreased to 450 +/- 59 ms 2 min before the onset of syncope (P=0.11). Although not statistically significant, QT intervals during syncope were longer than at 2 min before syncope (485 +/- 85 ms vs 450 +/- 59 ms; P=0.29). CONCLUSION: Our results suggest that patients with the LQTS are susceptible to neurally mediated syncope. Whether this susceptibility differs from control populations remains unresolved. From a clinical standpoint, neurocardiogenic syncope should be considered a diagnostic alternative in patients with LQTS.

Adolescent↗

Reproductive function in male rats with chronic nephrosis.

Endocrine dysfunction has been associated with renal diseases. The present study was conducted to explore reproductive function in male rats with chronic nephrosis. Experimental chronic nephrosis was induced by the administration of 7.5, 5.0 and 5.0 mg per 100 g body weight of puromycin aminonucleoside on days 0, 21 and 35, respectively. Reproductive function was evaluated on the basis of hormonal concentrations, mass of accessory sex organs and fertility during an 84 day period. Circulating LH, FSH, testosterone and oestradiol concentrations were measured by specific radioimmunoassays, while fertility was estimated by the rate of pregnancy induction. Samples were collected on days 7, 14, 28, 56 and 84. The results showed an important endocrine dysfunction characterized by low concentrations of LH and FSH during the first month, after which concentrations were similar to control values or even increased on days 56 and 84. Testosterone and oestradiol decreased significantly at all time points evaluated. The mass of the testes did not alter. However, the mass of the prostate and seminal vesicle decreased only during the first 2 weeks, and became essentially normal thereafter. The reproductive capacity of nephrotic males was eliminated on day 7, whereas on day 14, 16% of the group was able to mate successfully and subsequently most animals recovered their normal reproductive function. This study demonstrates for the first time that rats with experimental chronic nephrosis develop an important endocrine dysfunction, characterized mainly by persistent reduction in testosterone concentrations, which impairs reproductive capacity only transiently.

Animals↗

[Open clinical trial with oral acyclovir for the prophylaxis of disease by Cytomegalovirus in low risk liver transplant recipients].

OBJECTIVE: Checking the first 70 low risk liver transplantation performed in our hospital, who did not receive prophylaxis for Cytomegalovirus, we found that the incidence of Cytomegalovirus-infection and Cytomegalovirus-disease were 47% and 16% respectively. METHODS: For this reason we started a prospective, open clinical study, to address the safety of acyclovir prophylaxis in low-risk liver transplant patients. Seventy patients did not receive acyclovir. Fifty patients received oral acyclovir during 3 months (800-3,200 mg/day). RESULTS: The occurrence of Cytomegalovirus infection was not modified (40%) but Cytomegalovirus disease decreased dramatically (4%, p < 0.01) during the first year after transplantation. Acyclovir was well tolerated. The incidence of leukopenia and renal failure were similar in both groups. Acyclovir did not improved the global survival of patients. CONCLUSIONS: Thus, oral acyclovir does not reduce Cytomegalovirus infection although it is efficient and safe in the prevention of Cytomegalovirus disease in low-risk liver transplantation, and prevents Herpes-simplex and Varicela-zoster symptomatic disease in this group of patients.

Acyclovir↗

[Acyclovir may modulate clonal expansion of cd8+ lymphocytes induced by the Cytomegalovirus antigen].

BACKGROUND: Although the potent antiviral effect of acyclovir on the Herpes-simplex (HSV) and Varicela-zoster (VZV) virus and the scarce effectiveness versus Cytomegalovirus (CMV) is known, some data suggest that it may have an immunodulator implicated in the control of these viral disease. The aim of this study was to characterize this possible effect of acyclovir versus the CMV antigen. METHODS: We stimulated cultures of mononuclear cells obtained in 7 healthy patients who were seropositive for CMV and HSV with CMV antigen, HSV and with phitohemaglutinine (PHA). The proliferation index and culture cell phenotype were later determined in the absence and presence of acyclovir (2 micrograms/ml). In another group the proliferation index and cell phenotype following stimulation with the CMV antigen were studied prior to and after treating the same volunteers with acyclovir for one week (800 mg/6h). RESULTS: The CMV antigen and HSV induced T cell proliferation predominantly involving the CD8+ subpopulation leading to an inversion of the CD4/CD8 quotient. On addition of acyclovir to the cell culture a moderate reduction was produced in lymphoproliferative response versus the CMV antigen and HVS, characteristically modulating CD8+ cell proliferation, thereby leading to reestablishment of the CD4/CD8 quotient. However, the proliferation induced by PHA was not inhibited. These results were produced on oral administration of acyclovir. CONCLUSIONS: Acyclovir modulates the lymphoproliferative response induced by CMV antigen. Based on this observation, the authors hypothesize that this immunomodulation may be related to its preventive effect on CMV disease in transplanted patients.

Acyclovir↗