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Biomedical subjects

J C Millán

Publications and source records attributed to J C Millán.

12 recordsLinked to original sources
PubMed2006

Elemental distributions in femoral bone of rat under osteoporosis preventive treatments.

One of the abnormalities of bone architecture is osteoporosis as occurring in post-menopausal women. Especially long bones, such as femur, become more fragile and more prone to fracture. The efficiency of several osteoporosis preventative treatments based on oestrogen and progestin in bone structure and mineral recovery was studied using ovariectomized Wistar rats as an osteoporosis experimental model. Diagonal cross-sections of the proximal epiphysis of femoral bones were analysed using nuclear microscopy techniques in order to map and determine the concentration profiles of P, Ca, S, Fe and Zn from the epiphysis to diaphysis and across the cortical and trabecular bone structures. In control animals (not ovariectomized), the S and Zn contents significantly characterized differences between cortical and trabecular bone structures, whereas P and Ca showed increased gradients from the epiphyseal region to the diaphysis. After ovariectomy the differences observed were differential according to the type of hormonal supplementation. A significant decrease in P and Ca contents and depletion of minor and trace minerals, such as S, Fe and Zn, were found for both cortical and trabecular bone structures after ovariectomy relative to controls. Bone mineral contents were reversed to control levels by synthetic oestrogen supplementation, and combined oestrogen and progesterone treatment. Recovery was more evident in the femoral epiphysis and neck than in the diaphysis. The use of oestrogen alone did not lead to bone recovery after ovariectomy. Alterations in bone mineral composition observed for animals receiving synthetic oestrogen and combined oestrogen and progesterone supplement might reflect beneficial structural changes in critical regions of long bones, mostly affected in post-menopausal osteoporosis.

Animals↗
PubMed2004

Effect of hormone replacement therapy on the elemental contents of uterine tissue.

For the past years, different therapies based on steroid hormone supplementation or modulators of estrogen receptors have been used after menopause to prevent or manage osteoporosis. Although these treatments seem to be beneficial, they have some negative effects in the uterus and breast. The objective of this study was to assess variations for the concentrations of K, Ca, Mn, Fe, Cu, Zn, and Se in uterine tissue of Wistar rats. Ovariectomized rats were subjected to estrogen, progesterone, raloxifene, and tibolone supplementation and compared with nonovariectomized control animals. Elemental contents determined by the particle-induced X-ray emission (PIXE) technique revealed major alterations in Fe, Ca, Mn, and Se in the uterus of ovariectomized rats relative to control animals. After ovariectomy, a significant increase in Ca and Fe and a significant decrease in Mn and Se contents were determined in the uterus. For the ovariectomized groups in which animals received raloxifene, tibolone, estrogen, and estrogen combined with progesterone supplementation, an overall recovery in Mn, Fe, and Se contents was verified. Elemental concentration in the progesterone-supplemented group did not significantly differ from ovariectomized animals receiving placebo. The alterations found for ovariectomized animals receiving placebo and progesterone suggest tissue impairment and trace element imbalance, contrasting with the remaining supplemented groups where an enhancement of tissue activity might justify similar concentration levels relative to controls, because most of the elemental contents altered after ovariectomy.

Animals↗
PubMed2002

Influence of estradiol and gestagens on oxidative stress in the rat uterus.

OBJECTIVE: We studied the effect of ovariectomy, estradiol (E2), and E2 + medroxyprogesterone (MPA) on the Wistar rat uterus. METHODS: We used 15 adult female rats. The study was divided into the following four stages: (a) extirpation of the upper half of the left hemi-uterus (basal state) and ovariectomy; (b) animals were maintained for 15 days without treatment, performance of a new laparotomy, and extirpation of the remaining left hemi-uterus (OVX state); (c) beginning of E2 replacement therapy (ERT) (8 microg/day) for 15 days, followed by extirpation of the upper half of the right hemi-uterus (ERT state); and (d) the administration of E2 was continued, and oral treatment with MPA was begun (20 microg/day) to last for a further 15 days. At the end of the combined hormone replacement therapy (HRT) the remaining right hemi-uterus was extirpated (HRT state). At the end of each intervention, the plasma concentrations of E2 and PRG were measured. RESULTS AND DISCUSSION: The ovariectomy significantly reduced the malonaldehyde (MDA) levels (P < 0.0008) and catalase activity (P < 0.0006). The ERT very significantly (P < 0.0033) raised the catalase and MDA levels; these significance levels were maintained after the Bonferroni method was applied (overall error 5%). The HRT reduced the levels of MDA and catalase, but not significantly after the Bonferroni test was applied.Conclusions. Uterine oxidative stress is increased by E2, resulting in a significant increase in MDA. This may be modulated in part by the catalase activity. Although it cannot be confirmed categorically, MPA seems to intervene by decreasing the said oxidative stress.

Animals↗
PubMed2001

A phase I clinical trial of a multi-epitope polypeptide TAB9 combined with Montanide ISA 720 adjuvant in non-HIV-1 infected human volunteers.

A phase I clinical trial was performed to examine the safety and immunogenicity of a multi-epitope polypeptide comprising the central 15 amino acids of the V3 loop from six HIV-1 isolates. This protein called TAB9 was emulsified in Montanide ISA720 (Seppic, Paris) and administered intramuscularly at doses of 0, 0.2 and 1 mg to 24 healthy, HIV-1 seronegative adult males. Three immunisations were given at months 0, 1 and 6 in a randomised, double blind, placebo controlled clinical trial. The placebo was generally well tolerated. However, severe local reactions were observed in TAB9 vaccinated subjects after the second and third inoculations. Seven out of eight volunteers from the lower dose group showed moderate or severe local inflammation, while four out of eight subjects from the higher dose group developed granulomas and sterile abscesses. In general, the reactogenicity depended on the number of inoculations given and the dose of TAB9. Both doses were immunogenic, all immunised volunteers seroconverted and antibodies were broadly reactive against the V3 peptides included in the protein. All vaccine's sera reacted against gp120 in Western blot and 50% of them also neutralised at least one out of five laboratory isolates tested. No differences between doses were found. Anti TAB9 lymphoproliferative responses were observed, being more intense in the high dose group. Due to the strong local reactions that were found in this study, a change in the formulation will be required for further trials with this vaccine candidate in humans.

AIDS Vaccines↗
PubMed2001

Influence of estradiol on oxidative stress in the castrated rat uterus.

OBJECTIVE: We set out to study how the concentration of estradiol influences oxidative stress (malondialdehyde) and the superoxide dismutase and catalase antioxidant systems in the castrated female Wistar rat uterus. METHODS: We used 28 castrated female Wistar rats: 7 were left to evolve freely and the rest were divided into three groups of 7 animals receiving respective doses of 4, 8, and 16 microg/day of estradiol (E2) for 15 days. At the end of the study period, we determined the plasma concentrations of E2 and the concentrations of malondialdehyde (MDA) and superoxide dismutase and catalase activities in the uterus. RESULTS: There was a significant correlation (P < 0.000028) between the uterine malondialdehyde levels and the logarithm (base 10) of the plasma E2 concentrations and also between malondialdehyde and the uterine catalase activity (P < 0.002). The regression plane that best fitted the correlation among the three variables was MDA = 10.21 + 12.88 x Log [E2] - 0.49 x catalase activity. We found no significant relationships with the superoxide dismutase activity. CONCLUSIONS: There was a linear correlation between the base-10 logarithm of the estradiol plasma concentration and the phenomenon of uterine lipid peroxidation as measured by the MDA concentration in the uterus. This phenomenon was in part modulated by the inverse linear relationship between the antioxidant activity of the uterine catalase and the concentration of uterine MDA.

Animals↗
PubMed2000

Effect of bilateral ovariectomy and ovarian steroid hormones on the antioxidant systems and plasma malondialdehyde levels in Wistar rats.

We studied in the Wistar rat the effect of bilateral ovariectomy and of the administration of estradiol (E2) alone or together with medroxyprogesterone (MPA) on the lipid peroxidation (MDA) and the enzymatic (SOD and catalase) and non-enzymatic (vitamins A and E) antioxidant systems. At 15 days after castration, we observed no variations in the lipid peroxidation levels (MDA), with there being a slight increase in vitamins A and E (p<0.05), catalase (p<0.01), and SOD (n.s.) activity. The addition of estradiol led to a decline (n.s.) in the MDA values and in the catalase and SOD activity, with no modification of the vit. A and E concentrations. The combined (E2+MPA) therapy did not modify the results obtained with E2 alone, although the catalase decline did now reach significance (p<0.05).

Animals↗
PubMed1999

Fascioliasis: sonographic abnormalities of the biliary tract and evolution after treatment with triclabendazole.

Diagnosis of infection with the liver fluke Fasciola hepatica is usually difficult. Ultrasonography (US) might be a useful diagnostic alternative, and we assessed the value of sequential US in the diagnosis and monitoring of fascioliasis in 76 patients at baseline and for 60 days after treatment with triclabendazole. At baseline, biliary abnormalities were observed in 52 patients. Crescent-shaped parasites were seen in 11 patients; in 2 cases parasites were spontaneously moving and in 4 patients parasites were motionless. Postprandial examination revealed parasites adhering to the gallbladder wall in a further 5 cases. In 3 further cases, gallbladder contents were mobile but did not sediment downwards after patients changed position. Non-specific abnormalities were: impaired gallbladder contractility (n = 23), gallbladder tenderness (n = 19), debris (n = 6), calculi (n = 5), wall thickening (n = 2) and bile duct dilatation (n = 12). During day 1-7, Fasciola-like crescents in the gallbladder or passing through the bile duct were detected in another 15 patients, impaired gallbladder contractility in 16, gallbladder tenderness in 16, and bile duct dilatation in an additional 28 patients. Thirty-two patients with these US abnormalities experienced colic-like abdominal pain accompanied by increased alkaline phosphatase in 25 cases. During day 30-60, abnormalities regressed completely in 45 patients; 2/6 triclabendazole failures were evident by detection of living parasites. Biliary tract abnormalities are frequently observed by US, but the detection-rate of Fasciola hepatica is disappointingly low despite the parasite's relatively large size. US findings must therefore be interpreted together with other clinical measurements. The visualization of parasites being expelled through the dilated common bile duct allowed the causal interpretation of post-therapeutic abdominal pain and increase of liver enzymes. When triclabendazole is given on suspicion, visualization of worm expulsion and bile duct dilatation by US may be used to confirm diagnosis.

Adolescent↗
PubMed1999

Effects of amphetamine on development of oral candidiasis in rats.

Experiments were conducted to evaluate the effects of amphetamine (0. 4 mg/kg of body weight/day) on the development of oral candidiasis in Sprague-Dawley rats. Animals were submitted to surgical hyposalivation in order to facilitate the establishment and persistence of Candida albicans infection. Treatment with drugs (placebo or amphetamine) was initiated 7 days before C. albicans inoculation and lasted until the end of the experiments, day 15 postinoculation. Establishment of C. albicans infection was evaluated by swabbing the inoculated oral cavity with a sterile cotton applicator on days 2 and 15 after inoculation, followed by plating on YEPD (yeast extract-peptone-dextrose) agar. Tissue injury was determined by the quantification of the number and type (normal or abnormal) of papillae on the dorsal tongue per microscopic field. A semiquantitative scale was devised to assess the degree of colonization of the epithelium by fungal hyphae. Our results show that amphetamine exacerbates C. albicans infection of the tongues of rats. Significant increases in Candida counts, the percentage of the tongue's surface covered with clinical lesions, the percentage of abnormal papillae, and the colonization of the epithelium by fungal hyphae were found in amphetamine-treated rats compared to those found in the rats injected with a placebo. The last two parameters increased in rats treated with the placebo compared to the parameters of the untreated control rats.

Amphetamine↗
PubMedDate not supplied

Influence of estrogen replacement therapy on plasma lipid peroxidation.

OBJECTIVE: To observe whether any relationship exists between the concentration of plasma estradiol (E2) and the plasma concentrations of malondialdehyde (MDA) or whether a relationship exists between the concentration of plasma E2 and the activity of the erythrocyte enzymes, superoxide dismutase (SOD) and catalase, in ovariectomized female Wistar rats (treated and untreated with E2). DESIGN: We used 40 ovariectomized Wistar rats randomly assigned to four groups. The first group was allowed to evolve freely with no treatment. A gel containing 17beta-estradiol was administered transdermally to the other three groups at doses of 4, 8, and 16 microg/day, respectively. After 15 days of treatment, blood samples were obtained from the four groups. The concentrations of plasma MDA and E2 and the activities of erythrocyte catalase and SOD were determined. RESULTS: There were significant correlations between the MDA levels and the logarithm (base 10) of the plasma E2 concentrations in both linear (p = 0.00093) and quadratic (p = 0.000001) regression analyses. No relationship was found between the E2 concentrations and the catalase and SOD activities. CONCLUSIONS: There was a clear relationship between the plasma levels of MDA and the logarithm of the plasma E2 concentrations, which was best demonstrated with a quadratic regression. This model may explain the contradictory findings presented by estrogens with respect to their pro-or antioxidant action.

Animals↗
PubMedDate not supplied

The efficacy and tolerability of triclabendazole in Cuban patients with latent and chronic Fasciola hepatica infection.

Current chemotherapy for the treatment of infections caused by the liver fluke Fasciola hepatica is not satisfactory. Therefore, the efficacy and tolerability of triclabendazole (TCZ) was assessed for this indication. Eighty-two patients (51 female, 31 male, age 15-81 yr, mean 42 yr) with chronic or latent F. hepatica infection refractory to previous anti-helminthic chemotherapy were enrolled in a 60-day open, non-comparative trial. Patients received 20 mg/kg TCZ as two doses of 10 mg/kg administered after food 12 hr apart. Efficacy of treatment was assessed by stool microscopy, determination of Fasciola excretory-secretory antigen (FES) in feces, and by ultrasonography (US) which were systematically performed pre-therapy and on Days 1-7, 15, 30, and 60 post-therapy. For continuous safety assessment, patients were hospitalized during the first week after therapy and then monitored at home for the appearance of any adverse events. Clinical chemistry and hematology tests were carried out on Days 1, 3, 7, 15, and 60, and whenever an adverse effect occurred possibly related to therapy. Seventy-one (92.2%) of the 77 patients who completed the 60-day follow-up period became egg-negative. Efficacy of therapy was supported by the disappearance or decrease of FES antigen and of ultrasonography abnormalities. In the 6 remaining patients, parasitological cure was achieved by another single TCZ dose of 10 mg/kg on Day 60. A total of 74 adverse events possibly related to therapy was reported by 54 patients. The most important adverse event was colic-like abdominal pain (40 patients [49%]) consistent with the expulsion of the parasite through the bile ducts as confirmed by US on Days 2-7. Most adverse events (53) were graded as mild, 20 as moderate, and only 1 as severe (a biliary colic responding to spasmolytic therapy within two hours). Triclabendazole 20 mg/kg is an effective therapy for the treatment of F. hepatica infection in patients who have failed to respond to other antihelminthic agents. Biliary colics reflecting the expulsion of dead or damaged parasites usually occur during Day 3-7 and respond well to spasmolytic therapy.

Adolescent↗