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1.
Actas Dermosifiliogr ; 115(3): T293-T297, 2024 Mar.
Article in English, Spanish | MEDLINE | ID: mdl-38242433

ABSTRACT

Although subungual melanoma is uncommon, it is associated with worse outcomes than melanomas in other locations and accounts for 1% to 23% of all melanomas, depending on the population. The aim of this study was to describe the clinical and histopathologic features of subungual melanoma in a Mexican population. We identified 303 patients with melanoma, and of these, 19% (57 patients with a median age of 71 years) had subungual melanoma. The main sites affected were the lower limbs (52.6%) and the toe (75.4%). The most common histologic subtype was acral lentiginous melanoma (50.9%). Median Breslow thickness was 3 mm, and stage IA tumors were the most common (in 28.1% of patients). Recurrence and metastasis occurred in 19.3% and 8.8% of patients, respectively. The clinical and histopathologic features identified are similar to those described in the literature. Early diagnosis and treatment are crucial for improving prognosis.


Subject(s)
Melanoma , Nail Diseases , Skin Neoplasms , Humans , Aged , Melanoma/pathology , Cohort Studies , Skin Neoplasms/pathology , Nail Diseases/diagnosis , Prognosis
2.
Actas Dermosifiliogr ; 115(3): 293-297, 2024 Mar.
Article in English, Spanish | MEDLINE | ID: mdl-37871891

ABSTRACT

Although subungual melanoma is uncommon, it is associated with worse outcomes than melanomas in other locations and accounts for 1% to 23% of all melanomas, depending on the population. The aim of this study was to describe the clinical and histopathologic features of subungual melanoma in a Mexican population. We identified 303 patients with melanoma, and of these, 19% (57 patients with a median age of 71 years) had subungual melanoma. The main sites affected were the lower limbs (52.6%) and the toe (75.4%). The most common histologic subtype was acral lentiginous melanoma (50.9%). Median Breslow thickness was 3 mm, and stage IA tumors were the most common (in 28.1% of patients). Recurrence and metastasis occurred in 19.3% and 8.8% of patients, respectively. The clinical and histopathologic features identified are similar to those described in the literature. Early diagnosis and treatment are crucial for improving prognosis.


Subject(s)
Melanoma , Nail Diseases , Skin Neoplasms , Humans , Aged , Melanoma/pathology , Cohort Studies , Skin Neoplasms/pathology , Nail Diseases/diagnosis , Prognosis
3.
Braz J Med Biol Res ; 55: e12343, 2022.
Article in English | MEDLINE | ID: mdl-36477953

ABSTRACT

Adipose tissue-derived mesenchymal stromal/stem cells (ASCs) are considered important tools in regenerative medicine and are being tested in several clinical studies. Porcine models are frequently used to obtain adipose tissue, due to the abundance of material and because they have immunological and physiological similarities with humans. However, it is essential to understand the effects and safe application of ASCs from pigs (pASCs) as an alternative therapy for diseases. Although minipigs are easy-to-handle animals that require less food and space, acquiring and maintaining them in a bioterium can be costly. Thus, we present a protocol for the isolation and proliferation of ASCs isolated from adipose tissue of farm pigs. Adipose tissue samples were extracted from the abdominal region of the animals. Because the pigs were not raised in a controlled environment, such as a bioterium, it was necessary to carry out rigorous procedures for disinfection. After this procedure, cells were isolated by mechanical dissociation and enzymatic digestion. A proliferation curve was performed and used to calculate the doubling time of the population. The characterization of pASCs was performed by immunophenotyping and cell differentiation in osteogenic and adipogenic lineages. The described method was efficient for the isolation and cultivation of pASCs, maintaining cellular attributes, such as surface antigens and multipotential differentiation during in vitro proliferation. This protocol presents the isolation and cultivation of ASCs from farm pig as an alternative for the isolation and cultivation of ASCs from minipigs, which require strictly controlled maintenance conditions and a more expensive process.


Subject(s)
Adipose Tissue , Stem Cells , Humans , Swine , Animals , Swine, Miniature
4.
Rev. bras. pesqui. méd. biol ; Braz. j. med. biol. res;55: e12343, 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1403900

ABSTRACT

Adipose tissue-derived mesenchymal stromal/stem cells (ASCs) are considered important tools in regenerative medicine and are being tested in several clinical studies. Porcine models are frequently used to obtain adipose tissue, due to the abundance of material and because they have immunological and physiological similarities with humans. However, it is essential to understand the effects and safe application of ASCs from pigs (pASCs) as an alternative therapy for diseases. Although minipigs are easy-to-handle animals that require less food and space, acquiring and maintaining them in a bioterium can be costly. Thus, we present a protocol for the isolation and proliferation of ASCs isolated from adipose tissue of farm pigs. Adipose tissue samples were extracted from the abdominal region of the animals. Because the pigs were not raised in a controlled environment, such as a bioterium, it was necessary to carry out rigorous procedures for disinfection. After this procedure, cells were isolated by mechanical dissociation and enzymatic digestion. A proliferation curve was performed and used to calculate the doubling time of the population. The characterization of pASCs was performed by immunophenotyping and cell differentiation in osteogenic and adipogenic lineages. The described method was efficient for the isolation and cultivation of pASCs, maintaining cellular attributes, such as surface antigens and multipotential differentiation during in vitro proliferation. This protocol presents the isolation and cultivation of ASCs from farm pig as an alternative for the isolation and cultivation of ASCs from minipigs, which require strictly controlled maintenance conditions and a more expensive process.

5.
Folia Morphol (Warsz) ; 80(3): 575-582, 2021.
Article in English | MEDLINE | ID: mdl-32844389

ABSTRACT

BACKGROUND: The current study aims to determine the prevalence of variations of the aortic arch using computed tomography angiography (CTA), as well as morphometries and gender correlations. MATERIALS AND METHODS: A retrospective, transverse, observational and descriptive study of 220 CTA was performed. The branching pattern, most cranial vertebral level of the aortic arch, area of the proximal, middle and distal segments of the arch, area of each branch, and the path of atypical arteries were recorded. Results were analysed and stratified by gender. RESULTS: The typical aortic arch branching pattern was present in 77.7% without statistical significance between genders. The most common variant was a two-branch pattern with a common trunk and a left subclavian (13.6%), followed by a typical branching pattern with an added left vertebral artery (7.3%). T3 was the most frequent cranial level (32.3%), followed by T2-T3 (26.8%), and T3-T4 (23.2%). The mean areas of the aortic arch were 685.5 ± 183.9, 476.1 ± 124.1, and 445.0 ± 145.1 mm2 for the proximal, middle and distal segments, with statistical difference between men and women in the middle and distal segments. Three paths of atypical arteries were identified: bifurcated vertebral artery (0.5%), aberrant right subclavian artery (0.5%), and left subclavian ostium obstruction (0.5%). CONCLUSIONS: Mexican population has one of the highest prevalence of variations in the aortic arch branching pattern. The high probability of finding these should be taken into consideration when assessing patients. A standardised classification method would contemplate future un-reported findings, without causing confusion by the different numbers assigned by each author.


Subject(s)
Aorta, Thoracic , Cardiovascular Abnormalities , Aorta, Thoracic/diagnostic imaging , Computed Tomography Angiography , Female , Humans , Male , Retrospective Studies , Subclavian Artery/diagnostic imaging
6.
Ginecol Obstet Mex ; 84(8): 535-41, 2016 08.
Article in Spanish | MEDLINE | ID: mdl-29424516

ABSTRACT

Background: Uterine arteriovenous malformation is a rare disorder that can cause sudden life-threatening vaginal bleeding. Objetive: To present the clinical features in addition to the use of office gynecologic ultrasound and other imaging techniques in the diagnosis and minimally-invasive treatment of a patient with sudden vaginal bleeding resulting from a uterine arteriovenous malformation. Case report: A 31 year old woman presented sudden onset vaginal bleeding requiring the transfusion of 3 units of red blood cells. An initial diagnosis of uterine arteriovenous malformation was made using an office gynecological ultrasound and Color Doppler sonography. The patient was referred to interventional radiology for confirmation of the diagnosis and patient care. The diagnosis and localization of the uterine arteriovenous malformation was confirmed using magnetic resonance imaging. Therapeutic management proceeded with superselective angiography and embolization of the supplying arteries resulting in immediate symptomatic resolution. Conclusion: The use of office gynecologic ultrasound in combination with other imaging techniques is an important tool in the diagnosis and localization of uterine arteriovenous malformation. Embolization of supplying arteries is considered a safe and effective therapeutic option due to advances in radiologic intervention techniques. Advantages of this procedure include a minimally-invasive technique, low morbidity and preservation of uterine function.


Subject(s)
Arteriovenous Malformations/complications , Uterine Artery Embolization/methods , Uterine Hemorrhage/etiology , Uterus/blood supply , Adult , Arteriovenous Malformations/diagnostic imaging , Arteriovenous Malformations/therapy , Female , Humans , Magnetic Resonance Imaging , Ultrasonography, Doppler, Color , Uterine Hemorrhage/therapy
8.
An Pediatr (Barc) ; 77(1): 51-6, 2012 Jul.
Article in Spanish | MEDLINE | ID: mdl-22387331

ABSTRACT

INTRODUCTION: Kabuki syndrome (OMIM: #147 920) presents as large palpebral fissures with eversion of the lateral third of the lower eyelids, depressed nasal bridge, arched eyebrows, dysplastic ears and in most cases, with mental retardation. Patients have minor and major abnormalities in different systems. Its genetic basis is heterogeneous, but recently has been associated with mutations in gen MLL2. CASE REPORTS: We present two patients with clinical features compatibles with the syndrome, mainly: large palpebral fissures with eversion of the lateral third of the lower eyelids, depressed nasal bridge, arched eyebrows, flat nose, persistent fingertip pads, cardiopathies and renal anomalies. COMMENTARY: The diagnosis of this condition is clinical. The characteristics in the cases are compared with the patients reported in the literature. The importance of early diagnosis is to provide preventive management and an appropriate genetic counseling for the family.


Subject(s)
Abnormalities, Multiple/diagnosis , Hematologic Diseases/diagnosis , Vestibular Diseases/diagnosis , Child , Face/abnormalities , Humans , Male , Phenotype
9.
Arq. bras. med. vet. zootec ; 62(4): 875-882, ago. 2010. tab
Article in Portuguese | VETINDEX | ID: vti-5891

ABSTRACT

Avaliaram-se os efeitos da silagem de grãos úmidos de milho e da substituição parcial ou total de milho seco por polpa de citrus sobre a produção e a composição do leite de vacas mantidas em pastejo de capim-elefante, manejado intensivamente. Foram utilizadas 12 vacas da raça Holandesa, "de alta cruza" distribuídas em quatro tratamentos, em delineamento do tipo quadrado latino. Todas as vacas receberam concentrados que diferiram nas fontes de carboidratos: milho-grão seco moído, polpa de citrus mais milho grão seco moído, polpa de citrus e silagem de grãos úmidos de milho. Não foi detectada diferença (P>0,05) na produção de leite total, de leite corrigido para gordura (LCG 3,5) e para sólidos (LCS) entre tratamentos. Vacas que receberam milho-grão seco e silagem de milho de alta umidade apresentaram maior porcentagem de proteína e sólidos totais no leite (P<0,05), e as que receberam polpa de citrus, maior porcentagem de gordura (P<0,01). As que consumiram silagem de grãos úmidos apresentaram menor valor de nitrogênio ureico no leite (P<0,05). A ausência de resposta positiva ao processamento do milho pode ser razão do potencial de produção do sistema em pasto e do estresse calórico sofrido pelos animais. Em critérios de pagamento do leite em que a composição não tem valor econômico definido, qualquer uma das fontes de carboidratos testados no presente estudo pode ser utilizada.(AU)


Twelve Holstein dairy cows were assigned to one of four treatments in a 4x4 latin square design. Cows grazed Elephant grass and were supplemented with different concentrates which differed in the carbohydrate source as follows: ground dry corn (MG), citrus pulp plus ground dry corn (MP), citrus pulp (PC), and high moisture corn (MU). There was no difference (P>0.05) between treatments neither in total milk production corrected for 3.5 percent nor in milk production corrected for solids. Cows fed ground dry corn and high moisture corn showed higher levels of milk protein and milk total solids (P<0.05) and cows fed citrus pulp showed higher levels of milk fat (P<0.01). Cows that consumed high moisture corn showed lower levels of milk urea nitrogen (P<0.05), indicating that they used nitrogen more efficiently. The lack of positive statistical response in cows consuming high moisture corn could be caused by the production potential of grazing systems as well as by heat stress. For milk payment criteria without considering composition, any carbohydrate source tested may be used for feeding.(AU)


Subject(s)
Animals , Female , Cattle , Silage , Milk/chemistry , Animal Feed , Food Composition , Citrus , Zea mays , Food Quality
10.
Arq. bras. med. vet. zootec ; Arq. bras. med. vet. zootec. (Online);62(4): 875-882, Aug. 2010. tab
Article in Portuguese | LILACS | ID: lil-562055

ABSTRACT

Avaliaram-se os efeitos da silagem de grãos úmidos de milho e da substituição parcial ou total de milho seco por polpa de citrus sobre a produção e a composição do leite de vacas mantidas em pastejo de capim-elefante, manejado intensivamente. Foram utilizadas 12 vacas da raça Holandesa, "de alta cruza" distribuídas em quatro tratamentos, em delineamento do tipo quadrado latino. Todas as vacas receberam concentrados que diferiram nas fontes de carboidratos: milho-grão seco moído, polpa de citrus mais milho grão seco moído, polpa de citrus e silagem de grãos úmidos de milho. Não foi detectada diferença (P>0,05) na produção de leite total, de leite corrigido para gordura (LCG 3,5) e para sólidos (LCS) entre tratamentos. Vacas que receberam milho-grão seco e silagem de milho de alta umidade apresentaram maior porcentagem de proteína e sólidos totais no leite (P<0,05), e as que receberam polpa de citrus, maior porcentagem de gordura (P<0,01). As que consumiram silagem de grãos úmidos apresentaram menor valor de nitrogênio ureico no leite (P<0,05). A ausência de resposta positiva ao processamento do milho pode ser razão do potencial de produção do sistema em pasto e do estresse calórico sofrido pelos animais. Em critérios de pagamento do leite em que a composição não tem valor econômico definido, qualquer uma das fontes de carboidratos testados no presente estudo pode ser utilizada.


Twelve Holstein dairy cows were assigned to one of four treatments in a 4x4 latin square design. Cows grazed Elephant grass and were supplemented with different concentrates which differed in the carbohydrate source as follows: ground dry corn (MG), citrus pulp plus ground dry corn (MP), citrus pulp (PC), and high moisture corn (MU). There was no difference (P>0.05) between treatments neither in total milk production corrected for 3.5 percent nor in milk production corrected for solids. Cows fed ground dry corn and high moisture corn showed higher levels of milk protein and milk total solids (P<0.05) and cows fed citrus pulp showed higher levels of milk fat (P<0.01). Cows that consumed high moisture corn showed lower levels of milk urea nitrogen (P<0.05), indicating that they used nitrogen more efficiently. The lack of positive statistical response in cows consuming high moisture corn could be caused by the production potential of grazing systems as well as by heat stress. For milk payment criteria without considering composition, any carbohydrate source tested may be used for feeding.


Subject(s)
Animals , Female , Cattle , Animal Feed , Food Composition , Milk/chemistry , Silage , Citrus , Food Quality , Zea mays
11.
Parasitology ; 135(3): 347-57, 2008 Mar.
Article in English | MEDLINE | ID: mdl-17991305

ABSTRACT

We have previously reported that genetic immunization with Tc13Tul antigen of Trypanosoma cruzi, the aetiological agent of Chagas' disease, triggers harmful effects and non-protective immune responses. In order to confirm the role of Tc13 antigens during T. cruzi infection, herein we studied the humoral and cellular immune responses to the Tc13Tul molecule and its EPKSA C-terminal portion in BALB/c T. cruzi-infected mice or mice immunized with recombinant Tc13Tul. Analysis of the antibody response showed that B-cell epitopes that stimulate a sustained IgM production along the infection and high levels of IgG in the acute phase are mainly located at the Tc13 N- and C-terminal domains, respectively. DTH assays showed that T-cell epitopes are mainly at the Tc13 N-terminal segment and that they do not elicit an efficient memory response. Recombinant Tc13Tul did not induce IFN-gamma secretion in either infected or immunized mice. However, a putative CD8+Tc13Tul-derived peptide was found to elicit IFN-gamma production in chronically infected animals. Immunization with recombinant Tc13Tul did not induce pathology in tissues and neither did it protect against the infection. Our results show that in the outcome of T. cruzi infection the Tc13 family protein mainly triggers non-protective immune responses.


Subject(s)
Antigens, Protozoan/immunology , Chagas Disease/immunology , Trypanosoma cruzi/immunology , Animals , Antibodies, Protozoan/blood , Antibody Formation/immunology , Chagas Disease/prevention & control , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay/methods , Immunity, Cellular/immunology , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Interferon-gamma/biosynthesis , Interleukin-4/biosynthesis , Male , Mice , Mice, Inbred BALB C , Random Allocation , Time Factors
12.
Parasitology ; 132(Pt 6): 855-66, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16478565

ABSTRACT

Tc13 is a trans-sialidase family protein of Trypanosoma cruzi, the aetiological agent of Chagas' disease. Recently, in vitro studies had suggested that Tc13 might participate in the pathogenesis of the disease. In order to study the role of Tc13 antigens in an in vivo model, we administered plasmid DNA encoding a Tc13 antigen from the Tulahuén strain (Tc13 Tul) to BALB/c mice and evaluated the immunological and pathological manifestations as well as the capacity of this antigen to confer protection against T. cruzi infection. Tc13 Tul immunization did not elicit a detectable humoral immune response but induced specific memory T-cells with no capacity to produce IFN-gamma. Five months after DNA-immunization with Tc13 Tul, signs of hepatotoxicity and reactive changes in the heart, liver and spleen were observed in 40-80% of mice. When Tc13 Tul DNA-immunized animals were challenged with trypomastigotes, a significant decrease in parasitaemia in early and late acute phase was observed without modification in the survival rate. Surprisingly, Tc13 Tul-immunized mice chronically infected with T. cruzi showed a decrease in the severity of heart damage. We conclude that, in BALB/c mice, genetic immunization with Tc13 Tul mainly induces immune responses associated with pathology.


Subject(s)
Antigens, Protozoan/immunology , Chagas Disease/immunology , Gene Expression/physiology , Trypanosoma cruzi/immunology , Vaccines, DNA/immunology , Animals , Antibodies, Protozoan/blood , Antibody Formation/immunology , COS Cells , Chagas Disease/mortality , Chagas Disease/pathology , Chagas Disease/prevention & control , Chlorocebus aethiops , Female , Gene Expression/immunology , Immunity, Cellular/immunology , Interferon-gamma/biosynthesis , Mice , Mice, Inbred BALB C , Parasitemia/immunology , Parasitemia/prevention & control , Spleen/immunology , Spleen/pathology , Time Factors , Trypanosoma cruzi/genetics
13.
Parasitology ; 132(Pt 3): 345-55, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16238824

ABSTRACT

With the aim to study proteinases released to the culture medium during Trypanosoma cruzi metacyclogenesis, the presence of cysteine proteinases (CPs) was analysed in culture supernatants obtained throughout the differentiation induced by stimulation of epimastigotes with Triatoma infestans hindgut homogenate. In SDS-gelatin containing gels, an important endopeptidase activity with apparent molecular weight range between 97 and 116 kDa was encountered at pH 6, which was abolished by the specific cysteine proteinase inhibitor E-64 and TLCK, but not by pepstatin, 1,10 phenantroline or PMSF. This novel CP, named TcCPmet, showed affinity to cystatin-Sepharose, denoting its thiol-proteinase character as well as to ConA-Sepharose, indicating it contains N-linked oligosaccharides. However, it presented a different elution pattern on ConA-Sepharose than cruzipain and, in addition, it was not recognized by anti-cruzipain serum, facts that strongly suggest the different nature of both CPs. Moroever, evidence is presented indicating that TcCPmet was able to hydrolyse the same chromogenic peptides as cruzipain at optimal alkaline pH values, although with a different order of effectiveness. Our results indicate the presence of a novel CP secreted by metacyclic trypomastigotes and reinforces the important role of these enzymes in metacyclogenesis.


Subject(s)
Cysteine Endopeptidases/isolation & purification , Life Cycle Stages/physiology , Trypanosoma cruzi/enzymology , Trypanosoma cruzi/physiology , Animals , Blotting, Western/veterinary , Chromatography, Affinity/veterinary , Cross Reactions , Culture Media/chemistry , Culture Techniques/veterinary , Cysteine Endopeptidases/chemistry , Cysteine Endopeptidases/drug effects , Hydrogen-Ion Concentration , Protease Inhibitors/pharmacology , Triatoma/chemistry , Trypanosoma cruzi/growth & development
14.
Pharmacol Biochem Behav ; 73(4): 951-61, 2002 Nov.
Article in English | MEDLINE | ID: mdl-12213542

ABSTRACT

Levonorgestrel (LNG), a contraceptive progestin, exhibits, besides its progestational activity, other hormone-like effects at the peripheral level. To assess whether LNG and its metabolites exert androgenic and/or estrogenic actions at the central nervous system (CNS), their effects on male sexual behavior in castrated rats were examined. LNG, 5alpha-dihydro LNG (5alphaLNG), and the 3alpha,5alpha- and 3beta,5alpha-tetrahydro derivatives of LNG (3alphaLNG and 3betaLNG, respectively) were administered for 3 weeks either alone (1000 microg/day) or in combination (300 microg/day) with 5alpha-dihydrotestosterone (DHT, 300 microg/day) or with estradiol-17beta (E(2), 5 microg/day). Copulatory behavior was assessed twice per week and sex accessory organs weights recorded at the end of treatments. LNG restored full copulatory behavior comparable to that of testosterone treated animals, although with a slight delay, whereas 5alphaLNG induced male sexual behavior in a significantly lower number of subjects. 3betaLNG and 3alphaLNG induced mounting but failed to restore intromission and ejaculation. Combined LNG+E(2) treatment fully activated mounting and intromission, but ejaculation was only partially restored. Combined 5alphaLNG+E(2) treatment and the combinations of 3alphaLNG or 3betaLNG with E(2) were significantly less effective, activating fewer intromissions and ejaculations. 3alphaLNG and 5alphaLNG, in combination with DHT, restored male sexual behavior. LNG, but not its metabolites, induced a significant increase on the weight of sex accessory organs. The overall results demonstrated that high doses of LNG induce a potent androgen agonistic behavioral effect and that its A-ring reduction diminishes this potency and enables a shift towards a weak estrogen-like effect.


Subject(s)
Gonadal Steroid Hormones/metabolism , Gonadal Steroid Hormones/pharmacology , Levonorgestrel/metabolism , Levonorgestrel/pharmacology , Sexual Behavior, Animal/drug effects , Androgens/metabolism , Androgens/pharmacology , Animals , Estrogens/metabolism , Estrogens/pharmacology , Female , Male , Rats , Rats, Wistar , Sexual Behavior, Animal/physiology
15.
Eur J Pharmacol ; 427(2): 167-74, 2001 Sep 14.
Article in English | MEDLINE | ID: mdl-11557270

ABSTRACT

Levonorgestrel (13beta-ethyl-17alpha-ethynyl-17beta-hydroxy-4-gonen-3-one), a potent contraceptive progestin stimulates growth and proliferation of cultured breast cancer cells through a receptor-mediated mechanism, even though levonorgestrel does not bind to the oestrogen receptor (ER). To assess whether the oestrogen-like effects induced by this synthetic progestin are exerted via its metabolic conversion products, we studied the binding affinity of three A-ring levonorgestrel derivatives to the ER and their capability to transactivate an oestrogen-dependent yeast system co-transfected with the human ER gene and oestrogen responsive elements fused to a beta-galactosidase reporter vector. The results demonstrated that the 3beta,5alpha reduced levonorgestrel derivative and to a lesser extent its 3alpha isomer interact with the oestrogen receptor, with a significantly lower relative binding affinity (2.4% and 0.4%, respectively) than that of oestradiol (100%), while levonorgestrel does not. Both levonorgestrel metabolites were able to activate, in a dose-dependent manner, the beta-galactosidase reporter gene in the yeast expression system, an effect that was precluded by a steroidal antioestrogen. The oestrogenic potency of levonorgestrel metabolites was significantly lower (750-fold) than that of oestradiol. Furthermore, high doses of 3beta,5alpha levonorgestrel (2.5 mg/day/6 days) induced an increase of oestrogen-dependent progestin receptor in the anterior pituitary of castrated rats. The overall data offer a plausible explanation for the weak oestrogenic effects induced by high, non-pharmacological doses of levonorgestrel.


Subject(s)
Contraceptive Agents, Female/pharmacology , Estrogens/pharmacology , Levonorgestrel/pharmacology , Animals , Binding, Competitive , Contraceptive Agents, Female/metabolism , Dose-Response Relationship, Drug , Estradiol/analogs & derivatives , Estradiol/pharmacology , Estrogen Antagonists/pharmacology , Estrogens/metabolism , Female , Fulvestrant , Humans , Levonorgestrel/analogs & derivatives , Levonorgestrel/metabolism , Pituitary Gland, Anterior/drug effects , Pituitary Gland, Anterior/metabolism , Rats , Rats, Wistar , Receptors, Estrogen/genetics , Receptors, Estrogen/metabolism , Receptors, Progesterone/drug effects , Receptors, Progesterone/metabolism , Recombinant Fusion Proteins/drug effects , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , Saccharomyces cerevisiae/genetics , beta-Galactosidase/drug effects , beta-Galactosidase/genetics , beta-Galactosidase/metabolism
16.
Eur J Pharmacol ; 417(3): 249-56, 2001 Apr 13.
Article in English | MEDLINE | ID: mdl-11334857

ABSTRACT

Gestodene (13beta-ethyl-17alpha-ethynyl-17beta-hydroxy-4,5-gonadien-3-one), the most potent progestin ever synthesized, stimulates breast cancer cell growth through an oestrogen receptor-mediated mechanism, and its use in hormonal contraception has been associated with side effects attributable to oestrogenic actions. These observations have remained controversial, since gestodene does not bind to the oestrogen receptor or exert oestrogen-like activities. Recently, we have demonstrated that non-phenolic gestodene derivatives interact with oestrogen receptors and induce oestrogenic effects in cell expression systems. To assess whether gestodene is biotransformed to metabolites with intrinsic oestrogenic potency, [3H]- and [14C]-labelled gestodene were incubated in vitro with rat anterior pituitary, hypothalamus and ventral prostate homogenates under different experimental conditions. The most remarkable finding was the isolation and identification of 3beta,5alpha-tetrahydrogestodene and 3alpha,5alpha-tetrahydrogestodene as metabolic conversion products of gestodene, presumably with 5alpha-dihydrogestodene as intermediate. The overall results seem to indicate that the weak oestrogenic effects attributable to gestodene could be mediated by its tetrahydro metabolites.


Subject(s)
Hypothalamus/metabolism , Norpregnenes/chemistry , Norpregnenes/metabolism , Pituitary Gland, Anterior/metabolism , Prostate/metabolism , 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/metabolism , Animals , Biotransformation , Contraceptives, Oral, Synthetic/chemistry , Contraceptives, Oral, Synthetic/metabolism , Contraceptives, Oral, Synthetic/pharmacokinetics , Female , Hydrogen-Ion Concentration , Hypothalamus/enzymology , Male , NADP/metabolism , Norpregnenes/pharmacokinetics , Pituitary Gland, Anterior/enzymology , Progesterone Congeners/chemistry , Progesterone Congeners/metabolism , Progesterone Congeners/pharmacokinetics , Prostate/enzymology , Rats , Rats, Wistar , Testosterone/metabolism
17.
FEMS Microbiol Lett ; 189(2): 253-7, 2000 Aug 15.
Article in English | MEDLINE | ID: mdl-10930747

ABSTRACT

The complete sequence and genomic characterization of the tyrosine aminotransferase (TAT) gene from Trypanosoma rangeli is reported. The gene was found to be organized in a tandem multicopy gene array. A homologous mRNA species (2.5 kb) was identified in the epimastigote form of the parasite. From the deduced amino acid sequence, the gene encodes a protein of 420 amino acids with a predicted molecular mass of 46.4 kDa and a theoretical pI of 6.23. A high sequence identity was found with the Trypanosoma cruzi, human and rat enzymes. All the essential residues for TAT enzymatic activity are conserved, as well as a pyridoxal-phosphate attachment site typical of class-I aminotransferases. The recombinant enzyme was recognized by a monoclonal antibody against the T. cruzi enzyme. Additionally, the recombinant protein showed enzymatic activity when incubated with L-tyrosine and 2-oxoglutaric acid as substrates.


Subject(s)
Trypanosoma/enzymology , Trypanosoma/genetics , Tyrosine Transaminase/genetics , Amino Acid Sequence , Animals , Genes, Protozoan , Genome , Humans , Molecular Sequence Data , Protozoan Proteins/genetics , Rats , Sequence Alignment , Sequence Analysis
18.
Gac Med Mex ; 136(3): 207-12, 2000.
Article in Spanish | MEDLINE | ID: mdl-10893849

ABSTRACT

OBJECTIVE: Assess the degree of external consistency and validity of the EXP CLIN instrument has for measuring the quality information contained in medical charts. MATERIAL AND METHODS: In a transverse comparative study, two hundred and twelve clinical charts were randomly selected belonging to patients seen at a pediatric hospital. The charts were assessed using the EXP-CLIN for phases: 1) internal assessment: by hospital personnel of the pediatric hospital, and, II) external assessment: by personnel from other hospitals. The results were analyzed using the concordance method. RESULTS: The concordance percentages were found to be 76% for medical charts and medical notes related with the process of diagnosis-treatment, as well as the general characteristics of the clinical chart. The concordance percentages average was 88%, supporting the idea that when the EXP-CLIN instrument is applied twice to the same chart, good concordance is obtained between the two measures. CONCLUSIONS: Given that the application of the instrument documented a good level of external consistency, its use is justified for assessing the quality of the information contained in the charts of the patients seen at our unit.


Subject(s)
Medical Records/standards , Cross-Sectional Studies , Data Collection , Humans , Medical Records/statistics & numerical data , Observer Variation , Reproducibility of Results
19.
J Endocrinol ; 165(3): 693-702, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10828854

ABSTRACT

Gestodene (17 alpha-ethynyl-13 beta-ethyl-17 beta-hydroxy-4, 15-gonadien-3-one) is the most potent synthetic progestin currently available and it is widely used as a fertility regulating agent in a number of contraceptive formulations because of its high effectiveness, safety and acceptability. The observation that contraceptive synthetic progestins exert hormone-like effects other than their progestational activities, prompted us to investigate whether gestodene (GSD) administration may induce oestrogenic effects, even though the GSD molecule does not interact with intracellular oestrogen receptors (ER). To assess whether GSD may exert oestrogenic effects through some of its neutral metabolites, a series of experimental studies were undertaken using GSD and three of its A-ring reduced metabolites. Receptor binding studies by displacement analysis confirmed that indeed GSD does not bind to the ER, whereas its 3 beta,5 alpha-tetrahydro reduced derivative (3 beta GSD) interacts with a relative high affinity with the ER. The 3 alpha,5 alpha GSD isomer (3 alpha GSD) also binds to the ER, though to a lesser extent. The ability of the A-ring reduced GSD derivatives to induce oestrogenic actions was evaluated by the use of two different molecular bioassays: (a) transactivation of a yeast system co-transfected with the human ER alpha (hER alpha) gene and oestrogen responsive elements fused to the beta-galactosidase reporter vector and (b) transactivation of the hER alpha-mediated transcription of the chloramphenicol acetyl transferase (CAT) reporter gene in a HeLa cells expression system. The oestrogenic potency of 3 beta GSD was also assessed by its capability to induce oestrogen-dependent progestin receptors (PR) in the anterior pituitary of castrated female rats. The results demonstrated that 3 beta GSD and 3 alpha GSD were able to activate, in a dose-dependent manner, the hER alpha-mediated transcription of both the beta-galactosidase and the CAT reporter genes in the yeast and HeLa cells expression systems respectively. In both assays the 3 beta derivative of GSD exhibited a significantly greater oestrogenic effect than its 3 alpha isomer, while unchanged GSD and 5 alpha GSD were completely ineffective. Neither 3 beta GSD nor 3 alpha GSD exhibited oestrogen synergistic actions. Interestingly, the pure steroidal anti-oestrogen ICI-182,780 diminished the transactivation induced by 3 beta GSD and 3 alpha GSD in the yeast expression system. Furthermore, administration of 3 beta GSD resulted in a significant increase of oestrogen-dependent PR in the anterior pituitaries of castrated rats in comparison with vehicle-treated animals. The characteristics of the 3 beta GSD-induced PR were identical to those induced by oestradio benzoate. The overall results demonstrate that 3 beta GSD and its 3 alpha isomeric alcohol specifically bind to the ER and possess a weak intrinsic oestrogenic activity, whereas unmodified GSD does not. The data contribute to a better understanding of the GSD mechanism of action and allow the hypothesis to be advanced that the slight oestrogenlike effects attributable to GSD are mediated by its non-phenolic, tetrahydro reduced metabolites.


Subject(s)
Contraceptives, Oral, Synthetic/pharmacology , Norpregnenes/pharmacology , Progesterone Congeners/pharmacology , Animals , Binding, Competitive , Contraceptives, Oral, Synthetic/metabolism , Female , HeLa Cells , Humans , Norpregnenes/metabolism , Oxidation-Reduction , Pituitary Gland, Anterior/drug effects , Pituitary Gland, Anterior/metabolism , Progesterone Congeners/metabolism , Rats , Rats, Wistar , Receptors, Estradiol/metabolism , Receptors, Progesterone/biosynthesis , Saccharomyces cerevisiae/genetics , Transcriptional Activation/drug effects
20.
Contraception ; 59(5): 339-43, 1999 May.
Article in English | MEDLINE | ID: mdl-10494488

ABSTRACT

It has been suggested that some contraceptive derivatives of 19-nor-testosterone possess estrogenic activity that may facilitate the development of breast cancer. The aim of this work was to investigate the estrogenic properties of norethisterone (NET) and its A-ring-reduced derivatives by determining progesterone receptor (PR) and c-fos mRNA content of two estrogen-regulated genes in the uterus of ovariectomized rats. mRNA content was evaluated by Northern blot 1-6 h after 17 beta-estradiol administration. The highest PR and c-fos mRNA content was observed 3 h and 2 h after 17 beta-estradiol administration, respectively. NET did not modify either PR or c-fos mRNA content. In contrast, 5 alpha- and 3 beta, 5 alpha-NET significantly increased mRNA content of both genes. The increase in c-fos mRNA content induced by these reduced compounds was lower than that found with estradiol treatment. The overall results indicate that NET administration can indirectly induce estrogenic effects through the action of its 5 alpha-dihydro and 3 beta, 5 alpha-tetrahydro derivatives.


Subject(s)
Contraceptives, Oral, Synthetic/pharmacology , Gene Expression Regulation/drug effects , Genes, fos/drug effects , Norethindrone/analogs & derivatives , Norethindrone/pharmacology , Proto-Oncogene Proteins c-fos/genetics , Receptors, Progesterone/genetics , Uterus/metabolism , Animals , Estradiol/pharmacology , Female , Ovariectomy , RNA, Messenger/genetics , Rats , Rats, Long-Evans , Transcription, Genetic/drug effects , Uterus/drug effects
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