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1.
Biol Trace Elem Res ; 2024 Jan 20.
Article in English | MEDLINE | ID: mdl-38244175

ABSTRACT

Fluorosis decreases the learning and memory ability in humans and animals, while exercise can reduce the risk of cognitive decline. However, the effect of exercise on learning and memory in fluoride-exposed mice is unclear. For this purpose, in this study, mice were randomly allotted into four groups (16 mice per group, half male and half female): control group (group C), fluoride group (group F, 100 mg/L sodium fluoride (NaF)), exercise group (group E, treadmill exercise), and E plus F group (group EF, treadmill exercise, and 100 mg/L NaF). During 6 months of exposure, exercise alleviated the NaF-induced decline in memory and learning. In addition, NaF induced injuries in mitochondria and myelin sheath ultrastructure and reduced the neurons number, while exercise restored them. Metabolomics results showed that phosphatidylethanolamine, pregnenolone (PREG), and lysophosphatidic acid (LysoPA) were altered among groups C, F, and EF. Combined with previous studies, it can be suggested that PREG might be a biomarker in response to exercise-relieving fluorine neurotoxicity. The miRNA sequencing results indicated that in the differently expressed miRNAs (DEmiRNAs), miR-206-3p, miR-96-5p, and miR-144-3p were shared in groups C, F, and EF. After the QRT-PCR validation and in vitro experiments, it was proved that miR-206-3p could reduce cell death and regulate AP-1 transcription factor subunit (JunD) and histone deacetylase 4 (HDAC4) to alleviate fluoride neurotoxicity. To sum up, the current study reveals that exercise could alleviate NaF-induced neurotoxicity by targeting miR-206-3p or PREG, which will contribute to revealing the pathogenesis and therapeutic method of fluoride neurotoxicity.

2.
Mayo Clin Proc Innov Qual Outcomes ; 4(3): 295-304, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32542221

ABSTRACT

OBJECTIVE: To determine whether implementation of the Pregnancy Reasonably Excluded Guide (PREG) in a primary care gynecology clinic improves access to contraceptive procedures and affects the number of urine human chorionic gonadotropin (hCG) tests. PATIENTS AND METHODS: PREG was administered to 981 women aged 18 to 50 years (1012 visits) who were seen in a primary care gynecology clinic for contraceptive procedures from September 30, 2015, through April 30, 2018. Contraceptive procedures included insertion of an intrauterine contraceptive (IUC) or subdermal contraceptive implant. After PREG review and patient discussion, health care professional decided to perform the procedure with or without hCG measurement or to reschedule if the patient's pregnancy status was uncertain. We collected data on the rate of same-day contraceptive procedures and the rate of hCG testing. Data from the PREG implementation period were compared with historical data from 185 women undergoing contraceptive procedures before PREG implementation. RESULTS: Measurement of hCG was performed in 53% of women before and 24.1% (224 of 1,012 visits) after PREG implementation in the primary care setting. After PREG implementation, 974 0f 1012 patients (96.2%) were eligible for a same-day contraceptive procedure. If traditional criteria, current menses, or a preexisting IUC or implant in place were required for IUC or implant insertion, only 594 patients (58.7%) would have qualified for a same-day procedure. No contraceptive procedures occurred in pregnant women. CONCLUSION: PREG implementation allowed for same-day IUC or implant insertion in 974 women (96.2%) seen for a contraceptive procedure. Most of the women (75.9%) did not require preprocedure hCG measurement.

3.
Epigenetics ; 15(11): 1243-1258, 2020 11.
Article in English | MEDLINE | ID: mdl-32448018

ABSTRACT

DNA methylation is highly sensitive to in utero perturbations and has an established role in both embryonic development and regulation of gene expression. The foetal genetic component has been previously shown to contribute significantly to the timing of birth, yet little is known about the identity and behaviour of individual genes. The aim of this study was to test the extent genome-wide DNA methylation levels in umbilical cord blood were associated with gestational age at birth (GA). Findings were validated in an independent sample and evidence for the regulation of gene expression was evaluated for cis gene relationships in specimens with multi-omic data. Genome-wide DNA methylation, measured by the Illumina Infinium Human Methylation 450 K BeadChip, was associated with GA for 2,372 CpG probes (5% FDR) in both the Pregnancy, Race, Environment, Genes (PREG) and Newborn Epigenetic Study (NEST) cohorts. Significant probes mapped to 1,640 characterized genes and an association with nearby gene expression measures obtained by the Affymetrix HG-133A microarray was found for 11 genes. Differentially methylated positions were enriched for actively transcribed and enhancer chromatin states, were predominately located outside of CpG islands, and mapped to genes enriched for inflammation and innate immunity ontologies. In both PREG and NEST, the first principal component derived from these probes explained approximately one-half (58.1% and 47.8%, respectively) of the variation in GA. Gene pathways identified are consistent with the hypothesis of pathogen detection and response by the immune system to elicit premature labour as a consequence of unscheduled inflammation.


Subject(s)
DNA Methylation , Genetic Loci , Gestational Age , Adult , CpG Islands , Epigenome , Female , Fetal Blood/metabolism , Genome-Wide Association Study , Humans , Immunity, Innate/genetics , Infant, Newborn , Infant, Premature , Male , Premature Birth/genetics
4.
Mater Sci Eng C Mater Biol Appl ; 110: 110650, 2020 May.
Article in English | MEDLINE | ID: mdl-32204080

ABSTRACT

Antiepileptic drug (Preg) and neurotransmitters (Gpn, Gly, Asp, Glu, Ser, GABA and Ade) were used to synthesis a series of ternary Cu2+ complexes. Surface morphology and chemical composition of the complexes were using studied SEM and EDX spectra. Purity, molecular weight and formulae of the complexes were determined from GC-MS spectra and elemental analysis. XRD data and N-Treor implemented in Expo2014 computer program reveal monoclinic crystal system with space group P1 2/c 1 and P 1 21 1 of the complexes. IR spectra exhibited that Preg, Gpn and GABA coordinated to the Cu2+ as monodentate ligand through COOH whereas the amino acids bonded through the -NH2, COO- groups. UV-Vis spectra and magnetic moment values indicated pseudo tetrahedral stereochemistry. ESR spectra showed that the complexes have isotropic and axial structures with dx2-y2 ground state. TGA, DTG and DTA confirm the suggested structure and mechanism for thermal decomposition was suggested. Kinetic and thermodynamic parameters were calculated using Coats-Redfern equation. The complexes [Cu(Preg)(Ser)Cl] and [Cu(Preg)(Ade)Cl2] showed greater anticonvulsant activity compared against PTZ-induced seizures in male Albino mice. Recorded latency time for the complexes [Cu(Preg)(Ser)Cl] and [Cu(Preg)(GABA)(OH)Cl].2H2O was longer than that recorded with Preg indicating higher anticonvulsant effect.


Subject(s)
Anticonvulsants/therapeutic use , Coordination Complexes/therapeutic use , Copper/therapeutic use , Neurotransmitter Agents/metabolism , Pregabalin/therapeutic use , Animals , Electric Conductivity , Kinetics , Magnetic Phenomena , Male , Mice , Spectrometry, X-Ray Emission , Spectrophotometry, Infrared , Temperature , X-Ray Diffraction
5.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-824156

ABSTRACT

Objective To explore the application value of B -ultrasound examination in gynecological acute abdomen.Methods From October 2015 to October 2017,150 patients with suspected gynecological acute abdomen were selected in the People's Hospital of Lishui.The effect of B-ultrasound examination in diagnosis of gynecological acute abdomen was analyzed.Results The sensitivity,specificity and total accuracy of abdominal ultrasound in the diagnosis of gynecological acute abdomen were 75.00%( 99/132),44.44%(8/18) and 71.33%(107/150), respectively.The sensitivity,specificity and total accuracy of transvaginal ultrasound in the diagnosis of gynecological acute abdomen were 87.12%(115/132),72.22%(13/18) and 85.33%(128/150),respectively.The sensitivity, specificity and total accuracy of abdominal combined with transvaginal ultrasonography in the diagnosis of gynecological acute abdomen were 98.48%(130/132),94.44%(17/18) and 98.00%(147/150),respectively.The sensitivity, specificity and total accuracy of abdominal combined with transvaginal ultrasound in the diagnosis of gynecological acute abdomen were significantly higher than those of abdominal ultrasound and transvaginal ultrasound (χ2 =8.658, 10.699,9.075,all P<0.05).The diagnosis of acute pelvic inflammation ,ectopic pregnancy ,rupture of luteal cyst and torsion of ovarian cyst by abdominal combined with transvaginal ultrasound was better than abdominal ultrasound (χ2 =13.748,5.984,13.524,6.874,all P<0.05).Conclusion Abdominal ultrasound and transvaginal ultrasound can be used to diagnose gynecological acute abdomen.However,abdominal combined with vaginal ultrasound is more effective in the diagnosis of gynecological acute abdomen ,and it can effectively improve the accuracy of diagnosis.

6.
Gen Comp Endocrinol ; 265: 97-105, 2018 09 01.
Article in English | MEDLINE | ID: mdl-28919448

ABSTRACT

The brain synthesizes steroids de novo from cholesterol, which are called neurosteroids. Based on extensive studies on neurosteroids over the past thirty years, it is now accepted that neurosteroidogenesis in the brain is a conserved property across vertebrates. However, the formation of bioactive neurosteroids in the brain is still incompletely elucidated in vertebrates. In fact, we recently identified 7α-hydroxypregnenolone (7α-OH PREG) as a novel bioactive neurosteroid stimulating locomotor behavior in the brain of several vertebrates. The follow-up studies have demonstrated that the stimulatory action of brain 7α-OH PREG on locomotor behavior is mediated by the dopaminergic system across vertebrates. More recently, we have further demonstrated that the pineal gland, an endocrine organ located close to the brain, is a major site of the formation of bioactive neurosteroids. In addition to the brain, the pineal gland actively produces 7α-OH PREG de novo from cholesterol as a major pineal neurosteroid that acts on the brain to control locomotor rhythms. This review summarizes the identification, biosynthesis and mode of action of brain and pineal 7α-OH PREG, a new bioactive neurosteroid regulating locomotor behavior, across vertebrates.


Subject(s)
17-alpha-Hydroxypregnenolone/analogs & derivatives , Behavior, Animal/drug effects , Brain/metabolism , Motor Activity/drug effects , Pineal Gland/metabolism , Vertebrates/metabolism , 17-alpha-Hydroxypregnenolone/chemistry , 17-alpha-Hydroxypregnenolone/pharmacology , Animals , Brain/drug effects , Motor Activity/physiology , Pineal Gland/drug effects
7.
Gen Comp Endocrinol ; 227: 3-15, 2016 Feb 01.
Article in English | MEDLINE | ID: mdl-26145291

ABSTRACT

Obtaining new insights by discovering novel neuropeptides and neurosteroids regulating pituitary and brain functions is essential for the progress of neuroendocrinology. At the beginning of 1970s, gonadotropin-releasing hormone (GnRH) was discovered in mammals. Since then, it was generally accepted that GnRH is the only hypothalamic neuropeptide regulating gonadotropin release in vertebrates. In 2000, however, gonadotropin-inhibitory hormone (GnIH), a novel hypothalamic neuropeptide that actively inhibits gonadotropin release, was discovered in quail. The follow-up studies demonstrated that GnIH acts as a new key player for regulation of reproduction across vertebrates. It now appears that GnIH acts on the pituitary and the brain to serve a number of behavioral and physiological functions. On the other hand, a new concept has been established that the brain synthesizes steroids, called neurosteroids. The formation of neurosteroids in the brain was originally demonstrated in mammals and subsequently in other vertebrates. Recently, 7α-hydroxypregnenolone was discovered as a novel bioactive neurosteroid inducing locomotor behavior of vertebrates, indicating that neurosteroidogenesis in the brain is still incompletely elucidated in vertebrates. At the beginning of 2010s, it was further found that the pineal gland actively produces neurosteroids. Pineal neurosteroids act on the brain to regulate locomotor rhythms and neuronal survival. Furthermore, the interaction of neuropeptides and neurosteroids is becoming clear. GnIH decreases aggressive behavior by regulating neuroestrogen synthesis in the brain. This review summarizes these new insights by discovering novel neuropeptides and neurosteroids in the field of neuroendocrinology.


Subject(s)
Brain/metabolism , Hypothalamic Hormones/metabolism , Neuroendocrinology , Neuropeptides/metabolism , Neurotransmitter Agents/metabolism , Pituitary Gland/metabolism , Animals
8.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-601897

ABSTRACT

Objective To investigate the application of syphilis detection in the pre-pregnancy eugenics inspection.Methods 12 900 women who attended the national free pre-pregnancy eugenics inspection from March 201 1 to October 2013 were selected as subjects.The treponema pallidum particle agglutination assay(TPPA)and rapid plasma regain test(RPR)were conducted among them before pregnancy,and the results of syphilis detections were recorded and compared.Results In 12 900 women,63 cases (0.49%)were syphilis positive in RPR tests,129 cases(1.00%)were syphilis positive in TPPA test,and 45 cases(0.35%)were syphilis positive both in RPR and TPPA tests.There were significant differences in positive rates of syphilis between that in the RPR test and that in the TPPA test(P <0.05),while no significant differences were found in positive rates of syphilis between that in the RPR test and that in the combined detection of RPR test and TPPA test.There were significant differences in positive rate of syphilis between that in the TPPA test and that in the combined detection of RPR test and TPPA test(P <0.05).The sensitivity of RPR test and TPPA test was 71.4% and 34.9%,respectively.Conclusion Both the RPR test and TPPA test could be the fast and ef-fective method in diagnosis of syphilis.However,RPR test might be more sensitive,which could be widely used in the pre-pregnancy eugen-ics healthy screening.Moreover,the diagnosis results could be confirmed by combination of RPR test and TPPA test.

9.
Rev. colomb. enferm ; 9(1): 95-107, Agosto de 2014.
Article in Spanish | BDENF - Nursing, LILACS, COLNAL | ID: biblio-1006061

ABSTRACT

[{"text": "El estudio buscó explorar cuáles son los antecedentes de diez mujeres mayores de 35 años de edad, de estratos 1, 2 y \r\n3, atendidas por la red distrital de salud en cuatro localidades de Bogotá en cuanto a sus embarazos y cómo son sus \r\nvivencias al respecto. Según los resultados, se trata ante todo de embarazos no planeados que, a pesar de implicar un \r\n"volver a empezar" incluso quince o más años después de la última gestación, son aceptados por las mujeres porque \r\nrepresentan para ellas compañía en el hogar cuando ya los hijos están grandes, una forma de complacer a sus parejas \r\no un hijo más por sacar adelante en el caso de las madres cabezas de hogar. Las mujeres que en su gran mayoría han \r\ntenido riesgos obstétricos en anteriores embarazos temen eventuales complicaciones y al parto, y se preocupan por la \r\nposibilidad de morir. Se recomienda atender las necesidades y preocupaciones de las gestantes, ofreciendo un acompa\r\n-\r\nñamiento que les permita sentir confianza, aclarar dudas, conocer signos de alarma y desarrollar su autocuidado. Se \r\nsugiere empoderarlas para el ejercicio consciente de sus derechos sexuales y reproductivos y para vivir sus embarazos \r\nen armonía y como una oportunidad de desarrollo para su vida", "_i": "es"}, {"text": "The study is intended to explore the history and expe\r\n-\r\nriences of pregnancies of ten 35-year-old women of \r\nsocial stratum 1, 2 and 3, who attend the District Health \r\nNetwork in different areas of Bogotá. These pregnancies \r\nare generally unplanned and, despite having to "start \r\nover" -in seven cases fifteen years or more after the \r\nprevious pregnancy- are accepted by women because they \r\nrepresent new company at home when other children are \r\ngrown, or a way to satisfy their partners with another \r\nchild to raise, in the case of head-of-household mothers. \r\nMost of the women have had previous obstetrical risk \r\npregnancies and fear health complications and death at \r\nthe time of delivery. It is recommended to note the needs \r\nand concerns expressed by the pregnant women, provi\r\n-\r\nding support that allows them to feel confident, receive \r\nanswers, know warning signs and develop self-care. \r\nAdditionally, the study suggests empowering women to \r\nexercise their sexual and reproductive rights and to live in \r\nharmony with their pregnancies and treat the pregnancy \r\nas a development opportunity in their lives", "_i": "en"}, {"text": "O estudo teve o objetivo de explorar a história das \r\ngestações as experiências com a gravidez de dez mulheres \r\ncom mais de 35 anos de idade, níveis 1, 2 e 3, servidas \r\npela Rede de Saúde do Distrito em diferentes lugares de \r\nBogotá. Isso e geralmente gravidezes não desejadas, que \r\ntem que "começar novo", em sete casos, depois de quinze \r\nanos ou mais são aceitas por mulheres, porque elas repre\r\n-\r\nsentam a eles como fazer companhia em casa e quando \r\nas crianças são grandes, uma maneira de agradar seus \r\nparceiros ou outra criança para levar para a frente, no \r\ncaso dos mães quem são chefes de família. As mulheres, \r\nque em sua maioria tiveram gestações de risco obsté\r\n-\r\ntricos anteriores, medo e parto complicações, quem estão \r\npreocupados com a possibilidade de morte. Recomenda-\r\nse a satisfazer as necessidades expressas pelas mulheres \r\ngrávidas e as suas preocupações, fornecendo suporte \r\nque elas permite sentir confiança, responder perguntas, \r\nfazer sinais de alerta e desenvolver a se cuidar. Da mesma \r\nforma, o estudo capacitá-las para o exercício cons\r\n-\r\nciente de seus direitos sexuais e reprodutivos e viver em \r\nharmonia e sua gravidez como uma oportunidade de \r\ndesenvolvimento para suas vidas.", "_i": "pt"}]


Subject(s)
Pregnancy , Maternal Age , Pregnant Women , Gender Identity
10.
Gen Comp Endocrinol ; 205: 11-22, 2014 Sep 01.
Article in English | MEDLINE | ID: mdl-24704561

ABSTRACT

Bargmann-Scharrer's discovery of "neurosecretion" in the first half of the 20th century has since matured into the scientific discipline of neuroendocrinology. Identification of novel neurohormones, such as neuropeptides and neurosteroids, is essential for the progress of neuroendocrinology. Our studies over the past two decades have significantly broadened the horizons of this field of research by identifying novel neuropeptides and neurosteroids in vertebrates that have opened new lines of scientific investigation in neuroendocrinology. We have established de novo synthesis and functions of neurosteroids in the brain of various vertebrates. Recently, we discovered 7α-hydroxypregnenolone (7α-OH PREG), a novel bioactive neurosteroid that acts as a key regulator for inducing locomotor behavior by means of the dopaminergic system. We further discovered that the pineal gland, an endocrine organ located close to the brain, is an important site of production of neurosteroids de novo from cholesterol (CHOL). The pineal gland secretes 7α-OH PREG and 3α,5α-tetrahydroprogesterone (3α,5α-THP; allopregnanolone) that are involved in locomotor rhythms and neuronal survival, respectively. Subsequently, we have demonstrated their mode of action and functional significance. This review summarizes the discovery of these novel neurosteroids and its contribution to the progress of neuroendocrinology.


Subject(s)
Neuroendocrinology , Neuropeptides/metabolism , Neurotransmitter Agents/metabolism , Pineal Gland/metabolism , 17-alpha-Hydroxypregnenolone/analogs & derivatives , 17-alpha-Hydroxypregnenolone/metabolism , Animals , Humans , Motor Activity/physiology
11.
Prog Neurobiol ; 113: 56-69, 2014 Feb.
Article in English | MEDLINE | ID: mdl-23958466

ABSTRACT

Progesterone is synthesized and actively metabolized in the central and peripheral nervous system, into neuroactive steroid metabolites, such as dihydroprogesterone, allopregnanolone and isopregnanolone. Progesterone and/or its metabolites exert a variety of effects acting as physiological regulators of neuronal and glial development and plasticity, controlling reproduction, neuroendocrine events, mood and affection. In addition, these neuroactive steroids maintain neural homeostasis and exert neuroprotective actions. In agreement, metabolic pathways of progesterone are affected by modifications in the level of gonadal hormones and by pathology or injury with a regional specificity and in a sex-dimorphic way. Therefore, observations here summarized may provide a background to design sex-specific therapies based on progesterone metabolites. On this point of view, considering that one of the major limits of a therapy based on neuroactive steroids could be modifications in their plasma levels and their consequent peripheral effects, pharmacological treatments aimed to increase their levels in the nervous system could provide an interesting therapeutic option.


Subject(s)
Nervous System/metabolism , Neurodegenerative Diseases/metabolism , Progesterone/metabolism , Animals , Female , Humans , Male , Sex Characteristics
12.
Mol Cell Endocrinol ; 382(2): 871-80, 2014 Feb 15.
Article in English | MEDLINE | ID: mdl-24189438

ABSTRACT

Marsupial ELP (early lactation protein) and its eutherian orthologue, CTI (colostrum trypsin inhibitor) are expressed in the mammary gland only for the first 100 days postpartum (Phase 2A) in the tammar wallaby and during the bovine and canine colostrogenesis period 24-36h postpartum respectively. The factors which regulate temporal ELP and CTI expression are unknown. A tammar mammary gland explant culture model was used to investigate ELP gene regulation during pregnancy and early- and mid-lactation (Phase 1, 2A and 2B respectively). Tammar ELP expression could only be manipulated in explants in vitro if the gene was already expressed in vivo. ELP expression was maximal in Phase 1 explants treated with lactogenic hormones (insulin, hydrocortisone and prolactin), but unlike LGB (ß-lactoglobulin), ELP expression was maintained in insulin or insulin and hydrocortisone over a 12-day culture period. In contrast, ELP was down-regulated when cultured without hormones. ELP could not be induced in explants cultured from mid-lactation which suggested that transcriptional repressors may prevent ELP expression during this period.


Subject(s)
Colostrum/chemistry , Gene Expression Regulation , Lactation/genetics , Mammary Glands, Animal/metabolism , Milk Proteins/genetics , Animals , Female , Hydrocortisone/pharmacology , Insulin/pharmacology , Lactoglobulins/genetics , Lactoglobulins/metabolism , Macropodidae , Mammary Glands, Animal/drug effects , Milk Proteins/metabolism , Pregnancy , Prolactin/pharmacology , Time Factors , Tissue Culture Techniques , Transcription, Genetic
13.
Prog Neurobiol ; 113: 70-8, 2014 Feb.
Article in English | MEDLINE | ID: mdl-23948490

ABSTRACT

Because the treatment and management of neuropathic pain are extremely complicated, the characterization of novel analgesics and neuroprotectors with safe toxicological profiles is a crucial need to develop efficient therapies. Several investigations revealed that the natural neurosteroid allopregnanolone (AP) exerts analgesic, neuroprotective, antidepressant and anxiolytic effects. These effects result from AP ability to modulate GABA(A), glycine, L- and T-type calcium channels. It has been shown that AP treatment induced beneficial actions in humans and animal models with no toxic side effects. In particular, a multi-parametric analysis revealed that AP efficiently counteracted chemotherapy-evoked neuropathic pain in rats. It has also been demonstrated that the modulation of AP-producing enzyme, 3α-hydroxysteroid oxido-reductase (3α-HSOR), in the spinal cord regulates thermal and mechanical pain thresholds of peripheral nerve injured neuropathic rats. The painful symptoms were exacerbated by intrathecal injections of provera (pharmacological inhibitor of 3α-HSOR) which decreased AP production in the spinal cord. By contrast, the enhancement of AP concentration in the intrathecal space induced analgesia and suppression of neuropathic symptoms. Moreover, in vivo siRNA-knockdown of 3α-HSOR expression in healthy rat dorsal root ganglia increased thermal and mechanical pain perceptions while AP evoked a potent antinociceptive action. In humans, blood levels of AP were inversely associated with low back and chest pain. Furthermore, oral administration of AP analogs induced antinociception. Altogether, these data indicate that AP, which possesses a high therapeutic potential and a good toxicological profile, may be used to develop effective and safe strategies against chronic neuropathic pain.


Subject(s)
Neuralgia/drug therapy , Neuralgia/metabolism , Pregnanolone/metabolism , Pregnanolone/therapeutic use , Animals , Humans
14.
J Steroid Biochem Mol Biol ; 140: 17-25, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24189541

ABSTRACT

Helicobacter pylori, a pathogen responsible for gastric and duodenal diseases, absorbs various steroid compounds into the cell membrane even though some are toxic to this bacterium. An earlier study by our group has demonstrated that progesterone is bactericidal to H. pylori. In this study, we newly synthesized a steroid compound, 17α-hydroxyprogesterone linoleic acid ester (17hPL), to examine antibacterial activity against H. pylori. As expected, 17hPL acted as a bactericidal agent to H. pylori and had no effect on the survival of other common bacterial species. This steroidal substance interacted with phosphatidylethanolamine (PE) on the outer membrane of H. pylori to induce the release of PE from the bacterial cell membrane and to ultimately lyse the bacterial cells. One of the hormonal effects of progesterone is the inhibition of nitric oxide (NO) production from mouse macrophages activated by lipopolysaccharide (LPS). We therefore examined the inhibition effect of 17hPL on the NO production of RAW 264.7 cells, a murine macrophage-like cell line, stimulated with LPS and demonstrated that 17hPL is relatively weaker in its capability to inhibit NO production in LPS-activated cells than progesterone. These results suggest the possibility that 17hPL could be an oral medicine for selectively treating patients infected with H. pylori.


Subject(s)
Anti-Bacterial Agents/pharmacology , Helicobacter pylori/drug effects , Progesterone/analogs & derivatives , Animals , Bacteriolysis/drug effects , Cell Line , Cell Membrane/drug effects , Cell Membrane/metabolism , Macrophages/drug effects , Mice , Nitric Oxide/biosynthesis , Phosphatidylethanolamines/metabolism , Progesterone/metabolism , Progesterone/pharmacology
15.
Biochem Biophys Res Commun ; 443(1): 179-84, 2014 Jan 03.
Article in English | MEDLINE | ID: mdl-24299954

ABSTRACT

Cytochrome P450 CYP17A1 catalyzes a series of reactions that lie at the intersection of corticoid and androgen biosynthesis and thus occupies an essential role in steroid hormone metabolism. This multifunctional enzyme catalyzes the 17α-hydroxylation of Δ4- and Δ5-steroids progesterone and pregnenolone to form the corresponding 17α-hydroxy products through its hydroxylase activity, and a subsequent 17,20-carbon-carbon scission of pregnene-side chain produce the androgens androstenedione (AD) and dehydroepiandrosterone (DHEA). While the former hydroxylation reaction is believed to proceed through a conventional "Compound I" rebound mechanism, it has been suggested that the latter carbon cleavage is initiated by an iron-peroxy intermediate. We report on the role of Thr306 in CYP17 catalysis. Thr306 is a member of the conserved acid/alcohol pair thought to be essential for the efficient delivery of protons required for hydroperoxoanion heterolysis and formation of Compound I in the cytochromes P450. Wild type and T306A CYP17A1 self-assembled in Nanodiscs were used to quantitate turnover and coupling efficiencies of CYP17's physiological Δ4- and Δ5-substrates. We observed that T306A co-incorporated in Nanodiscs with its redox partner cytochrome P450 oxidoreductase, coupled NADPH only by 0.9% and 0.7% compared to the wild type (97% and 22%) during the conversion of pregnenolone and progesterone, respectively, to the corresponding 17-OH products. Despite increased oxidation of pyridine nucleotide, hydroxylase activity was drastically diminished in the T306A mutant, suggesting a high degree of uncoupling in which reducing equivalents and protons are funneled into non-productive pathways. This is similar to previous work with other P450 catalyzed hydroxylation. However, catalysis of carbon-carbon bond scission by the T306A mutant was largely unimpeded by disruption of the CYP17A1 acid-alcohol pair. The unique response of CYP17A1 lyase activity to mutation of Thr306 is consistent with a reactive intermediate formed independently of proton delivery in the active site, and supports involvement of a nucleophilic peroxo-anion rather than the traditional Compound I in catalysis.


Subject(s)
Catalytic Domain , Protons , Steroid 17-alpha-Hydroxylase/chemistry , Threonine/chemistry , Catalysis , Humans , Mutation , Pregnenolone/chemistry , Pregnenolone/metabolism , Progesterone/chemistry , Progesterone/metabolism , Steroid 17-alpha-Hydroxylase/genetics , Steroid 17-alpha-Hydroxylase/metabolism , Threonine/genetics
16.
Chongqing Medicine ; (36): 454-455,458, 2014.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-572812

ABSTRACT

Objective To investigate the reproductive outcome after high intensity focused ultrasound (HIFU ) ablation for pa-tients with adenomyosis who have fertility requirements .Methods From October 2010 to June 2013 ,38 patients with adenomyosis who have fertility requirements treated by HIFU in our hospital were analyzed .Results In 38 cases ,the menorrhagia severity score ,the dysmenorrhea pain score and adenomyosis lesions after HIFU ablation were significantly different from the levels before HIFU treatment(P<0 .05) .Successful pregnancy occurred in 15 patients ,full-term birth was seen in 7 patients(three of Cesarean section ,four of vaginal delivery);the remaining patients accept routine prenatal examination .All pregnant patients showed no ab-normality .Conclusion Although large sample size study with long-term follow up is need ,based on our results ,HIFU ablation for patients with adenomyosis might improve the pregnancy rate safely .

17.
Article in English | MEDLINE | ID: mdl-23948237

ABSTRACT

The H295R in vitro cell line produces the majority of the steroidogenesis, for which reason it is commonly used as a screening tool for endocrine disrupting chemicals. Simultaneous determination of the precursor cholesterol and key steroid hormones could give a broad insight into the mechanistic disruption of the steroidogenesis. Steroid hormones have primarily been extracted from H295R incubation medium by means of liquid-liquid extraction (LLE) and the obtained recoveries and matrix effects have typically not been stated or assessed. In the present study a solid-phase extraction (SPE) method was developed and validated for the simultaneous extraction of cholesterol and five key steroid hormones pregnenolone, 17-hydroxyprogesterone, testosterone, cortisol and aldosterone from H295R incubation medium, and finally detected by LC-MS/MS. Cholesterol was recovered at a level of 55.7%, while steroid hormone recoveries ranged from 98.2 to 109.4%. Matrix effects varied between -0.6% and 62.8%. Intra-day precision was deemed acceptable, but the inter-day precision for pregnenolone and aldosterone exceeded the precision limit of 15% RSD. Although LLE has been the most frequently used extraction method in H295R studies, however, our investigation has shown that SPE may relatively easily extract and recover steroid hormones, potentially replacing LLE.


Subject(s)
Chromatography, Liquid/methods , Solid Phase Extraction/methods , Steroids/analysis , Steroids/isolation & purification , Tandem Mass Spectrometry/methods , Cell Line, Tumor , Culture Media, Conditioned/chemistry , Culture Media, Conditioned/metabolism , Humans , Limit of Detection , Reproducibility of Results , Steroids/chemistry , Steroids/metabolism
18.
Rev. colomb. enferm ; 8(1): 161-174, Agosto de 2013.
Article in Spanish | LILACS, BDENF - Nursing, COLNAL | ID: biblio-1008529

ABSTRACT

[{"text": "El presente artículo es el resultado de un trabajo de revisión de tema basado en los hallazgos de dos estudios cuali\r\n-\r\ntativos descriptivos exploratorios acerca del embarazo en adolescentes, desarrollados en la línea de investigación \r\nAdolescentes del grupo Salud Sexual y Reproductiva de la Facultad de Enfermería de la Universidad El Bosque entre \r\n2010 y 2012. En el primer estudio se preguntó por las condiciones psicosociales que interactuaron para el embarazo \r\nen esa etapa de su vida a un grupo de adolescentes ­mujeres y hombres­ que esperaban su primer hijo o hija. En el \r\nsegundo, se identificaron las necesidades de educación integral en sexualidad para prevenir el embarazo en la adoles\r\n-\r\ncencia; dichas necesidades fueron reportadas por un grupo de adolescentes, madres de familia y expertos en salud \r\nsexual y reproductiva. Los resultados de estas dos investigaciones generaron las categorías que orientaron la revisión \r\nde las dimensiones fundamentales para la educación integral en sexualidad desde la niñez para la prevención del \r\nembarazo en la adolescencia que se exponen en el presente artículo.", "_i": "es"}, {"text": "This article is a review of two qualitative descriptive \r\nstudies about teenage pregnancy, developed in the \r\nResearch Teen Line, by the Sexual and Reproductive \r\nHealth Group, in the Nursing Faculty at the El Bosque \r\nUniversity between 2010 and 2012. In the first study we \r\ncontemplated the psychosocial conditions that interacted \r\nto pregnancy in a group of teenagers ­females and males­ \r\nwho were expecting their first son / daughter, in the \r\nsecond, the needs of integral sexual education were iden\r\n-\r\ntified, in order to prevent teenage pregnancy; those were \r\nreported by a group of teenagers, mothers and experts \r\nin sexual and reproductive health. The results of these \r\ntwo investigations generated the categories that guided \r\nthe revision of the fundamental aspects for an integral \r\nsexual education since childhood, to prevent teen preg\r\n-\r\nnancy and are presented in this article.", "_i": "en"}, {"text": "Este artigo é o resultado de uma revisão da questão que \r\nse baseia nas conclusões de dois estudos exploratórios \r\ndescritivos qualitativos sobre a gravidez na adolescên\r\n-\r\ncia, desenvolvidas na Linha de Pesquisa do Adolescente,\r\npelo Grupo de Saúde Sexual e Reprodutiva na Facul\r\n-\r\ndade de Enfermagem na Universidade El Bosque, entre \r\n2010 e 2012. No primeiro estudo foi-se investigado as \r\ncondições psicossociais que interagiram a gravidez num \r\ngrupo de adolescentes ­homens e mulheres­ que estavam \r\nesperando seu primeiro filho / filha. No segundo estudo, \r\nas necessidades da educação sexual foram identificadas, \r\nem ordem de prevenir a gravidez da adolescente; e essas\r\nnecessidades foram relatadas por um grupo de adolescentes,\r\nmães e especialistas em saúde sexual e reprodutiva. Os\r\nresultados dessas duas investigações geraram as categorias\r\nque orientaram a revisão dos aspectos fundamentais\r\npara a educação integral em sexualidade desde a infância \r\npara a prevenção da gravidez na adolescência que é apresentado neste artigo.", "_i": "pt"}]


Subject(s)
Adolescent , Pregnancy , Education
19.
Biochem Pharmacol ; 86(6): 734-47, 2013 Sep 15.
Article in English | MEDLINE | ID: mdl-23856290

ABSTRACT

Pregnancy is associated with uteroplacental and vascular remodeling in order to adapt for the growing fetus and the hemodynamic changes in the maternal circulation. We have previously shown upregulation of uterine matrix metalloproteinases (MMPs) during pregnancy. Whether pregnancy-associated changes in MMPs are localized to the uterus or are generalized in feto-placental and maternal circulation is unclear. Also, the mechanisms causing the changes in uteroplacental and vascular MMPs during pregnancy are unclear. MMPs expression, activity and tissue distribution were measured in uterus, placenta and aorta of virgin, mid-pregnant (mid-Preg) and late pregnant (late-Preg) rats. Western blots and gelatin zymography revealed increases in MMP-2 and -9 in uterus and aorta of late-Preg compared with virgin and mid-Preg rats. In contrast, MMP-2 and -9 were decreased in placenta of late-Preg versus mid-Preg rats. Extracellular MMP inducer (EMMPRIN) was increased in uterus and aorta of pregnant rats, but was less in placenta of late-Preg than mid-Preg rats. Prolonged treatment of uterus or aorta of virgin rats with 17ß-estradiol and progesterone increased the amount of EMMPRIN, MMP-2 and -9, and the sex hormone-induced increases in MMPs were prevented by EMMPRIN neutralizing antibody. Immunohistochemistry revealed that MMP-2 and -9 and EMMPRIN increased in uterus and aorta of pregnant rats, but decreased in placenta of late-Preg versus mid-Preg rats. Thus pregnancy-associated upregulation of uterine MMPs is paralleled by increased vascular MMPs, and both are mediated by EMMPRIN and induced by estrogen and progesterone, suggesting similar role of MMPs in uterine and vascular tissue remodeling and function during pregnancy. The decreased MMPs and EMMPRIN in placenta of late-Preg rats suggests reduced role of MMPs in feto-placental circulation during late pregnancy.


Subject(s)
Basigin/genetics , Enzyme Induction/drug effects , Estradiol/pharmacology , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 9/genetics , Pregnancy, Animal , Progesterone/pharmacology , Animals , Aorta/drug effects , Aorta/enzymology , Basigin/metabolism , Female , Gestational Age , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Placenta/drug effects , Placenta/enzymology , Pregnancy , Rats , Rats, Sprague-Dawley , Uterus/drug effects , Uterus/enzymology
20.
J Steroid Biochem Mol Biol ; 137: 176-82, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23770321

ABSTRACT

There is some confusion in the literature about steroidogenesis in endocrine glands and steroidogenesis in peripheral intracrine tissues. The objective of the present review is to bring some clarifications and better understanding about steroidogenesis in these two types of tissues. Concerns about substrate specificity, kinetic constants and place of enzymes in the pathway have been discussed. The role of 17α-hydroxylase/17-20 lyase (CYP17A1) in the production of dehydroepiandrosterone and back-door pathways of dihydrotestosterone biosynthesis is also analyzed. This article is part of a Special Issue entitled "Synthesis and biological testing of steroid derivatives as inhibitors".


Subject(s)
Steroid 17-alpha-Hydroxylase/metabolism , Steroids/biosynthesis , Humans
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