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2.
Sci Rep ; 14(1): 32, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38168502

RESUMO

The epidemiology of vertebral fractures (VF) in underrepresented populations is not well-documented. This cohort study was part of a longitudinal osteoporosis research project with the aim of determining the prevalence, incidence, and risk factors for VF. 401 individuals (155 men) aged 50 years and older without a clinical diagnosis of VF were took radiographs at baseline and 2 years later. VF were ascertained using the Genant's semi-quantitative method. Bone mineral density (BMD) of femoral neck and lumbar spine were measured by dual-energy X-ray absorptiometry (Hologic Inc). The association between VF and risk factors was analyzed by the multiple logistic regression. The 95% confidence interval for prevalence and incidence was estimated by exact Poisson test. At baseline, the prevalence of VF was 12.2% (n = 49, 95% CI 9.0-16.2%) and increased with advancing age with one-fifth of those aged 70 and older having a VF. During the follow-up period, we observed 6 new VF, making the incidence of 6.6/1000 person-years (n = 6, 95% CI 2.4-14.3). The risk of prevalent VF was associated with male gender (OR: 2.67; 95% CI 1.28-5.87) and T-score at the femoral neck (OR per one SD decrease: 1.1; 1.03-1.17). These data indicate that VF is common among adults, and that lower femoral neck BMD was a risk factor for VF.


Assuntos
Osteoporose , Fraturas da Coluna Vertebral , Adulto , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/etiologia , Estudos de Coortes , Prevalência , Incidência , Vietnã , Osteoporose/diagnóstico por imagem , Osteoporose/epidemiologia , Osteoporose/complicações , Densidade Óssea , Absorciometria de Fóton/métodos , Fatores de Risco , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/lesões
3.
Am J Obstet Gynecol ; 219(3): 277.e1-277.e7, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29959929

RESUMO

BACKGROUND: Informed consent is an integral part of the preoperative counseling process. It is important that we know the best way to relay this information to patients undergoing surgery, specifically, hysterectomy. OBJECTIVE: We sought to determine whether supplementing normal physician counseling with a video presentation improves patient comprehension during the informed consent process for hysterectomy. STUDY DESIGN: In a randomized, mixed factorial controlled trial, standard physician counseling (control arm) was compared to physician counseling plus video presentation (video arm) during the prehysterectomy informed consent process. Primary outcome was improvement in patient comprehension measured by assessments at baseline, postcounseling, day of surgery, and postsurgery. Patient satisfaction was measured by a validated questionnaire. Audiotaped patient-physician interactions were analyzed to determine time spent counseling, number of patient questions, and whether standard counseling included 11 predetermined critical components included in the video. A sample size of 60 per group (N = 120) was planned to compare both groups. RESULTS: From May 2014 through June 2015, 120 patients were enrolled and 116 randomized: 59 to the video arm and 57 to the control arm. All characteristics were similar between groups. Video arm subjects demonstrated greater improvement in comprehension scores in both postcounseling (9.9% improvement; 95% confidence interval, 4.2-15.7%; P = .0009) and day-of-surgery questionnaires (7.2% improvement; 95% confidence interval, 0.96-13.4%; P = .02). Scores 4-6 weeks after surgery returned to baseline for both groups. Control subjects were less likely to be counseled about risk of thrombosis (P < .0001), colostomy (P < .0001), further medical/surgical therapy (P = .002), hormone replacement therapy (P < .0001), or postoperative expectations (P < .0001). Physicians spent more time counseling patients who did not watch the video (8 vs 12 minutes, P = .003) but number of questions asked by patients in each group was similar. CONCLUSION: Enhancing prehysterectomy counseling with a video improves patient comprehension through day of surgery, increases thoroughness of counseling, and reduces physician time.


Assuntos
Recursos Audiovisuais , Compreensão , Histerectomia , Consentimento Livre e Esclarecido , Adulto , Colostomia , Aconselhamento , Feminino , Humanos , Histerectomia Vaginal , Laparoscopia , Pessoa de Meia-Idade , Satisfação do Paciente , Relações Médico-Paciente , Complicações Pós-Operatórias , Cuidados Pré-Operatórios , Inquéritos e Questionários , Trombose
4.
Mil Med ; 183(5-6): e266-e269, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29415121

RESUMO

Background: Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is a congenital condition characterized by aplasia of the vagina with or without concurrent uterine and/or cervical aplasia. Type II (MURCS) is a rare form involving MUllerian agenesis, Renal agenesis, and Cervicothoracic Somite anomalies. Case: A 17-yr-old virginal female presented for evaluation of primary amenorrhea and pelvic pain. Her medical history was significant for a bicuspid aortic valve and right radial dysplasia. She demonstrated normal secondary sexual development and a normal karyotype. Pelvic magnetic resonance imaging revealed an aplastic vaginal, no identifiable cervix or uterus, and normal ovaries. A laparoscopy was performed for the evaluation of pain and findings were significant for bilateral uterine horn and fallopian tube remnants noted along the pelvic sidewalls. This patient evaluation suggests a unique presentation of MURCS association. Conclusion: To our knowledge, this is the first case of MRKH presenting with a bicuspid aortic valve and radial dysplasia. A review of the literature reveals no other cases of MRKH with these unique anomalies.


Assuntos
Transtornos 46, XX do Desenvolvimento Sexual/diagnóstico , Anormalidades Congênitas/diagnóstico , Ductos Paramesonéfricos/anormalidades , Transtornos 46, XX do Desenvolvimento Sexual/complicações , Transtornos 46, XX do Desenvolvimento Sexual/diagnóstico por imagem , Adolescente , Amenorreia/etiologia , Anormalidades Congênitas/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Ductos Paramesonéfricos/diagnóstico por imagem
5.
Microbiology (Reading) ; 161(Pt 3): 553-64, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25573769

RESUMO

Stress conditions, such as a block in fatty acid synthesis, signal bacterial cells to exit the cell cycle. Caulobacter crescentus FabH is a cell-cycle-regulated ß-ketoacyl-acyl carrier protein synthase that initiates lipid biosynthesis and is essential for growth in rich media. To explore how C. crescentus responds to a block in lipid biosynthesis, we created a FabH-depletion strain. We found that FabH depletion blocks lipid biosynthesis in rich media and causes a cell cycle arrest that requires the alarmone (p)ppGpp for adaptation. Notably, basal levels of (p)ppGpp coordinate both a reduction in cell volume and a block in the over-initiation of DNA replication in response to FabH depletion. The gene ctrA encodes a master transcription factor that directly regulates 95 cell-cycle-controlled genes while also functioning to inhibit the initiation of DNA replication. Here, we demonstrate that ctrA transcription is (p)ppGpp-dependent during fatty acid starvation. CtrA fails to accumulate when FabH is depleted in the absence of (p)ppGpp due to a substantial reduction in ctrA transcription. The (p)ppGpp-dependent maintenance of ctrA transcription during fatty acid starvation initiated from only one of the two ctrA promoters. In the absence of (p)ppGpp, the majority of FabH-depleted cells enter a viable but non-culturable state, with multiple chromosomes, and are unable to recover from the miscoordination of cell cycle events. Thus, basal levels of (p)ppGpp facilitate C. crescentus' re-entry into the cell cycle after termination of fatty acid starvation.


Assuntos
Caulobacter crescentus/citologia , Caulobacter crescentus/genética , Replicação do DNA , Nucleotídeos de Guanina/metabolismo , Lipídeos/biossíntese , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Caulobacter crescentus/metabolismo , Regulação Bacteriana da Expressão Gênica
6.
Adv Biosci Biotechnol ; 4(7B): 10-14, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24073357

RESUMO

Harmful algal blooms (HABs) are a serious environmental problem globally. The ability of cyanobacteria, one of the major causative agents of HABs, to grow in heavy metal polluted areas is proving a challenge to environmental restoration initiatives. Some cyanobacteria secrete toxins, such as microcystin, that are potentially dangerous to animals and humans. In this study, the physiology of a cyanobacterium was assessed to nickel chloride exposure. Cell growths were monitored throughout the study with various nickel chloride concentrations (0, 10, 25 or 50 mg/L). Morphological abnormalities were observed with microscopic image analyses. Inductively coupled plasma mass spectrometry (ICP-MS) was carried out to trace the distribution of nickel during the growth period. This study provides insight on potential nickel response mechanisms in freshwater cyanobacteria, which may lead to effective HAB prevention strategy development.

7.
J Biol Chem ; 285(19): 14450-8, 2010 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-20231277

RESUMO

Spatiotemporal specificity of cAMP action is best explained by targeting protein kinase A (PKA) to its substrates by A-kinase-anchoring proteins (AKAPs). At synapses in the brain, AKAP79/150 incorporates PKA and other regulatory enzymes into signal transduction networks that include beta-adrenergic receptors, alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA), and N-methyl-d-aspartic acid receptors. We previously showed that AKAP79/150 clusters PKA with type 5 adenylyl cyclase (AC5) to assemble a negative feedback loop in which the anchored kinase phosphorylates AC5 to dynamically suppress cAMP synthesis. We now show that AKAP79 can associate with multiple AC isoforms. The N-terminal regions of AC5, -6, and -9 mediate this protein-protein interaction. Mapping studies located a reciprocal binding surface between residues 77-108 of AKAP79. Intensity- and lifetime-based fluorescence resonance energy transfer demonstrated that deletion of AKAP79(77-108) region abolished AC5-AKAP79 interaction in living cells. The addition of the AKAP79(77-153) polypeptide fragment uncouples AC5/6 interactions with the anchoring protein and prevents PKA-mediated inhibition of AC activity in membranes. Use of the AKAP79(77-153) polypeptide fragment in brain extracts from wild-type and AKAP150(-/-) mice reveals that loss of the anchoring protein results in decreased AMPA receptor-associated AC activity. Thus, we propose that AKAP79/150 mediates protein-protein interactions that place AC5 in proximity to synaptic AMPA receptors.


Assuntos
Proteínas de Ancoragem à Quinase A/metabolismo , Adenilil Ciclases/metabolismo , Hipocampo/metabolismo , Isoenzimas/metabolismo , Neurônios/metabolismo , Receptores de AMPA/metabolismo , Animais , Western Blotting , Membrana Celular/metabolismo , Células Cultivadas , Humanos , Técnicas Imunoenzimáticas , Imunoprecipitação , Rim/metabolismo , Camundongos
8.
Int J Pharm Compd ; 12(1): 83-5, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-23969575

RESUMO

The purpose of this study was to determine the room temperature stability over a period of several months of commercially available intravenous succinylcholine dichloride (Quelicin, 20 mg/mL) in vials. A previously validated electro-spray tandem mass spectrometry method developed for the determination of succinylcholine dichloride in plasma was used. This method was based upon a stable isotope dilution assay using hexadeuterosuccinylcholine diiodide as the internal standard and was shown to be specific, sensitive, and reproducible. Calibration curves were plots of the ratios of intensities of the major product ions in the collision-induced dissociation spectrum for known concentration ratios of succinylcholine dichloride and hexadeuterosuccinylcholine diiodide in solutions. The concentration of succinylcholine dichloride was shown to decline linearly. After 1, 3, and 6 months at room temperature, the vial contents retained approximately 98%, 95%, and 90% of their inital concentration, respectively. We suggest, therefore, that succinylcholine dichloride can be stored safely at room temperature under normal daylight for 6 months.

9.
Mol Cell ; 23(6): 925-31, 2006 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-16973443

RESUMO

Spatiotemporal organization of cAMP signaling begins with the tight control of second messenger synthesis. In response to agonist stimulation of G protein-coupled receptors, membrane-associated adenylyl cyclases (ACs) generate cAMP that diffuses throughout the cell. The availability of cAMP activates various intracellular effectors, including protein kinase A (PKA). Specificity in PKA action is achieved by the localization of the enzyme near its substrates through association with A-kinase anchoring proteins (AKAPs). Here, we provide evidence for interactions between AKAP79/150 and ACV and ACVI. PKA anchoring facilitates the preferential phosphorylation of AC to inhibit cAMP synthesis. Real-time cellular imaging experiments show that PKA anchoring with the cAMP synthesis machinery ensures rapid termination of cAMP signaling upon activation of the kinase. This protein configuration permits the formation of a negative feedback loop that temporally regulates cAMP production.


Assuntos
Adenilil Ciclases/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , AMP Cíclico/biossíntese , Isoenzimas/metabolismo , Proteínas de Ancoragem à Quinase A , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Células Cultivadas , Proteínas Quinases Dependentes de AMP Cíclico/fisiologia , Ativação Enzimática , Retroalimentação Fisiológica , Humanos , Modelos Biológicos , Fosforilação , Transdução de Sinais/fisiologia
10.
Ann N Y Acad Sci ; 1041: 272-9, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15956717

RESUMO

Relaxin has been shown previously to stimulate cyclic AMP production and the activation of MAPK. We reported that phosphoinositide-3 kinase (PI3K) activity is required for biphasic stimulation of cAMP by relaxin and that relaxin treatment increased PI3K activity in THP-1 cells. A downstream target of PI3K is protein kinase C zeta (PKCzeta). Relaxin stimulated translocation of PKCzeta to the plasma membrane in THP-1, MCF-7, pregnant human myometrial (PHM1-31), and mouse mesangial (MMC) cells. PKCzeta translocation is PI3K dependent and independent of cAMP production. Pharmacological and antisense approaches, utilized to inhibit or knock down PKCzeta, resulted in a 40% inhibition of relaxin-stimulated cAMP production. The stimulation of PKCzeta by relaxin therefore is downstream of PI3K leading to increased cAMP production. To determine the role of PI3K/PKCzeta stimulation by relaxin on downstream-mediated events, we examined the increase in vascular endothelial growth factor (VEGF) gene expression by relaxin. Treatment of THP-1 or MMC cells with the PI3K inhibitor, LY294002, abolished the relaxin-mediated stimulation of VEGF transcript levels. In summary, relaxin has pleiotropic signaling effects in THP-1 cells activating ERK1/2, cAMP, PI3K, and PKCzeta. We have described a novel bifurcated pathway by which relaxin stimulates Gs alpha and PI3K/PKCzeta leading to increased cAMP production and increased VEGF gene expression. Some, but not all, of these pathways are detected in other cell lines which may cause the unique diversity of downstream responses from this interesting hormone.


Assuntos
AMP Cíclico/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteína Quinase C/metabolismo , Relaxina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Linhagem Celular , Ativação Enzimática/efeitos dos fármacos , Humanos , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Inibidores de Proteínas Quinases/farmacologia , Células Estromais/efeitos dos fármacos , Células Estromais/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
11.
Ann N Y Acad Sci ; 1041: 296-9, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15956721

RESUMO

Relaxin stimulates cAMP production and activation of ERK and PI3K in THP-1 cells. Relaxin also stimulates protein kinase C zeta (PKCzeta) translocation to the plasma membrane in a PI3K-dependent manner in THP-1 and MCF-7 cells. However, relaxin did not increase cAMP production in MCF-7 cells. We overexpressed different adenylyl cyclase (AC) isoforms in MCF-7 cells to examine coupling of endogenous relaxin receptors to cAMP production. Overexpression of types II and IV AC had no effect on cAMP production by relaxin. However, overexpression of type V AC, which is activated by PKCzeta, showed synergistic stimulation of cAMP by relaxin and forskolin.


Assuntos
Adenilil Ciclases/classificação , Adenilil Ciclases/metabolismo , AMP Cíclico/biossíntese , Expressão Gênica , Relaxina/farmacologia , Adenilil Ciclases/genética , Linhagem Celular Tumoral , Humanos
12.
Mol Endocrinol ; 19(4): 1012-23, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15604116

RESUMO

Relaxin is a polypeptide hormone that activates the leucine-rich repeat containing G protein-coupled receptors, LGR7 and LGR8. In an earlier study, we reported that relaxin produces a biphasic time course and the second wave of cAMP is highly sensitive to phosphoinositide-3 kinase inhibitors (LY294002 and wortmannin). LY294002 inhibits relaxin-mediated increases in cAMP production by 40-50% across a large range of relaxin concentrations. Here we show that protein kinase C zeta (PKCzeta) is a component of relaxin signaling in THP-1 cells. Sphingomyelinase increases cAMP production due to the release of ceramide, a direct activator of PKCzeta. Chelerythrine chloride (a general PKC inhibitor) inhibits relaxin induced cAMP production to the same degree (approximately 40%) as LY294002. Relaxin stimulates PKCzeta translocation to the plasma membrane in THP-1, MCF-7, pregnant human myometrial 1-31, and mouse mesangial cells, as shown by immunocytochemistry. PKCzeta translocation is phosphoinositide-3 kinase dependent and independent of cAMP production. Antisense PKCzeta oligodeoxynucleotides (PKCzeta-ODNs) deplete both PKCzeta transcript and protein levels in THP-1 cells. PKCzeta-ODNs abolish relaxin-mediated PKCzeta translocation and inhibit relaxin stimulation of cAMP by 40%, as compared with mock and random ODN controls. Treatment with LY294002 in the presence of PKCzeta-ODNs results in little further inhibition. In summary, we present a novel role for PKCzeta in relaxin-mediated stimulation of cAMP.


Assuntos
AMP Cíclico/metabolismo , Proteína Quinase C/metabolismo , Relaxina/fisiologia , Animais , Membrana Celular/metabolismo , Células Cultivadas , Cromonas/farmacologia , Humanos , Camundongos , Monócitos/química , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Morfolinas/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Proteína Quinase C/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Transporte Proteico/efeitos dos fármacos , Transporte Proteico/fisiologia , Relaxina/farmacologia
13.
Mol Endocrinol ; 17(6): 1075-84, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12595573

RESUMO

The G protein-coupled receptors LGR7 and LGR8 have recently been identified as the primary receptors for the polypeptide hormone relaxin and relaxin-like factors. RT-PCR confirmed the existence of mRNA for both LGR7 and LRG8 in THP-1 cells. Whole cell treatment of THP-1 cells with relaxin produced a biphasic time course in cAMP accumulation, where the first peak appeared as early as 1-2 min with a second peak at 10-20 min. Selective inhibitors for phosphoinositide 3-kinase (PI3K), such as wortmannin and LY294002, showed a dose-dependent inhibition of relaxin-mediated increases in cAMP, specific for the second peak of the relaxin time course. Adenylyl cyclase activation by relaxin in purified plasma membranes from THP-1 cells was not inhibited by LY294002, consistent with a mechanism involving direct stimulation by a Galphas-coupled relaxin receptor. However, reconstitution of membranes with cytosol from THP-1 cells enhanced adenylyl cyclase activity and restored LY294002 sensitivity. In addition, relaxin increased PI3K activity in THP-1 cells. Neither the effects of relaxin nor the inhibition of relaxin by LY294002 was mediated by the activity of phosphodiesterases. Taken together, we show that PI3K is required for the biphasic stimulation of cAMP by relaxin in THP-1 cells and present a novel signal transduction pathway for the activation of adenylyl cyclase by a G protein-coupled receptor.


Assuntos
AMP Cíclico/metabolismo , Monócitos/metabolismo , Fosfatidilinositol 3-Quinases/fisiologia , Relaxina/metabolismo , Transdução de Sinais/fisiologia , Linhagem Celular , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , RNA Mensageiro/análise , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Peptídeos/genética , Receptores de Peptídeos/metabolismo
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