Friday, November 26, 2010

Placental microRNA expression in pregnancies complicated by preeclampsia.

Placental microRNA expression in pregnancies complicated by preeclampsia.: "

Placental microRNA expression in pregnancies complicated by preeclampsia.


Am J Obstet Gynecol. 2010 Nov 18;


Authors: Enquobahrie DA, Abetew DF, Sorensen TK, Willoughby D, Chidambaram K, Williams MA


OBJECTIVE:: The role of posttranscription regulation in preeclampsia is largely unknown. We investigated preeclampsia-related placental microRNA (miRNA) expression using microarray and confirmatory quantitative real-time polymerase chain reaction experiments. STUDY DESIGN:: Placental expressions of characterized and novel miRNAs (1295 probes) were measured in samples collected from 20 preeclampsia cases and 20 controls. Differential expression was evaluated using Student t test and fold change analyses. In pathway analysis, we examined functions/functional relationships of targets of differentially expressed miRNAs. RESULTS:: Eight miRNAs were differentially expressed (1 up-regulated and 7 down-regulated) among preeclampsia cases compared with controls. These included previously identified candidates (miR-210, miR-1, and a miRNA in the 14q32.31 cluster region) and others that are novel (miR-584 and miR-34c-5p). These miRNAs target genes that participate in organ/system development (cardiovascular and reproductive system), immunologic dysfunction, cell adhesion, cell cycle, and signaling. CONCLUSION:: Expression of miRNAs that target genes in diverse pathophysiological processes is altered in the setting of preeclampsia.


PMID: 21093846 [PubMed - as supplied by publisher]

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The "Great Obstetrical Syndromes" are associated with disorders of deep placentation.

The "Great Obstetrical Syndromes" are associated with disorders of deep placentation.: "

The 'Great Obstetrical Syndromes' are associated with disorders of deep placentation.


Am J Obstet Gynecol. 2010 Nov 20;


Authors: Brosens I, Pijnenborg R, Vercruysse L, Romero R


Defective deep placentation has been associated with a spectrum of complications of pregnancy including preeclampsia, intrauterine growth restriction, preterm labor, preterm premature rupture of membranes, late spontaneous abortion, and abruptio placentae. The disease of the placental vascular bed that underpins these complications is commonly investigated with targeted biopsies. In this review, we critically evaluate the biopsy technique to summarize the salient types of defective deep placentation, and propose criteria for the classification of defective deep placentation into 3 types based on the degree of restriction of remodeling and the presence of obstructive lesions in the myometrial segment of the spiral arteries.


PMID: 21094932 [PubMed - as supplied by publisher]

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D2-40/podoplanin expression in the human placenta.

D2-40/podoplanin expression in the human placenta.: "

D2-40/podoplanin expression in the human placenta.


Placenta. 2010 Nov 20;


Authors: Wang Y, Sun J, Gu Y, Zhao S, Groome LJ, Alexander JS


Placental tissue expresses many lymphatic markers. The current study was undertaken to examine if D2-40/podoplanin, a lymphatic endothelial marker, was expressed in the human placenta, and how it is altered developmentally and pathologically. We examined D2-40/podoplanin and VEGFR-3 expressions in placentas from normotensive pregnancies at different gestational ages and in placentas from women with clinically defined preeclampsia. D2-40 expression in systemic lymphatic vessel endothelium served as a positive control. Protein expression for D2-40, VEGFR-3, and β-actin was determined by Western blot in placentas from normotensive (n = 6) and preeclamptic (n = 5) pregnancies. Our results show that D2-40/podoplanin was strongly expressed in the placenta, mainly as a network plexus pattern in the villous stroma throughout gestation. CD31 was limited to villous core fetal vessel endothelium and VEGFR-3 was found in both villous core fetal vessel endothelium and trophoblasts. D2-40/podoplanin expression was significantly decreased, and VEGFR-3 significantly increased in preeclamptic placental tissues compared to normotensive placental controls. Placental villous stroma is a reticular-like structure, and the localization of D2-40 to the stroma suggests that a lymphatic-like conductive network may exist in the human placenta. D2-40/podoplanin is an O-linked sialoglycoprotein. Although little is known regarding biological functions of sialylated glycoproteins within the placenta, placental D2-40/podoplanin may support fetal vessel angiogenesis during placenta development and reduced D2-40/podoplanin expression in preeclamptic placenta may contribute to altered interstitial fluid homeostasis and impaired angiogenesis in this pregnancy disorder.


PMID: 21095001 [PubMed - as supplied by publisher]

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Maternal Cardiac Dysfunction and Remodeling in Women With Preeclampsia at Term.

Maternal Cardiac Dysfunction and Remodeling in Women With Preeclampsia at Term.: "

Maternal Cardiac Dysfunction and Remodeling in Women With Preeclampsia at Term.


Hypertension. 2010 Nov 22;


Authors: Melchiorre K, Sutherland GR, Baltabaeva A, Liberati M, Thilaganathan B


Preeclampsia is a disease associated with significant cardiovascular morbidity during pregnancy and in later life. This study was designed to evaluate cardiac function and remodeling in preeclampsia occurring at term. This was a prospective case-control study of 50 term preeclampsia and 50 normal pregnancies assessed by echocardiography and tissue Doppler analysis. Global diastolic dysfunction was observed more frequently in preeclampsia versus control pregnancies (40% versus 14%, P=0.007). Increased cardiac work and left ventricular mass indices suggest that left ventricular remodeling was an adaptive response to maintain myocardial contractility with preeclampsia at term. Approximately 20% of patients with preeclampsia at term have more evident myocardial damage. Diastolic dysfunction usually precedes systolic dysfunction in the evolution of ischemic or hypertensive cardiac diseases and is of prognostic value in the prediction of long-term cardiovascular morbidity. The study findings also have significant implications for the acute medical management of preeclampsia.


PMID: 21098311 [PubMed - as supplied by publisher]

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The Role of Embryonic Origin in Preeclampsia: A Comparison of Autologous In Vitro Fertilization and Ovum Donor Pregnancies.

The Role of Embryonic Origin in Preeclampsia: A Comparison of Autologous In Vitro Fertilization and Ovum Donor Pregnancies.: "

The Role of Embryonic Origin in Preeclampsia: A Comparison of Autologous In Vitro Fertilization and Ovum Donor Pregnancies.


Obstet Gynecol. 2010 Dec;116(6):1387-1392


Authors: Klatsky PC, Delaney SS, Caughey AB, Tran ND, Schattman GL, Rosenwaks Z


OBJECTIVE:: To compare the risk of gestational hypertension and preeclampsia in pregnancies conceived through standard in vitro fertilization (IVF) using autologous oocytes with pregnancies conceived using donated oocytes. METHODS:: We conducted a retrospective, matched cohort study of women undergoing IVF using autologous compared with donor oocytes between 1998 and 2005. Women with live births resulting from oocyte donor pregnancies were matched for age and plurality (singleton or twin) with women undergoing autologous IVF. Primary outcomes were the incidence of preeclampsia or gestational hypertension (with and without proteinuria) in the third trimester. Data on preterm delivery, low birth weight, and embryo cryopreservation were also recorded. RESULTS:: Outcome data were available for 158 pregnancies, including 77 ovum-donor recipient pregnancies and 81 pregnancies using autologous oocytes. There were no differences in age, parity, and gestational type between the two cohorts. The incidence of gestational hypertension and preeclampsia was significantly higher in ovum-donor recipients compared with women undergoing autologous IVF (24.7% compared with 7.4%, P<.01, and 16.9% compared with 4.9%, P=.02, respectively). Ovum-donor recipients were more likely than women undergoing autologous IVF to deliver prematurely (34% compared with 19%). This association remained after controlling for multiple gestation (odds ratio 2.6, 95% confidence interval 1.04-6.3). Sixteen pregnancies from cryopreserved embryos were more likely to have hypertensive disorders of pregnancy (odds ratio 5.0, 95% confidence interval 1.2-20.5). CONCLUSION:: Pregnancies derived from donor oocytes and cryopreserved-thawed embryos may be at a higher risk for hypertensive disorders of pregnancy. These findings inform future research and help counsel women using assisted reproductive technology. LEVEL OF EVIDENCE:: II.


PMID: 21099607 [PubMed - as supplied by publisher]

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Wednesday, November 24, 2010

Combination of loop diuretics with thiazide-type diuretics in heart failure.

Combination of loop diuretics with thiazide-type diuretics in heart failure.: "
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Combination of loop diuretics with thiazide-type diuretics in heart failure.


J Am Coll Cardiol. 2010 Nov 2;56(19):1527-34


Authors: Jentzer JC, DeWald TA, Hernandez AF


Volume overload is an important clinical target in heart failure management, typically addressed using loop diuretics. An important and challenging subset of heart failure patients exhibit fluid overload despite significant doses of loop diuretics. One approach to overcome loop diuretic resistance is the addition of a thiazide-type diuretic to produce diuretic synergy via 'sequential nephron blockade,' first described more than 40 years ago. Although potentially able to induce diuresis in patients otherwise resistant to high doses of loop diuretics, this strategy has not been subjected to large-scale clinical trials to establish safety and clinical efficacy. We summarize the existing literature evaluating the combination of loop and thiazide diuretics in patients with heart failure in order to describe the possible benefits and hazards associated with this therapy. Combination diuretic therapy using any of several thiazide-type diuretics can more than double daily urine sodium excretion to induce weight loss and edema resolution, at the risk of inducing severe hypokalemia in addition to hyponatremia, hypotension, and worsening renal function. We provide considerations about prudent use of this therapy and review potential misconceptions about this long-used diuretic approach. Finally, we seek to highlight the need for pragmatic clinical trials for this commonly used therapy.


PMID: 21029871 [PubMed - in process]

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Minocycline Protects against Neurologic Complications of Rapid Correction of Hyponatremia.

Minocycline Protects against Neurologic Complications of Rapid Correction of Hyponatremia.: "
Related Articles

Minocycline Protects against Neurologic Complications of Rapid Correction of Hyponatremia.


J Am Soc Nephrol. 2010 Nov 4;


Authors: Gankam-Kengne F, Soupart A, Pochet R, Brion JP, Decaux G


Osmotic demyelination syndrome is a devastating neurologic condition that occurs after rapid correction of serum sodium in patients with hyponatremia. Pathologic features of this injury include a well-demarcated region of myelin loss, a breakdown of the blood-brain barrier, and infiltration of microglia. The semisynthetic tetracycline minocycline is protective in some animal models of central nervous system injury, including demyelination, suggesting that it may also protect against demyelination resulting from rapid correction of chronic hyponatremia. Using a rat model of osmotic demyelination syndrome, we found that treatment with minocycline significantly decreases brain demyelination, alleviates neurologic manifestations, and reduces mortality associated with rapid correction of hyponatremia. Mechanistically, minocycline decreased the permeability of the blood-brain barrier, inhibited microglial activation, decreased both the expression of IL1α and protein nitrosylation, and reduced the loss of GFAP immunoreactivity. In conclusion, minocycline modifies the course of osmotic demyelination in rats, suggesting its possible therapeutic use in the setting of inadvertent rapid correction of chronic hyponatremia in humans.


PMID: 21051736 [PubMed - as supplied by publisher]

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Managing Overly Rapid Correction of Chronic Hyponatremia: An Ounce of Prevention or a Pound of Cure?

Managing Overly Rapid Correction of Chronic Hyponatremia: An Ounce of Prevention or a Pound of Cure?: "
Related Articles

Managing Overly Rapid Correction of Chronic Hyponatremia: An Ounce of Prevention or a Pound of Cure?


J Am Soc Nephrol. 2010 Nov 11;


Authors: Kamel KS, Halperin ML



PMID: 21071525 [PubMed - as supplied by publisher]

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Friday, November 19, 2010

Hereditary renal tubular disorders.

Hereditary renal tubular disorders.: "
Related Articles

Hereditary renal tubular disorders.


Semin Nephrol. 2009 Jul;29(4):399-411


Authors: Chadha V, Alon US


The multiple and complex functions of the renal tubule in regulating water, electrolyte, and mineral homeostasis make it prone to numerous genetic abnormalities resulting in malfunction. The phenotypic expression depends on the mode of interference with the normal physiology of the segment affected, and whether the abnormality is caused by loss of function or, less commonly, gain of function. In this review we address the current knowledge about the association between the genetics and clinical manifestations and treatment of representative disorders affecting the length of the nephron.


PMID: 19615561 [PubMed - indexed for MEDLINE]

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Thursday, November 4, 2010

New Alternatives to the Treatment of Acute Liver Failure

New Alternatives to the Treatment of Acute Liver Failure: "Publication year: 2010
Source: Transplantation Proceedings, Volume 42, Issue 8, October 2010, Pages 2959-2961
E., Pareja , M., Cortes , A., Bonora , P., Fuset , F., Orbis , ...
Introduction: Acute-on-chronic liver failure (ACLF) is defined as an acute deterioration of a chronic liver disease. The most effective treatment in these patients is orthotopic liver transplantation (OLT), which is highly limited by the donor shortage. The aim of this study was to increase the usefulness of hepatocyte transplantation (HT) as a bridge or alternative to OLT. Methods: During the last 2 years, we have performed HT in 3 patients with ACLF. The diagnosis was graft cirrhosis due to hepatitis C virus in 2 of them, who were already included on waiting lists for retransplantation, and the third, unknown alcoholic cirrhosis. Results: After the first..."

Epidemiology of Pneumonia in Kidney Transplantation

Epidemiology of Pneumonia in Kidney Transplantation: "Publication year: 2010
Source: Transplantation Proceedings, Volume 42, Issue 8, October 2010, Pages 2938-2940
I., Hoyo , L., Linares , C., Cervera , M., Almela , M.A., Marcos , ...
Background: Pneumonia remains an important cause of morbidity among solid organ transplant recipients. Methods: We prospectively evaluated all renal transplant patients at our center from July 2003 to December 2008 who had pneumonia that required hospitalization. We gathered data regarding underlying diseases as well as pretransplant, transplant, and posttransplant characteristics. Pneumonia defined according to the Centers for Disease Control and Prevention criteria was classified depending on its origin as community acquired or nosocomial. In all patients, microbiologic samples of respiratory secretions and blood were collected at the physician's discretion. The indication to perform a fiberoptic bronchoscopy was the presence of multiple, bilateral, or..."

Protective effect of immunosuppressive treatment before orthotopic kidney autotransplantation

Are we going to start immunosuppresion prior to transplant if this translates?


Protective effect of immunosuppressive treatment before orthotopic kidney autotransplantation: "Publication year: 2010
Source: Transplant Immunology, In Press, Accepted Manuscript, Available online 27 October 2010
Federico, Cicora , Natalia, Lausada , Daniela N., Vasquez , Paola, Cicora , Guerrieri, Diego , ...
Background: Ischemia reperfusion injury (IRI) is one of the risk factors for delayed graft function, acute rejection and long term allograft survival after kidney transplantation. It's an independent antigen inflammatory process that produces tissue damage. Our objective was to study the impact of immunosuppressive treatment (IS) on IRI applying only one dose of IS before orthotopic kidney autotransplantation. Methods: Twenty-four rats allocated in four groups were studied. One group served as control (G1: autotransplanted rats without IS) and the rest received IS 12 h before kidney autotransplantation (G2: Rapamycin, G3: Mycophenolate mofetil and G4: Tacrolimus). Results: Improved renal function and systemic inflammatory response were found..."

Effectiveness of a Barber-Based Intervention for Improving Hypertension Control in Black Men: The BARBER-1 Study: A Cluster Randomized Trial [Original Investigation]

Effectiveness of a Barber-Based Intervention for Improving Hypertension Control in Black Men: The BARBER-1 Study: A Cluster Randomized Trial [Original Investigation]: "

Background Barbershop-based hypertension (HTN) outreach programs for black men are becoming increasingly common, but whether they are an effective approach for improving HTN control remains uncertain.


Methods To evaluate whether a continuous high blood pressure (BP) monitoring and referral program conducted by barbers motivates male patrons with elevated BP to pursue physician follow-up, leading to improved HTN control, a cluster randomized trial (BARBER-1) of HTN control was conducted among black male patrons of 17 black-owned barbershops in Dallas County, Texas (March 2006–December 2008). Participants underwent 10-week baseline BP screening, and then study sites were randomized to a comparison group that received standard BP pamphlets (8 shops, 77 hypertensive patrons per shop) or an intervention group in which barbers continually offered BP checks with haircuts and promoted physician follow-up with sex-specific peer-based health messaging (9 shops, 75 hypertensive patrons per shop). After 10 months, follow-up data were obtained. The primary outcome measure was change in HTN control rate for each barbershop.


Results The HTN control rate increased more in intervention barbershops than in comparison barbershops (absolute group difference, 8.8% [95% confidence interval (CI), 0.8%-16.9%]) (P = .04); the intervention effect persisted after adjustment for covariates (P = .03). A marginal intervention effect was found for systolic BP change (absolute group difference, –2.5 mm Hg [95% CI, –5.3 to 0.3 mm Hg]) (P = .08).


Conclusions The effect of BP screening on HTN control among black male barbershop patrons was improved when barbers were enabled to become health educators, monitor BP, and promote physician follow-up. Further research is warranted.


Trial Registration clinicaltrials.gov Identifier: NCT00325533

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