- Guideline-Directed Medical Therapy and Survival Following Hospitalization in Patients with Heart Failure. [Journal Article]
- PPharmacotherapy 2018 Feb 09
- CONCLUSIONS: Our study suggests that GDMT initiation is associated with increased survival and discontinuation of therapy is associated with reduced survival in hospitalized patients with HF. Future studies should be conducted to confirm the impact of GDMT therapy modification in this population. This article is protected by copyright. All rights reserved.
- Use of Antihypertensive Medications During Delivery Hospitalizations Complicated by Preeclampsia. [Journal Article]
- OGObstet Gynecol 2018 Feb 05
- CONCLUSIONS: Use of multiple antihypertensive agents to treat preeclamptic women increased over the study period for women with mild, superimposed, and severe preeclampsia. There was substantial hospital variation in use of antihypertensive agents. This trend was associated with decreased risk of maternal stroke.
- Acrolein-mediated neuronal cell death and alpha-synuclein aggregation: Implications for Parkinson's disease. [Journal Article]
- MCMol Cell Neurosci 2018 Jan 29; 88:70-82
- Growing evidence suggests that oxidative stress plays a critical role in neuronal destruction characteristic of Parkinson's disease (PD). However, the molecular mechanisms of oxidative stress-mediate...
Growing evidence suggests that oxidative stress plays a critical role in neuronal destruction characteristic of Parkinson's disease (PD). However, the molecular mechanisms of oxidative stress-mediated dopaminergic cell death are far from clear. In the current investigation, we tested the hypothesis that acrolein, an oxidative stress and lipid peroxidation (LPO) product, is a key factor in the pathogenesis of PD. Using a combination of in vitro, in vivo, and cell free models, coupled with anatomical, functional, and behavioral examination, we found that acrolein was elevated in 6-OHDA-injected rats, and behavioral deficits associated with 6-OHDA could be mitigated by the application of the acrolein scavenger hydralazine, and mimicked by injection of acrolein in healthy rats. Furthermore, hydralazine alleviated neuronal cell death elicited by 6-OHDA and another PD-related toxin, rotenone, in vitro. We also show that acrolein can promote the aggregation of alpha-synuclein, suggesting that alpha-synuclein self-assembly, a key pathological phenomenon in human PD, could play a role in neurotoxic effects of acrolein in PD models. These studies suggest that acrolein is involved in the pathogenesis of PD, and the administration of anti-acrolein scavengers such as hydralazine could represent a novel strategy to alleviate tissue damage and motor deficits associated with this disease.
- ANA-Negative Hydralazine-Induced Pericardial Effusion. [Journal Article]
- CRCase Rep Med 2017; 2017:3521541
- This case describes a patient with pericardial effusion as a phenomenon of the drug-induced lupus erythematosus (DILE) syndrome due to hydralazine. The relevance of this case report lies in the fact ...
This case describes a patient with pericardial effusion as a phenomenon of the drug-induced lupus erythematosus (DILE) syndrome due to hydralazine. The relevance of this case report lies in the fact that although hydralazine has been a known causative agent of DILE, its presentation may involve a negative anti-nuclear antibody (ANA) study. Pericardial effusion is a documented adverse effect as a result of hydralazine use. It is typically common to screen for DILE with the serum ANA test prior to proceeding to more costly and specific tests (i.e., anti-histone antibody). As per our literature review, this is the second case of hydralazine causing DILE with a negative ANA. As in our case, although the screening serum ANA is the initial next best step for suspicion of DILE by hydralazine, it is important to consider the diagnosis without ANA positivity.
- A Triple Obstetric Challenge of Thoracopagus-Type Conjoined Twins, Eclampsia, and Obstructed Labor: A Case Report from Sub-Saharan Africa. [Journal Article]
- CRCase Rep Obstet Gynecol 2017; 2017:6815748
- Conjoined twins are very rarely seen. We present a case of thoracopagus that was undiagnosed prior to delivery and combined with eclampsia and obstructed labor in a low-resource setting in sub-Sahara...
Conjoined twins are very rarely seen. We present a case of thoracopagus that was undiagnosed prior to delivery and combined with eclampsia and obstructed labor in a low-resource setting in sub-Saharan Africa. A 27-year-old pregnant woman was presented to the maternity emergency unit of Princess Christian Maternity Hospital (PCMH) in Freetown at term in labor. Upon admission, the patient was awake and orientated and presented a blood pressure of 180/120 mmHg and a protein value of 3+ on urine dipstick test. Clinical examination-ultrasound was not available-led to the admission diagnosis: obstructed labor with intrauterine fetal death and preeclampsia. Application of Hydralazine 5 mg (i.v.) under close blood pressure monitoring was performed. Under spontaneous progression of labor, one head of the yet unknown conjoined twin was born. The patient developed eclamptic fits. Ceasing of seizures was achieved after implementing the loading dose of the MgSO4 protocol. A vaginal examination led to the unexpected diagnosis of conjoined twins. An emergency cesarean section under general anesthesia via a longitudinal midline incision was performed immediately. The born head was repositioned vaginally. The stillborn conjoined twins presented a female thoracopagus type that seemed to involve the heart. After 8 weeks, the woman was clinically fully recovered.
- A rapid and sensitive fluorometric method for determination of aldehyde oxidase activity. [Journal Article]
- TAToxicol Appl Pharmacol 2018 Feb 15; 341:30-37
- Previous research has characterized the important role of aldehyde oxidases (AOX) in biotransformation of N-heterocyclic therapeutic drugs and environmental contaminants in mammals. Research pertaini...
Previous research has characterized the important role of aldehyde oxidases (AOX) in biotransformation of N-heterocyclic therapeutic drugs and environmental contaminants in mammals. Research pertaining to AOX activity in non-mammalian vertebrates, however, is scarce, despite its biological role as a potentially important metabolic pathway for xenobiotics. One of the limiting factors of research on AOX is that available photometric methods are relatively insensitive, limited in throughput, and prone to cross-reactivity from other enzymes. Therefore, this study aimed to develop a novel and improved fluorometric AOX assay. This assay is based on the conversion of the exogenous aldehyde substrate 4-(dimethyl)amino cinnamaldehyde to its corresponding fluorescent acid by AOX, and was evaluated using partially purified hepatic cytosol from rat, human, and rainbow trout. Purification of native cytosol by heat treatment and ammonium sulfate precipitation resulted in increased specific activity of AOX. Michaelis-Menten kinetic parameters (Kmand Vmax) were comparable to values previously generated by photometric methods. Furthermore, effects of the inhibitor hydralazine on AOX activity revealed half maximal inhibitory concentrations comparable to those generated using conventional methods. Product identity was confirmed by liquid chromatography and mass spectrometry. In summary, this study successfully developed a rapid and sensitive assay for determination of AOX activity in across different vertebrate species that is 4- to 10-fold more sensitive compared to conventional absorbance-based methods. It can be applied in environmental, toxicological, and pharmacological studies relating to identification of AOX substrates, as well as the induction of AOX expression through drugs and environmental contaminants.
- Particulate matter and markers of glycemic control and insulin resistance in type 2 diabetic patients: result from Wellcome Trust Genetic study. [Journal Article]
- JEJ Expo Sci Environ Epidemiol 2017 Dec 21
- There is growing evidence that air pollution is associated with increased risk of type 2 diabetes (T2DM). However, information related to whether particulate matter (PM) contributing to worsened meta...
There is growing evidence that air pollution is associated with increased risk of type 2 diabetes (T2DM). However, information related to whether particulate matter (PM) contributing to worsened metabolic control in T2DM patients is inconsistent. We examined the association of PM10exposure with glucose-function parameters in young-onset T2DM patients. We investigated the association between a year ambient concentration of PM10at residential places, using AERMOD dispersion model, with fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), 2 h post meal plasma glucose (2hPG), homeostasis model assessment of insulin resistance (HOMA-IR), β-cell function (HOMA-β) and disposition index (DI) in 1213 diabetic patients from the Wellcome Trust Genetic study at the Diabetes Unit, KEM Hospital Research Center, Pune, India. We used linear regression models and adjusted for a variety of individual and environmental confounding variables. Possible effect modification by age, gender, waist-to-hip ratio (WHR) and smoking status were investigated. Sensitivity analysis assessed the impact of relative humidity (RH) and temperature a day before examination and anti-diabetic and HHR medication (Hydralazine, Hydrochlorothiazide and Reserpine). We found that 1 SD increment in background concentration of PM10at residential places (43.83 µg/m3) was significantly associated with 2.25 mmol/mol and 0.38 mmol/l increase in arithmetic means of HbA1c and 2hPG, respectively. A similar increase in PM10was also associated with 4.89% increase in geometric mean of HOMA-IR. The associations remained significant after adjustment to RH and temperature, and WHR and smoking enhanced the size of the effect. Our study suggests that long-term exposure to PM10is associated with higher glycaemia and insulin resistance. In context of our previous demonstration of association of SO2and NOxand plasma C-reactive protein, we suggest that air pollution could influence progression of diabetes complications. Prospective studies and interventions are required to define mechanism and confirm causality.
- StatPearls [BOOK]
- BOOKStatPearls Publishing: Treasure Island (FL)
- Hydralazine is used orally as a therapeutic agent to treat essential hypertension and intravenously to lower blood pressure urgently or emergently. FDA-approved hydralazine is usually not used as a f...
Hydralazine is used orally as a therapeutic agent to treat essential hypertension and intravenously to lower blood pressure urgently or emergently. FDA-approved hydralazine is usually not used as a first-line agent for the treatment of essential hypertension due to the stimulation of the sympathetic system. It is used in combination with other hypertensives to treat persistently elevated blood pressure.
- Retrospective review of the use of as-needed hydralazine and labetalol for the treatment of acute hypertension in hospitalized medicine patients. [Journal Article]
- TATher Adv Cardiovasc Dis 2018; 12(1):7-15
- CONCLUSIONS: As-needed oral hydralazine is frequently prescribed for acute blood pressure lowering with administration thresholds often less than what are used to define acute severe hypertension. Many patients are prescribed PRN antihypertensive medication instead of being continued on their home regimens, and most patients do not have the intensity of their home regimens increased. Providers need to be educated about the use of PRN antihypertensive medication for the management of severe asymptomatic hypertension in the hospital setting.
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- Hydralazine induces stress resistance and extends C. elegans lifespan by activating the NRF2/SKN-1 signalling pathway. [Journal Article]
- NCNat Commun 2017 Dec 20; 8(1):2223
- Nuclear factor (erythroid-derived 2)-like 2 and its Caenorhabditis elegans ortholog, SKN-1, are transcription factors that have a pivotal role in the oxidative stress response, cellular homeostasis, ...
Nuclear factor (erythroid-derived 2)-like 2 and its Caenorhabditis elegans ortholog, SKN-1, are transcription factors that have a pivotal role in the oxidative stress response, cellular homeostasis, and organismal lifespan. Similar to other defense systems, the NRF2-mediated stress response is compromised in aging and neurodegenerative diseases. Here, we report that the FDA approved drug hydralazine is a bona fide activator of the NRF2/SKN-1 signaling pathway. We demonstrate that hydralazine extends healthy lifespan (~25%) in wild type and tauopathy model C. elegans at least as effectively as other anti-aging compounds, such as curcumin and metformin. We show that hydralazine-mediated lifespan extension is SKN-1 dependent, with a mechanism most likely mimicking calorie restriction. Using both in vitro and in vivo models, we go on to demonstrate that hydralazine has neuroprotective properties against endogenous and exogenous stressors. Our data suggest that hydralazine may be a viable candidate for the treatment of age-related disorders.