scholarly journals The Role of Magnesium in the Management of Cerebral Vasospasm

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Mitchell J. Odom ◽  
Scott L. Zuckerman ◽  
J Mocco
Keyword(s):  
Cerebral Vasospasm ◽  
Muscle Relaxation ◽  
The United States ◽  
Phase Iii ◽  
Smooth Muscle Relaxation ◽  
Two Phase ◽  
Competitive Antagonist ◽  
Voltage Gated Calcium Channels ◽  
Phase Iii Trials

Subarachnoid hemorrhage (SAH) is characterized by bleeding into the subarachnoid space, often caused by ruptured aneurysm. Aneurysmal rupture occurs in 700,000 individuals per year worldwide, with 40,000 cases taking place in the United States. Beyond the high mortality associated with SAH alone, morbidity and mortality are further increased with the occurrence of cerebral vasospasm, a pathologic constriction of blood vessels that can lead to delayed ischemic neurologic deficits (DIND). Treatment of cerebral vasospasm is a source of contention. One extensively studied therapy is Magnesium (Mg) as both a competitive antagonist of calcium at theN-methyl D-aspartate (NMDA) receptor, and a noncompetitive antagonist of both IP3and voltage-gated calcium channels, leading to smooth muscle relaxation. In our literature review, several animal and human studies are summarized in addition to two Phase III trials assessing the use of intravenous Mg in the treatment of SAH (IMASH and MASH-2). Though many studies have shown promise for the use of Mg in SAH, there has been inconsistency in study design and outcomes. Furthermore, the results of the recently completed clinical trials have shown no significant benefit from using intravenous Mg as adjuvant therapy in the treatment of cerebral vasospasm.

Rational Use of Cytotoxic Chemotherapy for Recurrent Ovarian Cancer

2006 ◽  
Vol 4 (9) ◽  
pp. 947-953 ◽  
Author(s):  
Joyce Liu ◽  
Ursula Matulonis
Keyword(s):  
Ovarian Cancer ◽  
Treatment Options ◽  
Recurrent Ovarian Cancer ◽  
Disease Recurrence ◽  
The United States ◽  
Phase Iii ◽  
Optimal Timing ◽  
Duration Of Treatment ◽  
Phase Iii Trials

Ovarian cancer remains the leading cause of death among women with gynecologic malignancies, and the fifth leading cause of cancer mortality in women in the United States. Although many patients respond to first-line platinum-based therapy, most will experience disease recurrence. The role of further therapy in the setting of recurrent ovarian cancer is palliative, and large randomized phase III trials on treatment options for recurrent ovarian cancer are rare. Controversies exist as to the optimal timing and duration of treatment, and many issues regarding treatment of recurrent disease remain.

Phase III Trials in Pancreatic Cancer in the United States

2010 ◽  
Vol 9 (1) ◽  
pp. 59-60
Author(s):  
Edward Chu ◽  
David Cunningham ◽  
David Watkins
Keyword(s):  
United States ◽  
Pancreatic Cancer ◽  
The United States ◽  
Phase Iii ◽  
Phase Iii Trials

Role of cGMP in relaxation of vascular and other smooth muscle

1989 ◽  
Vol 67 (4) ◽  
pp. 251-262 ◽  
Author(s):  
Kanji Nakatsu ◽  
Jack Diamond
Keyword(s):  
Smooth Muscle ◽  
Muscle Relaxation ◽  
Smooth Muscles ◽  
Phosphodiesterase Inhibitors ◽  
Current Evidence ◽  
Smooth Muscle Relaxation ◽  
Drug Induced ◽  
Intracellular Cgmp ◽  
Tissue Content

The hypothesis that the relaxant action of many drugs on vascular and other smooth muscle is mediated by increases in intracellular cGMP, the "cGMP hypothesis," is gaining wide acceptance. While much information supporting this idea can be found in the literature, there is also a significant amount of information indicating that an elevation in the tissue content of cGMP is by itself insufficient to cause smooth muscle relaxation. The literature is reviewed with reference to the criteria that need to be fulfilled to consider cGMP as the second messenger mediating relaxation of smooth muscle by a drug; i.e., activation of guanylate cyclase, elevation of tissue content of cGMP, potentiation by phosphodiesterase inhibitors, antagonism by inhibitors of cGMP synthesis, and production of relaxation by cGMP analogues. For each criterion, key observations supporting the hypothesis are considered, followed by examples of important observations not consistent with the hypothesis. It is concluded that in some smooth muscles, for example, rat myometrium and vas deferens, cGMP is not a mediator of drug-induced relaxation. In other smooth muscles, including vascular smooth muscle, cGMP appears to play an important role in the relaxation process; but current evidence suggests that other factors are also important and that the cGMP hypothesis may need to be modified.Key words: cGMP, vascular relaxation, smooth muscle relaxation, vasodilators.

Anomalies of continental precipitation associated with El Niño Southern Oscillation: the role of moisture contribution from oceanic and terrestrial sources 

2021 ◽  
Author(s):  
Rogert Sorí ◽  
Raquel Nieto ◽  
Margarida L.R. Liberato ◽  
Luis Gimeno
Keyword(s):  
South America ◽  
Southern Oscillation ◽  
The United States ◽  
Precipitation Pattern ◽  
Two Phase ◽  
The North ◽  
Terrestrial Origin ◽  
Precipitation Anomalies ◽  
June July

<p>The regional and global precipitation pattern is highly modulated by the influence of El Niño Southern Oscillation (ENSO), which is considered the most important mode of climate variability on the planet. In this study was investigated the asymmetry of the continental precipitation anomalies during El Niño and La Niña. To do it, a Lagrangian approach already validated was used to determine the proportion of the total Lagrangian precipitation that is of oceanic and terrestrial origin. During both, El Niño and La Niña, the Lagrangian precipitation in regions such as the northeast of South America, the east and west coast of North America, Europe, the south of West Africa, Southeast Asia, and Oceania is generally determined by the oceanic component of the precipitation, while that from terrestrial origin provides a major percentage of the average Lagrangian precipitation towards the interior of the continents. The role of the moisture contribution to precipitation from terrestrial and oceanic origin was evaluated in regions with statistically significant precipitation anomalies during El Niño and La Niña. Two-phase asymmetric behavior of the precipitation was found in regions such the northeast of South America, South Africa, the north of Mexico, and southeast of the United States, etc. principally for December-January-February and June-July-August. For some of these regions was also calculated the anomalies of the precipitation from other datasets to confirm the changes. Besides, for these regions was calculated the anomaly of the Lagrangian precipitation, which agrees in all the cases with the precipitation change. For these regions, it was determined which component of the Lagrangian precipitation, whether oceanic or terrestrial, controlled the precipitation anomalies. A schematic figure represents the extent of the most important seasonal oceanic and terrestrial sources for each subregion during El Niño and La Niña.</p>

Interactions between nitroglycerin and endothelium in vascular smooth muscle relaxation

1991 ◽  
Vol 260 (3) ◽  
pp. H698-H701 ◽  
Author(s):  
J. L. Dinerman ◽  
D. L. Lawson ◽  
J. L. Mehta
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Muscle Relaxation ◽  
Smooth Muscle Relaxation ◽  
No Production ◽  
Cyclic Monophosphate ◽  
The Mean ◽  
Smooth Muscle Relaxant ◽  
Vascular Smooth Muscle Relaxation

To evaluate the role of endothelium in nitroglycerin (NTG)-mediated vascular relaxation, epinephrine-contracted rat thoracic aortic segments with and without intact endothelium were exposed to NTG (10(-10) to 10(-5) M). Aortic segments with intact (endo+, n = 15) and denuded endothelium (endo-, n = 9) exhibited typical NTG-induced relaxation. However, the mean effective concentration of NTG was lower for endo- than for endo+ segments (P less than 0.001). To determine if this phenomenon related to nitric oxide (NO) generation by endothelium, six endo+ segments were treated with NG-monomethyl-L-arginine (L-NMMA), an inhibitor of NO production. These endo+ segments exhibited greater (P less than 0.001) relaxation in response to NTG than the untreated endo+ segments. Oxyhemoglobin, an inhibitor of guanylate cyclase activation, greatly diminished NTG-mediated relaxation of all aortic segments. To determine if the enhanced NTG-mediated relaxation of endo- segments was unique to the guanosine 3',5'-cyclic monophosphate-dependent vasodilator NTG, other endo+ and endo- segments were exposed to adenosine 3',5'-cyclic monophosphate-dependent vasodilator papaverine (10(-8) to 10(-4) M), and no difference in EC50 was noted between endo+ and endo- segments. Thus endothelium attenuates NTG-mediated vasorelaxation, and this attenuation is abolished by inhibition of endothelial NO production with L-NMMA. These observations indicate that endothelium is a dynamic modulator of vascular smooth muscle relaxant effects of NTG. This modulation appears to result from a competitive interaction between endothelial NO and NTG.

scholarly journals Long-term Outcomes of Ranibizumab Therapy for Diabetic Macular Edema: The 36-Month Results from Two Phase III Trials

Ophthalmology ◽  
2013 ◽  
Vol 120 (10) ◽  
pp. 2013-2022 ◽  
Author(s):  
David M. Brown ◽  
Quan Dong Nguyen ◽  
Dennis M. Marcus ◽  
David S. Boyer ◽  
Sunil Patel ◽  
...  
Keyword(s):  
Macular Edema ◽  
Diabetic Macular Edema ◽  
Phase Iii ◽  
Long Term Outcomes ◽  
Two Phase ◽  
Phase Iii Trials
Sign in / Sign up

Export Citation Format

Share Document