Resistant Hypertension: Where are We Now and Where Do We Go from Here?

Resistant hypertension is an important subtype of hypertension that leads to an increased risk of cerebrovascular, cardiovascular, and kidney disease. The revised guidelines from the American College of Cardiology and American Heart Association now define resistant hypertension as blood pressure that remains above goal despite use of three maximally titrated anti-hypertensive medications including a diuretic or as a hypertensive patient who requires 4 or more agents for adequate BP control. These agents typically include a calcium-channel blocker, a renin-angiotensin system inhibitor, and a diuretic at maximal or maximally tolerated doses. As recognition of resistant hypertension increases, it is important to distinguish pseudo-resistant or apparent hypertension from true resistant hypertension. Etiologies of apparent resistant hypertension include measurement error and medication non-adherence. The prevalence of true resistant hypertension is likely much lower than reported in the literature when accounting for patients with apparent resistant hypertension. Evaluation of patients with true resistant hypertension includes screening for causes of secondary hypertension and interfering medications. Successful management of resistant hypertension includes lifestyle modification and optimization of medical therapy, often including the use of mineralocorticoid receptor antagonists. Looking ahead at developments in hypertension management, a slew of new device-based therapies are under active development. Of these, renal denervation is the closest to routine clinical application. Further study is needed before these devices can be recommended in the routine treatment of resistant hypertension.

Akt/protein kinase B prevents injury-induced motoneuron death and accelerates axonal regeneration.

Motoneurons require neurotrophic factors for their survival and axonal projection during development, as well as nerve regeneration. By using the axotomy-induced neuronal death paradigm and adenovirus-mediated gene transfer, we attempted to gain insight into the functional significances of major growth factor receptor downstream cascades, Ras-extracellular signal-regulated kinase (Ras-ERK) pathway and phosphatidylinositol-3 kinase-Akt (PI3K-Akt) pathway. After neonatal hypoglossal nerve transection, the constitutively active Akt-overexpressing neurons could survive as well as those overexpressing Bcl-2, whereas the constitutively active ERK kinase (MEK)-overexpressing ones failed to survive. A dominant negative Akt experiment demonstrated that inhibition of Akt pathway hastened axotomy-induced neuronal death in the neonate. In addition, the dominant active Akt-overexpressing adult hypoglossal neurons showed accelerated axonal regeneration after axotomy. These results suggest that Akt plays dual roles in motoneuronal survival and nerve regeneration in vivo and that PI3K-Akt pathway is probably more vital in neuronal survival after injury than Ras-ERK pathway.

Recurrent cholera epidemics in Kano--northern Nigeria.

OBJECTIVES: The study examined the factors associated with recurrent cholera epidemics in Kano State of Northern Nigeria, the management of the epidemics and health outcomes. METHODS: Using epidemiological data from the Public Health Department of the Kano State Ministry of Health, the study examined the frequency and geographical distribution of the epidemics for the period 1995 to 2001; procedures for detection; control measures as well as results of biological and bacteriological testing of water from different sources. Mapping and testing for significance of faecal contamination of water sources were done. RESULTS: The number of cholera cases in the city was 2 630; 847 and 2 347 in 1995/6, 1997 and 1999 respectively. The State Epidemiological Unit which is responsible for surveillance detected epidemics using set thresholds and activated multi-sectoral emergency responses. Control measures encompassed accurate diagnosis at the reference laboratory, Kaduna; registration of cases; case management and public health measures targeting personal hygiene and water treatment. The cholera epidemics attracted worldwide attention with emergency responses from many agencies including WHO, UNICEF and Medicens Sand Frontiers (MSF). Case fatality rates decreased from 15% in 1995/6 to 5% in 1997 and 2% in 1999. The organism responsible for all the outbreaks was Vibrio cholerae, el-tor of inaba serotype. Water contamination of all sources was the principal cause of the epidemics. There were statistically significant differences in levels of faecal contamination of water sources, wells being most affected, followed by piped water, chi2 = 11.556, (p < 0.02). Bore holes were relatively safer sources of water. Point source epidemics always started from Kano City before fanning out to the rest of the State. CONCLUSION: Multi-sectoral Epidemic Preparedness and Response (EPR) approaches have contributed to the reduction in case fatality rates over the years and should be sustained. However, in order to prevent future cholera epidemics, there is need to introduce intervention measures that address the root problems of poor sanitation and unsafe water supplies.

Up-regulation of thioredoxin expression in motor neurons after nerve injury.

A substantial up-regulation of thioredoxin, a dithiol/disulfide oxido-reductase, in adult rat motoneurons following hypoglossal nerve axotomy, was demonstrated by using both in situ hybridization and immunohistochemistry. Although thioredoxin is normally accumulated more in the nucleus of a motoneuron rather than in the cytoplasm, a dramatic increase of thioredoxin in the cytoplasmic region after nerve injury was observed. The up-regulation of mRNA lasted more than 9 weeks, whereas, the detectable up-regulation of protein was observed for more than 5 weeks.

Discordant expression of c-Ret and glial cell line-derived neurotrophic factor receptor alpha-1 mRNAs in response to motor nerve injury in neonate rats.

Adult motoneurons can survive following axotomy, whereas neonate motoneurons result in cell death. Following hypoglossal nerve axotomy in neonate rat, Glial cell line-Derived Neurotrophic Factor (GDNF) receptor alpha-1 (GFRalpha-1) mRNA expression was dramatically suppressed in the injured motoneurons, while a slight increase of c-Ret mRNA expression was observed. In adult, both GFRalpha-1 and c-Ret mRNAs increased substantially after axotomy. The present result suggests that the difference of motoneuron fate after axotomy may be partly due to the coordinate or discordant responses of GFRalpha-1 and c-Ret expression to nerve injury.