
Inhibiting GABA Transaminase to Relieve Obesity Induced Hyperinsulinemia and Insulin Resistance...
HyperinsulinismInsulin Resistance3 more50% of Arizonans are diabetic or pre-diabetic resulting in $6.4 billion in health care and productivity costs. The severity and incidence of Type 2 Diabetes Mellitus (T2DM) is directly related to the hepatic lipid concentration. The degree of hepatic lipid accumulation is communicated by the hepatic vagal afferent nerve (HVAN) to regulate pancreatic insulin secretion and whole body insulin sensitivity. We have shown that obesity enhances expression of GABA-Transaminase (GABA-T) decreasing hepatic release of the excitatory neurotransmitter, aspartate, and increasing release of the inhibitor neurotransmitter, GABA. This enhanced inhibitory tone decreases hepatic vagal afferent nerve activity, increasing pancreatic insulin release and decreasing skeletal muscle glucose clearance/insulin sensitivity. Pharmacological inhibition of GABA-T robustly improves glucose homeostasis in diet induced obese mice. We propose 2 clinical objectives that will test the effect of GABA-T inhibition on glucose tolerance and insulin sensitivity in obese, hyperglycemic, hyperinsulinemic patients.

Chinese Medicine Treat for Hypertensive Renal Injury
HypertensionRenal InjuryThis study evaluates whether the traditional chinese medicine (Qianyangyuyin formula) could prevent and treat early renal injury in patients with hypertension and microalbuminuria (defined as a urinary albumin to creatinine ratio between 30 and 300 mg/g) based on standard antihypertensive treatment.

The Effect of Moxonidine on Blood Pressure and Regression of Early Target Organ Damage in Young...
Abdominal ObesityHypertensionObesity is a major risk factor for the development of hypertension. Based on population studies, risk estimates indicate that at least two-thirds of the prevalence of hypertension can be directly attributed to obesity. Obesity per se is commonly associated with activation of the sympathetic nervous system with a predominant increase in sympathetic outflow to the kidneys and the peripheral vasculature and there is now conclusive evidence that heightened sympathetic nerve activity is a major contributor to the elevation in blood pressure associated with obesity, particularly in young subjects. In line with these findings, dietary weight loss has repeatedly been demonstrated to result in reduced sympathetic nerve activity and lower blood pressure levels. Several lines of evidence have well documented the significant role of SNS activation in obesity associated hypertension and target organ damage. Weight loss is the preferred treatment option for obesity and its consequences and reduces both SNS activation and blood pressure. In the real world however, weight loss maintenance is rarely achieved in obese patients highlighting the urgent need for alternative treatment strategies. Given the crucial involvement of SNS activation in various aspects of the obesity related increase in blood pressure, target organ damage and cardiovascular risk, the use of sympatho-inhibitory agents at an early stage is an obvious choice. The investigators therefore plan to examine the effects of the centrally sympatholytic agent moxonidine on blood pressure and the morning surge in blood pressure, sympathetic activity, regression of early target organ damage (heart, kidney and endothelium), metabolic and inflammatory markers in young obese subjects with hypertension in a randomized, double-blind clinical trial with the angiotensin receptor blocker irbesartan as an active comparator to achieve similar blood pressure reductions in both groups. The investigators hypothesize that moxonidine treatment will result in significant improvements in these outcome parameters and beneficial effects beyond simple blood pressure reduction. Findings from this study could pave the way for an early and pathophysiology- tailored treatment strategy of obesity related hypertension and its detrimental consequences.

Blood Pressure and Glucose Lowering Diet for Taiwanese
HypertensionPrevalence rates of hypertension and diabetes are high in Taiwan. Little attention is given to evidence-based dietary therapy in Taiwan. Patients, after confirmed diagnosis, are mostly prescribed with medications without comprehensive instructions on dietary therapy. DASH diet has been proven to be an effective dietary approach to reduce blood pressure for hypertension patients in US. However, dietary difference and patient profiles across countries are evident. In addition, hypertensive patients are often combined with hyperglycemia. Carbohydrate burden of DASH diet may be higher than most dietitians desire. Therefore, the investigators in tend to design a Taiwanese DASH diet and a lower carbohydrate DASH diet and test their efficacy on both blood pressure and fasting glucose lowering.

Genetic Mechanisms in Human Hypertension
HypertensionThank you for your interest in the investigators Genetics and Blood Pressure Research Study. The National Institutes of Health are sponsoring us to investigate why patients develop high blood pressure, atherosclerosis (hardening of the arteries), and heart disease. There are two parts of the investigators research program. The first part is a screening visit. At this visit you will be given a brief physical exam and will be asked questions concerning your medical history. During the same visit you will have your blood drawn for routine screening and to prepare DNA for genetic testing. You will also be asked to collect a urine sample for routine screening. If the doctor finds that you are a healthy candidate you will be invited to participate in the second part of the study. During Phase II, the investigators will perform physiological tests after you are placed on a low salt diet and again after you are placed on a high salt diet. If you are on blood pressure medication, it may be necessary to discontinue taking your present medication for up to three months before beginning the study. Patients discontinuing their current blood pressure medication may be placed on a different blood pressure medication during this washout period if necessary to maintain blood pressure at pre-study levels. The investigators will take you off all medications at about two weeks prior to your scheduled in-patient study (overnight visits). Once your blood pressure medications are discontinued, you will be closely monitored to make sure you do not encounter any difficulty. If you do not own a home blood pressure monitor, the investigators will provide one for you to use during the study so that you can keep a daily record of your blood pressure readings. The investigators will ask you to call us every three days to report your blood pressure readings. Less than 20% of patients have any significant increase in their blood pressure during this short time off of therapy. After you have stopped taking your medication, dieticians at the hospital will make you low salt meals to eat at home for seven days. On the seventh day of the low salt diet, you will be asked to begin a 24-hour urine collection that you will bring with you when you are admitted to the hospital that evening. That morning, you will be required to come to the Clinical Research Center for a one-hour test to check if your body is in the correct salt balance. You will return that evening to the inpatient Clinical Research Center where you will be admitted for your study that will occur the next morning. On the morning of your low salt study, you will have naturally occurring hormones administered and blood samples drawn from an intravenous needle. The investigators will also take ultrasound pictures of your heart to see how salt and hormones affect the way the heart functions. These tests will last approximately five hours and you will be discharged around 2:00 PM. For the next five days, you will be placed on a high salt diet. During these five days, you will eat all your own food, but the investigators will give you some supplements to eat with your meals. After five days on your high salt diet, on the morning of your second admission to the hospital, you will be asked to begin a final 24-hour urine collection. That morning, you will again be required to come to the Clinical Research Center for a one-hour test to check if your body is in the correct salt balance. You will return that evening to the inpatient Clinical Research Center where you will be admitted for your final study that will occur the next morning. The same study that was done for the low salt study will be repeated for the high salt study. You will be discharged around 2:00 p.m. This study will determine if you are salt-sensitive. In addition, the investigators hope to learn more about the hormones that regulate your blood pressure and the genes responsible for regulating those hormones. You will be placed back on your initial blood pressure medication (if you are on any) and returned to your regular physician for care. The investigators will provide clinically relevant information to you and your physician.

Right Ventricular Resynchronization Therapy
Right Ventricular FailureChronic Thromboembolic Pulmonary Hypertension1 moreThe purpose of this study is to determine whether cardiac resynchronization therapy with the use of an implanted electronic pacemaker reduces morbidity associated with chronic thromboembolic pulmonary hypertension

Safety and Efficacy of Chlorthalidone + Amiloride to Elderly Patients Treatment With Arterial Hypertension...
Arterial HypertensionThe purpose of this study is to assess the efficacy and safety of Chlorthalidone 25 mg + amiloride hydrochloride 5 mg association in the treatment of elderly patients with arterial hypertension.

Effect of Renin-angiotensin System Blockers on Glomerular Filtration Rate in Patients With Hypertension,...
DiabetesHypertensive DiseaseDiabetes is the leading cause of chronic kidney disease in developed countries. About 30-40% of patients with type 1 and type 2 diabetes mellitus will develop diabetic nephropathy. Microalbuminuria is often used as an early predictor of diabetic nephropathy. Many studies already demonstrated the renoprotective effect of Renin-angiotensin-system (RAS) blockers in patients with varying degree of albuminuria, few studies focus on studying the decline in glomerular filtration rate (GFR) among patients with normoalbuminuria. However a substantial number of diabetic patients exist with sub-normal GFR without microalbumin excretion. From literature, diabetes mellitus will have faster decline in GFR but the investigators do not know whether such decline can be slowed down by the use of RAS blockers as compared with other anti-hypertensive drugs. This Study investigate the effect of early treatment with RAS blockers on the decline rate of GFR in diabetic patients with normoalbuminuria.

The Links Between Water and Salt Intake, Body Weight, Hypertension and Kidney Stones: a Difficult...
Urinary StonesHypertension2 moreNephrolithiasis is a disease that strikes roughly 10% of the Italian population and its incidence in industrialized countries is on the increase. The most common form of the disease (80%) is Idiopathic Calcium Nephrolithiasis (ICN) with calcium-oxalate (CaOx) and/or calcium-phosphate (CaP) stones. The etiopathogenesis involves both genetic and acquired factors, the interplay of which leads to urinary biochemical anomalies at the root of stone formation. The elements and urinary compounds involved are known as "urinary stone risk factors". The risk factors for CaOx stones consist of low urine volume, hypercalciuria, hyperoxaluria, hyperuricosuria, hypocitraturia and hypomagnesuria. In the case of CaP stones, the hyperphosphaturia and pH parameters are of particular importance; a pH>7 promotes the formation of stones prevalently composed of phosphates, while a pH of between 6 and 7, associated with a volume <1l/day, can raise CaP supersaturation to a dangerously high level and lead to the formation of mixed CaOx and CaP stones. For uric acid stones, the elements involved are hyperuricosuria and pH<5.5. In general, the most prevalent alteration in ICN is hypercalciuria (50%). Hypertension and obesity are also social diseases with important epidemiological similarities to nephrolithiasis. These affinities have led to the search for a common pathogenic moment. As far as hypertension is concerned, various studies have demonstrated high calciuria in hypertensives with a linear relationship between 24-h calciuria and arterial blood pressure. The incidence of stone disease is greater in hypertensives than in normotensives and, by the same token, the incidence of hypertension is greater in stone formers than in non stone formers, but it is not clear whether nephrolithiasis is a risk factor for hypertension or vice versa. Moreover, a linear relationship exists between calciuria and natriuria, where the calcium is the dependent variable, with a much steeper slope of the straight line in stone formers and hypertensives compared to controls. It has, in fact, been demonstrated that to reduce calcium, it is more efficacious to reduce sodium intake as opposed to calcium intake. Finally, BMI and body weight are independently associated with an increase in stone risk even though, due to a number of bias (limited weight categories, low number of obese persons in the study populations, no control group, no recording of food intake) the studies published failed to be conclusive. In the final analysis, stone disease, arterial hypertension and excess weight/obesity prove to be closely interconnected and it is possible to intervene with targeted diets aimed at reducing the risk of illness and death from these diseases. Among such dietary approaches, the reduction of sodium chloride in food, increased hydration and an increased intake of foods with an alkaline potential seem to play an important role. For many years now, the investigators research unit has been involved in projects, partially financed by the Italian Ministry of University and Research (MIUR), geared towards studying the effects induced by dietary changes in patients with calcium stone disease. The aim of the present project is to analyse in depth the relationship between stone disease, hypertension, body weight and water and salt intake both in the general population of the area of Parma (where historically and by gastronomic tradition, the usual diet tends to have a high salt content) and in a selected population of stone formers and hypertensives not under treatment. A representative sample of the population of the area of Parma will be studied, divided on the basis of weight category, in order to assess water and salt intake and relationships with the presence of hypertension, and a sample of normal and hypertensive stone formers randomized to receive for one year either water therapy+low salt diet or water therapy alone.

Inhaled Iloprost for Disproportionate Pulmonary Hypertension in Chronic Obstructive Pulmonary Disease...
Chronic Obstructive Pulmonary DiseasePulmonary hypertension is frequently present in COPD and it is generally limited to a mild increase in mean pulmonary artery pressure. However some COPD patients are characterized by higher levels of mPAP at rest, fulfilling the definition of moderate or severe PH disproportionate PH . In these patients the elevated pulmonary pressures adversely affect the prognosis.At the present time the evidence for the the use of specific pulmonary vasodilators in the management of these patients are scarce and cannot be recommended.the aim of this study is to evaluate the medium term efficacy and safety of the inhaled prostacyclin stable analog, iloprost in patients with COPD and moderate to severe pulmonary hypertension