Medical Advisor Journals

Wednesday, August 8, 2012

Angina pectoris

Angina pectoris, also known as Angina, a symptoms of Ischemic heart disease, is defined as a condition of chest pain caused by poor blood flow through the blood vessels due to obstruction or spasm of the coronary arteries resulting of lack of blood that lead to lack of oxygen supply and waste removal.

Types of Angina pectoris
1. Stable angina res
Stable angina is the chest pain occurred after physical activity or stress and may last up to 10 minutes. the symptoms may improve or go away when stop or slow down the exercise.

2. Unstable angina
Unstable angina is a type of angina with chest pain occurs even at rest, with Crescendo angina and/or new-onset angina(1)

Symptoms
Beside chest pain or discomfort, patients with angina may also experience heaviness, tightness, squeezing, burning, or choking sensation of the chest and pain in the back, neck area, jaw, or shoulders. These are results of the pain perceived at a location other than the chest depending to the spinal level that receives visceral sensation.

Causes and risk factors
A. Causes
A.1. Stable angina
Physical exertion is the most common cause of stable angina as a result of severely narrowed arteries of that interfere with the blood flow to the heart.

A.2. Unstable angina
Unstable angina is a condition of blood clots causes of partially or totally block of an artery as a result of rupture of an artery. If severe case, large blood clot can increase the risk of cardiovascular diseases,
Blood clots may form, partially dissolve, and later form again. Angina can occur each time a clot blocks an artery.

B. Risk factors
1. Cigarette smoking
Men who are smokers are at higher risk to develop angina. According to the study of Framingham Heart Study, posted by Harvard University, indicated that those less than 60 years of age at angina onset who were nonsmokers or quitters during follow-up had a definite prognostic advantage over similarly aged continuing smokers. These results could not be explained by differences in coronary risk factors prior to symptom onset or by changes in factors other than smoking during follow-up. The findings suggest that stopping the cigarette smoking habit can improve both short-term and long-term prognosis in the younger patient and angina pectoris(2).

2. Obesity
in the study to evaluate the effects of moderate weight loss, in overweight patients with angina, on plasma coagulation, fibrinolytic indicies and pain frequency, at the University of Glasgow, researchers found that after the 12-week dietary intervention period, mean body weight fell by 3.5 (s.d. 2.6) kg or 4.3% (P=0.0001), range -11.7 to +1.7 kg. Mean angina frequency fell by 1.8 (s.d. 3.6) from 3.2 to 1.4 episodes/week (P=0.009) and plasma cholesterol by 0.4 (s.d. 0.7) from 6.3 to 5.9 mmol/l (P=0.0001). HDL cholesterol and triglyceride were unchanged. Of the coagulation and fibrinolytic factors, factor VII activity and RCA were significantly reduced by 5 (s.d. 20), IU/dl (P=0.04) and 1.3 (s.d. 1.3) arbitrary units (P=0.014), respectively(3).

3. Diabetes
In the study of nineteen diabetic and 25 nondiabetic patients with exertional angina were exercised on a treadmill to measure anginal perceptual threshold, researchers at the Newham General Hospital found that the diabetic group had a longer anginal perceptual threshold (138 +/- 64 seconds vs 34 +/- 51 seconds, p less than 0.001), which correlated positively with the somatic pain threshold (r = 0.5, p = 0.03); patients with more prolonged anginal perceptual thresholds tended to have higher somatic pain thresholds. In the diabetic group anginal perceptual (r = -0.3, p = NS) and somatic pain (r = -0.4, p = 0.05) thresholds tended to increase as the ratio of peak to minimal heart rate during the Valsalva maneuver fell below 1.21, but these variables were unrelated in the nondiabetic group(4).

4. High cholesterol
According to the study of The Heart Center of Chonnam National University Hospita of 34 stable angina pectoris (SAP) patients showed that these patients had unstable plaques (UPs) (61.6±9.2 years, 24 males, 12.8%). The percentage of plaque area in the minimum luminal area in high low density lipoprotein-cholesterol (LDL-C)/high density lipoprotein-cholesterol (HDL-C) ratio patients was significantly higher than in low LDL-C/HDL-C ratio patients (72.7±9.5% vs. 69.9±9.3%, p=0.035). An LDL-C/HDL-C ratio >2.0 was an independent predictor for UPs in SAP patients (odds ratio 5.252, 95% confidence interval 1.132-24.372, p=0.034)(5).

5. High blood pressure
Hypertension is associated to increased risk of Angina pectoris. In the study ofManagement of patients with hypertension and angina pectoris, reserachers showed that in managing the patient with hypertension and angina pectoris, it is important to determine whether the angina occurs in the setting of hypertensive hypertrophic disease alone or coexists with coronary arterial stenoses(6).

6. Sedentary lifestyle and Unhealthy diet
Lifestyle with no or irregular physical activity is associated with increased risk of Angina pectoris. Diet high in saturated and trans fat with less fruits and vegetables enhances the building up of blood cholesterol of that increase the risk of angina.

7. Family history of early heart disease
If you have a family history of early heart disease, you are at higher risk to develop angina pectoris as family history of premature coronary artery disease increase the risk of an imbalance between myocardial oxygen supply and demand that may result of angina.

8. Coronary artery disease
Coronary artery disease can cause decreased blood flow to the coronary arteries from the heart as a result of narrowing of the small blood vessels that supply blood and oxygen to the heart.

9. Other heart diseases
Increased blood flow for patients with preexisting ischemic heart disease may reduced the risk of angina pertoris, according to the study of Efficacy of early invasive strategy of diagnostics and treatment of unstable angina at the background of preexisting ischemic heart disease, indicated that detection of indications for myocardial revascularization in patients with unstable angina including those at medium and low risk confirms necessity of application of early invasive strategy as conventional strategy ensuring timeliness of pathogenetic treatment. Absence of indications to myocardial revascularization in a limited group of patients gives an opportunity to clarify diagnosis, prescribe drug therapy and prevent unjustified hospitalizations(7)

10. Previous heart attack
Heart attack victims may experience a diversity of symptoms, including chest pain, heaviness, tightness, squeezing, burning, or choking sensation of the chest and pain in the back, neck area, jaw, or shoulders.

11. Age and lower socioeconomic status
According to the study of Dr. Sekhri N, and the research team at the Barts and the London NHS Trust, here is evidence of underutilisation of chest pain clinics by older people and those from lower socioeconomic status. More robust and patient focused administrative pathways need to be developed to detect inequity, correction of which has the potential to substantially reduce coronary mortality(8).

12. Etc,

Diagnosis

Chest pain is not always as a indication of angina. Certain medication and medical conditions can cause chest pain, including Pleuritis ( Inflammation of the lining of the lungs), long term smoking cause depletion of lung function, Pericarditis: Pericarditis (inflammation of the lining around the heart), Shingles (Nerve irritation), etc. If you are exoerience chest pain or discomfort, several tests can help to determine the causes

1. Blood test

Blood test may be to rule out other conditions causes of angina or to check for levels of fats,
C-reactive protein (CRP), high levels of CRP may be a sign of CVD,

2. Chest X ray

the aim of the test is to show the structure of the chest to rule out other causes of angina, as it can reveal the sign of heart failure and lung disorder cause of chest pain, etc.

3. Electrocardiogram (ECG)

Electrocardiogram or electrocardiography (ECG) is the test to diagnose the heart conditions by measuring the electrical activity of the heart and highly recommendation for patients showing symptoms of severe chest pain. An abnormal patterns on the EKG may be an indication of Ischemia. In some cases, exercise testing, an exercise ECG test or 'stress test' as ECG recording is taken while you are exercising to induce the symptoms of chest pain in finding the causes.

4. Stress test

An exercise stress test such as walk or run on a treadmill or pedal a stationary bike is a screening tool used to test how your heart function under exercise stress. Medications can be necessary to simulate the stress on the heart normally brought on by exercise, if patient can not undergo exercise as a result of certain condition

5. Coronary angiography

Coronary angiography is an imaging test that uses a special dye (contrast material) and x-rays to see inside the arteries and how blood flows through your heart with the a mild sedative to help you relax.

6. Heart CT scan

Heart CT scan is a computed tomography (CT) scan of the heart with the use of uses x-rays to create detailed pictures of the heart and its blood vessels.

7. Computed Tomography angiography

A noninvasive way 3D technique with a contrast material to produce pictures of major blood vessels throughout the body with the use of x-rays with catheters, or computed tomography (CT) or magnetic resonance imaging (MRI).

8. Etc.

Preventions

A. The do and do not list

1. Life style change

a. Relaxation

Stress and emotion may increase the risk of Angina pectoris, a symptoms of schemic heart disease. According to the study of Emotional triggering of cardiac events at the University College London. Dr Steptoe A, and the research team indicated that the psychobiological processes underlying emotional triggering may include stress-induced haemodynamic responses, autonomic dysfunction and parasympathetic withdrawal, neuroendocrine activation, inflammatory responses involving cytokines and chemokines, and prothrombotic responses, notably platelet activation. These factors in turn promote coronary plaque disruption, myocardial ischaemia, cardiac dysrhythmia and thrombus formation(9). Music listening may have a beneficial effect on blood pressure, heart rate, respiratory rate, anxiety, and pain in persons with CHD. However, the quality of the evidence is not strong and the clinical significance unclear. Most studies examined the effects of listening to pre-recorded music. More research is needed on the effects of music offered by a trained music therapist(10). Other researchers in the study to determine the prevalence of anxiety and depressive symptoms in patients referred to a cardiology outpatient clinic for performing the stress test suggested that the prevalence of anxiety and depressive symptoms was estimated to be 42% and 31%, respectively, in the total chest pain population. Males with abnormal test were depressed but females experienced more anxiety symptoms. Patients with negative tests had significantly higher scores for anxiety and higher depression scores than those with positive tests. Eleven percent of the patients with positive tests were women and 23% were men(11).

b. If the disease is caused by physical activity, slow down or take rest more often can be helpful

2. Healthy diet

In the study to compare two strategies for atherosclerosis treatment: drugs and healthy lifestyle, found that Statins act mainly as lipid-lowering drugs but pleiotropic actions are also present. Healthy lifestyle, on the other hand, is effective and inexpensive and has no harmful effects. Five items are associated with lower cardiac risk: non-smoking, BMI ≤25, regular exercise (30 min/day), healthy diet (fruits, vegetables, low-saturated fat, and 5-30 g alcohol/day)(12).

a. Low intake of saturated and trans fats

High levels of bad cholesterol and triglyceride partial block the blood flow in the vessels, it not only increases the risk of high blood pressure but also the risk of ischemia if the blood circulation diminishes.

d. Increase intake fish and olive oil

Studies indicate that the use of fish oil is associated with coronary heart disease risk reduction. A number of mechanisms may be responsible for such effects. These include prevention of arrhythmias as well as lowering heart rate and blood pressure, decreasing platelet aggregation, and lowering triglyceride levels. The latter is accomplished by decreasing the production of hepatic triglycerides and increasing the clearance of plasma triglycerides(19). Other researchers indicated that in both sexes consumption of olive oil and vegetable oil was inversely associated with serum cholesterol and glucose levels and systolic blood pressure(13).

c. High amount intake of in fiber

Consumption of dietary fiber from cereals and fruits is inversely associated with risk of coronary heart disease. In a study of over 6 to 10 years of follow-up, 5249 incident total coronary cases and 2011 coronary deaths occurred among 91058 men and 245186 women. After adjustment for demographics, body mass index, and lifestyle factors, each 10-g/d increment of energy-adjusted and measurement error-corrected total dietary fiber was associated with a 14% (relative risk [RR], 0.86; 95% confidence interval [CI], 0.78-0.96) decrease in risk of all coronary events and a 27% (RR, 0.73; 95% CI, 0.61-0.87) decrease in risk of coronary death. For cereal, fruit, and vegetable fiber intake (not error corrected), RRs corresponding to 10-g/d increments were 0.90 (95% CI, 0.77-1.07), 0.84 (95% CI, 0.70-0.99), and 1.00 (95% CI, 0.88-1.13), respectively, for all coronary events and 0.75 (95% CI, 0.63-0.

Fiber is found in whole grains, fruits, and vegetables. A fiber-rich diet not only helps lower your LDL cholesterol level, but also provides nutrients that may help protect against CHD(14).

d. Low intake of salt and sugar

d.1. Manage your blood pressure and reduce intake of salt, beverage and sugar

The worldwide increase in the incidence of metabolic syndrome correlates with marked increase in total fructose intake in the form of high-fructose corn syrup, beverage and table sugar. Increased dietary fructose intake in rodents has been shown to recapitulate many aspects of metabolic syndrome by causing hypertension, insulin resistance and hyperlipidaemia(15).

d.2. Prevent weight gain and control diabetes and prediabetes

In the study to test a 16-week group-based weight reduction intervention combining exercise, diet and behaviour change strategies aimed to increase self-efficacy (Healthy Eating and Exercise Lifestyle Program-HEELP) on weight, body mass index (BMI), waist circumference and exercise, found that The HEELP resulted in weight loss and improved exercise behaviour in obese people with CHD and T2DM(16).

d.3. Mediterranean style low-carb diet

The best approach to the dietary prevention of CVD is a Mediterranean style low-carb diet represented in the LOGI pyramid. Dietary guidelines for the prevention of CVD should to be revised accordingly(17).

2. Tobacco
Cigarette contains high levels of cadmium, inhaling the chemical during smoking or second hand smoke can cause building up of plaque along to the arterial walls as a result of oxidation.

3. Moderate consumption of Green tea, coffee and alcohol

Regular consumption of moderate quantities of coffee and (green) tea seems to be associated with a small protection against CAD, results from randomized clinical trials about their beneficial effects are less evident. As for other diffuse consumption habits, such as that of alcohol, moderation is the key word. In fact, both for coffee and chocolate, the optimal healthy effects on CAD have been observed to be associated with a moderate intake, while healthy outcomes vanish at heavy consumption(18).

4. Maintaining a healthy weight

Obesity increases the risk of ischemia as it is normally associated with high levels of cholesterol, high blood pressure.

5. Managing stress

Music listening may have a beneficial effect on blood pressure, heart rate, respiratory rate, anxiety, and pain in persons with CHD. However, the quality of the evidence is not strong and the clinical significance unclear. Most studies examined the effects of listening to pre-recorded music. More research is needed on the effects of music offered by a trained music therapist(19). Other researchers in the study to determine the prevalence of anxiety and depressive symptoms in patients referred to a cardiology outpatient clinic for performing the stress test suggested that the prevalence of anxiety and depressive symptoms was estimated to be 42% and 31%, respectively, in the total chest pain population. Males with abnormal test were depressed but females experienced more anxiety symptoms. Patients with negative tests had significantly higher scores for anxiety and higher depression scores than those with positive tests. Eleven percent of the patients with positive tests were women and 23% were men(20).

6. Etc.

B. Foods to prevent angina
The aims of the diet is to reduce the unhealthy diet and coronary artery disease risk factors causes of Angina pectoris, the symptom of Ischemic heart disease
1. Avocados are a commercially valuable fruit and are cultivated in tropical climates throughout the world, it is a green-skinned, pear-shaped fruit that ripens after harvesting and native to the Caribbean, Mexico, South America and Central America, belonging to the flowering plant family Lauraceae.
a. Cholesterol
In the determination of the atherogenicity of avocado oil relative to saturated (coconut oil), monounsaturated (olive oil) and polyunsaturated (corn oil) fats found that Coconut oil was the most atherogenic fat. Corn oil was only slightly less atherogenic than either olive or avocado oils. Percentage of serum HDL cholesterol was highest in the rabbits fed the two monounsaturated fats, according to "Cholesterol vehicle in experimental atherosclerosis 24: avocado oil" by Kritchevsky D, Tepper SA, Wright S, Czarnecki SK, Wilson TA, Nicolosi RJ.(21)

b. Dietary fiber
Daily intake of right amount of fibers can prevent and treat Diabetes. Increased consumption of vegetables, whole grains, and soluble and insoluble fiber is associated with improved glucose metabolism in both diabetic and nondiabetic individuals. Improvements in insulin sensitivity and glucose homeostasis were more evident in participants following a plant-based diet compared with other commonly used diets, according to the study of "Efficacy of high-fiber diets in the management of type 2 diabetes mellitus" by Wolfram T, Ismail-Beigi F.(22)

c. Heart diseases
c.1.The chemical compound Beta-Sitosterol is found effectively in reducing the bad cholesterol and leaving the good cholesterol untouched by inhibiting the amount our body can absorb, thus reducing the risk of plague building up in the arterial walls, leading to heart diseases, according to the study of "The Effect of Beta Sitosterol on the Serum Lipids of Young Men with Arteriosclerotic Heart Disease" by JOHN W. FARQUHAR M.D.; RALPH E. SMITH M.D.; MARY E. DEMPSEY M.S., posted in Circulation(23)

c.2. It also reduce the risk of autoimmune diseases such as multiple sclerosis, according to the study of "Effect of vitamin D and β-sitosterol on immune function of macrophages" by Alappat L, Valerio M, Awad AB.(24)

2. Salmon is the common name for Salmonidae. They are anadromous, born in fresh water, migrate to the ocean, then travel thousands of miles in the deep sea cold water throughout their life cycle and within to five years returning to the exacted location where they were born to reproduce and die.
a. Triacylglycerols
In the investigation of Intake of fish and omega-3 (n-3) fatty acids is associated with a reduced concentration of plasma triacylglycerols (TAG) found that intake of cod or salmon when compared with the control group. In conclusion, both lean and fatty fish may lower TAG, possibly by reducing the 18:1n-9/18:0 ratio related to allosteric inhibition of SCD1 activity, rather than by influencing the synthesis of enzyme protein, according to "Daily Intake of Cod or Salmon for 2 Weeks Decreases the 18:1n-9/18:0 Ratio and Serum Triacylglycerols in Healthy Subjects" by Telle-Hansen VH, Larsen LN, Høstmark AT, Molin M, Dahl L, Almendingen K, Ulven SM.(25)

b. Weight loss
In the investigation of supplementation with n3 long-chain polyunsaturated fatty acids (n3-LCPUFA) and its effect in body weight, found that At the end of the 1-month period, 16 children lost weight and 27 children gained weight. Multiple analysis demonstrated that supplementation with n3-LCPUFA decreased HOMA-IR by 15% after adjusting for puberty, treatment adherence, changes in adipokines, and weight loss. Interaction between supplementation and weight loss was significant (p = 0.007), according to "Supplementation of n3 Long-chain Polyunsaturated Fatty Acid Synergistically Decreases Insulin Resistance with Weight Loss of Obese Prepubertal and Pubertal Children" by López-Alarcón M, Martínez-Coronado A, Velarde-Castro O, Rendón-Macías E, Fernández J.(26)

c. Cholesterol
In the assessment of an increasing drive to replace fish oil (FO) in finfish aquaculture diets with vegetable oils (VO), driven by the short supply of FO derived from wild fish stocks,
found that these effects are most likely mediated by SREBP2, which responds to reductions in dietary cholesterol. These changes are sufficient to maintain whole body cholesterol levels but not HUFA levels, according to "Functional genomics reveals increases in cholesterol biosynthetic genes and highly unsaturated fatty acid biosynthesis after dietary substitution of fish oil with vegetable oils in Atlantic salmon (Salmo salar)" by Leaver MJ, Villeneuve LA, Obach A, Jensen L, Bron JE, Tocher DR, Taggart JB.(27)

d. Coronary heart disease
In determination of Omega-3-fatty acids play a protective role in the prevention of CHD,
found that The treatment with salmon oil led to a decrease of triglycerides in patients with hypertriglyceridemia and to an increase of cholesterol in hypercholesterolemia. Following the increase of malondialdehyde as measure of the lipid peroxidation a substitution of antioxidants, like vitamin E and vitamin C, seems to be useful. Further investigations are necessary before wide use of fish-oil capsules, not least to avoid side-effects, according to "[Changes in parameters of lipid metabolism and anti-oxidative potentials in elderly hyperlipoproteinemic patients treated with omega-3 fatty acids].[Article in German]" by Reuter W, Vorberg B, Sauer I, Krumpolt C.(28)

e. Antioxidants
In the research of the antioxidant effect of vitamin E after ingestion of salmon found that that megadoses of vitamin E, far from having pro-oxidative activity, actually increase the anti-oxidative capacity of the liver, especially after ingestion of salmon oil, according to "Effects of megadoses of dietary vitamin E on the antioxidant status of rats fed lard or salmon oil" by Flader D, Brandsch C, Hirche F, Eder K.(29)

3. Soy sauce is a seasoning produced by fermenting soybeans and filamentous fungus, along with water and salt after a period of sometime, it yields a moromi or thick mash of cereal to obtain soy sauce by pressing it to liquid form. Tamari is made by collecting the liquid which was pressed and the liquid drained drains from miso after a certain time of fermentation.
a. Cardiovascular health
In the investigation of dietary proteins and their effect in heart diseases found that a direct cholesterol lowering effect of proteins has not been shown. Despite earlier research indicating that soy protein has cardioprotective effects as compared to other proteins, these observations have not been confirmed by randomized placebo-controlled trials. However, most experts recommend the consumption of foods rich in plant proteins as alternatives to meat and dairy products rich in saturated fat and containing cholesterol, according to "Dietary proteins and atherosclerosis" by Darioli R.(30)

b. Hypolipidemic effect
In the observation of Soy sauce (Shoyu), a traditional Japanese fermented seasoning and its effect on cholesterol level found that in a 4-week randomized, double-blind, placebo-controlled parallel group study, hyperlipidemic men (TG >150 mg/dl) were treated with 600 mg of SPS (n=15) or placebo (n=15) daily. After 4 weeks, serum TG levels in the SPS-treated group were significantly (P<0.05) lower than the baseline (0 week). In conclusion, SPS of soy sauce reduce lipid absorption, and soy sauce is a potentially promising seasoning for the treatment of hyperlipidemia through food, according to "Hypolipidemic effect of Shoyu polysaccharides from soy sauce in animals and humans" by Kobayashi M, Magishi N, Matsushita H, Hashimoto T, Fujimoto M, Suzuki M, Tsuji K, Saito M, Inoue E, Yoshikawa Y, Matsuura T.(31)

4. Tomato is a red, edible fruit, genus Solanum, belongs to family Solanaceae, native to South America. Because of its health benefits, tomato is grown world wide for commercial purpose
and often in green house.
a. Cardiovascular diseases
In the review of patents and products within the context of lycopene and CVD prevention and health claims indicated that in vitro data and results from animal experiments partly showed promising preventive mechanisms of lycopene. In contrast, until now, human intervention studies mostly failed to show any CVD prevention. However, there is still an encouraging situation, giving hints for antioxidant as well as anti-inflammatory effects of lycopene. These mechanisms could be the background for cardio-protective effects of tomatoes and tomato products, according to "Lycopene and heart health" by Böhm V.(32)

b. Antioxidative and Cancer Cell-Inhibiting Activities
In the research of Tomato ( Solanum lycopersicum ) plants synthesize nutrients, pigments, and bioactive compounds and their benefit in nutrition and human health found that Tomato extracts promoted growth in normal liver (Chang) cells, had little effect in normal lung (Hel299) cells, mildly inhibited growth of lung cancer (A549) cells, and first promoted and then, at higher concentrations, inhibited growth in lymphoma (U937) cells. The relationship of cell growth to measured constituents was not apparent, according to "Free Amino Acid and Phenolic Contents and Antioxidative and Cancer Cell-Inhibiting Activities of Extracts of 11 Greenhouse-Grown Tomato Varieties and 13 Tomato-Based Foods" by Choi SH, Kim HR, Kim HJ, Lee IS, Kozukue N, Levin CE, Friedman M.(33)

C. Phytochemicals to prevent angina

1. 1. Omega-3 Fatty Acids
a. Systolic blood pressure, triglycerides and LDL cholesterol
In the ccomparison of the cardiovascular risk-reduction potential of three major polyunsaturated fatty acids in a double-blind study. showed that for the diet supplemented with EPA plus DHA compared with the linoleic acid diet systolic blood pressure fell 5.1 mm Hg (p = 0.01); plasma triglyceride and VLDL cholesterol fell by 39% (p = 0.001) and 49% (p = 0.01), respectively; and LDL cholesterol rose by 9% (p = 0.01). There were no significant changes with the diet supplemented with alpha-linolenic acid. The net effect on cardiovascular risk therefore is complex and the systolic blood pressure reduction was substantial, according to "n-3 fatty acids of marine origin lower systolic blood pressure and triglycerides but raise LDL cholesterol compared with n-3 and n-6 fatty acids from plants" by Kestin M, Clifton P, Belling GB, Nestel PJ.(34)

b. Cardiovascular effects
In the comparison of the effects of alpha-linolenic acid (ALA, C18:3n-3) to those of eicosapentaenoic acid (EPA, C20:5n-3) plus docosahexaenoic acid (DHA, C22:6n-3) on cardiovascular risk markers in healthy elderly subjects, found that Both n-3 fatty acid diets did not change concentrations of total-cholesterol, LDL-cholesterol, HDL-cholesterol, triacylglycerol and apoA-1 when compared with the oleic acid-rich diet. However, after the EPA/DHA-rich diet, LDL-cholesterol increased by 0.39 mmol/l (P = 0.0323, 95% CI (0.030, 0.780 mmol/l)) when compared with the ALA-rich diet. Intake of EPA/DHA also increased apoB concentrations by 14 mg/dl (P = 0.0031, 95% CI (4, 23 mg/dl)) and 12 mg/dl (P = 0.005, 95% CI (3, 21 mg/dl)) versus the oleic acid and ALA-rich diet, respectively. Except for an EPA/DHA-induced increase in tissue factor pathway inhibitor (TFPI) of 14.6% (P = 0.0184 versus ALA diet, 95% CI (1.5, 18.3%)), changes in markers of hemostasis and endothelial integrity did not reach statistical significance following consumption of the two n-3 fatty acid diets, according to "Effects of alpha-linolenic acid versus those of EPA/DHA on cardiovascular risk markers in healthy elderly subjects" by Goyens PL, Mensink RP.(35)

c. Obesity
in the determination of whether obesity modifies the association between plasma phospholipid polyunsaturated fatty acids (PUFAs) and markers of inflammation and endothelial activation in Multi-Ethnic Study of Atherosclerosis (MESA) participants, found that the modifying effect of obesity on the association of plasma PUFAs with IL-6 and sICAM-1 suggests differences in fatty acid metabolism and may also have implications in dietary fatty acid intake for obese individuals, particularly for linoleic and EPAs. Further study is warranted to confirm and explain the strong associations of dihomo-γ-linolenic acid (DGLA) with inflammatory and endothelial activation markers, according to "Obesity modifies the association between plasma phospholipid polyunsaturated fatty acids and markers of inflammation: the Multi-Ethnic Study of Atherosclerosis" by Steffen BT, Steffen LM, Tracy R, Siscovick D, Hanson NQ, Nettleton J, Tsai MY.(36)

3. Catechin

Catechin is phytochemical of Flavan-3-ols, in the group of Flavonoids (polyphenols), found abundantly in white tea, green tea, black tea, grapes, wine, apple juice, cocoa, lentils, etc.
a. Body-weight regulation
Green tea has been proposed as a tool for obesity management as strategies for weight loss and weight maintenance, as researchers found that a green tea-caffeine mixture improves weight maintenance, through thermogenesis, fat oxidation, and sparing fat free mass. The sympathetic nervous system is involved in the regulation of lipolysis, and the sympathetic innervation of white adipose tissue may play an important role in the regulation of total body fat in general, according to "Green tea catechins, caffeine and body-weight regulation" by Westerterp-Plantenga MS.(37)

b. Antioxidant activity
In the research on polyphenolic compounds (included catechins) in the berries of edible honeysuckle and their biological effects, including recommended utilization, are reviewed found that These berries seem to be prospective sources of health-supporting phytochemicals that exhibit beneficial anti-adherence and chemo-protective activities, thus they may provide protection against a number of chronic conditions, e.g., cancer, diabetes mellitus, tumour growth or cardiovascular and neurodegenerative diseases, according to "Phenolic profile of edible honeysuckle berries (genus lonicera) and their biological effects" by Jurikova T, Rop O, Mlcek J, Sochor J, Balla S, Szekeres L, Hegedusova A, Hubalek J, Adam V, Kizek R.(38)

c. Cholesterol and glucose levels
In the examination of the effect of the main green tea catechin, epigallocatechin gallate (EGCG), taken in a green tea extract, Polyphenon E (PPE) and their effect on circulating hormone levels, an established breast cancer risk factor, found that Glucose and insulin levels decreased nonsignificantly in the PPE groups but increased in the placebo group; statistically significant differences in changes in glucose (P=0.008) and insulin (P=0.01) were found. In summary, green tea (400 and 800 mg EGCG as PPE; ~5-10 cups) supplementation for 2 months had suggestive beneficial effects on LDL cholesterol concentrations and glucose-related markers, according to "Effect of 2-month controlled green tea intervention on lipoprotein cholesterol, glucose, and hormonal levels in healthy postmenopausal women" by Wu AH, Spicer D, Stanczyk FZ, Tseng C, Yang CS, Pike MC.(39)

3. Theaflavin with reddish in color, is a phytochemical of Flavan-3-ols, in the group of Flavonoids (polyphenols), formed in tea leaves during fermentation.
a. Cholesterol
In the investigation of 240 men and women 18 years or older on a low-fat diet with mild to moderate hypercholesterolemia were randomly assigned to receive a daily capsule containing theaflavin-enriched green tea extract (375 mg) or placebo for 12 weeks, found that after 12 weeks, the mean ± SEM changes from baseline in total cholesterol, LDL-C, HDL-C, and triglyceride levels were -11.3% ± 0.9% (P = .01), -16.4% ± 1.1% (P = .01), 2.3% ± 2.1% (P = .27), and 2.6% ± 3.5% (P = .47), respectively, in the tea extract group. The mean levels of total cholesterol, LDL-C, HDL-C, and triglycerides did not change significantly in the placebo group. No significant adverse events were observed, according to "Cholesterol-Lowering Effect of a Theaflavin-Enriched Green Tea Extract" by David J. Maron, MD; Guo Ping Lu, MD; Nai Sheng Cai, MD; Zong Gui Wu, MD; Yue Hua Li, MD; Hui Chen, MD; Jian Qiu Zhu, MD; Xue Juan Jin, MS; Bert C. Wouters, MA; Jian Zhao, PhD.(40)

b. Antioxidant effects
In the investigation of four main TF derivatives (theaflavin (TF(1)), theaflavin-3-gallate (TF(2)A), theaflavin-3'-gallate (TF(2)B), and theaflavin-3,3'-digallate (TF(3))) in scavenging reactive oxygen species (ROS) in vitro, their properties of inhibiting superoxide, singlet oxygen, hydrogen peroxide, and the hydroxyl radical, and their effects on hydroxyl radical-induced DNA oxidative damage, found that compared with (-)-epigallocatechin gallate (EGCG), TF derivatives were good antioxidants for scavenging ROS and preventing the hydroxyl radical-induced DNA damage in vitro. TF(3) was the most positive in scavenging hydrogen peroxide and hydroxyl radical, and TF(1) suppressed superoxide. Positive antioxidant capacities of TF(2)B on singlet oxygen, hydrogen peroxide, hydroxyl radical, and the hydroxyl radical-induced DNA damage in vitro were found, according to "Evaluation of the antioxidant effects of four main theaflavin derivatives through chemiluminescence and DNA damage analyses" by Wu YY, Li W, Xu Y, Jin EH, Tu YY.(41)

c. Cardio-protective activities
In the analyzing the protective effect of theaflavin (TF1) and its underlying mechanism,
found that (1) compared with the control group, TF1 (10, 20, 40 μmol/l) displayed a better recovery of cardiac function after ischemia/reperfusion in a concentration-dependent manner. At 60 min of reperfusion, LVDP, ± LVdP/dt (max) and CF in the TF1 group were much higher than those in the control group, whereas left ventricular end-diastolic pressure (LVEDP) in the TF1 group was lower than that in the control group (P < 0.01). (2) Pretreatment with glibenclamide (10 μmol/l), a K(ATP) antagonist, completely abolished the cardioprotective effects of TF1 (20 μmol/l). Also, most of the effects of TF1 (20 μmol/l) on cardiac function after 60 min of reperfusion were reversed by 5-HD (100 μmol/l), a selective mitochondria K(ATP) antagonist. (3) Atractyloside (20 μmol/l), a mitochondrial permeability transition pore (mPTP) opener, administered at the beginning of 15 min of reperfusion completely abolished the cardioprotection of TF1 (20 μmol/l), according to "ATP-dependent potassium channels and mitochondrial permeability transition pores play roles in the cardioprotection of theaflavin in young rat" by Ma H, Huang X, Li Q, Guan Y, Yuan F, Zhang Y.(42)

4. Resveratrol is a type of natural phenol in the group of Stilbenoids, produced naturally by many plants when under attack by bacteria or fungi. It has been studied by many researchers for it health benefits in treating chronic diaereses, including cancer, diabetes, heart disease, etc.
a. In a study of "Resveratrol: a promising agent in promoting cardioprotection against coronary heart disease." by Penumathsa SV, Maulik N. (Source from Molecular Cardiology and Angiogenesis Laboratory, Department of Surgery, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-1110, USA.), posted in PubMed, researchers indicated in abstract that many studies have provided evidence that resveratrol possesses antioxidant and antiapoptotic effects apart from activation of longevity proteins (such as SIRT-1). We have recently reported the angiogenic, antihypercholesterolemic, and antihypercholesterolemic, antihypercholesterolemic, antidiabetic effects of resveratrol and the mechanisms involved in reduced ventricular remodeling and increased cardiac functions. We have also shown different strategic target molecules involved in resveratrol-mediated.
cardioprotection.

b. Lipid metabolism
in a study of " [Effects of resveratrol on lipid metabolism in C57BL/6J mice]."[Article in Chinese]

by Ren Y, Li Y, Zhao Y, Yu F, Zhan Z, Yuan Y, Yang J. (Source from Department of Nutrition and Food hygiene, School of Public Health, China Medical University, Shenyang 110001, China. renyahao0512@sohu.com) researchers found that The serum TC, LDL-C, HDL-C levels of high-fat diet and resveratrol groups were higher than those of control group (P < 0.05), and the serum TC and LDL-C levels of high-fat diet were also higher than those of resveratrol group (P < 0. 05). But the serum TG levels of high-fat diet and resveratrol groups were lower than those of control group (P < 0.05). The TC content of liver in high-fat diet group were higher than those of control and resveratrol groups (P < 0.05), and concluded that The TC content in C57BL/6J mice can be decreased by resveratrol (22.5 mg/kg BW).

c. Diabetes and Obesity
According to the study of " Resveratrol, obesity and diabetes." by Szkudelska K, Szkudelski T. (Source from Department of Animal Physiology and Biochemistry, Poznan University of Life Sciences, Poznan, Poland. tszkudel@jay.up.poznan.pl) posted in PubMed, researchers found that The accumulating evidence also indicates the benefits of resveratrol in diabetes and diabetic complications. It is known that resveratrol affects insulin secretion and blood insulin concentration. In animals with hyperinsulinemia, resveratrol was found to reduce blood insulin. Moreover, numerous data indicate that in diabetic rats, resveratrol is able to reduce hyperglycemia. The mechanism of resveratrol's action is complex and is demonstrated to involve both insulin-dependent and insulin-independent effects. These data point to the potential possibility of use of resveratrol in preventing and/or treating both obesity and diabetes.

D. Antioxidants to prevent angina

1. Nitric oxide (NO)
Nitric oxide (NO), one of the antioxidant and peroxynitrite can inhibit pathways of oxygen radical generation, and, in turn, oxidants can inhibit NO synthesis from NOS.

2. Glutathione and vitamin E
Reduced form of glutathione may act as a first line of defense against oxidative stress during ischemia–reperfusion while vitamin E may act later on during severe oxidative stress by rendering resistance to the heart against the ischemic–reperfusion injury

3. 2-dithiole-3-thione (D3T)
Researcher found that in rat cardiac H9c2 cells, D3T and time-dependent induction of a number of cellular antioxidants and phase 2 enzymes, including catalase, reduced glutathione (GSH), GSH peroxidase, glutathione reductase (GR), GSH S-transferase (GST), and NADH:quinone oxidoreduc- tase-1 (NQO1) help to protect against H9c2 cell injury caused by various oxidants and simulated ischemia-reperfusion. D3T pretreatment also resulted in decreased intracellular accumulation of reactive oxygen in H9c2 cells after exposure to the oxidants as well as simulated ischemia-reperfusion.

4. Selenium
Deficiency of of a co-enzyme selenium, which is required in maintaining the glutathione redox cycle, also promote more susceptible to oxidative injure.

5. Etc.

Treatments

A. In conventional medicine perspective

In the summation of the evidences of angina pectoris' optimal treatment, Dr. Jánosi A. at the Fovárosi Onkormányzat Szent János Kórház-Rendelointézet III. Belgyógyászat, indicated that the first steps of therapy are - after the diagnosis - the influence of risk factors, life-style changes and optimal medical therapy. The optimal medical therapy consists of statin, aspirin and ACE inhibitor treatment besides antianginal therapy, where the beta blockers are regarded as first drugs of choice. Percutaneous interventions as initial treatment option are not recommended because we have no evidences that this intervention prolongs life and prevents myocardial infarction. If the patient remains symptomatic after medical treatment, it is necessary to perform revascularization(43a).

A.1. Medical treatments
1. 1. Nitroglycerin
a. Nitroglycerin is used to treat ischemic cardiac pain. and improve blood flow to the heart. Transdermal nitrate delivery systems improve the quality of life in ambulant patients: anginal attacks are reduced with a minimum of side effects. The widespread acceptance of this novel form of drug delivery has stimulated its application in other therapeutic avenues. The efficacy of transdermal nitroglycerin in the suppression of silent ischemic attacks has been demonstrated(43)
b. Side effects are not limit to
b.1. Dizziness
b.2. Lightheadedness, or fainting when sitting up or standing
b.3. Flushing of face and neck
b.4. Headache
b.5. Irritation
b.6. Nausea
b.7. Vomiting
b.8. Etc.

1.2. Beta-blockers
a. Beta blocker has been used to lower heart rate, blood pressure, and enhance oxygen to the heart. In the study of The 248 cases presented with new coronary heart disease from 1982 through 1984, and the 737 controls were a probability sample of health maintenance organization patients free of coronary heart disease. A withdrawal syndrome immediately following the cessation of beta-blocker use may be an acute precipitant of angina and myocardial infarction in hypertensive patients who have no prior history of coronary heart disease(44).
b. Side effects are not limit to
b.1. the medicine can cause allergic reaction to certain people, such as: rash, itching, swelling, dizziness, trouble breathing.
b.2. Easy bruising or bleeding,
b.3. Swollen hands or feet,
b.4. Confusion,
b.5. Depression
b.6. Etc.

1.3. Calcium channel blockers
a. The medicine used to relax arteries, lower blood pressure, and reduce strain on the heart. Researchers suggested that Compared with clopidogrel without calcium-channel blockers (CCBs), clopidogrel with CCB does not increase the mortality or composite thromboembolic events in elderly CAD patients, but clopidogrel combined with nondihydropyridine CCB is associated with significantly increased composite thromboembolic events in comparison with dihydropyridine CCB(45).
b. Side effects are not limit to
b.1. Stomach pain
b.2. Constipation
b.3. Drowsiness
b.4. Fatigue Feelings of a rapidly or forcefully beating heart (palpitations)
b.5. Flushing or hot flashes
b.6. Headaches
b.7. Nausea
b.8. Etc.

1.4. Statins
a. The medicine used to lower cholesterol. Dr. Biasucci LM, and the scientists at the Sacro Cuore University, in the study of Statins and coronary artery disease:clinical evidence and future perspective said "The introduction of more powerful statins in the market offered the opportunity to study whether an intensive lipid lowering treatment could yields even better cardiovascular outcomes than a moderate statin therapy and several clinical trial confirmed this hypothesis. Statins have also pleiotropic effect behind their lipid lowering function: they reduce inflammation, which plays an important role in the atherosclerotic process"(46).
b. Side effects are limit to
b.1. Headache
b.2. Nausea
b.3. Vomiting
b.4. Constipation
b.5. Diarrhea
b.6. Weakness
b.7. Muscle pain
b.8. Etc.

1.5. Aspirin
a. Many researchers believe that daily intake aspirin can reduce the risk of blood clots from forming in your arteries. In the study to determine the cardiovascular and coronary risk thresholds at which aspirin for primary prevention of coronary heart disease is safe and worthwhile, Dr. Sanmuganathan PS and the research team at the Royal Hallamshire Hospital, indicated that Aspirin treatment for primary prevention is safe and worthwhile at coronary event risk >/= 1.5%/year; safe but of limited value at coronary risk 1%/year; and unsafe at coronary event risk 0.5%/year. Advice on aspirin for primary prevention requires formal accurate estimation of absolute coronary event risk(47).
b. Side effects are not limit to
b.1. Stomach pains
b.2. Feelings of nausea
b.3. Vomiting.
b.4. Allergic reaction to some people
b.5. Aspirin may interact with other medicine, such as blood thinning medicine
b.6. Etc.

2. If the underline causes of Angina is a result of Ischemic heart disease, then
a. Percutaneous Coronary Intervention (PCI )
Percutaneous Coronary Intervention (PCI ) is one therapeutic treatment used to treat the narrowed coronary arteries of the heart found in coronary heart disease and Ischemic heart disease. In study of a total of 282 patients (74.1% females) with mean age of 57.0±3.2 years were studied. Most of the patients (89.7%) underwent elective PCI. Angiographic and procedure success rates were 95.7% and 94.6%, respectively. In-hospital MACE included two cases of death (0.7%) and one MI (0.3%); 2/29 (6.9%) of the emergent PCI and 1/253 (0.4%) of the elective PCI cases. MACE during follow-up included three cases of death (1.0%) and two MI (0.7%); 2/252 (0.8%) of the elective PCI and 1/28 (3.5%) of the emergent PCI cases. The overall MACE was calculated as 8 cases (2.8%) which included 5/29 (17.2%) of the emergent and 3/253 (1.1%) of the elective cases; P<0.001, concluded that PCI is performed with an acceptable success rate in our center in Isfahan and mortality and complications are within the range reported by other highly specialized centers in IRAN. Further studies with larger sample size are needed to find predictive factors(48).

b. Coronary revascularisation
Coronary artery bypass grafting (CABG)
Coronary artery bypass grafting (CABG) is a surgical procedure performed to reduce the risk of death from coronary artery disease by bypass atherosclerotic narrowings as arteries or veins from elsewhere in the patient's body are grafted to the coronary arteries to improve the blood supply to the heart muscle. some researchers suggested that transthoracic echocardiography(TEE) prior to coronary artery bypass surgery can provides higher resolution images than transthoracic echocardiography (TTE). Therefore one can conclude that TEE is the imaging modality of choice for detecting aortic atheromatous plaques but in patients with low risk for stroke and aortic atheromas, a detailed TTE may be sufficient for the pre-operative assessment(49).

B. In herbal medicine perspective

1. Soybean is the genus Glycine, belonging to the family Fabaceae, one of the legumes that contains twice as much protein per acre as any other major vegetable or grain crop, native to Southeast Asia. Now, it is grown worldwide with suitable climate for commercial profit and a a healthy foods. The herb has been used in traditional medicine for the proper functioning of the bowels, heart, kidney, liver, stomach. etc.
a. Insulin sensitive
Soybean helps to normalize plasma glucose and insulin homeostasis, according to "Increased insulin sensitivity and changes in the expression profile of key insulin regulatory genes and beta cell transcription factors in diabetic KKAy-mice after feeding with a soy bean protein rich diet high in isoflavone content" by Nordentoft I, Jeppesen PB, Hong J, Abudula R, Hermansen K.(50)

b. Cardiovascular diseases
Soy protein reduces reduces the levels of serum lipoprotein, decrease in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), LDL-C/high-density lipoprotein cholesterol (HDL-C), triacylglycerol/HDL-C and TC/HDL-Cpostmenopausal women are at risk of cardiovascular disease, according to "Effects of soy bean on serum paraoxonase 1 activity and lipoproteins in hyperlipidemic postmenopausal women" by Shidfar F, Ehramphosh E, Heydari I, Haghighi L, Hosseini S, Shidfar S.(51)

2. Garlic (Allium sativum) is a species in the onion genus, belonging to family Amaryllidaceae, native to central Asia. It has been used popularly in traditional and Chinese medicine in treating common cold and flu to the Plague, blood pressure cholesterol levels, natural antibiotic, etc.
a. Cholesterol

Eating 4 cloves of garlic a day can cut total CHOLESTEROL by 70%(Fresh or Supplement). The member of the allium family fights poor circulation.The sulfur compound in garlic keep your platelets from clumping together. It helps UNCLOG your Arteries but check with your Doctor if you are taking Blood thinning medications. Cook with both Garlic and onion to fight high blood pressure effectively. Try to take them everyday if you have high blood pressure and Cholesterol.

b. Blood pressure
In the assessment of garlic extract and its effect of hypertension. found that Aged garlic extract was generally well tolerated and acceptability of trial treatment was high (92%) and aged garlic extract is superior to placebo in lowering systolic blood pressure similarly to current first line medications in patients with treated but uncontrolled hypertension, according to "Aged garlic extract lowers blood pressure in patients with treated but uncontrolled hypertension: a randomised controlled trial" by Ried K, Frank OR, Stocks NP.(52)

7. Atherosclerosis
In the demonstration of aged garlic extract therapy with supplements (AGE+S) and theirs effect on cardiovascular diseases found that CAC progression was significantly lower and TR significantly higher in the AGE+S compared to the placebo group after adjustment of cardiovascular risk factors (p<0.05). Total cholesterol, LDL-C, homocysteine, IgG and IgM autoantibodies to MDA-LDL and apoB-immune complexes were decreased, whereas HDL, OxPL/apoB, and Lp (a) were significantly increased in AGE+S to placebo and concluded that AGE+S is associated with a favorable improvement in oxidative biomarkers, vascular function, and reduced progression of atherosclerosis., according to "Aged garlic extract supplemented with B vitamins, folic acid and L-arginine retards the progression of subclinical atherosclerosis: a randomized clinical trial" by Budoff MJ, Ahmadi N, Gul KM, Liu ST, Flores FR, Tiano J, Takasu J, Miller E, Tsimikas S.(53)

3. Alfalfa
a. Antioxidant
In a study of measurements of pH, water holding capacity, color, oxymyoglobin content, TBARS and oxidation-reduction potential in evaluating the effects of a dietary protein-xanthophylls (PX) concentrate of alfalfa to turkey diets conducted by University of Life Sciences in Lublin, Skromna 8, 20-704 Lublin, (54), researchers found that TBARS and oxidation-reduction potential values suggested that the inclusion of the concentrate to turkey diets acts as an antioxidant in the raw meat.

2. Cholesterol
In a study to test the effect of Alfalfa used in traditional medicine to treat high blood cholesterol conducted by Malinow MR, McLaughlin P, Stafford C.(55), in 3 human volunteers during ingestion of diets containing alfalfa seeds (AS) for 3 weeks, researchers found that Plasma cholesterol concentrations were reduced and No signs of toxicity were detected through serum determinations of multiple parameters. The ingestion of AS in rats decreased the concentration of plasma cholesterol, reduced intestinal absorption of exogenous and endogenous cholesterol, and increased fecal biliary excretion.

3. Hyperlipoproteinemia
In a study of Fifteen patients with hyperlipoproteinemia (HLP), types IIA (n = 8), IIB (n = 3) and IV (n = 4) were given 40 g of heat prepared alfalfa seeds 3 times daily at mealtimes for 8 weeks with otherwise unchanged diet, conducted by Mölgaard J, von Schenck H, Olsson AG.(3), found that patients with type II HLP alfalfa treatment caused after 8 weeks a maximal lowering of pretreatment median values of total plasma cholesterol from 9.58 to 8.00 mmol/l (P less than 0.001) and low density lipoprotein (LDL) cholesterol from 7.69 to 6.33 mmol/l (P less than 0.01), which corresponds to decreases of 17% and 18%, respectively. Maximal decrease was 26% in total cholesterol and 30% in LDL cholesterol. In two patients with hypercholesterolemia the LDL cholesterol decreased less than 5%. Apolipoprotein B decreased in the same period from 2.17 to 1.43 g/l (P less than 0.05) in type II HLP, corresponding to 34% decrease, whereas apolipoprotein A-I did not change. Body weight increased slightly during the first 4 weeks of alfalfa treatment (P less than 0.001) probably because of the caloric content in the alfalfa seeds. After cessation of treatment, all lipoprotein concentrations returned to pretreatment levels. We conclude that alfalfa seeds can be added to the diet to help normalize serum cholesterol concentrations in patients with type II HLP.

4. Ginkgo biloba
a. Hypertension
Ginkgo enhanced endothelium-dependent vasodilation and elevation of the endothelial intracellular Ca(2+) level in SHR, resulting in hypotension, according to the study of "Effects of Ginkgo biloba extract on blood pressure and vascular endothelial response by acetylcholine in spontaneously hypertensive rats" by Kubota Y, Tanaka N, Kagota S, Nakamura K, Kunitomo M, Umegaki K, Shinozuka K.(56)

b. Cardiovascular tissues
Ginkgo biloba extract (EGb) has shown the protection of the cardiovascular tissues against HgCl(2)-induced oxidative damage, according to the study of "Protective effects of Ginkgo biloba extract against mercury(II)-induced cardiovascular oxidative damage in rats" by Tunali-Akbay T, Sener G, Salvarli H, Sehirli O, Yarat A.(57)

c. Hyperlipidemia
Ginkgo biloba leaves (EGB) has demonstrated the activities of limitation of the absorption of cholesterol, inactivation of HMGCoA and favorable regulation of profiles of essential polyunsaturated fatty acid (EFA), according to the study of "Application of GC/MS-based metabonomic profiling in studying the lipid-regulating effects of Ginkgo biloba extract on diet-induced hyperlipidemia in rats" by Zhang Q, Wang GJ, A JY, Wu D, Zhu LL, Ma B,(58)

5. Grape seed extract
Grape Seed Extract is the commercial extracts from whole grape seeds that contains many concentrations, including vitamin E, flavonoids, linoleic acid, oligomeric proanthocyanidins(OPCs), etc..The herb has been used in traditional medicine as antioxidant, anti-inflammatory agents and to treat skin wounds with less scarring, allergies, macular degeneration, arthritis, enhance circulation of blood vessels, lower cholesterol, etc.
a. Antioxidant Activity
in the assessment of phenolic content, antioxidant activity of White and red wines spiked with green tea extract and grape seed extract found that the green tea extract and grape seed extract increased antioxidant activity dose-dependently and the CRTs varied considerably between the Korean and Australian groups, with Koreans preferring wines spiked with green tea extract and Australians showing a preference for wines spiked with grape seed extract, according to "Total Phenolic Content, Antioxidant Activity and Cross-Cultural Consumer Rejection Threshold in White and Red Wines Functionally Enhanced with Catechin-Rich" by Yoo YJ, Saliba A, Prenzler PD, Ryan DM.(59)

b. Atherosclerosis
in the association of consumption of red wine and other polyphenolic compounds and prevention of cardiovascular diseases found that aortic atherosclerosis evaluated as the cholesterol content in aortic tissue was comparable in the control and GSE-dosed females, but it was significantly reduced in the abdominal part of GSE-dosed male compared to the controls (P < 0.05). In conclusion, feeding GSE extract to Watanabe heritable hyperlipidemic (WHHL) rabbits had no significant effects in females but was associated with transient less hypercholesterolemic response to semisynthetic diet, according to "Effects of red grape skin and seed extract supplementation on atherosclerosis in Watanabe heritable hyperlipidemic rabbits" by Frederiksen H, Mortensen A, Schrøder M, Frandsen H, Bysted A, Knuthsen P, Rasmussen SE.(60)

C. In traditional Chinese medicine perspective

Traditional Chinese medicine defines angina as a diseases as a result of Ischemic heart disease (belongs tothe categories of "xiong bi", "xin tong", "xin ji", "jue xin tong" and "zhen xin tong)either caused by Stagnation of Heart Blood of which leads to symptoms of localized stabbing chest pain aggravated at night, palpitation,restlessness, dark purple tongue, etc. in most cases or Heart Yin Deficiency of which lead to symptoms of chest pain and oppression, restlessness, insomnia, palpitation, night sweating, lumbago, weak waist and knees, dizziness, tinnitus. etc., in most cases

C.1. Formula

1. Jing Zhi Guan Xin Pian used for coronary heart disease, angina pectoris due to stagnation of heart blood

2. Ingredients

a. Radix Salviae Miltiorrhizae (Dan Shen)

b. Radix Rubra (Chi Shao)

c. Chuanxiong rhizome (Chuan Xion)

d. Flos Carthami. (Hong Hua)

e. Lignum Dalbergiae Odoriferae (Jiang Xiang0

C.2. Heart Yin Deficiency
1. Tian Wang Bu Xin Wan used for coronary heart disease, angina pectoris due to heart Yin Deficiency
2. Ingredients
a. Radix Salviae Miltiorrhizae (Dan Shen)
b. Rhizoma Acori Tatarinowii (Shi Chang Pu)
c. Radix Rehmanniae Glutinosae (Di Huang)
d. Radix Angelica Sinensis (Dang Gui)
e. Fructus Schisandrae Chinensis (Wu Wei Zi)
f. Tuber Ophiopogonis Japonici (Mai Men Dong)
g. Semen Ziziphi Spinosae (Suan Zao Ren)
h. Semen Biotae Orientalis (Semen Platycladi) (Bai Zi Ren)
i. Radix Codonopsis Pilosulae (Dang Shen)
j. Sclerotium Poriae Cocos (Fu Ling)
k. Radix Scrophulariae Ningpoensis (Xuan Shen)
l. Radix Polygalae Tenuifoliae (Yuan Zhi)
m. Radix Platycodi Grandiflori (Jie Geng)
n. Radix Glycyrrhizae Uralensis (Gan Cao)

Please consult with your doctor or related field specialist before applying

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Sources

Wednesday, June 20, 2012

Bladder Stone (Vesical calculi)

Bladder Stones (calculus) is a composed of mineral masses formed in the bladder as a result of Concentrated, stagnant urinary, dehydrated causes of crystallization. Small bladder stones in most cases, pass on their own in the flow of urine.

A. Symptoms
The symptoms are as results of irritation of bladder wall or the stones have blocked the flow of the urine causes of infection and complications. In most cases, Bladder stone large and small do not cause any symptoms at all.
1. Inability to walk, constipation and urinary incontinence
There is a report of a case of massive irreducible procidentia with a hard palpable mass in the anterior vaginal wall mimicking an impacted faecal mass in a 57-year-old multiparous, post-menopausal woman with symptoms of Inability to walk, constipation and urinary incontinence as her primary complaints. targeted plain X-ray and ultrasound of the prolapsed mass disclosed the existence of multiple vesical calculi(1).

2. Lower abdominal pain, pain during micturation and pollakuria
There is a report of a 48-year-old man hospitalized with the chief complaints of lower abdominal pain, pain during micturation and pollakuria, plain radiography showed 2 giant bladder stone shadows: one as 6.0 × 5.0 cm and the other one 5.0 × 5.0 cm in size(2).

3. Voiding symptoms (Poor stream, Hesitancy, Terminal dribbling, Incomplete voiding, Overflow incontinence) and hematuria (Blood in your urine)
There is a report of a case of 43 year old man with the diagnosis of giant bladder stone (more than 10 cm diameter) with symptoms of voiding symptoms and hematuria(3).

4. Others symptoms
a. Repeated cloudy or abnormally dark-colored urine as a result of infection of the urinary track.
b. In men, pain or discomfort in the penis due to blockage or infection
c. Etc.

B. Causes and Risk factors
B.1. Causes
1. Primary neurologic deficit
In the study of Medical management of urinary calculi in a stallion with breeding dysfunction, researchers at the University of Pennsylvania, showed that the stallion may have had a primary neurologic deficit affecting bladder control and function that was causing calculi to form secondarily because of delay in movement of urine through the urinary tract(4).

2. Urinary tract calculi and infections
Urinary tract calculi and infections are common causes of presentation to the emergency department. Computed tomography kidney-ureter-bladder is the initial imaging study of choice in patients presenting with symptoms of urinary tract calculi. As clinical evidence of superimposed infection can be atypical or absent, it is crucial to identify subtle imaging findings that suggest this complication(5).

3. The use of urinary catheters
Prolonged period of using urinary catheters can cause infection. There is strong experimental and epidemiological evidence that infection by Proteus mirabilis is the main cause of the crystalline biofilms that encrust and block Foley catheters. The ability of P. mirabilis to generate alkaline urine and to colonize all available types of indwelling catheters allows it to take up stable residence in the catheterized tract in bladder stones and cause recurrent catheter blockage(6).

4. Bladder cancer
There is a report of case of ileovesical fistula caused by a bladder carcinoma is presented. A 66-year-old male was referred with complaints of urinary pain. On admission, fecaluria and urinary tract infection with bladder stone were detected(7).

5. Schistosomiasis
Schistosomiasis is a parasitic infection that affects 200 million people and is directly responsible for an annual death of 20,000 patients. Three species are responsible for most of the morbidity in humans: Schistosoma hematobium in Africa, S. mansoni in Africa and South America, and S. Japonicum in the Far East. Renal involvement occurs mostly with S. hematobium infection as a consequence of fibrosis and calcification of tissue-trapped ova in the lower urinary tract, leading to obstruction, reflux, infection, and stone formation(8).

6. Prostatic hyperplasia (BPH)
Benign prostatic hyperplasia (BPH) is one of the most common diseases to affect older men. Histological disease is present in more than 60% of men beyond their sixties, and more than 40% of men in this age group have lower urinary tract symptoms (LUTS)(9).

7. Kidney stones
As a result of small kidney stones travel down the ureters into the bladder that are not passed through urination

8. Etc.

B.2. Risk factors
1. Cystinuria
Cystinuria is an inherited autosomal recessive disease. There is a report of an unusual cystine stone presented in 24-year-old man. Radiographs showed a giant bladder stone shadow, 8.0 x 10.0 x 5.0 cm in size(10).

2. Age and gender
If you are male and over 30 years of age, you are at increased risk of bladder stone. In the study of a series of 1,354 stones derived from urology departments in Western Algeria was studied by IRTF spectroscopy. Analysis of the results concerned the crystalline composition and anatomical site of the stones and the age and gender of the patients.found that the male/female ratio has remained almost constant at 2.23. The anatomical site has changed with a predominance in the upper tract (77.4% of stones). The nucleus showed that phosphates are predominant in 48.6% of cases versus 35.6% for oxalates. Carbapatite and struvite are more frequent in women, found in 50.8% and 6.7% of cases, respectively, than in man, found in 44.6% and 3.7% of cases, respectively. Calcium oxalate is predominantly found in the upper urinary tract (70.9%) rather than in the bladder (48.3%), regardless of gender. Calcium phosphate is more abundant in the upper tract of females with 23.7% of cases versus 10.7% in the bladder. It is equally distributed between the bladder and the upper tract in males (13.7% and 13.2%, respectively). Examination of the side affected by stones showed a predominance of the left side in both sexes.

4. Bladder outlet obstruction(11)
There is a report of a 48-year-old man was hospitalized with the chief complaints of lower abdominal pain, pain during micturation and pollakuria. Plain radiography showed 2 giant bladder stone shadows: one as 6.0 × 5.0 cm and the other one 5.0 × 5.0 cm in size. That were completely obstructing the bladder outlet and observed several years following pelvic traumahe(12). There are many causes of bladder outlet obstruction but enlarged prostate is one of primary risk factors.

6. Frequent bladder infections
Chronic bladder infections can lead to the formation of bladder stones.

7. Urinary track infection
Urinary tract infection can cause obstruction of the urinany flow that can lead to formation of bladder stone. Urinary tract bacterial infections are common in women. Moreover, they tend to recur throughout life and in the same relatively small group of women. In most cases, bladder and renal infections are asymptomatic and manifest by demonstrating coincidental bacteriuria. In some instances, however, especially with frequent sexual activity, pregnancy, stone disease, or diabetes, symptomatic cystitis or pyelonephritis develops and antimicrobial therapy is indicated(13)

8. Nutritional factors
In teh study to describe clinical cases of childhood bladder stones and associated risk factors. Forty children (9 girls), aged 1-14-years old, (means 4.7 +/- 0.5 years), who underwent surgical stone removal in the Saravane Provincial Hospital during a 13-month period, researchers at the Institut de la Francophonie pour la Médecine Tropicale, showed that the morbidity and social cost of childhood bladder stones may be high. A larger scale prospective and comparative study assessing their incidence and associated nutritional factors is warranted and feasible, and may lead to preventive measures(14).

9. Etc.

C. Complications and Diseases associated with Bladder stone
1. Bladder pain syndrome/interstitial cystitis
In the study of included 9,269 cases who had received their first-time diagnosis of bladder pain syndrome/interstitial cystitis (BPS/IC) between 2006 and 2007 and 46,345 randomly selected controls, BPS/IC was found to be significantly associated with prior urinary calculi (UC) regardless of stone location; the adjusted ORs of kidney calculus, ureter calculus, bladder calculus, and unspecified calculus when compared to controls were 1.58 (95 % CI = 1.38-1.81), 1.73 (95 % CI = 1.45-2.05), 3.80 (95 % CI = 2.18-6.62), and 1.83 (95 % CI = 1.59-2.11), respectively(15).

2. Irreducible uterine prolapse
A vesical calculus in a prolapsed cystocele is rare. There is a report of case of irreducible total uterine prolapse caused by multiple vesical calculi. Bladder stones were removed through vaginal cystolithotomy followed by vaginal hysterectomy(16).

3. Acute renal failure
There is a report of a 39-year-old man with repeated urinary tract infection and lower abdominal pain, kidney-ureter-bladder (KUB) and IVU film showed a huge 450-g elliptical pelvic calculus that was surgically removed with excellent results(17).

4. Enterovesical fistula
Enterovesical fistula is a very rare complication of primary urological malignancies. A case of ileovesical fistula caused by a bladder carcinoma is presented. A 66-year-old male was referred with complaints of urinary pain. On admission, fecaluria and urinary tract infection with bladder stone were detected. Cystography revealed the passage of contrast medium into the small bowel. Under the diagnosis ofileovesical fistula due to suspected inflammatory disease, sigmoidectomy and segmental small bowel resection with partial cystectomy were performed. Histological evaluation revealed a poorly differentiated urothelial carcinoma(18).

5. Spontaneous rupture of the urinary bladder
Spontaneous rupture of the urinary bladder is an uncommon occurrence. There is a report of a 36-year-old man with complaints of pain and progressive distension of abdomen and anuria for 2 days. His abdomen was tense, tender and distended with free fluid. Blood urea was 340 mg% and ascitic fluid urea was 337 mg%. An USG showed massive ascitis, a large vesical calculus and a left renal calculus, according to the study by University College of Medical Sciences and Guru Teg Bahadur Hospita(19).

6. Etc.

D. Diagnosis
After a complete physical examination (incluning rectal examination) and family history are recorded, if you are suspected to have developed bladder stones, the test which your doctor orders, may include
1. Bladder or pelvic x-ray
The aim of the test is to let your doctoe visualize the bladder, urethra (the tube connecting the bladder with the outside of the body), and the ureters (the tubes connecting the kidneys to the bladder) of the patient, for  the bladder's stones and abnormalities in the pelvic, including the a blockage in the urinary path.

2. Cystoscopy
Cystoscopy is the examination of the bladder and urethra with use of cystoscope. In the examination, smaller bladder stone can be removed if found. It is hekpful as smaller bladder stones sometime can not be detected by the X ray.

3. Urinalysis
The aim of the test is to rule out the infectious and other causes of urinary tract symptoms

4. CT scans
CT scans are the better test to identify very small stones not seen by other tests

5. Etc.

E. Prevention
E.1. The do's and do not's list
1. Avoid dehydration
Dehydration can cause increased urine concentration which can lead to crystallization.

2. Drinking 6 - 8 glasses of water or more per day
In most case smaller bladder stones can pass on their own in the flow of urine

3. Avoid eating too much foods contain high amount of axalates which can increase the risk of the risk of bladder stone.

4. Quit smoking
Smoking increased the risk of the accumulation of cadmium on the bladder wall

5. Enlarged prostate
Enlarged prostate is the primary cause of bladder stone in men.

6. Etc.

E.2. Diet to prevent bladder stone
1. Cranberry
Cranberries have long been the focus of interest for their beneficial effects in preventing urinary tract infections (UTIs). Cranberries contain 2 compounds with antiadherence properties that prevent fimbriated Escherichia coli from adhering to uroepithelial cells in the urinary tract(20).

2. Low calcium diet, low sodium diet or low calcium diet plus hydrochlorthiazide
Researchers showed that low calcium diet, low sodium diet or low calcium diet plus hydrochlorthiazide reduced hypercalciuria significantly (P less than 0.01). Low calcium diet combined with hydrochlorthiazide was the most effective treatment for hypercalciuria(21).

3. Balance diet with enough nutrient
In the study to evaluate Reduction of urinary stone in children from north-eastern Thailand, Dr. at the showed that bladder stones in children have decreased now compared with the previous decade. If we promote good nutrition for children, bladder stones will decrease and might be eradicated in the future. A seminar of doctors and health personnel from 19 hospitals in the north-eastern provinces of Thailand was conducted to survey bladder stones in children by weighting and interviewing bladder stone symptoms then giving supplementary diet milk and vitamins and teaching health education about nutrition and urinary stones through referring children with bladder stones to hospitals in north-eastern(22).

4. Water
Drink enough water daily. If you are exercising, drink more water to prevent dehydration as it is the main cause of bladder stone in athletics.

5. Pumpkin seeds
in the study of the effect of pumpkin-seed supplementation on oxalcrystalluria and urinary composition in 20 boys age 2-7 yr from a hyperendemic area of Ubol province in Thailand, found that Pumpkin seeds lowered calcium-oxalate crystal occurrence and calcium level but increased phosphorus, pyrophosphate, glycosaminoglycans, and potassium values in urine as compared with orthophosphate supplementation. Pumpkin seeds provide high phosphorus levels and can be used as a potential agent in lowering the risk of bladder-stone disease(23).

6. Lemon juice
In the study of Can lemon juice be an alternative to potassium citrate in the treatment of urinary calcium stones in patients with hypocitraturia? A prospective randomized study, researchers at the Bakirkoy Research and Training Hospital, showed that lemon juice can be an alternative in the treatment of urinary calcium stones in patients with hypocitraturia. Additionally, dietary recommendations can increase effectiveness of the treatment(24).

7. Etc.

F. Treatment
F.1. In conventional perspective
1. Drinking at least 6 - 8 glasses of water per day to increase urination to help small stones to pass on their own in the flow of urine.

2. If bladder stones are confirmed
2.1. Medication
Medication such as Potassium citrate can help to dissolve uric acid stones. In the study to evaluate by a prospective randomized controlled study the efficacy of the association of potassium citrate and dry extract of couch grass (Agropyrum repens) (CalcoMEV) in renal stone treatment, showed that potassium citrate and couch grass showed a significant reduction in the total number of stones (-1.0 +/- 0.2 vs. 0.0 +/- 0.2 stones) and in the larger diameter of the stones (-3.6 +/- 0.9 mm vs. 0.0 +/- 0.8 mm), as well as a statistically significant reduction of uric acid urinary excretion (-164.7 +/- 45.3 vs -38 +/- 42 mg/24 h). No significant differences in the two groups were observed with respect to urinary citrate, oxalate and calcium urinary excretions and urinary pH(25).

2.2. If possible, laser energy may be used to break up the stones
2.3. Surgery
a. Cystoscope
Smaller stones which can not be passed on their own in urination but discovered by Cystoscopy can be removed with local anesthesia
b. Open surgery
Other larger stone may need open surgery to remove them

F.2. In Herbal medicine perspective
1. Asparagus racemosus Willd
In the study of the ethanolic extract of Asparagus racemosus Willd. for its inhibitory potential on lithiasis (stone formation), induced by oral administration of 0.75% ethylene glycolated water to adult male albino Wistar rats for 28 days, showed that the histopathological findings also showed signs of improvement after treatment with the extract. All these observations provided the basis for the conclusion that this plant extract inhibits stone formation induced by ethylene glycol treatment(26).

2. Goldenrod
Investigations in molecular pharmacology could show new mechanisms responsible for the biological effect of natural product from goldenrod extracts. The use of such herbal preparations with a rather complex action spectrum (anti-inflammatory, antimicrobial, diuretic, antispasmodic, analgesic) is especially recommended for treatment of infections and inflammations, to prevent formation of kidney stones and to help remove urinary gravel. This therapy is safe at a reasonable price and does not show drug-related side-effects, according to the study of the Institut für Pharmazie der Freien Universität Berlin, Berlin(27).

3. Couch grass (Agropyrum repens)
Couch grass showed a significant reduction in the total number of stones (-1.0 +/- 0.2 vs. 0.0 +/- 0.2 stones) and in the larger diameter of the stones (-3.6 +/- 0.9 mm vs. 0.0 +/- 0.8 mm), as well as a statistically significant reduction of uric acid urinary excretion (-164.7 +/- 45.3 vs -38 +/- 42 mg/24 h)(25).

4. Etc.

F.3. In TCM perspective
C.1. According to the article of Chinese medicine Hospital for Chronic and Difficult diseases(25), traditional Chinese medicine defined formation of stones is a condition caused by
1. Qi stagnation
a. The aim of the herbal treatment is to Promotethe circulation of qi, inducing diuresis, relieving strangury and removing the stones.
b. Herbal formula: Modified Pyrrosia Decoction
Lysimachia, Pyrrosia leaf, Plantago seed, Cluster mallow fruit, Oriental water plantain rhizome, Citron fruit, Vaccaria seed, Radish seed and Rhubarb.

2. Damp-Heat Pattern
a. The aim of the herbal formula is to clear heat and dampness, relieve strangury and remove the stones.
b. Herbal formula: Modified Eight Health Restoring Powder
Lysimachia, Prostrate knotweed, Chinese pink herb, Talc, Phellodendron bark, Capejasmine fruit and Plantago seed , Rhubarb and Licorice root tip
3. Kidney deficiency
a. The aim of the herb used to treat kidney stones as a result of kidney deficiency is to tonify qi, reinforce the kidney, relieve stranguria and remove the stones.
b. Herbal formula: Modified Kidney-Reinforcing Decoction
Prepared rehmannia root, Wolfberry fruit, Dogwood fruit, Achyranthes root, Bighead atractylodes. Rhizome eucommia bark, Cinnamon bark, Pilose asiabell root, Lysimachia and Climbing fern spore

C.2. Chinese herbal formula Wu Ling San (Poria, Rhizoma Alismatis, Polyporus, Cortex Cinnamomi, Rhizoma Atractylodis Macrocephalae (stir-baked))
In the study to determine the effects of a traditional Chinese herbal formula, Wulingsan (WLS), on renal stone prevention using an ethylene glycol-induced nephrocalcinosis rat model. Forty-one male Sprague-Dawley (SD) rats were divided into four groups. Group 1 (n=8) was the normal control; group 2 (n=11) served as the placebo group, and received a gastric gavage of starch and 0.75% ethylene glycol (EG) as a stone inducer; group 3 received EG and a low dose of WLS (375 mg/kg); and group 4 received EG and a high dose of WLS (1,125 mg/kg), found that the rats of placebo group gained the least significant body weight; in contrast, the rats of WLS-fed groups could effectively reverse it. The placebo group exhibited lower levels of free calcium (p=0.059) and significantly lower serum phosphorus (p=0.015) in urine than WLS-fed rats. Histological findings of kidneys revealed tubular destruction, damage and inflammatory reactions in the EG-water rats. The crystal deposit scores dropped significantly in the WLS groups, from 1.40 to 0.46 in the low-dose group and from 1.40 to 0.45 in the high-dose group. Overall, WLS effectively inhibited the deposition of calcium oxalate (CaOx) crystal and lowered the incidence of stones in rats (p=0.035). In conclusion, WLS significantly reduced the severity of calcium oxalate crystal deposits in rat kidneys, indicating that Wulingsan may be an effective antilithic herbal formula(28).

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Sources
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(2) http://www.ncbi.nlm.nih.gov/pubmed/21806900
(3) http://www.ncbi.nlm.nih.gov/pubmed/21610285
(4) http://www.ncbi.nlm.nih.gov/pubmed/9743725
(5) http://www.ncbi.nlm.nih.gov/pubmed/22902855
(6) http://www.ncbi.nlm.nih.gov/pubmed/20368711
(7) http://www.ncbi.nlm.nih.gov/pubmed/17131870
(8) http://www.ncbi.nlm.nih.gov/pubmed/12563599
(9) http://www.ncbi.nlm.nih.gov/pubmed/21789983
(10) http://www.ncbi.nlm.nih.gov/pubmed/15198153
(11) http://www.ncbi.nlm.nih.gov/pubmed/16821346
(12) http://www.ncbi.nlm.nih.gov/pubmed/21806900
(13) http://www.ncbi.nlm.nih.gov/pubmed/16260529
(14) http://www.ncbi.nlm.nih.gov/pubmed/15906634
(15) http://www.ncbi.nlm.nih.gov/pubmed/22895546
(16) http://www.ncbi.nlm.nih.gov/pubmed/17103181
(17) http://www.ncbi.nlm.nih.gov/pubmed/20033143
(18) http://www.ncbi.nlm.nih.gov/pubmed/17131870
(19) http://www.ncbi.nlm.nih.gov/pubmed/17136584
(20) http://www.ncbi.nlm.nih.gov/pubmed/15156480
(21) http://www.ncbi.nlm.nih.gov/pubmed/6380301
(22) http://www.ncbi.nlm.nih.gov/pubmed/10659566
(23) http://www.ncbi.nlm.nih.gov/pubmed/3799495
(24) http://www.ncbi.nlm.nih.gov/pubmed/18946667
(25) http://www.ncbi.nlm.nih.gov/pubmed/22908773
(26) http://www.ncbi.nlm.nih.gov/pubmed?term=asparagus%20root%20and%20kidney%20stones
(27) http://www.ncbi.nlm.nih.gov/pubmed/15638071
(28) http://www.ncbi.nlm.nih.gov/pubmed/18040675

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