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Saturday, 2 November 2013

Cerebral Aneurysm

I. Cerebral aneurysm is defined as a cerebrovascular disorder causes of the blood vessel to bulge or balloon out of the wall of a blood vessel as a result of the weaken of blood vessels and veins and occurred mostly at the bifurcations and branches of the large arteries located at the Circle of Willis.

II. Types of Cerebral aneurysm
A. Cerebral aneurysm classification based on angioarchitecture 
 Dr. Pritz MB. at the Indiana University School of Medicine, suggested that Only aneurysms in which preoperative imaging studies and operative findings were sufficient for classification were included. All 329 reviewed aneurysms could be divided into 2 groups: fusiform (n=16) and saccular (n=313). Fusiform aneurysms could be subdivided into 2 types: simple (no branch vessel; n=10) and complex (one or more side branches; n=6). Saccular aneurysms could be subdivided into 3 groups: those not associated with a branch vessel (n=31), those associated with a side-branch vessel (n=125), and those located at a bifurcation (n=157). Each of these categories of aneurysms could be classified further based on its association with a conducting, primary, secondary, tertiary, or side-branch vessel. Classification of cerebral aneurysms according to this scheme adequately described all reviewed aneurysms. Grouping aneurysms according to this approach focuses on similarities in angioarchitecture and potential rheologic properties that should prove useful for evaluation of aneurysm growth, rupture, and treatment(1).

B. Cerebral aneurysms classified both by size and shape
Others researchers suggested that Cerebral aneurysms are classified both by size and shape
B.1. In sizes
1.  Diameter of less than 15 mm is classified into Small aneurysms
2.  Large aneurysms with size from 15 to 25 mm
3. Giant aneurysms with size from 25 to 50 mm
4. Super giant aneurysms for any aneurysms with size over 50 mm.

B.2. In shapes
1. Berry or Saccular aneurysms
Saccular aneurysms are the most common form of cerebral aneurysm and refers to any aneurysm with a saccular outpouching, including berry aneurysms. Berry aneurysm, is a saccular aneurysm with a neck or stem resembling a berry.
2. Dissecting aneurysmsis is defined as a condition of splitting or dissection of an arterial wall as a result of bleeding into the weakened wall splits the wall.
3. Fusiform aneurysm is also known as Richet's aneurysma is a localized dilation of an artery in which the entire circumference of the vessel is distended. The result is an elongated, tubular, or spindlelike swelling(2).

III. Symptoms
People may have an aneurysm without experiencing any symptoms at all, but if a cerebral aneurysm begins to leak it can cause certain symptoms. Dr. Lyrer P, and  Gratzl O. at the Neurologische Universitätsklinik, indicated that approximately two fifth of the patients with subarachnoidal hemorrhage complained of early symptoms prior to the major hemorrhage. The complaints may be
1. Headache as the most likely 

2. Cranial nerve palsies including the muscles of the face, and people's faces change as a result of the palsy. A patient may find it difficult to smile, to control eye movements, and to engage in other facial expressions.
3. Different vegetative symptoms, including the interference of the following, including thought, emotion, memory, comprehension, perception, purpose, etc.
4. Iransient neurologic deficits, etc.(3)
In the report of Dr. Henry J. Kaminski, M.D and the team at Cleveland Veterans Affairs Medical Center showed that transient neurologic deficits are an unusual presentation of chronic subdural hematoma. Presented herein are three patients with transient aphasia and right-sided sensory-motor abnormalities caused by subdural hematoma. Review of the literature revealed 32 cases similar to ours. Presenting complaints were aphasia (77%), sensory symptoms (57%), headache (48%), hemiparesis (50%), and visual disturbance (3%). Fifteen patients underwent cerebral angiography(4)

IV. Cause and Risk factors 
A. Causes 
Cerebral aneurysms develop as a result of the weaken of blood vessels and veins of which exhibit the risk of ruptured cerebral aneurysm. Aneurysms often occur mostly at the bifurcations and branches of the large arteries located at the Circle of Willis based of the brain.

B. Risk factors
1. Hypertension (significant risk factor for future SAH)
In the study to reveal and assess risk factors for intraoperative rupture (IOA) of aneurysms, which will reduce the incidence of this complication and improve the outcome of treatment, Dr.Taylor CL, and the research team at Case Western Reserve University indicated that for patients with an unruptured cerebral aneurysm as the primary diagnosis, hypertension was found to be a significant risk factor for future SAH (risk ratio: 1.46, 95% confidence interval (CI): 1.01-2.11), whereas surgical treatment (risk ratio: 0.29, 95% CI: 0.09-0.97) had a significant protective effect. Advancing age had a small but significant protective effect in both groups. Elderly patients identified with unruptured aneurysms are more likely to have coexisting hypertension than the general hospitalized population. In elderly patients hospitalized with an unruptured cerebral aneurysm as their primary diagnosis, hypertension is a risk factor for subsequent SAH, whereas surgical treatment is a protective factor against SAH(5).

2. Family history
In the study of the incidence of asymptomatic, unruptured cerebral aneurysms  among patients with a family history of SAH within the second degree of consanguinity. Forty-one unruptured cerebral aneurysms were found in 34 (13.9%) of 244 patients. This incidence was significantly higher than that found in a control group of healthy volunteers (6%). Furthermore, patients who had a family history of SAH combined with multiple systemic risk factors were found to have the highest incidence of unruptured aneurysms (32%; odds ratio 3.49, 95% confidence interval 1.37-8.9)(6).

3. Old Age and gender
a. Old age is considered as one of risk factor of Cerebral aneurysm. In the study of the complication of Three hundred fifty-five patients underwent 394 endovascular procedures treating 75 aneurysm recurrences and 319 untreated aneurysms. One hundred eight (30%) were elderly(7)
b. Women are at increased risk of Cerebral aneurysm than men,

4.  Smoking
In the study to investigate whether cigarette smoking increased the risk of developing cerebral aneurysms and of SAH. Degree of smoking was investigated in 182 patients with SAH and in 123 patients with an unruptured cerebral aneurysm incidentally detected during investigation of other diseases, showed that Smoking significantly increased the risk of both aneurysm formation and SAH; The odds ratio for SAH was 2.4, and for unruptured cerebral aneurysm 1.7. Smoking especially increased the occurrence of SAH in women and in youngsters. However, smoking did not influence the occurrence of cerebral vasospasm and multiplicity of aneurysms(8).

5. Arteriosclerosis
Disruption of the entire arterial wall may be a critical event in the development of IDA and result in the medial disruption and subadventitial haemorrhage. Non-atheromatous intima might function as a protective factor in arterial wall disruption. On the other hand, atherosclerosis may predispose to intra-atheromatous plaque haemorrhage type of IDA through intramural haemorrhage originating from the newly formed vessels(9).

6. Drug abuse
Dr. Vannemreddy P, and the team at the Louisiana State University Health Sciences Center suggested that Aneurysms were significantly smaller and ruptured at a younger age among cocaine users compared with nonusers. Although the poor clinical grade was not significantly different between the 2 groups, outcome was significantly worse in cocaine users(10).

7. Head injury 
There are a report of three cases of ruptured traumatic aneurysms of the peripheral anterior cerebral artery after closed head injury. These cases were all young men with closed head injury due to traffic accidents(11).

8. Heavy alcohol consumption 
"Heavy drinking impairs outcome mainly through severe rebleeding and delayed ischaemia and to a lesser extent through a poor initial condition and presence of intracerebral haematoma
". Dr. Juvela S. at the Helsinki University Hospital said(12).

9. Certain blood infections 
Certain blood infections may increased the risk of Cerebral aneurysm, including Streptococcus sanguinis(13), endocarditis(14), Etc.

10. Lower estrogen levels after menopause
Researchers at the Affiliated ZhongShan Hospital, DaLian University, in the study of The role of estrogen in the formation of experimental abdominal aortic aneurysm, showed that in the pathogenesis of abdominal aortic aneurysm (AAA), estrogen may play an inhibitory role by decreasing expression of MMP-2 and MMP-9 synthesis(15).

11. Risk factors present at birth
a. Ehlers-Danlos syndrome type IV is defined as a condition characterized by its clinical manifestations, which are easy bruising, thin skin with visible veins, and rupture of arteries, uterus, etc. There is a report of report a case presented with cervical radiculopathy due to a segmental fusiform aneurysm of the cervical vertebral artery(16).

b. Polycystic kidney disease 
Autosomal dominant polycystic kidney disease(ADPKD) is primarily associated with renal failure, but it also causes systemic diseases, including cysts of other systemic organs and cerebral or visceral aneurysm(17). Other suggested that Polycystic kidney disease has been associated with several aneurysms, most notably cerebral, but not popliteal. The patient's marfanoid habitus also may have played a part. This case emphasises the mixed aetiology of popliteal aneurysms(18).

c. Abnormally narrow aorta (coarctation of the aorta), the large blood vessel that delivers oxygen-rich blood from the heart to the body. There is a report of the frequency of IA among patients with CoA is approximately 5-fold that of the general population. Although no risk factors were identified in this cohort, additional prospective evaluation is warranted. These data suggest that noninvasive cerebral imaging to screen for IA should be considered in patients with CoA(19).

d. Cerebral arteriovenous malformation (brain AVM), 
There are reports of 2 cases of subarachnoid hemorrhage associated with neurofibromatosis type I (von Recklinghausen's disease) are reported. A 30-year-old male patient (case 1) had been diagnosed as having neurofibromatosis type I due to neurofibroma and café-au-lait spot. He suffered from subarachnoid hemorrhage and angiography showed multiple aneurysms in the right and left middle cerebral arteries and left internal carotid artery. He also had arteriovenous malformation in the left temporal lobe(20).

e. Etc.

V. Complications and diseases associated with Cerebral aneurysm
A. Complications
Complications during cerebral aneurysm embolization continue to occur even at high volume experienced centers. Such situations are unexpected, complex and can have devastating consequences(21). Others indicated that Systemic complications secondary to subarachnoid hemorrhage from an aneurysm are common (40%) and the mortality attributable to them (23%) is comparable to mortality from the primary lesion, rebleeding, or vasospasm(22).  Dr. Chen M. suggested that the two most serious neuroendovascular procedural complications-namely, aneurysm perforation and thromboemboli aims to propose a role based checklist(23). Other complications include 
1. Re-bleeding
there is a report of fifty-three of 236 consecutive patients (22.5%) who suffered a proved aneurysmal subarachnoid hemorrhage and who were admitted within 72 hours after subarachnoid hemorrhage to a primary emergency hospital had at least one rebleed within 6 months after the primary bleed. Two patients later had a rebleed within a mean of 3 years follow-up. Rebleeding was recorded if there was a sudden loss of consciousness and a verification by computed tomography, autopsy, lumbar puncture, or angiography. The peak incidence of rebleeding was within the first 24 hours and at the end of the first week after subarachnoid hemorrhage. The rebleed mortality rate was 74%, and only 19% of patients with a rebleed had a good outcome. The grade on admission, age, and sex do not affect the incidence nor the time of rebleeding(24).


2. Vasospasm.
In the continuation of a review of delayed vasospasm after aneurysmal subarachnoid haemorrhage, originally published in 1994 and partially updated at the ninth vasospasm conference in Turkey. The incidence of delayed ischaemic deficit (DID) or symptomatic vasospasm reported in 1994 was 32.5% in over 30,000 reported cases. In recent years, 1994-2009, it was 6,775/23,806, or 28.5%. Many of the recent reports did not specify whether a calcium antagonist was used routinely, and when this was stated (usually nimodipine or nicardipine), DID was noted in 22.0% of 10,739 reported patients. The outcome of delayed ischaemia in the earlier survey was a death rate of 31.6%, with favourable outcomes in 36.2%. In recent reports, though with fewer than 1,000 patients, the outcome is possibly better, with death in 25.6% and good outcome in 54.1%. It thus appears likely that delayed vasospasm is still common but less so, and that the overall outcome has improved(25).

3. Hydrocephalus
Dr. Harrigan MR and the team at University of Alabama at Birmingham indicated that Patients underwent treatment of the ruptured aneurysm an average of 47.4 hours after admission and received an average total dose of 40.6 g of EACA. The mean length of time of administration of EACA was 35.6 hours. There was a total of 5 rehemorrhages, for an overall rebleeding rate of 1.4% and a rate of rehemorrhage per 24-hour period of 0.71%. Overall, the rates of symptomatic vasospasm and permanent neurological deficits attributable to ischemic stroke were 11.5% and 7.2%, respectively, and the incidence of shunt-dependent hydrocephalus was 42.3%. Patients who were treated with coiling had higher rates of symptomatic vasospasm and ischemic complications than patients who had surgery(26).


4. Hyponatremia
Hyponatremia following subarachnoid hemorrhage (SAH) therefore appears to be the result of increased natriuresis, due to the inappropriate elevation of ANP rather than SIADH. In this situation, water restriction should not be recommended, since the circulatory volume is decreased(27).

5. Etc.

B. Diseases associated with Cerebral aneurysm
1. Von Recklinghausen's neurofibromatosis
Dr. J Baldauf and the research team at the Department of Neurosurgery, Helios Hospital Berlin report a case of an intracranial aneurysm associated with von Recklinghausen's neurofibromatosis. A 34-year-old woman presented with a history of headaches, unconsciousness and neck rigidity. Widespread cutaneous neurofibromas were found. Investigations revealed an aneurysm of the anterior communicating artery(28)


2. Behçet's disease
Although Cerebral aneurysms in Behçet's disease are very rare. Dr. S Nakasu and the research indicated there is a case of a 57 year old man with Behçet's disease is described, who had a subarachnoid hemorrhage due to rupture of a peripheral middle cerebral artery aneurysm. He underwent a successful aneurysmal clipping. Three years later he had seizures and was found to have a new aneurysm on the contralateral peripheral middle cerebral artery as well as some radiological features of vasculitis. After 3 months of steroid therapy, the aneurysm disappeared. Although surgical treatment is the first choice for ruptured aneurysms, steroid therapy may be effective for unruptured small aneurysms in patients with Behçet's disease(29).

3. Marfan syndrome
Marfan syndrome is an autosomal dominant connective tissue disorder commonly due to mutation of the fibrillin-1 (FBN-1) gene that causes disruption of elastic fibers in large- and medium-size arteries and predisposes to aneurysm formation and arterial dissection. Cardiovascular complications occur in most patients with Marfan syndrome, but interestingly, neurovascular complications of Marfan syndrome are rare(30). 

4. Pseudoxanthoma elasticum
Although intracranial aneurysms have been associated with many hereditary collagen disorders, the incidence of brain aneurysms in pseudoxanthoma elasticum (PXE) appears to be exceedingly low and uncertain. There is a rare case of a sisters with PXE who both developed intracranial aneurysms. This report supports the previously questioned hypothetical association between PXE and intracranial aneurysms(31).

5. Ehlers-Danlos syndrome
Ehlers-Danlos syndrome Type IV is a heritable connective tissue disorder with frequent neurovascular manifestations, such as intracranial aneurysms. Patients with this syndrome have notoriously fragile blood vessels, and the reported mortality rate for any type of vascular surgical procedure is 40%. This syndrome is rare, however, and the complication rate of aneurysm surgery may have been overestimated(32)

6. Hypoplasia and fibromuscular dysplasia
Fibromuscular dysplasia represents one of the more common types of arterial fibrodysplasia, a heterogeneous group of nonatherosclerotic vascular occlusive and aneurysmal diseases. There is a report of  the first case, to the knowledge, of an elderly man with infrarenal aortic fibromuscular dysplasia associated with aortic hypoplasia, without involvement of renal arteries, and contiguous aortoiliac aneurysm(33).

VI. Diagnosis and Tests
After report the physical exam and family health history,
1. Eye exam
Eye exam is the test which your doctor may order. The test may show evidences of increased pressure in the brain as a result of swelling of the optic nerve or bleeding into the retina of the eye. Dr, Damasceno RW and Corrêa MA at the Rio de Janeiro, RJ, Brasil, report A 59-year-old patient was attended in February 2006 complaining of headache with diplopia and blepharoptosis in the right eye. At the external ocular motility exam. Aduction, supraduction and infraduction defects with blepharoptosis in the right eye were observed. Regarding the internal ocular motility, mydriasis in the right eye(34).

2. Neurological examination
Even lthough the screening test and tool are not expect to find any neurological deficit but certain abnormalities. There is case of a 69-year-old woman without diabetes or hypertension presented with a large posterior communicating artery aneurysm projecting beneath the oculomotor nerve manifesting as a 2-week history of progressive diplopia. Neurological examination revealed external ophthalmoplegia and blepharoptosis without pupil involvement. Neuroimaging showed a large aneurysm in the left internal carotid artery projecting postero-inferiorly. Craniotomy and neck clipping of the aneurysm revealed the origin at the junction of the internal carotid artery and posterior communicating artery, and elevation of the oculomotor nerve(35).

3. Digital subtraction angiography and CT scan angiography of the head to reveal the location and size of the aneurysm. In the study to compare the computed tomographic angiography and digital subtraction angiography in diagnostic value of brain aneurysms, showed that mean age of patients was 49.5 ± 9.13 years. 57.9 % of subjects were female. CTA showed 89% sensitivity and 100% specificity whereas DSA demonstrated 74% sensitivity and 100% specificity. Positive predictive value of both methods was 100%, but negative predictive value of CTA and DSA was 85% and 69%, respectively, and concluded that CTA is a valuable diagnostic modality for detection of brain aneurysm and subarachnoid hemorrhage(36)


4. Cerebrospinal fluid exam (spinal tap)  
The aim of Cerebrospinal fluid (CSF) collection is a test to look at the fluid that surrounds the brain and spinal cord. University of Wisconsin School of Medicine and Public Health, Madison in the study comprised 648 patients who had TAA or TAAA repair from 1987 to 2008, found that Spinal drains were used in 486 patients. Spinal fluid pressure was measured continuously, except when draining fluid, and was reduced to <6 mm Hg during thoracic aortic occlusion and reperfusion. After surgery, spinal fluid pressure was kept <10 mm Hg until patients were awake with normal leg lift. Drains were removed 48 hours after surgery. Spinal and head computed tomography (CT) scans were performed in patients with bloody spinal fluid or neurologic deficit(37).
 5. Electroencephalogram (EEG)
There is areport of the Electroencephalogram (EEG) of 151 patients whose ruptured aneurysm was confirmed by CT scan and angiography was recorded on the first day (D1) and the fifth day (D5). On D1, EEG had a prognostic value: among 46 patients with normal EEG, 72% presented neither further electrical ischaemic features nor delayed angiographic vasospasm; on the other hand, when bilateral bursts of slow waves, "axial bursts" or slow delta waves were recorded (78 cases), 97% exhibited EEG signs of ischaemia and angiographic vasospasm a few days later(38).

6. MRI of the head 
Different Magnetic Resonance (MR) imaging techniques are used to evaluate intracranial aneurysms. • At 3T MR, 3D-TOF and CE-MRA appear equivalent for evaluating coiled aneurysms.. • Coils are better visualised on 3D-TOF than on CE-MRA. • Combined analysis of 3D-TOF and CE-MRA does not seem helpful. • At 3T, 3D-TOF techniques are recommended for monitoring patients with coiled aneurysms(39).

5. Etc.

VI. Preventions
A.1. The Do's and Do not's list 
1. Reduce intake saturated fat and trans fat
Intake of high amount of saturated fat and trans fat increase the risk of cholesterol building up in the arteries of that can cause increased risk of hypertension and arteriosclerosis causes of cerebral aneurysm.

2. Quick smoking
There are some report indicated that smoking is associated with increased risk of Cerebral Aneurysm. Smoking also enhance the deposit of cadmium to cause hardened arteries of that causing increased risk of the diseases.


3. Moderate drinking
Moderate drinking can increase blood circulation and pressure to move blood, it is considered healthy for normal person. But for people with Cerebral Aneurysm, alcohol can cause increased risk of rebleeding and rupture Cerebral Aneurysm

4. Eat your fruits and veggies
Fruits and veggies contains high amount antioxidants and phytochemicals of that enhance the immune system and decrease the risk of lipid peroxidation and infection causes of Cerebral Aneurysm.

5. Exercise
Exercise decrease the risk of Abdominal aortic aneurysm (AAA), a vascular disease resulting in a permanent, localized enlargement of the abdominal aorta(40)

6. Wear your seat belt and protective hat
Wear your seat belt and protective hat to prevent head injure if there is an auto accidence and accidence at work for people with the risk of falling objects.

7. Prevent bacterial blood infection
People who work in the health care service should wash their hand when deal with patient blood to avoid infection to the patient and themselves.

8. No drug
Drug used reduce the function of immune function of which enhances the risk of Cerebral Aneurysm(41)

9. Etc.

A.2. Diet against Cerebral Aneurysm
The aim of the diet is to enhance the immune function, prevent cholesterol and Lower estrogen levels after menopause causes of  Cerebral Aneurysm
1. Tofu or bean curd is soft white blocks made by coagulating soy milk with substance such as salt or acid or enzyne, a stable emulsion of oil, water, and protein that can be made into tofu, originated from Chinese and part of East and Southeast Asian. Since it is proven to be one of many healthy foods, it become synonymous with vegetarianism and others.
a. Metabolic syndrome
In the
assessment of the effect of low daily intake of soybeans in oxidative stress and it effects on the metabolic syndrome (MS) found that Low intake of soy protein for 90 days, besides being well tolerated by the patients, was able to improve several parameters related to the pathophysiology of MS, according to the study of "[Evaluation of the intake of a low daily amount of soybeans in oxidative stress, lipid and inflammatory profile, and insulin resistance in patients with metabolic syndrome].[Article in Portuguese] by Bahls LD, Venturini D, Scripes Nde A, Lozovoy MA, Simão TN, Simão AN, Dichi I, Morimoto HK.(42)


b. Cardiovascular Benefits
Research found that protein of tofu significantly decreases the serum cholesterol by decreasing the levels of bad cholesterol (LDL) but leaving the good cholesterol (HDL) remain the same According to the study of "Effect of soy and milk protein supplementation on serum lipid levels: a randomized controlled trial" by Wofford MR, Rebholz CM, Reynolds K, Chen J, Chen CS, Myers L, Xu J, Jones DW, Whelton PK, He J.(43). It also benefits the cardiovascular health (according to the study of "Soy protein, isoflavones, and cardiovascular health: an American Heart Association Science Advisory for professionals from the Nutrition Committee" by Sacks FM, Lichtenstein A, Van Horn L, Harris W, Kris-Etherton P, Winston M (44)
 
c. Superoxide dismutase
Superoxide dismutase are an important antioxidant defense in nearly all cells exposed to oxygen as a class of enzymes that catalyzes the dismutation of free radicals due to existence of copper and Zn in tofu (according to the study of "Cu,Zn-superoxide dismutase gene dosage and cell resistance to oxidative stress: a review" by Peskin AV., posted in Pubmed, researchers found thatt here are data that increasing only Cu,Zn-SOD can be toxic, and the balance between Cu,Zn-SOD and peroxide-removing enzymes is supposed to be of prime importance in the antioxidant defense. Role of Cu,Zn-SOD deregulation in carcinogenesis is discussed(45).
 
d. Selenium
Selenium is classified as one of antioxidant trace mineral that helps to increase the immune function to fight the forming of free radicals, infection and inflammation caused by oxidation, irregular cells growth, virus and bacteria, etc., according tothe study of "Protective role of intraperitoneally administrated vitamin E and selenium on the levels of total lipid, total cholesterol, and fatty acid composition of muscle and liver tissues in rats" by Yilmaz O, Celik S, Cay M, Naziroğlu M.(46), researchers found that the level of total lipid and cholesterol in muscle and liver tissues were reduced by administrating vitamin E and Se together. Additionally, the fatty acid synthesis in the muscle and liver tissues was decreased by this process) and prevent plague accumulated cause of Atherosclerosis (according to the study of 'Vitamin-mineral supplementation and the progression of atherosclerosis: a meta-analysis of randomized controlled trials" by Bleys J, Miller ER 3rd, Pastor-Barriuso R, Appel LJ, Guallar E.(47), thus reducing the risk of heart diseases and hypertension.
 
2. Dulse
Dulse is a red seaweed of genus Palmaria, belong to Family Palmariaceae that grows attached to rocks by a "holdfast" in the North Atlantic and Northwest Pacific. It is commonly used in Ireland and Atlantic Canada both as food and medicinally and is now shipped around the globe. Dulse is found in many health food stores or fish markets or can be ordered directly from local distributors.
a.  Health benefits
In the assessment of nutritional and physiological properties of edible seaweeds is presented. Seaweeds are traditionally consumed in Asia as sea vegetables found that Seaweeds showed important functional activities, such as antioxidant, antimutagenic and anticoagulant effect, antitumor activity, and an important role in the modification of lipid metabolism in human body. In conclusion, seaweeds have a high nutritional value, therefore an increase in their consumption, would elevate the foods offer to population, according to "[Nutritional evaluation and physiological effects of edible seaweeds].[Article in Spanish]" by Jiménez-Escrig A, Goñi Cambrodón I.(48)

b. Antioxidant
In assessment of polyphenol content of the dulse extract of two grades of dulse harvested from Canadian Maritime locations differing in UV radiation exposure (i.e. west versus east coasts of Grand Manan Island, New Brunswick) and their antiodant effects found that The 1-butanol soluble extract from Grade 1 dulse (reduced UV-exposure) exhibited lower reducing activity versus Grade 2 dulse (greater UV exposure) reflecting a lower requirement for endogenous antioxidant protection. Grade 1 and 2 dulse extracts both inhibited (p0.03) AAPH-induced lipid peroxidation, but had no effect on AMVN-induced lipid peroxidation, demonstrating the aqueous nature of the antioxidants involved, according to "Extracts from dulse (Palmaria palmata) are effective antioxidants and inhibitors of cell proliferation in vitro" by Yuan YV, Carrington MF, Walsh NA.(49)
 
c. Chlorophyll
Chlorophyll, a green pigment found in almost all plants, algae, and cyanobacteria, beside it is best known for its cleansing body and healing to vital organs properties. It also reduces the binding of carcinogens to DNA in the liver and other organs, thus reducing the risk of cancer according to the study of "Natural compounds in the human diet and their ability to bind mutagens prevents DNA-mutagen intercalation" by Osowski A, Pietrzak M, Wieczorek Z, Wieczorek J.(50), researchers indicated that in order to bind 50% of the mutagen in a complex, less than twice the concentration of chlorophyllin was needed......
 
3. Raspberries are perennial, the edible fruit of a multitude of plant species in the genus Rubus belong to the family Rosaceae, originated from Europe. Because of their commercial values and health benefits, they have been grown for processing of quick frozen (IQF) fruit, purée, juice, or as dried fruit used in a variety of grocery products.
a. Human healthIn the investigation of Raspberries and its effect on human health found that the nutritional and phytochemical compositions of red raspberries and their absorption, metabolism, and biological activity are reviewed. Finally, future directions of research are also identified, according to "Raspberries and human health: a review" by Rao AV, Snyder DM.(51)

b. Bioavailability of anthocyanins and ellagitannins

In the assessment of raspberries and its Bioavailability of anthocyanins and ellagitannins effects found that no intact or conjugated forms of ellagitannins were detected in urine from either healthy subjects or ileostomy volunteers. However, in healthy subjects, but not the ileostomists, ellagitannins were catabolized with the appearance of urolithin A-O-glucuronide, two of its isomers, and urolithin B-O-glucuronide in urine collected 7-48 h after raspberry consumption. There was marked variation in the urolithin profile of individual volunteers, indicating differences in the colonic microflora responsible for ellagitannin degradation, according to "Bioavailability of anthocyanins and ellagitannins following consumption of raspberries by healthy humans and subjects with an ileostomy" by
González-Barrio R, Borges G, Mullen W, Crozier A.(52)
c. Degenerative diseases of ageing
Long-term vitamin K inadequacy may reduce the function of supporting the carboxylation of at least some of these Gla-protein that can lead the development of degenerative diseases of ageing including osteoporosis and atherosclerosis, according to the study of "Vitamin K, osteoporosis and degenerative diseases of ageing" by Cees Vermeer and Elke Theuwissen(53)
 
d. Intracranial bleeding
In a study in the 4-year study period, 16/64 (25%) of the infants admitted with intracranial bleeding had late intracranial VKDB, resulting in an overall incidence of 2.1/100,000 live births (95% confidence interval 1.2-3.5) conducted by University Medical Center Utrecht(54) indicated that Intracranial bleeding may be associated with vitamin K deficiency

4.
Flax seed
Flax seed is native to the region of the eastern Mediterranean to India and also known as common flax or linseed. Flax is an erect annual plant, it can grow to 1.2 m tall. The leaves are 20–40 mm long and 3 mm broad.
a. Hyperlipidemia
In the
examination of the effects of flax and sesame seeds mixture on Hyperlipidemia
found that Diet supplemented with flax and sesame seeds mixture in pregnant diabetic rats ameliorated lipid parameters, antioxidant enzyme activities, level of reduced glutathione and significantly decreased malonaldialdehyde levels, according to "Dietary polyunsaturated fatty acid prevents hyperlipidemia and hepatic oxidant status in pregnant diabetic rats and their macrosomic offspring" by Makni M, Sefi M, Garoui el M, Fetoui H, Boudawara T, Zeghal N.(55)

b.
Hypolipidemic and hepatoprotective effects
In the evaluation of
a rich source of unsaturated fatty acids of Flax and pumpkin seedsand theirs anti-atherogenic and hepatoprotective activities. found that flax and pumpkin seed mixture had anti-atherogenic and hepatoprotective effects which were probably mediated by unsaturated fatty acids present in seed mixture, according to "Hypolipidemic and hepatoprotective effects of flax and pumpkin seed mixture rich in omega-3 and omega-6 fatty acids in hypercholesterolemic rats" by Makni M, Fetoui H, Gargouri NK, Garoui el M, Jaber H, Makni J, Boudawara T, Zeghal N.(56)

c. Cardiovascular diseases
In the research of
Flaxseed and its effect on cardiovascular risk found that flaxseed can modestly reduce serum total and low-density lipoprotein cholesterol concentrations, reduce postprandial glucose absorption, decrease some markers of inflammation, and raise serum levels of the omega-3 fatty acids, ALA and eicosapentaenoic acid. Data on the antiplatelet, antioxidant, and hypotensive effects of flaxseed, however, are inconclusive. More research is needed to define the role of this functional food in reducing cardiovascular risk, according to "Flaxseed and cardiovascular risk' by Bloedon LT, Szapary PO.(57)

d.
Hypercholesterolemic atherosclerosis
In the evaluation of
Flaxseed (Type I flaxseed) and CDC-flaxseed (Type II flaxseed) and theirs effect onhypercholesterolemic atherosclerosis found that Type II flaxseed reduced the development of atherosclerosis by 69%, according to "Reduction of hypercholesterolemic atherosclerosis by CDC-flaxseed with very low alpha-linolenic acid" by Prasad K, Mantha SV, Muir AD, Westcott ND.(58)

e. Anti-
hormono-dependant cancers
In the observation of Flax lignans belonging to the phytoestrogens, metabolised after ingestion into enterolignans and its protective effect against the onset and development of hormono-dependant cancers found that in vitro studies based on mammalian cellular models tend to confirm their beneficial effects observed during epidemiological studies and give us insights about their mechanisms of action, according to "[Interest of lignans in prevention and treatment of cancers].[Article in French]" by Lamblin F, Hano C, Fliniaux O, Mesnard F, Fliniaux MA, Lainé E.(59)
 
5. Green tea
Green tea contains more amount of antioxidants than any drinks or food with the same volume, and is the leaves of Camellia sinensis, undergone minimal oxidation during processing, originated from China. Green tea has been a precious drink in traditional Chinese culture and used exceptional in socialization for more than 4000 thousand years. Because of their health benefits, they have been cultivated for commercial purposes all over the world.
a. Immune system
Polyphenols, one of more powerful form of antioxidant not only helps to improve the immune system fighting against the forming of free radicals and guarding our body from foreign invasion, such as virus and bacteria, thus reducing the risk of inflammation and lessening the risk of oxidation of low-density lipoprotein (LDL) cause coronary heart disease, according to the study of "Plant polyphenols as dietary antioxidants in human health and disease" by Kanti Bhooshan Pandey and Syed Ibrahim Rizvi, (60)

b. Tannins
A group of simple and complex phenol, polyphenols, and flavonoid compounds, once are considered anti nutritional but it is now known of their beneficial depending to their chemical structure and dosage for its anti-inflammatory, antibacterial, antiviral, and antiparasitic effects due oxidative stress, according tothe study of "Effects of green tea tannin on cisplatin-induced nephropathy in LLC-PK1 cells and rats" Yokozawa T, Nakagawa T, Lee KI, Cho EJ, Terasawa K, Takeuchi S.(61)

c. Catechins
Catechins are a category of polyphenols contained epicatechin (EC), epigallocatechin (EGC), epicatechin gallate (ECG) and epigallocatechin gallate (EGCG) and 25-100 times more potent than vitamins C and E that help to protect the body from oxidative damage by enhancing the immune function in fighting against forming of free radicals cause of cancer, according to the study of "Green tea catechins augment the antitumor activity of doxorubicin in an in vivo mouse model for chemoresistant liver cancer" by Liang G, Tang A, Lin X, Li L, Zhang S, Huang Z, Tang H, Li QQ.(62)

d. Flavonoids
Flavonoids are best known as an antioxidant that help to protect our body from forming free-radical scavenging capacity, coronary heart disease, irregular cell causes of cancer activity and immunodeficiency virus functions, according to the study of "Vegetable flavonoids and cardiovascular disease" by Terao J, Kawai Y, Murota K.(63)
6. Etc.
   
A.3. Antioxidants against Cerebral Aneurysm
1. Bioflavonoids or vitamin P
Discovered by Szent-Gyorgyi and his colleagues back in the 1930`s. In Laboratory tests, B
bioflavonoids help to reduce the fragility and “permeability” in capillaries and prevent the clotting up of arterial as a result of oxidation.

2. Vitamins C and E, beta-carotene
Recent research findings have suggested that antioxidants such as vitamin C, E and beta carotene play an important role in the prevention of atherosclerosis. Data from animal studies showed they are able to prevent oxidative modification of low density lipoproteins (LDL).

3. Alpha-tocopherol
Alpha-tocopherol, a antioxidant found abundant in vitamin E, helps to decrease lipid peroxidation and platelet aggregation, adhesion and inflammatory. Epidemiological studies suggest that low levels of antioxidants are associated with increased risk for cardiovascular disease.

4. Vitamin C and E
Studies showed in take of 500mg of vitamin C and 400 IU of vitamin E helps to retard the progression of coronary atherosclersis.

5. Chlorophyl
Antioxidant chorophyll in the green algae shows to inhibit the chemical cadmium of smoking, by preventing from oxidation that cause building up of plaque along the walls of arteries.
6. 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.

7. 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

8. 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.

9. Selenium
Deficiency of of a co-enzyme selenium, which is required in maintaining the glutathione redox cycle, also promote more susceptible to oxidative injure.
 
10. Thymus
The declining of the thymus function contributes a direct effect on the immune system due to diminish of quantity of T cells and immune factors.

11. Lipid peroxidation
Researchers found that lipid peroxidation are able to attack immune cells membrane, leading to the impediment of cells membrane activities, causing susceptibility diseases found in aging person.

12. NADHP oxidase
NADHP oxidase (nicotinamide adenine dinucleotide phosphate-oxidase) is a membrane-bound enzyme complex found in the plasma membrane. Free radicals cause damage to membrane, leading to diminish of its function in fighting against foreign invasion.

13. Cytokine
Free radicals damage immune cells that affect the function of cytokines in transmitting intercellular signals, leading to many disease states and conditions ranging from major depression and Alzheimer's disease to cancer.
14. Etc.
 
A.4. Phytochemicals against Cerebral Aneurysm
1. 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. Cholesterol
In a systematic review and meta-analysis of randomized controlled trials evaluating the relationship between GTCs and serum lipid levels, including total, low-density lipoprotein (LDL), high-density lipoprotein (HDL) cholesterol, and triglycerides, found that the consumption of GTCs is associated with a statistically significant reduction in total and LDL cholesterol levels; however, there was no significant effect on HDL cholesterol or triglyceride levels, according to " Green tea catechins decrease total and low-density lipoprotein cholesterol: a systematic review and meta-analysis" by Kim A, Chiu A, Barone MK, Avino D, Wang F, Coleman CI, Phung OJ.(64)

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.(65)

c. Neuroprotective effects
In the evaluation the neuroprotective effects of theanine and catechins contained in green tea , found that the mechanism of the neuroprotective effect of theanine is related not only to the glutamate receptor but also to other mechanisms such as the glutamate transporter, although further studies are needed. One of the onset mechanisms for arteriosclerosis, a major factor in ischemic cerebrovascular disease, is probably the oxidative alteration of low-density lipoprotein (LDL) by active oxygen species. The oxidative alterations of LDL were shown to be prevented by tea catechins. Scavenging of *O(2)(-) was also exhibited by tea catechins. The neuroprotective effects of theanine and catechins contained in green tea are a focus of considerable attention, and further studies are warranted, according to "Neuroprotective effects of the green tea components theanine and catechins" by Kakuda T.(66)

2. Tangeritin, one of the flavones, is found in tangerine and many citrus peels
a. Cholesterol
In the investigation of the formulations containing citrus polymethoxylated flavones (PMFs), mainly tangeretin, or citrus flavanone glucosides, hesperidin and naringin and theirs anti hypercholesterolemia effect found that PMFs are novel flavonoids with cholesterol- and triacylglycerol-lowering potential and that elevated levels of PMF metabolites in the liver might be directly responsible for their hypolipidemic effects in vivo, according to "Hypolipidemic Effects and Absorption of Citrus Polymethoxylated Flavones in Hamsters with Diet-Induced Hypercholesterolemia" by Elzbieta M. Kurowska and John A. Manthey, KGK Synergize Inc.(67)

b. Neuroprotective effects
In the evaluation of neuroprotective effects of a natural antioxidant tangeretin, a citrus flavonoid and its effect on Parkinson's disease found that tangeretin crosses the blood-brain barrier. The significant protection of striato-nigral integrity and functionality by tangeretin suggests its potential use as a neuroprotective agent, according to "Tissue distribution and neuroprotective effects of citrus flavonoid tangeretin in a rat model of Parkinson's disease" by Datla KP, Christidou M, Widmer WW, Rooprai HK, Dexter DT.(68)

c. Antioxidants
In the comparison of hand-pressed juice of polymethoxylated flavones (PMFs) and flavanone glycosides (FGs) and the peeled fruit of 'Sainampueng' tangerines ( Citrus reticulata Blanco cv. Sainampueng) antioxidant effects found that hand-pressed juice of C. reticulata Blanco cv. Sainampueng serves as a rich source of PMFs, FGs, carotenoids, and antioxidants: 4-5 tangerine fruits ( approximately 80 g of each fruit) giving one glass of 200 mL hand-pressed juice would provide more than 5 mg of nobiletin and tangeretin and 36 mg of hesperidin, narirutin, and didymin, as well as 30 mg of ascorbic acid, >1 mg of provitamin A active beta-cryptoxanthin, and 200 microg of alpha-tocopherol, according to "Polymethoxylated flavones, flavanone glycosides, carotenoids, and antioxidants in different cultivation types of tangerines ( Citrus reticulata Blanco cv. Sainampueng) from Northern Thailand" by Stuetz W, Prapamontol T, Hongsibsong S, Biesalski HK.(69)

d. Antimicrobial activity
In the study of antibacterial and antifungal properties of wax and hexane extracts of Citrus spp. peels found that antimicrobial activity especially against M. canis and T. mentagrophytes: 4',5,6,7,8-pentamethoxyflavone (tangeritin) and 3',4',5,6,7,8-hexamethoxyflavone (nobiletin) from C. reticulata; and 6,7-dimethoxycoumarin (also known as escoparone, scoparone or scoparin) from C. limon, according to "Antimicrobial activity of wax and hexane extracts from Citrus spp. peels" by Johann S, Oliveira VL, Pizzolatti MG, Schripsema J, Braz-Filho R, Branco A, Smânia Jr A.(70)

3. Rosemarinol, is a phytochemical monophenols, found in essential oil of labiate herbs like Rosemary and also in variety of other plants.
a. Antimicrobial activity
In the observation of the essential oils from clove (Syzygium aromaticum (L.) Merr. et Perry) and rosemary (Rosmarinus officinalis L.) and their anti,icrobial effects found that The antimicrobial activity of combinations of the two essential oils indicated their additive, synergistic or antagonistic effects against individual microorganism tests. The time-kill curves of clove and rosemary essential oils towards three strains showed clearly bactericidal and fungicidal processes of (1)/(2) x MIC, MIC, MBC and 2 x MIC, according to "Antimicrobial activity of clove and rosemary essential oils alone and in combination" by Fu Y, Zu Y, Chen L, Shi X, Wang Z, Sun S, Efferth T.(71)

b. Anti-inflammatory effects
In the research of the extract of rosemary leaves from supercritical fluid extraction and its anti inflammatory effects found that the yield of 3.92% and total phenolics of 213.5 mg/g extract obtained from the most effective extraction conditions showed a high inhibitory effect on lipid peroxidation (IC(50) 33.4 μg/mL). Both the SC-CO(2) extract and CA markedly suppressed the LPS-induced production of nitric oxide (NO) and tumor necrosis factor-α (TNF-α), as well as the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), phosphorylated inhibitor-kappaB (P-IκB), and nuclear factor-kappaB (NF-κB)/p65 in a dose-dependent manner, according to the study of "Anti-inflammatory effects of supercritical carbon dioxide extract and its isolated carnosic acid from Rosmarinus officinalis leaves" by Kuo CF, Su JD, Chiu CH, Peng CC, Chang CH, Sung TY, Huang SH, Lee WC, Chyau CC.(72)


4. Rutin also known as rutoside, quercetin-3-O-rutinoside and sophorin is a Flavonols, belong to Flavonoids (polyphenols) of Phenolic compounds found orange, grapefruit, lemon, lime, berries mulberry, cranberries, buckwheat etc.
a. Anti-inflammatory activity
In the investigation of Rutin, a natural flavone derivative and its anti inflammatory effect found that Oral administration of rutin reduced rat paw swelling starting 2 hours after lambda-carrageenan injection. Rutin reduced significantly (p < 0.05) and in a dose-dependant manner the polymorphonuclear neutrophils chemotaxis to fMet-Leu-Phe, according to the study of "Anti-inflammatory effect of rutin on rat paw oedema, and on neutrophils chemotaxis and degranulation" by Selloum L, Bouriche H, Tigrine C, Boudoukha C.(73)

b.  Diabetes, Hyperglycemia and dyslipidemia
In the analyzing Dietary antioxidant compounds such as flavonoids and its protection against early-stage diabetes mellitus, found that Rutin (50 mg kg(-1)) reduced (p<0.05) blood glucose and improved the lipid profile in STZ-induced diabetic rats and concluded that that rutin can improve hyperglycemia and dyslipidemia while inhibiting the progression of liver and heart dysfunction in STZ-induced diabetic rats, acccording to "Influence of rutin treatment on biochemical alterations in experimental diabetes" by Fernandes AA, Novelli EL, Okoshi K, Okoshi MP, Di Muzio BP, Guimarães JF, Fernandes Junior A.(74)

c. Cardiovascular health
In the testing the hypothesis of the consumption of a diet rich in flavonoids can be associated with a reduced risk for cardiovascular disease found that hamster fed with 2% cranberry concentrate powder (HFHC+CE); a HFHC with 0.1% rutin (HFHC+Rutin); and a HFHC with 30 mg/kg vitamin E (HFHC+Vit.E) diet for either 12 or 20 weeks, found that Ratios of plasma high-density lipoprotein cholesterol (HDL-C) to very-low-density lipoprotein cholesterol and of plasma HDL-C to low-density lipoprotein cholesterol were significantly higher in animals consuming HFHC+Vit.E, according to the strudy of "Effects of a flavonol-rich diet on select cardiovascular parameters in a Golden Syrian hamster model" by Kalgaonkar S, Gross HB, Yokoyama W, Keen CL.(75)

d. Ischemia-reperfusion brain injury-related disorders
In the investigation of rutin's effect on cerebral ischemia-reperfusion (IR) injury caused by free radical induced neural damage found that the elevated level of thiobarbituric acid reactive species (TBARS), H(2)O(2) and protein carbonyl (PC) in MCAO group was attenuated significantly in rutin-pretreated group and concluded that rutin treatment may represent a novel approach in lowering the risk or improving the function of ischemia-reperfusion brain injury-related disorders, according to Rutin protects the neural damage induced by transient focal ischemia in rats" by Khan MM, Ahmad A, Ishrat T, Khuwaja G, Srivastawa P, Khan MB, Raza SS, Javed H, Vaibhav K, Khan A, Islam F.(76)

5. Glycitein is a phytochemical in the Isoflavones, belonging to the group of Flavonoids (polyphenols), found abundantly in food of the family of legumes, soy, peanuts, chick peas, fava beans, alfalfa, kudzu, etc.
a. Antioxidants
in the evaluation of the antioxidant activity and contents of various polyphenol classes in the seeds of seven soybean varieties of different seed color and one yellow seed cultivar, found that antioxidant activity of seed extracts was evaluated by the 2,2-diphenyl-1-picrylhydrazyl free radical scavenging activity assay. A positive linear correlation between antioxidant activity and contents of total polyphenols and anthocyanins was established. The highest antioxidant activity was observed in the extracts of black and brown varieties, which also showed high levels of all polyphenol classes examined. Yellow seed had the highest total isoflavone content (3.62 mg/g of dry material). The highest concentration of total daidzein was determined in black seeds (>2.0 mg/g of dry material), and the highest total glycitein and genistein contents occurred in the yellow cultivar (0.53 and 1.49 mg/g of dry material, respectively). According to our results, varieties of black and brown seeds could be of special interest not only for their large content of total polyphenols, ranging from 4.94 to 6.22 mg of gallic acid equivalents/g of dry material, but also for their high content of natural antioxidants such as anthocyanins, according to "Polyphenol content and antioxidant properties of colored soybean seeds from central europe" by Malenčić D, Cvejić J, Miladinović J.(77)

b. Hypolipidemic effects
In the comprison of whether Monascus-fermented soybean extracts (MFSE) enriched with bioactive mevinolins (natural statins) and aglycone isoflavones (daidzein, glycitein, and genistein) perform an additive hypolipidemic effect in hyperlipidemic ratsand unfermented soybean extracts (UFSE), which have a higher level of glucoside isoflavones (daidzin, glycitin, and genistin) without mevinolin, found that treatment with both MFSE200 and MFSE400 groups for 40 days significantly reduced the activities of serum aspartate aminotransferase and alanine aminotransferase by averages of 35.6 and 43.2%, respectively, as compared to the high-fat diet group (p < 0.01). The results indicate that MFSE performs a more potent hypolipidemic action via improvement of the lipid profiles and down-regulated HMG-CoA reductase activity than UFSE in hyperlipidemic rats, according to "Hypolipidemic effects of Monascus-fermented soybean extracts in rats fed a high-fat and -cholesterol diet" by Pyo YH, Seong KS.(78)

c. Post-menopausal effects
found that high-dose isoflavones is associated with improved QOL among women who have become menopausal recently. Hence, the timing of isoflavone supplementation with regards to the onset of menopause appears to be important. The use of isoflavones, as an alternative to estrogen therapy, may be potentially useful and seemingly safe in this group of women who are looking for relief from menopausal symptoms, according to "Effect of high-dose isoflavones on cognition, quality of life, androgens, and lipoprotein in post-menopausal women" by Basaria S, Wisniewski A, Dupree K, Bruno T, Song MY, Yao F, Ojumu A, John M, Dobs AS.(79)

VII. Treatments
A.1. In conventional medicine perspective
Treatment for a symptomatic aneurysm is to repair the blood vessels to prevent blood to enter the aneurysm to cause further growth or blood leakage.
1. Surgical Clipping was introduced by Walter Dandy of the Johns Hopkins Hospital in 1937
Clopping is the operation of the brain by cutting open the skull to find the damaged blood vessel and putting a clip across the aneurysm.


2. Endovascular coiling was introduced by Guido Guglielmi at UCLA in 1991
The operation passes a catheter into the femoral artery in the groin, through the aorta, into the brain arteries to the aneurysm and fill the aneurysm with coils of platinum wire or with latex.
Depending to he severity of the patient's condition, the EEG changes, an intracranial hematoma, and correspondence of the region of the operation with the zone of the vascular spasm were the most informative preoperative signs of the prognosis of the outcome of early operations. Bleeding during the operation and the duration of the arrest of the blood flow in the main vessel were the most informative intraoperative signs(80). Other study of One hundred and sixty of the aneurysms had ruptured; for 150 "typical" supratentorial aneurysms, the operative case fatality rate was 10%, and a satisfactory outcome was obtained in 85%. There were no deaths and little morbidity in 108 operations on grade 0 or 1 patients. Among a number of factors influencing outcome, the most obvious were age, hypertension, cerebral arterial spasm, and the clinical condition of the patient at the time of operation. The timing of surgery had no effect on results(81).
In a study to compare the quality of life (QOL) of surgically versus endovascularly treated patients with ruptured cerebral aneurysms.Methods We treated 45 patients surgically (surgical clipping [SC] group) and 44 by endovascular therapy (coil embolization [CE] group), the differences in QOL in the patients treated by either coiling or clipping were small and nonsignificant(82).

A.2. In herbal medicine perspective
1, Black Cohosh is a herbaceous perennial plant, genus Actaea, belonging to the family Ranunculaceae, native to eastern North America. The herb has been used in traditional medicine as analgesic, sedative, diuretic, emmenagogue anti-inflammatory agent and to treat rheumatism, symptoms of menopause, uterine cramps and muscle pain, etc.. Native Americans have used the root of the herb to treat snake bite.
a. Alternative to hormone replacement therapy
Black cohosh contains high amount of phytoestrogen of which helps to occupied the estrogen receptors or enhances the estrogen levels in the women in the stage of menopause, thus it may be considered as alternative to estrogen therapy, according to the study of "Black cohosh: an alternative therapy for menopause?" by Mahady GB, Fabricant D, Chadwick LR, Dietz B., posted in PubMed(83)

b. Antioxidants
Polyphenols in Black cohosh may be considered as an antioxidant which help to fight against the forming of free radicals cause of DNA damage and guarding our body against foreign invasion such as bacteria and virus, according to the study of "Black cohosh (Cimicifuga racemosa L.) protects against menadione-induced DNA damage through scavenging of reactive oxygen species: bioassay-directed isolation and characterization of active principles" by Burdette JE, Chen SN, Lu ZZ, Xu H, White BE, Fabricant DS, Liu J, Fong HH, Farnsworth NR, Constantinou AI, Van Breemen RB, Pezzuto JM, Bolton JL., posted in PubMed(84)

c. Anti-inflammation
Cimicifuga racemosa (Actaea racemosa, black cohosh)have exerted inflammatory activity by inhibiting nitric oxide production by reducing iNOS expression without affecting activity of the enzyme, according to the study of "Inhibition of inducible nitric oxide synthesis by Cimicifuga racemosa (Actaea racemosa, black cohosh) extracts in LPS-stimulated RAW 264.7 macrophages" by Schmid D, Gruber M, Woehs F, Prinz S, Etzlstorfer B, Prucker C, Fuzzati N, Kopp B, Moeslinger T., posted in PubMed(85)

2. Dang Qui (Angelica sinensis) is a herb of Genus Angelica from the family Apiaceae, indigenous to China. The herb has been used as a Queen herb in traditional Chinese medicine antispasmodic and vasodilatory agent, and to balance the hormones in women for a normal menstrual cycle and menstruation and strengthen heart, spleen, kidneys, and liver for both men and women, etc. In other words, it is used to treat gynecological ailments, fatigue, mild anemia and high blood pressure. It has analgesic, anti-inflammatory, etc.
a, Inflammatory effect
In the investigation of ethyl acetate (EtOAc) fraction from Angelica sinensis (Oliv.) and its anti-inflammatory effort found that AS EtOAc extract significantly inhibited NF-kappaB luciferase activity and TNF-alpha, IL-6, macrophage inflammatory protein-2 (MIP-2) and NO secretions from LPS/IFN-gamma-stimulated RAW 264.7 cells. The AS1 and PDTC groups, but not AS2, had significantly higher survival rate than the control group. This was characterized by the inhibition of the serum TNF-alpha and IL-12p40 levels after LPS injection (p<0.05). The major compounds of AS, ferulic acid and Z-ligustilide, also significantly decreased NF-kappaB luciferase activity, which may contribute to the anti-inflammatory activity of AS, according to "Inhibitory effects of Angelica sinensis ethyl acetate extract and major compounds on NF-kappaB trans-activation activity and LPS-induced inflammation" by Chao WW, Hong YH, Chen ML, Lin BF.(86)

b. Ischemia and Neurodegeneration
In the observation of 4 medical plants: astragali, ligusticum wallichii, angelica sinensis and carthamus tinctorius (saffron) have been the major medicines to treat ischemia for hundreds of years in China, Korea and Japan and theirs effects on Ischemia and Neurodegeneration found that The herbs have demonstrated the neuroprotective efficacy of the combination of these phyotmedicines on mitigating brain infarction and global ischemia as well as preventing the neurodegeneration following ischemia. Owing to their multi-function, including improving cerebral blood circulation, they therefore have the potential to alleviate the symptoms of degenerative diseases, Alzheimer's disease (AD) and Parkinson's disease (PD), according to the study of "Polyphenols and Neuroprotection against Ischemia and Neurodegeneration" by Lin B.(87)

c.  Immunomodulatory functions
In the evaluation of Ganoderma tsugae (Ganodermataceae), Codonopsis pilosula (Campanulaceae) and Angelica sinensis (Apiaceae) and their effects on immune system found that RG-CMH, which represents a mixture of rose geranium and extracts of G. tsugae, C. pilosula and A. sinensis, can improve the immune cell count of cancer patients receiving chemotherapy and/or radiotherapy to prevent leucopenia and immune impairment that usually occurs during cancer therapy. A total of fifty-eight breast cancer patients who received chemotherapy or radiotherapy were enrolled, according to "Effects of a Chinese medical herbs complex on cellular immunity and toxicity-related conditions of breast cancer patients' by Zhuang SR, Chiu HF, Chen SL, Tsai JH, Lee MY, Lee HS, Shen YC, Yan YY, Shane GT, Wang CK.(88)

d. Hypertension
In the investigation of Z-ligustilide, the main lipophilic component of the essential oil of Danggui on aortic tension induced by phenylephrine of Radix Angelica sinensis, and its anti-hypertensive effect found that ligustilide can significantly reduce the phenylephrine-induced aortic tension in vitro with IC(50) about 64 mug/ml, but has no in vivo effect on systolic blood pressure in SHR rats when administrated orally. The data on transport of ligustilide across Caco-2 monolayer suggested an efficient intestinal absorption of ligustilide in vivo, implying that the non-effectiveness of ligustilide in vivo is not due to the poor absorption in the gastrointestinal tract, according to "Ligustilide reduces phenylephrine induced-aortic tension in vitro but has no effect on systolic pressure in spontaneously hypertensive rats" by Du JR, Yu Y, Yao Y, Bai B, Zong X, Lei Y, Wang CY, Qian ZM.(89)

3. Hawthorn is a shrubs and trees of the genus Crataegus, belonging to the family Rosaceae, native to temperate regions of the Northern Hemisphere in Europe, Asia and North America. The herb has been used in traditional medicine to treat heart disease and symptoms of heart diseases such as irregular heartbeat, high blood pressure, chest pain, hardening of the arteries, etc., circulatory disorders and respiratory illnesses.
a, Hypotensive effects
In the investigation of Hawthorn (Crataegus laevigata) leaves, flowers and berries used by herbal practitioners in the UK to treat hypertension in conjunction with prescribed drugs indicated that this is the first randomised controlled trial to demonstrate a hypotensive effect of hawthorn in patients with diabetes takin, according to "Hypotensive effects of hawthorn for patients with diabetes taking prescription drugs: a randomised controlled trial" by Walker AF, Marakis G, Simpson E, Hope JL, Robinson PA, Hassanein M, Simpson HC(90)

b. Cardiac effects
In the evaluation of the potential cardiac effects of two alcohol extracts of commercially available hawthorn found that the mechanism of cardiac activity of hawthorn is via the Na(+),K(+)-ATPase and intracellular calcium concentrations are influenced, according to "A comparison of the effects of commercially available hawthorn preparations on calcium transients of isolated cardiomyocytes" by Rodriguez ME, Poindexter BJ, Bick RJ, Dasgupta A.(91)

c. Cardiovascular disease
In the analyzing the effect of hawthorn in prevention and protection of cardiovascular disease indicated that these beneficial effects may in part be due to the presence of antioxidant flavonoid components. While a number of studies have been performed to evaluate the clinical efficacy of hawthorn, an international, multicenter, prospective clinical study including a large number of New York Heart Association (NYHA) class II/III heart failure patients is ongoing to test hawthorn's long-term therapeutic effects, according to "Hawthorn: potential roles in cardiovascular disease"by Chang WT, Dao J, Shao ZH.(92)

4. Maitake Mushroom is an edible mushroom in the genus Grifola, belonging to the family Meripilaceae, native to Japan. The herb has been used as liver protector and to enhance immune function, maintain health, preserve youth, increase longevity, etc.
a. Hypertension
In the assessment of effect of two commercially-available fractions labeled SX and D derived from the edible maitake mushroom in overcoming many age-associated metabolic perturbations, found that maitake mushroom fractions lessen age-related hypertension, at least in part, via effects on the RAS; enhance insulin sensitivity; and reduce some aspects of inflammation--actions that should lead to a longer, healthier life span, according to "Maitake mushroom extracts ameliorate progressive hypertension and other chronic metabolic perturbations in aging female rats" by Preuss HG, Echard B, Bagchi D, Perricone NV.(93)

b. Hyperlipidemia, hypertension, and hepatitis
In the investigation of Maitake (Grifola frondosa) and the effect of polysaccharide compounds in health-promoting potential, found that the D-fraction, the MD-fraction, and other extracts, often in combination with whole maitake powder, have shown particular promise as immunomodulating agents, and as an adjunct to cancer and HIV therapy. They may also provide some benefit in the treatment of hyperlipidemia, hypertension, and hepatitis(94)

c. Antioxidant properties
In the The optimization of solid-state fermentation conditions for mycelial growth in wheat by culinary-medicinal maitake mushroom and its health benefits found that that fermented wheat was effective in antioxidant activity, reducing power, scavenging ability on 1,1-diphenyl-2-picrylhydrazyl radicals, and chelating ability on ferrous ions. Total phenol contents of both extracts were 13.35 and 23.01 mg/g, respectively. according to "Preparation of culinary-medicinal maitake mushroom, Grifola frondosa (Dicks.: Fr.) S.F. Gray (Aphyllophoromycetideae)-fermented wheat and its antioxidant properties" by Huang SJ, Tsai SY, Lin SY, Liang CH, Lian PY, Mau JL.(95)

5. Motherwort is a perennial plant in the genus Leonurus, belonging to the family Lamiaceae, native to the Central Asia. The herb has been used in traditional medicine in Central Europe, Asia and North America as relaxed agent to treat nervousness, insomnia, heart palpitation, promote milk flow, uterine contractions, menstrual flow and to relieve menopausal symptoms and menstrual complaints.
a. Cardiac and electrophysiological effects
In the investigation of European Lamiaceae Leonurus cardiaca (Ph.Eur.) used for centuries as a remedy against tachyarrhythmia and other cardiac disorders with aqueous Soxhlet extract, found that mapping experiments with 256 electrodes on the heart surface showed a reduction of left ventricular pressure and an increase of relative coronary flow at concentrations of 1.0 and 2.0 mg/mL LCRE. Furthermore, the PQ-interval was prolonged and both the basic cycle length and the activation recovery interval increased, according to "Cardiac and electrophysiological effects of primary and refined extracts from Leonurus cardiaca L. (Ph.Eur.)" by Ritter M, Melichar K, Strahler S, Kuchta K, Schulte J, Sartiani L, Cerbai E, Mugelli A, Mohr FW, Rauwald HW, Dhein S.(96)

b. Cerebral protection
In the analyzing neuroprotective effects of purified Herba Leonuri (pHL) were evaluated in Wistar rats undergone middle cerebral artery occlusion (MCAO) found that Under the treatment of pHL, the infarct volume was reduced significantly from 20.75+/-0.03% to 15.19+/-0.02% (p<0.05). The neurological impairment was alleviated to 1.82 as compared to vehicle (2.43). Plasma antioxidant concentration was increased from 0.31+/-0.03 mM to 0.42+/-0.05 mM (p<0.05). DNA oxidative damage was reduced to 1.19+/-0.03 in stroke pHL treated group (p<0.05 as compared to vehicle group, 1.78+/-0.03). pHL could reduce the level of apoptosis and also the pro-apoptotic proteins, but increase the level of anti-apoptotic proteins, according to "Cerebral protection of purified Herba Leonuri extract on middle cerebral artery occluded rats" by Loh KP, Huang SH, Tan BK, Zhu YZ.(97)

6. Etc.

A.3. In traditional Chinese medicine perspective
1. Dr. Wang C, and the research team of the Department of Neurology, Beijing Tiantan Hospital, in the study of Management of SAH with traditional Chinese medicine in China showed that the main cause of SAH in China is aneurysm which takes up 30-50%, while over 90% aneurysm locates at Willis circle. Early surgery for SAH after aneurysm rupture is the dominant procedure to deal with SAH in China. Moreover, calcium antagonists rank the absolute leading position for cerebral vascular spasm (CVS) among medication-based treatment options. However, traditional Chinese medicine such as Salvia miltiorrhiza, Acanthopanax senticosus, Ginkgo biloba, Pueraria lobata, Liguisticum chuanxiong, cow bezoar, Diospyros kaki and Gynostemma pentaphyllum have been proven beneficial in CVS prevention and treatment, while Salvia miltiorrhiza and TCM soup have unique effects on bleeding absorption. In addition, aescine and some TCM soup might relieve strong headache after SAH. In general, TCM integrated with western medicine have shown unique advantages in the current treatment of SAH in China. However, it is a pity that China still lacks larger scale randomized controlled trials and research on SAH treatment focusing on TCM and the related mechanism of TCM on SAH still need to be investigated further(98).

2. Other suggested that red yeast rice (RYR) extract administration suppressed AngII-induced AAA and atherosclerosis associated with regulating inflammation responses independent of lipid-lowering effects. Red yeast rice may have preventive potential for patients with Abdominal aortic aneurysm (AAA)(99).

3. In fact, in the comparison of the a total of 32 patients with acute subarachnoid haemorrhage were randomly assigned to either a Chinese herbs extra group (CH) in which the patients were given complementary therapies of Chinese medicine and standard treatment, or a standard treatment only group (ST) in which patients were given standard treatment only, found that the average Glasgow Outcome Scale score 3 months after admission was 3.7±1.4 in the CH was greater than 3.0±1.7 in the ST (p=0.041). Average total admission days were 53.9±28.6 (median 61) in the ST longer than 28.1±19.1 (median 20.5) in the CH (p=0.004) and concluded that TCM for the treatment of patients with acute subarachnoid haemorrhage is of value because they can increase Glasgow Outcome Scale scores 3 months after admission and also because they can reduce total admission days(100).

4. Etc.
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