Monday, December 17, 2012

Bladder & Prostate Problems Perspective


BACKGROUND
The involuntary muscle in the Bladder Wall is named the Detrusor.  Urine from the Bladder flows out of the body through a duct called the Urethra.  The Urethra extends from the Bladder Neck to the outside of the body. There are two Sphincters that control the outflow of urine from the Bladder through the Urethra.  One is referred to as the Internal Urethral Sphincter and the other as the External Urethral Sphincter.  While the Internal Sphincter is under involuntary control, the External Sphincter is under voluntary control.  In men, the External Sphincter muscle surrounds the entire length of the Urethra. 
The Prostate is a doughnut-shaped, muscular male reproductive gland about the size of a walnut that sits directly beneath the Urinary Bladder and surrounds the Bladder Neck and the Urethra.  During ejaculation, the Prostate gland secretes an alkaline fluid that constitutes an integral part of the semen.  In men, the Urethra passes through the Prostate first and then through the Penis.  Besides urine, the male Urethra discharges semen during ejaculation.  The Prostate gland contains the enzyme 5-alpha-reductase that converts the hormone Testosterone into the mutant hormone Dihydrotestosterone (DHT) which causes both Prostate Enlargement and Hair Loss.  
BLADDER EMPTYING
When the bladder gets about half full with approximately 250 mL of urine, receptors in the Bladder transmit signals to the brain that it’s about time to empty the Bladder.  Eventually, when a person is almost ready to urinate, voiding reflexes stimulate involuntary Detrusor muscle contraction (to expel urine from the Bladder) and involuntary Internal Sphincter muscle relaxation (to let urine flow out of the Bladder into the Urethra).  Concurrently, the person consciously relaxes the voluntary External Sphincter muscle to let urine drain from the Urethra to the outside.  Finally, the person may willfully stop the flow of urine in midstream or simply conclude the emptying phase by contracting the voluntary External Sphincter muscle. 
OVERACTIVE BLADDER
Overactive Bladder (OAB) is a debilitating medical condition caused by unpredictable muscle spasms in the Bladder due to overactivity of the involuntary Detrusor muscle.  When the Detrusor muscle contracts more often than usual, the abnormal muscle contractions create the urge to urinate even when the bladder is not completely full, resulting in the onset of urinary symptoms such as Urgency (with or without Incontinence), Frequency, and episodes of Nocturia.  For urine to exit the bladder, both internal and external sphincters must be open.  Malfunctioning of these sphincter muscles can lead to the loss of voluntary control over urinary continence, resulting in Urge Incontinence, which is another name for OAB. 
BENIGN PROSTATIC HYPERPLASIA
The term Benign Prostatic Hyperplasia (BPH) implies an overgrowth of the prostate cells during the aging process, leading to enlargement of the Prostate gland.  BPH is the most common, non-cancerous condition that occurs when Testosterone in the Prostate is transformed to DHT by the action of the enzyme 5-alpha-reductase.  By binding to its receptors in the Prostate, DHT stimulates Prostate cells to grow and multiply excessively and the Prostate gland to enlarge.  In summary, the excessive build-up of mutant DHT is the root cause of abnormal enlargement of the Prostate. 
Enlarged Prostate presses against the Urethra and obstructs the outflow of urine from the Bladder, causing Urinary Retention due to incomplete bladder emptying.  As a result of this, the Detrusor muscle becomes extraordinarily more irritable and prone to spasmodic contractions that elicit a constant urge to urinate, regardless of how much urine is left in the Bladder.  When the prostate enlarges too much, urination becomes difficult, and the risk of Urinary Tract Infection increases due to acute Urinary Retention.
Common Symptoms of an Enlarged Prostate Gland may include Urgency, Frequency, Incontinence, Nocturia, Incomplete Emptying, Weak Stream, Dribbling, Hesitancy, Urine Retention, Burning Urination, and Lower Back Pain.  Since these symptoms of BPH overlap those of OAB, the possibility of both the BPH and OAB conditions occurring at the same time should not be ruled out. 
ERECTILE DYSFUNTION
Erectile Dysfunction (ED), a common disorder in men, denotes the inability to achieve and maintain a full erection during sexual arousal.  This ED condition is attributed to the existence of the enzyme Phosphodiesterase-5 (PDE-5), which plays a key role as a major risk factor because it destroys the Nitric Oxide (NO) responsible for relaxing blood vessels to increase blood flow to the Penis.  Research has shown beyond the shadow of a doubt that inhibitors of the enzyme PDE-5 have the ability to relieve ED symptoms. 
Currently, drugs such as Cialis (tadalafil), Levitra (vardenafil), and Viagra (sildenafil), classified as PDE-5 inhibitors are often used to relieve ED symptoms in men.  Studies have found that there is an association between the BPH and ED conditions. 
DRUG THERAPY
The First out of the five categories of prescription drugs listed below deals with the treatment of OAB alone.  The next three categories are used to treat BPH condition as an underlying cause of OAB symptoms in men.  The last category based on the PDE-5 enzyme inhibition precepts is specifically for the treatment of both BPH and ED syndromes in men. 
  I.          Anticholinergics
Anticholinergic medications are the mainstay of OAB therapy.  Anticholinergic drugs approved for the treatment of OAB symptoms include: Detrol (tolterodine), Ditropan (oxybutynin), Enablex (darifenacin), Sanctura (trospium), Toviaz (fesoterodine), and Vesicare (solifenacin).  Most of these drugs have a host of annoying side effects such as: Dry Mouth, Urinary Retention, Constipation, Blurred Vision, and Rapid Heartbeat. 
II.          Alpha-1 Blockers
Classified as the alpha-1 adrenergic receptor blockers, Cardura (doxazosin), Hytrin (terazosin), Flomax (tamsulosin), Rapaflo (silodosin), and Uroxatral (alfuzosin) relax the smooth muscles of the Bladder Neck and the Prostate to relieve the symptoms of BPH without reducing the size of the Prostate.  Potential side effects including, but not limited to Skin Rash, Low Blood Pressure, Blurred Vision, Dry Mouth, Sleep Disruption, and Difficulty Ejaculating should not be overlooked. 
III.          5-Alpha-Reductase Inhibitors
When used in men with BPH, Avodart (dutasteride) and Proscar (finasteride) drugs inhibit the enzyme 5-alpha-reductase from converting Testosterone to DHT.  By suppressing the production of DHT, these drugs cause shrinkage of the Prostate.  As the Prostate shrinks, urine outflow improves and Overflow Incontinence is reduced.  Bothersome side effects of these two drugs include ED, and diminished libido. 
IV.          5-Alpha-Reductase Inhibitor and Alpha-1 Blocker Combo
Jalyn (dutasteride plus tamsulosin), a combination of 5-alpha-reductase inhibitor and alpha-1 blocker drugs, is designed to shrink the Prostate as well as relax the Prostate and Detrusor muscles in order to control the symptoms of both OAB and BPH. 
V.          Phosphodiesterase-5 Inhibitor
Ejaculation during frequent intercourse removes Prostatic fluid and shrinks the Prostate.  As a unique PDE-5 inhibitor, Cialis per se has been approved by the FDA for the treatment of men with both ED and BPH symptoms at the same time.  PDE5 inhibitors are contraindicated in those who are taking nitrate medications for chest pain.  Studies are underway to evaluate Cialis in combination with selective Alpha-1 Blockers. 
ALTERNATIVE THERAPY
Surgery is the last resort for OAB and BPH treatments.  Simply put, conventional treatments, designed to reduce Urinary Frequency by extending the time between Urge and Voiding, may not always be effective.  For those who tend to shy away from prescription drugs because of their adverse side effects, herbal alternatives come in very handy as the second best choice. 
People who don’t need Rx drugs or surgery might consider using Herbal remedies to relax the Prostate muscle and reduce the size of the Prostate.  Apparently, natural and herbal alternatives are relatively safe, effective, and less expensive than the counterpart drug therapies to relieve BPH symptoms without untoward side effects. 
Natural Remedies
Several herbs have been found to be effective in relieving OAB symptoms in men due to enlarged Prostate.  Medicinal herbs such as Saw Palmetto, Beta Sitosterol, Stinging Nettle, Pygeum Bark, and Pumpkin Seeds seem to have the potential to shrink the enlarged Prostate naturally by inhibiting the enzyme 5-alpha-reductase from converting Testosterone to DHT.  Likewise, Valerian herb does indeed help relax smooth muscles in the bladder, thereby reducing the spasms that create urinary urgency and easing the need to urinate frequently. 
·     Lipophilic extract of Saw Palmetto berries is the most commonly used non-prescription therapy for the treatment of BPH syndrome.  A daily dose of 320 mg Saw Palmetto Berry Extract standardized to 85-95% Fatty Acids and Sterols has been reported to be effective in alleviating BPH symptoms.  There are no official dosage recommendations available for Beta Sitosterol, Stinging Nettle, Pygeum Bark, Lycopene and Pomegranate Extracts, Pumpkin Seeds, Sesame Seeds, and Tribulus Terrestris (Gokhru) to improve Prostate health.  http://www.youtube.com/watch?v=09btsUyt1zk
·     Vitamins such as B6, B12, D and E, and minerals including Copper, Magnesium, Selenium, and Zinc also play an important role in treating the Enlarged Prostate.  Pumpkin seeds are a natural source of Zinc, a mineral essential to normal Prostate function. 
·     Sesame seeds have the potential to relieve BPH symptoms and lower Blood Cholesterol. Sesame seeds contain Phytosterols and Lignans (a class of Phytoestrogens with antioxidant activity) such as Sesamin and Sesamolin.  Sesame seeds are one of the richest sources of Phytosterols, whereas Sesame seeds and Flaxseeds are two of the richest sources of Lignans. The most abundant Phytosterol found in Sesame Seeds is none other than Beta Sitosterol. Other Phytosterols include Campesterol and Stigmasterol. Total Phytosterol content of Sesame Seeds and Pumpkin Seeds corresponds to 400 mg/100 g and 265 mg/100 g, respectively. Beta-Sitosterol in high doses helps shrink enlarged Prostate, improve Libido, and prevent Hair Loss. The presence of Selenium and Zinc minerals in Sesame Seeds may also help improve Prostate health.
·     Isoflavone Phytoestrogens are plant-derived compounds that have a chemical structure similar to that of human Estrogen.  By providing estrogen-like health benefits, Soy isoflavones help relieve OAB symptoms in women and BPH symptoms in men. 
·     Quercetin, a naturally occurring bioflavonoid found in Apples, Onions, and Red Grapes, has been shown to significantly reduce BPH symptoms by acting as a natural cofactor in reducing Prostate Swelling. 
·     Valerian Root Extract powder traditionally used as a sleep aid may also act as a natural muscle relaxant for urinary tract problems.  Valerian Root Extracts are prepared from the standardized dry extract containing 0.8% Valerenic acid. 
·    Freeze-dried (or spray-dried) Aloe Vera Extract preparations for Oral administration are used quite often to strengthen the muscles of the urinary system and relieve prostate-related symptoms of incontinence. 

·   Last but not least, the New Thermobalancing Medical Device invented by Dr Simon Allen is designed not only to treat Lower Back Pain and Sciatica, but also to reverse BPH and improve libido by reducing the Prostate Size naturally. For more information on this New Natural Thermobalancing Therapy for Enlarged Prostate, please watch the enclosed Video:
 


Saturday, October 6, 2012

BLEEDING & CLOTTING DISORDERS


Coagulation Basics
Coagulation is a process by which blood forms fibrin-bound platelet plugs to stop bleeding.  Fibrin threads play a key role in holding platelets together to form a durable Platelet Plug.  Disorders of blood coagulation can lead to an increased risk of abnormal clotting (thrombosis) or bleeding (hemorrhage). 
Clotting Cascade
·        Fibrin is formed from Fibrinogen in a series of reactions called the Clotting Cascade.
·       Enzymes that comprise the clotting system are called Clotting Factors.
·       Clotting Factor III is the primary cellular initiator of Clotting Cascade
·       Activation of Vitamin K-dependent Clotting Factors II, VII, IX, and X results in the conversion of Prothrombin to Thrombin which in turn initiates the conversion of soluble Fibrinogen to insoluble Fibrin, leading to the formation of a stable meshwork around the platelet plugs.
·       Damaged Vascular Walls trigger activation of blood Clotting Cascade by exposing the Collagen present under the layer of Endothelial Cells to the bloodstream.

Platelets
·        Thrombocytes (also called Platelets) circulate through the bloodstream to constantly monitor and coordinate blood coagulation.
·       Platelets convert Arachidonic Acid (AA) to Thromboxane (TXA2) via the Cyclooxygenase enzyme (COX-1) pathway.
·       Thromboxane constricts blood vessels and causes Platelets to Clump together
·       Platelet life-span is 8 to 10 days
Platelet Aggregation
·       When there is an injury to the blood Vessel Wall, the free-floating sentinel Platelets rush to the affected area and clump together (aggregate) to form a Plug to seal off the leak to prevent bleeding.
·       Once Platelets circulating in the blood adhere to exposed Collagen, they start to secrete the following chemical mediators:
1)     Thromboxane (TXA2) to stimulate Platelet Aggregation for blood clotting
2)     Serotonin (5-HT) to constrict blood vessels to prevent bleeding
3)     Thromboplastin (Clotting Factor III) to initiate the Clotting Cascade
·        Platelet Aggregation at Vascular Endothelium Injury Sites is a Prerequisite for the ensuing Clotting Cascade.
·       Both Platelet Aggregation and Clotting Cascade are involved in Thrombus Formation
·       Aspirin inhibits TXA2-induced Platelet Aggregation by irreversibly inactivating COX-1
·       Plavix (clopidogrel) inhibits TXA2-induced Platelet Aggregration






Endothelium
·        Vascular Endothelial Cells convert Arachidonic Acid (AA) to Prostacyclin (PGI2) by the Cyclooxygenase enzyme (COX-2) pathway.
·       Prostacyclin dilates blood vessels and inhibits Platelet Aggregation.
·       Persantine (dipyridamole) stimulates the release of PGI2 from blood vessels.
Natural Blood Thinners
After the leak has been repaired with a blood clot (thrombus), the body reacts by releasing the following chemical messengers to counteract the effects of endogenous clotting mediators:
·       Prostacyclin (PGI2) that inhibits Platelet Aggregation to promote blood thinning
·        Tissue Plasminogen Activator (TPA) that activates Plasminogen into Plasmin (a thrombolytic substance) that has the capacity to degrade and dissolve fibrin-based thrombus clots.
·       Antithrombin (AT), a naturally occurring Thrombin Inhibitor, binds to Heparin as a cofactor to inhibit Factor II (Thrombin) and Factor X.

Heparin is a group of straight-chain Anionic mucopolysaccharides

Drug Therapy Types
1)     Anticoagulants
·        Coumadin or Warfarin as Vitamin K Antagonists
·        Unfractionated Heparin (UFH) and Low Molecular Weight Heparin (LMWH)
2)     Antiplatelet Agents
·        Aspirin
·        Aggrenox (Aspirin / Dipyridamole Combo)
·        Aggrastat or Tirofiban for Intravenous Use
·        Integrilin or Eptifibatide for Intravenous Use
·        Persantine or Dipyridamole
·        Plavix or Clopidogrel
·        Pletal or Cilostazol
·        Reopro or Abciximab for Intravenous Use
·        Ticlid or Ticlopidine
3)     Thrombolytics
·        TPA for Intravenous Use
·        Activase or Alteplase (Recombinant TPA) for Intravenous Use
·        Streptokinase for Intravenous Use
·        Urokinase for Intravenous Use
Coagulation Monitoring
Anticoagulation medications including Warfarin are often prescribed to help prevent blood from clotting.  Patients with Atrial Fibrillation (AF) usually take Warfarin to reduce the risk of Strokes and Heart Attacks.  Anticoagulant Therapy should therefore be monitored frequently to avoid excessive bleeding due to over-dosing of the medication.  The blood testing to assess coagulation status includes the PT test using the INR as a standard unit of measurement. 
Standard Blood Tests
·        Prothrombin Time (PT) in seconds for the blood to clot
·        Traditional PT Ratio = (Patient PT ÷ Control PT)
·        International Sensitivity Index (ISI) to convert PT into INR
·        International Normalized Ratio (INR) = (Patient PT ÷ Control PT)ISI
·        Log INR = ISI x Log of PT Ratio of the Patient over the Control
·        INR testing used to monitor Coumadin or Warfarin Therapy
·        INR testing within target range will reduce the risk of bleeding and clotting
·        INR is about 1.0 in Healthy People
·        INR therapeutic range for Atrial Fibrillation (AF) is between 2 and 3
·        INR therapeutic range for Mechanical Heart Valve (MHV) is between 3 and 4
·        Activated Partial Thromboplastin Time (aPTT) in seconds for blood clotting
·        aPTT for monitoring Heparin Anticoagulant Therapy
Portable PT-INR Monitor
·        Approved by the FDA
·        Covered by Medicare and most Insurance Companies
·        Used as a Point-Of-Care (POC) Device for self-testing by Patients at Home
·        Prescribed by your Doctor so that you can do the test yourself
·        PT-INR testing on a regular basis helps those who are on Warfarin Therapy
·        CoaguChek XS PT-INR Meter manufactured by Roche

CAUTION
The downside of blood thinners is that they pose a risk of bleeding that may manifest itself in the form of Purple Skin Bruises. Therefore, dose-related blood thinning Therapy should be monitored Once a Week by the Patient at Home using a Portable PT-INR meter to adjust the dose to keep INR level within the target therapeutic range. 

OTC Supplements as Blood-Thinners
1)     Aspirin, 81 mg
·        Inhibits TXA2-induced Platelet Aggregration
2)     Ginkgo Biloba Leaf, 200 mg
·        Inhibits Platelet Aggregration induced by platelet-activating factor (PAF).
·        200 mg of Leaf Powder equivalent to 4 mg of (50:1) Leaf Extract
3)     Omega 3 Fish Oil, 1000 mg
·        Inhibits Platelet Aggregration by releasing Prostacycline (PGI3)
·        EPA 180 mg and DHA 120 mg from Fish Oil inhibit Platelet Aggregration
4)     Vitamin E, 400 IU
·        Inhibits Platelet Aggregration by promoting Prostacycline (PGI2) Synthesis
·        Estrogens in birth control pills can deplete Vitamin E.
Bleeding Disorders
  • Selective Serotonin Reuptake Inhibitor (SSRIs) increase the Risk of Bleeding Disorders
  • Serotonin Stored in the Delta Granules of Platelets
  • Serotonin stimulates Platelet Aggregation, resulting in Blood Clotting
  • SSRIs block Reuptake of Serotonin by Platelets, depleting Platelet Serotonin Content
  • SSRIs inhibit Platelet Aggregation, resulting in Blood Thinning