Slide

For Prostate Health


Anatomy of Male Reproductive System
 The prostate (from Greek- prostates, literally "one who stands before", "protector", "guardian") is an exocrine gland (secrete their products into ducts that lead directly into the external environment) of the male reproductive system in most mammals.  The prostate gland sits just below the bladder and in front of the rectum, partially surrounding the urethra which carries urine from the bladder out of the body.  Forming part of the male reproductive system, the prostrate is responsible for the production of a clear liquid which makes up about one third of the seminal fluid used to carry and protect the male sperm during intercourse. During ejaculation, the prostate squeezes this fluid into the urethra, and it's expelled with sperm as semen.


Anatomy of Male Reproductive System
 The prostate gland anatomy :  The outermost part is called the peripheral zone and consists of 70% of the normal prostate gland in adult men.  The central zone is 25% of the normal prostate gland that surrounds the ejaculatory ducts.  The third, transitional zone accounts for 5% of the prostate volume and
is responsible for the prostate enlargement problems.
Background
The Primary Male Hormones
Androgens also called androgenic hormone or testoid, are any of a group
of hormones that play a major role in the development and maintenance of the male reproductive system and of masculine secondary sexual characters, for example, the seminal vesicle and prostate gland.  Testosterone is the main and most active androgen, it works directly on
many tissues of the body. It is an anabolic steroid and primarily produced by cells in the testes, although small amounts are also secreted by the adrenal glands. In men, testosterone is responsible for the development of male sexual characteristics. It plays a key role in the development of male reproductive tissues such as the testis and prostate as well as promoting secondary sexual characteristics such as increased muscle, bone mass and hair growth.  In normal males, it is produced at the onset of puberty by the testes in response to stimulation by hormones called gonadotrophins that originate
in the anterior pituitary gland and the hypothalamus, a part of the brain.
The Primary Male Hormones
Androgens allow ejaculations to begin, usually between the ages of 11-15,
in response to sexual fantasies or masturbation. After puberty, the testes produce testosterone for the rest of a man's life, but in decreasing amounts as men reach their late 40s or early 50s.  Testosterone, the main circulating androgen, is not the primary nutrient
for the prostate. That role belongs to Dihydrotestosterone (DHT), which is
derived from testosterone within prostate cells by the action of the
enzyme 5α-reductase.
5-α reductase are enzymes involved in steroid metabolism. They participate in
3 metabolic pathways: bile acid biosynthesis, androgen and estrogen metabolism, and prostate cancer.  Testosterone in serum has approximately 10 times the concentration of
DHT, but in the prostate gland, the ratio is more or less reversed.
DHT mediates prostatic growth, acne, facial beard, and male pattern
Dihydrotestosterone (DHT)
 In men, approximately 5% of testosterone undergoes 5α-reduction to form the more potent androgen, dihydrotestosterone.
DHT has three times greater affinity for androgen receptors than
testosterone and has 15-30 times greater affinity than adrenal androgens.  During embryogenesis DHT has an essential role in the formation of the male
external genitalia,  and in the adult DHT acts as the primary androgen in the prostate and hair
follicles.  Within the prostate, DHT is present in higher concentration and also binds more tightly to the androgen receptor than does testosterone. Thus, DHT
remains at high levels in the prostate throughout life, without the age-
related decline seen in circulating testosterone. For this reason, DHT must
exert at least a permissive role in the development of BPH.


The Role of Female Hormones in
Prostate Growth

 Studies of the receptors' tissue distribution and expression pattern indicate that Estrogen Receptor (ER) α has a broad expression pattern, whereas ERβ has a more focused pattern with high levels in the prostate, epididymis, lung, and hypothalamus  Estrogens play a role in proliferation in the prostate, but interestingly are capable of stimulating as well as inhibiting growth. This duality of action is specifically due to activation of each ER: ERα and ERβ.  ERα and ERβ are distributed in the prostate in a different manner suggesting that the two receptors have different roles in this organ.  ERα is located in stromal tissue and is not detectable in the  ERβ is present in the epithelium, and it actually regulates AR. Prostate under a microscope


ERα and ERβ in Prostate
Pathophysiology

Risbridger G P et al. J Mol Endocrinol 2007;39:183-188  The two distinct estrogen receptors, ERα and ERβ, have unique and sometimes opposing roles.  ERβ in the epithelium may be important in regulating prostatic growth and acts to restrain the stimulatory action of ERα The Role of ERα and ERβ in Prostate
Growth vs. Restraint

 In prostates from mice in which the ERβ gene has been inactivated (βERKO), androgen receptor (AR) levels are elevated leading to prostatic hyperplasia with aging.  Thus, ERβ has an anti-proliferative role in prostatic epithelium.  Excessive exposure to estrogens during critical stages of development or long-term treatment with estrogens or androgens leads to prostatic neoplasia (microscopic lesion in the prostate, thought to be a precursor to prostate cancer).  In apparent contrast, diets rich in phytoestrogens, particularly soy products, are associated with a low risk of BPH, prostate cancer and have chemopreventive properties in experimental tumor models.


Introduction Benign Prostatic Hyperplasia


Introduction Benign
Prostatic Hyperplasia- BPH

Benign prostatic hyperplasia- BPH. "benign"
means "not cancerous" while "hyperplasia" or "hypertrophy" means "too much growth", is a non-cancerous disease.  It is a part of the normal aging process and not a dangerous medical condition, however, a considerably uncomfortable one, which can be progressive especially if left untreated.  It begins to develop before age 30 with almost  10% of men having histologic evidence of BPH by 40 years of age,  50% of men showing evidence by age 60 &  90% of men in their 80s.  Overall, nearly 80% of men will develop BPH. BPH Symptoms
 Prostate gland enlargement can cause bothersome urinary symptoms referred to as Lower Urinary Tract Symptoms (LUTS)  Pressure on the urethra and cause difficulty urinating,  Abnormally frequent urination, both day and night,  A perpetual, urgent need to urinate,  Blood in the urine.  If left untreated over time, BPH can completely block/squeeze the urethra, which can lead to other urinary tract problems that can damage the kidneys.


Stages of BPH
Normal Prostate Mild Hypertrophy Severe BPH
BPH Pathology
 BPH can be a progressive disease, especially if left untreated.  Incomplete voiding results in stasis of bacteria in the bladder residue and an increased risk of urinary tract infections.  Urinary bladder stones are formed from the crystallisation of salts in the residual urine.  Urinary retention, termed acute or chronic, is another form of  Acute urinary retention is the inability to void, while in  Chronic urinary retention the residual urinary volume gradually increases, and the bladder swells.  Some patients that suffer from chronic urinary retention may eventually progress to renal failure. Impact of BPH
 With the ever-increasing proportion of the population over 65 years of age worldwide, BPH is becoming an increasingly important medical problem in this millennium.  The disease can have a profoundly negative impact on men's quality of life, often causing them to limit or avoid basic activities of daily living.  Many men who develop BPH will seek treatment for bothersome lower urinary tract symptoms.  Many options exist to treat benign prostatic hyperplasia (BPH), including watchful waiting, medications, nonsurgical therapies, and surgery. Treatment for BPH is based on the severity of symptoms.  Available treatment options directed at decreasing symptoms and improving quality of life include: herbal or medical therapy, minimally invasive therapy, and surgical intervention.  All treatment options have been demonstrated to improve symptoms in patients with BPH; however, they are not all equally efficacious and are often associated with an increased risk of side effects or complications. BPH Current Treatment Options-
Medical Therapy

 Medical therapy for BPH attempts to shrink or stop the growth of the prostate or open the urethral channel within the prostate, without using  Two main types of medication are prescribed for BPH.  alpha blockers- They relax muscles around the bladder neck and in the
prostate, making urination easier. Alpha blockers don't prevent further prostate enlargement. But, for many men, they effectively relieve BPH symptoms (terazosin, doxazosin, tamsulosin (Flomax®), & alfuzosin).  The second type of medication inhibits the enzyme 5-alpha reductase,
which is needed for the production of dehydrotestosterone (DHT). For men with large prostates, these drugs may produce a noticeable improvement in symptoms. But they're generally not effective for men who have only a mildly to moderately enlarged prostate. (finasteride (Proscar®), and dutasteride).  Clinical data shows that finasteride (5-α reductase) and doxazosin (α blockers) together is more effective than using either drug alone to relieve symptoms and prevent BPH progression. The dual-drug regimen reduced the risk of BPH progression by 67%, compared with 39% for doxazosin alone and 34%
for finasteride alone… Important Safety Information- Flomax
(tamsulosin HCl)- Alpha Blocker

 Caution should be exercised with concomitant administration of warfarin (anticoagulant)and FLOMAX capsules  When taking FLOMAX, avoid driving or hazardous tasks until you know how FLOMAX will affect you, especially after your first dose or change in
dose, as a sudden drop in blood pressure may occur. Postural
hypotension, dizziness, and vertigo were detected more frequently and
there is a potential risk of syncope.
 FLOMAX may increase the risk of eye complications during and after a cataract operation.  The most common adverse events were headache, dizziness, rhinitis, infection, abnormal ejaculation, asthenia, back pain, diarrhea,
pharyngitis, chest pain, cough increased, somnolence, nausea, sinusitis,
insomnia, libido decreased, tooth disorder, and blurred vision.


Important Safety Information- Proscar®
(finasteride)- 5-alpha reductase inhibition

 PROSCAR may increase the chance of a more serious form of prostate  The most common side effects of PROSCAR include: trouble getting or keeping an erection (impotence) decrease in sex drive decreased volume of ejaculate ejaculation disorders enlarged or painful breast.  The following have been reported in general use with PROSCAR and/or finasteride at lower doses: allergic reactions, including rash, itching, hives, and swelling of the lips and face rarely, some men may have testicular pain trouble getting or keeping an erection that continued after stopping the medication in rare cases, male breast cancer has been reported. BPH Current Treatment Options –
Non-Surgical Therapies or Surgery

If medication is not well tolerated, or symptoms don't improve, the next step is nonsurgical therapies or surgery. Non-surgical therapies include:

Transurethral Microwave Therapy (TUMT)- uses heat in the form of
microwave energy
to destroy the inner portion of the prostate gland.
Transurethral Needle Ablation (TUNA)- uses radio waves to heat and
destroy the part of the prostate that's impeding urine flow.
 Although these procedures can reduce prostate size, they haven't been shown to be effective long-term. A recent addition to the minimally-invasive techniques for treating BPH is
GreenLight Laser PVP (Photoselective Vaporization of the Prostate)- It's a
procedure which uses the technology of high-powered laser light combined
with fiber optics
to vaporize the overgrowth of prostate cells. The intense
pulses of light emitted from the fiber are absorbed by the blood. Within
moments the temperature of the blood becomes so great it causes the
nearby cells to vaporize.
 This technique is too new for long-term studies to have been completed. BPH Current Treatment Options –
Non-Surgical Therapies or Surgery (cont.)

 The most common side effects experienced with GreenLight:  Hematuria – Blood in the urine  Bladder spasm or urgency – Cramping in the bladder or an urgent  Irritation of the urinary tract – Frequent urination, burning sensation  Retrograde ejaculation  Open prostatectomy is the most effective therapy for relieving symptoms of an enlarged prostate. However it is a major abdominal surgery requiring a lengthy hospital stay and months of recovery.  Furthermore the surgery has the highest risk of side effects, such as loss of bladder control and erectile dysfunction. BPH Current Treatment Options-
Phytotherapy

 Phytotherapy or the use of plant extracts for treating BPH symptoms was first described in Egypt in the 15th century BC.  Currently, phyto-therapy is common in Europe and is increasing in the western hemisphere.  Phytotherapeutic agents represent nearly half the medications dispensed for treatment of BPH in Italy, compared with 5% for a- blockers and 5% for 5 a-reductase inhibitors.  In Germany and Austria, phyto-therapy is the first-line treatment for mild-to-moderate lower urinary tract symptoms and represents more than 90% of all drugs prescribed for the treatment of BPH.  In the United States, phyto-therapies for BPH are readily available as non prescription dietary supplements. Most of these compounds are unlicensed and often promoted to "maintain a healthy prostate" and as a natural and harmless treatment of BPH symptoms. BPH Current Treatment Options-
Phytotherapy

Saw palmetto (Serenoa repens or Sabal serrulata) has long been used in
Europe to treat an enlarged prostate or benign prostatic hyperplasia (BPH).  Saw palmetto causes a drop in estrogen receptors within prostate cells relieving symptoms; easing urinary symptoms and increasing urine flow.  Some studies suggest that its effects are similar to finasteride, but with fewer and less severe side effects. While most of the research showed saw palmetto can cause mild reactions like headache, nausea, and dizziness, the prescription drug was more likely to cause impotence.  Another botanical, Pygeum africanum, which comes from an African
evergreen tree, has also been shown to relieve BPH. Researchers theorize that it either reduces prostate inflammation by displacing dehydrotestosterone in the prostate gland or by interfering with the production of pro-inflammatory prostaglandins through Beta sitosterol, one of the active ingredients in Pygeum africanum. A New Horizon for
Prostate Health

Proprietary Information Se-cure Pharmaceuticals Ltd. Do no copy or transfer without Se-cure's permission a Dietary Supplement for BPH
Management
 Brizo™ is a dietary supplement based on a new ingredient- soy extract.  Diets rich in phytoestrogens, particularly soy products, are associated with a low risk of BPH, prostate cancer and have shown chemopreventive properties.  The mechanism of action of Brizo™ targets several pathways that are at the base of BPH:  Brizo™ bonds to the Estrogen Receptors (ER), acting differently on ERβ and  Brizo™ bonds to Androgen Receptors (AR) blocking the ability of Dihydrotestosterone (DHT) to attach to the AR and mediate prostatic growth.  Brizo ™ provides a completely fresh approach for the management of Proprietary Information Se-cure Pharmaceuticals Ltd. Do no copy or transfer without Se-cure's permission Data to date
Proprietary Information Se-cure Pharmaceuticals Ltd. Do no copy or transfer without Se-cure's permission  A multi national open labeled prospective efficacy survey was conducted.  Countries: Norway, UK & Israel.  Survey incl. to date 178 males (to date) in general good health and at least 50 years of age, with symptoms of moderate to severe benign prostatic hyperplasia.  The men were asked to fill a questionnaire looking at BPH symptoms (International Prostate Symptom Score-IPSS) at enrollment and week 4, 8 and 12 of treatment. Proprietary Information Se-cure Pharmaceuticals Ltd. Do no copy or transfer without Se-cure's permission International prostate symptom score (IPSS)

Incomplete emptying
Over the past month, how often have you had a sensation of not emptying
your bladder completely after you finish urinating?
Frequency
Over the past month, how often have you had to urinate again less than
two hours after you finished urinating?
Intermittency
Over the past month, how often have you found you stopped and started
again several times when you urinated?
Urgency
Over the last month, how difficult have you found it to postpone
urination?
Weak stream
Over the past month, how often have you had a weak urinary stream?
Straining
Over the past month, how often have you had to push or strain to begin
Nocturia Over the past month, many times did you most typically get up to urinate from the time you went to bed until the time you got up in the morning? Total IPSS score
Total score: 0-7 Mildly symptomatic; 8-19 moderately symptomatic; 20-35 severely symptomatic.

Survey Results to date

Ave. IPSS Change - Baseline – week 12*
Total score:
20-35 Severely symptomatic. 8-19 Moderately symptomatic 0-7 Mildly symptomatic *p < 0.05
International Prostate Symptom Score
Proprietary Information Se-cure Pharmaceuticals Ltd. Do no copy or transfer without Se-cure's permission Proprietary Information Se-cure Pharmaceuticals Ltd. Do no copy or transfer without Se-cure's permission The Primary Male Hormones
Androgens play a major role in the development and maintenance of the
male reproductive system.  Dihydrotestosterone (DHT), an androgen derived from testosterone within
prostate cells by the action of the enzyme 5α-reductase, is the primary
nutrient for the prostate
 Approximately 5% of testosterone undergoes 5α-reduction to form the more potent androgen, DHT.
DHT mediates prostatic growth, acne, facial beard, and male pattern
DHT has three times greater affinity for Androgen Receptors than
testosterone and has 15-30 times greater affinity than adrenal androgens.  DHT remains at high levels in the prostate throughout life, without the
age-related decline seen in circulating testosterone. Proprietary Information Se-cure Pharmaceuticals Ltd. Do no copy or transfer without Se-cure's permission The Role of Female Hormones in
Prostate Growth

 Estrogens play a role in proliferation in the prostate, but interestingly are capable of stimulating as well as inhibiting growth.  ERα and ERβ are distributed in the prostate in a different manner suggesting that the two receptors have different roles in this organ.  ERα is located in stromal tissue and is not detectable in the epithelium.  ERβ is present in the epithelium, and it actually regulates AR and
prostatic growth, restraining the stimulatory action of ERα
 In prostates from mice in which the ERβ gene has been inactivated (βERKO), Androgen Receptor (AR) levels are elevated leading to prostatic hyperplasia with aging.  Thus, ERβ has an anti-proliferative role in prostatic epithelium. Proprietary Information Se-cure Pharmaceuticals Ltd. Do no copy or transfer without Se-cure's permission How does Manage BPH?
The Mechanism of Action of Brizo™ :
Brizo™ activates and bonds to ERβ (agonistic activity) which is an important
modulator of prostatic growth. By bonding to ERβ, Brizo™ regulates Androgen
Receptors (AR) and prostatic growth and acts to restrain the stimulatory action
of ERα, where Brizo
bonds and blocks (antagonist activity), reducing/limiting
prostatic growth.
Brizo™ bonds and blocks Androgen Receptors (antagonistic effect), blocking the
ability of Dihydrotestosterone (DHT) to attach to the AR and encourage prostate proliferation. Proprietary Information Se-cure Pharmaceuticals Ltd. Do no copy or transfer without Se-cure's permission  The combined effect of the different activities reduces the pressure on the urethra, easing urine flow, and decreases the prostate size.  A significant beneficial effect of Brizo™ on the bothersome symptoms can
be felt within the 1st month of treatment, which progresses with longer intake.  The improvement is felt by lessening of waking up in the middle of the night in order to urinate, significant ease of urination, full voidance…  Within 90 days a significant reduction in the prostate size can be seen. Proprietary Information Se-cure Pharmaceuticals Ltd. Do no copy or transfer without Se-cure's permission Safety in regards to Prostate Cancer
 In order to assure Brizo™'s safety in regards to its possible impact on
prostate cancer, a pre-clinical tissue culture model has shown that Brizo™
surpressed the growth of prostate cancer.
 Thus, Brizo™ was shown to minimize its creation of a potential risk factor
in the event of any development of prostate cancer. For more information contact:
Esti Grunbaum
VP BD & Marketing
Se-cure Pharmaceuticals Ltd.
Email: esti.g@se-curepharma.com
Tel: +972-3-9731111
www.se-curepharma.com
Proprietary Information Se-cure Pharmaceuticals Ltd. Do no copy or transfer without Se-cure's permission

Source: http://www.betterhealthinternational.com/lib_Brizo_Prostate_Support.pdf

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Estás de corazón Red Hispanoportuguesa de Espiritualidad Apostólica Marista A la memoria de Servando, Julio, Miguel Angel y Fernando que con su gesto de entrega total a los más pobres, hasta llegar al martirio, nos enseñaron cómo se unifica la vida en el amor, cómo se adora y sirve a Dios en la vida cotidiana y cómo ésta se hace presente

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Das 5. Buch Mose oder TitelDer Titel »Deuteronomium« entstammt einem Übersetzungsfehler des Ausdrucks »Abschrift dieses Gesetzes« in 17,18 aus der gr. Septuaginta (LXX), wo sich die Übersetzung »zweites Gesetz« findet, was in der lateinischen Version (Vulgata) mit Deuteronomium wiedergegeben wurde. Der hebr. Titel des Buches lautet übersetzt: »Dies sind die Worte« und leitet sich von den beiden ersten hebr. Worten des Buches ab. Der hebr. Titel liefert eine bessere Beschreibung des Buches, da es nicht ein »zweites Gesetz« ist, sondern vielmehr eine Aufzeichnung der erklärenden Worte Moses über das Gesetz. Deuteronomium vervollständigt die fünfteilige literarische Einheit, die Pentateuch genannt wird.

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