Skip to main content

Home/ Dr. Goodyear/ Group items tagged 4

Rss Feed Group items tagged

Filter: All | Bookmarks | Topics Simple Middle
Nathan Goodyear

The 4-Pregnene and 5α-Pregnane Progesterone Metabolites Formed in Nontumorous... - 0 views

cancerres.aacrjournals.org/...936.full

progesterone metabolism cancer risk 4-pregnene 5alpha-pregnane

shared by Nathan Goodyear on 17 Feb 12 - No Cached
  • We report here the first evidence that tumorous breast tissue exhibits elevated 5α-reductase activity, which promotes significant increases in 5α-pregnanes, especially 5αP,4 whereas the normal (nontumorous) breast tissue produces more 4-pregnenes, especially 3αHP
  • 3αHP and other 4-pregnenes inhibit, whereas 5αP and other 5α-pregnanes stimulate, breast cell proliferation and detachment
  • it is evident that breast tissue can convert progesterone into two classes of metabolites: the δ-4-pregnenes (which retain the C4–5 double bond), and the 5α-reduced 21-carbon steroids (5α-pregnanes)
  • ...12 more annotations...
  • irreversible action of 5α-reductase
  • in normal (nontumorous) breast tissue, the 4-pregnene metabolites of progesterone greatly exceeded the 5α-pregnanes, whereas in tumorous tissue, 5α-pregnanes exceeded 4-pregnenes.
  • These differences in 5α-pregnane and 4-pregnene amounts were largely attributable to differences in 5αP and 3αHP production in tumorous and nontumorous tissues
  • the metabolic activities were in general similar, regardless of the age and ER state of the patient or whether she was pre- or postmenopausal.
  • These findings suggest greatly elevated 5α-reductase activity in tumorous, as compared with nontumorous, breast tissue.
  • progesterone metabolites that retain the C-4 double bond (i.e., the 4-pregnenes) exert an antiproliferative effect in the three cell lines that were tested, whereas the 5α-pregnanes stimulate breast cell line proliferation.
  • the degree of mitogenicity would be determined by the ratio of 5α-pregnanes:4-pregnenes. Tissues with a high 4-pregnene:5α-pregnane ratio would maintain a higher degree of normalcy, whereas those with a high 5α-pregnane:4-pregnene ratio would tend toward tumorigenicity
  • The observations that progesterone metabolites affect both ER-positive and ER-negative cells as well as tumorigenic (MCF-7) and nontumorigenic (MCF-10A) cells strengthen the argument that these factors may be endocrinologically relevant for all forms of breast cancer.
  • progesterone metabolites as the active endocrine/paracrine/autocrine factors
  • Estrogen-based therapies elicit responses in only one-third of all breast cancer patients, and most of these show relapse.
  • the metabolic activities were in general similar, regardless of the age and ER state of the patient or whether she was pre- or postmenopausal.
    • Nathan Goodyear
      Nathan Goodyear on 27 Jan 14
       
      Interesting that the effect of progesterone metabolites were found to be independent from ER status, age, and pre/post menopause
  • Nathan Goodyear on 17 Feb 12
     
    Different progesterone metabolites shown to have different tumor effects.  Implications are that, just as estrogen metabolism effects cancer risk, so does progesterone metabolism.
Nathan Goodyear

Progesterone metabolites in breast cancer - 1 views

erc.endocrinology-journals.org/...717.full

progesterone metabolism tumor tumorigenesis cancer risk growth hormone hormones 5-beta-pregnanediol 5-alpha-pregnanediol 4-pregnenediol 5-alpha reductase

shared by Nathan Goodyear on 20 Feb 12 - No Cached
  • P metabolites produced within breast tissues might be independently active hormones functioning as cancer-promoting or -inhibiting regulatory agents
  • these P metabolites function as independent pro-or anti-cancer autocrine/paracrine hormones that regulate cell proliferation, adhesion, apoptosis and cytoskeletal, and other cell status molecules via novel receptors located in the cell membrane and intrinsically linked to cell signaling pathways
  • only a fraction of all breast cancer patients respond to this estrogen-based therapy and the response is only temporary
  • ...30 more annotations...
  • P serves as the precursor for the major steroid hormones (androgens, estrogens, corticosteroids) produced by the gonadal and adrenal cortical tissues.
  • 5α-pregnane, 5β-pregnane, and 4-pregnene metabolites of P
  • These P-metabolizing enzymes included 5α-reductase, 5β-reductase, 3α-hydroxysteroid oxido-reductase (3α-HSO), 3β-HSO, 20α-HSO, 20β-HSO, 6α(β)-, 11β-, 17-, and 21-hydroxylase, and C17–20-lyase
  • Reduction of P to 5α-pregnanes is catalyzed by 5α-reductase and the direct 5α-reduced metabolite of P is 5α-pregnane-3,20-dione (5αP). The 5α-reductase reaction is irreversible
  • The two 4-pregnenes resulting from direct P conversion are 4-pregnen-3α-ol-20-one (3αHP) and 4-pregnen-20α-ol-3-one (20αHP), catalyzed by the actions of 3α-HSO and 20α-HSO respectively
  • the P-metabolizing enzyme activities identified in human breast tissues and cell lines were: 5α-reductase, 3α-HSO, 3β-HSO, 20α-HSO, and 6α-hydroxylase
  • In normal breast tissue, conversion to 4-pregnenes greatly exceeded the conversion to 5α-pregnanes, whereas in tumorous tissue, conversion to 5α-pregnanes greatly exceeded that to 4-pregnenes
  • The results indicated that P 5α-reductase activity is significantly higher, whereas P 3α-HSO and 20α-HSO activities are significantly lower in tumor than in normal tissues
  • he results showed that production of 5α-pregnanes was higher and that of 4-pregnenes was lower in tumorigenic (e.g. MCF-7) than in nontumorigenic (e.g. MCF-10A) cells (Fig. 3c⇑), while differences in ER/P status did not appear to play a role
  • The 5α-pregnane-to-4-pregnene ratios were 7- to 20-fold higher in the tumorigenic than in the nontumorigenic cell lines
  • altered direction in P metabolism, and hence in metabolite ratios, was due to significantly elevated 5α-reductase and depressed 3α- and 20α-HSO activities in breast tumor tissues and tumorigenic cells. It appeared, therefore, that changes in P-metabolizing enzyme activities might be related to the shift toward mammary cell tumorigenicity and neoplasia
  • In vivo, changes in enzyme activity can result from changes in levels of the enzyme due to changes in expression of the mRNA coding for the enzyme, or from changes in the milieu in which the enzyme operates (such as temperature and pH, and concentrations of cofactors, substrates, products, competitors, ions, phospholipids, and other molecules)
  • Overall, the enzyme activity and expression studies strongly suggest that 5α-reductase stimulation and 3α- and 20α-HSO suppression are associated with the transition from normalcy to cancer of the breast
  • The level of expression of 5α-reductase is up-regulated by estradiol and P in the uterus (Minjarez et al. 2001) and by 5α-dihydrotestosterone (DHT) in the prostate
  • 3αHP inhibited whereas 5αP-stimulated proliferation
  • Stimulation in cell numbers was also observed when cells were treated with other 5α-pregnanes, such as 5α-pregnan-3α-ol-20-one, 5α-pregnan-20α-ol-3-one, and 5α-pregnane-3α,20α-diol, whereas other 4-pregnenes such as 20α-HP and 4-pregnene-3α,20α-diol resulted in suppression of cell proliferation
  • Stimulation of cell proliferation with 5αP and inhibition with 3αHP were also observed in all other breast cell lines examined, whether ER/P-negative (MCF-10A, MDA-MB-231) or ER/P-positive (T47D, ZR-75-1) and whether requiring estrogen for tumorigenicity (MCF-7, T47D) or not (MDA-MB-231), or whether they are nontumorigenic (
  • αHP resulted in significant increases in apoptosis and decreases in mitosis, leading to significant decreases in total cell numbers. In contrast, treatment with 5αP resulted in decreases in apoptosis and increases in mitosis.
  • The opposing actions of 5αP and 3αHP on both cell anchorage and proliferation strengthen the hypothesis that the direction of P metabolism in vivo toward higher 5α-pregnane and lower 4-pregnene concentrations could promote breast neoplasia and lead to malignancy.
  • he effects on proliferation and adhesion were not due to P, but due to the 5α-reduced metabolites
  • The studies showed that binding of 5αP or 3αHP occurs in the plasma membrane fractions, but not in the nuclear or cytosolic compartments
  • separate high-specificity, high-affinity, low- capacity receptors for 5αP and 3αHP that are distinct from each other and from the well-studied nuclear/cytosolic P, estrogen, and androgen and corticosteroid receptors
  • The studies thus provided the first demonstration of the existence of specific P metabolite receptors
  • the receptor results suggest that the putative tumorigenic actions of 5αP may be significantly augmented by the estradiol-induced increases in 5αP binding and decreases in 3αHP binding.
  • Estradiol and 5αP resulted in significant dose-dependent increases, whereas 3αHP and 20αHP each resulted in dose-dependent decreases in total ER
  • In combination, estradiol + 5αP or 3αHP + 20αHP resulted in additive increases or decreases respectively in ER numbers.
  • The data suggest that the action of 5αP on breast cancer cells involves modulation of the MAPK signaling pathway
  • current evidence does not appear to support the notion that increased 5α-reductase activity/ expression might significantly alter androgen influences on breast tumor growth.
  • both testosterone and DHT inhibit cell growth more or less to the same extent
  • Note that 5α-reductase reaction is not reversible
  • Nathan Goodyear on 20 Feb 12
     
    Fantastic read on the effects of progesterone metabolism on tumor and cancer growth.  Tumorigenesis is not just about the hormone, hormone balance, but about the metabolism of hormones.  This is why premarin is so carcinogenic: it is primarily metabolized by the 4-OH estrone pathway.
wheelchairindia9

Wheelchair 4 Wheel Drive - 0 views

www.wheelchairindia.com/...Wheelchair-With-4-Small-Wheels

Wheelchair Wheels Are Detachable And Foldable electric propulsion by motors safe operation Wheelchairs weigh maximum fixed or detachable armrests rear wheels by hand strong and durable frame low resistant Nylon

shared by wheelchairindia9 on 22 May 15 - No Cached
  • wheelchairindia9 on 22 May 15
     
    A wheelchair is a wheeled mobility device in which the user sits. The device is propelled either manually (by turning the wheels by the hand) or via various automated systems. Wheelchairs are used by people for whom walking is difficult or impossible due to illness (physiological or physical), injury, or disability. The chair seat size (width and depth), seat-to-floor height, footrests/leg rests, front caster outriggers, adjustable backrests, controls, and many other features can be customized on, or added to, many basic models, while some users, often those with specialised needs, may have wheelchairs custom-built. The usual size of the rear wheel ranges from twenty to twenty-six inches in diameter. A larger wheel increases the height of the seat off the ground and decreases the rolling resistance, thus easing the effort of pushing. The rear wheels can be solid or pneumatic. Solid wheels have a low rolling resistance and are very easy to maintain. They are ideal for use in institutional settings or for indoor use in noncarpeted areas. Pneumatic wheels have better grip on carpeted surfaces and are better if there is going to be significant outdoor use, but they run the risk of flats and require higher maintenance. The flat tire problem can be circumvented by the use of a foam insert that can prevent leaks. Wire spokes are lighter in weight but higher in maintenance. Most older persons will select large plastic spokes referred to as mag wheels. The wheels can be offset posteriorly to decrease the risk of tipping backwards. Wheelchair With 4 Small Wheels: Wheelchair With 4 Small Wheels foldable frame wheelchair made of chrome with 18" inches seat width, 8" Inches Front and Rear wheel, total weight 14 kg helps physical challenged person to move around indoor. Wheelchair With 4 Small Wheels Measurements: Seat Width : 16 inch., 18 inch. Frame Style : Foldable Frame Material : M.S. Chrome open position wheel to wheel width in : 22" (inches) Seat Width : 1
wheelchairindia9

Handicapped Two Wheeler - 0 views

www.wheelchairindia.com/...SIDE-WHEEL-ATTACHMENT

Innovative Scooter For The Benefit Of Disabled Scooter For Handicapped Person 2 Piece Tyre Size Handicapped Two Wheeler power-operated vehicle delta-style steering arrangement

shared by wheelchairindia9 on 24 Apr 15 - No Cached
  • wheelchairindia9 on 24 Apr 15
     
    Heavy duty mobility scooters are strong enough to accommodate almost any user. When compared with lighter units, mobility scooters models tend to feature bigger motors, wider bases, and larger tires. While a lighter model may be difficult to maneuver through rougher landscapes, mobility scooter is designed to tackle even the most challenging terrain.An excellent selection of scooters for sale. An extensive scooter accessories section, where find plenty of customization options to help ensure that the model select is a perfect fit. Side Wheels For Hero Pleasure: Side Wheel Attachment for Hero Pleasure or Side Wheels For Hero Pleasure or Three wheeler Hero Pleasure for handicapped is product, designed for use with bikes meant for the open road. Instead of shifting with a foot, a rider can drive easily their bike on road using his or her hand. This piece of equipment has been tested at well-known motorcycle tracks. This provides assembly and installation for all products at all facilities. Side Wheel Attachment For Hero Pleasure to fit the widest array of motorcycles and all-terrain vehicles possible. Side Wheel Attachment For Hero Pleasure Measurements: Frame : 38 mm 16 Gauge CR Pipe With Powder Coated Wheel Hub : Alloys Molded 2 Piece Tyre Size : 3.50 x 10 Inches 2 Piece Tube Size : 3.50 x 10 inches 2 Piece Shocks Up Heavy Duty 4 Piece ball baring 2 Piece pin bush 2 Piece mudguard chrome plated 2 Piece Disk with 4 Hole Wheel Type: Alloy Wheel Width: 40" to 48" inch Carrying Capacity: 100 -150 kg Side Wheels For Hero Pleasure Features: Independent Mobility Minimal Cost Heavy Duty International quality standards Comfort High level of performance Carrying Capacity: 100 -150 kg Sturdy design Provides excellent balance Provides excellent support High durability Side Wheels For CD Deluxe: Side Wheel Attachment for CD Deluxe or Side Wheels For CD Deluxe or Three wheeler CD Deluxe for handicapped is product, designed for u
wheelchairindia9

J6 Power Wheelchair - 0 views

www.wheelchairindia.com/...J6-Power-Wheelchair

J6 Power Wheelchair Quantum Wheelchair Quantum Power Chairs J6 Power Chair Pride J6 Wheelchair Quantum Motorized Wheelchairs J6 Power Wheelchair Price J6 Wheelchair

shared by wheelchairindia9 on 02 Mar 16 - No Cached
  • wheelchairindia9 on 02 Mar 16
     
    J6 Power Wheelchair The compact J6 is the ultimate choice for users who demand the superb stability of Mid-Wheel 6 design and tight-quarter maneuverability. Highly adaptable, the J6 accepts a wide range of seating and electronics options while its powerful drive train delivers high-performance torque. J6 Power Wheelchair Features: Mid-Wheel 6 allows six wheels on the ground for maximum stability. Compatible with TRU-Balance Tilt. OMNI-Casters (nylon, spherical-shaped casters) on front and rear prevent wheel hang-ups. Side-mounted, easily accessible freewheel levers. ATX Suspension (Active-Trac with extra stability) incorporates front OMNI-Casters for enhanced. Performance over more varied terrain. Easy front access to batteries. J6 Power Wheelchair Specifications: Drive Wheels: 10" Solid Optional: 10" Pneumatic Caster Wheels Front: 5" Solid Rear: 6" Solid Anti-Tip Wheels N/A Maximum Speed^4/^: Up to 4 mph Ground Clearance: 2.5" (frame) Turning Radius^5/^: 22" Overall Length: 34.74" without foot riggings Base Width: 23.19" Seating Sizes: TRU-Balance® 2 Synergy/Static: W: 10-20" D: 10-20" Power Tilt: W: 14-20" D: 14-20" Lift & Tilt: N/A Seat-to-Floor Heights: TRU-Balance® 2 Synergy/Static8: 16.5" - 17.5" Power Tilt8: 16.875" Lift & Tilt8: N/A Manual Tilt/Recline^10/^: Yes Battery Size^6/^: U-1 Battery Weight^14/^: 23.4 lbs. Available Electronics^12/^: 70A Q-Logic 2 NE 70A Q-Logic 2 NE+ 70A Q-Logic 2 EX Battery Charger 5A Off-board Motor Packages 2-Pole 4 mph Weight Capacity^7/^: 300 lbs.9 Base Weight: 100.2 lbs
wheelchairindia9

Wrist and Forearm Splints Causes and Recovery Period | Health | Article Point - 0 views

www.articlepoint.org/...auses-and-recovery-period.aspx

Wrist and Forearm Splints Causes and Recovery Period best orthopedic wrist braces comfortable support to hand muscular attachments to the bone hand side of the forearm Anatomical thumb opening

shared by wheelchairindia9 on 04 Apr 16 - No Cached
  • wheelchairindia9 on 04 Apr 16
     
    Wrist and forearm splints may be suggested for people with weak wrists or for those that have been previously injured, for tendonitis wrist support and even as a preventative for those who awaken in the morning with pain or numbness after sleeping on their hands at night. The best orthopedic wrist braces for carpal tunnel syndrome, occupational stabilization and relief from the pain of wrist strains and sprains. This Right hand wrist and forearm splint from tynor is meant to be used among patients suffering from any injury or sprain in these regions. The splint is meant to provide controlled compression in various orthopaedic conditions. The splint immobilizes the area that helps in a speedier recovery. It has anatomical thumb opening that allows free movement of the thumb. It provides a lot of comfort and is easily breathable. Forearm splint is the term used to describe the forearm pain similarly the pain of lower leg over the shin is known as shin splints. Forearm splint describes the painful disease of elbow or wrist joint. Continuous pain in forearm is often caused by tendonitis, joint injury or hairline fracture of forearm bones (proximal radius or ulna near elbow joint). Overstretching of the elbow joint often causes forearm injury. Symptoms consist of a dull pain in the forearm. Pain is minor initially but increases as activity continues. Often pin-pointed to the dorsal or back of the hand side of the forearm, mid-way between the wrist and elbow. The patient may experience weakness in the wrist extensor muscles and tenderness deep in the forearm. Pain may be reproduced by attempting to bend the wrist backwards against resistance. They provided wrist splints are used in different medical institutions and hospitals for management of hand fractures. Our offered wrist splints are manufactured by skilled professionals using optimum quality basic material and advanced technology as per the set norms of market. As well, these wrist splints can be availed in v
Nathan Goodyear

Activity and expression of progesterone metabolizing 5α-reductase, 20α-hydrox... - 0 views

www.ncbi.nlm.nih.gov/...PMC154104

progesterone metabolites breast cancer 5alpha-reductase 5-alpha pregnene 5-alpha pregnenes 4-pregnene 4-pregnenes

shared by Nathan Goodyear on 30 Jan 14 - No Cached
  • Exposure of human breast cell lines (MCF-7, MCF-10A, and ZR-75-1) to 5α-pregnanes results in changes associated with neoplasia, including increased proliferation and decreased attachment [1], depolymerization of F-actin [2] and decreases in adhesion plaque-associated vinculin
  • Exposure to 4-pregnenes results, in general, in opposite (anti-cancer-like) effects
  • 5αR1 has been detected in various androgen-independent organs, such as the liver and brain
  • ...10 more annotations...
  • 5αR2 has been found predominantly in androgen-dependent organs, such as epididymis and prostate
  • The 5α-pregnanes:4-pregnenes ratio was about 8-fold higher in tumorous than in nontumorous breast tissue after an 8-hour incubation with [14C]progesterone
  • Studies with breast cell lines, showing that 5α-pregnanes stimulate proliferation and decrease attachment of cells
  • both tissue and breast cell line studies suggest that an elevated level of progesterone 5α-reductase activity may be an indicator of breast tumorigenesis, regardless of presence or absence of ER and/or PR
  • 5αR1 is the main isoform expressed in human breast carcinomas [29] and that 5αR2 may not be associated with risk of breast cancer
  • the differences in 5α-pregnane production between the cells is due primarily to a difference in 5αR1 expression
  • As in the case of 5α-reductase activity, the presence or absence of ER and PR do not appear to be related to 5α-reductase expression.
  • the conversion of progesterone to the cancer promoting 5α-pregnanes is significantly higher in the human tumorigenic breast cell lines
  • lthough both 5αR1 and 5αR2 are expressed by these cells, the elevated 5α-reductase activity appears to be the result of significantly greater expression of 5αR1
  • Changes in progesterone metabolizing enzyme expression (resulting in enzyme activity changes) may be responsible for promoting breast cancer progression due to increased production of tumor-promoting 5α-pregnanes and decreased production of anti-cancer 20α – and 3α-4-pregnenes
  • Nathan Goodyear on 30 Jan 14
     
    balance of enzyme production between 5alpha-reductase and 20alpha-hydroxysteroid oxidoreductase and 3alpha(beta)-hydroxysteroid oxidoreductase play role in carcinogenesis and proliferation in the balance of production of progesterone metabolites. The 5alpha pregnenes are pro carcinogenic  and the 4-pregnenes are anti carcinogenic.
Nathan Goodyear

Estrogen Metabolism and Risk of Breast Cancer in Postmenopausal Women - 0 views

www.ncbi.nlm.nih.gov/...PMC3283536

estrogen metabolism estrogen metabolism breast cancer breast cancer

shared by Nathan Goodyear on 14 Oct 13 - No Cached
  • The ratio of the 2-hydroxylation pathway to parent estrogens was associated with a statistically significantly decreased risk of breast cancer
  • In this study, this ratio was more strongly associated with the risk of breast cancer compared with the ratio of 2-hydroxylation pathway to 16-hydroxylation pathway or unconjugated estradiol alone
  • 2-hydroxylation pathway catechols have relatively low affinities for estrogen receptors (4) and are rapidly cleared from circulation
  • ...6 more annotations...
  • In this study, the ratio of the 2-hydroxylation pathway to the 16-hydroxylation pathway was associated with a non-statistically significantly decreased risk of breast cancer
  • In this study, the ratio of catechols to methylated catechols in the 4-hydroxylation pathway was associated with statistically significantly increased risk of breast cancer.
  • This result is consistent with the hypothesis that mutagenic quinones derived from 4-hydroxylation pathway catechols contribute to pathogenesis of postmenopausal breast cancer.
  • Catechols in both the 2- and 4-hydroxylation pathways can be oxidized to form quinones; these reactive electrophiles can then react with DNA to form a variety of adducts
  • Methylation of the catechols prevents their conversion to reactive quinones
  • the most common DNA adducts derived from 4-hydroxylation pathway catechols are depurinating and highly mutagenic (7,40), most of those derived from 2-hydroxylation pathway catechols are stable and can be repaired with little error
  • Nathan Goodyear on 14 Oct 13
     
    Lower 2-OH estrone metabolism associated with lower risk of breast cancer, but 4-OH estrone associated with increased risk of breast cancer.
trungtamnamkhoa

Tư vấn cách xây nhà cấp 4 khoảng 200 triệu mà ít ai biết - 3 views

npgroup.vn/xay-nha-cap-4-khoang-200-trieu

Thiếtkế thiếtkếxâydựng côngtythiếtkếxâydựng bulding npgroup NguyênPhátGroup

shared by trungtamnamkhoa on 25 Feb 20 - No Cached
  • trungtamnamkhoa on 25 Feb 20
     
    Liệu với 200 triệu đồng thì hoàn toàn có thể xây được một ngôi nhà cấp 4 hay không? Đây là một trong những câu hỏi gần đây mà chúng tôi nhận được nhiều nhất. Nhiều người thường muốn sở hữu ngay cho mình một căn nhà riêng chứ không ai muốn phải đi thuê mướn cả. Vậy với 200 triệu thì có thể xây được một ngôi nhà cấp 4 hay không? Câu trả lời là có thể bạn nhé. Tuy nhiên, không phải đơn giản mà có thể sở hữu được căn nhà mới với mức chi phí như thế. Chính vì vậy, trong bài viết này, chúng tôi xin tư vấn xây nhà cấp 4 khoảng 200 triệu với hy vọng bạn sẽ có được một không gian sống thật đẹp nhé. Muốn xây được một căn nhà cần phải chú ý đến khá nhiều yếu tố, vì bạn biết đấy, xây nhà luôn phát sinh nhiều vấn đề khiến bạn phải chi nhiều hơn so với mức chi phí dự toán ban đầu. Vì vậy, nếu muốn xây nhà cấp 4 khoảng 200 triệu thì bạn cần phải chú ý nhiều hơn, tính toán và xem xét các yếu tố nhiều hơn để có thể xây được căn nhà trong mức dự tính của bạn nhé. Sau đây là những lưu ý mà chúng tôi tổng hợp dành cho bạn. Nguồn bài viết từ Công Ty Cổ Phần Tư Vấn Thiết Kế Xây Dựng Nguyên Phát https://npgroup.vn/tu-van-xay-nha-cap-4-khoang-200-trieu/
Nathan Goodyear

Availability of evidence of benefits on overall survival and quality of life of cancer ... - 0 views

www.bmj.com/bmj.j4530

cancer cancer treatment survival quality of life

shared by Nathan Goodyear on 20 Dec 17 - No Cached
  • Although the goal of cancer treatment is to improve the quantity and quality of life,123 clinical trials designed to gain regulatory approval for new drugs often evaluate indirect or “surrogate” measures of drug efficacy. These endpoints show that an agent has biological activity, but they are not reliable surrogates for improved survival4567891011 or quality of life46111213
  • two recent systematic reviews suggest that the strength of association between surrogates in cancer clinical trials and life extension is generally low
  • Available data from the US show that only a small proportion of cancer treatments approved by the US Food and Drug Administration (FDA) unequivocally show benefits on survival or quality of life.30
  • ...16 more annotations...
  • We sought to systematically evaluate the evidence base for all new drugs and new indications for the treatment of solid tumours and haematological malignancies approved by the EMA in the five year period 2009-13
  • Three investigators (AP, EP, and EG) independently extracted data on and descriptively analysed the following trial features: characteristics of the participant population, study design (randomisation, crossover from experimental to control group, and blinding of investigators and participants), experimental and control groups, enrolment, primary and secondary endpoints, magnitude of benefit on survival and quality of life, and narrative interpretation of the findings
  • Only 18 of the 68 (26%) were supported by a pivotal study powered to evaluate overall survival as the primary outcome
  • From 2009 to 2013, the EMA approved use of 48 oncology drugs
  • Seventeen drugs were approved for treatment of haematological malignancies and 51 for treatment of solid tumours
  • Overall, 72 clinical trials supported the approval of 68 novel drug uses
  • Our scoring was limited to drugs for solid tumours
  • Among 68 cancer drug indications approved by the EMA in the period 2009-13, and with a median of 5.4 years’ follow-up, only 35 (51%) were associated with a significant improvement in survival (26/35) or quality of life (9/35) over existing treatment options, placebo, or as add on treatment
  • Only two of the 26 drugs shown to extend life also showed benefits on quality of life
  • 33 (49%) had not shown any improvement on survival or quality of life
  • This systematic evaluation of oncology drug approvals by the EMA in 2009-13 shows that most of the drugs (39/68, 57%) entered the market without evidence of improved survival or quality of life
  • At a minimum 3.3 years after market entry, there was still no conclusive evidence that 33 of these 39 cancer drugs either extended or improved life
  • What are potential reasons for the paucity of drug approvals with demonstrable survival advantages over existing treatments?
  • Firstly, only 18 (26%) indications for use in our cohort were supported by trials in which extension of life was the primary outcome
  • None of the pivotal studies supporting oncology drug approvals from 2009 to 2013 included quality of life as a primary outcome measure
  • Most new oncology drugs authorised by the EMA in 2009-13 came onto the market without clear evidence that they improved the quality or quantity of patients’ lives
  • Nathan Goodyear on 20 Dec 17
     
    New study from European Medicines Agency questions alot of the new cancer drugs brought to the market 2009-2013.  57% of the new drugs (39/68) were brought to the market without evidence of improved survival or quality of life.
Nathan Goodyear

Ibuprofen alters human testicular physiology to produce a state of compensated hypogona... - 0 views

www.pnas.org/...1715035115.full

ibuprofen Testosterone epigenetics hormones low Testosterone low T

shared by Nathan Goodyear on 09 Jan 18 - No Cached
  • The levels of LH in the ibuprofen group had increased by 23% after 14 d of administration
  • This increase was even more pronounced at 44 d, at 33%
  • We found an 18% decrease (P = 0.056) in the ibuprofen group compared with the placebo group after 14 d (Fig. 1A) and a 23% decrease (P = 0.02) after 44 d (Fig. 1C). Taken together, these in vivo data suggest that ibuprofen induced a state of compensated hypogonadism during the trial, which occurred as early as 14 d and was maintained until the end of the trial at 44 d
  • ...27 more annotations...
  • We first investigated testosterone production after 24 and 48 h of ibuprofen exposure to assess its effects on Leydig cell steroidogenesis. Inhibition of testosterone levels was significant and dose-dependent (β = −0.405, P = 0.01 at 24 h and β = −0.664, P < 0.0001 at 48 h) (Fig. 2A) and was augmented over time
  • The AMH data show that the hypogonadism affected not only Leydig cells but also Sertoli cells and also occurred as early as 14 d of administration
  • Sertoli cell activity showed that AMH levels decreased significantly with ibuprofen administration, by 9% (P = 0.02) after 14 d (Fig. 1B) and by 7% (P = 0.05) after 44 d compared with the placebo group
  • Examination of the effect of ibuprofen exposure on both the ∆4 and ∆5 steroid pathways (Fig. 2B) showed that it generally inhibited all steroids from pregnenolone down to testosterone and 17β-estradiol; the production of each steroid measured decreased at doses of 10−5–10−4 M. Under control conditions, production of androstenediol and dehydroepiandrosterone (DHEA) was below the limit of detection except in one experiment with DHEA
  • Measuring the mRNA expression of genes involved in steroidogenesis in vitro showed that ibuprofen had a profound inhibitory effect on the expression of these genes (Fig. 3 B–D), consistent with that seen above in our ex vivo organ model. Taken together, these data examining effects on the endocrine cells confirm that ibuprofen-induced changes in the transcriptional machinery were the likely reason for the inhibition of steroidogenesis.
  • Suppression of gene expression concerned the initial conversion of cholesterol to the final testosterone synthesis. Hence, expression of genes involved in cholesterol transport to the Leydig cell mitochondria was impaired
  • A previous study reported androsterone levels decreased by 63% among men receiving 400 mg of ibuprofen every 6 h for 4 wk
  • We next examined the gene expression involved in testicular steroidogenesis ex vivo and found that levels of expression of every gene that we studied except CYP19A1 decreased after exposure for 48 h compared with controls
  • the changes in gene expression indicate that the transcriptional machinery behind the endocrine action of Leydig cells was most likely impaired by ibuprofen exposure.
  • Together, these data show that ibuprofen also directly impairs Sertoli cell function ex vivo by inhibiting transcription
  • ibuprofen use in men led to (i) elevation of LH; (ii) a decreased testosterone/LH ratio and, to a lesser degree, a decreased inhibin B/FSH ratio; and (iii) a reduction in the levels of the Sertoli cell hormone AMH
  • The decrease in the free testosterone/LH ratio resulted primarily from the increased LH levels, revealing that testicular responsiveness to gonadotropins likely declined during the ibuprofen exposure. Our data from the ex vivo experiments support this notion, indicating that the observed elevation in LH resulted from ibuprofen’s direct antiandrogenic action
  • AMH levels were consistently suppressed by ibuprofen both in vivo and ex vivo, indicating that this hormone is uncoupled from gonadotropins in adult men. The ibuprofen suppression of AMH further demonstrated that the analgesic targeted not only the Leydig cells but also the Sertoli cells, a feature encountered not only in the human adult testis but also in the fetal testis
  • ibuprofen displayed broad transcription-repression abilities involving steroidogenesis, peptide hormones, and prostaglandin synthesis
  • a chemical compound, through its effects on the signaling compounds, can result in changes in the testis at gene level, resulting in perturbations at higher physiological levels in the adult human
  • The analgesics acetaminophen/paracetamol and ibuprofen have previously been shown to inhibit the postexercise response in muscles by repressing transcription
  • Previous ex vivo studies on adult testis have indeed pointed to an antiandrogenicity, only on Leydig cells, of phthalates (41), aspirin, indomethacin (42), and bisphenol A (BPA) and its analogs
  • ibuprofen’s effects were not restricted to Leydig and Sertoli cells, as data showed that the expression of genes in peritubular cells was also affected
  • short-term exposure
  • In the clinical setting, compromised Leydig cell function resulting in increased insensitivity to LH is defined as compensated hypogonadism (4), an entity associated with all-cause mortality
  • compensated hypogonadic men present with an increased likelihood of reproductive, cognitive, and physical symptoms
  • an inverse relationship was recently reported between endurance exercise training and male sexual libido
  • AMH concentrations are lower in seminal plasma from patients with azoospermia than from men with normal sperm levels
  • inhibin B is a key clinical marker of reproductive health (32). The function of AMH, also secreted by Sertoli cells, and its regulation through FSH remain unclear in men
  • the striking dual effect of ibuprofen observed here on both Leydig and Sertoli cells makes this NSAID the chemical compound, of all the chemical classes considered, with the broadest endocrine-disturbing properties identified so far in men.
  • after administration of 600 mg of ibuprofen to healthy volunteers
  • 14 d or at the last day of administration at 44 d
  • Nathan Goodyear on 09 Jan 18
     
    ibuprofen alters genetic expression that results in decreased Testosterone production.
wheelchairindia9

Tynor Anklet Pair - 0 views

www.wheelchairindia.com/...Tynor-Anklet-Pair

Tynor Ankle Binder and Pair Used in Orthopedic Ankle binder Anklets pair tubular supports ankle sprain Effective compression Four way stretch support to the ankle joint wrap and compression sleeve

shared by wheelchairindia9 on 11 Mar 16 - No Cached
  • wheelchairindia9 on 11 Mar 16
     
    Tynor Anklet (Pair) Anklets are tubular supports widely used in orthopedic practice to provide mild compression, warmth & support to the ankle joint, to allay pain and inflammation generally associated with old age, arthritis, sports etc. Four way stretch Two layered fabric Hypoallergenic Uniform compression Simple pull on application Tynor Anklet (Pair) Features Bilayered , cotton on the inside Dermophillic interpahse with the skin Better sweat absorption Better comfort Better patient compliance. No allergies or rash Bilayered, nylon on the outside Ensures long life Excellent aesthetics Color fastness. Two layers enclose air space retains body heat effectively Provides therapeutic warmth and assuring support to the knee. Four-way stretchable seamless tubular fabric Effective compression Enhanced comfort. No vaso constriction. Adjusts compression even on uneven diameters Simple pull on application improves patient compliance. Tynor Anklet (Pair) Measurements Measure circumference approx 2 inches above the ankle joint. Size Chart - Size Inches CM Small 7.2-8.4 18-21 Medium 8.4-9.6 21-24 Large 9.6-10.8 24-27 XL 10.8-12 27-30
Nathan Goodyear

Testosterone and the Cardiovascular System: A Comprehensive Review of the Clinical Lite... - 0 views

jaha.ahajournals.org/...e000272.full

Testosterone men male cardiovascular disease low T

shared by Nathan Goodyear on 20 Nov 13 - No Cached
  • Low endogenous bioavailable testosterone levels have been shown to be associated with higher rates of all‐cause and cardiovascular‐related mortality.39,41,46–47 Patients suffering from CAD,13–18 CHF,137 T2DM,25–26 and obesity27–28
  • have all been shown to have lower levels of endogenous testosterone compared with those in healthy controls. In addition, the severity of CAD15,17,29–30 and CHF137 correlates with the degree of testosterone deficiency
  • In patients with CHF, testosterone replacement therapy has been shown to significantly improve exercise tolerance while having no effect on LVEF
  • ...66 more annotations...
  • testosterone therapy causes a shift in the skeletal muscle of CHF patients toward a higher concentration of type I muscle fibers
  • Testosterone replacement therapy has also been shown to improve the homeostatic model of insulin resistance and hemoglobin A1c in diabetics26,68–69 and to lower the BMI in obese patients.
  • Lower levels of endogenous testosterone have been associated with longer duration of the QTc interval
  • testosterone replacement has been shown to shorten the QTc interval
  • negative correlation has been demonstrated between endogenous testosterone levels and IMT of the carotid arteries, abdominal aorta, and thoracic aorta
  • These findings suggest that men with lower levels of endogenous testosterone may be at a higher risk of developing atherosclerosis.
  • Current guidelines from the Endocrine Society make no recommendations on whether patients with heart disease should be screened for hypogonadism and do not recommend supplementing patients with heart disease to improve survival.
  • The Massachusetts Male Aging Study also projects ≈481 000 new cases of hypogonadism annually in US men within the same age group
  • since 1993 prescriptions for testosterone, regardless of the formulation, have increased nearly 500%
  • Testosterone levels are lower in patients with chronic illnesses such as end‐stage renal disease, human immunodeficiency virus, chronic obstructive pulmonary disease, type 2 diabetes mellitus (T2DM), obesity, and several genetic conditions such as Klinefelter syndrome
  • A growing body of evidence suggests that men with lower levels of endogenous testosterone are more prone to develop CAD during their lifetimes
  • There are 2 major potential confounding factors that the older studies generally failed to account for. These factors are the subfraction of testosterone used to perform the analysis and the method used to account for subclinical CAD.
  • The biologically inactive form of testosterone is tightly bound to SHBG and is therefore unable to bind to androgen receptors
  • The biologically inactive fraction of testosterone comprises nearly 68% of the total testosterone in human serum
  • The biologically active subfraction of testosterone, also referred to as bioavailable testosterone, is either loosely bound to albumin or circulates freely in the blood, the latter referred to as free testosterone
  • It is estimated that ≈30% of total serum testosterone is bound to albumin, whereas the remaining 1% to 3% circulates as free testosterone
  • it can be argued that using the biologically active form of testosterone to evaluate the association with CAD will produce the most reliable results
  • English et al14 found statistically significant lower levels of bioavailable testosterone, free testosterone, and free androgen index in patients with catheterization‐proven CAD compared with controls with normal coronary arteries
  • patients with catheterization‐proven CAD had statistically significant lower levels of bioavailable testosterone
  • In conclusion, existing evidence suggests that men with CAD have lower levels of endogenous testosterone,13–18 and more specifically lower levels of bioavailable testosterone
  • low testosterone levels are associated with risk factors for CAD such as T2DM25–26 and obesity
  • In a meta‐analysis of these 7 population‐based studies, Araujo et al41 showed a trend toward increased cardiovascular mortality associated with lower levels of total testosterone, but statistical significance was not achieved (RR, 1.25
  • the authors showed that a decrease of 2.1 standard deviations in levels of total testosterone was associated with a 25% increase in the risk of cardiovascular mortality
  • the relative risk of all‐cause mortality in men with lower levels of total testosterone was calculated to be 1.35
  • higher risk of cardiovascular mortality is associated with lower levels of bioavailable testosterone
  • Existing evidence seems to suggest that lower levels of endogenous testosterone are associated with higher rates of all‐cause mortality and cardiovascular mortality
  • studies have shown that lower levels of endogenous bioavailable testosterone are associated with higher rates of all‐cause and cardiovascular mortality
  • It may be possible that using bioavailable testosterone to perform mortality analysis will yield more accurate results because it prevents the biologically inactive subfraction of testosterone from playing a potential confounding role in the analysis
  • The earliest published material on this matter dates to the late 1930s
  • the concept that testosterone replacement therapy improves angina has yet to be proven wrong
  • In more recent studies, 3 randomized, placebo‐controlled trials demonstrated that administration of testosterone improves myocardial ischemia in men with CAD
  • The improvement in myocardial ischemia was shown to occur in response to both acute and chronic testosterone therapy and seemed to be independent of whether an intravenous or transdermal formulation of testosterone was used.
  • testosterone had no effect on endothelial nitric oxide activity
  • There is growing evidence from in vivo animal models and in vitro models that testosterone induces coronary vasodilation by modulating the activity of ion channels, such as potassium and calcium channels, on the surface of vascular smooth muscle cells
  • Experimental studies suggest that the most likely mechanism of action for testosterone on vascular smooth muscle cells is via modulation of action of non‐ATP‐sensitive potassium ion channels, calcium‐activated potassium ion channels, voltage‐sensitive potassium ion channels, and finally L‐type calcium ion channels
  • Corona et al confirmed those results by demonstrating that not only total testosterone levels are lower among diabetics, but also the levels of free testosterone and SHBG are lower in diabetic patients
  • Laaksonen et al65 followed 702 Finnish men for 11 years and demonstrated that men in the lowest quartile of total testosterone, free testosterone, and SHBG were more likely to develop T2DM and metabolic syndrome.
  • Vikan et al followed 1454 Swedish men for 11 years and discovered that men in the highest quartile of total testosterone were significantly less likely to develop T2DM
  • authors demonstrated a statistically significant increase in the incidence of T2DM in subjects receiving gonadotropin‐releasing hormone antagonist therapy. In addition, a significant increase in the rate of myocardial infarction, stroke, sudden cardiac death, and development of cardiovascular disease was noted in patients receiving antiandrogen therapy.67
  • Several authors have demonstrated that the administration of testosterone in diabetic men improves the homeostatic model of insulin resistance, hemoglobin A1c, and fasting plasma glucose
  • Existing evidence strongly suggests that the levels of total and free testosterone are lower among diabetic patients compared with those in nondiabetics
  • insulin seems to be acting as a stimulant for the hypothalamus to secret gonadotropin‐releasing hormone, which consequently results in increased testosterone production. It can be argued that decreased stimulation of the hypothalamus in diabetics secondary to insulin deficiency could result in hypogonadotropic hypogonadism
  • BMI has been shown to be inversely associated with testosterone levels
  • This interaction may be a result of the promotion of lipolysis in abdominal adipose tissue by testosterone, which may in turn cause reduced abdominal adiposity. On the other hand, given that adipose tissue has a higher concentration of the enzyme aromatase, it could be that increased adipose tissue results in more testosterone being converted to estrogen, thereby causing hypogonadism. Third, increased abdominal obesity may cause reduced testosterone secretion by negatively affecting the hypothalamus‐pituitary‐testicular axis. Finally, testosterone may be the key factor in activating the enzyme 11‐hydroxysteroid dehydrogenase in adipose tissue, which transforms glucocorticoids into their inactive form.
  • increasing age may alter the association between testosterone and CRP. Another possible explanation for the association between testosterone level and CRP is central obesity and waist circumference
  • Bai et al have provided convincing evidence that testosterone might be able to shorten the QTc interval by augmenting the activity of slowly activating delayed rectifier potassium channels while simultaneously slowing the activity of L‐type calcium channels
  • consistent evidence that supplemental testosterone shortens the QTc interval.
  • Intima‐media thickness (IMT) of the carotid artery is considered a marker for preclinical atherosclerosis
  • Studies have shown that levels of endogenous testosterone are inversely associated with IMT of the carotid artery,126–128,32,129–130 as well as both the thoracic134 and the abdominal aorta
  • 1 study has demonstrated that lower levels of free testosterone are associated with accelerated progression of carotid artery IMT
  • another study has reported that decreased levels of total and bioavailable testosterone are associated with progression of atherosclerosis in the abdominal aorta
  • These findings suggest that normal physiologic testosterone levels may help to protect men from the development of atherosclerosis
  • Czesla et al successfully demonstrated that the muscle specimens that were exposed to metenolone had a significant shift in their composition toward type I muscle fibers
  • Type I muscle fibers, also known as slow‐twitch or oxidative fibers, are associated with enhanced strength and physical capability
  • It has been shown that those with advanced CHF have a higher percentage of type II muscle fibers, based on muscle biopsy
  • Studies have shown that men with CHF suffer from reduced levels of total and free testosterone.137 It has also been shown that reduced testosterone levels in men with CHF portends a poor prognosis and is associated with increased CHF mortality.138 Reduced testosterone has also been shown to correlate negatively with exercise capacity in CHF patients.
  • Testosterone replacement therapy has been shown to significantly improve exercise capacity, without affecting LVEF
  • the results of the 3 meta‐analyses seem to indicate that testosterone replacement therapy does not cause an increase in the rate of adverse cardiovascular events
  • Data from 3 meta‐analyses seem to contradict the commonly held belief that testosterone administration may increase the risk of developing prostate cancer
  • One meta‐analysis reported an increase in all prostate‐related adverse events with testosterone administration.146 However, when each prostate‐related event, including prostate cancer and a rise in PSA, was analyzed separately, no differences were observed between the testosterone group and the placebo group
  • the existing data from the 3 meta‐analyses seem to indicate that testosterone replacement therapy does not increase the risk of adverse cardiovascular events
  • the authors correctly point out the weaknesses of their study which include retrospective study design and lack of randomization, small sample size at extremes of follow‐up, lack of outcome validation by chart review and poor generalizability of the results given that only male veterans with CAD were included in this study
    • Nathan Goodyear
      Nathan Goodyear on 04 Dec 13
       
      The authors here present Total Testosterone as a "confounding" value
    • Nathan Goodyear
      Nathan Goodyear on 09 Dec 13
       
      This would be HSD-II
  • the studies that failed to find an association between testosterone and CRP used an older population group
  • low testosterone may influence the severity of CAD by adversely affecting the mediators of the inflammatory response such as high‐sensitivity C‐reactive protein, interleukin‐6, and tumor necrosis factor–α
  • Nathan Goodyear on 20 Nov 13
     
    Good review of Testosterone and CHD.  Low T is associated with increased all cause mortality and cardiovascular mortality, CAD, CHF, type II diabetes, obesity, increased IMT,  increased severity of CAD and CHF.  Testosterone replacement in men with low T has been shown to improve exercise tolerance in CHF, improve insulin resistance, improve HgbA1c and lower BMI in the obese.
wheelchairindia9

Choosing Correct Power wheel chair - 0 views

www.apsense.com/...correct-power-wheel-chair.html

Choosing Correct Power wheel chair Electric Power Wheel Chair folding or rigid design comfortable seating moving freely Life Mobility Center convenient to transport

shared by wheelchairindia9 on 22 Apr 15 - No Cached
  • wheelchairindia9 on 22 Apr 15
     
    Power wheel chair is one type of wheel chairs which is also referred and known as Electric Power Wheel Chair or (EPW). An Power wheel chair is used to move such wheel chairs instead of pushing by some attendant or by hand rims. It also has navigational controls so that it can be moved to any desired direction. Power wheel chairs are suitable for those, who are weaker to move the manual wheel chair using the hand rims and also provides its users a level of comfort. The user can control its speed and direction by a joystick sort of control while sitting on the chair. There are many different types of Power wheel chair and finding the appropriate one will depend on each individual's medical condition. Wheelchairs can be manual or electrically powered. Manual wheelchairs can come in either a folding or rigid design. Rigid type wheelchairs tend to be lighter and more easily maneuvered and should be used by more active wheelchair users. Folding wheelchairs would be an excellent choice for individuals needing to use the wheelchair for travel on a frequent basis. Many people have disabilities that make it difficult to propel themselves in a manual wheelchair and in this situation an electrically powered wheelchair may prove more useful. Power chairs are little bit more complex and the user can control it with minimum effort. This kind of chair will give extraordinary maneuverability, stability and power and it is perfect for people who want more from their wheelchairs. Better Life Mobility Center offers various models, so sure that won't have problem to choose one that will suit completely. All the power chairs that offer are the result of the extensive research and designed with the user's needs in mind. Karma latest power standing wheelchair is now available in India. Power Wheelchairs For Sale - Increase freedom Stand up again improve independence and be find of body. Karma KP 10.2 Power Wheelchair: Features: Seat, base & battery quickly detach f
wheelchairindia9

Choosing Correct Power wheel chair - 0 views

www.articlepoint.org/...correct-power-wheel-chair.aspx

Choosing Correct Power wheel chair Electric Power Wheel Chair folding or rigid design comfortable seating moving freely Life Mobility Center convenient to transport

shared by wheelchairindia9 on 23 Apr 15 - No Cached
  • wheelchairindia9 on 23 Apr 15
     
    Power wheel chair is one type of wheel chairs which is also referred and known as Electric Power Wheel Chair or (EPW). An Power wheel chair is used to move such wheel chairs instead of pushing by some attendant or by hand rims. It also has navigational controls so that it can be moved to any desired direction. Power wheel chairs are suitable for those, who are weaker to move the manual wheel chair using the hand rims and also provides its users a level of comfort. The user can control its speed and direction by a joystick sort of control while sitting on the chair. There are many different types of Power wheel chair and finding the appropriate one will depend on each individual's medical condition. Wheelchairs can be manual or electrically powered. Manual wheelchairs can come in either a folding or rigid design. Rigid type wheelchairs tend to be lighter and more easily maneuvered and should be used by more active wheelchair users. Folding wheelchairs would be an excellent choice for individuals needing to use the wheelchair for travel on a frequent basis. Many people have disabilities that make it difficult to propel themselves in a manual wheelchair and in this situation an electrically powered wheelchair may prove more useful. Power chairs are little bit more complex and the user can control it with minimum effort. This kind of chair will give extraordinary maneuverability, stability and power and it is perfect for people who want more from their wheelchairs. Better Life Mobility Center offers various models, so sure that won't have problem to choose one that will suit completely. All the power chairs that offer are the result of the extensive research and designed with the user's needs in mind. Karma latest power standing wheelchair is now available in India. Power Wheelchairs For Sale - Increase freedom Stand up again improve independence and be find of body. Karma KP 10.2 Power Wheelchair: Features: Seat, base & battery quickly detach f
wheelchairindia9

Choosing Correct Power wheel chair - 0 views

www.blogroll.net/article.php

Choosing Correct Power wheel chair Electric Power Wheel Chair folding or rigid design comfortable seating moving freely Life Mobility Center convenient to transport

shared by wheelchairindia9 on 25 Apr 15 - No Cached
  • wheelchairindia9 on 25 Apr 15
     
    Power wheel chair is one type of wheel chairs which is also referred and known as Electric Power Wheel Chair or (EPW). An Power wheel chair is used to move such wheel chairs instead of pushing by some attendant or by hand rims. It also has navigational controls so that it can be moved to any desired direction. Power wheel chairs are suitable for those, who are weaker to move the manual wheel chair using the hand rims and also provides its users a level of comfort. The user can control its speed and direction by a joystick sort of control while sitting on the chair. There are many different types of Power wheel chair and finding the appropriate one will depend on each individual's medical condition. Wheelchairs can be manual or electrically powered. Manual wheelchairs can come in either a folding or rigid design. Rigid type wheelchairs tend to be lighter and more easily maneuvered and should be used by more active wheelchair users. Folding wheelchairs would be an excellent choice for individuals needing to use the wheelchair for travel on a frequent basis. Many people have disabilities that make it difficult to propel themselves in a manual wheelchair and in this situation an electrically powered wheelchair may prove more useful. Power chairs are little bit more complex and the user can control it with minimum effort. This kind of chair will give extraordinary maneuverability, stability and power and it is perfect for people who want more from their wheelchairs. Better Life Mobility Center offers various models, so sure that won't have problem to choose one that will suit completely. All the power chairs that offer are the result of the extensive research and designed with the user's needs in mind. Karma latest power standing wheelchair is now available in India. Power Wheelchairs For Sale - Increase freedom Stand up again improve independence and be find of body. Karma KP 10.2 Power Wheelchair: Features: Seat, base & battery quickly detach f
wheelchairindia9

Wheelchair Detachable Wheels - 0 views

www.wheelchairindia.com/...Detachable-Wheelchair

Wheelchair Are Detachable And Foldable detachable footrests reversible desk arms wheelchair detachable wheels swing away footrests wheelchair 4 wheel

shared by wheelchairindia9 on 13 May 15 - No Cached
  • wheelchairindia9 on 13 May 15
     
    Wheelchairs is designed for those who prefer a removable armrest wheelchair. A removable armrest allows for easy patient transfer in and out of the chair.This chair is available in a different seat width and comes complete with swingaway footrests. It also incorporates solid rubber casters for a smooth and easy roll. Both detachable and flip-back arms are designed for easier lateral transfers. Most Wheelchairs in this category have Desk-Length arms, a shorter arm that allows rolling up to a desk or table. All are folding-frame chairs and are available in different seat widths. Detachable armrest for use in conjunction with wheelchairs. The armrest is comprised of a horizontal member supported at one end by a vertical member. The horizontal and vertical members are releasably attached to the wheelchair frame, and the attachment of the horizontal member to the wheelchair frame allows rotation of the horizontal member from the normal position to a position of non-use behind the back of the wheelchair. Wheelchairs - Arm Rests: The armrests support the arms and shoulders in comfortable positions and are often used to push off of for transferring from sitting to standing or held on to for balance. Desk-length armrests are shorter than standard length rests and are often chosen so that a person can pull up to a desk or table for easier access. The shorter length of these armrests is undesirable if the wheelchair user needs to use them to assist pushing into a standing position. In this case a full-length armrest would be preferred. Wheelchairs - Footrests: The footrest and legrest support protect the lower leg and feet. If they are too high they decrease the weight carried through the back of the thighs and can cause increased pressure over the buttock region. If they are two low they can cause pressure over the posterior thighs and cause problems with clearing barriers in the environment such as incline transitions. The suggested height of the footrest from th
wheelchairindia9

Karma Aurora 4 - 0 views

disabilityproduct.in/...-Aurora-4-Reclining-Wheelchair

Karma Aurora 4 Reclining Wheelchair Detachable with calf support for added comfort Hand brakes Fordable Karma Aurora 4

shared by wheelchairindia9 on 11 Sep 15 - No Cached
  • wheelchairindia9 on 11 Sep 15
     
    Karma Aurora 4 Reclining Wheelchair Frame Style : Fordable Frame Material : Aluminium (Light weight) Seat Width (inches) : 18" Total width in wheel to wheel : 11" Rear Wheel Size : 24" Front Wheel Size : 7" Seat to floor height (inches) : 20" Seat Depth (inches) : 16" Back height (inches) : 35" Total height (inches) : 50" Max User Weight Capacity (kgs) : 120 Frame Net Weight (kgs) : 13.5 k.g. Upholstery : Cloth water-proof. Armrest : Detachable, for easy transfer to bed. Leg-rest : Detachable, can also be elevated & with calf support for added comfort Wheel Quality : MAG WHEEL Rear Wheel Brakes : Available Hand brakes : Available
Nathan Goodyear

Urinary Estrogens and Estrogen Metabolites and Subsequent Risk of Breast Cancer among P... - 0 views

cancerres.aacrjournals.org/...696.full

estrogen metabolites estrogen metabolism ER estrogen receptors ROS hormones cancer breast cancer

shared by Nathan Goodyear on 07 Oct 15 - No Cached
  • both 2- and 4-catechol estrogen metabolites bind to the ER with affinities comparable with estradiol, 4-catechol estrogen metabolites have lower dissociation rates than estradiol and an enhanced ability to upregulate ER-dependent processes
  • 2-catechol estrogen metabolites act as either weak mitogens (39) or weak inhibitors of cell proliferation
  • While 16α-hydroxyestrone binds to the ER with lower affinity than estradiol, it binds covalently (41) and leads to a constitutively activated ER
  • ...15 more annotations...
  • 4-hydroxyestradiol and 16α-hydroxyestrone increasing proliferation and decreasing apoptosis in a manner similar to estradiol; however, these effects were achieved only at concentrations 10-fold higher than estradiol (39). In contrast, 2-hydroxyestradiol did not have substantial proliferative or antiapoptotic effects
  • In our study, the associations with both 2-hydroxyestrone and 16α-hydroxyestrone were nonsignificantly inverse and we did not observe a consistent trend or significant associations between the 2-hydroxyestrone:16α-hydroxyestrone ratio and breast cancer risk
  • Ratios of the 3 hydroxylation pathways were not significantly associated with risk although the 2:16-pathway and 4:16-pathway ratios were suggestively inversely associated
  • a significant inverse association with the ratio of parent estrogens to estrogen metabolites
  • several potentially estrogenic and genotoxic mechanisms
  • Estrogen metabolites also can be genotoxic
  • Catechol estrogens can be oxidized into quinones and induce DNA damage directly through the formation of DNA adducts, or indirectly via redox cycling and generation of reactive oxygen species
  • the oxidized forms of the catechol estrogens differ in their ability to damage DNA through adducts, with oxidized 2-catechols forming stable and reversible DNA adducts and oxidized 4-catechols forming unstable adducts, which lead to depurination and mutations
  • 2- and 4-catechols have been shown to produce reactive oxygen species and induce oxidative DNA damage
  • act independently from the ER
  • 16α-Hydroxyestrone also may be genotoxic
  • While the catechol estrogens have estrogenic and genotoxic potential, the methylated catechol estrogens, which are catechol estrogens with one hydroxyl group methylated, have been hypothesized to lower the risk of breast cancer
  • The suggested mechanisms are indirect, by decreasing circulating levels of catechol estrogens and thereby the opportunity for catechols to exert genotoxic or proliferative effects, or direct, by inhibiting tumor growth and inducing apoptosis
  • the balance between phase I (oxidation) and phase II (methylation) metabolism of estrogen may be important in hormonally related cancer development.
  • Despite the estrogenic and genotoxic potential of many of the estrogen metabolites, we only observed a significantly increased breast cancer risk with one estrogen metabolite, 17-epiestriol, which has particularly strong estrogenic activity and binds to both ERα and ERβ with an affinity comparable with estradiol
  • Nathan Goodyear on 07 Oct 15
     
    review of estrogen metabolites and breast cancer risk in premenopausal women.
Nathan Goodyear

PLOS ONE: Caramel Color in Soft Drinks and Exposure to 4-Methylimidazole: A Quantitativ... - 0 views

journals.plos.org/...article

4-MEI toxins nutrition carcinogen carcinogens

shared by Nathan Goodyear on 19 Feb 15 - No Cached
  • Nathan Goodyear on 19 Feb 15
     
    Study finds 4-MEI, a known carcinogen, is found in variable levels in soft drinks.  4-MEI is found in caramel flavoring.
1 - 20 of 654 Next › Last »
Showing 20▼ items per page