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krsnaphysio1

Physiotherapist in Gurgaon - 0 views

krsnaphysioplus.com/...physiotherapist-in-gurgaon

physiotherapist physiotherapy

shared by krsnaphysio1 on 26 Nov 19 - No Cached
  • krsnaphysio1 on 26 Nov 19
     
    Since its establishment in the year 2011, Krshna Physio Plus is aimed to provide patients with comprehensive, high quality and professional physiotherapy treatments and rehabilitation to people in need. The efficient team of three, Dr. Ravi Sahauta - A very well-known complex trauma surgeon and Orthopaedician, Dr. Dharm Pal Sharma - an ex-Air force Physio trainer and Dr. Parmila Sharma - an experienced and talented physio expert, Krshna Physio Plus is counted among the well-known Physiotherapy clinic in Gurgaon and Delhi/NCR regions.  This clinic is one of the oldest organizations which was started with a vision to help people suffering from diverse dysfunctionalities with proper guidance and treatment which encompasses mainly physical, psychological, emotional, and social well being. With 8 centers in Delhi/NCR and Bihar, we are aimed at setting over 300 centers across Asia by 2020 and become the Physiotherapy clinic in Gurgaon.  Moreover, KRSNA Physio Plus is well equipped with various advanced facilities and equipment used to treat people to assure patient satisfaction and fast recovery. We have with us Top Physiotherapist in Gurgaon and Delhi/NCR regions with us who are specialized in offering treatment in physiotherapy dealing with Orthopedic, Neurological, Pediatric, Cardio-pulmonary, and Sports Injury, etc. All the experts here put their best for providing the best results.  Our experienced team of doctors and physiotherapists in Gurgaon who would be better able to diagnose what might be making it impossible for you to crane your neck, or pick articles off the floor, or simply kneel before your deity. Sports-Related Injuries Could Happen to Anyone It could be just that badminton match on a winter evening, or an office football match. Before you realize what is happening you've pulled a back muscle or your hamstring. Playing tug-of-war in colleges and office parties is fraught with the risk of a rotator cuff injury. Cricketers diving to save
tom cruze

Clinical Trial Data Management Ensuring regulation and accuracy of clinical trial data | - 0 views

blog.worksure.org/clinical-trial-data-management

Clinical Trial Data Management

shared by tom cruze on 25 Feb 15 - No Cached
  • tom cruze on 25 Feb 15
     
    The data management of a clinical trial is a crucial step for the firms that are undergoing research studies in the hospitals. Maintaining the quality and integrity of clinical data is yet another daring task to perform. Many of recent studies showed numerous troubles with data management system (DMS) in clinical trials performed at academic organizations.
Nathan Goodyear

Journal Articles | The Riordan Clinic - 0 views

www.riordanclinic.org/...journal-articles

Riordan Clinic integrative medicine research articles

shared by Nathan Goodyear on 02 Jun 13 - No Cached
  • Nathan Goodyear on 02 Jun 13
     
    Nice review of the research published out of the Riordan Clinic.  This clinic is at the forefront of integrative medicine.
Dr. Jennifer Martinick

Martinick Hair Restoration Clinics - Effective Hair Restoration Solutions - 0 views

goarticles.com/...7898788

Martinick Hair Dr Jennifer reviews

shared by Dr. Jennifer Martinick on 27 Sep 13 - No Cached
  • Dr. Jennifer Martinick on 27 Sep 13
     
    Martinick Hair Restoration clinic is a well known name for providing effective and permanent hair restoration solutions. The clinic uses the latest technology for transplanting hair and offers expert services to all of its patients.
Dr. Jennifer Martinick

Martinick Hair Restoration Clinic: The Experts Behind - 0 views

www.briefingwire.com/...the-experts-behind-the-success

Dr Jennifer Martinick reviews Hair

shared by Dr. Jennifer Martinick on 30 Oct 13 - No Cached
  • Dr. Jennifer Martinick on 30 Oct 13
     
    Dr Jennifer Martinick of Martinick Hair Restoration Clinic is a globally acclaimed medical professional. Martinick Hair Restoration Clinics are known for providing quality hair restoration solutions and implementing latest techniques.
jiyaroy11

Clinical research for Hair Treatment - CRB Tech - 0 views

crbtech.in/...inical-research-hair-treatment

crb tech reviews crb tech solutions review clinical research

shared by jiyaroy11 on 01 Feb 16 - No Cached
  • jiyaroy11 on 01 Feb 16
     
    Clinical research for Hair Treatment Certain hair shampoos and conditioners and creams creatively become thick current locks, without having affected
FMS Dental Hospital

Best Cosmetic Dental Clinic in India - 0 views

FMS DENTAL is one of the top dental clinics in Hyderabad, India and 5th best dental center in the world (GCR Rating), with multi-specialty practice, in-patient facility and 24 hr. emergency dental ...

Best Cosmetic Dental Clinic in India Dentist

started by FMS Dental Hospital on 27 Mar 18 no follow-up yet
olivehealthcare

Olive Health & London Travel Clinic | Blood Tests | Private BCG London - 0 views

www.olivehealthandtravel.co.uk

BCG vaccination Travel vaccinations Travel clinic occupational health DNA Testing Lose weight quickly

shared by olivehealthcare on 06 Jun 18 - No Cached
  • olivehealthcare on 06 Jun 18
     
    Olive health & travel clinic ilford, London provide quality medical services in different fields like Private BCG london, Slimming jab, InterVax, Mobile phlebotomy, BCG NHS, Umrah vaccination, Ear irrigation, Hajj vaccination, BCG Injection. We also provide Travel vaccinations and antimalarials, Health Immunisations such as BCG, Shingles, HPV, Meningitis, Hepatitis B etc., Blood tests, Mobile phlebotomy (blood tests at home), Ear wax removal by irrigation method, Weight loss clinic (Saxenda), DNA/Paternity tests, and a range of health checks including STI testing.
Nathan Goodyear

Vitamin C Research - IVC Protocol | The Riordan Clinic - 0 views

www.riordanclinic.org/...protocol

IV vitamin C vitamin C IV intravenous Riordan clinic

shared by Nathan Goodyear on 18 Jun 13 - No Cached
  • therapeutic goal of reaching a peak-plasma concentration of ~20 mM (350- 400 mg/dL) is most efficacious
  • The first post IVC plasma level following the 15 gram IVC has been shown to be clinically instructive: levels below 100 mg/dL correlate with higher levels of existent oxidative stress, presumably from higher tumor burden, chemo/radiation damage, hidden infection, or other oxidative insult, such as smoking.
  • If after four infusions the post IVC dosage remains sub-therapeutic, the patient may have an occult infection, may be secretly smoking, or may have tumor progression
  • Nathan Goodyear on 18 Jun 13
     
    IV vitamin C protocol and review of experience from the Riordan Clinic.
kyra smith

Clinical Data Management Services & System - WorkSure® - 0 views

www.worksure.org/...clinical-data-management

Clinical Data Management System

shared by kyra smith on 16 Jan 17 - No Cached
  • kyra smith on 16 Jan 17
     
    Clinical Data Management System (CDM) is leading clinical development industry into a new innings of transformation. It also now faces an elevating attention from the safety and regulatory sectors, which have never been seen earlier. For the biopharmaceutical and medical devices companies, ineffectual data management can make it impossible to market the products efficiently in the multifaceted business and regulatory milieu.
Dr. Jennifer Martinick

Martinick Hair Restoration Clinic Offers World Class Facilities & Techniques - 0 views

www.pressreleasespider.com/feed142632.aspx

Dr Jennifer Martinick reviews Hair

shared by Dr. Jennifer Martinick on 27 Sep 13 - No Cached
  • Dr. Jennifer Martinick on 27 Sep 13
     
    Martinick Hair Restoration clinic is offering hygienic and world class facilities and techniques to deliver outstanding hair transplant results. The surgeons at the Martinick Hair Restoration clinics follow a multi-therapy approach to achieve the desired outcome.
Nathan Goodyear

Clinical controversies in screening women for thyr... [J Midwifery Womens Health. 2006 ... - 0 views

www.ncbi.nlm.nih.gov/...16647667

TSH screening

shared by Nathan Goodyear on 16 Dec 10 - No Cached
  • In November 2002, the American Association of Clinical Endocrinologists (AACE) released new guidelines for clinical practice for the diagnosis and treatment of hyperthyroidism and hypothyroidism, which includes a new thyroid-stimulating hormone (TSH) reference range of 0.3 to 3.0 mIU/
  • Nathan Goodyear on 16 Dec 10
     
    TSH "screening" needs to be between 0.3 and 3 according to American Association of Clinical Endocrinologists
Nathan Goodyear

Testosterone for the aging male; current evidence and recommended practice - 0 views

www.ncbi.nlm.nih.gov/...PMC2544367

leptin Testosterone low T low Testosterone male hormone hormones

shared by Nathan Goodyear on 27 Oct 14 - No Cached
  • Total serum testosterone consists of free testosterone (2%–3%), testosterone bound to sex hormone binding globulin (SHBG) (45%) and testosterone bound to other proteins (mainly albumin −50%)
  • Testosterone binds only loosely to albumin and so this testosterone as well as free testosterone is available to tissues and is termed bioavailable testosterone
  • Testosterone bound to SHBG is tightly bound and is biologically inactive
  • ...13 more annotations...
  • Bioavailable and free testosterone are known to correlate better than total testosterone with clinical sequelae of androgenization such as bone mineral density and muscle strength
  • peak levels seen in the morning following sleep, which can be maintained into the seventh decade
  • Samples should always be taken in the morning before 11 am
  • The reliable measurement of serum free testosterone requires equilibrium dialysis. This is not appropriate for clinical use as it is very time consuming and therefore expensive.
  • With increasing age, a greater number of men have total testosterone levels just below the normal range or in the low-normal range. In these patients total testosterone can be an unreliable indicator of hypogonadal status.
  • It is advised that at least two serum testosterone measurements, taken before 11 am on different mornings, are necessary to confirm the diagnosis.
  • Patients with serum total testosterone consistently below 8 nmol/l invariably demonstrate the clinical syndrome of hypogonadism and are likely to benefit from treatment. Patients with serum total testosterone in the range 8–12 nmol/l often have symptoms attributable to hypogonadism and it may be decided to offer either a clinical trial of testosterone treatment or to make further efforts to define serum bioavailable or free testosterone and then reconsider treatment. Patients with serum total testosterone persistently above 12 nmol/l do not have hypogonadism and symptoms are likely to be due to other disease states or ageing per se so testosterone treatment is not indicated.
  • Total testosterone levels fall at an average of 1.6% per year whilst free and bioavailable levels fall by 2%–3% per year.
  • With advancing age there is also a reduction in androgen receptor concentration in some target tissues and this may contribute to the clinical syndrome of LOH
  • Metabolic clearance declines with age
  • Gonadotrophin levels rise during aging (Feldman et al 2002) and testicular secretory responses to recombinant human chorionic gonadotrophin (hCG) are reduced
  • There are changes in the lutenising hormone (LH) production which consist of decreased LH pulse frequency and amplitude, (Veldhuis et al 1992; Pincus et al 1997) although pituitary production of LH in response to pharmacological stimulation with exogenous GnRH analogues is preserved
  • the decreases in testosterone levels with aging seem to reflect changes at all levels of the hypothalamic-pituitary-testicular axis
  • Nathan Goodyear on 27 Oct 14
     
    Leptin inhibits male Testosterone production at the level of the hypothalamus and at the testicle level.
jiyaroy11

Guidelines in Clinical Research Assessment - 0 views

crbtech.in/...elated-to-clinical-assessments

crb crb tech reviews tech solutions crb tech solutions review

shared by jiyaroy11 on 22 Jan 16 - No Cached
  • jiyaroy11 on 22 Jan 16
     
    What Are the Steps Related to Clinical Assessments? What's incorrect with Cynthia? There are several factors that can cause forgetfulness.
olivehealthcare

DNA Testing - Olive Health & Travel Clinic, Ilford, London - 0 views

www.olivehealthandtravel.co.uk/dna-testing

DNA Testing BCG NHS BCG vaccination BCG Injection Pregnancy Tests Travel clinic Travel vaccinations Travel jabs Travel clinic ilford

shared by olivehealthcare on 26 Jun 18 - No Cached
  • olivehealthcare on 26 Jun 18
     
    In legal cases, DNA Testing performed by only registered nurses, doctors or accredited individuals. At Olive Health & Travel Clinic We offer pregnancy tests by a choice of blood test and urine test. Blood tests are more sensitive than urine tests so we prefer urine test for assurance.
Nathan Goodyear

Pharmacologic ascorbic acid concentrations selectively kill cancer cells: Action as a p... - 0 views

www.pnas.org/...13604.full

IV vitamin C cancer ascorbic acid vitamin C H2O2 GPX glutathione Perioxidase

shared by Nathan Goodyear on 09 Feb 11 - Cached
  • Taken together, these data indicate that ascorbate at concentrations achieved only by i.v. administration may be a pro-drug for formation of H2O2, and that blood can be a delivery system of the pro-drug to tissues.
  • These findings give plausibility to i.v. ascorbic acid in cancer treatment, and have unexpected implications for treatment of infections where H2O2 may be beneficial
  • pharmacologic concentrations of ascorbate killed cancer but not normal cells, that cell death was dependent only on extracellular but not intracellular ascorbate, and that killing was dependent on extracellular hydrogen peroxide (H2O2) formation with ascorbate radical as an intermediate
  • ...48 more annotations...
  • Our data show that ascorbic acid selectively killed cancer but not normal cells, using concentrations that could only be achieved by i.v. administration
  • Ascorbate-mediated cell death was due to protein-dependent extracellular H2O2 generation, via ascorbate radical formation from ascorbate as the electron donor. Like glucose, when ascorbate is infused i.v., the resulting pharmacologic concentrations should distribute rapidly in the extracellular water space (42). We showed that such pharmacologic ascorbate concentrations in media, as a surrogate for extracellular fluid, generated ascorbate radical and H2O2. In contrast, the same pharmacologic ascorbate concentrations in whole blood generated little detectable ascorbate radical and no detectable H2O2. These findings can be accounted for by efficient and redundant H2O2 catabolic pathways in whole blood (e.g., catalase and glutathione peroxidase) relative to those in media or extracellular fluid
  • ascorbic acid administered i.v. in pharmacologic concentrations may serve as a pro-drug for H2O2 delivery to the extracellular milieu
  • H2O2 generated in blood is normally removed by catalase and glutathione peroxidase within red blood cells, with internal glutathione providing reducing equivalents
  • The electron source for glutathione is NADPH from the pentose shunt, via glucose-6-phosphate dehydrogenase. If activity of this enzyme is diminished, the predicted outcome is impaired H2O2 removal causing intravascular hemolysis, the observed clinical finding.
    • Nathan Goodyear
      Nathan Goodyear on 05 Mar 18
       
      The mechansism here is inadequate recycling of GSH due to lack of G6PD, build up of intracellular H2O2 and RBC lysis--hemolysis.
  • Only recently has it been understood that the discordant clinical findings can be explained by previously unrecognized fundamental pharmacokinetics properties of ascorbate
  • Intracellular transport of ascorbate is tightly controlled in relation to extracellular concentration
  • Intravenous ascorbate infusion is expected to drastically change extracellular but not intracellular concentrations
  • For i.v. ascorbate to be clinically useful in killing cancer cells, pharmacologic but not physiologic extracellular concentrations should be effective, independent of intracellular ascorbate concentrations.
    • Nathan Goodyear
      Nathan Goodyear on 05 Mar 18
       
      accumulation of extracellular vitamin C is the effect.
  • It is unknown why ascorbate, via H2O2, killed some cancer cells but not normal cells.
  • There was no correlation with ascorbate-induced cell death and glutathione, catalase activity, or glutathione peroxidase activity.
  • H2O2, as the product of pharmacologic ascorbate concentrations, has potential therapeutic uses in addition to cancer treatment, especially in infections
  • Neutrophils generate H2O2 from superoxide,
  • i.v. ascorbate is effective in some viral infections
  • H2O2 is toxic to hepatitis C
  • Use of ascorbate as an H2O2-delivery system against sensitive pathogens, viral or bacterial, has substantial clinical implications that deserve rapid exploration.
  • Recent pharmacokinetics studies in men and women show that 10 g of ascorbate given i.v. is expected to produce plasma concentrations of nearly 6 mM, which are >25-fold higher than those concentrations from the same oral dose
  • As much as a 70-fold difference in plasma concentrations is expected between oral and i.v. administration,
  • Complementary and alternative medicine practitioners worldwide currently use ascorbate i.v. in some patients, in part because there is no apparent harm
  • Human Burkitt's lymphoma cells
  • We first investigated whether ascorbate in pharmacologic concentrations selectively affected the survival of cancer cells by studying nine cancer cell lines
  • Clinical pharmacokinetics analyses show that pharmacologic concentrations of plasma ascorbate, from 0.3 to 15 mM, are achievable only from i.v. administration
  • plasma ascorbate concentrations from maximum possible oral doses cannot exceed 0.22 mM because of limited intestinal absorption
  • For five of the nine cancer cell lines, ascorbate concentrations causing a 50% decrease in cell survival (EC50 values) were less than 5 mM, a concentration easily achievable from i.v. infusion
  • All tested normal cells were insensitive to 20 mM ascorbate.
    • Nathan Goodyear
      Nathan Goodyear on 05 Mar 18
       
      meaning safe.
  • Lymphoma cells were selected because of their sensitivity to ascorbate
  • As ascorbate concentration increased, the pattern of death changed from apoptosis to pyknosis/necrosis, a pattern suggestive of H2O2-mediated cell death
  • Apoptosis occurred by 6 h after exposure, and cell death by pyknosis was ≈90% at 14 h after exposure
    • Nathan Goodyear
      Nathan Goodyear on 05 Mar 18
       
      work continued beyond the IVC therapy itself
  • In contrast to lymphoma cells, there was little or no killing of normal lymphocytes and monocytes by ascorbate
  • Ascorbate is transported into cells as such by sodium-dependent transporters, whereas dehydroascorbic acid is transported into cells by glucose transporters and then immediately reduced internally to ascorbate
  • Whether or not intracellular ascorbate was preloaded, extracellular ascorbate induced the same amount and type of death.
  • extracellular ascorbate in pharmacologic concentrations mediates death of lymphoma cells by apoptosis and pyknosis/necrosis, independently of intracellular ascorbate.
  • H2O2 as the effector species mediating pharmacologic ascorbate-induced cell death
  • Superoxide dismutase was not protective
  • Because these data implicated H2O2 in cell killing, we added H2O2 to lymphoma cells and studied death patterns using nuclear staining (19, 28). The death patterns found with exogenous H2O2 exposure were similar to those found with ascorbate
  • For both ascorbate and H2O2, death changed from apoptosis to pyknosis/necrosis as concentrations increased
  • Sensitivity to direct exposure to H2O2 was greater in lymphoma cells compared with normal lymphocytes and normal monocytes
  • There was no association between the EC50 for ascorbate-mediated cell death and intracellular glutathione concentrations, catalase activity, or glutathione peroxidase activity
  • H2O2 generation was dependent on time, ascorbate concentration, and the presence of trace amounts of serum in media
  • ascorbate radical is a surrogate marker for H2O2 formation.
  • whatever H2O2 is generated should be removed by glutathione peroxidase and catalase within red blood cells, because H2O2 is membrane permeable
  • The data are consistent with the hypothesis that ascorbate in pharmacologic concentrations is a pro-drug for H2O2 generation in the extracellular milieu but not in blood.
  • The occurrence of one predicted complication, oxalate kidney stones, is controversial
  • In patients with glucose-6-phosphate dehydrogenase deficiency, i.v. ascorbate is contraindicated because it causes intravascular hemolysis
  • ascorbate at pharmacologic concentrations in blood is a pro-drug for H2O2 delivery to tissues.
  • ascorbate, an electron-donor in such reactions, ironically initiates pro-oxidant chemistry and H2O2 formation
  • data here showed that ascorbate initiated H2O2 formation extracellularly, but H2O2 targets could be either intracellular or extracellular, because H2O2 is membrane permeant
    • Nathan Goodyear
      Nathan Goodyear on 05 Mar 18
       
      the conversion of ascorbate to H2O2 occurs extracellular
  • More than 100 patients have been described, presumably without glucose-6-phosphate dehydrogenase deficiency, who received 10 g or more of i.v. ascorbate with no reported adverse effects other than tumor lysis
  • Nathan Goodyear on 09 Feb 11
     
    IV vitamin C benefits cancer patients
Nathan Goodyear

High Progesterone Receptor Expression in Prostate Cancer Is Associated with Clinical Fa... - 0 views

www.ncbi.nlm.nih.gov/...PMC4344236

prostate cancer progesterone progesterone receptor hormones cancer prostate

shared by Nathan Goodyear on 03 Jun 18 - No Cached
  • Currently, there is a general agreement of PGR presence in the stromal cells of PCa
  • expressed in both stromal and tumor cells of the PCa tissue
  • In univariate analysis, a high density level of PGR in both TE and TS was associated with CF
  • ...17 more annotations...
  • High density level of PGR in the TE was an independent prognostic factor for CF.
  • Our large-sized study demonstrates a wide distribution of PGR in stromal and epithelial cells of both benign and malignant prostate tissue
  • there seems to be a general agreement of PGR presence in the stromal cells of PCa
  • In line with our findings, several have also reported a high PGR expression in TE of PCa [9,10,23,25]. In contrast, others have demonstrated a total lack of PGR expression in TE
  • the actions of progesterone are tissue specific
  • In our work univariate analysis demonstrated a high PGR expression in TS to be associated with clinical failure in PCa patients. So far we have not yet demonstrated the mechanism underlying this association
  • Several non-genomic proliferative actions of progesterone have been proposed in tumor cells of other organs, including breast [35–37], astrocytoma [38] and osteosarcoma [39] cell lines. However, such results are contradicted by suggestions of anti-proliferative actions of progesterone in endometrial cancer
  • Yu et al. found PGR to be negatively regulating stromal cell proliferation in vitro
  • high PGR density level in TE was associated with CF in patients with Gleason score ≥ 7
  • Bonkhoff et al. have suggested progressive emergence of PGR during PCa progression and metastasis
  • Latil and co-workers found a decreased PGR expression in clinically localized tumors and increased PGR expression in hormone-refractory tumors, when compared with normal prostate tissue
  • Our findings provide further support to these findings, indicating that PGR plays a role in the pathogenesis of PCa
  • Ki67 and PGR in TE were correlated with CF (S3 Text), indicating an association between PGR and proliferative activity
  • The mechanism behind the PGR up-regulation in PCa has not yet been elucidated
  • The PGR is, like the glucocorticoid receptor, similar to androgen receptor with 88% sequence homology in the ligand-binding domain
  • progesterone induced expression of androgen receptor-regulated genes could be a potential mechanism contributing to the development of castrate resistant PCa
  • A possibility of different roles by the two PGR isoforms in normal prostate tissue and PCa, as is suggested for the estrogen receptors [13], must also be taken into account
  • Nathan Goodyear on 03 Jun 18
     
    STudy finds that increased Progesterone receptor expression on epithelial and stromal cells is associated with increased clinical failure of therapy.  Several proposed mechanisms: 88% homologous with androgen receptor suggesting cross-stimulation and via progesterone induced increased androgen receptor gene stimulation i.e. epigenetics.
sofiawalker171

Benefit of A Clinical Hypnotherapist for Women - Trina Blum - Medium - 0 views

medium.com/...erapist-for-women-ce12a1c5e80e

a clinical hypnotherapist for women

shared by sofiawalker171 on 09 Jan 18 - No Cached
  • sofiawalker171 on 09 Jan 18
     
    Hypnotherapy in our opinion is a self belief to overcome a problem. We personally believe that hypnosis will be optimally effective when the person is highly motivated to overcome his problem and when the hypnotherapist is well trained in general considerations relating to the treatment of their particular problem and hypnosis both. Some patients seem to have higher native hypnotic capacity and talent that may allow them to benefit more efficiently from hypnosis. For women there are many benefits of a clinical hypnotherapist for women
indian-health

Get Your Old Smile Back With Dental Surgery India - 0 views

www.apsense.com/...with-dental-surgery-india.html

Dental Surgery India Dental Surgeons In Delhi Best Dental Surgeons of Delhi Top dental affordable clinics in new delhi. best dental clinics of new delhi dental affordable clinics surgery success stories top 14 dental surgeons of delhi top 14 dental surgeo

shared by indian-health on 27 May 22 - No Cached
  • indian-health on 27 May 22
     
    Around 15,000 foreigners travel every year for dental surgery India has come to be one of the hotspots due to its affordability. Getting dental works at best dental clinics of New Delhi are actually extra lower priced than western international countries.
Nathan Goodyear

Testosterone: a vascular hormone in health and disease - 0 views

joe.endocrinology-journals.org/...R47.full

testosterone hormone health disease hormones men male cardiovascular disease CVD

shared by Nathan Goodyear on 13 May 13 - No Cached
  • Testosterone has beneficial effects on several cardiovascular risk factors, which include cholesterol, endothelial dysfunction and inflammation
  • In clinical studies, acute and chronic testosterone administration increases coronary artery diameter and flow, improves cardiac ischaemia and symptoms in men with chronic stable angina and reduces peripheral vascular resistance in chronic heart failure.
  • testosterone is an L-calcium channel blocker and induces potassium channel activation in vascular smooth muscle cells
  • ...54 more annotations...
  • Animal studies have consistently demonstrated that testosterone is atheroprotective, whereas testosterone deficiency promotes the early stages of atherogenesis
  • there is no compelling evidence that testosterone replacement to levels within the normal healthy range contributes adversely to the pathogenesis of CVD (Carson & Rosano 2011) or prostate cancer (Morgentaler & Schulman 2009)
  • bidirectional effect between decreased testosterone concentrations and disease pathology exists as concomitant cardiovascular risk factors (including inflammation, obesity and insulin resistance) are known to reduce testosterone levels and that testosterone confers beneficial effects on these cardiovascular risk factors
  • Achieving a normal physiological testosterone concentration through the administration of testosterone replacement therapy (TRT) has been shown to improve risk factors for atherosclerosis including reducing central adiposity and insulin resistance and improving lipid profiles (in particular, lowering cholesterol), clotting and inflammatory profiles and vascular function
  • It is well known that impaired erectile function and CVD are closely related in that ED can be the first clinical manifestation of atherosclerosis often preceding a cardiovascular event by 3–5 years
  • no decrease in the response (i.e. no tachyphylaxis) of testosterone and that patient benefit persists in the long term.
  • free testosterone levels within the physiological range, has been shown to result in a marked increase in both flow- and nitroglycerin-mediated brachial artery vasodilation in men with CAD
  • Clinical studies, however, have revealed either small reductions of 2–3 mm in diastolic pressure or no significant effects when testosterone is replaced within normal physiological limits in humans
  • Endothelium-independent mechanisms of testosterone are considered to occur primarily via the inhibition of voltage-operated Ca2+ channels (VOCCs) and/or activation of K+ channels (KCs) on smooth muscle cells (SMCs)
  • Testosterone shares the same molecular binding site as nifedipine
  • Testosterone increases the expression of endothelial nitric oxide synthase (eNOS) and enhances nitric oxide (NO) production
  • Testosterone also inhibited the Ca2+ influx response to PGF2α
  • one of the major actions of testosterone is on NO and its signalling pathways
  • In addition to direct effects on NOS expression, testosterone may also affect phosphodiesterase type 5 (PDE5 (PDE5A)) gene expression, an enzyme controlling the degradation of cGMP, which acts as a vasodilatory second messenger
  • the significance of the action of testosterone on VSMC apoptosis and proliferation in atherosclerosis is difficult to delineate and may be dependent upon the stage of plaque development
  • Several human studies have shown that carotid IMT (CIMT) and aortic calcification negatively correlate with serum testosterone
  • t long-term testosterone treatment reduced CIMT in men with low testosterone levels and angina
  • neither intracellular nor membrane-associated ARs are required for the rapid vasodilator effect
  • acute responses appear to be AR independent, long-term AR-mediated effects on the vasculature have also been described, primarily in the context of vascular tone regulation via the modulation of gene transcription
  • Testosterone and DHT increased the expression of eNOS in HUVECs
  • oestrogens have been shown to activate eNOS and stimulate NO production in an ERα-dependent manner
  • Several studies, however, have demonstrated that the vasodilatory actions of testosterone are not reduced by aromatase inhibition
  • non-aromatisable DHT elicited similar vasodilation to testosterone treatment in arterial smooth muscle
  • increased endothelial NOS (eNOS) expression and phosphorylation were observed in testosterone- and DHT-treated human umbilical vein endothelial cells
  • Androgen deprivation leads to a reduction in neuronal NOS expression associated with a decrease of intracavernosal pressure in penile arteries during erection, an effect that is promptly reversed by androgen replacement therapy
  • Observational evidence suggests that several pro-inflammatory cytokines (including interleukin 1β (IL1β), IL6, tumour necrosis factor α (TNFα), and highly sensitive CRP) and serum testosterone levels are inversely associated in patients with CAD, T2DM and/or hypogonadism
  • patients with the highest IL1β concentrations had lower endogenous testosterone levels
  • TRT has been reported to significantly reduce TNFα and elevate the circulating anti-inflammatory IL10 in hypogonadal men with CVD
  • testosterone treatment to normalise levels in hypogonadal men with the MetS resulted in a significant reduction in the circulating CRP, IL1β and TNFα, with a trend towards lower IL6 compared with placebo
  • parenteral testosterone undecanoate, CRP decreased significantly in hypogonadal elderly men
  • Higher levels of serum adiponectin have been shown to lower cardiovascular risk
  • Research suggests that the expression of VCAM-1, as induced by pro-inflammatory cytokines such as TNFα or interferon γ (IFNγ (IFNG)) in endothelial cells, can be attenuated by treatment with testosterone
  • Testosterone also inhibits the production of pro-inflammatory cytokines such as IL6, IL1β and TNFα in a range of cell types including human endothelial cells
  • decreased inflammatory response to TNFα and lipopolysaccharide (LPS) in human endothelial cells when treated with DHT
  • The key to unravelling the link between testosterone and its role in atherosclerosis may lay in the understanding of testosterone signalling and the cross-talk between receptors and intracellular events that result in pro- and/or anti-inflammatory actions in athero-sensitive cells.
  • testosterone functions through the AR to modulate adhesion molecule expression
  • pre-treatment with DHT reduced the cytokine-stimulated inflammatory response
  • DHT inhibited NFκB activation
  • DHT could inhibit an LPS-induced upregulation of MCP1
  • Both NFκB and AR act at the transcriptional level and have been experimentally found to be antagonistic to each other
  • As the AR and NFκB are mutual antagonists, their interaction and influence on functions can be bidirectional, with inflammatory agents that activate NFκB interfering with normal androgen signalling as well as the AR interrupting NFκB inflammatory transcription
  • prolonged exposure of vascular cells to the inflammatory activation of NFκB associated with atherosclerosis may reduce or alter any potentially protective effects of testosterone
  • DHT and IFNγ also modulate each other's signalling through interaction at the transcriptional level, suggesting that androgens down-regulate IFN-induced genes
  • (Simoncini et al. 2000a,b). Norata et al. (2010) suggest that part of the testosterone-mediated atheroprotective effects could depend on ER activation mediated by the testosterone/DHT 3β-derivative, 3β-Adiol
  • TNFα-induced induction of ICAM-1, VCAM-1 and E-selectin as well as MCP1 and IL6 was significantly reduced by a pre-incubation with 3β-Adiol in HUVECs
  • 3β-Adiol also reduced LPS-induced gene expression of IL6, TNFα, cyclooxygenase 2 (COX2 (PTGS2)), CD40, CX3CR1, plasminogen activator inhibitor-1, MMP9, resistin, pentraxin-3 and MCP1 in the monocytic cell line U937 (Norata et al. 2010)
  • This study suggests that testosterone metabolites, other than those generated through aromatisation, could exert anti-inflammatory effects that are mediated by ER activation.
  • The authors suggest that DHT differentially effects COX2 levels under physiological and pathophysiological conditions in human coronary artery smooth muscle cells and via AR-dependent and -independent mechanisms influenced by the physiological state of the cell
  • There are, however, a number of systematic meta-analyses of clinical trials of TRT that have not demonstrated an increased risk of adverse cardiovascular events or mortality
  • The TOM trial, which was designed to investigate the effect of TRT on frailty in elderly men, was terminated prematurely as a result of an increased incidence of cardiovascular-related events after 6 months in the treatment arm
  • trials of TRT in men with either chronic stable angina or chronic cardiac failure have also found no increase in either cardiovascular events or mortality in studies up to 12 months
  • Evidence may therefore suggest that low testosterone levels and testosterone levels above the normal range have an adverse effect on CVD, whereas testosterone levels titrated to within the mid- to upper-normal range have at least a neutral effect or, taking into account the knowledge of the beneficial effects of testosterone on a series of cardiovascular risk factors, there may possibly be a cardioprotective action
  • The effect of testosterone on human vascular function is a complex issue and may be dependent upon the underlying androgen and/or disease status.
  • the majority of studies suggest that testosterone may display both acute and chronic vasodilatory effects upon various vascular beds at both physiological and supraphysiological concentrations and via endothelium-dependent and -independent mechanisms
  • Nathan Goodyear on 13 May 13
     
    Good deep look into the testosterone and CVD link.
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