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Nathan Goodyear

Exposure to volatile organic compounds and loss of pulmonary function in the elderly - 0 views

erj.ersjournals.com/...1270.abstract

volatile solvents benzene xylene toluene

shared by Nathan Goodyear on 14 Apr 11 - No Cached
  • is study suggests that exposure to toluene and xylene exert a harmful effect on pulmonary function by exacerbating oxidative stress in elderly people.
  • Nathan Goodyear on 14 Apr 11
     
    volatile solvents and lung damage
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
wheelchairindia9

Electronic Wheel chair - 0 views

www.wheelchairindia.com/...POWER-WHEELCHAIR

Shower Wheelchair Can Dramatically Improve Lives Electronic Wheel chair electric propulsion by motors a joy stick or push buttons shower wheelchair lightweight and portable for travel accessible seat frame

shared by wheelchairindia9 on 16 Apr 15 - No Cached
  • wheelchairindia9 on 16 Apr 15
     
    Golden Technologies takes all the worry out of purchasing a power wheelchair. Designers blend the most technologically advanced components with superior designs to provide with the almost in quality, comfort and style. Motorized wheelchairs to enter bike lanes if a sidewalk isn't available or passable by wheelchair. Wheelchair users would be required to yield the right-of-way to bikers. The proposal also adds motorized wheelchairs to current law affecting vehicles and bicycles on the road, including the required three foot law between bikers and drivers. Supporters bill would help wheelchair users get around quickly and that areas without sidewalks are often difficult to navigate. It's the standard chair, with the main frame attaches to the front. This isn't a futuristic design as such, but a very good way of maintaining or building strength in those who are bound to a wheelchair, and may hope to walk again in their future. Personally, this bike is pretty cool. It's got a front frame similar to a chopper, with the added comfort of a chair appose to a saddle. A new module is set to transform electric powered wheelchairs into communication hubs. An powerchair is more compact and has a better turning radius than an electric scooter; making it is easier to navigate narrow doorways and tight turns. Another advantage of the powerwheelchair is that its armchair joystick does not require an upright posture like an electric scooter's handlebars. Most power wheelchairs can also be taken apart and stowed, while scooters usually can't. Powerwheelchairs are also usually less expensive than scooters. For many disabled people, the only way to move around is by using a wheelchair. Those who cannot powered wheelchairs propel themselves with their arms, which often leads to fatigue, pain, and even permanent damage to arms and shoulders. BENEFITS: Activates circulation system and improves cardio-pulmonary function. Helps prevent decubitus sores. Improves bowel regu
Nathan Goodyear

Cancer cells metabolically "fertilize" the tumor microenvironment with hydrogen peroxid... - 0 views

www.ncbi.nlm.nih.gov/...PMC3180189

cancer reverse warburg effect warburg effect NF-kapppB HIF-1alpha Cav-1 H2O2

shared by Nathan Goodyear on 12 Nov 14 - No Cached
  • reducing oxidative stress with powerful antioxidants, is an important strategy for cancer prevention, as it would suppress one of the key early initiating steps where DNA damage and tumor-stroma metabolic-coupling begins. This would prevent cancer cells from acting as metabolic “parasites
  • Oxidative stress in cancer-associated fibroblasts triggers autophagy and mitophagy, resulting in compartmentalized cellular catabolism, loss of mitochondrial function, and the onset of aerobic glycolysis, in the tumor stroma. As such, cancer-associated fibroblasts produce high-energy nutrients (such as lactate and ketones) that fuel mitochondrial biogenesis and oxidative metabolism in cancer cells. We have termed this new energy-transfer mechanism the “reverse Warburg effect.
  • Then, oxidative stress, in cancer-associated fibroblasts, triggers the activation of two main transcription factors, NFκB and HIF-1α, leading to the onset of inflammation, autophagy, mitophagy and aerobic glycolysis in the tumor microenvironment
  • ...38 more annotations...
  • oxidative stress and ROS, produced in cancer-associated fibroblasts, has a “bystander effect” on adjacent cancer cells, leading to DNA damage, genomic instability and aneuploidy, which appears to be driving tumor-stroma co-evolution
  • tumor cells produce and secrete hydrogen peroxide, thereby “fertilizing” the tumor microenvironment and driving the “reverse Warburg effect.”
  • This type of stromal metabolism then produces high-energy nutrients (lactate, ketones and glutamine), as well as recycled chemical building blocks (nucleotides, amino acids, fatty acids), to literally “feed” cancer cells
  • loss of stromal caveolin (Cav-1) is sufficient to drive mitochondrial dysfunction with increased glucose uptake in fibroblasts, mimicking the glycolytic phenotype of cancer-associated fibroblasts.
  • oxidative stress initiated in tumor cells is transferred to cancer-associated fibroblasts.
  • Then, cancer-associated fibroblasts show quantitative reductions in mitochondrial activity and compensatory increases in glucose uptake, as well as high ROS production
  • These findings may explain the prognostic value of a loss of stromal Cav-1 as a marker of a “lethal” tumor microenvironment
  • aerobic glycolysis takes place in cancer-associated fibroblasts, rather than in tumor cells, as previously suspected.
  • our results may also explain the “field effect” in cancer biology,5 as hydrogen peroxide secreted by cancer cells, and the propagation of ROS production, from cancer cells to fibroblasts, would create an increasing “mutagenic field” of ROS production, due to the resulting DNA damage
  • Interruption of this process, by addition of catalase (an enzyme that detoxifies hydrogen peroxide) to the tissue culture media, blocks ROS activity in cancer cells and leads to apoptotic cell death in cancer cells
  • In this new paradigm, cancer cells induce oxidative stress in neighboring cancer-associated fibroblasts
  • cancer-associated fibroblasts have the largest increases in glucose uptake
  • cancer cells secrete hydrogen peroxide, which induces ROS production in cancer-associated fibroblasts
  • Then, oxidative stress in cancer-associated fibroblast leads to decreases in functional mitochondrial activity, and a corresponding increase in glucose uptake, to fuel aerobic glycolysis
  • cancer cells show significant increases in mitochondrial activity, and decreases in glucose uptake
  • fibroblasts and cancer cells in co-culture become metabolically coupled, resulting in the development of a “symbiotic” or “parasitic” relationship.
  • cancer-associated fibroblasts undergo aerobic glycolysis (producing lactate), while cancer cells use oxidative mitochondrial metabolism.
  • We have previously shown that oxidative stress in cancer-associated fibroblasts drives a loss of stromal Cav-1, due to its destruction via autophagy/lysosomal degradation
  • a loss of stromal Cav-1 is sufficient to induce further oxidative stress, DNA damage and autophagy, essentially mimicking pseudo-hypoxia and driving mitochondrial dysfunction
  • loss of stromal Cav-1 is a powerful biomarker for identifying breast cancer patients with early tumor recurrence, lymph-node metastasis, drug-resistance and poor clinical outcome
  • this type of metabolism (aerobic glycolysis and autophagy in the tumor stroma) is characteristic of a lethal tumor micro-environment, as it fuels anabolic growth in cancer cells, via the production of high-energy nutrients (such as lactate, ketones and glutamine) and other chemical building blocks
  • the upstream tumor-initiating event appears to be the secretion of hydrogen peroxide
  • one such enzymatically-active protein anti-oxidant that may be of therapeutic use is catalase, as it detoxifies hydrogen peroxide to water
  • numerous studies show that “catalase therapy” in pre-clinical animal models is indeed sufficient to almost completely block tumor recurrence and metastasis
  • by eliminating oxidative stress in cancer cells and the tumor microenvironment,55 we may be able to effectively cut off the tumor's fuel supply, by blocking stromal autophagy and aerobic glycolysis
  • breast cancer patients show systemic evidence of increased oxidative stress and a decreased anti-oxidant defense, which increases with aging and tumor progression.68–70 Chemotherapy and radiation therapy then promote further oxidative stress.69 Unfortunately, “sub-lethal” doses of oxidative stress during cancer therapy may contribute to tumor recurrence and metastasis, via the activation of myofibroblasts.
  • a loss of stromal Cav-1 is associated with the increased expression of gene profiles associated with normal aging, oxidative stress, DNA damage, HIF1/hypoxia, NFκB/inflammation, glycolysis and mitochondrial dysfunction
  • cancer-associated fibroblasts show the largest increases in glucose uptake, while cancer cells show corresponding decreases in glucose uptake, under identical co-culture conditions
  • Thus, increased PET glucose avidity may actually be a surrogate marker for a loss of stromal Cav-1 in human tumors, allowing the rapid detection of a lethal tumor microenvironment.
  • it appears that astrocytes are actually the cell type responsible for the glucose avidity.
  • In the brain, astrocytes are glycolytic and undergo aerobic glycolysis. Thus, astrocytes take up and metabolically process glucose to lactate.7
  • Then, lactate is secreted via a mono-carboxylate transporter, namely MCT4. As a consequence, neurons use lactate as their preferred energy substrate
  • both astrocytes and cancer-associated fibroblasts express MCT4 (which extrudes lactate) and MCT4 is upregulated by oxidative stress in stromal fibroblasts.34
  • In accordance with the idea that cancer-associated fibroblasts take up the bulk of glucose, PET glucose avidity is also now routinely used to measure the extent of fibrosis in a number of human diseases, including interstitial pulmonary fibrosis, postsurgical scars, keloids, arthritis and a variety of collagen-vascular diseases.
  • PET glucose avidity and elevated serum inflammatory markers both correlate with poor prognosis in breast cancers.
  • PET signal over-estimates the actual anatomical size of the tumor, consistent with the idea that PET glucose avidity is really measuring fibrosis and inflammation in the tumor microenvironment.
  • human breast and lung cancer patients can be positively identified by examining their exhaled breath for the presence of hydrogen peroxide.
  • tumor cell production of hydrogen peroxide drives NFκB-activation in adjacent normal cells in culture6 and during metastasis,103 directly implicating the use of antioxidants, NFκB-inhibitors and anti-inflammatory agents, in the treatment of aggressive human cancers.
  • Nathan Goodyear on 12 Nov 14
     
    Good description of the communication between cancer cells and fibroblasts.  This theory is termed the "reverse Warburg effect".
Nathan Goodyear

Role of IL-2 in cancer immunotherapy: OncoImmunology: Vol 5, No 6 - 1 views

www.tandfonline.com/...2162402X.2016.1163462

IL-2 cancer immune system

shared by Nathan Goodyear on 17 Apr 18 - No Cached
  • IL-2 is one of the key cytokines with pleiotropic effects on the immune system
  • IL-2 as “T-cell growth factor”
  • approved for the treatment of metastatic renal cell carcinoma (1992) and later for metastatic melanoma (1998) by FDA
  • ...13 more annotations...
  • It is produced predominately by antigen-simulated CD4+ T cells, while it can also be produced by CD8+ cells, natural killer (NK) cells, and activated dendritic cells (DC)
  • IL-2 is an important factor for the maintenance of CD4+ regulatory T cells
  • plays a critical role in the differentiation of CD4+ T cells into a variety of subsets
  • It can promote CD8+ T-cell and NK cell cytotoxicity activity, and modulate T-cell differentiation programs in response to antigen, promoting naive CD4+ T-cell differentiation into T helper-1 (Th1) and T helper-2 (Th2) cells while inhibiting T helper-17 (Th17) differentiation
  • Of note, Tregs, which act to dampen the immune response, constitutively express high levels of α chain
  • IL-2Rα is unique to IL-2 and is expressed by a number of immune cells including T regulatory cells (Treg), activated CD4+ and CD8+T cells, B cells, mature DCs, endothelial cells
  • some investigators evaluated the efficacy of regimens containing low-dose IL-2
  • IL-2 can promote the activation and cell growth of T and NK cells
  • Unfortunately, not all of patients would benefit from targeted therapy and nearly all patients who initially respond to targeted inhibitors inevitably develop acquired resistance to the treatment
  • IL-2 also stimulates T-regulatory cells that constitutively express CTLA-4 and can suppress immune reactions. Hence, IL-2 might enhance antitumor reactivity in the presence of CTLA-4 blockade
  • both HD and low-dose IL-2 therapy preferentially induce the expansion of CD4+CD25+Foxp3+ Treg and the Treg level remains elevated after each cycle of HD IL-2 therapy
  • Due to rapid elimination and metabolism via the kidney, IL-2 has a short serum half-life of several minutes
  • HD IL-2-induced severe toxicities including vascular leak syndrome (VLS), pulmonary edema, hypotension, and heart toxicities
  • Nathan Goodyear on 17 Apr 18
     
    Great historical and functional role of IL-2 in the fight against cancer.
Nathan Goodyear

Higher serum testosterone and dihydrotestosterone, but not estradio... - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...25660119

Testosterone DHT dihydrotestosterone Estradiol male men hormone hormones FEV1 FVC pulmonary function

shared by Nathan Goodyear on 16 Feb 15 - No Cached
  • Nathan Goodyear on 16 Feb 15
     
    Higher Testosterone and DHT levels in men was found to be positively associated with FEV1 and FVC; Estradiol was not.  The question here is cause or effect.   Also interesting is the fact that smokers had higher Testosterone levels compared to non-smokers.
Nathan Goodyear

IL-2: The First Effective Immunotherapy for Human Cancer | The Journal of Immunology - 0 views

www.jimmunol.org/...5451

cancer IL-2 Treg immune system immunology

shared by Nathan Goodyear on 17 Apr 18 - No Cached
  • IL-2 is a 15.5-kDa cytokine secreted predominately by Ag-simulated CD4+ T cells, but it can also be produced by CD8+ cells, NK cells, and activated dendritic cells
  • IL-2 is the predominant factor responsible for the maintenance of CD4+ regulatory T cells
  • A generalized capillary leak syndrome was induced by IL-2 in vivo that resulted in interstitial pulmonary infiltrates and substantial weight gain in patients
  • ...4 more annotations...
  • The side effects were transient and returned to baseline following treatment
  • Tumors do not express IL-2 receptors and thus the antitumor activity was the result of IL-2 stimulation of immune cell
  • Patients with metastatic melanoma or metastatic renal cell cancer were uniquely responsive to high-dose IL-2 administration, and except for patients with advanced non-Hodgkin’s lymphomas (35) only rare responses were seen in patients with other tumor types
  • The underlying toxicity of IL-2 results from a capillary leak that leads to fluid extravasation into visceral organs that can compromise their function
  • Nathan Goodyear on 17 Apr 18
     
    Great review of the history of IL-2 in the treatment of cancer.  IL-2 stimulates the immune system to attack cancer.  Don't reinvent the wheel; use what is already present and available.
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