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Hand Driven Tricycle India - 0 views

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    Tricycle is also better and will enable the rider to make sharper turns on roads. Every time a person needs to be seated in a conventional tricycle or disembark from it, the needs help. But attached footrests to help the rider. With a bigger seat and stronger tyres, the vehicle will also help vendors. And every part of the cycle can be dismantled too, which makes it easier to transport. Although tricycles are often associated with toddlers, they are also widely ridden by adults. 'Trikes' are often ridden by older adults or people with disabilities who prefer the extra balance offered by a third wheel. Characteristics of Tricycles: Three wheels. Easily balanced. Brakes. Gears. Often have a storage basket at the rear. Can buy electric powered tricycles. In tricycles distinct types of pedal-driven motion. The tricycle was conceived and produced especially for children from the outset, however bicycles for children were derived by a simple reduction of the scale of the adult counterpart. Standard Single Hand Drive Tricycle: Frame : Made by E.R.W. Tubes 22.22 mm- 18 G. Seat & Back : MS, CRC Sheet Seat Size 18"x 16" Wheel Size : Wheel Diameter 28"x 1 1/2" Tyre and Tube Standard Company. Parts : Standard Quality Color : Black Painted Brake : Front Wheel liver System Drive : Rear Wheel Right Side Tricycle with rear wheel chain-driven transmission and a diamond shaped frame, it quickly entered into widespread use for transportation, work, and leisure purposes. Tricycles are available to accommodate a vast array of special needs. Hand-pedaled recumbent tricycles make it possible for those without the use of their legs. Children, teens and adults with cerebral palsy and similar disorders can select tricycles specially designed to increase strength and coordination. Caregivers to autistic children can ride with their child on tandem special needs tricycles built to accommodate one adult and one child rider.
Nathan Goodyear

Seasonal variation of salivary testosterone in men, normally cycling women, and women u... - 0 views

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    study of 296 men with mean age at 22.7, have peak salivary Testosterone production in December and January. 
Nathan Goodyear

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

  • 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
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  • 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
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    review of estrogen metabolites and breast cancer risk in premenopausal women.
Nathan Goodyear

Urinary estrogens and estrogen metabolites and subsequent risk of breast cancer among p... - 0 views

  • 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 risk of breast cancer.
  • Despite the estrogenic and genotoxic potential of many of the EM, we only observed a significantly increased breast cancer risk with one EM, 17-epiestriol, which has particularly strong estrogenic activity and binds to both ERα and ERβ with an affinity comparable to estradiol
  • We did not observe reduced risk for higher concentrations of 2-pathway EM relative to 16-pathway EM, nor did we observe a consistent benefit of higher concentrations of methylated catechol EM compared with catechol EM.
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  • EM also can be genotoxic, but the individual EM vary in their ability to induce DNA damage
  • 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 (46). These catechols also induce neoplastic transformation in ER-cells, and thus act independently from the ER
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    Estrogen metabolites.
Nathan Goodyear

Pregnancy, progesterone and progestins in relation... [J Steroid Biochem Mol Biol. 2005... - 0 views

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    Bioidentical Progesterone does not increase breast cancer risk
Nathan Goodyear

Influences of percutaneous administration of estra... [Fertil Steril. 1995] - PubMed re... - 0 views

  • Increased P concentration significantly decreases the number of cycling epithelial cells.
  • CONCLUSION: Exposure to P for 10 to 13 days reduces E2-induced proliferation of normal breast epithelial cells in vivo.
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    Progesterone reduces Estradiol breast cell growth
Nathan Goodyear

Persistent sexual dysfunction after discontinuatio... [J Sex Med. 2008] - PubMed result - 0 views

  • SSRIs can cause long-term effects on all aspects of the sexual response cycle that may persist after they are discontinued
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    Sexual side effects often persist long after SSRIs stopped
Nathan Goodyear

Salivary estradiol and progesterone during the normal ovulatory menstrual cycle in Chin... - 0 views

  • Measurements of these salivary steroids may be used to assess follicular dynamics. Moreover, salivary sampling is simple, convenient and stress free.
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    salivary sampling is simple, convenient and stress free.
Nathan Goodyear

Salivary estradiol and progesterone levels in conception and nonconception cycles in wo... - 0 views

  • Salivary measurements of E2 and progesterone can be used as noninvasive methods for assessment of ovarian function. Salivary specimens can be collected at home and brought to the laboratory for analysis, obviating the need for frequent phlebotomy. The sensitivity and precision of the salivary E2 assay make it comparable with assays of serum E2 for assessing changes in hormone levels.
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    salivary estradiol and progesterone used to assess women with infertility
Nathan Goodyear

Antioxidants for male subfertility - 0 views

  • The evidence suggests that antioxidant supplementation in subfertile males may improve the outcomes of live birth and pregnancy rate for subfertile couples undergoing ART cycles
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    antioxidants as part of infertility treatment? yes.
Nathan Goodyear

Sensitive salivary estradiol assay for monitoring ovarian function -- Worthman et al. 3... - 0 views

  • This assay may be particularly helpful in investigating ovarian function and free estradiol in women at various stages of the reproductive cycle.
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    salivary estradiol testing proves to be very helpful in evaluating ovaring function in women
Nathan Goodyear

RPE, blood glucose, and carbohydrate oxidation dur... [Med Sci Sports Exerc. 1991] - Pu... - 0 views

  • The data suggest that ingestion of carbohydrate beverages during endurance cycling can maintain plasma glucose and CHO oxidation during the latter stages of prolonged exercise
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    carbohydrate drinks help to maintain glucose levels in exercise
Nathan Goodyear

NFkappaB-mediated metabolic inflammation in periph... [Cell Cycle. 2009] - PubMed result - 0 views

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    NF-KappaB mediated inflammation
Nathan Goodyear

Mechanism of Human SIRT1 Activation by Resveratrol - 0 views

  • The NAD+-dependent protein deacetylase family, Sir2 (or sirtuins), is important for many cellular processes including gene silencing, regulation of p53, fatty acid metabolism, cell cycle regulation, and life span extension
  • resveratrol was shown to increase life span in three model organisms through a Sir2-dependent pathway.
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    Resveratrol potentially increases life span through SIRT1 activation
Nathan Goodyear

A potential role of endogenous progesterone in mod... [Clin Endocrinol (Oxf). 2009] - P... - 0 views

  • These data also suggest that endogenous progesterone could play a modulation role on pituitary hormone secretion, stimulating GH and PRL release and enhancing the inhibitory action of sleep on TSH secretion.
  • normally cycling young women, daytime GH and PRL secretions are increased in luteal phase
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    normal luteal progesterone production stimulate HGH release
Nathan Goodyear

Glutathione restores normal cell activation and cell cycle progression in cis-platinum ... - 0 views

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    glutathione useful in cis-platinum chemotherapy
Nathan Goodyear

Diagnosing Growth Hormone Deficiency in Adults - 0 views

  • it is clear that serum IGF-1 and or IGFBP-3 can be normal in patients with undisputed GHD
  • Various investigators have reported normal IGF-1 values in 37–70% of GH deficient adults
  • The co-administration of arginine and GHRH (the combined test) is a powerful stimulus for GH production and has gained increasing acceptance as a useful method of diagnosing GHD [34]. This test has been advocated as a suitable alternative to ITT
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  • The glucagon stimulation test (GST) is a reliable, safe alternative to the ITT in the diagnosis of GHD
  • An intravenous infusion of arginine (0.5 g/kg body weight) together with an intravenous bolus of GHRH (1 mcg/kg body weight) is administered [30]. Serum samples for GH are then obtained every 15–30 minutes for two hours.
  • Obesity, particularly marked obesity, is associated with blunted GH secretion in response to provocative stimuli
  • It has also been suggested that that even mildly increased BMI (25–30 kg/m2) can result in diminished stimulated GH production in 13% of healthy subjects
  • Corneli et al. have defined BMI-specific cut-off points for diagnosing adult-onset GHD using GHRH + arginine—11.5 ng/mL for those with BMI < 25 kg/m2, 8.0 ng/mL for BMI 25–30 kg/m2, 4.2 ng/mL for those with BMI > 30 kg/m2
  • GH levels are higher during the luteal phase in comparison with the follicular phase of the cycle
  • Oral, in contrast to transdermal oestrogen, lowers IGF-1 levels and is associated with increased GH levels
  • Adequate pituitary replacement with thyroxine and hydrocortisone are needed for optimal GH production
  • one cannot rely on a low IGF-1 to diagnose GHD in women taking oral oestrogen preparations.
  • Numerous GH secretagogues are available with the insulin tolerance test being the gold standard and the glucagon stimulation test or the GHRH + arginine as acceptable alternatives
  • ain et al. found the GST to be at least as good as the ITT in provoking GH secretion
  • the GST is safe, with almost no contraindications, it causes nausea and sometimes vomiting in 15–20% of subjects
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    Nice, more recent analysis, of HGH testing.
Nathan Goodyear

PPARγ and human metabolic disease - 0 views

  • PPARα and PPARδ appear primarily to stimulate oxidative lipid metabolism
  • PPARγ is principally involved in the cellular assimilation of lipids via anabolic pathways
  • PPARs are members of the nuclear hormone receptor superfamily
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  • Expression of PPARγ is highest in adipose tissue,
  • PPARγ also plays a key role in the entraining of adipose tissue lipid metabolism to nutritional state
  • Its expression is highest postprandially
  • its activation leads to upregulation of genes that mediate FA uptake and trapping
  • PPARγ may also promote futile cycling in adipocytes between triglyceride (TG) esterification and de-esterification
  • its high expression in macrophages, which are now known to infiltrate the dysfunctional adipose tissue of obese subjects
    • Nathan Goodyear
       
      PPAR gamma is associated with adipocyte differentiation and lipid storage.
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    review of PPAR gamma
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    very informative! Thanks for sharing!
Nathan Goodyear

Nuclear TK1 expression is an independent prognostic factor for survival in pre-malignan... - 0 views

  • Thymidine kinase 1 (TK1) is a proliferation biomarker
  • Nuclear TK1 expression in early grade CIN predicts risk for progression to malignancy
  • Nuclear TK1 expression is also a prognostic factor for treatment outcome
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  • TK1 LI was found to be a more reliable prognostic marker for 5-year survival than pathological stages, FIGO stages and Ki-67,
  • nuclear TK1 expression is a reliable prognostic factor in CIN patients, a group of cervical lesion patients that respond positively to treatment
  • nuclear TK1 expression is correlated with advanced stage of invasive cervical carcinomas
  • a low TK1 LI can help to identify with a better survival
  • low TK1 expression in the tumors in these patients might indicate that these tumors have a lower proliferation rate
  • TK1 is a key kinase in the one-step salvage pathway by which thymidine is introduced into DNA via the salvage pathway
  • TK1 participates in DNA synthesis and is therefore closely related to the S-phase of the cell cycle, and is correlated with proliferation
  • TK1 intensity (TK1 synthesis rate) increases from CIN grade I to CIN grade III, but does not further increase in invasive cervical carcinomas.
  • TK1 intensity seems to be a prognostic factor particularly when pre-malignant cervical lesions progress to malignancy
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    TK-1 is a proliferation biomarker of DNA repair. TK-1 is a nuclear biomarker of cancer prognosis, survival, recurrence and predicts risk of progression of pre-malignant disease.
Nathan Goodyear

Antitumor activity of dichloroacetate on C6 glioma cell: in vitro and in vivo evaluation - 0 views

  • the oral bioavailability of DCA is nearly 100%
  • the oral bioavailability of DCA is almost 100%.
  • DCA can penetrate into the traditional chemotherapy sanctuary sites. Interestingly, it was reported that DCA could penetrate across the BBB,30 exhibiting the potential activity for brain therapy.
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  • Clinical studies of DCA have shown reduced lactate levels
  • It has been reported that DCA activates the PDH by inhibition of PDK in a dose-dependent manner, and results in increased delivery of pyruvate into the mitochondria
  • The antitumor activity of DCA on nonsmall cell lung cancer, breast cancer, glioblastomas, and endometrial and prostate cancer cells has been demonstrated
  • It is well known that many chemotherapeutic agents have a low therapeutic index in brain tumors.
  • The most common metabolic hallmark of cancer cells is their propensity to metabolize glucose to lactic acid at a high rate even in the presence of oxygen
  • Pyruvate dehydrogenase kinase (PDK) is a gate-keeping enzyme that regulates the flux of carbohydrates (pyruvate) into the mitochondria
  • In the presence of activated PDK, pyruvate dehydrogenase (PDH), a critical enzyme that converts pyruvate to acetyl-CoA instead of lactate in glycolysis, is inhibited, limiting the entry of pyruvate into the mitochondria.
  • the level of Hsp70 was significantly decreased
  • DCA can penetrate the BBB
  • It has been reported that DCA treatment resulted in an increase in the proportion of tumor cells in the S phase, showing a decrease in proliferation as well as the induction of apoptosis
  • Heat shock proteins (HSPs) are involved in protein folding, aggregation, transport, and/or stabilization by acting as a molecular chaperone, leading to the inhibition of apoptosis by both caspase-dependent and/or independent pathways
  • HSPs are overexpressed in a wide range of human cancers and are implicated in tumor cell proliferation, differentiation, invasion, and metastasis
  • Considering the fact that high expression of HSPs is essential for cancer survival, the inhibition of HSPs is an important strategy of anticancer therapy.
  • In addition, after 5 years of continued treatment with oral DCA at a dose of 25 mg/kg, the serum DCA levels are only slightly increased compared with the levels after the first several doses, also showing its safety for oral administration at this dose.
  • DCA can enter the circulation rapidly after oral administration and then generate the stimulation of PDH activity generally within minutes.
  • Our in vivo results in tumor tissues indicated that DCA significantly induced ROS production and decreased MMP in tumor tissues
  • The numbers of microvessels in the DCA treatment groups were significantly decreased, suggesting the potential antiangiogenic effect of DCA
  • Under hypoxic conditions, hypoxia-inducible factor (HIF-1α) is activated and induces angiogenesis
  • In addition, HIF-1α can also induce the expression of PDK,48 which can inhibit the activity of PDH
  • The inhibition effect of DCA on HIF-1α would decrease vascular endothelial growth factor and inhibit angiogenesis
  • the antiangiogenic effect in the 25 mg/kg treatment group was lower than that in 75 mg/kg or 125 mg/kg treatment groups
  • In conclusion, DCA induces the apoptosis of C6 cells through the activation of the mitochondrial pathway, arresting the cell cycle of C6 cells in S phase and down-regulating Hsp70 expression.
  • DCA significantly induced the ROS production and decreased the MMP in tumor tissues. Our in vivo antitumor activity results also indicated that DCA has an antiangiogenic effect
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    DCA as proposed therapy in cancer.
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