344 research outputs found
Studies of renal autoregulation in pancreatectomized and streptozotocin diabetic rats
Studies of renal autoregulation in pancreatectomized and streptozotocin diabetic rats. We studied renal autoregulation in pancreatectomized Munich-Wistar diabetic rats and in their sham-operated controls. In a second experiment we studied renal autoregulation in untreated and insulin treated streptozotocin diabetic Munich-Wistar rats and their nondiabetic controls. In the first experiment the diabetic rats had higher baseline renal blood flows (RBF). There was a fall in renal vascular resistance (RVR) and sustained RBF in both diabetic and control rats as renal perfusion pressures (RPP) was reduced from 130 and 110mm Hg. As RPP was reduced from 110 and 80mm Hg, there was no significant change in RVR in control rats and RBF began to fall. Below RPP of 80mm Hg RVR rose and RBF fell sharply in these rats. In contrast, there was a progressive fall in RVR as RPP was lowered to 60mm Hg in the diabetic rats and, thus, RBF was much better sustained in these animals. In the second experiment the plasma glucose level was 502 ± 52 mg/dl (X ± SD) in the untreated diabetic rats and only modestly reduced to 411 ± 49 mg/dl in the insulin treated animals. Untreated streptozotocin diabetic rats had moderately reduced and insulin-treated diabetic rats had mildly reduced baseline RVR and RBF. However, in these animals as in the pancreatectomized rats the increases in RVR noted in control rats at subautoregulatory RPPs were not seen. Thus, regardless of whether baseline RBFs were increased or decreased, diabetic rats sustained RBF at markedly reduced RPPs far more efficiently than did nondiabetic rats. The pathogenesis of these abnormalities in diabetic rats was not learned in these studies. However, it is likely that further study of autoregulation in diabetic rats could uncover factors influencing renal vascular tone which would be helpful in understanding the renal hemodynamic perturbations which may attend this experimental model
Insulin Assay Standardization: Leading to measures of insulin sensitivity and secretion for practical clinical care
Radio Occultation Measurements of Europa's Ionosphere From Juno's Close Flyby
On 29 September 2022 the Juno spacecraft flew within 354 km of Europa's surface while several instruments probed the moon's surroundings. During the close flyby, radio occultations were performed by collecting single-frequency Doppler measurements. These investigations are essential to the study of Europa's ionosphere and represent the first repeat sampling of any set of conditions since the Galileo era. Ingress measurements resulted in a marginal detection with a peak ionospheric density of 4,000 ± 3,700 cm−3 (3σ) at 22 km altitude. A more significant detection emerged on egress, with a peak density of 6,000 ± 3,000 cm−3 (3σ) at 320 km altitude. Comparison with Galileo measurements reveals a consistent picture of Europa's ionosphere, and confirms its dependence on illumination conditions and position within Jupiter's magnetosphere. However, the overall lower densities measured by Juno suggest a dependence on time of observation, with implications for the structure of the neutral atmosphere
Serum adiponectin is positively associated with lung function in young adults, independent of obesity: The CARDIA study
<p>Abstract</p> <p>Rationale</p> <p>Adipose tissue produces adiponectin, an anti-inflammatory protein. Adiponectin deficiency in mice is associated with abnormal post-natal alveolar development.</p> <p>Objective</p> <p>We hypothesized that lower serum adiponectin concentrations are associated with lower lung function in humans, independent of obesity. We explored mediation of this association by insulin resistance and systemic inflammation.</p> <p>Methods and Measurements</p> <p>Spirometry testing was conducted at years 10 and 20 follow-up evaluation visits in 2,056 eligible young adult participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Body mass index, serum adiponectin, serum C-reactive protein (a marker of systemic inflammation), and insulin resistance were assessed at year 15.</p> <p>Main Results</p> <p>After controlling for body mass index, years 10 and 20 forced vital capacity (FVC) were 81 ml and 82 ml lower respectively (p = 0.004 and 0.01 respectively) in the lowest <it>vs</it>. highest adiponectin quartiles. Similarly, years 10 and 20 forced expiratory volume in one second (FEV<sub>1</sub>) were 50 ml and 38 ml lower (p = 0.01 and 0.09, respectively) in the lowest <it>vs</it>. highest adiponectin quartiles. These associations were no longer significant after adjustment for insulin resistance and C-reactive protein. Serum adiponectin was not associated with FEV<sub>1</sub>/FVC or peak FEV<sub>1</sub>.</p> <p>Conclusions</p> <p>Independent of obesity, lower serum adiponectin concentrations are associated with lower lung function. The attenuation of this association after adjustment for insulin resistance and systemic inflammation suggests that these covariates are on a causal pathway linking adiponectin and lung function.</p
Ritonavir blocks AKT signaling, activates apoptosis and inhibits migration and invasion in ovarian cancer cells
<p>Abstract</p> <p>Background</p> <p>Ovarian cancer is the leading cause of mortality from gynecological malignancies, often undetectable in early stages. The difficulty of detecting the disease in its early stages and the propensity of ovarian cancer cells to develop resistance to known chemotherapeutic treatments dramatically decreases the 5-year survival rate. Chemotherapy with paclitaxel after surgery increases median survival only by 2 to 3 years in stage IV disease highlights the need for more effective drugs. The human immunodeficiency virus (HIV) infection is characterized by increased risk of several solid tumors due to its inherent nature of weakening of immune system. Recent observations point to a lower incidence of some cancers in patients treated with protease inhibitor (PI) cocktail treatment known as HAART (Highly Active Anti-Retroviral Therapy).</p> <p>Results</p> <p>Here we show that ritonavir, a HIV protease inhibitor effectively induced cell cycle arrest and apoptosis in ovarian cell lines MDH-2774 and SKOV-3 in a dose dependent manner. Over a 3 day period with 20 μM ritonavir resulted in the cell death of over 60% for MDAH-2774 compared with 55% in case of SKOV-3 cell line. Ritonavir caused G1 cell cycle arrest of the ovarian cancer cells, mediated by down modulating levels of RB phosphorylation and depleting the G1 cyclins, cyclin-dependent kinase and increasing their inhibitors as determined by gene profile analysis. Interestingly, the treatment of ritonavir decreased the amount of phosphorylated AKT in a dose-dependent manner. Furthermore, inhibition of AKT by specific siRNA synergistically increased the efficacy of the ritonavir-induced apoptosis. These results indicate that the addition of the AKT inhibitor may increase the therapeutic efficacy of ritonavir.</p> <p>Conclusion</p> <p>Our results demonstrate a potential use of ritonavir for ovarian cancer with additive effects in conjunction with conventional chemotherapeutic regimens. Since ritonavir is clinically approved for human use for HIV, drug repositioning for ovarian cancer could accelerate the process of traditional drug development. This would reduce risks, limit the costs and decrease the time needed to bring the drug from bench to bedside.</p
Sulforaphane induces cell cycle arrest by protecting RB-E2F-1 complex in epithelial ovarian cancer cells
<p>Abstract</p> <p>Background</p> <p>Sulforaphane (SFN), an isothiocyanate phytochemical present predominantly in cruciferous vegetables such as brussels sprout and broccoli, is considered a promising chemo-preventive agent against cancer. In-vitro exposure to SFN appears to result in the induction of apoptosis and cell-cycle arrest in a variety of tumor types. However, the molecular mechanisms leading to the inhibition of cell cycle progression by SFN are poorly understood in epithelial ovarian cancer cells (EOC). The aim of this study is to understand the signaling mechanisms through which SFN influences the cell growth and proliferation in EOC.</p> <p>Results</p> <p>SFN at concentrations of 5 - 20 μM induced a dose-dependent suppression of growth in cell lines MDAH 2774 and SkOV-3 with an IC50 of ~8 μM after a 3 day exposure. Combination treatment with chemotherapeutic agent, paclitaxel, resulted in additive growth suppression. SFN at ~8 μM decreased growth by 40% and 20% on day 1 in MDAH 2774 and SkOV-3, respectively. Cells treated with cytotoxic concentrations of SFN have reduced cell migration and increased apoptotic cell death via an increase in Bak/Bcl-2 ratio and cleavage of procaspase-9 and poly (ADP-ribose)-polymerase (PARP). Gene expression profile analysis of cell cycle regulated proteins demonstrated increased levels of tumor suppressor retinoblastoma protein (RB) and decreased levels of E2F-1 transcription factor. SFN treatment resulted in G1 cell cycle arrest through down modulation of RB phosphorylation and by protecting the RB-E2F-1 complex.</p> <p>Conclusions</p> <p>SFN induces growth arrest and apoptosis in EOC cells. Inhibition of retinoblastoma (RB) phosphorylation and reduction in levels of free E2F-1 appear to play an important role in EOC growth arrest.</p
Implications of the Ammonia Distribution on Jupiter from 1 to 100 Bars as Measured by the Juno Microwave Radiometer
The latitude-altitude map of ammonia mixing ratio shows an ammonia-rich zone at 0-5degN, with mixing ratios of 320-340 ppm, extending from 40-60 bars up to the ammonia cloud base at 0.7 bars. Ammonia-poor air occupies a belt from 5-20degN. We argue that downdrafts as well as updrafts are needed in the 0-5degN zone to balance the upward ammonia flux. Outside the 0-20degN region, the belt-zone signature is weaker. At latitudes out to +/-40deg, there is an ammonia-rich layer from cloud base down to 2 bars which we argue is caused by falling precipitation. Below, there is an ammonia-poor layer with a minimum at 6 bars. Unanswered questions include how the ammonia-poor layer is maintained, why the belt-zone structure is barely evident in the ammonia distribution outside 0-20degN, and how the internal heat is transported through the ammonia-poor layer to the ammonia cloud base
Highly depleted alkali metals in Jupiter's deep atmosphere
Water and ammonia vapors are known to be the major sources of spectral
absorption at pressure levels observed by the microwave radiometer (MWR) on
Juno. However, the brightness temperatures and limb darkening observed by the
MWR at its longest wavelength channel of 50 cm (600 MHz) in the first 9
perijove passes indicate the existence of an additional source of opacity in
the deep atmosphere of Jupiter (pressures beyond 100 bar). The absorption
properties of ammonia and water vapor, and their relative abundances in
Jupiter's atmosphere do not provide sufficient opacity in deep atmosphere to
explain the 600 MHz channel observation. Here we show that free electrons due
to the ionization of alkali metals, i.e. sodium, and potassium, with sub-solar
metallicity [M/H] (log based 10 relative concentration to solar) in the range
of [M/H] = -2 to [M/H] = -5 can provide the missing source of opacity in the
deep atmosphere. If the alkali metals are not the source of additional opacity
in the MWR data, then their metallicity at 1000 bars can only be even lower.
The upper bound of -2 on the metallicity of the alkali metals contrasts with
the other heavy elements -- C, N, S, Ar, Kr, and Xe -- which are all enriched
relative to their solar abundances having a metallicity of approximately +0.5.Comment: This manuscript has been accepted for publication in The
Astrophysical Journal Letters. The final version of the paper will be
available in the published journal. This arXiv version is provided for
informational purpose
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