Decreased O2 consumption by PMNL from humans and rats with CRF: Role of secondary hyperparathyroidism

Decreased O2 consumption by PMNL from humans and rats with CRF: Role of secondary hyperparathyroidism. Bactericidal ability of polymorphonuclear leukocytes (PMNL) is impaired in chronic renal failure (CRF). This function of PMNL is mediated by the generation of oxidizing radicals and the latter event requires O2 consumption by these cells. The present study examined both basal and FMLP-stimulated rise in cytosolic calcium ([Ca2+]i) and O2 consumption of PMNL from normal subjects and hemodialysis patients and from CRF rats, and evaluated the potential role of secondary hyperparathyroidism of CRF on these properties of PMNL. Basal levels of [Ca2+]i were significantly higher, and FMLP-induced increments in [Ca2+]i were significantly lower in PMNL of both humans and rats with CRF than in normals. Basal and FMLP-stimulated O2 consumption were significantly lower in CRF subjects and rats than in normals. These derangements were prevented by prior parathyroidectomy of CRF rats or by their treatment with verapamil from day one of CRF. Also, therapy of rats with pre-existing CRF with this drug reversed the abnormalities in [Ca2+]i and in O2 consumption of PMNL. The data indicate that: (1) CRF is associated with derangements in the homeostasis of [Ca2+]i of PMNL and their oxygen consumption, (2) these abnormalities are, most likely, mediated by the state of secondary hyperparathyroidism of CRF, and (3) verapamil, which blocks the PTH-induced entry of calcium into cells, and prevents as well as reverses these PMNL dysfunctions. These results implicate the excess PTH of CRF in the genesis of the defective bactericidal function of PMNL, and assign a new dimension to PTH toxicity in CRF

Enhanced self-administration of the CB1 receptor agonist WIN55,212-2 in olfactory bulbectomized rats: evaluation of possible serotonergic and dopaminergic underlying mechanisms

Depression has been associated with drug consumption, including heavy or problematic cannabis use. According to an animal model of depression and substance use disorder comorbidity, we combined the olfactory bulbectomy (OBX) model of depression with intravenous drug self-administration procedure to verify whether depressive-like rats displayed altered voluntary intake of the CB1 receptor agonist WIN55,212-2 (WIN, 12.5 μg/kg/infusion). To this aim, olfactory-bulbectomized (OBX) and sham-operated (SHAM) Lister Hooded rats were allowed to self-administer WIN by lever-pressing under a continuous [fixed ratio 1 (FR-1)] schedule of reinforcement in 2 h daily sessions. Data showed that both OBX and SHAM rats developed stable WIN intake; yet, responses in OBX were constantly higher than in SHAM rats soon after the first week of training. In addition, OBX rats took significantly longer to extinguish the drug-seeking behavior after vehicle substitution. Acute pre-treatment with serotonin 5HT1B receptor agonist, CGS-12066B (2.5-10 mg/kg), did not significantly modify WIN intake in OBX and SHAM Lister Hooded rats. Furthermore, acute pre-treatment with CGS-12066B (10 and 15 mg/kg) did not alter responses in parallel groups of OBX and SHAM Sprague Dawley rats self-administering methamphetamine under higher (FR-2) reinforcement schedule with nose-poking as operandum. Finally, dopamine levels in the nucleus accumbens (NAc) of OBX rats did not increase in response to a WIN challenge, as in SHAM rats, indicating a dopaminergic dysfunction in bulbectomized rats. Altogether, our findings suggest that a depressive-like state may alter cannabinoid CB1 receptor agonist-induced brain reward function and that a dopaminergic rather than a 5-HT1B mechanism is likely to underlie enhanced WIN self-administration in OBX rats

Insulin release from pancreatic islets: Effects of CRF and excess PTH

Insulin release from pancreatic islets: Effects of CRF and excess PTH. Insulin secretion may be impaired in chronic renal failure (CRF) and available data suggest that this abnormality may be related to the state of secondary hyperparathyroidism of renal failure. We directly measured insulin release from isolated islets of Langerhans obtained from normal rats, CRF-control and CRF-PTX (parathyroidectomized) rats, and parathyroid hormone (PTH)-treated animals. Both early and total glucose-induced insulin release from islets of CRF-control were markedly and significantly (P < 0.01) lower than from islets of normal rats. Insulin release from islets of CRF-PTX rats was significantly (P < 0.01) higher than that from islets of CRF-control rats, and not different from insulin release from islets of normal rats. Forskolin and IBMX, which cause a rise in cAMP, significantly stimulated glucose-induced insulin release from islets of normal, CRF-control and CRF-PTX rats, but the increments from baseline were not significantly different between the three groups. Both early and total insulin release from islets obtained from PTH-treated rats with normal renal function were markedly and significantly (P < 0.01) lower than values obtained from normal rats. Calcium contents of the pancreas of CRF-control and PTH-treated rats were significantly (P < 0.01) higher than that in pancreas of normal rats and CRF-PTX animals, and values in the latter two groups of animals were not significantly different. The results show that: 1) CRF impairs insulin release from pancreatic islets; 2) this abnormality is reversed by prior parathyroidectomy; and 3) hyperparathyroidism induced by PTH-treatment in normal rats impairs insulin release from pancreatic islets. The data provide a direct evidence for the role of secondary hyperparathyroidism in the genesis of abnormal carbohydrate metabolism in CRF. This effect of excess PTH is not related to alterations in cAMP production but may potentially be due to calcium accumulation in the pancreas

Impaired insulin secretion of aging: Role of renal failure and hyperparathyroidism

Impaired insulin secretion of aging: Role of renal failure and hyperparathyroidism. Available data indicate that insulin secretion is impaired with aging. Almost all the studies that examined insulin secretion by old animals did not take into consideration the state of renal function or the blood levels of parathyroid hormone (PTH). Old animals may have chronic renal failure (CRF) and secondary hyperparathyroidism, and both of these conditions impair insulin secretion. It is possible, therefore, that the impaired insulin secretion of aging is not due to old age per se, but rather to associated CRF and excess PTH. The present study examined this issue in adult (6 month old) and senescent rats (2 years old) with and without CRF and excess PTH. Senescent rats without CRF had normal renal function and normal blood levels of PTH, and the values were not different from those observed in adult rats. Creatinine clearance in senescent rats with CRF was significantly (P < 0.01) lower and serum levels of PTH were significantly (P < 0.01) higher than in senescent animals without CRF and than in the adult rats as well. Only the senescent rats with CRF displayed glucose intolerance during intravenous glucose tolerance test. For any given level of blood glucose, plasma insulin levels were lower in senescent rats with CRF than in the adult rat or senescent animals without CRF. Both initial phase (139 ± 45 pg/islet · 8 min) and total (808 ± 216 pg/islet · 33 min) insulin secretion from pancreatic islets of the senescent rats with CRF and excess PTH were significantly lower than those in senescent rats with normal renal function (658 ± 117 pg/islet · 8 min and 3294 ± 290 pg/islet · 33 min, respectively) or in adult rats (710 ± 134 pg/islet · 8 min and 3183 ± 366 pg/islet · 33 min, respectively). There were no significant differences in insulin secretion between the adult rats and the senescent ones with normal renal function. The data demonstrate that the impaired insulin secretion by the pancreatic islets in old rats is not necessarily related to the higher age per se, but is due to the associated CRF and secondary hyperparathyroidism that develops in many, but not all old animals. Our results indicate that studies examining the effect of aging on body function should take into consideration the level of renal function and of the serum PTH, since both CRF and excess PTH adversely affect the functional integrity of many organs

Spitzer 70 and 160-micron Observations of the COSMOS Field

We present Spitzer 70 and 160 micron observations of the COSMOS Spitzer survey (S-COSMOS). The data processing techniques are discussed for the publicly released products consisting of images and source catalogs. We present accurate 70 and 160 micron source counts of the COSMOS field and find reasonable agreement with measurements in other fields and with model predictions. The previously reported counts for GOODS-North and the extragalactic First Look Survey are updated with the latest calibration, and counts are measured based on the large area SWIRE survey to constrain the bright source counts. We measure an extragalactic confusion noise level of sigma_c = 9.4+/-3.3 mJy (q=5) for the MIPS 160-micron band based on the deep S-COSMOS data and report an updated confusion noise level of sigma_c = 0.35+/-0.15 mJy (q=5) for the MIPS 70-micron band.Comment: Accepted AJ, 15 Aug. 2009. Data available at http://spider.ipac.caltech.edu/staff/frayer/mycosmos/ until released by IRS

Decomposing Star Formation and Active Galactic Nucleus with Spitzer Mid-Infrared Spectra: Luminosity Functions and Co-Evolution

We present Spitzer 7-38um spectra for a 24um flux limited sample of galaxies at z~0.7 in the COSMOS field. The detailed high-quality spectra allow us to cleanly separate star formation (SF) and active galactic nucleus (AGN) in individual galaxies. We first decompose mid-infrared Luminosity Functions (LFs). We find that the SF 8um and 15um LFs are well described by Schechter functions. AGNs dominate the space density at high luminosities, which leads to the shallow bright-end slope of the overall mid-infrared LFs. The total infrared (8-1000um) LF from 70um selected galaxies shows a shallower bright-end slope than the bolometrically corrected SF 15um LF, owing to the intrinsic dispersion in the mid-to-far-infrared spectral energy distributions. We then study the contemporary growth of galaxies and their supermassive black holes (BHs). Seven of the 31 Luminous Infrared Galaxies with Spitzer spectra host luminous AGNs, implying an AGN duty cycle of 23+/-9%. The time-averaged ratio of BH accretion rate and SF rate matches the local M_BH-M_bulge relation and the M_BH-M_host relation at z ~ 1. These results favor co-evolution scenarios in which BH growth and intense SF happen in the same event but the former spans a shorter lifetime than the latter. Finally, we compare our mid-infrared spectroscopic selection with other AGN identification methods and discuss candidate Compton-thick AGNs in the sample. While only half of the mid-infrared spectroscopically selected AGNs are detected in X-ray, ~90% of them can be identified with their near-infrared spectral indices.Comment: ApJ Accepted. emulateapj style. 16 pages, 9 figures, 4 table

A Pair of Dopamine Neurons Target the D1-Like Dopamine Receptor DopR in the Central Complex to Promote Ethanol-Stimulated Locomotion in Drosophila

Dopamine is a mediator of the stimulant properties of drugs of abuse, including ethanol, in mammals and in the fruit fly Drosophila. The neural substrates for the stimulant actions of ethanol in flies are not known. We show that a subset of dopamine neurons and their targets, through the action of the D1-like dopamine receptor DopR, promote locomotor activation in response to acute ethanol exposure. A bilateral pair of dopaminergic neurons in the fly brain mediates the enhanced locomotor activity induced by ethanol exposure, and promotes locomotion when directly activated. These neurons project to the central complex ellipsoid body, a structure implicated in regulating motor behaviors. Ellipsoid body neurons are required for ethanol-induced locomotor activity and they express DopR. Elimination of DopR blunts the locomotor activating effects of ethanol, and this behavior can be restored by selective expression of DopR in the ellipsoid body. These data tie the activity of defined dopamine neurons to D1-like DopR-expressing neurons to form a neural circuit that governs acute responding to ethanol

The expression of monocarboxylate transporters in thyroid carcinoma can be associated with the morphological features of BRAF (V600E) mutation

BRAF (V600E) mutation, usually performed by DNA techniques, is one of the most common diagnostic markers in papillary thyroid carcinoma. Few papers have demonstrated that plump cells (eosinophilic cytoplasms and papillary thyroid carcinoma nuclei) and peculiar sickle-shaped nuclei represent morphological features of BRAF (V600E) on papillary thyroid carcinomas. These features seem to be linked to glycolytic phenotype whereby monocarboxylate transporters 1-4 are hypothesized to have a dominant role as lactate transporters. We investigated the association between these morphological features and monocarboxylate transporters 1 and 4 in 48 cyto-histological samples diagnosed as "positive for malignancy-favoring papillary thyroid carcinoma". These cases were processed with liquid-based cytology and underwent BRAF (V600E) mutational analysis (pyrosequencing) on liquid-based cytology and monocarboxylate transporters immunostaining on histology. The expression of monocarboxylate transporter 1, monocarboxylate transporter 4, glucose trasporter-1 and carbonic anhidrase were scored semi-quantitatively with expression from 0 to 3+ (strong positivity). The 33 mutated and 15 wild type cases showed 100 % cyto-histological concordance. The cytological evaluation revealed plump cells and sickle nuclear shape in 100 % mutated cases. Monocarboxylate transporter 1 yielded 76 % positivity in the mutated cases especially in both the plump cells and sickle-shaped nuclei, whereas the wild types showed 13.3 % positive monocarboxylate transporter 1 (p = 0.00013). Monocarboxylate transporter 4 resulted in 100 % positivity in mutated and 40 % in wild types (p 0.05). This is the first report analyzing the association between monocarboxylate transporter expression and the morphological features of BRAF (V600E) mutated papillary thyroid carcinomas suggesting the possible involvement of lactate in the morphological features.info:eu-repo/semantics/publishedVersio

SPT-CL J0546-5345: A Massive z > 1 Galaxy Cluster Selected Via the Sunyaev-Zel'dovich Effect with the South Pole Telescope

We report the spectroscopic confirmation of SPT-CL J0546-5345 at = 1.067. To date this is the most distant cluster to be spectroscopically confirmed from the 2008 South Pole Telescope (SPT) catalog, and indeed the first z > 1 cluster discovered by the Sunyaev-Zel'dovich Effect (SZE). We identify 21 secure spectroscopic members within 0.9 Mpc of the SPT cluster position, 18 of which are quiescent, early-type galaxies. From these quiescent galaxies we obtain a velocity dispersion of 1179^{+232}_{-167} km/s, ranking SPT-CL J0546-5345 as the most dynamically massive cluster yet discovered at z > 1. Assuming that SPT-CL J0546-5345 is virialized, this implies a dynamical mass of M_200 = 1.0^{+0.6}_{-0.4} x 10^{15} Msun, in agreement with the X-ray and SZE mass measurements. Combining masses from several independent measures leads to a best-estimate mass of M_200 = (7.95 +/- 0.92) x 10^{14} Msun. The spectroscopic confirmation of SPT-CL J0546-5345, discovered in the wide-angle, mass-selected SPT cluster survey, marks the onset of the high redshift SZE-selected galaxy cluster era.Comment: ApJ, in pres