149 research outputs found
Effects of Intraventricular Locus Coeruleus Transplants on Seizure Severity in Genetically Epilepsy-Prone Rats Following Depletion of Brain Norepinephrine
Audiogenic seizures (AGS) in genetically
epilepsy-prone rats (GEPR) of the moderateseizure
substrain (GEPR-3s) were investigated
to determine whether norepinephrine (NE)
depletion induced by 6-hydroxydopalnine (6-OHDA)
microinfusion into the locus coeruleus
(LC) could alter the efficacy of intraventricular
NE tissue grafts in promoting reductions in
seizure severity in AGS. GEPR-3s were
stereotaxically infused with 6-OHDA
(4μg/side/rat), or vehicle into the region of the
LC. Following 6-OHDA treatment all animals
were subjected to 3 AGS tests. GEPR-3s seizure
severities were increased in 39.5% of the
animals after microinfusion of 6-OHDA into the
region of the LC. Following the third AGS test,
each rat was stereotaxicaily implanted with 17
gestational day rat fetal tissue obtained from the
dorsal pons and containing the primordia of the
LC or with tissue obtained from the neocortex
or were sham-grafted. Subsequent to grafting,
rats were subjected to 3 additional AGS tests.
53% (10/19) of 6-OHDA treated GEPRs showed
a significant reduction in seizure severity
following transplantation of fetal LC tissue. In
contrast, only 20% (1/5) of GEPRs infused with
saline rather than 6-OHDA showed, a reduction
of seizure severity following fetal LC
transplantation. NE content in the cortex and
pons/medulla was decreased by 78% and 46%
respectively following 6-OHDA microinfusion
into the LC. Prominent grafts with numerous
TH positive neurons and neurites were present
within the third ventricle of grafted animals,
while cortex grafts contained no TH
immunostained structures. These findings
suggest that the efficacy of fetal LC tissue to
promote reductions in seizure severity in GEPRs
is increased following depletion of central NE by
microinfusion of 6-OHDA
Decreased Expression Of apM1 in Omental and Subcutaneous Adipose Tissue of Humans With Type 2 Diabetes
We have screened a subtracted cDNA library in
order to identify differentially expressed genes in
omental adipose tissue of human patients with
Type 2 diabetes. One clone (#1738) showed a marked
reduction in omental adipose tissue from patients
with Type 2 diabetes. Sequencing and BLAST analysis
revealed clone #1738 was the adipocyte-specific
secreted protein gene apM1 (synonyms ACRP30,
AdipoQ, GBP28). Consistent with the murine orthologue,
apM1 mRNA was expressed in cultured
human adipocytes and not in preadipocytes.
Using RT-PCR we confirmed that apM1 mRNA
levels were significantly reduced in omental adipose
tissue of obese patients with Type 2 diabetes compared
with lean and obese normoglycemic subjects.
Although less pronounced, apM1 mRNA levels
were reduced in subcutaneous adipose tissue of
Type 2 diabetic patients. Whereas the biological
function of apM1 is presently unknown, the tissue
specific expression, structural similarities to TNFα
and the dysregulated expression observed in obese
Type 2 diabetic patients suggest that this factor
may play a role in the pathogenesis of insulin resistance
and Type 2 diabetes
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The Edgewater Coolside process demonstration
The Edgewater Coolside process demonstration met the program objectives which were to determine Coolside SO[sub 2] removal performance, establish short-term process operability, and evaluate the economics of the process versus a limestone wet scrubber. On a flue gas produced from the combustion of 3% sulfur coal, the Coolside process achieved 70% SO[sub 2] removal using commercially-available hydrated lime as the sorbent. The operating conditions were Ca/S mol ratio 2.0, Na/Ca mol ratio 0.2, and 20[degree]F approach to adiabatic saturation temperature ([del]T). During tests using fresh plus recycle sorbent, the recycle sorbent exhibited significant capacity for additional SO[sub 2] removal. The longest steady state operation was eleven days at nominally Ca/S = 2, Na/Ca = 0.22, [del]T = 20--22[degree]F, and 70% SO[sub 2] removal. The operability results achieved during the demonstration indicate that with the recommended process modifications, which are discussed in the Coolside process economic analysis, the process could be designed as a reliable system for utility application. Based on the demonstration program, the Coolside process capital cost for a hypothetical commercial installation was minimized. The optimization consisted of a single, large humidifier, no spare air compressor, no isolation dampers, and a 15 day on-site hydrated lime storage. The levelized costs of the Coolside and the wet limestone scrubbing processes were compared. The Coolside process is generally economically competitive with wet scrubbing for coals containing up to 2.5% sulfur and plants under 350 MWe. Site-specific factors such as plant capacity factor, SO[sub 2] emission limit, remaining plant life, retrofit difficulty, and delivered sorbent cost affect the scrubber-Coolside process economic comparison
Imaging epileptogenic tubers in children with tuberous sclerosis complex usingΑ-[ 11 C]Methyl- L -tryptophan positron emission tomography
Several reports have indicated that cortical resection is effective in alleviating intractable epilepsy in children with tuberous sclerosis complex (TSC). Because of the multitude of cortical lesions, however, identifying the epileptogenic tuber(s) is difficult and often requires invaise intracranial electroencephalographic (EEG) monitoring. As increased concentrations of serotonin and serotonin-immunoreactive processes have been reported in resected human epileptic cortex, we used Α-[ 11 C]methyl-L-tryptophan ([ 11 C]AMT) position emission tomography (PET) to test the hypothesis that serotonin synthesis is increased interictally in epileptogenic tubers in patients with TSC. Nine children with TSC and epilepsy, aged 1 to 9 years (mean, 4 years 1 month), were studied. All children underwent scalp video-EEG monitoring, PET scans of glucose metabolism and serotonin synthesis, and EEG monitoring during both PET studies. [ 11 C]AMT scans were coregistred with magnetic resonance imaging and with glucose metabolism scans. Whereas glucose metabolism PET showed multifocal cortical hypometabolism corresponding to the locations of tubers in all 9 children, [ 11 C]AMT uptake was increased in one tuber (n = 3), two tubers (n = 3), three tubers (n = 1), and four tubers (n = 1) in 8 of the 9 children. All other tubers showed decreased [ 11 C]AMT uptake. Ictal EEG data available in 8 children showed seizure onset corresponding to foci of increased [ 11 C]AMT uptake in 4 children (including 2 with intracranial EEG recordings). In 2 children, ictal EEG was nonlocalizing, and in 1 child there was discordance between the region of increased [ 11 C]AMT uptake and the region of ictal onset on EEG. The only child whose [ 11 C]AMT scan showed to no regions of increased uptake had a left frontal seizure focus on EEG; however, at the time of his [ 11 C]AMT PET scan, his seizures had come under control. [ 11 C]AMT PET may be a powerful tool in differentiating between epileptogenic and nonepileptogenic tubers in patients with TSC.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50368/1/410440603_ftp.pd
Plasma Adiponectin and Insulin Resistance in Korean Type 2 Diabetes Mellitus
Insulin resistance, which implies impairment of insulin signaling in the target tissues, is a common cause of type 2 diabetes. Adipose tissue plays an important role in insulin resistance through the dysregulated production and secretion of adipose-derived proteins, including tumor necrosis factor-α, plasminogen activator inhibitor-1, leptin, resistin, angiotensinogen, and adiponectin. Adiponectin was estimated to be a protective adipocytokine against atherosclerosis, and also to have an anti-inflammatory effect. In this study, the relationship between fasting plasma adiponectin concentration and adiposity, body composition, insulin sensitivity (ITT, HOMAIR, QUICK), lipid profile, fasting insulin concentration were examined in Korean type 2 diabetes. The difference in the adiponectin concentrations was also examined in diabetic and non-diabetic subjects, with adjustment for gender, age and body mass index. 102 type 2 diabetics and 50 controls were examined. After a 12-h overnight fast, all subjects underwent a 75gram oral glucose tolerance test. Baseline blood samples were drawn for the determinations of fasting plasma glucose, insulin, adiponectin, total cholesterol, triglyceride, LDL-cholesterol, and HDL-cholesterol. The body composition was estimated using a bioelectric impedance analyzer (Inbody 2.0). The insulin sensitivity was estimated using the insulin tolerance test (ITT), HOMAIR and QUICK methods. In the diabetic group, the fasting adiponectin concentrations were significantly lower in men than in women. They were negatively correlated with BMI (r=-0.453), hip circumference (r=-0.341), fasting glucose concentrations (r=-0.277) and HOMAIR (r=-0.233). In addition, they were positively correlated with systolic blood pressure (r=0.321) and HDL-cholesterol (r=0.291). The systolic blood pressure and HDL-cholesterol were found to be independent variables, from a multiple logistic regression analysis, which influenced the adiponectin concentration. Compared with the non-diabetic group, the adiponectin concentrations were significantly lower in the diabetic group, with the exception of obese males. In conclusion, the plasma adiponectin concentrations were closely related to the insulin resistance parameters in Korean type 2 diabetic patients
Genetic Deletion of the Nociceptin/Orphanin FQ Receptor in the Rat Confers Resilience to the Development of Drug Addiction
The nociceptin (NOP) receptor is a G-protein-coupled receptor whose natural ligand is the nociceptin/orphanin FQ (N/OFQ) peptide. Evidence from pharmacological studies suggests that the N/OFQ system is implicated in the regulation of several addiction-related phenomena, such as drug intake, withdrawal and relapse. Here, to further explore the role of NOP system in addiction, we used NOP (-/-) rats to study the motivation for cocaine, heroin and alcohol self-administration in the absence of N/OFQ function. Conditioned place preference (CPP) and saccharin (0.2% w/v) self-administration were also investigated. Results showed that NOP (-/-) rats self-administer less cocaine (0.25, 0.125 or 0.5 mg/infusion) both under a Fixed Ratio 1 and a Progressive Ratio schedule of reinforcement compared to wild type (Wt) controls. Consistently, cocaine (10 mg/kg, i.p.) was able to induce CPP in Wt but not in NOP (-/-). When NOP (-/-) rats were tested for heroin (20 μg/infusion) and ethanol (10% v/v) self-administration, they showeda significantly lower drug intake compared to Wt. Conversely, saccharin self-administration was not affected by NOP deletion, excluding the possibility of nonspecific learning deficits or generalized disruption of reward mechanisms in NOP (-/-) rats. These findings were confirmed with pharmacological experiments using two selective NOP antagonists, SB-612111 and LY2817412. Both drugs attenuated alcohol self-administration in Wt rats but not in NOP (-/-) rats. In conclusion, our results demonstrate that genetic deletion of NOP receptors confers resilience to drug abuse and support a role for NOP receptor antagonism as a potential treatment option for drug addiction.Neuropsychopharmacology accepted article preview online, 26 August 2016. doi:10.1038/npp.2016.171
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