METHODS: A multi-institution observational study of stage I-IV ut

METHODS: A multi-institution observational study of stage I-IV uterine papillary serous carcinoma patients was performed. Histopathologic slides were reviewed by four expert pathologists, with determination

of the percentage serous histology within each tumor. The pre-existent endometrium was evaluated for the presence of endometrial intraepithelial carcinoma.

RESULTS: We included 108 uterine papillary serous Entinostat clinical trial carcinoma patients. Fifty-eight patients had mixed and 50 patients had pure uterine papillary serous carcinoma histology. On multivariable analysis, advanced International Federation of Gynecology and Obstetrics (FIGO) stage (hazard ratio [HR] 3.15, 95% confidence interval [CI] 1.57-6.32), mixed uterine papillary serous carcinoma histology (HR 0.35, 95% CI 0.19-0.66), and Fludarabine lymphovascular space invasion (HR 2.10, 95% CI 1.07-4.16) were significantly associated with recurrence. International Federation of Gynecology and Obstetrics stage (HR 4.67, 95% CI 2.25-9.70) and mixed uterine papillary serous carcinoma histology (HR 0.39, 95% CI 0.20-0.76) were significantly and independently associated with survival. Endometrial

intraepithelial carcinoma was identified in 83.9% of all cases, with no significant difference between mixed and pure uterine papillary serous carcinoma patients. Atrophic or weakly proliferative endometrium was found in 90.7% of pure uterine papillary serous carcinoma Acalabrutinib cases, whereas hyperplastic endometrium with atypia was more commonly found in 34.7% of mixed carcinoma patients with uterine papillary serous carcinoma (P=.004).

CONCLUSION: Pure uterine papillary serous carcinoma histology and FIGO stage are the most important risk factors for recurrence and survival

in patients with uterine papillary serous carcinoma. Adjusted for covariates, patients with pure uterine papillary serous carcinoma had a 2.9-times greater risk for recurrence and a 2.6-times higher risk of death compared with patients with mixed uterine papillary serous carcinoma. Furthermore, endometrial intraepithelial carcinoma was equally found among pure and mixed uterine papillary serous carcinoma cases, whereas the nonneoplastic endometrium was atrophic or weakly proliferative in pure uterine papillary serous carcinoma cases compared with more hyperplastic endometrium with atypia in mixed uterine papillary serous carcinoma cases. (Obstet Gynecol 2012;120:1371-81) DOI: http://10.1097/AOG.0b013e318273732e”
“OBJECTIVE: To estimate the effect of reference text in an electronic medical record (EMR) on the recommended use of preoperative antibiotics for cesarean deliveries.

METHODS: A retrospective cohort study of all cesarean deliveries at Stony Brook Hospital between May 2009 and June 2011, was performed. Reference text was added to the EMR in May 2010.

87 +/- 3 97 to 45 84 +/- 3 50 nmol/mg of protein) and LDH release

87 +/- 3.97 to 45.84 +/- 3.50 nmol/mg of protein) and LDH release (from 8.63 to 31.42 %) (p < 0.05). These results were accompanied by a decrease in mitochondrial membrane potential and up-regulation of Bid find more and caspase-3, -8, and -9 mRNA expressions. However, pretreatment

with different Rg1 concentrations (4, 8, and 16 mu mol/L) markedly attenuated these changes (p < 0.05).

Conclusion: Rg1 may protect HUVECs against H2O2-induced injury via the anti-oxidative and antiapoptosis mechanisms, which could be applied potentially for the prevention of endothelial cell dysfunctions associated with atherosclerosis.”
“Objectives: The purpose of this study was to objectively evaluate the position and migration of the cochlear implant receiver and ball electrode using 3-dimensional (3D) rendering of computed tomography.

Study Design: Retrospective case review.

Setting: Tertiary referral center.

Patients: Thirty-one

patients were treated for profound sensorineural hearing loss with cochlear implant. The operative methods were divided into 2 groups: an inverted J-shaped incision with bony tie-down suture, and a minimally invasive incision without tie-down suture.

Intervention(s): When the receiver www.selleckchem.com/products/semaxanib-su5416.html and ball electrode were detected in 3D imaging, the zygomatic process-receiver angle (ZRA), ear canal to receiver distance (ERD), and ear canal to ball electrode distance (EBD) were measured.

Main Outcome Measure(s): Comparison and statistical analysis of postoperative angle and distances.

Results: The mean ZRA, EBD, and ERD values were 139.1 degrees, 20.7 mm, and 36.0 mm, respectively. The mean 5-Fluoracil solubility dmso ZRA in patients with an inverted J-shaped incision was significantly wider than for those with a minimally invasive incision (151.2 versus 136.9, p = 0.002). In 10 patients who received postoperative computed tomography 2 times, ZRA increased from 138.6 to

144.4 degrees (p < 0.001) and ERD decreased from 37.0 to 34.9 mm (p = 0.001).

Conclusion: 3D computed tomography is a useful tool for localization and migration of the receiver and ball electrode. Micro downward movements of the receiver were found in both bony tie-down and non-tie-down suture groups.”
“Purpose: Anticoagulant tissue factor pathway inhibitor (TFPI) is released from its endothelial stores by heparin, which may lead to its untoward depletion. We investigated the effects of sulodexide – a commercially available mixture of heparan and dermatan sulfate, on plasma TFPI release and depletion.

Material and Methods: An open-label pilot trial of intravenous and/or oral sulodexide effects on plasma immunoreactive total TFPI antigen level was performed in 11 healthy men. The drug was initially administered i.v. at a single dose of 120 mg, then-orally for 12 days (50 mg b.i.d), and again by i.v route after 2 weeks.

Results: Sulodexide injections induced marked increases in plasma TFPI; they were more pronounced on day 14 than on study initiation (3-fold vs.

It is then advanced using the second segment as an intrachannel i

It is then advanced using the second segment as an intrachannel instrument. The double-pass turnaround is used if asymmetric segments are planned and obstruction is encountered with the second segment. This technique was used successfully in 4 eyes with a false channel.”
“We

report a patient with ventricular and atrial tachycardias PRT062607 cost reproducibly induced during exercise testing. Atrial tachycardia, but no sustained ventricular tachycardia, was induced during electrophysiological study. Catecholaminergic polymorphic ventricular tachycardia was considered because of normal echocardiogram, family history of sudden death, and polymorphic appearance of some of the nonsustained ventricular tachycardia episodes. However, most episodes of ventricular tachycardia were monomorphic. Cardiac magnetic resonance diagnosed isolated left ventricular noncompaction. (PACE 2011; 34:e94-e97)”
“This article presents a brief review of insights gained about metallic ferromagnetism using spin-polarized electrons as probes. In ferromagnets, the electronic structure

is spin-polarized because of the exchange interaction, allowing the fundamental properties of ferromagnets to be measured by spin-polarized versions of techniques such as photoemission and inverse photoemission. Not only can SB273005 the static electronic structure be measured, but also magnetic excitations can be measured using spin polarized versions of techniques like electron energy loss spectroscopy. Further, since the polarization is a vector, mapping it maps the underlying domain structure of the ferromagnet. A brief discussion is presented of both early and contemporary applications of spin polarized measurement techniques and what has been learned. [doi:10.1063/1.3537960]“
“PURPOSE: To assess the frequency and results of cataract surgery with concurrent vitrectomy due to zonule weakness in eyes with pseudoexfoliation (PXF).

SETTING: Private practice, Boston, Massachusetts, USA.

METHODS: This retrospective nonrandomized study assessed consecutive eyes with PXF having cataract surgery. High risk was YH25448 in vitro defined as preoperative

phacodonesis, iridodonesis, or lens subluxation (subgroup 1); preoperative anterior chamber depth or angle-depth asymmetry between eyes confirmed by slitlamp biomicroscopy or gonioscopy, respectively (subgroup 2); or complicated cataract extraction related to zonule weakness in the fellow eye (subgroup 3). Exclusion criteria were previous vitrectomy, scleral buckle, or trabeculectomy surgery and combined cataract glaucoma surgery. A comparative analysis of outcome parameters was performed.

RESULTS: Of the 1059 eyes evaluated, 38 had vitrectomy. Concurrent vitrectomy was required in 19 (15.6%) of 122 high-risk eyes and 19 (2.0%) of 937 non-high-risk eyes (P<.00001). The need for concurrent vitrectomy was greatest in subgroup 3 (72.7%) and subgroup 1 (42.9%).

The experiment was conducted using a randomized complete block de

The experiment was conducted using a randomized complete block design. Treatments VX-680 were arranged as a 2 (no zilpaterol vs. zilpaterol) x 2 (monensin and tylosin withdrawn vs. monensin and tylosin

fed during the final 35 d on feed) factorial. Steers were fed for a total of 161 to 167 d, and treatments were administered during the final 35 d that cattle were on feed. When included in the diet, zilpaterol, monensin, and tylosin were supplemented at 8.3, 33.1, and 12.2 mg/kg (DM basis), respectively. Zilpaterol was included in the diet for 30 d at the end of the finishing period and withdrawn from the diet for the last 5 or 6 d cattle were on feed. Cattle were harvested and carcass data collected. There were no zilpaterol x monensin/tylosin interactions (P = 0.12) for ADG or G: F. Feeding zilpaterol increased ADG (P < 0.001) by 0.20 kg and G: F (P < 0.001) by 0.029 kg/kg during the last 35 d on feed. Likewise, when feedlot variables were measured throughout the entire 161- to 167-d feeding trial, ADG ( 3.4%; P < 0.001) and G: F ( 3.9%; P < 0.001) were increased. Feeding zilpaterol increased ( P < PP2 0.001) dressing percent and HCW and decreased ( P < 0.001) total liver abscess rate compared with controls.

In addition, zilpaterol increased ( P < 0.001) LM area by an average of 8.0 cm(2). There was a zilpaterol x monensin/tylosin interaction (P = 0.03) for marbling score. Zilpaterol decreased

(P < 0.001) marbling score regardless of monensin and tylosin treatment, although withdrawal of monensin and tylosin for 35 d decreased marbling to a greater extent (31 vs. 17 degrees). Zilpaterol decreased (i. e., improved; P < 0.001) calculated yield BYL719 in vitro grade regardless of monensin and tylosin treatment, but feeding zilpaterol in combination with the withdrawal of monensin and tylosin for 35 d decreased calculated yield grade to a greater extent (0.49 vs. 0.29) compared with the zilpaterol, monensin, and tylosin combination treatment (zilpaterol x monensin/tylosin interaction, P = 0.03). Results suggest that monensin and tylosin can be withdrawn from the diet during the zilpaterol feeding period (final 35 d on feed) with minimal effect on animal performance, although feeding zilpaterol in combination with monensin and tylosin seemed to moderate effects on carcass quality.”
“We investigate electric GHz metamaterial resonator arrays with strong electric responses with the goal of reducing the resonator size in comparison to the excitation wavelength. By exploiting capactive coupling between adjacent resonators, we achieve a large effective capacitance and strong coupling to the applied electric field. By adding meander lines to connect the electrodes, we are able to lower the resonant frequency to about 3 GHz and obtain a ratio of wavelength to resonator size of about 30.

Hemodialysis was started, and we succeed to treat the patient wit

Hemodialysis was started, and we succeed to treat the patient without squeals. This case illustrates some of the factors that lead to lithium toxicity as well as the need to consider lithium toxicity to the differential diagnosis of a patient presenting with renal insufficiency with or without change in mental status and neurologic symptom.”
“The feline and human immunodeficiency viruses (FIV and HIV) target helper T cells selectively, and in doing so they induce a profound immune dysfunction. The primary determinant of HIV cell tropism is the expression pattern of the RG-7388 ic50 primary viral receptor CD4 and co-receptor(s),

such as CXCR4 and CCR5. FIV employs a distinct strategy to target helper T cells; a high affinity interaction with CD134 (OX40) is followed by binding of the virus to its sole co-receptor, Alpelisib price CXCR4. Recent studies have demonstrated that the way in which FIV interacts with its primary receptor, CD134, alters as infection progresses, changing the cell tropism of the virus. This review examines the contribution of the virus-receptor interaction to replication in vivo as well as the significance of these findings to the’ development of vaccines and therapeutics.”
“Accumulating evidence suggests that the nongenomic cardiovascular actions of aldosterone are produced by varied

cellular pathways and mediated by a multitude of messenger systems including the reactive oxygen and nitrogen species. Considering the involvement of the oxidative and nitrosative stress in the pathways leading to the activation of the angiotensin – aldosterone system, in the current study we tried to evaluate the functional interactions between aldosterone, angiotensin II and antioxidants in isolated selleck chemicals vascular smooth muscle of aortic rings from rats. Our data provide additional arguments that the nongenomic actions of aldosterone on aortic smooth muscle cells of rats are a question of cross-talk and balance between its rapid vasoconstrictor

and vasodilator effects, as result of the activation of reactive oxygen species in the first case and of nitrogen species in the second. In this way, it seems that at low ambient oxidative stress, aldosterone promotes nitric oxide (NO) production and vasodilatation, while in situations with increased oxidative stress the endothelial dysfunction and detrimental effects induced by vasoconstriction will prevail. Thus, aldosterone could be considered both “”friend and foe”". This could be relevant for the ways in which aldosterone damages cardiovascular functions and could lead to significant therapeutic improvements.”
“The FV pathway of replication is fundamentally different from what we know about the strategy employed by all known other retroviruses.

Our results will be helpful to prevent the detrimental effect cau

Our results will be helpful to prevent the detrimental effect caused by the cell death of non-motor neurons under stress

in SMA patients. In addition, the cell model we established can be used to study the mechanism and screen drugs to prevent the detrimental effects in cases of SMA disease.

(sic) Copyright (C) 2011, Elsevier Taiwan LLC. All rights reserved.”
“Objective. The aim of this study was to evaluate the microleakage of Resilon + Epiphany, EndoRez, Activ GP, and conventional AH Plus + gutta-percha technique using the glucose filtration model.

Study design. One hundred twenty maxillary incisors were AZD1080 concentration divided into 5 experimental and 2 control groups. After root canal shaping, the experimental groups were filled with AH Plus + gutta-percha (lateral compaction), Resilon + Epiphany (lateral compaction), AH Plus + Protaper’s proprietory cone, EndoRez + sealer, or Activ GP + sealer). The specimens were mounted on a glucose model and samples were taken for 3 weeks for leakage measurement.

Results. No statistically significant difference was observed between the leakage

of all groups at the 3 testing periods (P > .05).

Conclusion. The filling materials with the monoblock concept do not seem to be superior to the conventional AH Plus + gutta-percha system regarding microleakage. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;109:e96-e102)”
“This article was aimed to investigate the cadmium extraction behaviors of the two different polyvinyl chloride Ralimetinib solubility dmso membranes incorporating Aliquat 336-electrospinning and film-casting. An optimal investigation condition for membranes used in the extraction process was produced at 25 kV with 10 cm tip-to-collector distance. Membranes were electrospun for 8 h at 200 mu L/h. Membrane extraction studies were carried out using

a 127 mg/L Cd(II) solution. Scanning electron microscope (SEM) images revealed differences in fiber selleck inhibitor diameters and membrane morphology. The addition of Aliquat produced very fine fibers (7-722 nm) resulting Brunauer-Emmett-Teller (BET) surface areas of 4.67-11.3 m(2)/g for electrospun membranes and 1.70-5.44 m(2)/g for film-casted membranes. Extraction studies using membranes with different levels of Aliquat (0-40% w/w) revealed that the cadmium extraction performance of electrospun membranes was significantly better than conventional film-cast membranes. For 40% Aliquat 336, with an initial concentration of 127 mg/L Cd, the cast membrane extracted down to concentration to 115 mg/L as compared to electrospun membrane, which extracted down to 88 mg/L within 40 h. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci 121: 327-335, 2011″
“Pheochromocytomas and paragangliomas (extra-adrenal pheochromocytomas) are catecholamine-secreting tumors. The paraganglioma of the urinary bladder is an uncommon neoplasm with a higher malignancy rate. Only about 60% of bladder paragangliomas presented with hematuria, and most of them were microscopic hematuria.

Immediately after the noise exposure, 12 genes were downregulated

Immediately after the noise exposure, 12 genes were downregulated, whereas only one gene (Traf4) was upregulated. At 4 h post-exposure, eight genes were upregulated; three (Tnrsf1a, Tnfrsf1b, Tnfrst5) belonged to the Tnfrsf

family, three (Bir3, Mcl1 and Prok2) have anti-apoptotic properties and one (Gadd45a) is a target of p53. At 7 days post-exposure, all the upregulated genes returned to pre-noise levels. Interestingly, the normal control cochlea had high constitutive levels of several apoptosis-related genes. These constitutively expressed genes, together with the inducible genes, may participate in the induction of cochlear apoptotic activity. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Increased permeability of the blood-brain barrier (BBB) has been reported in different conditions accompanied by hyperthermia, but the Paclitaxel role of brain temperature per se in modulating brain barrier functions has not been directly examined. To delineate the contribution of this factor, we examined albumin immunoreactivity in several brain structures (cortex, hippocampus, selleckchem thalamus and hypothalamus) of pentobarbital-anesthetized rats (50

mg/kg i.p.), which were passively warmed to different levels of brain temperature (32-42 degrees C). Similar brain structures were also examined for the expression of glial fibrillary acidic protein (GFAP), an index of astrocytic selleck compound activation, water and ion content, and morphological cell abnormalities. Data were compared with those obtained from drug-free awake rats with normal brain temperatures (36-37 degrees C). The numbers of albumin- and GFAP-positive cells strongly correlate with brain temperature, gradually increasing from similar to 38.5 degrees C and plateauing at 41-42 degrees C. Brains maintained at hyperthermia also showed larger content of brain water and Na(+), K(+) and Cl(-) as well as structural abnormalities of brain cells, all suggesting

acute brain edema. The latter alterations were seen at similar to 39 degrees C, gradually progressed with temperature increase, and peaked at maximum hyperthermia. Temperature-dependent changes in albumin immunoreactivity tightly correlated with GFAP immunoreactivity, brain water, and numbers of abnormal cells; they were found in each tested area, but showed some structural specificity. Notably, a mild BBB leakage, selective glial activation, and specific cellular abnormalities were also found in the hypothalamus and piriform cortex during extreme hypothermia (32-33 degrees C); in contrast to hyperthermia these changes were associated with decreased levels of brain water, Na(+) and K(+), suggesting acute brain dehydration. Therefore, brain temperature per se is an important factor in regulating BBB permeability, alterations in brain water homeostasis, and subsequent structural abnormalities of brain cells. Published by Elsevier Ltd on behalf of IBRO.

We recently discovered that release of heat shock protein 27 (HSP

We recently discovered that release of heat shock protein 27 (HSP27) into the serum is atheroprotective and mediated by ovarian hormones, preferentially functioning via estrogen receptor-beta. HSP27 binds scavenger receptor-A, reduces cholesterol uptake in macrophages, and attenuates mediators of vascular inflammation. Therefore, Selleckchem AP24534 it is attractive to consider HSP27 as the active foot soldier of estrogens and potentially a novel therapeutic opportunity for vascular

disease. (Trends Cardiovasc Med 2010;20:53-57) (c) 2010, Elsevier Inc.”
“Mesolimbic dopamine projections to the nucleus accumbens (NAc) have been implicated in goal-directed behaviors for natural rewards and in learning processes involving cue-reward associations. The NAc has been traditionally subdivided into two anatomically distinct sub-regions with different functional properties: the shell and the core. The aim of the present study was to characterize rapid dopamine transmission across the two NAc sub-regions during cue-signaled operant behavior for a natural (sucrose) reward

in rats. Using fast-scan cyclic voltammetry (FSCV) we observed differences in the magnitude and dynamics of dopamine release events between the shell and core. Specifically, although cue-evoked dopamine release was observed in both sub-regions, it was larger and longer lasting in the shell compared with the core. Further, secondary dopamine release events were observed following the lever press response for sucrose in the NAc shell, but not the core. These findings demonstrate that the NAc displays regional ZIETDFMK specificity in dopamine transmission patterns during cued operant behavior for natural reward. (C) 2012 Elsevier Ltd. All rights reserved.”
“One of the common methods for assessing energy functions of proteins is selection of native or near-native 8-Bromo-cAMP structures from decoys. This is an efficient but indirect test of the energy functions because decoy structures are typically generated either by sampling procedures or by a separate energy function. As a result, these decoys

may not contain the global minimum structure that reflects the true folding accuracy of the energy functions. This paper proposes to assess energy functions by ab initio refolding of fully unfolded terminal segments with secondary structures while keeping the rest of the proteins fixed in their native conformations. Global energy minimization of these short unfolded segments, a challenging yet tractable problem, is a direct test of the energy functions. As an illustrative example, refolding terminal segments is employed to assess two closely related all-atom statistical energy functions, DFIRE (distance-scaled, finite, ideal-gas reference state) and DOPE (discrete optimized protein energy). We found that a simple sequence-position dependence contained in the DOPE energy function leads to an intrinsic bias toward the formation of helical structures.

Here, we describe the immunobiology of major lung cell subsets an

Here, we describe the immunobiology of major lung cell subsets and their cellular synapses, to reveal the dynamics of B. anthracis infection and its effects on lung immune mechanisms. Vaccines strategies that mobilize protective mucosal and systemic immunity against this deadly microbe are highlighted.”
“Human Zbtb7A was proved to be an important molecular switch in oncogenesis. However, it is difficult to obtain its

protein expression in prokaryotic system, due to high G + C content and rare codons in zbtb7a gene. Therefore, to further research the function and application of this protein, we optimized its coding sequence according to the cordon bias of Pichia pastoris, synthesized the sequence with two-step PCR and confirmed the accuracy by DNA sequencing. The assembled fragment was introduced into A pastoris expression vector pPIC9K and PS-341 purchase the resultant plasmid pPIC9K-zbtb7a-his(6) Was transformed into the A

pastoris strain GS1 15 by electroporation. The products of the transformants induced by methanol were analyzed by 10% SDS-PAGE and identified by Western Blot assay. The expression conditions of the selected transformant were optimized. Additionally, a two-step purification protocol was applied to purify the recombinant protein. The results showed that the synthetic coding sequence of human Zbtb7A was successfully obtained and inserted into pPIC9K vector. Human Zbtb7A protein was expressed in A pastoris and identified by western blot. The selleck products optimal conditions for its expression in P. pastoris were under a final concentration of 1% methanol and a time-course of 4d. Through the two-step purification, Zbtb7A protein was purified in high purity and its production reached up to as high as 18 mg/L. These results indicated that an effective procedure for expressing and purifying human Zbtb7A in P. pastoris was established. Crown copyright (c)

2008 Published by Elsevier Inc. All rights reserved.”
“Oliguria is a valuable marker of kidney function and a criterion for diagnosing and staging acute kidney injury (AKI). However, the utility of urine output as a specific metric for renal dysfunction is somewhat controversial. To JNJ-64619178 study this issue further we tested whether urine output is a sensitive, specific, and early measure for diagnosing and staging AKI in 317 critically ill patients in a prospective observational study. Urine output was assessed every hour and serum creatinine every 12 to 24h. The sensitivity and specificity of different definitions of oliguria for the diagnosis of AKI were compared with the Acute Kidney Injury Network serum creatinine criterion. The incidence of AKI increased from 24%, based solely on serum creatinine, to 52% by adding the urine output as a diagnostic criterion. Oliguric patients without a change in serum creatinine had an intensive care unit mortality rate (8.8%) significantly higher than patients without AKI (1.

Accumulating evidence suggests that the components of the metabol

Accumulating evidence suggests that the components of the metabolic syndrome may also adversely affect the microvasculature through several inter-related mechanisms. These include the following observations: classic risk factors for macrovascular disease such as high blood pressure and dyslipidaemia also accelerate microvascular complications of diabetes, lesser disturbances of glucose metabolism (i.e. impaired glucose tolerance) may be associated with some forms of microvascular

dysfunction, non-glucose intermediary metabolites may promote renovascular hypertension thereby damaging the microvasculature, and insulin resistance appears to be directly associated with microvascular dysfunction. In turn, microvascular CH5183284 order complications such as nephropathy and autonomic neuropathy may promote the development and progression of atherosclerosis. We argue that the vascular implications of the metabolic syndrome should be broadened to include the microvasculature. The hypothesis that vascular

events can be prevented, or at least deferred, through earlier therapeutic intervention in pre-diabetic subjects this website with glucose intolerance is amenable to testing in clinical trials. Copyright (C) 2009 S. Karger AG, Basel”
“The antidepressant desipramine inhibits the reuptake of norepinephrine (NE), leading to activation of both pre- and postsynaptic adrenergic receptors, including alpha-1, alpha-2, beta-1, Tryptophan synthase and beta-2 subtypes. However, it is not clear which adrenergic receptors are involved in mediating its antidepressant effects. Treatment of mice with desipramine (20 mg/kg, i.p.) produced an antidepressant-like effect, as evidenced by decreased immobility in the forced-swim test; this was antagonized by pretreatment

with the a-2 adrenergic antagonist idazoxan (0.1-2.5 mg/kg, i.p.). Similarly, idazoxan, administered peripherally (0.5-2.5 mg/kg, i.p.) or centrally (1-10 mu g, i.c.v.), antagonized the antidepressant-like effect of desipramine in rats responding under a differential-reinforcement-of-low-rate (DRL) 72-s schedule, ie, decreased response rate and increased reinforcement rate. By contrast, pretreatment with the beta-adrenergic antagonists propranolol and CGP-12177 or the alpha-1 adrenergic antagonist prazosin did not alter the antidepressant-like effect of desipramine on DRL behavior. The lack of involvement of beta-adrenergic receptors in mediating the behavioral effects of desipramine was confirmed using knockout lines. In the forced-swim test, the desipramine-induced decrease in immobility was not altered in mice deficient in beta-1, beta-2, or both beta-1 and beta-2 adrenergic receptors. In addition, desipramine (3-30 mg/kg) produced an antidepressant-like effect on behavior under a DRL 36-s schedule in mice deficient in both beta-1 and beta-2 adrenergic receptors.