Acute and repeated treatment with the 5-HT7 receptor antagonist SB 269970 induces functional desensitization of 5-HT7 receptors in rat hippocampus.

Background: SB 269970, a 5-HT(7) receptor antagonist may produce a faster antidepressant-like effect in animal models, than do antidepressant drugs, e.g., imipramine.

Repeated blockade of 5-HT₇ receptors depresses glutamatergic transmission in the rat frontal cortex.

The effects of the intraperitoneal administration of the 5-HT₇ receptor antagonist SB 269970 were studied in the rat frontal cortex. In ex vivo slices prepared from rats receiving 14 daily doses of the drug (1.25 mg/kg) the mean frequency and the mean amplitude of glutamate-mediated, spontaneous excitatory postsynaptic currents (sEPSCs) recorded from layer II/III pyramidal neurons, were decreased.

Relapsed and/or Refractory Mantle Cell Lymphoma: What Role for Temsirolimus?

Mantle Cell Lymphoma (MCL) is associated with a dismal prognosis. Recently, along with the improved understanding of the pathophysiology of this disease, new first line regimens have been established and in addition novel treatment options have entered the clinical arena. In consequence, prognosis of the disease has fortunately improved.

Clinical burden of illness in patients with neuroendocrine tumors.

Objective: The objective of this study was to evaluate the incremental risk of morbidities affecting the cardiovascular, hepatic, gastrointestinal, skeletal, and neuropsychiatric systems in patients with neuroendocrine tumors (NETs) compared with a noncancer cohort.

Methods: In a retrospective, matched-control study using US claims databases, noncancer control subjects (n = 3524) were matched 2:1 with patients with newly diagnosed NET (n = 1762) on age, sex, region, hospital data availability, and index year. Rates of select morbidities were compared between patients with NET and control subjects.

Chemoimmunotherapy with ofatumumab in combination with CHOP in previously untreated follicular lymphoma.

An international, Phase II trial was conducted to assess two doses of ofatumumab, a human CD20 monoclonal antibody, combined with cyclophosphamide (750 mg/m(2) ), doxorubicin (50 mg/m(2) ), prednisone (100 mg days 3-7) and vincristine (1·4 mg/m(2) ) (O-CHOP), as frontline treatment for follicular lymphoma (FL). 59 patients with previously untreated FL were randomized to ofatumumab 500 mg (n = 29) or 1000 mg (n = 30) day 1, with CHOP on day 3 every 3 weeks for six cycles. Median duration of FL was 0·1 years for both dose groups; 34% and 38% of patients had high-risk Follicular Lymphoma International Prognostic Index (FLIPI) scores in the 500- and 1000-mg dose groups, respectively.

Tubular markers are associated with decline in kidney function in proteinuric type 2 diabetic patients.

Unlabelled: Our aim was to investigate u-NGAL, u-KIM1 and p-FGF23 and prediction of decline in kidney function in type 2 diabetic patients with proteinuria.

Methods: We performed a follow-up study, follow-up median (range) 3.5 (1-5) years.

Imipramine counteracts corticosterone-induced enhancement of glutamatergic transmission and impairment of long-term potentiation in the rat frontal cortex.

The effects of corticosterone administration lasting for 7 and 21 days were studied ex vivo in rat frontal cortex slices prepared 48 h after the last dose of the hormone. In slices originating from corticosterone-treated animals, the amplitude of extracellular field potentials recorded in cortical layer II/III was increased. Corticosterone administration also resulted in an increase of the mean frequency, but not the mean amplitude, of spontaneous excitatory postsynaptic currents (sEPSCs) in layer II/III pyramidal neurons.

The 5-HT(7) receptor antagonist SB 269970 counteracts restraint stress-induced attenuation of long-term potentiation in rat frontal cortex.

The effects of restraint lasting for 10 min, repeated twice daily for 3 days, were studied ex vivo in rat frontal cortex slices prepared 24 h after the last stress session. In slices originating from stressed animals, the amplitude of extracellular field potentials recorded in cortical layer II/III was increased. Stress also resulted in a reduced magnitude of long-term potentiation (LTP) of field potentials.

Spironolactone diminishes urinary albumin excretion in patients with type 1 diabetes and microalbuminuria: a randomized placebo-controlled crossover study.

Aims: Adding aldosterone receptor blockade to standard renoprotective treatment may provide additional renoprotection in patients with overt nephropathy. We expected an impact of spironolactone in early diabetic nephropathy, and for this hypothesis we studied the effect on markers of glomerular and tubular damage in patients with Type 1 diabetes and persistent microalbuminuria.

Methods: A double-blind, randomized, placebo-controlled crossover study in 21 patients with Type 1 diabetes and microalbuminuria using spironolactone 25 mg or placebo once daily, for 60 days added to standard antihypertensive treatment.

The effect of RAAS blockade on markers of renal tubular damage in diabetic nephropathy: u-NGAL, u-KIM1 and u-LFABP.

Aim: Blockade of the renin-angiotensin-aldosterone system (RAAS) affects both the glomerulus and tubules. We aimed to investigate the effect of irbesartan on the tubular markers: urinary (u) neutrophil gelatinase associated protein (NGAL), Kidney injury molecule 1 (KIM1) and liver-fatty acid-binding protein (LFABP).

Methods: A substudy of a double-masked, randomized, cross-over study including 52 patients with type 2 diabetes, hypertension and microalbuminuria.

5-HT7 receptors modulate GABAergic transmission in rat hippocampal CA1 area.

The effects of the activation of serotonin-7 (5-HT(7)) receptors were investigated in the CA1 area pyramidal cells and stratum radiatum fast spiking GABAergic interneurons of rat hippocampal slices. To activate 5-HT(7) receptors, 5-carboxamidotryptamine (5-CT), a nonselective 5-HT(1A)/5-HT(7) agonist, was applied in the presence of N-[2-[4-(2-methoxyphenyl)-1piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide (WAY 100635), a selective 5-HT(1A) receptor antagonist. The activation of 5-HT(7) receptors resulted in a dose-dependent increase in the mean frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) recorded from pyramidal neurons while the mean amplitude of sIPSCs remained unaltered.

Land trust evaluation of progress toward conservation goals.

In the United States local land trusts preserve and conserve land to protect water quality and supply, farmlands, habitat for native plants and animals, areas of cultural or historical significance, and scenic views. We surveyed the 24 active, local land trusts in North Carolina (U.S.

Glutamate input to noradrenergic neurons plays an essential role in the development of morphine dependence and psychomotor sensitization.

The brain's noradrenergic system is involved in the development of behaviours induced by drugs of abuse, e.g. dependence and withdrawal, and also reward or psychomotor effects.

Ankle impingement syndromes: a review of etiology and related implications.

Ankle injuries are common occurrences in athletics involving and requiring extreme ranges of motion. Ankle sprains specifically occur with a 1 in 10,000 person rate in active individuals each day. If trauma is repetitive, the ankle structures have potential to experience secondary injury and dysfunction.

Update on the molecular pathogenesis and clinical treatment of mantle cell lymphoma: report of the 10th annual conference of the European Mantle Cell Lymphoma Network.

Mantle cell lymphoma (MCL) is a distinct subtype of malignant lymphoma characterized by the chromosomal translocation t(11;14)(q13;q32), resulting in constitutional overexpression of cyclin D1 and cell cycle dysregulation in virtually all cases. Clinically, MCL shows an aggressive clinical course with a continuous relapse pattern and a median survival of only 3-5 years. However, recently a subset of up to 15% long-term survivors has been identified with a rather indolent clinical course.

Sexual behaviour research using the survey method: a critique of the literature over the last six years.

Objectives: The survey method is often used to identify trends in sexual behaviour and attitudes. In order for research conclusions to be valid, however, data gathered from surveys must be unambiguous. For the current paper we reviewed survey research of sexual behaviour published in recent years.

High sensitive troponin T and heart fatty acid binding protein: novel biomarker in heart failure with normal ejection fraction? A cross-sectional study.

Background: High sensitive troponin T (hsTnT) and heart fatty acid binding protein (hFABP) are both markers of myocardial injury and predict adverse outcome in patients with systolic heart failure (SHF). We tested whether hsTnT and hFABP plasma levels are elevated in patients with heart failure with normal ejection fraction (HFnEF).

Methods: We analyzed hsTnT, hFABP and N-terminal brain natriuretic peptide in 130 patients comprising 49 HFnEF patients, 51 patients with asymptomatic left ventricular diastolic dysfunction (LVDD), and 30 controls with normal diastolic function.

Brief neck restraint stress enhances long-term potentiation and suppresses long-term depression in the dentate gyrus of the mouse.

We studied the effects of brief (10 min) neck restraint on long-term potentiation (LTP) and long-term depression (LTD) in mouse dentate gyrus (DG) slices. Brain slices were prepared immediately after neck restraint and LTP/LTD induction was attempted 3.5h later.

Growth-differentiation factor-15: a novel biomarker in patients with diastolic dysfunction?

Background: Growth differentiation factor-15 (GDF-15), a stress-responsive transforming growth factor-ß-related cytokine, is elevated and independently related to an adverse prognosis in systolic heart failure.

Objective: This study aimed to investigate plasma levels of GDF-15 in patients with preclinical diastolic dysfunction or heart failure with normal ejection fraction (HFnEF).

Methods: We evaluated 119 patients with normal ejection fraction referred for an elective coronary angiography, 75 (63%) of whom had coronary artery disease.

Chemoimmunotherapy with O-FC in previously untreated patients with chronic lymphocytic leukemia.

We conducted an international phase 2 trial to evaluate 2 dose levels of ofatumumab, a human CD20 mAb, combined with fludarabine and cyclophosphamide (O-FC) as frontline therapy for chronic lymphocytic leukemia (CLL). Patients with active CLL were randomized to ofatumumab 500 mg (n = 31) or 1000 mg (n = 30) day 1, with fludarabine 25 mg/m(2) and cyclophosphamide 250 mg/m(2) days 2-4, course 1; days 1-3, courses 2-6; every 4 weeks for 6 courses. The first ofatumumab dose was 300 mg for both cohorts.

Phase I/II study of pixantrone in combination with cyclophosphamide, vincristine, and prednisone in patients with relapsed aggressive non-Hodgkin lymphoma.

Pixantrone is a potentially more effective, less cardiotoxic alternative to doxorubicin for patients with aggressive non-Hodgkin lymphoma (aNHL). This phase I/II non-comparative study evaluated pixantrone in place of doxorubicin in the standard CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone), i.e.

Use of multicomponent reactions in developing small-molecule tools to study GABAA receptor mechanism and function.

We discuss the potential use of multicomponent reactions in developing small-molecule probes of GABA(A) receptor function. Two examples that illustrate this approach are presented: the synthesis of a class of compounds that specifically modulate the function of GABA(A) receptors containing the δ-subunit, and also 'caged' GABA derivatives. A caged GABA is a photolabile precursor of GABA that releases GABA upon photolysis.

Adsorption of CF4 on graphite preplated with a monolayer of CF3Cl.

We report a study of the adsorption of CF(4) on graphite preplated with a monolayer of CF(3)Cl, using infrared reflection absorption spectroscopy combined with ellipsometry. The saturated vapor pressure of CF(3)Cl is nearly 3 orders of magnitude smaller than that of CF(4) at the same temperature, so the main control variables are the temperature and the pressure (or chemical potential) of CF(4), together with the initial coverage of CF(3)Cl. The temperature range covered is 60-105 K.

Bortezomib retreatment in relapsed multiple myeloma - results from a retrospective multicentre survey in Germany and Switzerland.

Objectives: This multicenter, retrospective survey evaluated the efficacy and safety of bortezomib retreatment in patients with relapsed multiple myeloma who had responded to initial bortezomib treatment.

Methods: Clinical records of 94 patients receiving bortezomib retreatment in Germany and Switzerland were reviewed.

Results: Sixty patients were included according to prespecified criteria.