The orphan nuclear receptor COUP-TFII is required for angiogenesis and heart development

The embryonic expression of COUP-TFII, an orphan nuclear receptor, suggests that it may participate in mesenchymal-epithelial interactions required for organogenesis. Targeted deletion of the COUP-TFII gene results in embryonic lethality with defects in angiogenesis and heart development. COUP-TFII mutants are defective in remodeling the primitive capillary plexus into large and small microcapillaries. In the COUP-TFII mutant heart, the atria and sinus venosus fail to develop past the primitive tube stage. Reciprocal interactions between the endothelium and the mesenchyme in the vascular system and heart are essential for normal development of these systems. In fact, the expression of Angiopoietin-1, a proangiogenic soluble factor thought to mediate the mesenchymal-endothelial interactions during heart development and vascular remodeling, is down-regulated in COUP-TFII mutants. This down-regulation suggests that COUP-TFII may be required for bidirectional signaling between the endothelial and mesenchymal compartments essential for proper angiogenesis and heart development.     

Cardiac reoperations in octogenarians: analysis of outcomes

BACKGROUND: With the rapid growth of the elderly segment of the population, more octogenarians are referred for complex cardiac interventions, including reoperations. Data regarding the outcomes, quality of life, and long-term results after reoperative open-heart surgical procedures in octogenarians are scarce. METHODS: We retrospectively studied 113 consecutive octogenarians (mean age, 83+/-2.6 years) who underwent reoperative cardiac procedures within a 13-year period. Coronary artery bypass grafting (CABG) was performed in 49 patients (CABG group), valvular procedures (aortic, mitral, or tricuspid valve, alone or in combination) in 35 (valve group), and combined CABG and valve intervention in 29 (combined CABG and valve group). RESULTS: The 30-day mortality rate was 8% (4 of 49) for the CABG group, 9% (3 of 35) for the valve group, and 17% (5 of 29) for the combined CABG and valve group. One- and 5-year actuarial survival rates were, respectively, 85%+/-5% and 58%+/-10% for the CABG group, 78%+/-7% and 53%+/-12% for the valve group, and 69%+/-9% and 63%+/-10% for the combined CABG and valve group. Sixty-one percent of patients in the CABG group, 40% in the valve group, and 38% in the combined CABG and valve group were in New York Heart Association class I or II postoperatively at a mean follow-up time of 2.1+/-2.4 years. Similarly, 91%, 85%, and 80%, respectively, thought that they had an improved quality of life and were satisfied with their functional status. CONCLUSIONS: Cardiac reoperations can be performed successfully in most octogenarians, although with an increased risk, particularly in the combined CABG and valve group. Long-term survival is acceptable with improved quality of life and functional status. However, it is possible that these results could be improved in this high-risk group of patients with earlier referral and surgical intervention, for the effective use of health care resources.     

Rhenium-188-Labeled DTPA: a new radiopharmaceutical for intravascular radiation therapy

Balloon angioplasty is a standard treatment for artherosclerotic coronary artery disease. However, its clinical value is reduced by a high restenosis rate. A new concept in preventing restenosis is the use of a liquid-filled balloon containing a beta-emitting radioisotope. In this study, we performed biodistribution studies of Re-188 perrhenate and Re-188 diethylenetriaminopentaacetate (DTPA) to assess the resulting organ dose values in the event of balloon rupture if these agents are used for the clinical inhibition of restenosis after percutaneous transluminal coronary angioplasty (PTCA). After injecting Re-188 preparations intravenously, rats were killed at 10 min, 30 min, 60 min, 2 h, and 6 h ( n =5 per group). Tissue concentrations were calculated and expressed as percent injected dose per gram or per milliliter (%ID/g or %ID/mL). In addition, urine excretion and thyroid gland uptake were evaluated in rats ( n=5 per group) with a gamma camera after administration of 37 MBq (1 mCi) of each agent. Our data showed that both agents were excreted primarily via urine. However, the excretion of Re-188 DTPA was much faster than that of Re-188 perrhenate via the urinary system. The biodistribution data revealed that radioactivity levels in the stomach and the thyroid gland were high in the perrhenate group but low in the Re-188 DTPA group. The concentration levels in other tissues including lung, liver, testis, muscle, and blood were low throughout this study for both agents. The thyroid radiation value in the Re-188 perrhenate group was 0.163 mGy/MBq, which was much higher than that of the Re-188 DTPA group (0.0167 mGy/MBq). The stomach radiation value was as high as 0.127 mGy/MBq for Re-188 perrhenate, compared with 0.013 mGy/MBq for Re-188 DTPA. In conclusion, in the event of balloon rupture, the release of Re-188 DTPA results in lower radiation doses than Re-188 perrhenate, especially to the thyroid gland and the stomach. Our data suggest that Re-188 DTPA is a useful radiopharmaceutical for endovascular irradiation.     

No association between an intronic presenilin-1 gene polymorphism and schizophrenia in a Chinese population

We investigated the association between schizophrenic psychosis and an intronic polymorphism of the presenilin-1 (PS1) gene in a Chinese population. Schizophrenic and control groups had similar PS1 genotype distributions and allele frequencies, indicating that this polymorphism may not be involved in the development of schizophrenia.     

Prior short-term synaptic disinhibition facilitates long-term potentiation and suppresses long-term depression at CA1 hippocampal synapses

Long-term potentiation (LTP) and long-term depression (LTD) are two main forms of activity-dependent synaptic plasticity that have been extensively studied as the putative mechanisms underlying learning and memory. Current studies have demonstrated that prior synaptic activity can influence the subsequent induction of LTP and LTD at Schaffer collateral-CA1 synapses. Here, we show that prior short-term synaptic disinhibition induced by type A gamma-aminobutyric acid (GABA) receptor antagonist picrotoxin exhibited a facilitation of LTP induction and an inhibition of LTD induction. This effect lasted between 10 and 30 min after washout of picrotoxin and was specifically inhibited by the L-type voltage-operated Ca2+ channel (VOCC) blocker nimodipine, but not by the N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphopentanoic acid (D-APV). Moreover, this picrotoxin-induced priming effect was mimicked by forskolin, an activator of cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA), and was blocked by the adenylyl cyclase inhibitor 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ 22536) and the PKA inhibitor Rp-adenosine 3',5'-cyclic monophosphothioate (Rp-cAMPS). It was also found that following picrotoxin application, CA1 neurons have a higher probability of synchronous discharge in response to a population of excitatory postsynaptic potential (EPSP) of fixed slope (EPSP/spike potentiation). However, picrotoxin treatment did not significantly affect paired-pulse facilitation (PPF). These findings suggest that a brief of GABAergic disinhibition can act as a priming stimulus for the subsequent induction of LTP and LTD at Schaffer collateral-CA1 synapses. The increase in Ca2+ influx through L-type VOCCs in turn triggering a cAMP/PKA signalling pathway is a possible molecular mechanism underlying this priming effect.     

The efficacy of potassium citrate based medical prophylaxis for preventing upper urinary tract calculi: a midterm followup study

PURPOSE: We examined the efficacy of potassium citrate based medical prophylaxis for preventing upper urinary calculous recurrence, and compared it with the stone recurrence rate in patients who only received intermittent or no medical prophylaxis. MATERIALS AND METHODS: We retrospectively reviewed the records of 493 patients with upper urinary calculi, of whom 237 men and 76 women with a mean age of 56.1 and 51.4 years, respectively, were enrolled in the study. Of the 313 participants 64 (group 1, 20.4%) received regular medical prophylaxis for 24 to 42 months (mean 27.8), 80 (group 2, 25.6%) received intermittent medical prophylaxis for 1.5 to 19 months (mean 7.9) and 169 (group 3, 54%) did not receive any medical prophylaxis. RESULTS: At midterm followup of 24 to 60 months 107 patients (34.2%) had stone recurrence. In group 1 the stone recurrence rate was 7.8%, which was significantly less (p <0.001) than in groups 2 (30%) and 3 (46.2%). Similarly new calculous events in patients with a history of multiple stone recurrence were less frequent in group 1 than in groups 2 and 3 (9.7, 47.4 and 52.2%, respectively, p <0.001). Multiple stone recurrence history, hypercalciuria, hyperuricosuria and calcium oxalate dihydrate calculi were independent risk factors for stone recurrence. CONCLUSIONS: Regular medical prophylaxis may effectively prevent stone recurrence regardless of previous treatment modalities, stone composition, metabolic abnormalities and stone-free status. Cost effectiveness, patient compliance and gastrointestinal upset may limit patient acceptability and clinical use of medical prophylaxis. However, patients with a history of multiple stone recurrence, calcium oxalate dihydrate stones, hypercalciuria and hyperuricosuria benefit from regular medical prophylaxis.     

Anesthetic management for cesarean section in a pregnant woman with impending acute liver failure--a case report

Acute liver failure includes a constellation of clinical conditions resulting from rapid loss of hepatocyte function. The anesthesiologist may often be asked to anesthetize a patient with acute liver failure before the etiological entity of disease can be completely clarified. Most of the previous reports were concentrated in obstetric or hepatological periodicals. Reports about anesthesia for such patients are scanty. We present a case about a near term pregnant woman with a complication diagnosed as impending acute liver failure, who received total intravenous anesthesia for emergent cesarean section. Pros and cons of different anesthetic techniques for this condition are discussed.     

Hepatitis A vaccine in healthy adults: a comparison of immunogenicity and reactogenicity between two- and three-dose regimens

Inactivated hepatitis A virus (HAV) vaccine was administered to 55 healthy seronegative adult volunteers to evaluate the immunogenicity and adverse reactions of two doses of HAV vaccination (25 units) in comparison with a three-dose regimen. The volunteers were randomly assigned to receive one of the two regimens: 26 were vaccinated with two doses at 0 and 24 weeks (Group 1), and 29 were vaccinated with three doses at 0, 2, and 24 weeks (Group 2). The vaccine was well tolerated and there was no serious adverse reaction. In both groups, the seroconversion rate was 100% at week 28. At week 52, all remained positive for anti-HAV regardless of a two- or three-dose regimen. No statistically significant difference in seroconversion rates and geometric mean titers could be demonstrated between the two groups. Thus, the two-dose regimen may be favorable to save cost and time for active immunization against hepatitis A.     

Effect of synthetic triglycerides of myristic, palmitic, and stearic acid on serum lipoprotein metabolism.

OBJECTIVES: To determine relative effects of diets high in synthetic sources of myristic (14:0), palmitic (16:0) or stearic (18:0) acid on concentrations and metabolism of serum lipoproteins. DESIGN: Eighteen healthy women participated in a three-way cross-over study for five week periods separated by seven week washout periods, diets were assigned in random order. SUBJECTS: Premenopausal women, not on medication, were from three races (Caucasian, African-American, Asian) and four apolipoprotein E phenotype groups (3/3, 3/2, 4/3, and 4/2). INTERVENTION: During the first week the subjects consumed a baseline diet providing 11 energy (en)% saturated fat, 10en% polyunsaturated fat and 14en% monounsaturated fat. Followed by test diets with 19en% saturated fat (including 14en% test saturated fatty acid), 3en% polyunsaturated fat, and 14en% monounsaturated fat for four weeks. Synthetic fats (trimyristin, tripalmitin, and tristearin) were used in blends with natural fats and oils. RESULTS: Mean concentrations of serum total, esterified and LDL cholesterol were significantly lower after 18:0 than after 16:0 (n = 16-18, P < 0.01 for treatment effect). Myristic acid (14:0) had an intermediate effect. Receptor-mediated degradation of 125I-LDL in mononuclear cells obtained from the subjects was lower after 16:0 than after 14:0 and 18:0 (n = 16-18, P=0.05 for treatment effect). Differences in the digestibilities of the fats were not a major factor in the results. Strong cholesterolemic responses to the 16:0 diet were partly explained by apoE phenotype. CONCLUSIONS: As noted previously, stearic acid was neutral compared to 14:0 and 16:0. In contrast to studies involving natural fats, 14:0, fed as a synthetic triglyceride, was less cholesterolemic than 16:0 in a majority of subjects. ApoE phenotype influenced the cholesterolemic response particularly when diets high in 16:0 were eaten.     

Suppression of nitric oxide synthase and the down-regulation of the activation of NFkappaB in macrophages by resveratrol

Resveratrol, naringenin and naringin are naturally occurring flavonoids in grapes and grapefruits. The anti-inflammatory effects of these flavonoids have been well documented, but the mechanism is poorly characterized. High concentration of NO are produced by inducible NO synthase (iNOS) in inflammation, and the prevention of the expression of iNOS may be an important anti-inflammatory mechanism. In this study, the effects of these flavonoids on the induction of NO synthase (NOS) in RAW 264.7 cells activated with bacterial lipopolysaccharide (LPS, 50 ng ml(-1)) were investigated. Resveratrol was found strongly to inhibit NO generation in activated macrophages, as measured by the amount of nitrite released into the culture medium, and resveratrol strongly reduced the amount of cytosolic iNOS protein and steady state mRNA levels. However, the inhibitory abilities of naringenin were lower, and the inhibitory abilities of naringin were almost negligible. In electrophoretic mobility shift assays, the activation of NFkappaB induced by LPS for 1 h was inhibited by resveratrol (30 microM). Furthermore, in immunoblotting analysis, cells treated with LPS plus resveratrol showed an inhibition of phosphorylation as well as degradation of IkappaBalpha, and a reduced nuclear content of NFkappaB subunits. The flavonoids may be of value for inhibiting the enhanced expression of iNOS in inflammation through down-regulation of NFkappaB binding activity.