Effects of calcium supplementation on body weight reduction in overweight calcium stone formers

A randomized, placebo-controlled trial was conducted in overweight calcium stone-forming (CSF) patients, to evaluate the effect of calcium supplementation associated with a calorie-restricted diet on body weight (BW) and fat reduction and its potential changes upon serum and urinary parameters. Fifteen patients were placed on a hypocaloric diet for 3 months, supplemented with either calcium carbonate (CaCO₃, n = 8) or placebo (n = 7), 500 mg bid. Blood and 24-h urine samples were collected and body composition was assessed at baseline and after the intervention. At the end of the study, final BW was significantly lower vs baseline in both CaCO₃ (74 ± 14 vs. 80 ± 14 kg, P = 0.01) and placebo groups (80 ± 10 vs. 87 ± 9 kg, P = 0.02) but the mean percentage of loss of body weight and body fat did not differ between CaCO₃ and placebo (7.0 ± 2.0 vs. 8.0 ± 3.0%, P = 0.40 and 13.0 ± 7.0 vs. 13.0 ± 10.0%; P = 0.81, respectively). After CaCO₃ or placebo, no significant differences versus baseline were observed for urinary parameters in both CaCO₃ and placebo, except for a higher mean urinary citrate in placebo group. These data suggest that increasing calcium intake by calcium carbonate supplementation did not contribute to a further reduction of BW and fat in overweight CSF patients submitted to a hypocaloric diet nor altered urinary lithogenic parameters.     

Pregnancy Nutritional Indices and Birth Weight After Roux-en-Y Gastric Bypass

Background  Maternal metabolic profile and nutritional course of pregnancy after bariatric interventions is incompletely known. Their impact on birth weight has also not been hitherto addressed. Aiming to document such variables, a retrospective study was undertaken. Methods  Women previously submitted to silastic ring Roux-en-Y gastric bypass, who conceived after 0–5 years (n = 14), were investigated. Intake of selected macro- and micronutrients, representative laboratory measurements, and correlation of these findings with birth weight and time to conception was documented. Results  Mean calorie intake was restricted to about 1,800 kcal/day. Protein (71 ± 17 g/day) and supplementary iron (60 mg/day) were barely adequate, and calcium and vitamin B₁₂ did not meet current recommendations, only folic acid being optimal. Biochemical monitoring reflected these inconsistencies, with occasional low values for serum albumin (4.1 ± 0.4 g/dL), hemoglobin (11.4 ± 1.5 g/dL), iron (78 ± 50 μg/dL) and vitamin B₁₂ (193 ± 102 pg/mL) but not folate. Lipids, glucose, and uric acid were much better than before the anti-obesity intervention. Reduced plasma lipids, glucose, and uric acid were associated with larger birth weight, albeit within the normal range. Conclusions  (1) Anemia as well as additional nutritional deficits during pregnancy were not totally eliminated, despite dietary guidance and micronutrient supplementation; (2) alleviation of metabolic comorbidities was demonstrated, and improved normalization predicted higher birth weight; (3) energy and folate intake was sufficient, but other nutrients probably did not reach ideal levels; (4) recent dietary guidelines for this population represent a step forward, but additional studies are needed.     

钙相关蛋白43的肿瘤相关性

恶性肿瘤难以根治的一个非常重要的原因在于难以早期发现和早期诊断。肿瘤的免疫学诊断和基因诊断为肿瘤的早期诊断提供了可能。钙相关蛋白43基因是在研究镍化合物致癌机理中发现的新基因,研究发现其在正常组织表达很低或不表达,而在肿瘤组织表达显著上调,且为肿瘤发生、发展的早期事件之一。     

Classical inotropes and new cardiac enhancers

Acute heat failure syndromes are a heterogenous group of conditions. Chronic heart failure exacerbations represent the vast majority of cases. Pathophysiologic mechanisms, such as hypotension with peripheral tissue hypoperfusion, renal function impairment and myocardial ischemia and injury, adversely affect patients' clinical outcome. Classical inotropes, such as beta-agonists (dobutamine, dopamine) and phosphodiesterase inhibitors (milrinone), seem to improve clinical symptoms and hemodynamics of acutely decompensated chronic heat failure patients, but they have been associated with increased long-term mortality. Thus, on the basis of the available evidence, these agents can be used only as a temporary treatment of acute heart failure exacerbations with stringent criteria (ESC AHF guidelines), resistant to intravenous vasodilators and/or diuretics when systolic blood pressure (SBP) is >100 mmHg or as a first-line treatment in patients with worsening of chronic cardiac failure and low SBP (<100 mmHg). The calcium sensitizer levosimendan is a new cardiac enhancer that seems to be more effective than classical inotropes in improving cardiac mechanical efficiency and reducing congestion, without causing cardiomyocyte death or increasing myocardial oxygen uptake. Recent randomized trials showed that levosimendan is not superior to placebo or dobutamine in improving 1- and 6-month mortality, although it caused a greater reduction of neurohormonal response. More data are needed regarding patient selection and the optimum regimen and dosing of levosimendan before this treatment modality become the first line therapy of acutely decompensated chronic heart failure patients.     

Estrogen evokes a rapid effect on intracellular calcium in neurons characterized by calcium oscillations in the arcuate nucleus

Rapid estrogen effects became an interesting topic to explain estrogen effects not associated with the classical nuclear pathway. The rapid estrogen effect on intracellular calcium oscillations was characterized in neurons of the arcuate nucleus. Ratiometric calcium imaging (fura-2AM) was used to measure intracellular calcium in brain slices of female Swiss Webster mice (median of age 27 days p.n.). Calcium oscillations were dependent on intracellular calcium and also on calcium influx from the extracellular space. The perfusion of slices with calcium-free solution inhibited spontaneous calcium oscillations. The metabotropic glutamate receptor agonist t-ACPD (5 microM) and low concentrated ryanodine (100 nM) induced intracellular calcium release when slices were perfused with calcium-free solution. 17beta-estradiol (10 nM) also induced intracellular calcium release in calcium-free ACSF. This effect was inhibited by the preceding administration of thapsigargin (2 microM) indicating the association of the rapid estrogen effect with intracellular calcium stores. The administration of the non-selective phospholipase C-inhibitor ET-18 (30 microM), but not U73122 (10 microM), and the inhibition of protein kinase A by H-89 (0.25 microM) suppressed the rapid estrogen effect. Analyses indicated a qualitative, but not quantitatively significant effect of 17beta-estradiol on calcium oscillations.     

Proteasome inhibition-induces endoplasmic reticulum dysfunction and cell death of human cholangiocarcinoma cells

AIM： To determine if proteasome inhibition induces apoptosis in human cholangiocarcinoma cells, and if so, to elucidate the cellular mechanisms.
METHODS： Studies were performed in the human KMCH, KMBC, and Mz-ChA-1 cholangiocarcinoma, and normal rat cell lines. MG132, a peptide aldehyde, which inhibits the chymotrypsin-like activity of the proteaosome was employed for this study. Apoptosis was assessed morphologically by 4＇-6-Diamidino-2-phenylindole （DAPI） nuclear staining and fluorescence microscopy. Mitochondrial membrane potential was examined using a fluorescent unquenching assay. Ultrastructural changes during cell death were examined using transmission electron microscopy （TEM）. Caspase 3/7 activity was assessed using an enzymatic-based fluorescent assay. Cytosolic-free calcium concentrations were measured using Fura-2 and digitized fluorescent microscopy.
RESULTS： MG132, a proteasome inhibitor, induced apoptosis in all the cholangiocarcinoma cell lines examined. In contrast, minimal cytotoxicity was observed in normal rat cholangiocytes. Apoptosis was time- and -concentration-dependent. There was no change in the mitochondrial membrane potential between treated and untreated cells. Ultrastructural examination by transmission electron microscopy displayed the classic features of apoptosis, but in addition, there was also dramatic vacuolization of the endoplasmic reticulum （ER）. Unexpectedly, no increase in caspase 3/7 activity was observed in MG132 treated cells, nor did the pancaspase inhibitor, Q-VD-OPh prevent cell death. The protein synthesis inhibitor, cycloheximide, blocked apoptosis induced by proteosome inhibitor indicating that ER dysfunction was dependent upon the formation of new proteins.
CONCLUSION： Proteosome inhibition induces ER dysfunction and caspase-independent cell death selectively in human cholangiocarcinoma cells. Proteasome inhibitors warrant evaluation as anticancer agents for the treatment of human cholangiocarcinoma.     

我院门诊口服钙制剂临床应用分析

目的评估口服钙制剂的临床应用情况。方法对医院2007年11月至2008年1月口服钙制剂的门诊处方进行统计分析。结果口服钙制剂的临床应用广泛,女性与中老年人使用尤多,补钙现象普遍。结论钙制剂有过度使用的趋势,补钙需谨慎。     

Calcium overload in nerve terminals of cultured neurons intoxicated by alpha-latrotoxin and snake PLA2 neurotoxins

Snake presynaptic neurotoxins with phospholipase A2 (PLA2) activity cause degeneration of the neuromuscular junction. They induce depletion of synaptic vesicles and increase the membrane permeability to Ca²⁺ which fluxes from the outside into the nerve terminal. Moreover, several toxins were shown to enter the nerve terminals of cultured neurons, where they may display their PLA2 activity on internal membranes. The relative contribution of these different actions in nerve terminal degeneration remains to be established. To gather information on this point, we have compared the effects of β-bungarotoxin, taipoxin, notexin and textilotoxin with those of alpha-latrotoxin on the basis of the notion that this latter toxin is well known to cause massive Ca²⁺ influx and exocytosis of synaptic vesicles. All the parameters analysed here, including calcium imaging, are very similar for the two classes of neurotoxins. This indicates that Ca²⁺ overloading plays a major role in the degeneration of nerve terminals induced by the snake presynaptic neurotoxins.     

Effect of calcium on the hemolytic activity of Stichodactyla helianthus toxin sticholysin II on human erythrocytes

Sticholysin II (St II) is a toxin from the sea anemona Stichodactyla helianthus that produces erythrocytes lysis at low concentration and its activity depends on the presence of calcium. Calcium may act modifying toxin interaction with erythrocyte membranes or activating cellular processes which may result in a modified St II lytic action. In this study we are reporting that, in the presence of external K⁺, extracellular calcium decreased St II activity on erythrocytes. On the other hand an increase of intracellular calcium promotes Sty II lytic activity. The effect of intracellular calcium was specifically studied in relation to membrane lipid translocation elicited by scramblases and how this action influence St II lytic activity on erythrocytes. We used 0.5 mmol/L calcium and 10 mmol/L A23187, as calcium ionophore, for scramblases activation and found increased St II activity associated to increase of intracellular calcium. N-ethyl maleimide (activator) and 4,4′-diisothiocyanatostilbene-2,2′-disulfonate (inhibitor) were used as scramblases modulators in the assays which produced an increase and a decrease of the calcium effect, respectively. Results reported suggest an improved St II membrane pore-forming capacity promoted by intracellular calcium associated to membrane phospholipids translocation.     

The regulation of cnidocyte discharge

Because cnidocytes are exceedingly complex cells which can only be used once, their discharge is highly regulated by way of a variety of chemosensory, mechanosensory and endogenous pathways. The integration of these various inputs ultimately results in exocytosis and then discharge of the cnidocyte's diagnostic organelle, the cnidocyst. Here we review what is known about the sensory pathways that regulate cnidocytes, the electrical events that manifest in cnidocytes following sensory stimulation and the ionic mechanisms that underlie discharge.