Evidence for an Exaggerated Postprandial Lipemia in Chronic Paraplegia

Abstract

Background/Objective: Excessive delay in triglyceride (TG) metabolism after ingestion of dietary fatrepresents a significant cardiovascular disease (CVD) risk. The objective of this study was to compare thepostprandial lipemic responses of individuals with paraplegia with those of healthy nondisabled individuals.

Methods: The ability of 3 recreationally active individuals with paraplegia having normal fasting TG(mean= 103 mg/dl) to metabolize TG after ingestion of a high-fat test meal was compared with apreviously published cohort of 21 recreationally active individuals without paraplegia (TG mean= 86 mg/dl)who underwent identical testing. The subjects with paraplegia had venous blood taken under fastingconditions, and then ingested a milkshake containing premium ice cream blended with heavy whippingcream(~ 92% of calories from fat). Additional blood samples were obtained at 2, 4, and 6 hours afteringestion. The area under the curve (AUC) for TG clearance for both subject groups was measured with anarea planimeter.

Results: TG uptake for both groups was almost identical for the first 2 hours after ingestion. At 4 and 6 hoursafter ingestion, the TG levels were 50 and 35 mg/dl higher, respectively, in subjects with paraplegia than innondisabled subjects. When corrected for small baseline differences in TG concentrations (16 mg/dl), theAUC was 46.5% greater for the group with paraplegia than in the nondisabled group. A near mirrorassociation across time was observed between postprandial serum high-density lipoprotein cholesterol(HDL-C) and TG levels in subjects with paraplegia.

Conclusion: This case series finds an exaggerated postprandial lipemia (PPL) in persons with paraplegiawith normal fasting TGs. This finding is the first evidence, in a small population, of an unreported potentialCVD risk in persons with paraplegia.     

Problems with measuring peripheral oxytocin: Can the data on oxytocin and human behavior be trusted?

Research on the neurobiological and behavioral effects of oxytocin (OT), as well as on its possible therapeutic applications, has intensified in the past decade. Accurate determination of peripheral OT levels is essential to reach meaningful conclusions and to motivate, support and inform clinical interventions. Different, but concordant, methods for measuring plasma OT have been developed over the past four decades, but since 2004 several commercially available methods have been favored in research with humans. Evaluation of these methods reveals that they lack reliability when used on unextracted samples of human fluids, and that they tag molecules in addition to OT, yielding estimates that are wildly discrepant with an extensive body of earlier findings that were obtained using methods that are well validated, but more laborious. An accurate, specific, and readily available method for measuring OT that can be adopted as the standard in the field is urgently needed for advances in our understanding of OT's roles in cognition and behavior.     

Enlightenment about the new Architect-i2000 estradiol (Abbott Laboratories) immunoassay during in vitro fertilization

OBJECTIVE: We assessed a new estradiol (E2) immunoassay on the Architect-i2000 (Abbott Laboratories) for monitoring ovulation stimulation for IVF-ET and re-establishing clinical cut-off points. The method has been modified to improve E2 measurements especially at normal and low concentrations. DESIGN AND METHOD: E2 was determined for 552 samples, from 83 women, presenting normal follicular status and undergoing 100 cycles of IVF treatment. We assessed the value of this assay for down-regulation of E2 concentration limit using gonadoliberin-releasing hormone agonist (GnRHa), and monitoring of the ovarian hyperstimulation, expected range of E2 per mature follicle prior to the administration of exogenous hCG and day 3 concentration limit. We compared results with our routine method (E2-6II Advia-Centaur; Siemens-Diagnostics) for which decision-making values were known. RESULTS: Considering E2 concentrations obtained with the new Architect-i2000 assay for patients treated with GnRHa for 2 weeks, the cutoff-point for ovarian down-regulation should be set down at 110 pmol/L to maintain 100% of sensitivity. Considering day 3 concentration limit determination, results were not significantly different from those obtained with our routine method. The mean E2 values per mature follicle fell into the range generally expected. CONCLUSION: E2 determination with the new E2 Architect-i2000 assay could be used to monitor ovulation, in patients undergoing IVF-ET, in combination with transvaginal ultrasound.     

Percutaneous biliary drainage in acute suppurative cholangitis

One hundred and sixteen percutaneous drainage procedures of the biliary system were performed in a 2-year period. Eight of 9 acutely ill patients with the diagnosis of acute suppurative cholangitis were successfully treated nonoperatively. They represented 26% of all patients with benign or postsurgical obstruction referred for biliary decompression. Conversely, acute suppurative cholangitis only occurred in 2.3% of patients with underlying malignant disease. These observations are considered most relevant in predicting the purulent nature of the disease, with further implications for patient management. Early recognition and prompt decompression of the biliary system are mandatory, along with the appropriate antibiotic coverage. Our experience compares favorably with surgical results and the procedure is proposed as the method of choice for the initial treatment of acute suppurative cholangitis.     

巨噬细胞迁移抑制因子通过CC趋化因子配体2诱导巨噬细胞聚集

巨噬细胞迁移抑制因子最初是由于能抑制体外巨噬细胞随机迁移而被发现,现在它作为一种重要的调节因子参与一系列炎症性疾病过程.我们最近发现,巨噬细胞迁移抑制因子的缺失使一些由炎症介质诱发的白细胞-内皮细胞相互作用减弱,提示巨噬细胞迁移抑制因子在炎症反应中起作用的机制之一是促进白细胞聚集.……     

In vitro killing of neuroblastoma cells by neutrophils derived from granulocyte colony-stimulating factor-treated cancer patients using an anti-disialoganglioside/anti-Fc gamma RI bispecific antibody

Neutrophils isolated from cancer patients treated with granulocyte colony-stimulating factor (G-CSF) express high levels of Fc gamma RI. They exhibited an efficient killing of GD2+ neuroblastoma cells in the presence of an antidisialoganglioside (GD2) mouse monoclonal antibody (MoAb; 7A4, IgG3 kappa). However, this cytotoxicity was totally blocked by human monomeric IgG. In contrast, a bispecific antibody (7A4 bis 22/MDX-260), prepared by chemically linking an F(ab') fragment of 7A4 with an F(ab') fragment of an anti-Fc gamma RI MoAb, 22, which binds outside the Fc binding domain, triggered antibody-dependent cell cytotoxicity, even when neutrophils were preincubated with human monomeric IgG. F(ab')2 22 MoAb abrogated the MDX-260 killing without affecting that of 7A4. The 3G8 MoAb, directed against the Fc gamma RIII binding site, did not inhibit the cytotoxicity induced by either antibody. Thus, these results indicate that G-CSF-activated neutrophils exert their cytotoxic effect against neuroblastoma cells through Fc gamma RI and not Fc gamma RIII, and that the saturation of the high affinity Fc gamma RI by monomeric IgG can be overcome by the use of bispecific antibodies binding epitopes outside the IgG Fc gamma RI binding site. A combined administration of such bispecific antibodies and G-CSF may be, therefore, an efficient therapeutic approach to trigger tumor lysis by cytotoxic neutrophils in vivo.     

Role of guanylate cyclase-activating proteins (GCAPs) in setting the flash sensitivity of rod photoreceptors

The retina's photoreceptor cells adjust their sensitivity to allow photons to be transduced over a wide range of light intensities. One mechanism thought to participate in sensitivity adjustments is Ca(2+) regulation of guanylate cyclase (GC) by guanylate cyclase-activating proteins (GCAPs). We evaluated the contribution of GCAPs to sensitivity regulation in rods by disrupting their expression in transgenic mice. The GC activity from GCAPs-/- retinas showed no Ca(2+) dependence, indicating that Ca(2+) regulation of GCs had indeed been abolished. Flash responses from dark-adapted GCAPs-/- rods were larger and slower than responses from wild-type rods. In addition, the incremental flash sensitivity of GCAPs-/- rods failed to be maintained at wild-type levels in bright steady light. GCAP2 expressed in GCAPs-/- rods restored maximal light-induced GC activity but did not restore normal flash response kinetics. We conclude that GCAPs strongly regulate GC activity in mouse rods, decreasing the flash sensitivity in darkness and increasing the incremental flash sensitivity in bright steady light, thereby extending the rod's operating range.     

Topotecan, a topoisomerase I inhibitor, is active in the treatment of myelodysplastic syndrome and chronic myelomonocytic leukemia

The aim of this study was to evaluate the activity of topotecan in patients with myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML). Forty-seven patients with a diagnosis of MDS (n = 22) or CMML (n = 25) were treated. The median age was 66 years. Chromosomal abnormalities were present in 70% and thrombocytopenia less than 50 x 10(3)/microL in 51%. Evaluation of outcome and of differences among subgroups was performed according to standard methods; the criteria for response were those used for acute leukemia. Topotecan was administered as 2 mg/ m2 by continuous infusion over 24 hours daily for 5 days (10 mg/m2 per course) every 3 to 4 weeks until remission, then once every month for a maximum of 12 courses. Thirteen patients (28%) achieved a complete response (CR) and six (13%) had hematologic improvement. A CR was achieved in six of 22 patients with MDS (27%) and in seven of 25 with CMML (28%). All eight patients who presented with cytogenetic abnormalities (five chromosome 5 or 7 abnormalities) who achieved CR were cytogenetically normal in CR. Characteristics for which there was evidence of association with a higher response rate were lack of prior chemotherapy, less than 10% marrow monocytes, and absence of RAS oncogene mutations. In contrast, CR rates were similar in patients with or without abnormal karyotypes. Mucositis occurred in 64% of patients (severe in 19%) and diarrhea in 32% (severe in 13%). Febrile episodes occurred in 85% of patients and documented infections in 47%. With a median follow-up duration of 8 months, the 12-month survival rate was 38%, median survival time 10.5 months, and median remission duration 7.5 months. We conclude that topotecan has significant activity in MDS and CMML, with acceptable side effects. Future studies will investigate topotecan combined with topoisomerase II reactive agents, cytarabine, or hypomethylating agents (azacytidine and decitabine).