The action profile of lispro is not blunted by mixing in the syringe with NPH insulin

OBJECTIVE: To assess the effect of mixing the insulin analog lispro (Humalog) with NPH (Humulin I) before injection on lispro's fast, short action profile. RESEARCH DESIGN AND METHODS: A total of 12 healthy volunteers received subcutaneous abdominal injections of 0.1 U/kg regular insulin and 0.2 U/kg NPH insulin as follows: lispro and NPH injected separately (treatment group A), lispro and NPH mixed in the syringe up to 2 min before single injection (treatment group B), and human regular insulin and NPH mixed and injected as in group B (treatment group C), on separate occasions, in random order. Plasma glucose was maintained for 12 h by intravenous 20% glucose. Pharmacokinetic and pharmacodynamic parameters were compared by analysis of variance for repeated measures. RESULTS: Peak plasma insulin levels (2.6 +/- 0.8 vs. 2.2 +/- 0.6 vs. 1.9 +/- 0.6 ng/ml, P = 0.075), total glucose infused (121.5 +/- 32.8 vs. 135.0 +/- 49.0 vs. 117.3 +/- 39.9 mg.kg-1.min-1, P = 0.53), and maximum glucose infusion rate (GIRmax) (8.3 +/- 0.9 vs. 8.0 +/- 1.7 vs. 7.1 +/- 2.4 mg.kg-1.min-1, P = 0.65) were not significantly different between treatments. The times until peak insulin concentrations were similar in treatment groups A and B, but significantly shorter than in treatment group C (0.9 +/- 0.3 and 1.2 +/- 0.2 vs. 2.0 +/- 0.4 h, respectively, P = 0.042). The times until GIRmax were also not different (113.9 +/- 41 and 122.0 +/- 45 vs. 209.0 +/- 51.3 min, respectively, P = 0.002). The glucose infusion rate (GIR) then fell to 50% GIRmax more quickly in treatment groups A and B than in treatment group C (239.9 +/- 40.5 vs. 292.4 +/- 133.3 vs. 399.5 +/- 78.3, respectively, P = 0.005). CONCLUSIONS: The action profile of lispro is not attenuated by mixing lispro with NPH in the syringe immediately before injection. The advantages are available to those individuals who need to combine types of insulin before injection to achieve optimal diabetes control.     

Partial splenic embolization for treatment of disseminated intravascular coagulation in lymphangiomatosis

A 1-year-old boy presented with pericardial effusion, pulmonary infiltrates, and disseminated intravascular coagulation; lung biopsy indicated pulmonary lymphangiomatosis. He did not respond to medical therapy and was a poor surgical candidate; therefore, he underwent partial splenic embolization. The procedure resulted in a complete disappearance of the DIC and marked improvement in his cardiorespiratory status. He continues to thrive and is transfusion-independent 2 years after the procedure.     

High-resolution analysis of T-cell receptor beta-chain repertoires using DNA heteroduplex tracking: generally stable, clonal CD8+ expansions in all healthy young adults

Harringtonine (HT), an anticancer drug with high chemotherapeutic efficiency to human chronic granulocytic/myelomonocytic leukemia, has been reported to rapidly induce apoptosis in HL-60 cells in a wide scope/range of dosage by investigators from our lab and others. In the present studies, by using video enhancement contrast (VEC) microscopy, we dynamically analyzed changes in intracellular calcium distribution in a single HL-60 cell over the period from the initiation of apoptosis to the obvious appearance of chromatin condensation. The results from this paper demonstrated the striking distinction of intracellular calcium distribution at different time points after treatment with HT. Before treatment in normal HL-60 cells the highest [Ca2+]i accumulation was observed in the peri-nuclear area and the lowest was observed in the nucleus; after treatment with 1 microg/ml HT for 30 min intracellular calcium diffused all over the cell compartments, while intranuclear calcium increased comparatively and significantly. The phenomenon of intranuclear calcium accumulation was further confirmed by using laser scanning confocal microscopy (LSCM). In addition, co-localization of the highest calcium region with condensed chromatin in apoptotic HL-60 cells was also observed by LSCM. Our results suggest that two sequential alterations of intracellular calcium distribution occurred in apoptotic HL-60 cells induced by HT, i.e. (a) accumulation of calcium in the nucleus and (b) regionalization in a specific nuclear region.     

Epoxidation of olefins by cytochrome P450: evidence from site-specific mutagenesis for hydroperoxo-iron as an electrophilic oxidant

P450 cytochromes (P450) catalyze many types of oxidative reactions, including the conversion of olefinic substrates to epoxides by oxygen insertion. In some instances epoxidation leads to the formation of products of physiological importance from naturally occurring substrates, such as arachidonic acid, and to the toxicity, carcinogenicity, or teratogenicity of foreign compounds, including drugs. In the present mechanistic study, the rates of oxidation of model olefins were determined with N-terminal-truncated P450s 2B4 and 2E1 and their respective mutants in which the threonine believed to facilitate proton delivery to the active site was replaced by alanine. Styrene epoxidation, cyclohexene epoxidation and hydroxylation to give 1-cyclohexene-3-ol, and cis- or trans-butene epoxidation (without isomerization) and hydroxylation to give 2-butene-1-ol were all significantly decreased by the 2B4 T302A mutation. Reduced proton delivery in this mutant is believed to interfere with the activation of dioxygen to the oxenoid species, as shown earlier by decreased hydroxylation of several substrates and enhanced aldehyde deformylation via a presumed peroxo intermediate. Of particular interest, however, the T303A mutation of P450 2E1 resulted in enhanced epoxidation of all of the model olefins along with decreased allylic hydroxylation of cyclohexene and butene. These results and a comparison of the ratios of the rates of epoxidation and hydroxylation support the concept that two different species with electrophilic properties, hydroperoxo-iron (FeO2H)3+ and oxenoid-iron (FeO)3+, can effect olefin epoxidation. The ability of cytochrome P450 to use several different active oxidants generated from molecular oxygen may help account for the broad reaction specificity and variety of products formed by this versatile catalyst.     

The dorsal filament of the weakly electric Apteronotidae (Gymnotiformes; Teleostei) is specialized for electroreception

The Apteronotidae, a family of weakly electric fish from South America (Gymnotiformes), possess a structure called the dorsal filament with an unknown function and evolutionary origin. This study compared the gross anatomy of the dorsal filament of 13 species of apteronotids and used light microscopy to examine the filaments of Adontosternarchus balaenops, Apteronotus albifrons, and Apteronotus leptorhynchus. The dorsal filament is an unscaled, thin, tapering structure attached to a mid-dorsal groove on the posterior half of the fish's back. The interior of the filament is a gelatinous mucopolysaccharide matrix (connective tissue) containing blood vessels and a bilateral nerve in which nearly all the afferents are large (8-10 mu m) and heavily myelinated. The location of the anterior origin of the filament varies from 0.48 to 0.66 of the body length, posterior to the snout, in 13 species. The filament is covered with hundreds of large-type tuberous electroreceptors and some ampullary receptors, at approximately the same density and ratio as those on the nearby back. The morphology of the large-type tuberous receptors and their afferents suggests that they are phase-coding T-units. A double layer of epithelial cells separates the ventral side of the filament from the groove in the trunk of the fish, except at the anterior origin where the interior of the filament is continuous with the body. This specialized double epithelium could provide a high resistance barrier to electrical current. This study was unable to distinguish between two hypotheses: that the dorsal filament is a modified adipose fin (as suggested previously), retained only in this family of Gymnotiformes; or that it is a uniquely derived character of the Apteronotidae.     

Evaluating DSM: can an engineer count on it? A short note papersummarizing a panel session at the July 1992 summer power meeting

There is an increasing interest in demand-side management (DSM) by utilities and regulators throughout the USA. With this interest, there is an increasing need for DSM evaluation. Regulators expect utility engineers to use least cost planning and integrated resource planning approaches to adjust their generation capacity plans to reflect DSM. Increasingly, utilities are considering DSM to affect their T&D capacity plans. However, major utility DSM programs are less than a decade old. This leaves many utility engineers uneasy. How do they know that DSM will be there when they really need it? To verify and improve the contribution of DSM programs, utility analysts have developed a set of methodologies and procedures for evaluating DSM. The purpose of this panel session was to review these state of the art evaluations and the lessons learned from them so far. The authors explore the differences inherent in evaluating DSM at the T&D level versus the generation level, and review DSM's persistence and reliability in the residential, commercial, and industrial sectors     

Subcutaneous fat necrosis following traumatic pancreatitis

Agranulocytosis and septicaemia developing in a patient with rheumatoid arthritis after 3 years' intermittent treatment with diclofenac, cimetidine and flucloxacillin for staphylococcal osteomyelitis is described. Treatment with recombinant granulocyte-colony-stimulating factor and high-dose methylprednisolone had no effect on the neutropenia which resolved on stopping all drug therapy. Relapse of agranulocytosis followed reintroduction of flucloxacillin and cimetidine 3 months later.     

Lateralized changes in tympanic membrane temperature in relation to different cognitive tasks in chimpanzees (Pan troglodytes).

Lateralized changes in tympanic membrane (TM) temperature were assessed in chimpanzees. Subjects were engaged in 1 of 3 different cognitive tasks, including matching-to-sample, visual-spatial discrimination, and a motor task. During execution of each task, TM temperatures were taken from each ear over a 20-min time period. The TM temperatures at each time interval were subtracted from a baseline measure to assess relative change in blood flow. For the matching-to-sample and visual-spatial discrimination tasks, significant lateralized changes in TM temperature were found, with left-ear temperature increasing and right-ear temperature decreasing. No laterality effects were found for the motor or control tasks. These data provide the first evidence of laterality in physiological functioning in chimpanzees and suggest that transient asymmetries in cognitive functions are associated with changes in cerebral blood flow as assessed by TM temperature change. (PsycINFO Database Record (c) 2010 APA, all rights reserved)