Effect of Empagliflozin on Sphingolipid Catabolism in Diabetic and Hypertensive Rats

The profile of sphingomyelin and its metabolites shows changes in the plasma, organs, and tissues of patients with cardiovascular, renal, and metabolic diseases. The objective of this study was to investigate the effect of empagliflozin on the levels of sphingomyelin and its metabolites, as well as on the activity of acid and neutral sphingomyelinase (aSMase and nSMase) and neutral ceramidase (nCDase) in the plasma, kidney, heart, and liver of streptozotocin-induced diabetic and Angiotensin II (Ang II)-induced hypertension rats. Empagliflozin treatment decreased hyperglycemia in diabetic rats whereas blood pressure remained elevated in hypertensive rats. In diabetic rats, empagliflozin treatment decreased sphingomyelin in the plasma and liver, ceramide in the heart, sphingosine-1-phosphate (S1P) in the kidney, and nCDase activity in the plasma, heart, and liver. In hypertensive rats, empagliflozin treatment decreased sphingomyelin in the plasma, kidney, and liver; S1P in the plasma and kidney; aSMase in the heart, and nCDase activity in the plasma, kidney, and heart. Our results suggest that empagliflozin downregulates the interaction of the de novo pathway and the catabolic pathway of sphingolipid metabolism in the diabetes, whereas in Ang II-dependent hypertension, it only downregulates the sphingolipid catabolic pathway.     

Solitary intraosseous infantile myofibroma of the orbital roof

BACKGROUND: There are several rare tumors that can cause proptosis in an infant, including infantile myofibroma. METHODS: A 3-month-old infant developed a painless, bone-destructive superomedial orbital mass, raising concern for orbital malignant neoplasms. Computed tomography disclosed a bone-destructive mass of the sphenoid wing. On magnetic resonance imaging, the intraosseous mass was well-circumscribed, surrounded by cortical bone, and showed prominent enhancement. RESULTS: Superomedial orbitotomy and biopsy revealed a lesion composed of spindled to stellate cells, without mitotic activity, set in a fibromyxoid stroma. Immunohistochemical stains were positive for vimentin and actin. Ultrastructurally, there were actinlike thin filaments, mitochondria, and rough endoplasmic reticulum confirming a myofibroblastic proliferation and supporting the diagnosis of congenital infantile myofibroma. CONCLUSION: Infantile myofibroma is a benign tumor that occurs rarely in the ocular region but can cause prominent bone destruction, misleading the clinician to suspect a malignant neoplasm.     

Phase I control chart based on a kernel estimator of the quantile function

To measure the statistical performance of a control chart in Phase I applications, the in‐control average run length (ARL) is the most frequently used parameter. In typical start up situations, control limits must be computed without knowledge of the underlying distribution of the quality characteristic. Assumptions of an underlying normal distribution can increase the probability of false alarms when the underlying distribution is non‐normal, which can lead to unnecessary process adjustments. In this paper, a control chart based on a kernel estimator of the quantile function is proposed. Monte Carlo simulation was used to evaluate the in‐control ARL performance of this chart relative to that of the Shewhart individuals control chart. The results indicate that the proposed chart is more robust to deviations in the assumed underlying distribution (with respect to the in‐control ARL) and results in an alternative method of designing control charts for individual units. Copyright © 2011 John Wiley & Sons, Ltd.     

Artificial neural networks in neutron dosimetry

An artificial neural network (ANN) has been designed to obtain neutron doses using only the count rates of a Bonner spheres spectrometer (BSS). Ambient, personal and effective neutron doses were included. One hundred and eighty-one neutron spectra were utilised to calculate the Bonner count rates and the neutron doses. The spectra were transformed from lethargy to energy distribution and were re-binned to 31 energy groups using the MCNP 4C code. Re-binned spectra, UTA4 response matrix and fluence-to-dose coefficients were used to calculate the count rates in the BSS and the doses. Count rates were used as input and the respective doses were used as output during neural network training. Training and testing were carried out in the MATLAB environment. The impact of uncertainties in BSS count rates upon the dose quantities calculated with the ANN was investigated by modifying by +/-5% the BSS count rates used in the training set. The use of ANNs in neutron dosimetry is an alternative procedure that overcomes the drawbacks associated with this ill-conditioned problem.     

Flame retardant epoxy resins based on diglycidyl ether of isobutyl bis(hydroxypropyl)phosphine oxide

Phosphorous‐containing epoxy resins were prepared from diglycidyl ether of isobutyl bis(hydroxypropyl)phosphine oxide (IHPOGly) and diglycidyl ether of bisphenol A (DGEBA) by crosslinking with 2,4‐diaminotoluene. Several IHPOGly/DGEBA molar ratios were used to obtain materials with different phosphorous content. Thermal, dynamomechanical, and flame retardant properties were evaluated and related with the phosphorous content. The weight loss rate of phosphorous‐containing resins is lower than that of the phosphorous‐free resin for the thermoxidative degradation. Char yields under nitrogen do not show significant differences among the phosphorous‐containing resins and the phosphorous‐free resin, while under air char yields increase with the phosphorous content. The presence of phosphorous increases the limiting oxygen index (LOI) values even when the phosphorous content is low, and no significant differences with the phosphorous content are observed. V‐0 materials were obtained when the resins were tested for ignition resistance with the UL‐94 test. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 99: 1367–1373, 2006     

Antimicrobial resistance of Listeria monocytogenes isolated from various cabbage farms and packing sheds in Texas

Twenty-one isolates of Listeria monocytogenes from cabbage, environmental, and water samples were evaluated for antimicrobial resistance by the disk diffusion method. Ninety-five percent (20 of 21) of the isolates tested were resistant to two or more antimicrobial agents. This finding is significant, since multiresistant strains of Listeria spp. are not commonly found in nature. Eighty-five percent (17 of 20) of the multiresistant strains were resistant to penicillin, and the remaining multiresistant isolates were somewhat sensitive to penicillin. A multiresistant strain showing intermediate sensitivity to penicillin was resistant to gentamicin. One isolate was susceptible to all antimicrobial agents except penicillin. Penicillin- and gentamicin-resistant L. monocytogenes have not previously been reported from human, food, or environmental samples. This study provides evidence of the emergence of multiresistant L. monocytogenes strains, pointing to an increase in the potential threat to human health posed by this pathogen.     

Electroneutral Na-coupled cotransporter expression in the kidney during variations of NaCl and water metabolism

The antiproteinuric effect of angiotensin converting enzyme (ACE) inhibition in insulin-dependent diabetes mellitus (IDDM) patients with diabetic nephropathy varies considerably. Therefore, we tested the potential role of an insertion (I)/deletion (D) polymorphism of the ACE gene on this early antiproteinuric responsiveness in an observational follow-up study. Sixty (II, N = 13; ID, N = 26 and DD, N = 21) young hypertensive IDDM patients suffering from diabetic nephropathy were investigated during three months before and for the initial six month period during ACE inhibition [captopril 44 (SD 22) mg/24 hr, no differences in drug dose between groups]. Blood pressure (MABP) and albuminuria (ELISA) were measured three (1 to 6) times before and three (1 to 13) times during ACE inhibition. At baseline the groups (II/ID/DD) had comparable (1) mean arterial blood pressure (MABP mm Hg) of 113 +/- 10/108 +/- 9/114 +/- 8, (2) albuminuria (geometric mean with 95% CI) 1394 (747 to 2608)/1176 (844 to 1797) and 1261 (827 to 2017) mg/24 hr, and (3) serum creatinine (geometric mean with 95% CI), 80 (68 to 93)/85 (76 to 97)/103 (85 to 119) mumol/liter, respectively. Angiotensin converting enzyme inhibition induced a significant reduction in MABP, albuminuria and kidney function in all three groups (II/ID/DD; P < 0.05): (1) MABP (mean +/- SD) 12 +/- 7/5 +/- 7/8 +/- 9 mm Hg (ANOVA, P = 0.02); (2) albuminuria [mean (95% CI)] 61 (34 to 77)/22 (3 to 37)/31 (13 to 46) %, (ANOVA, P < 0.01); and (3) increasing serum creatinine [mean (95% CI)] 8 (4 to 12)/9 (3 to 16)/8 (0 to 16) % (ANOVA, NS), respectively. Adjusting for differences in reduction in MABP did not change the association between decrease in albuminuria and ACE/ID genotypes (P < 0.01). A multiple linear regression analysis revealed that the ACE/ID polymorphism, albuminuria and MABP at baseline independently influenced the decline in albuminuria after initiation of ACE inhibition (R2 = 0.21, P < 0.01). A significant association between changes in MABP and albuminuria was demonstrated (R2 = 0.16, P < 0.01). Our data show that hypertensive albuminuric IDDM patients with the II genotype are particularly susceptible to commonly advocated renoprotective treatment.     

Binary ionic porphyrin nanosheets: electronic and light-harvesting properties regulated by crystal structure

Crystalline solids self-assembled from anionic and cationic porphyrins provide a new class of multifunctional optoelectronic micro- and nanomaterials. A 1?:?1 combination of zinc(II) tetra(4-sulfonatophenyl)porphyrin (ZnTPPS) and tin(IV) tetra(N-methyl-4-pyridiniumyl)porphyrin (SnTNMePyP) gives porphyrin nanosheets with high aspect ratios and varying thickness. The room temperature preparation of the nanosheets has provided the first X-ray crystal structure of a cooperative binary ionic (CBI) solid. The unit cell contains one and one-half molecules of aquo-ZnTPPS(4-) (an electron donor) and three half molecules of dihydroxy-SnTNMePyP(4+) (an electron acceptor). Charge balance in the solid is reached without any non-porphyrinic ions, as previously determined for other CBI nanomaterials by non-crystallographic means. The crystal structure reveals a complicated molecular arrangement with slipped π-π stacking only occurring in isolated dimers of one of the symmetrically unique zinc porphyrins. Consistent with the crystal structure, UV-visible J-aggregate bands indicative of exciton delocalization and extended π-π stacking are not observed. XRD measurements show that the structure of the Zn/Sn nanosheets is distinct from that of Zn/Sn four-leaf clover-like CBI solids reported previously. In contrast with the Zn/Sn clovers that do exhibit J-aggregate bands and are photoconductive, the nanosheets are not photoconductive. Even so, the nanosheets act as light-harvesting structures in an artificial photosynthesis system capable of reducing water to hydrogen but not as efficiently as the Zn/Sn clovers.