Sphingolipids and the Orchestration of Endothelium-Derived Vasoactive Factors: When Endothelial Function Demands Greasing

Spijkers, Leon J.A.,Alewijnse, Astrid E.,Peters, Stephan L.M. Korean Society for Molecular and Cellular Biology 2010 Molecules and cells Vol.29 No.2

Vasomotor tone is regulated by a complex interplay of a variety of extrinsic neurohumoral and intrinsic factors. It is the endothelium that has a major influence on smooth muscle cell tone via the release of intrinsic vasoactive factors and is therefore an important regulator of vasomotor tone. Sphingolipids are an emerging class of lipid mediators with important physiological properties. In the last two decades it has not only become increasingly clear that sphingolipid signaling plays a pivotal role in immune function, but also its role in the vascular system is now becoming more recognized. In this mini-review we will highlight the possible cross-talk between sphingolipids and intrinsic vasoactive factors released by the endothelium. Via this cross-talk sphingolipids can orchestrate vasomotor tone and may therefore also be involved in the pathophysiology of disease states associated with endothelial dysfunction.

Perinatal/Postnatal Study of D-003, a Mixture of Long-Chain Fatty Acids, in Rats

M.D. Rodriguez,J.E. Gonzalez,E.F. Leon,A. Gutierrez,G. Marrero,R. Gamez,H Garcia,,E Goicochea,Y. Rodriguez,A. Gomez 한국식품영양과학회 2006 Journal of medicinal food Vol.9 No.2

D-003 is a mixture of long-chain fatty acids isolated and purified from sugar cane wax with cholesterol-low-ering and antiplatelet effects. In order to further characterize the developmental toxicity during the treatment period from lategestation up to weaning of the offspring, pregnant females received 0 (control), 500, and 1,000 mg/kg/day D-003 daily byoral gavage beginning at day 15 of pregnancy and through gestation until day 21 postpartum. Maternal clinical signs, bodyweight, and food intake were measured at regular intervals during gestation and lactation. Live pups were weighed, sexed,and examined for developmental signs. One female and male of each litter were randomly selected to evaluate the reproduc-tive potential. There were no spontaneous or dose-related maternal deaths during the course of this study. The general healthand behavioral condition of offspring was good in all groups. No significant differences among groups were found in com-parisons of litter size, survival through the weaning period, sex ratio, and male and female weights. This peri- and postnatalstudy conducted with D-003 in rats indicated that treatment of the dam during late gestation and lactation did not show ad-versely effects on reproductive performance or fetal development over two generations.

Improvement of HDL- and LDL-Cholesterol Levels in Diabetic Subjects by Feeding Bread Containing Chitosan

I.D. Bianco,S.F. Ausar,M. Morcillo,A.E. Leon,P.D. Ribotta,R. Masih,M. Vilaro Mainero,J.L. Amigone,G. Rubin,C. Lescano,L.F. Castagna,D.M. BeltramoG. Diaz 한국식품영양과학회 2003 Journal of medicinal food Vol.6 No.4

In this work we evaluated the efficacy and safety of a bread formulation containing chitosan in dyslipidemictype 2 diabetic subjects. For this purpose a total of 18 patients were allowed to incorporate to their habitual diets 120 g/dayof bread containg 2% (wt/wt) chitosan (chitosan group, n 5 9) or standard bread (control group, n 5 9). Before the studyand after 12 weeks on the modified diet, the following parameters were evaluated: body weight, plasma cholesterol, high-den-sity lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triglyceride, and hemoglobin A 1c(HbA1c). Com-pared with the control group, the patients receiving chitosan-containg bread decreased their mean levels of LDL-cholesteroland significantly increased their mean levels of HDL-cholesterol at the end of the study. There were no significant differencesin the body weight, serum triglyceride, and HbA 1c. These results suggest that chitosan incorporated into bread formulationscould improve the lipoprotein balance similar to typical biliary salts trappers, increasing the HDL- and lowering the LDL-cholesterol, without changing the triglyceride levels. These results warrant further studies over a longer period of time to eval-uate if a persistent improvement in levels of lipoproteins can be attained with this strategy.

Patterns of Esophageal Cancer in the National Cancer Institute at the University of Gezira, in Gezira State, Sudan, in 1999-2012

Gasmelseed, Nagla,Abudris, Daffalla,Elhaj, Ahmed,Eltayeb, Elgaylani A,Elmadani, Ahmed,Elhassan, Moawia M,Mohammed, Khadiga,Elgaili, Elgaili M,Elbalal, Moawia,Schuz, Joachim,Leon, Maria E Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.15

Background: Esophageal cancer (EC) is among the most common malignancies in Eastern Africa, but the occurrence of EC in Sudan has rarely been described in the scientific literature. This paper reports the results of a consecutive case series of all EC patients who visited one of the two public cancer treatment centers in the country in 1999-2012, providing a first description of this disease in a treatment center located in central Sudan. Materials and Methods: Clinical and demographic data for all EC patients who visited the Department of Oncology of the National Cancer Institute at the University of Gezira (NCI-UG) from 1999 to the end of 2012 were abstracted and tabulated by sex, tumor type and other characteristics. Results: A total of 448 EC patients visited NCI-UG in 1999-2012, and the annual number of EC cases increased steadily from 1999. Squamous cell carcinoma (SCC) was the predominant EC tumor type (90%), and adenocarcinoma (ADC) was reported in 9.4% of the EC cases. The overall male-to-female ratio for EC was 1:1.8, but the ratio was tumor type-dependent, being 1:2 for SCC and 2:1 for ADC. Only 20% of EC patients reported having ever used tobacco and/or alcohol, and the vast majority of these patients were male. At the time of EC diagnosis, 47.3% of the patients resided in Gezira State. Some EC patients from Gezira State seek out-of-state treatment in the national capital of Khartoum instead of visiting NCI-UG. Conclusions: The annual number of EC patients visiting NCI-UG has increased in recent years, approximately half of these patients being from Gezira State. Although this consecutive series of EC patients who visited NCI-UG was complete, it did not capture all EC patients from the state. A populationbased cancer registry would provide more complete data required to better understand EC patterns and risk factors.

Postharvest Behavior of Fresh-cut Limes (Citrus latifoia T.) under Two Different Cutting Procedures

Fernando Rivera-Cabrera,Fernando Diaz de Leon,Clara Pelayo-Zaldivar,Laura J. Perez-Flores,Susan E. Ebeler,Adel A. Kader 한국원예학회 2006 한국원예학회 기타간행물 Vol.- No.-

Tuberculosis and other opportunistic infections in tofacitinib-treated patients with rheumatoid arthritis

Winthrop, K L,Park, S-H,Gul, A,Cardiel, M H,Gomez-Reino, J J,Tanaka, Y,Kwok, K,Lukic, T,Mortensen, E,Ponce de Leon, D,Riese, R,Valdez, H BMJ Publishing Group 2016 Annals of the Rheumatic Diseases Vol.75 No.6

<P><B>Objectives</B></P><P>To evaluate the risk of opportunistic infections (OIs) in patients with rheumatoid arthritis (RA) treated with tofacitinib.</P><P><B>Methods</B></P><P>Phase II, III and long-term extension clinical trial data (April 2013 data-cut) from the tofacitinib RA programme were reviewed. OIs defined a priori included mycobacterial and fungal infections, multidermatomal herpes zoster and other viral infections associated with immunosuppression. For OIs, we calculated crude incidence rates (IRs; per 100 patient-years (95% CI)); for tuberculosis (TB) specifically, we calculated rates stratified by patient enrolment region according to background TB IR (per 100 patient-years): low (≤0.01), medium (>0.01 to ≤0.05) and high (>0.05).</P><P><B>Results</B></P><P>We identified 60 OIs among 5671 subjects; all occurred among tofacitinib-treated patients. TB (crude IR 0.21, 95% CI of (0.14 to 0.30)) was the most common OI (n=26); median time between drug start and diagnosis was 64 weeks (range 15–161 weeks). Twenty-one cases (81%) occurred in countries with high background TB IR, and the rate varied with regional background TB IR: low 0.02 (0.003 to 0.15), medium 0.08 (0.03 to 0.21) and high 0.75 (0.49 to 1.15). In Phase III studies, 263 patients diagnosed with latent TB infection were treated with isoniazid and tofacitinib concurrently; none developed TB. For OIs other than TB, 34 events were reported (crude IR 0.25 (95% CI 0.18 to 0.36)).</P><P><B>Conclusions</B></P><P>Within the global tofacitinib RA development programme, TB was the most common OI reported but was rare in regions of low and medium TB incidence. Patients who screen positive for latent TB can be treated with isoniazid during tofacitinib therapy.</P>

Corticospinal excitability in the non-dominant hand is affected by BDNF genotype

Chang, W. H.,Hwang, J. M.,Uhm, K. E.,Pascual-Leone, A.,Kim, Y. H. Springer 2017 NEUROLOGICAL SCIENCES Vol.38 No.2

<P>The objective of this study was to assess the functional state of corticospinal projections in the non-dominant hand according to brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms. We investigated this in 34 healthy right-handed individuals (12 men, mean age 27.4 +/- 3.4 years) who underwent two experimental sessions consisting of corticospinal excitability measurements with single-pulse transcranial magnetic stimulation (TMS) and hand motor function assessments with a sequential finger motor task of the non-dominant hand. Experimental sessions were separated by periods of at least 2 days to avoid carryover effects. Data were analyzed according to BDNF polymorphism (Val/Val vs. Val/Met vs. Met/Met group). Ten (29.4%), seventeen (50.0%), and seven (20.6%) participants were allocated to the Val/Val, Val/Met, and Met/Met groups, respectively. Motor thresholds to TMS did not differ among groups, but the amplitude of the motor-evoked potentials in the non-dominant hand induced by suprathreshold (120% of MT) TMS was significantly lower in the Met/Met group than in the other two groups (p < 0.05). Movement accuracy and reaction time in the sequential finger motor task showed no significant differences among groups. These results indicate that Met/Met BDNF homozygote status affects corticospinal excitability, and should be controlled for in studies of motor system function using brain stimulation. Our findings may have clinical implications regarding further investigation of the impact of BDNF genotype on the human motor system.</P>

Bone morphogenetic protein 7 (BMP7) gene polymorphisms are associated with inverse relationships between vascular calcification and BMD: the Diabetes Heart Study.

Freedman, Barry I,Bowden, Donald W,Ziegler, Julie T,Langefeld, Carl D,Lehtinen, Allison B,Rudock, Megan E,Lenchik, Leon,Hruska, Keith A,Register, Thomas C,Carr, J Jeffrey Mary Ann Liebert, Inc 2009 Journal of bone and mineral research Vol.24 No.10

<P>Inverse relationships have been observed between BMD and vascular calcification (VC), suggesting an underlying metabolic pathway linking these processes. Bone morphogenetic proteins (BMPs) are potential candidate genes that may mediate this relationship. Four single nucleotide polymorphisms (SNPs) in the BMP2 gene, 2 SNPs in BMP4, and 16 SNPs in BMP7 were tested for association with measures of VC using CT (coronary and carotid arteries, abdominal aorta), and BMD was measured using DXA (lumbar spine, hip, and distal radius) and quantitative CT (QCT; thoracic and lumbar spine) in 920 European Americans from 374 Diabetes Heart Study families: 762 with type 2 diabetes. Variance components quantitative trait locus association analysis was computed using SOLAR software, and a bivariate principal component analysis (PCA) assessed for genetic relationships between BMD and VC. Association was observed between several measures of BMD and BMP7 rs17404303 (thoracic spine QCT p = 0.03; lumbar spine QCT p = 0.02; hip DXA p = 0.06, dominant models). In addition, 6 of 16 BMP7 SNPs showed significant and opposing effects on the bivariate PCA for VC and BMD (two-sided exact test, p = 0.0143). Polymorphisms in BMP7 are associated with inverse relationships between bone mineralization and VC in the coronary, carotid, and abdominal aorta in a diabetes-enriched cohort of European Americans.</P>