Cyclosporin A inhibits PGE2 release from vascular smooth muscle cells

The influence of the fungoid undecapeptide cyclosporin A (CyA) on PGE2 release from cultured rat aortic smooth muscle cells was investigated in this study. We found that CyA time and concentration dependently (ED50:500 ng/ml) inhibited PGE2 release from the cells. CyA attenuated both basal and PGE2 release evoked by angiotensin II (10(-10)-10(-6) M), arginine vasopressin (10(-10)-10(-6) M) and ionomycin (10(-9)-10(-6) M). CyA (1 microgram/ml) did not affect the conversion of exogenous arachidonic acid (1 microM) into PGE2. The inhibitory effect of CyA was neutralized by high concentrations of the calcium ionophore ionomycin (greater than 3 X 10(-6) M). Taken together our results indicate that CyA inhibits both basal and vasoconstrictor evoked PGE2 release from vascular smooth muscle by impairing the availability of free arachidonic acid rather than by inhibiting the conversion of arachidonic acid into PGE2

99mTc-DTPA and 131I-hippuran findings in liver transplant recipients treated with cyclosporin A.

The effects of cyclosporin A (CyA), an immunosuppressive agent that is potentially nephrotoxic, on the kidneys of 9 liver transplant recipients were studied with serial 99mTc-DTPA and 131I-hippuran scans. In addition, renal function was determined by measuring serum creatinine levels during the second postoperative week in the 9 unselected CyA-treated patients and, retrospectively, in a control group of 29 liver transplant recipients who had not been treated with CyA and who were selected because they had survived for at least 3 months postoperatively. The early postoperative creatinine level was significantly greater in the CyA group. Eight of the 9 CyA patients showed imaging abnormalities in all preoperative and postoperative studies. Five of the 8 patients showed a pattern similar to that of acute tubular necrosis (relatively preserved perfusion) in at least one study. Lowering the dosage of CyA permitted the continuation of therapy, and all 9 patients are alive after 8 to 14 months

NEPHROTOXICITY OF CYCLOSPORIN A IN LIVER AND KIDNEY TRANSPLANT PATIENTS

In six of twelve orthotopic liver recipients nephrotoxicity was noted after 13-22 days of treatment with 16·3±2·9 (SEM) mg/kg per day of cyclosporin A (CyA). With a decrease in the daily CyA dose to 9·2±2·3 (SEM) mg/kg kidney function returned to normal. No hepatic rejections occurred on this lowered CyA dose. In 4 out of 66 kidney recipients a switch from a CyA dose of 5·2-10·7 mg/kg daily to azathioprine was done 4-8 months after transplant because of unsatisfactory kidney function, suspected to be due to nephrotoxicity. In three patients, this resulted in an improved graft function. A fourth transplant was lost to an irreversible rejection 13 days later. Thus CyA is nephrotoxic but this toxicity is easily reversed, even after many months of treatment, and the ease with which this complication can be managed suggests that nephrotoxicity should not diminish the high expectations that transplant surgeons have for CyA. © 1981

Cyclosporine measurement by FPIA, PC-RIA, and HPLC following liver transplantation

The factors affecting CyA dosing and kinetics in LT patients are complex, and have been thoroughly investigated and reviewed. Plasma or WB CyA concentration monitoring remains the best method presently available for adjusting CyA dosage in LT patients in a timely manner. The availability of an FPIA assay for CyA has produced rapid drug analysis for transplant patient monitoring, but adds additional factors that must be considered in interpreting CyA concentrations. Liver dysfunction may disproportionately elevate CyA plasma or blood levels when analyzed by FPIA in relation to PC-RIA or HPLC, and adjustment of the therapeutic range or analysis by a more specific assay method may be necessary for dosage adjustment in these patients. The availability of a more specific antibody in an FPIA assay may avert these problems, as would the development of immunologic monitoring techniques that provide a global assessment of immune suppression produced by increasingly complex immunosuppressive regimens in LT patients

A New Era in California Juvenile Justice

Behind the media and political attention focused on California prisons, which are plagued with severe levels of crowding, and a federal court order to reduce the inmate population by over 40,000, lies one of California's best-kept secrets: the state's youth correctional custodial population has declined over 80% in just over the past decade. Just since 2004 the California Youth Authority (CYA) population declined by over 5,000 inmates. The state has already closed five major juvenile facilities and four forestry camps for juvenile offenders.A number of factors have contributed significantly to the drop in the population of the CYA. The most frequently cited is the very negative media publicity in the early 2000s about the conditions inside facilities, the case of Farrell v. Harper in 2003, and realignment legislation passed in 2007 that required that more youthful offenders be managed at the county level. However, the CYA population began declining as early as 1997. The trend towards increased costs for counties to send youth to the CYA, and doubt that the CYA was an appropriate setting for many of the youth being sent there, had already begun in the late 1990s.While no single factor accounts for the drastic change in the CYA population, the research presented here points to multiple forces that came together in the mid- to late-1990s and early 2000s to change public perception, judicial behaviors, probation programs, sentencing policies, and state funding streams.We also find that this population reduction is particularly notable because it did not result in an increase in juvenile crime, as some had erroneously predicted

Diversité botanique dans le sud du parc national de Taï, Côte d’Ivoirean

Botanical diversity of the South of Taï National Park, Côte d’IvoireThe Tai National Park (TNP) is one of the last vestiges of ≪ primary ≫ forest remained in West Africa. The northern part is almost well known but the southern one is not. To mitigate this lack, we conducted a study in the South of the TNP. To achieve the inventory, two methods were used: “walk set up” and the “plot set up”. Nine hundred height plants species were recorded. They belonged to 550 genera and 116 families. The richest families were Rubiaceae, Euphorbiaceae and Caesalpiniaceae. Among all the species, 175 were endemic of West African forests, 11 endemic to Ivorian forests and 61 “sassandrian”. The study showed that for tree species with dbh ≥10 cm Hymenostegia afzelii, Strombosia pustulata,  Diospyros sanza-minika, Funtumia africana, Calpocalyx brevibracteatus and representatives of Caesalpiniaceae, Euphorbiaceae and Ebenaceae families were the richest and had the highest values of IVI and FIV. Endemic, “sassandrian”, rare and threatened species constitute the major characteristic of the TNP and confirm that it includes in the Guinean Forests of West Africa Hotspot

The dimension of a variety

We invent the notion of a {\it dimension of a variety} $V$ as the cardinality of all its proper {\it derived} subvarieties (of the same type). The dimensions of varieties of lattices, varieties of regular bands and other general algebraic structures are determined.Comment: The results of the paper were presented at the workshop AAA71 and CYA21 at B\c{e}dlewo, Poland on February 11, 2006. the paper is submitted to Discussiones Mathematicae Algebra and Stochastc Methods, special issu

Mind the gap: trajectory of cognitive development in young individuals with sickle cell disease: a cross-sectional study

STUDY OBJECTIVES: Compared to typically developing children and young adults (CYA-TD), those living with Sickle Cell Disease (CYA-SCD) experience more cognitive difficulties, particularly with executive function. Few studies have examined the relative importance of silent cerebral infarction (SCI), haemoglobin and arterial oxygen content on age-related cognitive changes using cross-sectional or longitudinal (developmental trajectory) data. This study presents cohort data from a single timepoint to inform studies with multiple timepoints. METHODS: We compared cross-sectional raw and scaled scores as age-related changes in cognition (trajectories) in CYA-SCD and age-and ethnicity-matched CYA-TD. We also compared cross-sectional age-related changes in cognition (trajectories) in CYA-SCD with and without SCI to CYA-TD. General cognitive abilities were assessed using Wechsler Intelligence Scales, including the Verbal Comprehension Index (VCI) and Perceptual Reasoning Index (PRI) underpinning IQ. Executive function was evaluated using the Delis-Kaplan Executive Function System (D-KEFS) Tower subtest and the Behaviour Rating Inventory of Executive Function (BRIEF) questionnaire. SCI were identified from contemporaneous 3 T MRI; participants with overt stroke were excluded. Recent haemoglobin was available and oxygen saturation (SpO2) was measured on the day of the MRI. RESULTS: Data were available for 120 CYA-SCD [62 male; age = 16.78 ± 4.79 years; 42 (35%) with SCI] and 53 CYA-TD (23 male; age = 17.36 ± 5.16). Compared with CYA-TD, CYA-SCD experienced a delayed onset in VCI and slower rate of development for BRIEF Global Executive Composite, Metacognition Index (MI), and Behaviour Regulation Index. The rate of executive function development for the BRIEF MI differed significantly between CYA-TD and CYA-SCD, with those with SCI showing a 26% delay compared with CYA-TD. For CYA-SCD with SCI, arterial oxygen content explained 22% of the variance in VCI and 37% in PRI, while haemoglobin explained 29% of the variance in PRI. CONCLUSION: Age-related cognitive trajectories of CYA-SCD may not be impaired but may progress more slowly. Longitudinal studies are required, using tests unaffected by practice. In addition to initiation of medical treatment, including measures to improve arterial oxygen content, early cognitive intervention, educational support, and delivery of extracurricular activities could support cognitive development for CYA-SCD.Graphical Abstract

Role of S-adenosylmethionine on the hepatobiliary homeostasis of glutathione during cyclosporine A treatment

[EN] The effects of cyclosporine A (CyA) treatment on the hepatic content and biliary output of reduced (GSH) and oxidized (GSSG) glutathione and lipid peroxidation in the liver, and the ability of S-adenosylmethionine (SAMe) to antagonize the CyA-induced alterations were studied in male Wistar rats. To evaluate the efficacy of SAMe, three CyA and SAMe protocols were used: Cotreatment with SAMe plus CyA, pretreatment with SAMe before starting cotreatment, and post-treatment with SAMe after beginning treatment with CyA alone. CyA treatment for one and four weeks depleted liver GSH, decreased the GSH/GSSG ratio and significantly reduced GSH and GSSG biliary concentrations and secretion rates. Additionally, long-term treatment enhanced lipid peroxidation. By contrast, when the rats were treated with CyA plus SAMe using any of the administration protocols, SAMe was seen to be efficient in antagonizing the GSH hepatic depletion, the changes in hepatic GSH/GSSG ratio and the increase induced by CyA in lipid peroxidation. Furthermore, SAMe also abolished the effects of CyA on the biliary secretion rates of GSH and GSSG. The efficacy of SAMe was similar, regardless of the administration protocols used. In conclusion, our results clearly demonstrate that SAMe is good for preventing, antagonizing and reversing the CyA-induced alterations in the hepatobiliary homeostasis of glutathione