Blood cyclosporine level soon after kidney transplantation is a major determinant of rejection: insights from the Mycophenolate Steroid-Sparing Trial

Target organs express antigens directly recognized by antigen-specific T cells, thereby precipitating rejection. When early T-cell activation is inhibited, there is a low risk of rejection. We sought to determine the predictive values of serial posttransplant blood cyclosporine trough (C(0)) concentrations to minimize the risk for a first rejection episode compared with 2-hour postdose (C(2)) drug concentrations. The final aim of the study was to identify a concentration range for the best predictive pharmacokinetic parameter that should be targeted to reduce the risk of rejection. This possibility was explored in 334 de novo kidney transplant recipients who participated in the prospective, multicenter Mycophenolate Steroid-Sparing Trial. Among measurements performed during the first 6 months postsurgery, cyclosporine C(0) levels measured early after transplantation were the strongest predictor of acute graft rejection. Levels within 300 to 440 ng/mL were associated with the lowest risk of rejection, while patients with levels lower than 300 ng/mL showed a more than double risk. Cyclosporine trough values predicted allograft rejection with an accuracy of 74%, while C(2) levels had no predictive value. These findings underline the need to target cyclosporine therapy early posttransplant to modulate T-cell activation.     

Effect of thyroid hormones and IGL in vivo on protein synthesis in the mitochondria of thyroidectomized animals

The effect of tri-iodothyronine (T₃) and IGL on the intensity of incorporation of L-[¹⁴C]tyrosine and on the rate of protein synthesis in the liver mitochondria of thyroidectomized rats and on the radioactivity of the amino-acid pool in the liver was investigated. The intensity of incorporation of L-[¹⁴C]tyrosine into proteins in the liver mitochondria of thyroidectomized animals and the rate of protein synthesis in them were found to be only half of their values in animals undergoing mock operations. Administration of T₃ or IGL to thyroidectomized rats restored protein synthesis in the liver mitochondria to normal. IGL had a similar effect to T₃ on all biochemical indices studied. The absence of thyroid hormones circulating in thyroidectomized animals or administration of T₃ or IGL to them did not change the radioactivity of the free tyrosine pool in the liver tissue.Central Biophysical Laboratory, Bulgarian Academy of Sciences, Sofia. (Presented by Academician of the Academy of Medical Sciences of the USSR N. A. Yudaev.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 86, No. 8, pp. 167–170, August, 1978.     

Family planning in big town conditions depending on the birthplace of the parents.

The purpose of this article is to determind what effect if any place of birth has upon family size, both actual and ideal, in the Bulgarian city of Plovdiv. It is a retrospective study of 181 families comprised of 2 cohorts, one with couples married for 5 years, the other with couples married for 10 years. The author found that place of origin, whether rural, other towns, Plovdiv itself, or a combination of any two of those, had no significant effect on desired or ideal family size. 79.1% of the women considered the two-child family ideal. When asked to specify an ideal family size in the light of their personal experience, however, 17.8% preferred a single-child family. 18.6% in the 10-year cohort preferred this size and 16.8% in the 5-year cohort. This evidence that individuals retrospectively modify their ideal family size downwards. Those couples in which both partners came from villages had the highest actual family size (1.62). For the total contingent the average number of children was 0.14, smaller than the planned one.     

Oxidative stress in term small for gestational age neonates born to undernourished mothers: a case control study

Background  

The objective of this study was to assess the status of oxidative stress in term small for gestational age (SGA) newborn infants born to undernourished mothers by estimating levels of erythrocyte superoxide dismutase (SOD), catalase, reduced glutathione, and serum malondialdehyde (MDA) in cord blood and comparing them to healthy appropriate for gestational age (AGA) controls. This was done in a case control design at a tertiary level teaching hospital.     

Association of CyclinD1 copy number changes with histological type in ovarian tumors

Literature data on the occurrence of CCND1 alterations in ovarian tumors are insufficient. The objective of this study was to assess the incidence of CCND1 copy number changes in a large number of ovarian tumors and its relation to the tumor phenotype: degree of malignancy, histological type, tumor stage, and grade. Fluorescence in situ hybridization (FISH) for analysis of CCND1 copy number changes was applied on a collection of 1 006 ovarian tumors--468 malignant, 48 with low malignant potency, and 490 benign tumors--arranged in tissue microarray. CCND1 amplification was found in 8.46% of the malignant cases and in 8.11% of those with low malignant potency. It was not found in benign ovarian tumors. CCND1 amplification was associated with the mucinous type of ovarian cancer (p<0.0001). CCND1 genetic gain was revealed in 9.06% of the malignant tumors, in 2.70% of the tumors with low malignant potency, and in 4.87% of the benign ovarian tumors. CCND1 gains and amplifications were not associated with the tumor grade and stage. Our results suggest that CCND1 gains are early events in ovarian tumorogenesis.     

Association between blood pressure level and the follow up of the guidelines concerning the use of self blood pressure measurement

OBJECTIVES: To evaluate the characteristics of hypertensive subjects who practise self measurement of blood pressure (SMBP) and their conditions of use, and to identify the properties of subjects using SMBP according the usual guidelines. METHODS: In 531 consecutive hypertensive subjects, referred to hypertension specialists, possessing a SMBP a questionnaire evaluating the condition of use of SMBP was given. Subjects following the guidelines about the use of SMBP have been compared to those using SMBP without specific design of supervision. RESULTS: In this population, aged 62 +/- 14 years, with 57% of men and a mean blood pressure of 147 +/- 23/82 +/- 12 mmHg, the SMBP devices have been bought without medical advice in 50% of cases (265/531). In 45% of cases (239/531), SMBP were made at the wrist. SMBP device was used every days in 26% of cases, every weeks in 27% of cases, every month or more in 22% of cases and only in case of uneasiness in 25% of cases. Blood pressure was measured only in the morning in 25% of cases, in the morning and evening in 31%, only the evening in 8% and at any time of the day in 36% of cases. More frequently 2 BP measurements were realized (47%) and in 19% of cases 3 measurements have been performed. In 15% of cases, the measurements were performed on 3 or 4 days consecutively, more frequently (85%) the measurements were realized without specific design ("once in awhile"). The data of SMBP were noted and showed to the doctor in 34% of cases. Only 12% (64/531) of subjects followed the usual guidelines concerning the use of SMBP (2 or 3 measurements, in the morning and the evening, during 3 or 4 consecutive days). Subjects following the guidelines for SMBP use have a higher SBP at the office than those using SMBP without specific design of supervision (155 +/- 25 mmHg vs 146 +/- 22 mmHg; p<0.01). CONCLUSION: Among hypertensives referred to hypertension specialists most of subjects use SMBP device without a specific design of supervision. Subjects with the most severe hypertension are those who have the best formation for SMBP.     

A regulatory role of prolactin, growth hormone, and corticosteroids for human T-cell production of cytokines

The release of the pituitary hormones, prolactin and growth hormone (GH), and of adrenal corticosteroids is subject to a profound regulation by sleep. In addition these hormones are known to be involved in the regulation of the immune response. Here, we examined their role for in vitro production of T-cell cytokines. Specifically, we hypothesized that increased concentrations of prolactin and GH as well as a decrease in cortisol, i.e., hormonal changes characterizing early nocturnal sleep, could be responsible for a shift towards T helper 1 (Th1) cytokines during this time. Whole blood was sampled from 15 healthy humans in the morning after regular sleep and was activated in vitro with ionomycin and two concentrations of phorbol myrestate acetate (PMA, 8 and 25 ng/ml) in the absence or presence of prolactin, prolactin antibody, GH, glucocorticoid receptor (GR) antagonist RU-486, or mineralocorticoid receptor (MR) antagonist spironolactone. Hormones were examined at physiological concentrations. Production of T-cell derived cytokines was measured at the single cell level using multiparametric flow cytometry. Generally, effects were more pronounced after stimulation with 8 rather than 25 ng/ml PMA. The following changes reached significance (p <.05): prolactin (versus prolactin antibody) increased tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) producing CD4+ and CD8+ cells and interleukin-2 (IL-2) producing CD8+ cells. Compared with control, prolactin antibody decreased, whereas GH increased IFN-gamma+CD4+ cells. RU-486 increased TNF-alpha, IFN-gamma, and IL-2 producing CD4+ and CD8+ cells. Surprisingly strong effects were found after MR blocking with spironolactone which increased TNF-alpha, IFN-gamma, and IL-2 producing CD4+ and CD8+ cells. No effects on IL-4+CD4+ cells were observed, while the IFN-gamma/IL-4 ratio shifted towards Th1 after spironolactone and after RU-486 plus GH. Results suggest that enhanced prolactin and GH concentrations as well as low cortisol levels during early nocturnal sleep synergistically act to enhance Th1 cytokine activity.     

Rate of cesarean section and perinatal infant mortality at "Maichin dom"

The aim of this retrospective study is to find the CS rate, which to maintain the perinatal mortality at a lowest possible level in groups of patients with normal and high risk pregnancies. There were 123598 births for a period from 1976 to 2000 years. The CS rate has increased from 4.8% to 24.5% and the PNM has decreased from 27.7@1000 to 11.4@1000. The statistical analysis shows that the for this period the CS rate is one of the factors to decrease the PNM (r = -0.776, p < 0.05). In the group of pregnancies with normal risk the PMN is between 8 and 11@1000 at the CS rate of 15-16% while in the group with high-risk pregnancies the same PNM is achieved with 24-26% CS rate. The antenatal mortality is not influenced by the CS rate and is almost unchanged for 24 years (r = -0.339, p > 0.05).     

The probiotic Lactobacillus acidophilus--an alternative treatment of bacterial vaginosis

The probiotics or biotherapeutical agents are microorganisms that have an antagonistic activity regarding pathogens in vivo. Therapeutic application of these microorganisms is mostly in cases of infections of non-sterile mucous surfaces--vagina and large intestines. With the help of the probiotic L. acidophilus bacterial vaginosis can be treated successfully in a natural way. The lack of systemic side effects makes it a drug of choice in the treatment of pregnant women. More studies in this direction and development of new strategies for treatment of bacterial vaginosis in pregnant and non-pregnant women are needed.