Tamar Shkolnik

Effect of oxygen tension on activity of antioxidant enzymes and on renal function of the postischemic reperfused rat kidney.

The aim of the present study was to examine the effect of exposing animals to 100% oxygen instead of room air on renal function and endogenous antioxidant enzymes of the postischemic reperfused rat kidney. Superoxide dismutase (SOD), catalase and glutathione peroxidase (GPX) were determined in the homogenate of the left kidney after 45 min of ischemia, caused by clamping the left renal artery, 10 and 90 min after reperfusion while the animals breathed room air or 100% O2. The right kidney served as a control. The possible influence of trapped blood in the clamped kidney was also investigated by the use of a correction factor based on the Hb concentration in the homogenate. The results indicate that such correction is necessary as the blood adds significant antioxidant activity. The activities of all 3 enzymes after 45 min of ischemia decreased significantly in the left (ischemic) compared to the right (control) kidney, to 64% of the control levels for catalase, 58% for SOD and 49% for GPX. After 10 min of reflow, a further decrease in the activities of catalase (to 49%) and of GPX (to 29%) was found. SOD activity, however, increased to 64%. After 90 min of reperfusion, restoration toward normal levels was noticed (SOD activity increased to 70%, catalase to 76% and GPX to 58%). Breathing 100% O2 resulted in a significant decrease in all enzyme activities (to 38.6% for catalase, 45% for SOD and to 27.4% for GPX). This inactivation can be explained by increased reactive oxygen species (ROS) activity during hyperoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Short-Term Effect of Erythropoietin on T-Cell Mitogenic Proliferation in Chronic Renal Failure Patients

Uremic patients undergoing hemodialysis (HD) are known to be highly susceptible to infections. Recent data indicate that in addition to its well-known stimulating effects on red cell production, erythropoietin (EPO) may also have immunomodulating properties. The aim of this study was to examine the effect of EPO on lectin-induced T-lymphocyte transformation in uremic patients, as part of its effect on the immune response. Sixteen HD patients and 20 age- and sex-matched healthy controls were compared before and after 6 and 20 weeks of EPO treatment. T lymphocytes were analyzed for their mitogenic activity following treatment with phytohemagglutinin (PHA), concanavalin A (CON A) and anti-CD3 by measuring 3H-thymidine incorporation. HD patients showed reduced mitogenic responses to all mitogens tested, compared to healthy controls. During the 6 weeks of EPO administration, a significant increase in T-lymphocyte activity could be demonstrated following exposure to all three mitogens (PHA, from 32 +/- 2 to 45 +/- 8; CON A, from 11 +/- 3 to 25 +/- 9; anti-CD3, from 11 +/- 3 to 22 +/- 5, means +/- SD). This increase was augmented after 5 months of EPO treatment. We conclude therefore that EPO improves in vitro T-cell mitogenic proliferation, even after short periods of treatment.

Histochemical Studies of Progressive p53 Mutations during Colonic Carcinogenesis in Sprague-Dawley Rats Induced byN-Methyl-N-Nitro-Nitrosoguanidine or Azoxymethane

We studied the increasing expression of the p53 tumor suppressor gene in Sprague-Dawley rats, chemically induced to develop colon cancer. p53 expression was evaluated histochemically at various stages of tumor progression (during a period of 40 weeks) that can be followed by colonic hyperproliferation labeled by 3H-thymidine incorporation. We found that high level nuclear expression of p53 protein correlates with progression of malignancy in carcinogen-induced animals, whereas cytoplasmic staining is related to the onset and early development of malignancy.

Red cell filterability in cigarette smokers and its relations to cardiac hypertrophy

The relationship among daily cigarette consumption, washed and non-washed RBC filterability time (FT) as an indicator of erythrocyte deformability and echocardiographic left ventricular mass (LVM) were examined in 25 clinically healthy smokers and in 25 non-smoking controls matched for sex and age. FT of non-washed RBC was significantly higher in smokers than in non-smokers (25.2 +/- 3.6 vs. 16.8 +/- 2.2 min, P < 0.001). A highly significant linear correlation between number of cigarette consumption and FT was found. These differences were not observed when RBC were washed three times with isotonic saline. LVM was significantly greater in smokers (85.5 +/- 13.4 g/m2) than in controls (61.8 +/- 6.7 g/m2, P < 0.001). A linear correlation between daily cigarette consumption and LVM was observed. A positive relationship between LVM and FT of non-washed RBC was also found. These results demonstrated that LVM is significantly elevated in smokers and is linearly correlated with both cigarette consumption and RBC filtratibility. The increased deformability found in smokers may be a determinant to the cardiac hypertrophy. The association of both elevated LVM and rheological impairment may indicate unfavourable prognosis.

Effect of Converting Enzyme Inhibitor Captopril on T Cell Functions in Essential Hypertension

T cell function tests were performed in 6 patients with uncomplicated essential hypertension (EH) before and after treatment with captopril, an angiotensin-converting enzyme inhibitor. Total T and T cell subsets were within normal range and were not affected by the drug. The response of PBL to lectin stimulation was significantly impaired. While the stimulation index (SI) was almost normal when washed PBL were used (32.2 +/- 6.90 with PHA and 20.17 +/- 4.1 with Con A) or after their incubation with serum taken from normal subjects (40.42 +/- 10.9 and 15.53 +/- 3.4, respectively), autologous serum significantly reduced the SI (15.04 +/- 5.9 with PHA, p less than 0.05 and 6.68 +/- 1.45 with Con A, p less than 0.005). While captopril seemed to suppress the SI of washed PBL after 1 week of treatment, it enhanced the SI from 32.21 +/- 6.91 to 55.32 +/- 10.76 for PHA and from 20.17 +/- 4.13 to 30.63 +/- 5.41 for Con A (p less than 0.001). This effect was more obvious when the stimulations were performed with normal serum (from 40.42 +/- 10.9 to 96.47 +/- 17.51 for PTH and from 15.53 +/- 3.43 to 40.02 +/- 8.0 for Con A, (p less than 0.001). These results confirm previous reports indicating that the cellular immune response is impaired in EH. It seems that an inhibitory factor found in the serum of these patients is responsible for this impairment. Our findings may suggest that this factor may be angiotensin II.

PROLIFERATIVE RESPONSE OF T LYMPHOCYTES TO MITOGENIC LECTINS IN ESSENTIAL HYPERTENSION

Several studies in human and experimental models indicate the existence of a partial relationship between essential hypertension (EH) and the immune system. In this study, cellular immune functions were investigated in 13 patients with untreated and uncomplicated essential hypertension (EHP) and in 10 of their offspring (EHO) and compared to 13 age- and sex-matched normotensive controls (NC) and 10 of their offspring (NCO). The total number of T cells and T cell subsets were similar in all groups examined. In the EHP, basal lymphocyte transformation without lectins was significantly lower (1,126 +/- 261 cpm of [3H]-thymidine uptake) than in the NC (3,223 +/- 736, p less than 0.01); the response to both phytohemagglutinin (PHA) and concanavalin A (ConA) revealed reduced [3H]-thymidine uptake as compared with NC (21,890 +/- 5,432 compared to 64,574 +/- 9,723 for PHA and 10,488 +/- 2,621 compared to 37,334 +/- 8,148 for ConA, respectively, p less than 0.01). However, the ability to proliferate as a response to lectins was normal. This was leading to a normal stimulation index in both groups. In the EHO, non-significant decrease in basal transformation and reduced uptake with PHA (49,537 +/- 7,478) versus NCO (69,911 +/- 7,254) and NC (64,574 +/- 9,723) were found. These findings suggest that the proliferative response of T lymphocytes is partially suppressed in EH.

The macrophage migration inhibition (MIF) assay as a marker of colorectal cancer

A specific macrophage migration inhibition assay, using patient lymphocytes incubated with a human colonic cancer extract, was studied in 92 patients with proven colorectal cancer and in 134 other individuals (20 normal controls, 80 patients with various nonmalignant gastrointestinal diseases, and 34 patients with extracolonic malignancies).A positive response was obtained in 78 of 92 colorectal cancer patients, but in none of the 20 normal controls. A positive response occurred in four of 34 patients with extracolonic malignancies and in approximately half of patients with colonic adenomas and in one third of patients with ulcerative colitis. The significance of positive results in these patients (with diseases considered premalignant) is unclear, and is being studied further. In patients with previous resection of colorectal cancers, positive responses were frequent during the first year following resection, and rare thereafter.The results suggest that this method may be useful as a clinical marker for colorectal cancer, and warrants further technical refinement and study of specific patient populations.

Between the Subjective and the Objective: How Informative Is Subjective Evaluation of Memory Among the Old-Old?

This study addresses the relationship between subjective evaluation of memory and objective cognitive dysfunction in old-old age. In a sample of 164 participants (mean age 91.9, range 87–106) drawn from a nationwide Israeli survey, 42% evaluated their memory positively and 30% negatively. Participants were no more concerned about being forgetful than younger adults. Subjective memory and concern about forgetfulness were not significantly correlated with cognitive dysfunction. Sociodemographic, physical, and well-being characteristics explained three times more variance of cognitive dysfunction than of subjective memory. The study suggests that subjective memory among old-old people who can undergo a survey interview may not reflect actual cognitive dysfunction. Apparently, the role of subjective evaluation resides in other areas of adaptation to very old age.

The elders of the kibbutz.

In order to test the hypothesis that retirement would be particularly stressful for this highly motivated cohort, forty retired members of Israeli kibbutzim (22 men, 18 women) were interviewed in an open—ended fashion, concerning their early history, their decision to join the kibbutz, their working life, and their post-retirement adaptation. Little evidence of significant psychopathology was found, and those instances were for the most part traceable to traumatic rearing in the family of orientation, rather than to current, post-retirement losses and insults. These findings are discussed in terms of the Habitat-Niche model developed by Gutmann.