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Z Sandor

Publications and source records attributed to Z Sandor.

22 records · Page 2Linked to original sources
PubMed1991

Cardiac output and organ blood flow in experimental septic shock: effect of treatment with antibiotics, corticosteroids, and fluid infusion.

Septic shock from intraperitoneal (i.p.) injection of live Escherichia coli bacteria in rats induces marked pathophysiological changes, including 40% decrease in plasma volume (PV), cardiac output, and oxygen consumption with 100% mortality within 24 hr. The present study evaluates cardiac output and organ blood flow before and after treatment of septic shock with an effective antibiotic (AB), plasma volume (PV) expansion, and corticosteroids (CS), alone and in combination. Treatment was initiated at 5.5 hr after bacterial injection, at a time when AB therapy did not improve 24 hr survival rate. Cardiac output decreased from 28.6 +/- 3.1 (SD) to 15.4 +/- 2.8 ml/min/kg (P less than .01) in septic rats concomitant with redistribution of blood flow from carcass to the heart, brain, intestines, liver, and adrenal glands. Absolute arterial blood flow increased only to the adrenal glands and the liver to 158% (P less than .01) and 167% (P less than .01) of control values, respectively. AB, CS, and Ringer's lactate (RL) alone or in combination did not significantly improve any organ blood flow compared to untreated septic animals but increased survival significantly to about 60% (P less than .01). Albumin (ALB) and CS in combination expanded PV to 138% (P less than .01), restored cardiac output to 100%, and achieved supranormal blood flow values to the brain (109%), liver (125%), small intestine (147%) (P less than .01), and kidneys (190%) (P less than .01) of preshock levels. More importantly, survival at 24 hr was 90% (9/10) (P less than .001). It is concluded that a colloid diluted in an electrolyte solution, combined with CS, and an effective antibiotic agent are necessary therapeutic ingredients for the successful recovery of experimental E. coli sepsis.

Adrenal Cortex Hormones↗
PubMed1989

Prevention of acute cyclosporine-induced renal blood flow inhibition and improved immunosuppression with verapamil.

Pretreatment with calcium antagonists such as verapamil (VP) and isradipine prevents CsA-induced decrease in renal microcirculation in mice. Recently, in posttransplant cadaver renal transplant (CRT) recipients, we demonstrated a CsA-induced 70% reduction in renal parenchymal diastolic blood flow velocity (PDBFV). Using duplex Doppler scanning, this randomized study of forty CRT patients examines the effect of pretreatment with VP on renal blood flow velocity and posttransplant function. Patients with initially low PDBFV (less than 8.0 cm/sec) who received VP therapy prior to administration of CsA experienced prompt restoration of flow, and continued to improve during CsA administration. With CsA alone, PDBFV diminished from 8.9 +/- 2.4 (SD) to 5.3 +/- 2.7 cm/sec (P less than 0.002). Although blood CsA levels were significantly higher at 1, 4, and 7 days (68, 184, and 235 ng/ml, respectively), after CsA induction, during VP treatment than in control patients (39, 105, and 156 ng/ml, respectively) (P less than 0.001), with the same daily doses of CsA, serum creatinines at day 7 were lower during VP treatment (1.28 +/- 0.44 vs. 1.66 +/- 0.44 mg%) than in controls (P less than 0.01). When the glomerular filtration rate was less than 45 ml/min on day 1. VP-treated patients showed greater improvement in GFR at day 7 by 34.1 +/- 10.9 ml/min compared with the 18 +/- 13 ml/min in controls (P less than 0.02). Only 3 of the 22 VP patients had rejection episodes within 4 weeks, versus 10 of the 18 recipients randomized to no drug (P less than 0.005). We conclude that VP is beneficial in CRT because it improves renal blood flow characteristics and prevents CsA-induced inhibition of blood flow. VP also ameliorates CsA-induced acute nephrotoxicity, and is associated with improved immunosuppression and fewer early rejections.

Cyclosporins↗
PubMedDate not supplied

Gene expression and gene therapy in experimental duodenal ulceration.

Gastroduodenal ulceration is still poorly understood and changes in gene expression may provide new mechanistic insights. Previously, we demonstrated that angiogenic growth factors are potent ulcer healing agents, and the synthesis of bFGF, PDGF and VEGF is enhanced early in duodenal ulcer healing. The initial molecular event in duodenal ulceration seems to be the organ-specific early release of ET-1 in the pre-ulcerogenic stages after the administration of duodenal ulcerogen cysteamine in rats. We also briefly review here data from literature indicating a central role of ET-1 in gastroduodenal ulceration. After studying the involvement of immediate early genes (e.g. egr-1, Sp1) in ulcer development, we now investigated expression of other genes in the duodenal mucosa in the early stages of chemically induced duodenal ulceration in rats. Following a brief review of principles of gene expression and gene therapy, we review our preliminary gene expression studies, involving monitoring about 1200 genes which revealed about 160 signals and prominent changes in about 30 genes in the early stages of experimental duodenal ulceration. Cysteamine enhanced ET-B receptor gene expression in 30 min, while transcription factors (MAX, STAT 3) showed increased expression in 12 h. We recently also initiated gene therapy studies to enhance the local synthesis of PDGF and VEGF to accelerate duodenal ulcer healing, using a single dose of naked DNA (ND) or adenoviral (AV) vectors of VEGF and PDGF in rats with cysteamine-induced duodenal ulcers. Gene therapy with ND or AV of VEGF or PDGF significantly accelerated chronic duodenal ulcer healing, and increased levels of VEGF and PDGF were detected by Western blotting and ELISA in duodenal mucosa after both VEGF and PDGF gene therapy. Thus, gene expression studies provide new insights into the molecular mechanisms of duodenal ulceration and VEGF or PDGF gene therapy seems to be a new option to achieve a rapid ulcer healing.

Animals↗