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Biomedical subjects

J Baust

Publications and source records attributed to J Baust.

6 recordsLinked to original sources

The roles of iNOS in liver ischemia-reperfusion injury.

To determine the contribution of the inducible nitric oxide synthase (iNOS) to hepatic injury following warm ischemia-reperfusion, we developed a model of partial hepatic ischemia-reperfusion in mice and studied the injury response in iNOS knockout (KO) mice. Compared with wild types, iNOS KO animals exhibited lower plasma transaminase levels after 1 and 6 h of reperfusion following 1 h of ischemia. At the 3-h time point, enzyme levels were not different between the two groups. iNOS mRNA was not detectable in the ischemic hepatic lobes of wild-type mice until 3 h of reperfusion; however, perfusion studies identified a significant delay in reperfusion of the ischemic lobe in the iNOS KO mice at the 1-h time point with similar perfusion rates at 3 and 6 h compared with wild type. By way of comparison, mice deficient in the endothelial NOS (eNOS) were also assessed for the degree of hepatic damage 3 h post-reperfusion. Plasma transaminase levels were significantly increased in eNOS KO animals compared with wild-type controls. These data suggest that systemic as well as local sources of iNOS regulate reperfusion, and local iNOS contributes to hepatic injury, while eNOS is protective in warm hepatic ischemia-reperfusion.

Alanine Transaminase↗

Mechanisms of tissue injury in cryosurgery.

As the modern era of cryosurgery began in the mid 1960s, the basic features of cryosurgical technique were established as rapid freezing, slow thawing, and repetition of the freeze-thaw cycle. Since then, new applications of cryosurgery have caused numerous investigations on the mechanism of injury in cryosurgery with the intent to better define appropriate or optimal temperature-time dosimetry of the freeze-thaw cycles. A diversity of opinion has become evident on some aspects of technique, but the basic tenets of cryosurgery remain unchanged. All the parts of the freeze-thaw cycle can cause tissue injury. The cooling rate should be as fast as possible, but it is not as critical as other factors. The coldest tissue temperature is the prime factor in cell death and this should be -50 degreesC in neoplastic tissue. The optimal duration of freezing is not known, but prolonged freezing increases tissue destruction. The thawing rate is a prime destructive factor and it should be as slow as possible. Repetition of the freeze-thaw cycle is well known to be an important factor in effective therapy. A prime need in cryosurgical research is related to the periphery of the cryosurgical lesion where some cells die and others live. Adjunctive therapy should influence the fate of cells in this region and increase the efficacy of cryosurgical techniques.

Animals↗

Minimally invasive cryosurgery--technological advances.

The technological advances which have caused renewed interest in cryosurgery are the development of intraoperative ultrasound to monitor the therapeutic process and the development of new cryosurgical equipment designed to use supercooled liquid nitrogen. The thin, highly efficient probes, available in several sizes, can be placed in diseased sites via endoscopy or percutaneously in minimally invasive procedures. The manner of use is to place the probe in the desired location in the diseased tissue with ultrasound guidance. If required by the size or location of the tumor, as many as five probes can be inserted and cooled to -195 degrees C simultaneously. The process of freezing is monitored by ultrasound which displays a hypoechoic (dark) image when the tissue if frozen. Rapid freezing, slow thawing, and repetition of the freeze/thaw cycle are standard features of technique. Clinical applications which have become common in the past 4 years include the treatment of prostatic cancer and liver tumors. The cases selected for cryosurgery are generally those for which no conventional treatment is possible. However, especially in prostatic cancer, the operative morbidity is so low and the results of therapy are sufficiently good in the short term to merit consideration of use in earlier stages of the disease. Diverse tumors in other sites, such as the brain, bronchus, bone, pancreas, kidney, and uterus, have also been treated in small numbers by cryosurgery. Judging from this experience, further expansion in the use of cryosurgical techniques seems certain.

Cryosurgery↗

Transrectal ultrasound-guided percutaneous radical cryosurgical ablation of the prostate.

BACKGROUND: The two major treatments for prostate cancer, radical prostatectomy and radiation therapy, are associated with considerable morbidity and variable results. This article presents the preliminary results using percutaneous radical cryosurgical ablation under ultrasound guidance to treat prostate cancer. METHODS: The patient group consisted of all patients with localized prostate cancer who underwent cryosurgery between June 1, 1990 and May 1, 1992. Patients in Group 1 were treated by freezing of the tumor with two cryoprobes placed multiple times. Group 2 patients were treated by freezing of the tumor with five cryoprobes placed simultaneously. Cryoprobes (3 mm in diameter) were placed percutaneously with a transperineal approach. Cryoprobe placement and freezing were monitored using the transrectal ultrasound. RESULTS: Of the 55 patients (68 procedures) undergoing treatment, 23 have 3 months of follow-up with associated biopsy (Group 1, 8 patients; Group 2, 15 patients). In Group 1, three (37.5%) patients had residual disease. In Group 2, one (6.7%) patient had residual disease, whereas 14 (93.3%) patients did not. Combining both groups, 19 (82.6%) patients had no residual disease, whereas 4 (17.4%) patients had positive results on postoperative biopsy. Complications included rectal freezing, urethrorectal fistula, sloughing urethral tissue, impotence, perineal ecchymosis, penile edema, and ileus. CONCLUSIONS: Preliminary results indicate that percutaneous transperineal ultrasound-guided prostate cryosurgery may be an effective treatment for prostate cancer with minimal associated morbidity.

Biomarkers, Tumor↗

Extracellular calcium does not contribute to cryopreservation-induced cytotoxicity.

The possible role of extracellular calcium ([Ca+2]e) in cryopreservation-induced cytotoxicity was tested using Madin-Darby canine kidney (MDCK) cells and a fluorescent multiple endpoint assay. MDCK cells maintained in 2 mM [Ca+2]e and treated with the calcium ionophore, ionomycin, increased their intracellular calcium ([Ca+2]i) as revealed by the calcium indicator dye, Fluo3 and the bottom-reading spectrofluorometer, CytoFluor 2300. The addition of 10 mM [ethylene bis (oxyethylenenitrilo)]-tetraacetic acid (EGTA) to the extracellular medium before treatment with ionomycin blocked this ionomycin-dependent increase in [Ca+2]i. A number of site and activity-specific fluorescent probes were surveyed to determine which indicator dye might best reveal the ionomycin-induced cytotoxic events during this increase in [Ca+2]i. Although most dyes changed their emission profiles in response to calcium, neutral red was found to best reflect the loss of [Ca+2]i homeostasis. The NR50 for a 15-min exposure to ionomycin in the presence of 2 mM [Ca+2]e was approximately 2 microM ionomycin, but ionomycin had little apparent effect on neutral red retention when 10 mM EGTA was added to the extracellular medium. Thus it was clear that an increase in [Ca+2]i could be cytotoxic to MDCK cells and that neutral red could monitor this cytotoxic episode. To test if [Ca+2]e was similarly cytotoxic during cryopreservation, MDCK cells were subjected to cryopreservation in the presence of dimethylsulfoxide (DMSO). In contrast to previous studies, plasma membrane integrity, not lysosomal function, seemed to best correlate with cell survival subsequent to cryopreservation. In addition, decreasing [Ca+2]e had no discernable effect on the retention of plasma membrane indicator dyes, neutral red, or cell survival. It is concluded that a) plasma membrane indicator dyes, not neutral red, might be better indicators of cytotoxicity occurring during cryopreservation; b) DMSO might be toxic to lysosomes during cryopreservation of cultured cells; and c) although [Ca+2]e can contribute to cytotoxicity, the presence of [Ca+2]e might not influence cryopreservation-induced cytotoxicity.

Aniline Compounds↗

Development of a high-performance multiprobe cryosurgical device.

The authors describe the design of the first multiprobe cryosurgical system (AccuProbe system). Compared with prior conventional cryosurgical devices, the new system has the following characteristics: 1) generation of subcooled liquid nitrogen, 2) optional use of up to five independently operated and controlled cryoprobes, 3) use of disposable probes of various sizes and shapes, 4) more accurate placement of the cryoprobes in the lesions due to probe miniaturization (3.4 mm in overall diameter), and 5) higher capacity freezing, which supports more accurate and controllable tissue temperatures. With the use of the newly developed system, numerous cryosurgical procedures, including those in the prostate, brain, and liver, have been successfully performed.

Animals↗