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Biomedical subjects

M C Ziskin

Publications and source records attributed to M C Ziskin.

At least 19 recordsLinked to original sources

Effect of ultrasound on the neonatal rat brain.

Six-day-old rat neonates were exposed to 2.25 MHz continuous wave (CW) ultrasound for 5 min at an intensity of 2.5 W/cm2 (SATA). The temperatures on the head surface and in the mouth were measured. There was a higher average temperature elevation in the mouth (9 degrees C) than on the head surface (7 degrees C). Survival differs between control and exposed groups at 30 days after exposure. Ninety percent of the control group lived to 30 days, versus 59.7% for the exposed group. At differing times following exposure, the brains of the pups were removed and tested for enzymatic activities. Changes in acetylcholine esterase and in 2',3'-cyclic nucleotide phosphohydrolase activities were not statistically significantly different from controls. There were no significant differences in brain weight and total protein between control and exposed pups.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase

Effect of ultrasound on regional cerebral blood flow in neonatal rats.

By employing a laser-Doppler flowmeter, an investigation was performed to determine whether ultrasound causes a change in regional cerebral blood flow (rCBF). rCBF in neonatal rats (age: 2-6 days postgestation) was measured before, during, and after exposure of both cerebral hemispheres to continuous-wave ultrasound (1.0 MHz) at an intensity of 2.0 W/cm2 (SATA) for a period of 5 min. After 3 min of ultrasound treatment, there was a statistically significant augmentation in rCBF (p less than 0.05) with rCBF increasing by a factor of 2.7 +/- 0.4 (mean +/- SEM) after 5 min of ultrasound. This response was demonstrated to be a transient effect, because rCBF returned to its original value 4-6 min after termination of the ultrasound treatment.

Animals

Reversible biochemical changes in the developing rat central nervous system following ultrasound exposure.

Rat embryos in utero at 10 days of gestation (gd) were exposed to the intensity of 2.5 W/cm2 (SATA) of 1 MHz continuous-wave ultrasound for 5 min. The right uterine horn was exteriorized, exposed to the ultrasound beam, and then reinserted into the abdominal cavity. Embryos from the unexposed left uterine horn served as controls. The cerebral hemispheres of each fetus were removed and analyzed for enzymatic activity at four different stages of development. There was an increase in the temperature at the surface of the intact uterus during the ultrasound exposure. No gross anatomical malformations were observed in the exposed embryos. There were no differences in brain weight or protein content between exposed and control fetuses. However, the ultrasound exposure caused a transient decrease in acetylcholine esterase and 2',3'-cyclic nucleotide phosphohydrolase activities of the insonated fetal brains compared to the control brains. Because of the relatively high temporal-average intensity, the relatively large volume of tissue exposed, and the minimal sound path through tissue, the biochemical changes observed in this experiment would be unlikely to occur in clinical examinations.

2',3'-Cyclic-Nucleotide Phosphodiesterases

Effects of ultrasound on DNA and RNA synthesis in preimplantation mouse embryos.

Ultrasound is used extensively to monitor the growth of ovarian follicles in in vitro fertilization and embryo transfer (IVF-ET) programs, as well as to follow the progress of early pregnancy. There have been scattered reports in the literature that exposure to ultrasound may have an adverse effect on reproduction in the rat (Bologne et al: CR Soc Biol 177:381-387, 1983; Demoulin et al: Ann NY Acad Sci 442:146-152, 1985), and also in humans (Demoulin et al: Ann NY Acad Sci 442: 146-152, 1985). We report here that diagnostic levels of pulsed ultrasound did not affect either the number of embryos produced, or the ability to incorporate labelled precursors into DNA and RNA, respectively. Measurements of temperature elevation of ovaries exposed to ultrasound showed that neither controls nor experimental tissue exhibited temperature elevation greater than 1 degree C.

Animals

Biochemical changes in the developing rat central nervous system due to hyperthermia.

Rat embryos at 10 days of gestation were exposed to 43 degrees C for 8 minutes by submerging the exteriorized right uterine horn in heated saline solution and then reinserting the uterine horn into the abdominal cavity. At 15 days, the fetuses were removed, and cells from the cerebral hemispheres were dissociated and grown as primary cultures. Embryos from the left uterine horn served as controls. No morphological changes were observed between the cultures of cells from control and heat-exposed embryos at different days in culture. However, exposure of embryos to hyperthermia at 10 days significantly affected the developmental pattern of activities of acetylcholine esterase associated with cholinergic neurons and of 2',3'-cyclic nucleotide phosphohydrolase associated with oligodendrocytes and myelin membrane formation. These results suggest that hyperthermia at 10 days of gestation in the rat may lead to an impairment in the development of neurons and oligodendrocytes in the central nervous system.

2',3'-Cyclic-Nucleotide Phosphodiesterases

Intraoperative venous dilation and subsequent development of deep vein thrombosis in patients undergoing total hip or knee replacement.

This patient study was based on the observation of characteristic intimal lesions in jugular and femoral veins removed from dogs a few hours following total hip replacement. The lesions, small localized intimal tears, suggested that smooth muscle and connective tissue, might have dilated beyond the ability of intima to accommodate. Intraoperative venous dilation correlated with the incidence of intimal lesions. It was postulated that surgical trauma resulted in circulating vasoactive substances which caused venous dilation and that dilation of smooth muscle and connective tissue beyond the yield point of intima resulted in intimal rupture. Similar intraoperative dilation and lesions, in patients might predispose to development of deep vein thrombosis (DVT). Total hip (THR) and total knee (TKR) replacement patients were selected for study because: (a) of the high incidence of DVT and (b) blood circulation is present in THR but not in TKR patients during operation. Ultrasound was used to monitor cephalic vein diameter during the perioperative period. Development of DVT postoperatively was compared with intraoperative venous dilation. In THR patients, intraoperative venous dilation ranged from 6%-56%. One of nine patients with dilation less than or equal to 17% developed DVT while 12 patients with dilation of greater than or equal to 22% developed DVT, giving a correct prediction of 95%. Of four patients in the intermediate range (19%, 20%), two developed DVT and two did not. The sharp demarcation was to be expected because of abrupt rupture of viscoelastic material when the critical point of elongation is exceeded.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Effect of scan format on refraction artifacts.

Refraction artifacts occur when the ultrasound beam is bent from its original direction as it passes through a boundary between tissues having different sound speeds. Refraction artifacts result in both the improper positioning and the improper brightness of echoes displayed in clinical sonograms. The effect of scan format on the sonographic appearance of several refraction artifacts due to a circular object possessing a sonic speed differing from its surrounding tissue was studied using a mathematical model and computer generated images. A quantitative index of artifact prominence was developed to compare the differences between the rectilinear and the sector scan formats. Theoretically predicted results were compared with actual sonograms of a specially designed phantom. Results included the finding that the retrolenticular afterglow was more prominent in the sector scan format, and that differences were most prominent when the refracting object was close to the transducer.

Animals

Transdermal absorption of radioprotectors using permeation-enhancing vehicles.

Radioprotectors are not currently used clinically due to concerns regarding toxicity and uncertainties regarding tumor protection. Topical radioprotection of skin might find clinical applications with protectors such as WR-2721, but laboratory studies in which protectors have been applied in water have not been promising. We have studied the absorption of 14C-WR-2721 and [14C]cysteine dissolved in skin permeation-enhancing vehicles through the skin of hairless mice and compared the absorption to that in water. Skin concentration of WR-2721 was increased most by dimethylformamide (DMF), but only propylene glycol increased absorption as far as the dermis, as measured by plasma concentration. Skin concentration of cysteine was improved by DMF, 2-pyrrolidone (2-P), and methyl-2-pyrrolidone (M-2-P); only dimethylsulfoxide (DMSO) resulted in increased plasma levels of the protector. Pretreating skin with DMSO before application of WR-2721, irrespective of the vehicle, improved its concentration within the skin. Plasma levels were improved (10 and 12 times) only with 2-P and DMF. Therefore, by choosing the appropriate vehicle, it is possible to breach the barrier of the stratum corneum and enhance the presence of the protector in all layers of the skin.

Administration, Cutaneous

Transdermal absorption of radioprotectors in the rat using permeation-enhancing vehicles.

Topical radioprotection of rat skin with WR-2721 has not been effective presumably because the drug does not cross the stratum corneum to reach the epidermis and dermis. Earlier, we showed in the mouse that WR-2721 and cysteine dissolved in permeation-enhancing vehicles passed through the skin more readily than when in water. However, the most effective vehicles in the mouse were not necessarily as effective in the rat. Here we report that the most effective transport vehicles in the rat were (1) water with WR-2721, (2) water and dimethylformamide (DMF) with cysteine, and (3) water and DMF with prostaglandin E2 (PGE2). Pretreatment of the skin with dimethylsulfoxide (DMSO) further improved the transfer of the radioprotectors across the skin in most cases. After pretreatment with DMSO, the most effective vehicles were (1) water for WR-2721, (2) water and methyl-2-pyrrolidone (M-2-P) for cysteine, and (3) DMF for PGE2.

Amifostine

Effects of ultrasound on ovulation in the mouse.

In vitro fertilization and embryo transfer (IVF-ET) programs use ultrasound extensively for monitoring the growth of ovarian follicles and, subsequently, for confirming the presence of a fetal sac. There have been few reports of the effects of ultrasound on ovulation rates in mammals, and we report here that following exposure to continuous wave ultrasound at a spatial average intensity of 3.0 W/cm2 for five minutes, ovulation rates measured 10 days later were significantly reduced in mice. When temperature elevation of the exposed ovary was measured with a thermocouple, hyperthermia correlated with reduction in ovulation.

Animals

Temperature elevation in the rat fetus due to ultrasound exposure.

The temperature elevation resulting from sonically generated heat in rat fetuses was measured for various intensity levels. The temperature elevation produced inside the fetus was higher than that on the outside surface. In live fetuses, a portion of the heat generated was carried off by the circulating blood. The temperature elevation curves were used to estimate the absorption coefficient of rat fetuses. Absorption coefficient values range from 0.065 to 0.086 Np/cm at 1 MHz. The present results are consistent with a theoretical model of temperature elevation in a heated sphere.

Animals

Biological consequences of hyperthermia.

Because of the potential for certain modalities of clinical ultrasound to cause tissue heating, it was deemed important to survey the literature for reports on temperatures and hyperthermia exposure durations at which biological effects occur in a wide spectrum of organisms. In general the higher the temperature or the longer the hyperthermia exposure, the greater the chance for observing a perturbation to the biological system. Special attention was given to ascertaining temperature exposure conditions below which no biological effects have been reported. The physical mechanism(s) by which heat produces biological effects is(are) not known but substantial quantities of empirically derived data have allowed for the calculation of exposure temperature-duration equivalences. It appears reasonably well established that short exposures to sharply-elevated temperatures result in a protective effect against further thermal insult; the generation of heat shock proteins by cells coincides with the onset of such "thermal protection." The information contained in this review indicates an absence of reported effects in animals below 39 degrees C.

Animals

Epidemiology of human exposure to ultrasound: a critical review.

Epidemiologic studies and surveys and widespread clinical usage over 25 years have yielded no evidence of any adverse effect from diagnostic ultrasound. Nonetheless, the inability to find convincing proof of an effect, either from epidemiology or from physicians' experience, does not preclude the possibility of it happening. Statistical reasoning shows that even with large population studies, it is difficult to identify a small increase in the rate of a commonly occurring event. Subtle effects, long-term delayed effects, and certain genetic effects, could easily escape detection.

Animals