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Biomedical subjects

L Hurwitz

Publications and source records attributed to L Hurwitz.

At least 19 recordsLinked to original sources

Synthesis of some substituted quinazolinediones as potential inhibitors of smooth muscle contraction.

3-Substituted 2,4(1H,3H)-quinazolinediones were prepared from the corresponding N-substituted 2-aminobenzamides by treatment with ethyl chloroformate and KOH in ethanol. Also, a series of 3-substituted and 1-methyl-3-substituted 2,4(1H,3H)-quinazolinediones were synthesized by the reaction of 1-methyl-1,4-dihydro- and 1,4-dihydro-2,4-dioxo-3(2H)-quinazolineacetic acid with the corresponding N-substituted piperazines. The 13C NMR spectra and mass spectra of the compounds were measured and signals were assigned. Some of the compounds showed inhibitory action on contractile function of smooth muscle.

Animals

Changes in pharmacy practice due to a clinical pharmacy training programme for a group of community hospitals.

Education for and the practice of Clinical Pharmacy in South Africa have been neglected. This paper describes one attempt to improve matters. An initial survey of pharmacies, pharmacists and other staff in a small group of private hospitals determined the level of Clinical Pharmacy organization and services. The results were used to design a Clinical Pharmacy (training) Programme for selected pharmacists in the group. The programme consisted of six units, each of which was presented in at least a full-day session, with strong audiovisual support, small group discussion and rigorous exercises. During and after each session, implementation and application in the respective hospitals were monitored, as were participants' reactions. Clinical Pharmacy services increased markedly as a result of the programme, as did job satisfaction and motivation among most of the participating pharmacists.

Curriculum

Cobalt-sensitive biphasic uptake of calcium ions in potassium-depolarized smooth muscle.

Isolated longitudinal muscle from guinea-pig ileum was immersed in a calcium-depleted, high-potassium medium for 10 min and then induced to contract by adding 1.8 mM CaCl2. It exhibited a biphasic response that consisted of an initial, rapid, transitory contraction--the phasic response--followed by a slower more sustained contraction--the tonic response. 45Ca uptake was also measured. Only that fraction of the accumulated calcium that could be inhibited by cobalt ion was considered to be intracellular calcium. The data showed that the phasic contraction was accompanied by a brief, rapid uptake of calcium ions and the tonic response was accompanied by a slower, more prolonged uptake of calcium ions. When the muscle, after undergoing an initial biphasic contraction, was reincubated in the calcium-depleted, high-potassium medium for 70 to 80 min, the phasic contraction that it exhibited upon the readdition of 1.8 mM CaCl2 remained unaltered, but the tonic contraction was delayed and substantially diminished. Under these conditions, the rate of the initial brief, rapid uptake of calcium was reduced by 20%, whereas the subsequent slow, prolonged uptake of calcium was measurably delayed and its rate was reduced by an average of 31.4%. Calcium pulse experiments showed that variations in the rate of calcium uptake were due primarily to variations in the rate of the inward movement of calcium ions. The results suggest that the biphasic mechanical response is a reflection of a biphasic influx of calcium ions in the potassium-depolarized longitudinal muscle.

Animals

Ultrastructural characteristics of freeze-dried smooth muscle.

The rapid freezing and vacuum dehydration of tissue has been employed to study the intracellular distribution of diffusible substances at the electron microscopic level. Hower, the ultrastructural detail of freeze-dried tissue is difficult to retain. Consequently, the ultrastructural preservation of freeze-dried smooth muscle has not been sufficient to permit satisfactorily definition of intracellular organelles. Therefore, determinations of the intracellular distribution of soluble ions have not been achieved in freeze-dried smooth muscle. In this study a freeze drying method is presented which provides more satisfactory definition of intracellular organelles than has been available in the past. Using this merens have been preserved. When these muscles are compared to convention preparer of surface vesicles that are observed, and the mitochondria are extremely electron opaque in the freeze-dried tissue. The smooth muscles which have been examined do not have the inherent contrast of other types of tissue nor do they contain the different types of mitochondria that have been observed in nonmuscle tissue.

Animals

Mechanism of isoproterenol-induced desensitization of tracheal smooth muscle.

Isolated rat tracheal smooth muscle became considerably less sensitive to the relaxing action of isoproterenol after being incubated with 5 x 10(-6) M isoproterenol for 30 minutes. Pretreatment of the tissue with propranolol, but not with methylprednisolone, clearly reduced the isoproterenol-induced desensitization. This suggested that propranolol by occupying the beta adrenergic receptor prevented isoproterenol from binding to this receptor, thereby preventing the isoproterenol-induced desensitization. Furthermore, an isoproterenol-desensitized tracheal preparation exhibited a diminished sensitivity to other beta agonists, but not to the spasmolytic actions of D600, hydralazine, sodium nitrite and aminophylline. These results suggested that the beta receptor is specifically involved in the desensitization induced by isoproterenol. A highly desensitized tissue could always be made to undergo complete relaxation by exposing it to sufficiently high concentrations of isoproterenol. Thus, there appeared to be no positive indication of a very large change in the apparent intrinsic activity of the isoproterenol in the desensitized tissue. However, the dissociation constant for the propranolol-beta receptor complex in the desensitized tissue was shown to be 180-fold larger than that in the normal tissue. These findings provide strong evidence that one demonstrable cellular change that occurs in the desensitized tissue is a pronounced reduction in the affinity of the beta receptors for isoproterenol.

Adrenergic beta-Agonists

Isosorbide dinitrate and cardiovascular adaptation to exercise.

Sixteen men with well-documented angina pectoris and without previous myocardial infarction performed a multistage exercise stress test to determine their levels of exercise-induced limitations, characterized by onset of chest discomfort or electrocardiographic ischemic changes, or both. Following a control study, each subject was assigned randomly to either a placebo- or vasodilator-treated group, received chewable medication, and was retested 30 minutes after chewing the medication. Blood pressure, heart rate, and electrocardiographic changes were measured during rest, peak exercise, and recovery. A phonocardiogram, carotid-pulse contour, and single-lead electrocardiogram were recorded simultaneously at supine rest before and immediately after exercise, and systolic time intervals were measured. Results indicated that chewable isosorbide dinitrate reduced systolic blood pressure and the triple product (systolic blood pressure X heart rate X ejection time) significantly during rest and reduced the left ventricular ejection time corrected for heart rate both at rest and peak exercise; no significant differences were observed in the placebo group. The ability to achieve an increased workload was observed in both groups, and the threshold for ischemic manifestations occurred at comparable triple-product levels in both during pretreatment and posttreatment studies.

Adaptation, Physiological

Energy-dependent calcium uptake activity of microsomes from the aorta of normal and hypertensive rats.

Energy-dependent calcium uptake activity of microsomes isolated from the rat aorta has been characterized. The microsomes consist of smooth membrane vesicles which in the presence of MG-ATP as an energy source continuously sequester calcium over a 60-min period. This calcium uptake is greatly stimulated by oxalate anion which serves as a calcium trapping agent. Unlike the calcium uptake of mitochondria this uptake is not inhibited by sodium azide. Sucrose density gradient analysis of the microsomal calcium uptake suggests that the system is associated with the sarcoplasmic reticulum. In presence of 5 mM Mg-ATP and 20 muM calcium approximately 38 nmol of calcium per mg of microsomal protein are taken up in 20 min. In the absence of ATP, less than 2 nmol of calcium per mg of protein are taken up in the first 2 min with no further uptake of calcium in subsequent time periods. When calcium uptake activity is plotted against calcium or ATP concentration of the medium, half maximal activity is calculated for 24.3 muM calcium and for 1.6 mM ATP. The calcium uptake characteristics of the rat aorta microsomes are compatible with a postulated role in the relaxation of the vascular smooth muscle and the provision of an intracellular calcium store for muscle contraction. Aorta microsomes from SHR rats (a genetic strain that is spontaneously hypertensive) have a significantly reduced uptake when compared with the corresponding nonhypertensive control strain. The level of calcium and ATP for half maximal activity of the rat aorta microsomal calcium uptake system is approximately the same in the SHR and the control strain. The rate of release of calcium from rat aorta microsomes is apparently identical in SHR strain and control. The calcium uptake activity of kidney and liver microsomes isolated from the SHR strain and control. The calcium uptake activity of kidney and liver microsomes isolated from the SHR rat appears to be identical to that found in the control strain.

Adenosine Triphosphate

Effects of temperature and inorganic ions on calcium accumulation in microsomes from intestinal smooth muscle.

Energy dependent calcium binding in microsomal vesicles from the longitudinal smooth muscle of the guinea pig intestine was investigated at two different temperatures (30 degrees C and 10 degrees C) and in the absence and presence of CdCl2, BaCl2 and MnCl2. The investigation was carried out to determine whether the effects of temperature and the effects of the divalent ions on microsomal calcium binding could be correlated with the effects of these interventions on the mechanical activity of the intact longitudinal fibers. A reduction in temperature from 30 degrees C to 10 degrees C inhibited both the uptake of calcium into the microsomes and the rate of release of calcium ions from the microsomes to the external medium. This exchange in temperature also slowed the rate of relaxation of the intact longitudinal muscle after it had been induced to contract with acetylcholine and subsequently allowed to relax by removing calcium ions from the bathing medium and adding 1 X 10(-3) M EGTA. The presence of CdCl2, like the reduction in temperature, decreased the uptake of calcium into the microsomal vesicles. However, the release of calcium from the microsomes was accelerated. BaCl2, produced the same effects as did CdCl2 on the uptake of calcium into microsomes but to a lesser extent. It had very little effect on the release of calcium ions from the microsomes. MnCl2 had no significant effects on either the uptake or release of calcium ions in the microsomal preparation. Both CdCl2 and MnCl2 exerted an inhibitory action on acetylcholine-induced contractile responses of the intact longitudinal fibers; whereas BaCl2 served to initiate a contractile response in the smooth muscle fibers. Thus, it would appear that the effects of a temperature change on microsomal calcium binding and on mechanical activity in intact fibers can be correlated; but the effects of CdCl2, BaCl2 and MnCl2 on these two cellular processes do not follow any consistent pattern.

Animals

Electron microscopic localization of calcium in vascular smooth muscle.

Potassium pyroantimonate has been employed in this study to localize calcium in the vascular smooth muscle of the thoracic aorta of the rabbit. The pyroantimonate ion precipitates sodium, magnesium and calcium. Incubation of theisolated thoracic aorta in a high potassium bathing medium which does not contain sodium, magnesium or calcium depletes the tissue of sodium. Addition of 10.8 mM CaC12 to the incubation medium results in well-localized depositions of reaction product, presumably that of calcium pyroantimonate, in mitochondria, sarcoplasmic reticulum, and at the plasma membrane. Some or all of these organelles may, therefore, play a vital role in the contraction-relaxation cycle of vascular smooth muscle.

Animals

New thoughts concerning xanthogranulomatous pyelonephritis (X-P).

A clinical and roentgenographic analysis of 13 patients with pathologically proved xanthogranulomatous pyelonephritis (X-P) has demonstrated that many previously accepted truisms associated with this disease may not be valid. As a result of this study it is suggested that X-P: 1. Does have a prominant female distribution. 2. May arise relatively acutely. 3. Can be associated with a well-functioning kidney. 4. May destroy the kidney and collecting system. 5. Does not demonstrate neovascularity. 6. Can be distinguished angiographically from hypernephroma. 7. May be associated with diabetes. Other important facts were again observed: 1. X-P is still often associated with staghorn calculi and urinary tract obstruction. 2. Proteus mirabilis is the main offending organism.

Adenocarcinoma

Localization of calcium pump activity in smooth muscle.

A microsomal fraction isolated from longitudinal smooth muscle of guinea pig ileum actively sequesters calcium ion in the presence of magnesium and adenosine triphosphate in a fashion previously described for microsomes of the rabbit aorta. This activity in guinea pig ileum appears to be associated primarily with the plasma membrane as is found in the red cell. By contrast the uptake of calcium in aortic smooth muscle appears to be associated to an appreciable extent with intracellular membranes, possibly analogous to the sarcoplasmic reticulum of skeletal muscle.

Adenosine Triphosphatases