David H. Baeder

Lipid mobilizer (LM) from posterior pituitary of hogs.

Summary and conclusions 1. Dialyzate of hog posterior pituitary lobe induced hyperlipemia in rats, mice, guinea pigs, dogs and rabbits. 2. The LM activity was indistinguishable from that of plasma dialyzate from cortisonized animals. 3. Neither Pitressin® nor Pitocin® had LM activity. 4. Hog anterior pituitary extracts had no LM activity. 5. LM appears to be a hitherto undescribed hormone either elaborated or stored in the posterior pituitary.

Lipid Mobilization by a Crystalline Peptide Isolated from Plasma of Horses Administered Cortisone.

Summary and conclusions (1) The active hyperlipemia inducing constituent of the dialyzate obtained from the plasma of horses administered cortisone has been crystallized and tentatively identified as a peptide. (2) Injection of 0.02 μg of crystalline material/kg IV induced marked hyperlipemia in intact mice, rats, guinea pigs, rabbits, dogs and humans as well as in hypophysectomized or adrenalectomized rats. (3) The animals used in this study were exposed to potential hepatotoxic agents.

Relation of endocrines and clearing factor inhibitors to hyperlipemia in fasted animals.

Summary 1. LM produced hyperlipemia only in animals primed for lipid mobilization. 2. Intravenous injection of toxic doses of protamine sulfate, convulsant doses of diisopro-pylfluorophosphate and pyrogenic doses of piromen produced hyperlipemia in intact animals. 3. The same doses of these substances injected into adrenalectomized and hypophy-sectomized rats did not produce hyperlipemia. 4. The hyperlipemic action of protamine or DFP is not attributable to direct inhibition of lipoprotein lipase but to a secondary effect mediated through the adrenals and pituitary. 5. The hyperlipemic action of protamine, DFP, pyrogens and possibly other stressors is best explained by release of LM.

Influence of hyaluronidase and steroids on permeability of synovial membrane.

Summary and Conclusions 1. The permeability of the synovial membrane as measured by speed of absorption and excretion into the urine of phenolsulphonphthalein (PSP) instilled into the joint was found to be surprisingly constant in a group of 16 normal rabbits. 2. Hyaluronidase markedly increased permeability of the synovial membrane. The effect was maximal and was not augmented by desoxycorticosterone acetate (DOCA). 3. Adrenal cortical extract decreased permeability of the synovial membrane and an tagonized the effect of hyaluronidase. This effect of adrenal steroids was more pronounced when they were released endogenously by the alarm reaction. Estrone also decreased the permeability of synovial membrane. 4. Desoxycorticosterone increased maximally the permeability of synovial membrane to the same extent as hyaluronidase and could not be augmented by hyaluronidase. 5. It is suggested that the normal permeability of the synovial membrane is in part controlled by the balance between adrenal steroids of the DOCA type and of the Compound E type. 6. These findings are consistent with current views of the etiology of rheumatoid arthritis either by hyaluronidases or from exposure to stressing stimuli. They are also consistent with the therapeutic effects of Compound E or of adrenocorticotrophic hormone in the treatment of arthritis.

Alteration in Permeability of Some Membranes by Hyaluronidase and Inhibition of this Effect by Steroids

Summary 1. Purified testicular hyaluronidase had no effect on the normal or altered permeability of skeletal muscle, cardiac muscle, or of isolated frog skin. 2. Hyaluronidase strikingly increased the permeability of the lens capsule and urinary bladder membranes, and abolished their semipermeable character. 3. The enhancing effect of hyaluronidase on osmosis through the bladder membrane was increased by desoxycorticosterone acetate. 4. Adrenal cortical extract, testosterone, and cholesterol abolished the enhancing effect of hyaluronidase. Estrone, Equilin, and Equilenin reversed the direction of flow through hyaluronidase treated membranes. 5. Hyaluronidase did not alter the complete inhibition of osmosis through the bladder membrane of rabbits which had been exposed to an alarming stimulus. 6. The products released in vivo during the alarm reaction rendered bladder membranes impermeable even in the presence of hyaluronidase.

Lipemia Clearing by Hyaluronidase, Hyaluronate, and Deoxycorticosterone, and its Inhibition by Cortisone, Stress, and Nephrosis

Summary 1. Partially depolymerized hyaluronic acid released a lipemia clearing factor following intravenous, subcutaneous and oral administration to rats. Hyaluronidase and DC A which were administered only to rats hypodermically were also effective. 2. Plasma from rats treated with cortisone prevented the lipemia clearing by heparin, DCA and partially depolymerized hyaluronic acid. The effect of exposure to cold was tested only against heparin lipemia clearing and was also found to inhibit it. 3. Release of a lipemia clearing inhibitor appears to be another manifestation of the general adaptation syndrome. 4. Plasma from rats made nephrotic by administration of low doses of anti-kidney serum also had an inhibitor of the clearing factor, and those given larger doses of anti-kidney serum had in addition gross lipemia suggesting that pathological lipemia may be preceded by the appearance of the inhibitor. 5. The lipemia clearing factor was inactivated by incubation with hyaluronidase in vitro suggesting that this factor contains a mucopolysaccharide moiety which is not heparin. 6. The activity of the inhibitor of the lipemia clearing factor was not affected by heating at 60°C for one hour.

Effect of Hyaluronidase on Experimental Hypercholesterolemia in Rabbits and Rats and Atheromatosis in Rabbits

Summary 1. Subcutaneous or intravenous injection of hyaluronidase depressed hypercholesterolemia in rabbits and rats. 2. Intraperitoneal injection of hyaluronic acid prevented hypercholesterolemia in nephrotic rats. 3. Hyaluronidase facilitated general lipidoses and aggravated atheromatosis in rabbits. 4. The advisability of indiscriminately lowering the blood cholesterol level in hypercholes-terolemics is questioned. 5. The antihyper-cholesterolemic effect of hyaluronidase was abolished when specific antibodies to the enzyme developed. 6. Endogenous experimental hypercholesterolemia in rabbits does not depend on the presence of the adrenals.

Occurrence in Plasma of an Extractable Lipid Mobilizer (LM)

Summary 1. Freeze dried dialyzates of plasma prepared from dogs, rats and horses receiving cortisone contained a lipid mobilizer (LM) which markedly elevated plasma levels of free and esterifled cholesterol, lipid P and total fatty acids when administered to fasted mice, rats, rabbits, guinea pigs, dogs and humans by intramuscular or intravenous injection. LM was not active by the oral route. The dialyzate also inhibited in vitro the delactescing action of heparin clearing factor. Plasma dialyzates prepared from untreated humans, horses, dogs and rats were 1/1000 as potent. 2. Cortisone injection failed to release LM in hypophysectomized rats. 3. LM activity of the dialyzate is not due to the same constituent responsible for CFI activity. 4. Hyperlipemia resulting from a single large dose persisted for at least one week in rabbits and dogs. 5. Repeated large doses of LM resulted in sustained and progressive hyperlipemia, hyperphagia and either loss in body weight or failure to gain. 6. Marked depletion of perirenal, mesenteric, omental, spermatic cord and subcutaneous fat were observed in dogs receiving weekly injections of LM.

Technical Factors Influencing Permeability of Synovial Membrane in Rabbits.

Summary 1. A critical method for evaluation of synovial permeability based on more than 5000 intra-articular injections in 1658 selected rabbits is presented. 2. The method depends on accurate injection of the talocrural articulation, selection of animals for size and excretion pattern, and undisturbed circulation to the joint. 3. Two workers in the same laboratory using identical technics in testing the permeability effects of various compounds obtained data that show a high degree of correlation. 4. A hitherto undescribed urinary bladder anomaly in rabbits is noted.

Role of Liver on Consequences of Lipid Mobilization.

Summary (1) The role of the liver on the consequences of lipid mobilization from the depots by LM was investigated in sensitized and desensitized rats. (2) Sensitization to the hyperlipemic action of LM involved administration of minute amounts of potential hepatotoxic agents which produced “subclinical” fatty liver as determined by chemical analysis. (3) Desensitization to the hyperlipemic action of LM occurred when the potential hepatotoxic agents were removed from the diet. (4) The liver in desensitized or fed sensitized rats was capable of handling the mobilized lipid without consequent hyperlipemia. (5) Fasted, sensitized rats were not capable of handling the fat load and hyperlipemia resulted. (6) The source of the cholesterol and lipid P in the hyperlipemic rats was the liver. (7) LM actively and immediately mobilized triglycerides from the depots and this action did not depend upon sensitization or fasting.