On the role of the kidneys in the pathogenesis of edema formation during permanent morphine application/an experimental study in rats.

In order to assess possible renal mechanisms causing the as yet unexplained side-effects of peripheral edema, weight gain and swollen limbs seen during the chronic administration of opioids in patients, a rat study was designed, mimicking a constant infusion (24 h) of morphine (CAS 57-27-2) using subcutaneous drug delivery device systems. Subcutaneous (s.c.

Determination of efficacy of linotroban by inducing a reduction of renal inulin/para-aminohippuric acid clearances with the thromboxane A2 mimetic U-46619 in the conscious female rat.

Linotroban (CAS 141443-73-4), a potent and selective thromboxane (TXA2) receptor antagonist, is known as a novel antithrombotic agent. It is suggested that pharmacological inhibition of TXA2 synthesis or action merits continued evaluation in the treatment of a variety of renal diseases. The aim of this study was the determination of efficacy of this new TXA2 receptor antagonist by assessing its effect on the reduction in inulin and para-aminohippuric acid (PAH) clearances induced by the TX/prostaglandin endoperoxide mimetic U-46619 in the conscious female rats.

Long-term intraspinal infusions of opioids with a new implantable medication pump.

Experiences with long-term intraspinal infusion of opioid drugs using the new implantable medication pump VIP 30 in patients with chronic non-malignant pain are reported. During a 19-month period 10 patients with chronic pain--mainly mixed nociceptive-neuropathic pain--underwent implantation of the medication pump for long-term treatment. The mean follow-up period was 9.

Perioperative catecholamine changes in cardiac risk patients.

Background: It has previously been found that in cardiac risk patients undergoing non-cardiac surgery post-operative cardiac complications are correlated with high post-operative serum levels of troponin T (TNT) and troponin I (TNI). We investigated whether perioperative changes in the release of free (fCAs) and conjugated catecholamines (cCAs) correlate with the increased serum level of TN (TN upward arrow).

Materials And Methods: Plasma levels of CAs were determined in 28 patients at risk for or with definite coronary artery disease.

Effects of the novel thromboxane (TXA2) receptor antagonist linotroban on inulin and para-aminohippuric acid clearances in the conscious male and female rat.

This paper reports the results of experiments designed to determine the effect of linotroban (CAS 141443-73-4) a selective thromboxane (TXA2) receptor antagonist with novel antithrombotic activity, on renal function in conscious male and female rats. Linotroban was administered subcutaneously at doses of 0, 6, 24, 48 and 96 mg/kg/24 h by osmotic minipumps over 6 days. Inulin (Inutest) and para-aminohippuric acid (PAH) clearances were determined on the last day of linotroban treatment.

Critical comments on the classic concept of hypoglycemia induced epinephrine secretion.

Our experiments showed that a continuous chronic administration of norepinephrine (NE) to rats for 20 h by means of subcutaneously implantable retard tablets, led to a highly significant epinephrine(E) depletion of the adrenal medulla during normoglycemia. The rise of free plasma NE was accompanied by increased free plasma E values at 12 hours. At this time the liver contents of glycogen and free intracellular glucose showed their most pronounced decrease.

Nephrotoxicity of fumaric acid monoethylester (FA ME).

The nephrotoxic actions of high single oral doses of fumaric acid monoethylester (FA ME) have been investigated in the rat. Fifty mg of this substance produced morphologic lesions of the glomeruli without reducing GFR. Following 100 mg, the lesions were more pronounced and GFR was diminished by about 40%.

Norepinephrine triggers medullar epinephrine depletion during normoglycemia.

Our experiments did show that chronic 12 hours administration of norepinephrine (NE) to rats by means of subcutaneously implantable retard tablets, led to a highly significant epinephrine (E) depletion of the adrenal medulla during normoglycemia. The expected rise of free plasma NE at 6 and 12 hours was accompanied by increased free plasma E values at 12 hours. At this very time point the liver contents of glycogen and free intracellular glucose showed their most pronounced decrease.

The suitability of a combined inulin/PAH retard tablet for measuring renal functions in the conscious rat.

As a further step in the development of implantable retard systems for simultaneous delivery of inulin and PAH, a system based on Eudragit matrix retard tablet has been deviced. It should be able to release a sufficient amount of both substances to maintain constant and well measurable serum and urine concentration in the 36 hours interval between 12-48 hours p.o.

[Development of combined inulin/p-aminohippuric acid (PAH) slow release implantation tablets for clearance determination in awake rats].

A new method has been developed for the simultaneous measurement of Inulin and PAH clearance in small laboratory animals (rats). An implantable Inulin/p-aminohippuric-acid matrix-retard tablet based on Eudragit was tested with the purpose to estimate renal clearances. Sufficiently high serum and urine levels of both substances can thus be maintained up to 12-48 hours.

Long-term adrenergic beta-action decreases and alpha-action enhances corticosterone levels in rats.

A 20 h hyperadrenalinemia in rats was produced by subcutaneously implanted A-retard tablets with an output rate of 1.8 micrograms/min/250 g. This caused a moderate (6 h, 20 h) to expressed (12 h) rise in Corticosterone.

Laboratory handling and its influence on hormonal and metabolic parameters during acute inflammation in rats. A critique of long-term treatment by repeated injections.

Twice a day, rats were exposed to handling stress by sham i.p. injections during a period of five days.

Adrenaline application by controlled release system shows that it does play a physiological role in glycogenolysis.

In a frequently cited paper Sokal , Sarcione and Henderson (1964) doubted the physiological glycogenolytic role of adrenaline (A). By using isolated perfused rat livers, they found adrenaline to be effective at doses higher than 140 ng/ml while a mere tenfold increase in glucagon leads to expressed glycogenolysis. Our in vivo experiments carried out with controlled release systems for adrenaline show that marked glycogenolysis takes place at an adrenaline serum level of not more than 20 ng/ml while endogenous glucagon levels do not differ from controls.

Peculiar long-term effects of catecholamines and their blockers in rats on insulin, glucose and pancreas.

To be able to study the long-term effects of moderately enhanced catecholamine levels in rats, we developed subcutaneously implantable retard systems, granting a linear output of various agents throughout the test time. Adrenaline application leads to hyperglycemia without elevation of serum immune-reactive-insulin (IRI) during 20 h of uninterrupted adrenaline (A) action. This we call an A-induced diabetes like reaction.

[Implantable repository adrenaline tablets for long-term studies on rats].

Implantable coated Eudragit matrix tablets containing adrenaline in various concentrations should overcome the problem of additional handling stress during long term infusions. The efficiency of those tablets was tested in vitro, as well as in vivo using labeled adrenaline. Both in vitro and in vivo testing yielded satisfactorily output rates up to 20 h whereby the liver and serum content of 14C-fragments served as an additional prove for the postulated mode of action.

Adrenal depletion during hypoglycemia without participation of the Golgi apparatus.

Adrenal depletion in rats due to hypoglycemia was effected by prolonged administration of adrenaline, without artificial increase in insulin levels. In spite of significantly enhanced catecholamine turnover in this stadium Golgi complexes - which are usually reported to develop hypertrophy during adrenal depletion using insulin induced hypoglycaemia - could never be observed. This leads to the conclusions, that firstly the presence of hypertrophic Golgi complexes is not necessarily linked with increased catecholamine turnover and secondly that permanent adrenalin application suppresses and insulin application promotes the formation of Golgi systems.