Effect of hydrophilic substances on liberation of quinidine from starch - alginate sphere.

The effect of selected hydrophilic agents on the quinidine loading and its release from potato starch alginate spheres prepared by instilling viscous suspensions into a desolvation liquid (saturated calcium chloride: paraffin liquid: heptan 1:1:1 v/v/v) was studied. The loading of quinidine in spheres was 59.77%-46.30% and it depended on the presence of auxiliary hydrophillic agents such as polyethylene glycol 2000 (59.77%), polyoxyethylene - 20 - sorbitan monostearate (49.55%), glyceryl monostearate (49.02%), sorbitan monooleate (46.30%). The drug release from spheres was diffusion controlled in accordance with the Higuchi model. It was concluded that the release rate constants depended on the drug - carrier - hydrophilic agent composition and dissolution media.

The dissolution kinetics of sulfamethoxazol, trimethoprim and oxytetracycline hydrochloride from multicomponent solid dispersion capsules ("Sulfoxytrim").

Release profiles and dissolution kinetics of active substance, viz. sulfamethoxazol (SMO), trimethoprim (TMP), and oxytetracycline hydrochloride (OTC) from capsulated multicomponent dispersions was studied in a flow-cell apparatus at 37 degrees C by using a dissolution medium of 0.1 mol/l HCl. The results revealed that the relative dissolution efficiency (DE) and dissolution profiles of one active ingredient were affected by the presence of the two others. Vitamin C added caused the decreased the dissolution rate constants (K) and DE--values of all the active substances studied.

Toward the border between neural and Markovian paradigms.

A new tendency in the design of modern signal processing methods is the creation of hybrid algorithms. This paper gives an overview of different signal processing algorithms situated halfway between Markovian and neural paradigms. A new systematic way to classify these algorithms is proposed. Four specific classes of models are described. The first one is made up of algorithms based upon either one of the two paradigms, but including some parts of the other one. The second class includes algorithms proposing a parallel or sequential cooperation of two independent Markovian and neural parts. The third class tends to show Markov models (MMs) as a special case of neural networks (NNs), or conversely NNs as a special case of MMs. These algorithms concentrate mainly on bringing together respective learning methods. The fourth class of algorithms are hybrids, neither purely Markovian nor neural. They can be seen as belonging to a more general class of models, presenting features from both paradigms. The first two classes essentially include models with structural modifications, while two later classes propose algorithmic modifications. For the sake of clarity, only main mathematical formulas are given. Specific applications are intentionally avoided to give a wider view of the subject. The references provide more details for interested readers.

Disintegration rate and release of aminophenazone from tablets.

Disintegration apparatus according to P.Ph was adepted to measure the disintegration rate of tablets. The data obtained for 10 batches of aminophenazone tablets with different content of gelatine (2-20%) showed that there is a linear correlation between the area under non-disintegrated tablets mass curves (AUDC) and the area under release curves (AURC) described by equation: AUDC = bcr AURC - acr.

Factors affecting the release of papaverine from spheres.

The effect of selected carriers and auxiliary hydrophilic agents on the papaverine loading and its release from spheres prepared by instilling viscous liquids into a 1% solution of calcium chloride in ethanol was studied. The most favourable loading of papaverine in potato starch, sodium alginate and sodium carboxymethylcellulose spheres was 97.4%, 95.7% and 91% respectively, and it depended on the presence of auxiliary hydrophilic agents such as polyethylene glycol 1500, polyethylene glycol 4000, glyceryl monostearate and sorbitan tristearate (Tween 65). The drug's release from spheres was diffusion controlled in accordance with the Higuchi model for the release of 80-95% of contents. It was concluded that the release rate constants depended on the drug-carrier-hydrophilic agent composition.

Effect of carriers and hydrophilic agents on papaverine spheres bioavailability.

The effect of carriers--potato starch, sodium carboxymethyl cellulose, sodium alginate, and hydrophilic agents--polyethyleneglycol 1500 (PEG 1500), PEG 4000, glyceryl monostearate (MSG), Tween 65, on bioavailability of papaverine from spheres were studied on rabbits. The data of pharmacokinetics parameters as absorption lag time, maximum plasma concentration (Cmax), time to peak concentration, absorption rate constant, elimination rate constant, bioavailability (F) depend on drug-carrier-hydrophilic agent composition. Potato starch-PEG 4000, potato starch-MSG, NaCMC-PEG 1500 spheres show best F-parameters of papaverine respectively 96%, 89%, 88%, Cmax 19.7, 21.3, 18.6 micrograms/ml reached in about 2 h.

[Unilateral exophthalmus in the course of spontaneous retrobulbar hemorrhage in a patient with arterial hypertension]. / Jednostronny wytrzeszcz w przebiegu samoistnego wylewu pozagalkowego u pacjenta z nadcisnieniem tetniczym.

In this paper we present a case of a 60-year-old patient with labile hypertension, who was admitted to hospital because of unilateral exophthalmus and loss of vision of the left eye. During the hospitalization basic laboratory investigations, USG and NMR of orbits and arteriography of internal carotid arteries were carried out. Body temperature and arterial blood pressure were monitored. Leucocytosis and high values of arterial blood pressure in the early hours of the morning were found. Accessory investigations didn't explain the cause of exophthalmus. Repeated NMR of orbits showed image characteristic for retrobulbar haemorrhage in the left orbit. During the hospitalization hypotensive, anti-inflammatory and oedema-reducing treatment was administered, without surgical intervention. This case demonstrates that modern diagnostic investigations must be preceded by precise history taking concerning the early symptoms of the disease, its course and accompanying systemic diseases. Although spontaneous retrobulbar haemorrhages occur rarely, they must be taken into consideration in differential diagnosis of unilateral exophthalmus, especially in elderly patients with atherosclerosis and hypertension.

Inosine--a natural modulator of contractility and myocardial blood flow in the ischemic heart?

The energetic role of inosine (INO) remains controversial. The aim of the present study was first to test whether endogenous INO consumption/production correlates with regional myocardial contractile performance and second to test whether locally increased levels of INO influence contractility and blood flow in severely ischemic myocardium. Fentanyl-anesthetized dogs with implanted sonomicrometry crystals and independently perfused left anterior descending coronary arteries were studied. Two relatively load-independent indexes of regional myocardial contractility derived from left ventricular pressure-segment length loops were used: the regional stroke work-end-diastolic segment length relationship (Wr/L(ed)) and the end-systolic pressure-segment length relationship (Plv/L(es)). Very good correlations between myocardial contractile performance (as measured by the slope of the regional Wr/L(ed) relationship) and endogenous INO consumption/production under both nonischemic and ischemic conditions were found. Ischemia severely depressed contractility, significantly shifting rightward the Wr/L(ed) and Plv/L(es) relationships. INO infused into the left anterior descending bypass, in a concentration of 600 to 800 mumol/L, partially restored contractile performance as evidenced by a significant leftward displacement of both relationships. Wr, measured at a common maximum L(ed), increased significantly by 61 +/- 5%. Border-zone collateral flow (microspheres) increased by 35 +/- 7% within the endocardial segments and by 34 +/- 9% in the epicardial segments, but no increase in flow in the ischemic region was measureable. With the current emphasis on recanalization with thrombolytic therapy and considering the apparent safety of INO, this naturally occurring nucleoside might prove to be a useful adjunctive agent in the treatment of acute myocardial ischemia.

Haemodynamic effects of inosine. A new drug for failing human heart?

Haemodynamic effects of inosine were studied in intact dogs and subsequently in patients suffering from prolonged otherwise intractable cardiogenic shock. The nucleoside significantly improve myocardial performance in patients with an extremely low cardiac index by 63 +/- 29% as well as animals with no signs of haemodynamic deterioration, increasing cardiac output by 12.2 +/- 4.3%. These results suggest that inosine may become a promising inotropic agent. Further studies though are necessary to elucidate the mechanism of inosine action.

Urate production by human heart.

Xanthine oxidoreductase has been demonstrated in the heart of various species. However, its presence in human heart is still debated. In the literature, high to undetectable levels have been reported. We studied the arterial-venous urate difference across the heart of patients undergoing both routine cardiac catheterization and percutaneous transluminal coronary angioplasty. Urate is the end product of the reaction catalysed by xanthine oxidoreductase. In 10 patients, studied before angioplasty, the plasma urate level in the great cardiac vein exceeded the arterial one by 26 +/- 10 nmol/ml (P = 0.028). In a further 13 patients, urate production was maximal immediately after the last of four consecutive occlusions (23 +/- 8 nmol/ml, P = 0.018) and concomitant with increased coronary sinus hypoxanthine levels. We conclude that xanthine oxidoreductase is probably present in the heart of patients, suffering from ischemic heart disease, and responsible for the increase in urate production during transient myocardial ischemia.

Apparent inosine uptake by the human heart.

Although inosine has been used clinically to support the myocardium, no data are available on the fate of exogenous inosine in the human heart. We therefore infused six patients, catheterised for coronary angiography, with inosine (5 mg.kg-1.min-1 intravenously) for 6 minutes. Before infusion, the arterio-venous difference of inosine, hypoxanthine and xanthine across the heart was nil. During infusion, arterial inosine increased substantially, exceeding the coronary sinus concentration by a maximum of 200 (SEM 53) mumol.litre-1, p = 0.02, at the fourth minute. Arterial hypoxanthine and xanthine also increased, while the arterio-venous difference became 16(11) and 10(3) (p = 0.04) mumol.litre-1, respectively. Left ventricular dP/dtmax increased by 22(7)% (p = 0.04) at the end of infusion. Thus, there seemed to be substantial uptake of inosine by the human heart, followed by improvement in haemodynamics.

ST 567 compared with propranolol in stable angina.

UNLABELLED: The aim of this study was to investigate the effectiveness of ST 567 in patients suffering from ischaemic heart disease and to compare the effects of this drug with those of propranolol. The study group consisted of 48 male patients, mean age 53, with stable, exercise-induced angina pectoris. After a two-week run-in-placebo period, the patients were randomized to treatment with ST 567 3 X 30 mg (N = 24) and propranolol, 3 X 40 mg (N = 24). The drugs were administered in a double blind fashion during four weeks. Heart rate at rest was decreased by ST 567 from 76 to 65 (P less than 0.005) by propranolol from 76 to 62 (P less than 0.001). Systolic blood pressure was lowered by ST 567 from 131 to 121 (NS) and by propranolol from 133 to 118 (P less than 0.05). Exercise tolerance was increased by ST 567 from 20 X 10(3) to 34 X 10(3) J (P less than 0.05), by propranolol from 26 X 10(3) to 32 X 10(3) J (P less than 0.01) (mean values). Anginal attacks (no. per week) were reduced by ST 567 from 14 to 7 (P less than 0.05) and by propranolol from 14 to 5 (P less than 0.01). Nitroglycerin consumption in no. of tablets per week decreased in ST 567 from 12 to 7 (P less than 0.01), in propranolol from 11 to 4 (P less than 0.0). There were 7 drop outs during treatment with ST 567:2 cases of myocardial infarction, exacerbation of angina in 2 patients, visual disturbances in 2 patients, vertigo in 1 patient. With propranolol we observed worsening of angina in 1 patient, with disturbances in sexual potency in 1. IN CONCLUSION: ST 567 is an effective agent in chronic angina but slightly less effective than propranolol in the dosages studied.

Mechanism of the inotropic action of inosine on canine myocardium.

The positive inotropic effect of inosine in intact dog hearts was approximately halved by beta-adrenergic blockade with sotalol. The same result was obtained in dogs with chronic denervation of the heart, in which the sympathetic nerve terminals had degenerated. Therefore part of the positive inotropic action of inosine appears to be non-adrenergic. Inosine infusion caused supersensitivity of the positive inotropic effect over a wide range of doses of adrenaline. It is postulated that inosine may act by blocking the desensitising action of cyclic AMP on the reaction between calcium ions and the contractile proteins.

The influence of inosine on the size of myocardial ischaemia and myocardial metabolism in the pig.

In acute experiments on open chest pigs 15 min occlusions of the left anterior descending coronary artery were performed, each occlusion followed by 45 min reperfusion. Myocardial ischaemia was defined by epicardial electrogram recorded from the border of the ischaemic area. Myocardial extraction of lactate and glucose as well as the extraction of FFA were measured before and at the 15th min of occlusion. Inosine (5 mg/kg/min) or 0.9% NaCl infusion was administered i.v. throughout the occlusion period. Inosine significantly diminished the number of ischaemic points and reduced an increase in R-wave voltage induced by coronary occlusion. Myocardial extraction of measured substrates was not significantly influenced by inosine administration. In conclusion, inosine decreases the area of ischaemic injury induced by acute coronary occlusion in the pig.