Permeability prediction in the beyond-Rule-of 5 chemical space: Focus on cyclic hexapeptides.

Cyclic peptides (CPs) are gaining more and more relevance in drug discovery. Since one of their main drawbacks is poor permeability, the discovery of new orally available CP drugs requires computational tools that predict CP permeability in very early drug discovery. In this study we used a literature dataset of 62 cyclic hexapeptides to evaluate the performances of a number of in silico tools based on different computational theory to model and rationalize PAMPA and Caco-2 permeability values.

Flexibility in early drug discovery: focus on the beyond-Rule-of-5 chemical space.

Large and flexible compounds are of interest in pharmaceutical programs aimed at challenging protein targets that cannot be modulated by Rule of Five (Ro5)-compliant small molecules. Given their particular structural features, early drug discovery is now in charge of identifying which molecular descriptors should be used in the often called beyond-Rule-of-5 (bRo5) chemical space. Here, we focus on flexibility descriptors.

Prospects for the use of antioxidant therapy in hypertension.

The purpose of this review is to examine the indications and contraindications of antioxidant therapy in arterial hypertension. It has been suggested that oxidative stress plays a role in hypertension, increasing pressure values and leading to complications. Oxidative stress, at present, appears as one of several metabolic abnormalities described in essential hypertension.

Reactive oxygen species and antioxidant status in essential arterial hypertension during therapy with dihydropyridine calcium channel antagonists.

Purpose: To evaluate reactive oxygen species and antioxidant status in essential arterial hypertension during therapy with dihydropiridine calcium channel antagonists.

Patients And Methods: Fifteen patients, affected by essential arterial hypertension, were examined. They received once a day oral dihydropyridine calcium antagonists for 10 weeks: five patients received felodipine (5 mg), five amlodipine (10 mg) and five lercanidipine (10 mg).

[Reactive metabolites of oxygen, lipid peroxidation, total antioxidant capacity and vitamin E in essential arterial hypertension].

Free radical oxidative stress has been implicated in the pathogenesis of a variety of human diseases. The purpose of this study was to explore the degree of oxidative stress in essential arterial hypertension (EAH). The study groups consisted of fifteen untreated EAH patients (WHO stages 1 and 2), aged 40 to 70 years, and fifteen, age and sex matched, normal controls.

L-carnitine adjuvant therapy in essential hypertension.

This study was undertaken to demonstrate L-carnitine therapeutical effect in patients with essential hypertension. Two groups were tested, A and B. First group (A) was split in two subgroups, A1 and A2.

Coenzyme Q10 in essential hypertension.

This study was undertaken to clarify the mechanism of the antihypertensive effect of coenzyme Q10 (CoQ10). Twenty-six patients with essential arterial hypertension were treated with oral CoQ10, 50 mg twice daily for 10 weeks. Plasma CoQ10, serum total and high-density lipoprotein (HDL) cholesterol, and blood pressure were determined in all patients before and at the end of the 10-week period.

[The benefits of L-carnitine therapy in essential arterial hypertension with diabetes mellitus type II].

Carnitine is a natural substance essential for the mitochondrial oxidation of long-chain fatty acids and therefore regulates the energy metabolism of the cells. Tissue carnitine levels are altered under diabetes mellitus or hypertension. The aim of this study was to evaluate the efficacy and tolerability of L-carnitine therapy in essential hypertension with diabetes mellitus type II.

[The combination of nifedipine and a low sodium diet with potassium supplement in the therapy of essential arterial hypertension].

Moderate dietary sodium restriction with moderate dietary potassium supplementation was used in patients with essential hypertension who were treated with nifedipine retard by mouth every twelve hours. Combination therapy of this diet with the nifedipine retard produced a significantly greater decrease in both lying and standing blood pressure that with the drug alone. No noticeable side effects were observed.

[Hormonal, beta-endorphin and renin activity changes in man during partial immersion, as a therapeutic method, in water at 38 degrees C].

This research was carried out to define the effects on men of head-out water immersion in a bath at 38.41 +/- 0.04 degrees C (mean +/- S.

[Hemorheologic and blood cell changes in humans during partial immersion, with a therapeutic method, in 38 C water].

This research was carried out to define the effects on man during head-out water immersion in a bath at 38.41 +/- 0.04 degrees C (mean +/- S.

[Plasma beta endorphin in man during partial immersion in water using the therapeutic method].

The following study was designed to evaluate plasma beta-endorphin (beta-EP) variations in healthy volunteers during thermoneutral head-out water immersion while prevalently in the standing position. The type of immersion was similar to that currently adopted for therapeutic rehabilitation. Plasma beta-EP was evaluated by RIA previous beta-lipotropin stripping and Sep-Pack cartridge methanol extraction.

[Flowmetric, thermometric and rheologic studies in obliterating arterial diseases of the lower extremities treated with buflomedil].

Ten subjects with peripheral arterial occlusive disease were treated with buflomedil, analysing the effect of every single intravenous administration of the drug, and the effect of the administration repeated for a period of 5 days. This controlled study was aimed at evaluating the state of the peripheral blood flow, not just relating to the flowmetric parameters, but also to those more directly connected to the metabolic and functional conditions of the microcirculation. During every single administration, blood flow, skin and muscular temperatures were recorded.

Magnesium in tumoral tissues, in the muscle and serum of subjects suffering from neoplasia.

Mg2+ content is significantly increased in malignant neoplastic mammary tissue compared with normal mammary tissue and benign neoplastic tissue of the breast. Significant variations of the ion were not found in the skeletal muscle tissue (rectus abdominis and pectoral muscle) of subjects suffering from malignant neoplasia with diffused metastasis. It seems that the variation of Mg2+ content in malignant neoplastic mammary tissue is a local factor linked with the biological anomalies of the neoplastic cell.

[Lysosomal lesions during a course of acute experimental muscular ischemia. Protective effect of a polypetitide proteinase inhibitor].

Three groups of rabbits were used: a) with acute ischaemia in a rear limb; b) with acute ischaemia in a rear limb and treated with i.v. 100,000 KIU of a proteinase-inhibitor polypeptide extracted from ox lung; c) normal controls.

Effect of a proteinase inhibitor on intermittent claudication or on pain at rest in patients with peripheral arterial disease.

Twenty patients with peripheral arterial disease and 10 normal controls were submitted to i.v. injection of aprotinin, polypeptide (mol.

Changes in enzyme levels in human skeletal muscle during obstructive arteriopathy of the lower limbs.

Some enzymatic activities have been assayed in the gastrocnemius muscle of patients with obstructive arteriopathy of the lower limbs. The specific activities of all the examined glycolytic enzymes, of malate dehydrogenase and of glycerol-3-phosphate dehydrogenase are significantly decreased while the specific activities of two lysosomal enzymes, beta-glucuronidase and cathepsin A, are significantly higher than in the controls. Therefore it may be inferred that the metabolic capacity of glycolysis and of Krebs cycle are lowered.