Paolo Arcangeli

Pycnogenol® in chronic venous insufficiency

Forty patients with chronic venous insufficiency (CVI) and varices of the legs were selected and double-blindly randomly assigned to a treatment with Pycnogenol (French maritime pine bark extract), 100 mg x 3/day or a placebo for 2 months, according to a double-blind experimental design. The effects of the treatment were evaluated by scoring the symptomatology with a semi-quantitative scale, and the venous blood flow by means of a hand-held Doppler ultrasound. The tolerability was evaluated by recording the adverse effects and by means of hematology and blood chemistry parameters, before and at the end of the treatment. Pycnogenol treatment induced a significant reduction in subcutaneous edema as well as heaviness and pain in the legs, on both after 30 and 60 days, the evaluation time periods. Approximately 60% of patients treated with Pycnogenol(R) experienced a complete disappearance of edema (the most rapidly disappearing symptom) and pain at the end of the treatment, while almost all the patients reported a reduction in leg heaviness which disappeared in approximately 33% of patients. These changes were statistically significant. No effect was observed in the placebo-treated subjects. No effect on the venous blood flow was observed in either of the experimental groups.

Aortic Connective Tissue in Ageing—A Biochemical Study

The biochemical analysis of samples of aortic connective tissue was carried out in 22 subjects from 9 to 84 years old. Aortic samples were taken at necropsy performed after sudden or, more often, traumatic death. The results suggest that aging of the aorta is accompanied by an increase both in collagen content and in total sugar content when expressed as mg/cm2 while the elastin content, when expressed in the same way, does not undergo any variation.

Changes in the activities of lysosomal enzymes in striated muscle following ischemia

Abstract Experimental acute ischemia of gastrocnemius muscle was produced in male rabbits. The changes in activity of four lysosomal enzymes ( α-galactosidase, β-galactosidase, acid phosphatase and N-acetyl-glucosaminidase) were examined in the soluble and particle-bound fraction of ischemic and contralateral muscle. Changes in the free fraction of ischemic muscle were as follows: α- and β-galactosidase increase in varying degrees during the first hours of ischemia, and then return to normal values after 24 hours, while acid phosphatase and N-acetyl-glucosaminidase, after a moderate rise at the onset of ischemia, decline below normal levels after 24 hours. The pattern of the changes in particle-bound enzyme activity observed was similar for all four enzymes and was characterized by a progressive decrease reaching the lowest levels after 24 hours. In the contralateral gastrocnemius muscle of operated rabbits changes in activity during the first hours are slight and generally similar for both free and particle-bound fractions, whereas subsequently there is a rise in the activity of soluble enzymes which coincides with a decrease in the particle-bound fraction. These findings suggest that lysosomal enzymes play a role in asphyctic damage to skeletal muscle.

Dissociation in the response of the adenylate cyclase system to thyrotropin and prostaglandin E2 in human thyroid carcinoma tissue

Because the existence of a damaged thyrotropin (TSH) receptor in thyroid tumors may be relevant in the perspective of a correct postsurgical therapy, the effect of TSH on cAMP intracellular accumulation in thyroid carcinoma (N = 16), follicular adenoma (N = 27) and normal tissue (N = 30) slices was studied and compared with that of nonspecific stimulus of thyroid adenylate cyclase‐cAMP system, such as prostaglandin E2 (PGE2). While in all follicular adenomas a normal behavior of basal and post‐TSH and ‐PGE2 stimulated cAMP accumulation was observed, basal cAMP levels were generally higher than in controls in 14 differentiated carcinomas, responses to TSH were reduced or absent, and response to PGE2 was close to normal. On the contrary, in two anaplastic carcinomas, both TSH and PGE2 produced a negligible modification of cAMP levels. Thus, in undifferentiated carcinomas, the adenylate cyclase‐cAMP system seems to be altered; in differentiated carcinomas, the catalytic part of the system appears unaffected as it is PGE2‐responsive. Therefore, some hypotheses are ruled out as an explanation for decreased sensitivity to TSH of differentiated carcinomatous cells.

EFFECTS OF TSH ON cAMP LEVELS AND THYROID HORMONE RELEASE IN HUMAN THYROID‘AUTONOMOUS’NODULES: RELATIONSHIP WITH IODOTHYRONINE AND IODINE CONTENT IN THYROGLOBULIN

The effect of TSH on the adenylate cyclase‐cAMP system and in vitro iodothyronine release, together with the iodothyronine and iodine content of 19s thyroglobulin, were studied in seven clinically euthyroid patients with autonomous thyroid nodules. Basal cAMP and cGMP content together with phosphodiesterase and protein‐kinase activities were normal in nodular, and suppressed in extranodular tissue. TSH‐dependent cAMP accumulation was reduced in nodular tissue, but normal in the suppressed extranodular tissue. In vitro TSH‐dependent iodothyronine release from nodular and extranodular tissue was absent. Thyroxine and iodine content of thyroglobulin extracted from nodular tissue was reduced, while triodothyronine content was normal but with a low T4/T3 ratio. In extranodular tissue T3, T4 and iodine contents were reduced. In conclusion, autonomous thyroid nodules produced a poorly iodinated thyroglobulin leading to preferential T3 secretion with increased circulating free thyroid hormones even in clinically euthyroid patients.

Effect of inhaled histamine on occlusion pressure and breathing pattern in asthmatic patients

In animals, histamine inhalation is known to increase either respiratory frequency or respiratory drive by stimulation of airway vagal sensitive endings. However, it is not well known whether these changes are concomitant in man. In order to elucidate this point, we carried out the present investigation in thirty‐five asthmatic patients who underwent bronchial provocation test by progressively doubling the dose of inhaled histamine. Bronchial reactivity to histamine allowed two populations of patients to be defined: group I with moderate and group II with mild, increased reactivity. In the twenty‐three group I patients, neuromuscular inspiratory drive, assessed by mouth occlusion pressure (P0.1), was found to be significantly increased while no significant changes in breathing pattern were noted. In the twelve group II patients histamine did not modify P0.1 or breathing pattern. However, we were able to separate in group I a sub‐group of ten patients, as with atopic asthma, in which histamine‐induced increase in P0.1 was paralleled by rapid and shallow breathing (RSB). Changes in P0.1 and breathing pattern did not depend on baseline airway calibre. In group I, after bronchoconstriction had been reversed by inhaling a β2‐agonist bronchodilator agent (fenoterol), P0.1 decreased significantly and RSB was found to be reversed; however, these changes were not interrelated. We concluded that: (i) in asthmatics, histamine‐induced increase in P0.1 is not necessarily paralleled by, nor related with, change in breathing pattern and (ii) in atopics a ‘sensitization’ of vagal receptors could account for the concomitance of enhanced P0.1 with RSB.

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. On the other hand the increased specific activity of lysosomal enzymes suggests the hypothesis that the above mentioned modifications and the morphologic alterations of the muscle and of the small blood vessels might be ascribed, at least partly, to a release of lysosomal hydrolases in active form.

TSH-responsive adenylate cyclase activity in thyroid tissue from patients with Graves’ disease

Basal adenylate cyclase activity of thyroid plasma membranes obtained from six patients with Graves’ disease was slightly but not significantly lower than normal (83.3 ± 13.9 pmol cAMP/10 min/mg of protein versus 120.9 ± 19.5 pmol cAMP/10 min/mg of protein). In five of these patients the adenylate cyclase activity was stimulated by bovine TSH with an apparent Km value similar to that of normal thyroid (3.1 ±0.5 × 10−9M versus 3.4 ±0.6 × 10−9M). The response to prostaglandin E2 was also normal. In the sixth patient adenylate cyclase activity was stimulated by prostaglandin Eabut not by bovine TSH. The distribution of basal adenylate cyclase activity in various gradient layers was studied in two TSH-responsive patients. A relative increase of this activity was found in the denser layer when compared to normal thyroid tissue. This could be the expression of an altered ratio between the protein and lipid components of the plasma membranes in patients with Graves’ disease.

Aortic Connective Tissue in Atherosclerotic Aorta— A Biochemical Study

Biochemical analysis of the extracellular matrix of human aortas was per formed on samples of ascending and descending aortas affected by atherosclero sis in comparison with a control group of nonatherosclerotic aortas. Ulcerated or heavily calcified atheromas were excised and excluded from the analysis in order to differentiate biochemical alterations leading to the forma tion of atheromas from those due to complications of already formed athero mas. Our results show that the development of atheromas brings about an exten sive destruction of elastic fibers and muscular cells, and their place is occupied by other components of the extracellular matrix, most notably, collagen, non uronic sugars, water, and lipids, which were found significantly increased.

Amino-oxidase and dermal connective tissue in scoliosis

SummaryThe amino-oxidase and collagen content of dermal tissue was evaluated in 10 patients with severe idiopathic scoliosis and in a control group of 7 patients with poliomyelitic scoliosis, that were to undergo surgical correction of their skeletal deformity. A greater dermal content of neutral salt soluble collagen was found in the patients with idiopathic scoliosis, compared with the control group. Statistically the difference was highly significant. Mono-amino-oxidase activity, however, was found to be significantly decreased in dermal extracts obtained from patients affected by idiopathic scoliosis in comparison with controls. The involvement of mono-amino-oxidase in the crosslinking of collagen and the possible classification of idiopathic scoliosis as a systemic disease of connective tissue are discussed.