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.

[Effect of thermal mud baths on normal, dry and seborrheic skin]. / Effetti dell'uso di un fango termale su cute normale, secca e seborroica.

PURPOSE: To investigate the curative effects of thermal water and thermal muds in various cutaneous pathologies. PATIENTS AND METHODS: Modifications of phmetry and sebometry using sulphur thermal muds in normal, dry and seborrheic skin have been studied. The three groups of patients have been submitted to a 14 day treatment with thermal muds. RESULT: The application of thermal mud normalized the value of cutaneous pH and sebometry. CONCLUSIONS: These beneficial effects are long-lasting in individuals who have a prolonged treatment with thermal muds.

[Effect of sulfur salt-bromine-iodine thermal waters on albumin and IgA concentrations in nasal secretions]. / Effetti indotti dalle acque termali sulfuree-salso-bromo-iodiche sulle concentrazioni di albumine e IgA secretorie del secreto nasale.

In chronic rhinopharyngotubaric phlogoses, the key pathogenic element sustaining phlogosis is a persistent modification of the biological, rheological features of the nasal mucus. For centuries sulphurous thermal waters have proved effective in clinically curing such phlogoses. In order to evaluate the effect of such sulphurous-salty-bromic-iodic thermal waters a randomized, double blind study was undertaken on a sampling of 50 patients. The effect such waters have on secretory IgA (sIgA) and albumin in the nasal secretions was tested against a placebo made of distilled water. Using the method of radial immunodiffusion, the response in the IgAs (mg/l) and albumin (mg/dl) concentrations in the nasal secretions was measured for 25 patients treated with the thermal waters and 25 patients treated with distilled water. The average concentrations were statistically compared using the Student t-test for paired samples. A significant increase (p < 0.0001) was seen in the mean IgAs concentration in the patients treated with the thermal waters. On the other hand, there was a weak, not statistically significant increase in the same data mean for the group treated with distilled water. The average increase in the albumin concentration in the nasal secretions proved significant in both cases although the significance was much more marked in the group treated with the thermal waters (p = 0.001) vs. the placebo group (p = 0.039).

Effective treatment of osteoarthritis with a 150 mg prolonged-release of diclofenac sodium.

A new oral dosage form of diclofenac sodium, enabling the single administration of the daily dose of 150 mg, has been tested for treatment of 20 patients suffering from osteoarthritis of the spine. A control group of 20 patients with the same diagnosis instead received 3 enteric-coated tablets/day, each containing 50 mg of the drug. Treatments lasted in both groups one month. Clinical efficacy was monitored by evaluating the changes in the disease's symptoms and signs (pain, cramps, alterations of function capacity, morning stiffness) and in some laboratory parameters (ESR, C-reactive protein, Rheuma test). Treatment tolerability was evaluated through the routine laboratory blood and urine tests, and by registering any complaint at the gastrointestinal level, as well as any adverse event. The two posology schemes were equally effective in favourably reducing the disease's clinical and laboratory manifestations. Also systemic and local tolerability were superimposable and on the whole good: only a few episodes of mild epigastralgia were reported (3 cases in each group), as expected during a treatment course with NSAIDs.

Neural respiratory drive and neuromuscular coupling during CO2 rebreathing in patients with chronic interstitial lung disease.

In 12 patients with CILD and 18 age-matched normal subjects we assessed the ventilatory control system at three levels: (a) neural, as assessed by EMGd (XP/Ti) and EMGint muscles via surface electrodes; (b) muscular, as assessed by mouth occlusion pressure (P0.1); and (c) ventilatory, as assessed by both ventilation (VE) and the related parameters, tidal volume (VT) and respiratory frequency (f). Compared with a normal control group, patients exhibited a significant decrease in lung volumes and in MIP; VT and inspiratory time (Ti) were significantly lower, while VT/Ti, P0.1, and both EMGd and EMGint were significantly greater in patients. During a CO2 rebreathing test, patients exhibited significantly greater EMGd, EMGint, and P0.1 responses to increasing PETCO2 than the control group. VE response slopes were similar in the two groups. For a given EMGd response slope (delta XP/Ti/delta PETCO2), the average P0.1 response slope (delta P0.1/delta PETCO2) was found to be significantly lower in patients than in the normal control group. Compared with normal subjects, CILD patients have a normal or increased neural component of respiratory activity and relatively low neuromuscular coupling (delta P0.1/delta XP/Ti). The decreased neuromuscular coupling could be explained in these patients by a reduced inspiratory muscle strength.

Control of breathing in patients with short-term primary hypothyroidism.

In 8 patients (3 men and 5 women) with short-term primary hypothyroidism before and during replacement therapy, and in an age-matched control group (9 men and 7 women), we assessed maximal inspiratory muscle force (Pimax) and the ventilatory control system at neural (EMG), muscular (P0.1), and ventilatory (VE and Vt/Ti) levels. While hypothyroid, patients exhibited a significantly lower Pimax. During a CO2 rebreathing test, hypothyroid patients exhibited similar diaphragmatic electromyographic (EMGd) and ventilatory (VE) response slopes to increasing end-tidal CO2 tension (delta EMGd/delta Pet CO2 and delta VE/delta PetCO2), but significantly less delta P0.1/delta PetCO2 (p less than 0.05) and delta(Vt/Ti)/delta PetCO2 (p less than 0.05) response slopes. During replacement therapy with L-triiodothyronine (L-T3), Pimax (p less than 0.05), delta P0.1/delta PetCO2, and delta(Vt/Ti)/delta PetCO2 response slopes were found to be significantly increased (p less than 0.05 for both) while neither EMGd nor VE response changed significantly. We concluded that short-term hypothyroidism does not seem to be associated with blunted neural inspiratory output (EMGd), the respiratory control system seems to be affected mostly at a peripheral (muscular) level, and L-T3 increases both force (P0.1 and Pimax) and velocity (Vt/Ti) of inspiratory muscle contraction.

Changes in neural drive (EMGd) and neuromuscular coupling during histamine-induced bronchoconstriction in patients with asthma.

This study was undertaken in order to assess the neural drive to the respiratory muscles and the inspiratory neuromuscular coupling in patients with bronchial asthma during histamine-induced bronchoconstriction. Bronchoconstriction was produced in a graded fashion, with histamine phosphate aerosol of increasing dose, in twelve asymptomatic asthmatic patients and was measured by FEV1. Inspiratory drive was measured by electromyographic activity of the diaphragm (EMGd) and the coupling of the neural drive to the respiratory muscles was assessed by the relationship of mouth occlusion pressure (P0.1) to EMGd. During the test we also measured electromyographic activity of the inspiratory intercostal (EMGint), sternomastoid (EMGsm) and expiratory abdominal (EMGab) muscles. Histamine caused a significant decrease in FEV1, a significant increase in P0.1, EMGd, EMGint, and a relevant increase in EMGsm, with no substantial increase in EMGab. An inverse significant relationship between the change in FEV1 and changes in P0.1, EMGd and EMGint and a significant correlation between the change in FEV1 and in the P0.1/EMGd ratio were observed. We conclude that a progressive increase in bronchospasm is accompanied by a progressive increase in respiratory neural drive and decrease in neuromuscular coupling. This could be caused both by an increase in lung volume and a lack of abdominal expiratory muscle recruitment.

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 beta 2-agonist bronchodilator agent (fenoterol), P0.1 decreased significantly and RSB was found to be reversed; however, these changes were not interrelated. We concluded that: in asthmatics, histamine-induced increase in P0.1 is not necessarily paralleled by, nor related with, change in breathing pattern and in atopics a 'sensitization' of vagal receptors could account for the concomitance of enhanced P0.1 with RSB.

Aortic connective tissue in atherosclerotic aorta--a biochemical study.

Biochemical analysis of the extracellular matrix of human aortas was performed on samples of ascending and descending aortas affected by atherosclerosis 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 formation of atheromas from those due to complications of already formed atheromas. Our results show that the development of atheromas brings about an extensive 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.

Effects of histamine and reproterol inhalation on mouth occlusion pressure in patients with bronchial asthma.

Both vagal and non-vagal afferences from the lung or chest wall contribute to increasing neural drive to the respiratory muscles, but only the former are known to change the breathing pattern by increasing respiratory frequency (RF) during bronchoconstriction. In order to evaluate the relative contribution of vagal and non-vagal afferences to increasing neural drive to the respiratory muscles in 14 asymptomatic asthmatic patients known to be responsive (decrease in FEV1 greater than 20% of the control values) to previous bronchial provocation test (BPT) with aerosolized histamine, we evaluated FEV1, breathing pattern and neuromuscular drive, as assessed by mouth occlusion pressure (PO.1), under control conditions, during BPT with progressive doubling doses of inhaled histamine (H) and 5 min after inhalation of a bronchodilator agent (Reproterol) (B). During HBPT FEV1 exhibited a significant decrease (p less than 0.01) while PO.1 was found to increase significantly (p less than 0.01). However, no significant changes were noted in breathing pattern. After B FEV1 returned to control values while PO.1, even if significantly reduced (p less than 0.01), did not. Changes in PO.1 were found to be significantly related to changes in FEV1 both during HBPT and B (p less than 0.05). The data suggest that in these patients non-vagal afferences, linked to the abnormalities of thoraco-pulmonary mechanics, could play a major role in changing neural drive to the respiratory muscles.

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.

Thyroid hormone receptors in human cultured fibroblasts: evidence for cellular T4 transport and nuclear T3 binding.

In cultured normal human skin fibroblasts specific and saturable binding sites for triiodothyronine (T3) have been revealed. In fact radiolabelled T3 binds rapidly to intact cells with maximum uptake after 1 hour, while nuclear binding is delayed, the equilibrium being reached after 2 hours. In intact cells it is possible to identify a single binding site for 125I-T3, with a Ka = 1.8 X 10(10)M-1 and Ro = 1.25 X 10(-11)M, similarly in nuclei it was possible to identify a single binding site of Ka = 8.8 X 10(9)M-1 and Ro = 2.3 X 10(-11)M. Intact human fibroblasts take up thyroxine (T4) even more rapidly than T3, with maximum after 5 min, showing a lower affinity for T4 than for T3 and a negligible specific and saturable binding sites for T4, the presence of a cellular transport system for T4 may be hypothesized, considering that iodothyronine cellular binding is increased by preincubation with low doses of T4.

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 triiodothyronine 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.

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.

Thyrotrophin-responsive adenylate cyclase activity in thyroid toxic adenoma.

The adenylate cyclase system was studied in hyperfunctioning autonomous nodules in comparison with normal thyroid tissue. The basal, TSH- and NaF-stimulated adenylate cyclase activities were tested in purified plasma membrane preparations. Basal enzyme activity in membranes from hyperfunctioning nodules was variable and the response to TSH was either normal, low or absent. The present study demonstrates that an intact adenylate cyclase activity, hyporesponsive to TSH, may exist in the cell membrane of the adenoma.

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 X 10-9 M versus 3.4 +/- 0.6 X 10-9 M). The response to prostaglandin E2 was also normal. In the sixth patient adenylate cyclase activity was stimulated by prostaglandin E2 but 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.

Plasma proinsulin-like components and insulin in chronic liver disease.

In order to explain the increase of total IRI frequently observed at basal status, and after glucose administration, in patients with chronic liver disease, plasma proinsulin-like component and insulin levels have been studied in fourteen patients with liver cirrhosis associated or not with clinical or subclinical diabetes mellitus. A significative increase of plasma insulin was observed at basal status and after a glucose load not only in subjects with clinical or subclinical diabetes but also in those patients without carbohydrate abnormalities. This increase is apparently not correlated to any clinical characteristic and is associated in fasting and after glucose load with increased proinsulin-like component levels especially in patients with clinical or subclinical diabetes.

Amino-oxidase and dermal connective tissue in scoliosis.

The 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 souble 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.