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Biomedical subjects

S Rosini

Publications and source records attributed to S Rosini.

At least 37 records · Page 2Linked to original sources
PubMed1989

Rhein reduces proteoglycan loss during the autolytic breakdown of cultured cartilage.

Rhein (R: 1,8-dihydroxy-3-carboxyanthraquinone) is the active metabolite of the drug diacerhein (DAR), an anthraquinone molecule which has recently been proposed for the long-term treatment of osteoarthrosis. In the present study we have examined the effects of rhein, as compared to indomethacin or hydrocortisone, on an in-vitro model of cartilage degradation, represented by the autolytic breakdown of the articular cartilage excised from rabbit knee and cultured for seven days. During this period there is a spontaneous loss of proteoglycans. At the end of the period we measured the amount of proteoglycans which remained bound to the cartilage. The samples treated with R revealed dose-dependent modifications in the amounts of cartilage-bound proteoglycans, with a 40% increase as compared with non-treated samples at the dose of 7 x 10(-5) M. We conclude that R shows a protective effect on the articular cartilage, and that at least a part of the beneficial effect that DAR has shown in the course of clinical trials in osteoarthrosis may be due to direct effects of its active metabolite (R) on cartilaginous tissue.

Animals↗
PubMed1988

Bone and renal components in hypercalcemia of malignancy and responses to a single infusion of clodronate.

Increased bone resorption (BR) and increased renal tubular reabsorption of calcium (TRCa) may both be involved in the pathogenesis of hypercalcemia of malignancy (HM). We have evaluated the relative importance of these two mechanisms in 33 patients with HM after extracellular volume expansion and after single infusion of clodronate (C12MDP: 500 mg iv over 8 h). The fasting urine Ca/creatinine ratio was taken as an index of BR (BRI). An index of TRCa was calculated (TRCaI) from a nomogram based on the relationship between urine Ca excretion per unit of glomerular filtration rate and plasma Ca (PCa). Mean (+/- SEM) PCa fell from 3.29 +/- 0.07 to 2.69 +/- 0.05 mmol/l three days after C12MDP (n = 33, p less than 0.001), a response similar to that obtained with repeated daily iv injections of 500 to 1000 mg C12MDP. The pathogenesis of hypercalcemia varied according to the type of neoplasm. BRI was the highest in multiple myeloma and breast tumors. TRCaI was markedly increased in squamous-cells lung, bladder, kidney and liver carcinomas, reaching levels observed in primary hyperparathyroidism. TRCaI was normal in most cases of multiple myeloma. Breast tumors appeared to be heterogeneous with respect to TRCaI. The fall in PCa in response to a single infusion of C12MDP was usually most marked in cancer patients with elevated BRI and normal TRCaI. It was very modest in patients with high TRCaI and slightly elevated BRI. In conclusion, this study confirms that stimulation of bone resorption is not the only mechanism of the maintenance of hypercalcemia of malignancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Resorption↗
PubMed1987

Aminohexane diphosphonate in the treatment of Paget's disease of bone.

We studied the effects of the intravenous or oral administration of aminohexane diphosphonate (AHDP) in 42 patients with active Paget's disease of bone. Treatment of mouth (400 mg daily for 1 month) or intravenously (25 mg or 50 mg daily for 5 days) induced marked suppression of biochemical indices of disease activity. Urinary excretion of hydroxyproline fell to 39 and 42% of pretreatment values (oral and IV treatments respectively), and was followed by a similar decrease in the serum activity of alkaline phosphatase. In both groups of patients, disease activity remained suppressed for the 6 months of followup, and pain improved in 34 out of 37 patients who had bone pain attributed to Paget's disease. Both biopsies indicated that osteoblast and osteoclast numbers decreased with no adverse effects on mineralization. Neither regime was associated with significant side effects. We conclude that short courses of AHDP provide a promising treatment for the long-term control of Paget's disease.

Administration, Oral↗
PubMed1987

The acute-phase response after bisphosphonate administration.

In patients who have never previously received bisphosphonate therapy, the intravenous administration of 4-amino-1-hydroxybuthilidene-1,1-bisphosphonate (AHButBP), 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (AHPrBP), or 6-amino-1-hydroxyhexylidene-1,1-bisphosphonate (AHHexBP) induced an acute-phase response (APR) irrespective of the underlying disease, manifested by a fall in circulating lymphocyte number and serum zinc concentration and in a rise in C-reactive protein (CRP); a febrile reaction occurred in 30% of the patients. The APR was maximally expressed within 28-36 hours of i.v. administration of the bisphosphonates and disappeared 2-3 days later despite continuous treatment. These effects were dose dependent and the lowest doses necessary for an APR were 10 mg of AHButBP and AHPrBP and 75 mg of AHHexBP. Doses up to 1,000 mg/day i.v. of dichloromethanebisphosphonate (Cl2MBP) were devoid of these side effects. In patients treated with either a single i.v. dose of amino-bisphosphonates which resulted in an APR or with a suboptimal dose, a subsequent challenge 12-160 days later of the high dose failed to cause a rise in CRP or a fall in the lymphocyte count. The desensitization to AHButBP or AHPrBP was also seen following pretreatment with Cl2MBP. These findings suggest that bisphosphonates interact with macrophage-like cells resident in the skeleton and stimulate interleukin-1 release which is responsible for the appearance of the APR. At the same time, however, the bisphosphonates render these cells insensitive to further stimulation for several months.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute-Phase Reaction↗
PubMed1987

Experimental studies on diacerhein: effects on the phagocytosis of neutrophil cells from subcutaneous carrageenan-induced exudate.

Diacerhein (DAR), a new drug which is particularly suitable for the treatment of osteoarthritis, was studied for its interference with the phagocytic capacity of cells coming from exudates of subcutaneous carrageenan oedema and from the peripheral blood of Sprague-Dawley rats. DAR was found to inhibit phagocytosis in both types of cells examined. This finding indicates that DAR may exert its action by means of a direct effect on the cells involved in the inflammatory process.

Animals↗
PubMed1986

Treatment of Paget's disease of bone with intravenous 4-amino-1-hydroxybutylidene-1,1-bisphosphonate.

4-amino-1-hydroxybutylidene-1,1-bisphosphonate (AHButBP) was given intravenously (2.5-25 mg/day for 4 days) to 14 patients with Paget's disease of bone, five of whom had been treated with dichloromethylidene bisphosphonate (C12MBP) 32 months earlier. In the nine patients who had not been treated previously with bisphosphonates, the short course of AHButBP induced a suppression of serum alkaline phosphatase and urinary hydroxyproline values down to 30% of initial values. The biochemical suppression of the disease was sustained for 2-18 months and the time to relapse did correlate to the logarithm of the dose (P less than 0.001). In the five patients previously treated for Paget's disease, an apparent resistance to treatment with AHButBP was observed. However, in these patients both serum alkaline phosphatase and urinary hydroxyproline fell to or even below the nadir values which had previously been achieved with C12MBP, irrespective of the degree of relapse. Thus the degree of suppression of Paget's disease of bone, achievable after treatment with bisphosphonates, seems to be constant for each patient, such that normal levels of serum alkaline phosphatase and urinary hydroxyproline cannot usually be attained in patients with extremely active disease.

Alendronate↗
PubMed1986

Quantitative morphometric evaluation of the inhibitory activity of new aminobisphosphonates on bone resorption in the rat.

Three new bisphosphonates of various chain length, namely, 4-amino-1-hydroxybutylidene-1,1-bisphosphonate (AHBuBP), 5-amino-1-hydroxypentylidene-1,1-bisphosphonate (AHPeBP), and 6-amino-1-hydroxyhexylidene-1,1-bisphosphonate (AHHexBP) were compared with 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (AHPrBP), and dichloromethylene bisphosphonate as to their effect on metaphyseal bone remodeling in the rat. The parameters assessed were growth in length, mineralization, metaphyseal density, mean trabecular diameter, and number of trabeculae. Both metaphyseal density, an index of metaphyseal Ca balance, and number of trabeculae, an index of bone resorption, showed the following sequence of potency: AHBuBP greater than AHPrBP = AHPeBP = AHHexBP greater than Cl2MBP. All compounds decreased trabecular diameter somewhat, an index of bone formation, with AHBuBP decreasing the least. AHBuBP and possibly AHHexBP appear to be interesting new bisphosphonates for future clinical use.

Animals↗
PubMed1985

Dichloromethylene-diphosphonate in patients with prostatic carcinoma metastatic to the skeleton.

A total of 17 patients with multiple osteoblastic bone metastases owing to prostatic carcinoma was treated with 2-dichloromethylene-diphosphonate, a powerful inhibitor of bone resorption. The drug was given intravenously (300 mg.) for 2 weeks and then orally (3,200 mg.) or intramuscularly (100 mg.) for 4 to 11 weeks. A definite improvement in pain, assessed by daily consumption of analgesic drugs and by an analogic scale, was observed within 10 days in 16 of the 17 patients. Four patients confined to bed rest for pain were able to walk after 2 weeks and reversal of paralysis also was noted in 1 patient. Transient changes in serum calcium (decreasing) and alkaline phosphatase (increasing) were observed in most patients. In the 3 patients in whom it was performed, repeated bone scanning showed a partial regression of pathological areas in 2 and the complete disappearance of most pathological areas in 1. Our results suggest that 2-dichloromethylene-diphosphonate may represent an important supportive treatment in patients with bone metastases owing to prostatic carcinoma, providing sustained relief of pain and regression of bone destruction without undesirable side effects.

Adult↗
PubMed1984

Sequential treatment of Paget's disease with human calcitonin and dichloromethylene diphosphonate (Cl2MDP).

Dichloromethylene diphosphonate (Cl2MDP), a powerful inhibitor of bone resorption, was given (daily dose: 500 mg i.v. for 2 months and then 1600 mg p.o.) to five patients with Paget's disease after 8 months treatment with 50-100 MRC u/day of human calcitonin (CT). During treatment with CT plasma alkaline phosphatase (ALP) and urinary hydroxyproline (HOP) levels fell to about 60% of pretreatment values within the first 2 months in all the patients. Cl2MDP therapy resulted in a further drop of urinary HOP to 20% of baseline values, while serum ALP rose impressively during the first 2 weeks of therapy and then slowly fell to 25% of baseline values. We conclude that Cl2MDP can induce a further biochemical response after the so-called plateau phenomenon to CT and that it may represent the therapy of choice for severe Paget's disease.

Aged↗
PubMed1983

[Treatment of hypercalcemia of myelomatous origin with intravenous diphosphonates].

Diphosphonates were administered intravenously to 4 patients with myeloma-induced hypercalcaemia. All patients received EHDP 4.3 mg/kg/day for 3 to 8 days. One of them, whose hypercalcaemia recurred, was later treated with Cl 2 MDP 5 mg/kg i.v. for 8 days. In 2 patients EHDP infusions were followed by EHDP administered orally (5 mg/kg/d) for 3 weeks, after which transiliac bone biopsy was performed. In all patients calcemia fell from 130 +/- 14 to 99 +/- 4 mg/l at the end of the intravenous treatment, with parallel decrease in calciuria. Histomorphometric analysis of the bone biopsies showed few osteoclasts but massive infiltration with plasmocytes. In one case, EHDP probably induced a deficit in mineralization. Intravenous diphosphonates therefore proved to be rapidly effective in the treatment of hypercalcaemia due to malignancy. However prolonged administration of EHDP in high doses is not recommended, as it may result in osteomalacia.

Aged↗
PubMed1977

Anticomplementary properties of 043/63 and 043/13 two new antiinflammatory drugs.

The anticomplementary properties of two indandione derivatives were studied in vitro on fresh human serum and in vivo on rabbits. In vitro the two substances block immunohemolysis and have direct effect on serum complement activity. One substance blocks the activation of the first complement component and the other the fourth complement component. In vivo, single doses, lower or block complement activity of rabbit serum.

Animals↗
PubMed1976

Piromidic acid and its ethylic ester: absorption, distribution, excretion.

The absorption, distribution and excretion of piromidic acid and its ethyl ester were investigated in the rat. When administered orally the ethyl ester was well absorbed and subsequently hydrolysed, giving much higher blood and tissue concentration than a corresponding dose of the parent compound. The antimicrobial activity of urine and bile samples was also investigated.

Animals↗