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Biomedical subjects

A Camporeale

Publications and source records attributed to A Camporeale.

At least 19 recordsLinked to original sources

ZAP-70 is expressed by normal and malignant human B-cell subsets of different maturational stage.

ZAP-70 tyrosine kinase is involved in signalling pathways following T-cell receptor stimulation and was originally described only in T cells and natural killer cells. ZAP-70 expression has been reported in normal mouse B lineage cells and in human malignant B lymphocytes, mainly in chronic lymphocytic leukemia (CLL) where it correlates with clinical outcome. We analyzed several B-cell lines and ex vivo malignant B cells, ranging from acute lymphoblastic leukemia to multiple myeloma and reflecting different stages of B-cell differentiation, and they showed ZAP-70 expression regardless their maturation stage. We then analyzed by Western blot and flow cytometry different human normal B-lymphocyte subpopulations: naïve, germinal center and memory B cells from tonsils, CD19+ CD5+ cells from cord blood and CD19+ lymphocytes from peripheral blood. All expressed ZAP-70 protein, though at different levels depending on their differentiation, activation and tissue localization. In addition, ZAP-70 expression levels could be modulated following stimulation via the B-cell receptor. These findings implicate a potential role of ZAP-70 in the signalling pathway of B lymphocytes at different maturational stages, indicate that ZAP-70 expression is not a CLL-specific feature among B-cell malignancies and suggest that the absence of ZAP-70 rather than its presence should be considered abnormal for malignant B lymphocytes.

Antigens, CD↗

Differential effects on CLL cell survival exerted by different microenvironmental elements.

Selected microenvironmental stimuli confer to leukemic cells a growth advantage and an extended survival. We aimed at dissecting the differential support provided by the different cellular components of the microenvironment where CLL cells accumulate. To this end we cultured purified CLL cells in vitro in the presence or absence of different accessory cells (stromal cells, autologous T lymphocytes) and/or soluble molecules (IL-4, sCD40L) and assessed the leukemic cell response in terms of cell viability and chemoattracting capacity. The results indicate that both T lymphocytes and stromal cells are involved in sustaining the survival of leukemic B cells, but indicate that their support is different in terms of time of onset and duration. T cells have a short-term support activity while stromal cells provide long-term support.

B-Lymphocytes↗

Importance of premeal injection time in insulin therapy: Humalog Mix25 is convenient for improved post-prandial glycemic control in type 2 diabetic patients with Italian dietary habits.

We investigated the use, in a short period, of Humalog Mix25 (Mix25) in a twice-daily administration regimen compared to a twice-daily injection therapy with Humulin 30/70 (30/70) in diabetic patients with Italian dietary habits. We studied 33 type 2 diabetic patients aged 59.1 +/- 8.1 years, BMI 29.8 +/- 2.7 kg/m2, duration of diabetes and insulin therapy of 14.4 +/- 9.8 and 4.2 +/- 4.6 years, respectively. After a 4-day lead-in period of twice-daily human insulin 30/70 treatment, patients were randomized to one of two treatment sequences: (1) a twice-daily regimen with Mix25 just 5 minutes before the morning and evening meals for 12 days, followed by a twice-daily therapy with human insulin 30/70 given 30 minutes before the morning and evening meals for an additional 12 days; or (2) the alternate sequence. Each patient underwent a mixed meal test: Humulin 30/70 was administered 30 minutes before the meal, while Mix25 was given 5 minutes before. The 2-hour post-prandial glucose concentration after breakfast was significantly lower during treatment with Mix25 than with Humulin 30/70 (157 +/- 43.2 vs. 180 +/- 43.2 mg/dl, p<0.05). The glycemic excursion after dinner on Mix25 treatment was significantly lower than with Humulin 30/70 (12.2 +/- 48.01 vs. 35.5 +/- 36.92 mg/dl, p<0.05). AUCglucose after Mix25 was lower than after Humulin 30/70. Glycemia after test meal was significantly lower with Mix25 than with Humulin 30/70. Insulin and free insulin concentrations after the test meal were significantly higher with Mix25 in comparison to Humulin 30/70. AUC serum insulin and free insulin curves after Mix25 were significantly higher than after Humulin 30/70 (p=0.028 and p=0.005, respectively). Twice-daily injections of Humalog Mix25, compared to human insulin 30/70 in type 2 diabetic patients with Italian dietary habits, provide improved and lasting post-prandial glycemic control, with the great convenience of the injection just before the meal.

Biphasic Insulins↗

Age-related decline of bone mass and intestinal calcium absorption in normal males.

Although about 25% of all hip fractures occur in men, little is known about the pattern of their age-related bone loss and its main determinants. The aim of this cross-sectional study was to evaluate the age-related changes of intestinal calcium absorption, bone mass, and bone turnover in normal men. In 70 normal males (age 17-91 years), we measured spinal and forearm bone density (FBD) (by DXA), fractional intestinal calcium absorption (by oral test), serum immunoreactive parathyroid hormone (PTH), dietary calcium intake (diet records), biochemical markers of bone turnover (serum alkaline phosphatase (ALP), osteocalcin, urine calcium, creatinine, and hydroxyproline), and 1,25(OH)2D3 serum levels. Vertebral bone density (VBD) showed a modest decline before age 50 and a greater decline after age 50, whereas FBD presented a significant decrease with advancing age starting at age 40, suggesting a predominant age-related cortical bone loss. Intestinal calcium absorption (47CaFA) and serum 1,25(OH)2D3 also presented an age-related decline similar to FBD. Simple correlation analysis revealed that age was significantly related to 47CaFA (r = 0.60), calcium intake (r = 0.32), VBD and FBD (r = 0.79 and 0.63, respectively), serum 1,25(OH)2D3 (r = 0.69), and serum iPTH (r = 0.72). No significant correlation was found between age and biochemical markers of bone remodeling. Partial correlation and stepwise variable selection analyses, using 47CaFA and bone mass as dependent variables, showed that in normal males, serum 1,25(OH)2D3 and dietary calcium intake were the main contributors (64%) to 47CaFA variability, whereas only age accounted for 63% of VBD and age and dietary calcium accounted for 45% of FBD variability. These results indicate that bone loss in men accelerates after age 50 years and that among other factors, intestinal calcium malabsorption and 1,25(OH)2D3 serum levels play a role.

Adolescent↗

Acute biochemical variations induced by two different calcium salts in healthy perimenopausal women.

Despite the potential utility of calcium supplementation and the availability of many calcium supplements in the market, there are few data concerning the absorbability of different calcium salts in different conditions. We have compared the acute metabolic responses following oral administration of calcium citrate (CC) or calcium gluconolactate and carbonate (CGC) given to 20 healthy perimenopausal women (aged 48-55 years). Ten women received two effervescent tablets of CC (each containing 500 mg of calcium) and 10 women received two effervescent tablets of CGC (each containing 500 mg of calcium). Before and on an hourly basis for 6 hours, serum total and ionized calcium, phosphate, and immunoreactive parathyroid hormone (iPTH) were measured. Urinary calcium and creatinine were also measured. Both calcium salts induced significant increase in serum total and ionized calcium and in urinary calcium excretion; they also significantly reduced circulating levels of iPTH. The analysis of ionized calcium and iPTH response curves to CC and CGC administration revealed a significantly greater bioavailability of CC compared with CGC. Our data suggest that CC could be prefered to CGC for its characteristics of absorbability and bioavailability.

Calcium↗

Management of osteoporosis and Paget's disease. An appraisal of the risks and benefits of drug treatment.

Osteoporosis is a major public health problem occurring primarily among the postmenopausal population. Osteoporosis is a preventable disease, but despite several advances in its prevention, treatment of the established disease to date remains a major challenge to be managed by primary care physicians. Stabilisation of bone mass and prevention of falls are of paramount importance in any therapeutic programme for osteoporotic patients with established vertebral fractures. Drug therapy for osteoporosis can be divided operationally into 2 main categories: those that inhibit bone resorption, and thus reduce bone turnover, and those that stimulate bone formation, exerting an anabolic effect. Therapeutic agents that inhibit bone remodeling would appear to be best suited to those patients with high turnover osteoporosis (about 30%). Included in this category are calcium, vitamin D and its metabolites, gonadal steroids, calcitonin, ipriflavone and bisphosphonates. Although estrogen replacement therapy has been proven to be effective in older females, calcitonin appears to be the treatment of choice for this population since it stabilises or increases bone mass and also has reported analgesic properties. Drugs that stimulate bone remodeling or bone formation would be best suited to patients with low turnover osteoporosis (about 70%). The agent in this class that is widely used is sodium fluoride. New therapies include intermittent injections of synthetic parathyroid hormone, and cyclic bisphosphonates to activate then depress resorption and formation. Any attempts to stabilise the skeleton with any drug regimen must be accompanied by an adequate calcium supply, i.e. 1200 to 1500 mg/day). The theoretical basis of tailoring treatment for osteoporosis to the underlying histology has not yet been fully proven, but there is increasing experimental support to this approach. Drugs that inhibit bone turnover, such as calcitonin, appear to be effective in increasing bone mass for 1.5 to 2 years, about the time it would take to replenish the remodeling space in a patient with high turnover osteoporosis. In contrast, although bone mass appears to increase for as long as 5 years in patients treated with sodium fluoride, there has been no consistent reduction in occurrence of vertebral or hip fractures. Paget' disease of bone is a focal disorder of the skeleton characterised by excessive resorption and subsequently disorganised formation of bone. The aetiology of the disease is unknown. Paget's disease may be mono-ostotic or polyostotic; pain and bone deformities due to enlargement of skeletal segments represent the main clinical aspects. However, in many patients the disease may be asymptomatic.(ABSTRACT TRUNCATED AT 400 WORDS)

Bone Development↗

Trends in the incidence of hip fracture in Siena, Italy, from 1980 to 1991.

There is general agreement that the crude incidence of proximal femur (hip) fractures is rising in conjunction with the ageing of the underlying population. To explore possible changes in hip fracture incidence over time we analysed all femoral fractures occurring in the county of Siena from 1980 to 1991. Data were collected from hospital record charts of the Department of Orthopaedics, recording all hip fractures occurring during the 12-year period. In this period, the mean resident population in Siena was 238,369 inhabitants (aged 0 to 90+ years) and the crude number of all femoral fractures was 2,238. However, in calculating incidence rates, only hip fractures occurring in the population aged over 50 years were considered. In this population, the number of hip fractures was 1,825 with a male/female ratio of 1:2.8. A time-series data analysis (temporal trend) of the incidence of hip fracture during the 12-year period revealed a linear and significant (p < 0.001) trend to increase, but only in males, with an annual increasing rate of 3.62 per 100,000 person-years. In the female population, the temporal analysis did not show any significant trend during the observation period.

Adolescent↗

Hip fracture in Italy: epidemiology and preventive efficacy of bone-active drugs.

In this paper we report the results on the epidemiology of hip fracture and the preventive efficacy of bone-active drugs in Italy, observed in men and women aged 50 years or over, recruited in the three Italian centres participating in the Mediterranean Osteoporosis Study (MEDOS), namely Parma, Rome, and Siena. The number of fractures observed was 1,437 in a catchment area population of 847,508 individuals, with a total incidence of 169.6/100,000--a female-to-male ratio of 3.5 and a doubling-time of about 5.5 years. The female excess becomes evident in the age groups over 60 years. The mean age of fractures was 77 years in females and 73 in males. From the data collected, the estimated number of fractures per year in the Italian population aged over 50 years is 32,000. The pattern of use and the preventive efficacy of bone-active drugs was examined in women. Calcitonin and calcium were the drugs mainly used; less than 3% had taken vitamin D or oestrogen and only a minor percentage had taken anabolic steroids. Fluorides were not used at all. As seen in the European sample, the protective effect of calcium and calcitonin is statistically significant even in Italy, while vitamin D is not. The use of anabolic steroids was associated with a decrease in risk. Oestrogen administration does not seem to reduce the relative risk of hip fracture in Italian women, probably due to the small sample size.

Aged↗

Long-term treatment with calcitonin in osteoporosis.

Many studies have shown that calcitonin has beneficial effects on the clinical and biological disturbances of diseases characterized by an excessive bone remodelling. Several controlled clinical studies have shown that long-term calcitonin treatment, given by parenteral or intranasal routes, exerts a beneficial positive effect on bone mass and bone turnover in established postmenopausal osteoporosis. Calcitonin therapy is particularly indicated for patients with high turnover osteoporosis where results show a net gain of bone mineral in the axial skeleton and a slowing of bone loss in the appendicular bones. Recently, calcitonin was shown to induce a significant reduction in postmenopausal osteoporotic vertebral fractures. Due to receptor down-regulation a resistance to the hormone may occur after 12-18 months of continuous treatment. Reported results of long-term calcitonin treatment demonstrated that it is possible to delay or to avoid the "resistance" to calcitonin by the cyclical or discontinued administration of the hormone.

Bone and Bones↗

[The evaluation of the antiarrhythmic activity of L-carnitine and propafenone in ischemic cardiopathy].

In order to evaluate a possible antiarrhythmic action of L-carnitine (C) in ischemic heart disease, 30 patients (20 males, 10 females, average age 64 years +/- 11) with ischemic heart disease who at examination with 24-hour dynamic ECG showed extrasystolic ventricular multifocal arrhythmia with a mean hourly rate of > 300 were randomized into three groups, the first of which was given a daily oral dose of 6 g C in three divided doses; groups 2 and 3 were given propafenone (P), 900 mg daily in three divided doses. After one week, all patients were again submitted to 24-hour dynamic ECG after which treatment was continued for another week as follows: group 1 continued on C (6 g daily), group 2 continued on P (900 mg daily), group 3 continued on P (900 mg daily) plus C (6 g daily). At the end of the second week, a further 24-hour ECG was performed the results of which showed that L-carnitine can significantly reduce the antiarrhythmic activity of the ischemic myocardium. In addition, at the end of the second week, a further significant reduction of the number of premature beats compared to the first week was found in patients for whom L-carnitine had been added to propafenone treatment.

Aged↗

Short-term treatment of Paget's disease of bone with ipriflavone.

Ipriflavone (IP), an isoflavone derivative, seems to prevent the loss of bone mass through the inhibition of bone resorption, mainly inhibiting the recruitment of osteoclasts. We investigated whether a brief course of treatment with IP can reduce biochemical parameters of accelerated bone turnover and bone pain in patients with active Paget's disease of bone. Sixteen patients (9 males and 7 females) with active Paget's disease were randomly allocated to two different crossed-over dose regimens of treatment with IP (600 mg/day vs. 1200 mg/day). Each treatment course lasted 30 days and the wash-out period between the two sequences was 15 days. Serum alkaline phosphatase (Al.Ph.) and urinary hydroxyproline/creatinine excretion (HOP/Cr) were reduced after each sequence. At the end of the 600/1200 mg/day treatment sequence, serum Al.Ph. and HOP/Cr decreased with 32% and 25.6% respectively. At the end of the 1200/600 mg/day treatment sequence, serum Al.Ph. and HOP/Cr decreased with 33% (P < 0.01) and 24.1% (P < 0.05) respectively. Furthermore, a significant decrease in bone pain was observed during the 1200/600 mg/day sequence (P < 0.01). Both treatment schedules were well tolerated and the patients' compliance resulted excellent. Our results indicate that short-term treatment with IP can reduce biochemical parameters of disease activity and bone pain in patients with active Paget's disease of bone.

Administration, Oral↗

Use of calcitonin in the treatment of bone pain associated with osteoporosis.

In osteoporosis, calcitonin exerts an analgesic effect that is unrelated to its effect on bone. Although the precise mechanism has yet to be clarified, there is some evidence that the analgesic effect of calcitonin may be mediated through the endogenous opioid system. The intranasal administration of calcitonin seems to be more effective in producing analgesia than parenteral administration.

Bone and Bones↗

Calcitonin and estrogens.

Estrogen deficiency is thought to be the main factor leading to postmenopausal osteoporosis (PMO). A role for calcitonin (CT) has been proposed as mediator of estrogen action on bone, and therefore, as pathogenetic factor of PMO. However, this hypothesis is still controversial. To further analyze the relationships between estrogens and CT in PMO, we studied the effects of one-year estro/progesterone therapy on CT secretory reserve, evaluated by a calcium infusion test in 12 postmenopausal women, as compared to 12 placebo treated subjects. In the hormone treated group, blood levels of CT showed a progressive increase during the study and a plateau was reached at 9 months, indicating that CT production achieved a new steady state. Hormonal therapy also significantly improved the CT response to calcium stimulation test. A concomitant increase of vertebral bone mass was observed in the hormone treated women, who also maintained initial bone density of femoral dyaphyses. On the contrary, the placebo treated group continued to lose bone mineral at both sites. Our study demonstrates that estrogens regulate CT secretion in postmenopausal women; thus, CT may be considered a mediator of estrogen action on bone.

Bone and Bones↗