Hormone replacement therapy in women with angina with normal coronary arteriograms. Pathogenetic or symptomatic therapy?
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Angina Pectoris↗
Biomedical subjects
M Fini
Publications and source records attributed to M Fini.
How progestins influence the cardiovascular effect of hormone replacement therapy.
Hormone replacement therapy aims to protect against osteoporosis and alleviate fastidious menopausal symptoms such as hot flushes, depression, sleep disturbances and vaginal dryness. In view of the acknowledgement of estrogen deficiency as a major trigger for the acceleration of cardiovascular risk after menopause, hormone replacement therapy may also be proposed as a substantial beneficial cardioprotective agent. The effects of progestins on lipoprotein profile and vasomotor tone are dependent on the chemical structure and the scheme of administration of progestins, with androgenic progestins and cyclical therapy having a potential detrimental effect. Prospective primary and secondary prevention studies, however, suggest that the adjunct of non-androgenic progestins to estrogen therapy is at least as effective as estrogen replacement therapy in reducing cardiovascular mortality and morbidity. Data from recent randomized secondary prevention studies have to be viewed with caution.
Animals↗
Pericellular partial oxygen pressure (pO2) measurement in osteopenic bone-derived osteoblast cultures.
In order to achieve further information on the in vitro behaviour of osteoblasts derived from osteopenic bone, in the present study comparative measurements of some parameters of cell proliferation, metabolism and differentiation and also of the pericellular partial oxygen pressure (pO2) were performed on normal and osteopenic bone derived osteoblasts from heathy and osteopenic rats. The respiration rate was increased in osteoblasts derived from osteopenic bone as compared to normal cells at 48 hours and 7 days, involving a significant decrease in pericellular pO2 in the culture medium. At 48 hours, in osteopenic bone-derived cells, a significant increase in MTT and a significant decrease of osteocalcin were observed. At 7 days, cell count highlighted a significant slowing down of the proliferation of osteopenic bone-derived osteoblasts. No significant differences were observed for alkaline phosphatase activity, nitric oxide and type I collagen production. The present preliminary results may be taken into consideration also in in vitro comparative biocompatibility or osteointegration studies of biomaterials in normal and osteopenic bone-derived cells because a decrease in pericellular pO2 in these tissue cultures could influence results on material behaviour.
Animals↗
Low-power diode laser stimulation of surgical osteochondral defects: results after 24 weeks.
The purpose of this study was to evaluate osteochondral lesions of the knee, treated intraoperatively with low-power laser stimulation, and assess results at 24 weeks. Surgery was performed under general anesthesia on six rabbits; a bilateral osteochondral lesion was created in the femoral medial condyles with a drill. All of the left lesions underwent immediate stimulation using the diode Ga-Al-As laser (780nm), whereas the right knees were left untreated as control group. After 24 weeks, the explants from the femoral condyles, either treated employing laser energy or left untreated, were examined histomorphometrically. Results obtained on the lased condyles showed good cell morphology and a regular aspect of the repaired osteocartilaginous tissue.
Animals↗
Bone tissue cultures: an in vitro model for the evaluation of bone defect healing after L-arginine and L-lysine administration.
The development of new therapeutic strategies and innovative biomaterials for the muscoloskeletal system, stresses the need for researchers to have reliable, easy, less time-consuming and ethical experimental models. The aim of the present study was to characterise an in vitro model of cultured rat femora and test the possibility of using this model in dynamic studies on bone healing. 24 femurs were explanted after 12 rats were killed for other experimental protocols. A standard bone defect was created in the distal femoral condyles and femurs were cultured in GBJb medium. Arginine and lysine were administered daily in the Arg-Lys group. The other femurs were left untreated (Control group). At 1, 7, 14 and 21 days, alkaline phosphatase activity, nitric oxide and calcium were measured on the supernatant. At 21 days, femurs were embedded in polymethylmethacrylate for histomorphometry and microhardness evaluation of the newly formed bone. The current results showed that it was possible to study bone healing in vitro by using cultured bones from adult animals. A process for bone healing was observed also in untreated bones. Moreover, the structural analysis of the cultured bone showed that it had characteristics similar to those of the femurs, when they were embedded in resin immediately after animal sacrifice. The effect of Arg and Lys confirmed data of a previous study, where a faster healing of bone defect and fracture was observed in rabbits after Arg and Lys administration.
Alkaline Phosphatase↗
Biocompatibility and osseointegration in osteoporotic bone.
We implanted nails made of titanium (Ti6Al4V) and of two types of glass ceramic material (RKKP and AP40) into healthy and osteopenic rats. After two months, a histomorphometric analysis was performed and the affinity index calculated. In addition, osteoblasts from normal and osteopenic bone were cultured and the biomaterials were evaluated in vitro. In normal bone the rate of osseointegration was similar for all materials tested (p < 0.5) while in osteopenic bone AP40 did not osseointegrate (p < 0.0005). In vitro, no differences were observed for all biomaterials when cultured in normal bone-derived cells whereas in osteopenic-bone-derived cells there was a significant difference in some of the tested parameters when using AP40. Our findings suggest that osteopenic models may be used in vivo in the preclinical evaluation of orthopaedic biomaterials. We suggest that primary cell cultures from pathological models could be used as an experimental model in vitro.
Alloys↗
Internal contamination of a 2-component implant system after occlusal loading and provisionally luted reconstruction with or without a washer device.
BACKGROUND: Microbial internal contamination of oral implants has been suggested as being responsible for inflammatory infiltration of peri-implant tissues at the fixture-abutment interface of 2-stage and 2-component implant systems; it is also considered as a potential source of pathogens. The present in vivo study evaluated contamination of the inner abutment-implant retaining screw, after occlusal loading and provisionally-luted reconstruction with or without a washer device. METHODS: Eight 2-component oral implants sealed with an o-ring silicon washer device and 9 without a seal were placed in 7 patients with high oral hygiene standards. Two months after prosthetic reconstruction, crowns and internal screws were removed, and organic and inorganic screw contamination was examined by scanning electron microscopy and energy dispersive x-ray spectroscopy (EDS) analysis. RESULTS: An amorphous and crystalline contamination, suggestive of calcium and phosphate compounds, was seen on all screw surfaces. Microbial contamination was more frequently observed in the unsealed group. No differences in bacterial morphotypes were observed between the sealed and unsealed implants. Cocci were the most representative morphotypes, while rods were seldom seen. CONCLUSIONS: In clinical situations, leakage occurs at the implant-abutment interface, although bacterial contamination is limited in patients with high oral hygiene standards. Contamination may be reduced by using a washer device.
Analysis of Variance↗
An elevated number of differentiated osteoblast colonies can be obtained from rat bone marrow stromal cells using a gradient isolation procedure.
Bone marrow stromal cells (BMSCs) for osteoblast differentiation studies can be obtained by gradient isolation techniques or by directly plating a filtered cell suspension. We compared these two procedures to evaluate whether this step is critical in order to obtain a high number of differentiated colonies. Isolated primary rat BMSCs were cultured in vitro with or without insulin-like growth factor II (IGFII), basic fibroblast growth factor (b-FGF), epidermal growth factor (EGF) or transforming growth factor beta 1 (TGF beta 1), and histochemically and biochemically analysed at different time points. The gradient procedure produced a significantly higher number of colonies capable of osteoblastic differentiation. The growth factors had different effects. In particular, b-FGF and EGF significantly increased the number of Alizarin red S positive colonics, while IGFII and TGF beta I exerted inhibitory effects. Nodules obtained on day 21 showed some alkaline phosphatase positive cells and were Von Kossa-positive. These data demonstrate that more differentiated colonies are obtainable from BMSCs isolated by the gradient procedure.
Alkaline Phosphatase↗
Evaluation of systemic metal diffusion after spinal pedicular fixation with titanium alloy and stainless steel system: a 36-month experimental study in sheep.
It is known that titanium alloys cause more extensive local metallosis due to fretting corrosion than stainless steel implants. The aim of the present study was to investigate possible systemic metal releases (Ti, Al, V, Cr, Ni) in sheep where L4-L5 were implanted with titanium alloy (Ti6Al4V, ASTM F 136) and stainless steel (AISI 316 L). 16 sheep were used: 8 were implanted with Ti6Al4V and 8 with stainless steel. At 6, 12, 24 and 36 months, the following examinations were performed: histology, atomic absorption spectrophotometry (AAS) and scanning electron microscopy (SEM), on liver, lung, kidney, brain, spleen and lumbo-aortic lymph nodes. Hair, urine and arteria blood samples were also analysed by AAS before implantation and at sacrifices. A histologic and ultrastructural study was performed on peri-implant tissues, too. Particular attention was paid to avoid contamination from dissection instruments or use of containers. In basal and in samples at 6 and 12 months, no metals were found in blood, urine, hair or other target tissues of the animals implanted with either Ti6Al4V or stainless steel. Regarding Al, V, Co and Ni, negative results in all tissues and body fluids were obtained also at 24 and 36 months. On the contrary, Ti traces were found in lumbo-aortic lymph nodes and lungs of one sheep only (10 and 30 ng/g, respectively) at 24 months. At 36 months, a systemic diffusion of Ti was observed in all tissues of both sheep instrumented with Ti6Al4V (2-16.5 ng/g), except for body fluids and hair. Metal research in target tissues by light and SEM micro-probe analysis provided negative results. Current data suggest that the amount of Ti found in organs after stable pedicular fixation is extremely low and not biologically available. This observation would lead us to exclude the hypothesis of any toxic reaction and such a release seems to be due to the passive diffusion through lymphatic fluids. Additional studies are needed to confirm if this long-term release of Ti particles might cause tissue damage.
Animals↗
Effect of intramuscular clodronate on bone mass and metabolism in osteoporotic women.
Bisphosphonates have significantly improved the treatment of postmenopausal osteoporosis. However, when administered orally, gastric intolerance is their main adverse effect. This makes patients reluctant to undergo treatment. As an alternative, intramuscular (i.m.) administration may be more acceptable to patients undergoing long-term treatment. Since clodronate has been easily available in Italy for many years, we carried out this study to evaluate its effect on bone mineral density (BMD) in 36 osteoporotic postmenopausal women who were intolerant to oral administration of bisphosphonates. Patients received 100 mg of clodronate i.m. every 10 days together with 500 mg/day of calcium orally for 2 years. A control group of 32 women received only oral calcium at the same dose and for the same length of time. In the control group a progressive but not statistically significant decrease in BMD was observed in the spine and femoral neck over the 2-year follow-up. In contrast, patients treated with clodronate had a statistically significant increase in BMD in the spine at the first yearly check-up (+2.63%) and a further but not statistically significant increase during the second year of treatment (+0.59%). The increase in BMD at the femoral neck was not statistically significant during the first and second years of treatment, being 1.21% and 0.37% respectively. In the women treated with clodronate, hydroxyproline was significantly suppressed. All the patients reported local pain at the injection site. This led 11.11% of the subjects to withdraw from treatment.
Aged↗
Tibial implants: biomechanical and histomorphometric studies of hydroxyapatite-coated and uncoated stainless steel and titanium screws in long-term ovariectomized sheep.
This study was designed to evaluate osteointegration of HA-coated and uncoated titanium and stainless steel screws in the cortical bone of long-term (24 months) ovariectomized sheep (OVX group), in comparison with Sham-aged sheep (control group). The screws were tested biomechanically (extraction torque) and histomorphometrically (affinity index: Al) 12 weeks after their implantation in tibial diaphyses. Tibial cortical bone parameters showed significant differences between the groups, showing a reduction of the selected parameters in the OVX group. ANOVA showed significant effects for both material and ovariectomy factors on obtained extraction torque (material: F=159.26, p < 0.0005; ovariectomy: F=20.04, p < 0.0005) and Al data (material: F=8.04, p < 0.001; ovariectomy: F=7, 17, p < 0.05). In both groups the extraction torque for coated screws of both materials was significantly higher than for uncoated screws, and uncoated titanium had a better extraction torque than uncoated stainless steel. In the OVX group, the HA-coated stainless steel and titanium Al data were significantly higher than uncoated Al data. In conclusion, the biomechanical and histomorphological results obtained suggest employing HA-coated screws in the presence of osteopenic cortical bone.
Animals↗
Effect of sildenafil citrate upon myocardial ischemia in patients with chronic stable angina in therapy with beta-blockers.
BACKGROUND: It has been suggested that phosphodiesterase 5 (PDE5) inhibition is potentially hazardous and that it increases the risk of cardiac events in patients with coronary artery disease. This study sought to evaluate whether PDE5 inhibition with sildenafil exerts any effect on exercise-induced myocardial ischemia in patients on beta-blockers. METHODS: Fourteen patients underwent a baseline exercise test off-therapy and were then started on atenolol (100 mg once daily). After a run-in phase of 1 week, patients underwent a second exercise test and were randomized to receive either sildenafil (50 mg) or placebo given in a random order on two different occasions, 2 days apart. Exercise test was repeated 2 hours after the administration of sildenafil or placebo. RESULTS: All patients had a > 1 mm ST-segment depression while off-therapy. Eight patients had a negative exercise test response after atenolol, which was unaltered by the adjunct of either sildenafil or placebo. In the remaining subjects, atenolol significantly prolonged the time to 1 mm ST-segment depression and the exercise time. Sildenafil and placebo did not reverse the beneficial effect of atenolol upon exercise-induced myocardial ischemia. CONCLUSIONS: PDE5 inhibition does not worsen exercise capacity and exercise-induced myocardial ischemia in patients with chronic stable angina whose symptoms and exercise test response are well controlled by beta-blocker therapy.
Adrenergic beta-Antagonists↗
The ovariectomized ewe model in the evaluation of biomaterials for prosthetic devices in spinal fixation.
The effect of surgical ovariectomy on cancellous bone was investigated by comparing mechanical properties and microarchitectural characteristics of the lumbar vertebrae in ovariectomized and sham-operated ewes. Eighteen mongrel ewes, 4+/-1 years old, were randomly divided into three groups: 6 animals served as a control group (Baseline), 6 were bilaterally ovariectomized (OVX), and the others were used as a sham-operated group (SHAM). OVX and SHAM ewes were euthanized 24 months after surgery; the L5 vertebrae were processed for mechanical and histomorphometric analyses. Maximum load, maximum strength (p<0.0005) and elastic modulus (p <0.005) decreased by about 28% in the OVX group in comparison with the other groups. In the OVX group, vertebral cancellous bone volume, trabecular thickness and trabecular number decreased by about 32% (p<0.0005), 15% (p=0.001) and 20% (p=0.019), respectively. An overall decrease in the bone turnover rate of the OVX group was registered in terms of bone formation rate (p=0.007) and activation frequency (p<0.0005). The variations observed in cancellous bone mechanics and histomorphometry would suggest the development of an osteopenic state in ewe vertebrae at 24 months. Such findings may be useful for future experimental investigations on biomaterials and prosthetic devices to be implanted in the osteopenic spine.
Animals↗
Sheep model in orthopedic research: a literature review.
The aim of the study reported here was to provide some basic and general information on the suitability of an experimental sheep model for conducting in vivo orthopedic studies. The authors have classified the fundamental aspects that should be carefully evaluated when using sheep as an experimental model in orthopedic research: factors strictly related to bone anatomy and formation; and factors strictly affecting bone physiology, such as gastrointestinal mineral and vitamin absorption, and reproductive cycle. Future investigations should address all of the aspects highlighted, since there is no animal with the same anatomic, biochemical, physiologic, and biological characteristics as those of human beings. Moreover, useful data for treating orthopedic patients are based not only on good planning and study design, but also on perfect knowledge of the animal used and the differences between the model and the human being. The authors hope that this report will contribute to extrapolation of reliable data for use of sheep in the orthopedics field.
Animals↗
Cardioprotective effects of ovarian hormones and the HERS in perspective.
The increased population of women in menopause living in the industrialized countries is associated with an increase of diseases which are dependent or facilitated by a state of estrogen deficiency such as cardiovascular and cerebrovascular diseases. Several studies have shown that estrogen replacement therapy reduces the occurrence of coronary and may be of cerebrovascular disease by nearly 50% in treated women compared to non-users. These findings are supported by the evidence that estrogens have a beneficial effect on cholesterol metabolism and deposition, contributing to the inhibition of atherosclerotic plaque formation in arterial walls as well as a direct effect on the vessel wall. Progestins may, in some cases, counteract the beneficial effect of estrogens upon cardiovascular functions. More androgenic progestins may have a detrimental effect upon vascular reactivity while less androgenic progestins seem not to reduce the beneficial effect of estrogens. Of interest, continuous combined administration of hormone replacement therapy seem to be preferable for women with coronary artery disease or for those with increased cardiovascular risk. Case-control and cohort studies have shown that estrogen progestin therapy is associated with a significant reduction of cardiovascular mortality and morbidity. The HERS study has added critical data regarding the cardioprotective effect of hormone replacement therapy in elderly women with proven coronary artery disease. Because of the several methodological and statistical flaws of the HERS study, further studies are warranted to evaluate the effect of hormone replacement therapy on cardiovascular prognosis. Large scale randomized studies will evaluate the effect of estrogen and estrogen-progestin replacement therapy upon cardiovascular events in menopausal women. Until completion of these studies hormone replacement therapy in women with increased cardiovascular risk should be seen with no enthusiasm but also with no fear.
Cardiovascular Diseases↗
Isolation and characterization of osteoblast cultures from normal and osteopenic sheep for biomaterials evaluation.
Being very useful in the analysis of bone cell differentiation and activity, osteoblast cultures are also used in the in vitro biocompatibility study of new materials. The aim of this work was to evaluate sheep osteoblast cultures derived from normal and ovariectomized animals, and then to assess the in vitro biomaterial behavior on these cultures, taking into account the quality of bone where orthopedic devices are clinically used. For this purpose, we characterized sheep osteoblast cultures, isolated from iliac crest bone of normal (NB osteoblast culture) and osteopenic after ovariectomy (OB osteoblast culture) sheep. Moreover, we studied cell behavior when cultured on different biomaterials (titanium and two biological glasses, RKKP and AP40). Cell characterization at baseline demonstrated that both cultures (NB and OB) showed normal osteoblastic behavior. On the contrary, osteoblasts derived from osteopenic bone and cultivated on AP40 for 6 days revealed a different behavior in terms of both cell morphology and metabolic activity. Statistical analysis (one-way analysis of variance and Scheffé's post hoc multiple-comparison tests) revealed significant differences in Ca level (p<0.0005), MTT test (p<0.0005) and OC production (p<0.05). These in vitro tests demonstrated that sheep osteoblast cultures can be useful when determining biocompatibility and osteointegration of orthopedic materials, and also when evaluating for the presence of osteoporosis.
Animals↗
Evaluation of pain and stress levels of animals used in experimental research.
This paper represents a contribution to researchers employing "in vivo" models in experimental surgery in order to obtain more reliable results in accordance with current legislation and Russel's "three R" statement: refinement, reduction, and replacement. After general consideration about the definition of pain and stress concerning laboratory animals, the authors suggest making an evaluation of the experimental protocol before approval by the local committee to allow assessment in terms of the costs/benefits of experimental research employing live animals.
Animals↗
Guided regeneration with resorbable conduits in experimental peripheral nerve injuries.
Guided tissue regeneration is a new approach in the reconstructive surgery of peripheral nerves. Artificial conduits can be constructed from biodegradable polymers. Lactic/caproic acid copolymers and polyphospazenes are biocompatible materials with a slow resorption rate. Conduits made from either poly-[1-lactide-co-6-caprolatone] or poly-[bis-(ethylalanate)-phosphazene] were assessed for use as guides for nerve regeneration in experimental animals. Under general anesthesia and by using a microsurgery technique both sciatic nerves were exposed in 2 groups of 9 Wistar rats. On the right side, a 10 mm segment of the nerve was removed, and the defect was then repaired using a conduit. On the left side, the same defect was bridged using as an autograft the nerve segment, which had been removed from the right sciatic nerve. Histological and electron microscopy investigations were performed after 30, 90 and 180 days and showed the gradual degradation of both types of conduits without any evidence of local toxicity. The regeneration of the nerve fibers in the lumen was not significantly different from that shown by the autologous grafts. Likewise, no differences were found at 180 days in the functional recovery of the nerve (evoked muscle action potential). Both conduits were found to be effective for guided nerve regeneration. Poly-[1-lactide-co-6-caprolactone] tubes were easier to insert, while polyphosphazene conduits allowed the use of neurite-promoting factors.
Animals↗