Biomedical subjects
Publications and source records attributed to Daniel Chappard.
The aim of this paper is to review the main physiologic features of bone metabolism in male. A brief description of bony cells and function is given. Hormonal influences on bone biology are described. Although androgens have been considered as essential in the regulation of bone metabolism in men, recent data have emphasised the fact that estrogens could play a dominant role.
The aim of this review is to detail the pathophysiologic mechanisms occurring during bone metastases. osteolytic and osteosclerotic metastases are observed after migration of malignant cells coming from a primitive tumour which can localize and grow inside the hematopoietic bone marrow. Bone lesions observed during hematologic malignancies (lymphomas and myeloma) are not detailed here. The various cytokine networks that are occurring in bone metastases are detailed: in both cases there is a "vicious circle" between the the tumoral cells and bone cells responsible for the physiological remodeling of bone. The knowledge of these interferences permits to understand the use of anti-osteoclastic treatments (bisphosphonates) in osteolytic as well as osteosclerotic metastases.
Osteoblasts are target cells for glucocorticoids and calcitriol, and their phenotype is greatly modified by these hormones. We investigated the effect of continuous or discontinuous hormonal exposure to osteoblasts derived from rat bone marrow stromal cells in long-term subcultures. Stromal cells were grown in primoculture in presence of dexamethasone (dex), but in following subcultures, dex and/or calcitriol were added just after seeding or after a 7-day hormone-free period. Cell proliferation, alkaline phosphatase (ALP) histochemical staining, and enzymatic bioactivity measurement, osteocalcin (OC), ALP and bone sialoprotein (BSP) mRNA expression were used to study the differential effect on osteoblastic phenotype of various conditions of treatment by dex and calcitriol. In primoculture, the osteoblastic differentiation was confirmed by the formation of calcified nodules and by strong expression of ALP, OC, and BSP mRNAs. In subcultures, proliferation of stromal cells was stimulated by dex and inhibited by calcitriol and by both hormones. Cell proliferation was not modified by hormonal lack during 7 days. Continuous hormonal treatment by dex strongly enhanced OC and BSP mRNAs, but apparently did not modified ALP mRNAs expression. Continuous treatment by calcitriol decreased ALP and the dex-induced BSP expression and stimulated the OC mRNAs level, strongly when associated with dex. The population of ALP+ cells and ALP bioactivity were strongly increased by dex, whereas calcitriol or both hormones decreased them. When the subcultures were undergone without hormonal treatment during 7 days, all osteogenic mRNAs strongly decreased even after hormonal recovery. Dex, calcitriol, and both hormones inhibited ALP mRNAs. OC messengers were only weakly detectable with both hormones. ALP+ cell population and ALP bioactivity were decreased after 14 days of hormonal treatment recovery. These results support that continuous presence of glucocorticoids appears as a major key for the permanent expression of the osteoblastic phenotype that is inhibited by calcitriol, in the rat bone marrow.
BACKGROUND/AIMS: To assess the effects of the early and chronic administration of losartan--a specific angiotensin II receptor antagonist--in the prevention of hepatic fibrosis and portal hypertension. METHODS/RESULTS: (1) In CCl(4) rats, losartan at 5 and 10 mg/kg per day significantly decreased portal pressure (-11, -18%, respectively), splenorenal shunt blood flow (-60, -80%) and liver fibrosis (liver hydroxyproline and area of fibrosis) without significant changes in mortality and mean arterial pressure (MAP). (2) In bile duct ligated (BDL) rats, losartan at 5 mg/kg per day significantly decreased portal pressure (-14%), splenorenal shunt blood flow (-70%) and liver fibrosis. Losartan at 10 mg/kg per day significantly worsened liver and renal functions, mortality and liver fibrosis, without significant changes in portal pressure and splenorenal shunt blood flow. Losartan at 5 and 10 mg/kg per day significantly decreased MAP (-24, -30%). (3) In portal vein ligated (PVL) rats, losartan significantly decreased MAP (-12%) but did not change portal pressure or splenorenal shunt blood flow. CONCLUSIONS: In BDL and CCl(4) rats, losartan has beneficial effects on splanchnic hemodynamics and liver fibrosis. Losartan might decrease hepatic resistances in fibrotic liver. Losartan decreased MAP except in CCl(4) rats. Higher dosage of losartan had deleterious effects in BDL rats.
Fractal analysis measures the complexity of geometric structures. The aim of this study was to evaluate the feasibility and accuracy of fractal analysis in liver fibrosis. A total of 77 rats were included: 10 sham, 46 with fibrosis secondary to bile duct ligation (BDL), and 21 with fibrosis due to CCl(4) intoxication. Measurements included the fractal dimension of Kolmogorov (D(k)), histologic lesions, the area of fibrosis by image analysis, liver hydroxyproline content, messenger RNA fibronectin, serum hyaluronate level, and portal pressure. Fibrotic rats were given placebo, octreotide, or O(2)-vinyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (V-PYRRO/NO). Intraobserver agreement of D(k) was excellent with the intraclass (ic) correlation coefficient r(ic) = 0.91 (P <.0001) as well as the interobserver agreement with r(ic) = 0.88 (P <.001). D(k) was correlated with other measurements or markers of fibrosis: the area of fibrosis (r = 0.75; P <.0001), hydroxyproline content (r = 0.51; P <.001), serum hyaluronate level (r = 0.52; P <.001), and portal pressure (r = 0.52; P <.01). D(k) was significantly different between the 2 models of fibrosis (P <.0001), unlike the area of fibrosis, and this relationship was independent of other histologic lesions. The significant decrease in fibrosis observed with octreotide or V-PYRRO/NO was similarly reflected by D(k) or the area of fibrosis. The diagnostic accuracy for the fibrosis model was 97% with the 5 main measurements or markers of fibrosis studied, with D(k) isolated at the first step by stepwise analysis. In conclusion, fractal analysis is suitable for analyzing liver fibrosis and has excellent reproducibility. This is the only quantitative morphometric method that can discriminate among the models of fibrosis and is sensitive enough to detect pharmacologically induced changes in liver fibrosis.
OBJECTIVE: The non-invasive diagnosis of liver fibrosis is based mainly on biochemical markers. The main aim was to validate whether the prothrombin index is an indirect marker of the severity of liver fibrosis. PATIENTS AND METHODS: The predictive value of the prothrombin index for liver fibrosis was first assessed in 243 patients with chronic liver disease, then validated in 193 other patients with chronic liver disease. The reproducibility of measurement of the prothrombin index in different laboratories was evaluated in 82 other patients. RESULTS: In the first group, the prothrombin index was predicted accurately by serum hyaluronate (R(2)= 0.67 at the first step by multiple regression). The relationship between the prothrombin index and the area of fibrosis was not influenced significantly by non-fibrotic pathological lesions. The prothrombin index began to decrease when the Metavir fibrosis score was 2 versus 3 for albumin. In the second group, the prothrombin index and the histological fibrosis score were well correlated (r= -0.70, P< 10(-4)). Prothrombin index < or =80% or < or =70% diagnosed severe fibrosis or cirrhosis, respectively, and prothrombin index > or =105% or > or =100% excluded a diagnosis of severe fibrosis or cirrhosis, respectively, at the 95% probability level. The prothrombin indices measured in different laboratories were similar (78+/-18% v. 78+/-14%) and well correlated (r= 0.91, P< 10(-4)). CONCLUSIONS: The prothrombin index was well correlated with pathological liver fibrosis score, had a high diagnostic accuracy for severe fibrosis or cirrhosis especially due to alcohol, and was not influenced by other pathological lesions. The prothrombin index was reproducible. Thus, the prothrombin index expressed as a percentage is an accurate, reproducible, inexpensive and easily available marker of severe liver fibrosis.
The aim of the present study was to assess the reproducibility and accuracy of measurements done on excised rat bone with three different generations of densitometers: Hologic QDR2000 pencil beam, Hologic QDR4500 fan beam, and Lunar PIXImus cone beam. The coefficients of variation for repeated measurements of bone mineral content (BMC) were 0.62 and 0.85% for pencil beam, 1.73 and 3.59% for fan beam, and 0.70 and 1.52% for cone beam for femur and tibia, respectively. BMC and ash weight were linearly correlated: 0.998 for pencil, 0.984 for fan, and 0.995 for cone beam. However, the three densitometers overestimated BMC by 10.9, 12.6, and 3.1%, respectively, and the overestimation was found to be dependent on the net BMC. The highest coefficient of correlation was found between BMC measurements from pencil and cone beam (r = 0.995). Data from cone-beam DXA were, respectively, 8.8 and 9.2% lower than those from penciland fan-beam DXA. We conclude that the three DXA instruments precisely and accurately measure BMC in excised rat bone; however, DXA overestimates BMC with a dependence on the bone ash weight. This dependence was less pronounced with the cone-beam technology.
PURPOSE: The aim of this study was to evaluate by finite element analysis the influence of the design of 3 different dental implants on micromovements, cervical shearing stress intensity, and stress distribution after occlusal loading. MATERIALS AND METHODS: The first investigated implant was a classical cylinder, the second was reinforced by 2 bicortical locking pins, and the third was an expanding dental implant. The parameters analyzed were the implant's geometry, the quality of the cancellous bone, and the orientation of occlusal loading. RESULTS: It was found that initial stability of the locking pin implant was greater than the initial stability of the other investigated implant designs, regardless of the quality of cancellous bone and orientation of occlusal loading; in low-rigidity cancellous bone, under a horizontal load (500 N), decreasing displacement compared to those of the other investigated implants was 16 microm. The apical expansion and locking pin implants exhibited favorable behavior regarding the distribution and intensity of cervical shearing stresses; in low-rigidity cancellous bone, under horizontal load, decreasing cervical stresses compared with those of the cylindric implant were 10 MPa for the apical expansion implant and 150 MPa for the locking pin implant. DISCUSSION: For the cylindric implant, stresses were concentrated in the neck region; for the apical expansion implant, stresses were evenly distributed from the neck to the apex of the implant. For the locking pin implant, stresses around the neck were moderate and appeared concentrated around the pins. CONCLUSIONS: Initial stability of the pin implant was greater than that of the expanding implant, but the expanding implant showed the most favorable stress distribution.