Biomedical subjects
Publications and source records attributed to D Ducassou.
Activation of the complement system in vitro by a series of microcapsules based on polylysine, alginate or polyacrylamide was determined. Least activation was observed with microcapsules whose outer layer was composed of polyacrylamide. Activation was further reduced using diacrylylpiperazine instead of bisacrylamide as crosslinker.
To compare the merits of 123I-isopropyl-iodoamphetamine (123I-IMP) and 99mTc-HMPAO in showing abnormal brain uptake distribution during cerebral ischemia, we studied ten patients during the subacute phase of their stroke, a period where metabolism and blood flow are frequently uncoupled. SPECT imaging was performed using both radiopharmaceuticals in the 10 patients from 48 h to 4 weeks after onset of symptoms. Two patients out of the 10 had similar defects with 123I-IMP and 99mTc-HMPAO SPECT, the location of the defects corresponding to the area of infarction observed on CT. Six patients had normal 99mTc-HMPAO SPECT and abnormal 123I-IMP SPECT with defects in the area of infarction shown by CT. The remaining 2 patients had hyperactive abnormalities on 99mTc-HMPAO in areas corresponding to defects on the 123I-IMP images. Two of the patients with SPECT mismatches were studied again more than 1 month after onset. On reexamination, 99mTc-HMPAO SPECT which was previously normal or hyperactive became hypoactive with a focal area of decreased activity corresponding to the defect on 123I-IMP. Crossed cerebellar diaschisis was found in 7 patients with 99mTc-HMPAO and was absent for both 123I-IMP and 99mTc-HMPAO in 3. We suggest that SPECT with 99mTc-HMPAO could show transient hyperemia not demonstrated by 123I-IMP whereas in some cases cerebral infarction would be more difficult to demonstrate with 99mTc-HMPAO than with 123I-IMP. SPECT with both tracers is recommended to follow the evolution of strokes in terms of regional cerebral blood flow and tissue metabolism.
In vitro studies have shown that glucocorticoids may increase atrial natriuretic-hormone (ANH) synthesis and/or release. This action of glucocorticoids has also been suggested in vivo in patients with Cushing's syndrome. However, in this circumstance, plasma AH elevation might be due to humoral disturbances associated with cortisol overproduction. We studied 16 patients with endogenous hypercorticism and 11 of them after successful treatment. Plasma levels of ANH, plasma renin activity (PRA), aldosterone, desoxycorticosterone (DOC), angiotensin II (AII), cortisol, osmolarity, sodium and potassium, urinary free cortisol (UFC), and blood pressure were measured. Before treatment the mean plasma ANH concentration in patients with Cushing's syndrome was significantly higher than in controls (11.3 +/- 2.6 vs. 4.9 +/- 2.3 pmol/l; p less than 0.001). ANH was correlated with cortisol and UFC (r = 0.715, r = 0.700; p less than 0.05). There was no significant correlation between plasma ANH, PRA, aldosterone, DOC, AII, osmolarity, sodium or blood pressure. After recovery, ANH concentration decreased in all patients and was not different from that of normal subjects (4.9 +/- 2.3 vs. 4.3 +/- 2.6 pmol/l). These results suggest that in Cushing's syndrome, ANH secretion is mainly dependent on the severity of hypercortisolism and independent of the other associated disturbances that we studied.
The biocompatibility of polyacrylamide microcapsules was investigated by implanting microcapsules in the peritoneal cavity or the spleen of rats. The capsules were retrieved every four weeks for twenty weeks. They remained isolated and free in the peritoneal cavity, but led to a slight inflammatory reaction in the spleen. These results were confirmed, in vitro, by determinations of chemiluminescence and interleukin I levels, and by evaluation of attachment and growth of human fibroblasts. The microcapsules did not enhance these inflammatory reactions, and they were a poor support for cellular proliferation.
Ten normal rabbits and seven rabbits with experimental acute renal failure by tubular necrosis were studied with dynamic MR to evaluate the reproducibility of intrarenal kinetics of Gd-DOTA. Sequential spin-echo sequences with short TR (200 msec)/TE (26 msec) were used yielding a 29 sec acquisition time. A usual semi-quantitative analysis of intrarenal contrast demonstrated the reproducibility of some phases of the dynamic sequence in particular a drop in the signal within inner medulla between the third and the fourth minute after infusion. This effect, related to a high concentration of Gd-DOTA within the tubules was observed in 9 over 10 normal rabbits and in none of the rabbits with acute renal failure. The quantitative analysis calculation was based on relative signal intensity and contrast-to-noise ratio from the absolute signal intensity measure on regions-of-interest (ROI) on the cortex, outer medulla and inner medulla. No reproducibility of the variations with time of these parameters could be assessed. A great number of factors of variations or error, mainly during the measurements of signal intensity with ROI, could explain this lack of reproducibility. At the present, dynamic MR is therefore not able to quantitatively evaluate the renal function. Only a semi-quantitative estimation of tubular concentration can be deduced.
A new process for microencapsulating living cells is described. Pancreatic islet cells in solution in agarose were extruded from a syringe into a paraffin-oil-containing medium. A rigid interface around each bead was produced when the agarose gelled. A polymerizable mixture of monomers containing 30% of acrylamide and 1.5% of bisacrylamide was then added to these beads. Polymerization was initiated by a photochemical process using riboflavin as a photosensitizer, which enabled use of oxygenated solutions. As other polymerizations initiated by an oxido-reduction reaction, this method did not require heating, and could thus be carried out at ambient temperature. The oil phase near the agarose beads effectively prevented any rise in temperature, and also led to formation of an acrylamide concentration gradient in the aqueous phase, which reduced the potential cytotoxicity of the reaction. Radioimmunoassay of insulin liberated from encapsulated islets of Langerhans demonstrated a good viability of the cells.
Heparin-like materials, characterized by a defined superficial density of functional groups which activate antithrombin III (AT III), when in contact with blood specifically inhibit thrombin as soon as it appears. This paper describes an isotopic method to estimate this density and to visualize the distribution of the affinity sites concerned, both directly with AT III labelled with 125Iodine and indirectly with an anti AT III monoclonal antibody labelled with 111Indium.
A new process for microencapsulating living cells is described. A cross linked network was polymerized using acrylamide and bisacrylamide monomers round agarose-embedded cells in an hydrophobic medium. The reaction was initiated by excitation of Vit. B2 under visible irradiation. The absence of toxic effect was evaluated from the insulin secretion of encapsulated islets of Langerhans.
The effect of S-adenosyl-L-methionine (SAMe) on human articular osteoarthritic chondrocytes was studied using a thick-layer culture model. Three SAMe concentrations were tested (1, 10, and 100 micrograms/ml). For 10 micrograms/ml, the most efficient dose, a significant rise in the incorporation levels of 35S-sulfate and 3H-serine was observed, as was as an increase in the hexuronic acid content. All the parameters seem to express a more active protein synthesis, particularly for proteoglycans. Under the same conditions, the proliferation rate of chondrocytes does not undergo important variations. These results point to a direct action on the cell metabolism but little is known concerning the mechanism involved.
In order to obtain a radioiodinated antithrombin III (AT III) with a good labelling yield and optimal biological properties towards heparin, thrombin and its anti-AT III monoclonal antibodies, we compared the classical labelling methods and found them wanting. Thus, we perfected a new labelling procedure which fulfils the above requirements.
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A gamma-camera on-line distortion corrector, based on a fast microprocessor, has been tested on two cameras. The original electronic design and the software algorithm are described. Performance measurements on phantoms and clinical results show an improvement of the pictures.
Functional investigations using radionuclides to study protein adsorption and platelet adhesion onto biomaterials are described. The authors' novel methods use radiotracers with a dynamic technique. This allows direct observation of the interaction between blood, or simpler biological substances, and artificial materials. Several radiotracers were used in this study, including 111In-platelets, 123I-fibrinogen, 123I-antithrombin III, and 99mTc-tagged red blood cells. The detectors employed were a semiconductor diode or gamma-camera equipped with special collimators. The acquisition and treatment of data were performed with an original device. These methods allowed precise comparisons, especially between platelet adhesion upon different materials in the form of tubes and also protein adsorption and desorption. The results are discussed in terms of materials to be used for work in vivo.
The kinetics of platelets labeled with indium-111 were investigated in 13 healthy subjects as well as in 9 patients in the asymptomatic interattack stage of asthma. The survival times of platelets in healthy subjects was 8.9 +/- 1 days; in asthmatic subjects it was 4.7 +/- 1.3 days (p less than 0.001). The survival curve is of a biexponential form in asthmatics, thus suggesting the presence of 2 populations: one with a short life span (23 +/- 7 h), representing a third of the total population (33 +/- 9%), and the other with a normal life span. No single preferred site of platelet sequestration was found. These results suggest the presence of functional or anatomic lesions of platelets in asthmatic patients, which can be explained only hypothetically at the present time.
In a patient with a prior history of cerebral abscess and cerebral ischemia, an unsuccessful perfusion lung scan led to a radionuclide angiocardiogram using an arm vein injection. This showed a total right-to-left (R-L) shunt from the superior vena cava (SVC) to the left atrium. Repeat radionuclide study, through a leg vein, demonstrated a moderate R-L shunt and an interpretable lung scan could be obtained. Catheterization and contrast cineangiogram did not provide the exact diagnosis, the preoperative conclusion being anomalous drainage of the SVC into the left atrium, with atrial septal defect (ASD) and partial anomalous pulmonary venous connection to the SVC. The operative diagnosis was high atrial (sinus venosus) septal defect. This example of major but clinically unsuspected R-L shunt emphasizes the value of performing a perfusion lung scan, preferably in conjunction with radionuclide angiocardiography in patients with a prior history of unexplained cerebral abscess or systemic ischemia. Implications of the site of an ASD on quantitation of L-R shunts by radionuclide methods are also discussed.
The effects of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) (10(-13)M-10(-8) M) and 24R ,25-dihydroxycholecalciferol ( 24R ,25-(OH)2D3) (10(-12)M-10(-7) M) on cell proliferation and proteoglycan deposition were examined in our newly developed multilayer culture system for rabbit and human articular chondrocytes. The cells are embedded in an extracellular matrix similar to that seen in vivo and maintain their in vivo phenotype. We extracted and purified native proteoglycans and degraded material from three culture compartments: the medium, intercellular matrix, and cells. Proteoglycan synthesis and deposition were analyzed by measuring 35SO4 incorporation, hexuronic acid, and galactose contents. In both rabbit and human chondrocyte cultures, chronic 1,25-(OH)2D3 treatment inhibited chondrocyte proliferation and stimulated proteoglycan synthesis and accumulation in the three compartments at 10(-12)-10(-8) M; maximal effect was at 10(-10)M. Cell proliferation was reduced by 55% and the content of hexuronic acid (or galactose) was increased to about three times that of controls in all compartments. 1,25-(OH)2D3 did not alter the proteoglycan composition. Chronic 24R ,25-(OH)2D3 treatment induced comparable effects with a maximum at 10(-8)M. When human dermal fibroblasts were treated as above both vitamin D metabolites increase mitosis. 1,25-(OH)2D3 mainly reduced the pericellular deposition of proteoglycans, while 24R ,25-(OH)2D3 appeared to reduce their synthesis and deposition in both medium and pericellular compartments. These results suggest that both 1,25-(OH)2D3 and 24R ,25-(OH)2D3 act specifically on articular chondrocytes to promote phenotype expression.