Biomedical subjects
Publications and source records attributed to N More.
Hyperkalemia is a commonly encountered electrolyte disturbance in patients with renal insufficiency. It develops very rapidly when potassium is supplemented while a patient is on a potassium-sparing diuretic. Most often it remains asymptomatic and manifests in the form of electrocardiographic changes. Muscle weakness and paralysis although described is seldom observed in clinical practice. We report one such case.
The immune and nervous systems communicate through an array of signalling molecules which includes substance P. This work investigates the anatomical relationship between substance P nerve fibers, receptors, and substance P positive cells in the thymus. Thymuses from rats were frozen or paraformaldehyde fixed. In vitro autoradiography was used to map the distribution of SP receptors. Immunostaining was used to localize SP positive cells and nerve fibers by transmitted light and confocal microscopy. SP receptors exhibited a broader distribution than previously reported, being present throughout the organ with a preferential concentration in the cortico-medullary zone. While SP fibers were frequently associated with the blood vasculature, they were also present throughout the organ independent of blood vessels and were most prominent in the cortico-medullary zone. SP positive cells followed a similar pattern of distribution as the SP fibers and were present as single cells or aggregates of SP positive cells. Confocal microscopy revealed close spatial contact between the SP positive nerve fibers and the SP positive thymic cells. The close spatial relationship between the SP positive thymic cells and SP positive nerve fibers supports the concept of a structural-functional unit between SP nerve fibers and their potential receptor-bearing target cells in the thymus.
The stability of two enzymes from extreme thermophiles (glutamate dehydrogenase from Thermococcales strain AN1 and beta-glucosidase from Caldocellum saccharolyticum expressed in Escherichia coli) has been exploited to allow measurement of activity over a 175 degrees C temperature range, from +90 degrees C to -85 degrees C for the glutamate dehydrogenase and from +90 degrees C to -70 degrees C for the beta-glucosidase. The Arrhenius plots of these enzymes, and those for two mesophilic enzymes (glutamate dehydrogenase from bovine liver and beta-galactosidase from Escherichia coli), exhibit no downward deflection corresponding to the glass transition, found by biophysical measurements of several non-enzymic mesophilic proteins at about -65 degrees C and reflecting a sharp decrease in protein flexibility as the overall motion of groups of atoms ceases.
The authors set out to assess the three diagnostic methods available which can detect early breaking of the membranes: radio-enzymatic assay of diamine-oxidase (DAO), radioenzymatic assay of alpha-fetoprotein (AFP), colorimetric method for determining pH (Amnicator). Between June 1991 and March 1992, 114 samples of vaginal secretions were taken from 104 pregnant patients being followed up at Maternity Unit A, Bordeaux (France). The results of the assays were expressed in quantitative terms (microU/ml for DAO and ng/ml for AFP); ROC (Receiver Operating Characteristic) curves were used to determine the positivity threshold in terms of the sensitivity and specificity (20 microU/ml for DAO and 15 ng/ml for AFP). The sensitivity of the pH test was 97.5%, which was significantly better than that of DAO (90.2%) and even that of AFP (82.9%). However, there was no difference between the specificities of the pH, DAO and AFP tests (93.3%, 96.6% and 93.5% respectively). The data were compared with those in the literature. The problems in collecting the vaginal secretions probably accounts for the better results of the colorimetric test. This is a reliable, fast and easily reproducible test; these qualities make it the preferred test in EBM, and it can be completed using a radioenzymatic method (DAO) or immunoradiometric test (AFP).
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There is a need for viable small diameter vascular grafts, the luminal surface of which could be seeded by endothelial cells (ECs) to prevent thrombosis. In order to select candidates for EC seeding before implantation, the in vitro cytocompatibility of three different Pellethanes (polyetherurethanes) using human ECs was investigated. The methodology included two stages depending on either direct contact between cells and materials or contact between cells and material extracts, obtained under standardized conditions. By the latter method, we observed a cytotoxic effect on cell growth with 2363-55 D Pellethane extract at a 50% (v/v) concentration in the nutrient medium, likely provoked by leachables and correlated with the lowest levels of tPA, PAI1, and vWF antigens in the supernatants. By the former method, we studied EC attachment and growth. Morphology was studied by classical means and completed by scintigraphy and microautoradiography after 111Indium-labeling of the EC monolayer. Differentiation was determined by the release of vWF antigen and measurement of vWF activity (multimeric organization) after human thrombin stimulation. Despite an inhibition of proliferation for both 55 D and 75 D types (compared to the control), a functional monolayer of ECs was obtained on 75 D. Pellethane 75 D could be the best support for in vitro endothelization.
Titanium nitride (TiN) is regarded as a potential biomaterial for blood-contact applications. Its in vitro haemocompatibility has been evaluated already and gave promising results. The purpose of this study was to continue studying its 'biological' behaviour through an ex vivo evaluation. The material was a physical vapour deposition elaborated TiN coating and the phenomena observed were leucocyte adhesion and albumin and fibrinogen adsorption. These ex vivo results were compared with in vitro results obtained previously. Two reference medical grade silicone elastomer and three TiN arterio-arterial extra-corporeal circuits were tested. No leucocyte was retained by TiN, as in in vitro experiments; the ex vivo fibrinogen adsorbed quantity was higher and albumin adsorption was about the same in in vitro and in ex vivo situations. TiN can be considered as a suitable blood-contacting material.
The new prosthetic heart valve that has been designed by FII Company and Pr. Baudet involves a new "composite" material: titanium alloy T16A14V coated with Diamond-like Carbon. The purpose of this study was to evaluate the in vitro hemocompatibility of this new material in terms of protein adsorption and platelet retention. The static protein adsorption test gave interesting results, particularly for the albumin assay (237%) compared to the results obtained with a silicone elastomer chosen as a reference; the fibrinogen quantity, adsorbed on the surface of the material was slightly higher than that adsorbed on the silicone surface. Platelets adhere quite twice as much as they do on the reference surface. Such investigations showed good hemocompatibility results and should initiate further studies.
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Carbon-carbon composites are well known in the field of aerospace technology. Such composites have been proposed to be used as biomaterials, particularly in contact with blood. To evaluate their haemocompatibility, samples were tested in vivo and in vitro, using radiotracers. In vivo study showed the accumulation of platelets on the exposed surface material with any surface morphology, whereas platelet concentration in blood remained constant. In vitro study allowed us to distinguish, among entrapped platelets, active adhering platelets from those mechanically retained and it appeared that the bulk structure of materials influenced the adhesion mechanism of platelets.
Several uncertainties have to be resolved concerning the in vivo erosion of carbon-carbon composite materials and the outcome of the resulting particles. We studied these phenomena with implants superficially doped with 14carbon, specially prepared using the usual production processes of these materials. The samples implanted in rats presented changes in their measured radioactivity which proved erosion. Autoradiographies of the whole animal as well as pathological studies of peri-implanted tissues with histoautoradiographies of the related sections revealed the presence of carbon at a distance from the implant. However, the majority of the eroded particles were retained in the fibrous capsule surrounding the implant. The methods of electron-diffraction, associated with electron microscopy, seem to be a tool suitable to characterize the nature (fibrous or pyrolytic) of the carbon particles present in the capsule.
Hepatic arterial blood flow (HABF) in the liver lobes and splanchnic nonhepatic arterial blood flow were measured in rats with and without right portal branch ligation for 1 month using 57Co microspheres. Portal branch ligation led to 60% atrophy of the ligated lobe and to hypertrophy of the nonligated lobe. In nonligated lobes of the portal branch ligation model and in the lobes of controls, HABF expressed per gram liver was comparable. In both models splanchnic non-HABF was also comparable. In the atrophic lobe, HABF remained constant; expressed per gram liver, it increased. In this lobe the net result was a significant decrease in total hepatic blood flow (ml/min/g liver).
Doxorubicin possesses high affinity for binding to cardiolipin. We have utilized these properties in preparing stable liposomes of doxorubicin and cardiolipin with a net positive charge. Doxorubicin liposomes were formed by using 11.2 mumol of drug, 5.6 mumol of cardiolipin, 28.5 mumol of phosphatidylcholine, 19.5 mumol of cholesterol, and 11.1 mumol of stearylamine. These liposomes were sonicated for 90 min at 37 degrees followed by extensive dialysis against buffer. The pharmacological, toxicological, and therapeutic effects of doxorubicin entrapped in cardiolipin liposomes were compared with those of free doxorubicin in mice. At a dose of 4 mg/kg i.v., the peak cardiac concentration was achieved in 30 min following free doxorubicin administration, the value being 8.1 micrograms/g. The peak cardiac concentration with doxorubicin in cardiolipin liposomes was obtained at 5 min with a value of 2.8 micrograms/g of tissue. The cardiac concentration X time values for free doxorubicin for the 24-hr period of observation were 55.1 micrograms X hr/g, whereas it was only 7.8 micrograms X hr/g with the drug entrapped in cardiolipin liposomes. Compared to free drug, the liposomal entrapped doxorubicin significantly reduced the histopathological lesions in cardiac tissue of mice at a dose of 15 mg/kg as determined by electron microscopy. The nadir of peripheral white blood cell counts in mice with free drug, 6 mg/kg, was observed on Day 3 which was 50% of control, whereas with liposomal encapsulated drug it was reduced only 23% on Day 7. Doxorubicin in cardiolipin liposomes demonstrated enhanced chemotherapeutic potential against murine ascitic P388 leukemia with a 144% increased life span compared to 55% increased life span with free drug at a dose of 7.5 mg/kg on Days 1, 3, and 7. We conclude that doxorubicin liposomes developed in these studies possess improved therapeutic action as demonstrated by their ability to reduce the toxicity of the drug substantially.
Portal branch ligation (PBL) leads to atrophy of the corresponding lobe (AL) and hypertrophy of the non ligated lobes (HL). Liver architecture of AL is preserved. In this model we assessed in rats, one month after PBL, the acute hepatotoxicity of carbon tetrachloride (CCl4) given i.p. or i.v. Grading of necrosis, steatosis and ballooning demonstrated that at 24 and 48 h, AL were less severely damaged than HL and lobes of sham operated rats. Changes in hepatic blood flow, drug metabolism and/or in sinusoidal cells may represent causes involved in the partial hepato-protection.
With indirect methods, it was shown in rats with portacaval shunts (PCS) that total hepatic blood flow (THBF) remained constant when expressed per gram of liver. These results implied an absolute increase in hepatic arterial blood flow (HABF). The aim of this study was to investigate HABF and splanchnic nonhepatic arterial blood flow (SNHABF) with a direct method (57Co microspheres) in PCS rats. One month after surgery, the following results were obtained in PCS rats compared with pair-fed, sham-operated rats: 1) liver mass atrophy was 42.3 +/- 10.9%, 2) HABF (ml X min-1 X g liver-1) was increased by a factor of 2.7, 3) SNHABF (ml X min-1 X 100 g body wt-1) was higher (9.8 +/- 3.3 vs. 5.6 +/- 2.7) (P less than 0.05) and 4) THBF (ml X min-1 X g liver-1) was decreased (1.36 +/- 0.34 vs. 1.85 +/- 0.86) but not significantly. Increases in HABF and SNHABF were not the direct consequence of an increase in cardiac output as attested by a normal cerebral blood flow (ml X min-1 X g organ-1) in PCS rats. In PCS rats, an increase in HABF may prevent the further spread of liver necrosis. The cause and the reason for an increase in SNHABF remain unknown.
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The chronic cardiotoxicity of doxorubicin as a free drug or entrapped in positive and negative liposomes was morphologically evaluated in mice treated seven times i.v. at a dose of 4 mg/kg. Liposomes were composed of phosphatidylcholine, cholesterol, and stearylamine (positive charge) or phosphatidylserine (negative charge). Administration of free doxorubicin caused a pattern of cardiac damage characterized by loss of myofiber elements, mitochondrial damage, nuclear abnormalities, swollen and distended sarcoplasmic reticulum leading to vacuolization, and increasing myeloid body accumulation. Cardiac tissues of mice treated with doxorubicin entrapped in negatively charged liposomes demonstrated pronounced loss of filaments, enlarged mitochondria, disruptive loss of crests, and expanded nuclear membrane. However, electron microscopic examination of the cardiac muscles of mice treated with positive liposomes demonstrated a significant protection from drug-induced toxicity, with only minor loss of parallel fibrillar arrangement and myofilaments in limited focal areas. The majority of the tissue demonstrated normal vasculature and intercalation of myocytes as compared to control groups. The mean qualitative and quantitative scores of toxic lesions for free doxorubicin and entrapped in negative liposomes are 2.7 and 2.23, respectively. However, the mean score for the group of mice treated with positive liposomes is only 1.12, showing a better than 2-fold scoring protection of both the extent and severity of cardiac lesions.