fibrin and Body-Weight

Topics: Antigens; Body Weight; Fibrin; Humans; Postoperative Complications; Prognosis; Risk; Serum Globulins; Thrombophlebitis; Time Factors; Varicose Veins

Adequate linezolid blood concentrations have been shown to be associated with an improved clinical outcome. Our goal was to assess new predictors of inadequate linezolid concentrations often observed in critically ill patients. Fifty-two critically ill patients with severe infections receiving standard dosing of linezolid participated in this prospective observational study. Serum samples (median, 32 per patient) were taken on four consecutive days, and total linezolid concentrations were quantified. Covariates influencing linezolid pharmacokinetics were identified by multivariate analysis and a population pharmacokinetic model. Target attainment (area under the concentration-time curve over 12 h [AUC12]/MIC ratio of >50; MIC = 2 mg/liter) was calculated for both the study patients and a simulated independent patient group (n = 67,000). Target attainment was observed for only 36% of the population on both days 1 and 4. Independent covariates related to significant decreases of linezolid concentrations included higher weight, creatinine clearance rates, and fibrinogen and antithrombin concentrations, lower concentrations of lactate, and the presence of acute respiratory distress syndrome (ARDS). Linezolid clearance was increased in ARDS patients (by 82%) and in patients with elevated fibrinogen or decreased lactate concentrations. In simulated patients, most covariates, including fibrinogen and lactate concentrations and weight, showed quantitatively minor effects on target attainment (difference of ≤9% between the first and fourth quartiles of the respective parameters). In contrast, the presence of ARDS had the strongest influence, with only ≤6% of simulated patients reaching this target. In conclusion, the presence of ARDS was identified as a new and strong predictor of insufficient linezolid concentrations, which might cause treatment failure. Insufficient concentrations might also be a major problem in patients with combined alterations of other covariate parameters. (This study has been registered at ClinicalTrials.gov under registration number NCT01793012.).

Topics: Aged; Anti-Bacterial Agents; Body Weight; Creatinine; Critical Illness; Drug Administration Schedule; Drug Dosage Calculations; Female; Fibrin; Fibrinogen; Humans; Lactic Acid; Linezolid; Male; Middle Aged; Models, Statistical; Multivariate Analysis; Prospective Studies; Respiratory Distress Syndrome; Risk Factors

In trauma patients, resuscitation to endpoints below normal blood pressure (BP) levels may reduce further blood loss due to the rebleeding often caused by more aggressive resuscitation. However, patients whose BP is maintained at lower levels for extended periods are at increased risk for organ failure. The purpose of this study was to determine whether recombinant activated factor VII (rFVIIa) raises the BP level at which rebleeding occurs in a prospective, randomized, blinded study using a porcine model of uncontrolled hemorrhage and resuscitation. Thirty anesthetized 40-kg pigs were assigned to three groups (n = 10/group): control, low-dose rFVIIa (180 microg/kg), or high-dose (720 microg/kg). Vehicle or drug was infused 5 min before creating a 2.0-mm infrarenal aortotomy. Ten minutes later, resuscitation with lactated Ringer's (LR) solution at 100 mL/min was begun. Hemorrhage and LR volumes and BP were recorded continuously. We found that pretreatment with rFVIIa increased the mean arterial pressure at which rebleeding occurred during resuscitation (45 +/- 3, 69 +/- 5, and 66 +/- 6 mmHg in the control, low-dose, and high-dose groups, respectively, P = 0.003). Rebleed hemorrhage volume was reduced with rFVIIa (39 +/- 9, 22 +/- 7, and 26 +/- 5 mL/kg for control, and low and high dose, respectively; P = 0.055). This is the first study to show that rFVIIa increases the BP at which rebleeding occurs during resuscitation in an injury to a major artery, suggesting the formation of a tight, stronger fibrin plug in the presence of high concentrations of rFVIIa.

Topics: Animals; Antithrombins; Aorta; Aortic Diseases; Blood Pressure; Body Weight; Disease Models, Animal; Factor VII; Factor VIIa; Female; Fibrin; Hemorrhage; Pressure; Prospective Studies; Recombinant Proteins; Resuscitation; Secondary Prevention; Swine; Thrombin; Time Factors; Treatment Outcome

Topics: Amino Acids; Apnea; Birth Weight; Blood Glucose; Body Weight; Chromatography, Thin Layer; Fibrin; Gestational Age; Glucose; Humans; Infant, Newborn; Infant, Premature; Nitrogen; Osmolar Concentration; Parenteral Nutrition; Protein Hydrolysates

Fibrin gel-based scaffolds have promising potential for microtia reconstruction. Autologous chondrocytes and chondrocyte cell sheets are frequently used seed cell sources for cartilage tissue engineering. However, the aesthetic outcome of chondrocyte-based microtia reconstruction is still not satisfactory. In this study, we aimed to fabricate the chondrocytes/chondrocyte-microtissues laden fibrin gel auricular scaffold for microtia reconstruction. We designed a unique auricular mold that could fabricate a fibrin gel scaffold resembling human auricle anatomy. Primary chondrocytes were harvested from rabbit auricular cartilage, and chondrocyte cell sheets were developed. Chondrocyte-microtissues were prepared from the cell sheets. The mixture of chondrocytes/chondrocyte-microtissues was laden in fibrin gel during the auricular scaffold fabrication. The protrusions and recessed structure in the auricular scaffold surface were still clearly distinguishable. After a one-week in vitro culture, the 3 D structure and auricular anatomy of the scaffold were retained. And followed by eight-week subcutaneous implantation, cartilaginous tissue was regenerated in the artificial auricular structure as indicated by the results of H&E, Toluidine blue, Safranin O, and type II collagen (immunohistochemistry) staining. Protrusions and depressions of the auricular scaffold were slightly deformed, but the overall auricular anatomy was maintained after 8-week in vivo implantation. Extracellular matrix components content were similar in artificial auricular cartilage and rabbit native auricular cartilage. In conclusion, the mixture of chondrocytes/chondrocyte-microtissues laden fibrin gel auricular scaffold showed a promising potential for cartilaginous tissue regeneration, suggesting this as an effective approach for autologous chondrocyte-based microtia reconstruction.

Topics: Animals; Body Weight; Cartilage; Chondrocytes; Congenital Microtia; Ear Auricle; Ear Cartilage; Extracellular Matrix; Fibrin; Gels; Humans; Male; Mice; Mice, Nude; Rabbits; Silicones; Swine; Tissue Engineering; Tissue Scaffolds

Obesity promotes a chronic inflammatory and hypercoagulable state that drives cardiovascular disease, type 2 diabetes, fatty liver disease, and several cancers. Elevated thrombin activity underlies obesity-linked thromboembolic events, but the mechanistic links between the thrombin/fibrin(ogen) axis and obesity-associated pathologies are incompletely understood. In this work, immunohistochemical studies identified extravascular fibrin deposits within white adipose tissue and liver as distinct features of mice fed a high-fat diet (HFD) as well as obese patients. Fibγ390-396A mice carrying a mutant form of fibrinogen incapable of binding leukocyte αMβ2-integrin were protected from HFD-induced weight gain and elevated adiposity. Fibγ390-396A mice had markedly diminished systemic, adipose, and hepatic inflammation with reduced macrophage counts within white adipose tissue, as well as near-complete protection from development of fatty liver disease and glucose dysmetabolism. Homozygous thrombomodulin-mutant ThbdPro mice, which have elevated thrombin procoagulant function, gained more weight and developed exacerbated fatty liver disease when fed a HFD compared with WT mice. In contrast, treatment with dabigatran, a direct thrombin inhibitor, limited HFD-induced obesity development and suppressed progression of sequelae in mice with established obesity. Collectively, these data provide proof of concept that targeting thrombin or fibrin(ogen) may limit pathologies in obese patients.

Topics: Adipose Tissue; Adiposity; Amino Acid Motifs; Animals; Blood Glucose; Body Composition; Body Weight; Coagulants; Dabigatran; Diet, High-Fat; Fatty Liver; Female; Fibrin; Genotype; Homozygote; Inflammation; Liver; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Obesity; Thrombin; Weight Gain

Recently, bioretention and toxicity of injected nanoparticles in the body has drawn much attention in biomedical research. In the present study, 5 mg Fe per kg body weight of magnetic fibrin nanoparticles (MFNPs) were injected into mice intravenously and investigated for their blood clearance profile, biodistribution, haematology and pathology studies for a time period of 28 days. Moderately long circulation of MFNPs in blood was observed with probable degradation and excretion into the bloodstream via monoatomic iron forms. Inductively coupled plasma optical emission spectrometry (ICP-OES) and Prussian blue staining results showed increased accumulation of MFNPs in the liver, followed by spleen and other organs. Body weight, spleen/thymus indexes, haematology, serum biochemistry and histopathology studies demonstrated that MFNPs were biocompatible. These results suggest the feasibility of using MFNPs for drug delivery and imaging applications.

Topics: Animals; Biocompatible Materials; Body Weight; Dynamic Light Scattering; Female; Fibrin; Hemolysis; Liver; Magnetite Nanoparticles; Mice; Mice, Inbred BALB C; Spleen; Time Factors; Tissue Distribution

A significant challenge in the design and development of biomaterial scaffolds is to incorporate mechanical and biochemical cues to direct organized tissue growth. In this study, we investigated the effect of hepatocyte growth factor (HGF) loaded, crosslinked fibrin (EDCn-HGF) microthread scaffolds on skeletal muscle regeneration in a mouse model of volumetric muscle loss (VML). The rapid, sustained release of HGF significantly enhanced the force production of muscle tissue 60 days after injury, recovering more than 200% of the force output relative to measurements recorded immediately after injury. HGF delivery increased the number of differentiating myoblasts 14 days after injury, and supported an enhanced angiogenic response. The architectural morphology of microthread scaffolds supported the ingrowth of nascent myofibers into the wound site, in contrast to fibrin gel implants which did not support functional regeneration. Together, these data suggest that EDCn-HGF microthreads recapitulate several of the regenerative cues lost in VML injuries, promote remodeling of functional muscle tissue, and enhance the functional regeneration of skeletal muscle. Further, by strategically incorporating specific biochemical factors and precisely tuning the structural and mechanical properties of fibrin microthreads, we have developed a powerful platform technology that may enhance regeneration in other axially aligned tissues.

Topics: Animals; Biomechanical Phenomena; Body Weight; Cattle; Cell Differentiation; Collagen; Cross-Linking Reagents; Fibrin; Hepatocyte Growth Factor; Immunohistochemistry; Isometric Contraction; Mice, SCID; Muscle, Skeletal; Muscular Diseases; Myoblasts; Neovascularization, Physiologic; Platelet Endothelial Cell Adhesion Molecule-1; Regeneration

Protein kinase C epsilon (PKCε) has been shown to play a role in experimental steatosis by acute alcohol. The "two-hit" hypothesis implies that preventing steatosis should blunt more advanced liver damage (e.g., inflammation and necrosis). However, the role of PKCε in these pathologies is not yet known. The goal of this current work was to address this question in a model of chronic alcohol exposure using antisense oligonucleotides (ASO) against PKCε.. Accordingly, PKCε ASO- and saline-treated mice were fed high-fat control or ethanol (EtOH)-containing enteral diets for 4 weeks.. Chronic EtOH exposure significantly elevated hepatic lipid pools as well as activated PKCε. The PKCε ASO partially blunted the increases in hepatic lipids caused by EtOH. Administration of PKCε ASO also completely prevented the increase in the expression of fatty acid synthase, and tumor necrosis factor α caused by EtOH. Despite these protective effects, the PKCε ASO was unable to prevent the increases in inflammation and necrosis caused by chronic EtOH. These latter results correlated with an inability of the PKCε ASO to blunt the up-regulation of plasminogen activator inhibitor-1 (PAI-1) and the accumulation of fibrin. Importantly, PAI-1 has been previously shown to more robustly mediate inflammation and necrosis (vs. steatosis) after chronic EtOH exposure.. This study identifies a novel potential mechanism where EtOH, independent of steatosis, can contribute to liver damage. These results also suggest that PAI-1 and fibrin accumulation may be at the center of this PKCε-independent pathway.

Topics: Animals; Biomarkers; Body Weight; Central Nervous System Depressants; Diglycerides; Enzyme Activation; Ethanol; Fatty Liver, Alcoholic; Fibrin; Gene Expression; Hepatitis, Alcoholic; Lipid Metabolism; Liver; Male; Mice; Mice, Inbred C57BL; Necrosis; Protein Kinase C-epsilon

To investigate whether the combined endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) could enhance angiogenesis and wound healing in diabetic mice. Balb/c nude mice were divided into five groups, including a control group, diabetic group (DM), DM injected with 1 × 10(6) cells MSCs, DM injected with 1 × 10(6) cells EPCs, and DM injected with combined 0.5 × 10(6) cells MSCs and 0.5 × 10(6) cells EPCs. After seven weeks, the mice were anesthetized, and bilateral full-thickness excision skin wounds were made on the dorsorostral back. The percentage of wound closure in DM group decreased significantly than in control and all other treated groups on day 7 and day 14 (P < 0.005). On day 14, the percentage of capillary vascularity in combine-treated group was significantly higher than in DM (P < 0.005). In the present study, we have demonstrated that the combined EPCs and MSCs can increase vascular endothelial growth factor (VEGF) level and angiogenesis which resulted in reduced neutrophil infiltration, decreased malondialdehyde (MDA) levels, and enhanced wound healing in diabetic mice model.

Topics: Animals; Blood Glucose; Body Weight; Capillaries; Diabetes Mellitus, Experimental; Endothelial Cells; Fibrin; Humans; Male; Malondialdehyde; Mesenchymal Stem Cells; Mice; Mice, Inbred BALB C; Mice, Nude; Neovascularization, Physiologic; Neutrophil Infiltration; Oxidative Stress; Stem Cell Transplantation; Vascular Endothelial Growth Factor A; Wound Healing

The goal of our work was to study the changes in the bone tissue, bone marrow and surrounding tissues in animals during early stages of experimental osteomyelitis. Osteomyelitis was simulated in 30 infants rabbits aged 3-4 months whose body weight accounted 1200-1600 grams through the insertion of 5-6 million of aurococcus into the marrow channel of a shinbone. The study of bone marrow, bone tissue and surrounding tissue was conducted 30 minutes, 6, 12, 24, 48 and 60 hours after the contamination with the help of light and electronic (transmission and scanning) microscopy. It was proved that the first changes are characterized by the evident changes in the vessel's walls which cause the swelling of bone marrow and suppurative inflammation in the bone tissue occurs only in the end of the 3d day of the experiment. These data confirm the necessity of osteoperfortation during the first 24 hours of contamination in order to remove the swelling and to correct vessel disorders.

Topics: Animals; Body Weight; Bone and Bones; Bone Marrow; Disease Models, Animal; Fibrin; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; Osteomyelitis; Rabbits; Staphylococcal Infections; Time Factors

The cellular and molecular mechanisms and safety after drug-eluting stent (DES) implantation in diabetic patients are still poorly understood; therefore, in this study, we evaluated the pathologic responses of the sirolimus-eluting stent (SES) or paclitaxel-eluting stent (PES) in a type I diabetes mellitus (DM) rat model.. The type I DM rat model was manipulated by intra-peritoneal streptozotocin injection. Two weeks later, DES was implanted in the aorta of rats with hyperglycemia or not as a control. Four weeks after DES implantation, the stented aorta was isolated and histomorphometric analysis was performed.. On histomorphometric analysis, increased thrombus, inflammatory cell infiltration, and neointimal hyperplasia (NIH) without change of the smooth muscle cell number after DES implantation were observed in DM rats compared with non-DM (NDM) rats. Furthermore, delayed coverage of mature endothelial cells defined as a von Willebrand factor expression and increased immature endothelial cells as a c-kit expression after DES implantation were observed in DM rats compared with NDM rats. Increased fibrin deposition and decreased hyaluronic acid accumulation at NIH after DES implantation were also observed in DM rats compared with NDM rats.. In conclusion, the main mechanism of restenosis after DES implantation under hyperglycemic conditions was initial thrombus with changes of the extracellular matrix rather than SMC proliferation. These results provided a therapeutic clue for the selection of DES and application of combination therapy using anti-thrombotic and anti-inflammatory drugs in diabetic patients.

Topics: Animals; Anti-Inflammatory Agents; Aorta; Body Weight; Coronary Restenosis; Diabetes Mellitus, Type 1; Disease Models, Animal; Drug-Eluting Stents; Fibrin; Humans; Hyaluronic Acid; Hyperglycemia; Inflammation; Male; Paclitaxel; Rats; Rats, Sprague-Dawley; Sirolimus; Thrombosis

The purpose of this study was to assess the therapeutic and toxicological effects of cesium chloride (CsCl) administration in mice bearing prostate cancer tumors.. Three CsCl dose titration studies were completed in tumor-bearing and non-tumor-bearing athymic nude mice. All mice were administered either vehicle (controls), 150, 300, 600, 800, 1,000, or 1,200 mg/kg of CsCl once daily by oral gavage for 30 consecutive days. Body mass was measured daily, food and water consumption were measured every 2 days, and tumor volume was measured twice weekly. Histopathological analysis was conducted on tissues collected from each of the studies. Serum AST/ALT and creatinine were also measured.. Administration of 800-1,200 mg/kg CsCl reduced PC-3 tumor growth but had no effect on LNCaP tumors. Administration of 800-1,200 mg/kg CsCl also resulted in increased water consumption, bladder crystal development, and higher prevalence of cardiac fibrin clots. An observed loss in body mass was dependent on the xenograft type and concentration of CsCl administered. CsCl did not affect serum AST/ALT and creatinine levels.. CsCl may have a therapeutic effect against prostate cancer, but one cannot overlook the acute toxicities also described.

Topics: Administration, Oral; Animals; Antineoplastic Agents; Body Weight; Cell Line, Tumor; Cesium; Chlorides; Crystallization; Disease Models, Animal; Dose-Response Relationship, Drug; Fibrin; Heart; Liver; Liver Function Tests; Male; Mice; Mice, Nude; Prostate-Specific Antigen; Prostatic Neoplasms; Random Allocation; Thirst; Thrombosis; Urinary Bladder; Xenograft Model Antitumor Assays

We evaluated the neuroprotective effect of UK-279,276 (also referred to as recombinant neutrophil inhibitory factor), a selective CD11b/CD18 antagonist, in combination with thrombolytic therapy on focal cerebral ischemia.. Male Wistar rats (n=88) were subjected to embolic middle cerebral artery occlusion. Animals were randomly assigned to the following groups (n=11 in each group): vehicle treatment alone at 2 or 4 hours, UK-279,276 treatment alone at 2 or 4 hours, recombinant human tissue plasminogen activator (rhtPA) treatment alone at 2 or 4 hours, or the combination of UK-279,276 and rhtPA at 2 or 4 hours. Infarct volume, neurological function, hemorrhagic transformation, neutrophil accumulation, and parenchymal fibrin deposition were measured 7 days after middle cerebral artery occlusion.. Treatment with UK-279,276 significantly (P<0.05) improved neurological severity scores, an index of neurological functional deficit, but had no effect on infarct volume compared with vehicle-treated animals. Treatment with rhtPA alone at 2 but not 4 hours significantly (P<0.05) reduced infarct volume and improved neurological function compared with vehicle-treated animals. Combination treatment with UK-279,276 and rhtPA at 2 or 4 hours significantly (P<0.01) reduced infarct volume and enhanced recovery of neurological function compared with control. Neutrophil accumulation and fibrin deposition in the brain parenchyma of combination-treated rats at 2 and 4 hours after stroke were significantly reduced (P<0.05) compared with corresponding vehicle-treated control groups. The neuroprotective effect of the combined treatments was superior to the additive effects from each treatment of rhtPA or UK-279,276 alone.. These data suggest that the combination treatment with UK-279,276 and rhtPA may extend the window of thrombolytic therapy for the acute treatment of stroke.

Topics: Animals; Body Weight; Brain; CD11b Antigen; Cerebral Hemorrhage; Disease Models, Animal; Fibrin; Glycoproteins; Helminth Proteins; Humans; Infarction, Middle Cerebral Artery; Intracranial Embolism; Male; Membrane Proteins; Neurologic Examination; Neuroprotective Agents; Peroxidase; Rats; Rats, Wistar; Recombinant Proteins; Severity of Illness Index; Stroke; Tissue Plasminogen Activator

The stentless xenograft with its favorable hemodynamic performance on the left side of the heart seems an attractive, readily available alternative for the reconstruction of the right ventricular outflow tract in children.. To assess its function in a preclinical animal investigation, we replaced the pulmonary root with a Freestyle stentless aortic xenograft in 18 piglets of 26.6 +/- 3.2 kg weight. The animals were allowed to grow as much as possible and slaughtered when symptoms of heart failure developed or body weight reached more than 160 kg. All valve explants were analyzed by gross examination and photography and, in 4 representative pigs, by histologic examination.. Fourteen animals died prematurely after 2 weeks to 11 months. Twelve xenograft explants showed thick, immobilized, large nodular structures as cuspal remnants causing significant stenosis. At microscopy, large cuspal masses of degenerating collagen and fibrin and various inflammatory cells were frequently found. In the growing pig, most of the xenografts implanted in the pulmonary position showed early degeneration causing severe stenosis.. Use of this valve for right ventricular outflow tract reconstruction in children cannot be recommended.

Topics: Animals; Aortic Valve; Bioprosthesis; Body Weight; Calcinosis; Cardiac Output, Low; Cause of Death; Collagen; Constriction, Pathologic; Disease Models, Animal; Endocarditis; Fibrin; Growth; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Prosthesis Design; Prosthesis Failure; Pulmonary Valve; Surface Properties; Swine

SHP female mice were fed 100 mg/kg carbonic fibrilous sorbent Akvalen 5 times a week, from the age of 3 months until death. The treatment failed to have a significant influence on body weight dynamics or mean lifespan. However, sorbent-treated animals survived 4 months longer until 90% of them died. Although there were no significant differences in the frequency of either all or only malignant tumors between study group and controls, the former showed fewer multiple tumors (1.4 times) as well as a tendency of decreased incidence of neoplasms of the hemopoietic system and uterine polyps. Tumor-bearing sorbent-treated mice survived 4 months longer, while those with malignant tumors only survived 5 months longer (p < 0.05). The investigation failed to detect any carcinogenicity of Akvalen. It is suggested that the sorbent possesses certain geroprotective and anti-tumor properties.

Topics: Animals; Antineoplastic Agents; Body Weight; Carbon; Female; Fibrin; Mice; Survival Analysis

It has been reported that plasma fibrinolytic activity is abnormal in some patients with chronic low back pain. In an attempt to confirm this finding we studied 22 patients with chronic mechanical low back pain and compared them with 18 healthy controls who denied symptoms of back pain. Factors known to interfere with plasma fibrinolysis such as age, weight, seasonal and diurnal variation, exercise, smoking and drugs were controlled as far as possible. Plasma fibrinogen was significantly higher (2.8 versus 2.3 g/l, P < 0.005) in patients than in controls, but there were no significant differences in the median plasma concentrations of euglobulin clot lysis time, fibrin plate lysis area, plasminogen, alpha-2-antiplasmin, tissue plasminogen activator activity, and antigen, tissue plasminogen activator inhibition and plasminogen activator inhibitor-1 antigen level. The results fail to confirm abnormalities of plasma fibrinolytic activity in a group of unselected cases of chronic low back pain.

Topics: Adult; Aged; Aging; alpha-2-Antiplasmin; Body Weight; Female; Fibrin; Fibrinolysis; Humans; Low Back Pain; Male; Middle Aged; Plasminogen; Plasminogen Activator Inhibitor 1; Seasons; Serum Globulins; Tissue Plasminogen Activator

Individual and age-dependent variations in the venoms of 23 specimens of Bothrops atrox were studied using SDS-polyacrylamide gel electrophoresis, isoelectric focusing and different enzymic activity measurements. The electrophoretic patterns showed a decrease in total protein band numbers and a shifting from components with higher to those with lower molecular weights with increasing age of the snakes. The venoms of individuals younger than 12 months showed isoelectric focusing patterns within a pH range of 3.5-6.0, whereas those of older specimens extended from pH 3.5 to 7.0. Individual variations were found in fibrinogen-clotting and fibrinolytic activities. Despite the fact that important quantitative differences were also found in amidolytic activities measured on five chromogenic proteinase substrates, all the venoms showed the same activity profile. Specimens of the oldest age group (8 years) showed absence of some enzymatic activities.

Topics: Aging; Animals; Blood Coagulation; Body Weight; Crotalid Venoms; Electrophoresis, Polyacrylamide Gel; Female; Fibrin; Isoelectric Focusing; Male; Peptide Hydrolases; Snakes; Time Factors

The efficiency of alpha-ketoisocaproate as a dietary substitute for leucine was assessed in rats by two techniques: first, the minimal dose of alpha-ketoisocaproate required, as a supplement to a leucine-free diet, to achieve a growth rate as great as animals receiving leucine was found to be between 2.2 and 4.4 times larger. Therefore the nutritional efficiency of alpha-ketoisocaproate lies between 0.23 and 0.46. Second, alpha-[1-14C]-ketoisocaproate and [3H]leucine were administered orally and the ratio of 14C/3H incorporated into the leucine of whole-body protein and fibrin was measured. This ratio, divided by the ratio 14C/3H injected, was the same in fibrin as in whole-body protein and averaged 0.39. Thus both techniques yield the same value, within the error of measurement, for the relative nutritional efficiency of alpha-ketoisocaproate. We also found that alpha-ketoisocaproate feeding at varying dosage did not alter this ratio in whole-body protein (measured in rats fasted overnight), suggesting that neither wide variations in growth rate nor exposure for 10 days to alpha-ketoisocaproate (in a diet of constant protein content) alters the relative rates of utilization (or oxidation) of alpha-ketoisocaproate vs. leucine.

Topics: Animals; Body Weight; Carbon Radioisotopes; Diet; Dose-Response Relationship, Drug; Eating; Fibrin; Keto Acids; Leucine; Male; Nutritional Physiological Phenomena; Protein Biosynthesis; Rats; Rats, Inbred Strains; Tritium

Protein C is a circulating proenzyme which, upon activation, exerts a potent anticoagulant activity. Infusion of activated bovine protein C into dogs is accompanied by an increase of circulating tissue plasminogen activator (PA) activity. However, the evidence that human protein C shares a similar profibrinolytic capacity is still lacking. Therefore, we investigated the profibrinolytic properties of human protein C in squirrel monkeys (Samiri sciureus). Injection of activated human protein C resulted in prolongation of the activated partial thromboplastin time but was not associated with increased fibrinolytic activity of blood. Similarly, activation of endogenous protein C (up to 20-30%) by infusion of thrombin-thrombomodulin complex markedly reduced blood coagulability without being accompanied by an increase of circulating PA activity. The in vivo-generated anticoagulant activity was identified as activated protein C by the following observations. It was neutralized by rabbit anti-human protein C-IgG, was slowly inhibited by plasma but not by anti-thrombin III, was adsorbable on barium citrate, and expressed amidolytic activity. Activation of protein C appeared to be selective since other parameters such as thrombin time, platelet count, fibrinogen, and factor V levels were unaffected by thrombin-thrombomodulin infusion. Infusion of human plasma derived from whole blood incubated in vitro with human activated protein C also did not induce a fibrinolytic response, suggesting that no second messengers with PA-releasing activity were being generated in blood. It is concluded that in a primate, neither the administration of activated human protein C nor the activation of endogenous protein C are associated with an increase of fibrinolytic activity. These findings question the role of this enzyme in the regulation of PA release in man.

Topics: Animals; Blood Coagulation; Blood Coagulation Factors; Body Weight; Enzyme Activation; Fibrin; Fibrinolysis; Glycoproteins; Humans; Kinetics; Protein C; Saimiri

To test the hypothesis that individual proteins have specific effects on calcium absorption, two proteins, casein and fibrin, were pair-fed in diets to rats for 3 weeks. Each protein was fed at normal (1.2%) and low (0.02%) calcium intakes. Diets were matched in other nutrients. Calcium absorption, measured in vitro as serosal-to-mucosal concentration ratio of 45Ca developed by duodenal sacs, was the same for both protein groups when calcium intake was normal and was increased by both low-calcium diets. Comparing low-calcium diets, absorption was greater in fibrin-fed than casein-fed groups. Balance studies showed that casein- and fibrin-fed rats taking normal calcium diets excreted the same amounts of calcium and phosphorus in urine and feces. Fibrin-fed rats taking low calcium excreted twice as much calcium as casein-fed rats and had decreased serum calcium. The balance data suggest that, compared to casein, fibrin prevents absorption or promotes excretion of calcium when calcium intake is low, and the response to calcium depletion is enhanced calcium absorption. It is concluded that individual proteins can alter calcium transport through effects on overall calcium homeostasis.

Topics: Animals; Body Weight; Calcium; Caseins; Dietary Proteins; Fibrin; Homeostasis; Intestinal Absorption; Intestinal Mucosa; Male; Phosphorus; Rats; Time Factors

A prospective study was carried out to confirm the validity of a predictive index for patients at risk of developing deep vein thrombosis. The index, which correctly identified nine out of 10 patients and incorrectly identified seven out of 52 patients as being at risk, is based on five variable--namely, the euglobulin lysis time, serum concentration of fibrin-related antigen, age, percentage overweight for height, and presence of varicose veins. Thus a population of patients at particularly high risk of developing postoperative deep vein thrombosis may be identified preoperatively by means of this index, so that prophylaxis may be used more rationally.

Topics: Adult; Aged; Antigens; Blood Coagulation Tests; Body Weight; Female; Fibrin; Humans; Postoperative Complications; Risk; Serum Globulins; Thrombophlebitis; Varicose Veins

Administration of prophylactic low-dose subcutaneous heparin to prevent postoperative deep vein thrombosis is expensive, entails treating many patients unnecessarily, and causes some side effects. By using a predictive index a population of patients who are at particularly high risk of developing postoperative deep vein thrombosis may be identified preoperatively. Prophylaxis was given only to these patients, resulting in an incidence of deep vein thrombosis of 3.8% compared with 16.1% in previous studies in which no specific prophylaxis was given. By limiting prophylaxis to the group of patients identified by the predictive index as being at high risk of developing postoperative deep vein thrombosis results may be obtained that are as good as those expected from treating the whole population. Thus many patients are saved from exposure to low-dose subcutaneous heparin.

Topics: Aged; Antigens; Blood Coagulation Tests; Body Weight; Drug Administration Schedule; Female; Fibrin; Heparin; Humans; Middle Aged; Postoperative Complications; Risk; Serum Globulins; Thrombophlebitis; Time Factors

Topics: Animals; Body Weight; Dogs; Fibrin; Hemodynamics; Iodine Radioisotopes; Lung; Organ Size; Pulmonary Edema; Pulmonary Embolism; Time Factors; Tranexamic Acid

A range of clinical data was obtained from 124 patients about to undergo operation and several coagulation tests were performed. No patient received prophylaxis for deep vein thrombosis, and isotopic scanning after operation showed that 20 patients had developed thrombosis. a simiple prognostic index for predicting which patients would develop postoperative deep vein thrombosis was constructed using the clinical and coagulation data obtained before operation. The five variables with the best predictive power-euglobulin lysis time, age, presence of varicose veins, fibrin related antigen, and percentage overweight-produced an equation that identfied 95% of those who developed deep vein thrombosis and misallocated only 28% of those who did not develop thrombosis. In view of the complications that low-dose heparin and dextran can cause, giving prophylaxis to under a third of the patients who will not develop deep vein thrombosis is clearly better than giving it to all.

Topics: Adult; Age Factors; Antigens; Body Weight; Fibrin; Humans; Middle Aged; Postoperative Complications; Prognosis; Serum Globulins; Thrombophlebitis; Varicose Veins

Topics: Blood Glucose; Blood Urea Nitrogen; Body Weight; Caseins; Catheterization; Cholesterol; Dietary Carbohydrates; Emulsions; Esophagitis; Fibrin; Gastrointestinal Diseases; Hemoglobins; Humans; Insulin; Lipids; Liver; Liver Function Tests; Nutritional Requirements; Parenteral Nutrition; Protein Hydrolysates; Sepsis; Staphylococcal Infections; Triglycerides

Topics: Alloxan; Animals; Autoradiography; Blood Pressure; Body Weight; Bronchi; Dogs; Exudates and Transudates; Fibrin; Heparin; Lung; Organ Size; Pulmonary Alveoli; Pulmonary Artery; Pulmonary Edema; Time Factors; Water

In a study of 41 fasting subjects it was confirmed that fibrinolytic activity was reduced in obese persons: an increase in fibrinogen was also associated with obesity. There was no correlation between obesity and the platelet count, platelet adhesiveness to glass, the level of serum fibrin degradation products, or the whole blood clotting time in plastic tubes.

Topics: Blood Cell Count; Blood Coagulation; Blood Coagulation Tests; Body Weight; Fasting; Female; Fibrin; Fibrinogen; Fibrinolysis; Humans; Male; Obesity; Plasminogen; Platelet Adhesiveness

Topics: Adult; Body Weight; Chyle; Diet Therapy; Female; Fibrin; Fistula; Humans; Kidney Diseases; Lymphatic Diseases; Lymphatic System; Urine; Urography

Topics: Adult; Aged; Anemia, Hemolytic; Blood Cell Count; Body Weight; Erythrocyte Aggregation; Female; Fibrin; Fibrinogen; Fibrinolysis; Hemoglobinometry; Heparin; Humans; Iodine Isotopes; Leukocyte Count; Male; Middle Aged; Plasma; Plasma Volume; Urea

Topics: Amino Acids; Animals; Body Weight; Cold Temperature; Diet; Dietary Proteins; Eating; Environmental Exposure; Fibrin; Hypothalamus; Male; Methionine; Phenylalanine; Rats; Thyroxine

Topics: Amino Acids; Aminoisobutyric Acids; Body Weight; Caseins; Cold Temperature; Diet; Fibrin; Leucine; Metabolism; Nitrogen; Rats; Research; Temperature; Tissue Distribution; Tryptophan