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At least 721 records · Page 40Linked to original sources
PubMed2002

Hormone-sensitive lipase deficiency in mice changes the plasma lipid profile by affecting the tissue-specific expression pattern of lipoprotein lipase in adipose tissue and muscle.

Hormone-sensitive lipase (HSL) is believed to play an important role in the mobilization of fatty acids from triglycerides (TG), diglycerides, and cholesteryl esters in various tissues. Because HSL-mediated lipolysis of TG in adipose tissue (AT) directly feeds non-esterified fatty acids (NEFA) into the vascular system, the enzyme is expected to affect many metabolic processes including the metabolism of plasma lipids and lipoproteins. In the present study we examined these metabolic changes in induced mutant mouse lines that lack HSL expression (HSL-ko mice). During fasting, when HSL is normally strongly induced in AT, HSL-ko animals exhibited markedly decreased plasma concentrations of NEFA (-40%) and TG (-63%), whereas total cholesterol and HDL cholesterol levels were increased (+34%). Except for the increased HDL cholesterol concentrations, these differences were not observed in fed animals, in which HSL activity is generally low. Decreased plasma TG levels in fasted HSL-ko mice were mainly caused by decreased hepatic very low density lipid lipoprotein (VLDL) synthesis as a result of decreased NEFA transport from the periphery to the liver. Reduced NEFA transport was also indicated by a depletion of hepatic TG stores (-90%) and strongly decreased ketone body concentrations in plasma (-80%). Decreased plasma NEFA and TG levels in fasted HSL-ko mice were associated with increased fractional catabolic rates of VLDL-TG and an induction of the tissue-specific lipoprotein lipase (LPL) activity in cardiac muscle, skeletal muscle, and white AT. In brown AT, LPL activity was decreased. Both increased VLDL fractional catabolic rates and increased LPL activity in muscle were unable to provide the heart with sufficient NEFA, which led to decreased tissue TG levels in cardiac muscle. Our results demonstrate that HSL deficiency markedly affects the metabolism of TG-rich lipoproteins by the coordinate down-regulation of VLDL synthesis and up-regulation of LPL in muscle and white adipose tissue. These changes result in an "anti-atherogenic" lipoprotein profile.

Adipose Tissue↗
PubMed1991

Measurement of small-angle photon scattering for some breast tissues and tissue substitute materials.

For photon energies encountered in diagnostic radiology the shape of the scattering distributions for low-atomic-number media exhibits peaks in intensity close to the forward direction that are not predicted by conventional theoretical models. The positions and shapes of the peaks depend upon the interatomic and intermolecular configurations of the scatterers. The phenomenon is of particular interest because of its relevance to the understanding and modelling of x-ray imaging processes and the possibility that the peaking may be characteristic of tissue type. In the present study, peaks in the forward scattering distributions have been demonstrated for 19 samples of breast tissue and three tissue substitute materials using a position-sensitive photon detector and a 60 kVp x-ray source. Prominent features were observed for all samples investigated. Large differences were found in the shapes of the distributions between adipose and fibroglandular tissues and only small differences were found between carcinomas and fibroglandular tissues.

Adenofibroma↗
PubMed2002

Tissue-engineered repair of osteochondral defects: effects of the age of donor cells and host tissue.

Transplantation of a tissue-engineered construct containing cells of a chondrocytic phenotype into an osteochondral defect provides a biological solution to this type of injury. Among the factors that affect cell proliferation and phenotypic expression, age is one that has not been well characterized. In this study adult and aged male donor cells, derived from perichondrium, were cultured and adsorbed into a polylactic acid (PLA) scaffold and transplanted into osteochondral defects created in adult (8- to 10-month-old) and aged (4- to 5-year-old) female rabbits. Three groups were investigated: (1) adult cells transplanted into aged defects, (2) aged cells transplanted into aged defects, and (3) aged cells transplanted into adult defects. In vitro characterization of adult and aged cells and in vivo assessment of osteochondral repair tissue at 12 weeks posttransplantation were carried out. The in vitro studies demonstrated that the proliferation rate of aged cells was less than that of mature cells during the earliest stage of culture. Also, the chondrocytic phenotype was reduced in aged cells compared with mature cells. The in vivo results showed that donor (SRY-positive) cell survival differed among the three groups: survival of adult cells into aged defect > survival of aged cells into aged defect > survival of aged cells into adult defect. The biological acceptability of the repair, defined as smooth firm cartilaginous tissue filling the defect, was < 25% of the operated specimens in each of the three groups. This repair tissue contained only 20-25% of the amounts of type II collagen and glycosaminoglycans found in normal articular cartilage. These data suggest that the outcome of tissue-engineered repair of osteochondral defects is affected by both the age of donor cells and the age of the host.

Age Factors↗
PubMedDate not supplied

In situ tissue engineering of periodontal tissues by seeding with periodontal ligament-derived cells.

The feasibility of an in situ tissue-engineering method employing cell-based therapy with autologous periodontal ligament-derived cells was investigated. Periodontal ligament cells were obtained from six beagle dogs. Periodontal fenestration defects (6 x 4 mm) were created bilaterally at a location 6 mm apical to the marginal alveolar crest in the maxillary canines. Alkaline phosphatase-positive periodontal ligament cells (3 x 10(5) cells) were seeded onto a collagen sponge scaffold just before implantation. One defect was filled with the cell-scaffold construct, and another was left empty as the control. All animals were killed 4 weeks after surgery, and specimens were evaluated histomorphometrically. All the histomorphometrical data were analyzed by three-way analysis of variance with the Bonferroni multiple comparisons test. Regeneration of apical tissue was faster than that of coronal and isolated tissues on the control side (apical > coronal > isolated; p < 0.0001). On the other hand, on the cell-seeded side, regeneration of the cementum was observed uniformly on the root surface. Our data suggest that the seeded cells induced cementum regeneration on the root surface, indicating the potential of in situ tissue engineering using autologous cells for the regeneration of periodontal tissues.

Alkaline Phosphatase↗
PubMed2000

Localization of connective tissue growth factor in human uterine tissues.

Connective tissue growth factor (CTGF) is a recently described heparin-binding mitogen for fibroblasts and smooth muscle cells. The aim of this study was to investigate the production of CTGF by human uterine tissues using immunohistochemical and Northern blotting analyses. For immunohistochemistry, formalin-fixed human proliferative (n = 5), early secretory (n = 5; days 15-19), mid-secretory (n = 5; days 20-23), late secretory (n = 5; days 24-28) endometrial, and decidual (n = 5) tissues were stained using a highly specific affinity-purified polyclonal antibody raised against residues 81-94 of human CTGF. Myometrial (n = 5) and leiomyoma (n = 5) tissues were also used for CTGF immunochemistry. In proliferative endometrium, epithelial and vascular endothelial cells showed strong CTGF immunoreactivity, whereas stromal cells were negative or only weakly positive for the CTGF protein. Throughout the entire secretory stage, CTGF was detected in epithelial and endothelial cells of endometrium. Stromal cells showed strong immunoreactivity to CTGF only in oedematous areas for early and mid-secretory endometrium, and in decidualized regions of late secretory endometrium. During pregnancy, the decidual, epithelial and endothelial cells of the endometrium were all immunoreactive to CTGF. In myometrial and leiomyoma samples, CTGF immunoreactivity was found only in the endothelial cells. Northern blotting of mRNA from normal uterus (n = 2) or leiomyoma (n = 6) using a 320 bp human CTGF cDNA probe revealed a single 2.4 kb transcript. This study is the first to demonstrate CTGF gene expression and localization of its encoded protein in human uterine tissues. The cell- and cycle-specific localization of CTGF support a role for this molecule in regulating aspects of uterine cell growth, migration, and/or matrix production during the menstrual cycle and pregnancy.

Adult↗
PubMed1994

Tissue distribution of isoforms of type-1 protein phosphatase PP1 in mouse tissues and its diabetic alterations.

The amounts of four isoforms of the catalytic subunit of type-1 protein phosphatase, PP1 alpha, PP1 gamma 1, PP1 gamma 2, and PP1 delta have been determined in extracts of various mouse tissues including brain, liver, skeletal muscle, kidney, small intestine, heart, lung, spleen, thymus, and testis by Western blot analysis. Immunoreactive bands for PP1 isoforms were detected at 39.5, 38.5, and 40 kDa for PP1 alpha, PP1 gamma 1, and PP1 gamma 2, respectively, and at 39 and 37 kDa for PP1 delta. The amount of PP1 alpha was at comparable levels in all tissues examined except skeletal and heart muscles, in which it was detected slightly or not detectable, respectively. The amount of PP1 gamma 1 was at higher levels in brain, small intestine, and lung, being 2 to 3 times those in other tissues except heart and spleen, in which PP1 gamma 1 was not detectable. The amount of PP1 gamma 2 was extremely large in testis, small in brain, lung, spleen, and thymus, but it was not detectable in the other tissues. The amount of PP1 delta was at comparable levels in all the tissues except skeletal muscle, in which it was at a low but detectable level. Then, the amounts of the four PP1 isoforms were determined in non-obese diabetic (NOD) mice. The amounts of PP1 alpha were progressively decreased in livers of NOD mice as a function of increasing concentrations of blood glucose, whereas the amounts of PP1 gamma 1 and PP1 delta were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1978

GM3 ganglioside in various tissues of rabbit. Tissue-specific distribution of N-glycolylneuraminic acid-containing GM31.

Molecular species and concentrations of GM3 ganglioside in rabbit tissues, brain, thymus, lung, liver, stomach, intestine, kidney, testis, muscle, and erythrocytes were determined. The highest concentration was found in lung (431.7 nmol/g wet tissue). With the exceptions of brain, thymus, and erythrocytes, GM3 was the dominant ganglioside and comprised more than 50% of the total gangliosides. In brain and thymus, GM3 composed 0.76% and 17.28% of the total gangliosides, respectively. The sialic acid composition of GM3 was determined by mild methanolysis and neuraminidase treatment combined with either permethylation or trimethylsilylation. N-Glycolylneuraminic acid-containing GM3 was found in thymus, lung, kidney, and intestine in addition to N-acetylneuraminic acid-containing GM3, but N-acetylneuraminic acid was the sole sialic acid of GM3 in the other tissues. Sixty-four percent of the thymus GM3 consisted of N-glycolylneuraminic acid. High concentrations of C-20 sphingosine and stearic acid were characteristic for brain GM3 and the major long chain base of the other tissues was C-18 spingosine. The fatty acid composition of GM3 varied in each tissue. The difference in mobility on a thin-layer plate was due to the difference in its molecular constitution, being derived from a combination of fatty acid, long chain base, and sialic acid.

Animals↗
PubMed1992

Vascularized tissue transfer for closure of irradiated wounds after soft tissue sarcoma resection.

During the years 1985 to 1989, 82 patients were included in the soft tissue sarcoma protocol. Preoperative irradiation (50-54 Gy) was performed in all patients before tumor extirpation. Microwave hyperthermia was performed in conjunction with radiation in patients who had gross tumor remaining after initial biopsy. Primary closure with vascularized tissue (flaps) in lieu of conventional wound closure by skin approximation led to less complications (19% versus 51%), fewer secondary procedures for wound closure (10% versus 35%), shorter average hospitalization (15 versus 48 days) and greater limb salvage rate (97% versus 91%). The authors conclude that vascularized tissue (flaps) for primary wound closure in irradiated tissue leads to improved wound healing, and should be considered the procedure of choice for heavily irradiated soft tissue sarcoma defects.

Combined Modality Therapy↗
PubMedDate not supplied

Tissue engineering of heart valves: formation of a three-dimensional tissue using porcine heart valve cells.

Tissue engineering is a promising approach to obtaining lifetime durability of heart valves. The goal of this study was to develop a heart valve-like tissue and to compare the ultrastructure with normal valves. Myofibroblasts and endothelial cells were seeded on a type I collagen scaffold. The histologic organization and extracellular matrix were compared in light and electron micrographs. Radiolabeled proteoglycans were characterized by enzymatic degradation experiments. In tissue engineered specimens, cross sectional evaluation revealed that the scaffold (300 microm) was consistently infiltrated with myofibroblasts. Both sides were covered with a multicellular layer of myofibroblasts and overlaid by endothelial cells (50 microm). A newly formed extracellular matrix containing collagen fibrils and proteoglycans was found in the interstitial space. Collagen fibrils with a 60 nm banding pattern were found in both specimens. Small sized proteoglycans (65 nm) were associated and aligned at intervals of 60 nm with collagen fibrils. Large sized proteoglycans (180 nm) were located outside the collagen bundles in amorphous compartments of the extracellular matrix. The majority of glycosaminoglycans were chondroitin/dermatan sulfate, and a minority were heparan sulfate. The morphology and topography of cells and the organization of extracellular matrix in artificial tissues strongly resembles those of native valve tissues.

Animals↗
PubMed1996

Immune response to nonspecific and altered tissue antigens in soft tissue allografts.

Soft tissue allografts have many uses in orthopaedic surgery, including knee ligament reconstruction, hand tendon surgery, shoulder instability, and rotator cuff reconstruction. The predictable biologic incorporation of soft tissue allografts without rejection or fear of disease transmission continues to be a goal of basic science researchers. A review of the current knowledge if the immune system response to donor specific, nonspecific, and altered tissue antigens in soft tissue or tendon allografts is presented. An in vitro study was done in an attempt to decrease immunogenicity of a frozen bone-ligament graft by adding irrigation with Betadine scrub solution and hydrogen peroxide to the conventional storage process of freezing. Although the irrigation with cytotoxic agents would undoubtedly further decrease immunogenicity, it also decreased stiffness and maximum load by 15%. Whether this decreased strength and stiffness would compromise the incorporation and long term success of soft tissue allografts would need to be studied by in vitro experiments.

Anti-Infective Agents, Local↗
PubMed1998

Tissue at risk of infarction rescued by early reperfusion: a positron emission tomography study in systemic recombinant tissue plasminogen activator thrombolysis of acute stroke.

Thrombolytic therapy of acute ischemic stroke can be successful only as long as there is penumbral tissue perfused at rates between the thresholds of normal function and irreversible structural damage, respectively. To determine the proportion of tissue at risk of infarction, cerebral perfusion was studied in 12 patients with acute ischemic stroke who underwent treatment with systemic recombinant tissue plasminogen activator (0.9 mg/kg body weight according to National Institute of Neurological Disorders and Stroke protocol) within 3 hours of onset of symptoms, using [15O]-H2O positron emission tomography (PET) before or during, and repeatedly after thrombolysis. The size of the regions of critically hypoperfused gray matter were identified on the initial PET scans, and changes of perfusion in those areas were related to the clinical course (followed by the National Institutes of Health stroke scale) and to the volume of infarcted gray matter demarcated on magnetic resonance imaging 3 weeks after the stroke. Whereas the initial clinical score was unrelated to the size of the ischemic area, after 3 weeks there was a strong correlation between clinical deficit and volume size of infarcted gray matter (Spearman's rho, 0.96; P < 0.001). All patients with a severely hypoperfused (< 12 mL/100 g/min) gray matter region measuring less than 15 mL on first PET showed full morphologic and clinical recovery (n = 5), whereas those with ischemic areas larger than 20 mL developed infarction and experienced persistent neurologic deficits of varying degree. Infarct sizes, however, were smaller than expected from previous correlative PET and morphologic studies of patients with acute stroke: only 22.7% of the gray matter initially perfused at rates below the conventional threshold of critical ischemia became necrotic. Actually, the percentage of initially ischemic voxels that became reperfused at almost normal levels clearly predicted the degree of clinical improvement achieved within 3 weeks. These sequential blood flow PET studies demonstrate that critically hypoperfused tissue can be preserved by early reperfusion, perhaps related to thrombolytic therapy. The results correspond with experimental findings demonstrating the prevention of large infarcts by early reperfusion to misery perfused but viable tissue.

Acute Disease↗
PubMed2002

Limb salvage for soft-tissue malignancies of the foot: an evaluation of free-tissue transfer.

Free flaps may safely allow meaningful ambulation, durable limb preservation, and better quality of life in patients undergoing resections of soft-tissue cancers of the foot. To prove this, the records of a series of patients at The University of Texas M. D. Anderson Cancer Center (n = 67) who underwent limb salvage following tumor-related resection (n = 71 procedures) from 1989 to 1999 were retrospectively reviewed. Eighteen patients who were not candidates for local flaps or skin grafts received a total of 20 free flaps to preserve their limbs. Most defects (mean size, 78 cm2; range, 20 to 150 cm2) were on a weight-bearing surface of the foot (nine on a weight-bearing heel, three on a plantar foot); the remainder were on a non-weight-bearing surface (six on dorsum, two on a non-weight-bearing heel). Melanoma was diagnosed in nine cases (50 percent); soft-tissue sarcoma, in seven (39 percent); and squamous cell carcinoma, in two (11 percent). Fasciocutaneous and skin-grafted muscle flaps were used on both weight-bearing and non-weight-bearing surfaces. Free-tissue transfer was successful in 17 of 20 cases (85 percent); the three flap losses occurred in two patients. Minor complications (i.e., small hematoma, partial skin graft loss, and delayed wound healing) occurred in five patients. In all cases of successful free-tissue transfer, patients began partial weight bearing at a mean of 7.4 weeks (range, 2 to 12 weeks), and all ultimately achieved full weight bearing. Sixty-seven percent still required special footwear. In one patient, an ulceration on the weight-bearing portion of the flap resolved after a footwear adjustment. Only one patient was lost to follow-up (mean, 23 months). In the 17 remaining patients, limb salvage succeeded in 15 (88 percent). Of these, nine (60 percent) were alive without evidence of disease, three (20 percent) were alive with disease, and three (20 percent) had died of disease. Local recurrence developed in two patients but was successfully treated by excision and closure. No late amputations were required for local control. Thus, it seems that free flaps help facilitate limb salvage and that they may preserve meaningful limb function in patients who undergo resection of soft-tissue malignancies of the foot.

Adult↗
PubMed1990

The survival and nature of the immune response to soft-tissue and composite-tissue allografts in rats treated with low-dose cyclosporine.

We studied a variety of soft-tissue and composite-tissue allografts (CTA) in a histoincompatible rat model to determine the outcome and the nature of the immunologic responses to these tissues using continuous low-dose cyclosporine (CsA) therapy. Brown-Norway (RT1n) rats served as donors of soft tissue and CTA to Lewis (RT1l) rat recipients given low-dose CsA immunosuppressive therapy by gavage. Nine groups were studied. Three control groups were not treated with CsA: group 1, skin grafts alone; group 2, skin flaps alone; and group 3, skin grafts and delayed vessel allotransplants. Six groups were treated with CsA: group 4, skin grafts alone; group 5, skin flaps alone; group 6, skin grafts and delayed vessel allotransplants; group 7, aortas alone; group 8, muscle flaps alone; and group 9, bone grafts alone. Isografts were performed in all groups as technical controls. The appearance posttransplant of donor-directed cytotoxic antibodies was determined in recipient serum using a complement-mediated cytotoxicity assay and was compared to control and pretransplant sera. In the absence of CsA therapy, recipients in groups 1, 2, and 3 rejected their allografts early (8.5-9.4 days) and developed profound antidonor cytotoxic antibody activity posttransplant by day 7. Groups 4, 5, 6, 7, and 9 had prolonged graft survival in the presence of low-dose CsA, despite the presence of antidonor antibody activity. By contrast, group 8 (muscle flaps) were all uniformly rejected in the presence of profound recipient cytotoxic antidonor antibody activity. These results suggest that long-term soft-tissue and CTA survival can be achieved in histoincompatible rat recipients using continuous low-dose CsA immunosuppressive therapy despite the presence of cytotoxic antidonor antibodies.

Animals↗
PubMed2000

Tissue-binding properties of a synthetic peptide DNA vector targeted to cell membrane integrins: a possible universal nonviral vector for organ and tissue transplantation.

BACKGROUND: Gene delivery through a nonviral, receptor-mediated system widely expressed in transplanted tissue would have important advantages in transplantation, where gene delivery is performed ex vivo. Integrins are widely expressed cell surface receptors and can be targeted for gene delivery. METHODS: A synthetic 31 amino acid DNA vector (polylysine-molossin) comprising a 15-amino acid moiety for targeting cellular integrins (derived from the snake venom, molossin) and a 16-amino acid polylysine moiety for DNA-binding, has been evaluated. The 31-amino acid vector, as well as its separate 15-amino acid integrin-binding and (lys)16 components, were individually synthesized, and a monoclonal antibody was raised to the molossin peptide for these studies. Binding to cell lines and tissue sections and capacity for gene delivery were examined. RESULTS: Flow cytometric studies with the ECV304 cell line demonstrated that the binding of polylysine-molossin and polylysine-molossin/DNA complexes involved both electrostatic and integrin-mediated interactions with the cells, with the electrostatic binding being sufficient for maximal binding. However, binding to cellular integrins was essential for successful gene transfer. Binding studies on frozen tissue sections of the rat and pig demonstrated that the molossin peptide bound to many cell types of interest in transplantation, but not to all. Among the negative tissues were vascular endothelium and pancreatic islets. Small species differences in tissue binding were noted between the rat and pig. CONCLUSIONS: This study defines the cooperative nature of the binding of this vector system to target cells and establishes the cell types most likely to be effectively targeted for DNA transfer.

Antineoplastic Agents↗
PubMed2005

Tissue engineering of functional salivary gland tissue.

OBJECTIVES: Treatment of conditions that lead to salivary hypofunction, such as radiation induced xerostomia, is currently limited to the administration of saliva substitutes and sialogogues. The transient effect of these medications necessitates frequent administration, and systemic side effects may be intolerable. The creation of implantable, functional salivary gland tissue from autologous glandular cells would provide a physiologic solution to this problem. We investigated the feasibility of engineering such tissue in vivo. METHODS: Primary human salivary gland cells were grown, expanded, and seeded on biodegradable polymer scaffolds. A total of 48 scaffolds with cells and 16 control polymers without cells were implanted subcutaneously in athymic mice. The implants were retrieved 2, 4, and 8 weeks after the implantation for phenotypic and functional analyses. RESULTS: Human salivary gland epithelial cells retained their phenotypic and functional characteristics at all culture stages. Histologically, formation of acinar gland-like structures was observed within the engineered tissue by 4 weeks after implantation. Immunocytochemical and Western blot analyses of the implanted tissues demonstrated the expression of human a-amylase, cytokeratins AE1/AE3, and aquaporin-5 using cell-specific antibodies. Reverse-transcription polymerase chain reaction analyses confirmed the expression of human salivary type of alpha-amylase (sigma-amylase) mRNA. The retrieved tissues demonstrated the production of human alpha-amylase over time using a biochemical amylase detection system.

Animals↗
PubMed2003

Tissue engineering skin flaps: which vascular carrier, arteriovenous shunt loop or arteriovenous bundle, has more potential for angiogenesis and tissue generation?

This study was designed to clarify which vascular carrier, the arteriovenous shunt loop or the arteriovenous bundle, has more potential as a vascular carrier for an artificial skin flap in rats. An arteriovenous shunt loop was constructed between the femoral artery and vein using an interpositional artery (group I) or vein (group II) graft. For arteriovenous bundle groups, the femoral artery and vein were used and subdivided into two groups: distal ligation type (group III) and flow-through type (group IV). The vascular pedicle was wrapped with an artificial dermis and implanted beneath the inguinal skin for 4 weeks. For the control group, a folded sheet of artificial dermis without any vascular carrier was embedded. In experiment 1, the volumes of generated tissue within the artificial dermis were measured in the experimental and control groups (n = 5 in each group). In experiment 2, the origin of new blood vessels sprouting from the arteriovenous shunt loop and arteriovenous bundle were evaluated histologically. The volume of generated tissue in the shunt groups was significantly greater than that in the bundle groups (p < 0.01). However, the bundle groups also showed a great potential for producing new tissue. Serial histological studies showed that new capillaries were derived not only from the vasa vasorum of the femoral vessels but directly from the femoral vein in both the shunt and the bundle groups. This "sprouting" was extensively exhibited in the group III. Although the arteriovenous shunt loop showed a greater potential for producing new tissue and capillaries, the distal ligation type of bundle was thought to be an effective and practical vascular carrier for producing a tissue-engineered skin flap.

Anastomosis, Surgical↗
PubMed1987

Soft tissue gliomatosis--heterotopic glial tissue in the subcutis: a case report.

A subcutaneous nodule composed of heterotopic glial tissue is reported. The lesion was present in the subcutaneous tissue of the chest wall in a 2-year-old female. Histologically it was composed of loosely textured fibrillary neuroglial tissue in a densely hyalinized collagenous stroma. Immunohistochemical staining for glial fibrillary acidic protein was positive. The possible origin of this soft tissue glial heterotopia is discussed and the subject of heterotopic glial tissue is reviewed.

Axilla↗
PubMed1991

Distribution of oxytetracycline to tissue cages and granuloma pouches in calves and effect of acute inflammation on distribution to tissue cages.

The effect of acute inflammation on oxytetracycline (OTC) distribution was studied in a tissue cage model in calves. An acute inflammatory reaction was induced in tissue cages by injecting lipopolysaccharide (LPS) from Salmonella typhimurium. The distribution of OTC to tissue cage fluid (TCF) was also compared with distribution to fluid from granuloma pouches (GPF). Tissue from LPS-injected cages showed histological changes indicating an acute inflammatory reaction. Concentrations of OTC were higher in LPS cages than in controls; at 1, 2, 4 and 10 h the difference was statistically significant (P less than 0.05). Numerically the overall elimination rate constant (kel) was larger, elimination half-life (t1/2) shorter, peak concentration (Cmax) higher, and time of peak concentration (Tmax) shorter in LPS cages than in controls. The area under the curve (AUC) of OTC was greater and the ratio AUCTCF/AUCserum was higher in LPS cages than in controls. Although statistically significant differences were not found for all the pharmacokinetic parameters, it was concluded that distribution to and elimination from LPS cages were both faster than in controls. Concentration-time profiles of OTC were similar in TCF and GPF in that concentrations were lower and elimination was more prolonged than in serum. Levels were higher in GPF than in TCF up to 3 h after injection; thereafter the relationship was reversed. Distribution to and elimination processes from GPF appeared to be faster than from TCF as numerically kel was higher, t1/2 shorter and Tmax shorter in GPF than in TCF. It was concluded that the granuloma pouch model and the tissue cage model have similarities in distribution and elimination patterns and that differences are most probably due to differences in the ratio of the surface area to the volume.

Acute Disease↗