Because leukocyte-mediated tissue damage is an important component of the pathologic picture in ischemia/reperfusion, we have sought mechanisms by which PMNs are directed into hypoxic tissue. Incubation of human endothelial cells (ECs) in hypoxia, Po2 -14-18 Torr, led to time-dependent release of IL-8 antigen into the conditioned medium; this was accompanied by increased chemotactic activity for PMNs, blocked by antibody to IL-8. Production of IL-8 by hypoxic ECs occurred concomitantly with both increased levels of IL-8 mRNA, based on polymerase chain reaction analysis, and increased IL-8 transcription, based on nuclear run-on assays. Northern analysis of mRNA from hypoxic ECs also demonstrated increased levels of mRNA for macrophage chemotactic protein-i, another member of the chemokine superfamily of proinflammatory cytokines. IL-8 gene induction was associated with the presence of increased binding activity in nuclear extracts from hypoxic ECs for the NF-kB site. Studies with human umbilical vein segments exposed to hypoxia also demonstrated increased elaboration of IL-8 antigen compared with normoxic controls. In mice exposed to hypoxia (Po2 30-40 Torr), there was increased pulmonary leukostasis, as evidenced by increased myeloperoxidase activity in tissue homogenates. In parallel, increased levels of transcripts for IP-10, a murine homologue in the chemokine family related to IL-8, were observed in hypoxic lung tissue. Taken together, these data suggest that hypoxia constitutes a stimulus for leukocyte chemotaxis and tissue leukostasis. (J. Clin. Invest. 1994. 93:1564-1570

Tissue injury that accompanies hypoxemia/reoxygenation shares features with the host response in inflammation, suggesting that cytokines, such as IL-1, may act as mediators in this setting. Human endothelial cells (ECs) subjected to hypoxia (Po2 12-14 Torr) elaborated IL-1 activity into conditioned media in a time-dependent manner; this activity was completely neutralized by an antibody to IL-la. Production of IL-1 activity by hypoxic ECs was associated with an increase in the level of mRNA for IL-ia, and was followed by induction of endothelial-leukocyte adhesion molecule-1 and enhanced expression of intercellular adhesion molecule-1 (ICAM-1 ) during reoxygenation. During reoxygenation there was a three-to fivefold increased adherence of leukocytes, partly blocked by antibodies to endothelial-leukocyte adhesion molecule-1 and ICAM-1. Suppressing endothelial-derived IL-1, using either antibodies to IL-la, specific antisense oligonucleotides or the IL-1 receptor antagonist, decreased leukocyte adherence to reoxygenated ECs, emphasizing the integral role of IL-1 in the adherence phenomenon. Mice subjected to hypoxia (Po2 30-40 Torr) displayed increased plasma levels of IL-la, induction of IL-ia mRNA in the lung, and enhanced expression of ICAM-1 in pulmonary tissue compared with normoxic controls. These data suggest that hypoxia is a stimulus which induces EC synthesis and release of IL-la, resulting in an autocrine enhancement in the expression of adhesion molecules. (J.

Current organ preservation strategies subject graft vasculature to severe hypoxia (Po2 -20 Torr), potentially compromising vascular function and limiting successful transplantation. Previous work has shown that cAMP modulates endothelial cell (EC) antithrombogenicity, barrier function, and leukocyte /EC interactions, and that hypoxia suppresses EC cAMP levels. To explore the possible benefits of cAMP analogs/agonists in organ preservation, we used a rat heterotopic cardiac transplant model; dibutyryl cAMP added to preservation solutions was associated with a time-and dose-dependent increase in the duration of cold storage associated with successful graft function.Preservation was also enhanced by 8-bromo-cAMP, the SP isomer of adenosine 3',5'monophosphorothioate, and types III (indolidan) and IV (rolipram) phosphodiesterase inhibitors. Neither butyrate alone nor 8-bromoadenosine were effective, and the cAMP-dependent protein kinase antagonist Rp isomer of adenosine 3',5'monophosphorothioate prevented preservation enhancement induced by 8-bromo-cAMP. Grafts stored with dibutyryl cAMP demonstrated a 5.5-fold increase in blood flow and a 3.2-fold decreased neutrophil infiltration after transplantation. To explore the role of cAMP in another cell type critical for vascular homeostasis, vascular smooth muscle cells were subjected to hypoxia, causing a time-dependent decline in cAMP levels. Although adenylate cyclase activity was unchanged, diminished oxygen tensions were associated with enhanced phosphodiesterase activity (59 and 30% increase in soluble types III and IV activity, respectively). These data suggest that hypoxia or graft ischemia disrupt vascular homeostasis, at least in part, by perturbing the cAMP second messenger pathway. Supplementation of this pathway provides a new approach for enhancing cardiac preservation, promoting myocardial function, and maintaining vascular homeostatic properties. (J.

ABSTRACT:The purpose of this study was to examine selected serum biochemical parameters and acute phase protein levels in a herd of Saanen goats showing signs of pregnancy toxaemia. Seventy five female goats were used and divided into three groups. Group 1 (n = 57) (blood serum glucose levels were within the physiological range), Group 2 (n = 11) (serum glucose values were low) and Group 3 (n = 7) (serum glucose values were high). Goats in Groups 2 and 3 were diagnosed with pregnancy toxaemia. Apart from serum glucose, β-hydroxybutyrate (BHB), triglycerides, blood pH, calcium (Ca), sodium (Na), potassium (K), aspartate aminotransferase (AST), alanine aminotransferase (ALT), haptoglobin (Hp), serum amyloid A (SAA) and tumour necrosis factor-α (TNF-α) were measured in all animals. In Group 3 average Hp and SAA values were found to be significantly (P < 0.001) higher than in Groups 1 and 2, and also higher in Group 2 than in Group 1. Acute phase proteins in goats with pregnancy toxaemia may be used in the course and the prognosis of the disease. The evaluation of acute phase proteins is useful and also quicker in cases of suspected pregnancy intoxication.

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ABSTRACT:A 3-month-old male kitten was presented to our clinic with malaise, vomiting and jaundice. In the anamnesis, we learned that the cat had a history of anorexia, sneezing, and nasal discharge and that the owner had administered 100 mg/day (t.i.d.) nimesulide orally for three days. In the laboratory study, high levels of serum alkaline phosphatase, γ-glutamyl transtransferase, total bilirubin, direct bilirubin, indirect bilirubin, urea, and creatinine were detected. All the clinical signs and laboratory abnormalities returned to normal levels after cessation of the nimesulide and supportive treatment. In this case, clinical and laboratory findings were thought to be compatible with nimesulide-induced acute biliary injury and renal failure. This case report indicates that the household pets are at risk of toxic drugs administered by their owners and great caution should be taken in administering NSAIDs in cats.

Bu çalışmada sıstıtısin tamsında çift kontrast sistografinin yararlılığı ve tedavisinde enrofloksasinin etkinliğinin araştırılması amaçlandı. Ankara Üniversitesi Veteriner Fakültesi İç Hastalıklar Anabilim Dalı Kliniği'ne idrar yapma düzensizlikleri ile getirilen 6'sl kedi, 8'i köpek toplam 14 hayvan araştırmanın materyalini oluşturdu. Anamnez bilgileri, klinik ve bazı laboratuvar bulguları sonucu sistitis tanısı konulan olguların çift kontrast sistografi tekniği ile radyogramları alındı. Bu teknik ile idrar kesesindeki lokal veya yaygın duvar kalınlaşmaları ve dolma defektIeri belirlendi. Sistosentez ile alınan idrar örneklerinin uygun besi yerlerinde kültürleri yapıldı. Sekiz köpeğin Yinde (%62) E.coli, 2'sinde (%25) Proleus spp ve i'inde (%12) Klebsiella spp. üredi. Altı kediden 4'ünde (%66), E.coli ürerken 2'sinde üreme olmadı. Antibiyogram sonuçları doğrultusunda tüm hayvanlar enrofloksasin ile antibiyotik tedavisine alındı. Ayrıca tedavi C vitamini ile desteklendi. Yapılan tedavi sonucu 6 kedinin tümü (%100) ve 8 köpekten Yi,7 gün, i 'i, ii gün ve 2'si 14 gün süren tedavi sonucu tamamen iyileşti. Tedavinin bitirilmesinden iki hafta sonra tekrarlanan kültür sonuçlarında herhangi bir bakteri üremesinin olmaması tedavinin etkinliği ortaya koydu. Sonuç olarak, kedi ve köpeklerde çift kontrast sistografi tekniği ile sistitislerin tanılarının kolaylıkla yapılabileceği belirlendi. Ayrıca sistitis olaylarında en fazla E.coli'nin üremesi, bu ve diğer etkenlerin enrofloksasine duyarlılık göstermeleri nedeniyle kültür ve antibiyogram yapılma olanağı bulunmayan sistitis olgularında antibiyotik olarak enrofloksasinin öncelikle tercih edilmesinin yararlı olacağı kanısına varıldı.

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