Involvement of HSP90 in ischemic postconditioning-induced cardioprotection by inhibition of the complement system, JNK and inflammation

Abstract Purpose To investigate whether heat shock protein 90 (HSP90) is involved in complement regulation in ischemic postconditioning (IPC). Methods The left coronary artery of rats underwent 30 min of occlusion, followed by 120 min of reperfusion and treatment with IPC via 3 cycles of 30s reperfusion and 30s occlusion. The rats were injected intraperitoneally with 1 mg/kg HSP90 inhibitor geldanamycin (GA) after anesthesia. Eighty rats were randomly divided into four groups: sham, ischemia-reperfusion (I/R), IPC and IPC + GA. Myocardial infarct size, apoptosis index and the expression of HSP90, C3, C5a, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1β and c-Jun N-terminal kinase (JNK) were assessed. Results Compared with the I/R injury, the IPC treatment significantly reduced infarct size, release of troponin T, creatine kinase-MB, and lactate dehydrogenase, and cardiomyocyte apoptosis. These beneficial effects were accompanied by a decrease in TNF-α, IL-1β, C3, C5a and JNK expression levels. However, all these effects were abrogated by administration of the HSP90 inhibitor GA. Conclusion HSP90 exerts a profound effect on IPC cardioprotection, and may be linked to the inhibition of the complement system and JNK, ultimately attenuating I/R-induced myocardial injury and apoptosis.

Serum antibody & Th2 cytokine profiles in patients with cystic echinococcosis.

Background & objectives: Human cystic echinococcosis (CE), caused by Echinococcus granulosus, is one of the most important and widespread parasitic zoonoses. T helper cell-2 (Th2) dominated immunity in CE is associated with increased susceptibility to the disease, while T helper cell-1 (Th1) cell activation is assumed to induce protective immunity. Hence, in order to investigate in vivo Th2 cell activation and serum complement levels, the present study was aimed to detect serum levels of specific IgG, IgE, interleukin (IL)-4, IL-10, C3c and C4 in confirmed CE patients. Methods: Specific IgG levels in serum was measured by enzyme linked immunosorbent assay using recombinant E. granulosus antigen-B/2 (RecEg-AgB/2) and serum IgE, IL-4, IL-10, C3c and C4 were quantified by nephelometry in 45 surgically confirmed patients with CE, and 10 healthy controls. Results: Specific IgG (P<0.0001), IgE (P<0.05), IL-4 (P=0.0197) and IL-10 (P<0.01) levels were significantly elevated in CE cases compared to healthy controls. IL-4 could be detected in 34 patients (75.55%) and six controls (60%) in a low concentration. The IgE concentration was elevated (>120 U/ml) in 36 (80%) cases of CE and in one healthy control. Interpretation & conclusion: Our results showed higher C3c and C4 levels in CE patients than healthy controls. No significant association was found between IgE concentrations and cytokine levels. The results of this study point to a cytokine profile suggestive of Th2 cell dominance in vivo in CE.

Action of chlorogenic acid on the complement system

Previous research on plants used in folk medicine as antidotes against snake-bite revealed some constituents responsible for such protection. Chlorogenic acid (3-0-caffeoyl quinic acid) was one of these substances, studied with more attention. It has been shown that this substance binds to proteins through hydrophobic interactions and hydrogen bonds. This paper shows the preliminary results about the anti-complementary action of chlorogenic acid. Human and guinea pig sera, treated with chlorogenic acid, were added to the hemolytic system (sheep erythrocyte sensitized with hemolysin) to study its effect on the activation of the classical complement pathway. The action on the alternative pathway was studied with human serum treated with chlorogenic acid and zymosan. Our results show that chlorogenic acid presents anti-complementary action at the classical pathway, since the sera are not able to lysis the indicator system. The presence of C3b fragments on the surface of the yeast cells demonstrates that the alternative pathway was not affected.

Exchange transfusion in septic neonates with sclerema: effect on immunoglobulin and complement levels.

OBJECTIVE: To study the effect of exchange transfusion (ET) on the levels of immunoglobulins (Ig) and C3 in neonatal sepsis with sclerema. DESIGN: Randomized controlled trial in a referral neonatal unit of a teaching hospital. SUBJECTS: Consecutive culture positive septic neonates with sclerema were enrolled and were randomized to undergo ET (study group, n = 20) or no ET (controls, n = 20). RESULTS: Mortality was 50% in the study group and 95% in controls. Gram negative organisms accounted for 85% in study group and 90% in controls. IgG, IgA and IgM levels rose significantly while C3 levels did not show significant rise 12-24 hours after ET. Ig and C3 levels did not change significantly in the controls. CONCLUSION: ET with fresh whole blood in septicemic newborns with sclerema improves survival, particularly in the more premature group and significantly enhances, IgG, IgA and IgM levels.

Descenso del complemento sérico en niños con infección estreptococicia: ¿factor de riesgo de glomerulonefritis aguda? / Dicrease of seric complement in children with streptococal infections: risk factor of acute glommerulonephritis?

La glomerulonefritis aguda es una entidad clínica de comienzo agudo cuyas características son: edema, hematura (macro o microscópica) proteinuria, hipertensión arterial y oliguria. Generalmente es de origen infeccioso, siendo lo más frecuente la infección por estreptococo grupo A-B hemolítico. Ello ha significado que el término glomerulonefritis aguda implique habitualmente glomerulonefritis aguda post estreptococica (GNAPS)

Alterations of humoral immunity in patients with gastric cancer.

For better understanding of the alterations of humoral immunity in gastric cancer patients, IgG, IgA, IgM, complement C3, C4, CH50, natural antibody (isohemagglutinin-IgM class), ESR, CRP, albumin and globulin were quantitated in sera taken preoperatively from 81 patients with gastric cancer and from 29 control patients with hernia. The results from patients with gastric cancer were grouped according to pTNM staging (including stage I + II, III, and IV). Serum globulin and IgG levels in all stages of cancer patients were significantly lower than that of the controls (p less than 0.05). The CRP and ESR levels in stage III and IV cancer patients were significantly higher (p less than 0.05). There was no difference between cancer and hernia patient groups in IgA, IgM, isohemagglutinin-IgM class, C3, C4, CH50, albumin, WBC and total lymphocyte counts. In conclusion, the significant changes in humoral immunity in patients with gastric cancer include: (1) decrease in serum IgG and globulin levels, and (2) increased levels of acute phase reactants (ESR, CRP). These results imply that patients with gastric cancer have lower acquired humoral immunity and have acute phase reactions.

Coagulopathy in patients with hemorrhagic fever with renal syndrome

Hemorrhagic fever with renal syndrome in Korea (Korean hemorrhagic fever) is an acute viral disease characterized by fever, hemorrhage and renal failure. In Korean patients, the disease manifests more distinctive bleeding tendencies than those of hemorrhagic fever with renal syndrome found in western countries. To investigate the nature and role of the coagulation, fibrinolysis, kinin and immune system in the pathogenesis of such a hemorrhagic manifestation, alterations of these systems were assessed from the early phase of the disease. Decreased platelet count and shortened platelet survival were observed with giant platelets in the peripheral blood. The marked prolongations of bleeding time, prothrombin time and partial thromboplastin time were noticed with the decreased plasma activities of coagulation factors II, V, VIII, IX and X. Shortened half life of fibrinogen, increased fibrinogen-fibrin degradation product, with decreased plasma levels and activities of plasminogen, alpha 2-plasmin inhibitor and antithrombin III were found. On thrombelastogram, the existence of procoagulant activity was confirmed, and prolonged reaction time and clot formation time with decreased maximum amplitude were observed. The appearance of circulating immune complexes was found along with decreased C3 and normal C4 in the serum. Significant decrease of serum C3 was evident in the patients with disseminated intravascular coagulation. These findings of coagulopathy were normalized within ten days of the illness in most cases. Therefore, it can be concluded that disseminated intravascular coagulation and thrombocytopenia in the early phase, and azotemia developing later might play an important role in the pathogenesis of bleeding tendency in Korean hemorrhagic fever.

Diferenciación entre Trypanosoma cruzi y T. rangeli en el intestino del vector Rhodnius prolixus, en base al comportamiento de estos flagelados frente a la actividad lítica del complemento / Differentiatiofn between Trypanofsofma cruzi and T. rangeli, based ofn the resistance of the lytic activity of the cofmplement

Se infectaron Rhodnius prolixus con Trypanosoma cruzi (stock Molino) ó T. rangeli (stock San Agustín) y las formas intestinales de desarrollo de los flagelados se incubaron con suero normal de cobayo durante una hora a 20-C. Se compararon los resultados de la actividad lítica del complemento del suero de cobayo sobre las diferentes formas de las dos especies de tripanosomas de recuento en hemocitómetro de Neubauer antes y después de la incubación y por examen de preparaciones coloreadas con Giemsa. Todas las formas intestinales de T. rangeli fueron resistentes a la actividad lítica del complemento; por el contrario, con T. cruzi se observó que las formas similares a amastigotes, esferomastigotes y epimastigotes fueron lisadas, con excepción del 1% de los epimastigotes durante la décima semana de infección. Los tripomastigotes de T. cruzi quedaron intactos y activos después de la incubación. Los resultados sugieren que el uso del suero de cobayo puede ser de utilidad prática para el examen del contenido intestinal de los vectores utilizados en el xenodiagnóstico o en estudios epidemiológicos, especialmente en aquellos casos en que el estudio morfalógico no permita la diferenciación entre las dos especies de tripanosomas