Reticuloendothelial Function Research Articles

#4219 NON-INVASIVE ASSESSMENT OF LIVER STIFFNESS, HEPATIC FIBROSIS RISK MARKERS AND OUTCOMES IN A DIALYSIS POPULATION

Abstract Background and Aims People with end stage kidney disease (ESKD) commonly co-exhibit multiple risk factors (type 2 diabetes mellitus, obesity and hypertension) for non-alcoholic fatty liver disease (NAFLD) and its progressive, fibroinflammatory form non-alcoholic steatohepatitis (NASH). NAFLD and NASH both associate with increased risk of fatal cardiovascular events. NASH will additionally soon become the leading cause of cirrhosis both in the UK and worldwide. The cause of systemic inflammation driving early mortality in patients with ESKD is unclear. It is thought that liver disease can contribute to inflammation due to reduced reticuloendothelial function and subsequent penetration of gut-derived toxins into the systemic circulation. Very little is currently known about prevalence of NAFLD and NASH in ESKD, or how these conditions affect patients. By identifying the scale of the risk, this study will help better understand the extent of NAFLD and NASH and their links to clinical outcomes in advanced kidney disease. We report interim results from this study looking non-invasively for liver disease in patients with ESKD. Method This prospective study involves prevalent patients with ESKD treated with dialysis (for >3 months) at five participating UK kidney centres. Results from this study are derived from analysis of the first 238 patients (final recruitment target 450). A FibroScan® (Echosens) device was used to measure both hepatic steatosis using controlled attenuation parametrography (CAP) and fibrosis using transient elastography. A fibrosis-4 index score was calculated to assess fibrosis risk. These results were supplemented by baseline clinical and radiological data, serum beta-D-glucan levels taken pre- and post-dialysis, clinical assessment of fluid status, and bioimpedance spectroscopy (Fresenius Medical Care). Survival analyses were performed using Kaplan-Meier estimates. Results The mean age of participants was 63 years (67% male). Mean body mass index was 27.8kg/m2. 97% of participants had hypertension, 53% diabetes mellitus and 65% hyperlipidaemia. 231 participant FibroScan scores (97%) were valid (interquartile range ≤30% over 10 consecutive readings) and available for analysis. 74 participants (31%) had suspected hepatic steatosis of grade S1-S3 and 72 participants (30%) had suspected hepatic fibrosis of grade F2-F4. 53 participants (22%) had suspected F2-F3 fibrosis (moderate fibrosis) and 19 (8%) had suspected F4 fibrosis (advanced fibrosis/cirrhosis). There was increased mortality associated with suspected hepatic fibrosis/steatosis (9.1% absolute risk of mortality with an abnormal CAP or fibrosis score compared to 1.6% in those with normal FibroScan imaging). The majority of mortality in people with suspected hepatic fibrosis was from cardiovascular disease. Overall mortality in participants with suspected hepatic fibrosis remained significant even after adjustment for univariate predictors of survival (median CRP, baseline BDG levels and age) (Figure 1). Other univariate predictors of survival were Charlson Comorbidity Score and diabetes status. Conclusion These results demonstrate a significant burden of suspected hepatic steatosis and hepatic fibrosis in people with ESKD. Suspected hepatic fibrosis assessed by FibroScan imaging is an independent risk factor for mortality based on this interim analysis and strategies to improve liver health in the setting of advanced kidney disease may be of benefit to this group of patients.

What are the Current Indications and Contraindications for a Splenectomy?

Splenectomy can treat conditions characterized by hemolysis or thrombocytopenia caused by autoantibodies or splenic reticuloendothelial function, as well as disorders characterized by massive splenomegaly and hypersplenism with cytopenias, such as hereditary spherocytosis, transfusion-dependent thalassemia, immune thrombocytopenia, autoimmune hemolytic anemia, splenic marginal zone lymph Splenectomy is no longer used for Hodgkin disease staging and is typically avoided in autoimmune lymphoproliferative syndrome, hereditary stomatocytosis or xerocytosis, cold agglutinin disease, paroxysmal cold hemoglobinuria, Gaucher disease, and cirrhosis-related hypersplenism.

Measurement of erythrocyte membrane mannoses to assess splenic function.

SummaryRed blood cells (RBCs) lose plasma membrane in the spleen as they age, but the cells and molecules involved are yet to be identified. Sickle cell disease and infection by Plasmodium falciparum cause oxidative stress that induces aggregates of cross‐linked proteins with N‐linked high‐mannose glycans (HMGs). These glycans can be recognised by mannose‐binding lectins, including the mannose receptor (CD206), expressed on macrophages and specialised phagocytic endothelial cells in the spleen to mediate the extravascular haemolysis characteristic of these diseases. We postulated this system might also mediate removal of molecules and membrane in healthy individuals. Surface expression of HMGs on RBCs from patients who had previously undergone splenectomy was therefore assessed: high levels were indeed observable as large membrane aggregates. Glycomic analysis by mass spectrometry identified a mixture of Man5‐9GlcNAc2 structures. HMG levels correlated well with manual pit counts (r = 0.75–0.85). To assess further whether HMGs might act as a splenic reticuloendothelial function test, we measured levels on RBCs from patients with potential functional hyposplenism, some of whom exhibited high levels that may indicate risk of complications.

Requirement of Biliary Decompression Prior to Pancreatoduodenectomy for Distal Malignant Biliary Obstruction

The role of biliary decompression prior to definitive surgery in patient with distal malignant obstruction remains controversial.Many authors put their views in favor; because of improvement of liver functions and reticulo-endothelial function after decompression resulting in uneventful postoperative outcome and many others are against because of increase the risk of postoperative morbidity and mortality. We found the patients who underwent prior biliary decompression had unusual development of organisms in their bile which are found frequently resistant to usual antibiotics and most of them developed postoperative complications. Several other studies concluded in between that preoperative drainage should be performed in selected patients; delaying of surgery for any cause, presence of severe cholangitis, severe jaundice and poor nutrition and where hepatic resection is required along with pancreatoduodenectomy. We therefore concluded that biliary decompression should not routinely be performed except in special situations in patients with distal malignant biliary obstructionbefore pancreatoduodenectomy.
 Journal of Surgical Sciences (2020) Vol. 24 (2) : 66-69

The potential of radionuclide diagnostic imaging in diffuse liver disease and portal hypertension

Objective. The study objective was to assess the scintigraphy potential in the evaluation of portal hypertension and the severity of liver damage in diffuse diseases and after liver transplantation.Material and methods. The study enrolled 325 patients suffering from hepatitis and liver cirrhosis of various etiology and severity, including those after liver transplantation, namely, the patients with hepatitis (n=96), patients with liver cirrhosis of Child–Pugh class A (n=24), class B (n=87), and class C (n=118); 11 more healthy volunteers without clinical and laboratory signs of diffuse liver disease were enrolled as controls. The assessment of liver reticuloendothelial system was performed by scintigraphy with (99m)Tc-phytate colloid in a static planar mode and "whole body" mode by SPECT (Infinia II, GE).Results. In contrast to the control group, significant radionuclide signs of hepatosplenomegaly were revealed with the predominant functional activity of the left lobe; the liver function was found impaired that correlated with the cirrhosis severity evaluated according to the Child–Pugh Сlassification. The analysis of scintigraphy quantitative parameters showed that the most informative of them were the intensity of radiopharmaceutical accumulation in the spleen (S%) and in bone marrow (Вm%), and the radiopharmaceutical uptake by the reticuloendothelial cells of the liver and spleen in percentage from the administered activity (Lwb%, Swb%). Depending on the cirrhosis severity assessed by the Child–Pugh Score, the changes in quantitative parameters were accompanied by a progressive enlargement of the spleen, liver left lobe, the increase of (99m)Tc-phytate uptake by the bone marrow with a decreased radiopharmaceutical uptake by the liver. The study results showed that among the Child–Pugh class C patients, the impairment of liver reticuloendothelial function was more pronounced in the patients with cirrhosis of viral and mixed etiology, when compared to those with alcoholic cirrhosis.Conclusion. The paper has identified the most informative parameters characterizing portal hypertension and the reticuloendothelial function for all Child–Pugh defined classes of cirrhosis. These parameters include the increase of (99m) Tc-phytate accumulation in the spleen (S%) and bone marrow (Bm%); the liver and spleen uptake of the radiopharmaceutical in percentage from the administered activity (Lwb%, Swb%). The calculation of the remaining parameters is necessary for a detailed description of the organ function and for the assessment of the portal hypertension severity in repeated studies.Summary. Criteria for the objective assessment of reticuloendothelial function and portal hypertension in diffuse liver diseases, including after liver transplantation, have been developed. Contrary to the control group, in patients with diffuse liver diseases, the radionuclide signs of hepatosplenomegaly (or a decreased liver size) with a predominant functional activity of the left lobe were identified, as were the changes in the quantitative parameters of the radiopharmaceutical uptake by the liver (Lwb%), including the radiopharmaceutical accumulation in the liver left lobe (Ll%), spleen (Swb%), bone marrow (Bm%), and the liver-to-spleen area ratio (Lar/Sar). The informative and reliable (p<0.05) parameters of the function Lwb%, S%, Swb% and Bm% correlating with the cirrhosis classes assessed by Child–Pugh were identified. The radionuclide method, being highly reproducible one, can be recommended for an objective assessment of liver function and the detection of portal hypertension in hepatitis and cirrhosis, as well as for post-transplant monitoring of the liver function to prevent complications in the early and late postoperative periods.

In vivo imaging of hepatic neutrophil migration in severe alcoholic hepatitis with 111In-radiolabelled leucocytes.

The study’s aim was to image severe alcoholic hepatitis (SAH) using 111In-labelled leucocytes with two objectives in mind: firstly for non-invasive diagnosis and secondly to provide a platform for experimental therapies aiming to inhibit intrahepatic neutrophil migration. 111In-leucocyte scintigraphy was performed 30 min and 24 h post-injection in 19 patients with SAH, 14 abstinent patients with alcohol-related cirrhosis and 11 normal controls. Eleven with SAH and seven with cirrhosis also had 99mTc-nanocolloid scintigraphy. Change in hepatic 111In radioactivity was expressed as decay-corrected 24 h:30 min count ratio and, in SAH, compared with histological grading of steatohepatitis and expression of granulocyte marker, CD15. Hepatic microautoradiography on biopsy specimens obtained 24 h post-injection of 111In-leucocytes was performed in one patient. Median 24 h:30 min hepatic 111In activity ratio was higher in SAH (2.5 (interquartile range (IQR): 1.7–4.0) compared with cirrhotics and normal controls (1.0 (0.8–1.1) and 0.8 (0.7–0.9) respectively, P<0.0001). In SAH, it correlated with CD15 expression (r = 0.62, P=0.023) and was higher in marked compared with mild/moderate steatohepatitis (4.0 (3.0–4.6) compared with 1.8 (1.5–2.6), P=0.006). Hepatic-to-splenic 99mTc count rate ratio was reduced in SAH (0.5 (0.4–1.4)) compared with cirrhotics (2.3( 0.6–3.0)) and three historic normal controls (4.2 (3.8–5.0); P=0.003), consistent with impaired hepatic reticuloendothelial function. Scintigraphic findings in SAH included prominent lung radioactivity at 30 min, likely the result of neutrophil primimg. Microautoradiography demonstrated cell-associated 111In in areas of parenchymal neutrophil infiltration. In conclusion, 111In-leucocyte scintigraphy can non-invasively diagnose SAH and could provide a platform for evaluation of novel treatments aiming to inhibit intrahepatic neutrophil migration.

Prognostic Utility of 90Y Radioembolization Dosimetry Based on Fusion 99mTc-Macroaggregated Albumin–99mTc-Sulfur Colloid SPECT

Planning hepatic (90)Y radioembolization activity requires balancing toxicity with efficacy. We developed a dual-tracer SPECT fusion imaging protocol that merges data on radioactivity distribution with physiologic liver mapping. Twenty-five patients with colorectal carcinoma and bilobar liver metastases received whole-liver radioembolization with resin microspheres prescribed as per convention (mean administered activity, 1.69 GBq). As part of standard treatment planning, all patients underwent SPECT imaging after intraarterial injection of 37 MBq of (99m)Tc-macroaggregated albumin ((99m)Tc-MAA) to simulate subsequent (90)Y distribution. Immediately afterward, patients received 185 MBq of labeled sulfur colloid ((99m)Tc-SC) intravenously as a biomarker for normal hepatic reticuloendothelial function and SPECT was repeated. The SPECT images were coregistered and fused. A region-based method was used to predict the (90)Y radiation absorbed dose to functional liver tissue (DFL) by calculation of (99m)Tc-MAA activity in regions with (99m)Tc-SC uptake. Similarly, the absorbed dose to tumor (DT) was predicted by calculation of (99m)Tc-MAA activity in voxels without (99m)Tc-SC uptake. Laboratory data and radiographic response were measured for 3 mo, and the survival of patients was recorded. SPECT-based DT and DFL were correlated with parameters of toxicity and efficacy. Toxicity, as measured by increase in serum liver enzymes, correlated significantly with SPECT-based calculation of DFL at all time points (P < 0.05) (mean DFL, 27.9 Gy). Broad biochemical toxicity (>50% increase in all liver enzymes) occurred at a DFL of 24.5 Gy and above. In addition, in uni- and multivariate analysis, SPECT-based calculation of DT (mean DT, 44.2 Gy) correlated with radiographic response (P < 0.001), decrease in serum carcinoembryonic antigen (P < 0.05), and overall survival (P < 0.01). The cutoff value of DT for prediction of 1-y survival was 55 Gy (area under the receiver-operating-characteristic curve = 0.86; P < 0.01). Patients who received a DT of more than 55 Gy had a median survival of 32.8 mo, compared with 7.2 mo in patients who received less (P < 0.05). Dual-tracer (99m)Tc-MAA-(99m)Tc-SC fusion SPECT offers a physiology-based imaging tool with significant prognostic power that may lead to improved personalized activity planning.

Choline treatment affects the liver reticuloendothelial system and plasma fatty acid composition in diabetic rats

This study investigated effects of choline treatment on hepatic reticuloendothelial and biliary functions and plasma fatty acid composition in diabetic rats. Diabetes was induced by streptozotocin (STZ). Choline was administered to untreated rats and a portion of STZ-treated rats for two sequences of five consecutive days, separated by a 2-day interval. Hepatic functions were studied using (99m) Tc Tin (II) colloid (TIN) and 99 mTc mebrofenin [bromo-iminodiacetic acid (BrIDA)] imaging. The TIN-uptake ratios (organ/whole body) of heart, liver and spleen, and the BrIDA-uptake ratios (organ or tissue/whole body) of liver, biliary tree and abdomen were obtained following imaging studies. Fatty acids were analysed by GC/MS. Choline treatment did not attenuate hyperglycaemic development. Diabetic rats showed (i) a decreased TIN-uptake ratio in liver with co-increased ratios in heart and spleen; choline treatment diminished these changes, (ii) elevated BrIDA-uptake ratios in biliary tree and abdomen but not in liver; choline treatment did not attenuate the elevations and (iii) decreases in plasma palmitoleic acid and oleic acid, reflecting an impaired stearoyl-CoA desaturase function; choline treatment did not affect the diminutions, but caused a decrease in arachidonic acid with a co-increase in linoleic acid. Some rats developed hypoproteinemia (HPO). HPO rats also exhibited decreases in plasma palmitoleic acid and oleic acid. Diabetes caused almost absence of palmitoleic acid in HPO rats. Choline treatment exerted no effect on the plasma fatty acid composition of diabetic HPO rats. Choline treatment affected hepatic reticuloendothelial function and plasma fatty acid composition, but not hepatobiliary function, in diabetic rats. Whether choline treatment is beneficial requires further studies.

閉塞性黄疸における網内系機能の in vivo および in vitro による実験的研究

閉塞性黄疸における網内系機能の in vivo および in vitro による実験的研究

Fever and rhomboid target lesion in decompensated cirrhosis

A 53-year-old woman with Child-Pugh B, hepatitis C virus-related cirrhosis presented with a 3 day history of high fever (peak 39·5°C) and a non-itchy rash. On admission, physical examination showed mild ascites, and a temperature of 38·5°C, a pulse rate of 88 beats per min, and a respiratory rate of 18 breaths per min were recorded. Many large (about 15 cm diameter) target lesions were present on the patient’s trunk and arms and legs, seen as concentric rings of a dull red, pink, or violet colour surrounding a clear centre (fi gure). No mucosal lesions were noted. Laboratory tests recorded a white-blood-cell count of 12×109 cells per L and a C-reactive protein concentration of 3·4 mg/L. Abdominal ultrasound confi rmed the presence of ascites, and echocardiography did not indicate endocarditis. Treatment with oral levofl oxacin was started; 2 days later, the patient’s fever was reduced, all lesions gradually ameliorated acquiring a rhomboid aspect, and liver decompensation diminished progressively. Meanwhile, two blood cultures yielded Grampositive bacteria identifi ed as Erysipelothrix rhusiopathiae. The patient attended the outpatient’s clinic at the Clinical and Molecular Hepatology Unit of the University Hospital of Messina 1 month after discharge from hospital and every 3 months thereafter. At the last visit (January, 2012) no signs of worsening liver disease were noted and the skin lesions had not reappeared. E rhusiopathiae is a common commensal or pathogen of many vertebrate and invertebrate species. Pigs are a major reservoir. Human disease is mainly an occupationally acquired zoonosis. The portal of entry is typically a puncture wound or abrasion on the hand; however, it can also be acquired from eating contaminated food. The patient does not work with animals and denied any injuries while preparing food. However, the week before she became unwell she ate raw pork meat. Liver dysfunction could be associated with E rhusiopathiae bacteraemia because of the noted impairment of reticuloendothelial function in the patient. Three clinical forms of infection with E rhusiopathiae have been reported in human beings: a localised cutaneous form, or erysipeloid of Rosenbach; a diff use cutaneous form; and a bacteraemic form that occurs with or without endocarditis. The diff use cutaneous form constitutes a rare situation in which violaceous cutaneous lesions can arise at remote areas as widespread urticaria with the rhomboid pattern characteristic of swine erysipelas. In our patient, the pattern was associated with bacteraemia without endocarditis.

Splenic changes in sickle cell anaemia

The spleen is one of the most frequently affected organ in Sickle cell anaemia (SCA). This has been attributed to its complex anatomy and prominent reticuloendothelial functions which include clearance of unwanted particulate matter in blood ( culling), defense against infection and reservoir for blood cells. This paper aims to highlight the current information on the changes that occur in the spleen of Sickle Cell Disease patients in this environment. A review of relevant literature on the subject of splenic changes in Sickle Cell Disease sourced by manual library and medline search. The essential splenic change in SCA is splenomegaly and subsequent shrinkage in size (autosplenectomy), which maybe due to several factors. These include: high levels of irreversible sickle cells, decreased HbF associated with increased intravascular sickling and chronic Malaria infection secondary to hyperplasia of the reticulo-endothelial system and increased antibody production especially IgG and IgM. Finally, the clinical complications of these splenic changes such as increased susceptibility to infection, acute splenic sequestration and hypersplenism are also reviewed in this paper. In view of the above changes, it is important to ensure regular monitoring and follow-up in order to prevent complications, recurrent crisis and death.

Prolonged thrombocytopenia after allogeneic hematopoietic stem cell transplantation: associations with impaired platelet production and increased platelet turnover

To evaluate the mechanisms underlying prolonged thrombocytopenia after allogeneic hematopoietic stem cell transplantation (SCT), an index for plasma glycocalicin normalized for the individual platelet count (GCI), plasma thrombopoietin (TPO), and circulating B cells producing anti-GPIIb-IIIa antibodies were measured in 50 SCT recipients with or without prolonged thrombocytopenia, 42 patients with idiopathic thrombocytopenic purpura, nine patients with aplastic anemia, and 22 healthy individuals. All three indices were significantly higher in the SCT recipients with thrombocytopenia than in those without (P < 0.01 for all comparisons), and were significantly correlated with the platelet count in SCT recipients. Stepwise multiple regression analysis of the samples from the SCT recipients revealed that GCI and TPO independently pointed to specific mechanisms of thrombocytopenia. The GCI and TPO status in SCT recipients with thrombocytopenia had a pattern similar to that seen in aplastic anemia, suggesting a major role for impaired thrombopoiesis. An antiplatelet antibody response was frequently detected in SCT recipients, but the development of thrombocytopenia is likely to depend on additional factors, such as reticuloendothelial function. In summary, post transplant prolonged thrombocytopenia is associated with complex mechanisms, including impaired thrombopoiesis and increased platelet turnover.

Effect of acute starvation on plasma fibronectin response to sepsis

There is evidence that undernutrition may contribute to the reduction in plasma fibronectin concentration and the depression of the reticuloendothelial (RE) system associated with severe sepsis. We have investigated the effects of fasting, surgical trauma and sepsis on plasma fibronectin concentrations and RE function. In experiment 1, plasma fibronectin was measured in rabbits (n = 14) before and 48 h after fasting. In experiment 2, sepsis was induced by devascularization of the appendix in animals on a normal diet (sepsis group, n = 7). A third group of animals underwent only a laparotomy (laparotomy only group, n = 7). Plasma fibronectin concentrations and the blood clearance and organ distribution of 99mtechnetium tin colloid (TTC) were measured 24 h after operation. Compared with pooled reference plasma, fasting in experiment 1 resulted in a reduction in mean(s.e.m.) plasma fibronectin concentration from 98(1.5) per cent to 86(3.7) per cent (T = 2, P less than 0.005). Mean(s.e.m.) plasma fibronectin concentration was raised in the sepsis group to 117(4.6) per cent, compared with 97(2.5) per cent in the laparotomy only group (U = 5, P less than 0.02), but there was no such increase in the fasting and sepsis group. There was a delay in the blood clearance and reduced hepatic uptake of TTC in both sepsis groups. The dissociation between fibronectin concentrations and RE function in animal models of sepsis casts doubt on the importance of fibronectin in RE function.

Effects of a somatostatin analogue (SMS 201-995) on hepatic and splenic reticulo-endothelial function in the rat.

The effects of a long acting somatostatin analogue, SMS 201-995, on reticulo-endothelial system (RES) activity were studied in rats. Administration of 2 micrograms SMS 201-995 subcutaneously twice a day for 7 days significantly increased the splenic and hepatic uptake of 99mTc-sulphur colloid and damaged 51mCr-red blood cells. Furthermore, SMS 201-995 administration significantly increased the plasma clearance of colloidal carbon as indicated by a lower area under the curve and an increased elimination constant. SMS 201-995 administration also significantly improved survival after intraperitoneal injection of Escherichia coli endotoxin. These results suggest that SMS 201-995 stimulates RES activity in rats. It is suggested that SMS 201-995 may be of value in stimulating RES activity in patients with cirrhosis and portal hypertension.

Reticuloendothelial failure in chronic intra-abdominal sepsis: the role of opsonic fibronectin.

Severe sepsis leads to depression of the reticuloendothelial (RE) system with delayed bloodstream clearance of particulate matter and bacteria. Fibronectin may be an important opsonin of the RE system and low fibronectin levels often accompany severe sepsis in man. We have investigated the effect of prolonged intra-abdominal sepsis on plasma fibronectin concentrations and RE function. Serial plasma fibronectin concentrations were determined in rabbits for 2 weeks after either the induction of sepsis (appendix abscess) (n = 6) or laparotomy only (n = 6). RE function was measured at 2 weeks by determining the clearance kinetics and organ distribution of low dose technetium tin colloid (TTC). There was an early transient depression in plasma fibronectin values followed by elevated concentrations at 48-72 h which were more marked in the sepsis group. There was a delay in the blood clearance with reduced hepatic and increased bone uptake of TTC. We conclude that depletion of opsonic fibronectin is unlikely to be an important factor contributing to the impairment of RE function associated with intra-abdominal sepsis and that RE depression in septic animals is due to intrinsic Kupffer cell dysfunction.

Reticulo-endothelial function in rats with obstructive jaundice.

Reticulo-endothelial function was evaluated by measuring the biokinetics of a standardized 99mTc-sulphur colloid using scintillation camera technique in rats with biliary obstruction. There was no difference in the uptake of the colloid in the liver (K1) between sham operation and biliary obstruction at 1 week and 3 weeks. However, when corrected for changes in liver volume, the corrected colloidal uptake rate (cK1) of the liver was significantly decreased in 1 week's biliary obstruction (P less than 0.005 compared with sham operation) and 3 weeks' biliary obstruction (P less than 0.025 compared with 1 week obstruction). Colloidal uptake rate of the extrahepatic reticulo-endothelial system (K2) was significantly increased (P less than 0.005) in rats with 3 weeks' biliary obstruction. Activity distribution of 99mTc-sulphur colloid in 3 weeks' biliary obstruction was significantly decreased in both total organ basis and per gram basis (P less than 0.005). The results demonstrated a depression of RE activity of the liver in biliary obstruction.

Reticulo-endothelial function in obstructive jaundice.

A study of reticulo-endothelial function was performed in 30 patients with obstructive jaundice. Reticulo-endothelial phagocytic function, measured by the clearance of intravenous human micro-aggregated albumin, was significantly depressed in jaundiced patients compared with non-jaundiced controls (P less than 0.001). There was a significant correlation (P less than 0.001) between phagocytic function and plasma bilirubin level but not with transaminase or bile salt level. Phagocytic function was not related to the presence of malignancy, but was markedly reduced in patients with cholangitis. There was no reduction in hepatic sinusoidal blood flow, opsonin levels (fibronectin, IgG, complement) or serum opsonic activity to account for the reticulo-endothelial dysfunction.

Can antibodies with specificity for soluble antigens mimic the therapeutic effects of intravenous IgG in the treatment of autoimmune disease?

Intravenous Ig (IVIg) mediates protection from the effects of immune thrombocytopenic purpura (ITP) as well as numerous other autoimmune states; however, the active antibodies within IVIg are unknown. There is some evidence that antibodies specific for a cell-associated antigen on erythrocytes are responsible, at least in part, for the therapeutic effect of IVIg in ITP. Yet whether an IVIg directed to a soluble antigen can likewise be beneficial in ITP or other autoimmune diseases is also unknown. A murine model of ITP was used to determine the effectiveness of IgG specific to soluble antigens in treating immune thrombocytopenic purpura. Mice experimentally treated with soluble OVA + anti-OVA versus mice treated with OVA conjugated to rbcs (OVA-rbcs) + anti-OVA were compared. In both situations, mice were protected from ITP. Both these experimental therapeutic regimes acted in a complement-independent fashion and both also blocked reticuloendothelial function. In contrast to OVA-rbcs + anti-OVA, soluble OVA + anti-OVA (as well as IVIg) did not have any effect on thrombocytopenia in mice lacking the inhibitory receptor FcgammaRIIB (FcgammaRIIB(-/-) mice). Similarly, antibodies reactive with the endogenous soluble antigens albumin and transferrin also ameliorated ITP in an FcgammaRIIB-dependent manner. Finally, broadening the significance of these experiments was the finding that anti-albumin was protective in a K/BxN serum-induced arthritis model. We conclude that IgG antibodies directed to soluble antigens ameliorated 2 disparate IVIg-treatable autoimmune diseases.

Immunomodulating Effects of Black Seed and Oxytetracycline in Pigeons

Chronic administration of oxytetracycline (OXT) (incorporated at a level of 0.05 g per kg of feed for 50 days) to pigeons, significantly decreased total leukocyte and lymphocyte counts, increased heterophil:lymphocyte ratio and lysosomal enzyme activity, and decreased reticuloendothelial system function compared with controls. Coadministration of black seed (BS) at a level of 2.5% with OXT completely blocked the effects elicited by OXT and produced immunostimulant effects in pigeons. The addition of BS to feed of pigeons could act as an immunoprotective agent when chronic administration of antibiotics are considered.

Temporal Effect of Hemoglobin Resuscitation on Sepsis Survival

Hemoglobin (Hb)-based oxygen carriers are promising resuscitation fluids for hemorrhagic shock. However, infusion of large amounts of Hb-based material could interfere with reticuloendothelial function potentiating postresuscitation sepsis mortality. We investigated the temporal relationship between hemorrhage-resuscitation and sepsis survival. Male SD rats were subjected to hemorrhage and resuscitated with shed blood volumes of purified human hemoglobin solution (HS). Sepsis was induced by cecal ligation and puncture (CLP) 24 h before, 0, 24, or 72 h after hemorrhage/resuscitation (H/R) and survival was monitored. In additional animals with or without Hb resuscitation, hepatic heme oxygenase-1 (HO-1) gene expression and HO activity were assessed. Seven-day survival for animals resuscitated with HS prior to sepsis induction was significantly higher than other groups. Animals resuscitated with HS showed hepatic HO-1 gene expression while non-HS resuscitated animals did not. In addition, hepatic HO activity levels were significantly higher in HS resuscitated animals than non-HS resuscitated animals. In conclusion, HS resuscitation does not appear to enhance postresuscitation sepsis mortality. Rather, when conducted concomitantly or prior to sepsis, HS resuscitation appears to improve survival from a subsequent sepsis challenge.