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Objective and Design: Rats treated with aggregated IgG (Aggr.) become 'refractory' to the hypotensive action of a second dose of Aggr. The objective of this study was to assess the responsiveness of animals pretreated with Aggr. to bacterial LPS and vice versa.¶Material or Subjects: Female Wistar rats (250–300 g) were used. Each experiment was carried on at least 4 animals.¶Treatment: A human IgG preparation containing 30% aggregates (10–16 mg/100 g) or E. coli serotype 0111.B4 (0.005–1 mg/100 g) was administered i.v. Certain groups of animals were pretreated with 1 mg/100 g GdCl3 or with 10 mg/100 g pentoxyphylline (PTX).¶Methods: Arterial blood pressure was monitored in the carotis using a polyethylene cannula and an electronic tension meter. Tumor necrosis factor alpha (TNF-α) activity was estimated by the use of an L-929 cell cytotoxicity assay.¶Results: Pretreatment of rats with a sublethal dose of LPS impaired the hypotensive reaction of the animals to Aggr. Rats made 'refractory' to Aggr. reacted to the injection of LPS with hypotension and a second phase milder than in the controls. Hypotension could not be elicited by Aggr. in rats pretreated with GdCl3. The same pretreatment had no effect on the first phase of hypotension induced by intravenous injection of LPS, whilst a mitigation of the second phase was observed. Infusion of PTX immediately prior to Aggr. administration prevented the drop of blood pressure. A sizeable level of TNF-α was detected only later than blood pressure had reached its minimum level following Aggr. administration.¶Conclusions: Hypotension induced by LPS may involve a macrophage population broader than that responsible for the vascular action of Aggr. The data presented do not support a primary role for TNF-α in Aggr. induced hypotension.

Objective and design: The consequences of Kupffer cell phagocytosis blockade were studied in endotoxemic rats with obstructive jaundice.¶Material or Subjects: 159 male Wistar rats.¶Treatment: Obstructive jaundice was induced by bile duct ligation (BDL). Gadolinium chloride (1 mg/100g iv) was given 6 days after BDL to inhibit Kupffer cell activity and the animals were challenged with 1 mg/g endotoxin 24 h later.¶Methods: Endotoxin sensitivity, tumor necrosis factor-α and interleukin-6 production were studied, liver and lung injury were assessed by neutrophil infiltration assay, tissue adenosine triphosphate, aspartate aminotransferase, alanine aminotransferase level determinations and histology, respectively. For statistics non-parametric methods were used.¶Results: BDL sensitized the animals to endotoxin, increased endotoxin-induced tumor necrosis factor-α and interleukin-6 production and reduced ATP contents of the liver and the lung. Kupffer cell blockade significantly increased the resistance against endotoxin, diminished the inflammatory cytokine release and reduced endotoxin-induced tissue injury in BDL animals.¶Conclusion: Attenuation of Kupffer cell function decreases endotoxin-induced lethality and morbidity in obstructive jaundice.

Although the pathogenesis of cervical inlet patch (CIP) is not fully understood, most authors consider it as a congenital abnormality, whereas others surmise it to be related to gastroesophageal reflux disease (GERD). We aimed to evaluate esophageal function and the prevalence of GERD and Barrett's esophagus in patients with CIP. GERD is defined by the presence of erosive esophagitis or an abnormal pH monitoring. Seventy-one consecutive patients with endoscopic and histological evidence of CIP were prospectively evaluated. Esophageal symptom analysis, 24-hour simultaneous biliary reflux and double-channel pH-monitoring, and esophageal manometry were carried out in 65/71 (92%) patients and in 25 matched controls. Six patients were not suitable for testing and were, therefore, excluded. The histological evaluation of the heterotopic islands showed cardia and/or oxyntic mucosa in 64/65 (98%) patients and specialized intestinal metaplasia (SIM) in one patient (2%). The cardia and/or oxyntic mucosa was accompanied by focally appearing pancreatic acinar metaplasia and pancreatic ductal metaplasia in 7/64 (11%) and in 1/64 (2%), superficial mucous glands in 6/64 (9%), and SIM in 2/64 (3%) cases. In total, SIM was present in three patients (5%), and one of them had low-grade dysplasia. At the gastroesophageal junction, 28 (43%) patients had columnar metaplasia, including nine (14%) patients with SIM. Erosive esophagitis was present in 37 (57%) cases. Thirty-two patients (49%) had abnormal acid reflux in the distal and 25 (38%) in the proximal esophagus. Abnormal biliary reflux was present in 25 (38%) cases. On the basis of endoscopic and pH studies, GERD was established in 44/65 (68%) patients. Typical reflux symptoms were common (33/65, 51%). The combined 24-hour biliary and double-channel pH-monitoring detected significantly more significant acidic reflux at both measurement points and significantly longer bile exposure time in the distal esophagus in patients with CIP. Acid secretion in the CIP was detected in three (5%) cases. Esophageal manometry revealed decreased LES pressure and prolonged relaxation with decreased peristaltic wave amplitude, and an increased number of simultaneous contractions in the esophageal body. The detailed evaluation of the esophageal morphology and function in subjects with CIP showed a high prevalence of GERD and Barrett's esophagus. Further studies are needed to evaluate whether combined acidic and biliary reflux is able to promote similar histomorphological changes in the CIP, as it is shown distally in patients with Barrett's esophagus.

The effects of glucocorticoids on acute pancreatitis (AP) have remained contradictory. The aim of this study was to investigate the time courses of the effects of the exogenous glucocorticoid agonists dexamethasone (DEX) and hydrocortisone (HYD) and a glucocorticoid antagonist (RU-38486) and to characterize the local and systemic responses in AP in rats. The glucocorticoid antagonist and agonists were administered just before AP induction. Serum amylase activity determinations, IL-6 bioassays, pancreatic weight/body weight ratio measurements, and survival analysis were performed. Liver and lung injuries were assessed via neutrophil leukocyte infiltration in myeloperoxidase (MPO) assays, tissue adenosine triphosphate (ATP) level determinations, and histology. In the glucocorticoid agonist groups, the survival rate increased, while the serum amylase level, the IL-6 activity, and the pancreatic weight/body weight ratio decreased significantly as compared with the control and RU-treated groups. AP resulted in significant decreases in tissue ATP levels in both the liver and the lung. In the DEX- or HYD-treated groups, the liver ATP levels were significantly elevated, while both the liver and the lung MPO levels were attenuated as compared with the AP and RU-treated groups. These results suggest that glucocorticoids may play important roles in mitigating the progression of the inflammatory reaction during the early phases of AP.

THE IMMUNOLOGIC consequences of xenogenic islet transplantation remain unsolved. Gadolinium chloride (GdCl3) is known to depress reticuloendothelial activity by selectively blocking the function of hepatic Kupffer cells. We previously reported that xenotransplantation of insulinoma cells normalized blood glucose levels in diabetic rats after a single intravenous GdCl3 injection. 1 In the present work, we investigate the effects of GdCl3-induced long-term Kupffer cell blockade on the survival of human fetal islet xenografts.

Data in the literature concerning the role of macrophages in anaphylaxis are contradictory. In the present study, the effect of macrophage blockade induced by gadolinium chloride (GdCl3) on anaphylactic shock is investigated. Our observations show that GdCl3 prevents lethal anaphylactic shock in mice sensitized to ovalbumin. Gadolinium chloride given i.v. in a dose of 1 mg/100 g body weight 24 or 48 h before the elicitation of anaphylactic shock resulted in 80% survival, compared with the 43% survival in the control group. The same dose of this rare-earth metal salt also greatly reduced the mortality in mice sensitized with ovalbumin containing Bordetella pertussis vaccine, and similarly abrogated the symptoms of anaphylaxis, including the accumulation of serotonin and histamine in the liver. The results suggest that macrophages play an important role in mouse anaphylaxis.

SummaryOur experiments revealed that Phlogodym had a marked adverse effect on the sublethal tourniquet shock of rats. This effect was associated with a simultaneous drop in fibrinogen levels and platelet counts. In the hind limbs of the animals treated with Phlogodym and submitted to tourniquet, a thrombo-hemorrhagic phenomenon which macroscopically and microscopically resembled the Shwartzman Reaction, developed 5 to 20 hrs after the removal of the tourniquet.