Reversal of ischemic liver failure by intrasplenic liver cell transplantation

A model of ischemic hepatic failure in Sprague-Dawley rats (SD) with 100% mortality has been developed by one-hour occlusion of the right portal vein and hepatic artery followed by left 70% hepatectomy. The intrasplenic injection of 40 x 10(6) syngeneic adult or three-day neonatal single liver cell suspensions decreased the mortality from 100% to 50% and 36%, respectively. Mortality decreased with increasing time from the intrasplenic injection of neonatal liver cells to the time of acute hepatic ischemia. Mortality also decreased with increasing interval between hepatic ischemia and removal of the transplanted liver cells by splenectomy. Intrasplenic injection of graded doses of neonatal liver cells decreased mortality from 75% at a dose of 10 x 10(6) cells, to 36% at 160 x 10(6) cells. Treatment of neonatal liver cells with metabolic inhibitors did not significantly affect their ability to reverse acute hepatic ischemia.     

Dysphagia aortica

Three patients with dysphagia caused by compression of the distal esophagus by a tortuous nonaneurysmal atherosclerotic aorta are described. All three patients were elderly women; systemic hypertension and cardiomegaly were present in two patients. Barium studies of the esophagus showed displacement and compression of the distal esophagus by the thoracic aorta. Debilitating dysphagia was treated surgically in one patient. The other two patients had milder symptoms and were managed conservatively. Esophageal manometry in these three patients showed superimposed pulsations and elevated intraluminal pressure just proximal to the lower esophageal sphincter. To evaluate the significance of these manometric findings and their correlation with clinical symptoms, we reviewed manometric tracings in 47 normal subjects. Ten of these subjects had an elevation of baseline intraluminal esophageal pressure as a result of superimposed vascular pulsations. We conclude that (1) compression of the distal esophagus by a tortuous atherosclerotic aorta in the appropriate setting can lead to clinically significant dysphagia and (2) a manometric finding of vascular compression of the esophagus does not necessarily correlate symptomatic dysphagia.     

Arteriovenous shunt construction for vascular access in the rat

A method is described that allows high-frequency venous and arterial blood sampling in the laboratory rat. After distal ligation and division of the external jugular vein and carotid artery, sections of Teflon intravenous catheters are inserted and secured with circumferential ligatures. Between these Teflon segments, a vascular circuit is maintained with the interposition of silicone tubing. The silicone tube segment has been filled with heparinized saline, divided in half, and joined at its center by another segment of the catheter. This in situ arteriovenous (AV) shunt system is secured in the neck of the host animal by creating a subcutaneous tunnel and externalization of a portion of the shunt loop. The shunt facilitates repetitive blood sampling from the conscious rat. The procedure time is approximately 45 minutes, and patency can be assured over several days. Additional uses of the system include pretreatment injection protocols and postoperative drug therapy.     

Reversible changes in tumor growth and metastatic behavior induced by immune pressure

Prolonged exposure to host immunity was studied for its effect on several characteristics of a cloned 3-methylcholanthrene-induced fibrosarcoma. One million cells of a clone 10-O were injected subcutaneously into normal C3H/HeJ mice (clone 10-N) or tumor-immune mice (clone 10-I). After 10 passages in immune mice, 1 X 10(6) cells from 10-I tumor were transferred back into normal mice (clone 10-R). After 5 to 10 additional in vivo passages, clone 10-O, 10-N, 10-I, and 10-R tumors were transplanted into normal mice and observed for tumor growth rate, tumorigenicity, antigen specificity, metastatic potential, and plating efficiency. Clone 10-I after 10 passages in immunized mice grew significantly more slowly than did 10-O or 10-N clones, required more tumor cells to cause 50% tumor incidence in normal mice (tumorigenicity), and completely lost its capacity to metastasize spontaneously or experimentally. The plating efficiency in vitro of 10-I was also less than that of 10-O or 10-N. All these changes reversed after 5 to 10 passages of 10-I clone back into normal mice (10-R). Although immune pressure induced qualitative antigenic changes, as demonstrated by a tumor-rejection assay, and resulted in no cross-reactivity with control tumor clones (antigen specificity), the degree of immune response to its autologous clone in immune mice (immunogenicity) remained constant. These results suggest that several unrelated characteristics of this clone 10 can be phenotypically changed during the same period by immune pressure.     

Autoregulation by eicosanoids of human Kupffer cell secretory products. A study of interleukin-1, interleukin-6, tumor necrosis factor-alpha, transforming growth factor-beta, and nitric oxide.

OBJECTIVE: Methods employed previously to analyze the secretory behavior of rodent Kupffer cells (KC) were used to examine the human KC's secretory response to lipopolysaccharide (LPS). SUMMARY BACKGROUND DATA: As the resident hepatic macrophage, the KC resides at the interface between the portal and systemic circulations. Consequently, this cell may play an integral role in the immune response to antigens and bacteria in the sinusoid. Study of cytokine production by the KC has relied predominantly on the rat as the source of these cells. Whether human KCs respond similarly to rat KCs after LPS stimulation has been a matter of speculation. METHODS: Kupffer cells obtained from seven human livers were tested under conditions identical to those used to study rat KCs. Kupffer cells rested for 12 hours after isolation were stimulated with LPS (2.5 micrograms/mL). Arginine concentration in the culture medium varied from 0.01 to 1.2 mM. To examine the role of eicosanoids, parallel culture wells received indomethacin (10 microM). Culture supernatants were assayed for interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), prostaglandin E2 (PGE2), and nitric oxide. RESULTS: Similar to the rat KC, LPS-stimulated human KCs released IL-1, IL-6, TNF-alpha, TGF-beta, and PGE2. However, unlike rat KCs, nitric oxide could not be detected, regardless of whether the human KCs were exposed to LPS, interferon-gamma (INF-gamma), or LPS + IFN-gamma. Similar to rat KCs, indomethacin prevented PGE2 release while significantly upregulating TNF-alpha, IL-1, and IL-6, but not TGF-beta, consistent with an autoregulatory control of eicosanoids over proinflammatory cytokines. As has been shown in the rat, physiologic levels of L-arginine (0.01 mM) significantly enhanced LPS-induced PGE2 secretion relative to the response in medium containing standard L-arginine concentration (1.2 mM); however, unlike the rat KC, the human's cytokine response to LPS was not downregulated by this enhanced PGE2 release. CONCLUSIONS: Although many functional features are shared by rat and human KCs, significant differences do exist. Such discrepancies reinforce the need to proceed with caution when generalizing from the results obtained in other species to human physiology.     

Genital infections with Chlamydia trachomatis in pregnant women in New Caledonia]

Chlamydia trachomatis was researched from 400 pregnant women. 76 of them were found infected and 129 carried serological signs of infection. We purpose a detection at the end of pregnancy interesting women with sexually transmitted diseases background and those with serological positive results (greater than 1/64). Then, treatment of the mother will be an useful method of prevention against neonatal infection.     

Interleukin-6 production by endotoxin-stimulated Kupffer cells is regulated by prostaglandin E2

Although its impact on the acute phase response is clear, little is known regarding the regulation of interleukin-6 (hepatocyte-stimulating factor) production. We evaluated its relationship with the potent immunosuppressive eicosanoid PGE2 in endotoxin (LPS)-stimulated Kupffer cells (KC). KC were harvested from collagenase-digested Wistar-Furth rat livers and purified (greater than 95% by phagocytosis) by adherence. Following overnight culture with or without the cyclooxygenase inhibitor indomethacin (10 microM), 5 X 10(5) KC were repleted with fresh media with or without 2.5 micrograms/ml LPS. Supernatant IL-6 levels (ng/ml) were measured with the B9.9 hybridoma proliferative bioassay, and PGE2 levels (ng/ml) by radioimmunoassay. Negligible supernatant IL-6 and PGE2 were measured at all culture intervals in unstimulated KC or those cultured with the LPS-inhibitor polymyxin-B (10 micrograms/ml). With LPS, KC IL-6 production increased in parallel with PGE2 for 24 hr before decreasing as PGE2 continued to rise. When indomethacin treatment blocked KC PGE2 production, IL-6 levels significantly increased. We conclude that PGE2 produced by activated Kupffer cells appears to down-regulate IL-6 secretion. Autocrine effects by PGE2 may locally regulate the hepatic acute phase response by limiting the KC-derived IL-6 available to act on neighboring hepatocytes.