Cooperative cargo transportation by a swarm of molecular machines.

Cooperation is a strategy that has been adopted by groups of organisms to execute complex tasks more efficiently than single entities. Cooperation increases the robustness and flexibility of the working groups and permits sharing of the workload among individuals. However, the utilization of this strategy in artificial systems at the molecular level, which could enable substantial advances in microrobotics and nanotechnology, remains highly challenging. Here, we demonstrate molecular transportation through the cooperative action of a large number of artificial molecular machines, photoresponsive DNA-conjugated microtubules driven by kinesin motor proteins. Mechanical communication via conjugated photoresponsive DNA enables these microtubules to organize into groups upon photoirradiation. The groups of transporters load and transport cargo, and cargo unloading is achieved by dissociating the groups into single microtubules. The group formation permits the loading and transport of cargoes with larger sizes and in larger numbers over long distances compared with single transporters. We also demonstrate that cargo can be collected at user-determined locations defined by ultraviolet light exposure. This work demonstrates cooperative task performance by molecular machines, which will help to construct molecular robots with advanced functionalities in the future.

Intravenous allicin improves pulmonary blood flow after ischemia-reperfusion injury in rats.

BACKGROUND: Allicin is a sulfur-containing compound extracted from garlic, with antiaggregatory, anti- migratory, anti-oxidant and pulmonary vasodilator actions. We hypothesized that allicin might be beneficial in lung ischemia-reperfusion. METHODS: A non-nothermic rat lung ischemia-reperfusion model was established by clamping left pulmonary artery (PA) for 1 hr, followed by reperfusion for 2 hrs by clamping right PA to reflect solely the function of left lung. Groups were control (n=7), allicin 0.1 mg (n=8) and allicin 0.01 mg (n=4). In the beginning of reperfusion allicin/saline were injected. Pulmonary artery pressures (PAP), pulmonary artery flow (PAF), left atrial pressure (LAP) were monitored. At the end of reperfusion period arterial blood gas (ABG) analysis was done. RESULTS: Six of 7 control and 3 of 8 group 2 animals died before completing the experiment. In group 1 all animals completed the experiment (p=0.015 vs control). PAF was significantly increased after 30, 60 and 120 min of reperfusion in group 1 (p=0.0028, 0.0009, 0.0003 respectively vs control) and after 60 and 120 minutes in group 2 (p=0.0453, 0.018 respectively vs control). Pulmonary vascular resistance was lower at 30 min in allicin 0.01 mg group (p=0.0017 vs control). PAP was increased after 60 and 120 min of reperfusion in group 1 (p=0.016, 0.0029 respectively vs control) and after 120 min in group 2 (p=0.0104 vs control). CONCLUSIONS: This study shows that allicin improves postischemic PAF in this model. Allicin needs further investigation of potential utility and mechanism(s) of action.

[Th1/Th2 imbalance in HCV-related liver cirrhosis].

The mechanism by which Hepatitis C virus(HCV) infection promotes the development of hepatocellular carcinoma(HCC) is not known exactly. HCV related HCC occurs frequency in the patients with cirrhosis. There have been reports indicating that Th2-type cytokines down-regulated antitumor immunity, and the activation of type 1 T cell responses produced antitumor immunity. We thought Th1/Th2 imbalance in HCV-related liver cirrhosis might be closely related to the development of HCC. In this study, therefore, we investigated the Th1/Th2 balance at the single lymphocyte level of the patients with HCV-related liver cirrhosis and compared with normal controls by using flow cytometry. Th1-type cytokines(IFN-gamma, IL-2) production was significantly decreased in patients with cirrhosis, whereas Th2-type cytokine production(IL-10) was increased. These suggest Th1/Th2 imbalance in HCV-related cirrhosis would decrease the antitumor immunity and its improvement might present the protective effect from HCC.

Characteristics of the cell proliferation profile of activated rat hepatic stellate cells in vitro in contrast to their fibrogenesis activity.

PURPOSE: Alterations in the kinetics of hepatic stellate cells (HSCs) after the cells are activated once have not been well documented. We investigated the characteristic profiles of cell proliferation of once-activated HSCs in contrast to the in fibrogenesis activity. METHODS: HSCs from male Wistar rats were submitted to primary culture for 14 days and to secondary culture for 7 days. The potential for cell proliferation was evaluated by the number of the cells in G2/M phase, based on flow cytometric analysis of the cell cycle. The fibrogenesis activity was assessed by Northern blot analysis of the expression of type I and type III procollagen mRNA. RESULTS: The number of HSCs in G2/M phase was maintained at a low level in primary culture after 6 days, while a significantly (P < 0.05) elevated number of HSCs in G2/M phase was observed on days 3 to 4. In secondary culture, the number of HSCs in G2/M phase was also consecutively maintained at a decreased level. By contrast, HSCs showed progressively increased type I and type III procollagen mRNA expression during the experimental periods of primary culture. CONCLUSIONS: These results clearly demonstrated consecutively decreased proliferative activity, evaluated by the potential for cell mitogenesis, in once-activated HSCs, in contrast to their progressively increased fibrogenesis activity.

HBV-related fulminant hepatic failure: successful intensive medical therapy in a candidate for liver transplantation.

Fulminant hepatic failure (FHF) usually has a fatal prognosis without liver transplantation. We describe the case of a woman who developed FHF, and was evaluated as a candidate for liver transplantation, but who was cured without transplantation through intensive medical care that included glucagon-insulin therapy, methylprednisolone pulse therapy, interferon beta and lamivudine administration, cyclosporine administration, and high-volume hemodiafiltration and plasma exchange. In a patient with FHF who is a candidate for liver transplantation but for whom the transplantation cannot be performed for some reason, intensive medical therapy, including regeneration-promoting therapy, immunosuppressive therapy, antiviral therapy, and vigorous hepatic support, should be carried out.

Preventive effect of FK 506 (tacrolimus hydrate) on experimentally induced acute liver injury in rats.

The aim of the study was to investigate the effect of the immunosuppressant FK 506 (tacrolimus hydrate) on acute liver injury induced by Propionibacterium acnes and lipopolysaccharide (LPS). Acute liver injury was induced in male Wistar rats by injecting the animals with P. acnes (10 mg/rat), and administering LPS (10 microg/rat) seven days later. One group was given FK 506 (1 mg/kg) 24 and 2 hr before administration of LPS, and the other group was given the same dose of saline. The 24-hr survival rate, serum alanine aminotransferase (ALT) concentration, and tumor necrosis factor (TNF) -alpha mRNA and protein concentrations in the liver and spleen were then compared. Hepatic macrophages were also isolated from rats seven days after P. acnes injection, LPS, and FK 506 or saline were added to the culture supernatant, and TNF-alpha production was studied. The 24-hr survival rate was 100% in the FK 506-treated group, in contrast with 16.6% in the saline group. Four hours after LPS injection, the serum ALT concentration was 755 +/- 401 in the saline group versus 119 +/- 42 units/ml (P < 0.01) in the FK 506-treated group. The serum TNF-alpha concentration was lower in the FK 506-treated group (1,419 +/- 957 pg/ml) than in the saline group (9205 +/- 2215) (P < 0.01). The mRNA and protein concentrations in the liver and spleen in the two groups did not differ significantly 1 hr after LPS injection but were significantly lower in the FK 506-treated group after 4 hr. FK 506 did not directly inhibit TNF-alpha production by isolated cultured hepatic macrophages. FK 506 is unable to inhibit initial TNF-alpha production by hepatic macrophages (or probably that by splenic macrophages either) stimulated by injection of LPS in P. acnes + LPS-induced acute liver injury. However, the immunosuppressant does limit hepatic damage by inhibiting subsequent aggravation of inflammation by the cytokine network.

[Automated infant auditory screening using the Natus-ALGO 2e in the NICU].

Natus-ALGO 2e, an automated ABR screener(Natus Medical, Foster City, CA, USA), compares the V wave of ABR evoked by 35-dB-nHL click stimuli by using a template-matching detection algorithm that provides only a pass-refer outcome. The aim of this study was to compare Natus-ALGO 2e with conventional ABR, and to evaluate its usefulness. The Natus-ALGO 2e screener was used to screen 202 ears of 101 neonates in our neonatal intensive care unit. The mean conceptional age at the time of screening was 40.4 +/- 3.0 weeks. 60 ears of 30 infants at high-risk of hearing impairment, including "refer" infants, were tested by the Natus-ALGO 2e and conventional ABR methods, and the results were compared. All neonates were tested with the Natus-ALGO 2e screener in a state of natural sleep, and screening time averaged 2 minutes 58 seconds. There were 97 cases in which both ears were passed, 3 cases in which both ears were referred, and one case in which one ear was referred. In comparison with conventional ABR, 53 of the 60 ears of 30 high-risk infants passed by the Natus-ALGO 2e method, whereas 14 of the 53 ears initially failed the conventional ABR screening. Of these 14 ears disagreements (the results of the Natus-ALGO 2e method passed, but the results of the conventional ABR failed), the results of the ABR screening changed to normal in 11 ears, and ABR showed improved threshold and latency in the other 3 ears after 5 weeks to 12 months. Among those that passed the Natus-ALGO 2e screening, the number of sweeps that failed the ABR screen was significantly greater than with normal ABR. Of the 7 ears of 4 patients that were referred on the basis of the Natus-ALGO 2e screening and failed by the conventional ABR method, 3 ears screened by the ABR method were normal when retested, and one ear passed by the Natus-ALGO 2e screening 12 weeks to 11 months later. In conclusion, Natus-ALGO 2e is useful for screening infant hearing because it can be performed quickly while the patient is sleeping naturally. In infants at high-risk for hearing impairment, the results of Natus-ALGO 2e and conventional ABR screening conflicted in numerous sweeps. Therefore, when there are many sweeps in high-risk infants, a retest should be performed that includes conventional ABR, even if they passed with Natus-ALGO 2e.

[Value of upper gastrointestinal endoscopic examination of head and neck cancer patients].

Between January 1995 and March 1999, we performed the upper gastrointestinal endoscopic examinations on 287 patients with head and neck cancers and detected 23 cases (8%) of esophageal cancer and 8 cases (2.8%) of gastric cancer, showing how frequently esophageal cancer occurs in head and neck cancer. The esophageal cancer involved the oral cavity in 8 cases (9.5%), the oropharynx in 3 cases (8.6%), the hypopharynx in 10 cases (19.6%), and the larynx in 2 cases (2%). Esophageal cancer occurred most frequently in hypopharyngeal cancer, particularly the pyriform sinus type and the postcricoid type. We conclude that upper gastrointestinal endoscopic examination, including Lugol staining, is necessary in head and neck cancer patients.

Antisense intercellular adhesion molecule-1 (ICAM-1) oligodeoxyribonucleotide delivered during organ preservation inhibits posttransplant ICAM-1 expression and reduces primary lung isograft failure.

Transiently increased expression of leukocyte adhesion receptors after lung preservation contributes to early graft demise by recruiting leukocytes, activating complement, and causing microcirculatory stasis. We hypothesized that inhibiting intercellular adhesion molecule-1 (ICAM-1) expression even briefly may significantly improve lung graft function and that the preservation period might provide a unique window to deliver a therapeutic pulse of antisense oligonucleotide ICAM-1 to inhibit ICAM-1 expression after transplantation. Interleukin-1beta-treated rat pulmonary endothelial cells given a 20-mer phosphorothioate oligonucleotide comprising an antisense span targeted to the 3'-untranslated region of rat ICAM-1 demonstrated an oligonucleotide dose-dependent reduction in ICAM-1 expression. Using a cationic liposomal carrier, this same antisense oligonucleotide (but not the sense control) instilled into the pulmonary vasculature at the time of preservation reduced subsequent graft ICAM-1 expression and graft leukostasis and markedly improved oxygenation, pulmonary blood flow, and graft survival. These experiments demonstrate that the preservation period presents a window during which to target an anti-ICAM-1 expression strategy to inhibit early adhesion receptor expression and improve functional outcome after lung transplantation.

Identification of optimal conditions for lung graft storage with Euro-Collins solution by use of a rat orthotopic lung transplant model.

BACKGROUND: Lung preservation disrupts normal vascular homeostasis, resulting in increased permeability, vasoconstriction, and endothelial cell adhesion for neutrophils. We hypothesized that a storage strategy that best preserves post-lung transplantation (LTX) vascular homeostasis might be organ and species specific. Because of the potential utility of a rat LTX model for developing improved lung preservation strategies, we have attempted to identify the optimal physical conditions for rat lung graft storage. METHODS AND RESULTS: Conditions that were tested included harvest inflation pressure (0, 10, or 20 mm Hg), inflation gas composition (100% N(2), room air, or 100% O(2)), and storage temperature (4 degrees, 10 degrees, or 15 degrees C). Modified Euro-Collins solution served as the base preservation solution for all experiments, with a preservation duration of 4 to 6 hours. Arterial oxygenation (PaO(2), mm Hg), pulmonary vascular resistance (mm Hg/mL per minute), recipient survival (%), and graft neutrophil infiltration (DeltaAbs(460 nm)/min) were measured 30 minutes after transplantation of the left lung and exclusion of the right lung from the circulation. All tested conditions significantly affect post-LTX vascular homeostasis. Inflation at 10 mm Hg pressure preserved lungs significantly better than did other pressures. There was a tendency for room air to improve all measured variables compared with 100% N(2) or 100% O(2) and a significant improvement in recipient survival with room air storage. Of the 3 storage temperatures investigated, 10 degrees C storage provided the best preservation in terms of PaO(2), graft neutrophil infiltration, and survival. CONCLUSIONS: We conclude that storage at 10 degrees C, 10 mm Hg inflation pressure, with room air establishes optimal lung storage conditions with Euro-Collins solution in this rat LTX model. These data suggest that these conditions should be used to evaluate new and potentially improved preservation strategies.

Superior protection in orthotopic rat lung transplantation with cyclic adenosine monophosphate and nitroglycerin-containing preservation solution.

BACKGROUND: Primary lung graft failure is common, and current lung preservation strategies are suboptimal. Because the decline in lung levels of cyclic adenosine monophosphate and cyclic guanosine monophosphate during preservation could enhance adhesiveness of endothelial cells for leukocytes as well as increase vascular permeability and vasoconstriction, we hypothesized that buttressing these levels by means of a preservation solution would significantly improve lung preservation. METHODS: An orthotopic rat left lung transplantation model was used. Lungs were harvested from male Lewis rats and preserved for 6 hours at 4 degrees C with (1) Euro-Collins solution (n = 8); (2) University of Wisconsin solution (n = 8); (3) low-potassium dextran glucose solution (n = 8); (4) Columbia University solution (n = 8), which contains a cyclic adenosine monophosphate analog (dibutyryl cyclic adenosine monophosphate) and a nitric oxide donor (nitroglycerin) to buttress cyclic guanosine monophosphate levels; or (5) Columbia University solution without cyclic adenosine monophosphate or nitroglycerin (n = 8). PaO2, pulmonary vascular resistance, and recipient survival were evaluated 30 minutes after left lung transplantation and removal of the nontransplanted right lung from the pulmonary circulation. RESULTS: Among all groups studied, grafts stored with Columbia University solution demonstrated the highest Pa O2 (355 +/- 25 mm Hg for Columbia University solution versus 95 +/- 22 mm Hg for Euro-Collins solution, P <.01, 172 +/- 55 mm Hg for University of Wisconsin solution, P <.05, 76 +/- 15 mm Hg for low-potassium dextran glucose solution, P <.01, and 82 +/- 25 mm Hg for Columbia University solution without cyclic adenosine monophosphate or nitroglycerin, P <.01) and the lowest pulmonary vascular resistances (1 +/- 0.2 mm Hg * mL-1 * min-1 for Columbia University solution versus 12 +/- 4 mm Hg * mL-1 * min-1 for Euro-Collins solution, P <.01, 9 +/- 2 mm Hg * mL-1 * min-1 for University of Wisconsin solution, 14 +/- 6 mm Hg * mL-1 * min-1 for low-potassium dextran glucose solution, P <.01, and 8 +/- 2 mm Hg * mL-1 * min-1 for Columbia University solution without cyclic adenosine monophosphate and nitroglycerin). These functional and hemodynamic improvements provided by Columbia University solution were accompanied by decreased graft leukostasis and decreased recipient tumor necrosis factor alpha and interleukin 1alpha levels compared with the other groups. In toto, these improvements translated into superior survival among recipients of Columbia University solution-preserved grafts (100% for Columbia University solution, 37% for Euro-Collins solution, P <.01, 50% for University of Wisconsin solution, P <.05, 50% for low-potassium dextran glucose solution, P <.05, and 13% for Columbia University solution without cyclic adenosine monophosphate and nitroglycerin, P <.01). CONCLUSION: Nitroglycerin and cyclic adenosine monophosphate confer beneficial vascular effects that make Columbia University solution a superior lung preservation solution in a stringent rat lung transplantation model.

Inhibitory effects of the herbal medicine Sho-saiko-to (TJ-9) on cell proliferation and procollagen gene expressions in cultured rat hepatic stellate cells.

BACKGROUND/AIMS: It is of extreme importance to prevent liver fibrosis and subsequent progression to liver cirrhosis. The aim of our study was to elucidate in vitro whether Sho-saiko-to exerted inhibitory effects on hepatic stellate cells. METHODS: Hepatic stellate cells were isolated from male Wistar rats. Water-soluble ingredients of Sho-saiko-to were obtained at concentrations of 10, 100, 250, 500 and 1000 microg/ml. Morphological transformation was observed under a phase-contrast microscope. Flow cytometric analysis was performed on day 4 after culture to evaluate the potential to proliferate of the stellate cells by analyzing cell cycles. Northern blot analysis was carried out on day 3 after culture to determine the expressions of type I and type III procollagen mRNAs. RESULTS: (i) Sho-saiko-to 500 and 1000 microg/ml inhibited morphological transformation of the stellate cells to myofibroblast-like cells. (ii) Sho-saiko-to 500 and 1000 microg/ml significantly (p<0.0001) accumulated the cells in the G0/G1 phase (118.8+/-0.7%, 119.2+/-0.5%, respectively as compared with control) and significantly (p<0.0001) decreased cell numbers subsequently in G2/M phase (47.5+/-8.1%, 48.9+/-2.0%, respectively). (iii) Sho-saiko-to 500 and 1000 microg/ml also significantly (p<0.05 or p<0.0001) suppressed procollagen mRNA expression of type I to 51.5+/-6.4%, 34.9+/-3.7%, respectively, and type III to 51.3+/-12.3%, 46.7+/-11.4%, respectively. CONCLUSIONS: We have clarified the inhibitory effects of Sho-saiko-to on hepatic stellate cells in vitro. Sho-saiko-to could be a potent inhibitor in the pathogenesis of liver fibrosis.

Fibrosis accelerates the development of enzyme-altered lesions in the rat liver.

Injection of pig serum into rats twice a week for 8 weeks induced stellate cell activation resulting in liver fibrosis without parenchymal cell injury. Administration of a choline deficient L-amino acid defined (CDAA) diet for 6 weeks with or without pig serum pretreatment led to the development of preneoplastic lesions that were positive for the placental form of glutathione S-transferase (GSTP). Pig serum pretreatment induced more activated stellate cells in the livers of rats subsequently fed a CDAA diet for 6 weeks compared with rats fed the CDAA diet alone. Activated stellate cells were detected as smooth muscle actin (SMA)-positive cells and by the expression of SMA messenger RNA. These cells caused severe fibrosis as assessed by the hepatic hydroxyproline content. Pre-existing fibrosis induced by the activation of stellate cells with pig serum pretreatment increased hepatic malondialdehyde (MDA) level in parallel with GSTP-positive lesions. These results indicate that pre-existing fibrosis with the activated stellate cells accelerates the development of preneoplastic lesions in a CDAA diet model.

Preventive effect of cyclosporin A on experimentally induced acute liver injury in rats.

We examined the effect of cyclosporin A (CsA) on the pathogenesis of acute experimental liver injury in rats induced by injection of heat-killed Propionibacterium acnes (P. acnes) and subsequent injection of lipopolysaccharide (LPS). Pretreatment with CsA significantly reduced serum alanine aminotransferase (ALT), serum tumor necrosis factor-alpha (TNF-alpha) production, without changing the TNF-alpha mRNA level in the liver, and plasma interferon-gamma (IFN-gamma), following LPS injection in this model. Twenty-four-hour mortality was also markedly improved, from 100% in the P. acnes plus LPS group to 0% in the CsA-pretreated group. Although direct addition of CsA to isolated hepatic macrophages from P. acnes-pretreated rats did not prevent the production of TNF-alpha and active oxygen species, isolated hepatic macrophages from P. acnes plus CsA-pretreated rats significantly reduced their production in response to the addition of LPS. These results suggest that CsA protects against P. acnes plus LPS-induced acute liver injury, not by direct inhibition of hepatic macrophage activation, but by indirect prevention of hepatic macrophage activation, presumably related to the reduction in plasma IFN-gamma levels.

Failure to express the P-selectin gene or P-selectin blockade confers early pulmonary protection after lung ischemia or transplantation.

Endothelial P-selectin expression contributes to the first wave of neutrophil (polymorphonuclear leukocyte: PMN) influx in several inflammatory conditions. Although remote tissue ischemia, such as a crush injury to the hindlimb, may result in P-selectin-mediated pulmonary leukosequestration, it is not known whether the lungs exhibit a similar response after hypothermic preservation or when subjected to a direct ischemic insult. To determine if P-selectin may mediate early primary graft failure, left lungs harvested from male Lewis rats were preserved for 6 hr at 4 degrees C and transplanted orthotopically into isogeneic recipients. Recipients immunodepleted of PMNs before transplantation demonstrated improved graft function; pulmonary vascular resistance was reduced approximately 6-fold, arterial oxygenation was increased approximately 3-fold, and recipient survival was increased approximately 4-fold (P < 0.05, 0.05, and 0.005, respectively). Administration of a blocking anti-P-selectin IgG 10 min before reperfusion diminished graft PMN infiltration and resulted in improved graft function and recipient survival compared with controls. To establish the role of P-selectin in normothermic pulmonary ischemia, mice were subjected to temporary left pulmonary artery ligation. After functional removal of the nonischemic right lung, mice deletionally mutant for the P-selectin gene (P-selectin-/-) exhibited reduced PMN infiltration (approximately 2-fold), improved arterial oxygenation (approximately 2-fold), and improved survival (approximately 3-fold) compared with P-selectin +/+ control mice (P < 0.05, 0.01, and 0.05, respectively). These studies isolate and identify the central role of a single gene product (P-selectin) in early PMN recruitment and tissue injury after frank pulmonary ischemia and in the setting of lung transplantation after hypothermic preservation.

[Thoracoscopic surgery for pneumothorax with bullous emphysema in an elderly patient: a case report].

Recent advances in optical and endoscopic operating instruments have made thoracoscopic surgery easier. The authors report the case of an 83-year-old patient who was referred to our hospital for right spontaneous pneumothorax associated with severe bullous emphysema. Chest X-ray films showed 40% collapse of right lung and the right spontaneous pneumothorax was treated by chest tube drainage for 3 weeks. However air leak was not decreased and subcutaneous emphysema appeared. Chest computerized tomography revealed multiple bullae. Thoracoscopic surgery was performed because of preservation of the respiratory function. The ruptured bulla was resected by using ENDO GIA and the other multiple bullae were resected similarly in order to improve the pulmonary function. A surgical drain was removed on the 14th postoperative day because of a little air leak continuing. His postoperative course was uneventful after removal of the chest drain. He was discharged on 27th postoperative day and had no shortness of breath in daily life. From our experience, thoracoscopic surgery appears to be much better than thoracotomy for spontaneous pneumothorax because of much less postoperative disability and preservation of respiratory function.

The prolyl 4-hydroxylase inhibitor HOE 077 prevents activation of Ito cells, reducing procollagen gene expression in rat liver fibrosis induced by choline-deficient L-amino acid-defined diet.

No effective therapy has yet developed for liver fibrosis by directory inhibiting the accumulation of extracellular matrix. The effect of a newly synthesized prolyl4-hydroxylase (PH) inhibitor, HOE 077 (pyridine-2, 4-di-carboxylic-di(2-methoxyethyl)amide), was examined using the model of choline-deficient L-amino acid (CDAA) defined diet-induced liver fibrosis in 16-week-old male Wistar rats. HOE 077 at doses up to 200 ppm prevented fibrosis in a dose-dependent manner, as indicated by reduced hydroxyproline content in liver as well as inhibition of increased serum fibrotic markers (PIIIP, 7S, hyaluronic acid). HOE 077 at 200 ppm reduced expression of type III procollagen alpha 1, messenger RNA (mRNA) in the liver, with a good correlation with serum PIIIP and hydroxyproline content of the liver. Histologically, HOE 077 at 200 ppm also reduced proliferation of myofibroblastlike cells (activated Ito cells). These results indicate that a PH inhibitor can prevent fibrosis by inhibiting not only the hydroxylation of proline but also the activation of Ito cells, which are considered the main collagen-producing cells, resulting in reduced expression of procollagen mRNA.

Functional differences between activated and normal rat liver macrophages: LPS uptake capacity by flow cytometric analysis in contrast with TNF-alpha release.

Activated liver macrophages are considered to play an important role in the development of liver injuries. Functional differences between activated and normal rat liver macrophages were investigated. In addition, from the therapeutic point of view, the effects of prostaglandin E1, prostaglandin I2 and E3330 ((2E)-3-[5-(2,3-dimethoxy-6-methyl-1,4- benzoquinoyl)]-2-nonyl-2-propenoic acid) on the functions of liver macrophages were also determined. Rat liver macrophages were primed by Propionibacterium acnes and activated by a small dose of lipopolysaccharide. Lipopolysaccharide uptake capacity was evaluated quantitatively by flow cytometric analysis. Tumor necrosis factor-alpha activities were measured by bioassay. There were no significant differences in lipopolysaccharide uptake capacity between activated and normal liver macrophages, while activated liver macrophages had a significantly (P < 0.01) higher capacity in the release of tumor necrosis factor-alpha. Prostaglandin E1 and E3330 inhibited tumor necrosis factor-alpha release without suppressing lipopolysaccharide uptake capacity. In this study we have clarified the functional differences between activated and normal liver macrophages. The beneficial effects of prostaglandin E1 and E3330 on the functions of liver macrophages were also demonstrated.