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Biomedical subjects

M Nakano

Publications and source records attributed to M Nakano.

At least 253 records · Page 14Linked to original sources

Minute nodular intrahepatic cholangiocarcinoma.

BACKGROUND: This study describes the clinicopathologic features of minute intrahepatic cholangiocarcinoma (ICC) and clarifies the relation between minute nodular ICC and hepatitis viral infection. METHODS: The presence of hepatitis C virus antibody (anti-HCV) and hepatitis B surface antigen (HBsAg) was examined in the serum of 50 patients with ICC who underwent hepatectomy from 1990-1996. The ICCs included 12 minute tumors (<3 cm in greatest dimension), 6 of which were nodular type and 6 others were nonnodular type (5 of periductal spreading or infiltrating type and 1 of intraductal type). RESULTS: Of these 50 patients with ICC, 16 (32%) were positive for anti-HCV, 5 (10%) were positive for HBsAg, and 1 (2%) was positive for both. The prevalence of hepatitis viral infection in cases of minute nodular-type tumor (83%; 5 patients positive for anti-HCV) was significantly higher than that in cases of minute nonnodular-type tumor (0%; P < 0.05). These minute nodular-type tumors were detected during follow-up of patients with chronic hepatitis or cirrhosis. All patients were treated with hepatectomy alone. At last follow-up, 3 patients had been free of disease for >5 years after surgery. However, 1 patient died 2 years after surgery because of remnant liver and lymph node recurrence. CONCLUSIONS: Minute nodular ICC appears to be related to hepatitis viral infection and could be detected at an early stage, similar to hepatocellular carcinoma, by following up cases of chronic hepatitis or cirrhosis.

Adult↗

Structural significance of the benzoyl group at the C-3'-N position of paclitaxel for nitric oxide and tumor necrosis factor production by murine macrophages.

The antitumor agent paclitaxel (Taxol) mimics the actions of lipopolysaccharide (LPS) on murine macrophages (M phi). Recently, we have shown that the benzoyl group at the C-3' position of paclitaxel is the most important site to induce nitric oxide (NO) and tumor necrosis factor (TNF) production by C3H/HeN M phi (Biochem. Biophys. Res. Commun. 210, 678-686, 1996). In the present study, synthetic analogs of paclitaxel with replacement of the C-3'-N position were examined for their potencies to induce NO and TNF production by peritoneal M phi of LPS-responsive C3H/HeN mice and LPS-hyporesponsive C3H/HeJ mice, by human blood cells and human M phi. In this structure-activity relationship study, we found that (i) the p-substitution of the benzoyl group definitely affects the activity to activate C3H/HeN M phi, (ii) the analogs having a methyl or chloro group at the p-position exhibit stronger activity than that of paclitaxel, (iii) there is good correlation between NO and TNF production by the M phi in response to compounds, (iv) the compounds tested do not induce either NO or TNF production by C3H/HeJ M phi or TNF production by human cells, (v) a previous treatment of C3H/HeN M phi with the inactive compounds can hardly affect either paclitaxel- or LPS-induced TNF production by the M phi, (vi) paclitaxel and its analogs marginally affect LPS-induced TNF production by human blood cells, and (vii) there is no correlation between the NO/TNF inducibility to C3H/HeN M phi and growth inhibitory activity against M phi-like J774.1 and J7.DEF3 cells.

Animals↗

Preferential hydrolysis of oxidized phosphatidylcholine in cholesterol-containing phosphatidylcholine liposome by phospholipase A2.

Hydrolysis of 1-palmitoyl-2-linoleoyl-phosphatidylcholine (PLPC) hydroperoxide (PLPC-OOH) in PLPC liposomal membrane by Crotalus adamanteus venom phospholipase A2 (PLA2) was studied by measuring the decay of PLPC and PLPC-OOH and the formation of linoleate and linoleate hydroperoxide. We demonstrate that PLA2 has a preference to hydrolyze PLPC-OOH over PLPC when more than 25 mole % of cholesterol is incorporated into the PLPC liposomal membrane. Similar results were obtained for PLPC hydroxide (PLPC-OH). These results suggest that cholesterol displaces the hydrophilic hydroperoxyl and hydroxyl moieties of PLPC-O(O)H to the surface interface of the liposomal membrane where they are more accessible to PLA2 hydrolysis.

Cholesterol↗

Tumor necrosis factor-alpha confers resistance to hypoxic injury in the adult mammalian cardiac myocyte.

BACKGROUND: Previous studies in isolated cardiac myocytes have shown that tumor necrosis factor (TNF)-alpha provokes increased expression of 27- and 70-kD stress proteins as well as manganese superoxide dismutase, suggesting that TNF-alpha might play a role in mediating stress responses in the heart. METHODS AND RESULTS: To determine whether TNF-alpha stimulation would protect isolated cardiac myocytes against environmental stress, myocyte cultures were pretreated with TNF-alpha for 12 hours and then subjected to continuous hypoxic injury (O2 content, 3 to 5 ppm) for 12 hours, followed by reoxygenation. Cell injury was assessed in terms of lactic dehydrogenase (LDH) release, 45Ca2+ uptake, and MTT metabolism. Pretreatment with TNF-alpha concentrations > or = 50 U/mL significantly attenuated LDH release by hypoxic cells compared with diluent-treated hypoxic cells. Similar findings were observed with respect to 45Ca2+ uptake and MTT metabolism in TNF-alpha-pretreated cells that were subjected to prolonged hypoxia. To determine the mechanism for the TNF-alpha-induced protective effect, the cells were pretreated with heat shock protein (HSP) 72 antisense oligonucleotides. These studies showed that the protective effect of TNF-alpha was not inhibited by antisense oligonucleotides, despite use of a concentration of antisense that was sufficient to attenuate the TNF-alpha-induced increase in HSP 72 expression. Subsequent studies using mutated TNF ligands showed that activation of both types 1 and 2 TNF receptors was sufficient to confer a protective response in isolated cardiac myocytes through an as yet unknown pathway(s). CONCLUSIONS: Taken together, the above observations demonstrate that TNF-alpha pretreatment confers resistance to hypoxic stress in the adult cardiac myocyte through a novel mechanism that appears to be different from but not necessarily exclusive of the protective response conferred by HSP 72 expression.

Analysis of Variance↗

Localization of carbohydrate chains of pig sperm ligand in the glycoprotein ZPB of egg zona pellucida.

The three glycoproteins of pig zona pellucida (ZPA, ZPB and ZPC) can be separated into ZPA and a mixture of ZPB/ZPC by gel-filtration HPLC. We have shown previously that the neutral complex-type N-linked carbohydrate chains obtained from ZPB/ZPC possess sperm-binding activity. Intact ZPB and ZPC cannot be separated from each other unless acidic N-acetyllactosamine regions of their carbohydrate chains are removed by endo-beta-galactosidase digestion. The endo-beta-galactosidase-digested ZPB retains the sperm-binding activity. Recently, we have reported that N-linked carbohydrate chains of N-terminal fragment (residues 137-247) obtained from endo-beta-galactosidase-digested ZPB are involved mainly in sperm binding [Yonezawa, N., Mitsui, S., Kudo, K. & Nakano, M. (1997) Eur. J. Biochem. 248, 86-92]. In this study, we separated the intact neutral N-linked chains from the ZPB/ZPC mixture into diantennary chains and triantennary and tetraantennary chains by affinity chromatography on Concanavalia ensiformis agglutinin. An in vitro competition assay revealed that triantennary and tetraantennary chains possess a sperm-binding activity stronger than that of diantennary chains. Three glycopeptides, having one Asn residue to which the carbohydrate chain is linked, were obtained by lysyl endopeptidase digestion of the heat-solubilized zonae containing intact ZPB and lysyl endopeptidase and chymotrypsin A digestion of endo-beta-galactosidase-digested ZPB. From sugar-mapping analysis of the carbohydrate chains from these glycopeptides and comparison with the carbohydrate structures of the main intact neutral N-linked chains of ZPB/ZPC, the triantennary and tetraantennary chains were shown to be localized mainly at Asn220 of ZPB, and diantennary chains were present on all the three potential residues (Asn203, Asn220 and Asn333). These results suggest that the carbohydrate chains linked to Asn220 of ZPB participate predominantly in sperm-egg binding.

Amino Acid Sequence↗

Postlaminectomy adhesion of the cauda equina. Inhibitory effects of anti-inflammatory drugs on cauda equina adhesion in rats.

STUDY DESIGN: Effects of the systemic administration of anti-inflammatory drugs on cauda equina adhesion after lumbar laminectomy were evaluated in rats. OBJECTIVES: To obtain basic data on preventive measures for lumbar adhesive arachnoiditis. SUMMARY OF BACKGROUND DATA: Laminectomy-induced cauda equina adhesion has been proved by rat experiments and postoperative serial magnetic resonance imaging tests in humans. In rats, laminectomy induces an increase in vascular permeability, resulting in cauda equina adhesion. METHODS: Wistar rats laminectomized from L5 to L6 were divided into three groups: the control group received only vehicle solutions, the indomethacin group received oral indomethacin for 7 days, and the steroid group was administered intraperitoneal methylprednisolone for 3 days. At 24 hours and 3 weeks and 6 weeks after laminectomy, cauda equina adhesion and leakage of a protein tracer from the nutrient vessels were histologically compared in the three groups. RESULTS: Both indomethacin and methylprednisolone significantly suppressed cauda equina adhesion and protein leakage from the nutrient vessels at 24 hours after laminectomy. Rats treated with the anti-inflammatory drugs showed diminution of cauda equina adhesion and the neural degeneration at 3 weeks and 6 weeks after laminectomy. CONCLUSIONS: Anti-inflammatory drug administration before and after laminectomy suppressed cauda equina adhesion as well as facilitating recovery from cauda equina adhesion.

Animals↗

Age-related changes in the activation of aortic cholesteryl ester hydrolases by protein kinases in rats.

Age-related changes in the activities of acid and neutral cholesteryl ester hydrolases (ACEH and NCEH) and their activation by protein kinase A (PKA) and also by protein kinase C (PKC) were examined in the aortae of 4-, 8-, 12- and 20-week-old rats in relation to their aortic lipid and lipid peroxides and lipid contents. The physiological basal activity as well as total activities of the ACEH and NCEH activated by the two kinases, which were high in the aortae of the 4- and 8-week-old rats, decreased gradually with increasing age to about 40% (ACEH) and 50% (NCEH) by 20 weeks of age. The vitamin E intake and ad libitum-diet intake of the rats each modified the age-related decline of CEH activities. The aortic PKA and PKC activities were reflected by the CEH activities to some degree. The in vitro exposure of the aortic CEH to active oxygen (AO) generators revealed the PKC-mediated activation of CEH, which was inhibited by superoxide dismutase and catalase. These results suggested that the activities of ACEH and NCEH and their regulatory enzymes may be modulated by the dual effect of endogenous AO; an activation of CEH at low doses and an inactivation at high doses, or upon a long-term exposure in aging to a low level of endogenous AO.

Aging↗

Sister chromatid exchange analysis of human cells carrying retroviral DNA.

Chromosomal abnormalities have been seen in human cells following infection with human T lymphotropic virus type I (HTLV-I). Effects on sister chromatid exchange (SCE) in cells carrying HTLV-I related DNA were examined by treatment with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Peripheral blood specimens were obtained from 16 donors. Cells were processed for SCE analysis and sera were tested for HTLV-I antibodies by Western blot analysis. DNA from fresh lymphoid cells was analyzed by PCR-SSCP for HTLV-I genes. Of 16 donors, eight were HTLV-I seropositive and eight seronegative. Five HTLV-I infected lymphocyte cultures were also analyzed for SCE. Cells were stained immunocytochemically with anti-p19 for the viral expression. By MNNG treatment, SCE was significantly enhanced in cells derived from two seropositive donors with HTLV-I genes. In cells of six seropositive and eight seronegative donors with or without HTLV-I related DNA, SCE frequency was influenced insignificantly. Cells from all persons were negative for the p19 expression. SCE was greatly enhanced by MNNG treatment in cells from three productively infected cultures when compared with SCE in two nonproductively infected cultures.

Adult↗

Poor outcome in disseminated intravascular coagulation or thrombotic thrombocytopenic purpura patients with severe vascular endothelial cell injuries.

Various hemostatic and vascular endothelial cell markers were measured in patients with disseminated intravascular coagulation (DIC), non-DIC, or thrombotic thrombocytopenic purpura (TTP) and in healthy volunteers to examine the relationships between the hemostatic abnormalities or vascular endothelial cell injuries and the patients' outcomes. Although the plasma levels of soluble fibrin monomer, thrombin-antithrombin complex, plasmin-plasmin inhibitor complex, and D-dimer were significantly increased in the DIC patients, there were no significant differences in these markers between the DIC patients who survived and those who died, suggesting that these markers might not be directly related to the patient outcome. The plasma thrombomodulin (TM) levels in the DIC and TTP patients were significantly higher than those in the healthy volunteers, and the plasma TM levels in the patients who died were significantly higher than those in the patients who survived. These findings showed that the TM level reflected the outcome, and that the outcome of the diseases underlying DIC and TTP might depend on vascular endothelial cell injuries. The plasma protein C and antithrombin activities were markedly reduced in the DIC, non-DIC, and TTP patients who died compared to those who survived. These findings suggest that reduced plasma antithrombin and protein C activities are useful markers of systemic vascular endothelial injuries. Although the plasma tissue factor (TF) levels were significantly increased in the DIC patients, there was no significant difference in the plasma TF levels between the DIC patients who died and those who survived. In conclusion, we found that the outcome of the diseases underlying DIC and TTP is related to vascular endothelial cells, and that plasma TM, antithrombin, and protein C are useful markers for systemic vascular endothelial cell injury.

Antifibrinolytic Agents↗

Does gross appearance indicate prognosis in intrahepatic cholangiocarcinoma?

BACKGROUND AND OBJECTIVES: Survival after surgery for intrahepatic cholangiocarcinoma (ICC) is usually poor. The objective of this study was to investigate whether the gross appearance of ICC indicates postoperative prognosis. METHODS: Seventy patients with ICC underwent hepatectomy, with a 50% curative resection rate. Tumors were classified according to gross appearance [mass-forming (n=28), periductal-infiltrating (n=14), intraductal growth (n=10), and mass-forming plus periductal-infiltrating (n=18)], and the presence of lymph node or intrahepatic metastasis was studied microscopically. RESULTS: The incidence of positive lymph nodes was significantly higher in the patients with mass-forming plus periductal-infiltrating tumors than in those with intraductal growth tumors (P=0.0089). The curative resection rate was significantly lower in patients with mass-forming plus periductal-infiltrating tumors than in those with either mass-forming or intraductal growth tumors (P=0.0001, P=0.0048, respectively). The 5-year survival rate after surgery in patients with mass-forming plus peri-ductal-infiltrating tumors (0%) was significantly lower than that in patients with mass-forming tumors (39%) or intraductal growth tumors (69%) (P=0.0036, P=0.0011, respectively). Multivariate analysis using Cox's hazards model revealed that lymph node metastasis (P=0.0109) and curative resection (P=0.0315) were statistically significant independent prognostic factors; however, macroscopic types were not. CONCLUSIONS: Patients with mass-forming plus periductal-infiltrating ICCs have a poor prognosis; however, the macroscopic types may not be a statistically significant independent prognostic factor.

Adult↗

Characteristic difference in gastrointestinal excretion of clarithromycin and roxithromycin.

Excretion characteristics of two new macrolides; clarithromycin and roxithromycin, into the intestinal and the gastric lumens was studied by in situ single-pass perfusion and loop methods in rats. Roxithromycin maintained higher serum levels than clarithromycin after their intravenous administrations at a dose of 5 mg kg(-1) each. Radioactivities of clarithromycin and roxithromycin exsorbed into the intestinal lumen were 8.6 and 18.9% of dose in 2 h, respectively, whereas clarithromycin and roxithromycin excreted into the bile were 28.4 and 5.9%, respectively. These results suggest that roxithromycin is transported mainly by exsorption across the intestinal membrane, whereas clarithromycin mainly by excretion through the biliary tract. On the other hand, radioactivities of clarithromycin and roxithromycin exsorbed into the gastric lumen were much less then those into the intestinal lumen and were 0.72 and 1.34% of dose in 4 h, respectively. Thus, the exsorption into the gastric lumen seems to be a minor route for the elimination of both macrolides. Consequently, the transport into the intestinal lumen via the intestinal membrane and/or the bile tract may play a significant role in the overall elimination of both macrolides.

Animals↗

Measurement of regional N-acetylaspartate after transient global ischemia in gerbils with and without ischemic tolerance: an index of neuronal survival.

We investigated the correlation between N-acetylaspartate (NAA) level and neuronal density in the hippocampal CA1 region of the brain after occlusion of both common carotid arteries for 5 minutes and reperfusion for 3 hours to 4 weeks in gerbils with and without ischemic preconditioning (tolerance). Animals were divided into four groups--the sham operated group, the nonpreconditioning (non-p) group, the single-preconditioning (single-p) group with 2-minute ischemia once 2 days before 5-minute ischemia, and the double-preconditioning (double-p) group with 2-minute ischemia twice 2 days before 5-minute ischemia (n = 6 for each group). The CA1 region was dissected out from freeze-dried sections for high-performance liquid chromatographic assay of NAA, and adjacent sections were stained with cresyl violet for measurement of the neuronal density. Both NAA (pmol/microg dry weight) and the neuronal density (cells/mm) decreased in the non-p group after 3 days (NAA = 24.0 +/- 3.0; neuronal density = 65 +/- 38 cells/mm) and 7 days (NAA = 17.9 +/- 2.5; neuronal density = 20 +/- 15 cells/mm) and in the single-p group after 7 days (26.4 +/- 3.0, 106 +/- 30) compared with the control group (NAA = 32.9 +/- 3.0; neuronal density = 203 +/- 9 cells/mm). There was no decrease in the double-p group. The NAA level and the neuronal density showed a good linear correlation. The regional NAA level may be used as an index of neuronal viability.

Animals↗

Longitudinal follow-up of pulmonary function after lobectomy in childhood - factors affecting lung growth.

We examined the changes in pulmonary function values in 27 patients who underwent a lobectomy due to cystic lung disease and compared the results regarding such factors as disease type, age at operation, and preoperative infections. Percent vital capacity (%VC) decreased immediately after lobectomy, but recovered to normal values within 2 postoperative years and remained within or above the normal range. The ratio of residual volume to total lung capacity (RV/TLC) rose temporally with the increase in %VC, but then remained normal after 2 postoperative years. There was no difference in %VC and RV/TLC between diseases, while bronchial atresia showed a significantly lower correlation with percent of forced expiratory volume at 1 s. The older group operated upon at over 4 years of age and the group that had infections before operation showed relatively low %VC and high RV/TLC. Some patients demonstrated extremely low %VC along with funnel chest deformities. Our study suggests that overinflation of the remaining lung compensates VC in the early period after lobectomy while subsequently alveolar multiplication occurs. Factors affecting compensatory lung growth were considered to be operation later than 4 years of age, preoperative infection, and a thoracic deformity.

Child↗

Assay of centromere function using a human artificial chromosome.

In order to define a functional human centromere sequence, an artificial chromosome was constructed as a reproducible DNA molecule. Mammalian telomere repeats and a selectable marker were introduced into yeast artificial chromosomes (YACs) containing alphoid DNA from the centromere region of human chromosome 21 in a recombination-deficient yeast host. When these modified YACs were introduced into cultured human cells, a YAC with the alphoid DNA from the alpha21-I locus, containing CENP-B boxes at a high frequency and a regular repeat array, efficiently formed minichromosomes that were maintained stably in the absence of selection and bound CENP-A, CENP-B, CENP-C and CENP-E. The minichromosomes, 1-5 Mb in size and composed of multimers of the introduced YAC DNA, aligned at metaphase plates and segregated to opposite poles correctly in anaphase. Extensive cytological analyses strongly suggested that the minichromosomes had not acquired host sequences and were formed in all cases by a de novo mechanism. In contrast, minichromosomes were never produced with a modified YAC containing alphoid DNA from the alpha21-II locus, which contains no CENP-B boxes and has a less regular sequence arrangement. We conclude that alpha21-I alphoid DNA can induce de novo assembly of active centromere/kinetochore structures on minichromosomes.

Autoantigens↗

The combined method: a novel access technique for fetal endoscopic surgery.

BACKGROUND/PURPOSE: To develop practical and less invasive techniques for fetal endoscopic surgery, new methods of lifting the uterine wall to allow fetal surgery without maternal laparotomy were developed and assessed. METHODS: Fetal endoscopic surgical procedures, including tracheostomy and umbilical vascular cannulation, were performed using one of the three methods to enter the uterus without maternal laparotomy in pregnant goats (n = 6; 105 to 115 days' gestation): (1) direct uterine lifting with an air-cushion device; (2) indirect uterine lifting, in which the uterine wall was fixed to the maternal abdominal wall using balloon tip ports inserted percutaneously by Seldinger's method, then the maternal abdomen was lifted mechanically; and (3) combined method, in which low pressure CO2 (5 mm Hg for initial inflation and 2 mm Hg for maintenance) was insufflated into the uterus in addition to the indirect uterine lifting cited above. RESULTS: The direct uterine lifting caused massive injury of myometrium and uterine membranes. The creation of intrauterine space and the protection of the membranes were not accomplished effectively by the indirect uterine lifting only. The combined method provided the adequate intrauterine space and excellent endoscopic visibility for completion of the endoscopic procedures with minimal uterine injury. CONCLUSION: The fetal endoscopic surgery may be accomplished simply and safely by the combined method, a novel technique of uterine lifting to allow fetal surgery without maternal laparotomy.

Animals↗

Detection of Mycoplasma genitalium in patients with urethritis.

PURPOSE: We attempted to detect Mycoplasma genitalium in urethral swab specimens by a polymerase chain reaction based assay to determine the prevalence of M. genitalium in patients with urethritis. MATERIALS AND METHODS: We examined a total of 171 Japanese men who presented to our hospital from February 1995 through January 1997. Of these men 150 had symptoms and signs compatible with acute urethritis and 21 had no symptoms or signs of urethritis. Urethral swab specimens were used to culture Neisseria gonorrhoeae, to detect Chlamydia trachomatis by an enzyme immunoassay and to detect M. genitalium by a polymerase chain reaction based assay. RESULTS: Gonococcal urethritis was diagnosed in 74 symptomatic men, and nongonococcal urethritis was diagnosed in 76 symptomatic men. Of the 74 cases of gonococcal urethritis 3 (4.1%) were positive for M. genitalium, and 14 (18.9%) were positive for C. trachomatis. Of the 76 cases of nongonococcal urethritis 10 (13.2%) were positive for M. genitalium, and 42 (55.2%) were positive for C. trachomatis. While only 1 of the 42 cases with chlamydial nongonococcal urethritis (2.4%) was positive for M. genitalium, 9 of the 34 chlamydia negative nongonococcal urethritis cases (26.5%) were positive for the mycoplasma. In contrast, all 21 cases men were negative for N. gonorrhoeae, M. genitalium, and C. trachomatis. CONCLUSIONS: The prevalences of M. genitalium in patients with gonococcal urethritis and nongonococcal urethritis who attended our clinic were 4.1 and 13.2%, respectively. M. genitalium was detected significantly more often in men with nongonococcal urethritis than in asymptomatic men. In addition, its prevalence in men with chlamydia negative nongonococcal urethritis (26.5%) was significantly greater than in those with chlamydia positive nongonococcal urethritis (2.4%). These findings suggest that M. genitalium may be associated with the development of nongonococcal urethritis independent of C. trachomatis.

Adolescent↗

Suppression of recurrent genital herpes simplex virus type 2 infection by Rhus javanica in guinea pigs.

Rhus javanica has been shown to exhibit anti-herpes simplex virus (HSV) activity and potentiate the anti-HSV activity of acyclovir in vitro and in vivo. This extract was examined for its suppressive efficacy on recurrent genital infection in guinea pigs. Guinea pigs were primarily infected intravaginally with HSV type 2 (HSV-2). Prophylactic oral administration, at the dose corresponding to human use, of R. javanica significantly reduced the incidence, severity and/or frequency of spontaneous and severe skin lesions as compared with latently infected guinea pigs administered with water. This prophylactic efficacy was confirmed by the crossover administration, for more than 2 months, of R. javanica and water to the infected guinea pigs. Toxicity, such as weight loss, from R. javanica administration was not observed in the guinea pigs. When recurrent HSV-2 disease was induced by ultraviolet irradiation 3 months after primary infection, the prophylaxis with R. javanica was also significantly effective in reducing the severity of ultraviolet-induced skin lesions. Thus, prophylaxis of recurrent genital HSV-2 infection with R. javanica may preserve the efficacy of acyclovir by reducing both the use of acyclovir and the appearance of acyclovir-resistant viruses.

Administration, Intravaginal↗

Dietary carbohydrate intake plays an important role in preventing alcoholic fatty liver in the rat.

BACKGROUND/AIMS: Dietary carbohydrate intake during ethanol ingestion augments the induction of hepatic cytochrome P450 2E1 (CYP2E1) by ethanol. This study addresses the role of carbohydrate intake in the development of alcoholic fatty liver in the rat. METHODS: Male Sprague-Dawley rats were pair-fed on liquid diets containing ethanol (3.5 g/day, 36% of total calories) with different amounts of carbohydrate and fat for 4 weeks, and the development of fatty liver was observed biochemically and morphologically. RESULTS: An ethanol-containing low-carbohydrate diet (protein 17%; fat 36%; carbohydrate 11%; ethanol 36%) had more markedly adverse effects on the liver of rats than did an isocaloric ethanol-containing high-carbohydrate diet (protein 17%; fat 5%; carbohydrate 42%; ethanol 36%). The hepatic triglyceride level in the rats that consumed the low-carbohydrate diet was higher than that in the rats kept on the high-carbohydrate diet, a finding that was confirmed histologically. The ethanol-containing low-carbohydrate diet caused a marked increase in the activity of hepatic CYP2E1. The CYP2E1 protein level, as measured by Western blot analysis, matched the activity of CYP2E1, as measured by the rates of dimethylnitrosamine, p-nitrophenol and ethanol metabolism. The severity of the fatty liver was well correlated with the increased CYP2E1 activity. CONCLUSIONS: Dietary carbohydrate intake plays an important role in the development of alcoholic fatty liver by affecting CYP2E1 activity in the liver. A liquid diet containing ethanol in which the ethanol is included at the expense of fat is more acceptable to rats than a diet in which the ethanol replaces carbohydrate.

Animals↗