Abstract  The whole plant of Phyllanthus wightianus (PW) was investigated for the antioxidant effects of three successive extracts: hexane (PWHE), chloroform (PWCE) and methanol (PWME), using standard in vitro models. The PWME exhibited a strong scavenging effect on 2,2-diphenyl-2-picryl hydrazyl (DPPH) free radicals and nitric oxide radical inhibition activity, due to possessing the highest content of tannins. The free radical scavenging effect of PWME was comparable with that of reference antioxidants. The extracts were subjected to isolation of their compounds: isomeric sterol mixture (1) [stigmasterol (1a), compesterol (1b) and β-sitosterol (1c)], fredilin (2), lupeol (3), gallic acid (4), bergenin (5), geraniin (6), corilagin (7) and ellagic acid (8) were established through the use of column chromatographic methods and spectral data. The percentage of tannins was also determined and estimated using the HPLC method. The data suggest that tannins are the active antioxidant compounds of P. wightianus. This study provides proof for the ethnomedical claims and reported biological activities of this plant. The plant therefore has very good therapeutic potential.

Abstract  Well-defined nanoporous palladium (np-Pd) fabricated by a modified electrochemical dealloying procedure is demonstrated to be an excellent electrocatalyst material for reductive degradation of both carbon tetrachloride and chlorobenzene.

Abstract  Rosmarinus officinalis (Lamiaceae) possesses antioxidant activity and hepatoprotective effects, and so may provide a possible therapeutic alternative for chronic liver disease. The effect produced by a methanolic extract of Rosmarinus officinalis on CCl(4)-induced liver cirrhosis in rats was investigated using both prevention and reversion models. Over the course of the development of cirrhosis, the increased enzymatic activities of gamma-glutamyl transpeptidase and alanine aminotransferase, and the rise in bilirubin levels caused by CCl(4) administration, were prevented by Rosmarinus officinalis co-administration. When the cirrhosis by oxidative stress was evaluated as an increase on liver lipoperoxidation, total lipid peroxides, nitric oxide in serum, and loss of erythrocyte plasma membrane stability, R. officinalis was shown to prevent such alterations. On cirrhotic animals treated with CCl(4), histological studies showed massive necrosis, periportal inflammation and fibrosis which were modified by R. officinalis. These benefits on experimental cirrhosis suggest a potential therapeutic use for R. officinalis as an alternative for liver cirrhosis.

Abstract  The effect of acetone (67641) on trichloroethylene (79016) and carbon-tetrachloride (56235) hepatotoxicity was studied in rats. Male Sprague-Dawley-rats were administered 0, 0.25, 0.75, or 1.5 milliliters per kilogram (ml/kg) acetone orally. Eighteen hours later they were injected intraperitoneally with 0 or 0.25ml/kg trichloroethylene or 0.1 or 0.6ml/kg carbon-tetrachloride alone or in combination. The rats were killed 24 hours later, the livers were removed, and assayed for hepatotoxicity by determining plasma alanine-aminotransferase (ALT) activity, total bilirubin, and by histological examination. Acetone alone or combined with trichloroethylene had no effect on ALT activity or total bilirubin. ALT activity was higher in rats treated with trichloroethylene plus either dose of carbon-tetrachloride than with carbon-tetrachloride alone. Bilirubin concentration was increased only by trichloroethylene plus 0.6ml/kg carbon-tetrachloride. Acetone enhanced carbon-tetrachloride liver injury to a greater extent than trichloroethylene. Acetone markedly potentiated liver injury induced by trichloroethylene plus carbon-tetrachloride in a dose/dependent manner. Histological analyses showed no statistical differences in the percentages of normal, degenerated, or necrotic hepatocytes between carbon-tetrachloride or trichloroethylene treated rats and controls. Trichloroethylene plus carbon-tetrachloride significantly reduced the percentage of normal hepatocytes and increased the percentage of degenerated or necrotic hepatocytes. Acetone pretreated rats given the carbon-tetrachloride plus trichloroethylene mixtures showed a significant dose related decrease in the percentage of normal hepatocytes and a dose related increase in the percentage of necrotic hepatocytes. The authors conclude that trichloroethylene can potentiate carbon-tetrachloride induced liver injury. Acetone exerts a potentiating effect on the hepatotoxic response of the carbon-tetrachloride plus trichloroethylene mixtures.

Abstract  We review the experimental evidence for various shapes of dose-response relationships for carcinogens and summarize those experiments that give the most information on relatively low doses. A brief review of some models is given to illustrate the shapes of dose-response curve expected from them. Our major interest is in the use of dose-response relationships to estimate risks to humans at low doses, and so we pay special attention to experimentally observed and theoretically expected nonlinearities. There are few experimental examples of nonlinear dose-response relations in humans, but this may simply be due to the limitations in the data. The several examples in rodents, even though for high dose data, suggest that nonlinearity is common. In some cases such nonlinearities may be rationalized on the basis of the pharmacokinetics of the test compound or its metabolites.

Abstract  The percutaneous absorption of 8 chlorinated solvents were studied. The ex-perimental method consisted of the application of the solvent to the abdominal mouse skin and quantitating its absorption through the skin by its presence in whole body and its appearance in expiration. Determination of the solvent in tissues and expiration was carried out by gas chromatographic methods. There was a great diversity of ability among solvents to penetrate the mouse skin. Dichloromethane was absorbed to an amount which was 53 times as large as the amount of tetrachloroethyene. Among tested solvents, those which had the highest solubility in water showed the greatest absorption rate, while those having the lowest solubility in water gave the smallest absorption rate from skin. The linear relationship between the absorption rate from skin and the solubility in water was found: in case of X ?? 16, Y=30.8+2.13X, r=0.87; in case of X ?? 16, Y= -52.8+6.59X, r=1.00; where Y is the percutaneous absorption rate (nM/min/cm2 of skin) and X is the solubility in water of solvent (mM at 25°C).

Abstract  The present research was conducted to evaluate the effect of mitogen pre-exposure on CCl4-induced hepatotoxicity. Male Wistar rats were administered a single i.p. injection of CCl4 (0.3 ml kg-1 in corn oil) 48 h following either a single dose of lead nitrate (0.33 mg kg-1) or distilled water via i.v. injection. Hepatotoxicity, as measured by serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, was monitored 6, 24, 48, 72 and 120 h after CCl4 exposure. The lead nitrate-pretreated rats displayed markedly lower serum ALT and AST levels at 24, 48 and 72 h than rats pretreated with distilled water. However, treatment with the antimitotic agent colchicine did not alter the lead-induced protection. These findings suggest that the lead-induced protection is not associated with the major mitogenic response of lead, despite its strong temporal association. A critical review of the available toxicological data also argues against the lead protection being a function of its capacity to inhibit cytochrome P-450.

Abstract  Pesticides are associated with excess risk of multiple myeloma, albeit inconclusively. We included 678 men (30-94 years) from a well-characterized prospective cohort of restricted-use pesticide applicators to assess the risk of monoclonal gammopathy of undetermined significance (MGUS). Serum samples from all subjects were analyzed by electrophoresis performed on agarose gel; samples with a discrete or localized band were subjected to immunofixation. Age-adjusted prevalence estimates of MGUS were compared with MGUS prevalence in 9469 men from Minnesota. Associations between pesticide exposures and MGUS prevalence were assessed by logistic regression models adjusted for age and education level. Among study participants older than 50 years (n = 555), 38 were found to have MGUS, yielding a prevalence of 6.8% (95% CI, 5.0%-9.3%). Compared with men from Minnesota, the age-adjusted prevalence of MGUS was 1.9-fold (95% CI, 1.3- to 2.7-fold) higher among male pesticide applicators. Among applicators, a 5.6-fold (95% CI, 1.9- to 16.6-fold), 3.9-fold (95% CI, 1.5- to 10.0-fold), and 2.4-fold (95% CI, 1.1- to 5.3-fold) increased risk of MGUS prevalence was observed among users of the chlorinated insecticide dieldrin, the fumigant mixture carbon-tetrachloride/carbon disulfide, and the fungicide chlorothalonil, respectively. In summary, the prevalence of MGUS among pesticide applicators was twice that in a population-based sample of men from Minnesota, adding support to the hypothesis that specific pesticides are causatively linked to myelomagenesis.

Abstract  Samples of mother's milk were collected from Bayonne, NJ; Jersey City, NJ; Pittsburgh, PA; Baton Rouge, LA; and Charleston, WV, and analyzed for volatile (purgeables) and semivolatile (extractable) organics using glass capillary gas chromatography/mass spectrometry/computer. In the volatile fraction, 26 halogenated hydrocarbons, 17 aldehydes, 20 ketones, 11 alcohols, 2 acids, 3 ethers, 1 epoxide, 14 furans, 26 other oxygenated compounds, 4 sulfur-containing compounds, 7 nitrogen-containing compounds, 13 alkanes, 12 alkenes, 7 alkynes, 11 cyclic hydrocarbons, and 15 aromatics were found, including major peaks for hexanal, limonene, dichlorobenzene, and some esters. The levels of dichlorobenzene appeared to be significantly higher in the samples from Jersey City and Bayonne than in samples from other sites. Jersey City samples also appeared to have significantly higher levels of tetrachloroethylene. Charleston and Jersey City samples appeared to have significantly higher levels of chloroform; however, chloroform was observed in the blanks at about 20% of that in the samples. Due to the small sample size and lack of control over the solicitation of sample donors, the data cannot be used to extrapolate to the general population. Fewer semivolatile compounds of interest were found. Polychlorinated naphthalenes, polybrominated biphenyls, chlorinated phenols, and other compounds were specifically sought and not detected (limit of detection about 20-100 ng/mL milk). Polychlorinated biphenyls (PCBs) and DDE were found.

Abstract  The document presents a compilation of measured values for physiological parameters used in pharmacokinetic modeling. The physiological parameters include body weight, tissue volumes, cardiac output distribution, and respiration parameters. Reference values for use in risk assessment are given for each of the physiological parameters based on analyses of valid measurements obtained from the literature and other reliable sources. The proposed reference values are for generic mice and rats without regard to sex or strain. Reference values for humans are without regard to age or sex. Differences between the sexes in mice, rats, and humans are accounted for by scaling the reference parameters within species on the basis of body weight. Reference physiological parameters are for a 0.025 kg mouse, 0.25 kg rat, and a 70 kg man.

Abstract  Simultaneous administration of trichloroethylene (TCE), at an oral dose of 0.5 ml/kg, resulted in a marked potentiation of liver injury caused by an oral dose of carbon tetrachloride (CCl4, 0.05 ml/kg). Hepatic glutathione levels were depressed at 24 hr only in the rats given TCE and CCl4. Using serum enzyme (ALT and SDH) as indicators of hepatotoxicity, potentiation of CCl4-injury was most apparent at 24 hr. Upon histological examination of H&E stained liver sections, the differences between livers obtained from TCE and CCl4-treated rats versus CCl4-treated rats were most apparent at later time points (48 and 72 hr). At 48 hr after CCl4, livers showed a distinctive and uniform pattern of injury with regeneration features predominating over necrosis. At this time, livers from TCE and CCl4-treated rats were characterized by extensive zone 3 coagulative necrosis. Inflammatory infiltrations were less prominent. At 72 hr, morphological features of livers from TCE and CCl4 rats were similar to those from rats given CCl4 alone at 48 hr. From the results obtained, it appears that the regenerative activity of the liver may be delayed in rats simultaneously administered TCE and CCl4 as compared to rats administered only CCl4.

Abstract  The public depends on competent risk assessment from the federal government and the scientific community to grapple with the threat of pollution. When risk reports turn out to be overblown--or when risks are overlooked--public skepticism abounds. This comprehensive and readable book explores how the U.S. Environmental Protection Agency (EPA) can improve its risk assessment practices, with a focus on implementation of the 1990 Clean Air Act Amendments. With a wealth of detailed information, pertinent examples, and revealing analysis, the volume explores the "default option" and other basic concepts. It offers two views of EPA operations: The first examines how EPA currently assesses exposure to hazardous air pollutants, evaluates the toxicity of a substance, and characterizes the risk to the public. The second, more holistic, view explores how EPA can improve in several critical areas of risk assessment by focusing on cross-cutting themes and incorporating more scientific judgment. This comprehensive volume will be important to the EPA and other agencies, risk managers, environmental advocates, scientists, faculty, students, and concerned individuals.

Abstract  A series of halogenated compounds was tested by oral intubation in 200 Osborne-Mendel rats and 200 B6C3F1 mice of both sexes. Carbon tetrachloride, used as a positive control, induced liver and adrenal tumors in mice and neoplastic nodules in the livers of rats. 1,2-Dibromoethane and 1,2-dibromo-3-chloropropane caused stomach tumors with many metastases in both rats and mice. Chloroform, known to cause hepatocellular carcinomas in mice, led in addition to kidney tumors in male rats. 1,2-Dichloroethane was much weaker than the analog, 1,2-dibromoethane, and induced only a few stomach tumors in rats. It increased liver and lung tumors in mice. Most of the compounds, namely, trichloroethylene, 1,1-dichloroethane, 1,1,2-trichloroethane, hexachloroethane, and tetrachloroethylene, increased hepatocellular carcinomas in mice but had little or no action in rats. Iodoform tended to increase thyroid tumors in male rats and hepatocellular carcinomas in male mice. The action of 3-chloropropene was questionable. No tumors could be attributed to 1,1,1-trichloroethane (methylchloroform).

Abstract  Neurophysiologic, neurobehavioral, and neuropsychologic profiles in 17 grain storage workers, 1 grain inspector, and 4 malting laboratory workers are described. The effects of CS2 toxicity as seen in viscose rayon workers as well as in experimental animals is remarkably similar to the clinical profile of our grain storage workers. CS2 use explains the dysfunction of peripheral axons, auditory nerve, the optic nerve, and the extrapyramidal system, as well as altered behavior and cognition changes. The signs and symptoms in these workers seem to be dose-related and we note that workers separated out from the areas where fumigation took place reported improvement not seen by fellow workers who continued the fumigant treatment routine. Likewise, malting laboratory workers exposed only to the grain dust from 3 to 7 years showed only minimal symptoms. Though a number of mechanism have been suggested for the alteration of neuropsychological function, the chelating ability of DDC derived from CS2 and its ability to markedly increase copper and zinc within the central nervous system suggests a mechanism of toxicity analogous to copper intoxication as in Wilson's Disease and may explain the production of extrapyramidal symptoms in these patients. Chelation of copper might prove therapeutic in CS2 poisoning. It is obvious that both basic and clinical research will be necessary to sort out the questions raised. We applaud the EPA's decision to ban the use of 80/20 fumigants and also methyl bromide, and trust that similar toxic substances be carefully studied before their selection for replacing these previous toxic agents. We further decry the technique of re-introducing grain dust into the food chain rather than destroying it, since the dust contains very high residues of fumigant material. We speculate on the possible role of CS2 and other pesticides in the food chain and the incidence of Parkinsonian symptoms in these patients and the general public.

Abstract  Carbon tetrachloride (CCl4) induced hepatotoxicity and chloroform (CHCl3) induced nephrotoxicity were evaluated in male Sprague‐Dawley rats pretreated with acetone (A), methyl ethyl ketone (MEK), and methyl isobutyl ketone (MiBK). Dose‐response relationships for A, MEK, and MiBK potentiation of CCl4‐induced hepatotoxicity and CHCl3‐induced nephrotoxicity were compared. A, MEK, and MiBK pretreatment at a dosage of 6.8 mmol/kg, given daily for 3 d, markedly potentiated CCl4‐induced liver toxicity as indicated by a decrease in the CCI4 ED50 to 3.4, 4.6, and 1.8 mmol/kg, respectively, compared to vehicle‐pretreated rats (17.1 mmol/kg). Similarly, pretreatment with these ketones (13.6 mmol/kg) potentiated CHCl3 kidney toxicity but to a lesser degree; CHCl3 ED50 values for vehicle‐, A‐, MEK‐, and MiBK‐pretreated rats were 3.4, 1.6, 2.1, and 2.2 mmol/kg, respectively. Our results indicate a potency ranking profile for the potentiation of CCI4 hepatotoxicity of MiBK >A> MEK and of A > MEK ≥ MiBK for CHCl3 nephrotoxicity. These dissimilar ranking profiles could be due to differences in mechanisms of action for the two target sites.

Abstract  One hundred and six compounds, subdivided into 12 chemical classes (5 polycyclic aromatic hydrocarbons, 7 epoxides and N-oxides, 5 nitro aromatics and heterocyles, 12 aromatic and heterocyclic amines, 2 azo compounds, 17 hydrazine derivatives, 16 miscellaneous aliphatics, 5 miscellaneous heterocycles, 11 miscellaneous organics, 11 hexavalent and 7 trivalent chromium compounds, 8 miscellaneous inorganics), were studied in the Salmonella/microsome test. Fifty-eight of them (54.7%) were found to be mutagenic and 4 additional compounds (3.8%) yielded a positive response following nitrosation in human gastric juice. The results are presented in a tabulated form, providing the following information for each test compound: (a) mutagenic response in 5 S. typhimurium his - strains (TA1535, TA1537, TA1538, TA98, TAI00); (b) ranged of activity for positive compounds or maximum dose tested for negative compounds (in nmol/plate); (c) mutagenic potency (in revertants/umol compound), varying over a 6.5 x 106-fold range; (d) effect of S-9 mix containing rat (Aroclor) liver S-9 fractions on the mutagenic response (activation, increase, no change or decrease): (e) remarks concerning the influence of other metabolic systems (up to 10 different rat tissue S-9 fractions, mouse S-9 fractions, human S-9 fractions, cell reparations or biological fluids), the interaction between different compounds, the stability and the formation of mutagenic derivatives in human gastric juice and other experimental details. Overlapping of mutagenicity and carcinogenicity data was not evaluated, since the experimental protocol intentionally included a number of non-carcinogenic mutagens and of non-mutagenic carcinogens with the aim of explaining in some cases the conflicting nature of in vivo and in vitro conclusions.

Abstract  Three hundred chemicals were tested for mutagenicity, under code, in Salmonella typhimurium, using a preincubation protocol. All tests were performed in the absence of exogenous metabolic activation, and in the presence of liver S-9 from Aroclor-induced male Sprague-Dawley rats and Syrian hamsters. The results and data from these tests are presented.

Abstract  Chemically inert substances can be transformed in the body to active intermediates that mediate a variety of toxicities including cellular necrosis, methemoglobinemia, porphyria, tumor formation and mutagenic effects. In addition, many hypersensitive reactions and fetotoxic reactions and probably mediated by active intermediates. In some instances the active intermediate apparently acts by combining reversibly with vitally important intracellular components but in others the intermediate acts by combining covalently with tissue macromolecules. This paper is concerned with some of the factors that affect covalent binding and toxicity of drugs.

Abstract  Within 5 minutes of intravenous injection into rats of radioactively labeled carbon-tetrachloride (56235), liver lipids were found labeled. Most of the radioactivity was found in the phospholipid fraction. The metabolites were shown to comprise a heterogeneous group of branched long-chain chlorinated fatty acids, probably containing the trichloromethyl side chain.

Abstract  In this study, the possible protective effect of glycyrrhizin (GL), an active compound derived from licorice root, was examined on T cell-mediated liver injury in mice.

Mice were subjected to liver injury by intravenous injection of concanavalin A (Con A). They had been treated with GL (i.p.) 30 min before the injection. Liver injury was estimated by measuring serum levels of alanine aminotransaminase (ALT) and aspartate aminotransaminase (AST), and by examining liver sections with hematoxylin-eosin staining. Expression of inducible nitric oxide synthase (iNOS) mRNA and protein in the liver was determined by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting.

Serum transaminases and hepatic iNOS levels increased with time after Con A treatment. Expression of iNOS mRNA in the liver was elevated for up to 8 h, and at 8 h, GL (ED(50): 10.5 mg/kg) suppressed the increases in AST and ALT in response to Con A. An increase in iNOS mRNA expression and protein was inhibited by treatment with GL. Furthermore, GL inhibited cell infiltration and the degeneration of hepatocytes in the liver of Con A-treated mice.

The present study suggests that the prevention by GL of Con A-induced hepatitis is due partly to the modulation of hepatic iNOS induction and of degeneration of hepatocytes.

Abstract  In this study, the hepatoprotective effects of hyperoside (1), a flavonoid glycoside isolated from Artemisia capillaris, have been examined against carbon tetrachloride (CCl4)-induced liver injury. Mice were treated intraperitoneally with vehicle or 1 (50, 100, and 200 mg·kg(-1)) 30 min before and 2 h after CCl4 (20 μL·kg(-1)) injection. Levels of serum aminotransferases were increased 24 h after CCl4 injection, and these increases were attenuated by 1. Histological analysis showed that 1 prevented portal inflammation, centrizonal necrosis, and Kupffer cell hyperplasia. Lipid peroxidation was increased and hepatic glutathione content was decreased significantly after CCl4 treatment, and these changes were reduced by administration of 1. Protein and mRNA expression of tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and heme oxygenase-1 (HO-1) and nuclear protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) significantly increased after CCl4 injection. Compound 1 suppressed TNF-α, iNOS, and COX-2 protein and mRNA expression and augmented HO-1 protein and mRNA expression and Nrf2 nuclear protein expression. These results suggest that 1 has protective effects against CCl4-induced acute liver injury, and this protection is likely due to enhancement of the antioxidative defense system and suppression of the inflammatory response.

Abstract  This position paper delineates the expert recommendations of the Regulatory Affairs Committee of the American Society for Veterinary Clinical Pathology for the use of preclinical, clinical pathology endpoints in assessment of the potential for drug-induced hepatic injury in animals and humans. Development of these guidelines has been based on current recommendations in the relevant preclinical and human clinical trial literature; they are intended to provide a method for consistent and rigorous interpretation of liver-specific data for the identification of hepatic injury in preclinical studies and potential liability for hepatic injury in human patients.

Abstract  Recently, the sonocatalytic technology using various semiconductors combined with ultrasonic irradiation has been received much attention to solve the environmental problems. In this paper, nano-sized titanium dioxide (TiO(2)) powder as a sonocatalyst was irradiated by ultrasound and the generation of reactive oxygen species (ROS) during sonocatalytic reaction process has been estimated by the method of Oxidation-Extraction Photometry (OEP). That is, the 1,5-diphenylcarbohydrazide (DPCI) can be oxidized by ROS into diphenylcarbonzone (DPCO), which can be extracted by the mixed solution of benzene and carbon tetrachloride and show the great absorbance at 563 nm wavelength. The synergistic effect of TiO(2) and ultrasonic irradiation was estimated and some influencing factors, such as ultrasonic irradiation time and TiO(2) addition amount on the generation of ROS were reviewed. The results indicate that the quantities of generated ROS increase with the increase of ultrasonic irradiation time and TiO(2) addition amount. Moreover, the relationship between quantities of generated ROS and DPCI concentration was also studied. And then, several quenchers were used to determine the kind of the generated ROS. At last, the researches on the sonocatalytic degradation of organic dyes and the corresponding reaction kinetics have also been performed, which is found to follow the pseudo first-order kinetics approximately. This paper may offer some important subjects for broadening the applications of sonocatalytic technology.

Abstract  The lymphatic network plays a major role in maintaining tissue fluid homoeostasis. However, the role of the lymphatic system in the pathogenesis of ascites and edema formation in cirrhosis has not been fully clarified. The aim of this study was to investigate whether the inability of the lymphatic system to drain tissue exudate contributes to the edema observed in cirrhosis. Cirrhosis was induced in rats by CCl4 inhalation. Lymphatic drainage was evaluated using fluorescent lymphangiography. Expression of endothelial nitric oxide synthase (eNOS) was measured in primary lymphatic endothelial cells (LyECs). Inhibition of eNOS activity in cirrhotic rats with ascites (CH) was carried out by L-NG-methyl-L-arginine (L-NMMA) treatment (0.5 mg/kg/day). The (CH) rats had impaired lymphatic drainage in the splanchnic and peripheral regions compared with the control (CT) rats. LyECs isolated from the CH rats showed a significant increase in eNOS and nitric oxide (NO) production. In addition, the lymphatic vessels of the CH rats showed a significant reduction in smooth muscle cell (SMC) coverage compared with the CT rats. CH rats treated with L-NMMA for 7 days showed a significant improvement in lymphatic drainage and a significant reduction in ascites volume, which were associated with increased plasma volume. This beneficial effect of L-NMMA inhibition was also associated with a significant increase in lymphatic SMC coverage. Thus, up regulation of eNOS in the LyECs of CH rats causes long-term lymphatic remodeling, which is characterized by a loss of SMC lymphatic coverage. The amelioration of this lymphatic abnormality by chronic eNOS inhibition results in improved lymphatic drainage and reduced ascites.