Complete Regression of Recurrent Advanced Hepatocellular Carcinoma After Liver Transplantation in Response to Sorafenib Treatment: A Case Report.

Liver transplantation is a potentially curative treatment for hepatocellular carcinoma. However, patients with recurrent hepatocellular carcinoma after liver transplantation have few treatment options and local treatment may not be feasible. Sorafenib, an orally active multikinase inhibitor approved for the treatment of advanced hepatocellular carcinoma, significantly improves progression-free and overall survival. However, only a few studies have evaluated the efficacy of sorafenib in patients with recurrent hepatocellular carcinoma following liver transplantation. Here, we report a case of a patient with recurrent advanced hepatocellular carcinoma after living donor liver transplantation who achieved complete remission in response to sorafenib treatment. The patient has survived for more than 4 years post-transplantation.

Impact of co-existent thyroiditis on clinical outcome in papillary thyroid carcinoma with high preoperative serum antithyroglobulin antibody: a retrospective cohort study.

OBJECTIVES: The aim of this study was to investigate the impact of co-existent chronic lymphocytic thyroiditis (CLT) on changes in serum antithyroglobulin antibody (TgAb) and clinical outcome in papillary thyroid carcinoma (PTC) patients with high preoperative serum TgAb. DESIGN: A retrospective cohort study. SETTING: University teaching hospital. PARTICIPANTS: Thirty-seven PTC patients with high preoperative serum TgAb level (≥100 U/mL) were evaluated. All patients underwent total thyroidectomy followed by high-dose I-131 ablation. MAIN OUTCOME MEASURES: Per cent changes of TgAb between pre-treatment and post-treatment, and disease-free survival were calculated. RESULTS: Twenty-two patients (59.5%) had co-existent CLT, and seven had residual/recurrent tumours. There was a higher proportion of females among the patients with CLT compared to those without CLT (95.5% versus 66.7%; P = 0.0306). There were trends towards more aggressive pathologies, such as tumour size, extrathyroidal extension, surgical margin and lymph node stage, in PTC without CLT than in that with co-existent CLT. Pre-treatment and post-treatment TgAb were all higher in PTC with co-existent CLT. But, per cent changes of TgAb between pre-treatment and post-treatment were no significant difference between PTC with and without CLT (P < 0.05). Patients with co-existent CLT showed a significantly lower residual/recurrent tumour rate than those without CLT (4.5% versus 40%; P = 0.0113). CONCLUSION: Residual/recurrent tumour rate was lower in PTC patients with co-existent CLT than in those without CLT.

Egg white proteins and their potential use in food processing or as nutraceutical and pharmaceutical agents--a review.

Egg white contains many functionally important proteins. Ovalbumin (54%), ovotransferrin (12%), ovomucoid (11%), ovomucin (3.5%), and lysozyme (3.5%) are among the major proteins that have high potentials for industrial applications if separated. The separation methods for these proteins from egg white have been developed since early 1900, but preparation methods of these proteins for commercial applications are still under development. Simplicity and scalability of the methods, use of nontoxic chemicals for the separation, and sequential separation for multiple proteins are very important criteria for the commercial production and application of these proteins. The separated proteins can be used in food and pharmaceutical industry as is or after modifications with enzymes. Ovotransferrin is used as a metal transporter, antimicrobial, or anticancer agent, whereas lysozyme is mainly used as a food preservative. Ovalbumin is widely used as a nutrient supplement and ovomucin as a tumor suppression agent. Ovomucoid is the major egg allergen but can inhibit the growth of tumors, and thus can be used as an anticancer agent. Hydrolyzed peptides from these proteins showed very good angiotensin I converting enzyme inhibitory, anticancer, metal binding, and antioxidant activities. Therefore, separation of egg white proteins and the productions of bioactive peptides from egg white proteins are emerging areas with many new applications.

Separation of ovotransferrin from chicken egg white without using organic solvents.

Ovotransferrin is one of the major egg white proteins that have antimicrobial activity as well as iron binding capability. The objective of this study was to develop a simple and easy method to separate ovotransferrin without using organic solvents. Egg white was separated from yolk, added in a 1:1 ratio to distilled water (DW), and then homogenized. The ovomucin in the diluted egg white was removed by centrifugation, adjusting the pH to 4.5 to 5.0. The resulting supernatant was added to different ratios of ammonium sulfate and citric acid, and then centrifuged after holding overnight at 4°C. The precipitant, which contains ovotransferrin, was dissolved in DW, and ovotransferrin was precipitated using different ratios of ammonium sulfate and citric acid. The precipitant collected after centrifugation was dissolved with DW and subjected to ultrafiltration to remove salts and concentrate the solution. The purity of the ovotransferrin was determined using SDS-PAGE, the protein identified using Western blot, and the estimated yield calculated by weighing the ovotransferrin after freeze drying. Over 85% purity and over 83% yield were obtained from the combinations of 5.0% (wt/vol) ammonium sulfate and 2.5% (wt/vol) citric acid followed by 2.0% (wt/vol) ammonium sulfate and 1.5% (wt/vol) citric acid. Activity of the ovotransferrin showed similar activity with previously separated ovotransferrin. However, this method is simpler and more cost effective than the previous method. The isolated ovotransferrin can be used as is or after modifications for various applications such as antimicrobial treatments, anticancer treatments, and iron-supplementing agents for humans.

Effect of co-existing copper and calcium on the removal of As(V) by reused aluminum oxides.

Among the various heavy metals, arsenic is frequently found in abandoned mine drainage and the environmental fate of arsenic in real aqueous solutions can be highly dependent on the presence of co-existing ions. In this study, removal of arsenate through adsorption on the reused aluminum oxide or through precipitation was investigated in a single and in a binary system as a function of pH and concentration. Different removal behaviors of arsenate were observed in the presence of different cations as well as a variation of the molar ratios of arsenate to cations. Co-operative effects on arsenate removal by precipitation in solution occurred with an increase of copper concentration, while a decrease of arsenate removal resulted in increasing calcium concentration. It was observed that the arsenate removal in the presence of calcium would be highly dependent on the molar ratios of both elements.

Immature Rubus coreanus Shows a Free Radical-Scavenging Effect and Inhibits Cholesterol Synthesis and Secretion in Liver Cells.

Rubus coreanus fruits have been employed as a traditional medicine for centuries in the Asia-Pacific region. Its pharmacological action differs according to the different extraction methods utilized and the degree of fruit ripening. In this study, we determined the cellular effect of different ethanol extracts of mature and immature Rubus coreanus fruits in human hepatic cell line, HepG2 cells. The antioxidant activity, effect on superoxide dismutase activity and cholesterol biosynthesis efficiency was also evaluated. Immature Rubus coreanus extract showed higher antioxidant capability, compared with that of its mature fractions. Cellular antioxidant proteins including HO-1, Cu/Zn-superoxide dismutase and catalase were highly expressed in the presence of Rubus coreanus. Cholesterol levels in HepG2 cells treated with the water fraction of immature Rubus coreanus were significantly reduced. This antihyperlipidaemic action of Rubus coreanus is a consequence of cholesterol biosynthesis and extracellular secretion in HepG2 cells. These results indicate that among different ethanol fraction of mature and immature Rubus coreanus fruit extracts, water extract of immature fruit extract shows higher antioxidant as well as higher antihyperlipidaemic action.

Factors associated with the intention to have colorectal cancer screening in Korean adults.

The purpose of this study was to investigate the factors related to screening intention in a population-based screening programme for colorectal cancer. The data were taken from the 2008 Korean National Cancer Screening Survey. We conducted a nationwide survey with trained interviewers using a questionnaire. A total of 2038 participants agreed to answer the survey. There were 955 study subjects aged ≥ 50 years in the target age group for colorectal cancer screening. Colorectal cancer screening behaviour and demographic characteristics were collected to evaluate intention for colorectal cancer screening and related factors. Descriptive statistics and multiple logistic regression were used in the analysis. The lifetime screening rate was 50.4% (50.9% for men and 49.8% for women). The screening rate with recommendation was 39.7% (39.3% for men and 40.1% of women). The odds ratios of intention to be screened increased significantly in younger subjects and those screened with double-contrast barium enema or colonoscopy. 'Without any symptoms' was reported as the most frequent reason for non-attendance or no intention to be screened. Age and recent screening methods were important factors related to intention to be screened for colorectal cancer. Further research is needed to identify remaining barriers to screening.

Kinetics of microbial hydrogenation of free linoleic acid to conjugated linoleic acids.

AIMS: To investigate the ability of selected probiotic bacterial strains to produce conjugated linoleic acid (CLA) and also to estimate the biohydrogenation kinetics of Lactobacillus acidophilus on the production of CLA from free linoleic acid (LA). METHODS AND RESULTS: Six probiotic bacteria, Lact. paracasei, Lact. rhamnosus GG, Lact. acidophilus ADH, and Bifidobacterium longum B6, Lact. brevis, and Lact. casei, were used to examine their ability to convert LA to CLA. LA tolerance was evaluated by addition of different LA concentrations in MRS broth. Lact. acidophilus showed the major tolerant to LA and the greatest CLA-producing ability (36-48 microg ml(-1) of CLA). The rate-controlling steps were k(2) and k(1) for the addition of 1 and 3 mg ml(-1) of LA, respectively. The percentage of CLA conversion was higher in MRS broth supplemented with 1 mg ml(-1) (65%) than 3 mg ml(-1) (26%). CONCLUSION: The results provide useful information and new approach for understanding the biohydrogenation mechanisms of CLA production. SIGNIFICANCE AND IMPACT OF THE STUDY: This study would help elucidate the pathway from LA to stearic acid (SA), known as biohydrogenation. In addition, the use of selected probiotic bacteria might lead to a significant improvement in food safety.

Environmental risk assessment of genetically engineered herbicide-tolerant Zoysia japonica.

Herbicide-tolerant Zoysia grass (Zoysia japonica Steud.) has been generated previously through Agrobacterium tumefaciens-mediated transformation. The genetically modified (GM) Zoysia grass survived Basta spraying and grew to maturity normally while the wild-type (WT) grass stopped growing and died. GM Zoysia grass will permit more efficient weed control for various turf grass plantings such as home lawns, golf courses, and parks. We examined the environmental/biodiversity risks of herbicide-tolerant GM Zoysia before applying to regulatory agencies for approval for commercial release. The GM and WT Zoysia grass' substantial trait equivalence, ability to cross-pollinate, and gene flow in confined and unconfined test fields were selectively analyzed for environmental/biodiversity effects. No difference between GM and WT Zoysia grass in substantial traits was found. To assess the potential for cross-pollination and gene flow, a non-selective herbicide, Basta, was used. Results showed that unintended cross-pollination with and gene flow from GM Zoysia grass were not detected in neighboring weed species examined, but were observed in WT Zoysia grass (on average, 6% at proximity, 1.2% at a distance of 0.5 m and 0.12% at a radius of 3 m, and 0% at distances over 3 m). On the basis of these initial studies, we conclude that the GM Zoysia grass generated in our laboratory and tested in the Nam Jeju County field does not appear to pose a significant risk when cultivated outside of test fields.

Plasma protein regulation by thyroid hormone.

Thyroid hormones (THs) regulate growth, development, differentiation and metabolic processes by interacting and activating thyroid hormone receptors (TRs). Although much progress has been made in our understanding of the transcriptional regulation of many TR target genes, little is known of the regulation of plasma protein gene expression by TRs. To investigate the role of TRs in plasma protein expression we used human hepatocellular carcinoma cell lines and carried out cDNA microarray analysis. Our results indicate that several plasma proteins including transferrin, prothrombin, angiotensinogen, haptoglobin, alpha-2-HS-glycoprotein alpha and beta chain, complement, lipoproteins and fibrinogen are up-regulated by THs. Furthermore, clusterin, alpha-2-macroglobulin precursor, prothymosin alpha and alpha-fetoprotein were found to be down-regulated by THs.Transferrin, an iron-binding protein expressed in all mammals, and mainly synthesized in the liver, was investigated further. Immunoblot and Northern blot analyses revealed that exposure of HepG2-TRalpha1 sub-lines and HepG2-Neo cells to tri-iodothyronine (T(3)) induced time- and dose-dependent increases in the abundance of transferrin mRNA and protein, with the extent of these effects correlating with the level of expression of TRalpha1. Nuclear run-on experiments indicate that this induction is functioning at the transcriptional level. Moreover, cyclohexamide treatment did not eliminate the induction of transferrin by TH. Thus, our results suggest that the induction of transferrin by TH is direct and may in fact be mediated by an as yet unidentified response element in the promoter region.

Kuwanon G: an antibacterial agent from the root bark of Morus alba against oral pathogens.

Kuwanon G was isolated from the ethyl acetate fraction of methanol extract of Morus alba and its structure was elucidated by 13C-NMR, 1H-NMR and FAB-MS. Antibacterial activity of kuwanon G was investigated by the minimum inhibitory concentration (MIC) test and the viable cell count method. MIC of kuwanon G against Streptococcus mutans causing dental caries was determined to be 8.0 microg/ml. The bactericidal test showed that kuwanon G completely inactivated S. mutans at the concentration 20 microg/ml in 1 min. Kuwanon G also significantly inhibited the growth of other cariogenic bacteria such as Streptococcus sobrinus and Streptococcus sanguis, and Porpyromonas gingivalis causing periodontitis. Transmission electron microscopy (TEM) of kuwanon G treated cells demonstrated remarkable morphological damage of the cell wall and condensation of the cytoplasm.

Release characteristics of pectin microspheres prepared by an emulsification technique.

The potential application of pectin as a matrix polymer for making microspheres by an emulsification technique was explored, and the drug release property of these pectinate microspheres containing drug cores of varying aqueous solubilities: sulphanilamide, sulphaguanidine and sulphathiazole, was investigated using different dissolution media. The size and size distribution, specific surface area, drug content and drug release property of the pectinate microspheres were determined. The solubility and solution pH of drugs and their propensity to interact with pectin were characterized. Pectinate microspheres were successfully prepared by external gelation, using a modified emulsification technique. The kinetics of drug release from the microspheres best fitted Higuchi's model. Interestingly, the lowest percentage of drug released was produced by microspheres which were smallest in size and, therefore, largest in specific surface area, and containing sulphanilamide, the most aqueous soluble and the lowest molecular weight drug. Mathematical correlation study indicated that the drug release profile of pectinate microspheres was notably affected by the drug content and the extent of drug-pectin interaction in the microspheres. Generally, a higher percentage of drug was released from the microspheres with a higher drug content and/or lower extent of drug-pectin interaction. The extent of drug-pectin interaction was highest in microspheres containing sulphanilamide, followed by sulphaguanidine and sulphathiazole, opposite to that of drug content.

Photoinactivation of photosystem II complexes and photoprotection by non-functional neighbours in Capsicum annuum L. leaves.

Leaf segments from Capsicum annuum plants grown at 100 micromol photons m(-2) s(-1) (low light) or 500 micromol photons m(-2) s(-1) (high light) were illuminated at three irradiances and three temperatures for several hours. At various times, the remaining fraction (f) of functional photosystem II (PS II) complexes was measured by a chlorophyll fluorescence parameter (1/Fo -1/Fm, where Fo and Fm are the fluorescence yields corresponding to open and closed PS II traps, respectively), which was in turn calibrated by the oxygen yield per saturating single-turnover flash. During illumination of leaf segments in the presence of lincomycin, an inhibitor of chloroplast-encoded protein synthesis, the decline of f from 1.0 to about 0.3 was mono-exponential. Thereafter, f declined much more slowly, the remaining fraction (approximately equals 0.2) being able to survive prolonged illumination. The results can be interpreted as being in support of the hypothesis that photoinactivated PS II complexes photoprotect functional neighbours (G. Oquist et al. 1992, Planta 186: 450-460), provided it is assumed that a photoinactivated PS II is initially only a weak quencher of excitation energy, but becomes a much stronger quencher during prolonged illumination when a substantial fraction of PS II complexes has also been photoinactivated. In the absence of lincomycin, photoinactivation and repair of PS II occur in parallel, allowing f to reach a steady-state value that is determined by the treatment irradiance, temperature and growth irradiance. The results obtained in the presence and absence of lincomycin are analysed according to a simple kinetic model which formally incorporates a conversion from weak to strong quenchers, yielding the rate coefficients of photoinactivation and of repair for various conditions, as well as gaining an insight into the influence off on the rate coefficient of photoinactivation. They demonstrate that the method is a convenient alternative to the use of radiolabelled amino acids for quantifying photoinactivation and repair of PS II in leaves.

Epidemiological survey of oral submucous fibrosis and leukoplakia in aborigines of Taiwan.

A population-based survey was designed to investigate the prevalence of areca/betel quid chewing, oral submucous fibrosis and leukoplakia in a typical aboriginal community of southern Taiwan. Three hundred and twelve people 20 years of age or older were collected in the study. The prevalence of chewing areca/betel quid was 69.5%, with an average of 17.3 portions a day for an average 24.4 years. More women (78.7%) than men (60.6%) chewed areca/betel quid. The prevalences of oral submucous fibrosis and leukoplakia were 17.6% and 24.4%, respectively. It was found that the odds ratio for chewing areca/betel quid and having at least one of the above oral mucosal lesions was 8.21. Any additional smoking or drinking habits were not significant for having oral mucosal lesions. Although the areca/betel quid in Taiwan does not contain any tobacco, a significant association was still identified between areca/betel quid chewing and oral mucosal lesions.

Suppression by a sesquiterpene lactone from Carpesium divaricatum of inducible nitric oxide synthase by inhibiting nuclear factor-kappaB activation.

Excessive nitric oxide (NO) produced by inducible NO synthase (iNOS) acts as a causative regulator in various inflammatory disease states. Carpesium divaricatum has been used in Korean traditional herbal medicine for its antipyretic, analgesic, vermifugic, and anti-inflammatory properties. We investigated the molecular mechanism for the suppression of lipopolysaccharide/interferon-gamma (LPS/IFN-gamma)-induced NO production in RAW 264.7 macrophages by the sesquiterpene lactone 2beta,5-epoxy-5,10-dihydroxy-6alpha-angeloyloxy-9beta-isobutyloxy-germacran-8alpha,12-olide (C-1), which has been identified recently as a new compound from C. divaricatum. C-1 decreased NO production in LPS/IFN-gamma-stimulated RAW 264.7 cells in a concentration-dependent manner, with an IC50 of approximately 2.16 microM; however, it had no direct effect on the iNOS activity of fully LPS/IFN-gamma-stimulated RAW 264.7 cells. Furthermore, treatment with C-1 led to a decrease in iNOS protein and mRNA. These effects appear to be due to inhibition of nuclear factor-kappaB (NF-kappaB) activation through a mechanism involving stabilization of the NF-kappaB/inhibitor of the kappaB (I-kappaB) complex, since inhibition of NF-kappaB DNA binding activity by C-1 was accompanied by a parallel reduction of nuclear translocation of subunit p65 of NF-kappaB and I-kappaBalpha degradation. Taken together, the results suggest that the ability of C-1 to inhibit iNOS gene expression may be responsible, in part, for its anti-inflammatory effects.

The anti-inflammatory and hepatoprotective effects of fractions from Cudrania cochinchinensis var. gerontogea.

Various fractions of the ethanol extract from the root wood of Cudrania cochinchinensis var. gerontogea (Moraceae) were evaluated for their anti-inflammatory effects on carrageenan-induced edema and hepatoprotective activities on carbon tetrachloride (CCl4)-induced and D-galactosamine-(D-GalN) induced acute hepatotoxicity in rats. The fractions (n-hexane, CHCl3, EtOAc, n-BuOH, and H2O) displayed significant inhibitory activity against carrageenan-induced edema, and the active anti-inflammatory components were further localized in the n-BuOH fraction, which exhibited the greatest anti-inflammatory effect, an effect 5% greater than indomethacin (which was used as a standard reference substance). Each fraction exerted a significant hepatoprotective effect by reducing enzymatic alteration (sGOT and sGPT) and by improving hepatic lesions, including liver centrilobular inflammation, cell necrosis, fatty change, ballooning degeneration in CCl4-induced acute hepatitis; and necrosis of the portal area in D-GalN-induced acute liver injury. The n-BuOH and EtOAc fractions had the greatest hepatoprotective effects on CCl4-induced liver injury; in contrast, the CHCl3 fraction was most potent against D-GalN intoxication, which is comparable to silymarin, as a recognized hepatoprotective drug.

Characteristic immunostimulation by angelan isolated from Angelica gigas Nakai.

The immunopharmacological characteristics of angelan, a polysaccharide purified from Angelica gigas Nakai, were investigated in relation to the specificity to immune cells. The treatment of angelan increased the expression of IL-2, IL-4, IL-6, and IFN-gamma. The expression of IL-6 and IFN-gamma was rapidly augmented but that of IL-2 responded later. In the case of IL-4, angelan stimulated at early time after exposure but down-regulated thereafter. These results suggested that macrophages and natural killer cells involved in nonspecific immunity were primarily activated and helper T cells were secondarily affected by angelan. Angelan also had lympho-proliferative potential to B cells, specifically. The specificity of angelan was also elucidated in a cell fractionation experiment. The activated B cells by angelan also increased antibody production. The direct activation of B cells, macrophages, and accessory cells and the indirect activation of helper T cells coordinately increased immune functions such as in vitro and in vivo T-dependent immunization and antibody production. The experiment of host resistance to syngeneic tumors also showed that angelan potentiated the immune functions. In conclusion, angelan, a purified polysaccharide from an oriental herbal drug, showed characteristic immunostimulation, which was different from clinically used polysaccharides such as lentinan and PSK.

In vitro induction of differentiation by ginsenoides in F9 teratocarcinoma cells.

The aim of this study was to determine the ability of the ginsenosides, extracts of Panax ginseng C.A. Meyer, to cause differentiation of F9 teratocarcinoma stem cells as a model system. F9 stem cells cultured in the presence of the ginsenosides together with dibutyryl cyclic AMP (dbcAMP) became parietal endoderm-like cells. Moreover, the expression of differentiation marker genes, such as laminin B1 and type IV collagen, was increased after treatment with the ginsenosides. Among the various purified ginsenosides, Rh1 and Rh2 were the most effective at causing differentiation of F9 cells. Since ginsenosides and glucocorticoid hormone have similar chemical structures, we examined the possibility of the involvement of a glucocorticoid receptor (GR) in the differentiation process induced by the ginsenosides. According to Southwestern blot analysis, a 94 kDa protein regarded as a GR was detected in F9 cells cultured in the medium containing the ginsenosides Rh1 or Rh2. In addition, F9 stem cells treated with the ginsenosides Rh1 or Rh2 and with RU486, a glucocorticoid antagonist with a high affinity for the GR, did not differentiate into endoderm cells morphologically, and the expression of laminin B1 gene was not induced in these cells. In a gel mobility shift assay, protein factors capable of binding to the glucocorticoid responsive element (GRE) specifically were detected in nuclear extracts of the ginsenoside-treated F9 cells. Moreover, overexpression of GR by cotransfection of GR expression vector and GRE-luciferase vector enhanced the transactivation activity of GRE promoter in the presence of ginsenosides Rh1 or Rh2 and was further augmented by dbcAMP. In addition, ginsenosides Rh1 and Rh2 bound to a GR assessed by whole-cell binding assay, even though the specific binding affinity was weaker compared to dexamethasone. Based on these data, we suggest that the ginsenosides Rh1 and Rh2 cause the differentiation of F9 cells and the effects of ginsenosides might be exerted via binding with a GR or its analogous nuclear receptor.

Enhancement of the attachment on microcarriers and tPA production by fibroblast cells in a serum-free medium by the addition of the extracts of Centella asiatica.

The addition of ethanol extracts of Centella asiatica showed a remarkable enhancement of fibroblast cells attachment to Cytodex beads in serum-free (SF) medium. It also improves tPA production in both batch and perfusion cultivations. The optimal concentration for SF medium was determined as 2 ppm of the extracts when using Cytodex III. In batch cultivation a high specific tPA production rate was obtained, compared to that from 5% FBS containing medium. However, a fast specific growth rate was observed in 5% FBS medium. In perfusion cultivation a reasonably good cell density and tPA production was achieved at a perfusion rate of 2.4 x 10(6) (viable cell/ml) and 0.65 (micrograms/ml), respectively at 22 ml/min.

Effects of dietary electrolyte supplementation on gentamicin nephrotoxicity.

The effects of electrolyte supplementation via drinking solutions on gentamicin-induced nephrotoxicity were studied in rats. Four groups of animals were injected with gentamicin, 120 mg/kg daily for 5 days and were studied 2-4 days after the last injection. Electrolyte supplements were begun before the gentamicin injections and were continued throughout the study. The drinking solutions were tap water, NaCl, NaCl + KCl, or NaHCO3 + KHCO3 + diamox. At the end of the study, blood urea nitrogen (BUN) and serum creatinine were markedly increased only in the group receiving tap water. Nevertheless, 24 hour creatinine clearance in awake rats and inulin clearance in anesthetized rats were found to be severely reduced in all gentamicin-treated animals. However, the rats receiving NaHCO3 + KHCO3 + diamox had significantly higher creatinine clearance than all other experimental groups. Proximal intratubular free-flow pressure, measured by micropuncture, and internal proximal diameters were significantly increased above normal controls in all groups, but were least abnormal in the rats receiving HCO3- and diamox. Semiquantitative histologic evaluation revealed significantly less tubular necrosis and cast formation in this group than in all the other experimental groups. The observations suggest that dietary sodium, potassium, and chloride supplements, even accompanied by large fluid intake, provide relatively little protection against gentamicin nephrotoxicity. In contrast, HCO3- and diamox supplements resulted in significant, albeit incomplete, protection of GFR and renal histology.