Evaluation of cardiopulmonary and inflammatory markers in dogs with heartworm infection treated using the slow kill method.

This study evaluated the changes in the levels of cardiac, hemostatic, and inflammatory biomarkers in 12 dogs with different severities of heartworm infection treated using the slow kill protocol, consisting of 6-10µg/kg of ivermectin and 10mg/kg of doxycycline combination. The serum levels of cardiac troponin-I, D-dimer, C-reactive protein, and interleukin-6 were measured on the day of diagnosis (D0), after termination of doxycycline administration (D30), after termination of the slow kill treatment (D180), and 10 months after the initiation of therapy (D300). Heartworm antigenemia was cleared in 4/4 class I dogs, 3/4 class II dogs, and 1/4 class III dogs at the end of the therapy (D180), and in 4/4 class I, 4/4 class II, and 1/4 class III dogs at the end of the study (D300). The serum levels of the markers in class I dogs on the day of diagnosis (D0) were within the reference range, while the levels in class II and III dogs were above the reference range. Further, the serum levels of the markers in all dogs decreased significantly at the end of the study (D300), although some markers in class III dogs remained at pathological levels. This study revealed that the slow kill method should be used only as an alternative therapeutic protocol for dogs with low worm burden (class I and II). As the slow kill method alone may not effectively reduce all pathological changes in dogs with heavy worm burden and severe clinical signs (class III), adjuvant therapies including steroids and anti-thromboembolics should be used to minimize the risk of complications.

Changes in treatment outcomes of multidrug-resistant tuberculosis.

SETTING: After several changes in treatment modalities, it is time to re-evaluate treatment outcomes of multidrug-resistant tuberculosis (MDR-TB). OBJECTIVE: To evaluate treatment outcomes, elucidate changes in outcomes over time and identify predictors of treatment success for MDR-TB. DESIGN: Patients diagnosed with MDR-TB at a tertiary referral centre in South Korea between January 2006 and December 2010 were included. Treatment modalities and outcomes were assessed. Predictors of treatment success were analysed using multiple logistic regression. The treatment modalities and outcomes of these patients were compared with those of MDR-TB patients between January 1996 and December 2005. RESULTS: Of the 123 MDR-TB patients diagnosed during the later study period, treatment was successful in 103 (83.7%). Extensive drug resistance (OR 0.31, P = 0.044) and additional resistance to fluoroquinolones (OR 0.23, P = 0.039) were inversely associated with treatment success. The treatment success rate improved from 53.5% in 1996-2000 to 68.8% in 2001-2005 and 83.7% in 2006-2010 (P < 0.001). Improved outcomes were accompanied with more frequent use of later-generation fluoroquinolones and linezolid and less frequent surgical resection. CONCLUSION: Treatment outcomes for MDR-TB improved at a tertiary referral centre in South Korea. The improvement was associated with more frequent use of later-generation fluoroquinolones and linezolid.

Effects of exogenous enzyme supplementation to corn- and soybean meal-based or complex diets on growth performance, nutrient digestibility, and blood metabolites in growing pigs.

Two experiments were conducted to determine the effects of dietary supplementation of exogenous enzymes on growth performance, apparent total tract digestibility (ATTD) of energy and nutrients, blood metabolites, fecal VFA, and fecal ammonia-N in growing pigs (Sus scrofa) fed a corn (Zea mays L.)- and soybean [Glycine max (L.) Merr.] meal (SBM)-based diet. In Exp. 1, 240 growing barrows (initial BW: 55.6 ± 0.9 kg) were randomly allotted to 5 treatments on the basis of BW. There were 4 replicates in each treatment with 12 pigs per replicate. The 5 treatments consisted of a corn-SBM-based control diet and 4 additional diets were similar to the control diet, with the exception that 0.05% ß-mannanase (M), α-amylase + ß-mannanase (AM), ß-mannanase + protease (MPr), or α-amylase + ß-mannanase + protease (AMP) was added to the diets, which were fed for 28 d. Pigs fed the AM, MPr, or AMP diet had greater (P < 0.05) ADG than pigs fed the control diet. Pigs fed the AMP diet also had greater (P < 0.05) ADG than pigs fed the M, AM, or MPr diet. Pigs fed the AMP diet had greater (P < 0.05) G:F than pigs fed the control diet. The G:F of the pigs fed the M, AM, or MPr diet were not different (P > 0.05) from the G:F in pigs fed the AMP or control diet. The ADFI, ATTD of nutrients, blood metabolites, and fecal VFA and ammonia-N concentrations were not different among treatments. In Exp. 2, 192 growing barrows (initial BW: 56.9 ± 1.0 kg) were allotted to 4 treatments. There were 4 replicates in each treatment with 12 pigs per replicate. Pigs were fed a corn-SBM-based diet (CSD) or a complex diet (CD) that contained corn, SBM, 3% rapeseed (Brassica napus L.) meal, 3% copra (Cocos nucifera L.) meal, and 3% palm (Elaeis guineensis Jacq.) kernel meal. Each diet was prepared without exogenous enzymes or with 0.05% AMP and all diets were fed for 28 d. The ADG and G:F of pigs fed the CSD were greater (P < 0.05) than pigs fed the CD. However, the type of diet had no effect on the ATTD of nutrients, blood metabolites, or fecal VFA and ammonia-N, and there was no diet × enzyme interaction for any of the measured variables. Supplementation of diets with exogenous enzymes resulted in greater (P < 0.05) ADG, G:F, ATTD of DM, GE, and CP, and blood urea nitrogen (BUN) concentration. These results indicate that supplementation of 0.05% of AMP enzymes to a corn-SBM diet or a complex diet may improve the performance of growing pigs.

Effect of supplementation of multi-microbe probiotic product on growth performance, apparent digestibility, cecal microbiota and small intestinal morphology of broilers.

The present study investigated the effect of inclusion of multi-microbe probiotic product on growth performance, apparent digestibility of nutrients, cecal microbiota and small intestinal morphology in broilers. Four hundred days-old Ross chicks were randomly allotted to five treatments on the basis of body weight (BW). Each treatment had four replicates of 20 chicks in each. Experimental diets were fed in two phases, starter (day 0-21) and finisher (day 22-35). Dietary treatments were; basal diet without any antimicrobial (NC), basal diet added with 20 mg Avilamycin/kg of diet (PC), 10(7) cfu multi-microbe probiotic/kg of diet (P1), 10(8) cfu multi-microbe probiotic/kg of diet (P2), and 10(9) cfu multi-microbe probiotic/kg of diet (P3). Overall BW gain and feed conversion ratio were better (p < 0.05) for treatments PC, P2 and P3 compared with NC and P1, with P1 being better (p < 0.05) than NC. Overall feed intake in treatments PC, P1, P2 and P3 were greater (p < 0.05) than NC. Apparent digestibility of dry matter and crude protein were greater (p < 0.05) in treatments PC, P2 and P3 compared with NC, with P1 being intermediate and not different form NC, PC, P2 and P3. At d 21 and 35, treatments PC, P1, P2 and P3 showed lower (p < 0.05) cecal Clostridium and Coliforms count in relation to NC. Moreover, cecal Clostridium (d 21) and Coliforms (d 21 and 35) count were lower (p < 0.05) in treatment PC in relation to P1; with P2 and P3 being intermediate and not different from PC. However, there was no effect of dietary treatments on cecal total anaerobic bacteria and Bifidobacterium spp. count. The villus height of duodenum in treatment PC was greater (p < 0.05) than NC, with P1, P2 and P3 being intermediate. Villus height of ileum in treatment PC was greater (p < 0.05) than in treatments P1 and NC, whereas it remained comparable among treatments PC, P2 and P3. Villus height to crypt depth ratio of ileum was greater (p < 0.05) for treatment PC, P2 and P3 compared with that in P1 and NC. It is concluded that multi-microbe probiotic inclusion at 10(8) and 10(9) cfu/kg diet had beneficial effects on broilers growth performance, apparent digestibility of nutrients and intestinal morphology and can be used as replacement to antibiotics growth promoter in broiler nutrition.

Effect of supplementation of Bacillus subtilis LS 1-2 to broiler diets on growth performance, nutrient retention, caecal microbiology and small intestinal morphology.

Present study investigated the effect of dietary supplementation of Bacillus subtilis LS 1-2 on growth performance, apparent nutrient retention, caecal microbial population and intestinal morphology in broilers. Three hundred and twenty day-old Ross broiler chicks were randomly allotted to four treatments on the basis of BW in a randomized complete block design. Experimental diets were fed in two phases: starter (d 0-21) and finisher (d 22-35). Dietary treatments were basal diet supplemented with 0% (control), 0.15%, 0.30% and 0.45% B. subtilis LS 1-2. Supplementation of increasing levels of B. subtilis LS 1-2 showed linear improvement (P<0.05) in growth performance and apparent nutrient retention. At d 35, birds supplemented with increasing levels of B. subtilis LS 1-2 showed decrease in caecal Clostridium and Coliform count (linear, P<0.05). Moreover, supplementation of B. subtilis LS 1-2 increased (linear, P<0.05) villus height and villus height to crypt depth ratio in both duodenum and ileum. Results obtained in the present study indicate that B. subtilis LS 1-2 can be used as a growth promoter in broiler diets and can improve intestinal microbial balance and gut health of broilers.

Recurrence after successful treatment among patients with multidrug-resistant tuberculosis.

A retrospective review was conducted of patients with multidrug-resistant tuberculosis (MDR-TB) to elucidate the rate of recurrence after successful treatment. Of 123 MDR-TB patients, 90 were declared as 'cured' or 'treatment completed' after individualised treatment; four (4.4%) experienced recurrence. All patients with recur- rent MDR-TB were documented as 'treatment completed' after treatment. Recurrence of MDR-TB is possible after successful treatment, particularly among those documented as 'treatment completed'.

Effects of mannanase and distillers dried grain with solubles on growth performance, nutrient digestibility, and carcass characteristics of grower-finisher pigs.

Four experiments were conducted to determine the effects of dietary supplementation of corn distillers dried grain with solubles (DDGS) diets with mannanase on performance, apparent total tract digestibility (ATTD) of energy and nutrients, blood metabolites, and carcass characteristics of grower-finisher pigs. In Exp. 1, 96 grower pigs (initial BW, 57.6 kg), 6 pigs per pen and 4 pens per treatment, were fed corn-soybean meal-based diets containing 10% DDGS and 0, 200, 400, or 600 units (U) of mannanase/kg. The ADG and blood glucose increased (linear, P < 0.05) with increasing concentrations of dietary mannanase. Pigs fed diets containing increasing levels of mannanase had improved ATTD of DM and CP (quadratic, P < 0.05). In Exp. 2, 64 finisher pigs (initial BW, 92.7 kg) were allotted to 4 treatment groups with 4 pigs per pen and 4 pens per treatment. Pigs were fed corn-soybean meal-based diets containing 15% DDGS and 0, 200, 400, or 600 U of mannanase/kg. Linear increases (P < 0.05) in ADG, blood glucose, and ATTD of DM, GE, and CP were observed with increasing levels of dietary mannanase supplementation. In Exp. 3, 208 grower pigs (initial BW, 60.5 kg) were allotted to 4 treatment groups with 13 pigs per pen and 4 pens per treatment. Pigs were fed diets containing 0 or 10% DDGS and 0 or 400 U of mannanase/kg in a 2 x 2 factorial arrangement. An increase (P < 0.05) in ADG and blood glucose for pigs fed diets containing mannanase was observed. The ATTD of DM and CP (P < 0.05) was decreased with the inclusion of DDGS, whereas pigs fed the mannanase-supplemented diets had an increased (P < 0.05) ATTD of CP. In Exp. 4, 208 finisher pigs (initial BW, 86.5 kg), with 13 pigs per pen and 4 pens per treatment, were fed diets containing 0 or 15% DDGS and 0 or 400 U of mannanase/kg in a 2 x 2 factorial arrangement. The ADG and blood glucose increased (P < 0.05) when mannanase was included in the diets. The ATTD of DM (P < 0.05), GE (P < 0.10), and CP (P < 0.05) increased by the supplementation with mannanase in the diets of finisher pigs. The carcass characteristics and meat quality were not affected by the DDGS or mannanase inclusion. These results indicated that including 10 and 15% DDGS in conventional swine grower and finisher diets had no detrimental effects on growth performance or carcass characteristics. In addition, supplementation with 400 U of mannanase/kg to diets containing 10 and 15% DDGS fed to grower and finisher pigs may improve growth performance and the ATTD of CP.

Oral insertion of a flexible bronchoscope is associated with less discomfort than nasal insertion for Korean patients.

OBJECTIVE: The route of bronchoscope insertion varies between centres, without a firm rationale based on well-designed studies. We therefore compared nasal and oral insertion of a flexible bronchoscope and evaluated efficacy and patient satisfaction. DESIGN: Prospective randomised study of patients who underwent flexible bronchoscopy from May to September 2003 and who were randomly assigned to nasal and oral insertion approaches. RESULTS: Clinical characteristics, factors related to the procedure and patient satisfaction were analysed. In total, 307 patients were randomly assigned to the nasal (n = 158) or oral insertion groups (n = 149). No difference in baseline characteristics was identified between the groups. Insertion by the oral route was associated with a smaller amount of lidocaine use during the procedure (P = 0.04) and less frequent insertion site bleeding (P = 0.005). Patients assigned to oral insertion reported less discomfort during anaesthesia (P = 0.01) and scope insertion (P < 0.001), as well as less dyspnoea (P = 0.04) and coughing (P = 0.03). CONCLUSION: Oral insertion of a flexible bronchoscope was associated with less discomfort for patients than nasal insertion, although the route of insertion had no significant effect on outcome.

Natural killer cell activity and quality of life were improved by consumption of a mushroom extract, Agaricus blazei Murill Kyowa, in gynecological cancer patients undergoing chemotherapy.

A mushroom extract, Agaricus blazei Murill Kyowa (ABMK), has been reported to possess antimutagenic and antitumor effects. Here, we investigate the beneficial effects of ABMK consumption on immunological status and qualities of life in cancer patients undergoing chemotherapy. One hundred cervical, ovarian, and endometrial cancer patients were treated either with carboplatin (300 mg / m(2)) plus VP16 (etoposide, 100 mg / m(2)) or with carboplatin (300 mg / m(2)) plus taxol (175 mg / m(2)) every 3 weeks for at least three cycles with or without oral consumption of ABMK. We observed that natural killer cell activity was significantly higher in ABMK-treated group (ANOVA, n = 39, P < 0.002) as compared with nontreated placebo group (n = 61). However, no significant difference in lymphokine-activated killer and monocyte activities was observed in a manner similar to the count of specific immune cell populations between ABMK-treated and nontreated groups. However, chemotherapy-associated side effects such as appetite, alopecia, emotional stability, and general weakness were all improved by ABMK treatment. Taken together, this suggests that ABMK treatment might be beneficial for gynecological cancer patients undergoing chemotherapy.

Protein kinase C modulates telomerase activity in human cervical cancer cells.

Telomerase, a ribonucleoprotein reverse transcriptase that extends telomeres of eukaryotic chromosomes is repressed in normal somatic cells but is activated during development and neoplasia. The regulation mechanism of telomerase activity in cancer cells is not clearly known. In this report, a possible affect of PKC on telomerase activity was examined using HeLa and CUMC-6 cervical cancer cell lines. Exposure of cells to PKC inhibitor, bisindolylmaleimide I and Gö6976, and high levels of PKC activator, 12-O-tetradecanoyl phorbol 13-acetate (TPA) resulted in the inhibition of PKC activity in both cells. Telomerase activities were also inhibited by bisindolyl-maleimide I and Gö6976, respectively, in a time-dependent manner. As PKC activity changes in TPA-treated cervical cancer cells, telomerase activities were increased at low dose of TPA and decreased at high dose. The expression levels of human telomerase subunits, human telomerase RNA (hTR) were not influenced by PKC modulating drugs. In contrast, the expression of full-length human telomerase reverse transcriptase (hTERT) was decreased after exposure to bisindolylmaleimide I and Gö6976 in a time-dependent manner. hTERT expression was not affected by low dose of TPA. In contrast, high dose of TPA inhibited hTERT expression level. But the expression patterns of beta-deletion transcript of hTERT after 72 h of treatment with PKC inhibitors or high dose of TPA exposure were not discernable as compared with those of full-length hTERT transcripts to PKC modulating drugs. These results suggest that PKC-modulating drugs altered telomerase activities by affecting full-length hTERT expression profile in human cervical cancers.

Synthesis and phosphodiesterase 5 inhibitory activity of novel phenyl ring modified sildenafil analogues.

New sildenafil analogues containing an ether ring fused into the phenyl moiety, 6a--d and 7a--d, were efficiently synthesized from the readily available starting materials, 1a--d and 2, in five steps. Ab initio calculations indicated that introduction of a cyclic ether to the phenyl group might enhance the co-planarity of the molecule. The torsional angles were calculated to be 2--3 degrees for the 5-membered cyclic ether derivatives, 6a, 6c, 7a, and 7c, and 12--16 degrees for the 6-membered ones, 6b, 6d, 7b, and 7d. On the other hand, sildenafil showed the least co-planarity with the torsional angle of 23 degrees compared with the target compounds, 6a--d and 7a--d. In the enzyme assay, however, the in vitro PDE 5 inhibitory activity was found out to be inversely related to the degree of co-planarity. In other words, the least planar sildenafil showed the highest activity, and the most planar 5-membered cyclic ether derivatives were least active by 100--200-fold compared with sildenafil. Our study clearly demonstrated that the open chain 2'-alkoxy group of the phenyl ring, although less effective for inducing the co-planarity, seemed to act as a much better lipophilic requirement than the cyclic alkoxy moiety.

Pharmacokinetic studies of 2-amino-9-(3-acetoxymethyl-4-isopropoxycarbonyl-oxybut-1-yl)purine, an oral prodrug for the antiviral agent penciclovir.

2-Amino-9-(3-acetoxymethyl-4-isopropoxycarbonyloxybut-1-yl)- purine (SK1899) was tested as an oral prodrug for penciclovir. SK1899 was administered orally to rats and dogs at doses up to 2 and 0.68 mmol/kg, respectively. SK1899 was well absorbed, and the major metabolites detected in plasma and urine were penciclovir, the active antiviral compound, and 6-deoxypenciclovir (M4) in both species. In rats, SK1899 was rapidly and extensively metabolized to penciclovir, which reached the peak plasma concentration (C(max)) of 39.5 microM at 0.5 h after 0.2-mmol/kg dosing. The area under the plasma concentration-time curve (AUC) for penciclovir was 57.5 microM x h. After an oral dose of 0.034 mmol/kg to dogs, extensive conversion of SK1899 to penciclovir also occurred with slower rate of formation of penciclovir from M4 than in rats. The mean C(max) and AUC for penciclovir were 4.5 microM at 2.7 h and 28.2 microM x h, respectively. The 0- to 24-h urinary recovery of penciclovir represented 36.1 and 36.3% of dose to rats and dogs, respectively. Radioactivity was found in fetuses following an oral administration of [(14)C]SK1899 to pregnant rats, but no significant accumulation was observed. Although substantial milk transfer of [(14)C]SK1899 occurred in rats, the radioactivity in milk was rapidly cleared. The values of C(max), AUC, and urinary recovery of penciclovir after dosing with SK1899 to rats and dogs were similar or slightly higher than those from famciclovir. These data indicate that introduction of an isopropoxy carbonate group into one of the two hydroxyl groups of M4 did not significantly alter the oral bioavailability of penciclovir compared with famciclovir.

In vitro infection of Cryptosporidium parvum to four different cell lines.

To determine a suitable condition for in vitro infection model of Cryptosporidium parvum, four different cell lines, AGS, MDCK, HCT-8 and Caco-2, were used as host cell lines which were cultured at various concentrations of added supplements. These supplement include fetal bovine serum (FBS), sodium choleate, ascorbic acid, folic acid, calcium pantothenate, para-aminobenzoic acid and pyruvate and their effects on the cell lines which were infected with C. parvum were evaluated. The results of this study showed that the AGS cell line was most susceptible to C. parvum whereas the Caco-2 cells appeared to be least susceptible to C. parvum. In regards to the serum condition, 10% FBS was suitable for the growth of AGS and HCT-8 cells, and 1% FBS was good for the growth of the MDCK cells when they were inoculated with C. parvum. Vitamins had a positive effect on the AGS cells, and pyruvate also showed positive effects on all of the cell lines except for Caco-2. Modified medium for each cell line was prepared by adding appropriate amounts of each supplement which resulted in the highest parasite infection number. Modified media increased the number of parasites infected on AGS cells to 2.3-fold higher when compared to the control media. In this study, we found that the AGS cell line was a suitable host model for evaluating C. parvum in vitro study and the media contents for the optimal infection conditions were suggested.

Long-term oral administration of ginseng extract decreases serum gamma-globulin and IgG1 isotype in mice.

Effects of long-term oral administration of ginseng extract on serum protein profile and immunoglobulin (Ig) isotypes were studied in mice. Ginseng extract was orally administered to healthy female mice for 52 days at doses of 30 and 150 mg/kg per day and serum protein electrophoretograms and Ig isotypes levels were evaluated. Serum level of gamma-globulin was decreased dose dependently to 82% (P < 0.05) and 56% (P < 0.01) of control values at the doses of 30 and 150 mg/kg per day, respectively. Levels of total protein, albumin, alpha2- and beta-globulin fractions, as well as the ratio of albumin to globulin (A/G) did not change significantly. However, the alpha1-globulin level increased by 24% (P < 0.05) at the doses of 30 and 150 mg/kg per day. Among the Ig isotypes, including IgG1, IgG2a, IgG2b, IgG3, IgM and IgA, serum IgG1 was dose dependently decreased to 68% (P < 0.05) of control values at the dose of 150 mg/kg per day without significant changes in other Ig isotypes. As IgG1 isotype is rarely cytotoxic and can act as a blocking antibody, it is suggested that the selective decrease in serum IgG1 induced by ginseng extract without changes in the cytotoxic antibodies such as IgG2a may be helpful for the prevention and inhibition of cancer.

Molecular cloning and expression of a cDNA encoding a protein tyrosine phosphatase from mouse brain.

A mouse brain cDNA library was screened with a radioisotope-labeled probe of human placental protein tyrosine phosphatase. The isolated clone (MBPTP1B) was found to contain an open reading frame of 1,296 nucleotides as well as 5' (709 nucleotides) and 3' (341 nucleotides) non-coding regions. This cDNA encodes a PTP of 432 amino acids having a mass of 49,563 daltons and exhibiting 83% and 93.5% sequence identity to that of human PTP1B and rat PTP1, respectively. The expression of the cDNA in yeast was identified by western blot analysis and PTP activity assay.

Enhancement of cytotoxicity of cisplatin in vitro by recombinant human tumor necrosis factor and/or recombinant human interferon-alpha, -beta and -gamma.

This study was conducted to investigate the modulatory effects of recombinant human tumor necrosis factor (rH-TNF) and recombinant human interferon (rH-IFN)-alpha, -beta and -gamma, either alone or in combination, on the cytotoxicity of cisplatin, using MTT assay, against MKN-45 (human stomach adenocarcinoma). MKN-45 was resistant to rH-TNF even at doses up to 10(3) U/ml. rH-IFN-gamma inhibited the survival of MKN-45 dose-dependently, while rH-IFN-alpha and -beta did not inhibit the survival of MKN-45 even at the highest concentrations tested (10(4) U/ml). Combination of rH-TNF with rH-IFN-alpha, -beta or -gamma did not significantly inhibit the survival of MKN-45, except for a combination of 10 U/ml of rH-TNF and 10(3) U/ml of rH-IFN-gamma (P less than 0.05). Cisplatin inhibited the survival of MKN-45 dose-dependently. By the simultaneous combination of cisplatin with rH-TNF and/or rH-IFN-alpha, -beta or -gamma, cytotoxicity of cisplatin was enhanced and the combination effects were additive. The effects of rH-TNF and rH-IFN-alpha, -beta and -gamma on the modification of cytotoxicity of cisplatin were evaluated in terms of modification index (MI), demonstrating that rH-TNF, rH-IFN-alpha, -beta and -gamma all augmented the cytotoxicity of cisplatin: MI values at 10(3) U/ml of rH-IFN-alpha, -beta and -gamma were 1.4, 1.4 and 2.3, respectively; those at the same concentrations of rH-IFN-alpha, -beta and -gamma in the presence of 10 U/ml of rH-TNF were 3.6, 2.5 and 5.1, respectively. These results demonstrating that the cytotoxicity of cisplatin was enhanced by rH-TNF and/or rH-IFN-alpha, -beta or -gamma suggest that cancer may be more effectively treated with the combination of cisplatin with these biological response modifiers than with cisplatin alone.

Induction of threonine imbalance by dispensable amino acids: relation to competition for amino acid transport into brain.

The ability of low protein diets containing small neutral, dispensable amino acids to induce threonine imbalance has been examined. Diets containing amino acids which compete for threonine transport in vitro (serine, alanine, alpha-amino-n-butyrate) caused depressions of growth and food intake which could be corrected to varying degrees by adding threonine to the diet. Large neutral, indispensable amino acids, moderately inhibitory of threonine transport, also induced the imbalance. Some amino acids that had little or no effect on threonine transport in vitro (acidic amino acids and proline) did not cause growth and food intake depressions. Other non-inhibitory amino acids (arginine and lysine) caused growth depressions which were not satisfactorily corrected by additional threonine alone, but were prevented by supplements of all the indispensable amino acids including threonine. Ornithine which was also not inhibitory of threonine transport was an exception. It induced a moderate growth depression which was corrected by additional threonine. Similar studies showed that histidine or tryptophan imbalance could be induced by feeding diets containing only those large neutral amino acids which compete for histidine or tryptophan transport in vitro. These experiments show that, based on the results of transport competition experiments, it is generally possible to devise amino acid supplements which can induce a dietary imbalance of a given amino acid.