Assessment of home care aides' respiratory exposure to total volatile organic compounds and chlorine during simulated bathroom cleaning: An experimental design with conventional and "green" products.

Home care (HC) aide visits to clients' homes often involve cleaning and disinfecting (C&D) bathrooms. Some ingredients in C&D household products are associated with respiratory illness, including sodium hypochlorite (bleach) and quaternary ammonium compounds (quats). "Green" products may be safer for the environment, however there are limited quantitative evaluations of their respiratory risks. This study assessed airborne concentrations and time profiles of total volatile organic compounds (TVOC) and chlorine generated during typical bathroom cleaning performed by aides using conventional and green products. Aides performed cleaning tasks in a simulated residential bathroom constructed in an environmental air sampling laboratory. A balanced experimental design involved each aide coming to the lab for four visits during which she performed two 20-min cleaning sessions using one of three C&D products (bleach-based, 1-5% sodium hypochlorite by weight; quats-based, 0.1-1% by weight quaternary ammonium compounds; and "green," 0.05% by weight thymol, a component of botanical thyme oil) or distilled water as a control. TVOC and chlorine direct reading instruments were attached to aides with sample inlets located in the breathing zone. Ten-second averages of TVOC and chlorine gas concentrations and instantaneous peak concentrations were recorded for the sessions' duration. TVOC concentrations by methods of C&D application (spraying, streaming, wiping) also were evaluated. The study completed 169 air sampling sessions with 22 aides. The quats-based product generated more than twice the average TVOC concentrations (mean = 1,210 ppb) than the bleach-based (mean = 593 ppb) or green (mean = 498 ppb) products. Each product generated TVOC concentrations that rose rapidly within the first few minutes of application. Spraying produced the highest TVOC exposures, wiping the lowest. Thirteen aides (65%) experienced peak chlorine exposures above the OSHA PEL ceiling limit (1 ppm) when using the bleach-based product. HC aides may experience respiratory hazards from use of conventional or green C&D products formulated with bleach or other respiratory irritants and sprayed in small, poorly ventilated spaces typical of bathrooms. Spraying should be avoided.

Particle and vapor emissions from vat polymerization desktop-scale 3-dimensional printers.

Little is known about emissions and exposure potential from vat polymerization additive manufacturing, a process that uses light-activated polymerization of a resin to build an object. Five vat polymerization printers (three stereolithography (SLA) and two digital light processing (DLP) were evaluated individually in a 12.85 m3 chamber. Aerosols (number, size) and total volatile organic compounds (TVOC) were measured using real-time monitors. Carbonyl vapors and particulate matter were collected for offline analysis using impingers and filters, respectively. During printing, particle emission yields (#/g printed) ranged from 1.3 ± 0.3 to 2.8 ± 2.6 x 108 (SLA printers) and from 3.3 ± 1.5 to 9.2 ± 3.0 x 108 (DLP printers). Yields for number of particles with sizes 5.6 to 560 nm (#/g printed) were 0.8 ± 0.1 to 2.1 ± 0.9 x 1010 and from 1.1 ± 0.3 to 4.0 ± 1.2 x 1010 for SLA and DLP printers, respectively. TVOC yield values (µg/g printed) ranged from 161 ± 47 to 322 ± 229 (SLA printers) and from 1281 ± 313 to 1931 ± 234 (DLP printers). Geometric mean mobility particle sizes were 41.1-45.1 nm for SLA printers and 15.3-28.8 nm for DLP printers. Mean particle and TVOC yields were statistically significantly higher and mean particle sizes were significantly smaller for DLP printers compared with SLA printers (p < 0.05). Energy dispersive X-ray analysis of individual particles qualitatively identified potential occupational carcinogens (chromium, nickel) as well as reactive metals implicated in generation of reactive oxygen species (iron, zinc). Lung deposition modeling indicates that about 15-37% of emitted particles would deposit in the pulmonary region (alveoli). Benzaldehyde (1.0-2.3 ppb) and acetone (0.7-18.0 ppb) were quantified in emissions from four of the printers and 4-oxopentanal (0.07 ppb) was detectable in the emissions from one printer. Vat polymerization printers emitted nanoscale particles that contained potential carcinogens, sensitizers, and reactive metals as well as carbonyl compound vapors. Differences in emissions between SLA and DLP printers indicate that the underlying technology is an important factor when considering exposure reduction strategies such as engineering controls.

Identifying the determinants of viable microorganisms in the air and bulk metalworking fluids.

Exposure assessment was conducted for an epidemiologic study of the respiratory effects of exposure to metalworking fluids (MWF). As part of the study, airborne microorganisms were collected with a two-stage microbial impactor, and a sample of the bulk soluble MWF was collected from each machine sump, as well as information about the work environment. These data were then used to develop multivariate statistical models of the determinants bulk MWF and airborne microbial levels. Microbial concentrations in the bulk MWF ranged from 5 x 10(4) to 5 x 10(10) colony-forming units (CFU)/mL, with a geometric mean of 3.4 x 10(7) CFU/mL. The geometric mean airborne microbial level was 182 CFU/m3 (for particles size <8 microm) with a range of 1 to 8,308 CFU/m3. In modeling the determinants of bulk microorganisms, fluid-related factors were the most important characteristics associated with microbial levels, followed by process-related and environmental factors. The final full multivariate model predicted a significant reduction in bulk microbial levels by increasing pH of the fluid and reducing the amount of tramp oil leaking into the fluid. For the airborne microbial models, process-related factors were the major characteristics associated with microbial levels, followed by factors related to worker activities and environmental factors. The final full multivariate model predicted a significant control of airborne microorganisms by increasing worker distance from the machine, reducing the number of machines within 10 feet of the worker, decreasing the bulk microbial levels, and adding machine enclosures. These models can be used to prioritize nonbiocidal interventions to control microbial contamination of the bulk MWF and the air.

Biomarkers of liver regeneration allow early prediction of hepatic recovery after acute necrosis.

Acute toxic hepatic necrosis is common and may be fatal. Predicting clinical outcome may be aided by following serum markers that could indicate recovery or may signify massive (substantial) destruction of functional liver mass. Previously, in a published case of chloroform poisoning, we serially assayed serum biomarkers of hepatocellular necrosis (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase) and markers of hepatocellular regeneration (alpha-fetoprotein, retinol-binding protein, gamma-glutamyl transferase, and des-gamma-carboxyprothrombin). We noted a decline in necrotic markers and a synchronous elevation in regenerative markers, which could be suggestive of a favorable outcome in similar cases. We now report 6 Amanita mushroom poisonings with favorable outcome and 2 fatal acetaminophen poisonings in which the same markers were observed. Our results further support our hypothesis that a sustained decline in serum markers of hepatocyte necrosis with a concurrent elevation in regenerative markers could aid in prediction of favorable outcome in patients with acute liver injury.

A field investigation of the acute respiratory effects of metal working fluids. I. Effects of aerosol exposures.

A study of cross-shift change in pulmonary function was conducted among workers exposed to metal working fluids (MWF) in an automobile parts manufacturing company. Three hundred eighty-six workers (216 machinists exposed to straight or soluble MWFs, and 170 nonmachinists) were studied for 1 day, performing spirometry at the beginning and end of their shift. Airborne concentrations of inhalable particulate, culturable bacteria, and endotoxin were measured. We observed an approximately threefold increase in the incidence of 5% or greater cross-shift decrement in forced expiratory volume during the first second among those with exposures above about 0.15 mg/m3, compared to those with exposures below about 0.08 mg/m3. There was some evidence that chronic respiratory symptoms were more prevalent among machinists than among nonmachinists, notably for chronic cough. Baseline FEV1 was about 3% lower on average among those with soluble MWF exposure compared to nonmachinists. These findings are consistent with earlier studies showing respiratory effects of MWFs.

A field investigation of the acute respiratory effects of metal working fluids. II. Effects of airborne sulfur exposures.

An investigation of the acute respiratory effects of workers exposed to metal working fluids (MWF) was conducted in an automobile parts manufacturing facility. After observing an association between cross-shift decline in forced expiratory volume in the first second (FEV1) and aerosol mass concentration, improved characterization of the exposure was sought through investigation of four elements of a priori interest (Cl, Cr, Ni, S). Of these, only sulfur showed an association with cross-shift FEV1 decrement. The relative risk of 5% cross-shift FEV1 decrement was 2.7 (95% confidence interval = 1.0-6.0) comparing those with > 4.4 micrograms/m3 to those with < 2.5 micrograms/m3 sulfur exposure. Because the concentrations of sulfur in this environment were relatively low and other respiratory irritants were present, sulfur is more likely to be an indicator of more irritating conditions than the sole agent responsible for the observed acute respiratory effects.

Concise parathyroidectomy: the impact of preoperative SPECT 99mTc sestamibi scanning and intraoperative quick parathormone assay.

BACKGROUND: Results of initial operation for sporadic primary hyperparathyroidism are generally excellent, yet today there is pressure to improve outcome and resource utilization. METHODS: We designed a prospective longitudinal cohort study comparing two approaches to concise parathyroidectomy. Strategy A was defined as the palpation method for selective unilateral exploration. Strategy B was defined as the routine use of both preoperative 99mTc sestamibi single photon emission computed tomography (SPECT) imaging and intraoperative quick parathormone assay. With either strategy the study period was 19 months and patients explored unilaterally were candidates for same-day discharge. We compared surgical outcome for 128 consecutive consenting patients each with 6 months or more of follow-up (mean 12 +/- 7.6 months). RESULTS: Demographic, biochemical and pathologic findings did not differ between groups. SPECT imaging precisely localized hyperfunctioning parathyroid tissue. Compared with Strategy A (n = 61), the 67 patients treated by use of Strategy B experienced a higher rate of unilateral exploration (41.0% versus 62.7%, p < 0.00001) and a shorter length of stay (1.07 versus 1.90 days, p < 0.00001) and tended to have shorter operative times, fewer operative failures, and less morbidity. Total perioperative costs did not differ between groups. CONCLUSIONS: Routine use of intraoperative quick parathormone measurement and preoperative 99mTc sestamibi SPECT is as safe, effective, and cost-effective as conventional approaches to parathyroidectomy. Use of this strategy is associated with significant reductions in extent of surgery and length of hospital stay.

Exposure assessment for a field investigation of the acute respiratory effects of metalworking fluids. I. Summary of findings.

The exposure assessment summarized here is part of an epidemiologic study of the acute respiratory health effects of metalworking fluid (MF) exposures. Exposures were measured as the inhalable concentrations of the MF aerosol, a variety of metals and elements, and endotoxin as well as the level of culturable bacteria in the aerosol size fraction less than 8 microns. Bulk samples of soluble MFs were tested for pH, mineral and tramp oil fraction, endotoxin, culturable bacteria, and lipopolysaccharide levels. The MF exposed workers had higher geometric mean inhalable aerosol exposures (0.181 mg/m3) than the MF unexposed workers (0.046 mg/m3). The MF exposed workers had higher geometric mean (GM) airborne culturable microbial counts (102 colony-forming units (CFU)/m3 for bacteria < 8 microns) than the unexposed workers (GM = 14 CFU/m3). Among the unexposed, Bacillus was the predominant airborne species, while among the exposed workers, Pseudomonas predominated. Exposed workers also had higher geometric mean airborne endotoxin levels (GM = 7.1 endotoxin units (EU)/m3) than the unexposed workers (GM = 1.9 EU/m3). Elemental concentrations of iron, chlorine, and sulfur were substantially higher among the exposed workers compared to the unexposed workers. For soluble metalworking fluids, the levels of bulk constituents were examined by three categories of time since the machine sump was refilled with fresh MF (< 4 days, 4-21 days, > 21 days). Univariate analyses of percent oil, pH, culturable bacteria, tramp oil percent, endotoxin, or fatty acid levels all showed no statistically significant changes in level over time.

Ionized hypomagnesemia in patients undergoing orthotopic liver transplantation: a complication of citrate intoxication.

Using a new ion-selective electrode, plasma concentration of ionized magnesium was measured in nine adult patients undergoing orthotopic liver transplantation. Baseline plasma ionized magnesium (IMg2+) concentration (0.49 +/- 0.07 mmol/L) was slightly below normal values (0.55-0.66 mmol/L, 95% CI): Six patients had ionized hypomagnesemia and two of these had total hypomagnesemia. Ionized IMg2+ concentration progressively decreased during the dissection (0.45 +/- 0.07 mmol/L, p < 0.05) and anhepatic stage (0.38 +/- 0.07 mmol/L, p < 0.05) and returned toward baseline values by 2 hours after graft reperfusion. Plasma ionized calcium levels and acid-base status were maintained within normal limits during surgery. Serum citrate concentration increased during the dissection (0.58 +/- 0.60 mmol/L) and anhepatic stages (1.18 +/- 0.78 mmol/L), the result of transfusion of citrate-rich blood products in the absence of adequate hepatic function, and gradually returned toward baseline values after graft reperfusion. IMg2+ concentration inversely correlated with the plasma citrate concentration (r2 = 0.54). The results of this study demonstrate that ionized hypomagnesemia invariably occurs during liver transplantation and suggest that this derangement may be a clinical concern, because magnesium is an important cofactor for the maintenance of cardiovascular homeostasis. The data further suggest the clinical importance of supplementation with magnesium based on the monitoring of plasma IMg2+ concentration.

Normotest and abnormal prothrombin in liver transplantation.

Postoperative changes in coagulation parameters, including the abnormal plasma prothrombin level, were studied in 95 patients who underwent liver transplantation, and the results were compared with the clinical outcome. The patients were classified into four groups: Group I had a satisfactory postoperative course, (n = 76), Group II suffered graft failure or death at 31 days or more after transplantation (n = 9); Group III suffered graft failure or death from 8 to 30 days after transplantation (n = 4); and Group IV suffered graft failure or death within 7 days of transplantation (n = 6). The Normotest, which closely reflected liver graft function, showed an increase immediately after transplantation in Group I, II, and III, but showed a marked decrease in Group IV. In patients with severe acute cellular rejection, the plasma level of abnormal prothrombin (des-gamma-carboxy prothrombin) was compared with the histology of the liver biopsy specimen. When liver graft function was good after orthotopic transplantation, the Normotest value recovered to the normal range of 70% or more. Subsequently, graft function remained good when the des-gamma-carboxy prothrombin level stayed low, whereas acute cellular rejection was indicated by an elevation of des-gamma-carboxy prothrombin was not produced by graft with early failure, the des-gamma-carboxy prothrombin level also remained low. Thus, the Normotest value and the des-gamma-carboxy prothrombin level were both useful parameters for assessing hepatic function and rejection after transplantation.

Serum-ethanol determination: comparison of lactate and lactate dehydrogenase interference in three enzymatic assays.

Gas chromatography is considered to be the reference method for ethyl alcohol determination. However, enzymatic ethanol assays have been developed for use in the clinical laboratory by several commercial vendors. Essentially, these assays utilize the oxidation of ethyl alcohol to acetaldehyde with concurrent reduction of nicotinamide adenine dinucleotide (NAD) to NADH while monitoring the increase in absorbance at 340 nm. The increase in absorbance is theoretically proportional to the ethanol concentration in the sample. Previously, several authors reported that increased concentrations of lactate and lactate dehydrogenase (LDH) can cause false-positive results with certain enzymatic ethyl alcohol assays. In the present investigation, we further studied the interference of lactate and LDH in three enzymatic assays. Apparent ethyl alcohol concentrations in serum spiked with lactate and LDH, as well as patient and autopsy samples, were determined by the Syva, Abbott, and Roche enzymatic assays and by gas chromatography. The effect of coenzyme depletion on the rate of reaction and the interference of hemolysis were also investigated. Based on our results we suggest that coenzyme depletion plays a major role in the severity of the false-positive ethyl alcohol result, and the interference from hemolysis has a negligible effect on these results. We also confirm the previous studies in showing that elevated serum-lactate and LDH concentrations can result in varying degrees of false-positive ethyl alcohol concentrations in the three enzymatic assays. This should be taken into consideration in the management of patients in a tertiary care medical center.

Role of serum markers for liver function and liver regeneration in the management of chloroform poisoning.

Accidental or intentional chloroform poisoning is rare, but a few such cases have been reported in literature. We report here a successful management of acute chloroform toxicity in a 33-year-old white female who attempted suicide by injecting one half milliliter of chloroform, followed by drinking half a cup the next morning. Plasma chloroform levels, measured by headspace gas chromatography declined rapidly. Sequential measurement of biomarkers in serum for liver cell necrosis, liver function, and liver regeneration indicated the presence of initial liver damage followed by recovery. These results suggest that in addition to biomarkers for liver cell necrosis, serial determinations of markers for liver regeneration provide objective evidence for recovery from chloroform poisoning and possibly other hepatotoxins.

Plasminogen activator and its inhibitor in cancer patients treated with tumor necrosis factor.

BACKGROUND: We noted the presence of plasma fibrin degradation products in patients treated with recombinant human tumor necrosis factor (TNF) in a phase I trial. PURPOSE: To further define this observation, we investigated the effects of TNF on the fibrinolytic system in patients entered in the same trial. METHODS: In the 14 patients studied, fibrinolytic parameters were measured by analyzing blood samples for tissue plasminogen activator and inhibitor at 0, 1, 2, 4, 6, and 18-24 hours after initiation of TNF treatment. We used a chromogenic substrate method to determine activity of plasminogen activator and its inhibitor and an enzyme-linked immunosorbent assay (ELISA) to determine levels of antigen (tissue-type plasminogen activator). Molecular weight was determined by zymographic assay. RESULTS: TNF treatment was associated with tissue-type plasminogen activator induction within 1 hour of TNF initiation. The plasminogen activator produced was consistent with tissue-type plasminogen activator derived from endothelium as evidenced by molecular weight analysis and ELISA. Moreover, induction of plasminogen activator inhibitor occurred following the release of tissue-type plasminogen activator, and our data suggest a dose-response effect for TNF. At high doses (i.e., 200 and 240 micrograms/m2), there was a more rapid and prolonged release of plasminogen activator inhibitor, which had an inverse relationship with the level of antigenic tissue-type plasminogen activator. Zymographic analysis showed urokinase-type plasminogen activator activity in 13 of 14 patients. In three patients, simultaneous measurements of white blood cells and tissue-type plasminogen activator revealed a temporal association between the TNF-associated rapid granulocytopenia at 30 minutes after TNF initiation and release of tissue-type plasminogen activator antigen. CONCLUSIONS: The results suggest a positive association between TNF and rapid induction of plasminogen activator activity that is consistent with an endothelial product. It is possible that, at high doses, TNF may interact directly with vascular endothelium, leading to rapid and prolonged production of plasminogen activator inhibitor. There was a dose-response effect between TNF and release of tissue-type plasminogen activator. The release of tissue-type plasminogen activator was preceded by granulocytopenia, which may indicate an association between a proposed TNF-induced granulocyte-endothelial interaction in vivo and release of tissue-type plasminogen activator. IMPLICATIONS: These findings demonstrating the effects of TNF on the fibrinolytic system can be analyzed further in experimental systems to determine the implications for use of this agent as a biological response modifier in cancer therapy.

Enhancement of cell production in long-term bone marrow culture.

In an effort to increase the long-term production of hematopoietic cells in vitro, Origen hybridoma cloning factor (HCF) was added at the initiation of Dexter type cultures, in which whole bone marrow (BM) was seeded into tissue culture flasks and formed an adherent stromal layer that supported the proliferation and differentiation of primitive cells. After about six weeks, all the cultures were fully established, and continuous production of nonadherent cells was maintained for at least 27 weeks. In the groups with 20% HCF, there was a significant (three- to fourfold) increase in the steady-state cell production of 106 +/- 17 x 10(4) cells/ml compared to 26 +/- 10 x 10(4) in controls. In some cases the ability of HCF to increase productivity was limited by the nutrients and metabolic products in the culture medium. Cell number varied inversely with glucose and pH. HCF increased the concentration and absolute number of myeloid progenitors (granulocyte-macrophage colony forming units and spleen colony forming units) in the nonadherent layer and shifted the differentiation of granulocyte-macrophage colony forming units toward the production of cells of the monocyte/macrophage lineage. Spleen colonies produced from 10(5) cells from cultures with HCF were more numerous (8 +/- 2 versus 4 +/- 2) and larger than those from control cultures (2.6 versus 0.2 mg/colony), but they contained the usual cell lineages (erythrocytic, granulocytic and megakaryocytic).

Effect of chronic undernutrition on hepatocyte insulin receptors in rats.

The effect of moderate chronic undernutrition on insulin receptors was studied in male rats, pair-fed 60% of the daily food intake of ad libitum-fed littermates, for 8 weeks. Body weights of undernourished rats were consistently found to be 35% to 40% less than control littermates, with no period of growth arrest at any point in the 8-week study. The binding-displacement curves of labeled insulin to hepatocyte receptors in the two groups in the presence of unlabeled insulin were significantly different (P = .0258 after repeated measures ANOVA). Significantly lower binding was observed in hepatocytes from the undernourished group (P less than .01) at all unlabeled insulin concentrations less than 20 nmol/L. In the absence of any unlabeled insulin, specific binding was reduced from 8.8% +/- 0.7%, (mean +/- SE) in controls, to 7.4% +/- 0.3% in undernourished rats (P less than .01). Half-maximal specific hormone binding to hepatocytes was achieved at a free insulin concentration of 362 nmol/L in the control group, compared with 447 nmol/L in the undernourished group, reflecting an increase of approximately 20%. The hypoglycemic response to intravenous insulin (0.1 U/kg body weight) was tested in a parallel experiment involving seven paired littermate rats, and found to be significantly impaired in the undernourished group (P = .0041 by repeated measures ANOVA).(ABSTRACT TRUNCATED AT 250 WORDS)

Ionization and hemodynamic effects of calcium chloride and calcium gluconate in the absence of hepatic function.

Serial serum ionized calcium concentrations were measured before and after administration of either calcium chloride or calcium gluconate during the anhepatic stage of liver transplantation in 15 patients to determine the release of ionized calcium in the absence of hepatic function. When hypocalcemia (Ca++ less than 0.8 mM) occurred during the anhepatic stage, patients were randomly assigned to treatment with chemically equivalent doses of either calcium chloride (10 mg/kg, n = 8) or calcium gluconate (30 mg/kg, n = 7). Serum concentrations of ionized calcium and citrate, hematocrit, arterial blood gas tensions, acid-base state, and hemodynamic profiles were determined before and up to 10 min after calcium therapy. In both groups of patients initial similar and rapid increases in Ca++ (0.98 +/- 0.14 mM in the calcium chloride group and 1.05 +/- 0.10 mM in the calcium gluconate group) were followed by gradual decreases over the next 10 min. Measured hemodynamic values were similar in the two groups, and neither group showed improvement in cardiovascular function after calcium therapy, possibly because of the decrease in preload that occurred during the anhepatic stage. Equally rapid increases in Ca++ after administration of calcium chloride and gluconate in the anhepatic state suggest that calcium gluconate does not require hepatic metabolism for the release of Ca++ and is as effective as calcium chloride in treating ionic hypocalcemia in the absence of hepatic function.

The effect of menhaden oil on choline-deficiency-induced hepatic ornithine decarboxylase activity and hepatocyte insulin receptor binding.

The effects of menhaden oil on the choline-deficient (CD) diet tumor promotion regimen-induced alterations in hepatocyte insulin receptors and the cellular ornithine decarboxylase (ODC) activity have been investigated in this study. Male Sprague-Dawley rats exposed to the tumor-promoting regimen of a CD diet for 10 days showed increases in hepatic ODC activity from 2.68 +/- 0.42 pmol 14CO2/mg protein/h in the animals fed basal control chow (C) to 13.54 +/- 2.38 (P less than 0.02) in the rats fed CD diet. These changes in ODC occur simultaneously with the alterations in hormone receptor binding as reported previously for insulin. Replacement of the lipid present in the control diet with 15% menhaden oil (CMO) had no significant effect on ODC activity (0.91 +/- 0.21), or on the number of insulin receptors (206,000 +/- 37,000) and the Kd (7.4 +/- 1.6). Sequential treatment with 10 days of CD diet and then 10 days of the C diet, resulted in a reversal in the elevated, CD-induced hepatic ODC activity to the control levels; however, substituting 15% menhaden oil for the fat present in the CD diet (CDMO) enhanced this enzymatic activity. In contrast, both sequential and CDMO treatments prevented the insulin receptor alterations induced by the CD diet. These data demonstrate that the CD diet-induced insulin receptor alterations occur concurrently with the induction of ODC activity. But insulin receptor changes and the increased ODC activity are affected differently by CDMO treatment, suggesting that their induction by the CD diet is through distinct mechanisms and only the receptor alterations correspond with the tumor-promoting action of CD diet regimen.

Hypoaminoacidemia caused by imipramine but not by clenbuterol is dissociable from hyperglycemia and hyperinsulinemia.

The effects of the tricyclic antidepressant imipramine (20 mg/kg) and the beta-adrenoceptor agonist clenbuterol (0.5 mg/kg) on the serum concentrations of tyrosine, tryptophan, glucose and insulin were compared 30 min after intraperitoneal injection. The drugs had nearly identical effects on serum tyrosine, which was reduced to 73% of control by both drugs, and on tryptophan, which was reduced to 72% by imipramine and to 66% by clenbuterol. In contrast, whereas clenbuterol raised serum glucose to 174% and insulin to 379% of control, imipramine had no significant effects on either glucose or insulin. The results clearly demonstrate that the effects of imipramine on blood amino acid levels are dissociable from effects on glucose and insulin. We conclude, therefore, that hypoaminoacidemia caused by imipramine is not mediated by stimulating insulin release.