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Biomedical subjects

R Barr

Publications and source records attributed to R Barr.

At least 37 records · Page 2Linked to original sources
PubMed1996

Cardiorespiratory status after treatment for acute lymphoblastic leukemia.

The use of certain chemotherapeutic agents is associated with dose-related cardiotoxicity and, potentially, with restrictive lung disease. Therefore, we assessed the cardiopulmonary status and exercise capacity of 19 patients (pts; 9M:10F) 1.1 to 7.1 years (mean 4.6 +/- 1.5 years) after successful treatment of acute lymphoblastic leukemia (ALL) with Dana Farber Cancer Institute protocols. As body mass and nutritional status may influence exercise capacity, we also evaluated their anthropometric status and the plasma levels of rapid turnover proteins. Seven pts designated as "standard risk for relapse" (SR) had received low cumulative doses of doxorubicin (50 +/- 21 mg/m2), while twelve pts at "high or very high risk for relapse" (HR/VHR) had received higher doses (349 +/- 16 mg/m2). The evaluations included a questionnaire, anthropometric assessments, echocardiography, pulmonary function studies, exercise testing, and nutritional assays. Patients' data were compared with published normative data or with control values from our laboratories. In addition, we compared SR pt data with HR/VHR pt data. No pt had overt symptoms or signs of cardiorespiratory compromise. The pts had a higher percent of body fat than age-matched healthy controls (29.7 +/- 7.9% vs. 20 +/- 6%; P < 0.001). On echocardiography, cardiac systolic function was within normal limits in all. However, HR/VHR pts had lower left ventricular (LV) shortening fractions than SR pts (P < 0.05). LV filling velocity, indicative of diastolic function (the E/A ratio), was normal in most pts. Pulmonary function studies were normal. Exercise capacity was below predicted in most cases but heart rates at peak exercise and leg muscle function were within normal limits, suggesting a deconditioned state. Plasma levels of rapid turnover proteins were also normal. Despite lack of overt morbidity in our pt population, subtle abnormalities persist in cardiac function while pulmonary function is normal. Longitudinal studies will identify if further abnormalities or overt morbidity develop. In later years, continuing obesity and a sedentary state may contribute to clinically relevant heart disease.

Anthropometry↗
PubMed1996

Effects of ranolazine on oxidative substrate preference in epitrochlearis muscle.

Ranolazine is an novel investigational antianginal agent that stimulates glucose oxidation in isolated rat hearts. This study determined its effects on metabolic substrate and O2 utilization in an in vitro skeletal muscle preparation, the rat epitrochlearis muscle. Muscles were superfused with Krebs-Henseleit buffer containing 3% albumin, 0.4 mM palmitate, 5.5 mM glucose, 0.5 mM lactate, and a physiological amino acid mixture. Perfusate also contained either 1) [U-14C]glucose for measurement of glucose oxidation or 2) [9,10-3H]palmitate and [U-14C]lactate for measurement of palmitate and lactate oxidation. Addition of ranolazine (10 microM) significantly stimulated glucose oxidation and decreased palmitate oxidation but had no effect on lactate oxidation. Overall, the calculated relative contribution of glucose oxidation to aerobic ATP production increased from 12 to 33%, whereas from palmitate it decreased from 55 to 26%. Ranolazine did not alter tissue malonyl-CoA contents, making it unlikely that the decrease in palmitate oxidation caused by ranolazine is due to a decrease in the activity of acetyl-CoA carboxylase. These data demonstrate that ranolazine can shift energy substrate preference in skeletal muscle, which could potentially prove useful in ischemic disorders of skeletal muscle.

Acetanilides↗
PubMed1996

Economic evaluation of allogeneic bone marrow transplantation: a rudimentary model to generate estimates for the timely formulation of clinical policy.

PURPOSE: To provide an evidence-based approach to the formulation of clinical policy with respect to allogeneic bone marrow transplantation (BMT) that involves perceived trade offs between two major factors: costs and consequences. The report also highlights key informational deficiencies. PATIENTS AND METHODS: Adults with acute myeloid leukemia (AML) in second complete remission (2CR) and those with acute lymphoblastic leukemia (ALL) in first complete remission (1CR) were assigned to BMT or control groups solely on the availability of a suitable donor. All hospital-borne costs were estimated, based on services used according to manual chart review, in four categories: diagnostic and therapeutic costs, professional fees, drug costs, and ward costs. Incremental costs and incremental life-years were calculated, and the quotient determined a cost per life-year gained by BMT for AML (2CR) and ALL (1CR). RESULTS: The incremental cost (in 1992 Canadian dollars) per life-year gained by BMT (cost-effectiveness) for AML (2CR) was $29,200; and for ALL (1CR) it was minus $29,200. CONCLUSION: For AML (2CR), allogeneic BMT creates better outcomes than standard treatment, but is more costly. For ALL (1CR), both the costs and outcomes are similar for BMT and standard therapy. Quality adjustments made to life-years gained did not change these conclusions.

Adolescent↗
PubMed1995

Determination of structure-activity relationships of Annonaceous acetogenins by inhibition of oxygen uptake in rat liver mitochondria.

A new group of natural compounds, the Annonaceous acetogenins, have recently been determined to inhibit ATP production at a similar site of action and higher levels of potency as rotenone, i.e., at NADH-ubiquinone oxido-reductase, complex I of the mitochondrial electron-transport chain. The acetogenins had earlier been determined to be pesticidal, antimalarial, antimicrobial, anti-parasitic, cytotoxic, and in vivo active as potentially new antitumor agents. In order to determine structural activity relationships (SARs) among these compounds, at the subcellular level, several available acetogenins have been tested. Data obtained, from the inhibition of oxygen consumption by rat liver mitochondria, demonstrated that all of the twenty acetogenins tested are active with IC50 values in the range of 15-800 nM/mg protein. The IC50 value of rotenone was 17 nM/mg protein. The bis-adjacent THF ring acetogenins and the bis-nonadjacent THF ring compounds are about ten times more active than the mono-THF ring acetogenins. Overall, 30-OH and 31-OH-bullatacinone were the most active and were slightly more active than rotenone. The least active were the 4-deoxy bis-adjacent THF ring compounds followed by the mono-THF ring group. There was some variation between the groups, e.g., within the bis-adjacent and mono-THF ring groups, the alpha, beta-unsaturated-gamma-lactones were less active than the keto-lactones, but this observation was reversed for one of the pairs of bis-nonadjacent THF ring acetogenins. Additional hydroxylations, to a maximum of three, seemed to increase activity within all of the groups. Before final decisions on SARs can be made, additional comparisons of the results of this subcellular assay (as an in vitro assay) with the results of in vivo assays should be made. Also, future investigations into the exact site of action within complex I and other possible sites of action (such as the NADH oxidase of plasma membranes) need to be conducted for a more. complete understanding of the utility and potential of this new group of very potent compounds.

Acetylation↗
PubMed1995

"I hardly cried when I got my shot!" Influencing children's reports about a visit to their pediatrician.

We examined, in 2 phases, the influence of postevent suggestions on children's reports of their visits to a pediatrician. Phase 1 examined the effect of giving one of 3 types of feedback to 5-year-old children immediately following their Diphtheria Pertussis Tetanus (DPT) inoculation. Children were given pain-affirming feedback (the shot hurt), pain-denying feedback (the shot did not hurt), or neutral feedback (the shot is over). 1 week later, they did not differ in their reports concerning how much the shot hurt or how much they cried. In Phase 2, the same children were visited approximately 1 year after their inoculation. During 3 separate visits, they were either given additional pain-denying or neutral feedback. They were also given misleading or nonmisleading information about the actions of the pediatrician and the assistant. Children given pain-denying feedback reported that they cried less and that the shot hurt less than did children given neutral feedback. Those who were given misleading information about the actions of the assistant and the pediatrician made more false allegations about their actions than did children who were not given this information. These results challenge the view that suggestibility effects are confined to peripheral, nonaction events; in this study children's reports about salient actions involving their own bodies in stressful conditions were influenced.

Child↗
PubMed1995

Randomized trial of interferon maintenance in multiple myeloma: a study of the National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: To determine whether interferon maintenance therapy improves overall survival and response duration in patients with multiple myeloma who have responded to induction therapy with melphalan and prednisone. PATIENTS AND METHODS: In a multicenter trial, patients with symptomatic clinical stage I and stage II and III multiple myeloma were registered at diagnosis and those who responded to melphalan-prednisone (MP) were randomized either to receive interferon (2 mU/m2) subcutaneously three times per week or no maintenance. MP was discontinued in both groups once a stable response plateau of the monoclonal protein was reached. Interferon was continued until relapse, and then was restarted on subsequent response to MP. Interferon toxicity was recorded using a self-report diary. Survival and response duration were calculated using life-table methods, and were adjusted in the analysis for imbalances in baseline prognostic factors. RESULTS: Four hundred two patients were registered and 176 responders were randomized (85 to interferon and 91 to control). At a median follow-up time of 43 months, the median survival duration was 43 months for interferon and 35 months for control (P = .16), but when adjusted for chance imbalances in baseline prognostic factors (mainly performance status), the median survival duration was 44 months and 33 months for interferon and control, respectively (P = .049). Progression-free survival from randomization to first relapse also favored interferon (unadjusted P < .002; adjusted P < .003). Interferon toxicity caused 58% of patients to reduce their dose, of which 84% were able to return to the initial dose; 14% had to discontinue interferon treatment. CONCLUSION: Interferon maintenance therapy improves progression-free and overall survival of patients with multiple myeloma who respond to melphalan and prednisone. Toxicity is substantial and must be weighed by patients against the potential benefits in response duration and survival.

Aged↗
PubMed1994

Acetyl-CoA carboxylase involvement in the rapid maturation of fatty acid oxidation in the newborn rabbit heart.

Fatty acid oxidation rapidly increases in the rabbit heart following birth. By inhibiting carnitine palmitoyltransferase 1 (CPT1), malonyl-CoA is a potent regulator of fatty acid oxidation in the heart. We therefore addressed the hypothesis that a decrease in acetyl-CoA carboxylase (ACC) activity and/or malonyl-CoA inhibition of CPT1 could account for the increase in the ability of the heart to oxidize fatty acids following birth. ACC activity and expression, malonyl-CoA levels, and mitochondrial CPT1 activity were measured in hearts from 1-day, 7-day, and 6-week-old rabbits. CPT1 activity and sensitivity to malonyl-CoA inhibition did not differ between 1-day, 7-day, or 6-week hearts (the IC50 for malonyl-CoA was 32.0 +/- 1.5, 36.0 +/- 0.3, and 36.3 nM, respectively). Western blot analysis with streptavidin showed that all hearts expressed similar amounts of both a 265-kDa (ACC-265) and 280-kDa isoform (ACC-280) of ACC. A progressive and significant decrease in malonyl-CoA levels was seen in 1-day, 7-day, and 6-week hearts (47 +/- 2, 40 +/- 2, and 26 +/- 2 nmol/g dry weight, respectively), paralleling a decline in ACC activity. We hypothesized that these developmental changes could be due to changes in hormonal regulation of cardiac ACC in the postnatal period. In isolated hearts from 1-day-old rabbits, the fatty acid oxidation rate was 9.01 +/- 1.10 nmol.g dry weight-1.min-1. Glucagon (1 ng/ml) did not alter this rate (11.03 +/- 1.42 nmol.g dry weight-1.min-1), but insulin (100 microunits/ml) resulted in a significant decrease in rate (4.81 +/- 0.82 nmol.g dry weight-1.min-1). ACC activity was markedly elevated in 1-day-old hearts perfused with insulin compared to control hearts or glucagon perfused hearts (0.415 +/- 0.052, 0.095 +/- 0.018, and 0.133 +/- 0.013 nmol of malonyl-CoA produced.g dry weight-1.min-1, respectively). Malonyl-CoA levels were also markedly elevated in 1-day hearts perfused with insulin (123.0 +/- 8.3, 2.0 +/- 0.4, and 1.8 +/- 0.6 nmol/g dry weight in insulin, control, and glucagon hearts, respectively). In 7-day-old rabbit hearts, the basal fatty acid oxidation rate had increased to 24.5 +/- 4.8 nmol.mg-1.min-1. In contrast to the 1-day-old hearts, insulin had no significant effect on fatty acid oxidation, although glucagon resulted in a significant increase in rates (38.9 +/- 12.2 and 80.7 +/- 9.1 nmol.g dry weight-1.min-1, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

Acetyl Coenzyme A↗
PubMed1994

An acute care physical therapy clinical practice database for outcomes research.

Clinical practice databases are frequently used to assess outcomes in various medical specialties. Formulating a computerized physical therapy medical record requires standardization of clinical assessments among the users. The purpose of this article is to describe an acute care physical therapy database system that emphasizes high-quality measures of function. The logic underlying the development of a physical therapy computerized medical record is described. Selected uses of the database are demonstrated by projects that assess data quality, generate clinical hypotheses, manage clinical data, develop clinical measures, and generate pilot data on patient variability. Patients seen in physical therapy for total joint replacement, pain, and decreased ambulation were studied to demonstrate some of the present capabilities of the database. Clinical practice databases contribute to the overall research mission, provided the data are of high quality. The use of databases in conjunction with randomized clinical trials may serve an important role in determining effective physical therapy interventions to reduce disability.

Database Management Systems↗
PubMed1993

Islet transplantation improves glucose oxidation and mechanical function in diabetic rat hearts.

In poorly controlled diabetes an impairment of glucose use can contribute to a depression in mechanical function of rat hearts. In this study we determined the effects of islet transplantation on glucose use and heart function in streptozotocin-induced diabetic rats. Myocardial function, glycolysis, and glucose oxidation were measured in isolated working hearts obtained from control, diabetic, and islet-transplanted diabetic Wistar-Furth rats. Islets (1200) were transplanted beneath the kidney capsule 2 weeks after a single i.v. dose of streptozotocin (55 mg/kg). The study consisted of three groups: (i) islet-transplanted diabetic rats, (ii) untreated diabetic controls, and (iii) normal controls. Following 11 weeks of monitoring, working hearts were perfused at a 11.5-mmHg (1 mmHg = 133.3 Pa) preload and 80-mmHg afterload, with buffer containing 11 mM [5-3H,14C(U)]glucose, 1.2 mM palmitate, and 100 microU/mL insulin. In untreated diabetic rat hearts, glucose oxidation rates were markedly depressed compared with control hearts (30.4 +/- 4 and 510 +/- 68 nmol.g-1 dry wt..min-1, respectively). Low glucose oxidation rates in diabetic rats were significantly improved in islet-transplanted animals (234 +/- 39 nmol.g-1 dry wt..min-1). The low glucose oxidation rates in untreated diabetic rat hearts were accompanied by an impaired mechanical function compared with control hearts, which was improved by islet transplantation (heart rate x developed pressure x 10(-3) was 10.6 +/- 0.9, 14.8 +/- 1.3, and 14.8 +/- 1.5 beats.mmHg.min-1, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Aerobiosis↗
PubMed1993

A suburban focus of endemic typhus in Los Angeles County: association with seropositive domestic cats and opossums.

Thirty-three cases of locally acquired murine typhus were reported in Los Angeles County residents from May 1984 through February 1988. Only eight cases were reported over the previous 20-year period. Thirty (91%) cases resided within a suburban area encompassing approximately 50 km2 in northcentral Los Angeles or had contact with an animal from this area. Serologic testing (complement fixation and indirect fluorescent antibody) of selected animals in close association with human cases revealed a high prevalence of seropositivity among domestic cats and opossums. Nine (90%) of 10 resident cats tested had demonstrable antibody titers compared with none (0%) of 20 cats from a control area (P < 0.001). Suburban typhus cases were more likely than neighborhood controls to own a cat or dog (odds ratio = 6.9, 95% confidence interval = 1.8, 25.9, P = 0.002). Sixteen (42%) of 38 opossums trapped in close proximity to the residences of cases were seropositive versus none (0%) of 36 opossums from control areas (P < 0.001) A low frequency (2.8%) of seropositivity was found in commensal rodents, and the classic vector of murine typhus, Xenopsylla cheopis, was not found. Ectoparasite indices form seropositive opossums revealed heavy infestations with the cat flea, Ctenocephalides felis (mean flea count = 104.7), a species that readily bites humans. These data provide evidence that a suburban focus of murine typhus exists in Los Angeles that differs substantially from the classic transmission cycle, and that cats, opossums and C. felis may play an important role in the occurrence of human cases.

Adolescent↗
PubMed1993

The effect of boron on plasma membrane electron transport and associated proton secretion by cultured carrot cells.

Plasma membrane electron transport reactions and associated proton secretion were studied in boron-deficient carrot cells. It was found that the hormone-sensitive plasma membrane NADH oxidase was inhibited by boron deficiency and that under such conditions activity could be restored by exogenous boric acid with or without 2,4-dichlorophenoxy acetic acid. Gramicidin, a channel-forming protonophore, further stimulated NADH oxidase by carrot cells. Proton secretion, associated with plasma membrane H(+)-ATPase, was also affected by boron deficiency, but not as severely as ferricyanide-generated proton secretion, reflecting plasma membrane electron transport. The addition of 1 mM boric acid and 1 microM 2,4-dichlorophenoxy acetic acid to carrot cells fully restored the H+ secretion in presence of ferricyanide. The effect of boron deficiency in cultured carrot cells can, therefore, be directly associated with cell growth through its effect on the plasma membrane NADH oxidase and H+ secretion. Ferricyanide provides a probe which activates transmembrane electron transport that is only coupled to proton release when boron is present.

2,4-Dichlorophenoxyacetic Acid↗
PubMed1992

A growth factor- and hormone-stimulated NADH oxidase from rat liver plasma membrane.

NADH oxidase activity (electron transfer from NADH to molecular oxygen) of plasma membranes purified from rat liver was characterized by a cyanide-insensitive rate of 1 to 5 nmol/min per mg protein. The activity was stimulated by growth factors (diferric transferrin and epidermal growth factor) and hormones (insulin and pituitary extract) 2- to 3-fold. In contrast, NADH oxidase was inhibited up to 80% by several agents known to inhibit growth or induce differentiation (retinoic acid, calcitriol, and the monosialoganglioside, GM3). The growth factor-responsive NADH oxidase of isolated plasma membranes was not inhibited by common inhibitors of oxidoreductases of endoplasmic reticulum or mitochondria. As well, NADH oxidase of the plasma membrane was stimulated by concentrations of detergents which strongly inhibited mitochondrial NADH oxidases and by lysolipids or fatty acids. Growth factor-responsive NADH oxidase, however, was inhibited greater than 90% by chloroquine and quinone analogues. Addition of coenzyme Q10 stimulated the activity and partially reversed the analogue inhibition. The pH optimum for NADH oxidase was 7.0 both in the absence and presence of growth factors. The Km for NADH was 5 microM and was increased in the presence of growth factors. The stoichiometry of the electron transfer reaction from NADH to oxygen was 2 to 1, indicating a 2 electron transfer. NADH oxidase was separated from NADH-ferricyanide reductase, also present at the plasma membrane, by ion exchange chromatography. Taken together, the evidence suggests that NADH oxidase of the plasma membrane is a unique oxidoreductase and may be important to the regulation of cell growth.

Animals↗
PubMed1992

Effects of high levels of fatty acids on functional recovery of ischemic hearts from diabetic rats.

In this study we determined the effects of high levels of fatty acids on recovery of heart function when present either during or after ischemia. Isolated working hearts from 6-wk streptozotocin diabetic and control rats perfused with 11 mM glucose were subjected to 25 min of global ischemia followed by 30 min of aerobic reperfusion. Four groups were studied: 1) 1.2 mM palmitate present before, during, and after ischemia; 2) 1.2 mM palmitate present before and during ischemia, followed by reperfusion in the absence of palmitate; 3) no palmitate before and during ischemia, followed by 1.2 mM palmitate during reperfusion; and 4) no palmitate before and during ischemia or during reperfusion. In control hearts, palmitate during reperfusion depressed recovery of function regardless of whether palmitate was present or absent during ischemia. In contrast, palmitate present during reperfusion did not depress recovery of mechanical function in the diabetic rat hearts. However, the presence of palmitate during ischemia itself in diabetic rat hearts was detrimental to recovery of mechanical function. The presence of palmitate during ischemia resulted in an accelerated rate of ATP loss and a decreased rate of lactate accumulation during ischemia, although this effect was similar in control and diabetic rat hearts. Our results demonstrate that high concentrations of fatty acids depress functional recovery of control rat hearts during the reperfusion period but depress recovery of function in diabetic rat hearts when present during ischemia itself.

Adenosine Triphosphate↗
PubMed1992

Is rectal biopsy necessary in irritable bowel syndrome?

Many physicians obtain a rectal biopsy from patients with irritable bowel syndrome (IBS) in order to exclude melanosis coli and collagenous or microscopic colitis. To determine the value of routine rectal biopsy in IBS, 89 patients and 59 controls were administered a bowel questionnaire, and a rectal biopsy was obtained at sigmoidoscopy. IBS patients were 82% female and averaged 44 yr. Eighty-nine percent fulfilled three or more Manning criteria, and 84% fulfilled the Rome criteria for IBS. The 59 control subjects were 37% female, and averaged 57 yr. Only 15% fulfilled three or more Manning criteria, and 5% the Rome criteria. The 148 rectal biopsies were examined histologically by a pathologist whose methods were validated by a second pathologist. Although minor changes previously reported with phosphate enemas were observed, not a single subject had melanosis coli or fulfilled criteria for microscopic or collagenous colitis. Thus, patients with an endoscopically normal colon and a diagnosis of IBS made by established criteria are unlikely to have histologic abnormalities in the rectum. Rectal biopsies are costly and unnecessary in the investigation of IBS.

Adult↗
PubMed1992

Destruction of vitamin K1 of cultured carrot cells by ultraviolet radiation and its effect on plasma membrane electron transport reactions.

The effect of ultraviolet radiation on plasma membrane electron transport reactions was studied in cultured carrot cells. It was found that a 90 min treatment inhibited transmembrane hexacyanoferrate reduction greater than 50%. Extraction of lipophilic quinones from irradiated cells showed that vitamin K1 and coenzyme Q were totally destroyed, while control unirradiated cells showed the presence of 0.4 mumole vitamin K1 g dry wt.-1. The addition of exogenous vitamin K1 in concentrations of 1-10 microM partially restored plasma membrane electron transport with impermeable hexacyanoferrate as the electron acceptor. Total restoration of activity was given by growing irradiated cells in vitamin K1 supplemented growth media for 6 days. This shows that vitamin K1 may function as a member of the transplasma membrane electron transport chain in cultured carrot cells.

Cell Membrane↗
PubMed1992

Effects of diltiazem on glycolysis and oxidative metabolism in the ischemic and ischemic/reperfused heart.

We have recently demonstrated that calcium channel blockers can protect the ischemic myocardium at concentrations which do not decrease myocardial workload or metabolic demand before ischemia. In this study, we extended these observations by determining what effect the calcium channel blocker, diltiazem, has on overall myocardial energy substrate metabolism in aerobic, ischemic and reperfused ischemic hearts. Isolated working rat hearts were perfused at a 11.5-mm Hg preload, 80-mm Hg afterload, with Krebs-Henseleit buffer containing 11 mM glucose, 1.2 mM palmitate and 500 microU/ml insulin. Glycolysis and glucose oxidation rates were determined in aerobic and reperfused ischemic hearts perfused with [3H]/[14C]glucose, whereas fatty acid oxidation rates were determined under similar conditions in hearts perfused with [14C]palmitate. Addition of diltiazem (0.8 microM) before subjecting hearts to a 30-min period of global no-flow ischemia resulted in a significant improvement in recovery of mechanical function (heart rate x developed pressure during reperfusion recovered to 28 and 53% of preischemic levels, in control and diltiazem-treated hearts, respectively). If diltiazem was added at reperfusion, no improvement of functional recovery was seen. Addition of diltiazem before or after ischemia had no effect on palmitate or glucose oxidation during reperfusion, but did significantly decrease rates of glycolysis during reperfusion. In hearts subjected to low-flow ischemia (coronary flow = 0.5 ml/min), diltiazem significantly decreased glycolytic rates during ischemia (glycolytic rates were 2.09 +/- 0.25 and 1.58 +/- 0.28 mumol/min.g dry wt. in control and diltiazem-treated hearts, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1991

Chloroquine-sensitive transplasmalemma electron transport in Tetrahymena pyriformis: a hypothesis for control of parasite protozoa through transmembrane redox.

Plasma membrane electron transport was studied in a protozoan cell, Tetrahymena pyriformis, by assaying transmembrane ferricyanide reduction and the reduction of iron compounds. The rates of ferricyanide reduction varied between 0.5 and 2.5 mumol/g dry wt. per min, with a pH optimum at 7.0-7.5. Other active non-permeable electron acceptors, with redox potentials from +360 to -125 mV, were cytochrome c, hexaammine ruthenium chloride, ferric-EDTA, ammonium ferric citrate, and indigo di-, tri- and tetrasulfonates. It was found that Tetrahymena cells can reduce external electron acceptors with redox potentials at pH 7.0 down to -125 mV. Ferricyanide stimulates ciliary action. Transmembrane ferricyanide reduction by Tetrahymena was not inhibited by such mitochondrial inhibitors as antimycin A, 2-n-heptyl-4-hydroxyquinoline N-oxide, or potassium cyanide, but it responded to inhibitors of glycolysis. Transmembrane ferricyanide reduction by Tetrahymena appears to involve a plasma membrane electron transport chain similar to those of other animal cells. As in other cells, the transmembrane electron transport is associated with proton release which may be involved in internal pH control. The transmembrane redox system differs from that of mammalian cells in a 20-fold greater sensitivity to chloroquine and quinacrine. The Tetrahymena ferricyanide reduction is also inhibited by chlorpromazine and suramin. Sensitivity to these drugs indicates that the transplasma membrane electron transport and associated proton pumping may be a target for drugs used against malaria, Trypanosomes and other protozoa.

Animals↗