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PubMed2005

Acclimation to diverse environmental stresses caused by a suppression of cytosolic ascorbate peroxidase in tobacco BY-2 cells.

The active oxygen species (AOS) that arise from normal metabolic processes are kept under tight control by various antioxidant mechanisms. AOS are important signal molecules that regulate many physiological processes, including environmental stress responses. In this work, we have investigated the effect of lowered cytosolic ascorbate peroxidase (APX) activity in transgenic tobacco BY-2 cells, using two transformed BY-2 cell lines, cAPX-S2 and cAPX-S3, resulting from co-suppression by expression of Arabidopsis APX1 cDNA under the cauliflower mosaic virus (CaMV) 35S promoter. cAPX-S2 and cAPX-S3 possessed 50 and 75% lower cytosolic APX activity, respectively, compared with that in the untransformed cells. Chemical fluorescence analysis indicated that the AOS levels were markedly higher in the two APX-suppressed cell lines than in the wild-type cells. However, there were no substantial differences in the activity levels of the various other antioxidant enzymes. Interestingly, the APX-suppressed cells showed different responses and tolerances to environmental stresses, such as heat and salinity. Suppression subtractive hybridization revealed that several heat- and salt stress-inducible genes were up-regulated in cAPX-S3 cells. HSP70, DnaJ-like protein and purple acid phosphatase were among the constitutively induced genes. An in-gel kinase assay suggested that a mitogen-activated protein (MAP) kinase of approximately 46 kDa was predominantly active in the APX-suppressed cells, and transcript levels of both nicotiana protein kinase 1 (NPK1) and nucleoside diphosphate kinase 2 (NDPK2) were up-regulated. These data suggest the possibility that MAP kinase cascades are activated by subtle imbalances in the homeostasis of the cellular redox status caused by lowered cytosolic APX activity.

Ascorbate Peroxidases↗
PubMed2004

Safety and effectiveness of a new saline filled testicular prosthesis.

PURPOSE: Testicular prostheses have been used for 50 years to replace missing or removed testes. In 1995 the manufacture of the silicone gel filled testis prosthesis in the United States was discontinued because of concern about the safety profiles of other implants. We assessed the safety and effectiveness of a new, saline filled implant for testicular replacement. MATERIALS AND METHODS: This open label, multicenter, prospective, case controlled clinical trial was done at 18 American tertiary referral centers. Adult and pediatric male patients missing 1 or 2 testes and without evidence of active malignancy or rheumatological disease were enrolled. All patients underwent formal rheumatological and urological evaluation prior to and after prosthesis placement. Main outcome measures were prosthesis safety assessed by adverse events and effectiveness assessed by changes in testis dimension. Secondary outcome measures were quality of life assessments with 3 validated instruments. All patients were followed a minimum of 1 year in this 5-year study. RESULTS: Postoperative adverse events observed in 19% of 149 patients included device related discomfort or pain in 3%, scrotal edema in 1.3%, infection in 1.3%, extrusion in 2.6%, deflation in 0.7% and pulmonary emboli in 0.7%. No patient reported rheumatological symptoms at 1 year. Testis dimensions were significantly increased in patients missing a testis at baseline (p <0.001). Subjective assessment of testicular appearance was significantly improved (p <0.001) and scores were stable or significantly improved in 2 of 3 quality of life instruments. CONCLUSIONS: At short-term followup a new, saline filled testis prosthesis appears safe and well tolerated. Importantly validated self-esteem measures also suggest improvement in quality of life after prosthesis placement.

Adolescent↗
PubMed1998

Comparison of spontaneous and induced sputum for investigation of airway inflammation in chronic obstructive pulmonary disease.

BACKGROUND: Although sputum induction is used as a technique to investigate lower airway inflammation in asthmatic subjects, advantages over spontaneous sputum in patients with chronic obstructive pulmonary disease (COPD) have not been investigated. METHODS: Samples of spontaneous sputum and sputum induced with 3% hypertonic saline for 14 minutes were collected from 27 patients with chronic obstructive pulmonary disease (COPD) who usually produced spontaneous sputum. Spirometric indices and oxygen saturation (Sao2) were measured at seven minute intervals. The spontaneous, seven and 14 minute sputum samples were analysed for total and differential cell counts, cell viability, and interleukin 8 levels. RESULTS: Analysis of the sputum revealed that median cell viability was higher in the seven minute (62.8%; p = 0.004) and 14 minute (65%; p = 0.001) induced sputum samples than in spontaneous sputum (41.2%). There was no significant difference in total and differential cell counts or in interleukin 8 levels between spontaneous and induced sputum. During the sputum induction procedure the mean (SD) fall in forced expiratory volume in one second (FEV1) was 0.098 (0.111) 1 (p < 0.001) and in forced vital capacity (FVC) was 0.247 (0.233) 1 (p < 0.001). There was a small but significant fall in Sao2 during sputum induction (p = 0.03). CONCLUSIONS: Induced sputum contains a higher proportion of viable cells than spontaneous sputum. There are no significant differences between the sputum samples obtained at seven minutes and at 14 minutes of hypertonic saline nebulisation. Sputum induction is safe and well tolerated in patients with COPD.

Aged↗
PubMed2004

Effects of short-term chemical ablation of the GIP receptor on insulin secretion, islet morphology and glucose homeostasis in mice.

Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone secreted by endocrine K-cells in response to nutrient absorption. In this study we have utilized a specific and enzymatically stable GIP receptor antagonist, (Pro3)GIP, to evaluate the contribution of endogenous GIP to insulin secretion and glucose homeostasis in mice. Daily injection of (Pro3)GIP (25 nmol/kg body weight) for 11 days had no effect on food intake or body weight. Non-fasting plasma glucose concentrations were significantly raised (p<0.05) by day 11, while plasma insulin concentrations were not significantly different from saline treated controls. After 11 days, intraperitoneal glucose tolerance was significantly impaired in the (Pro3)GIP treated mice compared to control (p<0.01). Glucose-mediated insulin secretion was not significantly different between the two groups. Insulin sensitivity of 11-day (Pro3)GIP treated mice was slightly impaired 60 min post injection compared with controls. Following a 15 min refeeding period in 18 h fasted mice, food intake was not significantly different in (Pro3)GIP treated mice and controls. However, (Pro3)GIP treated mice displayed significantly elevated plasma glucose levels 30 and 60 min post feeding (p<0.05, in both cases). Postprandial insulin secretion was not significantly different and no changes in pancreatic insulin content or islet morphology were observed in (Pro3)GIP treated mice. The observed biological effects of (Pro3)GIP were reversed following cessation of treatment for 9 days. These data indicate that ablation of GIP signaling causes a readily reversible glucose intolerance without appreciable change of insulin secretion.

Animals↗
PubMedDate not supplied

Radiofrequency capacitive heating of deep-seated tumours using pre-cooling of the subcutaneous tissues: results on thermometry in Dutch patients.

The capacity of a radiofrequency, 13.56 MHz, capacitive hyperthermia system using extensive pre-cooling of the subcutaneous tissue to induce locoregional deep heating has been investigated in 11 patients. Tumour location was presacral in nine--and eccentric towards the lateral side of the pelvis in two patients. For thermometry multiple catheters (mean 2.7) were inserted into the treatment volume. The mean numbers of temperature measuring points per treatment were 9.4 in tumour, 5.5 in muscle and 7.2 in subcutaneous fat. RF energy was applied after 30 min of cooling through two flexible boli perfused with saline water at 5-10 degrees C. Patient tolerance to pre-cooling was very good and after some initial discomfort the patient became rapidly accustomed to the cold water boli. For some patients better temperatures were achieved when the conventional anterior-posterior applicator set-up was replaced by a set-up with an applicator on each lateral side of the patient. As patients can tolerate temperatures within the fat tissue as high as 45.5 degrees C without complaining it appears important to monitor the temperature at the transition of fat to muscle tissue to prevent subcutaneous burns. The study shows that pre-cooling cannot avoid preferential heating at the interface from fat to muscle tissue. In this patient group the quality of the hyperthermia treatment appeared to be rather poor: 60% of the measured tumour temperatures were below 40 degrees D.

Adipose Tissue↗
PubMed1993

Intrathecal baclofen down-regulates GABAB receptors in the rat substantia gelatinosa.

At present, it is not clear why drug tolerance develops in patients receiving intrathecal baclofen for the chronic treatment of spasticity of spinal origin. To investigate the mechanisms of tolerance to the gamma-aminobutyric acid (GABAB) agonist baclofen, rats were implanted with intrathecal catheters and continuously infused with either the drug or saline for 1, 3, or 7 days. The dose chosen, 1 microgram/hr, initially caused profound hindlimb motor weakness, but by Day 7 the rats had adapted to the drug and exhibited only minimal motor impairment. The animals were sacrificed on Day 1, 3, or 7 and quantitative autoradiography was used to determine the binding density and affinity of the GABAB receptors in the substantia gelatinosa of the lumbar spinal cord. After 1 day of drug infusion there was no change in binding parameters, but after 3 and especially after 7 days there was a significant decrease in the GABAB binding density (74% and 66%, respectively) in baclofen-treated rats as compared to saline-treated control rats. This GABAB receptor down-regulation correlated with tolerance to the motor weakness in the baclofen-treated animals and suggests that similar mechanisms contribute to drug tolerance in patients.

Animals↗
PubMedDate not supplied

[Methods for studying the motility in the small intestine, colon and recto-anal area].

Small bowel and colonic motility can be studied either indirectly by the determination of the transit time or directly in recording bowel contractions. Small bowel transit time is usually assessed with the H2-breath test when colonic transit time is mainly determined fluoroscopically in studying the progression of radiopaque markers along the large bowel. Scintigraphic techniques are promising but not routinely used techniques. In the small bowel, gut contractions are recorded with manometric probes. To study colonic movements, electromyography is more usual than manometry. In both cases, whatever the technique employed, the large inter- and intra (topographic and nycthemeral) variability need to be considered for the interpretation of the motor patterns. Rectoanal studies led to consider two aspects: how the rectum acts as a reservoir and anal function. The ability of the rectum to be a reservoir is assessed either by the volume remaining in the rectum during the rectal perfusion with saline or by the determination of the maximal tolerable volume of distension. Manometry and/or electromyography test anal function at rest and during a rectal distension, straining or a voluntary contraction.

Anal Canal↗
PubMed1988

Glucose kinetics in rats infused with endotoxin-induced monokines or tumor necrosis factor.

This study was conducted to determine if macrophage elaborated monokines in general, and human recombinant tumor necrosis factor (hrTNF alpha) in particular alter glucose metabolism in a manner analogous to that observed in endotoxin-treated animals. Endotoxin-tolerant rats were infused for 3 hr with saline, E. coli endotoxin (100 micrograms/l weight) or monokines contained in conditioned media from endotoxin-stimulated RAW 264.7 cells (1 microgram/ml). Compared to saline- and endotoxin-infused rats, animals receiving the monokine mixture had no change in mean arterial blood pressure or heart rate but exhibited overt signs of morbidity including stupor and diarrhea. Monokine-infused rats remained euglycemic but had elevated lactate concentrations and a 15-30% increase in glucose rate of appearance (Ra). Nontolerant rats received a 3 hr infusion of saline, hrTNF alpha (15 micrograms/100 g), or heat-treated hrTNF alpha. HrTNF alpha infusion increased glucose Ra about 25% compared to the two control groups but did so without producing signs of morbidity seen in the monokine infused animals. Serum TNF levels were 6-fold higher in rats infused with the monokine mixture compared to animals infused with hrTNF alpha, and this reflected the different levels of TNF contained in the monokine mixture and hrTNF alpha infusates. Plasma insulin, glucagon, and catecholamine concentrations were increased in rats infused with either the monokine mixture or hrTNF alpha, but the increases were more pronounced in rats receiving the monokine mixture. The results demonstrate that monokines and hrTNF alpha increase glucose production in vivo, and that the effect may be mediated by endocrine changes known to influence glucose homeostasis.

Animals↗
PubMed1977

Fibrinolytic, factor VIII and pulse rate responses to repeated adrenaline infusion followed by haemorrhage.

The role of catecholamines in the activation of coagulation and fibrinolysis following surgery remains controversial. In this study 5 dogs were infused with 1,2,3,6,9 and 12 microgram kg-1 min-1 of adrenaline at twice weekly intervals and were then reexposed to 3 microgram kg-1 min-1. Pulse rate and factor VIII increased after infusion of 1,2 and 3 microgram kg-1 min-1 but thereafter there was a diminished response and no response on reexposure to 3 microgram kg-1 min-1 although this was not significant in the case of pulse rate. Euglobulin lysis time shortened after each infusion of adrenaline and showed no development of tolerance. A control series of dogs infused with saline showed no similar changes. Both groups of animals were then bled to a blood pressure of 60 mm Hg for 60 minutes. Pulse rate and factor VIII did not change but euglobulin lysis time shortened in both groups. The results suggest that the activation pathways for changes in factor VIII and euglobulin lysis time induced by adrenaline are separate.

Animals↗
PubMed1994

Intranasal administration of retinal antigens suppresses retinal antigen-induced experimental autoimmune uveoretinitis.

Bovine retinal extract (RE) is a heterologous mixture of highly uveitogenic proteins including S-Antigen (S-Ag), interphotoreceptor retinol binding protein (IRBP) and rhodopsin, and is a potent inducer of experimental autoimmune uveoretinitis (EAU). Intranasal inoculation of Lewis rats with RE performed daily for 10 days prior to immunization with RE suppresses both the severity and the incidence of the clinical response and histopathological changes in EAU. Significant suppression of the disease in treated animals could be achieved with a total (cumulative) intranasal inoculum of 42 micrograms of antigen. Animals which were treated with extract exhibited a normal total antibody response to S-Ag, IRBP and retinal extract when compared with controls [phosphate-buffered saline (PBS) treated] animals. The antibody response in tolerized animals was predominantly anti-S-Ag IgG2a with suppression of anti-S-Ag IgM response. Treated animals had a significantly suppressed delayed-type hypersensitivity (DTH) response to retinal extract but normal response to purified protein derivative (PPD) compared to control animals. Adoptive transfer of splenocytes from treated animals also demonstrated some protection against RE-induced EAU. These results demonstrate that tolerance induction impairs the onset and severity of EAU by inhibiting the DTH response to heterologous mixture of retinal antigens.

Administration, Intranasal↗
PubMed1993

[Preventive treatment of hemodynamic disorders during conventional spinal anesthesia].

The prevention of blood pressure fall during a conventional spinal anaesthesia effected with 20 mg (4 ml) of isobaric 0.5 p. 100 bupivacaine relies on the use of vascular filling and/or a vasoconstrictor. A randomized prospective study was performed to evaluate the comparative efficacy of these two treatments. 148 patients were included and divided into three groups. Group I (n = 50): 2.5 mg IV bolus of etilefrine followed by continuous infusion (0.35 mg.kg-1.h-1). Group II (n = 50): 30 ml.kg-1 infusion of saline isotonic solution for 90 min, with infusion rate according to blood pressure. Group III (n = 48) did not receive any preventive treatment. A blood pressure fall of more than 30% of the initial value was observed in 59 patients: 18% of the etilefrine group, 28% of the saline infusion group, 54% of the control group. This peculiar frequency of hypotension in the control group emphasizes the need of a preventive treatment. Haemodynamic changes were fewer and less important in the etilefrine group compared with the saline infusion group. No failure and a better tolerance in the vasoconstrictor group were also to be noticed. These clinical data suggest that etilefrine could meet satisfactorily the therapeutic requirements.

Anesthesia, Spinal↗
PubMed1984

Use of nitrifying activity measurements for describing the effect of salinity on nitrification in the Scheldt estuary.

Nitrifying activity measurements, carried out on freshly collected samples from an estuarine environment, show that the composition of the nitrifier population undergoes a progressive modification during the mixing of freshwater masses in seawater, with increasing tolerance to salt. As a result, the overall effect of increasing salinity on nitrification is much less severe than the direct effect of salt on the freshwater nitrifying population.

Fresh Water↗
PubMed1994

Glucagon-like peptide 1 enhances glucose tolerance both by stimulation of insulin release and by increasing insulin-independent glucose disposal.

Glucagon-like peptide 1 [7-36 amide] (GLP-1) has been shown to enhance insulin secretion in healthy and type II diabetic humans, and to increase glucose disposal in type I diabetic patients. To further define its action on glucose kinetics, we studied six healthy subjects who received either GLP-1 (45 pmol/kg per h) or 150 mM saline on two mornings during which a modified intravenous glucose tolerance test was performed. Plasma insulin and glucose levels were analyzed using Bergman's minimal model of glucose kinetics to derive indices of insulin sensitivity (SI) and glucose effectiveness at basal insulin (SG), the latter a measure of glucose disposition independent of changes in insulin. In addition, basal insulin concentrations, the acute insulin response to glucose (AIRg), plasma glucagon levels, and the glucose disappearance constant (Kg) were measured on the days that subjects received GLP-1 or saline. Compared with saline infusions, GLP-1 increased the mean Kg from 1.61 +/- 0.20 to 2.65 +/- 0.25%/min (P = 0.022). The enhanced glucose disappearance seen with GLP-1 was in part the result of its insulinotropic effect, as indicated by a rise in AIRg from 240 +/- 48 to 400 +/- 78 pM (P = 0.013). However, there was also an increase in SG from 1.77 +/- 0.11 to 2.65 +/- 0.33 x 10(-2).min-1 (P = 0.038), which was accounted for primarily by insulin-independent processes, viz glucose effectiveness in the absence of insulin. There was no significant effect of GLP-1 on SI or basal insulin, and glucagon levels were not different during the glucose tolerance tests with or without GLP-1. Thus, GLP-1 improves glucose tolerance both through its insulinotropic action and by increasing glucose effectiveness. These findings suggest that GLP-1 has direct effects on tissues involved in glucose disposition. Furthermore, this peptide may be useful for studying the process of insulin-independent glucose disposal, and pharmacologic analogues may be beneficial for treating patients with diabetes mellitus.

Adult↗
PubMed1989

The growth factor from plerocercoid larvae of the tapeworm, Spirometra mansonoides, stimulates growth but is not diabetogenic.

A factor produced by plerocercoids of the tapeworm Spirometra mansonoides is similar to human growth hormone (hGH) in that it stimulates body growth, binds to hGH receptors, cross-reacts with anti-hGH antibodies, and has lactogenic and insulin-like activities. The purpose of this study was to determine whether plerocercoid growth factor (PGF) is similar to hGH in expressing diabetogenic activity in the genetically obese (ob/ob) mouse. To determine an effective dose for use in the obese mice, the ability of daily injections of PGF to stimulate growth of phenotypically normal mice of the same strain was assessed in a 10-day weight gain assay. Injections of PGF stimulated a dose-dependent weight gain (r = 0.83) and 25 ng eq/day of PGF stimulated a response not significantly different from that produced by 100 micrograms of bovine growth hormone/day. Diabetogenicity was assessed using fasting blood glucose and glucose tolerance tests in obese mice that had been injected for 3 days with saline, hGH, or PGF. Human growth hormone caused a significant increase (P less than 0.005) in fasting blood glucose and glucose tolerance of the obese mice was impaired (P less than 0.01). All of the doses of PGF used to test diabetogenicity in the obese mice were at least twice that required to stimulate a maximal growth response in normal mice, yet none of the doses of PGF increased fasting blood glucose or decreased glucose tolerance. These results show that PGF was a potent growth stimulant but was not diabetogenic.

Animals↗
PubMed1992

Tolerance to nicotine following chronic treatment by injections: a potential role for corticosterone.

C57BL/6 male mice were injected intraperitoneally with nicotine (2.0 mg/kg) or saline three times each day (0800 h, 1300 h and 1800 h) for a period of 12 days and then tested for nicotine tolerance using a series of behavioral and physiological tests. For each of these tests, animals that received chronic nicotine treatment were significantly less sensitive to nicotine challenge than were animals that received chronic saline treatment, as indicated by shifts to the right of dose-response curves. Animals were retested for nicotine sensitivity 2 weeks following cessation of chronic nicotine injections. Tolerance to acute nicotine challenge persisted in nicotine-treated animals. Chronic nicotine treatment by injections did not alter the binding of L-[3H]-nicotine or alpha-[125I]-bungarotoxin in any of eight brain regions. Plasma corticosterone (CCS) levels were determined in animals prior to the initiation of the injection series (day 0), and on days 4, 8 and 12 of chronic treatment, immediately before the first injection of the day. CCS levels in nicotine-treated animals were elevated as compared to saline-injected controls by day 12 of treatment. Nicotine-treated animals also had elevated CCS levels 2 weeks after the last chronic injection. Nicotine-treated animals were, however, tolerant to nicotine-induced CCS release. Since previous studies from our laboratory have demonstrated that plasma CCS levels are inversely correlated with sensitivity to nicotine, it is possible that the tolerance to nicotine measured following chronic treatment by injections is due, at least in part, to the elevation in plasma CCS levels.

Animals↗
PubMed1998

Interaction of intrathecally infused morphine and lidocaine in rats (part II): effects on the development of tolerance to morphine.

BACKGROUND: There has been little information regarding the effects of local anesthetics on tolerance to opioids, although chronic use of combination of opioids and local anesthetics is popular for pain control. This study was designed to examine the effects of lidocaine on morphine tolerance to somatic and visceral antinociception. METHODS: Rats received a continuous intrathecal infusion of morphine (0.3-10 microg x kg(-1) x h(-1)), lidocaine (30-1000 microg x kg(-1). h(-1)), a combination of those, or saline. After 6- day infusion, intrathecal morphine challenge test (5 microg/10 microl) was performed, and time-response curve was constructed to assess the magnitude of tolerance. The tail flick (TF) test and colorectal distension (CD) test were used to measure somatic and visceral antinociceptive effects, respectively. RESULTS: Antinociceptive effects in the TF and CD tests caused by morphine challenge were reduced (P < 0.01) in the morphine infused groups. The magnitude of the tolerance was inversely associated with the amount of morphine infused. Lidocaine infusion induced no different change in the morphine challenge test from that seen in the saline infusion group. Development of tolerance was greater in morphine 3 microg x kg(-1) h(-1) than in morphine 0.75 microg x kg(-1) x h(-1) + lidocaine 150 microg x kg(-1) x h(-1) despite their similar antinociceptive effects during intrathecal infusion. The infusion of a low dose of morphine (0.3 microg kg(-1) x h(-1)) did not reduce the antinociceptive effects in the challenge test. CONCLUSION: Lidocaine in combination with morphine does not reduce tolerance to morphine nor develop cross-tolerance. The intrathecal infusion of morphine induced tolerance to somatic and visceral antinociception in a dose-dependent fashion.

Analgesics↗
PubMed1983

Response specificity of behaviorally augmented tolerance to ethanol supports a learning interpretation.

A modified before-after design was used to assess the influence of behavioral contingencies on the development of tolerance to ethanol, monitored with both a behavioral (moving belt, shock avoidance) task and a physiological (body temperature) response measure. Male Long-Evans rats received ethanol (2.0 g/kg IP) and daily moving belt training under one of four conditions: (1) daily injection of ethanol before moving belt sessions; (2) daily injection of ethanol after belt sessions, with intermittent intoxicated practice; (3) daily injection of ethanol after belt sessions, with no intoxicated practice; (4) daily injections of saline, with intermittent intoxicated practice. After a 28-day tolerance acquisition phase, all groups received a final moving belt test and temperature assessment after injection of ethanol. Development of tolerance to the motor effects of ethanol was seen only in animals receiving daily injections before behavioral training. By contrast, tolerance to the hypothermic effect of ethanol developed equally in all groups. The augmented development of tolerance to the motor effects of ethanol may not, therefore, indicate a generalized state of neuronal adaptation; rather, it appears to reflect a fairly specific response acquired by the organism.

Animals↗
PubMed1975

Uptake into brain proteins of 35S-methionine during morphine tolerance.

Effect of morphine sulfate on protein synthesis in rat brain was evaluated in tolerant and nontolerant rats. Male Wistar-Lewis rats were randomly distributed to control, tolerant and nontolerant groups. The rats were made tolerant by giving morphine sulfate (25 mg/kg b.i.d.) for either 42 or 84 days. An aqueous solution of 35S-methionine (0.5 muc/g b.w.t.) was administered i.v. Rats from each group were then sacrificed at 20 minutes, 1 hour and 2 hours after 35S-methionine. The 35S-activity in trichloroacetic acid-precipitated proteins and supernatant fractions from cortex, hypothalamus, putamen, corpus callosum, thalamus, cerebellum, kidney and liver was determined. In addition the amounts of label in lipid, saline-soluble and insoluble proteins of whole brain for tolerant and control rats were determined. The 35S-activity in brain proteins of non-tolerant rats did not differ from those of controls. The six brain areas in tolerant rats 1 and 2 hours after injection of 35S-methionine showed a 15 percent, then 30 percent increase in radioactivity (disintegrations per minute per milligram of protein). Proteins from putamen and corpus callosum had w/w 60 percent of the 35S-activity found in hypothalamus and cortex. There was no difference in 35S-activity in kidney and liver between control and tolerant rats. The radioactivity of the brain lipids was 2 percent of that found in proteins in both tolerant and control groups. Protein synthesis in morphine tolerant rat brain is significantly (P smaller than .01) increased as judged by incorporation of 35S-methionine.

Animals↗