Concomitant Disturbances Research Articles

The Activity of Ornithine Transcarbamoylase and Arginase During Mechanical Jaundice in the Rat Model

The pathogenesis of morbidity and mortality associated with intervention of the biliary system in patients with obstructive jaundice is unknown. Mechanical jaundice initiates the development of morphological changes in hepatocytes with concomitant disturbances in metabolism. These are followed by changes in enzyme activity in hepatocytes and peripheral blood. Wistar rats were divided into three groups: group 1, sham-operated controls; group 2, rats with permanent jaundice; and group 3, rats with temporary mechanical jaundice. The animals were examined at 2 weeks (groups A), 4 weeks (groups B) and 6 weeks (groups C) after surgery. We explored the impact of induced mechanical jaundice on the activity of selected urea cycle enzymes (arginase [E.C.3.5.3.1] and ornithine transcarbamoylase (OTC) [E.C.2.1.3.3]). Mechanical jaundice was found to induce changes in hepatocytic metabolism, which in turn led to disturbances in the urea cycle and the process of transamination. After relief of the mechanical jaundice (recanalization of the common bile duct), the urea cycle activity in the liver was greatly increased despite the normalization of the basic biochemical indices. The results of the experiment confirmed the hypothesis that long-term mechanical jaundice causes lasting disturbances in hepatocytic metabolism. We conclude that the rate of nitrogen metabolism is higher after recanalization of the bile duct.

Incidence and rate characteristics of atrial tachyarrhythmias in patients with a dual chamber defibrillator.

Atrial tachyarrhythmias play an important role in the treatment of patients with malignant ventricular tachyarrhythmias not only with respect to inappropriate discharges but also to left ventricular function and stroke risk. A combined dual chamber defibrillator provides separate therapies for atrial and ventricular tachyarrhythmias. To assess the incidence of atrial tachyarrhythmias in patients with this dual chamber implantable defibrillator, 40 patients with ventricular tachyarrhythmias and concomitant atrial tachyarrhythmias and/or AV conduction disturbances were included in a prospective study. During a mean follow-up of 25 +/- 11 months, 26 of 40 patients had a total of 1,430 recurrences of atrial tachyarrhythmias. The vast majority of the atrial tachyarrhythmias with regular atrial cycles had a mean median atrial cycle length of 235 +/- 37 ms and a mean duration of 34 +/- 144 minutes. Atrial tachyarrhythmias with irregular atrial cycles exhibited a median atrial cycle length of 198 +/- 31 ms and had a mean duration of 246 +/- 1,264 minutes. In addition, 67% of 375 tachyarrhythmias, in which the median ventricular cycle length during the ongoing episode could be documented, had a ventricular rate <100 beats/min. Continuous atrial arrhythmia detection with a dual chamber ICD reveals a high incidence of atrial tachyarrhythmias with a predominantly short duration of paroxysmal recurrences <1 hour in the vast majority of episodes.

Organic contaminants in soil

For scientists, there is no shortcut to performing serious soil ecotoxicology. A fate description of the contaminants is included to explain effects; sometimes the effect assessment must be used to point to the presence of a chemical even though the fate is not clearly understood. Details of fate and effects are sometimes useless for risk assessment due to a lack of precision or a failure to link convincingly the fate to the effects or the biological parameters to the healthiness of the ecosystem. This is not a surprise in the single risk assessment case because limited resources preclude an iterative research strategy to reveal the mechanisms. Widespread risk assessment practices based on legislation, however, provide shortcuts by requiring an effect assessment derived from single-species laboratory tests. To derive predicted no-effect concentrations (PNECs) such tests have hitherto been used in connection with assessment factors and more recently with species sensitivity distribution models [1]. The latter assumes that the PNEC can be based on a complement of independent single-species toxicity data. During a conference held in Copenhagen Denmark that focussed on the fate and effects of organic contaminants in soil, it was shown that species interactions indeed are important for the toxicity levels of the individual species. Multispecies tests performed in a standardized manner are now slowly emerging, and they obviously include species interactions. Realism is gained at the cost of interpretability. This does not pose a problem, however, because interpretability is not paramount for risk assessment. There is still an important need to integrate the available information on the effects of all kinds of factors exerting environmental influences. Aging and bioavailability of the organic contaminants must be included and will greatly change the ecotoxicological setting of limit concentration in soil [2]. Subtle knowledge of chemical fate and effects is useless in the process of making sound environmental risk assessment if concomitant disturbances from other human or natural sources are not included. The risk assessment procedure would gain respect from all parties—academia, industry and environmental protection agencies—if it could be done in an integrated risk assessment process. Soil management in agriculture is a good example of an important factor whose impact can surmount effects of chemicals in many cases or change bioavailability in others. The reluctance to provide more environmental information is not rational; improved risk assessments will most probably ease the burden of administrating low-limit values and ensure that hazard is not overestimated. Variability in soil physicochemical properties represents a substantial scientific challenge to understanding the toxicology of soil contaminants. Bioavailability of organic soil contaminants became the driving theme of the Copenhagen meeting, and the role of this subject will have increased importance in the future. Scientists must focus on the general applicability of their results and consider the soil-aging factor as a major sink of persistent organic compounds. The political importance of this subject was clearly demonstrated: One leading Danish newspaper devoted its front page to quoting Martin Alexander on the role of aging in risk assessment of contaminated soils. In this issue of Environmental Toxicology and Chemistry you will find a selection of papers presenting current research on biodegradation and chemical availability.

Effects of PEEP on systemic venous capacitance.

The aim of the present study was to determine effects of positive end expiratory pressure (PEEP) application on peripheral venous capacitance and relate them to concomitant central hemodynamic disturbances. The venous volume-pressure (V/P) relationships were studied in 6 intact anesthetized pigs to describe the effects of PEEP on systemic venous compliance (computed as the slope of the V/P relationship) and unstressed volume (referred to as the extrapolated volume intercept). Cardiac volumes as well as partitioning of circulating blood volume between central (ITBV) and peripheral (PBV) compartments were assessed by thermo-dye dilution techniques. During a 15 cm H2O PEEP application, venous compliance was reduced by 48%, while unstressed volume was increased by 25% and peripheral blood pooling increased from 63 to 74%. As a result, left heart and right ventricular end diastolic volumes were decreased by 8% and by 44%, respectively. It is concluded that increased venous unstressed volume and reduced compliance depicted the distension of the venous tree secondary to PEEP which acted as an impediment to venous return. As a consequence, cardiac output was reduced because of decreased preload.

Oxidative Damage to Nucleic Acids in Human Prion Disease

Recently, several studies proposed a physiological role for the cellular prion protein (PrPc) in defense against oxidative stress. Since the pathogenesis of prion disease necessarily involves a disturbance of PrPc homeostasis, we hypothesized that such diseases would be associated with concomitant disturbances in oxidative balance. In support of such a notion, in this study we show increased oxidative damage to nucleic acids in affected brains of patients with Creutzfeldt–Jakob disease. These data suggest that damage by free radicals is a likely cause for neurodegeneration in human prion disease, and antioxidants are a potential therapy for these disorders. Further, our data support the hypothesis that loss of the anti-oxidant function of PrPc plays a key role in the pathogenesis of these disorders.

Diagnosis of aphasia on the stroke unit

The first weeks of aphasia are called the acute stage. The rapid change and possible fluctuation of language deficits at that stage as well as concurrent phenomena such as drive disturbances, apraxia, or perseveration pose particular requirements for aphasia diagnosis. Professional language diagnosis in a stroke unit is necessary for detailed description of the language deficits, differential diagnosis of concomitant cognitive or functional disturbances, and a description of the dynamics of the deficits to start with specific therapeutical interventions as soon as the patient's health status allows. There are three published German aphasia test batteries especially constructed for diagnosis of acute aphasia language deficits. They differ with respect to content and pragmatic aspects and offer a range of applications, including the diagnosis of aphasia, recommendations for therapy, and the use in scientific studies.

Radiotherapy-related fatigue: how to assess and how to treat the symptom. A commentary.

Acute and chronic radiotherapy-related fatigue occurs in up to 80% and 30%, respectively, of patients undergoing irradiation for cancer. Frequently, the symptom is not expected by the patients and is underestimated by medical and nursing staff. Fatigue can affect global quality of life more than pain, sexual dysfunction and other cancer- or treatment-related symptoms. Its etiology and correlates are not clear. Published reports are mainly descriptive, and in many of them numerous methodological biases are present. One of the limitations is lack of a standard method of assessment that could simplify the comparison between different series. In the last decade, modern instruments have been designed to measure fatigue. They include uni- and multidimensional tools. Use of these specific instruments is highly recommended for research on radiation-related fatigue. In daily practice when time is limited, simple assessment is necessary. For example, systemic use of plain and easily understandable questions about fatigue, its level and impact on daily life could be sufficient and reliable. Therapeutic strategies for radiotherapy-induced fatigue have not yet been clearly defined, but a few randomized studies have been recently published. Physical exercise, group psychotherapy and relaxation therapy have been demonstrated to be effective. Moreover, pharmacological treatment of concomitant disturbances (anemia, pain, insomnia, depression, dehydration, infection, malnutrition) and other radiotherapy side effects (diarrhea, hormonal insufficiency etc.) should be considered. Further methodologically correct studies are warranted to better define the causes, optimal prevention, assessment and management of this symptom.

Inhibition of platelet aggregation in baboons: therapeutic implications for xenotransplantation.

Activation of endothelial cells and platelet sequestration play major roles in rejection of xenografts. The histopathology of both hyperacute and acute vascular or delayed rejection of vascularized discordant xenografts is characterized by interstitial hemorrhage and intravascular thrombosis. Agents that prevent platelet activation and consequent microthrombus formation have proven beneficial in xenograft rejection but do not fully preclude vascular thrombosis. Recently, several new anti-platelet therapies have undergone extensive clinical testing for atherosclerotic thrombotic vascular disorders; other putative therapies are undergoing pre-clinical evaluation. We have investigated the effect of several of these novel agents on platelet aggregation in baboons in order to screen for future potential in xenograft rejection models. Drugs tested in these experiments were aurintricarboxylic acid (ATA, von Willebrand Factor-GPIb inhibitor), fucoidin (a selectin-inhibitor), 1-benzylimidazole (1-BI, thromboxane synthase antagonist), prostacyclin (PGI2, endothelial stabilizer), heparin (thrombin antagonist), nitroprusside sodium or nicotinamide (NPN or NA, both NO-donors), and eptifibatide (EFT, GPIIb/IIIa receptor antagonist). These were infused intravenously to nine baboons. Coagulation parameters and platelet counts were monitored and baboons were observed for adverse side-effects. The efficacy of these agents in inhibiting platelet aggregation was assayed in a platelet aggregometer. Treatment with ATA and fucoidin resulted in complete inhibition of platelet aggregation but also in major perturbation of coagulation parameters. 1-BI and PGI2 had no effect when administered alone, but in combination resulted in moderate inhibition of aggregation without disturbance in PT or PTT. NPN and NA had no substantive effects on platelet aggregation. Heparin resulted in specific inhibition of thrombin-induced platelet aggregation and, as anticipated, was associated with moderate prolongation of PTT. Importantly, EFT caused complete inhibition of platelet aggregation without changes in coagulation. Platelet counts, fibrinogen levels, and fibrinogen degradation products remained within the normal ranges in all experiments. Although excellent inhibition of platelet activation was obtained with ATA and fucoidin, clinical use may be precluded by concomitant disturbances of coagulation. Combinations of heparin and EFT may prove beneficial in preventing the thrombotic disorders associated with xenograft rejection while maintaining adequate hemostatic responses. These agents are to be evaluated in our pig-to-primate xenotransplantation models.

Donepezil in the treatment of cognitive dysfunction associated with traumatic brain injury.

Cholinesterase inhibitors are known to enhance cognitive function among patients with dementia of the Alzheimer's type. It is quite possible that this clinical benefit may extend to other patient groups, yet this issue awaits further exploration. This study examines the use of the cholinesterase inhibitor donepezil in the treatment of patients with a history of brain injury and subsequent cognitive impairment. The sample was comprised of 53 ambulatory psychiatric patients who were receiving care for psychiatric sequelae of brain injury. In this sample, residual cognitive impairment was treated with adjunctive donepezil. This study reports the clinical assessments of this patient sample in outpatient follow-up for up to two years duration. Assessments of cognition with the Wechsler Adult Intelligence Scale-Revised and the Hooper Visual Organization Test were obtained on a subset of this sample (N = 22). Clinician assessment ratings were analyzed for the entire sample. Results indicated an improvement in full-scale IQ (t = 2.5, p = 0.02) score as well as clinician-based ratings (t = 12.2, p < 0.0001). Further research will likely delineate whether specific types of brain injuries are most responsive to cholinesterase inhibitors. These findings suggest that donepezil may enhance clinical response by complementing the medication management of other concomitant psychiatric disturbances related to brain injury.

The epidemiology of functional gastrointestinal disorders.

Functional gastrointestinal disorders are most commonly divided into gastro-oesophageal reflux disease (GORD), dyspepsia and the irritable bowel syndrome (IBS). GORD is defined as having predominant reflux symptoms, and is nowadays not considered to be a subgroup of dyspepsia. Dyspepsia is divided into subgroups (ulcer-like, dysmotility-like, unspecified and sometimes, when reflux symptoms are combined with abdominal complaints, reflux-like dyspepsia). The clinical relevance of this is however doubtful. If dyspeptic symptoms occur with concomitant bowel habit disturbances, the subject is said to have IBS. In the clinical situation, the patients often present with symptom overlap, and with change in main symptom profile from time to time. Different definition makes prevalence reports less comparable. An approximate average in the literature of the three-month period prevalence of GORD is that it is reported by 10% of the population, of overall reflux symptoms by 25%, of dyspepsia (without predominant reflux symptoms) by 25%, of dyspepsia without concomitant reflux symptoms by 15% and of IBS by 15% of the population.

Therapy of Hypertension and Metabolic Syndrome: Today's Standard and Tomorrow's Perspectives

Treatment of arterial hypertension is known to reduce cardiovascular morbidity and mortality and has a positive effect against stroke, where benefit is strongly linked to reduction in blood pressure per se. The protective effects against coronary heart disease (CHD) have also been significant but numerically less impressive than the effect against stroke. It is conceivable that this due to the fact that not just blood pressure, but also a number of metabolic variables need to be considered in this context. The insight that hypertension is often just one of the components of the so-called metabolic syndrome suggests that a modern antihypertensive drug should not only lower blood pressure; to exert optimal cardioprotective properties it should also have a neutral or even positive metabolic profile as regards its effects on lipids, glucose and insulin in order to achieve a better protection against CHD. Against this background the centrally acting selective imidazoline receptor (I1) agonist moxonidine is of considerable interest. Moxonidine has been shown to improve glucose tolerance in man, probably by two different mechanisms, i.e. by augmenting insulin sensitivity in peripheral tissues and by enhancing glucose-stimulated insulin release from the pancreas. By employing a therapeutic intervention against hypertension that not only lowers elevated arterial pressure but also positively affects some of the frequently occurring concomitant metabolic disturbances, it appears that today's standard of antihypertensive therapy may be surpassed in tomorow's perspective.

Insulin resistance in cardiac syndrome X and variant angina: Influence of physical capacity and circulating lipids

Insulin resistance has been demonstrated in patients with angina pectoris irrespective of detectable atherosclerosis at coronary angiograms. We compared insulin sensitivity, lipid profiles, and exercise capacity in 20 patients with syndrome X, 15 patients with variant angina, and 20 healthy controls to investigate whether the presentation of the insulin resistance syndrome differs between the two patient groups with disparate vascular abnormalities. All patients had angiographically normal coronary arteries. Maximal oxygen uptake (V O2 max ) was determined at bicycle exercise testing. Insulin sensitivity (S I ) was assessed by the minimal model analysis of the intravenous glucose tolerance test. Patients with variant angina had significantly lower V O2 max than controls (mean ± SE, 25.6 ± 1.5 vs 30.6 ± 1.4 ml × kg –1 × min –1 , p < 0.05), whereas V O2 max in patients with syndrome X was intermediate (27.1 ± 1.3 ml × kg –1 × min –1 ). Compared with controls, patients with syndrome X and variant angina had reduced insulin sensitivity (controls, 1.47 ± 0.16 10 –4 × min –1 /per pmol / L vs syndrome X, 0.86 ± 0.11 10 –4 × min –1 per pmol / L and variant angina, 0.96 ± 0.15 × 10 –4 × min –1 per pmol / L; analysis of variance, p < 0.05). Only patients with syndrome X exhibited fasting hyperinsulinemia. Patients with syndrome X also had higher fasting concentrations of triglycerides and total cholesterol and lower concentrations of high-density lipoprotein cholesterol than controls. When adjusting S I for variances of V O2 max , differences in S I vanished between controls and patients with variant angina but not between controls and patients with syndrome X. Thus syndrome X and variant angina are both associated with insulin resistance, but lipid abnormalities are only prominent in patients with syndrome X. A variable expression in terms of concomitant disturbances of lipid profiles and disparate influences of physical capacity suggests different underlying mechanisms. (Am Heart J 1997;134:229-37.)

Effects of PEEP on Systemic Venous Capacitance

The aim of the present study was to determine effects of positive end expiratory pressure (PEEP) application on peripheral venous capacitance and relate them to concomitant central hemodynamic disturbances. The venous volume-pressure (V/P) relationships were studied in 6 intact anesthetized pigs to describe the effects of PEEP on systemic venous compliance (computed as the slope of the V/P relationship) and unstressed volume (referred to as the extrapolated volume intercept). Cardiac volumes as well as partitioning of circulating blood volume between central (ITBV) and peripheral (PBV) compartments were assessed by thermo-dye dilution techniques. During a 15 cm H2O PEEP application, venous compliance was reduced by 48%, while unstressed volume was increased by 25% and peripheral blood pooling increased from 63 to 74%. As a result, left heart and right ventricular end diastolic volumes were decreased by 8% and by 44%, respectively. It is concluded that increased venous unstressed volume and reduced compliance depicted the distension of the venous tree secondary to PEEP which acted as an impediment to venous return. As a consequence, cardiac output was reduced because of decreased preload.

Elevation of plasminogen activator inhibitor 1 in borderline hypertension is linked to concomitant metabolic disturbances.

In the present study we investigated plasma levels of plasminogen activator inhibitor 1 (PAI-1), fibrinogen and von Willebrand factor (vWF) in borderline hypertensive (BHT) men [diastolic blood pressure (DBP) 85-94 mmHg, n = 75] and age-matched normotensive (NT) control subjects (DBP < or = 80 mmHg, n = 75), in relation to smoking, body mass index (BMI) and fasting lipoprotein and insulin levels. PAI-1 levels were elevated in the BHT group [16.3 vs. 13.7 arbitrary units (AU), P = 0.032], whereas levels of fibrinogen and vWF were similar in the two groups. The PAI-1 elevation was even more pronounced in dyslipidaemic BHT subjects than in normolipidaemic NT subjects (20.0 vs. 10.3 arbitrary units (AU), P = 0.001). PAI-1 levels showed strong correlations with insulin, lipoproteins and BMI (P < 0.01-0.001), but not with DBP. The results show that disturbances in the fibrinolytic system appear even in borderline hypertension. The elevation of PAI-1 levels seems to be more strongly linked to concomitant metabolic disturbances than to blood pressure levels.

Standardization and quality assurance exemplified by tinnitus

Quality management will become another discipline for intensive care and research for the physician. Therefore, the first step in this process will be the need for standardised evaluation criteria and case record forms for documentation, leading to effective quality assessment and control. Only this approach may promote our attempts to improve the quality of patient care. Tinnitus is, due to the lack of objective measurable parameters and a missing rational basis of therapy, up to now a "crux medicorum" for every involved person. In this paper we reproduce a case record form and a patient's questionnaire for patients suffering from tinnitus. The presented forms are based on a consensus conference concerning the evaluation of treatment regimens held at the Fourth International Tinnitus Seminar in Bordeaux in August 1991. Epidemiological data, collected with this questionnaire, are presented and analysed. In conclusion, the presented case record form will lead to a standardised evaluation of symptoms according to tinnitus and improve our understanding of concomitant disturbances in tinnitus sufferers. Furthermore, this form of evaluation and documentation will produce comparable data in different centres allowing a pooling of patients data and history. A comparison of clinical trials in which the items are collected by the procedure shown here will be facilitated and lead us to a new understanding in determining the causes of the disease and the outcome of different therapeutic regimens.

Relationship between Venous and Arterial Haemodynamics during Postural Changes in Venous Insufficiency

Objective: To study the changes in central haemodynamics and the relationship between arterial blood pressure and the venous dynamics of the lower limbs in patients with venous insufficiency. Design: Prospective haemodynamic study during postural changes in 14 patients with venous insufficiency with no other concomitant cardiovascular disease or disturbances in autonomic nervous system. Setting: Department of Cardiology and Angiology, University Hospital, Gent, Belgium. Patients: Fourteen patients with venous valve insufficiency in the lower limbs. Interventions: Measurements of arterial blood pressure, heart rate, stroke volume and cardiac output were performed in the supine position after 30 min rest and 5, 15 and 30 min after standing and during the recovery. Venous pressure at the ankle and calf circumference were also measured. Main outcome measures: Changes in cardiac output and total peripheral vascular resistance in order to maintain blood pressure during postural changes. Results: Arterial blood pressure was maintained constant owing to an increase in total peripheral vascular resistance despite a decrease in cardiac output. Venous pressure is also related to arterial blood pressure. Conclusions: The arterial and venous systems, even in venous insufficiency, are integrated to maintain blood pressure constant during postural changes.

The epidemiology of obsessive-compulsive disorder in an Italian population

SummaryThis study presents the clinical and demographic characteristics of a sample of 131 patients, who met DSM III-R criteria for obsessive-compulsive disorder (OCD). Our aim was to compare our epidemiological data with non-European research, and to investigate the relationship between OCD symptoms and other clinical features, ie other Axis I concomitant disturbances, personality disorders (Axis II) and family history. Furthermore, we evaluated the age at onset distribution according to sex, family history and presence/absence of a comorbid diagnosis of mood disorder, by means of survival analysis.

EMS-induced translocation in Nigella damascena L.

Two morphological variants (P-11/2/2 and P-9/2/3) showing translocation were isolated in an EMS treated M1 population of Nigella damascena L. The plant P-11/2/2 exhibited complex chromosomal translocations forming ring of four, six and twelve chromosomes and chain of four and six chromosomes, while the plant P-9/2/3 manifested interchange involving four chromosomes in chain configruation only. Possibly, multiple translocation observed in the plant P-l 1/2/2 has resulted in complete pollen and seed sterility following unbalanced microspore formation and concomitant disturbances in fertilization. On the contrary, 78.64% pollen and total seed sterility noted in the plant P-9/2/3 may be ascribed to changes in the genomic balance or physiological disturbances as a consequence of chromosomal interchanges induced by the mutagen or can be attributed to defective female gametogenesis.

Vincristine-induced abnormalities of gastrointestinal regulatory peptide cells of the rat

The microtubule-disrupting drug vincristine is a common component of anti-cancer chemotherapeutic regimes, which produces acute constipation as a side effect. Although generally attributed to damage to the myenteric plexus, the precise mechanism of this disturbance is unknown. In addition, vincristine causes marked aberrations in the secretory response of pancreatic endocrine tissue in both man and rats. No information is available on its possible effect on regulatory peptides of the gastrointestinal tract. In this study we have produced vincristine-induced constipation in rats at a dosage comparable with that employed in the treatment of human subjects. Immunocytochemistry revealed concomitant disturbances in cells exhibiting immunoreactivity for gastrin in the antrum, for gastric inhibitory polypeptide and 5-hydroxytryptamine in the duodenum, for enteroglucagon in the colon, and for somatostatin in all three sites. These widespread effects are transient in nature with normal cell numbers and morphology being reestablished within 6 days. It is suggested that the observed effects are a direct result of microtubule disruption and that gastrointestinal regulatory peptide and amine immunoreactive cells have a rapid regeneration potential.

Daily increase in noradrenaline turnover in brain regions of activity-stressed rats

Changes in contents of noradrenaline (NA) and its major metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO 4) in brain regions (the hypothalamus, amygdala, thalamus, hippocampus, midbrain, cerebral cortex, pons plus medulla oblongata and basal ganglia) of male Wistar rats were evaluated after 1,3 or 5 days of exposure to the activity-stress paradigm, wherein rats were housed in a cage with a running-wheel and restricted to 1-hr of feeding per day. When compared to the non-stressed control rats, contents of MHPG-SO 4 in all the brain regions except of the basal ganglia in the stressed rats increased as rapidly as 1 day and continued to increase throughout the 5-day activity-stress period. Contents of NA did not change significantly in most of these brain regions. The daily increase in regional NA turnover by continuous exposure to the activity-stress paradigm was related to the large increases in running activity and gastric ulcers, and to body weight loss at the 3-day and 5-day testing period. These data suggest that pathological states produced by a 5-day activity-stress paradigm may reflect concomitant disturbances of noradrenergic function in various brain regions. The activity-stress paradigm is regarded as an intense and progressive stress, because it induces an increase in NA response in extended brain regions.