Determination of soluble tumor necrosis factor receptor II and secretory immunoglobulin A in saliva of patients with dementia.

The prevalence of pain and dementia increases with age, affecting a significant percentage of the population due to aging. Both pathologies are connected through the inflammatory process, specifically through the tumor necrosis factor. The effect of this cytokine is mediated through the modulation of its TNFRI and TNFRII receptors, which are linked to the dementia process. In addition, immunoglobulins such as secretory immunoglobulin A (sIgA) have been recognized as one of the main biomarkers of pain in saliva. sTNFRII and sIgA levels were determined in saliva samples by ELISA from healthy people and patients with dementia in GDS stages 5-7. The concentrations of these markers were also correlated with the GDS stage and sex. We observed a significant decrease (*** p ≤ 0.001) in the levels of sTNFRII (pg/mL) and a significant increase (** p ≤ 0.01) in the levels of sIgA (ng/mL) in the saliva of patients with dementia compared to the healthy control group. We did not observe a correlation with the data of the biomarkers regarding the GDS stage and sex. The results obtained for sTNFRII are consistent with those obtained by other authors on brain tissue, who conclude that unopposed neuronal TNFRI signaling, when TNFRII is selectively downregulated, leads to a more severe course of AD pathogenesis. Regarding sIgA, the elevated values of sIgA may reflect the immune status of these patients. Therefore, these biomarkers can provide us with relevant information through a non-invasive method such as saliva analysis.

Assessment of Diet-Related Changes on Albendazole Absorption, Systemic Exposure, and Pattern of Urinary Excretion in Treated Human Volunteers.

Soil-transmitted-helminth (STH) infections are a persistent global public health problem. Control strategies for STH have been based on the use of mass drug administration (MDA) mainly targeting preschool- and school-aged-children, although there is increasing interest in expanding treatment to include adults and others through community-wide MDA. Coverage assessment is critical to understanding the real effectiveness of albendazole (ALB) treatment in those MDA programs. The work described here aims to (i) evaluate the effect of type of diet (a heavy or light meal) and fasting before ALB treatment on the systemic disposition of ALB and its metabolites in treated human volunteers and (ii) evaluate the potential feasibility of detecting albendazole metabolites in urine. The data reported here demonstrate that the systemic availability of the active ALB-sulfoxide (ALBSO) metabolite was enhanced more than 2-fold after food ingestion (a heavy or light meal). ALB dissolution improvement related to the ingestion of food may modify the amount of drug/metabolites reaching the parasite, affecting drug efficacy and the overall success of MDA strategies. The measurement in urine samples of the amino-ALB-sulfone (NHALBSO2) derivative and ALBSO for up to 96 h suggests that it may be feasible to develop a noninvasive tool to evaluate compliance/adherence to ALB treatment.

Gender differences in the antioxidant response of oral administration of hydroxytyrosol and oleuropein against N-ethyl-N-nitrosourea (ENU)-induced glioma.

Brain tumorigenesis has been associated not only with oxidative stress, but also with a reduced response of non-enzyme and enzyme antioxidant defense systems. In fact, the imbalance between free-radical production and the efficiency of the antioxidant defense systems triggers the process because the central nervous system (CNS) is very sensitive to free-radical damage. Phenolic compounds, mainly oleuropein and its major metabolite hydroxytyrosol, derived from olives and virgin olive oil, have been shown to exert important anticancer activities both in vitro and in vivo due to their antioxidant properties. The present study analyzes the effects of the oral administration of oleuropein, hydroxytyrosol and the mixture of both phenolic compounds in rats with transplacental N-ethyl-N-nitrosourea (ENU)-induced brain tumors to analyze their potential effect against brain tumorigenesis through the modification of redox system components. Oxidative stress parameters, non-enzyme and enzyme antioxidant defense systems and blood chemistry were assayed in the different experimental groups. The treatment with oleuropein, hydroxytyrosol and/or the mixture of both phenolic compounds promotes a limited beneficial effect as anticancer compounds in our ENU-induced animal model of brain tumor. These effects occur via redox control mechanisms involving endogenous enzymatic and non-enzymatic antioxidant defense systems, and are highly dependent on the gender of the animals.

Sex differences exist in brain renin-angiotensin system-regulating aminopeptidase activities in transplacental ethyl-nitrosourea-induced gliomas.

INTRODUCTION: The renin angiotensin system (RAS) is emerging as an important target for the treatment of glioma. We had described that the local RAS is involved in vivo in tumor growth in the rat model of experimental C6 glioma implanted at the subcutaneous region, through the modification of several proteolytic regulatory enzymes of aminopeptidase type. METHODS: We analyze RAS-regulating aminopeptidase activities in plasma and brain tissue of control male and female rats and rats with transplacental ethylnitrosourea-induced gliomas. RESULTS: No differences were found either the mean total number of tumors per animal or the tumor volume between male and female animals. However, we have found increased levels in aspartyl aminopeptidase in both males and females and of aminopeptidase B only in males. On the contrary, decreased levels were found in aminopeptidase N and insulin-regulated aminopeptidase activities in both males and females, whereas aminopeptidase A only decreased in females. Decreased levels of aminopeptidase N, aminopeptidase B and insulin-regulated aminopeptidase were also shown in plasma of only female rats. CONCLUSIONS: Under the complexity of RAS cascade, the changes found suggest the predominant actions of angiotensin III against a decreased action of angiotensin II and angiotensin IV. We conclude that angiotensin peptides are involved in tumor growth in this rat model of glioma and that their role in tumor growth can be analyzed through their corresponding proteolytic regulatory enzymes, which make them new and attractive therapeutic targets beyond the use or angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs).

Dental sealant knowledge, opinion, values and practice of Spanish dental hygienists.

OBJECTIVES: Dental sealants have proved to be an effective approach to prevent pit and fissure caries. This study examines the knowledge, opinion, values and practice (KOVP) of dental hygienists concerning sealant use in the southwest region of Andalusia, Spain. METHODS: Spanish dental hygienists (n = 400) volunteered to complete a 31-item, self-administered, pretested questionnaire to assess their knowledge, opinion, values and practice regarding pit and fissure sealants. Wilcoxon matched-pairs signed ranks test, the Friedman nonparametric repeated-measures anova and Spearman's correlation were used to analyse the data. RESULTS: The mean scores for knowledge, opinion, values and practice were 3.57 ± 0.41; 2.17 ± 0.42; 2.58 ± 0.77 and 3.56 ± 0.46, respectively. Knowledge differed by years of experience (P < 0.01) and place of work (P < 0.01); opinion differed by years of experience (P = 0.03) and sector (P < 0.01). Similarly, practice about sealants differed by years of experience (P < 0.01). Conversely, values around sealant placement did not statistically differ by sex, years of experience, practice sector or place of work. Statistically, significant correlations were found between knowledge, opinion and value, while it was found no significant correlation between practice and the other variables (P > 0.05). CONCLUSIONS: Most dental hygienists have sufficient knowledge about pit and fissure sealants. They also acknowledge the importance of use of dental sealants and have positive opinion/attitude about using sealants. Practice of dental sealants in clinics was found adequate. However, they were not following the specific guidelines and standardized procedures.

Treatment of Fluorosis Spots Using a Resin Infiltration Technique: 14-month Follow-up.

The aim of this study was to report a clinical case of moderate fluorosis spots treated with infiltration of low-viscosity resin. A commercial resin was applied to the facial surfaces on the anterior teeth in both the maxillary and mandibular arches. The white spots of fluorosis lost their whitish appearance and appeared similar to sound enamel. This technique, which might constitute an alternative to white-masking of fluorosis spots, showed optimal esthetic results.

Local thyroid renin-angiotensin system in experimental breast cancer.

UNLABELLED: An association between breast cancer and thyroid dysfunction exists although the underlying mechanisms remain to be elucidated. Numerous studies have characterized the role of thyroid hormones in controlling the synthesis and secretion of renin-angiotensin system (RAS) components, but little information is available on the putative role of the local RAS on thyroid function. AIMS: Here we analyze several soluble and membrane-bound RAS-regulating aminopeptidase activities in thyroid gland from rats with mammary tumors and the relationship with the circulating levels of thyroid stimulating hormone (TSH) and free thyroxin (fT4). MAIN METHODS: We analyze soluble and membrane-bound RAS-regulating aminopeptidase activities fluorometrically using their corresponding aminoacyl-ß-naphthylamide as the substrate. KEY FINDINGS: We have found in rats with mammary tumors a concomitant change of thyroid RAS-regulating enzymes and thyroid hormone production. SIGNIFICANCE: We suggest that existence of alterations in the regulatory mechanisms mediated by the angiotensins of the local tissue RAS as a consequence of the carcinogenic process which could act alone or in combination with alterations at a higher level of regulation such as the hypothalamus-pituitary axis.

Circulating aminopeptidase activities in men and women with essential hypertension.

Essential hypertension is one of the major contributors to premature morbidity and mortality due to the incresased risk for coronary heart disease, stroke, renal disease, peripheral vascular disease and vascular dementia for both men and women. However, its basic causes remain unknown. In the present work we studied the activity of several proteolytic regulatory enzymes related to renin-angiotensin-system (RAS) (aminopeptidase A, APA; aminopeptidase N, APN; aminopeptidase B, APB; and insulin-regulated aminopeptidase, IRAP); with oxytocin regulation (oxytocinase); with the metabolism of GnRH and TRH (pyrrolidone carboxypeptidase, Pcp); and with enkephalins metabolism (enkephalindegrading activity, EDA), to elucidate their role in the mechanisms responsible of essential hypertension and to discuss the possible gender differences. Serum samples of 53 individuals with essential hypertension and 60 healthy volunteers were collected and used to assay enzyme activities, gonad hormones testosterone and estradiol, TSH and free thyroxin (fT4). Differences were observed in APA, APN, Pcp and EDA specific activities, and in serum gonad hormone levels between hypertensive and control groups. Only Pcp activity showed gender differences. Regarding the RAS, APA is reduced while APN is increased, suggesting increased levels of angiotensin II and a facilitation of the conversion of angiotensin III in angiotensin IV. Thus, the changes in several RAS-regulating specific activities and other enzyme activities involved in the neuroendocrine modulation of gonad and stress-related functions are related to essential hypertension with minor gender differences. Therefore, aminopeptidases constitute new elements for the knowledge of the causes of essential hypertension and an alternative as therapeutic targets against the illness.

Intraoperative sentinel node biopsy by one-step nucleic acid amplification (OSNA) avoids axillary lymphadenectomy in women with breast cancer treated with neoadjuvant chemotherapy.

BACKGROUND: There is no evidence that supports the recommendation of sentinel lymph node biopsy (SLNB) in patients with breast cancer who have treated with neoadjuvant chemotherapy (NAC) to downsize tumors in order to allow breast conservation surgery, because NAC induces anatomical alterations of the lymphatic drainage. We evaluated the effectiveness of SLNB using intraoperative one-step nucleic acid amplification (OSNA) method to detect microscopic metastases or isolated tumor cells after NAC in patients with clinically negative axillary nodes at initial presentation. PATIENTS AND METHODS: We evaluated in patients with breast cancer and clinically negative axilla at presentation, the effectiveness of SLNB by OSNA after NAC (71 patients) or prior to NAC (40 patients). RESULTS: The rate of SLN identification was 100% in both groups. 17 women with SLNB prior to systemic treatment showed positive nodes (14 macrometastases and 3 micrometastases), and positive SLNB were detected in 15 women with SLNB after NAC, which were 14 macrometastases and 1 micrometastase. The negative predictive value of ultrasonography was 57.5% in patients with SLNB prior to neoadjuvant therapy and 78.9% in patients with chemotherapy followed by SLNB. CONCLUSIONS: Intraoperative SLNB using OSNA in women with clinically negative axillary lymph nodes at initial presentation who received NAC could predict axillary status with high accuracy. Also it allows us to take decisions about the indication or not to perform an axillary dissection at the moment, thus avoiding delay in the administration of chemotherapy and benefiting the patients from a single surgical procedure.

Plasma oxidative stress parameters in men and women with early stage Alzheimer type dementia.

It is well known that oxidative stress is one of the earliest events in Alzheimer's disease pathogenesis, indicating that may play a key role in this disease. In our study, we measured the levels of oxidative stress indicators (TBARS and protein carbonyls content) and the non-enzymatic (glutathione (GSH) and oxidized glutathione (GSSG)) and enzymatic (glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD)) defense systems in the plasma of 46 patients diagnosed of ATD and 46 age-matched controls. We found decreased levels in total GSH in ATD patients, although healthy control women showed lower levels of total GSH than healthy control men. On the contrary, we found increased levels of TBARS and carbonyl groups content in ATD patients in both genders. The activity of the plasma antioxidant enzymes showed no changes for SOD activity in ATD patients, independently of the gender, although western blot analysis showed an increase in SOD-1 protein. CAT activity was also decreased in ATD patients, although this decrease is mainly due to the decrease found in men but not in women. However, western blot analysis did not show differences in CAT protein between controls and ATD patients. Finally, a decrease of GPx activity was found in ATD patients in both genders. However, as with CAT protein, western blot analysis did not show differences in GPx protein between controls and ATD patients. Our results suggest that there is a defect in the antioxidant defense system that is incapable of responding to increased free radical production, which may lead to oxidative damage and the development of the pathological alterations that characterize the neurodegenerative disorder of patients with ATD. Thus, oxidative damage could be one important aspect for the onset of ATD and oxidative stress markers could be useful to diagnose the illness in their earliest stages through both non-invasive, reliable and cost-affordable methods.

Dissolving efficacy of eucalyptus and orange oil, xylol and chloroform solvents on different root canal sealers.

AIM: To evaluate the solubility of five root canal sealers in orange oil, eucalyptol, xylol and chloroform solvents. METHODOLOGY: The solubility of RoekoSeal, Sealer 26, Epiphany, Endomethasone and EZ-Fill sealers was assessed in orange oil, eucalyptol, xylol, chloroform and distilled water. Seventy-five samples of root canal sealers were prepared and then divided into five groups for immersion in solvent for 2, 5 or 10 min. The means of loss weight were determined for each material in each solvent at all immersion periods, and the values were compared by factorial analysis of variance (anova) and SNK multiple comparisons. RESULTS: In the orange and eucalyptus oil groups, there was no significant difference among RoekoSeal, Sealer26, Epiphany and EZ-Fill at the three immersion periods (P > 0.05). With xylol, no significant differences were found at 5 and 10 min (P > 0.05) for each root sealer. Orange and eucalyptus oil solvents were as effective as chloroform at 2 min in dissolving all the root sealers. CONCLUSIONS: Xylol was the most effective solvent followed by the chloroform and the essential oils (eucalyptol and orange oil). Orange oil behaved in a similar way to eucalyptus oil.

[Effect of a multidisciplinar protocol on the clinical results obtained after bariatric surgery]. / Comparación de resultados previos y posteriores a la aplicación de un protocolo de actuación en cirugía bariátrica.

INTRODUCTION: Bariatric surgery has been shown to be an effective therapy for weight loss in patients with severe obesity, and the implementation of a multidisciplinar management protocol is recommended. OBJECTIVES: To assess the usefulness of the implementation of a management protocol in obesity surgery based on the Spanish Consensus Document of the SEEDO. METHODS: Retrospective comparative study of the outcomes in patients previously operated (51 patients) and after the implementation of the protocol (66 patients). The following data were gathered: anthropometry, pre-and post-surgery comorbidities, post-surgical nutritional and surgical complications, validated Quality of Life questionnaire, and dietary habits. RESULTS: Withdrawals (l7.6%) and alcoholism (5.8%) were higher in patients pre- versus post-implementation of the protocol (4.5% vs. 3%, respectively), the differences being statistically significant. The mortality rate was 2% in the pre-protocol group and 0% in the postprotocol group. The dietary habits were better in the post-protocol group, the pre-protocol group presenting a higher percentage of feeding-behavior disorders (5.1%) although not reaching a statistical significance. The improvement in quality of life was higher in the post-protocol group for all items, but only reaching statistical significance in sexual activity (p = 0.004). In the pre-protocol group, 70.5% of the patients had more than one nutritional complication vs. 32.8% in the post-protocol group (p < 0.05). There were no differences regarding the percentage of weight in excess lost at two years (> 50% in 81.3% in the pre-protocol group vs. 74.8% in the pos-protocol group) or the comorbidities. CONCLUSIONS: Bariatric surgery achieves excellent outcomes in weight loss, comorbidities, and quality of life, but presents nutritional, surgical, and psychiatric complications that require a protocol-based and multidisciplinary approach. Our protocol improves the outcomes regarding the withdrawal rates, feeding-behavior disorders, dietary habits, nutritional complications, and quality of life.

VOC removal and deodorization of effluent gases from an industrial plant by photo-oxidation, chemical oxidation, and ozonization.

The efficiency of photo-oxidation, chemical oxidation by sodium hypochlorite, and ozonization for the industrial-scale removal of volatile organic compounds (VOCs) and odors from gaseous emissions was studied by applying these treatments (in an experimental system) to substances passing through an emission stack of a factory producing maize derivatives. Absorption and ozonization were the most efficient treatment, removing 75% and 98% of VOCs, respectively, while photo-oxidation only removed about 59%. The emitted chemical compounds and odors were identified and quantified by gas chromatography-mass spectrometry (in full-scan mode). In addition to presenting the results, their implications for selecting optimal processes for treating volatile emissions are discussed.

Actual and potential agents and biomarkers in the treatment of cancer.

It is well known that cancer is defined as a group of diseases that differ both regarding the tissues they affect as well as their origin. For this reason, much effort is being made in the development of new drugs with the aim of increasing survival and patients' quality of life. There is already a wide spectrum of anti-cancer agents that follow different mechanisms of action, such as the inhibitors of topoisomerases I and II and anti-mitotic chemicals, among others. Usually, these drugs are able to increase the patient's survival, although their toxicity worsens the patient's quality of life. Therefore, we should seriously consider alternative mechanisms, as well as the co-administration of these drugs with non-toxic compounds, such as melatonin or retinoic acid. This would increase the toxic effects of these drugs at low doses. Obviously, a better understanding of modified physiological systems during the development of these diseases would improve the diagnostic tools. This would be translated, in turn, into a higher survival index. The alteration of the proteolytic enzymes involved in the renin-angiotensin system and in the regulation of the gonadotrophins and TRH synthesis in breast cancer are examples of the above. These two proteins are regulated by the same enzyme, pyrrolidon carboxipeptidase, and both are directly involved in the initiation and development of breast cancer. Therefore, the aim of the present review is to revise the different options available at present to improve patients' survival and to show alternative mechanisms that may be beneficial to patients' well being.

Anatomical evaluation of some morphological abnormalities related to periodontal diseases

The presence of some dental abnormalities as a predisposal factor to installation of localized periodontal alterations. The present study was to evaluate the frequency of development abnormalities present on a sample of molars that may predispose to occurrence and progression of periodontal disease. Two hundred and seventy seven molars (141 maxillary and 136 mandibular molars) were selected for this study. The evaluations were performed by two examiners together who was trained and calibrated for the study. All measurements were made by direct visualization with a magnifying glass. The following clinical parameters were measured: Enamel cervical projections; Root trunk: in the three different extensions (<3 mm, >3 mm and <6 mm, >6 mm); Enamel pearls: presence (1) or absence (0). The anatomic observations were made on four surfaces of the tooth: mesial, distal, vestibular and palatal/lingual. Descriptive statistics and percentage distribution were performed. A total of 130 molars showed at least some degree of enamel cervical projection and the most frequent score was the degree 1, according to Masters and Hoskins classification. Fifteen teeth presented enamel pearls and the root trunk was more evident on the group with variation from 3 to 6 mm of extension, observed in 64 teeth. It can be concluded that the presence of development abnormalities is a frequent finding in molars and it has to be taken into consideration during periodontal examination and therapy.

Topographical evaluation of the major apical foramen in permanent human teeth.

AIM: To determine the distance from the anatomical root apex to the major apical foramen and the position of the major foramen on the root apex. METHODOLOGY: Crowns of 926 human teeth were sectioned at the cementum-enamel junction. Specimens were mounted on microscope slides for measurement parallel to the long axis of the teeth. The major foramen was identified as the largest-diameter opening at the root apex. A total of 1331 root specimens were evaluated using an optical stereomicroscope to an accuracy of 0.01 mm at 40 x (+/-10) magnification. The distance from the anatomical apex to the most apical point of the major foramen was measured, and its location (central, buccal, lingual, mesial and distal) was recorded. RESULTS: The mean distance between the major foramen and the anatomical root apex was 0.69 mm; the mean distance was larger in posterior teeth (0.82 mm) and smaller in anterior teeth (0.39 mm). A wide range of anatomical apex to major foramen distances were observed in all tooth groups: the greatest distance was in maxillary molars (0.95 mm) followed by mandibular pre-molars (0.87 mm) and mandibular molars (0.80 mm). The major foramen was at the tip of the root in 40% of teeth. The most frequent deviations of the foramen were to the buccal (20%) and distal (14%). CONCLUSION: In this sample of teeth without apical resorption the distance between the major foramen and the anatomical root apex was always <1 mm. Deviation of the major foramen from the anatomic apex varied widely amongst tooth groups.

Carcass characteristics, fatty acid composition, and meat quality of Criollo Argentino and Braford steers raised on forage in a semi-tropical region of Argentina.

The purpose of this study was to characterize and compare the carcass characteristics, cholesterol concentration, fatty acid composition of intramuscular fat and subcutaneous fat, and meat quality of Criollo Argentino and Braford steers reared in an extensive system, without supplementation, and slaughtered at approximately 400kg live weight. The Braford steers had greater (P<0.05) carcass weight, yield, conformation score, marbling degree, fat thickness and fatness score than Criollo Argentino steers. The tissue composition of the 10th rib was: 68.1% vs. 63.6% muscle, 23.9% vs. 20.4% bone and 8.2% vs. 16.3% fat for the Criollo Argentino and Braford breeds, respectively. The meat of Longissimus muscle from Braford steers was lighter, redder, yellower and more tender than that from Criollo Argentino steers. The meat of Longissimus muscle from Braford steers had a higher fat content, similar protein and ash contents and a lower (P⩽0.001) cholesterol concentration than that from Criollo Argentino steers. The subcutaneous depot was the most saturated, while the intramuscular fat had the most polyunsaturated fatty acids. Intramuscular fat showed the highest ∑h fatty acids, and PUFA/SFA and n-6/n-3 ratios and for MUFA/SFA, 16:0/18:0 and h/H ratios were not significantly different between adipose tissue depots. The influence of breed on the fatty acid profile varies among adipose tissues. In general, both intramuscular fat and subcutaneous fat from Criollo steers contained more unsaturated fatty acids and less saturated fatty acids, than did fat from Braford steers.

The pharmacology and therapeutic relevance of endocannabinoid derived cyclo-oxygenase (COX)-2 products.

The discovery of anandamide and 2-arachidonyl glycerol (2-AG) as naturally occurring mammalian endocannabinoids has had important and wide-reaching therapeutic implications. This, to a large extent, ensues from the complexity of endocannabinoid biology. One facet of endocannabinoid biology now receiving increased attention is the cyclo-oxygenase-2 (COX-2) derived oxidation products. Anandamide and 2-AG are oxidized to a range of PG-ethanolamides and PG-glyceryl esters that closely approaches that of the prostaglandins (PGs) formed from arachidonic acid. The pharmacology of these electrochemically neutral PG-ethanolamides (prostamides) and PG-glyceryl esters appears to be unique. No meaningful interaction with natural or recombinant prostanoid receptors is apparent. Nevertheless, in certain cells and tissues, prostamides and PG-glyceryl esters exert potent effects. The recent discovery of selective antagonists for the putative prostamide receptor has been a major advance in further establishing prostamide pharmacology as an entity distinct from prostanoid receptors. Since discovery of the prototype prostamide antagonist (AGN 204396), rapid progress has been made. The latest prostamide antagonists (AGN 211334-6) are 100 times more potent than the prototype and are, therefore, sufficiently active to be used in living animal studies. These compounds will allow a full evaluation of the role of prostamides in health and disease. To date, the only therapeutic application for prostamides is in glaucoma. The prostamide analog, bimatoprost, being the most effective ocular hypotensive drug currently available. Interestingly, PGE(2)-glyceryl ester and its chemically stable analog PGE(2)-serinolamide also lower intraocular pressure in dogs. Nevertheless, the therapeutic future of PGE(2)-glyceryl ester is more likely to reside in inflammation.

Analysis of caspase activities in rat mammary tumours induced by N-methyl-nitrosourea.

Normal breast development is controlled by a balance between cell proliferation and apoptosis. The balance between the two parameters is crucial for determining the growth or regression of breast tumours in response to therapies and treatments. Therefore, it is necessary to understand the role of apoptosis in tumour progression. Active caspases participate as essential elements in the execution of apoptotic mechanisms. In the present study, we analysed the activities of caspase-3, -8 and -9 as well as cytochrome c release in N-methyl-nitrosourea (NMU)-induced rat mammary tumours, in order to establish the apoptotic events that occur in tumour growth in this animal model. Forty female virgin Wistar rats were randomly divided into two groups. One group was injected intraperitoneally with three doses of 50 mg/kg body weight of NMU. The control group received the vehicle only. After 122 days of NMU injection, the rats were sacrificed and the tumours were excised and processed. Results showed that in mammary tumours induced by NMU, the apoptotic death receptor-mediated pathway is activated through caspase-3 and -8, but the apoptotic mitochondrial pathway is suppressed through a non-activating process of caspase-9 activity, despite the release of cytochrome c. In conclusion, these findings have demonstrated a suppression of the apoptotic mitochondrial pathway through a non-activating process of caspase-9 activity, despite the release of cytochrome c in mammary tumours induced by NMU. Although the apoptotic death receptor-mediated pathway is activated, it is not enough to maintain the balance between proliferation and apoptosis, and thus determine the overall growth of the tumour.