Self-Completion Questionnaire on Sleep Evaluation in Patients Undergoing Oxaliplatin Therapy: An Observational Study.

Sleep is a fundamental human need; sleep disruption, in fact, causes an increase in the activity of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis, metabolic effects, changes in circadian rhythms, and pro-inflammatory responses. The scientific literature is finally starting to pay attention to the central role of sleep alterations in patients health. Oxaliplatin is extensively used for the treatment of gastrointestinal cancer and other malignancies, with an increased frequency of use in recent years. This study aims to understand the effects of sleep complaints on health and quality of life in cancer patients treated with oxaliplatin. A study has been conducted through the creation and distribution of questionnaires to patients to investigate their complaints about sleep quality. We observed significant differences between males and females in evaluating sleep hygiene scores, the Pittsburgh Sleep Quality Index, and previous difficulty sleeping. Moreover, in females, stress, worries, and anxiety seem to play a negative role in the sleep hygiene score. The obtained results could improve the interest of healthcare personnel and caregivers in sleep quality in patients undergoing chemotherapy.

Sexual Violence and Alcohol Intake: A Population-Based Explorative Study in a Northwestern Italian Area.

Background and Objectives: Sexual violence (SV) is a major global public health concern. While socioeconomic factors and familial relationships have been widely reported to contribute to SV, the role of alcohol consumption should not be ignored. Indeed, alcohol can impair cognition, distort reality, increase aggression, and ease drug-facilitated sexual assault. This retrospective study aims to explore the relationship between alcohol consumption and SV by examining the prevalence, characteristics, and consequences of violence episodes. Materials and Methods: A total of 1481 women accessed the Rape Centre "Centro Soccorso Violenza Sessuale" in Turin, Italy between 2008 and 2019, with 223 reporting alcohol consumption before the assault. Results: The alcohol group had a younger age profile, predominantly within the 18-25-year-old category. SV incidents involving alcohol consumers were more likely to occur in public places or in someone else's home, while the non-alcohol-consuming group experienced more violence in their own homes. Acquaintances and unknown individuals were primarily responsible, whereas partners were the most common perpetrators of violence against non-alcohol-consuming women. Alcohol consumers sought medical attention sooner after the assault and exhibited more symptoms and injuries, particularly of neurological origin. Concurrent use of recreational drugs was higher among alcohol consumers. The logistic regression analysis revealed higher odds of injury for Italian women and those in the 18-35 age groups after consuming alcohol. Conclusions: This study contributes to the understanding of the relationship between alcohol consumption and SV. The prevalence of alcohol-related sexual aggression is lower compared to that shown in previous studies. Nationality, age, and assailant identity influence SV dynamics. These findings can guide well-targeted interventions and prevention strategies to address SV and inform communities facing similar challenges.

The Strange Case of Orotic Acid: The Different Expression of Pyrimidines Biosynthesis in Healthy Males and Females.

Orotic acid (OA) is an intermediate metabolite of pyrimidine nucleotide biosynthesis and represents a minor diet constituent. The measurement of urinary orotic acid is useful in confirming the diagnosis of hereditary metabolic diseases. Moreover, it could be of interest to know how the physiological concentration of this metabolite changes in relation to different conditions of clinical normality. The purpose of this study was to determine the orotic acid concentration in the urine of healthy patients, to observe normal oroticuria and to evaluate if the expression of pyrimidine intermediate biosynthesis differs between healthy males and females. The orotic acid concentration in urine was performed via the ICH M10-validated analytical method. Unexpectedly, females showed a greater oroticuria than males in pediatric age (0-10); conversely, we did not find significant differences until 70 years of age. The LC-MS/MS method was suitable for use in the differential diagnosis of hereditary metabolic disease and metabolic monitoring of anticancer drug-induced toxicity. The analytical protocol was found to be rapid and ideal, and was used in the routine analysis of a clinical chemistry laboratory. The biochemical aspects related to the expression of pyrimidine biosynthesis should be further investigated in light of the obtained results.

Metformin Protects Rat Skeletal Muscle from Physical Exercise-Induced Injury.

Metformin (Met) is a drug commonly prescribed in type 2 diabetes mellitus. Its efficacy is due to the suppression of hepatic gluconeogenesis, enhancement of peripheral glucose uptake and lower glucose absorption by the intestine. Recent studies have reported Met efficacy in other clinical applications, such as age-related diseases. Despite the wide clinical use of Met, its mechanism of action on muscle and its effect on muscle performance are unclear. We investigated the effects of Met combined with training on physical performance (PP) in healthy rats receiving Met for 8 weeks while undergoing daily moderate exercise. We evaluated the following: PP through graded endurance exercise test performed before the beginning of the training protocol and 48 h before the end of the training period; blood ALT, AST, LDH and CK-MB levels in order to address muscle damage; and several blood and muscle myokines and the expression of factors believed to be involved in muscle adaptation to exercise. Our data demonstrate that Met does not improve the positive effects of exercise on performance, although it protects myocytes from exercise-induced damage. Moreover, given that Met positively affects exercise-induced muscle adaptation, our data support the idea of the therapeutic application of Met when muscle function and structure are compromised.

Cystatin SN (CST1) as a Novel Salivary Biomarker of Periodontitis.

Identification of biomarkers could help in assessing periodontal health status and monitoring treatment outcomes. Therefore, the aim of this cross-sectional study was to identify potential innovative salivary biomarkers for the diagnosis of periodontitis using an untargeted proteomic approach. Forty-five healthy non-smoker participants diagnosed as having periodontally healthy conditions (H), severe periodontitis (P), and healthy but reduced periodontium after active periodontal treatment (T) were consecutively enrolled (15 per each group) in the study. A higher number of spots were identified in the proteome of unstimulated whole saliva collected from H and T subjects compared with P group, mainly within the range of 8-40 kDa. Protein spots of interest were analysed by MALDI-TOF-MS, allowing the identification of cystatin SN (CST1) isoform, as confirmed by Western blot. CST1 was markedly expressed in the H group, while it was absent in most P samples (p < 0.001). Interestingly, a distinct CST1 expression was observed in saliva from T patients. CST1 was negatively correlated with the percentage of pathological sites (p < 0.001) and was effective in discriminating active periodontitis from healthy periodontal status (whether H or T). Therefore, salivary CST1 may be a promising non-invasive biomarker for periodontal disease diagnosis and monitoring.

Metformin regulates myoblast differentiation through an AMPK-dependent mechanism.

This study aims to investigate how metformin (Met) affects muscle tissue by evaluating the drug effects on proliferating, differentiating, and differentiated C2C12 cells. Moreover, we also investigated the role of 5'-adenosine monophosphate-activated protein kinase (AMPK) in the mechanism of action of Met. C2C12 myoblasts were cultured in growth medium with or without Met (250µM, 1mM and 10mM) for different times. Cell proliferation was evaluated by MTT assay, while cell toxicity was assessed by Trypan Blue exclusion test and Lactate Dehydrogenase release. Fluorescence Activated Cell Sorting analysis was performed to study cell cycle. Differentiating myoblasts were incubated in differentiation medium (DM) with or without 10mM Met. For experiments on myotubes, C2C12 were induced to differentiate in DM, and then treated with Met at scalar concentrations and for different times. Western blotting was performed to evaluate the expression of proteins involved in myoblast differentiation, muscle function and metabolism. In differentiating C2C12, Met inhibited cell differentiation, arrested cell cycle progression in G2/M phase and reduced the expression of cyclin-dependent kinase inhibitor 1. These effects were accompanied by activation of AMPK and modulation of the myogenic regulatory factors. Comparable results were obtained in myotubes. The use of Compound C, a specific inhibitor of AMPK, counteracted the above-mentioned Met effects. We reported that Met inhibits C2C12 differentiation probably by blocking cell-cycle progression and preventing cells permanent exit from cell-cycle. Moreover, our study provides solid evidence that most of the effects of Met on myoblasts and myotubes are mediated by AMPK.

Comparing Ionic Profile of Gingival Crevicular Fluid and Saliva as Distinctive Signature of Severe Periodontitis.

Although increasing evidence is emerging on the contribution of chemical elements in periodontal health, no studies have concomitantly evaluated the ionic profile in gingival crevicular fluid (GCF) and saliva in relation to the underlying periodontal status. Our hypothesis is that these biofluids have distinctive ionic content. Therefore, the aim of this cross-sectional study was to analyze the elemental composition of GCF and saliva in order to explore which biological matrix and which combination of elements could discriminate between periodontitis and periodontal health. Twelve ions were analyzed in GCF and unstimulated saliva from 54 subjects (18 periodontally healthy, 18 untreated severe periodontitis and 18 treated severe periodontitis) using inductively coupled plasma-mass spectrometry (ICP-MS) and inductively coupled plasma-optical emission spectroscopy (ICP-OES). These analytical techniques were able to determine levels of sodium (Na), potassium (K), calcium (Ca) and magnesium (Mg), while the other elements were below the detection threshold. Na and K ions were detected at elevated concentration in untreated periodontitis compared with treated periodontitis and healthy periodontium. Ca was increased in untreated periodontitis, but the difference was not significant. In saliva, only Na was significantly associated with periodontitis. The combination of Na and K in GCF enabled the correct assignment of a subject to the periodontitis or healthy group. Based on these preliminary results, GCF demonstrated higher clustering potential than saliva.

Chemical Oral Cancerogenesis Is Impaired in PI3Kγ Knockout and Kinase-Dead Mice.

We investigated the role of PI3Kγ in oral carcinogenesis by using a murine model of oral squamous carcinoma generated by exposure to 4-nitroquinoline 1-oxide (4NQO) and the continuous human cancer cell line HSC-2 and Cal-27. PI3Kγ knockout (not expressing PI3Kγ), PI3Kγ kinase-dead (carrying a mutation in the PI3Kγ gene causing loss of kinase activity) and wild-type (WT) C57Bl/6 mice were administered 4NQO via drinking water to induce oral carcinomas. At sacrifice, lesions were histologically examined and stained for prognostic tumoral markers (EGFR, Neu, cKit, Ki67) and inflammatory infiltrate (CD3, CD4, CD8, CD19 and CD68). Prevalence and incidence of preneoplastic and exophytic lesions were significantly and similarly delayed in both transgenic mice versus the control. The expression of prognostic markers, as well as CD19+ and CD68+ cells, was higher in WT, while T lymphocytes were more abundant in tongues isolated from transgenic mice. HSC-2 and Cal-27 cells were cultured in the presence of the specific PI3Kγ-inhibitor (IPI-549) which significantly impaired cell vitality in a dose-dependent manner, as shown by the MTT test. Here, we highlighted two different mechanisms, namely the modulation of the tumor-infiltrating cells and the direct inhibition of cancer-cell proliferation, which might impair oral cancerogenesis in the absence/inhibition of PI3Kγ.

An Innovative Strategy for Oral Biofilm Control in Early Childhood Based on a Resveratrol-Cyclodextrin Nanotechnology Approach.

The purpose of this randomized controlled study was to evaluate the clinical efficacy of a novel oral spray containing resveratrol (RV) in controlling bacterial biofilm and gingival inflammation in early childhood. RV, a natural polyphenol, known for its anti-inflammatory and anti-infective activities, was included in a nanovector of 2-hydroxypropyl-beta-cyclodextrins (HPßCD) to improve its bioavailability. A total of 64 children between two and five years of age with plaque-induced gingivitis were randomly included in two equal groups. Both groups were enrolled in a mechanical plaque control program for a period of four weeks, while the test group was also instructed to use the RV-HPßCD mouthwash (in spray formulation) once daily, after toothbrushing. All children underwent three oral hygiene motivation sessions, 14 days apart, during which the full-mouth presence of bacterial plaque, gingival inflammation, dental stain and salivary pH were recorded. At two-week appointment, they also received professional plaque removal. The use of RV-based oral spray significantly reduced the amount of dental plaque and the percentage of bleeding sites and improved salivary pH compared to the control group at both two- and four-week examinations. Based on these promising results, the local delivery of RV-HPßCD via oral spray could enhance the control of dental biofilm in early childhood, when antiseptic mouthwashes are not recommended.

Subchronic nandrolone administration reduces cardiac oxidative markers during restraint stress by modulating protein expression patterns.

Nandrolone decanoate (ND), an anabolic-androgenic steroid prohibited in collegiate and professional sports, is associated with detrimental cardiovascular effects through redox-dependent mechanisms. We previously observed that high-dose short-term ND administration (15 mg/kg for 2 weeks) did not induce left heart ventricular hypertrophy and, paradoxically, improved postischemic response, whereas chronic ND treatment (5 mg/kg twice a week for 10 weeks) significantly reduced the cardioprotective effect of postconditioning, with an increase in infarct size and a decrease in cardiac performance. We wanted to determine whether short-term ND administration could affect the oxidative redox status in animals exposed to acute restraint stress. Our hypothesis was that, depending on treatment schedule, ND may have a double-edged sword effect. Measurement of malondialdehyde and 4-hydroxynonenal, two oxidative stress markers, in rat plasma and left heart ventricular tissue, revealed that the levels of both markers were increased in animals exposed to restraint stress, whereas no increase in marker levels was noted in animals pretreated with ND, indicating a possible protective action of ND against stress-induced oxidative damage. Furthermore, isolation and identification of proteins extracted from the left heart ventricular tissue samples of rats pretreated or not with ND and exposed to acute stress showed a prevalent expression of enzymes involved in amino acid synthesis and energy metabolism. Among other proteins, peroxiredoxin 6 and alpha B-crystallin, both involved in the oxidative stress response, were predominantly expressed in the left heart ventricular tissues of the ND-pretreated rats. In conclusion, ND seems to reduce oxidative stress by inducing the expression of antioxidant proteins in the hearts of restraint-stressed animals, thus contributing to amelioration of postischemic heart performance.

Transient receptor potential vanilloid 1 expression and functionality in mcf-7 cells: a preliminary investigation.

PURPOSE: Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel belonging to the transient receptor potential family, and it is expressed in different neoplastic tissues. Its activation is associated with regulation of cancer growth and progression. The aim of this research was to study the expression and pharmacological characteristics of TRPV1 in cells derived from human breast cancer MCF-7 cells. METHODS: TRPV1 presence was assessed by binding studies and Western blotting. Receptor binding characteristics were evaluated through competition assays, while 3-(4,5-dimethylthiazol-2-yl)-2,5,-dipheyltetrazolium bromide reduction assays were performed to confirm an early hypothesis regarding the modulation of cancer cell proliferation. The functionality of TRPV1 was evaluated by measuring Ca(2+) uptake in the presence of increasing concentrations of TRPV1 agonists and antagonists. RESULTS: Binding studies identified a single class of TRPV1 (Bmax 1,492±192 fmol/mg protein), and Western blot showed a signal at 100 kDa corresponding to the molecular weight of human TRPV1. Among the different tested agonists and antagonists, anandamide (Ki: 2.8×10(-11) M) and 5-iodoresiniferatoxin (5-I-RTX) (Ki: 5.6×10(-11) M) showed the highest degrees of affinity for TRPV1, respectively. All tested TRPV1 agonists and antagonists caused a significant (p<0.05) decrease in cell growth rate in MCF-7 cells. For agonists and antagonists, the efficacy of tested compounds displayed the following rank order: resiniferatoxin>anandamide>capsaicin and 5-I-RTX=capsazepine, respectively. CONCLUSION: These data indicate that both TRPV1 agonists and antagonists induce significant inhibition of MCF-7 cell growth. Even though the mechanisms involved in the antiproliferative effects of TRPV1 agonists and antagonists should be further investigated, it has been suggested that agonists cause desensitization of the receptor, leading to alteration in Ca(2+)-influx regulation. By contrast, antagonists cause a functional block of the receptor with consequent fatal dysregulation of cell homeostasis.

Experimental model for the study of the effects of platelet-rich plasma on the early phases of muscle healing.

BACKGROUND: There is abundant evidence suggesting that growth factors may play a key role in the healing process, especially in the early stages of inflammation. Despite the reported clinical successes with the use of growth factors there is still a lack of knowledge on the biological mechanism underlying the activity of platelet-rich plasma during the process of muscle healing. The aim of this study was to analyse the early effects of platelet- rich plasma in an easily reproducible animal model. MATERIALS AND METHODS: Wistar male adult rats (n=102) were used in this study. The muscle lesion was created with a scalpel in the flexor sublimis muscles. Platelet-rich plasma was applied immediately after surgery. Treated, untreated and contralateral muscles were analysed by morphological evaluation and western blot assay. RESULTS: Leucocyte infiltration was significantly greater in muscles treated with platelet-rich plasma than in both untreated and contralateral muscles. The latter showed greater leucocyte infiltration when compared to the untreated muscles. Platelet-rich plasma treatment also modified the cellular composition of the leucocyte infiltration leading to increased expression of CD3, CD8, CD19 and CD68 and to decreased CD4 antigen expression in both platelet-rich plasma treated and contralateral muscles. Blood vessel density and blood vessel diameters were not statistically significantly different between the three groups analysed. DISCUSSION: The results of this study showed that treatment with platelet-rich plasma magnified the physiological early inflammatory response following a muscle injury, modifying the pattern of cellular recruitment. Local platelet-rich plasma treatment may exert a direct or, more plausibly, indirect systemic effect on healing processes, at least in the earliest inflammatory phase.

Effects of sub-chronic nandrolone administration on hormonal adaptive response to acute stress in rats.

Androgenic-anabolic steroid (AAS) misuse has been associated with depression. It has been proposed that stress has a role in depression and that serotonin is involved in both endocrine responses to stress and depressive physiopathology. Although reports demonstrate that AAS chronic administration modifies components of stress-responsive hypothalamic-pituitary-adrenal axis (HPAA), no study has evaluated AAS effect on the response to stressful stimuli. We studied the effects of the subchronic administration (once a day for 14 days in rats) of a supratherapeutical dose of nandrolone decanoate (ND) on HPAA and cortical serotoninergic system response to acute restraint stress (RS). Acute RS produced the following effects: increase in CORT (in blood) and ACTH (both in blood and in pituitary corticotropes), GR depletion in hippocampus and hypothalamus cytosol and GR translocation in hippocampus nuclear fraction, cortical serotonin re-uptake stimulation and hippocampus cytosolic ERK2 activation. ND by itself, i.e. in non-stressed rats, did not modify these parameters, except for a decrease of plasma CORT and ACTH levels and an increase in hippocampus cytosolic phospho-ERK1/2. On the contrary, in stressed rats ND affected stress-induced plasma ACTH increase and prevented all other above reported stress effects, except the increase in pituitary ACTH positive cell density. Our results show that the prolonged administration of a supratherapeutical dose of ND in rats, albeit did not affect in a notable way HPAA and serotonin transporter activity in the absence of stress, may deregulate the stress-induced hormonal cascade which plays a crucial role in depressive psychopathology.

Differential expression of determinants of glucocorticoid sensitivity in androgen-dependent and androgen-independent human prostate cancer cell lines.

Glucocorticoids (GCs) are widely used for the treatment of hormone refractory prostate cancer. However, few data are available on the expression and regulation of glucocorticoid and mineralocorticoid receptors (GR and MR) and 11beta-hydroxysteroid dehydrogenase (11beta-HSD) 1 and -2 activities in prostate cancer cells. Here we show that GR is expressed in both the androgen-independent PC-3 cell line and, at very low levels, in the androgen-dependent LNCaP cells, and MR is expressed in both cell lines. IL-1beta increased GR expression in both cell lines. In LNCaP cells IL-1beta also increased MR expression. Significant 11beta-HSD oxidase activity and 11beta-HSD2 protein were found in LNCaP cells, but not in PC3 cells, and no ketoreductase activity was detected in either cell lines. GR function was assessed by measuring the inhibitory effect of dexamethasone on constitutive and IL-1beta-inducible IL-6 and osteoprotegerin (OPG) production. In PC-3 cells, IL-1beta stimulated IL-6 and OPG release, and dexamethasone dose-dependently inhibited IL-1beta-inducible IL-6 release, and constitutive and IL-1beta-inducible OPG release. In LNCaP cells, IL-1beta stimulated only OPG release. While dexamethasone was ineffective, cortisol dose-dependently inhibited IL-1beta-inducible OPG release. Eplerenone (Epl), a selective mineralocorticoid antagonist, reverted this effect. We conclude that different patterns of expression of receptors and 11beta-HSD activity were associated with different responsiveness to GCs in terms of regulated gene expression. GR and MR expression may vary as a function not only of the malignant phenotype, but also of local conditions such as the degree of inflammation. Inhibition of IL-6 and OPG release by GCs may contribute to the antitumor efficacy in prostate cancer.

Time-dependent acetylsalicylic acid effects on liver CYP1A and antioxidant enzymes in a rat model of 7,12-dimethylbenzanthracene (DMBA)-induced mammary carcinogenesis.

7,12-Dimethylbenzanthracene (DMBA) is an abundant environmental contaminant, which undergoes bioactivation, primarily by the CYP1 family, both in liver and extra-hepatic tissues. Dietary acetylsalicylic acid (ASA) has been recently reported to inhibit DMBA-mediated mammary tumour formation in rats. Chemopreventive substances may reduce the risk of developing cancer by decreasing metabolic enzymes responsible for generating reactive species (phase I enzymes) and/or increasing phase II enzymes that can deactivate radicals and electrophiles. To test these hypotheses, Sprague-Dawley female rats were orally administered ASA as lysine acetylsalicylate (50 mg per capita/day for 21 days in water), DMBA (10 mg per capita in olive oil on day 7, 14, and 21), ASA and DMBA in combination, and vehicles only, respectively. Six rats for each group were sacrificed on day 8, 15, and 22. The DMBA-mediated increase in hepatic CYP1A expression and related activities was not significantly affected by ASA, which, conversely, enhanced in a time-dependent manner the liver reduced glutathione content (up to 52%) and the activity of NAD(P)H-quinone oxidoreductase (up to 34%) in DMBA-treated rats. It is proposed that the positive modulation of the hepatic antioxidant systems by ASA may play a role in the chemoprevention of mammary tumourigenesis induced by DMBA in the female rat.

Nandrolone-pretreatment enhances cardiac beta(2)-adrenoceptor expression and reverses heart contractile down-regulation in the post-stress period of acute-stressed rats.

To investigate whether nandrolone decanoate (ND)-pretreatment can modulate (1) beta-adrenoceptor expression and (2) myocardial contractility in response to beta-adrenoceptors stimulation with isoproterenol (ISO), in hearts of both normal and stressed rats. Rats were treated with 15 mg/(kgday) of Deca-Durabolin (ND, 1 ml i.m.) or with vehicle (oil) for 14 days. The day after the last injection, the dose-response to ISO (1 x 10(-8), 5 x 10(-8) and 10(-7)M), was studied in isolated rat hearts harvested from unstressed animals (unstressed+vehicle (control) or unstressed+ND) or from stressed animals (stressed+vehicle or stressed+ND): acute stress protocol consisted in restrain for 1h immediately before sacrifice. ND-pretreatment increased beta(2)-adrenoceptor expression. In baseline conditions all hearts had a similar left ventricular developed pressure (LVDP) and maximum rate of increase of LVDP (dP/dt(max)). In hearts of unstressed+vehicle or unstressed+ND, ISO caused a similar increase in LVDP (+90-100%) and dP/dt(max) (+120-150%). However, hearts of stressed+vehicle animals showed a marked depression of inotropic response to ISO (i.e. for ISO 1 x 10(-8),-55% in LVDP response versus unstressed). Yet, in hearts of stressed+ND-animals the effect of stress was reversed, showing the highest response to ISO (i.e. for ISO 1 x 10(-7), +30% LVDP response versus unstressed). The ND-induced beta(2)-adrenoceptor overexpression does not affect ISO-response in unstressed animals. However, acute stress induces a down-regulation of ISO-response, which is reversed by ND-pretreatment. Since the physiological post-stress down-regulation of adrenergic-response is absent after nandrolone treatment, the heart may be exposed to a sympathetic over-stimulation. This might represent a risk for cardiovascular incidents in anabolic steroid addicts under stressing conditions.

The aspirin metabolite, salicylate, inhibits 7,12-dimethylbenz[a]anthracene-DNA adduct formation in breast cancer cells.

There is evidence that aspirin and other non-steroidal anti-inflammatory drugs may be protective agents against cancer in the gastrointestinal tract. These effects are particularly well documented for the colon and rectum. Some epidemiological and experimental studies have suggested that aspirin could also be a chemopreventive agent against breast cancer. We investigated the effects of the aspirin metabolite, salicylate (SA), on 7,12-dimethylbenz[a]anthracene (DMBA)-DNA adduct formation as well as on the expression of the enzymes involved in the carcinogen bioactivation pathway, in particular cytochrome P450 1A (CYP1A) and cyclooxygenases (COX-1 and COX-2). The effects of the test drug were examined in both the human mammary carcinoma cell line, MCF-7, and mammary cells derived from DMBA-induced rat mammary tumours (RMTCs). In this study, we also reported the effects of SA on cell growth and viability in breast cancer cells (BCCs). The results demonstrated that DMBA-DNA adduct formation in both cancer cell lines was inhibited by SA at concentrations of > or = 2.5 mM. CYP1A was undetectable in RMTCs while CYP1A induction by beta-naphthoflavone in MCF-7 cells was significantly inhibited by SA in a concentration-dependent manner. Aspirin did not affect COX-1 expression in either of the BCCs. COX-2 was not detected in MCF-7 cells, but its expression in RMTCs was inhibited by SA treatment, which also significantly reduced BCC growth, but failed to cause cell death by necrosis or apoptosis. These data suggest that inhibition of DMBA-DNA adduct formation may contribute to aspirin breast cancer chemopreventive action and indicate that this drug can act in the first stage of carcinogenesis.

Effects of swim stress and alpha-MSH acute pre-treatment on brain 5-HT transporter and corticosterone receptor.

The forced swim test (FST) can lead to stress-related diseases such as depression, through activation of hypothalamic-pituitary-adrenal axis (HPAA) and corticosteroid disregulation. Among the proopiomelanocortin (POMC)-derived peptides, alpha-melanocyte-stimulating hormone (alpha-MSH) has been shown to regulate long-lasting behavioral responses. Moreover, serotonergic pathways in various brain areas are activated by stressors, a feature that suggests a role for serotonin in both stress-induced HPAA disregulation and depressive physiopathology. Taking all together these data, we investigated the effects of the FST exposure and the effects of pre-treatment with alpha-MSH on cortical synaptosomal serotonin transporter (SERT) activity, corticosterone (CORT) plasma levels and on glucocorticoid receptor (GR) occupancy and expression in rat hippocampus. Young male rats were divided into three groups treated with saline or with alpha-MSH at doses of 1 or 4 microg/rat, 15 min prior to FST. Our data show that FST increased CORT secretion; GR levels in hippocampus decreased in density after stress without variations in affinity; GR redistributed from the cytosolic to the nuclear tissue fraction; finally, SERT activity strongly increased. All these effects were blocked by pre-treatment with alpha-MSH at the higher dose.