Manuel Freire-Garabal

• University of Santiago de Compostela

Red cell distribution width (RDW) could be of interest by its potential use in the assessment of celiac disorder (CD). The main objective of this study was to evaluate the case positive rate of CD and the utility of red cell distribution width (RDW) in the CD diagnosis. This prospective study included 9.066 middle adult (≥45 years old) and elderly...

Background: The diagnosis of celiac disease (CD) has been substantially improved with the availability of highly sensitive CD-specific IgA-TG2, Ig-GDP, and IgA-EMA. The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) published (2012) and updated (2020) diagnostic criteria for CD in order to simplify CD diagnosi...

Prostate (PC) and breast cancer (BC) are heterogeneous hormonal cancers. Treatment resistance and adverse effects are the main limitations of conventional chemotherapy treatment. The use of sensitizing agents could improve the effectiveness of chemotherapeutic drugs as well as obviate these limitations. This study analyzes the effect of single cate...

We present and thoroughly characterize a large collection of 3,4-dihydropyrimidin-2(1H)-ones as A2BAR antagonists, an emerging strategy in cancer (immuno) therapy. Most compounds selectively bind A2BAR, with a number of potent and selective antagonists further confirmed by functional cyclic adenosine monophosphate experiments. The series was analyz...

Antibiotic resistance is an emerging worldwide concern with serious repercussions in terms of morbi-mortality. Bearing in mind that the inadequate use of antibiotics, by healthcare staff as well as by the general population, is one of its main causes, a multidisciplinary approach is required to try to combat it. The aim of the present study was to...

Glucosinolate-degradation products (GS-degradation products) are believed to be responsible for the anticancer effects of cruciferous vegetables. Furthermore, they could improve the efficacy and reduce side-effects of chemotherapy. The aim of the present study was to determine the cytotoxic effects of GS-degradation products on androgen-insensitive...

Breast cancer (BC) is the most common cancer in women worldwide, with a mortality rate that has been forecasted to rise in the next decade. This is especially worrying for people with triple-negative BC (TNBC), because of its unresponsiveness to current therapies. Different drugs to treat TNBC have been assessed, and, although platinum chemotherapy...

Isothiocyanates (ITCs) have gained increasing attention since they have been attributed the merits for the potential beneficial effects of cruciferous vegetable dietary consumption on cancer. The aim of the present study was to determine the cytotoxic effects of 3-butenyl ITC (3-BI) on prostate cancer (PC) cells under in vitro conditions. Two andro...

Prostate cancer (PCa) is the second main cause of death by cancer in men. Although most PCa are initially responsive to treatment, they are difficult to manage clinically after their progression to a hormone independent state. During the last years different approaches to treating PCa have been assessed based mainly on specific targets such as aden...

Despite the major progress made in the field of cancer biology, cancer is still one of the leading causes of mortality, and prostate cancer (PCa) is one of the most encountered malignancies among men. The effective management of this disease requires developing better anticancer agents with greater efficacy and fewer side effects. Nature is a large...

Currently approved antimitotic therapies used in chemotherapy are microtubule-targeting agents (MTAs). Despite they achieved some level of success, they have limited efficacy as single agents, with issues of slippages and resistance, and cause significant side effects. The advances in the identification of other mitosis-related targets led to the d...

An integrated multidisciplinary approach that combined structure-based drug design, multicomponent reaction synthetic approaches and functional characterization in enzymatic and cell assays led to the discovery of new kinesin spindle protein (KSP) inhibitors with antiproliferative activity. A focused library of new benzimidazoles obtained by a Ugi+...

Clinical and animal studies now support the notion that psychological factors such as stress might be implicated in the pathogenesis of several disorders. Psychological stress stimulates major two neuroendocrine pathways, the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic branch of the autonomic nervous system (ANS). Their activation...

During periods of psychological stress, excess amounts of free radicals are produced. Bilirubin oxidative metabolites (biopyrrins; BOM) are generated from bilirubin as a result of its scavenging action against free radicals. We investigated whether the urinary excretion of biopyrrins is altered by anxiolytics. In the present study, mice were immobi...

Stress can cause adverse reactions in the body that induce a wide range of biochemical and behavioral changes. Oxidative damage is an established outcome of stress that has been implicated in the pathogenesis of mood and anxiety disorders. Anxiolytic drugs are widely prescribed to treat these conditions; however, no animal study has investigated th...

Emotional stress can be viewed as a cause of adverse circumstances that induces a wide range of biochemical and behavioural changes. Oxidative stress is a critical route of damage in various psychological stress-induced disorders such as depression. Antidepressants are widely prescribed to treat these conditions; however, no animal study has invest...

The progression and development of multiple sclerosis (MS) has long been hypothesized to be associated with stress. Benzodiazepines have been observed to reduce negative consequences of stress on the immune system in experimental and clinical models, but there are no data on their effects on MS, or experimental autoimmune encephalomyelitis (EAE), a...

To investigate the effects of resveratrol, a naturally occurring polyphenol, on the expression of vascular endothelial growth factor (VEGF) in human gingival fibroblast culture in response to vesicles and outer membrane proteins from periodontopathic bacteria. Human gingival fibroblasts were stimulated with vesicles and outer membrane proteins from...

Psychological stress has been found to suppress cell-mediated immune responses that are important for limiting the proliferation of Candida albicans. Fluoxetine has been observed to reduce negative consequences of stress on the immune system in experimental and clinical models, but there are no data on its effects on oral candidiasis. We designed e...

A review about the effects of phytosterols and pholyphenols on prostate cancer models.

The present experiment deals with the effects of amphetamine and cocaine on the development and course of experimental allergic encephalomyelitis (EAE) induced in Lewis rats. Rats were immunized at the age of eight weeks with purified myelin basic protein isolated from guinea pig brain in complete Freund's adjuvant. Drug administration and recordin...

We studied the effects of fluoxetine, a non-tricyclic antidepressant drug that selectively inhibits re-uptake of serotonin by presinaptic neurons in the brain, on cellular immune responses in mice exposed to a chronic auditory stressor. The natural killer (NK) cell activity was reduced after 4, 8, 12, 16 and 20 days of stress exposure with a partia...

Tobacco use is the leading risk factor for lung cancer, yet in addition to smoking habit, diet may also play a role in the disease's appearance. While there are reports to indicate that antioxidant vitamins and carotenoids may decrease the risk of lung cancer, results to date have been somewhat ambiguous. This review aimed to describe the results y...

Anxiety and depression are commonly encountered in patients with cancer and constitute risk and prognostic factors for the disease. Although previous findings do not support an overall association between the use of antidepressants and higher prevalence of cancer, results for serotonin uptake inhibitors are not entirely reassuring. We evaluated the...

Multiple sclerosis (MS) is a common inflammatory disease of the central nervous system. Although the etiology of MS remains unknown, studies in experimental autoimmune encephalomyelitis (EAE) have suggested that foreign molecules, which show molecular mimicry with myelin antigens, may play an important role as causative agents of the human disease....

Myelin oligodendrocyte glycoprotein (MOG) is a minor component of central nervous system myelin presumably implicated in the pathogenesis of Multiple Sclerosis (MS). Immunization with MOG leads to the development of Experimental Autoimmune Encephalomyelitis (EAE), the experimental model of MS. It has been suggested that its encephalitogenic potenti...

Crude polysaccharide extracts were obtained from aqueous extracts of the microalgae Chlorella stigmatophora and Phaeodactylum tricornutum. The crude extracts were fractionated by ion-exchange chromatography on DEAE-cellulose columns. The molecular weights of the polysaccharides in each fraction were estimated by gel filtration on Sephacryl columns....

In this study, we investigated whether serotonin could regulate the in vitro activity of phagocytosis through 5-hydroxytryptamine or serotonin (5-HT1A) receptors. Mouse peritoneal macrophages were cultured with serotonin and the activity of phagocytosis was assessed by the uptake of zymosan and latex particles added to the culture media. Specific b...

Experimental allergic encephalomyelitis (EAE) is a T-cell inflammatory disease of the central nervous system (CNS) widely considered as an animal model of multiple sclerosis. In Lewis rats, myelin basic protein-complete Freund's adjuvant (MBP-CFA)-induced EAE is an acute monophasic disease from which animals recover fully. In our experiments, daily...

We studied the effects of 1, 2, 5, 10 and 20 mg/kg of fluoxetine on the activity of phagocytosis in mice subjected to a chronic auditory stressor. Both the in vitro and in vivo activity of phagocytosis, measured using the zymosan-particle uptake method and the carbon clearance test, respectively, were reduced after 2, 4, 8 and 16 days of stress exp...

Late-onset ethanol (EtOH) consumption is related to life and social stressors of aging. The stress system (hypothalamic-pituitary-adrenal, HPA, axis) coordinates the adaptive response of the organism to stressors, but age-related deficits in HPA function seem to be associated with disorders such as late-onset EtOH consumption, anxiety and depressio...

Psychological stress has been found to suppress cell-mediated immune responses that are important in limiting the proliferation of Candida albicans. Since anxiolytic drugs can restore cellular immunity in rodents exposed to stress conditions, we designed experiments conducted to evaluate the effects of alprazolam (1 mg/kg of body weight/day), a cen...

The effects of music on the immune system and cancer development were evaluated in rodents subjected to sound stress. Animals were exposed daily to broad band noise around midnight and/or music for 5 hours on the following morning. Thymus and spleen cellularity, peripheral T lymphocyte population, the proliferative response of spleen cells to mitog...

Mice exposed to a chronic auditory stressor and treated with nefazodone (10 mg/kg/day s.c.), showed a reduction in stress-induced suppression of thymus and spleen cellularity, and in peripheral T-Iymphocyte population. The in vitro blastogenic response of spleen lymphoid cells to mitogen concanavalin A, the in vitro and in vivo activity of phagocyt...

Experiments were conducted to evaluate the effects of amphetamine (0. 4 mg/kg of body weight/day) on the development of oral candidiasis in Sprague-Dawley rats. Animals were submitted to surgical hyposalivation in order to facilitate the establishment and persistence of Candida albicans infection. Treatment with drugs (placebo or amphetamine) was i...

Late-onset drinking is a common problem in elderly people related to stress induced by social isolation. Experiments were performed in order to evaluate the effects of alprazolam, a benzodiazepine agonist anxiolytic, on the free-choice ethanol consumption in aged rats subjected to isolation stress. The animals we offered a two-bottle choice consump...

Mice exposed to a chronic auditory stressor and treated with nefazodone (10 mg / kg / day s.c.), showed a reduction in stress-induced suppression of thymus and spleen cellularity, and in peripheral T-Iymphocyte population. The in vitro blastogenic response of spleen lymphoid cells to mitogen concanavalin A, the in vitro and in vivo activity of phag...

Experiments were conducted to evaluate the effects of amphetamine (0. 4 mg/kg) on the development of autochthonous tumors induced by the Moloney sarcoma virus (MSV) in Balb/c female mice. Enhancement of MSV-induced tumor incidence and tumor growth was observed, together with a delay in the usual prompt regression of the tumors, when mice were daily...

Experiments were performed in order to evaluate the effects of fluoxetine, a selective inhibitor of neural serotonin transporter antidepressant, on the development lung metastases in rats subjected to laparotomy and injected (i.v.) with 10(4) Walker 256 (W-256) carcinosarcoma cells. The number of metastatic nodules on the surface of the lungs, as w...

Experiments were performed in order to evaluate the effects of buspirone (1 mg/kg s.c.), a 5-HT1A agonist anxiolytic, on the development of oral candidiasis in Sprague-Dawley rats exposed to a chronic auditory Stressor. Stress application caused a significant increase of the size of macroscopic lesions appearing in the dorsal surface of the tongues...

Experiments were conducted to evaluate the effects of nefazodone (10 mg/kg/day) on the delayed type hypersensitivity (DTH) response of mice exposed to an auditory stressor. Our results show that the DTH response to sheep red blood cells (SRBC) was inhibited by the stress and this difference was greater when stress was administered before SRBC sensi...

Mice exposed to a chronic auditory stressor and treated with fluoxetine (5 mg/kg) showed a reduction in stress-induced suppression of thymus and spleen cellularity, and in peripheral T lymphocyte population. The blastogenic response of spleen lymphoid cells and the delayed type hypersensitivity response (DTH) to sheep red blood cells (SRBC) were al...

Experiments were conducted to evaluate the effects of alprazolam (1 mg/kg i.p.) on the development of autochthonous tumors induced by the Moloney sarcoma virus (MSV) in BALB/c female mice subjected to stress. Enhancement of MSV-induced tumor incidence and growth was observed, together with a delay in the usual prompt regression of the tumors, when...

Mice injected with amphetamine showed a dose-related suppression of the natural killer cell activity. The capacity of T-cells to generate cytotoxic T-lymphocytes (CTL) in mixed lymphocyte cultures and in vivo was also assayed and amphetamine was found to inhibit CTL responses.

Experiments were performed in order to evaluate the effects of buspirone (1 mg/kg s.c.), a 5-HT(1A) agonist anxiolytic, on the development of lung metastases in rats subjected to laparotomy and injected (i.v.) with 104 Walker 256 (W-256) carcinosarcoma cells. The number of metastatic nodules on the surface of the lungs, as well as the percentage-ar...

Several experiments were conducted to evaluate the effects of buspirone, a selective 5-hydroxytryptamine-1A (5-HT1A) anxiolytic, on the immune system of mice exposed to a chronic auditory stressor. Daily injection with 0.5 and 1 mg/kg (intraperitoneally) of buspirone resulted in a dose-dependent reduction in the stress-induced suppression of the na...

Experiments were conducted to evaluate the effects of chronic buspirone (1 mg/kg/day) on the influenza A (PR-8/34) virus specific immune injury in CD-1 mice exposed to a chronic auditory stressor. Treatment with buspirone resulted in a decrease of the stress-induced increase of virus titers and pulmonary vascular permeability as well as in a reduct...

Experiments were performed in order to evaluate the effects of cocaine (0.5 mg/kg/day) on the development of lung metastases in rats injected i.v. with 104 Walker 256 (W-256) carcinosarcoma cells. The number of metastatic nodules on the surface of the lungs, as well as the percentage-area of metastases in the frontal section through the pulmonary h...

The effect of immobilization stress on precursor cell migration from bone marrow to the thymus was studied in C57BL/6 mice. The in vitro migration assays, using Nucleopore chambers, showed that precursor cell migration to thymus supernatants was strongly inhibited in stressed animals. This inhibition of migration seemed to be cell-associated what c...

Experiments were conducted to evaluate the effects of cocaine (0.5 mg/kg) on the development of autochthonous tumors induced by the Moloney sarcoma virus (MSV) in adult BALB/c female mice. Enhancement of MSV-induced tumor incidence and tumor growth together with a delay in the usual prompt regression of the tumors were observed when mice were daily...

Mice submitted to surgical stress and treated with chronic midazolam (1 mg/kg) showed a reduction in stress-induced suppression of the in vitro and in vivo activity of phagocytosis, both measured using the zymosan-particle uptake method and the carbon clearance test, respectively.

The review of the literature shows that stress can adversely affect influenza A virus infection. In this report, we study the effects of chronic alprazolam (1 mg/kg/day), a central benzodiazepine agonist anxiolytic, on the influenza A (PR-8/34) virus specific immune injury in mice exposed to a chronic auditory stressor. Treatment with alprazolam re...

Mice exposed to surgical stress induced by laparotomy and treated with chronic alprazolam (0.5-2 mg/kg) showed a dose-dependent reduction in stress-induced suppression of the natural killer (NK) cell activity. These immunoenhancing effects of alprazolam were more intense when it administered before the surgery was performed.

Mice exposed to a chronic auditory stressor and treated chronically with buspirone (1 mg/kg) showed a reduction in stress-induced suppression of the resistance and development of immunity to Listeria monocytogenes. Attempts to passively transfer immunity with spleen cells were also performed. Stressed, immunized mice had a reduced capacity to trans...

Mice exposed to a chronic auditory stressor and daily injected with alprazolam (1 mg/kg/day, s.c.) showed a reduction in stress-induced suppression of the in vitro and in vivo activity of phagocytosis, measured using the zymosan particle uptake method and the carbon clearance test, respectively. Pretreatment with Ro-15-1788 (10 mg/kg, s.c.), a cent...

Several experiments were conducted to evaluate the effects of chronic amphetamine on the influenza A (PR-8/34) virus specific immune injury in CD-1 mice. Treatment with amphetamine resulted in a significant increase of lung virus titers and pulmonary vascular permeability. Amphetamine also increased the lethality of infected mice.

Mice submitted to surgical stress induced by laparotomy and treated with chronic midazolam (1 mg/kg) showed a reduction in stress-induced suppression of thymus and spleen cellularity and in peripheral lymphocyte population. The blastogenic response of spleen lymphoid cells was also assessed and midazolam was found to partially attenuate the suppres...

In order to clarify the mechanism of hypotensive activity of platelet activating factor (PAF), the effects of this drug on blood pressure in anaesthetized normotensive rats, on KCl- and noradrenaline-induced 45Ca uptake and contractile responses in rat aorta rings with and without endothelium were studied. PAF (3 micrograms kg-1, i.v.) showed long-...

After 125I-beta-endorphin was intravenously injected in rats, an autoradiographic study of distal femur growth plates was performed. Results show a specific binding of the radiolabelled peptide to chondrocytes suggesting the possible existence of an opiate modulation of growth plate physiology.

Female C3H/He mice carrying the mammary tumor virus (MTV) were monitored for mammary tumor incidence and latent periods while subjected to a daily intraperitoneal (i.p.) injection of placebo or alprazolam (1 mg/kg per day). Although all of the mice were potential candidates for MTV-induced breast cancer, those injected with alprazolam were partiall...

Experiments were conducted to evaluate the influences of chronic treatment with amphetamine (0.4 mg/kg/day) on the activity of phagocytosis in mice. Results show a decrease of the in vitro and in vivo phagocytosis measured by using the zymosan-particle uptake method and the carbon clearance test, respectively.

Female C3H/He mice carrying the mammary tumor virus (MTV) were monitored for mammary tumor incidence and latent periods while submitted to a daily subcutaneous injection with amphetamine (0,4 mg/kg/day). Results show that amphetamine caused an increase in incidence and a decrease in latency of tumors compared with placebo. There was also appreciate...

Mice exposed to a chronic auditory stressor and treated with buspirone (1 mg/kg/day) showed a reduction in stress-induced suppression of thymus and spleen cellularity, and in peripheral T-lymphocyte population. The blastic response of spleen lymphoid cells was also assessed and buspirone was found to partially suppress the inhibitory effect of stre...

Mice submitted to surgical stress induced by laparotomy and treated with chronic alprazolam (1 mg/kg) showed a reduction in stress-induced suppression of thymus and spleen cellularity, as well as in peripheral T lymphocyte population. The blastic response of spleen lymphoid cells was also assessed and found to partially supress the inhibitory effec...

Mice chronically injected with amphetamine (0.4 mg/kg/day) showed a reduction in thymus and spleen cellularity, and in peripheral T lymphocyte population. The blastogenic response of spleen lymphoid cells was assessed and amphetamine was found to inhibit T-cell proliferation. Amphetamine also reduced the capacity of mice to the development and pass...

After 125I-beta-endorphin was intravenously injected to rats, an autoradiographic study of distal femur articular cartilage was performed. Results show a specific binding of 125I-beta-endorphin to chondrocytes, suggesting the possible existence of an opiate modulation of articular cartilage.

After ¹²⁵I-β-endorphin was intravenously injected to rats, an autoradiographic study of distal femur articular cartilage was performed. Results show a specific binding of ¹²⁵I-β-endorphin to chondrocytes, suggesting the possible existence of an opiate modulation of articular cartilage.

Tumor induction by 7,12-dimethylbenx[α]anthracene (DMBA) was studied in rats submitted to a chronic treatment with amphetamine (0.4 mg/kg/day). Our results show that amphetamine causes a decrease in the number and weight of DMBA-induced mammary tumours.

Mice exposed to surgical stress induced by laparotomy and treated chronically with diazepam (1 mg/kg) showed a reduction in stress-induced suppression of resistance and development of immunity to Listeria monocytogenes. Attempts to transfer immunity passively with spleen cells were also performed. Stressed immunized mice had a reduced capacity to t...

Tumour induction by 7,12-dimethylbenx[α]anthracene (DMBA) was studied in rats submitted to chronic auditory stress and injected daily with diazepam, alprazolam or midazolam. The results show that stress causes a decrease in the number and weight of DMBA-induced mammary tumours, and all benzodiazepines assayed partially reversed these effects.

Stress qualitatively and quantitatively impairs immune function via the activation of main two neuroendocrine pathways, the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic branch of the autonomic nervous system (ANS). Stress-induced immune impairments appear to be large enough to alter the course of viral diseases, including enhancing...