CENTRAL AND PERIPHERAL EFFECT OF MPTP VIA DOSE-DEPENDENT MAGNESIUM MODULATION.

Background: Recent studies suggested that MPTP could cause gastrointestinal motility deficits additionally to its nonconclusive and controverted effects on the CNS (behavior and brain oxidative stress) in rats. A possible interaction between MPTP typical impairments and magnesium modulatory potential was previously suggested, as magnesium role was described in neuroprotection, gastrointestinal function, and oxidative stress. Aim: To investigate the possible modulatory effect of several magnesium intake formulations (via drinking water) in MPTP neurotoxicity and functional gastrointestinal impairment induction. Materials and Methods: Adult male Wistar rats were subjected to 3-week magnesium intake-controlled diets (magnesium depleted food and magnesium enriched drinking water) previously to acute subcutaneous MPTP treatment (30 mg/ kg body weight). Gastrointestinal motility (one hour stool collection test), and behavioral patterns (Y maze task, elevated plus maze test, open field test, forced swim test) were evaluated. Followingly, brain and bowel samples were collected, and oxidative stress was evaluated (glutathione peroxidase activity, malondial-dehyde concentrations). Results: MPTP could lead to magnesium intake-dependent constipation-like gastrointestinal motility impairments, anxiety- and depressive-like affective behavior changes, and mild pain tolerance defects. Also, we found similar brain and intestinal patterns in magnesium-dependent oxidative stress. Conclusion: While the MPTP effects in normal magnesium intake could be regarded as not fully relevant in rat models and limited to the current experimental conditions, the abnormalities observed in the affective behavior, gastrointestinal status, pain tolerance, peripheric and central oxidative status could be indicative of the extent of the systemic effects of MPTP that are not restricted to the CNS level, but also to gastro-intestinal system.

EXPERIMENTAL INDUCTION OF TYPE 2 DIABETES MELLITUS AND THE EFFICIENCY OF BARIATRIC SURGERY IN ITS REVERSAL IN RATS.

BACKGROUND: Following recent years, there is an increased body of literature on the connections that might exist between type 2 diabetes mellitus and the efficiency of bariatric surgery in its reversal compared to other medical approaches such as dieting. AIM: To induce experimentally type 2 diabetes mellitus in rats in order to observe the effects of bariatric surgery in the recovery as well as the reestablishment of normal insulin levels in order to extend the findings in house animals. MATERIALS AND METHODS: This study was conducted in three stages: the first consisted in inducing type 2 diabetes mellitus (T2DM) in 40 young Wistar male rats, by initially feeding them human food high in vegetal fats, oleaginous seeds, simple and complex carbohydrates, sugars, lipids, fats, proteins and fructose for a period of 8 weeks followed by a single low dose of streptozotocin (STZ), administered through intraperitoneal injection. The second stage of the study started when the rats became obese and therefore qualified for the bariatric procedure and the third stage consisted of post-operation supervision and care. The surgical procedure, performed on 10 obese rats, consisted in reducing the size of the stomach by partial gastrectomy of a 1.5 - 2.0 cm wide and 6.5 - 7.5 cm long area on the large curvature. RESULTS: Showed rapid improvements in body weight and blood sugar control after 9 days. CONCLUSION: After putting the rats on a diet high in carbohydrates, sugars, lipids and fats and administering them STZ, the induction of type 2 diabetes was successful and the partial gastrectomy led to a better blood sugar control. The bariatric procedure provides a faster therapeutic response than conventional diets.

PERCEIVED STRESS AND GASTROINTESTINAL HABITS IN COLLEGE STUDENTS.

CONTEXT: Many negative effects of stress regarding cognitive performances and gastrointestinal habits were previously reported in both animal models and human participants. OBJECTIVE: We aimed to compare perceived stress levels with declared gastrointestinal habits changes in a small cohort of college students during academic acquisition and evaluation periods. DESIGN: College students were recruited and divided into two groups: the control group evaluated during the acquisition period of the academic year and the stressed group evaluated during the examination period. SUBJECT AND METHODS: The students' psychological and gastrointestinal status was evaluated using a common stress questionnaire and a gastrointestinal habits survey. RESULTS: Our results showed increased perceived stress in college students during stressful conditions, as compared to lesser demanding periods. Similarly, more than 40%of the participants declared that gastrointestinal habits changes occurred during stressful periods. We observed significant correlations between the perceived stress levels and gastrointestinal habits changes. CONCLUSION: This small-sized survey study showed that the occurrence of the stressful event in young adults recorded higher perceived stress scores and frequent functional gastrointestinal symptoms, as compared to the lower stressful periods. Also, we showed that functional gastrointestinal symptoms are rather common and could be regarded as a negative response to stress.

IS OXYTOCIN RELEVANT FOR THE AFFECTIVE DISORDERS?

Oxytocin is a complex molecule involved in a variety of biological processes at both the central and the peripheral level. Although its role was initially associated almost exclusively with birth and breastfeeding, recent studies are suggesting that in fact oxytocin could be involved in many other physiological and pathological processes. In this way, lately there is a growing interest towards a possible involvement of oxytocin in many etiopathogenic and psychopathological processes, as for example in the affective disorders, where the roles of oxytocin are not yet clearly understood. In this paper we shortly describe the main aspects regarding the relevance of oxytocin administration or its mechanisms in the affective disorders, as well as its relations with the hypothalamic-pituitary-adrenal axis and cortisol secretion. It seems that although the researches on the importance of oxytocin in the affective disorders are rather at the beginning, an increasing number of evidence is supporting the involvement of oxytocin in the pathogenic processes of these psychiatric disorders. Still, the studies covering this topic are still in their early days, and the results that are trying to understand if there is a major role of oxytocin in affective disorders are not consistent enough to draw definitive conclusions and establish with certainty where the place of oxytocin in the affective disorders pathology is.

THE IMPORTANCE OF CLINICAL AND INSTRUMENTAL DIAGNOSTIC IN THE MAMMARY GLAND CANCER.

Breast cancer is the most common oncology disease in women and is one of the major public health issues. Worldwide, is the second leading cause of cancer death in women and cancer research is a priority in all the laboratories of the world, in terms of uncovering the appearance causes of the malignant process, understanding the mechanisms of development, but most of all, the discovery of early diagnostic methods and effective treatment. Ignorance, fear of diagnosis, lack of health education and of efficient programmes for prevention and screening could cause diagnosis of the disease to be detected in the majority of cases in advanced stages, when treatment remains only palliative and very costly, in this cases the patient's suffering being immense. In this way, regarding the clinical diagnosis in stage I mammary gland cancer, in the 496 stage I MGC patients, during the primary clinical investigation the diagnosis of stage I MGC was established only in 165 (33.3%) patients, and in 232 (46,8%) patients the diagnosis of suspicion MGC was obtained. Also, in terms of instrumental diagnosis, such as mammography, ultrasonography in mammary gland cancer stage I, it seems that in accordance with literature data the pathological process features assessment in the mammary gland is problematic especially in young age. Thus, it seems that MGC represents a polymorphic and pathogenic disease and it cannot be admitted that all subgroups of patients will obtain identical results from one tactic of treatment determined for all the patients with MGC. In this way, the concept of MGC both clinical and patho morphological, combines different cell clones depending on its microstructure and biology. As a result, the evolution of the disease, the prognosis and the effectiveness of the treatment may vary in different patients at the same stage, depending on the degree of malignancy of the tumor, its histopathological structure, the degree of expression of molecular markers identification and also immune resistance.

Prognostic factors in resectable pancreatic cancer.

The pancreatic cancer is a disease with exponentially increased incidence, especially over the last decades, being the sixth or even fifth cause of death by cancer in most of the modern societies. Moreover, it is estimated that almost 95% of the patients with this disease are presenting to the doctor in the advanced and unresectable stages. Also, over the past few decades the development and advance of the surgical methods and techniques have improved only morbidity and hospital postoperative mortality, without significant impact on survival. In this way, in the present mini-review we want it to make a short description for some modern aspects regarding the factors implicated in pancreatic cancer survival.

The role of rifaximine in the prevention of the spontaneous bacterial peritonitis.

UNLABELLED: Cirrhosis is characterized by an increased susceptibility to infection. Spontaneous bacterial peritonitis (SBP) is the most common infectious complication, the main causes being the bowel bacterial overpopulation, the increased intestinal permeability and bacterial translocation. Antibiotic prophylaxis with Norfloxacin increases the rate of PBS with G+ multiresistant bacteria. PURPOSE: To demonstrate the advantage of using rifaximin, nonresorbable broad spectrum antibiotic, in SBP prophylaxy. MATERIAL AND METHODS: The study is a prospective case-control, which included 46 patients diagnosed with Child class C cirrhosis and refractory ascites, based on clinical, biological, ultrasound and endoscopic findings, followed over a period of 6 months. Protein level in ascitic fluid (AF) was higher 14 g/dl. SBP was defined as the presence of > 250 PMN/mm3. Patients were divided into 2 groups, group 1 comprised 22 patients who received rifaximin treatment during the study for a previous episode of hepatic encephalopathy (HE), and group 2 consisted of 24 patients who did not receive antibiotic treatment during follow-up. RESULTS: Rifaximin significantly decreases the polymorpho-nucleares (PMN) in ascitic fluid from patients, one single case of neutroascitic SBP with negative cultures were recorded in this group, with a net improvement of the general condition. In group 2 who did not follow any antibiotic treatment, SBP was recorded in 4 patients, an increase of PMN in ascitic fluid at 14 patients, an approximately constant value in 4 patients, a decrease in 2 subjects. CONCLUSIONS: The study suggests that rifaximin causes a significant decrease in PMN in AF, producing a decrease in SBP frequency and improvement of life in cirrhotic patients with refractory ascites. In this study, the effects of rifaximin on intestinal bacterial overpopulation and bacterial translocation, decisive factors in SBP, are consistent with literature data. Use of rifaximin as an alternative method to prevent SBP deserves more attention.

Different profile of peripheral antioxidant enzymes and lipid peroxidation in active and non-active inflammatory bowel disease patients.

BACKGROUND: The role of oxidative stress in inflammatory bowel diseases (IBD) has been extended lately from a simple consequence of inflammation to a potential etiological factor, but the data are still controversial. Active disease has been characterized before by an enhanced production of reactive oxygen species and the increased peroxidation of lipids, but patients in remission were generally not considered different from healthy people in terms of oxidative stress. AIMS: We evaluated the antioxidant defense capacity and lipid peroxidation status in the serum of patients with active and non-active disease compared with healthy matched control subjects. METHODS: The study included 20 patients with confirmed IBD in clinical and biological remission, 21 patients with active disease, and 18 controls. We determined the serum levels of two antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GPX), and a lipid peroxidation marker, malondialdehyde (MDA). RESULTS: Active disease patients had an increased activity of both SOD and GPX, as well as significant high values of MDA versus controls. Furthermore, patients being in remission had significantly lower values of antioxidant enzymes (SOD and GPX) and increased lipid peroxidation measured by MDA serum levels, as compared with healthy control subjects. CONCLUSIONS: Our study confirmed the presence of high oxidative stress in active IBD. More importantly, we have demonstrated a lower antioxidant capacity of patients in remission versus control group. This may represent a risk factor for the disease and can be an additional argument for the direct implication of oxidative stress in the pathogenesis of IBD.

The influence of antibiotic treatment on the dynamics of oxidative stress in spontaneous bacterial peritonitis.

UNLABELLED: Bacterial infections play an important role in liver cirrhosis complications, being together with variceal bleeding and hepatic encephalopathy an important cause of morbidity and mortality in cirrhotic patients. Spontaneous bacterial peritonitis (SBP) is a major complication of liver cirrhosis, with a significant mortality. Recent studies have demonstrated the involvement of oxygen free radicals in the pathogenesis of liver cirrhosis, but the role of oxidative stress in the development of SBP is not very clear yet. PURPOSE: This study aims to evaluate the role of oxidative stress in the pathogenesis of spontaneous bacterial peritonitis and its changes after therapy. MATERIAL AND METHODS: The study is a prospective case-control, which included 33 patients divided into 3 groups: group I- 10 patients with decompensated cirrhosis and SBP, group II - 17 patients diagnosed with decompensated liver cirrhosis with ascites, and group Ill - 6 patients with compensated liver cirrhosis. The control group consisted of 19 healthy subjects recruited from hospital staff, adapted to patients by age and sex. Malonildyaldehida (MDA), a product of lipid peroxidation, was dosed in the blood and ascitic fluid of patients by assay thiobarbituric acid reactive substances (TBARS). RESULTS: Serum MDA significantly increased in the group with decompensated cirrhosis and SBP compared with the control group. MDA levels in ascitic fluid showed a statistically significant increase in the SBP group compared with patients without SBP. There was a decrease of MDA after 6 months of antibiotic treatment compared with the initial stage, while MDA values increased in the absence of treatment. CONCLUSIONS: The study demonstrates the increased oxidative stress markers in the blood and ascitic fluid of cirrhotic patients with SBP, which can be considered a predictor of SBP and also a marker of treatment response. KEYWORDS: SPON-

Interactions between the oxidative and nitrosative stress in nociceptive processing in rat.

During the last years, special emphasis was directed towards the relation between the molecular and cellular alterations produced by free oxygen radicals and the normal and pathologic implications of nitric oxide. Moreover, lately it is believed that a true radical cascade might exist between the reactive species of oxygen and nitrogen during stress of various causes. In this way, their succession would produce a temporal prolongation of the complex cellular alterations produced by stressing aggressions. In the present paper, we were interested in presented some selective aspects regarding the interactions between oxidative and nitrosative stress in the modulation of the nociceptive behavior in rats. We report here a significant correlation between the results of the hot-plate latency time and the values of some oxidative and nitrosative stress markers.

Effects of serotonin depletion on behavior and neuronal oxidative stress status in rat: relevance for anxiety and affective disorders.

PURPOSE: We lesioned the hypothalamic paraventricular nucleus (PVN) of male Wistar rats using two different doses (8µg/3µl and 16µg/3µl) of 5,7-dihydroxytryptamine (5,7-DHT) and then animals were subjected to a battery of behavioral tests designed to assess anxiety and memory formation. Further, we were interested to know whether this lesion would result in neuronal oxidative stress and also if there is a correlation between the behavioral response to this lesion and brain oxidative stress. MATERIAL/METHODS: Behavioral tests included elevated plus maze, used to assess exploration/anxiety status and radial armmaze, used for determining spatial short-term and reference memory errors. Regarding the oxidative stress, we measured the extent of some lipid peroxidation products like malondialdehyde and defense enzymes such as superoxide dismutase and glutathione peroxidase. RESULTS: 5,7-DHT lesioned rats spent more time in the open arms of the elevated maze compared to sham-operated rats, suggesting that the lesion significantly diminished anxiety-like behavior. Also, short-term memory was significantly impaired, as shown by the working memory errors in radial arm-maze task. Further analyses revealed that the 5,7-DHT lesion did not result in a significant change of reference memory errors. Regarding the oxidative stress, no significant modification of both superoxide dismutase and glutathione peroxidase specific activities from the temporal lobe were observed. However, the malondiadehyde level was significantly increased, suggesting pro-oxidant effects. Also, the linear regression between the working memory errors vs. malondiadehyde resulted in significant correlations. CONCLUSION: 5,7 DHT lesion of the PVN affects behavioral performance via interactions with systems governing novel and/or fear-evoking situations and also by increasing neuronal oxidative stress.

[The effects of some cholinergic drugs on cognitive processes and oxidative stress in rat]. / Efectele unor diversi agenti colinergici asupra proceselor cognitive si stresului oxidativ la sobolan.

Reactive oxygen species (ROS) are produced within the body during oxygen metabolism and living organisms have developed several defense mechanisms to protect themselves from oxidative stress. Under normal conditions, ROS and antioxidant systems are in balance. Oxidative stress is caused by the imbalance between production of pro-oxidants and the antioxidant defenses. The defense mechanisms include antioxidant enzymes like superoxide dismutase (SOD) or glutathione peroxidase (GPX) and several no enzymatic free radical scavengers. It has been proposed that the progressive increase in ROS and consequent oxidative damage play the major role in neurodegenerative disorders. Learning and memory show an age-related decline and this age-associated impairment extends to spatial memory tasks. Furthermore, the neural circuits between the prefrontal cortex and striatum are also involved in spatial memory. In our previous studies, we have shown the facilitatory role of nicotine and cholinergic system in learning and memory processes. In the present study, we examined whether oxidative stress contributes to the memory deficits induced by muscarinic acetylcholine receptors (mAchRS) blocked by scopolamine. We also examined the effect of nicotine on oxidative stress, and also if nicotine could attenuated the learning and memory deficits induced by blocked of mAchRS. We observed that the levels of SOD and GPX decrease in rats mAchRS blockade by scopolamine (0.75 mg/kg body weight i.p.), and the level of malondialdehyde (MDA) increase in same rats, compared with saline-treated rats. Therefore, our results suggest that the oxidative stress contributes to the learning and memory deficits in rats.