Showing papers in "European Review for Medical and Pharmacological Sciences in 2013"

The role of intestinal microbiota and the immune system

Abstract: BACKGROUND: The human gut is an ecosystem consisting of a great number of commensal bacteria living in symbiosis with the host. Several data confirm that gut microbiota is engaged in a dynamic interaction with the in- testinal innate and adaptive immune system, af- fecting different aspects of its development and function. AIM: To review the immunological functions of gut microbiota and improve knowledge of its therapeutic implications for several intestinal and extra-intestinal diseases associated to dys- regulation of the immune system. METHODS: Significant articles were identified by literature search and selected based on con- tent, including atopic diseases, inflammatory bowel diseases and treatment of these condi- tions with probiotics. RESULTS: Accumulating evidence indicates that intestinal microflora has protective, meta- bolic, trophic and immunological functions and is able to establish a "cross-talk" with the im- mune component of mucosal immunity, compris- ing cellular and soluble elements. When one or more steps in this fine interaction fail, autoim- mune or auto-inflammatory diseases may occur. Furthermore, it results from the data that probi- otics, used for the treatment of the diseases caused by the dysregulation of the immune sys- tem, can have a beneficial effect by different mechanisms. CONCLUSIONS: Gut microbiota interacts with both innate and adaptive immune system, play- ing a pivotal role in maintenance and disruption of gut immune quiescence. A cross talk between the mucosal immune system and endogenous microflora favours a mutual growth, survival and inflammatory control of the intestinal ecosys- tem. Based on these evidences, probiotics can be used as an ecological therapy in the treat- ment of immune diseases.

Heavy metals and placental fetal-maternal barrier: a mini-review on the major concerns.

Abstract: BACKGROUND: Heavy metals (HMs) are environmental contaminants with toxic properties for wildlife and humans.The placenta is a privileged organ that, along with the fetal mem - branes and amniotic fluid, enables growth and de - velopment of the fetus during the physiological pregnancy. It also acts as a filter reducing the pas - sage of harmful substances, protecting the em - bryo and then the fetus from exposure to pollu - tants. The placental barrier is not completely im - permeable to the passage of harmful substances; indeed, HMs were detected not only in placental tissues, but also in amniotic fluid and umbilical cord blood. The amniotic fluid can be considered as a valuable marker of prenatal exposure to ex - ogenous factors, and as an indicator of the integri - ty of placental barrier.The effect of an intrauterine exposure to heavy metals has been amply evaluat - ed during the last decades. Several studies inves - tigated the exposure to HMs in order to evaluate the mechanism of placental transfer and the im - pact on fetuses and later children's health. In par - ticular, the early exposure to Pb, Hg, and Cd was correlated to infant health effects, such as neuro - logical, developmental, and endocrine disorders. The aim of this mini-review is to summarise the current state of knowledge about the interaction between HMs and placental barrier, considering possible implications on fetal health.

Neutrophil lymphocyte ratios in stroke subtypes and transient ischemic attack.

Abstract: OBJECTIVES: This investigation was conducted to test the value of Neutrophil Lymphocyte Ratio (NLR), which has been shown in some recent studies to be a prognostically im - portant and an easy-to-measure inflammatory marker, in patients presenting to Emergency Service with stroke (ischemic and hemorrhagic) and transient ischemic attack. MATERIALS AND METHODS: A total of 868 patients were enrolled, who presented to our Emergency Service with cerebrovascular acci - dent (stroke and transient ischemic attack) and admitted to Neurology Clinic. Demographic char - acteristics and comorbidities of patients were recorded. The patients were divided into 3 groups as acute ischemic stroke (AIS), acute he - morrhagic stroke (AHS) and transient ischemic attack (TIA). Patients with AIS were classified in - to subgroups in terms of TOAST (trial of 10172 stroke treatment) criteria. Admission NLR levels were compared across all groups. RESULTS: A total of 868 patients were enrolled, 51.6% of which were male and 48.4% were female. AIS rate was 75.3%, AHS rate was 14.3% and TIA rate was 10.7%. In all of patients, mortality rate was 10.7%. NLR was significantly higher in pa - tients who died ( p < 0.001). NLR level in patients with TIA was significantly lower than those of AIS and AHS groups ( p < 0.001). Among AIS sub - groups, NLR level was significantly higher in group with great artery atherosclerosis or atherothrom - bosis compared to other groups ( p < 0.001). CONCLUSIONS: NLR may be used as a simple and easy-to-measure marker for prediction of short-term prognosis and in-hospital mortality in both ischemic and hemorrhagic stroke patients.

Could platelet indices be new biomarkers for inflammatory bowel diseases

Abstract: BACKGROUND AND AIM : Ulcer - ative colitis (UC) and Crohn 's disease (CD) are chronic inflammatory diseases. Many serum bio - markers have been studied for diagnosis and monitoring of disease activity in inflammatory bowel diseases (IBD). Platelets play an important role in inflammation.The aim of the present study is to determine whether platelet indices; mean platelet volume (MPV), platelet distribution width (PDW) and platelet-crit (PCT) would be useful, cheap, non-invasive biomarkers for following up and determining severity of IBD . MATERIALS AND METHODS: The study group consiste d of 175 patients with IBD (UC n: 103 and CD n: 72) and the control group included 40 healthy subjects. Disease activity was evaluated both by endoscope and clinically. Platelet in - dices and inflammatory parameters were mea - sured for all study participants. Patients were checked in both active and remission phase of the diseases. RESULTS: In patients with active UC and CD, there was a statistically significant decrease in MPV, PDW levels and increase in PCT levels when compared to healthy controls. In remission phase of IBD while MPV levels were lower, PDW and PCT levels were higher than control group. Both PDW (r: -0.271 p: 0.032) and PCT (r: 0.295 p: 0.027) had a significant correlation with UC disease activity. There was statistically signifi - cant change in all platelet indices during dis - eases follow-up. CONCLUSIONS: The present report revealed that changes of platelet indices in IBD are note - worthy.They can be added to other inflammatory markers especially to monitor disease from ac - tive phase to remission phase.

Kaposi' s sarcoma in HIV-positive patients: The state of art in the HAART-era

Abstract: Kaposi's sarcoma (KS) is a multicentric angioproliferative cancer of endothelial origin typically occurring in the context of immunodeficiency, i.e. coinfection with Human Immonodeficiency Virus (HIV) or transplantation. The incidence of KS has dramatically decreased in both US and Europe in the Highly Active Antiretroviral Therapy (HAART) era. However, KS remains the second most frequent tumor in HIV-infected patients worldwide and it has become the most common cancer in Sub-Saharan Africa. In 1994, Yuan Chang et al discovered a novel γ-herpesvirus in biopsy specimens of human KS. Epidemiologic studies showed that KS-associated herpesvirus (KSHV) or human herpesvirus-8 (HHV-8) was the etiological agent associated with all subtypes of KS. KS has a variable clinical course ranging from very indolent forms to a rapidly progressive disease. HAART represents the first treatment step for slowly progressive disease. Chemotherapy (CT) plus HAART is indicated for visceral and/or rapidly progressive disease. The current understanding of KS as a convergence of immune evasion, oncogenesis, inflammation and angiogenesis has prompted investigators to develop target therapy, based on anti-angiogenic agents as well as metalloproteinase and cytokine signaling pathway inhibitors. These drugs may represent effective strategies for patients with AIDS-associated KS, which progress despite chemotherapy and/or HAART. In this review, we focus on the current state of knowledge on KSHV epidemiology, pathogenesis and therapeutic options.

Can we prevent, reduce or reverse intestinal fibrosis in IBD?

Abstract: Intestinal fibrosis is a common complication of in inflammatory bowel disease (IBD) and can occur in both ulcerative colitis (UC) and Crohn's disease (CD), but is much more prevalent in CD Fibrosis is a consequence of local chronic inflammation and is characterized by abnormal deposition of extracellular matrix (ECM) proteins producted by activated myofibroblasts Current anti-inflammatory therapies used in IBD do not prevent nor they reverse established fibrosis and strictures Despite the therapeutic advance in the treatment of IBD in the last two decades, the incidence of intestinal strictures in CD has not significantly changed This implies that control of intestinal inflammation does not necessarily affect the associated fibrotic process The conventional view that intestinal fibrosis is an inevitable and irreversible process in patients with IBD is progressively changing in light of improved understanding of the cellular and molecular mechanisms that underline the pathogenesis of fibrosis Comprehension of the mechanisms of intestinal fibrosis may pave the way for the developments of anti-fibrotic agents and of new possible therapeutic approches in IBD Nevertheless, there are important clinical issues that need further investigations, in particular the identification of factors relevant for the development of the intestinal fibrosis in IBD and the need of accurate and effective monitoring of the fibrotic progression and of effectiveness of the new proposed treatments

Metformin-associated lactic acidosis requiring hospitalization. A national 10 year survey and a systematic literature review.

Abstract: BACKGROUND: Metformin is known to be rarely associated with lactic acidosis, a serious condition with a poor prognosis. AIM: To review the National Pharmacovigi- lance Network of the Italian Medicines Agency reporting cases of metformin-associated lactic acidosis. MATERIALS AND METHODS: The National Pharmacovigilance Network of the Italian Medi- cines Agency, was searched for cases of lactic acidosis that occurred in a 10 years period (from November 2001 to October 2011). Data were ana- lyzed, to identify associated clinical features. A systematic literature research was performed to identify other large case series on metformin as- sociated lactic acidosis. RESULTS: Metformin was the antidiabetic drug most frequently associated with lactic acidosis in the assessed period. Metformin-associated lactic acidosis was the most frequent serious adverse reaction related to metformin reported to the national authority (18.2% of all 650 ad- verse drug reactions reported). There were 59 cases of metformin-associated lactic acidosis (mortality rate of 25.4%). In most patients (89.8%) there was at least one risk factor for the occurrence of lactic acidosis. The predictors of death were low arterial blood pH and absence of acute renal failure. The systematic research of the literature identified only six case-series with more than 30 patients. CONCLUSIONS: This is the second largest case series ever reported on metformin-associ- ated lactic acidosis. We confirmed that this rare complication of metformin is frequently fatal. Death can be predicted when the patient arrive in the hospital with low pH and, not intuitively, if the patient has no acute kidney injury. Risk min- imisation measures taken at national level to prevent this serious complication are described.

Vitamin D deficiency in HIV infection: An underestimated and undertreated epidemic

Abstract: Hypovitaminosis D is a very common disorder, regarding both Western and developing countries. A growing amount of data over the last years have shown vitamin D defi - ciency to be high prevalent among HIV-positive subjects. In addition to "classic" risk factors, such as female sex, low dietary intake, dark skin pigmentation and low sun exposure, HIV-related factors, including immune activation and anti - retroviral adverse effects, may affect vitamin D status. Even if both protease inhibitors and non- nucleoside reverse transcriptase inhibitors have been associated with low vitamin D levels, avail - able evidences have failed to univocally associ - ate hypovitaminosis D with specific antiretroviral class effects. Low vitamin D is known to have a negative im - pact not only on bone health, but also on neu - rocognitive, metabolic, cardiovascular and im - mune functions. Similarly to the general popula - tion, several studies conducted on HIV-infected subjects have associated hypovitaminosis D with a greater risk of developing osteopenia/os - teoporosis and fragility fractures. Analogously, vitamin D deficiency has been described as an independent risk factor for cardiovascular dis - ease and metabolic disorders, such as insulin resistance and type 2 diabetes mellitus. Last EACS guidelines suggest to screen for hypovitaminosis D every HIV-positive subject having a history of bone disease, chronic kidney disease or other known risk factors for vitamin D deficiency. Vitamin D repletion is recommended when 25-hydroxyvitamin D levels are below 10 ng/ml. Furthermore, it may be indicated in pres - ence of 25OHD values between 10 and 30 ng/ml, if associated with osteoporosis, osteomalacia or increased parathyroid hormone levels. The opti - mal repletion and maintenance dosing regimens remain to be established, as well as the impact of vitamin D supplementation in preventing co - morbidities.

Diagnosis of small intestinal bacterial overgrowth in the clinical practice

Abstract: BACKGROUND: Gut microbiota plays several beneficial effects on the human host. Its qualitative and/or quantitative unbal - ance may facilitate the occurrence of small in - testinal bacterial overgrowth (SIBO). AIM: To review the available data in order to propose a practical approach to SIBO diagno - sis in the clinical setting. MATERIALS AND METHODS : Full papers from 1990 to present available on the Pubmed database concerning the topic of SIBO diagno - sis were critically reviewed. RESULTS : SIBO is common in the presence of one or more predisposing conditions. The clini - cal picture of SIBO patients is extremely variable, depending of underlying disorders, and both pa - tients and microbiota characteristics. SIBO could be asymptomatic, or leading to aspecific gas - trointestinal IBS-like symptoms. In worst cases it may configure a real malabsorption syndrome. Culture of intestinal aspirates remains at present the gold standard for SIBO diagnosis. However a lot of limitations including high costs and inva - sivity prevent from using this test in the clinical practice. Hydrogen lactulose and especially glu - cose breath tests are at present the most utilized to reach SIBO diagnosis in the clinical setting, due to their low costs, non invasivity, sufficient accuracy and reproducibility. CONCLUSIONS: SIBO should be suspected in the presence of IBS-like symptoms and/or mal - absorption syndrome occurring in the presence of disorders predisposing to SIBO develop - ment. The most common diagnostic tool is rep - resented at present by hydrogen breath tests.

Do Akiskal & Mallya's affective temperaments belong to the domain of pathology or to that of normality?

Abstract: BACKGROUND: Kraepelin and Kretschmer hypothesized a continuum between full-blown affective pathology and premorbid temperaments. More recently Akiskal proposed a putative adaptive role for the four fundamen - tal temperaments: the hyperthymic one charac - terized by emotional intensity, the cyclothymic one by emotional instability, the depressive one by a low energy level, and the irritable one by an excessive response to stimuli. Today it is widely debated whether affective temperaments belong to the domain of pathology or to that of normality. PURPOSE: To make clear, by applying an inte - grated model, the position of affective tempera - ments within the continuum between normality and pathology. METHODS: We reviewed several papers that explore the distribution of affective tempera - ments among the general population, and their involvement both in pathological conditions (so - matic and psychiatric) and in human activities (professions and other occupations). RESULTS: Far from being intrinsically patho - logical conditions, affective temperaments seem to represent adaptive dispositions whose dys - regulation can lead to full-blown affective pathol - ogy. All the temperamental types display some impact on people's lives by influencing personal skills and professional choices over a wide field of human activities. CONCLUSIONS: Affective temperaments are not problematic when they appear in a mild form, but when they occur in extreme form we have observed a gap between the hyperthymic tem - perament, which represents the most functional and desirable, and the cyclothymic, depressive, irritable and phobic anxious ones, which are closer to mood, anxiety, and substance use dis - orders, and imply a component of somatic dis - eases and life stressors. Eur opean Rev iew for Med ical and Pharmacol ogical Sci ences

Infectious complications in patients with lung cancer

Abstract: Infections remain a part of the natural course of cancer. During the course of their disease, patients with lung cancer frequent- ly present with an infection that can ultimately be fatal. Pathogenesis of infectious syndromes is usually determined by the underlying disease, as well as, the iatrogenic manipulations that oc- cur during its management. Hence, lung cancer infections include lower respiratory tract infec- tions in the context of COPD, aspiration, ob- struction and opportunistic infections due to im- munosuppression. Moreover, treatment-related infectious syndromes including post operative pneumonia, febrile neutropenia and superim- posed infection following radiation/chemothera- py toxicity is common. Importantly, diagnosis of infection in the febrile lung cancer patient is challenging and requires a high index of suspi- cion in order to distinguish from other causes of fever, including malignant disease and pul- monary embolism. Prompt initiation of treatment is pivotal to avoid increased mortality. Careful consideration of infection pathogenesis can pre- dict most likely pathogens and guide antibiotic management, thus, ensuring most favourable outcome.

Our experience in complications of orthognathic surgery: a retrospective study on 3236 patients.

Abstract: Background and objectives From 1989 to 2009, at the Department of Cranio-Maxillo-Facial Surgery, Umberto I Polyclinic, "Sapienza" University of Rome, 3236 patients affected by maxillo-mandibular malformations were submitted to orthognathic surgery, by means of rigid internal fixation. Follow-up highlighted the surgical complications and the possible functional and/or esthetical disorders in the treatment of those pathologies. The data collected have been compared with the ones reported in the literature. Materials and methods 3236 patients were evaluated clinically and radiographically. The X-rays have been performed before the study, after 24-48 hours, at 6 months and year after surgery. Results The most frequent surgical complication was the mandibular nerve sensitivity deficit (19%), irreversible only in 2% of the cases. Temporomandibular joint disorders (TMD), which are widely reported in the international literature, have been relevant in our study too. In particular, TMD occurred in those patients who were already affected by the disorder (from 28.3% to 18.1%); besides, in 11% of cases the symptom appeared after surgery and was treated by means of splint or physiotherapy. Infectious complications occurred in 2% of cases and fractures of the bone elements in 1.5% of cases. The other complications quoted internationally occurred in an irrelevant percentage in our study. Conclusions We believe that orthognathic surgery complications are quite rare and the percentages reported both in our study and in the literature have to be considered as surgical mistakes related to the surgeon experience or as real complications of the orthognathic surgery. Furthermore, as the success of this kind of surgery depends upon many factors, surgical complications represent only one of the causes of the failure. Other causes could be mistakes in planning, unsuitable orthodontic treatment and, finally, an unsuitable assessment of the patients' esthetical and functional problems.

Curcumin decreases oleic acid-induced lipid accumulation via AMPK phosphorylation in hepatocarcinoma cells.

Abstract: BACKGROUND AND OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is one of the most common metabolic syndromes and is characterized by the accumulation of hepatic triglycerides (TG), which result from an imbal - ance between uptake, synthesis, export, and oxi - dation of fatty acids. Curcumin is a polyphenol derived from the herbal remedy and dietary spice turmeric, was found to prevent obesity and diabetes in mouse models. However, a hypolipi - demic effect of curcumin in oleic acid- induced hepatocarcinoma cells has not been reported. In this study, we examined the effect of curcumin on reducing lipid accumulation in hepatic cells. MATERIALS AND METHODS: Hepatocytes were treated with oleic acid (OA) containing with or without curcumin to observe the lipid accumulation by Oil Red O stain.We also tested the effects of curcumin on triglycerides (TG) and total cholesterol (TC) in HepG2 cells. West - ern blot and reverse transcription polymerase chain reaction (RT-PCR) was used to measure sterol regulatory element binding proteins-1 (SREBP-1), fatty acid synthase (FAS), peroxi - some proliferator-activated receptor (PPAR)- α, and adenosine 5'-monophosphate (AMP)-acti - vated protein kinase (AMPK) expression. RESULTS: Curcumin suppressed OA-induced lipid accumulation and TG and TC levels. Also, curcumin decreased hepatic lipogenesis such as SREBP-1, and FAS. Besides, we also found out the antioxidative effect of curcumin by in - creasing the expression of PPAR α. Curcumin increased AMPK phosphorylation in hepato - cytes. CONCLUSIONS: These results indicated that curcumin has the same ability to activate AMPK and then reduce SREBP-1, and FAS expression, finally leading to inhibit hepatic lipogenesis and hepatic antioxidative ability. In this report, we found curcumin exerted a regulatory effect on lipid accumulation by decreasing lipogene - sis in hepatocyte. Therefore, curcumin extract may be active in the prevention of fatty liver.

Propofol suppresses proliferation, invasion and angiogenesis by down-regulating ERK-VEGF/MMP-9 signaling in Eca-109 esophageal squamous cell carcinoma cells.

Abstract: Background and aims Propofol (2,6-diisopropylphenol), one of the most commonly used intravenous anaesthetic agents during cancer resection surgery, has been reported to have the ability of influencing the invasion of human cancer cells. However, the mechanisms are not very clear. In this study, we investigated the effects of propofol on the proliferation, invasion and angiogenesis of human Eca-109 cells, and explored the mechanism. Methods The human Eca-109 cells was treated with propofol at the concentrations of 10-100 µmol/L for 72 hours or at the concentration of 100 µmol for 8-72 hours. Cell viability was determined by the MTT assay; the effect of propofol on apoptosis by 5'-triphosphate-biotin nick end labeling (TUNEL) staining. The effect of propofol on angiogenesis was determined by the chicken chorioallantoic membrane (CAM) angiogenesis assay. The effect of propofol on cell invasion using a modified Matrigel Boyden chamber assay. ERK1/2, MMP-9 and VEGF leves was detected by western blotting assay. Results In human Eca-109 cells, propofol significantly promoted cell apoptosis and inhibited proliferation in a dose and time-dependent manner. Furthermore, propofol inhibited dose and time-dependent invasion and angiogenesis. Propofol significantly dose and time-dependently down-regulated gene expression and protein production of ERK/pERK, VEGF and MMP-9. The functional effects and MMP-9/VEGF inhibition were shown to be dependent on the ERK/VEGF and ERK/MMP-9 signaling pathways. It was noteworthy that the ERK activator (phorbol 12-myristate 13-acetate [PMA]) treatment increased the MMP-9/VEGF levels after propofol treatment, and led to significant increase of proliferation, invasion and angiogenesis. Conclusions These findings indicate that propofol inhibited proliferation, invasion and angiogenesis of human Eca-109 cells in vitro through modulation of ERK-VEGF /MMP-9 signaling. Propofol not only can be an anesthesia agent which reduces pain but plays an important role of inhibiting the migration and angiogenesis of ESCC cells in the therapy of ESCC patients.

Quercetin potentially attenuates cadmium induced oxidative stress mediated cardiotoxicity and dyslipidemia in rats.

Abstract: BACKGROUND: Cadmium is one of the potent cardiotoxic heavy metals in the en - vironment, which induces oxidative stress, dys - lipidemia and membrane disturbances in heart. Quercetin is an effective antioxidant and free radical scavenger against oxidative stress. This study was designed to evaluate the protective effect of quercetin (QE) on cardiac marker en - zymes, lipid peroxidation products, lipid profile, membrane bound ATPases and antioxidant sta - tus in cadmium (Cd)-intoxicated rats. MATERIALS AND METHODS: Twenty four male albino rats were used. Cadmium induced oxidative cardiotoxicity was induced by the oral administra - tion of Cd for four weeks. Quercetin was pretreat - ed along with Cd for four weeks to assess its car - dioprotective effect against Cd intoxication. Rats treated with vehicles alone were used as controls. RESULTS: Rats intoxicated with cadmium (5 mg/kg/day) for 4 weeks in combination with quercetin (50 mg/kg/day) respectively. Cd-in - duced cardiotoxicity and dyslipidemia was indi - cated by increased activities of marker enzymes such as creatine kinase-MB, aspartate transami - nase, alanine transaminase, alkaline phos - phatase and lactate dehydrogenase in serum. In addition, the levels of lipid peroxidation products and protein carbonyl contents in heart were sig - nificantly ( p < 0.05) increased and the activities of enzymic antioxidants such as superoxide dis - mutase, catalase, glutathione peroxidase, glu - tathione reductase and glutathione-S-transferase in the heart and non-enzymic antioxidants such as glutathione, vitamin C and E in the heart were significantly ( p < 0.05) decreased in Cd intoxicat - ed rats. The levels total cholesterol (TC), triglyc - erides (TG), phospholipidis (PL), free fatty acids (FFA), LDL andVLDL were significantly ( p < 0.05) increased and the level of HDL was significantly decreased in the serum of Cd-treated rats. Cd in - toxication also increased the levels ofTC,TG and FFA and decreased the level of PL in the heart tissue. Further Cd treatment significantly ( p < 0.05) decreased the levels of membrane bound ATP ases in heart. QE treatment along with Cd showed significant protective effect on all the biochemical parameters studied. Histopathologi - cal findings of QE and Cd treated heart con -

Adolescent depression: clinical features and therapeutic strategies.

Abstract: BACKGROUND: Major depres - sive disorder (MDD) is a common disorder dur - ing adolescence and it is associated with an in - creased risk of suicide, poor school perfor - mance, impaired social skills, social withdrawal and substance abuse. Further, as many depres - sive episode in adolescents do not reach the di - agnostic threshold for MDD, the disorder re - mains undetected. AIM: This review aims to provide an update of clinical features of adolescent MDD and to focus on the most appropriate therapeutic strategies to adopt in clinical practice. MATERIALS AND METHODS: We reviewed the international literature to identify studies fo - cusing on clinical features and therapeutic op - tions in adolescents affected by MDD. PubMed, Medline and Cochrane Library databases were searched for English language papers. RESULTS: The clinical picture of depression is variable with sex and age. Somatic complaints, particularly headache and fatigue, are a common presentation in adolescent MDD. Irritability is pre - sent most frequently in female and it is related to the severity of MDD. Adolescent MDD is also char - acterized by a high rates of suicides. The thera - peutic strategy in adolescent depression includes psychotropic medications, psychotherapy or a combination of both treatments, with selection of the most appropriate strategy depending on symptom severity. As first-line treatment the tradi - tional cognitive behavioural therapy (CBT), as well as the cognitive Post-Rationalist (PR) approach, are so far considered the goal standard. CONCLUSIONS: The therapeutic approach to the adolescent affected by MMD should respect the person in his/her psycho-physical entirety. The intervention may help the subject in seeking a more stable and adaptable identity. It is rele - vant to have a good knowledge of the peculiar clinical picture of adolescent MDD in order to make an early identification of the disorder and to define an appropriate personalized therapeu - tic program.

Partial role of multiple pathways in infarct size limiting effect of quercetin and rutin against cerebral ischemia-reperfusion injury in rats.

Abstract: Background Reperfusion therapy used in the treatment of cerebral ischemia often causes reperfusion neurological injury. Multiple pathological processes are involved in this injury including oxidative stress and components of the inflammatory response appear to play key roles in these deleterious effects. Thus new therapeutic strategies aimed at neutralization of OS-induced neurotoxicity support the application of natural antioxidant bioflavonoids. Both experimental and epidemiological evidence demonstrate that bioflavonoid such as quercetin and rutin are neuroprotective in models of cerebral ischemia reperfusion injury. However, recent studies indicate that the radical scavenger property of quercetin and rutin is unlikely to be the only reason for their cerebroprotective actions and in fact, a wide spectrum of cellular signaling events may well account for their biological actions. Aim In this study we attempted to establish the various mechanisms involved in the cerebroprotective activity of quercetin and rutin. Methods Adult Sprague Dawely rats were anesthetized with thiopentone and subjected to global cerebral ischemia by occlusion of bicommon carotid arteries. Infarct size (TTC staining), SOD, MDA, CAT and MPO levels was assessed 4 h after the onset of ischemia. Results Quercetin (50 mg/kg) and rutin (10 mg/kg) administered 10 min before reperfusion resulted in significant reduction of infarct size, MDA, and MPO levels and significant increase in SOD and CAT levels. Administration of L-NAME prior to administration of quercetin and rutin, significantly reduced the cerebroprotection offered by quercetin and rutin. Conclusions Possible partial role of antioxidant, anti-inflammatory and involvement of NO in the beneficial effects of bioflavonoids quercetin and rutin against cerebral ischemia reperfusion injury was observed.

The role of intestinal mucosa oxidative stress in gut barrier dysfunction of severe acute pancreatitis.

Abstract: BACKGROUND : Severe acute pan - creatitis (SAP) is a serious s ystemic disease with a sustained high mortality rate. Extensive evidence has shown that gut barrier dysfunc - tion plays a critical role in the pathophysiology of SAP . AIM: Investigating the role of intestinal mucosa oxidative stress in gut barrier dysfunction of SAP. MATERIALS AND METHODS: Twenty-four BALB/c mice were randomly divided into two groups with twelve mice each group. The SAP group mice received six intraperitoneal injec - tions of cerulein (50 µg/kg) at 1-hour intervals, then given one intraperitoneal injection of 10 mg/kg lipopolysaccharide (LPS from E. coli ) for inducing SAP. Normal saline was given to the mice of control group. The animals of each group were averaged to two batches. Four and eight hours after the final injection, respectively, mice were anesthetized and blood and tissue samples were harvested for examination. The pathological changes of pancreas and gut were observed and scored. The serum levels of di - amine oxidase (DAO), amylase and tumor necro - sis factor-alpha (TNF- α) were measured. The contents of malondialdehyde (MDA) and reduced glutathione (GSH) and activity of superoxide dis - mutase (SOD) and xanthine oxidase (XO) in gut mucosa were detected. In gut mucosa, the cas - pase-3 activity was measured and the cell apop - tosis and apoptosis index (AI) were determined by terminal deoxynucleotidyl transferase-mediat - ed dUTP nick end labeling (TUNEL) assay. The data were analyzed by ANOVA and t-test. RESULTS: At four and eight hours after SAP in - duction, the SAP group mice had significantly higher pancreatic and gut pathological scores ( p < 0.01) and increased serum levels of amylase ( p < 0.05), DAO and TNF- α (p < 0.01 ) and increased MDA contents and XO activity of gut mucosa ( p < 0.01) compared with those of control mice. There were significantly lower GSH contents ( p < 0.05) and SOD activity ( p < 0.01) of gut mucosa in the SAP mice. It was also observed that the gut mu - cosa cells of SAP mice had significantly higher caspase-3 activity and apoptosis index ( p < 0.01). CONCLUSIONS: In SAP, waterfall-style re - lease of inflammatory factors such as TNF- α led to ischemia-reperfusion injury of gut mu - cosa which resulted in serious oxidative stress and activation of caspase-3 pathway and se - vere apoptosis of gut mucosa. Therefore, in - testinal mucosal oxidative stress may play an important role in the mechanism of gut barrier dysfunction.

Propofol inhibits invasion and enhances paclitaxel- induced apoptosis in ovarian cancer cells through the suppression of the transcription factor slug.

Abstract: BACKGROUND AND AIM: Propofol is one of the most commonly used in - travenous anaesthetic agents during cancer re - section surgery. It has recently found that propofol has the effect to inhibit cancer cell mi - gration and invasion and sensitize cancer cells to chemotherapy. However, the role of the propofol on the ovarian cancer cells is un - known. In the present study, we explored the ef - fect of propofol on invasion and chemosensiti - zation of ovarian cancer cells to paclitaxel. MATERIALS AND METHODS: The paclitaxel sensitivity of ovarian cancer cell lines HO- 8910PM, H0-8910, SKOV-3, OVCAR-3, COC1 and ES-2 were determined by MTT assays. The Slug levels in the cell lines and the effects of propofol on Slug levels in the cell lines were determined by western blot assays.The effect of propofol on invasion, migration and paclitaxel -induced ovari - an cancer apoptosis was determined by Boyden chamber assays, cell MTT,TUNEL assays. RESULTS : The results showed that the cell lines COC1, H0-8910 and ES-2 were sensitive, whereas HO-8910PM, OVCAR-3, SKOV-3, were resistant to paclitaxel. Significant correlation was observed between basal Slug levels and paclitaxel sensitivity. Paclitaxel treatment in - creased Slug levels.Treatment with propofol in - duced apoptosis and increased paclitaxel killing of all paclitaxel-sensitive and -resistant ovarian cancer cells followed by significant de - crease in the Slug levels.Treatment with propo - fol inhibits invasion and migration. CONCLUSIONS: These data suggest a new mechanism by which the propofol inhibits inva - sion and metastasis,enhances paclitaxel -in - duced ovarian cancer cell apoptosis through suppression of Slug.

Influence of PRF in the healing of bone and gingival tissues. Clinical and histological evaluations.

Abstract: INTRODUCTION: The healing of bone tissues around dental implants is based primarily on a correct osseointegration. BACKGROUND: Typically, implants stability and peri-implant tissues health are anticipated to decrease during the early weeks of healing; this is followed by an increase in stability. AIM: The aim of the present study is to as - sess a predictable protocol in order to increase the peri-implant tissues maintenance around post-extractive dental implants, thanks to the use of Platelet-Rich Fibrin (PRF) membrane. MATERIALS AND METHODS: This is a retro - spective observational study of 127 tapered den - tal implants placed in the immediate post-extrac - tion sites of maxillary bone of 59 patients. Atraumatic dental extraction and flapless im - plant surgery was performed in all reported cas - es. The cortical bone position relative to the im - plant reference point was evaluated at implant placement and 10 to 24 months following im - plantology. The gap between bone tissue and the implant surface was measured up to a maxi - mum of 3 mm. After placing implants we have filled the surgical site with a PRF gel, so as to fill the gap between bone tissue and the implant surface, and then we have covered the surgical site with a PRF membrane, so as to coat the gap between the alveolar crest and the implant. RESULTS: In all cases, we observed the com - plete covering of the dental implants, with new - ly formed soft tissue of variable thickness be - tween 1 and 3 mm. Cortical bone adaptation from the time of implant placement up to 30 months following prosthetic restoration ranged from 0.4 mm to 1.7 mm. CONCLUSIONS: Our study showed a series of successful rehabilitations, with post-extraction implantology technique, in 99.8 percent of cas - es, despite the success rates in the medium and long-term post-extraction implantology reported in the literature range between 92.7 percent and 98.0 percent. Long-term maintenance of crestal bone and the rapid healing of soft tissue dimen - sion with maintenance of peri-implant papilla were observed as outcomes after post-extrac - tive implants insertion.

Arthroscopic debridement compared to intra-articular steroids in treating degenerative medial meniscal tears.

Abstract: OBJECTIVES: Virtually all early cases of knee osteoarthritis have degenerative medial meniscus lesions accompanying the chondral defects on MRI. It is difficult to deter - mine if the symptoms are caused by the unsta - ble meniscus or by osteoarthritis, hence unclear guidance towards treatment. We, therefore, aimed to determine the clinical improvement fol - lowing arthroscopic meniscectomy compared to intraarticular administration of corticosteroids for degenerative ruptures of the medial menis - cus in the presence of early stage medial com - partment knee osteoarthritis. PATIENTS AND METHODS: We included 120 consecutive cases of nontraumatic symptomatic knees which had degenerative lesions of the me - dial compartment (cartilage and meniscus) on MRI's.They were randomized to receive either in - traarticular steroid injection or arthroscopic de - bridement. We also analyzed the correlation be - tween BMI, age, gender, MRI, intraoperative as - pect of the meniscus and cartilage and clinical improvement using the Oxford Knee Score up to one year. At one month there was significant im - provement of the scores for all the examined cases. Also at one month, the arthroscopic group performed better in terms of symptom im - provement. This was maintained for 79% of the knees in the arthroscopic group and 61% in the intraarticular steroid injection respectively, out of those available for follow up at one year. RESULTS: At one month, symptoms reappeared for 12 patients in the steroid group and 7 in the arthroscopy respectively. Gender and age did not correlate with treatment, whereas extrusion of the meniscus, bone marrow edema, duration of the clinical symptoms, obesity and a low preoperative score were negative prognostic factors. CONCLUSIONS: Degenerative medial menis - cal tears, in the presence of osteoarthritis, can only marginally benefit from arthroscopic de - bridement over intraarticular steroid injections in short term follow up. When considering indi - vidual cases, factors become more predictive when analyzed in group.

The Combined therapy myo-inositol plus D-Chiro-inositol, in a physiological ratio, reduces the cardiovascular risk by improving the lipid profile in PCOS patients.

Abstract: BACKGROUND Women with Polycystic Ovarian Syndrome (PCOS) present several factors that increase the cardiovascular risk, such as insulin resistance and dyslipidemia. Myo-inositol and D-chiro-inositol have been shown to improve insulin resistance, hyperandrogenism and to induce ovulation in PCOS women. However, their effects on dyslipidemia are less clear. The aim of the present study was to evaluate whether the combined therapy myo-inositol plus D-chiro-inositol (in a in a physiological ratio of 40:1) improve the metabolic profile, therefore, reducing cardiovascular risk in PCOS patients. PATIENTS AND METHODS Twenty obese PCOS patients [BMI 33.7 ± 6 kg/m2 (mean ± SD)] were recruited. The lipid profile was assessed by measuring total cholesterol, LDL, HDL and triglycerides before and after 6 months treatment with the combined therapy. Secondary end points included changes in BMI, waist-hip ratio, percentage of body fat, HOMA-IR and blood pressure. RESULTS The combined therapy myo-inositol and D-chiro-inositol improved LDL levels (3.50 ± 0.8 mmol/L versus, 3 ± 1.2 mmol/L p < 0.05), HDL (1.1 mmol/L ± 0.3 versus 1.6 mmol/L ± 0.4 p < 0.05) and triglycerides (2.3 ± 1.5 mmol/L versus 1.75 ± 1.9 mmol/L p < 0.05). Furthermore, significant improvements in HOMA-IR were also observed. CONCLUSIONS The combined therapy myo-inositol plus D-chiro-inositol is able to improve the metabolic profile of PCOS women, therefore, reducing the cardiovascular risk.

The evaluation of selected serum mineral concentrations and their association with insulin resistance in obese adolescents.

Abstract: Background In obesity, elevated insulin resistance is observed, which may be associated with disturbances in mineral status in the body. The few studies concerning the status of minerals and their relationships with insulin resistance and body composition in adolescent populations have brought inconclusive results. Aim of this study is, thus, to assess serum mineral concentration in obese adolescents, and to evaluate their potential association with insulin resistance. Subjects and methods Seventy-eight obese adolescents and 20 healthy volunteers aged 12-18 years were recruited for the study. Selected anthropometrical measurements and levels of iron, zinc, copper, calcium, and magnesium were assessed in serum. Insulin resistance in the participants was evaluated according to the homeostatic model of assessment for insulin resistance (HOMA-IR) protocol. Levels of iron, zinc, copper, calcium, and magnesium were assessed in serum. Results Obese subjects had significantly higher HOMA-IR indices than the control group. Compared to healthy subjects, the serum concentration of zinc, calcium, and magnesium was significantly lower in obese subjects. A significant inverse relation was found between HOMA-IR and zinc levels in serum. Conclusions Obese adolescents have a poorer mineral status (especially zinc) than adolescents of normal weight, which can contribute to insulin resistance.

Lactose intolerance: from diagnosis to correct management.

Abstract: This review discusses one of the most relevant problems in gastrointestinal clinical practice: lactose intolerance The role of lactase-persistence alleles the diagnosis of lactose malabsorption the development of lactose intolerance symptoms and its management Most people are born with the ability to digest lactose, the major carbohydrate in milk and the main source of nutrition until weaning Approximately, 75% of the world's population loses this ability at some point, while others can digest lactose into adulthood Symptoms of lactose intolerance include abdominal pain, bloating, flatulence and diarrhea with a considerable intraindividual and interindividual variability in the severity Diagnosis is most commonly performed by the non invasive lactose hydrogen breath test Management of lactose intolerance consists of two possible clinical choice not mutually exclusive: alimentary restriction and drug therapy

Neonatal sevoflurane anesthesia induces long-term memory impairment and decreases hippocampal PSD-95 expression without neuronal loss

Abstract: AIM: Volatile anesthetics are widely used in the clinic, and sevoflurane is the most prevalent volatile anesthetic in pediatric anesthesia. Recent findings question the poten - tial risks of volatile anesthetics on brain devel - opment. Evidence suggests that sevoflurane may cause neuronal deficiency.This study inves - tigates the long-term effect of sevoflurane in the developing brain. MATERIALS AND METHODS: We anes - thetized 7 day-old rats for 4 h with 2.5% sevoflu - rane. A Morris water maze was used to evaluate hippocampal function 7 weeks after sevoflurane exposure. Nissl staining was performed to ana - lyze neuronal loss. PSD-95 (postsynaptic density protein-95) expression in the hippocampus was measured using a western blot. RESULTS: The exposure to 2.5% sevoflurane caused long-term deficits in hippocampal func - tion and decreased hippocampal PSD-95 expres - sion without neuronal loss. This study demon - strates that P7 rats exposed for 4 h to 2.5% sevoflurane have significant spatial learning and memory impairment 7 weeks after anesthesia. In addition, PSD-95 expression in the hippocampus decreased at P56 without neuronal loss. CONCLUSIONS: These data suggest that sevoflurane causes neurotoxicity in the develop - ing brain, which may be attributed to decreased PSD-95 in the hippocampus.

S100A4 silencing suppresses proliferation, angiogenesis and invasion of thyroid cancer cells through downregulation of MMP-9 and VEGF.

Abstract: BACKGROUND AND AIM : It is well documented that S100A4 is upregulated in many cancers and plays a pivotal role in tumor proliferation, invasion, metastasis and angiogene - sis. However, the precise role and mechanism S100A4 exerts in the thyroid cancer have not been fully elucidated to date. In the present study, we investigated the effect of S100A4 on prolifera - tion, invasion, metastasis and angiogenesis in thyroid cancer cells. MATERIALS AND METHODS: A plasmid con -

Comparative evaluation of the efficacy of ginger and orlistat on obesity management, pancreatic lipase and liver peroxisomal catalase enzyme in male albino rats.

Abstract: Background Obesity is a disease involving body weight gain. Several synthetic drugs of better efficacy are being introduced in the modern system of medicine. Orlistat is a pharmacological agent promoting weight loss in obese subjects via inhibiting of gastric and pancreatic lipase. Ginger (Zingiber officinale Roscoe, Zingiberacae) is one of the most commonly used spices around the world; it has long been used in traditional medicine as a cure for some diseases. Objective To evaluate the effect of ginger and orlistat on rats fed high fat diet. Materials and methods Forty male Albino rats were either not treated (control), or fed high fat diet, or fed high fat diet with dietary orlistat supplementation (200 mg/kg diet), or fed high fat diet supplemented with 5% ginger powder. After four weeks of treatment, final body weight and food intake were determined. Blood samples were collected, lipid parameters, total bilirubin, pancreatic lipase were determined. Liver peroxisomes were isolated from rat livers and peroxisomal catalase activity was determined. Results Treatment with both ginger and orlistat had significant effect in reducing body weight, besides, supplementing diet with orlistat increase food intake. Both ginger and orlistat had the ability to reduce lipid profile, ginger had great effect in increasing HDL-cholesterol than orlistat. When compared to the control group, ginger treatment did not alter either total bilirubin or pancreatic lipase activity while orlistat clearly reduced their concentration. Orlistat supplementation induced a significant reduction in peroxisomal catalase level, while ginger has been reported to interfere with enzyme activity increasing its level. Conclusions Ginger has a great ability to reduce body weight without inhibiting pancreatic lipase level, or affecting bilirubin concentration, with positive effect on increasing peroxisomal catalase level and HDL-cholesterol.

Relationships between serum osteocalcin levels versus blood glucose, insulin resistance and markers of systemic inflammation in central Indian type 2 diabetic patients.

Abstract: BACKGROUND : Recent studies have demonstrated an endocrine role of osteoblast derived protein osteocalcin in the regulation of blood glucose homeostasis. In addition emerging evidence suggests that subclinical inflammation is associated with altered bone metabolism. Howev - er, the relationship between osteocalcin and in - flammatorymarkersisstillunclear. AIM: This study was aimed to investigate the association of serum osteocalcin with fasting plasma glucose, insulin resistance and markers of systemic inflammation - interleukin-6 (IL-6) and high sensitivity C-reactive protein (hs-CRP) in central Indian type 2 diabetic patients. PATIENTS AND METHODS: This study includ - ed 108 individuals with newly diagnosed type 2 diabetes mellitus (DM) and 50 age and body mass index (BMI) matched healthy subjects as controls. Blood samples were analyzed for fast - ing plasma glucose, fasting insulin, interleukin- 6, hs-CRP and serum osteocalcin. Insulin resis - tance was calculated by homeostasis model as - sessment (HOMA-IR). RESULTS: In the present study we observed significantly lower level of osteocalcin in type 2 diabetic group compared to non diabetic control (p< 0.0001). In linear regression analysis adjusted for age, gender, BMI, waist circumference and waist to hip ratio, serum level of osteocalcin was inversely associated with fasting plasma glucose (beta = -0.015; p = 0.0004), fasting insulin (beta = -0.059; p = 0.0242), HOMA-IR (beta = -0.149; p = 0.0011), interleukin-6 (beta = -0.071; p = 0.0036) and hs-CRP levels (beta = -0.506; p = 0.0085) in thediabeticsubjects. CONCLUSIONS: Our findings suggest that os - teoblast derived protein osteocalcin may have a wide ranging role in the pathophysiology of type 2 diabetes by being associated with both blood glucosehomeostasisandsystemicinflammation.

Ameliorating effects of curcumin on 6-OHDA-induced dopaminergic denervation, glial response, and SOD1 reduction in the striatum of hemiparkinsonian mice.

Abstract: BACKGROUND: Inflammation and oxidative stress are believed to contribute to neu - ronal degeneration of the nigrostriatal dopaminer - gic (DA) pathway in Parkinson's disease. Curcum - in, a component of the yellow curry spice, has been reported possessing anti-inflammatory and anti-oxidative effects. AIM: The present study investigated the ef - fects of curcumin on the extent of DA innerva - tion, glial response, and Cu/Zn superoxide dis - mutase (SOD1) expression in the striatum of 6- hydroxydopamine (6-OHDA)-lesioned mice. MATERIALS AND METHODS: 6-OHDA was unilaterally injected into the right striatum of ICR male mice. Curcumin (200 mg/kg) was adminis - tered daily for 7 days starting instantaneously after 6-OHDA injection. Seven days after 6-OHDA insult, mice were euthanized and striatal sec - tions were collected, immunohistochemically stained, and quantitated for tyrosine hydroxylase (TH), glial fibrillary acidic protein (GFAP), ionized calcium binding adapter molecule 1 (Iba1), and SOD1 immunoreactivity. RESULTS: 6-OHDA injection triggered a signifi - cant loss of TH-immunoreactive (-IR) axons, in - duced reaction of GFAP-IR astrocytes and Iba1- IR microglia, and decreased SOD1 expression in the 6-OHDA-lesioned striatum. Curcumin attenu - ated loss of TH-IR fibers, diminished activation of astrocytes and microglia, and sustained SOD1 level in the lesioned striatum. CONCLUSIONS: These results suggest that cur - cumin counteracts the neurotoxicity of 6-OHDA through its anti-inflammatory properties (inhibi - tion of glial response) and preservation of SOD1 expression.

Copper, ceruloplasmin and oxidative stress in patients with advanced-stage endometriosis.

Abstract: AIM To compare patients with advanced stage endometriosis with control patients without endometriosis with respect to serum Copper (Cu) and Ceruloplasmin (Cp) levels and oxidative stress markers in order to evaluate the importance of these parameters in the pathogenesis of endometriosis. PATIENTS AND METHODS A total of 72 women who underwent laparoscopy or laparotomy for evaluation of infertility, pelvic pain, pelvic mass, tubal ligation or endometriosis were enrolled for this prospective clinical study. Patients were divided into two groups by visual diagnosis at surgery and histological confirmation of endometriosis: control patients (n=41) without endometriosis and study group (n=31) with stage III/IV (advanced stage) endometriosis. Serum Cu, Cp, total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), paraoxonase-1 (PON-1), malondialdehyde (MDA), triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels were compared between the two groups. Correlations between Cu, Cp and oxidative stress markers were determined. RESULTS Serum TOS, OSI, Cu, Cp, TG, TC, LDL were significantly higher, whereas TAS, PON-1 activity and HDL were significantly lower, in women with advanced-stage endometriosis than in control groups. There was no difference in serum MDA activities between the two groups. Positive correlations were found between Cu and TOS, Cu and OSI, Cu and Cp, while a negative correlation was found between Cu and PON-1 in the advanced-stage endometriosis group. Positive correlations were found between Cp and TOS, and Cp and OSI in the advanced-stage endometriosis group. CONCLUSIONS Cu and Cp appear to be associated with the etiopathogenesis of and oxidative stress in endometriosis.