Assessment of Systemic Condition and Smoking Impact Over Incidence of Apical Periodontitis.

This study aimed to assess the prevalence of apical periodontitis in a subset of the population of south-eastern Romania and to analyze the overall health status of the group of patients with apical periodontitis. The medical and dental history, including age, gender, background, presence of smoking, level of education, the total number of teeth present and with apical periodontitis, and the general health status were recorded from a total of 200 patients. The periapical status was analyzed using an orthopantomogram and periapical radiographs of teeth that were diagnosed with periapical lesions by the same dental professional. The periapical status was classified according to the periapical index (PAI), with apical periodontitis being present if the PAI score ≥3. The majority of patients were female (58.5%), with secondary or higher education from urban areas and the mean number of teeth with apical periodontitis was 2.29 ± 1.26, with a median of 2 teeth. A total of 17.1% of patients were smokers, these patients had two more teeth with periapical pathology, and 16% of all patients had general diseases, the most common of which was cardiovascular disease (8.2%). Compared with those without the disease, these patients had a higher number of teeth with apical periodontitis (median = 2.5, IQR = 2-4 vs. median = 2, IQR = 1-3). As a result, this scientific research suggests an association between smoking, cardiovascular disease, and gastritis with apical periodontitis, but no association could be demonstrated between apical periodontitis and other systemic diseases.

Safety, Efficacy and Persistence of Advanced Therapies in Inflammatory Bowel Disease: Results from ORIGINS. A Retrospective Observational Study.

BACKGROUND AND AIMS: Real-world assessments of efficacy and safety of advanced therapies used for inflammatory bowel disease (IBD) patients are limited. We aimed to report safety, efficacy and treatment persistence of new molecules (infliximab, adalimumab, vedolizumab, tofacitinib, ustekinumab) in a retrospective multicentric national Romanian analysis. METHODS: We conducted a nationwide, retrospective observational multicentric study. Data were collected retrospectively from electronic and paper files. Patients who started on one of the five investigated molecules during December 2019-December 2021 were included. The main outcome measures were clinical remission, endoscopic healing, persistence on treatment and safety data. RESULTS: A total of 678 adult patients from 24 Romanian IBD centers with a diagnosis of ulcerative colitis or Crohn's disease were included. Participants had previously failure to one (268, 39.5%), two (108, 15%) or more treatment lines and only 38% (259) were biologic naïve. In the 24 months study period, most patients were started on vedolizumab (192, 28%), followed by adalimumab, infliximab, ustekinumab and tofacitinib. In biologic-naïve patients, most physicians (72%) preferred anti-TNF treatment as first line biologic (93 patients started on infliximab, 92 on adalimumab), followed by vedolizumab, ustekinumab and tofacitinib. During follow-up, 71% (470, p=0.05) of patients achieved clinical remission and 36% (134, p=0.03) achieved mucosal healing. The 6 months milestone for persistence was reached in 78% (530) of cases. Almost half of patients (47%, 316 patients) persisted on their current treatment for over 12 months. Overall, an adverse reaction was reported for 67 (10.4%) patients, with no lethal events. CONCLUSIONS: Population of biologic-experienced IBD patients in Romania is increasing and is becoming more difficult to achieve long-term disease control. Discontinuation rates for advanced therapies are high.

Probiotics and the microbiota-gut-brain axis: focus on patients with depression. A review of current research.

This review covers recent data on the relationship between major depressive disorder (MDD) and faecal microbiome and examines the co-relations between the use of probiotics and changes in psychiatric state. We conducted a thorough search of academic databases for articles published between 2018 and 2022, using specific keywords and previously established inclusion/exclusion criteria regarding faecal microbiota, depressive disorder, and probiotics. Of 192 eligible articles (reviews, original papers, and clinical trials), we selected 10 that fully met our criteria and performed a careful review to determine any correlation between microbiome, probiotic treatment, and depression. All patients were adults (mean age, 36.8), with at least one MDD episode and onset of depression during adolescence (duration of 31.39 years of depressive episodes). We found mixed but mostly positive results regarding the influence of probiotic/prebiotic/postbiotic effects on depression. We could not identify the precise mechanism of action that led to their improvement. Antidepressants did not alter the microbiota, according to studies that evaluated this aspect. Probiotic/prebiotic/postbiotic treatments were proven to be safe, with few and mild side effects. Probiotics seemingly could be beneficial in patients with depression, as evidenced by well-established depression scales. Based on this finding and the high tolerability and safety of probiotics, no caveats against their routine use can be made. Some unmet needs in this field include determination of the dominant type of microbiota in specific patients with depression; study of microbiome-directed/driven treatment regarding dose and duration adjustments; and multiple versus single strain treatments.

Role of Phytonutrients in Nutrigenetics and Nutrigenomics Perspective in Curing Breast Cancer.

Breast cancer (BC) is one of the most common type of cancer and an important contributor to female mortality. Several genes and epigenetic modifications are involved in the development and progression of BC. Research in phytochemistry, nutrigenomics, and nutrigenetics has provided strong evidence that certain phytonutrients are able to modulate gene expression at transcriptional and post-transcriptional levels. Such phytonutrients may also be beneficial to prevent and treat BC. In this review, we will focus on the nutrigenomic effects of various phytochemicals including polyphenols, phytosterols, terpenoids, alkaloids, and other compounds from different sources. Overall, these phytonutrients are found to inhibit BC cell proliferation, differentiation, invasion, metastasis, angiogenesis, and induce apoptotic cell death by targeting various molecular pathways. They also alter epigenetic mechanisms and enhance the chemosensitivity and radiosensitivity of cancer cells. Such phytochemicals may be used for the effective management of BC patients in the clinical setting in the future. The present article aims to summarize the specific molecular pathways involved in the genetic effects of phytochemicals in BC.

Recognizing the Benefits of Pre-/Probiotics in Metabolic Syndrome and Type 2 Diabetes Mellitus Considering the Influence of Akkermansia muciniphila as a Key Gut Bacterium.

Metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) are diseases that can be influenced by the structure of gut microbiota, whose improvement is often neglected in metabolic pathology. This review highlights the following main aspects: the relationship between probiotics/gut microbes with the pathogenesis of MetS, the particular positive roles of Akkermansia muciniphila supplementation in the onset of MetS, and the interaction between dietary polyphenols (prebiotics) with gut microbiota. Therefore, an extensive and in-depth analysis of the often-neglected correlation between gut microbiota and chronic metabolic diseases was conducted, considering that this topic continues to fascinate and stimulate researchers through the discovery of novel strains and their beneficial properties.

Cross-talks among GBA mutations, glucocerebrosidase, and α-synuclein in GBA-associated Parkinson's disease and their targeted therapeutic approaches: a comprehensive review.

Current therapies for Parkinson's disease (PD) are palliative, of which the levodopa/carbidopa therapy remains the primary choice but is unable to modulate the progression of neurodegeneration. Due to the complication of such a multifactorial disorder and significant limitations of the therapy, numerous genetic approaches have been proved effective in finding out genes and mechanisms implicated in this disease. Following the observation of a higher frequency of PD in Gaucher's disease (GD), a lysosomal storage condition, mutations of glycosylceramidase beta (GBA) encoding glucocerebrosidase (GCase) have been shown to be involved and have been explored in the context of PD. GBA mutations are the most common genetic risk factor of PD. Various studies have revealed the relationships between PD and GBA gene mutations, facilitating a better understanding of this disorder. Various hypotheses delineate that the pathological mutations of GBA minimize the enzymatic activity of GCase, which affects the proliferation and clearance of α-synuclein; this affects the lysosomal homeostasis, exacerbating the endoplasmic reticulum stress or encouraging the mitochondrial dysfunction. Identification of the pathological mechanisms underlying the GBA-associated parkinsonism (GBA + PD) advances our understanding of PD. This review based on current literature aims to elucidate various genetic and clinical characteristics correlated with GBA mutations and to identify the numerous pathological processes underlying GBA + PD. We also delineate the therapeutic strategies to interfere with the mutant GCase function for further improvement of the related α-synuclein-GCase crosstalks. Moreover, the various therapeutic approaches such as gene therapy, chaperone proteins, and histone deacetylase inhibitors for the treatment of GBA + PD are discussed.

Exploring the Multifaceted Therapeutic Potential of Withaferin A and Its Derivatives.

Withaferin A (WA), a manifold studied, C28-steroidal lactone withanolide found in Withania somnifera. Given its unique beneficial effects, it has gathered attention in the era of modern science. Cancer, being considered a "hopeless case and the leading cause of death worldwide, and the available conventional therapies have many lacunae in the form of side effects. The poly pharmaceutical natural compound, WA treatment, displayed attenuation of various cancer hallmarks by altering oxidative stress, promoting apoptosis, and autophagy, inhibiting cell proliferation, reducing angiogenesis, and metastasis progression. The cellular proteins associated with antitumor pathways were also discussed. WA structural modifications attack multiple signal transduction pathways and enhance the therapeutic outcomes in various diseases. Moreover, it has shown validated pharmacological effects against multiple neurodegenerative diseases by inhibiting acetylcholesterinases and butyrylcholinesterases enzyme activity, antidiabetic activity by upregulating adiponectin and preventing the phosphorylation of peroxisome proliferator-activated receptors (PPARγ), cardioprotective activity by AMP-activated protein kinase (AMPK) activation and suppressing mitochondrial apoptosis. The current review is an extensive survey of various WA associated disease targets, its pharmacokinetics, synergistic combination, modifications, and biological activities.

Exploring the Potential of Therapeutic Agents Targeted towards Mitigating the Events Associated with Amyloid-ß Cascade in Alzheimer's Disease.

One of the most commonly occurring neurodegenerative disorders, Alzheimer's disease (AD), encompasses the loss of cognitive and memory potential, impaired learning, dementia and behavioral defects, and has been prevalent since the 1900s. The accelerating occurrence of AD is expected to reach 65.7 million by 2030. The disease results in neural atrophy and disrupted inter-neuronal connections. Amongst multiple AD pathogenesis hypotheses, the amyloid beta (Aß) cascade is the most relevant and accepted form of the hypothesis, which suggests that Aß monomers are formed as a result of the cleavage of amyloid precursor protein (APP), followed by the conversion of these monomers to toxic oligomers, which in turn develop ß-sheets, fibrils and plaques. The review targets the events in the amyloid hypothesis and elaborates suitable therapeutic agents that function by hindering the steps of plaque formation and lowering Aß levels in the brain. The authors discuss treatment possibilities, including the inhibition of ß- and γ-secretase-mediated enzymatic cleavage of APP, the immune response generating active immunotherapy and passive immunotherapeutic approaches targeting monoclonal antibodies towards Aß aggregates, the removal of amyloid aggregates by the activation of enzymatic pathways or the regulation of Aß circulation, glucagon-like peptide-1 (GLP-1)-mediated curbed accumulation and the neurotoxic potential of Aß aggregates, bapineuzumab-mediated vascular permeability alterations, statin-mediated Aß peptide degradation, the potential role of ibuprofen and the significance of natural drugs and dyes in hindering the amyloid cascade events. Thus, the authors aim to highlight the treatment perspective, targeting the amyloid hypothesis, while simultaneously emphasizing the need to conduct further investigations, in order to provide an opportunity to neurologists to develop novel and reliable treatment therapies for the retardation of AD progression.

Distinctive Evidence Involved in the Role of Endocannabinoid Signalling in Parkinson's Disease: A Perspective on Associated Therapeutic Interventions.

Current pharmacotherapy of Parkinson's disease (PD) is symptomatic and palliative, with levodopa/carbidopa therapy remaining the prime treatment, and nevertheless, being unable to modulate the progression of the neurodegeneration. No available treatment for PD can enhance the patient's life-quality by regressing this diseased state. Various studies have encouraged the enrichment of treatment possibilities by discovering the association of the effects of the endocannabinoid system (ECS) in PD. These reviews delineate the reported evidence from the literature on the neuromodulatory role of the endocannabinoid system and expression of cannabinoid receptors in symptomatology, cause, and treatment of PD progression, wherein cannabinoid (CB) signalling experiences alterations of biphasic pattern during PD progression. Published papers to date were searched via MEDLINE, PubMed, etc., using specific key words in the topic of our manuscript. Endocannabinoids regulate the basal ganglia neuronal circuit pathways, synaptic plasticity, and motor functions via communication with dopaminergic, glutamatergic, and GABAergic signalling systems bidirectionally in PD. Further, gripping preclinical and clinical studies demonstrate the context regarding the cannabinoid compounds, which is supported by various evidence (neuroprotection, suppression of excitotoxicity, oxidative stress, glial activation, and additional benefits) provided by cannabinoid-like compounds (much research addresses the direct regulation of cannabinoids with dopamine transmission and other signalling pathways in PD). More data related to endocannabinoids efficacy, safety, and pharmacokinetic profiles need to be explored, providing better insights into their potential to ameliorate or even regress PD.

Psychosocial profile of the patients with inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic, disabling entity of unknown aetiology, with negative impact on the patient's life, including psychological patterns. This study assessed multiple psychosocial factors (satisfaction with life, coping mechanisms, emotional profile, mental recognition of the disease and cognition schemes related to patients' demographic characteristics, clinical picture, form and duration of the disease, therapeutic plans) in IBD patients vs. a healthy group. This non-interventional study comprised 60 participants who attended for medical advice/check-up as an ambulatory visit or during hospitalization. The patients completed questionnaires after receiving explanations from the psychologist. Statistical analyses (Kolmogorov-Smirnov test, Independent-Samples t-test, One-Way ANOVA and Post Hoc Multiple Comparisons) were conducted using IMB for the Social Sciences (SPSS), version 20 (P≤0.05). IBD patients (G1) are more hostile when compared to the healthy group (G2). Those who experience abdominal pain are more likely to use active coping mechanisms and those who experience fatigue are more likely to use acceptance, emotional venting, behavioural disengagement and mental disengagement. G1 have higher levels of others-downing vs. G2. Regarding negative emotions, IBD patients generally experience more negative emotions compared to healthy participants (who have higher levels of life satisfaction). Regarding the perception of illness, there are no differences between patients in terms of illness coherence, personal or treatment control, consequences, timeline, or emotional representations. Results indicate that psychological factors and different characteristics of IBD patients play a relevant role in the way these patients deal with their disease.

Clinical, Pathological and Microbiological Evaluation of Diabetic Foot Syndrome.

Background and objectives: Diabetic foot ulcer (DFU) is one of the serious complications of diabetes, being related to frequent and long-term hospitalisation, reduced quality of life of the patient, amputations, a high rate of morbidity and mortality. The bacterial aetiology is complex, sometimes involving more than one pathogen, playing a major role in the infection prognosis and development of microbial resistance. This study evaluated the current state of the aetiology, clinical and pathological characteristics of DFU in a single diabetes centre in order to provide some specific measures to prevent it. Materials and Methods: This retrospective study was conducted on patients with diabetes mellitus (252 individuals diagnosed with DFU) between January 2018-December 2019. All participants were assessed based on their clinical characteristics, including complications of diabetes and pathological and microbiological evaluations. Results: The present research revealed that diabetic foot ulcer prevalence was higher in males than in females and higher in type 2 diabetic patients than in type 1 diabetic patients. The patients with diabetic foot ulcer were older, had a higher body mass index (BMI), longer diabetic duration and had more diabetic complications, such as retinopathy, diabetic polyneuropathy and diabetic kidney disease, than patients without diabetic foot ulceration. Conclusions: Taking into account all factors involved, including the aetiology and the antibiotic susceptibility pattern of these isolates, planning the suitable treatment options of patients is possible.

Botulinum toxin in low urinary tract disorders - over 30 years of practice (Review).

Botulinum toxin is a substance produced by Clostridium Botulinum and is responsible for human botulism. This substance is a poison, a neurotoxin, but used in limited quantities it can be a cure for some diseases. It is well connected to a large variety of medical applications. The mechanism of action relies on blocking the acetylcholine at the neuromuscular junction, which blocks the transmission of the nervous impulse with secondary flaccid paralysis. In urology, its role in idiopathic overactive bladder and neurogenic bladder is well known. We performed a thorough review using PubMed and other databases, revising the mechanisms of botulinum toxin action in urologic pathology, treatment procedures and other options. Botulinum toxin is a well-studied substance with a large number of applications in medicine. In urologic pathology, overactive bladder and neurogenic bladder are backed by robust studies that support the therapeutic role of this substance. The toxin has multiple effects, such as inhibition of the nerve growth factor, blocking the bladder sensory afferent pathway and apoptotic effect on the prostate tissue, by inhibiting the substance P, altering the nociceptive pathways. Interstitial cystitis and other rare pathologies show promising results, but further studies are needed. The role of botulinum toxin in benign prostatic hyperplasia is still not elucidated.

Influence of inflammation and adipocyte biochemical markers on the components of metabolic syndrome.

Metabolic syndrome is associated with increased risk of cardiovascular disease. This study investigated the correlation between adipocyte and inflammation biomarkers, and metabolic syndrome and its components. The study included 80 patients with normal body-mass index and 80 obese patients. The groups were assessed for serum values of adiponectin, leptin and highly sensitive C reactive protein (hsCRP), the homeostatic model assessment of insulin resistance (HOMA-IR), as well as the influence of these biochemical markers on the prevalence of metabolic syndrome and its components. Leptin, HOMA-IR and hsCRP had statistically significant (P<0.01) higher values in the group of obese subjects, while adiponectin had statistically significant (P<0.01) lower values. The prevalence of metabolic syndrome was 35% in the obese group and 5% in the normal weight group. Adiponectin and HOMA-IR were the variables significantly associated with metabolic syndrome (P<0.01), adiponectin/HOMA-IR ratio and leptin/adiponectin ratio were also associated with metabolic syndrome (P<0.01). No relationship was found between metabolic syndrome and hsCRP. Adiponectin and adiponectin/HOMA-IR were associated with all the components of metabolic syndrome and they can be useful to identify patients with high risk of diabetes mellitus and cardiovascular disease.

Risk factors for adiposity in the urban population and influence on the prevalence of overweight and obesity.

Obesity and overweight are major contributors to the morbidity and mortality of modern civilization. This study determined the prevalence of certain risk factors for adiposity and assesses their impact on overweight/obesity prevalence. Nine hundred individuals were evaluated, aged between 18-65 years, including clinical examination, evaluation of medical history, BMI determination and completion on questionnaires assessing nutritional intake and presence of depression symptoms. Overweight prevalence was 29.56% and obesity prevalence was 21.33%. Fast-food consumption was the most frequent risk factor for adiposity found in 61.67% of individuals, eating <3 meals/day was found in 58.89%, sedentary lifestyle in 53.33%, sleeping time <6 h/day in 44.22%, hypercaloric nutrition in 43.56%, excessive alcohol consumption in 42.89% and depression symptoms in 31.78%. Unhealthy lifestyle a composite risk factor was identified in 67.33% of individuals. Fast-food consumption increases the risk for adiposity by 1.85-fold while sedentary lifestyle by 1.79-fold. Risk factors for adiposity play an important role in increasing the prevalence of overweight and obesity. Public health measures are necessary in order to educate the general population regarding the importance of healthy nutrition and physical exercise.

Acute Coronary Syndromes in Chronic Kidney Disease: Clinical and Therapeutic Characteristics.

Background and Objectives: This study evaluated the clinical characteristics of the acute coronary syndromes (ACS) in chronic kidney disease (CKD) patients and established prognostic values of the biomarkers and echocardiography. Materials and Methods: 273 patients admitted to the cardiology department of the Clinical County Emergency Hospital of Oradea, Romania, with ACS diagnosis were studied. Two study groups were formed according to the presence of CKD (137 patients with ACS + CKD and 136 with ACS without CKD). Kidney Disease: Improving Global Outcomes (KDIGO) threshold was used to assess the stages of CKD. Results: Data regarding the medical history, laboratory findings, biomarkers, echocardiography, and coronary angiography were analysed for both groups. ACS parameters were represented by ST-segment elevation myocardial infarction (STEMI), which revealed a greater incidence in subjects without CKD (43.88%); non-ST-segment elevation myocardial infarction (NSTEMI), characteristic for the CKD group (28.47%, with statistically significance p = 0.04); unstable angina and myocardial infarction with nonobstructive coronary arteries (MINOCA). Diabetes mellitus, chronic heart failure, previous stroke, and chronic coronary syndrome were more prevalent in the ACS + CKD group (56.93%, p < 0.01; 41.61%, p < 0.01; 18.25%, p < 0.01; 45.26%, p < 0.01). N-terminal pro b-type natriuretic peptide (NT-proBNP) was statistically higher (p < 0.01) in patients with CKD; Killip class 3 was evidenced more frequently in the same group (p < 0.01). Single-vessel coronary artery disease (CAD) was statistically more frequent in the ACS without CKD group (29.41%, p < 0.01) and three-vessel CAD or left main coronary artery disease (LMCA) were found more often in the ACS + CKD group (27.01%, 14.6%). Conclusions: Extension of the CAD in CKD subjects revealed an increased prevalence of the proximal CAD, and the involvement of various coronary arteries is characteristic in these patients. Biomarkers and echocardiographic elements can outline the evolution and outcomes of ACS in CKD patients.

Antibiotic Consumption and Microbiological Epidemiology in Surgery Departments: Results from a Single Study Center.

The spectrum and antibiotic sensitivity of isolated strains vary between departments, hospitals, countries; the discrepancies are related to the use and dosage of these antibiotics. The purpose of our research was to compare the type of pathogens and the susceptibility of the isolated strains, as well as the use of antibiotics in the surgical departments of the Emergency Clinical County Hospital, Oradea, Romania; for one year, all the patients admitted to the mentioned sections were monitored. Antibiotic sensitivity of isolated strains was expressed using cumulative antibiogram. The total consumption of antibiotics was 479.18 DDD/1000 patient-days in the surgical sections. The most commonly used drugs were cephalosporins third and first generation, and clindamycin. Infections of wounds, urinary tract and fluids were most commonly diagnosed, and the most isolated was Escherichia coli, followed by Staphylococcus aureus and Enterococcus faecalis. The most commonly prescribed antimicrobial was ceftriaxone, but its sensitivity was low. This study revealed that the intake of antimicrobials in the surgical sections is increased and the comparison of antimicrobial prescriptions, sensitivity rates, and the spectrum of isolated pathogens showed differences between antimicrobials.

Financial Burden of Stroke Reflected in a Pilot Center for the Implementation of Thrombolysis.

Stroke represents a serious illness and is extremely relevant from the public health point of view, implying important social and economic burdens. Introducing new procedures or therapies that reduce the costs both in the acute phase of the disease and in the long term becomes a priority for health systems worldwide. The present study quantifies and compares the direct costs for ischemic stroke in patients with thrombolysis treatment versus conservative treatment over a 24-month period from the initial diagnosis, in one of the 7 national pilot centres for the implementation of thrombolytic treatment. The significant reduction (p < 0.001) of the hospitalization period, especially of the days in the intensive care unit (ICU) for stroke, resulted in a significant reduction (p < 0.001) of the total average costs in the patients with thrombolysis, both at the first hospitalization and for the subsequent hospitalizations, during the period followed in the study. It was also found that the percentage of patients who were re-hospitalized within the first 24-months after stroke was significantly lower (p < 0.001) among thrombolyzed patients. The present study demonstrates that the quick intervention in cases of stroke is an efficient policy regarding costs, of Romanian Public Health System, Romania being the country with the highest rates of new strokes and deaths due to stroke in Europe.

Epidemiology of human giardiasis in Romania: A 14 years survey.

Giardia spp. is the most common intestinal protozoan (causing gastrointestinal illness) and the most frequent cause of parasitic gastroenteritis in humans and animals worldwide. The aim of this study was to highlight new data in a specific area regarding clinical presentation and epidemiological prevalence over a long period of time. Patients (a total number of 54,623 patients) admitted in a tertiary center for infectious diseases serving a county for a period of 14 years were tested for infection with Giardia. Positive cases were recorded through analyzing the clinical complaints, the month of incidence and the demographic area from which the patients came from. Longitudinal trends have been evaluated. The incidence of giardiasis among the tested patients was 4.47%. A decreasing trend was observed regarding the annual incidence. Patients between the ages of 15 and 44 presented most commonly giardiasis, especially those from urban areas and women. The most common symptoms are loss of appetite (71.24%) and abdominal pain (69.07%). The highest monthly incidence was quoted in July (10.65%), August (10.49%) and June (10.20%). This epidemiological study allows a better knowledge of the infection with Giardia spp. It gives the long-term changes in demographic characteristics of the infected patients in a specific area and the monthly incidence.

Effects of simvastatin in patients with viral chronic hepatitis C.

BACKGROUND/AIMS: A geranyl-geranylated protein is synthesized during chronic hepatitis C virus replication; statins can inhibit this synthesis. We aimed at studying the effects of administrating simvastatin to patients who finished the standard antiviral therapy and who did not have hepatic cytolysis. METHODOLOGY: A total of 101 patients were divided into 3 groups. Those without liver cytolysis were divided as follows: In group A1 patients were treated with simvastatin for 3 months and in group A2 the patients were non-treated controls. Those patients with hepatic cytolysis were placed in group B and treated for 3 months with simvastatin. The patients were biologically monitored monthly and the initial viremia was compared with the final one. The results were then statistically analysed. RESULTS: Significant changes of viremia were not observed in the patients from groups A1 and A2. In 24 patients in group B (58.54%) the viremia was significantly reduced (p=0.018), and in 6 patients (39.02%) it increased insignificantly. After 1 and 2 months of treatment, the cholesterolemy and the serum alkaline phosphatase significantly decreased to the patients from group B. CONCLUSIONS: In this study, more than half of the patients chronically infected with the hepatitis C virus, who had hepatic cytolysis and were treated with simvastatin, showed a significant reduction in the level of viremia.

Ultrastructural evidence of mucosal healing after infliximab in patients with ulcerative colitis.

BACKGROUND: Infliximab is a monoclonal anti-TNF-alpha antibody that has been shown to be effective in Crohn's disease therapy. However, data are scarce about the mechanism of action and its efficacy in ulcerative colitis (UC). AIM: To assess intracellular changes of the colonic mucosa in patients with UC before and after infliximab treatment. METHODS: 7 patients (18-65 years, 4 men) with active, refractory, moderate to severe UC (Lichtiger's Clinical Activity Index > 6, Endoscopic Index > 4) underwent colonoscopy before and 4 weeks after the initial infusion of infliximab 5mg/kg of body weight. Endoscopically obtained biopsy specimens were processed specifically, stained with uranyl-acetate and lead citrate and examined with a JEOL-1010 transmission electron microscope. RESULTS: Before treatment we noticed severe alterations of the epithelium: microvilli depletion, shattering of the epithelial junctions, cytoplasmic vacuolization, dilatation of the endoplasmic reticulum, pycnotic nuclei, altered structure of mitochondria and Golgi complexes. Rarefaction of the goblet cells, and abnormal mucus formation and secretion were also observed. The corresponding chorion showed structural alteration of component cells, obstructed capillaries, erythrocyte extravasation, and many plasmocytes and neutrophils. After infliximab, improvement in morphology and function of the epithelial organelles, rich mucus secretion and recovery of the chorionic components were noticed. CONCLUSIONS: Our study revealed important intracellular alterations of the UC mucosa that were restored after infliximab therapy. These features may contribute to a better understanding of UC pathogenesis and mechanism of action of the anti-TNF-alpha therapies.