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NASH consists in lipid accumulation in hepatocytes that trigger oxidative stress, secretion of proinflammatory cytokines leading to steatohepatitis (NASH). The study aimed to investigate the levels of proinflammatory (TNF-αand IL-6) along with anti-inflammatory cytokine IL-10 in patients with NASH and to correlate the cytokines’ level with their polymorphism. Sixty-six patients with NASH and 30 healthy volunteers were included in the study. The plasmatic level of IL-6, IL-10, and TNF-αwere determined by ELISA. IL-10 -1082 G/A, IL-6 -174 G/C, and TNF-α-308 G/A polymorphisms were determined using the PCR-RFLP technique. IL-6, TNF-α, and CRP levels were significantly higher in patients with NASH. There was a positive correlation between proinflammatory cytokines and a negative correlation between IL-10 and proinflammatory markers. The G allele and GG genotype of IL-6 -174 G/C polymorphism were more frequently noticed in NASH patients. Regarding IL-10 -1082 G/A polymorphism, the AA genotype was correlated with NASH and with a low plasmatic level of IL-10. The A allele in position 308 of the TNF-αgene was associated with high level of cytokine. In conclusion, there was an imbalance between pro- and anti-inflammatory cytokines in NASH patients. IL-10 -1082 G/A and TNF-α-308 G/A genotypes were correlated with the plasmatic levels of cytokines.

Background: Non-alcoholic fatty liver disease (NAFLD) is an important cause of chronic liver diseases around the world. Paraoxonase-1 (PON1) is an enzyme produced by the liver with an important antioxidant role. The aim of this study was to evaluate PON1 serum concentration and PON1 gene polymorphisms in patients with NAFLD. Materials and methods: We studied a group of 81 patients with NAFLD with persistently elevated aminotransferases and a control group of 81 patients without liver diseases. We collected clinical information and performed routine blood tests. We also measured the serum concentration of PON1 and evaluated the PON1 gene polymorphisms L55M, Q192R, and C-108T. Results: There was a significant difference (p &lt, 0.001) in serum PON1 concentrations among the two groups. The heterozygous and the mutated homozygous variants (LM + MM) of the L55M polymorphism were more frequent in the NAFLD group (p &lt, 0.001). These genotypes were found in a multivariate binary logistic regression to be independently linked to NAFLD (Odds ratio = 3.4, p = 0.04). In a multivariate linear regression model, the presence of NAFLD was associated with low PON1 concentration (p &lt, 0.001). Conclusions: PON1 serum concentrations were diminished in patients with NAFLD, and the presence of NAFLD was linked with low PON1 concentration. The LM + MM genotypes of the PON1 L55M polymorphism were an independent predictor for NAFLD with persistently elevated aminotransferases.

Cisplatin is one of the most used drugs in the therapy of different types of cancer. However, its use is limited by nephrotoxicity. This study investigated the effects of a commercially available grape pomace extract (GE) from Vitis vinifera on cisplatin-induced kidney toxicity in rats. Sixty-four male Wistar albino rats were randomly divided into eight groups. Groups 1&ndash, 3 were controls, receiving 0.9% saline and doses 1 and 2 of GE respectively. Cisplatin was given to groups 4&ndash, 8. Two groups received pretreatment with GE, while another two groups received pre- and post-treatment with GE. Blood samples were collected and all animals sacrificed. Kidneys were harvested for histopathological analysis. GE significantly increased blood creatinine and urea levels, the severity of kidney histopathological damage, and mortality in all cisplatin groups, except for group 7 which received pre- and post-treatment with a low dose of GE. Renal toxicity was determined by mortality and severe histopathological renal lesions. Additionally, the serum total antioxidant capacity (TAC) was not significantly modified in the treated groups compared to the control. These results indicate that the GE did not have a protective effect on cisplatin-induced nephrotoxicity, on the contrary, GE accentuated the toxic effect of cisplatin.

Background and Objectives: Prior studies have identified a number of predictors for Atrial fibrillation (AF) ablation success, including comorbidities, the type of AF, and left atrial (LA) size. Ectopic foci in the initiation of paroxysmal AF are frequently found in pulmonary veins. Our aim was to assess how pulmonary vein anatomy influences the recurrence of atrial fibrillation after radiofrequency catheter ablation. Materials and Methods: Eighty patients diagnosed with paroxysmal or persistent AF underwent radiofrequency catheter ablation (RFCA) between November 2016 and December 2017. All of these patients underwent computed tomography before AF ablation. PV anatomy was classified according to the presence of common PVs or accessory PVs. Several clinical and imagistic parameters were recorded. After hospital discharge, all patients were scheduled for check-up in an outpatient clinic at 3, 6, 9, and 12 months after RFCA to detect AF recurrence. Results: A total of 80 consecutive patients, aged 53.8 &plusmn, 9.6 years, 54 (67.5%) men and 26 (32.5%) women were enrolled. The majority of patients had paroxysmal AF 53 (66.3%). Regular PV anatomy (2 left PVs, 2 right PVs) was identified in 59 patients (73.7%), a left common trunk (LCT) was detected in 15 patients (18.7%), an accessory right middle pulmonary vein (RMPV) was found in 5 patients (6.25%) and one patient presented both an LCT and an RMPV. The median follow-up duration was 14 (12, 15) months. Sinus rhythm was maintained in 50 (62.5%) patients. Age, gender, antiarrhythmic drugs, and the presence of cardiac comorbidities were not predictive of AF recurrence. The diagnosis of persistent AF before RFCA was more closely associated with an increase in recurrent AF after RFCA than after paroxysmal AF (p = 0.01). Longer procedure times (&gt, 265 minutes) were associated with AF recurrence (p = 0.04). Patients with an LA volume index of over 48.5 (mL/m2) were more likely to present AF recurrence (p = 0.006). Multivariate analysis of recurrence risk showed that only the larger LA volume index and variant PV anatomy were independently associated with AF recurrence. Conclusion: The study demonstrated that an increased volume of the left atrium was the most important predictive factor for the risk of AF recurrence after catheter ablation. Variant anatomy of PV was the only other independent predictive factor associated with a higher rate of AF recurrence.

Psoriasis is a chronic, systemic, inflammatory disorder which accelerates the life process of skin cells, based on a genetically induced deviant immune response. High-frequency ultrasonography (HF-USG) is a painless, non-invasive imaging technique that can be performed and repeated whenever the need arises. We evaluated lesional and non-lesional skin of psoriatic patients with the use of HF-USG, focusing on the immune-induced inflammation and skin thickness. Previous studies suggested that HF-USG, being a non-invasive technique, is useful as an aid to clinical evaluation of the severity of psoriatic plaques. Our goal was to determine whether the skin of psoriatic patients is influenced by the background or habits of the patients. The study included a total of 27 patients affected by psoriasis vulgaris. The thickness of the epidermis and dermis and the skin echogenicity were documented for the active plaques, as well as for the non-affected skin of all the patients included in the study, using a high-frequency ultrasonographic system. The patient's local background, sex, family history of psoriasis, smoking habits and sun exposure were analyzed. HF-USG of the psoriatic plaques exposes a three-band structure that is easily distinguished from the surrounding unaffected skin, due to a hypoechoic band in the upper dermis. Although not specific for psoriasis, it is a strong marker of inflammation. The obtained results confirm that, indeed, skin thickness is greater in lesional skin compared to non-lesional skin, by a mean of 1,180 µm (±340 µm). We consider that skin HF-USG should be used as a quantitative method in the clinical evaluation of the patients with psoriasis and may help as an objective means of assessing inflammation in lesional skin.

Background and Objectives: Deep vein thrombosis (DVT) is a common cause of intra-hospital morbidity and mortality, and its most severe complication is pulmonary thromboembolism. The risk factors that influence the apparition of DVT are generally derived from Virchow&rsquo, s triad. Since the most severe complications of DVT occur in proximal rather than distal deep vein thrombosis, the aim of this study was to identify the factors influencing the apparition of proximal DVT. Materials and Methods: This was a transversal, cohort study. The study included 167 consecutive patients with lower limb DVT over a two-year period. The following data were recorded or determined: general data, conditions that are known to influence DVT, medical history and coagulation or thrombophilia-related genetic variations. Results: In the univariate analysis, male gender, neoplasia, previous DVT and mutated factor V Leiden were all associated with proximal DVT, while bed rest was associated with distal DVT. In the multivariate analysis, male gender, previous DVT and factor V Leiden mutation were independently correlated with proximal DVT, while bed rest was independently associated with distal deep vein thrombosis. Conclusion: Our observations point out that the factors indicating a systemic involvement of coagulation were correlated with proximal DVT, while local factors were associated with distal DVT.

Background Inflammation plays a major role in the development of metabolic syndrome (MetS) and its progression. Recent studies have shown that pentraxin-3 (PTX-3), osteoprogerin (OPG), and tumor necrosis factor-alpha (TNF-α) are key factors in MetS pathophysiology, but evidence for endorsing their clinical use is currently unclear and insufficient. Aim The study aimed to evaluate the association between the inflammatory biomarkers’ levels and the severity of MetS. Methods The study was observational, transversal, prospective, cohort, and analytical type. We enrolled 80 patients (M:F = 1, mean age = 55 ± 10.77 years) who met MetS criteria. The study protocol included: medical history, physical examination, 6-min walk test distance (6MWTD), biochemical tests, electrocardiogram, echocardiography, and carotid ultrasonography. We also performed plasmatic measurement of PTX-3, OPG, and TNF-α, in addition to standard biochemical tests. Results Subjects with severe MetS had higher values of body mass index (BMI) and waist circumference (p p = 0.001). PTX-3 levels were significantly higher in patients with severe MetS (p = 0.03) and the values were not influenced by age or gender. OPG positively correlated with BMI (r = 0.264, p = 0.018). 6MWTD was lower in patients with severe MetS (p = 0.005), whereas CCA-IMT was higher in this group of patients (p = 0.005). In addition, the receiver operating characteristic (ROC) curve analysis for PTX-3 identified a cut-off value of 10.7 ng/dl that differentiates between mild and severe MetS [AUC 0.656; sensitivity =47.1% (95% CI = 36.1%–62.3%); specificity = 78.9% (95% CI = 54.4%–93.9%)]. Conclusion PTX-3 was correlated with the severity of MetS, with other inflammatory parameters and cardiovascular tests. CCA-IMT and 6MWTD are useful in differentiating between mild and severe MetS.

In recent years, increased attention has been paid to the relationship between microbiota and various diseases, especially immune-mediated diseases. Because conventional therapy for many autoimmune diseases is limited both in efficacy and safety, there is an increased interest in identifying nutraceuticals, particularly probiotics, able to modulate the microbiota and ameliorate these diseases. In this review, we analyzed the research focused on the role of gut microbiota and skin in immunity, their role in immune-mediated skin diseases (IMSDs), and the beneficial effect of probiotics in patients with this pathology. We selected articles published between 2009 and 2019 in PubMed and ScienceDirect that provided information regarding microbiota, IMSDs and the role of probiotics in these diseases. We included results from different types of studies including observational and interventional clinical trials or in vivo and in vitro experimental studies. Our results showed that probiotics have a beneficial effect in changing the microbiota of patients with IMSDs; they also influence disease progression. Further studies are needed to better understand the impact of new therapies on intestinal microbiota. It is also important to determine whether the microbiota of patients with autoimmune diseases can be manipulated in order to restore homeostasis of the microbiota.

Psoriasis is a chronic, immune mediated, inflammatory condition, which primarily affects the patient's skin. It is known to associate a variable array of comorbidities such as cardiovascular, metabolic and psychiatric ones, with an important impact on the patients' quality of life. The purpose of this study is to provide a first image of the prevalence, comorbidities, as well as the social impact of psoriasis in Romania. We devised a questionnaire, and with the aid of general practitioners throughout the country, delivered it to patients seeking medical care in their office. The questionnaire assessed demographic criteria as well as patient-related issues. It was completed in the presence of the general practitioner, and clear written instructions for completion were included. After statistical analysis, the resulting data formed the basis of this study. The reported prevalence of psoriasis in Romania is 5.18%. Almost half of the subjects who completed the questionnaire stated they knew somebody affected by the disease, yet almost a third believed it is a contagious condition. Cardiovascular and psychiatric comorbidities, as well as negative impact on social interactions were reported by the subjects in the study. These findings indicate the clear need for better quality of life for patients in a social context and increased awareness of the disease. All these could, in turn, help decrease the rate of psoriasis complications in Romania.

Background. Although amiodarone is a drug with many side effects, it is one of the most commonly used drugs in the treatment and prophylaxis of supraventricular and ventricular arrhythmias. Aim. The purpose of this pilot study was to evaluate plasma concentrations of amiodarone in patients with atrial fibrillation (AF) and to identify possible drug-drug interactions between amiodarone and concomitant medications. Method. A prospective observational study was conducted in 27 consecutive patients treated with amiodarone from May to July 2017 in a Clinical University Hospital. The patients included met our inclusion criteria. HPLC-UV was the device used to determine the plasma concentration of amiodarone. Results. Only 51.8% of the patients had amiodarone plasma concentration within therapeutic interval (500-2500 ng/ml). The drugs associated to amiodarone in the therapeutic plan were diuretics, beta blockers, statins, antiplatelets, fluoroquinolones, non-steroidal anti-inflammatory drugs. We observed a statistically significant difference between the plasmatic concentrations of amiodarone in patients treated with furosemide vs. patients concomitantly treated with other drugs. Interactions between other mentioned drugs and amiodarone were not registered. We can report an underuse of amiodarone for more than 50% of the patients. Also, we found a significant interaction between furosemide and amiodarone, most likely through the interaction with MDR. Conclusion. Furosemide may influence the pharmacokinetics of P-gp-interfering drugs. However, the relevance of these findings needs to be confirmed and further research is needed to characterize the interaction between amiodarone and furosemide.

Postpartum psychosis has long-lasting consequences for mother and child. Beside depression, sleep and eating disturbances, exhaustion, social withdrawal, and anxiety, postpartum depression can also interfere with normal maternal-infant bonding and adversely affect child development. Recent reports show that most affected pregnant women are hesitant about taking antidepressant drugs, with a high percentage discontinuing their use. Some authors suggest that the reluctance of pregnant women to take antidepressant drugs should encourage clinicians to discuss with their patients the use of psychological interventions or alternative forms of treatment. In this article, a case of severe postpartum depression, treated successfully with homeopathic therapy, is presented. Considering the high noncompliance of women suffering from postpartum depression with conventional antidepressant medication, research in safe complementary medical methods is justified. One of these methods should be homeopathy.

Aim: The present study aim to analyze the relationship between GST M/T genotypes of glutathione S-transferases and cervical intraepithelial neoplasia. Materials and Methods: A prospective case-control study has been designed including 69 cases with different degrees of cervical dysplasia and 107 controls. All patients had been examined colposcopically. For every patient both cervical and blood specimen have been obtained. The peripheral blood was used for GST M/T genotyping. The statistical analysis was performed using OR and chi-square at a level of significance inferior to 0.05. Results: No statistically significant differences had been found between cases and controls for GST T-/M- geno-type (T-/M-, χ2=0.03, p= 0.8610) and T+/M+ χ2=0.65, p = 0.4197. Patients with in situ carcinoma had significant GST genotype association for T-/M+ genotype (OR=4.66, CI 95% [0.6528,24.9725], χ2=4.6, p=0.0314) and for T+/M- genotype (OR=0.12, CI 95% [0.0027,0.9465], χ2=0.05, p=0.0219). Conclusion: The combination of GST genotypes can be included in a predictive score for patients with cervical carcinoma.

Background/Aims: Attention deficit hyperactivity disorder (ADHD) is frequently associated with other psychiatric pathologies. Therefore, the present study investigated a possible pharmacokinetic interaction between atomoxetine (ATX), a treatment option for ADHD, and an antidepressant, namely, fluvoxamine (FVX). Methods: Designed as an open-label, non-randomized clinical trial, the study included 2 periods. In period 1 (reference), each subject received ATX 25 mg (single-dose), whereas in period 2 (test), all subjects were given a combination of ATX 25 mg + FVX 100 mg, following a 6-day pretreatment regimen with the enzymatic inhibitor. Non-compartmental methods were employed to determine the pharmacokinetic parameters of ATX and its main active metabolite (glucuronidated form), 4-hydroxyatomoxetine-O-glucuronide. Results: The results revealed significant differences between the study periods for Cmax, AUC0-t and AUC0-∞ values corresponding to ATX and its metabolite. Small, but statistically significant increases in AUC values were reported for both parent drug (1,583.05 ± 1,040.29 vs. 2,111.55 ± 1,411.59 ng*h/ml) and 4-hydroxyatomoxetine-O-glucuronide (5,754.71 ± 1,235.5 vs. 6,293.17 ± 1,219.34 ng*h/ml) after combined treatment of ATX and the enzymatic inhibitor. Conclusion: FVX had a modest effect on the pharmacokinetics of ATX and 4-hydroxyatomoxetine-O-glucuronide. The presence or absence of any clinical consequences associated with this pharmacokinetic drug-drug interaction needs to be established in future studies.

Aim: The purpose of the research was to study the influence of several genetic factors, especially the -1693 G>A polymorphism of the VKORC1 gene, on the risk of acute unprovoked lower extremity deep vein thrombosis (DVT). Materials and Methods: The study included 127 patients (median age 63 [53.2; 72] years; 61 [48%] women and 66 [52%] men) who were diagnosed with acute lower extremity DVT and 114 controls (median age 62 [53; 73] years; 64 [56.1%] women and 50 [43.9%] men) without DVT. We recorded data regarding the history of DVT and the presence of varicose veins. We determined the genotypes for factor V Leiden (FVL) mutation, prothrombin G20210A mutation, VKORC1 -1639 G>A mutation, and PAI-1 -675 4G/5G polymorphism. Results and conclusion: Varicose veins were found in 67 (52.8%) patients and 29 (25.4%) controls ( P < .001). FVL was present in 29 (22.8%) patients and 10 (8.8%) controls ( P = .005). The VKORC1 (-1693 G>A) GG genotype was found in 42 (33.1%) patients and 41 (36%) controls, the GA genotype in 71 (55.9%) patients and 47 (41.2%) controls, and AA genotype in 14 (11%) patients and 26 (22.8%) controls ( P = .020). Multivariate analysis showed that the presence of varicose veins, FVL, and VKORC1 -1639 G>A was independently associated with the risk of DVT. The VKORC1 (-1693 G>A) AA genotype was associated with fewer cases of DVT (odds ratio = 0.435; 95% confidence interval 0.205-0.991; P = .031).

Background/Aims: The study aimed at investigating the effects of multiple-dose bupropion (potent inhibitor of CYP2D6) on the pharmacokinetics (PKs) of single-dose nebivolol (CYP2D6 substrate) and to evaluate the clinical relevance of this potential drug interaction. Methods: This open-label, nonrandomized clinical study had a 2-period design: during period 1 (reference), a single dose of 5 mg nebivolol was administered, while during period 2 (test), 5 mg nebivolol + 300 mg bupropion were ingested concomitantly, after a pretreatment regimen with bupropion (7 days). The PK parameters of nebivolol and its active metabolite were analyzed by noncompartmental modeling, while the pharmacodynamic (PD) parameters (blood pressure and heart rate) were assessed at rest. Results: Bupropion plus nebivolol increased the mean peak plasma concentrations (Cmax) of nebivolol (1.67 ± 0.69 vs. 3.80 ± 1.70 ng/ml) and its active metabolite (0.68 ± 0.22 vs. 1.13 ± 0.38 ng/ml) compared to nebivolol alone. After bupropion pretreatment, the exposure to nebivolol was increased by 7.2-fold for the parent drug and 4-fold for the hydroxylated active metabolite. The difference between the PD parameters measured during the 2 periods was not significant. Conclusion: The study concluded that bupropion influenced the PKs of nebivolol in healthy volunteers, but a clinical relevance was not established. However, this latter aspect requires further investigation.

Psoriasis is one of the most common chronic dermatological conditions, with a strong impact on patients' quality of life. Currently, psoriasis benefits from conventional therapy with a high rate of adverse effects and an increase in non-compliance and self-medication of patients. As such, there is a need to pinpoint low-adverse effects and accessible remedies for this condition. Our single-blind, placebo-controlled study assessed the effect of sea buckthorn extract on psoriasis lesions in previously untreated patients. Our results showed an improvement in Psoriasis Area Severity Index (PASI) scores and in Dermatology Life Quality Index (DLQI) scores when compared to the baseline values, as well as at the 4- and 8-week time marks for the lesions treated with sea buckthorn extract. By contrast, the measurements for the placebo treated lesions showed no alteration at the 4-week mark, and significant worsening at the end of the trial. These findings provide a solid, optimistic base for the in-depth research of sea buckthorn as an adjuvant or a component in psoriasis care protocols.

Berberine-containing plants have been traditionally used in different parts of the world for the treatment of inflammatory disorders, skin diseases, wound healing, reducing fevers, affections of eyes, treatment of tumors, digestive and respiratory diseases, and microbial pathologies. The physico-chemical properties of berberine contribute to the high diversity of extraction and detection methods. Considering its particularities this review describes various methods mentioned in the literature so far with reference to the most important factors influencing berberine extraction. Further, the common separation and detection methods like thin layer chromatography, high performance liquid chromatography, and mass spectrometry are discussed in order to give a complex overview of the existing methods. Additionally, many clinical and experimental studies suggest that berberine has several pharmacological properties, such as immunomodulatory, antioxidative, cardioprotective, hepatoprotective, and renoprotective effects. This review summarizes the main information about botanical occurrence, traditional uses, extraction methods, and pharmacological effects of berberine and berberine-containing plants.

Background Atrial fibrillation (AF) is one of the most common sustained cardiac arrhythmia. It is associated with significant morbidity, mortality and poor quality of life. This is the reason why it is very important to closely follow its treatment. Amiodarone is one of the most frequently used antiarrhythmic drugs in patients with AF both in prophylaxis and treatment. However, the treatment with this drug results in high healthcare resource use and costs due to its poor safety profile. Purpose The objective of this study was to assess the plasmatic concentration of amiodarone in patients with AF and also to identify possible factors that could influence it. The results were correlated with used doses, with concomitantly administered drugs, renal and liver function. Material and methods A prospective observational study was conducted in 27 consecutive patients treated with amiodarone from May to July 2017 in a Clinical University Hospital. The patients included met our inclusion criteria. HPLC-MS was the device used to determine the plasma concentration of amiodarone. Results The mean age of those 27 included patients was 65/6±11 years, 44.4% females. The used doses were 200 mg or 400 mg/day. In our patients, plasmatic concentration was given in a therapeutic interval (500–2,500 ng/ml) to 51.8%. In the patients with lower plasmatic concentrations of amiodarone, the drugs associated in the therapeutic plan belonged to: diuretics (furosemide), beta-blockers, statins, antiplatelets (clopidogrel), fluoroquinolones (ciprofloxacine) and non-steroidal anti-inflammatory drugs. It was observed that there was a statistically significant difference between the plasmatic concentrations of amiodarone in patients treated with furosemide vs patients treated concomitantly with other drugs. The interactions between other mentioned drugs and amiodarone were not registered. It was observed that an increase in transaminases or creatinine is correlated with an increase in amiodarone’s plasmatic concentration. Conclusion 48.2% of the patients with AF under chronic treatment with amiodarone had the plasmatic concentration of amiodarone out of the therapeutic range. We can report an underuse of amiodarone for these patients. It was found that there was a significant interaction between furosemide and amiodarone. In order to confirm this interaction, we need to continue the research on a larger sample. References and/or Acknowledgements Thanks to all the collaborators. No conflict of interest

Background: Allergic rhinitis is characterized by a chronic inflammation of nasal mucosa and represents a risk factor for asthma occurrence. H1 antihistamines reduce the symptoms of rhinitis, but some compounds may have anti-inflammatory properties. Aims: We evaluated the plasma level of some cytokines in patients with persistent allergic rhinitis (PAR) and their evolution after a 4-week treatment with H1 antihistamines, as well as the risk of asthma after 1.5 years. Study Design: Randomized clinical trial. Methods: Eighty-five patients with PAR and 30 healthy volunteers were included in the study. The patients with PAR were randomly divided into 2 groups: 41 patients treated with 5 mg/day desloratadine and 44 patients under 5 mg/day levocetirizine for 4 weeks. The clinical and biological evaluations were performed before and after treatment and included rhinitis symptoms and total symptoms score, type of sensitization, and plasmatic levels of total IgE, IL-1β, IL-6, IL-8 and TNF-α. Results: IL-8 and TNF-α were significantly increased in patients with PAR compared to healthy volunteers (5.85 vs 3.12, p

Pain relief using drugs with high efficacy provides significant improvement in the patients' lives. Drugs like lamotrigine (LTG) and gabapentin (GBP) have the ability to overcome the symptoms of neuropathic pain.The present study offers a comparative analysis of LTG and GBP efficacy in a rat model of nociceptive pain after single administration.Sixty-three Wistar-Bratislava rats randomized into 7 groups were included: a control group treated with saline solution and 6 groups treated with different doses of LTG and GBP. Nociceptive responses to thermal and mechanical stimulations were evaluated before and after drug administration, at different time intervals, using paw pressure and hot plate tests. The obtained data were statistically analyzed, with significance at p value0.05.LTG 100 mg/kg and 50 mg/kg presented a significant analgesic effect in both mechanical and thermal tests, 1 and 2 hours after administration. GBP 100 mg/kg increased latency time in hot plate test. The effect of both anticonvulsant drugs occurred rapidly after administration, but had a short duration.LTG and GBP had an analgesic effect in a single dose administration. The effect of LTG was more evident since it was observed in both tests. Their effect was dose dependent.

Stroke-like presentation of multiple sclerosis is a challenging diagnosis requiring quick and efficient decision in order to provide the best possible therapeutical option. This case presentation focuses on the difficulties of the differential diagnostic process. Even if signs were misleading, the stepwise and structured approach with the use of adequate diagnostic tools revealed the most likely diagnosis and, thus, assured the best clinical care. Orv. Hetil., 2015, 156(37), 1514–1518.

Rationale: Vitamin K antagonists (VKA), such as warfarin and acenocoumarol, are widely used for the prevention and treatment of thromboembolic diseases and they are some of the most commonly prescribed types of medications. They are characterized by narrow therapeutic indices and inter-individual or intra-individual variability in response to the treatment. Objective: to establish the influence of several genetic factors on VKA efficacy and adverse reactions. Methods and Results: The metabolism of VKA differs depending on their chemical structure: indandiones derivatives (fluindione) or coumarin derivatives (acenocoumarol, phenprocoumon or warfarin). They are mostly metabolized in hepatocytes via a monooxygenase, cytochrome P450 2C9 (CYP2C9), resulting in inactive products. The gene encoding CYP2C9 is polymorphic, its genetic variants being associated with differences in the enzymatic activity of CYP2C9. The most important in terms of their frequency in the general population are CYP2C9*2 and CYP2C9*3. Both alleles are associated with a marked decrease in CYP2C9 enzyme activity. VK epoxide reductase (VKOR) is an enzyme with an important role in VK metabolism. Various polymorphisms in the VKORC1 gene have been described. VKORC1*2 haplotype seems to be the most important in relation to the variability in response to VKA. Discussions: Various studies have shown a relationship between the genotype and the mean warfarin maintenance dosing: in patients carrying 2C9*1/ *2 alleles, the dose is reduced by 18-40% in patients carrying 2C9*2/ *2 alleles, by 21-49% in patients carrying 2C9*1/ *3 alleles. The A allele of the c.-1639G>A polymorphism in the VKORC1 gene is associated with the need for a lower dose of acenocoumarol in patients on anticoagulant therapy. Abbreviations: SNP = Single Nucleotide Polymorphism, VKA = vitamin K antagonists, C1 - VKORC1 = vitamin K epoxide reductase complex subunit, INR = International Normalized Ratio

The association between two autoimmune diseases is known in the literature as overlap syndrome. We present the case of an 18-year-old boy, diagnosed at the age of 13 with an overlap syndrome between type I autoimmune hepatitis and sclerosing cholangitis. The response to immunosuppressant therapy was hampered by azathioprine-induced toxicity causing severe pancytopenia, as a result of thiopurine methyltransferase enzyme genetic deficiency. Treatment was replaced by mycophenolate mofetil. Although the relapse rate was reduced, the disease progressed to cirrhosis. Specific features of this case were the overlap syndrome, young age of onset, especially for sclerosing cholangitis, azathioprine toxicity that influenced the prognosis and the treatment problems regarding the use and efficiency of alternative immunosuppressant agents in pediatric patients.

Background Pathogenic bacteria contribute to various globally important diseases, killing millions of people each year. Various fields of medicine currently benefit from or may potentially benefit from the use of nanotechnology applications, in which there is growing interest. Disease-related biomarkers can be rapidly and directly detected by nanostructures, such as nanowires, nanotubes, nanoparticles, cantilevers, microarrays, and nanoarrays, as part of an accurate process characterized by lower sample consumption and considerably higher sensitivity. There is a need for accurate techniques for pathogenic bacteria identification and detection to allow the prevention and management of pathogenic diseases and to assure food safety. Conclusion The focus of this review is on the current nanoparticle-based techniques for pathogenic bacterial identification and detection using these applications.

Multidrug-resistant bacterial infections that have evolved via natural selection have increased alarmingly at a global level. Thus, there is a strong need for the development of novel antibiotics for the treatment of these infections. Functionalized carbon nanotubes through their unique properties hold great promise in the fight against multidrug-resistant bacterial infections. This new family of nanovectors for therapeutic delivery proved to be innovative and efficient for the transport and cellular translocation of therapeutic molecules. The current review examines the latest progress in the antibacterial activity of carbon nanotubes and their composites.

Background. Stigmatizing attitudes to mental illness, and especially schizophrenia, are not limited to the general population but are also common among health professionals. Health professionals are in a position to model health related attitudes both in the general public and patients. Medical students are an interesting group to focus upon, since they are future health professionals and correcting stigmatizing attitudes is still possible during their educational curriculum. Methods. This study investigated the attitude toward mental illness in medical students at the Iuliu Hatieganu University of Medicine and Pharmacy. We surveyed first year students, since they have not yet received specific classes or internships in psychiatry; 322 students from the Romanian and English sections participated, representing a response rate of 94.7%. The questionnaire consisted of the Romanian and English versions of Link's Social Distance Scale towards people with mental illness scale. Results . Overall, medical students had a relatively negative attitude towards people with mental illness, with moderate social distance and stereotypical attitudes. The level of personal contact with people with mental illness was correlated with positive attitudes. International students had scored lower then Romanian students on social distance toward mentally ill patients. Conclusions. Medical education can play an important role in the attitudes of students toward mental illness. Medical students have stigmatizing attitudes about mentally ill patients. Personal contact with people suffering from mental illness might contribute to a positive attitude from the medical students toward mentally ill patients.

Military personnel are often subjected to sleep deprivation (SD) for long hours during combat or peacekeeping operations across the Globe. Recent reports suggests that sound sleep for less than 4 h results in confusion, simple task calculations, and affects decision making. However, in military life SD of 12–72 h is quite common. It appears that longer duration of SD is related to brain dysfunction. Model experiments carried out in our laboratory show that 12–72 h of SD in rats results in progressive breakdown of the blood-brain barrier (BBB) to proteins and induce brain edema formation. Selective neuronal, glial cell and axonal injuries also occurred in SD that is progressive in nature. Interestingly, the magnitude and intensity of SD depends on environmental temperature and cardiovascular health of the animals. Thus, SD at 34 °C induces 2- to 4- fold brain damage, BBB breakdown and edema formation in rats as compared to identical SD at room temperature (21 ± 1 °C). Also hypertensive rats when subjected to identical SD showed greater degree of brain pathology as compared to normotensive animals. Treatment with a multimodal drug Cerebrolysin that is a balanced composition of several neurotrophic factors and active peptide fragments significantly reduced the brain pathology in healthy animals at room temperature. However, TiO2-nanowired delivery of cerebrolysin is needed to attenuate SD induced brain pathology of normotensive rats at hot environment or hypertensive animals at room temperature. These observations suggest that nanodrug delivery in SD is needed to induce neuroprotection at hot environment or in hypertensive animals, not reported earlier.

Untargeted metabolomics coupled with chemometric analysis was applied to evaluate and discriminate six Romanian sea buckthorn (Hippophae rhamnoides L.) berries and leaves. Total carotenoids and total phenolics were determined quantitatively by UV-Vis spectrometry. The qualitative evaluation and discrimination was obtained using the FTIR fingerprints (by using Fourier Transform Infrared spectroscopy) of raw carotenoid and phenolic extracts. The average concentration of total carotenoids was 54 and 3.9 mg carotenoids/ 100g DW in berries and leaves, respectively. The average concentration of total phenolics was 746 mg GAE/100g DW in berries, approximately 1.8 times lower than total phenolics found in leaves. By PCA (Principal Component Analysis) of fingerprints (900-1800 cm-1), the responsible bands for samples discrimination were identified. In case of total carotenoids extract the biomarker bands were: 1745, 1743, 1500 cm-1 for berries and 1458 cm-1 and 1735 cm-1 for leaves, while for total phenolic extract the key bands were 1731, 1033, 1622 cm-1 for berries and 1047 cm-1, 1616, 1512 and 1454 cm-1 for leaves. FTIR spectroscopy proved to be a simple and sensitive analytical technique that can be successfully used in sample discrimination and classification.

Untargeted metabolomics coupled with chemometric analysis was applied to evaluate and discriminate six Romanian sea buckthorn (Hippophae rhamnoides L.) berries and leaves. Total carotenoids and total phenolics were determined quantitatively by UV-Vis spectrometry. The qualitative evaluation and discrimination was obtained using the FTIR fingerprints (by using Fourier Transform Infrared spectroscopy) of raw carotenoid and phenolic extracts. The average concentration of total carotenoids was 54 and 3.9 mg carotenoids/ 100g DW in berries and leaves, respectively. The average concentration of total phenolics was 746 mg GAE/100g DW in berries, approximately 1.8 times lower than total phenolics found in leaves. By PCA (Principal Component Analysis) of fingerprints (900-1800 cm-1), the responsible bands for samples discrimination were identified. In case of total carotenoids extract the biomarker bands were: 1745, 1743, 1500 cm-1 for berries and 1458 cm-1 and 1735 cm-1 for leaves, while for total phenolic extract the key bands were 1731, 1033, 1622 cm-1 for berries and 1047 cm-1, 1616, 1512 and 1454 cm-1 for leaves. FTIR spectroscopy proved to be a simple and sensitive analytical technique that can be successfully used in sample discrimination and classification.

Prostate cancer has an increasing incidence and there is an urgent need for development of new serum biomarkers for early diagnostic as the ones known are ineffective. The aim of the study was to use untargeted metabolomics in order to identify and characterize small metabolite fingerprints in patients with normal vs pathologic values of PSA ( previously determined by electrochemiluminiscence). A cohort of one hundred patients with different Prostate Specific amtigen values were investigated by untargeted metabolomics. The serum small metabolite profile determined by high performance liquid chromatography coupled with mass spectrometry, LC-QTOF(ESI+)MS in order to identify specific biomarkers, for normal patient group (PSA = 0-4 ng.ml) and four pathologic groups, having PSA values from 4 to >1000 ng/ml. The major molecules identified in the samples were polar phospholipids, maily lysophosphatidyl choline derivatives, having m/z values from 496 to 524, like LPC(O-16:0/O-1:0), LPC(18:1/2:0) or PS(18:1(9Z)/0:0), LPC(18:2(9Z,12Z)/0:0 and their isomers and LPC(O-18:1(11Z)/2:0), respectively. Also, small molecules (free fatty acids and prostaglandin derivatives) were identified and are significantly different in pathologic vs normal serum samples. Generally the pathologic samples had increased concentrations of all above mentioned molecules. The Principal Component analysis showed , by plot and loadings scores, significant clustering of normal vs pathological groups.

Scop: Această cercetare are drept scop stabilirea unei corelaţii genotip-fenotip la pacienţii trataţi cu acenocumarol şi studierea factoriilor genetici (polimorfismele VKORC1 şi CYP2C9), care ar putea influenţa valorile INR în timpul iniţierii terapiei anticoagulante orale cu acenocumarol. Material şi metode: Am inclus 131 de pacienţi care necesitau tratament cu acenocumarol, 70 (53,4%) femei şi 61 (46,6%) bărbaţi, internaţi în Clinica Medicala 5 din Cluj-Napoca, între 2009-2011. Am studiat influenţa vârstei, sexului, medicaţiei concomitente şi a genelor CYP2C9 şi VKORC1 asupra valorii INR măsurate în ziua a treia de tratament şi asupra diferenţei dintre această valoare şi valoarea INR măsurată la debutul tratamentului (INRDIF). Rezultate şi concluzii: Am demonstrat o diferenţă semnificativă statistic pentru INR3 şi valorile INRDIF la pacienţii cu genotip AA şi cei cu genotip GG ai polimorfismului c.- 1639G>A al genei VKORC1. Prezenţa genotipului AA al polimorfismului c.- 1639G>A al genei VKORC1 a determinat o creştere de 15,7 ori a riscului ca un pacient să prezinte INR supraterapeutic după 2 zile de tratament cu 4 mg de acenocumarol.

SummaryWhat is known and objective Nebivolol is a highly selective beta-blocker with additional vasodilator properties, widely used in the clinical practice for the treatment of hypertension and heart failure. Paroxetine is a second-generation antidepressant and a potent inhibitor of CYP2D6, the same isoenzyme involved in the metabolism of nebivolol. The objective of this study was to investigate the effect of multiple-dose paroxetine intake on the pharmacokinetics of nebivolol in healthy volunteers and its potential consequences upon nebivolol pharmacodynamics. Methods The study included 23 healthy subjects and was designed as an open-label, single-centre, non-randomized, two-period clinical trial. During period 1 (reference), each volunteer received a single dose of 5 mg nebivolol, whereas during period 2 (test), each volunteer received a single dose of 5 mg nebivolol and 20 mg paroxetine, after a pretreatment regimen with paroxetine (20–40 mg/day for 6 days). The pharmacokinetic parameters of nebivolol and its active metabolite were analysed by non-compartmental modelling. The pharmacodynamic parameters (blood pressure and heart rate) were assessed at rest, after each nebivolol intake. Results and discussion Pretreatment with paroxetine increased the mean peak plasma concentrations (Cmax) for unchanged nebivolol (1·78 ± 1·17 vs. 4·24 ± 1·67 ng/mL) and for its active metabolite (0·58 ± 0·21 vs. 0·79 ± 0·24 ng/mL) compared to nebivolol alone. The time (tmax) to reach Cmax was 1·37 ± 0·88 (h) and 3·11 ± 1·76 (h) for the parent compound and its active metabolite after nebivolol administered alone and 3·96 ± 1·76 (h), respectively, 7·33 ± 7·84 (h) after pretreatment with paroxetine. Also, the total areas under the curve (AUC0-∞) were significantly increased from 17·26 ± 43·06 to 106·20 ± 65·56 h ng/mL for nebivolol unchanged and 13·03 ± 11·29 to 74·56 ± 88·77 h ng/mL for its hydroxylated metabolite, before and after paroxetine intake. All the pharmacokinetic parameters presented statistically significant differences when paroxetine was administered with nebivolol. Nonetheless, statistical analysis did not show a significant difference between the vital signs measured during the two periods. What is new and conclusion After pretreatment with paroxetine, the exposure to nebivolol was increased by 6·1-fold for the parent drug and 5·7-fold for the hydroxylated active metabolite. Paroxetine influenced nebivolol pharmacokinetics in healthy volunteers, but it did not have a significant effect on nebivolol pharmacodynamic parameters measured at rest, although the clinical relevance of this drug interaction needs further investigation.

Background and aim . Morbid obesity represents a proinflammatory and pro-oxidative state associated with dysregulation of adipokines. We aimed to evaluate the circulating levels of chemerin and omentin-1 in morbidly obese (MO) patients and to investigate the relationship between these two adipokines and between each of them and anthropometric, metabolic, oxidative stress and chronic inflammatory parameters. Material and methods . 32 MO patients and 20 controls were investigated in this study. Anthropometric, metabolism parameters, inflammatory markers, oxidative stress indicators as well as chemerin and omentin-1 were measured. Results . Serum levels of chemerin were increased while omentin-1 levels were decreased in MO patients when compared with controls. Chemerin correlated positively with insulin, HOMA-IR, LDL cholesterol and negatively with total antioxidant response. Omentin-1 correlated negatively with tumor necrosis factor alpha and total cholesterol. In a multiple linear stepwise regression analysis we learnt that only HOMA-IR (β=0.70, p

Objectives This study aimed to assess the relationship between bone mineral density and genotypes of four polymorphisms in previously detected osteoporosis-candidate genes (FDPS rs2297480, LRP5 rs3736228, SOST rs1234612, VKORC1 rs9934438) in postmenopausal Romanian women with primary osteoporosis. Methods An analytical, prospective, transversal, observational, case-control study on 364 postmenopausal Romanian women was carried out between June 2016 and August 2017 in Cluj Napoca, Romania. Clinical data and blood samples were collected from all study participants. Four polymorphisms were genotyped using TaqMan SNP Genotyping assays, run on a QuantStudio 3 real-time PCR machine. Results Women with TT genotype in FDPS rs2297480 had significantly lower bone mineral density values in the lumbar spine and total hip, and the presence of the T allele was significantly associated with the osteoporosis. Women carrying the CC genotype in LRP5 rs3736228 tend to have lower bone mineral density values in the femoral neck and total hip. No significant association was found for the genotypes of SOST rs1234612 or VKORC1 rs9934438. Conclusions Our study showed a strong association between bone mineral density and polymorphisms in the FDPS gene, and a borderline association with LRP5 and SOST polymorphisms in postmenopausal Romanian women with osteoporosis. No association was found for VKORC1.

Background and objectives: Ragweed pollen is a major source of allergen, which has rarely been observed in Romania until now. In this study, we evaluated the symptoms and associated factors in patients with allergic rhinitis to ragweed pollen in two distinct regions of Romania. Materials and Methods: We evaluated the records of patients newly diagnosed with allergic rhinitis induced by ragweed pollen in two allergological centers from North-West (NW) and Central parts of Romania between 2013 and 2015. The patients were clinically evaluated regarding disease length, presence, and severity of the allergic rhinitis symptoms and the association with other allergic manifestations (asthma and conjunctivitis). Results: The sensitization to ragweed was significantly higher in the NW part compared to the Central part (18.27% vs 4.1%, p &lt, 0.001). More patients with monosensitization to ragweed pollen were observed in the NE center (27%) compared to the Central one (20.7%). Patients with monosensitization to ragweed pollen presented more severe forms of rhinitis (70% vs 31.5%, p = 0.02) in the NW part compared to polysensitized patients. The total symptoms score was significantly higher in patients from the Central part compared to the NW part (9.21 &plusmn, 2.01 vs 5.76 &plusmn, 1.96, p &lt, 0.001). Bronchial asthma was associated at a similar frequency to allergic rhinitis in both centers, but it was more frequently observed in monosensitized patients in the NW center. Allergic conjunctivitis was more frequently reported by patients from the Central part (75.86 vs 41.9, p = 0.02), while in the NW region it was noticed more commonly in monosensitized patients (65% vs 33.33, p = 0.02). Conclusions: Allergic rhinitis to ragweed pollen has been more frequently reported in the NW part of Romania. Patients with severe forms of rhinitis were observed in the central part, while in the NW the severe forms of disease were reported by patients with monosensitization. Ragweed pollen is intensely allergogenic and determines association of ocular and asthma symptoms. Co-sensitization increases the risk of asthma association.

Dysbiosis is a condition that can cause various clinical disorders, from gastrointestinal problems to allergies or even cancer. Resetting the microbiota using antibiotics and/or probiotics could be a possible therapy for many diseases. The aim of this study was to evaluate the effects of three treatment regimens in patients with irritable bowel syndrome (IBS). The regimens were short-term rifaximin treatment (10 days) followed by either a nutraceutical agent (G1) or a low- Fermentable, Oligo-, Di-, Monosaccharide and Polyol (FODMAP) diet (24 days) (G3) or treatment with MegaSporeBiotic a mixture of spores of five Bacillus spp. for medium-term (34 days) (G2). Ninety patients with IBS without constipation were enrolled and divided into three groups (G1, G2, G3). Patients in G1 and G3 were evaluated over four visits (baseline/first day (V1), 10 days (V2), 34 days (V3), 60 days (V4)), and, those in G2 over three visits (V1, V3, V4). Severity score, quality of life, and parameters from the rectal volume sensation test were determined. The results demonstrated that patients treated with MegaSporeBiotic, compared with those treated with rifaximin followed by nutraceutical or low-FODMAP diet, had similar severity scores and rectal volume sensation test results for all parameters tested and statistically significant improvement in measurements of quality of life.

Introduction - Sea buckthorn (Hippophae rhamnoides L.) is known to be rich in many bioactive compounds (such as vitamins, phenolics, carotenoids) important for human health and nutrition. Among the phenolics, berries and leaves contain a wide range of flavonols that are good quality and authenticity biomarkers. Objective - To compare the composition of the main flavonols of Romanian sea buckthorn berry and leaf varieties and to identify the specific biomarkers that contribute to sample differentiation among varieties. Material and methods - Six varieties of cultivated sea buckthorn (ssp. Carpatica) berries and leaves were analysed by UHPLC/PDA–ESI/MS. Results - Berries and leaves contained mainly isorhamnetin (I) glycosides in different ratios. Whereas I-3-neohesperidoside, I-3-glucoside, I-3-rhamnosylglucoside, I-3-sophoroside-7-rhamnoside and free isorhamnetin were predominant for berries (out of 17 compounds identified), I-3-rhamnosylglucoside, I-3-neohesperidoside, I-3-glucoside, quercetin-3-pentoside, kaempferol-3-rutinoside, and quercetin-3-glucoside were predominant in leaves (out of 19 compounds identified). Berries contained, on average, 917?mg/100?g DW flavonol glycosides. Leaves had higher content of flavonol glycosides than berries, on average 1118?mg/100?g DW. The variation of the quantitative dataset analysed using principal component analysis accounted for 91% of the total variance in the case of berries and 73% in case of leaves, demonstrating a good discrimination among samples. Conclusion - Based on quantitative analysis, by principal component analysis, the flavonol derivatives can be considered as biomarkers to discriminate among varieties and to recognise specifically the berry versus leaf composition

To develop and validate an algorithm for the prediction of therapeutic dose of acenocoumarol in Romanian patients. The inclusion criteria for entry to the study was age ≥18 years and starting acenocoumarol treatment for at least one of the following clinical indications: acute deep vein thrombosis of the lower limbs, persistent or permanent atrial fibrillation, and/or the presence of valvular prostheses requiring prolonged oral anticoagulant therapy. The patients were followed up for 3 months. Patients admitted to the internal medicine, cardiology, and geriatrics wards of the Municipal Clinical Hospital, Cluj-Napoca and “Niculae Stancioiu” Heart Institute between October 2009 and June 2011 who fulfilled the inclusion criteria were included in the study. Clinical and demographic data that could influence the acenocoumarol stable dose were recorded for each patient. Genetic analysis included the genotyping the CYP2C9*2 and *3, and the VKORC1 -1693 G > A polymorphisms. The patients were randomly divided into two groups: (1) the main group on which the development of the clinical and genetic algorithms for acenocoumarol dose prediction was based; (2) the validation group. The study included 301 patients, of whom 155 were women (51.5 %) and 146 were men (48.5 %). The median age of the patient cohort was 66 (women, 57; men, 73) years. After randomization the main group comprised 200 patients (66.4 %) and the validation group 101 patients (33.6 %). Age and body mass index explained 18.8 % (R 2) of the variability in acenocoumarol weekly dose in patients in the main group. When the genetic data were added to the algorithm, the CYP2C9*2 and *3 polymorphisms and the VKORC1 -1693 G > A polymorphism accounted for 4.7 and 19. 6 % of acenocoumarol dose variability, respectively. For the main group, we calculated a mean absolute error of 5 mg/week (0.71 mg/day). In the validation group, clinical parameters explained 22.2 % of the weekly acenocoumarol dose variability. Genetic polymorphisms increased the R 2 coefficient to 32.8 %. We have developed and validated an accurate algorithm for prediction of the stable therapeutic dose of acenocoumarol in a Romania population.

Multiple sclerosis is an inflammatory neurological disease of young adults that leads to numerous therapeutic problems and to severe disability. Glatiramer acetate (GA) is a disease-modifying drug used frequently for long-term treatment of the disease. We investigated the impact of GA treatment on the parameters of reversal-pattern visual evoked potentials and event-related P300 wave (reflecting visual acuity and cognitive dysfunction). Relapsing-remitting multiple sclerosis patients either subjected to one-year-long continuous treatment with GA or without any disease-modifying therapy and also healthy controls were involved in the study. The above-mentioned parameters were analyzed at two time points, at the first recording and after one year. It was found that GA did not exert a significant influence on the phenomena studied at least during the one-year follow-up. This finding is in contrast to most of the clinical observations.

We have used albumin (BSA) bound to gold nanoparticles (GNPs) as active vectors to target liver cells. Our incentive to develop an original model of living liver cancer sprang from the ethical drawbacks that hindered the assessment of the selective character and the therapeutic capacity of these nano-biosystems in cancer patients. Ex vivo-perfused liver specimens were obtained from hepatocellular carcinoma patients similarly to the surgical technique of transplantation. Albumin bound to GNPs was inoculated intra-arterially onto the resulting specimen and determined the specific delivery of the nano-bioconjugate into the malignant tissue by means of the capillary bed. The extent of necrosis was considerable following laser therapy and at the same time surrounding parenchyma was not seriously affected. The selective photothermal ablation of the malignant liver tissue was obtained after the selective accumulation of BSA bound to GNPs into tumor cells following ex-vivo intra-vascular perfusion.

Cristian Berce,1,* Ciprian Lucan,2,* Bobe Petrushev,3,4 Sanda Boca,5 Mirela Miclean,6 Orsolya Sarpataki,7 Simion Astilean,5 Anca Buzoianu,8 Ciprian Tomuleasa,3,9 Anca Bojan9,10 1Animal Facility, 2Department of Surgery, 3Research Center for Functional Genomics and Translational Medicine, 4Department of Pathology, Iuliu Hatieganu University of Medicine and Pharmacy, 5Nanobiophotonics and Laser Microscopy Center, Interdisciplinary Research in Bio-Nano-Sciences – Faculty of Physics, Babes-Bolyai University, 6Institute for Research in Analytical Instruments, 7Department of Pathophysiology, University of Veterinary Medicine, 8Department of Pharmacology, Iuliu Hatieganu University of Medicine and Pharmacy, 9Department of Hematology, Ion Chiricuta Oncology Institute, 10Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania *These authors contributed equally to this work Introduction: The present study aimed at evaluating the biodistribution of Tween®20-gold nanoparticle (GNP) conjugates and their potential toxicity on the bone marrow before moving on to Phase I clinical trials.Materials and methods: Tween®20-conjugated GNPs were injected intravenously for 21days in male Crl:CD1(ICR) mice. Body weight of the mice was evaluated each day. After the sub-chronic Tween®20-GNPs administration, blood samples were harvested, and a full blood count was done individually. Total Au quantity from all major organs was assessed using inductively coupled plasma mass spectrometry. One femur and the sternum obtained from each animal were used for histological assessment.Results: Our data showed that the Tween®20-GNP conjugates were found in large quantities in the bladder. Au was shown to accumulate in the hematopoietic bone tissue, with significant side effects such as leucopoiesis and megakaryopoiesis. The mice had a higher white blood cell and platelet count as opposed to the control group. This suggested that the previously described leukopenic effects of isoflurane were overridden by the leucopoietic effects of Tween®20-GNPs.Conclusion: It was uncertain whether the mice were reactive to Au as it is a foreign substance to the tissues or whether the side effects observed were a precursor condition of a more severe hematological condition. Au was found to be hepatotoxic, urging the need for further studies in order to achieve better in vivo compliance and exploit the immense potential of GNPs in cancer pharmacology. Keywords: GNPs, Tween®20, in vivo toxicology

Introduction. Oxidative stress is one of the key mechanisms responsible for disease progression in non-alcoholic fatty liver disease. The aim of this study was to evaluate the serum levels of oxidative stress markers in patients with type 2 diabetes mellitus (DMT2) and non-alcoholic steatohepatitis (NASH) and test their relationships with clinical and biochemical patient characteristics, compared to patients with DMT2 without non-alcoholic fatty liver disease (NAFLD), and controls. Materials and methods. In all, 60 consecutive patients with DMT2 and NASH, 55 with DMT2 without NAFLD, and 50 age-and-gender-matched healthy subjects participated in the study. The serum levels of protein carbonyls and 8-isoprostane were determined by ELISA methods, while the serum levels of malondialdehyde (MDA) were detected by means of the spectrophotometric method. Clinical, demographic, and laboratory parameters were examined for all the subjects included in the study. Multivariate logistic regression was used to test the independent predictive factors in the relationships investigated here. Results. Patients with DMT2 and NASH displayed significantly higher serum levels of protein carbonyls (1.112 ± 0.42 nmol/dL), MDA (6.181 ± 1.81 ng/mL), and 8-isoprostane (338.6 ± 98.5 pg/mL) compared to patients with DMT2 without NAFLD, and controls. Results of multivariate logistic regression analyses indicate that in patients with DMT2 and NASH, the serum levels of oxidative stress markers were independently and positively associated with: HbA1c, duration of diabetes, the UKPDS cardiovascular risk score (for protein carbonyls); age, LDL-cholesterol (for 8-isoprostane); and triglycerides serum levels (for MDA). Conclusions. Our findings indicate that the process of oxidative stress tends to increase in patients with DMT2 and NASH, compared to patients with DMT2 without NAFLD, and controls. This evidence suggests that an antioxidant therapy might prove useful in the treatment of patients with DMT2 and NASH.