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The ubiquitin-proteasome system (UPS) is responsible for up to 90% of intracellular protein degradation. Alterations in UPS are extensively involved in the development and advancement of malignant pathologies. Thus, the components of the... more
The ubiquitin-proteasome system (UPS) is responsible for up to 90% of intracellular protein degradation. Alterations in UPS are extensively involved in the development and advancement of malignant pathologies. Thus, the components of the UPS can become potential targets for cancer therapeutics. KPC1 is an E3 ubiquitin ligase component of the UPS that regulates key pathways and processes in cancer. KPC1 sustains the ubiquitination of cytoplasmic p27, determining its elimination and transition between cell-cycle phases. KPC1 also regulates NF-κB signaling by inducing ubiquitination of p105 to allow subsequent proteasomal processing to the functional form p50. It has been shown that the KPC1-p50 duo is reduced or absent in multiple malignancies and that therapeutic reinforcement of the functional axis can exhibit significant tumor suppressor activity. Here, we highlight the potential role of KPC1 as a tumor suppressor by fully describing its crucial role in p27 signaling and the canonical NF-κB pathway.
H2 receptors' antagonists (H2RA) are widely used drugs and they are generally well-tolerated. Ranitidine hypersensitivity reactions (HR) are rarely reported. The article emphasizes the importance of recognizing ranitidine as a cause... more
H2 receptors' antagonists (H2RA) are widely used drugs and they are generally well-tolerated. Ranitidine hypersensitivity reactions (HR) are rarely reported. The article emphasizes the importance of recognizing ranitidine as a cause of anaphylaxis and the advantages and limits of allergological evaluation to establish a positive diagnose. We reviewed a series of published cases of ranitidine-induced hypersensitivity reactions, starting from a clinical case presentation. Moreover, we analyzed the ranitidine related adverse events in the Eudravigilance European database of adverse reactions. Most of the allergic reactions induced by ranitidine are type I HR with immediate onset after exposure, with variable clinical presentation. But in a few cases, there were also described delayed reactions, some after occupational exposure. The article underlines the importance of allergy evaluation to avoid future contact with the drug to reduce the risk of more severe reactions. The suspected reactions should be reported, allowing pharmacovigilance systems to analyse them and to establish further recommendations for clinicians.
... Search result page. Title: Pace and sotalol – three case reports of the benefits and potential hazards associated with sotalol administration in sinus node dysfunction. Author: Ştefan H. Roşianu ; Anca D. Buzoianu ; Adela Roşianu ;... more
... Search result page. Title: Pace and sotalol – three case reports of the benefits and potential hazards associated with sotalol administration in sinus node dysfunction. Author: Ştefan H. Roşianu ; Anca D. Buzoianu ; Adela Roşianu ; Radu Căpâlneanu. ...
Atrial fibrillation (AF) recurrence after radiofrequency catheter ablation (RFCA) remains a challenging issue. This study aims to explore the left atrial appendage function by transesophageal echocardiography (TEE) and assess its value in... more
Atrial fibrillation (AF) recurrence after radiofrequency catheter ablation (RFCA) remains a challenging issue. This study aims to explore the left atrial appendage function by transesophageal echocardiography (TEE) and assess its value in predicting AF recurrence following RFCA in paroxysmal AF patients. Eighty-one patients with paroxysmal AF that underwent RFCA were recruited. TEE was performed before ablation with the assessment of left atrial appendage emptying flow velocity (LAAeV). AF recurrence occurred in 24 patients (29.6%) within 12 months after RFCA. The left atrium diameter (LAD) and left atrium volume index (LAVI) were both significantly higher in the recurrence group compared to the non-recurrence group, while the LAAeV was significantly lower in the recurrence group. LAD, LAVi and LAAeV were univariately significant risk factors for AF recurrence after ablation. Based on receiver operating curve (ROC), LAAeV < 40.5 cm/s, LAVi > 40.5 mL and LAD > 41 mm were ide...
Cerebral ischemia reperfusion injury is a debilitating medical condition, currently with only a limited amount of therapies aimed at protecting the cerebral parenchyma. Micro RNAs (miRNAs) are small, non-coding RNA molecules that via the... more
Cerebral ischemia reperfusion injury is a debilitating medical condition, currently with only a limited amount of therapies aimed at protecting the cerebral parenchyma. Micro RNAs (miRNAs) are small, non-coding RNA molecules that via the RNA-induced silencing complex either degrade or prevent target messenger RNAs from being translated and thus, can modulate the synthesis of target proteins. In the neurological field, miRNAs have been evaluated as potential regulators in brain development processes and pathological events. Following ischemic hypoxic stress, the cellular and molecular events initiated dysregulate different miRNAs, responsible for long-terming progression and extension of neuronal damage. Because of their ability to regulate the synthesis of target proteins, miRNAs emerge as a possible therapeutic strategy in limiting the neuronal damage following a cerebral ischemic event. This review aims to summarize the recent literature evidence of the miRNAs involved in signalin...
Usually, the first responses against new communicable diseases are quarantines and travel bans. As of March, the 16th, 2020 until May, the 14th, 2020 The State of Emergency was declared on all the territory of Romania. People had to... more
Usually, the first responses against new communicable diseases are quarantines and travel bans. As of March, the 16th, 2020 until May, the 14th, 2020 The State of Emergency was declared on all the territory of Romania. People had to comply with "stay-at-home orders" while some regions were under total lockdown. In late April 2020, we created and distributed an online survey, via www.psysafe.org. We addressed ethical issues towards both the individual and populational levels measures designed to prevent and reduce COVID-19, as well as assessed the attitudes towards hypothetical public health sanctions infringed on people who do not follow the regulations. In total, 3.122 respondents took part in the survey. The majority consider that physical distancing, self-isolation, quarantine, and nation/region-wide lockdown imposed to prevent and reduce COVID-19 are both necessary and morally justified. The participants do not agree with a hypothetical sanction of not offering medical treatment but would agree with a hypothetical sanction of having to pay for the medical treatment. In the end, we examined the justice of quarantine and isolation from an ethical point of view.
The sinus node dysfunction is associated with conduction system disease and supraventricular tachyarrhythmias (atrial fibrillation and atrial flutter). The only effective treatment for patients with chronic symptomatic sinus node... more
The sinus node dysfunction is associated with conduction system disease and supraventricular tachyarrhythmias (atrial fibrillation and atrial flutter). The only effective treatment for patients with chronic symptomatic sinus node dysfunction is pacemaker therapy. In tachy-brady syndrome patients, in addition to pacemaker therapy, the pharmacological treatment is necessary to avoid tachycardia episodes. Because of the frequent paroxysmal atrial fibrillation episodes a good choice to maintain the sinus rhythm is represented by sotalol. This article will present three patients that provide examples of beneficial effects of sotalol and also on the risk of severe adverse events in some cases.
N-Pep-12 is a dietary supplement with neuroprotective and pro-cognitive effects, as shown in experimental models and clinical studies on patients after ischemic stroke. We tested the hypothesis that N-Pep-12 influences quantitative... more
N-Pep-12 is a dietary supplement with neuroprotective and pro-cognitive effects, as shown in experimental models and clinical studies on patients after ischemic stroke. We tested the hypothesis that N-Pep-12 influences quantitative electroencephalography (QEEG) parameters in patients with subacute to chronic supratentorial ischemic lesions. We performed secondary data analysis on an exploratory clinical trial (ISRCTN10702895), assessing the efficacy and safety of 90 days of once-daily treatment with 90 mg N-Pep-12 on neurocognitive function and neurorecovery outcome in patients with post-stroke cognitive impairment against a control group. All participants performed two 32-channel QEEG in resting and active states at baseline (30–120 days after stroke) and 90 days later. Power spectral density on the alpha, beta, theta, delta frequency bands, delta/alpha power ratio (DAR), and (delta+theta)/(alpha+beta) ratio (DTABR) were computed and compared across study groups using means comparison and descriptive methods. Secondarily, associations between QEEG parameters and available neuropsychological tests were explored. Our analysis showed a statistically significant main effect of EEG segments (p<0.001) in alpha, beta, delta, theta, DA, and DTAB power spectral density. An interaction effect between EEG segments and time was noticed in the alpha power. There was a significant difference in theta spectral power between patients with N-Pep-12 supplementation versus placebo at 0.05 alpha level (p=0.023), independent of time points. A 90-day, 90 mg daily administration of N-Pep-12 had significant impact on some QEEG indicators in patients after supratentorial ischemic stroke, confirming possible enhancement of post-stroke neurorecovery. Further research is needed to consolidate our findings.
1Cristian I. Crăciun, 2,3Anca E. Crăciun, 1Ioana C. Bocşan, 2Adriana Rusu, 2Cornelia Bala, 4Camelia A. Coadă, 2Gabriela Roman, 1Anca D. Buzoianu 1 Department of Pharmacology, Toxicology and Clinical Pharmacology, “Iuliu Hațieganu”... more
1Cristian I. Crăciun, 2,3Anca E. Crăciun, 1Ioana C. Bocşan, 2Adriana Rusu, 2Cornelia Bala, 4Camelia A. Coadă, 2Gabriela Roman, 1Anca D. Buzoianu 1 Department of Pharmacology, Toxicology and Clinical Pharmacology, “Iuliu Hațieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 2 Department of Diabetes, Nutrition and Metabolic Diseases, “Iuliu Hațieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 3 „Regina Maria” Policlinic, Cluj-Napoca, Romania; 4 Department of Medical and Surgical Sciences (DIMEC), Bologna University, Bologna, Italy.
1Florin Casoinic, 2Dorina Baston, 1Dorel Sampelean, 3Catalina Badau, 4Anca D. Buzoianu, 5Nicolae Hancu 1 Department of Internal Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 2 Cardiovascular and... more
1Florin Casoinic, 2Dorina Baston, 1Dorel Sampelean, 3Catalina Badau, 4Anca D. Buzoianu, 5Nicolae Hancu 1 Department of Internal Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 2 Cardiovascular and Vascular Surgery Inpatient Unit, Toronto General Hospital, Toronto, Canada; 3 “N. Stancioiu” Heart Institute, Cluj-Napoca, Romania; 4 Department of Pharmacology, Toxicology and Clinical Pharmacology, “Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania; 5 Department of Diabetology, “Iuliu Hatieganu” University of Medicine and Pharmacy, ClujNapoca, Romania.
Viral B and C hepatitis are a major current health issue, both diseases having a chronic damaging effect on the liver and its functions. Chronic liver disease can lead to even more severe and life-threatening conditions, such as liver... more
Viral B and C hepatitis are a major current health issue, both diseases having a chronic damaging effect on the liver and its functions. Chronic liver disease can lead to even more severe and life-threatening conditions, such as liver cirrhosis and hepatocellular carcinoma. Recent years have uncovered an important interplay between the liver and the gut microbiome: the gut-liver axis. Hepatitis B and C infections often cause alterations in the gut microbiota by lowering the levels of ‘protective’ gut microorganisms and, by doing so, hinder the microbiota ability to boost the immune response. Treatments aimed at restoring the gut microbiota balance may provide a valuable addition to current practice therapies and may help limit the chronic changes observed in the liver of hepatitis B and C patients. This review aims to summarize the current knowledge on the anato-functional axis between the gut and liver and to highlight the influence that hepatitis B and C viruses have on the microbiota balance, as well as the influence of treatments aimed at restoring the gut microbiota on infected livers and disease progression.
This prospective meta-analysis summarizes results from the CAPTAIN trial series, evaluating the effects of Cerebrolysin for moderate-severe traumatic brain injury, as an add-on to usual care. The study included two phase IIIb/IV... more
This prospective meta-analysis summarizes results from the CAPTAIN trial series, evaluating the effects of Cerebrolysin for moderate-severe traumatic brain injury, as an add-on to usual care. The study included two phase IIIb/IV prospective, randomized, double-blind, placebo-controlled clinical trials. Eligible patients with a Glasgow Coma Score (GCS) between 6 and 12 received study medication (50 mL of Cerebrolysin or physiological saline solution per day for ten days, followed by two additional treatment cycles with 10 mL per day for 10 days) in addition to usual care. The meta-analysis comprises the primary ensembles of efficacy criteria for 90, 30, and 10 days after TBI with a priori ordered hypotheses based on multivariate, directional tests. A total 185 patients underwent meta-analysis (mean admission GCS = 10.3, mean age = 45.3, and mean Baseline Prognostic Risk Score = 2.8). The primary endpoint, a multidimensional ensemble of functional and neuropsychological outcome scales indicated a “small-to-medium” sized effect in favor of Cerebrolysin, statistically significant at Day 30 and at Day 90 (Day 30: MWcombined = 0.60, 95%CI 0.52 to 0.66, p = 0.0156; SMD = 0.31; OR = 1.69; Day 90: MWcombined = 0.60, 95%CI 0.52 to 0.68, p = 0.0146; SMD = 0.34, OR = 1.77). Treatment groups showed comparable safety and tolerability profiles. The meta-analysis of the CAPTAIN trials confirms the safety and efficacy of Cerebrolysin after moderate-severe TBI, opening a new horizon for neurorecovery in this field. Integration of Cerebrolysin into existing guidelines should be considered after careful review of internationally applicable criteria.
Natural products black cumin—Nigella sativa (N. sativa) and wild garlic—Allium ursinum (AU) are known for their potential role in reducing cardiovascular risk factors, including antracycline chemotherapy. Therefore, this study... more
Natural products black cumin—Nigella sativa (N. sativa) and wild garlic—Allium ursinum (AU) are known for their potential role in reducing cardiovascular risk factors, including antracycline chemotherapy. Therefore, this study investigates the effect of N. sativa and AU water and methanolic extracts in a cellular model of doxorubicin (doxo)-induced cardiotoxicity. The extracts were characterized using Ultraviolet-visible (UV-VIS) spectroscopy, Fourier-transform infrared (FT-IR) spectroscopy, Liquid Chromatography coupled with Mass Spectrometry (LC-MS) and Gas Chromatography coupled with Mass Spectrometry (GC-MS) techniques. Antioxidant activity was evaluated on H9c2 cells. Cytosolic and mitochondrial reactive oxygen species (ROS) release was evaluated using 2′,7′-dichlorofluorescin-diacetate (DHCF-DA) and mitochondria-targeted superoxide indicator (MitoSOX red), respectively. Mitochondrial membrane depolarization was evaluated by flow cytometry. LC-MS analysis identified 12 and 10 p...
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... more
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 p...
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... more
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.
Experimental and clinical studies have shown the importance of inflammation in the pathophysiology of atrial fibrillation (AF). The renin-angiotensin-aldosterone system (RAAS) may play an important role in the pathogenesis of AF in... more
Experimental and clinical studies have shown the importance of inflammation in the pathophysiology of atrial fibrillation (AF). The renin-angiotensin-aldosterone system (RAAS) may play an important role in the pathogenesis of AF in correlation with the inflammatory process. RAAS inhibition may have important therapeutic value in limiting AF. The aim of this study was the correlation between inflammatory markers and recurrent episodes of AF in patients with known paroxysmal atrial fibrillation, with and without treatment with RAAS inhibitors. We studied 82 patients with paroxysmal AF recorded at "Niculae Stancioiu" Heart Institute Cluj-Napoca, divided into two groups: group A treated with angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB) and group B without this medication. All patients underwent clinical examination, ECG, echocardiography and determination of plasma levels of inflammatory markers represented by high sensitivity C-reactiv...
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... more
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 regressio...
Multiple sclerosis is a neurological disease with diverse treatment options, but one of the main tools of maintaining a relatively acceptable life quality is the pharmacological approach through disease modifying therapies. The objective... more
Multiple sclerosis is a neurological disease with diverse treatment options, but one of the main tools of maintaining a relatively acceptable life quality is the pharmacological approach through disease modifying therapies. The objective of this paper is to give a brief presentation of the main feasible drug options, a higher attention being offered to glatiramer acetate.

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