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Volume XIII, Number 2, 2009 - Therapeutics Pharmacology and Clinical Toxicology

Review


The management of invasive fungal infections

A. Streinu-Cercel, D. Tulbure
Abstract: The past decade has revealed the fact that critical patients are at risk for developing invasive fungal infections (IFI). In such context, we have to gather and systematize the necessary tools in order to be able to promptly diagnose this type of infections and to immediately install the necessary and adequate antifungal therapy.

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Original Papers


Assessment of effective dose of nerve agents following different routes of administration

Jiri Bajgar, Victor Voicu
Abstract: Background. The predominant types of poisonous gases included in the armies as chemical weapons are nerve agents like sarin, soman, and VX. As a basic trigger mechanism of the nerve agents action is described their infl uence on cholinergic nerve transmission caused by inhibition of acetylcholinesterase, butyrylcholinesterase and other hydrolases. The toxic eff ect of nerve agents will depend on the penetration rate of NA into the structures containing mentioned enzymes and on the rate and step of inhibition of functionally most important enzyme - acetylcholinesterase. Material and methods. The compounds studied were administered to female Wistar rats (Valez Praha) weighing 180 - 220 g by different routes of administration (i.v., i.m., i.p., p.o., s.c. and p.c.). The monitoring of blood acetylcholinesterase activity and normal activity (serving as a individual control value for each animal) was registered. Following intoxication, registered decrease of acetylcholinesterase activity was evaluated in semilogarithmical transformation and the half-times (t0.5) of inhibition in vivo were calculated. For every compound and route of administration, 4-8 animals were used. Results. The decrease of acetylcholinesterase activity is very fast, practically without delay after the injection of EDMM [O-ethyl-S-(2-dimethylaminoethyl) methylphosphothioate]; following s.c. administration, the rate of acetylcholinesterase activity decrease was not so high as that observed for i.m. administration and this decrease was slower following p.o. and p.c. administration, respectively. Conclusions. Comparison of the eff ective doses shows that this dose is lowest one for VX followed by EDMM, sarin and soman. From this point of view, VX is the most eff ective compound from the nerve agents studied and therefore its including in the military arsenals is also comprehensible taking into account its mechanism of action.

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Nosocomial infections caused by acinetobacter baumani

Victoria Birlutiu
Abstract: Nosocomial infections are known for the severity of the clinical symptoms and the reserved prognosis due to the involvement of multidrugresistant germs, most of which are frequently identified as Staphylococcus aureus, Pseudomonas aeruginosa, E coli, Klebsiella pneumoniae extended-spectrum - lactamase production (ESBL +); during the past two decades we have witnessed an alarming increase in the occurrence of the Acinetobacter baumanii multiresistant infections in the intensive care units (ICU), surgical units, thus turning into a fearful emergent pathogen agent. We decided to describe the clinical aspects associated to Acinetobacter baumanii nosocomial infections in the County Emergency Clinical Hospital in Sibiu and also their present susceptibility to antibiotherapy, evolution and prognosis. Nosocomial infections were generated by Acinetobacter in 95 cases out of 258, in tumoral diseases in 23 cases, politrauma or abdominal surgical interventions - 9 cases each, fractures - 13 cases with an unfavorable evolution in 7 cases. Th e sensitivity of the isolated stems is preserved in the cases of colistin - 98.15%, meropenem - 93.75% and imipenem - 86.02%.

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The influence of the experimental stress on homocysteine plasma levels in rat

Elena Albu, Cristina Filip, Nina Zamosteanu, Irina M. Jaba, Nastasia Gheorghita, Luminita Jerca, O. C. Mungiu
Abstract: Nowadays it is generally accepted that in the aging processes an important role is played by stress. The main mechanism through which stress is involved in the aging processes seems to be the reactive species generation. On the other hand, it is also known that hyperhomocysteinemia is a risk factor in cardiovascular diseases, as it disturbs the normal endothelium functions and generates thrombosis. The mechanism through which homocysteine triggers these eff ects is not yet clarifi ed, but it is believed that a possible explanation is the reactive species involvement. In our work we have studied the influence of experimentally induced stress on homocysteine levels, in rats. Experimental stress was induced by reversing the normal day/night cycle (18oo - 6oo light). The activities of intracellular superoxide dismutase (SOD), glutathione peroxidase (GPx) and total antioxidant status (TAS) were measured in order to establish if stress by itself generates reactive species. The plasmatic concentrations of homocysteine were also measured. Our data show an increase in SOD activity, simultaneously with the decrease in GPx activity. The total antioxidant status and homocysteine levels have registered no signifi cant changes. In conclusion, subacute stress activated the antioxidant defense systems, but did not infl uence the total antioxidant capacity and homocysteine levels, in rats.

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The cardiovascular system effects of aluminum salts

Dana Gosa, Anca Dana Buzoianu, Ruxandra Schiotis, S. Vlaicu, Corina Neculita
Abstract: Introduction. The ionic mechanism that stands at the base of the central arrhythmias it is not known exactly yet. The current researches at the UMF Cluj-Napoca, Department of Pharmacology and Toxicology showed that there are substances which could cause changes of cardiac rhythm and cardiac frequency when were administrated by microinjections into the cerebral lateral ventricle of rats in narcosis. In this study we examined the eff ects of aluminium chloride on central cardiac arrhythmia using pharmacological means. Material and methods. We used for the study Wistar white rats, with weight between 130-180 grams, in narcosis produced by ethyl urethane. Results. We obtained central caused cardiac arrhythmias by giving aluminium chloride into the cerebral lateral ventricle. Conclusion Aluminium chloride is not a protective agent against the arrhythmic eff ect of sodium glutamate which is known as the reference arrhythmic substance

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Challenges and promises of pharmacogenetics in cancer therapeutics

Raluca Dumache, Marinela Popovici, B. Bumbacila, Maria Puiu
Abstract: Genetic constitution represents an important cause for individual variations in the response and tolerance to drug treatment. These variations are due to the germline mutations in genes that encode for drug-metabolizing enzymes, transporters, cellular targets and signaling pathways. The identifi cation of genetic variations that predict for drug response is an important step towards the translation of pharmacogenetics into clinical practice. The knowledge of pharmacogenetics can aid in the discovery, development and individualization of anticancer drugs.

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Cytochemical study regarding the effect of trichostatin a on cell cultures

R. G. Hertzog, D. I. Hertzog, B. Patrinichi
Abstract: Objectives. Trichostatin A (TSA) is an antifungal antibiotic and a potent reversible inhibitor of histone deacetylase (HDAC). Pharmacologically, TSA is an antitumoral agent, but it is also a therapeutic agent in some non-tumoral diseases. The molecular mechanisms through which TSA inhibits the proliferation of cancerous cells are not well understood. Because the main target of HDAC inhibitors (HDI) is nuclear chromatin, we proposed to determine the eff ects of TSA morphologically, genetically and immunochemically in HeLa (Henrietta Lacks) cells, derived from cervix cancer cells. Material and methods. As biologic material, we used HeLa cell line that has an unlimited proliferative ability in vitro. After subcultivation (1:5), the cultures were treated with TSA in four fi nal concentrations (10, 50, 200, 400 ìg/ml) for 8, 16 and 24 hours. We used morphometric, genetic methods, nucleolus organizers staining (that refl ect the transcription function of ribosomal genes) and the study of chromosomal alterations, analysis of the condensed and decondensed state of the nuclear chromatin, apoptosis and visualization of acetylated nuclear proteins by an indirect immunocytochemistry. Results. By means of morphometric measurements, we emphasized that the cell nuclei treated with TSA were slightly larger than those in control samples. Nucleolus organizer regions (NOR), visualized with AgNO3 and localized in second constrictions level of acrocentric chromosomes, exposed various sizes. The analysis of chromosomal damages shows that TSA often induces mono- and bichromatid breaks whose frequency increased in a concentration and time of treatment - dependent manner. At a small frequency deletions and dicentric chromosomes were identifi ed. TSA induced a decondensed chromatin that was observed both on the chromosomal preparations and interphase nuclei. By immunofl uorescence, we observed that chromatin was uniformly distributed in the nucleus, and no chromatic dense ring was seen at nuclear periphery in every examined cell. By acridin orange-ethidium bromide approach, we emphasized apoptotic cells whose frequency increased in a concentration and time of treatment - dependent manner. The nuclear proteins were strongly acetylated in TSA presence. Conclusions. The increase in HeLa cells nuclei size is consistent with chromatin decondensation which is also preserved during the cell division phases. The presence of NOR in most of the cells suggests that ribosomal gene transcription is mostly active and that protein biosynthesis is not aff ected. The chromosome breaks might cause cell death by apoptosis. The overacetylation of nuclear proteins leads to the active state of chromatin which is also preserved during the cell division phases.

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Pharmacokinetic evaluation after percutaneous administration of some non steroidal antiinflamatory drug preparations using animal experiments

Ani-Simona Sevastre, Florica Popescu, Anca Berbecaru, O. Croitoru, Mihaela Baniceru
Abstract: Background and purpose The non-steroidal antiinflamatory drugs (NSAIDs) are used as elective medication in the therapy of various inflammatory diseases. Th is treatment ameliorates most of the clinical indices of inflammation, improving the exudative-congestive inflammatory process, without influencing the proliferative processes. They are used for the anti-inflammatory effect in the treatment of skin, joints and genital area located chronic inflammatory diseases. The aim of the study was to determine the plasma concentrations of some of the NSAIDs after single dose percutaneous administration in laboratory animals and to monitor their plasma concentrations within 24 hours. Experimental approach We used: male adult rabbits of 3 kg weight, 5% Diclac gel (HEXAL), Indometacin 4% cream (MARK PHARMACEUTICS), FINNIGAN - SURVEYOR liquid chromatograph (BDS - HYPERSIL C18 250X4,6 column, 5 micrometers particle size). For each NSAID, the experiment was simultaneously conducted on 5 rabbits. 24 hours before the experiment, the rabbits were kept fasting. During the experiment, they received water ad libitum. Each rabbit was weighed before the experiment. 24 hours before applying the investigated pharmaceutical formulas on the skin, the hair was removed on the dorsal area of 50 cm2, using a manual cutting mashine. 24 hours after the epilation, the control samples were collected (3 ml of blood). The collection was conducted from the marginal ear vein under the conditions of asepsie, using single use needles and syringes. 2 g of the NSAID pharmaceutical prepation was applied on a 50 cm2 area. The probes were collected at 1,2,3,6,12 and 24 h after the aplication. Each plasma sample was processed for chromatographic analysis. Samples were then analyzed using a FINNIGAN - SURVEYOR liquid chromatograph. During the procedures, the international rules concerning the experiments on laboratory animals were followed as recommended. Results In the fi rst 12 hours, both Diclofenac and Indometacin had a similar progressive increasing of the plasma concentration, which then gradually decreased and maintained up to 24 hours after the percutaneous appliacation. Conclusions and implications Our results support the idea that the topical administered diclofenac and indometacin achieved plasma levels similar to the oral administration plasma levels, but later. The systemic absorption of the topical applied substances emphasizes the possibility of appearance of the corresponding side effects.

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Mitotic index in clear cell odontogenic tumors

Sabina Zurac, P. J. Slootweg
Abstract: Clear cell (CC) variants of odontogenic tumors have bland morphology and may be diffi cult to diagnose especially in small biopsies. We address our study to mitotic index in benign and malignant odontogenic tumors as criterion for diff erential diagnosis. We reviewed 14 cases of odontogenic carcinomas (malignant group including 6 CC odontogenic carcinomas (CCOC), 6 ameloblastic carcinomas (AC) and 2 primary intraosseous squamous cell carcinoma (PISCC)) and 30 cases of ameloblastoma with clear cell component (benign group). We compared the mitotic index of the benign group versus the malignant group; the mitoses were counted in consecutive high power fi elds (hpfs) without necrosis or stromal deposition and the mitotic index was reported as number of mitoses per 10 hpfs. Th e statistical calculations were performed using EXCEL and EPIINFO programs. Th e mitotic index was lower in benign tumors (most benign cases had less than 20 mitoses / 10 hpfs) but almost half of the odontogenic carcinomas had similar mitotic count. Th ere is no statistical signifi cance of higher mitotic index in malignant tumors compared to benign ones (P = 0,057). Th ere was also a tendency towards higher number of mitoses in solid / multicystic ameloblastoma than in desmoplastic variant. Frank malignant tumors present strikingly numerous mitoses; otherwise, ordinary ameloblastomas may reveal an impressive number of mitoses, sometimes in such a proportion that the examiner could be induced to consider that certain tumor as being malignant. Unfortunately, in daily practice, the main problem is not represented by high mitotic index in ameloblastoma but by low mitotic index in CCOC. An odontogenic tumor with clear cells may present a reduced number of mitoses but the overall behavior (destruction of the cortical bone, invasion in the soft tissue or even metastases) may allow its classifi cation as malignant. When dealing with an individual case, mitotic index is not a reliable parameter for diff erentiating benign ameloblastomas from odontogenic carcinomas since many ameloblastomas may have an increased number of mitoses while CCOC may show a not very prominent mitotic activity.

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Comparative study on the efficienty of the inhibitors of the angiotensis conversion enzyme and receptor antagonists for angiotensin ii on the endothelial dysfunction in patients with essential arterial hypertension

Gabriela Cioca, Minerva Boitan, Ioan Manitiu, Radu Cojan, Liviu Safta, Radu Trambitas
Abstract: The endothelial function is a barometer of the health of the cardiovascular system, and its quantifi cation in patients suff ering from a cardiovascular disorder, particularly arterial hypertension, represents a useful method for the evaluation of cardiovascular risk, of the severity of the disease and a useful method for the quantifi cation of the eff ectiveness of several therapeutic strategies. We have performed a comparative clinical study, open, randomized, non-interventional on parallel groups of subjects with essential arterial hypertension degrees 1, 2 and 3 for the comparison of the effi ciency of the angiotensin II conversion enzyme inhibitors (IECA) and the receptor antagonists for angiotensin II (ARA) on the endothelial dysfunction evaluated through the fl ow-mediated vasodilatation (FMD). Comparing the average of the FMD increase after 12 months of treatment for the two treatments we concluded that there are no statistically signifi cant diff erences.

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Evaluation of hypoglycemic effect of some vegetal species on streptozotocin induced diabetes in rats

Anca Berbecaru-Iovan, G. D. Mogosanu, S. Berbecaru-Iovan, F. Gorunescu, Cristiana Iulia Dumitrescu, Florica Popescu
Abstract: Diabetes mellitus, the most common endocrine disorder, despite current therapies, has numerous and serious long term complications, leading to signifi cant morbidity and mortality. The traditional methods of treatment of diabetes should be further investigated. A multitude of vegetal remedies have been utilized for the treatment of diabetes throughout the world for many centuries. Phytotherapy offers a valuable opportunity to discover new natural compounds with benefi cial eff ects on glucose homeostasis, compounds that stimulate insulin biosynthesis and secretion or promote peripheral glucose uptake and utilization. The purpose of this study is to investigate the oral hypoglycemic eff ect of six vegetal products (Cynosbati fructus, Myrtilli folium, Myrtilli fructus, Phaseoli sine seminibus fructus, Trigonellae foenum-graeci semen, Violae tricoloris herba) in streptozotocin-induced diabetic rats. Some of these vegetal remedies are used in the treatment of diabetes mellitus, but for Cynosbati fructus and Violae tricoloris herba, so far, there is no certitude about the hypoglycemic action. This study indicates that the vegetal products used possess hypoglycemic eff ect, but they are smooth remedies and could offer solutions for the newly discovered patients who only need diet and exercise or as complementary treatment in diabetic patients after initiating pharmacological therapy.

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Abuse drugs between offence and consumption

C. Serban, M. Tudosie, R. Macovei, V. Negulescu, Zoie Ghiorghiu
Abstract: The analysis has focused on the judicial treatment applied to drugs and psychoactive substances according to the national and international conventions which regulate the fi eld under study. The analysis of the legislative premises were based on the study of the existent laws. The through and well - founded research of the multiple types and forms of legal and illegal drugs, of the legal and illegal drugs consumption and of the consequences of drugs consumption shows the necessity of preventing and fighting against drug traffic and illegal drugs consumption. Therefore, the eradication of the crimes connected to the circulation of psychoactive substances and narcotics must concern both the state organs and the whole society. Finaly, the study presents a retrospective statistical analysis of abuse drugs phenomenon, based on the hospitalized patients in ICU Toxicology between 1998 and 2008. The statistical data shows the alarming increase of abuse drug consumption every year, with the highest percentage of heroin. These data represent a quality indicator of the process.

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Health care costs 2008 Update and perspective on public health

D. Cosmescu, V.A. Voicu, A.O. Berea
Abstract: The article provides a quick review of the healthcare costs in Romania, for the 2004-2008 period, with a further interpretation of possible evolution of spenditure components. Although the funding of public healthcare system has been increased, the current economic and fi nancial context imposes a profound analysis of underlying mechanisms. The economic recession introduce supplementary pressure on healthcare providers by reduced fi nancing and increased number of uninsured and underinsured persons, imposing reforms and costs restructuring.

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Therapeutical Practice


Chronic cough in childhood - A clinical and therapeutic approach

Doina Plesca, Victoria Hurduc, Iulia Ioan, Anca Badarau
Abstract: The article is divided of two parts. In the first part, the authors discuss about the chronic cough, a subject of a great interest in pediatric practice. Physiopathology, the most important etiologic categories, clinical and paraclinical data, principles of therapy of chronic cough are reviewed. The authors underline the importance of the history of the disease, in establishing the cause of chronic cough in children. A cough that worsens at night may be caused by sinusitis, asthma, or gastroesophageal refl ux. The cough that disappears during sleep, suggests a psychogenic cause. Clinical examination has to be thorough, complete and repeated, focused on ENT segment, chest, respiratory and cardio-vascular system. When clinical data and history cannot establish the cause of chronic cough, paraclinical evaluation is necessary. Any child with chronic cough, no matter the age, must have chest X-Ray examination to eliminate aspiration of foreign body or another severe disease (congenital anomaly, cystic fi brosis, bronchiectasis, cardiomegaly, mediastinal mass). In the second part, the authors present the main clinical entities (cough variant asthma and eosinophilic bronchitis, cough during and after respiratory infections, allergic rhinitis, chronic sinusitis and rhinoadenoiditis, passive smoking, gastroesophageal refl ux, bronchiectasis, aspiration syndrome / foreign body aspiration, deglutition diffi culties, vocal cords dysfunction, compression syndrome, psychogenic cough, otogenic causes - Arnold ear - cough reflex, cough as a side effect of the medication) and the etiologic treatment. The indications of an etiologic treatment have to be infl uenced by a detailed history of the disease and by clinical examination. In the absence of an etiologic factor, the patient will receive symptomatic treatment only if the cough is responsible for awakeness, vomiting and fatigue. Tolerability of cough is the element that determines the indications for inhibitors of cough.

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promising results with rituximab in a case of severe systemic arthritis juvenile idiopathic arthritis refractory to multiple drugs

N. Iagaru, A.V. Cochino
Abstract: Background. Systemic arthritis belongs to a heterogeneous group of pediatric rheumatic diseases known as juvenile idiopathic arthritis (JIA). Th is subtype is defi ned by extraarticular signs which, even today, lead to diagnosis without specifi c lab tests. Patients with systemic arthritis (sJIA) also have a range of other prominent features, including elevation of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), leukocytosis with high neutrophil counts and thrombocytosis. Ferritin concentrations are high and correlate with systemic disease activity. Systemic arthritis is often extraordinarily resistant to treatment with steroids, methotrexate, etanercept, etc. We will present one such case, with persistent evolution refractory to multiple conventional and biological remissive drugs

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Aminoglycoside induced destruction of the cochlea

VR. Moroti Constantinescu, M. Georgescu, E. Kovacs, A. Hristea, V. Arama, A. Pascu
Abstract: The inner ear houses the hearing organ of Corti (inner and outer hair cells), where the sound pressure is transduced to electrical energy. The inner and outer hair cells both play active roles in this transduction. Drugs ototoxicity is defi ned as functional and/or anatomical impairment of the inner ear caused by certain therapeutic agents. Aminoglycosides are widely prescribed despite their toxicity, because of their availability, good spectrum and low cost. These antibiotics cause hearing loss, starting with high frequencies and progressing toward conversational frequencies (0.5-2 kHz), by destroying the acoustic hair cells in the inner ear. The hearing loss is often irreversible and bilateral. In neonates, aminoglycoside ototoxicity is more severe, causing profound bilateral hearing loss (all frequencies are aff ected) which will impede language development. The management of cochlear toxicity entails monitoring, appropriate schedules of therapy, association of presumed protectors and in extremis referral to the ENT specialists for cochlear implant.

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Tuberculous meningoencephalitis in immunocompetent child

Simona Claudia Cambrea, Claudia Nina Rugina, Clementina Urjan, E. Vasiliu, S. Rugina
Abstract: Tuberculous involvement of the central nervous system (CNS) is an important and serious type of extra-pulmonary involvement. It has been estimated that approximately 10% of all patients with TB have CNS involvement. The incidence of CNS tuberculosis is directly proportional to the prevalence of tuberculous infection in general. In developing countries CNS tuberculosis is a disease of younger age group, usually childhood. The high morbidity and mortality of tuberculous meningoencephalitis (TBM) warrants an early diagnosis and treatment. In Constanta County in the fi rst 3 months of the year 2007 we noticed the presence of 5 cases of TBM in children with ages ranging from 6 months to 6 years. In Romania BCG vaccine is mandatory and it has been proven to reduce the incidence of severe disseminated disease in children. In this context we report a case of TB meningoencephalitis (TBM), in a 2 years and 3 months old metiss child without BCG vaccine. We analyze the aspect of cerebrospinal fl uids, electroencephalography (EEG), infl ammatory blood tests and cerebral MRI examination. Diagnosis of TBM was delayed in this case. In the fi rst month of treatment the child presented a toxic hepatitis due to antituberculosis treatment. Hydrocephaly was present at the onset of the disease. In evolution, we noticed transient decrease of visual acuity, cranial nerve paralysis, and severe motor defi cit.

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Colorectal adenosquamous carcinoma

Florica Staniceanu, Liana Tudorica, Sabina Zurac, Gianina Micu, Eliza Gramada, Alexandra Bastian, Cristiana Popp, Luciana Nichita, Al. Croitoru
Abstract: Adenosquamous carcinoma (AdSqCa) is a rare aggressive subtype of colorectal carcinoma with interesting issues concerning histogenesis, prognosis and appropriate management. We analyzed 9 cases of colonic AdSqCa diagnosed in our department in the last 4 years from a total of 330 cases of colonic epithelial malignancies. Histological features were reviewed and histochemical and immunohistochemical studies were performed in order to highlight specifi c characteristics of the tumors. The gross appearance of carcinomas varied within large limits but all of them showed the same rectosigmoidian location. Most of the cases had high grade of anaplasia as well as other histopathological signs of tumoral aggressiveness: ulceration, necrosis, perivascular and perineural invasion, tumoral emboli, extension to the entire colonic wall. Moreover, 3 patients presented advanced stage disease - either regional lymph node or liver metastasis. The cytonuclear pleomorphism was more pronounced and the proliferation indexes were higher in the squamous component than in the pure adenocarcinomatous counterpart. Its high biological aggressiveness should draw attention to the importance of correct diagnosis of these rare colonic neoplasms. We report our experience regarding an increased incidence and exclusive rectosigmoidian location of AdSqCa, singular features of this type of tumor identifi ed in medical literature. Moreover, the overall histopathological appearance and the immunohistochemical phenotype of the analyzed cases sustain the hypothesis of squamous metaplasia of the glandular adenomatous epithelium with subsequent malignant transformation as possible mechanism of AdSqCa histogenesis.

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Actual data regarding rosuvastatin therapy

Lavinia Codruta Gligor, Serban Gligor, Virginia Gligor
Abstract: Statins have an important role in stabilizing atherom plaque, in endothelial function improve and also has anti-infl ammatory properties. Th e last inserted market statin is rosuvastatin calcium (Crestor). Th is is a synthetic statin wich has similar action mechanism like other statins, being a competitive inhibitor of the HMG-CoA reductase. Compared with other statins, rosuvastatin, besides the main eff ect of decreasing LDLC, has tended to increase more than HDLC. Increase HDLC, like apolipoprotein A1 (apo A1) is probably mediated by decreasing cholesteryl ester transfer protein (CETP) activity, with a benefi cial eff ect on cardiovascular morbidity and mortality. In addition, rosuvastatin can signifi cantly decrease plasma triacylglycerol through its action on lipoproteins rich in this substance, having benefi cial eff ects in preventing atherosclerosis in diabetes type 2 patients. Treatment with 10 mg rosuvastatin has a greater eff ect of decreasing total cholesterol and LDLC and increasing adiponectin levels than atorvastatin. In addiction, it has a better eff ect of decreasing vascular biomarkers (hs-CRP, MMP 9, TNF- á, PAI 1, ET 1, tPA). A recent trial has shown a benefi cial eff ect of rosuvastatin 20 mg lowering LDLC, triglycerides and total apoB, along with a decrease of large and small particles of VLDL (VLDL1 and VLDL2) and IDL particles. Th is was achieved by signifi cantly increasing the catabolism of LDL-apoB, VLDL1-apoB, VLDL2-apoB, IDL-apoB and VLDL1-apoB production rate decrease. Also, it seems that rosuvastatin apparently acting modulating LDL size and subclass, in patients with increased risk of cardiovascular events. METEOR trial showed that maximum dose (40 mg/dL) rosuvastatin has signifi cantly slowed carotid intima media thickness, with a simultaneous reduction of cardiovascular events. Th is decrease was observed in middle-aged patients, with low Framingham score, low risk of coronary disease and evidence of subclinical atherosclerosis.

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The value of ultrasound and upper digestive endoscopy for the follow up of propranolol therapy in patients with portal hypertension in liver cirrhosis

Cristiana Iulia Dumitrescu, S.M. Cazacu, Daniela Dumitrescu, Anca Iovan Berbecaru, Florica Popescu
Abstract: Portal hypertension is characterized by increased portal pressure above 12 mm Hg. 2/3 of the patients also have esophageal varices and over 50% have a variceal bleeding during their life. Treatment with unselective beta-blockers had a great potential for lowering the risk of bleeding and mortality. Noninvasive techniques (transabdominal ultrasound including Doppler, upper digestive endoscopy, endoscopic ultrasound) may be used for the assessment of portal pressure. Material and method. We analyzed 52 patients with liver cirrhosis, Child A and B score, treated by internal medicine or gastroenterology specialty physicians between August 2007 and August 2008. Th e patients were treated with Propranolol for the reduction of portal pressure, the usual dosage was 80 mg/day. Results and discussions. After Propranolol therapy the hepatic blood fl ow had remained hepatofugal. After treatment we noted a reduction in the diameter of the portal vein by 2 mm, in the diameter of the splenic vein by 1 mm and in the diameter of the mesenteric vein by 2 mm. Th e median velocity of the portal blood fl ow was increased by 1 cm/ sec. Th e repermeabilisation of the umbilical vein was unchanged. We noted a reduction of the diameter of the esophageal varices between 10-32%. Secondary eff ects appeared in 49,9%, but were minor. Most of those eff ects disappeared after dose reduction. Th e thrombocyte count was seldom below 140000/mm3, values not associated with high risk on uncontrolled bleeding. Conclusions. Th e use of beta-blockers imposes a good compliance of the patients during treatment. Propranolol signifi cantly reduces variceal volume and pressure, fact associated with lower risk of ascites.

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