Category Archives: AMM 2011, Volume 57, Number 2

New Perspectives: Quinolones as Complexation Agents

Rusu Aura, Gyéresi Á., Hancu G.

University of Medicine and Pharmacy Târgu Mureş, Faculty of Pharmacy, Department of Pharmaceutical Chemistry

Background: Quinolones are synthetic antibacterial agents, with a 4-oxo-1,4-dihydroquinolinic structure, which is based on the nalidixic acid model. The 4-oxo and 3-carboxyl groups confer quinolones excellent chelatation properties with metallic ions.
Aim: To highlight a few theories regarding the complexation phenomenon of quinolones.
Methods: Complexes with metallic ions have been characterized (stoichiometry, in vitro physical-chemicals properties, stability studies, and behavioral studies in different biological mediums).
Results: New availabilities have been identified: bioavailability of the complexed quinolones and formulation of new pharmaceutical products with a superior bioavailability and therapeutic effect; the antimicrobial activity of quinolone complexes; quinolone complexes as antitumor drugs with the aim of obtaining less toxic compounds; understanding the mechanism of action of quinolones, which is a challenge especially regarding their selectivity at the bacterial DNA level; development of new determination methods, based on the complexation of quinolones with metallic ions.
Conclusions: The 21st century may provide new useful therapeutic aspects on the basis of complexation between quinolones and metals.

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Erythrodermia Associated to Lung Cancer

Simu Lia-Maria1, Morariu S.H.1, Turcu M.2, Podeanu Maria-Daniela3, Şincu Nina4, Marian D.5

1 Department of Dermatology and Venereology, University of Medicine and Pharmacy Tg. Mureş
2 Department of Pathology, University of Medicine and Pharmacy Tg. Mureş
3 Department of Radiology and Imaging, University of Medicine and Pharmacy Tg. Mureş
4 Department of Infectious Diseases, University of Medicine and Pharmacy Tg. Mureş
5 Department of Surgery, University of Medicine and Pharmacy Tg. Mureş

There are a few skin lesions which are conected with internal malignancies, being important especially if they appear prior to neoplasia.
We are presenting the case of a patient who had desquamative erythrodermia associated to lung carcinoma. The patient was also diagnosed with a cerebral metastasis. The appearance of skin lesions suggested the presence of a subacute immune vasculitis, this was confirmed by immunohystochemical examinations, which revealed a leukocytoclastic vasculitis. Given the fact that previous erythematous lesions improved during the treatment of cerebral metastasis, the reccurence of erythrodermia suggests the evolution of metastasis. On the other hand, we can not rule out the possible role of the received chemotherapy in the development of the vasculitic process. The observation that these events do not occur in all cancer patients leads to the conclusion that the triggering mechanisms responsible for these paraneoplastic syndromes are individually conditioned.

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T-cell/Histiocyte-rich B-cell Lymphoma

Turcu M.1, Horvath Emoke2, Chira Liliana3, Cotoi O.S.4

1 Department of Pathology, University of Medicine and Pharmacy, Department of Pathology, Emergency County Hospital, Targu-Mures
2 Department of Pathology, University of Medicine and Pharmacy, Department of Pathology, Emergency County Hospital, Targu-Mures
3 Department of Pathology, University of Medicine and Pharmacy, Department of Pathology, Emergency County Hospital, Targu-Mures
4 Department of Cellular and Molecular Biology, University of Medicine and Pharmacy, Department of Pathology, Emergency County Hospital, Targu-Mures

Background: T-cell/histiocyterich B-cell lymphoma (T/HRBCL) is an uncommon morphologic variant of diffuse large B-cell lymphoma (DLBCL), representing less than 10% of all DLBCL cases. T/HRBCL has attracted considerable attention as a result of the difficult task of distinguishing it from similar entities, such as nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), classic Hodgkin lymphoma and peripheral T/cell lymphoma, nonspecific.
Case report: We present the case of a 70-year-old female patient addressing her primary care physician for headaches, nausea and a large, painful tumor in her left axilla. The paraclinical examinations revealed minimal deviations of hematological tests, but showed elevated LDH values. Surgery was performed and a specimen, composed of 13 lymph nodes, (the largest one having the surface diameter of 130 mm) was removed and examined histologically. On microscopic evaluation, the HE stain showed portions of lymph node completely effaced and replaced by a vaguely nodular lymphoid proliferation composed of scattered, large cells, with abundant cytoplasm, multilobated vesicular nuclei and proeminent nucleoli, consistent with lymphocytes and histiocytes. The immunohistochemical study proved the proliferative mass to be constituted of a limited number of large, CD20 positive B-cells, with proeminent nucleolus, in a background of CD3 positive T-cells, together with a variable number of histiocytes, highlighted with CD68. The large B-cells were scattered and did not form any clusters or strips. A diagnosis of T/HRBCL was made.
Conclusion: T/HRBCL is a rare variant of DLBCL, with an aggressive clinical outcome. In such cases immunohistochemical analyses are mandatory to reach correct diagnosis.

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The Detection of Premalignant and Malignant Gastric Lesions by Conventional Endoscopy in a General Population Sample

Boeriu Alina1, Dobru Daniela1, Pascarenco Ofelia2, Mocan Simona3

1 Department of Gastroenterology, University of Medicine and Pharmacy Targu Mures
2 Department of Gastroenterology, Targu Mures County Hospital
3 Department of Pathology, Targu Mures County Emergency Hospital

Background and Aims: The identification of patients with premalignant lesions and endoscopic surveillance could improve the early detection of gastric cancer, with better therapy and prognosis. We performed conventional endoscopy with biopsies to identify the incidence rates of premalignant and malignant gastric lesions and the risk of patients for this pathology.
Methods: A total of 1651 patients were investigated with conventional endoscopy. We took biopsies from 1493 patients. Biopsy specimens were analyzed for gastric inflammation, atrophy, intestinal metaplasia, dysplasia and neoplasia.
Results: We demonstrated that major symptoms had a sensitivity of 95.2%, and a specificity of 54.5% for the detection of gastric neoplasia, with a sensitivity of 61.6% and a specificity of 57.2% for the detection of premalignant lesions. We showed the risk of patients over 45 years, with major or minor symptoms, for premalignant and malignant gastric lesions (p < 0.001; RR = 3.34; 95%CI: 2.41–4.61). We emphasized the importance of histological evaluation by biopsies of entire gastric mucosa in case of polyps, ulcers, gastric atrophy detection or remnant stomach, for the evaluation of premalignant lesions (p < 0.,05). We showed that the prevalence of premalignant lesions increased with age and the presence of Hp infection. We demonstrated the risk of the inflammation in the gastric body for premalignant lesions.
Conclusions: The patient’s symptoms were not predictive of endoscopic and histologic findings. Not only symptoms, but also the age, the presence of Helicobacter pylori infection, the histological detection of the extent and location of gastric inflammation and premalignant lesions define the risk for the dyspeptic patients.

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Bacteriological Study of Urinary Stones

Tudor Bianca1, Toma Felicia1, Boja R.2, Oşan V.2, Cigir Teodora3, Szavuj J.1, Man A.1

1 Discipline of Microbiology, University of Medicine and Pharmacy Tîrgu Mureş
2 Discipline of Urology, University of Medicine and Pharmacy Tîrgu Mureş
3 Laboratory, Mures County Clinical Emergency Hospital, Tîrgu Mureş

Background: Despite modern antibiotic therapy and technological advances in lithotripsy, the presence of infection in patients with urinary stones, as well as with infectious stones is still a significant cause of morbidity and mortality. Recent findings lend more theories as to how infection leads to stone formation.
Aim: The bacteriological study of urine and stone samples from patients with urinary tract infections (UTI) and the correlation of the bacteriological analysis results of stones and urine culture.
Method: We enrolled patients admitted to the urology department of Mures Emergency Hospital, from December 2008 to March 2009; all 50 patients who were diagnosed by the urologist as having urinary stones were included in this study. Bacteriological study was conducted on pre-operative urine and operated renal stones. Pre-operative urine sam¬ples were collected aseptically for macroscopic and micro¬scopic examination. Both pre-operative urine and operated renal stones were processed for bacteriological culture. The isolated microorganisms were identified by standard techniques.
Results: From the 50 patients included in this study, 20 had both infected stones and UTI. While correlating the results of bacteriologi¬cal analysis of stones and urine culture, the same microorganisms from urine culture and stone culture were isolated in 12 (60%) out of 20 cases, but different microorganisms in 8 (40%). The bacteriological study of urine and stone samples revealed that the most common pathogens were E.coli, Pseudomonas aeruginosa.
Conclusion: The incidence of infectious urinary stones in patients with UTI was higher than in the sterile ones. The preponderant identified microorganisms were E. coli, followed by Pseudomonas aeruginosa. In more than half of the cases, the same microorganisms were found both in UTI and within the urinary stones.

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Evaluation of Pulmonary Vasodilator Therapy with Endothelin-Receptor Antagonist in Eisenmenger Syndrome

Togănel Rodica1, Făgărăşan Amalia1, Muntean Iolanda1, Şuteu Carmen2, Blesneac Cristina3,
Sglimbea Anca1, Gozar Liliana2, Paşc Sorina2, Koncsag-Szasz E.3

1 University of Medicine and Pharmacy Tg. Mures, Department of Paediatric IIIrd
2 Pediatric Cardiology Department, Institute of Cardiovascular Disease and Transplant Tg. Mureş
3 County Emergency Clinic Hospital Tg. Mureş

Objective: To assess the effect of treatment with endothelin-receptor anatagonists on patients with Eisenmenger syndrome, by monitoring oxygen saturation, exercise capacity and echocardiography.
Methods: A total of 14 pediatric patients diagnosed with Eisenmenger syndrome were evaluated clinically by systemic pulse-oximetry, 6-minute walk test and by echocardiography at the beginning of pulmonary vasodilator treatment with endothelin-receptor antagonist, at 3 and 6 months after treatment initiation.
Results: NYHA functional class, systemic arterial blood saturation and distance walked in 6 minutes improved after 3 and 6 months of pulmonary vasodilator treatment. In our study we observed that Tei index right ventricle has improved after 3 months of therapy. We found no statistically significant changes in other ecocardiographic parameters of pulmonary hypertension evaluation.
Conclusions: Endothelin-receptor antagonist improved exercise capacity and hemodynamics, without compromising peripheral oxygen saturation.
Study perfomed in the research project MAMI no. 41-042/2007, financed by the Roumanian Ministry of Education, Research and Youth

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Rheological Behavior of Sodium Valproate Suppositories

Tăurean Alexandrina1, Ciurba Adriana2, Todoran Nicoleta2, Bumb Doina3, Cazacincu R.4

1 Clinical County Hospital Mureş, Pharmacy number 3, Tg. Mureş, Romania
2 Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Medicine and Pharmacy Tg. Mureş, Romania
3 Regional Center of Public Health, Tg. Mureş, Romania
4 Department of Pharmaceutical Industry, Faculty of Pharmacy, University of Medicine and Pharmacy “Ovidius”, Constanţa, Romania

Background: Because the valproic derivates are frequently used in the treatment of epilepsy, bipolar disorders, major depression cases, migraines and other neurological disorders at children, the rectal administration is a real advantage.
Aim: In this study we aimed to assess the influence of the formulation on the rheological characteristics of lipophilic suppository bases Suppocire NAI, Witepsol W35, Massa Estarinum299, Lipex403, containing Cetyl alcohol and Solutol HS15, respectively.
Methods: Spreadability was determined by the Pozo Ojeda-Sune Arbussa method. Half a gram suppository was placed on the bottom plaque of the extensiometer, and the upper plaque was added over it. After equal intervals of time (1 minute) different weights (2, 5, 10, 20, 30, 40, 50, 100, 150, 200, 250, 300, 350, 400, 500 g) were placed. Following each weight addition, the diameters of the obtained circles were measured, and the corresponding area was calculated. The viscosity was determined using the Brookfield (DV-II +Pro) rotational viscosimeter. The measurements were performed at 37±0.5°C and 5, 10, 20, 50, 100, 50, 20, 10, 5 rpm.
Results: The experimental results demonstrated that sodium valproate as active substance induces an increase in viscosity and consequently a decrease in the spreading capacity of the lipophilic suppository bases used. Lipex403 (a base consisting in fatty acids) manifests the lowest viscosity compared to the bases consisting in mixtures of glycerides (Suppocire NAI, Witepsol W35, Massa Estarinum 299). Solutol HS15 as emulsifier determines a higher decrease in viscosities and a better spreading capacity than Cetyl alcohol. Sodium valproate suppositories obtained with Lipex403 as excipient base show plastic flow characteristics without thixotropy.
Conclusions: The experimental results demonstrated that sodium valproate as active substance induces an increase in viscosity and consequently a decrease in the spreading capacity of the lipophilic suppository bases used. Solutol HS15 determines a higher decrease in viscosities and a better spreading capacity than Cetyl alcohol.

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Syndactyly as Symptome or Part of Plurimalformative Syndrome in Pediatric Patology. Clinical and Therapeutical Considerations

Szilveszter Mónika¹, Albean M.2, Pap Z.3

1 Sfantu Gheorhe County Hospital
2 Pediatric University Hospital,Braşov
3 Second Pediatric Clinic, Faculty of Medicine, UMPh Targu Mures

Background: Syndactyly is the most common congenital malformation of the limbs. Syndactyly can be classified as simple when it involves soft tissues only and classified as complex when it involves the bone or nail of adjacent fingers. Syndactyly can occur as isolated condition or in conjuction with other symptoms as one aspect of a multi-symptom disease.
Aim: The author’s purpose is to present this condition in hospitalized patients in order to make some considerations about the frequency of association with other anomalies and the treatment of this condition.
Material and methods: Between 2000–2009, 83 cases of hand malformations were diagnosed and treated at Plastic Surgical Department of Children Hospital Brasov and Fogolyan Kristof Hospital Sfantu Gheorghe. Observational retrospective study on this group found that 39 of these were syndactyly and 44 polidactyly (control group).
Results: We have found 2 cases of sinpolidactyly and 12 cases of plurimalformation. The Apgar score as well the birth weight of children with plurimalformations were lower than of those with simple syndactyly (p = 0.0153). The average age of surgical intervention was 3.370 years (SD = 4.267, p = 0.0001). The hand malformation was bilateral in 26 cases. Out of the 39 cases of syndactyly, 17 needed full-thickness skin graft.
Conclusions: The goal of syndactyly release is to create a functional hand with the fewest surgical procedures while mimimizing complication. Reconstruction of the web commisure is the most technically challenging part of the operation, followed by separation of the remaining digits.

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Characterization and Molecular Modelling of Cyclodextrin/Fluoroquinolone Inclusion Complexes

Székely-Szentmiklósi Blanka1, Tőkés B.2

1 Gedeon Richter Romania S.A., Târgu Mureş
2 Department of Physical-Chemistry, University of Medicine and Pharmacy, Târgu Mureş

Background: Cyclodextrins are widely used as complexing agents to increase the solubility of poorly water-soluble drugs, to improve their bioavailability and stability, to reduce or prevent gastrointestinal or ocular irritation, to reduce or eliminate unpleasant smells or tastes and to prevent drug-drug or drug-additive interactions. In recent years, cyclodextrins have been proven to be effective as host compounds in molecular recognition and chiral separation.
Aim: To evaluate the complexation role of cyclodextrins toward fluoroquinolones (FQ) in an attempt to assess their potential as new formulation additives for more efficient fluoroquinolone delivery and as chiral selectors in case of racemic mixture compounds.
Material and methods: Guest-host interactions of three second generation quinolones, ciprofloxacin, ofloxacin and norfloxacin with two parent cyclodextrins, beta-cyclodextrin (b-CD), gamma-cyclodextrin (g-CD) and a beta-cyclodextrin derivative, 2-hydroxypropyl beta-cyclodextrin (HP-b -CD), were tested. Computer aided molecular modelling (ChemBio3D Ultra 12.0) was utilized to predict the preferred orientation of fluoroquinolones in the cyclodextrin cavity and the main structural features responsible for the enhancement of their solubility and photostability. Ciprofloxacin/b-cyclodextrin complex was prepared and the formation of inclusion complex was
demostrated by IR spectroscopy.
Results: Our studies show that the orientation with the piperazinyl group included in the CD cavity is energetically more favorable.
Conclusions: The CDs act as complexing agents with the three FQ derivatives, which enter inside the CD torus, and interact with the hydroxyl groups of CD by Van der Waals, electrostatic forces ang hydrogen bonding. Our results suggest the 1:1 stoichiometry in the complex formation.

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Surgical Strategies in the Differentiated Cancers of the Thyroid

Sala Daniela1, Copotoiu C.2, Borda Angela3,5, Bancu Ş.1, Neagoe R.1, Popescu G.1, Cătană Ramona4,
Boilă Adela5

1 Discipline of Surgery I, Clinic of Surgery I, Faculty of Medicine, University of Medicine and Pharmacy, Targu-Mures
2 Discipline of Surgery I, Clinic of Surgery II, Faculty of Medicine, University of Medicine and Pharmacy, Targu-Mures
3,5 Discipline of Histology, Faculty of Medicine, University of Medicine and Pharmacy, Targu-Mures
4 Discipline of Endocrinology, Clinic of Endocrinology, Faculty of Medicine, University of Medicine and Pharmacy, Targu-Mures
5 Discipline of Pathology, Department of Pathology, Faculty of Medicine, University of Medicine and Pharmacy, Targu-Mures

Introduction: Amongst all epithelial cancers of the thyroid, the papillary and folicular types are usually histologically differentiated and have a more favourable outcome compared to the undifferentiated tumours. The aim of our study is to evaluate the surgical treatment of differentiated thyroid neoplasms both in terms of surgical indication and type of surgery.
Material and method: The study was conducted on 1349 patients suffering from different thyroid diseases that requested surgery between 2005–2009, within the First and Second Department of Surgery Tg-Mures.
Result: There have been taken into account data regarding the demographic aspecs, the pre- and postoperative diagnosis, surgical indication and the type of surgical procedure according to the histological type.
Conclusions: Surgery has proven to be the most efficient therapy in the differentiated forms of thyroid cancer including different types of total/near-totally thyroidectomies, and partial thyroidectomy comes into question only in exceptional cases.

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