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Volume XV, Number 4, 2011 - Therapeutics Pharmacology and Clinical Toxicology


Disease modifying pharmacological approach of Multiple Sclerosis. A focus on glatiramer acetate

Vacaras V., Major Z. Z., Buzoianu Anca Dana
Abstract: 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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Oxidative stress and antioxidant theraphy in intracerebral hemorrhage

Papacocea T., Papacocea R., Badarau A., Ion A.D., Buraga I., Gaman L., Papacocea A
Abstract: Intracerebral hemorrhage (ICH) represents the most lethal form of stroke and has deleterious conequences. Primary injuries are generated by the blood collection itself and consist in local tissue destruction. They are prolonged and amplified by a combination of secondary injuries involving the toxic effects of blood, oxidative stress, recruitment of activated microglia/macrophages and neutrophils and excitotoxicity. Brain tissue is particulary vulnerable oxidative attack due to its rich content in polyunsaturated fatty acids which favors lipid peroxidation. Different from other tissues, brain presents only reduced amounts of antioxidant enzymes - catalase (CAT), glutation peroxidase (GPX) and superoxid dismutase ( SOD) and their activity decreases with age. It also contains elevated amounts of non-heme iron. The study of neuroprotection in ICH use as targets pathological processes like oxidative stress, inflammation, cerebral edema. In this context, the role for oxidative stress in and potential antioxidant therapies were analysed.

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Original Papers

The relevance of dissolution testing for trimetazidine

Mourad Ali, Miron Dalia Simona, Lupuleasa Dumitru, Budura Emma Adriana, Voicu A. Victor
Abstract: The paper describes the applicability of in-vitro in-vivo correlations previously developed for modified-release formulations of trimetazidine dihydrochloride (35 mg) to the immediate release products (20 mg). The dissolution profiles obtained in three different media were used for prediction of the invivo pharmacokinetic profiles, after oral administration as single dose. The accuracy of prediction were analyzed by comparison of estimated versus experimental values of peak and global exposure. Although water is far from being a biorelevant media, the integration of the corresponding in-vitro drug release profiles resulted in the most adequate prediction of peak exposure for this particular, high solubility, high permeability drug.

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In Situ Modifications of NADH2-cytochrome-C-reductase and lactate dehydrogenase in liver

Draghia F., Draghia Alina, Paunescu H., Coman L., Gaiu Irina, Badarau Anca
Abstract: The present study tried to determine the variations in the enzymatic, oxidoreductive and aerobic activity of the NADH2 -cytochrome-C-reductase (diaphoresis) by histochemical methods, in comparison to that of the glycolic anaerobic enzyme (lactate dehydrogenase), using an experimental model of poisoning with carbon tetrachloride (CCl4) in rats. The liver was investigated at 24 hours after poisoning. Two standardized histochemical techniques were used. Intensity of reaction, the parameter used, was determined by qualitative evaluation of color, as visualized with optical microscope. The diaphorase presented an intense and very intense decrease of reaction in vascular endothelia and in hepatocytes .In hepatocytes, the decrease of the enzymatic, oxidative and aerobic activity appeared especially in the pericentrolobular area. The intensity of reaction was unequal in middle area of the lobular cells and maintained its intensity in the periportal biliary hepatocytes. The lactate dehydrogenase presented different changes from a liver lobule to another, either by highly diminishing of reaction in the hepatocytes of the entire lobule, or by diminishing of reaction unequal from a hepatocyte to another in the same lobule. In some liver lobules appeared modifications in the metabolism of the hepatic lobule for both of the studied oxidative enzymes. It was more obvious for the lactate dehydrogenase. There were also noticed some structural modifications, with cellular necrosis and/or numerous lipid drops in the cytoplasm. The observations and the results of the experimental intoxication emphasize the noxious consequences which some pesticides will have on the organism, expressed on the liver in the present study.

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Exogenous atypical opioid peptides inhibit hyperalgesia associated with carrageenan peripheral inflammation

Jaba Irina M., Tamba B., Albu Elena, Leon Magdalena, Mungiu O. C.
Abstract: Studies examining the role of the endogenous opioid system in modulating edema and hyperalgesia in animal models of inflammatory pain are contradictory. The present study investigates whether exogenous atypical opioid peptides contribute to the modulation of localized inflammatory nociception. Inflammation was induced by intraplantar injection of carrageenan into the right hindpaw. Mechanical and thermal thresholds were determined respectively in order to determine the potential of the tested peptides in inhibiting hyperalgesia during inflammation. The evolution of the edema was monitored using a plethysmometer. Delta opioid agonist ([D-Ala2]deltorphin II) and miu opioid agonist 1-3 beta casomorphin were administered peripherally into the right hind paw. The exogenous opioid peptides tested induced a signifficant antihyperalgesic effect. The peptides were antihyperalgesic without significantly affecting edema, indicating that peripheral opioid receptors are not involved in edema formation due to acute inflammation. These results demonstrate the peripheral analgesic potential of atypical opioid peptides such as casomorphins and deltorphins. The differential effects of on mechanical versus thermal thresholds support the notion that distinct neuroanatomical or neurochemical mechanisms modulate the processing of thermal versus mechanical stimuli.

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Methods for monitoring mitochondrial toxicity of nucleoside-analogue reverse-transcriptase inhibitors in HIV patients during antiretroviral therapy

Tiliscan Catalin, Arama Victoria, Mihailescu Raluca, Streinu-Cercel Adrian, Ion Daniela, Arama Stefan Sorin
Abstract: Various side effects have been associated to HIV antiretroviral therapy (ART) containing nucleoside reverse transcriptase inhibitors (NRTIs) as a result of mitochondrial toxicity. Mitochondrial DNA (mtDNA) depletion has important clinical consequences: lipodystrophy, hepatic toxicity, lactic acidosis, myopathy and polyneuropathy. Several methods have been developed in recent years in order to prevent the clinical and biological side effects during NRTIs treatment. These methods aim to predict the metabolic risk using non invasive tools. The present study aims to evaluate the current laboratory methods for mitochondrial toxicity and to assess their utility for monitoring ART toxicity.

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Peri-prosthetic Joint Infection - a diagnostic and treatment hospital analysis

Cismasiu R.S., Vasile Laura2
Abstract: Peri-prosthetic joint infection (PJI) is a major and severe complication after joint replacement. Although it occurs in a small percentage (1-3%) of patients undertaking arthroplasty it results in substantial morbidity and a decline of the final functional outcome. Therefore, deep peri-prosthetic joint infections lead to a significant both clinic, but also economic burden regarding diagnosis and treatment. Paper goal. The aim of the present article is to retrospectively analyse and evaluate the rate, diagnosis procedures and treatment management and results of the peri-prosthetic joint infections (PJI) in our hospital. Material and method. Between 2007 and 2010, in the Clinical Hospital of Orthopaedics and Traumatology -Foisor-, we identified a total of 96 peri-prostetic joint infection (PJI) episodes in 89 patients. We analysed the cases from diagnostic and treatment management point of view and withdraw conclusions reported to the actual peri-prosthetic joint infection (PJI) guideline. Results. The overall prevalence rate of peri-prosthetic joint infection (PJI) after THR and TKR together was 2.87%, but however higher in TKR (3.30%) than in THR (2.70%). The diagnostic protocol led to a specific antibiogram in 90% of the cases. Except early infections cases, the treatment attitude was -two-stage- revision for late, haematogenous or intraoperative infection, with a success rate of 87.50%. Conclusions. The -two stage- exchange revision arthroplasty seems to be a successful procedure in the treatment of peri-prosthetic joint infection (PJI) and therefore we recommend this surgical attitude in similar cases of infection. As final remark, early recognition and proper management of these infections is important, not only from a medico-legal standpoint, but also from the significant implications of this pathologic entity upon public health and economic costs.

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The influence of the cannabinoid and opioid antagonists on the sedative effect of the diethylamine

Segarceanu Ana, Fulga I.
Abstract: iethylamine is an analgesic substance with unknown mechanism of action but due to its chemical structure resemblance with anandamide, one hypothesis suggested that diethylamine could act as an endocannabinoid precursor. The aim of this study is the experimental research of the sedative effect of diethylamine and the influence of cannabinoid and opioid antagonists on the diethylamine-induced sedation. Albino mice were used for the experiments and the tested substances were diethylamine, a selective CB1 cannabinoid receptor antagonist - AM281 and an opioid antagonist - naloxone. The control groups received saline solution. The sedative effect was investigated through the simple exploration test at 60 or 120 minutes after the administration of the substances. The statistical analysis was performed using ANOVA test followed by post-hoc tests. The results showed that diethylamine has a dose and time dependent sedative effect. The diethylamine-induced sedation has not been reversed by cannabinoid or opioid antagonists at the administered doses, indicating that the cannabinoid and opioid receptors are not responsible for the sedative effect of diethylamine.

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Therapeutical Practice

Evaluation of the mood-stabilizers associated neurocognitive effects in bipolar patients

Vasile D., Vasiliu O., Mangalagiu A. G., Ojog Diana Gabriela
Abstract: Cognitive impairments in domains like attention, verbal memory, verbal learning and executive function are now considered a feature of bipolar disorder, due to their persistence during the remission periods. Beside that fact, in bipolar patients there are cognitive dysfunctions induced by mood-stabilizers, which are the first line drugs used in this specific pathology. The evaluation of memory and attention functioning, motor speed reaction, associative productivity and creativity represents a necessary step for the monitoring of bipolar patient, because of the anticonvulsants impact over these cognitive variables. The functional prognosis, bipolar patient ability to cope with professional and social duties, as well as his quality of life depend, in a significant proportion, upon monitoring symptoms and decreasing the factors associated with a negative impact on cognitive functions.

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Valproic acid a possible therapeutic alternative in spinal muscular atrophy management

Teleanu Raluca Ioana
Abstract: Spinal muscular atrophy (SMA) is an autosomal-recessive disorder caused by homozygous mutations in the survival motor neuron (SMN) gene. This can lead to dysfunction and loss of motor neurons of the anterior horn of the spinal cord and lower brain stem. The molecular pathophysiology of the disease is incompletely understood. Authors have reviewed current concepts on the treatment strategies for patients with spinal muscular atrophy. Valproic acid, known as an anticonvulsant, is a histone deacetylase inhibitor that can increase SMN protein levels in some SMA cells or SMA patients, through activation of SMN2 gene.

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The versatile bilobed flap in nasal reconstruction

Darmanescu Monica, Trifu V, Chivu Sorina
Abstract: The nose is the most frequent localization of skin cancer at the cephalic extremity. The dermatologist is familiar with all clinical aspects and the carcinologic properties of skin tumors, so he is at the forefront of the oncological skin surgery. The increasing incidence of cutaneous carcinomas has fueled the interest for refinement of the methods of nasal reconstruction. The bilobed flap, by its double transposition , can redistribute the tension vectors as to prevent distortion of the nasal pyramid. This article addresses the option of nasal reconstruction following skin cancer excision with anatomically adapted bilobed flaps. Special attention is given to discussions regarding the flap execution, from preoperative planning and design to the meticulous technique of suturing. We consider that intraoperative modifications of the standard technique should be a rule in approaching every individual case. The versatile bilobed flap represents a good reconstructive option for nasal reconstruction, being mindful that a well-known flap can be modified in innovative ways to reconstruct a defect.

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Antimicrobial prophylaxis in laparoscopic cholecystectomy and hernioplasty

Truta E., Firulescu S., Vartic M., Beuran M., Cristea A. N.
Abstract: The objective of our study was to characterize the pattern of surgical antibioprophylaxis in cholecystectomy and hernioplasty performed in the Surgical Clinic of the Emergency Clinical Hospital. This prospective study was conducted based on using a protocol established according to literature in this field and specific risks associated to surgical procedure. We recommended cefazolin 1g or cefuroxim 1.5g i. v., in a single dose for cholecystectomy. If the patients are allergic gentamicin, 1.7 mg/kg was recommended. We, also, chose cefazolin 1g i.v. in a single dose for hernia repair. Antibiotic was not routinely recommended in case of hernia repair without mesh or in laparoscopic cholecystectomy. Collected data were compared to our protocol and to the National Guide SRATI by conformities rate for each parameter. This study has identified several areas for improvement in SAP. We consider that the protocol should be revised and updated more often in order to improve the quality of the protocol and improvable of the medical staff and, also, to have in view the introduction of new antibiotics to be used. It is important for these medicines to be found in the Romanian market. Lately, we have had difficulty in being supplied with cefazolin therefore, we have used especially cefuroxim. The pharmaceutical varying market proves that the protocol should have a larger choice of antibiotics.

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Relationsip between carotid and cardiac ultrasonographic changes and risk factors in hemodialysis patients

Budurea C., Budurea Claudia, Racasan Simona, Lotrean Lucia, Patiu I.M., Gherman-Caprioara Mirela
Abstract: Cardiovascular disease is the leading cause of mortality in hemodialysis patients. Carotid and cardiac ultrasonographic abnormalities are the rule in these patients. The aim of this study is to evaluate the interrelation between these changes and cardiovascular risk factors in our patients. In 54 stable chronic hemodialysis patients current demographic and biochemical parameters were recorded. Ultrasonographic measurement of intima-media thickness, diastolic diameter of common carotid artery, evaluation of carotid atherosclerotic plaques and transthoracic ecocardiography with evaluation of left ventricular mass index and valvular calcifications were performed, and correlated with cardiovascular risk factors. We found a high frequency of ultrasonographic abnormalities. Remarkably, nontraditional cardiovascular risk factors such as malnutrition, anemia and calcium-phosphate imbalance seem more important than traditional risk factors such as age, gender, smoking, diabetes mellitus, arterial hypertension or obesity for these ultrasonographic changes in hemodialysis patients.

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Case Report

Particular diagnosis and treatment features of a case of common variable immunoglobulin deficiency associated with gluten intolerance and severe malabsorption syndrome

Georgescu A., Georgescu D., Dorobantu D.
Abstract: The authors present the case of a Common variable immunoglobulin deficiency (CVID) patient who has hypogammaglobulinemia, bowel involvement and severe malabsorption syndrome. Various problems related to positive and differential diagnosis are discussed within the framework of a very severe progression due to malabsorption syndrome with cachexia, numerous intercurrent pulmonary, intestinal, genital and skin infections and thrombophilia secondary to malabsorption. Eventually the course of disease is favourable partially thanks to the multidisciplinary approach undertaken.

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