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Volume XV, Number 2, 2011 - Therapeutics Pharmacology and Clinical Toxicology


Augmentation strategies in Selective Serotonin Reuptake Inhibitors resistant Obsessive-Compulsive disorder

D. Vasile, O. Vasiliu, A. G. Mangalagiu, Diana Gabriela Ojog
Abstract: The efficacy of selective serotonin reuptake inhibitors (SSRIs) in the treatment of obsessivecompulsive disorder (OCD) has some important limitations, as almost half of these patients are nonresponders. Therefore, an increasing number of pharmacological augmentation strategies have been developed in order to cope with SSRIs non-responders: increasing dosages to the maximum tolerated level, antidepressants switch, augmentation with pharmacologic agents or psychotherapy, alternative ways of treatment administration etc. In this systematic review we evaluated studies which focused upon the efficacy of the pharmacologic augmentation strategies in SSRIs resistant cases of OCD. Atypical and typical antipsychotics, antidepressants and other agents such as beta-blockers, psychostimulants or omega 3 fatty acids were detected in clinical studies and included in our review. The most supported strategies are typical antipsychotics (especially haloperidol), atypical antipsychotics (mainly risperidone), antidepressants like clomipramine or trazodone and the beta-blocker pindolol. More research is needed in order to evaluate the efficacy of other pharmacologic agents, such as newer antipsychotics and antidepressants, mood-stabilizers and various serotoninergic agents.

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Metabolic syndrome in clinical practice: considerations on diagnostic criteria and prevalence

R. Vasilescu
Abstract: The metabolic syndrome is defined as an association of risk factors of metabolic origin, combined with a heightened risk for cardiovascular diseases and for type 2 diabetes mellitus. The pathogenesis of the metabolic syndrome is multifactorial, the main risk factors being: obesity (abdominal obesity in particular) and insulin resistance. The prevalence of the metabolic syndrome is increasing in all countries, regardless of their developmental status. In non-diabetic patients, the prevalence of metabolic syndrome ranges between 15% to 30% and in subjects with type 2 diabetes mellitus, the prevalence is of 70%-90%. Prestigious medical associations have devised, over time, several models of diagnostic criteria, which differ both through the attention directed to the main risk factors and through the cut-off limits for the components. The existence of several definitions of the metabolic syndrome makes it difficult to compare the results of the large number of studies which have evaluated the presence of the metabolic syndrome and its association with the cardiovascular risk. Currently, there is an intense debate on the clinical utility of the metabolic syndrome diagnosis.

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Statins and the skin

Adina M. Dobritiu, D. G. Forsea
Abstract: Statins and are by far the most widely used class of lipid-lowering drugs and they are the class of choice for LDL-C reduction. Their cutaneous side effects reported in medical literature so far can be classified into four types: autoimmune reactions, reactions due to dryness of the skin, severe reactions like -DRESS, and allergic reactions. Recent research has proven that statins also have immunomodulatory activities and thus they can be used in the treatment of several immunological conditions which are characterized by a Th1 immune response. Statins are reported to be effective against psoriasis, to improve altered wound repair in diabetic skin, to decrease the incidence of skin cancer or to decrease fibroblasts activities in systemic sclerosis. The recently reported beneficial properties need further investigations.

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Original Papers

Health disparities among people with substance dependence in Romania

A. O. Abagiu, F. M. Duna, A. Streinu-Cercel
Abstract: Health disparities, health inequalities or health inequities are terms frequently used as synonyms, but with different content or meaning. Methodology: We have tried first to tackle the definitions problem and than through a secondary analysis of national published data to assess health disparities within the marginalized populations of Substance dependent people. Discussions: Analyzing health inequities in populations with potentially important impact on public health can offer targets for the actual health reform project in order to improve gaps between Romania and the other UE countries;

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Arterial stiffness in HIV infected patients

Anamaria Papita, Adriana Albu, Daniela Fodor, Corina Itu, D. Carstina
Abstract: Cardiovascular disease is an increasing cause of morbidity and mortality in HIVinfected patients. The increased cardiovascular risk in HIV infected patients is linked to traditional risk factors but also to HIV infection itself which can damage the arterial wall. The antiretroviral treatment (ART) is implicated in metabolic disturbances which can also affect the arterial wall. The aim of our study was to identify the effects of HIV and ART on the aortic artery and the cardiovascular risk by the evaluation of arterial stiffness parameters. Material and methods: A cross-sectional case-control study of 59 HIV-infected patients (55 exposed to ART, 5 ART-naive) and 40 controls matched by age and sex was performed. Aortic stiffness parameters and brachial parameters were measured using a device called Arteriograf TensioMed attached to a laptop with a TensioMed special software which provided automatic calculations of these markers. Results: HIV-infected patients had a greater aortic pulse wave velocity than the control group (p=0.02) and an increased heart rate (p=0.02). HIV infection and ARV treatment are additional risk factors for rapid onset and progression of atherosclerosis. Conclusions: HIV infection and ARV treatment are associated with increased arterial stiffness and increased heart rate. These vascular alterations are possible causes of the increased cardiovascular risk observed in HIV infected patients.

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Therapeutic strategies in HIV infected patients in treatment failure

Andreea Cristina Stoian, Florentina Dumitrescu, A.Cupsa, Cristina Iocu, Irina Niculescu, L. Giubelan, Liliana Marinescu
Abstract: Objectives: Analisys of clinical course after changing antiretroviral therapy (ART) in HIV infected patients (Px) with treatment failure (TF). Methods: A retrospective study in Craiova Regional Center for Monitoring and Evaluation of HIV/AIDS from 01/01/2009 to 12/31/2009, on two groups of Px in TF with at least 3 previous ARV scheme, Px in whom a new ART scheme was introduced: group A (16 Px) according to resistance test results and previous ART schemes and group B (23 Px) depending on previous ART schemes. Results: Clinical and immunological CDC staging- group A versus B was similar : B2 stage 1 Px (6.25%)/1 Px (4.34%), B3 stage 9 Px (56.25%)/7 Px (30.43%), C2 stage 1 Px (6.25%)/2 Px (8.69%), C3 stage 5 Px (31.25%)/13 Px (56.25%), median CD4=104 vs 181 cells/mm≥, median HIV-RNA=4.49 vs 4.30 lg copies/ml. Darunavir (DRV), Etravirine (ETV), Raltegravir (RAL) were included in ART of 8 Px (50%) of group A vs. 9 Px (39.14%) in group B. Clinical outcome was good in 14 Px in group A and all Px in group B. In group A, 1 Px died with lymphoma and 1 Px had cerebral toxoplasmosis. HIV-RNA level, at 4 and 12 month, in group A vs group B, were: HIV-RNA <50 copii/ml- 13 Px (81.25%) vs 18 Px (78.26%) (p> 0.05; 0.19 0.05; 0.12 0.05; 0.26
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Ertapenem resistance among extended-spectrum-B-lactamase-producing Klebsiella pneumoniae isolates

Mirela Flonta , Mihaela Lupse , Cornelia Craciunas, Ariana Almas, D. Carstina
Abstract: Correct detection of carbapenemase-producing strains is of crucial importance. Carbapenem resistance in Klebsiella pneumoniae is rare. Aim: The purpose of our study was to analyze the resistance to carbapenems of Klebsiella pneumoniae strains isolated from different pathological products. Methods: The resistance mechanism of 58 Klebsiella pneumoniae isolates, with decreased susceptibility to carbapenems collected from 2007 to 2009 was investigated. Detection of the resistance mechanisms included a screening step, an optional phenotypic confirmatory step, followed by a genotypic step. Results: Hyper production of ESBL type enzymes combined with porin loss is regarded as the main mechanism of resistance. Analysis of ß-lactamases showed that all isolates possessed ESBL genes. Other ß-lactamases belonging to class A, including bla-KPC-1, class B or OXA-type carbapenemases, were not detected. Conclusions: The emergence of multiresistant Klebsiella pneumoniae isolates is of major concern and highlights the need for further surveillance.

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The influence of cannabinoid receptor antagonist AM281 on paracetamol effect in the writhing test in mice

H. Paunescu, Oana Andreia Coman, L. Coman, F. Draghia, Cristina Musa, Isabel Ghita, I. Fulga
Abstract: Introduction. Paracetamol has been known as analgesic for over 100 years and has a mechanism of action that still remained not elucidated until now. There are authors who state a possible cannabinoid component of the analgesic effect of paracetamol administered in high doses. Background. This work has tried to study a possible cannabinoid component of the analgesic effect of orally administered paracetamol in the writhing test with acetic acid 0.75% v/v, 0.15 ml/10 g body weight, by using AM281 as a cannabinoid receptor antagonist. Materials and methods. In two experiments, 24 respectively 40 mice, separated in 4 groups each, have been used. In the first experiment 3 doses of paracetamol in geometric progression have been used to determine the ED50 (Effective Dose 50). In the second experiment 600 mg/kg (approximated as ED80) of paracetamol, AM 281 1mg/kg body weight, or combinations of both have been used. Paracetamol or vehicle have been administered 1 hour before testing, AM281 or vehicle 30 minutes before testing and the writhes have been observed over a 5 minutes period. The statistical analysis has required the use of ANOVA and of post hoc multiple comparison tests. Microsoft Excel and SPSS 15 programs have been used. Results. Statistically significant analgesia has been obtained for groups treated with paracetamol 300 and 600 mg/kg respectively in the first experiment. The ED50 was 301 mg/kg. No effect has been obtained for the AM281, and the AM281 has not antagonized the analgesic effect of paracetamol administered in a dose of 600 mg/kg body weight in the second experiment. Discussion and conclusions. There has been a dose-effect relationship for paracetamol in the writhing test. AM281 has had no effect per se and has not influenced the effect of paracetamol administered in a 600 mg/kg dose. The blockade of the cannabinoid receptors under our experimental conditions has not produced any effect. Paracetamol in moderate doses (600 mg/kg) did not seem to interfere with the metabolism of the endogenous cannabinoids to such an extent as to produce an analgesic effect through this mechanism. Our results might be due to the fact that AM 404, a compound derived from paracetamol and arachidonic acid, which is supposed to interfere with the cannabinoid system, did not accumulate at the moderate doses of paracetamol used in the present experiment.

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Role of epidemiologic data in management of hydatidosis in Constanta county

Irina Magdalena Dumitru, E. Dumitru, S. Rugina
Abstract: Introduction: Constanta county is a Romanian region characterized by a high endemicity (6 cases/100.000 inhabitants) of hydatidosis. This represents a public health problem due to medical and social implications. Specific traditional way of life in Constanta: high number of domestic animals (sheep, cows, goats) are complicated by new epidemiological issues, such as high number of stray dogs, lack of anthelmintics prophylaxis and recommended vaccination in well- cared and stray dogs, specifically presence of dogs on the beach, contaminating the sand. In this article we describe the epidemiological data obtained during a more complex study. The results of the study were presented at the 17th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) and 25th International Congress of Chemotherapy (ICC) in April 2007. Objectives. Evaluation of the interdependence between the links of the epidemic process (source of infection, route of transmission and vulnerable population) and various environmental factors that directly or indirectly contribute to the complex epidemiology of this disease. Material and method. We perform a prospective study on 320 patients diagnosed with hydatid cysts between 2001 -2006 from different places in Constanta county. Studied patients were ask to respond to a questionnaire regarding epidemiological aspects of hydatidosis. Results. The patients distribution per sex showed a higher incidence of this disease in women, compared to men; however, there is no significant relationship between hydatidosis and the risk of emergence in women. It is noticed that the highest number of studied cases is the age group 50-59 years old, that was contaminated at the active age, around 40 years old. The case distribution based on the social environment highlighted: a high number of cases from the urban area (234 cases, 72%), especially in Constanta city (182 cases), compared to the rural area (88, 28%). The greatest number of patients belong to the Romanian ethnic group and they represent the majority in our city and county. The second group are the Macedo-Romanians who represent a significant group in Constanta county and are well-known animal breeders, especially sheep. The epidemiologic inquiry was positive in most of the cases, the most of the patients admitted the contact with domestic animals (sheep, cattle, goats and dogs). Out of the 320 patients, 71 had already diagnosed with hydatid cyst in the past. It is noticed that the number of cases diagnosed with hydatidosis in our clinic significantly increased in the last years. Conclusions. The numerous sources of infection (dogs) and intermediary hosts (herbivorous) living in Dobrogea area maintain the disease endemicity. Given the minimization of the direct transmission through the improvement of the individual hygiene, the indirect transmission route is preponderant through contamination of the environment and a collective faulty hygiene.

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The antioxidant potential of saliva

Daniela Miricescu, Maria Greabu., Alexandra Totan, R. Radulescu
Abstract: The use of saliva as a diagnostic fluid is a relatively recent trend. Saliva is a mixed oral fluid derived from major and minor salivary glands. Oral fluid, often called the mirror of the bodys health, is a perfect medium to be explored for health and disease surveillance. Saliva is considered to be the first line of defense against oxidative stress (OS), the main cause for many systemic and oral diseases. Important sources of oral free radicals and reactive oxygen species (ROS) are tobacco smoke, periodontitis and other oral diseases. Saliva is rich in antioxidants: uric acid, albumin, ascorbate and enzymes which constitute the antioxidant potential of saliva. Aim of the study: To test possible correlations between several salivary biomarkers and oral diseases associated with OS. Material and methods: We have determined the salivary antioxidant potential in patients with periodontitis (20), oral lichen planus (OLP) (20) smokers (20) versus controls (20). The following salivary biomarkers were evaluated: uric acid, albumin and total antioxidant capacity (TAC). Salivary biomarkers were performed using analysis kits on automatic analyzer. Analysis kits were provided by Biosystems Diagnostics (Spain) and by Randox (UK). Results: Analysis revealed statistically significant changes of the mentioned parameters in patients saliva versus controls. Conclusions: Our results illustrate that OS caused a depletion of antioxidant status in the oral cavity. Uric acid, albumin and TAC are very important and promising salivary biomarkers for monitoring the oral OS.

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Therapeutical Practice

Cerebral palsy management

Ioana Minciu
Abstract: At this moment there are no treatment guidelines for cerebral palsy, and also no treatment for the brain lesion that leads to characteristic motor dysfunctions. Therefore the therapeutic intervention is only symptomatic, targeting the motor and associate disturbances equally (co morbidities). This paper reviews the existent therapeutic options, based on the literature data. Functional therapy, orthosis, injecting botulium toxin, occupational therapy, intrathecal Baclofen, surgical treatment, are available as options at the moment. Unfortunately, there are not enough studies to prove the superiority of a treatment over another.

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Management of a treatment experienced HIV patient

Andrea Incze, Carmen Lucia Chiriac, Iringo Zaharia Kezdi
Abstract: Treatment experienced patients had limited treatment options during the past decade. The situation has changed with the arrival of the new antiretrovirals. We describe the case of a human immunodeficiency virus (HIV) infected patient with previous therapeutic failures, low levels of T CD4+ cell count and high viral load, three-drug class resistant virus. Undetectable viral load lasting for more than 80 weeks has been obtained using a regimen containing three fully active antiretrovirals: raltegravir, darunavir and enfuvirtide. Lamivudine was associated to this regimen, to reduce viral fitness. This combination conducted to favourable clinical, immunological and virological outcome. These new antiretrovirals offer new hope to treatment experienced patients in a way that could not have been possible before.

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Case Report

Repeated supratherapeutic acetaminophen use resulting in a fatality

Edward P. Krenzelok , Gordon J Vanscoy
Abstract: In the United States acetaminophen (paracetamol) is the most commonly used nonprescription analgesic. In addition to its nonprescription use, acetaminophen is also a common ingredient of prescription opioid combination products. This case report describes an acetaminophen-related fatality that occurred as a consequence of an unintentional overdose of a prescribed hydrocodone/acetaminophen product. While these deaths are uncommon, they can be prevented if the prescriptions for these products are written and dispensed properly and if patients are warned not to exceed the proper dosage recommendations.

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Pigmented purpuric dermatitis

N. Iagaru, Monica Darmanescu, Irina Margaritescu, D. Chirita
Abstract: The pigmented purpuric dermatoses are a group of chronic diseases of unknown etiology that have a distinctive clinical appearance. They are characterized by extravasation of erythrocytes in the skin with marked hemosiderin deposition. The pigmented purpuric dermatoses are infrequently reported in preadolescent children, except for the Schamberg disease that may occur in persons of any age. Usually, for all the pediatricians, purpura is a concerning sign of a possible systemic (infectious, hematologiconcologic or immunologic) disease, especially in small children. We report a case of a 7 year-old male with progressive purpura who underwent extensive laboratory investigations to rule out a systemic disease. Based on the laboratory findings and clinical course, the diagnosis of purpuric pigmentary dermatitis (Schamberg`s purpura) was established.

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Severe neurological impairment as initial manifestation of HIV infection

A. Vata, Carmen Manciuc, Cristina Nicolau, L. Prisacariu, Gabriela Juganariu, Gh. Dorobat, D. Duiculescu, Carmen Dorobat
Abstract: The neuro-cognitive impairmen in HIV infected patients may take an extremely wide range of clinical manifestations and can occur early (acute retroviral syndrome) or late in the history of the infection We present three case reports of patients in whom some complex and atypical neurological manifestations led to the diagnosis of HIV infection after close colaboration of neurologists and infectious diseases specialists from several counties; the outcome and therapeutic approach are discussed. This kind of manifestations could become more frequent now in the newly diagnosed, late presenter, slow progressor patient.

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