Assessment of genotoxic effects in nurses handling cytostatic drugs

Several antineoplastic drugs have been classified as carcinogens by the International Agency for Research on Cancer (IARC) on the basis of epidemiological findings, animal carcinogenicity data, and outcomes of in vitro genotoxicity studies. 5-Fluorouracil (5-FU), which is easily absorbed through the skin, is the most frequently used antineoplastic agent in Portuguese hospitals and therefore may be used as an indicator of surface contamination. The aims of the present investigation were to (1) examine surface contamination by 5-FU and (2) assess the genotoxic risk using cytokinesis-block micronucleus assay in nurses from two Portuguese hospitals. The study consisted of 2 groups: 27 nurses occupationally exposed to cytostatic agents (cases) and 111 unexposed individuals (controls). Peripheral blood lymphocytes (PBL) were collected in order to measure micronuclei (MN) in both groups. Hospital B showed a higher numerical level of contamination but not significantly different from Hospital A. However; Hospital A presented the highest value of contamination and also a higher proportion of contaminated samples. The mean frequency of MN was significantly higher in exposed workers compared with controls. No significant differences were found among MN levels between the two hospitals. The analysis of confounding factors showed that age is a significant variable in MN frequency occurrence. Data suggest that there is a potential genotoxic damage related to occupational exposure to cytostatic drugs in oncology nurses.

Antineoplastic drugs contamination of workplace surfaces in two Portuguese hospitals

Despite the classification as known or suspected human carcinogens, by the International Agency for Research on Cancer, the antineoplastic drugs are extensively used in cancer treatment due to their specificity and efficacy. As human carcinogens, these drugs represent a serious threat to the healthcare workers involved in their preparation and administration. This work aims to contribute to better characterize the occupational exposure of healthcare professionals to antineoplastic drugs, by assessing workplace surfaces contamination of pharmacy and administration units of two Portuguese hospitals. Surface contamination was assessed by the determination of cyclophosphamide, 5-fluorouracil, and paclitaxel. These three drugs were used as surrogate markers for surfaces contamination by cytotoxic drugs. Wipe samples were taken and analyzed by HPLCDAD. From the total of 327 analyzed samples, in 121 (37%) was possible to detect and quantify at least one drug. Additionally, 28 samples (8.6 %) indicate contamination by more than one antineoplastic drug, mainly in the administration unit, in both hospitals. Considering the findings in both hospitals, specific measures should be taken, particularly those related with the promotion of good practices and safety procedures and also routine monitoring of surfaces contamination in order to guarantee the appliance of safety measures.

Sulfadiazine-potentiometric sensors for flow and batch determinations of sulfadiazine in drugs and biological fluids

New PVC membrane electrodes for the determination of sulfadiazine (SDZ) are presented. The electrodes are fabricated with conventional and tubular configurations with a graphite-based electrical contact, and no internal reference solution. The selective membranes consist of bis(triphenylphosphoranilidene)ammonium·SDZ (electrode A), tetraoctylammonium bromide (electrode B), or iron(II)-phthalocyanine (FePC) (electrode C) electroactive materials dispersed in a PVC matrix of o-nitrophenyl octyl ether (o-NPOE) plasticizer. The sensors A, B, and C displayed linear responses over the concentration ranges 1.0*10-2 – 1.0*10–5, 1.0*10–2 – 7.5*10–6, and 3.2*10–2 – 7.0* 10–6 mol l–1 (detection limits of 1.09, 2.04 and 0.87 mg ml–1) with anionic slopes of –57.3 ± 0.1, –46.7 ± 0.5, and –65.1 ± 0.2 mV decade–1, respectively. No effect from pH was observed within 4.0 – 5.5, 4.8 – 10, and 4.5 – 8, respectively, and good selectivity was found. The sensors were applied to the analysis of pharmaceuticals and biological fluids in steady state and in flow conditions.

Drug use in college students: a 13-year trend

OBJECTIVE: To analyze drug use trends among college students in 1996, 2001 and 2009. METHODS: A cross-sectional epidemiological study with a multistage stratified cluster sample with 9,974 college students was conducted in the city of São Paulo, southeastern Brazil. An anonymous self-administered questionnaire was used to collect information on drug use assessed in lifetime, the preceding 12 months and the preceding 30 days. The Bonferroni correction was used for multiple comparisons of drug use rates between surveys. RESULTS: There were changes in the lifetime use of tobacco and some other drugs (hallucinogens [6.1% to 8.8%], amphetamines [4.6% to 8.7%], and tranquilizers [5.7% to 8.2%]) from 1996 to 2009. Differences in the use of other drugs over the 12 months preceding the survey were also seen: reduced use of inhalants [9.0% to 4.8%] and increased use of amphetamines [2.4% to 4.8%]. There was a reduction in alcohol [72.9% to 62.1%], tobacco [21.3% to 17.2%] and marijuana [15.0% to 11.5%] use and an increase in amphetamine use [1.9% to 3.3%] in the preceeding 30 days. CONCLUSIONS: Over the 13-year study period, there was an increase in lifetime use of tobacco, hallucinogens, amphetamines, and tranquilizers. There was an increase in amphetamine use and a reduction in alcohol use during the preceding 12 months. There was an increase in amphetamine use during the preceding 30 days.

Characterization of the effects of antiepileptic drugs on bone metabolism: in vitro studies with human osteoblastic and osteoclastic cells

Bone is constantly being molded and shaped by the action of osteoclasts and osteoblasts. A proper equilibrium between both cell types metabolic activities is required to ensure an adequate skeletal tissue structure, and it involves resorption of old bone and formation of new bone tissue. It is reported that treatment with antiepileptic drugs (AEDs) can elicit alterations in skeletal structure, in particular in bone mineral density. Nevertheless, the knowledge regarding the effects of AEDs on bone cells are still scarce. In this context, the aim of this study was to investigate the effects of five different AEDs on human osteoclastic, osteoblastic and co-cultured cells. Osteoclastic cell cultures were established from precursor cells isolated from human peripheral blood and were characterized for tartrate-resistant acid phosphatase (TRAP) activity, number of TRAP+ multinucleated cells, presence of cells with actin rings and expressing vitronectin and calcitonin receptors and apoptosis rate. Also, the involvement of several signaling pathways on the cellular response was addressed. Osteoblastic cell cultures were obtained from femur heads of patients (25-45 years old) undergoing orthopaedic surgery procedures and were then studied for cellular proliferation/viability, ALP activity, histochemical staining of ALP and apoptosis rate. Also the expression of osteoblast-related genes and the involvement of some osteoblastogenesis-related signalling pathways on cellular response were addressed. For co-cultured cells, osteoblastic cells were firstly seeded and cultured. After that, PBMC were added to the osteoblastic cells and co-cultures were evaluated using the same osteoclast and osteoblast parameters mentioned above for the corresponding isolated cell. Cell-cultures were maintained in the absence (control) or in the presence of different AEDs (carbamazepine, gabapentin, lamotrigine, topiramate and valproic acid). All the tested drugs were able to affect osteoclastic and osteoblastic cells development, although with different profiles on their osteoclastogenic and osteoblastogenic modulation properties. Globally, the tendency was to inhibit the process. Furthermore, the signaling pathways involved in the process also seemed to be differently affected by the AEDs, suggesting that the different drugs may affect osteoclastogenesis and/or osteoblastogenesis through different mechanisms. In conclusion, the present study showed that the different AEDs had the ability to directly and indirectly modulate bone cells differentiation, shedding new light towards a better understanding of how these drugs can affect bone tissue.

Biological drugs for the treatment of psoriasis in a public health system

OBJECTIVE To analyze the access and utilization profile of biological medications for psoriasis provided by the judicial system in Brazil.METHODSThis is a cross-sectional study. We interviewed a total of 203 patients with psoriasis who were on biological medications obtained by the judicial system of the State of Sao Paulo, from 2004 to 2010. Sociodemographics, medical, and political-administrative characteristics were complemented with data obtained from dispensation orders that included biological medications to treat psoriasis and the legal actions involved. The data was analyzed using an electronic data base and shown as simple variable frequencies. The prescriptions contained in the lawsuits were analyzed according to legal provisions.RESULTS A total of 190 lawsuits requesting several biological drugs (adalimumab, efalizumab, etanercept, and infliximab) were analyzed. Patients obtained these medications as a result of injunctions (59.5%) or without having ever demanded biological medication from any health institution (86.2%), i.e., public or private health services. They used the prerogative of free legal aid (72.6%), even though they were represented by private lawyers (91.1%) and treated in private facilities (69.5%). Most of the patients used a biological medication for more than 13 months (66.0%), and some patients were undergoing treatment with this medication when interviewed (44.9%). Approximately one third of the patients discontinued treatment due to worsening of their illness (26.6%), adverse drug reactions (20.5%), lack of efficacy, or because the doctor discontinued this medication (13.8%). None of the analyzed medical prescriptions matched the legal prescribing requirements. Clinical monitoring results showed that 70.3% of the patients had not undergone laboratory examinations (blood work, liver and kidney function tests) for treatment control purposes.CONCLUSIONS The plaintiffs resorted to legal action to get access to biological medications because they were either unaware or had difficulty in accessing them through institutional public health system procedures. Access by means of legal action facilitated long-term use of this type of medication through irregular prescriptions and led to a high rate of adverse drug reactions as well as inappropriate clinical monitoring.

Prescription, dispensation and marketing patterns of methylphenidate

OBJECTIVE To analyze the patterns and legal requirements of methylphenidate consumption. METHODS We conducted a cross-sectional study of the data from prescription notification forms and balance lists of drugs sales – psychoactive and others – subject to special control in the fifth largest city of Brazil, in 2006. We determined the defined and prescribed daily doses, the average prescription and dispensation periods, and the regional sales distribution in the municipality. In addition, we estimated the costs of drug acquisition and analyzed the individual drug consumption profile using the Lorenz curve. RESULTS The balance lists data covered all notified sales of the drug while data from prescription notification forms covered 50.6% of the pharmacies that sold it, including those with the highest sales volumes. Total methylphenidate consumption was 0.37 DDD/1,000 inhabitants/day. Sales were concentrated in more developed areas, and regular-release tablets were the most commonly prescribed pharmaceutical formulation. In some regions of the city, approximately 20.0% of the prescriptions and dispensation exceeded 30 mg/day and 30 days of treatment. CONCLUSIONS Methylphenidate was widely consumed in the municipality and mainly in the most developed areas. Of note, the consumption of formulations with the higher abuse risk was the most predominant. Both its prescription and dispensation contrasted with current pharmacotherapeutic recommendations and legal requirements. Therefore, the commercialization of methylphenidate should be monitored more closely, and its use in the treatment of behavioral changes of psychological disorders needs to be discussed in detail, in line with the concepts of the quality use of medicines.

Stability of Schistosoma mansoni progeny to antischistosomal drugs

The susceptibility of the MAP Brazilian strain (F1 to F5 progenies) of S. mansoni to four antischistosomal drugs has been reported in a previous study. In the present investigation, progeny F14 of the same strain, was tested for stability to the same 4 drugs. A new medication, Oltipraz (35,972 RP), was added to the study. Five groups of 12 mice infected with cercariae by tail immersion were treated with hycanthone, oxamniquine, niridazole, praziquantel and Oltipraz. An untreated group was used as control. Schistosomal activity was assessed by the localization of worms in the portal vein system, by oogram changes, and percentage of parasite reduction. The stability of the susceptibility of progeny F14 did not change in relation to generations F1 to F5; the progeny was resistant to hycanthone and oxamniquine; but sensitive to niridazole, praziquantel and Oltipraz. We emphasize the importance of the phenomenon of resistance of the worm in view of the fact that oxamniquine has been widely used in Brazilian areas where mansonic schistosomiasis is endemic.

Schistosoma mansoni: effects of anesthetics and antimonial drugs on worm shift in the mouse

Mice experimentally infected with Schistosoma mansoni were injected with sodium thiopental or sodium antimonyl gluconate (Triostib R), or submitted to halothane inhalation, with or without a previous injection of thiopental. Data obtained showed that halothane and thiopental induce worm shift to the liver (99 and 76%, respectively). Sodium gluconate and antimonium (Triostib R) shifted 52% of worms towards the liver. These results seem to indicate that the use of antimonium would be unnecessary, when surgical removal of schistosomules is carried out through the extracorporeal filtration technique, in patients with portal hypertension.

Efficacy of oxamniquine, praziquantel and a combination of both drugs in schistosomiasis mansoni in Brazil

A randomized clinical trial was carried out to compare the efficacy of a low-dosage combination of oxamniquine (7.5 mg/kg) plus praziquantel (20 mg/kg) against either agent, oxamniquine (15 mg/kg) or praziquantel (40 mg/kg) alone, in the treatment of schistosomiasis mansoni in the Brazilian north-east. The drugs were randomly administered per os to 91 patients. Six and twelve months after treatment 89% of those admitted to the trial were reexamined by Kato-Katz method (ten slides) and MIF technique (one gram of stool) The achieved cure rates, as defined by absence of S. mansoni eggs in the faeces of individual patients at all points during the parasitological follow-up, were 81.8%, 81.2% and 67.6% for praziquantel, oxamniquine and the combination respectively. The reduction of eggs excretion in non cured patients six months after therapy ranged from 93.8-96.8% with praziquantel, 32.5-97% with oxamniquine and 76.9-99.5% with the combination. It is concluded that, at the used dosages, the three therapeutical regimens give similar and satisfactory results in the treatment of uncomplicated S. mansoni infection in Brazil.

Screening the mutagenic activities of coomonly used antiparasite drugs by the Simultest, a simplified Salmonella/microsome plate incorporation assay

The mutagenic activities of 16 anti-parasite drugs were screened by the Simultest in both qualitative (spot test) and quantitative (plate incorporation) assays with a Salmonella typhimurium pool composed by the indicator strains TA97, TA 98, TA100 and TA102. Four anti Chagas' disease drugs (nifurtimox, benznidazole, CL 64,855, and MK 436) and two anti-amebae drugs (metronidazole and tinidazole) gave positive results in qualitative tests and incorporation of rat liver microsomes did not alter the results. Comparative dose response curves of the mutagenic activities of CL 64,855, metronidazole and benznidazole obtained by the simultest and by individual Salmonella indicator strains demonstrated that both approachs have similar sensitivities. The results corroborate the validity of the Simultest, as a simplified, fast and economic version of the Ames test in preliminary screening of potential mutagenic drugs.

Drugs in ads and news: educating people in the nineteenth century press

This research aims at finding out how scientific knowledge reached the common people in nineteenth century Portugal, using newspapers as the main source of information. Collecting news on science and technology is part of a larger research project focused on producing a History of the Popularization of Science and Technology in Portugal, following a model already developed in the UK and the USA (Bauer 2007). This source was probably the most widespread vehicle to divulge the latest scientific news at the time to an unspecialised audience. The following themes are approached: Drug advertisements in the nineteenth century. How did scientific knowledge on diseases and treatments reach the consumer? How did newspapers deal with epidemics? What were the prevention measures and the known treatments at the time? And what was the role of newspapers as educators? Ads show us the interest on divulging new products and the role of publicity as moulder of minds. All these questions introduce us to the role of the media on the subject of social perception of science and technology and the way scientific knowledge reached the common citizen.

On similarities in infrared spectra of complex drugs

A chromatographic separation of active ingredients of Combivir, Epivir, Kaletra, Norvir, Prezista, Retrovir, Trivizir, Valcyte, and Viramune is performed on thin layer chromatography. The spectra of these nine drugs were recorded using the Fourier transform infrared spectroscopy. This information is then analyzed by means of the cosine correlation. The comparison of the infrared spectra in the perspective of the adopted similarity measure is possible to visualize with present day computer tools, and the emerging clusters provide additional information about the similarities of the investigated set of complex drugs.