Hair testing for drugs of abuse

Hair testing for drugs of abuse is a developing technology, which offers the possibility of longer detection times than is commonly obtained with urine analysis. It is the main method for evaluation of an individual's drugs of abuse history. In many countries hair analysis is routinely used to detect drug abuse in forensic cases, occupational and traffic medicine and clinical toxicology. Hair analysis in pregnant women, neonates and infants is a useful tool for the detection of drug exposure in utero. In Croatia hair testing for drugs of abuse is performed at the Institute for Medical Research and Occupational Health. Three-year experience in drugs of abuse analysis in hair is described. In 331 hair samples (270 from adolescents and 61 from adults) opiates and metabolites, cocaine, methadone, and amphetamines were analyzed by gas chromatography/mass spectrometry. Most prevalent drugs of abuse in adolescents were amphetamines, and in adults heroin. From the examples cited and samples analyzed it is evident that hair testing is emerging as a reliable biological marker for cumulative account of individual exposure to drugs of abuse.     

Linker regions of the RhaS and RhaR proteins

Substitutions within the interdomain linkers of the AraC/XylS family proteins RhaS and RhaR were tested to determine whether side chain identity or linker structure was required for function. Neither was found crucial, suggesting that the linkers do not play a direct role in activation, but rather simply connect the two domains.     

Versatile use of Schizosaccharomyces pombe plasmids in Saccharomyces cerevisiae

The two model yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe appear to have diverged 1000 million years ago. Here, we describe that S.?pombe vectors can be propagated efficiently in S.?cerevisiae as pUR19 derivatives, and the pREP and pJR vector series carrying the S.?cerevisiae LEU2 or the S.?pombe ura4(+) selection marker are maintained in S.?cerevisiae cells. In addition, genes transcribed from the S.?pombe nmt1(+) promoter and derivatives are expressed in budding yeast. Thus, S.?pombe vectors can be used as shuttle vectors in S.?cerevisiae and S.?pombe. Our finding greatly facilitates the testing for functional orthologs of protein families and simplifies the cloning of new S.?pombe plasmids by using the highly efficient in vivo homologous recombination activity of S.?cerevisiae.     

Lapatinib in the treatment of HER-2 overexpressing breast cancer

Lapatinib is the only clinically available agent for the treatment of patients with human epidermal growth factor receptor-2 (HER-2) positive tumors that have progressed on treatment with trastuzumab, taxanes and anthracyclines. Moreover, when given with letrozole in postmenopausal patients with estrogen receptor (ER) and HER-2 positive disease it induces clinically meaningful benefit. Recently presented neoadjuvant data suggests an important place for the combination of trastuzumab and lapatinib in the therapy of early HER-2 positive breast cancer. This article reviews the current status and future perspectives of lapatinib.     

Immeasurable levels of serum phosphate--an unidentified cause of respiratory failure in a diabetic patient

We report a case of immeasurable levels of serum phosphate in a patient with juvenile type Diabetes mellitus and diabetic ketoacidosis who developed respiratory failure. A 27-year-old female with juvenile type insulin-dependent Diabetes mellitus was admitted because of suspected acute mediastinitis and respiratory failure, probably, among other responsible factors, caused and complicated by undetectable levels of serum phosphate. The serum phosphate concentration three days after aggressive treatment was only 0.2 mmol/L. Furthermore, a significant improvement in weakness and lethargy was observed. To the best of our knowledge, this is the first described case of immeasurable levels of serum phosphate. In patients with Diabetes mellitus, serum phosphate concentrations should be routinely checked in order to avoid additional complications.     

Biomarkers of mild hyperthermia related to flashover training in firefighters

Flashover phenomenon occurs when surfaces exposed to thermal radiation reach the ignition temperature, and the fire rapidly spreads in enclosed area. Flashover training (FOT) performed by firefighters is a simulation of flashover phenomenon under controlled conditions. The study aimed to test thermal and physical strain in male firefighters and instructors attending FOT and its influence on DNA damage, exhaled breath condensate (EBC) pH, and fraction of exhaled nitric oxide (FeNO). DNA damage markers were analyzed in 51 attendees and 7 instructors, and EBC pH and FeNO in 40 respiratory healthy non-smoking subjects (34 attendees and 6 instructors).The average body temperature and pulse increase was 1.1 °C and 30 beats per minute, respectively. A prominent increase in the alkali-labile sites' level has been observed in instructors' peripheral leukocytes compared to first-time attendees (tail length p=0.050, % of DNA in tail p=0.005). FOT was related only to physiological FVC and FEV₁ increase (by 4% and 2.7% on average), and FeNO dropped after the exercise by 2 ppb in comparison with basal values (P=0.034). EBC pH did not change during FOT, but FeNO was inversely correlated to EBC pH after the exercise (Spearman's rho=−0.66, P=0.013). With respect to the thermal and physical strain, FOT is considered to be a safe training procedure for healthy firefighters. The increase rate in primary DNA damage found in the instructors' peripheral leukocytes requires further examination in a larger sample size.     

New bispyridinium oximes: in vitro and in vivo evaluation of their biological efficiency in soman and tabun poisoning

Improving the efficacy of antidotal treatment of poisonings with nerve agents is still a challenge for the scientific community. This study investigated the interactions of four bispyridinium oximes with human erythrocyte acetylcholinesterase (AChE) and their effects on soman- and tabun-poisoned mice. Oximes HI-6 and TMB-4 were used for comparison. These oximes inhibited AchE with inhibitory potency (IC(50)) ranging from 0.02 to 1.0 mM. The best reactivating potency (%R) was obtained with K074, when AChE was inhibited by tabun. The protective potency (P(50)) of all oximes in human erythrocyte AChE inhibited by soman and tabun could not be determined. In tabun-poisoned mice very good antidotal efficacy was obtained with K027, K048, and K074, which makes them interesting for future investigation. The combination of HI-6 and atropine is the therapy of choice for soman poisoning.     

Novel thiosemicarbazone derivatives as potential antitumor agents: Synthesis, physicochemical and structural properties, DNA interactions and antiproliferative activity

The paper describes synthesis of several novel thiosemicarbazone derivatives. Furthermore, crystal and molecular structure of 4-diethylamino-salicylaldehyde 4-phenylthiosemicarbazone revealed planarity of conjugated aromatic system, which suggested the possibility of DNA binding by intercalation, especially for here studied naphthalene derivatives. However, here presented DNA binding studies excluded this mode of action. Physicochemical and structural properties of novel derivatives were compared with previously studied analogues, taken as reference compounds, revealing distinctive differences. In addition, novel thiosemicarbazone derivatives (1, 2 and 5–8) clearly display stronger antiproliferative activity on five tumor cell lines than the reference compounds 3 and 4, which supports their further investigation as potential antitumor agents.     

Contact allergy caused by fragrance mix and Myroxylon pereirae (balsam of Peru)--a retrospective study

Because of their widespread use, fragrances are among the most common causes of contact allergic dermatitis, second only to nickel. During a five-year period 3,065 patients with contact dermatitis were patch tested using a specific mix of fragrances. 509 (16.6%) patients were allergic to the fragrance mix, while 258 (8.4%) patients exhibited an allergic reaction to Myroxylon pereirae (balsam of Peru). Between those 509 patients, 157 were patch tested with eight individual substances contained in the fragrance mix: cinnamal, cinnamyl alcohol, eugenol, isoeugenol, geraniol, hydroxycitronellal, alpha-amyl cinnamal and Evernia prunastri (oak moss). The most frequent allergens were isoeugenol 57.9% (91/157), eugenol 55.4% (87/157), cinnamyl alcohol 34.4% (54/157) and Evernia prunastri (oak moss) 24.2% (38/157). There were 62 patients (39.5%) who exhibited an allergic reaction to both the fragrance mix and Myroxylon pereirae (balsam of Peru). The results prove the importance of avoiding allergens in daily life, especially in industrial and cosmetic products. In order to prevent ACD, better cooperation between industry and dermatologists is needed.