Band 6, Heft 5

Paclitaxel is isolated from the Pacific yew. It can be obtained from the European yew, but only after chemical modification of the isolated compound by a semi-synthesis procedure. The procedure for total synthesis of paclitaxel is very complicated, involving multiple steps, and the yields of paclitaxel are meagre. This substance is also a metabolite of certain kinds of fungus. The microbiological pathway for producing paclitaxel compared with isolation from plant material involves shorter procuction times but a small yield. Cyclodextrins are usually used for improving the solubility of paclitaxel in aqueous media, with polymeric and other substances added. Paclitaxel has anticancer activity and use for preparing the formulations intravenously administrated to patients with tumors. The paclitaxel concentration in these formulations is determined using validated HPLC methods.

Breast sarcoidosis is extremely rare, substantially less frequent than other extrapulmonary manifestations of sarcoidosis. It can mimic a benign or malignant tumor of the breast. We describe the case of a patient with a history of pulmonary sarcoidosis referred to our hospital for a screening mammography. Mammographic findings raised the suspicion for a breast mass. An additional breast ultrasound and fine -needle aspiration biopsy were performed. Finally, patient underwent a excisional biopsy of the left breast and the histopathological report revealed sarcoidosis.

Apparent hematological symptoms rarely dominate the clinical picture of an underlying non-hematological malignancy. Malignancy-associated eosinophilia can result from clonal or non-clonal proliferation of eosinophils. Here, we report the case of a 59-year-old man with metastatic adenocarcinoma of the lung with an unknown primary tumor site, which presented as hypereosinophilia, anemia, lymphadenopathy, weight loss, and malaise. Bone marrow biopsy disclosed metastatic adenocarcinoma positive in immunohistochemistry for cytokeratin 7. Further assessment of specimens obtained from the bronchoalveolar lavage and biopsy of the mediastinal lymph nodes confirmed the diagnosis of the metastatic lung cancer, although the primary tumor site remained undiscovered. This case underlines that eosinophilia may represent a rare primary manifestation of an undetected malignancy, and it is thus important to consider this as part of the differential diagnosis in patients presenting with unexplained eosinophilia.

The melanocortin system plays a pivotal role in the regulation of appetite and energy balance. It was recognized to play an important role in the development of cancer-related cachexia, a debilitating condition characterized by progressive body wasting associated with anorexia, increased resting energy expediture and loss of fat as well as lean body mass that cannot be simply prevented or treated by adequate nutritional support. The recent advances in understanding of mechanisms underlying cancer-related cachexia led to consequent recognition of the melanocortin system as an important potential therapeutic target. Several molecules have been made available for animal experiments, including those with oral bioavailability, that act at various checkpoints of the melanocortin system and that might confer singificant benefits for the patients suffering from cancer-related cachexia. The application of melanocortin 4 receptor antagonists/agouti-related peptide agonists has been however restricted to animal models and more pharmacological data will be necessary to progress to clinical trials on humans. Still, pharmacological targeting of the melanocortin system seem to represent an elegant and promising way of treatment of cancer-related cachexia.

The aim was to evaluate vitamin D levels in young healthy Lithuanian males in winter and to find possible associations of vitamin D concentration to body composition, cognitive functioning, emotional state. Subjects and Methods A total of 130 healthy males (age range, 18–26 years) were divided into the subgroups according to vitamin D concentration. The Profile of Mood States (POMS) questionnaire and Hospital Anxiety and Depression Scale were employed in the assessment of emotional state. Cognitive functioning was assessed by the Trail Making Test and the Digit Symbol Test of the Wechsler Adult Intelligence Scale. Results The mean concentration of vitamin D for the entire sample was 13.0±5.3 ng/ml. Only 2 persons (1.6%) had the recommended vitamin D level. Nearly half (45.4%) of study participants had vitamin D deficiency. Lower concentrations were associated with a significantly higher score on the POMS confusion-bewilderment scale. A tendency toward a lower mean depression-dejection score in the participants with a sufficient vitamin D level was observed. Vitamin D concentration correlated positively with body mass index (BMI) and inversely with the confusion-bewilderment score. In conclusion almost half of the young healthy males participating in the study were detected to have vitamin D deficiency in winter. Low vitamin D concentrations are associated with a worse emotional state.

The aim of this study was to present the properties of insulin sensitivity indices formulas to justify selection of formulas to evaluate of insulin sensitivity for calculation from an oral glucose tolerance test (OGTT) data. Twelve of the most applicable formulae for ISI calculation were analyzed in the view of two sets of results: 1) point contrasts, calculated as the ratio of average ISI values in lean and obese groups of patients; and 2) interval contrasts, calculated as ratios of T from the two-sided t-test, evaluated as dimensionless, mutually comparable contrasts within a continuous scale. Statistical significance of individual ISIs in terms of their contrasts was evaluated by two-sided t-tests. P<0.001 was a considered statistically significance between a group of 59 healthy volunteers with BMI<25 kg/m2 and a group of 63 volunteers with BMI≥25 kg/m2 who underwent frequent OGTT sampling. To compare data of an individual subject with the standard, we recommend selecting the formulas with a high point contrast. To compare of data of several subject groups, we recommend using the formulas with a high interval contrast.

The aim of the prospective, multicenter project was to evaluate the effect of standardized information on the decision of woman when selecting application routes for combined hormonal contraceptives (CC). Selection the route of CC’s administration before and after consultation with the physician was evaluated on the group of 1326 women in 125 centres in the Czech Republic using a questionnaire. Analysis of the difference between the intended (4,1%) and selected (33,9%, CI 95% 31%–38%, 451 women) contraception shows that the vaginal ring preference increased by 29,8% (CI 97,5% 26,9%–32,8%, p < 0,0001). The difference for the weekly patch after (5,7%) and prior (4,2%) to the counseling of 1,4% was borderline statistically significant (CI 97,5%–0,002%–3,0%, p = 0,05). Preference of COC remained practically unchanged at 53,5%. Vaginal ring was selected by 45,2% of undecided women and 28,0% of women, who considered other than combined hormonal contraception. Easibility of application, efficacy and cycle control are the most important predictors for contraception choice. Following expert advice, including information on all forms of combined oral contraceptives, more than 33% of women chose the latest application form of combined hormonal contraceptives - vaginal ring.

Organophosphate pesticides are known to induce oxidative stress and cause oxidative tissue damage, as has been reported in studies concerning acute and chronic intoxication with these compounds. Our objective was to investigate the activities of brain antioxidant enzymes and malonyldialdehyde, as well as the level of carbonyl groups, in rats sub-chronically intoxicated with chlorpyrifos at doses of 0.2, 2 and 5 mg per kg of body weight per day. It was found that chlorpyrifos induces change in brain antioxidant enzymes, such as superoxide dismutase, catalase and glutathione peroxidise, but to a different degree in comparison to proper control values; however, the elevated antioxidant enzymes activities failed to check lipid and protein peroxidation in the brains of rats. Thus, in sub-chronic intoxication with chlorpyrifos, as evidenced by increased level of malonyldialdehyde and carbonyl groups, oxidative stress is induced. Measurements of protein carbonyl groups appeared to give more consistent responses in the rats’ brains when compared to the malonyldialdehyde level after sub-chronic chlorpyrifos treatment.

A 76 year old patient underwent a laparoscopic rectal resection performed under thoracic epidural anaesthesia and general anaesthesia. He was inadvertently given 1 g of paracetamol epidural and reported a position-independent holocephalic headache one day later. A severe nausea and vomiting lead to a gastrointestinal bleeding. The last neurological examination after 3 months revealed no nausea, no headaches and no sensory disturbances.

Direct deciphering of past genes may reflect real characteristics of forebears, even of whole ancestral populations. This is obviously one of the most powerful and direct methods to follow evolutionary changes of the species. We attempted to apply ancient DNA (aDNA) technology to analyse a polymorphism at codon 129 of PRNP which probably plays a role in susceptibility to a variant Creutzfeldt - Jakob (vCJD) disease. As previously suggested, 129 Val-Val and heterozygous individuals are nearly completely protected from vCJD, in contrast to 129 Met-Met homozygous ones. We examined the frequency of the alleles encoding methionine and valine at codon 129 in DNA isolated from 100 skeletal remains of individuals who lived between 10th and 13th century. Our results confirmed significant alteration in previously studied alleles frequency between the populations of medieval Polish Lands and contemporaries. The calculated frequency of the alleles in medieval Poland (51% as compared to contemporary 65% for 129Met, and appropriately 49% vs. 35% for 129Val) implies a selection process that shaped 129 Met-Val distribution profiles in the Middle Ages. We suggest that the study of the genetic relationship between past and present-day populations could be a useful tool to follow allelic composition of particular genes (here: of the PRNP) over a span of time which may contribute to the understanding of evolutionary and selective mechanisms including epidemiological cases.

Lung cancer is mainly a lifestyle-associated disease with poor prognosis and the lowest five year survival rate of all types of cancer. Lung cancers are divided into two main groups: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Surgical treatment is generally indicated in cases of early stage NSCLC, and those patients treated with radical and aggressive surgery have a somewhat better survival rate. The main problems with lung cancer treatment are due to late diagnosis, rapidly developing drug resistance and side effects of the treatment that are experienced by almost all patients. The next step for distinguishing histologically complicated lung cancers and determining optimal treatment strategies is gene expression analysis. Supported by gene expression data, it is possible to prognosticate the course of the disease.

We conducted a 10-cM genome-wide linkage scan in two extended pedigrees, ascertained from two diverse Dagestan genetic isolates with high aggregation of major depressive disorder (MDD) and suicides. Using genome wide multipoint parametric linkage analyses with short tandem repeat markers, we found two previously undetected genomic regions with significant linkage in isolate #6007 with LODs=3.1–3.4 at 2p13.2–p11.2 (and some signal in same region for #6008) and in 14q31.12–q32.13. We also obtained suggestive evidence for linkage with MDD at 9q33.3–q34.2 (#6008), 13q31.1–q31.2(#6007), 11p15(#6008), 17q25.3(#6007) and 19q13.31–q13.33 (#6008). Five regions (1p36.1–p35.2, 2p13.2–p11.2, 17q25.3, 18q22 and 22q12.3) demonstrated at least nominal linkage in both isolates’ pedigrees, while all other linkage regions demonstrated population-specific genetic heterogeneity.

We present the case of a 20-year-old man referred to the clinical geneticist because of mental retardation and dysmorphic features because of concerns about hereditability when his older, healthy brother was expecting a child. Deletion of proximal 3q arm was found with standard G-banding, and array comparative genomic hybridisation (array-CGH) was used to further locate the breakpoints. A unique interstitial deletion del 3q13.11q13.33 was confirmed. The first clinical symptoms in the 20-year-old were described at the age of 4 months when the pediatrician reported muscle hypertonia of the lower limbs, which later evolved into hypotonia. Later clinical observations revealed that the patient’s psychomotor development was delayed: he exhibited craniofacial abnormalities, cryptorchidism, thoracic kyphosis, and tapering fingers. Interstitial deletions of the proximal long arm of chromosome 3 have rarely been reported:; there are only 12 previously reported cases. The breakpoints and sizes of described deletions vary greatly, which makes definite genotype-phenotype conclusions impossible at this time. Developmental delay is one of the common features described in the majority of reported cases. The BTB-zinc finger gene ZBTB20 might be a potential candidate gene: it was shown in the mouse hippocampus to be expressed during the important period of neurogenesis of pyramidal neurons. Also, four of patients reported to date had agenesis of the corpus callosum and one, holoprosencephaly. We suggest that the GAP43 gene is involved in the development of structural neurological abnormalities in patients with 3q deletion.

We report a 71-year-old male with microscopic polyangiitis (MPA) who developed sudden-onset, progressive, bilateral visual loss associated with a relapse of MPA symptoms. The patient was referred to our hospital, and treated with intravenous pulse steroid therapy and high-dose oral prednisolone. Although the right eye remained vision deficient, visual acuity in the left eye recovered. Ocular manifestations of MPA are quite uncommon. This case emphasizes the necessity of early detection and initiation of prompt therapy where ocular manifestations of MPA occur.

The aim of the study was to analyze changes of systolic and diastolic blood pressure values over five and ten years separately boys and girls and to estimate correlation between them. Three age groups from 8 centers in Serbia were evaluated: Group 1: 10 year old patients, Group 2: 15 year old and Group 3: 20 year old. Group with normal blood pressure values, prehypertensive and hypertensive group were analyzed. Regarding the period of follow-up we analyzed: 10/15 years period-children between 10 and 15 years, 15/20 years period-children between 15 and 20 years, and 10/20 years period-children between 10 and 20 years. Significant increase of diastolic blood pressure was noticed for both genders in 10/15 years period of prehypertensive population, while in hypertensive children, boys showed decline in frequency for systolic and diastolic blood pressure and girls only for diastolic. In 15/20 years period there was significant decrease of prehypertensive and significant increase of hypertensive diastolic blood pressure frequency. In 10/20 years period significant reduction in frequency of prehypertensive systolic blood pressure was noticed, while only hypertensive group of boys showed significant reduction regarding systolic blood pressure frequency. Prehypertensive diastolic and hypertensive systolic blood pressure fluctuations are more related to age.

Multiple sclerosis (MS) is one of the most disabling neurodegenerative disorders. Depression is the most frequent psychiatric disorder accompanying MS. Although much attention is given to correlations between depression and MS clinical factors, analysis of correlations between depression and life activities (social, household, professional activities and family life) and the well-being of MS patients’ is insufficient. However, improvement of these functions could positively influence the outcomes of MS treatment. The aim of this study was to evaluate relationships between depression, life activities of MS patients, and their proposals how to improve the well-being. Materials and methods. The study lasted three years with 270 adult MS patients involved in it. ICD-10 criteria were used to diagnose depression. Original questionnaire was used to measure life activities and the well-being of the patients. Results. Prevalence of depression was 20.7% with no difference regarding the gender. Almost 84% of depressed respondents indicated, that MS disturbs their family life, 71.4% recommended to assign more attention to MS in general and 64.3% — to include more medications into reimbursement list. Conclusions. MS patients diagnosed with depression significantly more often than non-depressed indicate that MS disturbs their family life; recommend to assign more attention to MS in general and to include more medications into reimbursement list.

Withdrawal-emergent adverse effects of antipsychotics are an infrequently identified condition which can appear during antipsychotic dose reduction and medication change. In this paper, we present the case of severe extrapyramidal symptoms after a dose reduction of risperidone is presented. A patient, 23 years of age, was admitted to a health care facility due to an unexpected change in his behavior, with paranoid delusions, incoherent thinking, and significant anxiety. An initial risperidone treatment was soon changed to zuclopenhixol. Subsequently, severe extrapyramidal symptoms appeared, after which the medication was switched back to resperidone. Following this treatment, the patient left the health care facility and stopped the medication of his own volition. Psychotic symptoms and massive extrapyramidal symptoms again occurred. These symptoms subsided only slowly during a subsequent treatment with olanzapine. The development of adverse neurological effects together with a worsening of productive psychotic symptomatology may be explained by withdrawal of antipsychotic medication. These symptoms are often attributed to new medications, which are prematurely discontinued after the appearance of an adverse effect, but which are potentially beneficial to a patient, provided that enough time for a spontaneous subsidence of withdrawal-emergent effects is given. Any change in antipsychotic treatment should be carefully considered and thoroughly planned.

The aim of the study is to investigate the most frequent cause of superficial mycoses in patients from the territory of city Niš Southeast Serbia in the period from 1998 to 2010. A total of 3223 samples from 2887 patients with suspected dermatomycoses were examined. Superficial mycoses were diagnosed using standard microbiology techniques (conventional microscopy and cultivation). Dermatophytes were determined on the basis of their macroscopic and microscopic morphological and morphometric characteristics. Morphometric characteristics were obtained by Laboratory Universal Computer Image Analysis system (Lucia M, 1996). Species of genus Candida were identified using the test of production of germ tube in sera, by growth on comertial chromatogen medium (Chromotogenic Candida, Liofichem/Bacteriology products, Italy) and by using Auxacolor TMBioRad, France. The results were elaborated with the statistical method of descriptive and quantitative analysis (SPSS 14.0 for Windows 2003). The prevalence of superficial mycoses was 25,1%. Dermatophytes were identified in 67.6% of all positive cultures. Microsporum canis was the most prevalent (50.3%) dermatophyte isolated, followed by Trichophyton metagrophytes var. mentagrophytes (35.4%). Yeast genus Candida has become a more frequent cause of superficial fungal infection since 2001. and C. albicans was the dominant yeast (61.1%).

Due to the increasing number of infections related to injecting drug use, both the pattern of hepatitis C virus (HCV) transmission, and the circulating genotypes in Europe have changed. As there are little available data in this respect for Romania, the aim of our study was a preliminary analysis of the distribution of HCV genotypes circulating among injecting drug users (IDUs). Of the 45 IDUs evaluated (86.7% men, mean age − 27.6 ± 3.7 years, mean age at first drug use − 17.5 ± 3.9 years), 88.9% presented anti-HCV antibodies, with higher rates in those with an injecting history of more than 10 years; 57.8% of the subjects had detectable HCV viral load. Only 6.7% had markers of chronic hepatitis B infection, and none had anti-HIV antibodies. While HCV subtype 1b is still prevalent (in 50% of the viraemic subjects), other subtypes begin to emerge, especially in younger patients (1a — in 23.1%, 4 — in 11.5%, 3a — in 7.7% of the cases). These data indicate the possibility of major shifts in the distribution of the dominant subtype, underlining the need for close surveillance of HCV infections in IDUs, who can act as a bridging group toward the general population.

To evaluate the possibilities of physical activity in developing inmates’ healthy lifestyle and social skills. The research, which was conducted in 2009 in Pravieniskes First and Second Correction Houses, was local and cross-sectional using a written questionnaire. The questionnaire consisted of four groups of questions/statements: I — demographic questions; II — questions/statements about inmates’ physical (sports) activities (was created for this study) and III — assessment of inmates’ social skills. And IV — assessment of inmates’ self esteem. Sufficiently physically active inmates (n=185) comprised 57.8 percent of the total number of respondents. Inmates’ physical activity statistically significantly (p<0.05) correlates with their younger age. Secondary education is prevailing in the group of physically active inmates, while primary — lower secondary education predominates in the group of physically inactive inmates (n=135). Only less than 6 percent of inmates have higher education. The average age of physically active inmates is statistically significantly lower than that of physically inactive inmates, 26 and 31.6 years respectively (p=0.01). The analysis of inmates’ contentment with their psychological state and satisfaction with health care services, food quality, and conditions for sports activities showed that physically active inmates are more critical about these factors than physically inactive inmates. Only the contentment with psychological state in physically active inmates is statistically significantly higher than in inactive inmates. Out of eleven social skills assessed in the study, only two skills (ability to initiate conversation with a stranger and sense of responsibility) are statistically significant (p<0.05). The probability that the convicts who have a strong sense of responsibility tend to be more physically active than the inmates who do not consider themselves responsible is 7.4 times higher. The study results showed that self-esteem in physically active inmates is statistically significantly higher that in physically inactive inmates (p=0.033). Low self-esteem was not determined in any inmates.