Investigations of anti-inflammatory and analgesic activities of prednisolone solid dispersion prepared with skimmed milk

Prednisolone is an analgesic and anti-inflammatory drug. It possesses poor aqueous solubility and has irritant effects on stomach mucosa. In order to modulate its gastric side effect and increase aqueous solubility, physical mixture and solid dispersion of prednisolone were prepared with skimmed milk. In this study, anti-inflammatory and analgesic effects of these formulations were investigated in comparison to the plain drug itself employing hind paw edema test and Randall's analgesia test. Based on the data, it was determined that the drug maintained its pharmacological activity even after formulating in the form of physical mixture and solid dispersion.     

Hodgkin's type of Richter's syndrome in familial chronic lymphocytic leukemia treated with cladribine and cyclophosphamide

Second malignancies are frequent complications in patients with chronic lymphocytic leukemia (CLL). Hodgkin's disease (HD) has been observed in approximately 0.5% of the patients with CLL and is known as Hodgkin's type Richter's syndrome (H-RS). We present a 64-year-old male patient with a familial history of CLL who developed H-RS in abdominal lymph nodes 6 years after CLL diagnosis and 18 months after treatment with cladribine (2-CdA) and cyclophosphamide. HD was diagnosed by fine needle aspiration. The disease was refractory to treatment with two courses of CHOP and three courses of ABVD chemotherapy. In the current literature we found case reports of only 6 patients with H-RS who were treated with fludarabine (FA) before transformation, and, to our knowledge the presented patient is the first to develop H-RS after treatment with 2-CdA combined with cyclophosphamide. He is also the first published patient with familial CLL in whom this complication developed.     

Evaluation of Certain Risk Factors for Lung Cancer in Cracow (Poland): A Case-Control Study

The relationship of lung cancer risk to cigarette smoking, occupational exposure, air pollution at permanent residence and usual frequency of consumption of fruits and vegetables was analysed in a case-control study in Cracow, Poland. The cases were 176 male lung cancer patients diagnosed in 1992-1994 with histological confirmation of the diagnosis, obtained from the population-based Cracow Cancer Registry, and 341 controls randomly selected from the general population. Classification of exposure to outside air pollution was based on measured level of total suspended particular matter and sulphur dioxide by particular districts of town (from 1973 to 1980). Except calculation of odds ratios for male lung cancer associated with exposures among all study subjects, the association between lung cancer risk and frequency of consumption of fruit and vegetables was examined among drinkers of vodka above average. Risk of lung cancer was increased significantly with increasing number of pack-years of smoking (OR = 18.7 for more than 40 pack-years). The significant inverse association of frequent usual consumption of boiled vegetables was present both among all subjects and among vodka drinkers (OR = 4.6 and 12.5, respectively, for a rare consumption). The risk of male lung cancer was negatively associated with the level of air pollution but positively with the percentage of occupationally exposed. Our study provides no evidence of a significant harmful effect of air pollution and found a strong inverse association between frequent fruit and vegetables consumption and lung cancer risk.     

Fatty acids and selected endocannabinoids content in cerebrospinal fluids from patients with neuroinfections

Neuroinfections are a significant medical problem and can have serious health consequences for patients. Their outcome, if not fatal, can be associated with permanent residual deficits. Cerebrospinal fluid (CSF) examination is commonly used for meningitis confirmation. Fatty acids (FA) are precursors of lipid mediators with pharmacological activity. They actively modulate inflammation as well as contribute to its resolution. Therefore the aim of this study was to determine the FA and selected endocannabinoids (ECB) content in the CSF obtained from patients with bacterial (BM) and viral meningitis (VM) using chromatographic techniques. A significantly lower level of saturated FA was found in patients with BM and VM as compared to controls. There was a significantly higher concentration of long-chain monounsaturated FA and polyunsaturated n-6 FA in the CSF obtained from patients with neuroinfection. Moreover, a significant reduction of n-3 FA in CSF obtained from patients with BM and VM was demonstrated. The highest amount of ECB was detected in the CSF of patients with VM: eicosapentaenoyl ethanolamide (1.65 pg/mL), docosahexaenoyl ethanolamide (655.5 pg/mL) and nervonoyl ethanolamide (3.09 ng/mL). Results indicate the participation of long-chain monounsaturated and polyunsaturated FA and their derivatives in the inflammatory process and likely in the process of resolution of inflammation during neuroinfection. It seems that the determination of the FA and ECB profile in CSF may be a valuable biomarker of health and may allow the development of new pharmacological strategies, therapeutic goals and fatty acids supplementation necessary in the fight against inflammation of the central nervous system.

     

The N363S and I559N single nucleotide polymorphisms of the h-GR/NR3C1 gene in patients with bronchial asthma

Bronchial asthma is a disease of multifactorial etiology. The natural variability of the DNA sequence within the h-GR/NR3C1 gene affects both the conformation and the activity of glucocorticoid receptors. There are 2 major types of resistance to glucocorticoids (GCS)-resistant asthma failing to respond to treatment with high doses of inhaled and oral glucocorticoids. Type I GCS-resistant asthma is cytokine-induced or acquired. Type II GCS resistance involves generalized primary cortisol resistance, which affects all tissues and is likely to be associated with a mutation in the glucocorticoid receptor (GCR) gene or in genes that modulate GCR function. There are clear examples of glucocorticoid gene h-GR/NR3C1 polymorphisms that can influence responses and sensitivity to glucocorticosteroids. Among the numerous polymorphisms observed within this gene, N363S and I559N single nucleotide polymorphisms (SNPs) may play an important role in the development of bronchial asthma and in the alteration of sensitivity to GCS in severe bronchial asthma. The aim of this research project was to study the correlation between the N363S and I559N polymorphisms of the h-GR/NR3C1 gene and the occurrence of asthma in a population of Polish asthmatics. Peripheral blood was obtained from 210 healthy volunteers and 234 asthma patients. Structuralized anamnesis, spirometry and allergy skin prick tests were performed in all participants. Genotyping was carried out using the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) and PCR-HRM methods. In the healthy, non-atopic population, the GG variant of the N363S polymorphism was found with a 5.7% frequency. In asthma patients, GG SNP of N363S occurred with the frequency of 6.4%. In the groups of patients with uncontrolled moderate asthma and uncontrolled severe disease, the genotype distribution for the investigated polymorphisms were as follows: N363S, AA, AG, GG occurring with 0.8750/0.0834/0.0416 frequency and I559N, TT, TA, AA occurring with 1.000/0.000/0.000 frequency. The analysis demonstrated a significantly higher frequency of the A and G variants of the N363S polymorphisms in uncontrolled moderate asthma and uncontrolled severe disease than in the healthy population. No variant-related differences in the frequency of the studied I559N polymorphism were demonstrated in healthy controls and asthma patients. In conclusion, the N363S polymorphism of the h-GR/NR3C1 gene is significantly associated with an increased sensitivity to glucococorticoids in vivo and susceptibility to the development of a moderate to severe form of uncontrolled bronchial asthma in the Polish population. This observation needs to be confirmed in a larger group of subjects.     

N,N'-methyleno-didemnin A from the ascidian Trididemnum solidum. Complete NMR assignments and confirmation of the imidazolidinone ring by strategic analysis of 1J(CH)

The complete NMR assignments of N,N'-methyleno-didemnin A from Trididemnum solidum Van Name 1902 are reported along with a strategic analysis of (1)J(CH) coupling constants that confirm the presence of the imidazolidinone ring.