Verification of the authenticity of drugs by means of NMR relaxometry-Viagra® as an example.

1H spin-lattice Nuclear Magnetic Resonance (NMR) relaxometry, vibrational spectroscopy and Atomic Force Microscopy (AFM) have been applied to differentiate between original and counterfeit Viagra®. The relaxation studies have been performed in a frequency range covering four orders of magnitude, from 4kHz to 40MHz. It has been shown that for the counterfeit product the relaxation is bi-exponential in the whole frequency range, while for the original Viagra® the relaxation process is always single exponential. Thus, even a qualitative analysis of the relaxation data makes it possible to identify the falsified medicine. Moreover, it has been demonstrated that vibrational spectroscopy does not allow for differentiating between the products, while AFM studies are likely to lead one to deceptive conclusions regarding the originality of the medicine. Furthermore, a quantitative analysis of the relaxation data has been performed to describe in detail the relaxation properties of the original and falsified products.

Sympathovagal balance fluctuates during colonoscopy.

BACKGROUND AND STUDY AIM: Colonoscopy is a common gastroenterological procedure for investigation of the bowel. The main side effects of colonoscopy are pain during investigation, cardiovascular complications and very rarely even death. The aim of this study was to compare the continuous fluctuation of heart rate variability (HRV) components during colonoscopy under normal conditions, analgesia/sedation, and total intravenous anesthesia. PATIENTS AND METHODS: 37 consecutive patients (aged 35 - 65), were randomly allocated to three groups: no sedation (control group 1); analgesia/sedation (group 2); and total intravenous anesthesia (group 3). Holter electrocardiography and subsequent frequency domain analysis were undertaken. The low-frequency (LF, 0.04 - 0.15 Hz) and the high-frequency (HF, 0.15 - 0.40 Hz) components were estimated using spectral analysis in the usual way. Normalized units (nu) were calculated from the following equations: LFnu = LF/(LF + HF), and HFnu = HF/(LF + HF). RESULTS: Groups 2 and 3 were found to have a significantly lower HFnu and higher LFnu than group 1 essentially throughout the procedure. A one-way analysis of variance and t-test confirmed that the differences were significant when the colonoscope reached the splenic flexure as were the LF/HF balances at the splenic and hepatic flexures and the cecum. The percentage change in LF/HF was also analyzed, and it was found that in group 3 the mean change was over 136 % when the colonoscope reached the sigmoid flexure, which was significantly higher than in the other two groups. CONCLUSION: Most changes in HRV components occurred during colonoscopy of the left side of the bowel. Analgesia/sedation and total intravenous anesthesia increased HRV by increasing the LF component.

Reduction of CD45RA isoform expression and decrease in CD4 and CD8 receptor density in lymphocytes of patients with primary biliary cirrhosis.

BACKGROUND: The immunological background of primary biliary cirrhosis (PBC) remains largely obscure. METHODS: Using double colour flow cytometry, we estimated the distribution of functionally different lymphocyte subpopulations in the peripheral blood of 25 PBC patients and 18 controls. We examined: 1) the expression of CD3, CD4, CD8, CD19 and CD56 surface receptors, 2) the distribution of lymphocyte subsets bearing 'naive' (CD45RA+) and 'memory' (CD45RO+) phenotypes in both CD4+ and CD8+ cell populations, 3) the expression of an early activation marker (CD69), 4) the distribution of C1.7 mAb binding cytotoxic effectors in CD3+, CD8+ and CD56+ cells. The surface marker expression was evaluated in terms of percentage of positive cells and receptor density. RESULTS: We found: 1) a decrease in the percentage of total CD3+ and CD4+ cells, an unchanged proportion of CD8+ cells but elevated proportion of CD19+ cells and NK lymphocytes; 2) a reduction in the percentage of 'naive' CD4+ but normal proportion of 'naive' CD8+ as well as CD4+ and CD8+ 'memory' cell subsets; 3) a decrease in the density of CD4 and CD8 receptors in the subsets of 'naive' and 'memory' T cells, 4) an increase in the percentage of CD69 receptor bearing T cells but unchanged proportion of C1.7 mAb. CONCLUSIONS: It is concluded that the reduction in number of 'suppressor-inducer-like 'naive' CD4+ T-cell subsets in association with the decrease in fluorescence intensity for CD4 and CD8 may significantly contribute to the mechanisms that could account for a development of PBC.

Reduction of CD45RA Isoform Expression and Decrease in CD4 and CD8 Receptor Density in Lymphocytes of Patients with Primary Biliary Cirrhosis.

BACKGROUND: The immunological background of primary biliary cirrhosis (PBC) remains largely obscure. METHODS: Using double colour flow cytometry, we estimated the distribution of functionally different lymphocyte subpopulations in the peripheral blood of 25 PBC patients and 18 controls. We examined: 1) the expression of CD3, CD4, CD8, CD 19 and CD56 surface receptors, 2) the distribution of lymphocyte subsets bearing 'naive' (CD45RA+) and 'memory' (CD45RO+) phenotypes in both CD4+ and CD8+ cell populations, 3) the expression of an early activation marker (CD69), 4) the distribution of C1.7 mAb binding cytotoxic effectors in CD3+, CD8+ and CD56+ cells. The surface marker expression was evaluated in terms of percentage of positive cells and receptor density. RESULTS: We found: 1) a decrease in the percentage of total CD3+ and CD4+ cells, an unchanged proportion of CD8+ cells but elevated proportion of CD 19+ cells and NK lymphocytes; 2) a reduction in the percentage of 'naive' CD4+ but normal proportion of 'naive' CD8+ as well as CD4+ and CD8+ 'memory' cell subsets; 3) a decrease in the density of CD4 and CD8 receptors in the subsets of 'naive' and 'memory' T cells, 4) an increase in the percentage of CD69 receptor bearing T cells but unchanged proportion of C1.7 mAb. CONCLUSIONS: It is concluded that the reduction in number of 'suppressor-inducer-like 'naive' CD4+ T-cell subsets in association with the decrease in fluorescence intensity for CD4 and CD8 may significantly contribute to the mechanisms that could account for a development of PBC.

Lymphocyte subsets in peripheral blood and bronchoalveolar lavage in patients with primary biliary cirrhosis.

BACKGROUND: The objective of this study was to examine the hypothesis that total blood and bronchoalveolar lavage (BAL) lymphocytes and their subsets in patients with primary biliary cirrhosis (PBC) with coexistent alveolitis are different from those in patients with PBC alone. Total blood and BAL lymphocytes and their subsets were evaluated in both types of patients and compared with a control group of normal healthy subjects. MATERIAL AND METHODS: 17 patients with well-documented PBC were divided into two groups: Group A--patients with coexisting alveolitis and Group B--patients with no alveolitis. Diagnosis was based on bronchoalveolar lavage. The control group consisted of healthy subjects. The lymphocyte subsets, including CD3, CD4, CD8, CD20 and CD56 were identified in blood and BAL cytospin smears using specific monoclonal antibodies. RESULTS: The percentage of CD3 and CD8 lymphocytes in BAL was significantly lower in a Group A, whereas the percentage of NK was significantly increased in group B as compared with the reference group. The percentage of blood CD4 lymphocytes in both subgroups of the PBC patients was significantly decreased as compared with the controls. The percentage of NK in both groups was significantly increased as compared with the controls. CONCLUSIONS: The relationship between the blood and BAL lymphocyte subsets in both studies groups were similar. Therefore, we suggest that PBC is a systemic disease in which lymphocytic infiltrations are not limited to the liver but may also involve lungs and probably other organs.

Cardiac sympathovagal balance during endoscopic retrograde cholangiopancreatography.

BACKGROUND AND STUDY AIMS: Cardiopulmonary complications have been reported during upper gastrointestinal endoscopy and endoscopic retrograde cholangiopancreatography (ERCP). The aim of this study was to evaluate the sympathovagal response to the stretching of the common bile duct caused by contrast medium injection during ERCP. PATIENTS AND METHODS: The 16 patients included in the study were assigned to two groups according to the size of common bile duct. Group A consisted of patients with normal-sized bile ducts, while Group B patients had dilated common bile ducts. The heart rate variability (HRV) technique was used to assess the sympathovagal balance. The HRV data were gathered using the Holter technique, and frequency domain analysis revealed two main spectral components of HRV: low frequency (LF) and high frequency (HF). RESULTS: In patients with normal-sized bile ducts, contrast injection initiated a rapid increase in the power spectra (ms2) of both the HF and LF components. In patients with dilated common bile ducts, this phenomenon was not observed. CONCLUSIONS: During ERCP, contrast injection into a dilated common bile duct does not stimulate the autonomic nervous system in the same way as it does when the common bile duct is of normal size.

[Peroxisomes and peroxisomal diseases]. / Peroksysomy i choroby peroksysomalne.

This paper is on peroxisomes ("microbodies") dealing with various aspects of their physiological significance including the central question of biogenesis of peroxisomes. Attention is also focused on how peroxisomes are involved in human pathology and the so-called peroxisomal diseases are described.