Ureaplasma urealyticum induces apoptosis in human lung epithelial cells and macrophages

Chronic lung disease (CLD) of prematurity remains a significant cause of morbidity among premature infants. It is a multifactorial disorder and characterized by an early increased number of neutrophils and alveolar macrophages, with later architectural epithelial and endothelial cell damage. Recently, apoptosis of type 2 pneumocytes in the lung of preterm neonates with acute and chronic lung disease has been examined and apoptosis of mesenchymal cells was detected in the chronic stage of bronchopulmonary dysplasia. Infection and inflammatory responses in the lungs play important roles. However, the contribution of Ureaplasma urealyticum to the development of CLD is debated. We found that U. urealyticum induced apoptosis in human type II lung epithelial cells (A549 cell line) and macrophages (derived from human monocytic cell line THP-1) by measuring the outer leaflets translocation of phosphatidylserine (flow cytometry analysis and fluorescence microscopy assessment), DNA fragmentation analysis, cell morphology changes such as diminution in cell volume, increased cytoplasmic staining, and nuclear pyknosis (hematoxylin and eosin staining) and viable counting (trypan blue exclusion). Anti-TNF-alpha monoclonal antibody partially protected the macrophages from undergoing apoptosis after infection with U. urealyticum. Our findings imply that U. urealyticum might be involved in impairing lung structure and host immune response during the development of CLD.     

Time for a "vision zero" concerning premature death from ischaemic heart disease?

OBJECTIVE: To study the trend in premature mortality (before 75 years of age) from ischaemic heart disease (IHD) in a Swedish primary health care district compared to communities of similar demographic situation and all Sweden. DESIGN: Mortality from IHD in men and women was compared between the community of Habo and other Swedish communities of similar size and all Sweden for the period 1984-96. SETTING: The community of Habo in Sweden with about 9600 inhabitants. INTERVENTION: Intensified efforts by the local primary health care organisation, in co-operation with the community, in respect of primary and secondary cardiovascular prevention since the beginning of the 1980s. RESULTS: Mortality from IHD has decreased significantly both in Habo and in Sweden during these years. The decrease has been more prominent in Habo than in Sweden as a whole and other Swedish communities of similar demographic situation. CONCLUSION: With increased and purposeful efforts in primary and secondary prevention, in co-operation between the community and primary health care, it is possible to substantially decrease mortality from IHD in the community.     

Spinal substance P release in vivo during the induction of long-term potentiation in dorsal horn neurons

Long-term potentiation (LTP) in wide dynamic range (WDR) neurons in the dorsal horn has been suggested to contribute to central sensitization and the development of chronic pain. Indirect experimental evidence indicates an involvement of substance P (SP), in this respect. The aim of the present study was to monitor the extracellular level of substance P-like immunoreactivity (SP-LI) in the dorsal horn of the rat during and after induction of LTP in WDR neurons in vivo. Electrophysiological recordings of single (WDR) neurons were performed in parallel with microdialysis in the dorsal horn under urethane-anaesthesia. The amount of SP-LI in the microdialysate was determined by radioimmunoassay. As previously shown, high frequency conditioning stimulation of the sciatic nerve induced an increased firing response of WDR neurons. An increased response to C-fibre stimulation, but not A-fibre stimulation, could be determined. A significant increase of the extracellular level of SP-LI in the dorsal horn was detected during, but not after, induction of LTP. These data suggest that SP may be involved in the induction of LTP by high frequency stimulation. However, the maintenance of spinal LTP following high frequency peripheral nerve stimulation does not seem to depend on an increased release of SP.     

Quantification of breast tumor microvascular permeability with feruglose-enhanced MR imaging: initial phase II multicenter trial

PURPOSE: To investigate use of the macromolecular contrast agent feruglose for differentiating and grading of human benign and malignant breast tumors on the basis of their microvascular characteristics. MATERIALS AND METHODS: Sixty-three women with 63 primary breast lesions were examined with dynamic T1-weighted gradient-echo magnetic resonance (MR) imaging after intravenous injection of feruglose. A two-compartment unidirectional kinetic model applied to the dynamic data yielded estimates of the endothelial transfer coefficient, KPS, and the fractional plasma volume of the tumors. These MR imaging-derived parameters were correlated with the histologic tumor grade and quantified according to the Scarff-Bloom-Richardson (SBR) score by means of Pearson product moment correlation analyses. Differences between malignant and nonmalignant breast lesions with respect to KPS for feruglose were evaluated by means of the chi2 test and by calculating the sensitivity, specificity, and positive and negative predictive values. RESULTS: Histologic analysis revealed 26 benign and 37 malignant tumors. A moderate yet statistically significant correlation between KPS and SBR score was found (R = 0.496, P <.001). No significant correlation was observed between fractional plasma volume and SBR score (R = 0.085, P =.507). The KPS values were zero for 19 (73%) of the 26 benign tumors and were greater than zero for 27 (73%) of the 37 carcinomas. This distribution was significantly different (chi2 = 13.035, P =.001). With the criterion KPS > 0 in carcinomas, sensitivity was 0.73, specificity was 0.73, and the positive predictive value was 0.79. CONCLUSION: Quantitative measures of tumor microvascular permeability can be used for breast tumor characterization. The probability of breast tumor microvascular hyperpermeability to be associated with malignancy is 79%.     

How to promote prevention--economic incentives or legal regulations or both?

Legal regulations of the work environment are probably regarded as the main tools for promoting prevention at the workplace. Legal regulations are expressed as occupational exposure limits, bans, and taxes. Taxes can be regarded as economic incentives as well, and other economic incentives are insurance systems for employers' and consumers' actions. The latter have been found to have profound effects regarding environmental issues and may also, in the future, be a powerful tool for workplace-related prevention. The research in this area is rather limited, but there are some research results that can be obtained from the area of environmental economics. This paper discusses some examples in which legal regulations, economic incentives, or both have been used. Legal regulations and market-based economic incentives may produce similar results, but the economic cost and political feasibility typically differ. This situation makes the selection and design of instruments an important field for future research.     

Pediatric excretory MR urography: comparative study of enhanced and non-enhanced techniques

Our purpose was to compare the quality of ureteral imaging in pediatric patients using two different MR sequences: the non-enhanced heavily T2-weighted (W) turbo spin-echo sequence (TSE) and the gadolinium-enhanced T1W fast-field-echo sequence (T1 FFE). An experimental study on three pigs was first performed. The TSE, before and after furosemide injection, was followed by the T1 FFE sequence. The clinical study included 11 infants and 10 children. With some modifications the same MR parameters and techniques were used as in the animal study. The TSE with TR 8000 ms and TE 650 ms implied 6 radial stacks each of 40 mm thickness. The T1 FFE included TR 18 ms, TE 2.9 ms, flip angle 60 , and 50 slices with thickness 0.7 mm. After post-processing, image reconstructions qualitative and quantitative analysis were performed. Complete visualization of the ureters was achieved in 35 of 42 (83%) cases. Seventy-four percent of the ureters were completely visualized with T1 FFE compared with only 19% with TSE. Sixty-nine percent of the ureters were better imaged with T1 FFE than TSE and 21% equally well imaged. Four ureters (10%), either obstructed or due to poor renal function, were better imaged with TSE. The two sequences are complementary. Visualization of non-obstructed ureters is excellent with T1 FFE and the sequence is superior to TSE. The TSE, however, may be equal to or even better than T1 FFE in visualizing obstructed ureters or ureters draining malfunctioning kidneys. Electronic Publication     

Perception of dental fluorosis among adolescents living in urban areas of Ethiopia

The objective of the study was to assess the perception of dental fluorosis among adolescents residing in two urban areas in Ethiopia: Addis Ababa (low-fluoride drinking water) and Nazreth (high-fluoride drinking water). Students aged 12-15 years, enrolled in two junior secondary schools in Addis Ababa (n = 161) and two similar schools in Nazreth (n = 177) responded to evaluative statements concerning the appearance of anterior maxillary teeth. Color photographs depicting dental fluorosis (TF score 2, 3, 5 and 7) in maxillary front teeth were used as reference during structured interviews. A majority of the students from Addis Ababa and Nazreth were dissatisfied with the appearance of teeth having TF scores 2 and above. More than 66% of the students from both areas confirmed a need for dental consultation concerning fluorotic teeth with TF > or = [corrected] 2. As compared to their counterparts in Nazreth, children in Addis Ababa felt more embarrassed with TF score 2 and 3 (p < 0.01). TF scores 5 and 7 were found unacceptable both in Addis Ababa and in Nazreth. Students in Addis Ababa, more frequently than their counterparts in Nazreth, believed (erroneously) that dental fluorosis were related to neglect on the part of the child. The present findings confirm that fluorotic teeth constitute a social problem among junior secondary school children residing in low-fluoride as well as in high-fluoride urban areas in Ethiopia and, thereby, corroborate the public concern for safe drinking water.     

Molecular mechanisms and therapeutical implications of intramembrane receptor/receptor interactions among heptahelical receptors with examples from the striatopallidal GABA neurons

The molecular basis for the known intramembrane receptor/receptor interactions among G protein-coupled receptors was postulated to be heteromerization based on receptor subtype-specific interactions between different types of receptor homomers. The discovery of GABAB heterodimers started this field rapidly followed by the discovery of heteromerization among isoreceptors of several G protein-coupled receptors such as delta/kappa opioid receptors. Heteromerization was also discovered among distinct types of G protein-coupled receptors with the initial demonstration of somatostatin SSTR5/dopamine D2 and adenosine A1/dopamine D1 heteromeric receptor complexes. The functional meaning of these heteromeric complexes is to achieve direct or indirect (via adapter proteins) intramembrane receptor/receptor interactions in the complex. G protein-coupled receptors also form heteromeric complexes involving direct interactions with ion channel receptors, the best example being the GABAA/dopamine D5 receptor heteromerization, as well as with receptor tyrosine kinases and with receptor activity modulating proteins. As an example, adenosine, dopamine, and glutamate metabotropic receptor/receptor interactions in the striatopallidal GABA neurons are discussed as well as their relevance for Parkinson's disease, schizophrenia, and drug dependence. The heterodimer is only one type of heteromeric complex, and the evidence is equally compatible with the existence of higher order heteromeric complexes, where also adapter proteins such as homer proteins and scaffolding proteins can exist. These complexes may assist in the process of linking G protein-coupled receptors and ion channel receptors together in a receptor mosaic that may have special integrative value and may constitute the molecular basis for some forms of learning and memory.     

Expression of somatostatin receptor subtypes 1 to 5 in tumor tissue and intratumoral vessels in malignant endocrine pancreatic tumors

Somatostatin analogs are well established in the treatment of malignant endocrine pancreatic tumors (EPTs). Our goal is to individualize their treatment using receptor-subtype-specific analogs and, therefore, exploring the receptor expression is highly important. We have examined the expression of somatostatin receptor (sst) subtypes 1–5 on tumor cells and in intratumoral vessels in 28 tumor tissues from malignant EPTs with immunohistochemistry using sst-subtype-specific polyclonal antibodies. We found that sst₂ and sst₄ stained positive in 90% and sst₁ in 70% of the tumor tissues, whereas sst₃ and sst₅ stained positive in only 50% of the tumor tissues. Sst expression in intratumoral vessels was high for sst₂ and sst₄ (80%), moderate for sst₁ (40%), and low for sst₃ and sst₅ (10%). The ssts were evenly distributed among the different tumor subtypes. However, tumors belonging to the same subgroup of EPTs showed a variable expression of receptor subtypes. No differences in receptor-subtype expression could be seen between poorly and well-differentiated tumors, nor between primary tumors and metastases. Prior medical treatment did not influence sst expression pattern. In conclusion, sst₂ and sst₄ were expressed in most tumor tissues and intratumoral vessels from EPTs. However, sst₃ and sst₅ were lacking in half of the tumor tissues and in most of the intratumoral vessels. These differences indicate the importance of determining each tumor’s subset of receptors before treatment with receptor-subtype-specific analogs is initiated. The importance of sst expression in intratumoral vessels is not yet known.