New insights on P2X purinoceptors

Significant advances in understanding of P_2X purinoceptor pharmacology have been made in the last few years. The limitations of nucleotide agonists as drug tools have now been amply demonstrated. Fortunately, inhibitors of the degrading ecto-ATPase enzymes are becoming available and it has become apparent that the complete removal of all divalent cations can be used experimentally in some systems to prevent nucleotide breakdown. Despite these issues, convincing evidence for P_2X receptor heterogeneity, from data with agonists, has recently been reported.A number of new antagonists at P_2X purinoceptors have also recently been described which to some degree appear to be more specific and useful than earlier antagonists like suramin. It is now apparent that suramin is a poor antagonist of ATP in many tissues because it potently inhibits ATPase activity at similar concentrations to those at which it blocks the P_2X purinoceptor.Advances in the use of radiolabelled nucleotides as radioligands for binding studies has allowed the demonstration of P_2X purinoceptors in a variety of tissues throughout the body including the brain. These studies have also provided evidence for receptor heterogeneity. Excitingly, two P_2X purinoceptor genes have been cloned but operational studies suggest that more than two types exist. The cloning studies have also demonstrated a unique structure for the P_2X purinoceptor which differentiates it from all other ligand-gated ion channel receptors. Further studies on P_2X purinoceptor operation and structure are needed to help resolve controversies alluded to regarding the characterization and classification of nucleotide receptors. Hopefully such studies will also lead to a better understanding of the physiological and pathological importance of ATP and its activation of P_2X purinoceptors. This will require the identification of better drug tools, in particular antagonists which may also provide the basis for novel therapeutic agents.     

MHC class II (I-A) region control of the IgE antibody repertoire to the ABA-1 allergen of the nematode Ascaris

ABA-1 is an approximately 14,000 molecular weight (MW) allergen which is among the most abundant proteins synthesized by the nematode parasite Ascaris. IgG and IgE responses to it are major histocompatibility complex (MHC)-restricted in rodents and have only been found to occur in rats of the RT1u haplotype and mice of the H-2s haplotype. Humans infected with the parasite vary substantially in their immune response to the allergen, but the genetic basis for this unknown. H-2 recombinant mice were used to identify the region within the MHC controlling antibody responses to the allergen. IgG antibody to immunoaffinity purified ABA-1 was assayed by radio-immunoassay and IgE by passive cutaneous anaphylaxis. This showed that the restriction element is the I-A molecule and that there was some evidence for I-E modulation of the level of response.     

A model for the prediction of osmolalities of modular formulas

A model is proposed for evaluation of osmolality of multicomponent formulas composed of modular ingredients. Nonlinear curve-fitting techniques applied to empirical data result in prediction of the osmolality of ingredients for any concentration desired. Osmolality of a multicomponent formula can be obtained by adding osmolalities of ingredients. Data handling is made possible by the use of simple microcomputer programs. The model is tested with products available for construction of amino acid-restricted diets.     

Calcium phosphate in catheter encrustation

Encrusted catheters from nine female patients were the source of samples of deposits which were examined by X-ray diffraction, atomic absorption spectroscopy, infra-red spectroscopy and extended X-ray absorption fine structure (EXAFS) spectroscopy. In eight samples the only crystalline phase which could be clearly distinguished by X-ray diffraction was ammonium magnesium orthophosphate hexahydrate, NH4MgPO4 X 6H2O, which occurs naturally as the mineral struvite. However, atomic absorption spectroscopy revealed an appreciable concentration of calcium in all samples. Calcium phosphates have previously been detected in catheter deposits. Infra-red and EXAFS spectra were consistent with the calcium phosphate being present as a poorly crystalline hydroxyapatite. Thus the deposits appear to consist of a mixture of crystalline struvite and a form of hydroxyapatite which is not fully crystalline.     

Changes in Escherichia coli resistance to co-trimoxazole in tuberculosis patients and in relation to co-trimoxazole prophylaxis in Thyolo,Malawi

In Thyolo district, Malawi, an operational research study is being conducted on the efficacy and feasibility of co-trimoxazole prophylaxis in preventing deaths in HIV-positive patients with tuberculosis (TB). A series of cross-sectional studies were carried out to determine i) whether faecal Escherichia coli (E.coli) resistance to co-trimoxazole in TB patients changed with time and ii) whether the resistance pattern was different in HIV positive TB patients who were taking co-trimoxazole prophylaxis. Co-trimoxazole resistance among E.coli isolates in TB patients at the time of registration was 60% in 1999 and 77% in 2001 (p<0.01). Resistance was 89% among HIV-infected TB patients (receiving co-trimoxazole), while in HIV negative patients (receiving anti-TB therapy alone) it was 62% (p<0.001). The study shows a significant increase of E.coli resistance to co-trimoxazole in TB patients which is particularly prominent in HIV infected patients on co-trimoxazole prophylaxis. Since a high degree of plasmid-mediated transfer of resistance exists between E.coli and the Salmonella species, these findings could herald limitations on the short and long term benefits to be anticipated from the use of co-trimoxazole prophylaxis in preventing non-typhoidal salmonella bacteraemia and enteritis in HIV infected TB patients in Malawi.     

A review of intra-articular knee injuries in racquet sports diagnosed by arthroscopy

Because of the recent rapid increase in the number of knee injuries related to racquet sports, the authors undertook a retrospective study of such injuries seen over a 5-year period at the Toronto Western Hospital Sports Medicine Institute. The 121 patients who presented over the study period with a racquet-sports-related knee injury requiring arthroscopy represented 30% of all racquet-sports related injuries seen during that period. The mean age at presentation was 32.8 years and two-thirds of the patients were men. All the major racquet sports were represented. In all, 213 lesions (7 bilateral) were seen at 128 arthroscopies, and 165 arthroscopic procedures were performed. The most common lesion was meniscal followed by chondromalacia patellae, anterior cruciate ligament tears, chondral lesions and pathologic plicae. Over 90% of the patients returned to their chosen racquet sport within 3 months of the arthroscopy and most were playing at a similar performance level to that before the initial injury.