MIF, CD74 and other partners in kidney disease: tales of a promiscuous couple.

Macrophage migration inhibitory factor (MIF) is increased in kidney and urine during kidney disease. MIF binds to and activates CD74 and chemokine receptors CXCR2 and CXCR4. CD74 is a protein trafficking regulator and a cell membrane receptor for MIF, D-dopachrome tautomerase (D-DT/MIF-2) and bacterial proteins. MIF signaling through CD74 requires CD44. CD74, CD44 and CXCR4 are upregulated in renal cells in diseased kidneys and MIF activation of CD74 in kidney cells promotes an inflammatory response. MIF or CXCR2 targeting protects from experimental kidney injury, CD44 deficiency modulates kidney injury and CXCR4 activation promotes glomerular injury. However, the contribution of MIF or MIF-2 to these actions of MIF receptors has not been explored. The safety and efficacy of strategies targeting MIF, CD74, CD44 and CXCR4 are under study in humans.

[Anesthetic treatment of patients with osteogenesis imperfecta]. / Experiencia en el tratamiento anestésico de los pacientes afectos de osteogénesis imperfecta.

BACKGROUND AND OBJECTIVE: Although the prevalence of osteogenesis imperfecta is low, the effect of this hereditary disease on patients' quality of life is considerable. We report our experience in the perioperative management of patients with this condition in our hospital. PATIENTS AND METHODS: Retrospective study describing the interventions on patients with this disease in our hospital from 1991 to 2009. We analyzed demographic data, disease variants, concomitant disorders, surgical procedures, type of anesthesia, and intraoperative and postoperative complications. RESULTS: From 1991 to 2009, 105 procedures were performed on 29 patients (ages 1 to 25 years) with osteogenesis imperfecta (37.9% women and 62.1% men). The most common type of osteogenesis imperfecta was type III (65.5%). Most patients (93%) had no associated diseases. Two patients were allergic to latex. No complications occurred in 62% of interventions. Reported complications during surgery were 1 case of non-malignant hyperthermia and 1 contralateral femur fracture. CONCLUSIONS: The prevalence of osteogenesis imperfecta is low. Treatment requires a multidisciplinary approach, in which appropriate perioperative management must be based on a proper understanding of the skeletal and extraskeletal abnormalities associated with this disease.

[Transcriptomics illustrate a deadly TRAIL to diabetic nephropathy]. / La transcriptómica ilustra nuevas vías letales en la nefropatía diabética.

Diabetic nephropathy is the most common cause of endstage renal disease. Approaches targeting angiotensin II significantly delay its progression. However, many patients still need renal replacement therapy. High throughput techniques such as unbiased gene expression profiling and proteomics may identify new therapeutic targets. Cell death is thought to contribute to progressive renal cell depletion in chronic nephropathies. A European collaborative effort recently applied renal biopsy transcriptomics to identify novel mediators of renal cell death in diabetic nephropathy. Twenty-five percent of cell death regulatory genes were upor downregulated in diabetic kidneys. TNF-related apoptosisinducing ligand (TRAIL) and osteoprotegerin had the highest level of expression. In diabetic nephropathy, tubular cells and podocytes express TRAIL. Inflammatory cytokines, including MIF via CD74, upregulate TRAIL. A high glucose environment sensitized renal cells to the lethal effect of TRAIL, while osteoprotegerin is protective. These results suggest that, in addition to glucose levels, inflammation and TRAIL are therapeutic targets in diabetic nephropathy.

[A study on anti-infective agent self-medication in 2 pharmacy offices]. / Estudio sobre automedicación de antiinfecciosos en dos oficinas de farmacia.

OBJECTIVE: To describe and analyse the demand for unprescribed drugs against infections in two pharmacy departments, as a first step towards constructing closer cooperation between primary care physicians, chemists from the pharmacy service and chemists from a pharmacy department. DESIGN: A descriptive and prospective study based on observation. SITE. This study was carried out at two pharmacy departments: the Embajadores Health Centre and the pharmacy service of the hospital to which patients were referred from Embajadores. PATIENTS AND PARTICIPANTS: The target population were all those patients who requested a drug to combat infection in the pharmacy departments during the six months of the study (July to December, 1991). MAIN MEASUREMENTS AND RESULTS: A total of 186 requests without a prescription for drugs to combat infection was recorded. The profile of those so requesting was of an almost equal number for men and women between 31 and 50 years old. The main reasons behind the requests were throat, dental and urinary-genital infections. The consumption of drug per category of illness was, from greater to lesser, penicillin, sulfamides, urinary chemotherapies, tetracyclines, macrolides and cephalosporins. CONCLUSIONS: Although there appears to be consistency between the drug infection requested and the reason for requesting it, some health education activities aimed at the general population need to be organised, in order to raise awareness of the use and abuse of antibiotics.

Glyoxylic compounds as radiosensitizers of hypoxic cells.

The radiosensitizing effect of five glyoxal derivatives on the survival of TC-SV40 cells has been measured, under aerobic and hypoxic conditions. A toxicity study was previously performed in order to use nontoxic concentrations. The OER for the TC-SV40 cells was 2.74. None of the glyoxylic compounds showed radiosensitizing activity under aerobic conditions while in hypoxia their radiosensitizing factors decreased in the order phenylglyoxylic acid (1.68 at 8 x 10(-3) mole dm-3) greater than phenylglyoxal (1.55 at 5 x 10(-6) mole dm-3) greater than 2-2' furil (1.48 at 5 x 10(-5) mole dm-3) greater than glyoxylic acid (1.39 at 1 x 10(-3) mole dm-3) greater than glyoxal (1.30 at 5 x 10(-5) mole dm-3). The dose-modifying factors were also determined at two equimolar concentrations 5 x 10(-5) and 5 x 10(-6) mole dm-3. A concentration effect was noticed for all the compounds although their relative radiosensitizing activity kept, independently of the concentration, the same order noted above. Glyoxals with aromatic or heterocyclic rings exert a greater radiosensitization than the others. The acidic compounds have less radiosensitizing activity than their aldehydic counterparts. Interaction of these glyoxals with NPSH cellular groups was tested and the low degree of inhibition shows that this mechanism would contribute very little, if any, to the radiosensitization effect.

Radiosensitization by quaternary salts of 5-nitroimidazole derivatives.

The radiosensitizing effects of five newly synthesized quaternary salts of 5-nitroimidazole derivatives on the survival of TC-SV40 mammalian cells have been measured. A toxicity study was carried out in order to determine the concentrations to be used in the radiosensitizing experiments. The oxygen enhancement ratio (OER) for TC-SV40 cells was 2.74. None of the five 5-nitroimidazole derivatives showed radiosensitizing activity in aerobic conditions, while in hypoxia their dose-modifying factors (DMF) at the concentration of 0.2 mmol dm-3 range from 1.52 to 1.03 in this order: unsubstituted pyridinium greater than carbamoyl pyridinium greater than trimethyl pyridinium greater than t-butyl pyridinium greater than imidazolium. This latter product at the concentration of 2 mmol dm-3 has a DMF of 1.64. As comparison, metronidazole was also tested on this cell line and its DMF at 0.2 mmol dm-3 was 1.35. The response-concentration dependences for the unsubstituted pyridinium 5-nitroimidazole derivative and for metronidazole (comparing charged and uncharged structures) showed the flattening response-concentration curve of quaternary compounds. The electron affinity was evaluated through the CNDO/S theoretical method, and an exponential relationship between these values and the DMFs of the pyridinium derivatives was demonstrated.