The comparative metabolism of diisopropyl methylphosphonate in mink and rats

This study reports the metabolism of carbon-14labeled diisopropyl methylphosphonate (DIMP) in mink and rats, undertaken to better understand the dose-related mortality reported for mink in a previous study. In both male and female mink and rats, DIMP was rapidly absorbed after oral administration; it was metabolized by a saturable pathway to a single metabolite, isopropyl methylphosphonate (IMPA), which was rapidly excreted, primarily in the urine (90%). Fecal radioactivity, also identified as IMPA, was 1.7-3.1% of the administered dose. Female rats had a slower rate of conversion of DIMP to IMPA and less total excretion of IMPA than male rats. Metabolism of DIMP administered intravenously was not very different from that given orally in both species. These data indicate that mink absorb, metabolize, and excrete DIMP (as IMPA) in a manner very similar to mice, rats, and dogs.     

Extradural application of bismuth iodoform paraffin paste causing relapsing bismuth encephalopathy: a case report with CT and MRI studies

Bismuth iodoform paraffin paste (BIPP) is used in dressings in ear, nose, and throat, dental, and neurosurgical practice. Neurotoxicity due to absorption of bismuth from the BIPP pack is rare. It is preventable and reversible but likely to be fatal if unrecognised. A case of relapsing but reversible toxic encephalopathy due to a large extradural BIPP pack is reported in a 57 year old Caucasian woman, operated on for a huge basal cell carcinoma of the vertex invading the skull and extradural space. Clinical, neuroradiological (CT and MRI), and biochemical studies are presented and discussed in the light of the available literature.     

Effects of oral glucose administration on plasma growth hormone levels in women with polycystic ovary syndrome

OBJECTIVE: To evaluate the sensitivity of GH secretion to the suppressive effect of oral glucose administration in women with polycystic ovary syndrome (PCOS). DESIGN: Comparison of the GH response to an oral glucose load in women with PCOS and in weight-matched normally menstruating women (controls). SETTING: Reproductive endocrinology unit. PATIENT(S): Eighteen obese and 11 nonobese patients and 10 obese and 10 nonobese controls. INTERVENTION(S): After an overnight fast, each woman underwent a 75-g, 3-hour oral glucose tolerance test (OGTT). MEAN OUTCOME MEASURE(S): Growth hormone, glucose, and insulin responses to OGTT. RESULT(S): No significant differences in the glycemic and insulinemic responses were found between the patients and the weight-matched controls. No decrease in plasma GH was observed in both obese and nonobese patients and in obese controls during the OGTT, whereas a significant GH decrease occurred in nonobese controls 60 and 120 minutes after glucose intake. CONCLUSION(S): Oral glucose administration was unable to suppress GH levels in nonobese as well as in obese women with PCOS and in obese control women. These data suggest that both PCOS and obesity are associated with a reduced sensitivity of GH secretion to glucose suppression.     

GM-CSF receptor targeted treatment of primary AML in SCID mice using Diphtheria toxin fused to huGM-CSF

The severe combined immunodeficient (SCID) mouse model may be used to evaluate new approaches for the treatment of acute myeloid leukemia (AML). We have previously demonstrated the killing of SCID mouse leukemia initiating cells by in vitro incubation with human GM-CSF fused to Diphtheria toxin (DT-huGM-CSF). In this report, we show that in vivo treatment with DT-huGM-CSF eliminates AML growth in SCID mice. Seven cases of AML were studied. SCID mice were treated intraperitoneally with the maximally tolerated dose of 75 microg/kg/day for 7 days. Antileukemic efficacy was determined at days 40 and 80 after transplantation, by enumerating the percentages of human cells in SCID bone marrow using flow cytometry and short tandem repeat polymerase chain reaction (STR-PCR) analysis. Four out of seven AML cases were sensitive to in vivo treatment with DT-huGM-CSF at both evaluation time points. In three of these cases, elimination of human cells was demonstrated by flow cytometry and STR-PCR. One AML case showed moderate sensitivity for DT-huGM-CSF, and growth of the two remaining AML cases was not influenced by DT-huGM-CSF. Sensitivity was correlated with GM-CSFR expression. Our data show that DT-huGM-CSF can be used in vivo to reduce growth of AML and warrant further development of DT-huGM-CSF for the treatment of human AML.     

The serum mannose-binding protein and the macrophage mannose receptor are pattern recognition molecules that link innate and adaptive immunity

The innate immune system evolved to protect the host in the early phases of an infectious challenge. The soluble mannose binding protein, and the cell surface mannose receptor are two key pattern recognition molecules of innate immunity. The ligand binding specificity of these molecules enables them to differentiate 'self' from 'non-self'. These pattern recognition capabilities are coupled to effector functions, which enable them to interact with other molecules of the immune system. In this way, these pattern recognition molecules are able to serve as a link between the innate and adaptive immune systems.     

Assessment of the psychotropic activity of analogs of cholecystokinin tetrapeptide fragment]

BACKGROUND: Both dermabrasion and high-energy pulsed carbon dioxide (CO2) laser resurfacing can improve the appearance of surgical scars. Although the results of these two procedures have been compared using historical data, a prospective evaluation has never been performed in humans. OBJECTIVE: To prospectively compare the clinical effects of dermabrasion and high-energy pulsed CO2 laser resurfacing in the revision of surgical scars. METHODS: Facial surgical scars in four patients were prospectively revised using a split scar model. One half of the scar was dermabraded and the other half was resurfaced with the high-energy pulsed CO2 laser. Comparisons of the two treatment modalities were performed through clinical assessment, photographic evaluation, and textural analysis of the scars. RESULTS: The high-energy pulsed CO2 laser-resurfaced halves of the scar were bloodless with less postoperative crusting in comparison with the dermabraded halves. Reepithelialization time and degree and duration of postoperative erythema were similar for both treatment halves. Photographic evaluation and textural analysis showed comparable improvement in the clinical appearance and surface texture of the scars with both treatment modalities. CONCLUSIONS: Both the high-energy pulsed CO2 laser and dermabrasion can achieve comparable clinical improvement in the revision of surgical scars. The high-energy pulsed CO2 laser offers the advantage of a bloodless field and a more precise method of tissue ablation. Postoperative erythema, however, is an expected finding with both treatment modalities.     

Role of thrombolytic therapy in the treatment of patients with unstable angina

Thrombolytic therapy (TT) was performed in 39 of 81 patients with unstable angina pectoris (UAP) resistant to conventional treatment. TT was found to improve prognosis of UAP, to quicken UAP stabilization. Predictors of UAP unfavorable course were discovered. TT is indicated in patients suffering from resistant UAP with markers of poor prognosis.