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Cl- regulates cryoglobulin structure: a new hypothesis for the physiopathological mechanism of temperature non-dependent cryoprecipitation
No full textCryoglobulins are pathological cold-precipitable immunoglobulins associated with a number of infectious, autoimmune and neoplastic disorders. Patients, when exposed to low temperatures, show symptoms related to intravascular precipitation of such immunoglobulins. The formation of cryoaggregates induced by exposure to cold temperature is the key pathogenetic mechanism. The subsequent intravascular precipitation can account for some clinical signs of peripheral vasculitis, but fails to explain the precipitation of cryoglobulins in regions where no significant temperature changes take place. We studied, in vitro, the activity of different ions on temperature-dependent aggregation of cryoglobulins and found that the concentration of Cl- present in solution is the most important variable that controls the size and the rate of formation of aggregates, both at low temperature and at 37degreesC. We suggest that chloride anion could be the most important factor involved in the pathogenesis of events in visceral regions, such as in the kidneys, where no temperature changes occur but where the local Cl- concentration changes to maintain blood electrolytic homeostasis and acid-basic equilibrium. Moreover, identification of a specific structural domain responsible for Cl- binding may provide new targets for drugs selectively designed to interfere with cryoglobulin aggregation
Simultaneous determination of lamivudine, lopinavir, ritonavir, and zidovudine concentration in plasma of HIV-infected patients by HPLC-MS/MS.
No full textThe nucleoside reverse transcriptase inhibitors lamivudine and zidovudine and the protease inhibitors lopinavir and ritonavir are currently used in anti-human immunodeficiency virus (HIV) therapy. Here, a high-performance liquid chromatography- mass spectrometry (HPLC-MS/MS) method, using a hybrid quadrupole time-of-flight mass analyzer, is reported for the simultaneous quantification of lamivudine, lopinavir, ritonavir, and zidovudine in plasma of HIV-infected patients. The volume of plasma sample was 600 μL. Plasma samples were extracted by solid-phase using 1 cc Oasis HLB Cartridge (divinylbenzene and N-vinylpyrrolidone) and evaporated in a water bath under nitrogen stream. The extracted samples were reconstituted with 100-μL methanol. Five microliters of the reconstituted samples were injected into a HPLC-MS/MS apparatus, and the analytes were eluted on a Vydac column (250 x 1.0 mm i.d.) filled with 3-μm C 18 particles. The mobile phase was delivered at 70 μL/ min with a linear gradient elution, both acetonitrile and ultrapure water solvents contained 0.2% formic acid. The calibration curves were linear from 0.47 to 20 ng/mL. The absolute recovery ranged between 91 and 107%. The minimal concentration of lamivudine, lopinavir, ritonavir, and zidovudine detectable by HPLC-MS/MS is 0.47, 0.28, 0.30, and 0.66 ng/mL, respectively. The great advantage of the new HPLC-MS/MS method here reported is the possibility to achieve a very high specificity toward the selected anti-HIV drugs, despite the simple and rapid sample preparation. Moreover, this method is easily extendible to the analysis of co-administrated drugs
Evaluation of the BDProbeTec strand displacement amplification assay in comparison with the AMTD II direct test for rapid diagnosis of tuberculosis
No full textTargeting the antioxidant defense system in the human protozoan parasite Giardia intestinalis
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Giardia intestinalis escapes oxidative stress by colonizing the small intestine: A molecular hypothesis.
No full textGiardia intestinalis is the microaerophilic protozoon causing giardiasis, a common infectious intestinal disease. Giardia possesses an O(2)-scavenging activity likely essential for survival in the host. We report that Giardia trophozoites express the O(2)-detoxifying flavodiiron protein (FDP), detected by immunoblotting, and are able to reduce O(2) to H(2)O rapidly (similar to 3 mu M O(2) x min x 10(6) cells at 37 degrees C) and with high affinity (C(50) = 3.4 +/- 0.7 mu M O(2)). Following a short-term (minutes) exposure to H(2)O(2) >= 100 mu M, the O(2) consumption by the parasites is irreversibly impaired, and the FDP undergoes a degradation, prevented by the proteasome-inhibitor MG132. Instead, H(2)O(2) does not cause degradation or inactivation of the isolated FDP. On the basis of the elevated susceptibility of Giardia to oxidative stress, we hypothesize that the parasite preferentially colonizes the small intestine since, compared with colon, it is characterized by a greater capacity for redox buffering and a lower propensity to oxidative stress
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