Erythropoietin (Epo) induces erythrocytosis by suppressing erythroid progenitor cell apoptosis through the Janus-activated kinase-signal transducers and activators of transcription (JAK-STAT) pathway. Since apoptosis contributes to cisplatin (CP)-induced nephrotoxicity and Epo receptors (EpoR) are expressed in the kidney, we examined the role of antiapoptosis in recombinant human erythropoietin (rHuEpo)-mediated renal protection. In human renal proximal tubular epithelial (RPTE) cells in culture, rHuEpo, but not inactive rHuEpo (I-rHuEpo), the receptor-binding sites of which are mutated, caused a significant reduction in CP-induced apoptosis at > or = 100 U/ml. rHuEpo, but not I-rHuEpo, increased STAT5 and Akt/PKB phosphorylation, demonstrating functional EpoR expression on RPTE cells. Furthermore, the JAK2 inhibitor tyrphostin AG-490 attenuated rHuEpo protection, suggesting a role of the JAK-STAT pathway in rHuEpo-mediated antiapoptosis. In rats, intravenous administration of 5,000 U/kg rHuEpo, but not an equivalent peptide mass of I-rHuEpo, before a single 5.5 mg/kg iv injection of CP, significantly increased hematocrit (Hct) and reduced the CP-induced increase in serum creatinine. Serum creatinine on day 4 was 3.4 +/- 0.3, 1.9 +/- 0.3, and 3.5 +/- 0.4 mg/dl in the CP, CP + rHuEpo, and CP + I-rHuEpo groups, respectively. Similarly, darbepoietin-alpha (DA), a hyperglycosylated analog of rHuEpo with prolonged in vivo activity when injected at 25 microg/kg iv before CP, significantly increased Hct and reduced serum creatinine. Renal clearance studies based on glomerular filtration rate and renal blood flow confirmed the significant renal protection by DA against CP. Tubular apoptosis and necrosis were significantly reduced in the kidneys of the CP + DA vs. the CP + saline group. Moreover, the equalization of Hct by venesection did not abrogate the DA-mediated renal protection. Administration of DA 48 h after CP injection also conferred significant renal protection. Thus our experiments confirm a role for erythropoiesis-stimulating proteins, including the new analog DA, in limiting CP-induced nephrotoxicity and suggest that antiapoptosis via the Epo-EpoR interaction is an important mechanism for renal protection.

Objective: To see whether it was possible to replicate in a prospective study the association recently reported between infection with the more virulent (type 1) cytotoxin associated gene A (CagA) antigen carrying strains of Helicobacter pylori and increased risk of coronary heart disease. Design and setting: Nested case-control study in a clinical outcomes trial. Subjects: Participants in the West of Scotland coronary prevention study. Methods: H pylori CagA serological status was determined in plasma samples of 201 subjects (cases) who subsequently had a coronary event during follow up and in 414 subjects (controls) matched for age and smoking who remained event-free, using a semiquantitative commercial enzyme linked immunosorbent assay (ELISA) kit against the p120 antigen of CagA. Results: 105 (52%) in the case group and 176 (43%) in the control group were seropositive (odds ratio (OR) 1.49, 95% confidence interval (CI) 1.06 to 2.10, p = 0.022). The association remained significant after adjustment for blood pressure, body mass index, plasma concentrations of low density lipoprotein and high density lipoprotein cholesterol, history of hypertension and diabetes, statin treatment, and socioeconomic status (OR 1.51, 95% CI 1.06 to 2.16, p = 0.023). Baseline inflammatory markers (white cell count, C reactive protein, fibrinogen) were not significantly increased in either H pylori CagA positive cases or controls. Conclusions: The findings provide support from a prospective study for the hypothesis that there is an association between infection with CagA bearing strains of H pylori and coronary heart disease. The mechanism(s) underlying the association remain to be elucidated.

All reported cases of WA1 babesiosis have occurred in the Pacific coast region of the United States, suggesting that WA1 is limited to this geographic area. However, we detected WA1 IgG in 27% of clinical sera sent to our laboratory for WA1 IgG testing from across the United States over a 2-year period, suggesting that exposure to WA1 or a closely related organism occurs outside Pacific coast states. We sought to determine if this high WA1 IgG detection rate among clinical specimens merely reflects WA1 seroprevalence outside the Pacific region. WA1 IgG, as well as Babesia microti IgG, was measured in 900 blood donor specimens from 9 states. Overall seroprevalence was 2.0% for WA1 and 0.4% for B. microti; regional seroprevalences ranged from 0 to 4% and 0 to 2%, respectively. Additional studies were performed to determine if WA1 IgG reactivity was attributable to polyclonal B-cell activation associated with acute Epstein-Barr virus (EBV) infection; 40 WA1 IgG-positive clinical sera and the 18 WA1 IgG-positive blood donor specimens were all negative for EBV capsid antigen (EBVCA) IgM (a marker of acute EBV infection), and 40 EBVCA IgM-positive sera were all negative for WA1 IgG. These findings indicate that the high WA1 IgG detection rate among clinical specimens does not simply reflect the national WA1 seroprevalence among blood donors or nonspecific reactivity due to acute EBV infection. Rather, the findings suggest that infection with WA1 or a related organism is more common than indicated by the literature and is not limited to Pacific coast states.The babesial piroplasm WA1 was first described in 1991 following its isolation from a Washington state resident with fever, chills, and myalgia (15). Morphological and ultrastructural studies revealed that WA1 is very similar to the wellcharacterized piroplasm Babesia microti; phylogenetic analysis, however, placed WA1 in a clade separate from B. microti and other Babesia species. Based on these findings, the recommended taxonomic designation for WA1 is Babesia duncani (1). Like other piroplasms, WA1 is transmitted to humans via a tick bite, but the animal reservoir has not been identified (8).An additional 8 cases of WA1 infection have been described in the medical literature (4, 9, 13), all in males residing in Washington or California; two of these cases reflected transmission by transfusion of infected blood products from an asymptomatic donor. In serologic investigations, titers of WA1 IgG were markedly elevated (Ն1:5,120) in convalescent-phase sera from all patients and in sera from the asymptomatic blood donors implicated in transfusion-transmitted cases (4, 9, 13). Consistent with the phylogenetic data, antibodies induced by WA1 infection did not cross-react with B. microti. Small seroprevalence studies conducted in California and Washington yielded wide variation in WA1 IgG detection rates, ranging from 1% to 20% (2,4,13,15).In response to the documented emergence of WA1 as a disease-causing agent, in 1997 our laboratory (Focus Diagnostics, Inc., Cypress, C...

Thirsty rats were trained to collect small water rewards from the end of each arm of an eightarm radial maze. During these training trials and subsequent testing trials, the subjects were allowed to choose a maximum of eight arms. "Preference" for a target maze location was studied by noting when, in the sequence of eight choices, the target was selected. During testing, when one maze location was consistently devoid of water, rats decreased their preference for this arm over trials (Experiment 1). Similarly, rats that learned a saccharin-lithium association demonstrated lower preferences for a maze location that consistently held the conditioned saccharin solution. This was true for animals that received saccharin-lithium conditioning on the maze (Experiment 3A) and for animals conditioned to saccharin in a separate context (Experiment 3B). An increase in preference for a target maze location consistently containing a sweet chocolate milk solution was observed in animals that were water-and food-deprived (Experiment 2). These studies demonstrate that animals will modify their responses toward (preferences for) maze locations that predictably contain an altered reward.

Aquasomes are the self-assembling nanobiopharmaceutical carrier system, contains nanocrystalline calcium phosphate or ceramic diamond, is covered by a glassy polyhydroxyl oligomeric film. Aquasomes are spherical (5-925nm) particles used for drug and antigen delivery. Aquasomes are called as "bodies of water" their water like properties protect and preserve fragile biological molecules. Its high degree of surface exposure is used in targeting of bio-active molecules to specific sites. Three types of core materials are mainly used for producing aquasomes: Tin oxide, Nanocrystalline carbon ceramics and Brushite. Calcium phosphate is the core of interest, due to its natural presence in the body. The brushite is unstable and converts to hydroxyapatite upon prolong storage and seems a better core for the preparation of aquasomes. It is widely used for the preparation of implants. Aquasomes exploited as a RBC substitutes, vaccines for delivery of viral antigen and as targeted system for intracellular gene therapy. Enzyme activity and sensitivity towards molecular conformation made aquasome as a novel carrier for enzymes like DNAses and pigment/dyes. This report reviews the principles of self assembly, the challenges of maintaining both the conformational integrity and biochemical activity of immobilized surface pairs. KEYWORDS Aquasomes, Self assembling carrier system, Carbon ceramics (diamonds) and Brushite (calcium phosphate dihydrate)