Value of Adenine,Various Nucleosides,and Ouabain in Maintenance of Integrity of Red Blood Cells Under Blood Bank Conditions1

Summary. The effects of adenine and various nucleosides on adenine nucleotide metabolism in red cells, as well as on other factors related to the storability of blood were compared during six weeks of storage under blood bank conditions. Adenosine triphosphate (ATP) and total adenine nucleotides were maintained at higher levels, and higher ratios of ATP to adenine diphosphate were observed, in blood containing citrate-phosphate-dextrose (CPD) solution than in blood containing acid-citrate-dextrose (ACD) solution. Higher levels of ATP and total adenine nucleotides were maintained in blood containing ACD together with both adenine and inosine than in blood containing ACD alone or together with only one of the two purines. ACD-adenine was more effective in maintaining adenine nucleotides than was ACD-inosine. Addition of uridine did not have any effect on adenine nucleotides in red cells. ATP and total adenine nucleotides were maintained at higher levels in CPD-adenine than in CPD alone. The effect of CPD-inosine or CPD-adenine-inosine was not investigated. ACD-inosine caused a marked increase in plasma lactate, and inhibited glucose utilization, during storage. An increase in plasma inorganic phosphate was delayed by the addition of inosine, and this effect was augmented by adenine and guanosine. There were no findings suggestive of a beneficial effect of these additives on active cation transport, osmotic fragility, hemolysis, or the deterioration of blood cell morphology. Ouabain, an inhibitor of ATPase, had little effect on red cell nucleotide patterns or on other biochemical or morphological criteria for blood storage, possibly because of the low activity of ATPase at 4°C.     

C1s,the protease messenger of C1. Structure,function and physiological significance

C1s is the modular serine protease, which executes the catalytic function of the C1 complex: the cleavage of C4 and C2. Like other complement serine proteases C1s has restricted substrate specificity and it is engaged into specific interactions with other subcomponents of the complement system. There has been a rapid progress in determining the 3D structure of complement serine proteases and in revealing the role of the individual domains in the protein-protein interaction properties. In this review we summarize recent findings on the structure of C1s, and on the mechanism of action of this protease. The results obtained by genetic engineering, physico-chemical and functional studies are reviewed. The physiological relevance of the proteolytic action of C1s and its possible implications in health and disease will also be discussed.     

Treatment of lead poisoning with an immobilized chelator comparison with conventional therapy

Lead poisoning is a global public health problem. In pregnant women it may result in developmental delays of the fetus, in children it my produce learning disability. Available chelators are nephrotoxic when eliminated as lead-chelator complexes. For safe removal of lead from the body we developed a "Lead-Hemopurifier" (L-HP), a device with an immobilized chelator. In vitro, applied to lead solutions, this device reduced the lead concentration. Applied to dogs with lead intoxication, Lead-HP-s removed lead from the blood; this was continuously replaced by lead from the bones until the skeleton was cleared from lead deposit. Treatment of lead poisoning in dogs with Lead-HP-s compared favorably with Versenate treatment of children with lead toxicity. This report demonstrates the in vivo efficiency and safety of this new detoxfication method. Methods to induce lead poisoning in dogs and procedures to identify lead released from skeletal deposits are described.     

Detailed studies on expression and function of CD19 surface determinant by using B43 monoclonal antibody and the clinical potential of anti-CD19 immunotoxins

Extensive immunologic surface marker analyses and binding competition assays demonstrated that B43 monoclonal antibody (MoAb) is a new member of the CD19 cluster that recognizes the same surface epitope as several other anti-CD19 MoAbs. We used B43 MoAb to test for CD19 expression on neoplastic cells from 340 leukemia and 151 malignant lymphoma patients and on nonneoplastic cells in normal lymphohematopoietic and nonlymphohematopoietic tissues. Our study more than doubles the total number of cases with classified hematologic malignancies that have been examined for CD19 antigen expression. The data presented confirm that CD19 is the most reliable B lineage surface marker and support our view that this B lineage-restricted surface determinant may be an important functional receptor. Our findings provide unique and direct evidence that (a) CD19 is expressed on leukemic B lineage lymphoid progenitor cells freshly obtained from B lineage acute lymphoblastic leukemia patients but not on normal myeloid, erythroid, megakaryocytic, or multilineage bone marrow progenitor cells; (b) ligation of CD19 with B43 MoAb induces sustained increases in [Ca2+]i when crosslinked and inhibits high-molecular weight B cell growth factor (HMW-BCGF)-induced proliferation of activated B cells without affecting their low-molecular weight B cell growth factor (LMW-BCGF) response; therefore CD19 may be a unique signal receptor; (c) HMW-BCGF and LMW-BCGF augment expression of CD19, which suggests that CD19 and BCGF receptors may be under coordinate regulatory control; (d) approximately two million B43 MoAb molecules per cell can be bound to target B lineage lymphoma cells with a Ka of 1.9 x 10(8)/mol/L; (e) CD19 can undergo B43 MoAb-induced internalization; and (f) the opportunity is thus provided for using anti-CD19 MoAb to deliver toxins to B lineage neoplastic cells for more effective treatment of high-risk leukemia/lymphoma patients.     

Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes

The endocannabinoid system (ECS) regulates multiple physiological processes, including cutaneous cell growth and differentiation. Here, we explored the effects of the major nonpsychotropic phytocannabinoid of Cannabis sativa, (-)-cannabidiol (CBD), on human sebaceous gland function and determined that CBD behaves as a highly effective sebostatic agent. Administration of CBD to cultured human sebocytes and human skin organ culture inhibited the lipogenic actions of various compounds, including arachidonic acid and a combination of linoleic acid and testosterone, and suppressed sebocyte proliferation via the activation of transient receptor potential vanilloid-4 (TRPV4) ion channels. Activation of TRPV4 interfered with the prolipogenic ERK1/2 MAPK pathway and resulted in the downregulation of nuclear receptor interacting protein-1 (NRIP1), which influences glucose and lipid metabolism, thereby inhibiting sebocyte lipogenesis. CBD also exerted complex antiinflammatory actions that were coupled to A2a adenosine receptor-dependent upregulation of tribbles homolog 3 (TRIB3) and inhibition of the NF-κB signaling. Collectively, our findings suggest that, due to the combined lipostatic, antiproliferative, and antiinflammatory effects, CBD has potential as a promising therapeutic agent for the treatment of acne vulgaris.     

Mesenteric traction syndrome in pigs: A single‐blinded,randomized controlled trial

BackgroundMesenteric traction syndrome is commonly observed in patients undergoing upper abdominal surgery and is associated with severe postoperative complications. A triad of hypotension, tachycardia, and facial flushing seems provoked by prostacyclin (PGI₂) release from the gut in response to mesenteric traction. The administration of nonsteroidal anti‐inflammatory drugs (NSAID) inhibits PGI₂ release, stabilizing the hemodynamic response. Here, we examined the effect of mesenteric traction on splanchnic blood flow in pigs randomized to NSAID or placebo treatment.Materials and MethodsTwenty pigs were allocated to either ketorolac or placebo treatment. Five minutes of manual mesenteric traction was applied. Plasma 6‐keto‐PGF1_α, a stable metabolite of PGI₂, hemodynamic variables, and regional blood flow (laser speckle contrast imaging) to the liver, stomach, small intestine, upper lip, and snout (laser Doppler flowmetry) were recorded prior to traction and 5 and 30 minutes thereafter.ResultsBoth groups of pigs presented a decrease in systemic vascular resistance (P = .01), mean arterial blood pressure (P = .001), and blood flow in the gastric antrum (P = .002). Plasma 6‐keto‐PGF1_α did not increase in either group (P = .195), and cardiac output, heart rate, central venous pressure, and blood flow to the liver, small intestine, upper lip, and snout remained unchanged.ConclusionMesenteric traction resulted in cardiovascular depression, including reduced blood flow in the gastric antrum. Plasma 6‐keto‐PGF1_α did not increase, and ketorolac administration did not alter the response to mesenteric traction. Furthers studies are needed to identify which substance is responsible for eliciting the cardiovascular response to mesenteric traction in pigs.     

Evaluation of salivary gland protein 1 antibodies in patients with primary and secondary Sjogren's syndrome

Sjogren's syndrome (SS) has been associated with the expression of anti-Ro and anti-La antibodies. Anti-salivary gland protein 1 (SP1) antibodies have recently been identified in patients with SS.