Mature and immature platelets during the first week after birth and incidence of patent ductus arteriosus.

BACKGROUND: Thrombocytopenia is a risk factor for patent ductus arteriosus. Immature and mature platelets exhibit distinct haemostatic properties; however, whether platelet maturity plays a role in postnatal, ductus arteriosus closure is unknown. METHODS: In this observational study, counts of immature and mature platelets (=total platelet count - immature platelet count) were assessed on days 1, 3, and 7 of life in very low birth weight infants (<1500 g birth weight). We performed echocardiographic screening for haemodynamically significant patent ductus arteriosus on day 7. RESULTS: Counts of mature platelets did not differ on day 1 in infants with (n = 24) and without (n = 45) haemodynamically significant patent ductus arteriosus, while infants with significant patent ductus arteriosus exhibited lower counts of mature platelet on postnatal days 3 and 7. Relative counts of immature platelets (fraction, in %) were higher in infants with patent ductus arteriosus on day 7 but not on days 1 and 3. Receiver operating characteristic curve analysis unraveled associations between both lower mature platelet counts and higher immature platelet fraction (percentage) values on days 3 and 7, with haemodynamically significant ductus arteriosus. Logistic regression analysis revealed that mature platelet counts, but not immature platelet fraction values, were independent predictors of haemodynamically significant patent ductus arteriosus. CONCLUSION: During the first week of postnatal life, lower counts of mature platelets and higher immature platelet fraction values are associated with haemodynamically significant patent ductus arteriosus. Lower counts of mature platelet were found to be independent predictors of haemodynamically significant patent ductus arteriosus.

Tobacco Mosaic Virus-Delivered Cisplatin Restores Efficacy in Platinum-Resistant Ovarian Cancer Cells.

Platinum resistance in ovarian cancer is the major determinant of disease prognosis. Resistance can first appear at the onset of disease or develop in response to platinum-based chemotherapy. Due to poor response to alternate chemotherapies and lack of targeted therapies, there is an urgent clinical need for a new avenue toward treatment of platinum-resistant (PR) ovarian cancer. Nanoscale delivery systems hold potential to overcome resistance mechanisms. In this work, we present tobacco mosaic virus (TMV) as a nanocarrier for cisplatin for treatment of PR ovarian cancer cells. The TMV-cisplatin conjugate (TMV-cisPt) was synthesized using a charge-driven reaction that, like a classic click reaction, is simple and reliable for large-scale production. Up to ∼1900 cisPt were loaded per TMV-cisPt with biphasic release profiles characterized by a fast half-life ( t1) of ∼1 h and slow half-life ( t2) of ∼12 h independent of pH. Efficient cell uptake of TMV was observed when incubated with ovarian cancer cells, and TMV-cisPt demonstrated superior cytotoxicity and DNA double strand breakage (DSB) in platinum-sensitive (PS) and PR cancer cells when compared to free cisplatin. The cytotoxicity in PR ovarian cancer cells and overall lower effective dosage requirement makes TMV-cisPt a powerful candidate for improved ovarian cancer treatment strategies.

Quantitative Understanding of Nanoparticle Uptake in Watermelon Plants.

The use of agrochemical-nutrient fertilizers has come under scrutiny in recent years due to concerns that they damage the ecosystem and endanger public health. Nanotechnology offers many possible interventions to mitigate these risks by use of nanofertilizers, nanopesticides, and nanosensors; and concurrently increases profitability, yields, and sustainability within the agricultural industry. Aerosol based foliar delivery of nanoparticles may help to enhance nanoparticle uptake and reduce environmental impacts of chemical fertilizers conventionally applied through a soil route. The purpose of this work was to study uptake, translocation, and accumulation of various gold nanostructures, 30-80 nm, delivered by aerosol application to a watermelon plant. Cellular uptake and accumulation of gold nanoparticles were quantified by Inductively Coupled Plasma-Mass Spectroscopy (ICP-MS). Observations suggested that nanoparticles could be taken up by the plant through direct penetration and transport through the stomatal opening. Observed translocation of nanoparticles from leaf to root shows evidence that nanoparticles travel by the phloem transport mechanism. Accumulation and transport of nanoparticles depend on nanoparticle shape, application method, and nature of plant tissues.

Mesenchymal stem cells remain host-derived independent of the source of the stem-cell graft and conditioning regimen used.

BACKGROUND: Human bone marrow contains hematopoietic stem cells and stroma cells known as mesenchymal stem cells (MSC). MSC are cells with the morphological features of fibroblasts, which, in addition to their nursing function for hematopoietic stem cells, retain the ability to differentiate into cartilage, bone, fat, muscle, and tendon and have an important immunmodulatory function. To understand in more detail hematopoietic engraftment and immune modulation after hematopoietic cell transplantation, we investigated the ability of donor MSC to engraft after hematopoietic cell transplantation in dependency to the conditioning regimen (myeloablative vs. reduced intensity) and source of the graft (bone marrow vs. peripheral blood). METHODS: Bone marrow MSC of 12 patients were analyzed, a median of 23.4 (range 0.9-137.8) months after human leukocyte antigen matched but gender mismatched bone marrow transplantation after myeloablative conditioning (n=4) or peripheral blood cell transplantation after myeloablative (n=4) or reduced intensity conditioning (n=4). MSC were characterized by morphology, positivity for CD 105+, CD73+, CD 44+, and CD 90+, and by their capacity to differentiate into adipocytic and osteogenic cells. Recipient and donor origins were determined by fluorescent in situ hybridization for sex chromosomes. RESULTS: While overall blood and bone marrow chimerism was 100% donor type, MSC remained in all patients of recipient origin (>96%). There was no difference between patients receiving bone marrow and peripheral blood grafts, nor was any difference observed between patients receiving full intensity in comparison with reduced intensity conditioning. CONCLUSIONS: We conclude that MSC remain of host type irrespective of the conditioning regimen and graft source.

Imatinib improves but may not fully reverse the poor prognosis of patients with CML with derivative chromosome 9 deletions.

Deletions of the derivative chromosome 9 occur in a subset of patients with Philadelphia chromosome-positive chronic myeloid leukemia (CML) and are associated with a poor prognosis on standard drug therapy. However, it is currently unknown if the presence of deletions influences the response to imatinib, an Abl-specific tyrosine kinase inhibitor, that has recently shown excellent hematologic and cytogenetic responses in patients with CML. We, therefore, compared hematologic and cytogenetic responses with imatinib in 397 patients with CML, and survival and progression in 354 of these patients, according to deletion status and disease phase. We found no difference in survival between patients with and without deletions, contrasting with previous reports in cohorts with a lower proportion of patients treated with imatinib. However, the time to disease progression on imatinib treatment was significantly shorter for patients with deletions, both in chronic phase (P =.02) and advanced phases (P =.02). Moreover, both in chronic phase and more advanced phases of CML, hematologic and cytogenetic responses were uniformly lower in patients with deletions, with significant differences seen for hematologic response (P =.04), for major cytogenetic response (P =.008) in chronic phase, and for hematologic response in advanced phases (P =.007) of CML. This finding suggests that differences in survival may become apparent with longer follow-up.

Emergence of clonal cytogenetic abnormalities in Ph- cells in some CML patients in cytogenetic remission to imatinib but restoration of polyclonal hematopoiesis in the majority.

Chronic myelogenous leukemia (CML) is characterized by the presence of a Bcr-Abl fusion protein with deregulated tyrosine kinase activity that is required for maintaining the malignant phenotype. Imatinib, a selective inhibitor of Bcr-Abl, induces major cytogenetic remission (MCR) or complete cytogenetic remission (CCR) in the majority of patients with CML in first chronic phase. However, thorough re-evaluation of cytogenetics in a cohort of patients in MCR or CCR demonstrated clonal karyotypic abnormalities in more than 10% of cases, some of which were clinically associated with a myelodysplastic syndrome (MDS). Further analysis identified previous exposure to cytarabine and idarubicin as significant risk factors for the subsequent occurrence of abnormalities in Philadelphia chromosome-negative (Ph-) cells. To investigate if cytogenetically normal but clonal hematopoiesis might be present in other patients in cytogenetic remission, we studied X-chromosome inactivation as a marker of clonality by polymerase chain reaction analysis of the human androgen receptor (HUMARA). We find that imatinib restores a polyclonal pattern in most patients in CCR and MCR. Nonetheless, our results are consistent with the notion that targeted therapy of CML with imatinib favors the manifestation of Ph- clonal disorders in some patients. They indicate that patients on imatinib should be followed with conventional cytogenetics, even after induction of CCR.

Cloning and functional characterization of a novel aquaporin from Xenopus laevis oocytes.

We have cloned a novel aquaporin (AQP) from Xenopus laevis oocytes, which we have provisionally named AQPxlo. The predicted protein showed highest homology (39-50%) to aquaglyceroporins. Northern blot analysis showed strong hybridization to an approximately 1.4-kb transcript in X. laevis fat body and oocytes, whereas a weaker signal was obtained in kidney. We injected in vitro transcribed cRNA encoding AQPxlo into Xenopus oocytes for functional characterization. AQPxlo expression increased osmotic water permeability (P(f)), as well as the uptake of glycerol and urea. However, AQPxlo excluded larger polyols and thiourea. An alkaline extracellular pH (pH(o)) increased P(f) and to a lesser extent urea uptake but not glycerol uptake. Remarkably, low HgCl(2) concentrations (0.3-10 microm) reduced P(f) and urea uptake, whereas high concentrations (300-1000 microm) reversed the inhibition. We propose that AQPxlo is a new AQP paralogue unknown in mammals.