An unusual case of autoimmune hemolytic anemia with reticulocytopenia, erythroid dysplasia, and an IgG2 autoanti-U

BACKGROUND: Autoantibodies with anti-U specificity, usually in combination with autoantibodies of other specificities, have occasionally been identified in association with autoimmune hemolytic anemia. A case of life-threatening autoimmune hemolytic anemia, characterized by several atypical features, including apparent intravascular hemolysis associated with an IgG2 anti-U, reticulocytopenia, and bone marrow dyserythropoiesis is described. CASE REPORT: A 36-year-old man with a severe case of acute-onset autoimmune hemolytic anemia was admitted to another hospital; he had a hematocrit of 15 percent, elevated bilirubin and lactate dehydrogenase, and positive direct and indirect antiglobulin tests. He received 7 units of incompatible red cells without improvement in hematocrit, and he was transferred to University Hospitals of Cleveland (OH). He was jaundiced and became syncopal in the sitting position. His serum was reddish pink; he had a hematocrit of 11.8 percent and a reticulocyte count of 2.5 percent. No spherocytes were observed in the peripheral blood smear. Shortly after admission, the hematocrit fell to 6.9 percent. He was given 3 units of “least-incompatible” red cells and was started on prednisone, with little improvement. An IgG2 autoanti-U was detected in his serum. Seven units of U- red cells were transfused over the next 4 days. The hematocrit improved to 23 percent and continued to rise without further transfusion. A bone marrow examination, initially revealing erythroid hyperplasia accompanied by dyserythropoiesis, became morphologically normal. Drug studies failed to show evidence of drug-related hemolysis. He remains well 2 years after discharge without evidence of recurrent hemolysis. CONCLUSION: Severe life-threatening autoimmune hemolytic anemia, in this instance induced by an autoanti-U, may be associated with IgG2 autoantibody and characterized by apparent intravascular hemolysis and bone marrow dyserythropoiesis. Early treatment with U- blood, in addition to steroids, may be beneficial.     

Pluronic F127 self-assembled MoS2 nanocomposites as an effective glutathione responsive anticancer drug delivery system

In this study, bio-responsive polymeric MoS₂ nanocomposites were prepared for use as a drug carrier for cancer therapy. Herein, we report the synthesis and demonstrate the self-assembly of pluronic F127 (PF127) on a cystamine–glutathione–MoS₂ (CYS–GSH–MoS₂) system, which can be used for GSH-triggered drug release under biological reducing conditions. The reduction-sensitive disulfide bond containing CYS was incorporated between the amphiphilic copolymer PF127 and GSH–MoS₂ to achieve feasible drug release. Percent drug loading capacity and encapsulation efficiency were 51.3% and 56%, respectively. In addition, when the MoS₂–GSH–CYS–PF127 nanocomposite was incubated in a GSH environment, the morphology of the nanocomposite tended to change, ultimately leading to drug release. The drug-loaded PF127–CYS–GSH–MoS₂ polymeric nanocomposites efficiently released 52% of their drug content after 72 h of incubation in a GSH reduction environment. The HeLa cells treated with DOX loaded MoS₂–GSH–CYS–PF127 showed 38% toxicity at drug concentration of 40 μg, which indicated that the successfully released of drug from carrier and caused the cell death. Further, fluorescence microscopy images of HeLa cells revealed the potential behavior of the MoS₂–GSH–CYS–PF12 nanocomposite during the 2- and 4 h incubation periods; the nanocomposite was only found in the cytoplasm of HeLa cells. Interestingly, after 6 h of incubation, the drug was slowly released from the nanocomposite and could enter the nucleus as confirmed by fluorescence imaging of HeLa cells. Altogether, our synthesized PF127-coated MoS₂ nanocomposite could be effectively adopted in the near future as a GSH-sensitive drug carrier.

In this study, bio-responsive polymeric MoS₂ nanocomposites were prepared for use as a drug carrier for cancer therapy.     

Computed tomography-guided percutaneous core needle biopsy in pancreatic tumor diagnosis

AIM: To evaluate the techniques, results, and complications related to computed tomography(CT)-guided percutaneous core needle biopsies of solid pancreatic lesions.METHODS: CT-guided percutaneous biopsies of solid pancreatic lesions performed at a cancer reference center between January 2012 and September 2013 were retrospectively analyzed. Biopsy material was collected with a 16-20 G Tru-Core needle(10-15 cm; Angiotech, Vancouver, CA) using a coaxial system and automatic biopsy gun. When direct access to the lesion was not possible, indirect(transgastric or transhepatic) access or hydrodissection and/or pneumodissection maneuvers were used. Characteristics of the patients, lesions, procedures, and histologic results were recorded using a standardized form. RESULTS: A total of 103 procedures included in the study were performed on patients with a mean age of 64.8 year(range: 39-94 year). The mean size of the pancreatic lesions was 45.5 mm(range: 15-195 mm). Most(75/103, 72.8%) procedures were performed via direct access, though hydrodissection and/or pneumodissection were used in 22.2%(23/103) of cases and indirect transhepatic or transgastric access was used in 4.8%(5/103) of cases. Histologic analysis was performed on all biopsies, and diagnoses were conclusive in 98.1%(101/103) of cases, confirming3.9%(4/103) of tumors were benign and 94.2%(97/103) were malignant; results were atypical in 1.9%(2/103) of cases, requiring a repeat biopsy to diagnose a neuroendocrine tumor, and surgical resection to confirm a primary adenocarcinoma. Only mild/moderate complications were observed in 9/103 patients(8.7%),and they were more commonly associated with biopsies of lesions located in the head/uncinate process(n =8), than of those located in the body/tail(n = 1) of the pancreas, but this difference was not significant.CONCLUSION: CT-guided biopsy of a pancreatic lesion is a safe procedure with a high success rate, and is an excellent option for minimally invasive diagnosis.     

Green synthesis of methyl-12-hydroxyoctadec-9-enoate

In the current paper, methyl-12-hydroxyoctadec-9-enoate was synthesized by biocatalytic transesterification of castor oil with methanol in presence of two different indigenously immobilized lipase preparations. Aiming for optimum yield (94% methyl-12-hydroxyoctadec-9-enoate), the batch reaction was conducted to evaluate the influence of reaction time, oil to methanol ratio, and water content. The atom economy (91.67%) and E-factor (0.297) for the studied reaction was uncovered, as well as an analysis of the adherence of the twelve principles of green chemistry was summarized. The green credentials were assessed using an efficient tool in strategic planning, a strengths-weaknesses-opportunities-threats (SWOT) analysis. The operational stability of immobilized lipase reactor column (60 °C) was determined for a prolonged period (>300 h) with the intermittent water addition to maintaining live enzyme. Furthermore, the purification of methyl-12-hydroxyoctadec-9-enoate using liquid-liquid extraction aided purity of 98%, confirmed by HPLC and GC-MS analysis.     

Characterization and toxicology evaluation of zirconium oxide nanoparticles on the embryonic development of zebrafish,Danio rerio

Zirconia oxide nanoparticles (ZrO₂NPs) are known to be one of the neutral bioceramic metal compounds that has been widely used for their beneficial applications in many biomedical areas, in dental implants, bone joint replacements, drug delivery vehicles, and in various industrial applications. To study the effects of ZrO₂NPs on zebrafish model, we used early life stages of the zebrafish (Danio rerio) to examine such effects on embryonic development in this species. ZrO₂NPs were synthesized by the sol-gel method, size about 15–20?nm and characterized by SEM, EDX, XRD, FTIR, UV-Vis Spectra. In this study, zebrafish embryos were treated with ZrO₂NPs 0.5, 1, 2, 3, 4, or 5?μg of nanoparticles/ml during 24–96?hour post fertilization (hpf). The results showed that ≥0.5–1?μg/ml of ZrO₂NPs instigated developmental acute toxicity in these embryos, causing mortality, hatching delay, and malformation. ZrO₂NPs exposure induced axis bent, tail bent, spinal cord curvature, yolk-sac, and pericardial edema. A typical phenotype was observed as an unhatched dead embryo at ≥1?μg/ml of ZrO₂NPs exposure. This study is one of the first reports on developmental toxicity of zebrafish embryos caused by zirconium oxide nanoparticles in aquatic environments. Our results show that exposure of zirconium oxide nanoparticles is more toxic to embryonic zebrafish at lower concentrations. The results will contribute to the current understanding of the potential biomedical toxicological effects of nanoparticles and support the safety evaluation and synthesis of Zirconia oxide nanoparticles.     

Preclinical safety and biodistribution assessment of Ad-KCNH2-G628S administered via atrial painting in New Zealand white rabbits

Post-operative atrial fibrillation (POAF) is the most common complication after cardiac surgery. Despite implementation of several pharmacological strategies, incidence of POAF remains at approximately 30%. An adenovirus vector encoding KCNH2-G628S has proven efficacious in a porcine model of AF. In this preclinical study, 1.5 × 10¹⁰ or 1.5 × 10¹² Ad-KCNH2-G628S vector particles (vp) were applied to the atrial epicardium or 1.5 × 10¹² vp were applied to the whole epicardial surface of New Zealand White rabbits. Saline and vector vehicle served as procedure controls. Animals were followed for up to 42 days. Vector genomes persisted in the atria up to 42 days, with no distribution to extra-thoracic organs. There were no adverse effects attributable to test article on standard toxicological endpoints or on blood pressure, left atrial or ventricular ejection fractions, electrocardiographic parameters, or serum IL-6 or troponin concentrations. Mononuclear infiltration of the myocardium of the atrial free walls of low-dose, but not high-dose animals was observed at 7 and 21 days, but these changes did not persist or affect cardiac function. After scaling for heart size, results indicate the test article is safe at doses up to 25 times the maximum proposed for the human clinical trial.     

A pilot clinical study of treatment guided by personalized tumorgrafts in patients with advanced cancer

Patients with many advanced solid cancers have very poor prognosis, and improvements in life expectancy are measured only in months. We have recently reported the remarkable clinical outcome of a patient with advanced, gemcitabine-resistant, pancreatic cancer who was later treated with DNA-damaging agents, on the basis of the observation of significant activity of this class of drugs against a personalized tumorgraft generated from the patient's surgically resected tumor. Here, we extend the approach to patients with other advanced cancers. Tumors resected from 14 patients with refractory advanced cancers were propagated in immunodeficient mice and treated with 63 drugs in 232 treatment regimens. An effective treatment regimen in the xenograft model was identified for 12 patients. One patient died before receiving treatment, and the remaining 11 patients received 17 prospectively guided treatments. Fifteen of these treatments resulted in durable partial remissions. In 2 subjects, no effective treatments were found. Overall, there was a remarkable correlation between drug activity in the model and clinical outcome, both in terms of resistance and sensitivity. The data support the use of the personalized tumorgraft model as a powerful investigational platform for therapeutic decision making and to efficiently guide cancer treatment in the clinic.