Nanoformulation of natural products for prevention and therapy of prostate cancer

There is a need for developing improved therapeutic options for the management of prostate cancer, able to inhibit proliferation of precancerous and malignant lesions and/or to improve the effectiveness of conventional chemopreventive and chemotherapeutic agents. In this perspective, application of nanotechnology based strategies for the delivery of natural compounds for effective management of the disease is being actively researched. Here, after highlighting the most promising natural compounds for chemoprevention and chemotherapy of prostate cancer, the state of the art nanotherapeutics and the recent proof-of-concept of “nanochemoprevention”, as well as the clinical development of promising targeted nanoprototypes for use in the prostate cancer treatment are being discussed.     

"Early-peak" carbon monoxide production in certain erythropoietic disorders

The "early-labeled" peak (ELP) of 14CO excretion following injection of glycine-2-14C was used to study erythropoiesis in a patient with sideroblastic anemia and in four subjects with myeloproliferative disorders. The ELP was greatly enlarged in all patients, as compared with a normal volunteer. The contour of the peaks from the hematologically abnormal subjects suggested the presence of increased erythroid heme degradation. In the patient with sideroblastic anemia, all hours of the early peak were significantly reduced after transfusion. This was interpreted to mean that even the earliest or "nonerythroid" phase of the peak is influenced by erythropoietic activity, at least under conditions of erythropoietic stress.     

Acute pancreatitis during sickle cell vaso-occlusive painful crisis

Sickle cell disease is characterized by chronic hemolytic anemia and vaso-occlusive painful crisis. The vascular occlusion in sickle cell disease is a complex process and accounts for the majority of the clinical manifestations of the disease. Abdominal pain is an important component of vaso-occlusive painful crisis and may mimic diseases such as acute appendicitis and cholecystitis. Acute pancreatitis is rarely included as a cause of abdominal pain in patients with sickle cell disease. When it occurs it may result form biliary obstruction, but in other instances it might be a consequence of microvessel occlusion causing ischemia. In this series we describe four cases of acute pancreatitis in patients with sickle cell disease apparently due to microvascular occlusion and ischemic injury to the pancreas. All patients responded to conservative management. Acute pancreatitis should be considered in the differential diagnosis of abdominal pain in patients with sickle cell disease.     

Recombinant human interleukin-11 stimulates multilineage hematopoietic recovery in mice after a myelosuppressive regimen of sublethal irradiation and carboplatin

Interleukin-11 (IL-11) is a novel multifunctional hematopoietic cytokine capable of stimulating cells of the myeloid, lymphoid, erythroid, and megakaryocytic lineages in vitro. We have tested the pleiotropic properties of this cytokine on the hematopoietic recovery of mice after a combined regimen of sublethal irradiation and carboplatin administration. This regimen results in severe myelosuppression, characterized by a prolonged period of thrombocytopenia and severe anemia. Administration of recombinant human IL-11 (rhIL-11; 250 micrograms/kg/d) had multilineage effects on bone marrow and spleen hematopoietic activity, increasing the number of megakaryocyte, erythroid, granulocyte, and macrophage progenitors compared with the vehicle-treated controls. This was reflected in the peripheral circulation by a reduction of both the platelet and hematocrit nadirs and a significantly reduced period of thrombocytopenia and anemia in the rhIL-11-treated mice. The results from this study support the broad spectrum of biologic activities that have been attributed to rhIL-11 in vitro and suggest that this cytokine may be an effective agent in the treatment of myelosuppression associated with cancer chemotherapy and bone marrow transplantation.     

X-linked chronic granulomatous disease: correction of NADPH oxidase defect by retrovirus-mediated expression of gp91-phox

Chronic granulomatous disease (CGD) is an inherited immunodeficiency resulting from the inability of an individual's phagocytes to produce superoxide anions because of defective NADPH oxidase. The disease may be treated by bone marrow transplantation and as such is a candidate for somatic gene therapy. Two thirds of patients have defects in an X- linked gene (X-CGD) encoding gp91-phox, the large subunit of the membrane cytochrome b-245 component of NADPH oxidase. Epstein-Barr virus-transformed B-cell lines from patients with CGD provide a model system for the disease. We have used retrovirus-mediated expression of gp91-phox to reconstitute functionally NADPH oxidase activity in B-cell lines from three unrelated patients with X-CGD. The protein is glycosylated and membrane associated, and the reconstituted oxidase is appropriately activated via protein kinase C. The kinetics of superoxide production by such reconstituted cells is similar to that of normal B-cell lines. These data show the potential of gene therapy for this disease.     

Effect of known history of heart disease on survival outcomes after out‐of‐hospital cardiac arrests

Objective

We aimed to investigate the effect of known heart disease on post‐out‐of‐hospital cardiac arrest (OHCA) survival outcomes, and its association with factors influencing survival.

Methods

This was an observational, retrospective study involving an OHCA database from seven Asian countries in 2009–2012. Heart disease was defined as a documented diagnosis of coronary artery disease or congenital heart disease. Patients with non‐traumatic arrests for whom resuscitation was attempted and with known medical histories were included. Differences in demographics, arrest characteristics and survival between patients with and without known heart disease were analysed. Multivariate logistic regression was performed to identify factors influencing survival to discharge.

Results

Of 19 044 eligible patients, 5687 had known heart disease. They were older (77 vs 72 years) and had more comorbidities like diabetes (40.9 vs 21.8%), hypertension (60.6 vs 36.0%) and previous stroke (15.2 vs 10.1%). However, they were not more likely to receive bystander cardiopulmonary resuscitation (P = 0.205) or automated external defibrillation (P = 0.980). On univariate analysis, known heart disease was associated with increased survival (unadjusted odds ratio 1.16, 95% confidence interval 1.03–1.30). However, on multivariate analysis, heart disease predicted poorer survival (adjusted odds ratio 0.76, 95% confidence interval 0.58–1.00). Other factors influencing survival corresponded with previous reports.

Conclusions

Known heart disease independently predicted poorer post‐OHCA survival. This study may provide information to guide future prospective studies specifically looking at family education for patients with heart disease and the effect on OHCA outcomes.