Adenosine-mediated bronchoconstriction and lung inflammation in an allergic mouse model

In this study, we studied the role of adenosine on airway responsiveness and airway inflammation using an allergic mouse model. Mice were sensitized by two i.p. injections of ragweed and three consecutive ragweed aerosol challenges. It was found that inhalation of adenosine causes a dose-related bronchoconstriction in this model. Ragweed sensitized and challenged mice showed increased sensitivity to airway challenge to adenosine compared to control animals. Theophylline, a non-selective adenosine receptor antagonist, blocked adenosine-induced bronchoconstriction, but was unable to inhibit bronchoconstrictor response to methacholine. Mice systemically sensitized and airway challenged with allergen showed a marked airway inflammation manifesting increases in eosinophils, lymphocytes and neutrophils, and decrease in macrophages. Twenty-four hours after airway challenge with allergen, aerosolization of adenosine further potentiated the allergen-induced airway inflammation. Cells in bronchoalveolar lavage fluid after adenosine aerosolization increased by 3.07-fold as compared to control mice, and by 1.8-fold compared to ragweed sensitized and challenged mice. The increases in eosinophils, lymphocytes, and neutrophils caused by allergen were potentiated after adenosine challenge. Unexpectedly, macrophages significantly decreased after adenosine challenge. Theophylline attenuated adenosine-enhanced airway inflammation, but could not reverse allergen-induced airway inflammation. These findings suggested that specific adenosine receptors contribute to airway responsiveness and airway inflammation associated with this model of allergic asthma.     

Flixweed vs. Polyethylene Glycol in the Treatment of Childhood Functional Constipation: A Randomized Clinical Trial

Background:

Polyethylene glycol (PEG) is often considered as the first-line treatment for functional constipation in children. Descurainia sophia (L.) Webb et Berth (D. sophia) is a safe recommended medicine in Iranian folk and Traditional Persian Medicine for the treatment of constipation.

Objectives:

To clinically compare D. sophia with PEG 4000 (without electrolyte) in pediatric constipation and to assess its efficacy and side effects.

Patients and Methods:

120 patients aged 2 - 12 years with constipation for at least 3 months were included in an 8 weeks lasting randomized controlled trial within two parallel-groups. Children received either PEG, 0.4 g/kg/day, or D. sophia seeds, 2 grams (for children aged 2 - 4 years) and 3 grams (for those aged > 4 years) per day.

Results:

A total of 109 patients completed the study (56 in D. sophia and 53 in PEG group). At the end of the study, 36 (64.3%) patients in D. sophia group and 29 (54.7%) in PEG group were out of Rome III criteria (P = 0.205). Median weekly stool frequency in 0, 1, 2, 3 weeks of the treatment was found to be 2, 5, 5, 5 in D. sophia and 3, 4, 4, 5 in PEG group (P = 0.139, 0.076, 0.844, 0.294), respectively. The number of patients who suffered flatulence was less (5, 8.9%) in D. sophia group as compared to PEG group (6, 11.3%) at the end of the trial (P = 0.461). D. sophia taste was less tolerated.

Conclusions:

D. sophia is introduced as a cheap and available medication which can be applied as a safe alternative to conventional PEG in the management of pediatric chronic functional constipation.     

The social ecology of girls' bullying practices: exploratory research in two London schools

This exploratory study adopts a socio‐ecological approach to examine the context of school bullying. It asks: (1) what are students' accounts of bullying practices?; (2) how are these enabled and constrained by the school‐environment?; (3) how is gender implicated? Qualitative data were collected from girls in two schools in London via focus groups (one in each school; students aged 12‐15) and seven semi‐structured interviews (in one school; students aged 16‐18); and from school policy documents. Our interpretation of girls' accounts, informed by Giddens' structuration theory, suggests that bullying practices were spatially patterned in the schools and often characterised by the regulation of girls' sexuality and sexual‐harassment. Repeated acts of aggression were fluid with regard to the bully and victim role, challenging the dominant view of bullying as characterised by consistent disparities in power between individuals. Schools structured bullying behaviour via policies and practices that ignored these forms of abuse and which focused on and may have been complicit in the making of stable ‘bully’ and ‘victim’ roles, thus indirectly contributing to the reproduction of unhealthy relationships between students. In terms of gender, traditional gendered and sexual discourses appear to structure the identities of the schools and girls in our study.     

Dual antiplatelet agents and Rivaroxaban for massive intracoronary thrombus in STEMI

Management of intracoronary thrombus in patients presenting more than 12 hours after the onset of ST elevation myocardial infarction is challenging. We present such a case which had massive thrombus in left anterior descending artery. It was managed successfully with dual antiplatelet agents and factor Xa inhibitor rivaroxaban administered orally.     

Bone marrow aspirates as part of routine donor assessment for allogeneic blood and marrow transplantation can reveal presence of occult hematological malignancies in otherwise asymptomatic individuals

Pre transplant screening work-up of donors for allogeneic blood and marrow transplantation is essential in an effort to minimize risks to the recipient and protect the donor. At Princess Margaret Hospital, every potential donor is screened with a bone marrow aspirate. The case histories of three asymptomatic potential donors who presented within 1 year with normal complete blood counts, history and physical examination are presented. A 65-year-old male patient was diagnosed with smouldering multiple myeloma, a 72-year-old male patient with chronic lymphocytic leukemia and a 42-year-old male patient with myelodysplastic syndrome. Bone marrow examination led to the diagnosis in each one of these cases. Of note is that each of the potential donors was discovered to have the same disease as the transplant recipient. In vitro clonogenic hemopoietic progenitor assays were compared to those of 20 normal volunteers. Inferior growth of hemopoietic progenitor colonies in all three was noted. In conclusion, particularly in older donors and donors with potential for familial malignancies, more screening investigations including bone marrow aspiration may be reasonable to investigate for occult hematological malignancies prior to stem cell donation. Clonogenic assays can contribute to detect hemopoietic abnormalities pre transplant.     

Successful closure of iatrogenic femoral artery pseudoaneurysm: a new minimally invasive technique

Pseudoaneurysm following diagnostic or interventional procedures is a well-known complication. We describe a new method of closing a femoral pseudoaneurysm in a case where ultrasound-guided compression had failed. Instead of packing the sac permanently with coils, thrombus formation was successfully induced by temporary placement of a coil transcutaneously in the psendoaneurysm sac, which resulted in closure of the pseudoaneurysm.     

Allogeneic or autologous bone marrow transplantation (BMT) for non-Hodgkin's lymphoma (NHL): results of a provincial strategy. Ontario BMT Network, Canada

In 1986, the bone marrow transplant centers in Ontario agreed to a strategy for the treatment of patients with NHL. Suitable patients would undergo autotransplant but be referred for allotransplant if they had persistent marrow involvement or an inadequate marrow/stem cell harvest. Data of all patients were recorded in a database. We reviewed this database to compare these transplant modalities with respect to overall survival, rate of relapse and treatment-related mortality. Between January 1986 and August 1997, 429 patients underwent BMT for NHL - 385 autotransplants and 44 allotransplants. Sixty-eight percent of patients received their transplant for aggressive NHL, while the others had indolent lymphoma. Three-year actuarial survival did not differ between allogeneic and autologous BMT: 71% vs 62%, respectively (P = 0.5330 by log-rank testing). Three-year actuarial rate of relapse was lower after allotransplant than autotransplant: 6% vs 41%, respectively (P = 0.0006 by log-rank testing). Treatment-related mortality was higher after allotransplant than autotransplant: 23% vs 6%, respectively (P = 0.001 by chi2 analysis). For further comparison, autotransplant patients were randomly matched 2:1 with the allotransplant patients for age +/- 5 years, disease status at BMT, disease histology, and year of BMT. In the matched comparison, survival did not differ (relative risk of death after allotransplant: 0.711 (95% CI: 0.309-1.637)). Relapse rate was significantly lower in the allotransplant group (relative risk of relapse for allotransplant: 0.190 (95% CI: 0.043-0.834)) and treatment-related mortality was not significantly different (relative risk for allotransplant: 1.425 (95% CI: 0.527-3.851)). In conclusion, a review of a provincial strategy for treatment of NHL, shows that survival is not different after allogeneic or autologous BMT, but the rate of relapse is lower after allotransplant. These data support continuing the current provincial strategy.     

Design and formulation of polymeric nanosponge tablets with enhanced solubility for combination therapy

Three drugs namely caffeine, paracetamol, and aceclofenac are commonly used for treating various acute and chronic pain related ailments. These 3 drugs have varied solubility profiles, and formulating them into a single tablet did not have the desired dissolution profile for drug absorption. The objective of the present research was to tailor the drug release profile by altering drug solubility. This was achieved by loading the drug into nanosponges. Here, three-dimensional colloidal nanosponges were prepared using β-cyclodextrin with dimethyl carbonate as a cross-linker using the hot-melt compression method. The prepared nanosponges were characterized by FTIR, ¹H NMR spectroscopy, DSC, XRPD studies and SEM. The FTIR and DSC results obtained indicated polymer-drug compatibility. The ¹H NMR spectroscopy results obtained indicated the drug entrapment within nanosponges with the formation of the inclusion complex. XRPD studies showed that the loaded drug had changed crystalline properties altering drug solubility. SEM photographs revealed the porous and spongy texture on the surface of the nanosponge. Box–Behnken experimental design was adopted for the optimization of nanosponge synthesis. Among the synthesized nanosponges containing paracetamol, aceclofenac and caffeine, batch F3–P31, F3–A31 and F3–C31 were considered optimized. Their particle size was 185, 181 and 199 nm with an entrapment efficiency of 81.53, 84.96, and 89.28% respectively. These optimized nanosponges were directly compressed into tablets and were studied for both pre and post-compression properties including in vitro drug release. The prepared tablet showed desired drug dissolution properties compared to the pure drug. The above outcomes indicated the applicability of nanosponges in modulating the drug release with varied solubility for combination therapy.

Polymeric nanosponges as potential carriers for successful combination therapy of poorly soluble drugs (paracetamol, aceclofenac, caffeine).