Biochemical manifestations of anti-tuberculosis drugs induced hepatotoxicity and the effect of silymarin.

In the present study, the biochemical manifestations of liver toxicity caused by co-administration of anti-TB drugs, rifampicin (RIF), isoniazid (INH) and pyrazinamide (PZA), in a sub-chronic mode (12 weeks), were investigated. Significant alterations were revealed in (a) increased levels of alanine aminotrasferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) and a high bilirubin content in serum; (b) elevated lipid peroxidation (LPO), intracellular calcium [Ca(2+)](i) and CYP4502EI activity in liver; and (c) decreased glutathione (GSH) content, glutathione peroxidase (GPx) and catalase activities in liver. Silymarin reversed these abnormal alterations. The biochemical changes were supported by histological observations.     

Treatment patterns and outcomes in adolescents and young adults with nodular lymphocyte-predominant Hodgkin lymphoma: an IMPACT cohort study

We leveraged population-based clinical and healthcare data to identify treatment patterns and long-term outcomes among adolescents and young adults (AYA) with nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). All Ontario, Canada, AYA aged 15–21 years at diagnosis with NLPHL between 1992 and 2012 were identified, and their detailed clinical data were collected. Linkage to healthcare databases identified additional events (subsequent malignant neoplasms [SMN], relapses and deaths). Event-free survival (EFS) and overall survival (OS) were compared by locus of care (adult vs. paediatric) and predictors of outcomes determined. Of 1014 AYA with Hodgkin lymphoma, 54 (5.3%) had NLPHL; 15 (27.8%) were treated at a paediatric centre. No paediatric centre patient received radiation only versus 16 (41.0%) of adult centre patients. Excision only was more common in paediatric centres (p < 0.001). The 20-year EFS and OS rates were 82.9% ± 5.2% and 100% respectively. Advanced stage (hazard ratio: 4.9, 95% CI: 1.3–18.4; p = 0.02) was associated with inferior EFS. Although the 25-year cumulative incidence of SMN was 19.3% ± 9.6% for the entire cohort, there were no SMN among the patients treated with excision only. AYA with NLPHL have outstanding long-term survival. Resection alone was rare outside of paediatric institutions but associated with excellent outcomes. Given substantial SMN risks, chemotherapy-sparing and radiation-sparing strategies for appropriate subsets of patients are warranted.     

Impact of Donor Arm Cleaning with Different Aseptic Solutions for Prevention of Contamination in Blood Bags

Transfusion associated sepsis cases are encountered occasionally and bacterial transmission remains the major cause. The goal of our study was to compare the efficacy of disinfectants in phlebotomy site preparation. After selection of donor the antecubital fossa area of the arm was disinfected with different types of disinfectants namely sprit (70% isopropyl alcohol), povidone iodine (0.5% w/v available iodine in distilled water), savlon (1.5% v/v chlorhexidine gluconate solution and 3.0% cetrimide solution) and combination of sprit and povidone iodine. Swabs were collected from 20 donors using a sterile forceps, after cleaning with different antiseptic solutions. Swab was streaked on blood agar plate aseptically and the plate was incubated at 37°C for 24 h. Colonies were counted and a single colony was re-cultured by growing on nutrient and Mac-Conkey agar. The biochemical characteristics were determined by performing Gram staining, Motility, Catalase and Oxidase tests. The mean values of colonies were significantly higher with savlon compared to other three solutions. The difference was statistically significant by “t” test (t values 1.7–3.0; P < 0.05). Staphylococcus epidermidis, Staphylococcus sp., Streptococcus sp., Micrococcus sp., Bacillus megaterium and Bacillus cereus were the organisms identified. After completion of bleeding, samples from the bag were aseptically inoculated in aerobic and anaerobic culture bottles to be tested on BacT/Alert system. The bag containing donor’s blood did not show any contamination when three cleanings were carried out using sprit, povidone iodine and spirit respectively.     

Ursolic Acid Loaded PLGA Nanoparticles: <Emphasis Type="Italic">in vitro</Emphasis> and <Emphasis Type="Italic">in vivo</Emphasis> Evaluation to Explore Tumor Targeting Ability on B16F10 Melanoma Cell Lines

Purpose

Ursolic acid (UA), a pentacyclic triterpenoid extracted from plants, shows promising inhibitory effect in different tumor bearing cell lines. In the present study we fabricated UA loaded PLGA nanoparticles (UA-NPs) as the drug carrier and thoroughly evaluated in vitro and in vivo the differential tumor targeting effects of UA and UA-NPs in B16F10 melanoma cells.

Methods

Ursolic acid loaded PLGA nanoparticles were prepared by emulsion solvent evaporation technique and evaluated for particle size, polydispersity, zeta potential and drug release potency. MTT assay as well as flow cytometric and confocal microscopic analyses were done in B16F10 mouse melanoma cell lines. Formulations were labeled with technetium-99m to evaluate the biodistribution and perform scintigraphic imaging studies following intravenous administration in tumor bearing mice model.

Results

Single emulsification technique produced smooth spherical nanoparticles of small size with relatively narrow size distribution (154?±?4.56 nm). On B16F10 cell line, the formulation showed higher cytotoxicity compared to the free drug due to increased in vitro cellular uptake. The formulation was successfully radiolabeled and remained substantially (>90%) stable when incubated (37°C, 6 h) separately in normal saline or freshly collected rat serum or histidine solution. The radiolabeled UA-NPs exhibited slower blood clearance and comparatively high uptake in tumor region as evidenced by biodistribution and scintigraphic studies.

Conclusions

The in vitro and in vivo studies have proved the tumor targeting potential of UA-NPs in B16F10 melanoma cell lines.

     

Polycaprolactone microspheres as carriers for dry powder inhalers: effect of surface coating on aerosolization of salbutamol sulfate

This study reports the factors controlling aerosolization of salbutamol sulfate (SS) from mixtures with polycaprolactone (PCL) microspheres fabricated using an emulsion technique with polyvinyl alcohol (PVA) as stabilizer. The fine particle fraction (FPF) of SS from PCL measured by a twin-stage impinger was unexpectedly found to be zero, although scanning electron microscopy showed that the drug coated the entire microsphere. Precoating the microspheres with magnesium stearate (MgSt) excipient solutions (1%-2%) significantly increased (p < 0.05, n = 5) the FPF of SS (11.4%-15.4%), whereas precoating with leucine had a similar effect (FPF = 11.3 ± 1.1%), but was independent of the solution concentration. The force of adhesion (by atomic force microscopy) between the PCL microspheres and SS was reduced from 301.4 ± 21.7?nN to 110.9 ± 30.5 nN and 121.8 ± 24.6 nN, (p < 0.05, n = 5) for 1% and 2% MgSt solutions, respectively, and to 148.1 ± 21.0 nN when coated with leucine. The presence of PVA on the PCL microspheres (detected by X-ray photoelectron spectroscopy) affected the detachment of SS due to strong adhesion between the two, presumably due to capillary forces acting between them. Precoating the microspheres with excipients increased the FPF significantly by reducing the drug-carrier adhesion.     

Cancer Patients First Treated with Chemotherapy: Are They More Likely to Receive Surgery in the Pandemic?

Due to the ramping down of cancer surgery in early pandemic, many newly diagnosed patients received other treatments first. We aimed to quantify the pandemic-related shift in rate of surgery following chemotherapy. This is a retrospective population-based cohort study involving adults diagnosed with cancer between 3 January 2016 and 7 November 2020 in Ontario, Canada who received chemotherapy as first treatment within 6-months of diagnosis. Competing-risks regression models with interaction effects were used to quantify the association between COVID-19 period (receiving a cancer diagnosis before or on/after 15 March 2020) and receipt of surgical reSection 9-months after first chemotherapy. Among 51,653 patients, 8.5% (n = 19,558) of them ultimately underwent surgery 9-months after chemotherapy initiation. Receipt of surgery was higher during the pandemic than before (sHR 1.07, 95% CI 1.02–1.13). Material deprivation was independently associated with lower receipt of surgery (least vs. most deprived quintile: sHR 1.11, 95% CI 1.04–1.17), but did not change with the pandemic. The surgical rate increase was most pronounced for breast cancer (sHR 1.13, 95% CI 1.06–1.20). These pandemic-related shifts in cancer treatment requires further evaluations to understand the long-term consequences. Persistent material deprivation-related inequity in cancer surgical access needs to be addressed.     

Periodic screening for breast and cervical cancer in women with diabetes: a population-based cohort study

Cancer Causes & Control - Diabetes is associated with poorer cancer outcomes. Screening for breast and cervical cancer is recommended by clinical guidelines; however, utilization of these tests...     

Trajectory of End-of-Life Pain and Other Physical Symptoms among Cancer Patients Receiving Home Care

Purpose: To describe the trajectory of physical symptoms among cancer decedents who were receiving home care in the six months before death. Patients and Methods: An observational cohort study of cancer decedents in Ontario, Canada, who received home care services between 2007 and 2014. To be included, decedents had to use at least one home care service in the last six months of life. Outcomes were the presence of pain and several other physical symptoms at each week before death. Results: Our cohort included 27,295 cancer decedents (30,368 assessments). Forty-seven percent were female and 56% were age 75 years or older. The prevalence of all physical symptoms increased as one approached death, particularly in the last month of life. In the last weeks of life, 69% of patients reported having moderate–severe pain; however, only 20% reported that the pain was not controlled. Loss of appetite (63%), shortness of breath (59%), high health instability (50%), and self-reported poor health (44%) were also highly prevalent in the last week of life. Multivariate regression showed that caregiver distress, high health instability, social decline, uncontrolled pain, and signs of depression all worsened the odds of having a physical symptom in the last 3 months of life. Conclusion: In this large home care cancer cohort, trajectories of physical symptoms worsened close to death. While presence of moderate–severe pain was common, it was also reported as mostly controlled. Covariates, such as caregiver distress and social decline, were associated with having more physical symptoms at end of life.     

Red cell alloimmunization in multitransfused patients and multiparous women

Purpose  To determine the incidence of alloimmunization against red cell antigens and the thermal amplitude and specificity of antibodies in multitransfused patients and multiparous women. Methods  Antibody screening was performed in 30 nontransfused orthopedic surgery cases (control), 504 multitransfused patients and 325 multiparous women. Antibody screening at 4°C, 22°C and 37°C was carried out in a saline phase, by indirect antiglobulin technique (IAT), using papain cystein, low ionic strength solution (LISS) and polyethylene glycol (PEG). Results  In multitransfused patients IgM antibodies were more frequently detected at 4°C and the IgG antibody incidence was 7.1% by enzyme method, 7.7% IAT, 9.4% LISS, 10.2% using PEG & 10.2% multiparous women. Bad obstetric history cases had significantly higher incidence of alloimmunization. The antibody specificity of antibodies was mainly in Lewis, Rh, Kidd and MN systems. Conclusion  Antibody screening before transfusion, at set time intervals after transfusion and during antenatal period is recommended.