PEGylation of Carbonate Apatite Nanoparticles Prevents Opsonin Binding and Enhances Tumor Accumulation of Gemcitabine

pH sensitives carbonate apatite (CA) has emerged as a targeted delivery vehicle for chemotherapeutics agent with tremendous potential to increase the effectivity of breast cancer treatment. The major challenge for intravenous delivery of drug-incorporated nanoparticles is their rapid opsonization, resulting in accumulation within the organs of reticuloendothelial system, such as liver and spleen. Therefore, surface modification by polyethylene glycol was implemented to improve the half-life of drug-particle complexes and enhance their uptake by target tissues. A simple, rapid, and sensitive triple quadrupole liquid chromatography–mass spectrometry method was developed and validated for quantification of gemcitabine in plasma, various organs and tumor tissues of mice with breast carcinoma, whereas sodium dodecyl sulfate-polyacrylamide gel electrophoresis, quadrupole-time of flight liquid chromatography–mass spectrometry and analysis by SwissProt.Mus_musculus database were performed for protein separation, identification, and homology search by comparing the de novo sequence tag. PEGylated CA exhibited almost 6-fold increase in gemcitabine accumulation in tumor with significant reduction in other organs within 1 h of intravenous administration, compared to free drug. In addition, plasma drug amount was found to be higher in PEGylated particles, implying their role in prolonging blood circulation time of particle-bound gemcitabine. Investigation of protein corona composition demonstrated notable reduction in opsonin interactions after PEGylation of CA particles. Overall, the results indicate that the composition and dynamics of protein corona subjected to alteration by PEGylation play crucial roles in affecting successful nanoparticle-based targeted delivery of a cytotoxic drug.     

Effect of black tea on teeth

Dental caries is the prime cause of premature loss of teeth in children. Tea contains high percentage of fluoride along with polyphenolic constituents which act on GTF of S. mutans in plaque synthesis. Combination of fluoride and polyphenolic constituents inhibit caries activity.     

Possible link between glycolysis and apoptosis induced by sodium fluoride

Fluoride has been used to prevent caries in the dentition, but the possible underlying mechanisms of cytotoxicity induction by this compound are still unclear. Since fluoride is known as an inhibitor of glycolytic enzymes, we investigated the possible connection between NaF-induced apoptosis and glycolysis in human promyelocytic leukemia HL-60 cells. NaF-induced apoptotic cell death is characterized by caspase activation, internucleosomal DNA fragmentation, loss of mitochondrial membrane potential, and production of apoptotic bodies. Higher activation of caspases-3 and -9, as compared with that of caspase-8, suggested the involvement of an extrinsic pathway. Utilization of glucose was nearly halted by NaF, whereas that of glutamine was rather enhanced. NaF enhanced the expression of Bad protein, but not that of Bcl-2 and Bax proteins, and reduced HIF-1alpha mRNA expression. Analysis of these data suggests a possible link between glycolysis and apoptosis.     

Valproic acid inhibits invasiveness in bladder cancer but not in prostate cancer cells

Histone deacetylase inhibitors (HDACIs) represent a promising new class of antineoplastic agents that affect proliferation, differentiation, and apoptosis in both solid and hematologic malignancies. In addition, HDACIs can alter the expression of at least one cellular adhesion molecule, the coxsackie and adenovirus receptor, in bladder cancer. Because HDACIs can increase expression of a known cellular adhesion molecule, we hypothesized that migration and/or invasion may also be affected. We evaluated this hypothesis using valproic acid (VPA), a commonly prescribed anticonvulsant recently shown to have potent HDACI activity, in the bladder cancer cell lines T24 TCC-SUP, HT1376, and RT4. Analyses of cell migration and invasion were both qualitative (fluorescent microscopy) and quantitative (static and dynamic migration/invasion assays). Our results show that acute VPA treatment (72 h) causes a dose-dependent decrease in invasion for all bladder cancer cell lines, except RT4, a noninvasive papilloma. Migration, in contrast, was not affected by VPA treatment. The inhibitory effect of VPA may be cancer type-specific, because there was no difference in invasion between treated and untreated prostate cancer cell lines LNCaP, PC3, and DU145. Furthermore, when administered chronically (34 days), VPA significantly inhibits growth of T24t tumor xenografts. Our data suggest that VPA exerts some of its antineoplastic effects by inhibiting invasion as well as tumor growth, and thus it may represent a novel adjuvant strategy for patients at high risk of recurrence and/or progression of muscle invasive bladder cancer.     

Primary motor cortex long‐term plasticity in multiple system atrophy

In humans, intermittent and continuous theta‐burst stimulation (iTBS and cTBS) elicit long‐term changes in motor‐evoked potentials (MEPs) reflecting long‐term potentiation (LTP)‐ and depression (LTD)‐like plasticity in the primary motor cortex (M1). In this study, we used TBS to investigate M1 plasticity in patients with MSA. We also assessed whether responses to TBS reflect M1 excitability as tested by short‐interval intracortical inhibition (SICI), intracortical facilitation (ICF), short‐interval intracortical facilitation (SICF), and the input/output curves. We studied 20 patients with MSA and 20 healthy subjects (HS). Patients were clinically evaluated with the Unified Multiple System Atrophy Rating Scale. The left M1 was conditioned with TBS. Twenty MEPs were recorded from the right first dorsal interosseous muscle before TBS and 5, 15, and 30 minutes thereafter. In a subgroup of 10 patients, we also tested MEPs elicited by SICI, ICF, SICF, and input/output curves, before TBS. Between‐group analysis of variance showed that at all time points after iTBS MEPs increased, whereas after cTBS they decreased only in HS. In both subgroups tested, patients with predominant parkinsonian and cerebellar features, iTBS and cTBS left MEPs unchanged. MSA patients had reduced SICI, but normal ICF, SICF, and input/output curves. No correlation was found between patients' clinical features and responses to TBS and M1 excitability variables. These findings suggest impaired M1 plasticity in MSA. © 2013 International Parkinson and Movement Disorder Society     

Use of designing for behaviour change framework in identifying and addressing barriers to and enablers of animal source feeding to children ages 8–23 months in Bandarban Hill District in Bangladesh: Implications for a nutrition-sensitive agriculture programme

Inadequate diet quality is a cause of undernutrition among children 6–23 months of age in Bangladesh, particularly in remote and isolated areas such as Bandarban District. Feeding animal source foods can help to combat stunting and wasting problems among children, but it may not be accessible or acceptable. A barrier analysis using the Designing for Behavior Change Framework was conducted in Bandarban district with participants from 4 ethnic groups, to explore potential barriers and key motivators by examining 12 behavioural determinants of consumption of animal-source food in complementary feeding for children 8–23 months. Data were collected from 45 mothers of children 8–23 months, who provided animal-source foods to their children (doers), and from 45 mothers who did not (non-doers), for a total of 90 interviews. Nine determinants were statistically significantly different between doers and non-doers as follows: self-efficacy, positive consequences, negative consequences, social norms, access, reminders, perceived risk, perceived severity and perceived action efficacy. Nearby access to purchase animal-source foods, rearing poultry or livestock at home and the support of household and community members are enablers to feeding animal-source food. In contrast, these same factors are barriers for non-doers. The lack of money to spend on animal-source foods is also a barrier. An integrated nutrition-sensitive and gender-transformative animal-based food production, and inclusive market programme could increase access to meat and eggs at the household level, increase opportunities to earn income and support gender-equitable household workloads and decision-making for optimal child feeding.     

Gender identity shows a high correlation with Prader score in patients with disorders of sex development (DSD) presenting in mid childhood

Objective

In developing countries like Bangladesh, delayed presentation for disorders of sex development (DSD) is common, and provides some special problems for management. There remains significant controversy about appropriate sex assignment in this group. We aimed, therefore, to assess gender identity (GI) in 50 consecutive patients with DSD presenting to a referral centre in Chittagong, Bangladesh, and correlate it with Prader score, to see if the latter could be used to predict GI.

Methods

A cross-sectional, case–control study of 50 consecutive children with DSD and 50 children with vascular anomalies was conducted in the Pediatric Surgical Clinic, Chittagong Medical College and Hospital. After informed consent, patients and controls provided oral answers to a GI questionnaire and had a detailed history and physical examination. Sex-typed activities were assessed by observations of a structured toy play and the child’s selection of a toy to keep. Both patients and parents then completed the Child Game Participation Questionnaire.

Results

There were no differences in age (2–16 years, mean 8.74) between controls and DSD patients (11 46, XX DSD, 32 46, XY DSD, 4 MGD, 3 ovo-testicular DSD). Fifteen of the DSD patients (30 %) came from consanguineous marriages and only 2 of the control patients had consanguinity of their parents. For the 13-question GI interview, there was no overall difference between DSD cases and controls. For the 46, XX DSD subgroup, there was a significantly higher score (11.1 ± 7.1) compared with control girls (4.5 ± 4.7) (p < 0.05), while for DSD and control boys, there was a positive correlation with age and GI (p < 0.01). Prader score correlated with GI score in both control (r = 0.91) and DSD patients (r = 0.75) (p < 0.01), DSD girls played significantly less with girls’ toys than controls (p < 0.01), but there was no differences for the boys. Composite scores on GI and gender-related behaviour correlated with Prader score for DSD patients (r = 0.61) (p < 0.01).

Conclusion

This study supports the view that GI and gender-role behaviour should be assessed routinely in DSD patients presenting after the neonatal period, so that sex assignment is in accordance with behaviour. Prader scores showed a good correlation with GI and gender role behaviour.