Characterization of hydroxypropylmethylcellulose films using microwave non-destructive testing technique

The applicability of microwave non-destructive testing (NDT) technique in characterization of matrix property of pharmaceutical films was investigated. Hydroxypropylmethylcellulose and loratadine were selected as model matrix polymer and drug, respectively. Both blank and drug loaded hydroxypropylmethylcellulose films were prepared using the solvent-evaporation method and were conditioned at the relative humidity of 25, 50 and 75% prior to physicochemical characterization using microwave NDT technique as well as ultraviolet spectrophotometry, differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR) techniques. The results indicated that blank hydroxypropylmethylcellulose film exhibited a greater propensity of polymer-polymer interaction at the O-H and C-H domains of the polymer chains upon conditioned at a lower level of relative humidity. In the case of loratadine loaded films, a greater propensity of polymer-polymer and/or drug-polymer interaction via the O-H moiety was mediated in samples conditioned at the lower level of relative humidity, and via the C-H moiety when 50% relative humidity was selected as the condition for sample storage. Apparently, the absorption and transmission characteristics of both blank and drug loaded films for microwave varied with the state of polymer-polymer and/or drug-polymer interaction involving the O-H and C-H moieties. The measurement of microwave NDT test at 8GHz was sensitive to the chemical environment involving O-H moiety while it was greatly governed by the C-H moiety in test conducted at a higher frequency band of microwave. Similar observation was obtained with respect to the profiles of microwave NDT measurements against the state of polymer-polymer and/or drug-polymer interaction of hydroxypropylmethylcellulose films containing chlorpheniramine maleate. The microwave NDT measurement is potentially suitable for use as an apparent indicator of the state of polymer-polymer and drug-polymer interaction of the matrix.     

Microwave non-destructive testing technique for characterization of HPMC-PEG 3000 films

The capacity of microwave non-destructive testing (NDT) technique to characterize the matrix property of binary polymeric films for use as transdermal drug delivery system was investigated. Hydroxypropylmethylcellulose (HPMC) and polyethylene glycol (PEG) 3000 were the choice of polymeric matrix and plasticizer, respectively with loratadine as the model drug. Both blank and drug loaded HPMC-PEG 3000 films were prepared using the solvent-evaporation method. These films were conditioned at the relative humidity of 25, 50 and 75% prior to physicochemical characterization using the established methods of ultra-violet spectrophotometry, differential scanning calorimetry and Fourier transform infrared spectroscopy methods, as well as, novel microwave NDT technique. Blank films exhibited a greater propensity of polymer-polymer interaction at the O-H domain upon storage at a lower level of relative humidity, whereas drug loaded films exhibited a greater propensity of polymer-polymer, polymer-plasticizer and/or drug-polymer interaction via the O-H, C-H and/or aromatic C=C functional groups when they were stored at a lower or moderate level of relative humidity. The absorption and transmission characteristics of both blank and drug loaded films for microwave varied with the state of polymer-polymer, polymer-plasticizer, and/or drug-polymer interaction of the matrix. The measurements of microwave NDT test at 8 and 12 GHz were sensitive to the polar fraction of film involving functional group such as O-H moiety and the less polar environment of matrix consisting of functional groups such as C-H and aromatic C=C moieties. The state of interaction between polymer, plasticizer and/or drug of a binary polymeric film can be elucidated through its absorption and transmission profiles of microwave.     

Effect of silica coating and silanization on flexural and composite-resin bond strengths of zirconia posts: An in vitro study

STATEMENT OF PROBLEM: The bond strength of composite resin cores to the smooth surface of prefabricated zirconia-based ceramic posts is problematic because it might not be sufficient to ensure stability of the post-and-core system. It is also not clear whether any alteration of the post surface to provide additional mechanical or chemical retention would compromise flexural strength of the posts. PURPOSE: This study tested the effect of a tribochemical treatment on the bond strength (BS) between zirconia-based ceramic posts and composite resin and on the flexural strength (FS) of the posts. MATERIAL AND METHODS: For the BS test, 2 groups of specimens (n = 10) were prepared as follows: In the experimental (E) group, zirconia-based ceramic posts (Cosmopost), 21 mm long and 1.7 mm in diameter, were treated with a tribochemical silica coating and silanization system (Rocatec). For the control (C) group, zirconia-based ceramic posts were used as supplied by the manufacturer. For the 2 groups, posts were centered and vertically positioned in a metal mold, and composite resin (Tetric Ceram) was polymerized around the posts to form rings (6 mm diameter x 4 mm height). All specimens were positioned in a universal testing machine, and a load was applied axially on the protruding heads of posts in a shear push-out mode test until bond failure (MPa). Fracture mode was assessed as cohesive, cohesive/adhesive, or adhesive. Following this, the FS of the posts was measured in MPa using a 3-point bending test. Data were recorded and statistically analyzed using the Student t test for both tests (alpha = .01). RESULTS: Mean fracture load values +/- SDs for the BS test were 28.1 +/- 2.3 MPa and 8.9 +/- 3.97 MPa for the E and C groups, respectively. The mean FS values were 1544.9 +/- 214.1 MPa and 844.8 +/- 50.8 MPa for the E and C groups, respectively. The tribochemically treated posts exhibited significantly higher values for both bond strength to composite resin and resistance to fracture when compared to posts in the control group (P < .001). Fracture analysis showed 100% cohesive/adhesive fractures for group E specimens and 100% adhesive fractures for group C specimens. CONCLUSIONS: The use of a tribochemical silica coating process and silanization on zirconia-based ceramic posts increased both the bond strength to composite resin as well as the fracture strength of posts.     

Tissue microarrays characterise the clinical significance of a VEGF-A protein expression signature in gastrointestinal stromal tumours

A tissue microarray analysis of 22 proteins in gastrointestinal stromal tumours (GIST), followed by an unsupervised, hierarchical monothetic cluster statistical analysis of the results, allowed us to detect a vascular endothelial growth factor (VEGF) protein overexpression signature discriminator of prognosis in GIST, and discover novel VEGF-A DNA variants that may have functional significance.     

Extended Versus Limited Pelvic Lymph Node Dissection During Radical Prostatectomy for Intermediate- and High-risk Prostate Cancer: Early Oncological Outcomes from a Randomized Phase 3 Trial

BackgroundThe role of extended pelvic lymph node dissection (EPLND) in the surgical management of prostate cancer (PCa) patients remains controversial, mainly because of a lack of randomized controlled trials (RCTs).ObjectiveTo determine whether EPLND has better oncological outcomes than limited PLND (LPLND.Design, setting and participantsThis was a prospective, single-center phase 3 trial in patients with intermediate- or high-risk clinically localized PCa.InterventionRandomization (1:1) to LPLND (obturator nodes) or EPLND (obturator, external iliac, internal iliac, common iliac, and presacral nodes) bilaterally.Outcome measurements and statistical analysisThe primary endpoint was biochemical recurrence–free survival (BRFS). Secondary outcomes were metastasis-free survival (MFS), cancer-specific survival (CSS), and histopathological findings. The trial was designed to show a minimal 15% advantage in 5-yr BRFS by EPLND.Results and limitationsIn total, 300 patients were randomized from May 2012 to December 2016 (150 LPLND and 150 EPLND). The median BRFS was 61.4 mo in the LPLND group and not reached in the EPLND group (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.63–1.32; p = 0.6). Median MFS was not reached in either group (HR 0.57, 95% CI 0.17–1.8; p = 0.3). CSS data were not available because no patient died from PCa before the cutoff date. In exploratory subgroup analysis, patients with preoperative biopsy International Society of Urological Pathology (ISUP) grade groups 3–5 who were allocated to EPLND had better BRFS (HR 0.33, 95% CI 0.14–0.74, interaction p = 0.007). The short follow-up and surgeon heterogeneity are limitations to this study.ConclusionThis RCT confirms that EPLND provides better pathological staging, while differences in early oncological outcomes were not demonstrated. Our subgroup analysis suggests a potential BCRFS benefit in patients diagnosed with ISUP grade groups 3–5; however, these findings should be considered hypothesis-generating and further RCTs with larger cohorts and longer follow up are necessary to better define the role of EPLND during RP.Patient summaryIn this study, we investigated early outcomes in prostate cancer patients undergoing prostatectomy according to the anatomic extent of lymph node resection. We found that extended removal of lymph nodes did not reduce biochemical recurrence of prostate cancer in the expected range.     

Breast cancer therapy affects the expression of antineonatal Nav1.5 antibodies in the serum of patients with breast cancer

Neonatal Nav1.5 (nNav1.5) is the alternative splice variant of Nav1.5 and it has been widely associated with the progression of breast cancer. The immunological context of nNav1.5 with respect to breast cancer metastases remains unexplored. The presence of antibodies against nNav1.5 may highlight the immunogenicity of nNav1.5. Hence, the aim of the present study was to detect the presence of antineonatal Nav1.5 antibodies (antinNav1.5-Ab) in the serum of patients with breast cancer and to elucidate the effects of breast cancer therapy on its expression. A total of 32 healthy female volunteers and 64 patients with breast cancer were randomly recruited into the present study as the control and breast cancer group, respectively. Patients with breast cancer were divided equally based on their pre- and ongoing-treatment status. Serum samples were tested with in-house indirect enzyme-linked immunosorbent assay (ELISA) to detect antinNav1.5-Ab, CD25 (T regulatory cell marker) using an ELISA kit and Luminex assay to detect the expression of metastasis-associated cytokines, such as vascular endothelial growth factor (VEGF), interleukin (IL)-6, IL-10, IL-8, chemokine (C-C motif) ligand 2 and tumor necrosis factor-alpha (TNF-α) The mean difference in the expression of antinNav1.5-Ab among the three groups (control, pretreatment and ongoing-treatment) was significant (P=0.0005) and the pretreatment breast cancer group exhibited the highest expression. The concentration of CD25 was highest in the pretreatment breast cancer group compared with the control and ongoing-treatment groups. There was a significant positive correlation between antinNav1.5-Ab and IL-6 in the pretreatment group (r=0.7260; P=0.0210) and a significant negative correlation between antinNav1.5-Ab and VEGF in the ongoing-treatment group (r=−0.842; P-value=0.0040). The high expression of antinNav1.5-Ab in the pretreatment group was in accordance with the uninterrupted presence of metastasis and highlighted the immunogenicity of nNav1.5 whereas the low expression of antinNav1.5-Ab in the ongoing-treatment group reflected the efficacy of breast cancer therapy in eliminating metastases. The augmented manifestation of T regulatory cells in the pretreatment group highlighted the functional role of nNav1.5 in promoting metastasis. The parallel expression of antinNav1.5-Ab with the imbalanced expression of cytokines promoting metastasis (IL-8, IL-6 and TNF-α) and cytokines that prevent metastasis (IL-10) indicated the role of nNav1.5 in breast cancer growth. The expression of antinNav1.5-Ab in accordance to the metastatic microenvironment indicates the immunogenicity of the protein and highlights the influence of breast cancer therapy on its expression level.     

Reproductive factors influencing bone mineral density in postmenopausal women

This study examined the relationship between reproductive characteristics and bone mineral density (BMD) in postmenopausal women who had been referred to the menopause clinics of the National Population and Family Development Board and of the Hospital Kuala Lumpur from July 2011 to January 2012. The participants of this study were 201 postmenopausal Malaysian women aged 45–71 years. Some socio-demographic, lifestyle, and reproductive factors were recorded. Calcaneal BMD was measured by quantitative ultra-sonography. Correlations of reproductive factors with BMD were assessed by Pearson’s correlation test and multiple regression analysis. Age at menopause was not significantly correlated with BMD, while the years after menopause, age at the first menstrual period, number of pregnancies, and total lactation periods were inversely correlated with it. Among reproductive factors, only the association between lactation duration and BMD remained significant after adjusting for age, body mass index, activity, and calcium intake. The results indicated that except for prolonged total time of lactation, other reproductive factors were not significantly associated with BMD in postmenopausal women.     

Impact of seasonality on the prevalence and risk factors of Giardia lamblia infections among the aborigines

Objective: To determine the prevalence and risk factors of Giardia(G.) lamblia infections among the aboriginal community during the wet and dry seasons. Methods: A total of 473 stool samples from the aborigines in Temerloh, Pahang, Malaysia were collected during wet(n=256) and dry seasons(n=217). Smear of all the PVA-preserved stool samples were subjected to Trichrome staining and microscopic examination under 1 000 伊magnification(Nikon eclipse E100) for the detection of G. lamblia. Positivity was recorded based on the presence of G. lamblia in trophozoite and/or cyst forms. Results: The prevalence of giardiasis was 12.10% and 8.29% during the wet and dry season, respectively. Age of less or equal to 15 years old and presence of other family members with G. lamblia infection were found to be the significant risk factors to acquire G. lamblia infections during both seasons. Untreated water supply was the significant risk factor of giardiasis during the dry season. This study highlighted the possibility of anthroponotic transmission of G. lamblia during both seasons and waterborne transmission during the dry season in the aboriginal community. Conclusions: This study suggests that seasonal variation plays an important role in the prevalence and risk factor of G. lamblia infection in the aboriginal community. Therefore, close contact with Giardia-infected family members and water-related activities or usage of untreated water must be avoided to reduce the burden of G. lamblia infection in this community.