Clinical Evaluation of the Cook Advance Enforcer 35 Focal-Force PTA Balloon Catheter for Treatment of Hemodialysis Fistula Stenoses: A Feasibility Study

Purpose

A prospective, single-center, single-arm feasibility study evaluated procedural and short-term performance of the Advance Enforcer 35 focal-force percutaneous transluminal angioplasty (PTA) balloon catheter in treating stenoses of mature native arteriovenous (AV) hemodialysis access circuits.

Development and validation of stability-indicating high performance liquid chromatography method to analyze gatifloxacin in bulk drug and pharmaceutical preparations

Quantitative determination of gatifloxacin in tablets, solid lipid nanoparticles (SLNs) and eye-drops using a very simple and rapid chromatographic technique was validated and developed. Formulations were analyzed using a reverse phase SUPELCO® 516 C-18-DB, 50306-U, HPLC column (250 mm × 4.6 mm, 5 μm) and a mobile phase consisting of disodium hydrogen phosphate buffer:acetonitrile (75:25, v/v) and with orthophosphoric acid pH was adjusted to 3.3 The flow rate was 1.0 mL/min and analyte concentrations were measured using a UV-detector at 293 nm. The analyses were performed at room temperature (25 ± 2 °C). Gatifloxacin was separated in all the formulations within 2.767 min. There were linear calibration curves over a concentration range of 4.0–40 μg.mL⁻¹ and correlation coefficients of 0.9998 with an average recovery above 99.91%. Detection of analyte from different dosage forms at the same R_t indicates the specificity and stability of the developed method.     

COVID-19 impact on pharmacy education in Saudi Arabia: Challenges and opportunities

The first case of COVID-19 was announced at the end of year 2019, and later many cases were identified worldwide. In Saudi Arabia, the first case was announced on 2 March 2020. To prevent the spread of this pandemic disease, many precautionary actions were taken by Saudi government. One of these actions was closing public and private schools and universities and transfer the educational activities to virtual platforms. All colleges of Pharmacy in Saudi Arabia, whether the 21 public or the eight private ones, were affected by those sudden transitions and their responses varied according to their preparedness levels. Here we shared our experience in king Saud University in the curricular components of pharmacy school that includes classroom teaching, laboratory teaching, experiential training, assessment, and extracurricular activity and student support during COVID-19 compulsory lockdown. Lastly, we presented the lesson learned toward pharmacy education from COVID-19 pandemic.     

Prevalence of dental caries in primary and permanent teeth and its relation with tooth brushing habits among schoolchildren in Eastern Saudi Arabia

Objectives:

To determine the prevalence of dental caries in the primary and permanent teeth, and evaluate the brushing habits of school children in Dammam, Kingdom of Saudi Arabia (KSA).

Methods:

This study was conducted at Dammam, KSA. Oral examination of the participants was conducted from February to May 2014. The total sample size for this cross-sectional study was 711. There were 397 children between the age of 6-9 years, who were examined for primary teeth caries, and 314 between the age 10-12 years were examined for permanent teeth caries. Primary and permanent dentitions were studied for decayed, missing, and filled teeth (dmft [primary teeth], DMFT [permanent teeth]).

Results:

The overall prevalence of dental caries in primary and permanent teeth was almost 73% (n=711). Among the 6-9-year-old, the prevalence of caries was approximately 78% (n=397) whereas, among the 10-12-year-old children, it was approximately 68% (n=314). Mean dmft value among the 6-9-year-olds was 3.66±3.13 with decayed (d) component of 3.28±2.92, missing (m) component of 0.11±0.69, and filled (f) component of 0.26±0.9. Mean DMFT value among the 10-12-year-old children was 1.94±2.0 with decayed (D) component of 1.76±1.85, missing (M) component of 0.03±0.22, and filled (F) of component 0.15±0.73. Daily tooth brushing had a positive effect on caries prevention, and this effect was statistically significant for caries in primary teeth.

Conclusion:

Although the prevalence of dental caries in primary and permanent teeth was not found to be as high as other researchers reported from different cities of KSA, still the prevalence was high considering the World Health Organization future oral health goals. Awareness should be provided to students, as well as, teachers and parents regarding the importance of good brushing habits and regular dental visits.Dental caries is one of the most common cause of extraction of primary teeth in Saudi Arabia.1 In the past few decades, an increase in the prevalence of dental caries has been observed, which can be attributed to a change in lifestyle of Saudis, involving increased consumption of sugary food, carbonated drinks, and lack of awareness towards proper oral health maintenance.2,3 Generally, the prevalence of dental caries in developed countries is decreasing, while in underdeveloped and developing countries, the prevalence is on the rise.4 According to the statistics available from the World Health Organization (WHO), caries prevalence among the 12-year-old children from many European Union states (EU) has decreased considerably from 1970’s to 2006.5 This decline in the caries’ prevalence among EU countries over a period of 35 years could be attributed to an increased awareness of oral hygiene maintenance, and use of fluoridated toothpaste.6 However, among underdeveloped countries where fluoridated toothpaste is not easily available, or not affordable in some cases, caries prevalence is still high.7 The area of dental caries prevalence is of great interest to local and international researchers, which can be indicated by a number of studies that have been performed in developed and developing countries regarding caries’ prevalence.8-10 A study conducted in the urban and rural areas of Lahore, Pakistan to determine whether urbanization and family earnings are related to dental caries reported caries prevalence of 40.5%, and decayed (d), missing (m), and filled (f) teeth (dmft [primary teeth]) score of 1.85 ± 3.26 in preschool children aged 3-5 years,11 while another cross-sectional study performed in Chikar, Pakistan with convenience sampling of 311 schoolchildren revealed an overall DMFT (permanent teeth) score of 3.3 in 5-20-year-olds.12 Several studies have been conducted in different parts of the Kingdom of Saudi Arabia (KSA) to report the prevalence of dental caries in schoolchildren. A study performed in Riyadh reported a dmft score of 6.1, decayed factor of 4.6, and no significant difference in the prevalence of caries in relation to gender among 789 pre-school children.13 Farsi14 conducted a study to develop an association between enamel defects and caries occurrence in Jeddah, KSA, and reported a dmft score of 3.9, and a strong association between enamel defects and caries prevalence among 4-5-year-olds.14 In 2012, caries prevalence in the maxillary and mandibular first molar in the age group of 7-10 years schoolchildren was determined in Abha city, and a mean DMFT of 2.74 was reported.15 It was also concluded in the same study that caries prevalence in the first permanent molars from this region is higher than the recommended standards of the WHO.15 Extensive literature search was carried out to find studies regarding caries’ prevalence from Dammam, KSA. The search resulted in only one study, which was conducted in 2008 on children with cleft lip and palate aged 1-6 years, and it reported a high dmft of 10.54 from Dammam region.16 Since Dammam is one of the largest cities of the Eastern province of KSA, it would be interesting to observe caries’ prevalence among schoolchildren from this city. Therefore, the aim of the present study was to determine the prevalence of dental caries in schoolchildren aged 6-12 years in Dammam, KSA using the dmft/DMFT index of dental caries.     

STAT3-siRNA induced B16.F10 melanoma cell death: more association with VEGF downregulation than p-STAT3 knockdown

STAT3 knockdown by small interfering RNA (siRNA) has been described to inhibit carcinogenic growth in various types of tumors. Earlier we have reported delivery of siRNA by oleic acid- and stearic acid-modified-polyethylenimine and enhancement of silencing of STAT3 by small interfering RNA (siRNA) in B16.F10 melanoma cell lines and consequent tumor suppression. Present investigation mainly focused on the downstream events involved in B16.F10 melanoma cell death and consequent tumor suppression following knockdown of p-STAT3 by siRNA. Lipid-substituted polyethylenimine (PEI)-p-STAT3-siRNA were prepared and characterized by measuring its N/P ratio, zeta potential, size, association and dissociation with siRNA. B16.F10 melanoma cells were treated with six different concentrations of PEI-p-STAT3-siRNA (200, 100, 50, 25, 12.5 and 6.25?nM). Downregulation of p-STAT3 and VEGF were studied using western blot and ELISA in association with the melanoma cell death. PEI-p-STAT3-siRNA hydrodynamic diameter ranged from 110 to 270?nm. PEI assisted p-STAT3-siRNA delivery exhibited increased uptake by B16.F10, when analyzed by fluorescent and confocal microscopy along with flowcytometry. It induced concentration-dependent knockdown of the p-STAT3 that also downregulated VEGF expression in similar fashion and induced B16.F10 cell death. Higher concentrations of p-STAT3-siRNA appear to significantly downregulate the VEGF expression via p-STAT3 knockdown. Decreasing survival of B16.F10 cells with the increasing concentration of p-STAT3-siRNA significantly correlated with VEGF downregulation, not with p-STAT3 expression. Data suggest that VEGF downregulation following knockdown of p-STAT3 may be a key event in survival reduction in B16.F10 melanoma cells and.     

Biomarker discovery in cardiac allograft vasculopathy using targeted aptamer proteomics

Cardiac allograft vasculopathy (CAV) limits long-term survival after heart transplantation. Non-invasive evaluation is challenging, and currently, there is no validated biomarker for CAV diagnosis or prognostication. To identify potential candidate CAV biomarkers, we utilized the Slow Off-rate Modified Aptamer (SOMAscan) assay, which evaluates over 1000 serum proteins, including many relevant to biological pathways in CAV. We evaluated three heart transplant patient groups according to angiographic ISHLT CAV grade: CAV_1-2 (mild-moderate CAV), CAV₃ (severe CAV), and CAV₀ (normal control). SOMAscan assays were performed and proteins quantitated. Comparisons of proteins between study groups were performed using one-way ANOVA (false discovery rate q-value < 0.10). Thirty-one patients (12 mild-moderate CAV, 9 severe CAV, 10 controls) were included: 81% male, median age 57 years and median 1.1 years post-transplant. Compared to controls, patients with mild-moderate CAV had similar characteristics, while patients with severe CAV had longer time from transplant and increased allosensitization. Statistical/bioinformatics analysis identified 14 novel biomarkers for CAV, including 4 specific for mild-moderate CAV. These proteins demonstrated important actions including apoptosis, inflammation, and platelet/coagulation activation. Upon preliminary receiver operating characteristics curve analysis, our protein biomarkers showed moderate-to-high discriminative ability for CAV (area under curve: 0.72 to 0.94). These candidate biomarkers are being validated in prospective studies.     

The role of oxygen-derived free radicals in the management of venous (varicose) ulceration: A new approach

This double blind controlled study examined whether oxygen-derived free radicals interfere with the healing of venous ulceration occurring on the medial side of the leg for the first time. Graduated compression bandages exerting a mean ankle pressure of 42.1±0.3 mmHg and a mean pressure of 17.3±0.2 mmHg just below the knee healed 70% of ulcers within 12 weeks (n=44). Addition of the radical scavengers allopurinol (n=45) or dimethyl sulfoxide (n=44) to the compression bandages (daily application of the powder for 7 days, then once weekly applications to the end of the study at 3 months) significantly (p < 0.01) stimulated the healing of venous ulceration relative to controls when studied 4, 8, and 12 weeks after commencing treatment. After 3 months of treatment, allopurinol healed 93% and dimethyl sulfoxide healed 95% of the venous ulcers. The results suggest that oxygen-derived free radicals are directly implicated in the mechanism of venous ulceration and are responsible for its persistence. Scavenging such radicals stimulates the healing of ulceration.

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Resumen El presente estudio doble ciego controlado fue diseñado para investigar si los radicales libres derivados del oxígeno interfieren con la cicatrización de ulceraciones venosas que se presentan por primera vez sobre el aspecto interno de la pierna. El uso de vendas de compresión graduada que ejercen una presión media sobre el tobillo de 42.1±0.3 mm Hg y una presión media de 17.3±0.2 mm Hg justo por debajo de la rodilla, resultó en la cicatrizatión de 70% de las úlceras en un período menor de 12 semanas (n=44). La adición de los depuradores de radicales libres, alopurinol (n=45) o sulfóxido de metilo (n=44) a la venda compresiva (aplicación diaria del polvo por 7 días y luego aplicación semanal hasta el final del estudio a los 3 meses) estimuló en forma significativa (p<0.01) la cicatrizatión de las úlceras venosas en comparación con los controles, según estudios a las 4, 8, y 12 semanas de iniciado el tratamiento. Después de 3 meses de tratamiento, el alopurinol cicatrizó 93% y el sulfóxido de metilo 95% de las úlceras venosas. Los resultados sugieren que los radicales libres derivados del oxíogeno se hallan directamente comprometidos en el mecanismo de la ulceratión venosa y que son responsables de su persistencia. La depuration de tales radicales estimula la cicatrizatión de la ulceratión.

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Résumé Cette étude contrôlée en double aveugle a cherché à déterminer si les radicaux libres à oxygène jouaient un rôle bénéfique sur la cicatrisation de l'ulcère variqueux primitif localisé sur la face interne de la jambe. Un bandage compressif gradué exerçant une pression moyenne de 42.1±0.3 mm Hg au niveau de la cheville et une pression moyenne de 17.3±0.2 mm Hg juste sous le genou a permis la guérison de 70% des ulcères en 12 semaines (n=44). Le fait d'ajouter des radicaux d'allopurinol (n=45) ou de sulfoxyde de diméthyl (n=44) au bandage compressif (application quotidienne de poudre pendant 7 jours, puis une application une fois par semaine jusqu'à la fin de l'étude à quatre mois) augmente de façon significative (p<0.01) la cicatrisation de l'ulcère variqueux en comparaison des contrôles à 4, 8, et à 12 semaines après le début du traitement. Après 3 mois de traitement, l'allopurinol a guéri 93% des ulcères variqueux et le diméthyl sulfoxyde en a guéri 95%. Ces résultats suggèrent que les radicaux libres à oxygène sont directement impliqués dans le mécanisme de l'ulcère variqueux et sont responsables de leur persistance. Eliminer ces radicaux stimule la cicatrisation de l'ulcération.