Bisphenol S increases cell number and stimulates migration of endometrial epithelial cells / Journal of the ASEAN Federation of Endocrine Societies

Objective@#To determine whether bisphenol S (BPS), a common substitute for bisphenol A (BPA), induces cell proliferation and migration in human endometrial epithelial cells (Ishikawa) and adult mouse uterine tissues.@*Methodology@#Human endometrial Ishikawa cells were exposed to low doses of BPS (1 nM and 100 nM) for 72 hours. Cell proliferation was assessed through the viability assays MTT and CellTiter-Glo®. Wound healing assays were also used to evaluate the migration potential of the cell line. The expression of genes related to proliferation and migration was also determined. Similarly, adult mice were exposed to BPS at a dose of 30 mg/kg body weight/day for 21 days, after which, the uterus was sent for histopathologic assessment.@*Results@#BPS increased cell number and stimulated migration in Ishikawa cells, in association with the upregulation of estrogen receptor beta (ESR2) and vimentin (VIM). In addition, mice exposed to BPS showed a significantly higher mean number of endometrial glands within the endometrium.@*Conclusion@#Overall, in vitro and in vivo results obtained in this study showed that BPS could significantly promote endometrial epithelial cell proliferation and migration, a phenotype also observed with BPA exposure. Hence, the use of BPS in BPA-free products must be reassessed, as it may pose adverse reproductive health effects to humans.

Emerging role of natural products in cancer immunotherapy

Cancer immunotherapy has become a new generation of anti-tumor treatment, but its indications still focus on several types of tumors that are sensitive to the immune system. Therefore, effective strategies that can expand its indications and enhance its efficiency become the key element for the further development of cancer immunotherapy. Natural products are reported to have this effect on cancer immunotherapy, including cancer vaccines, immune-check points inhibitors, and adoptive immune-cells therapy. And the mechanism of that is mainly attributed to the remodeling of the tumor-immunosuppressive microenvironment, which is the key factor that assists tumor to avoid the recognition and attack from immune system and cancer immunotherapy. Therefore, this review summarizes and concludes the natural products that reportedly improve cancer immunotherapy and investigates the mechanism. And we found that saponins, polysaccharides, and flavonoids are mainly three categories of natural products, which reflected significant effects combined with cancer immunotherapy through reversing the tumor-immunosuppressive microenvironment. Besides, this review also collected the studies about nano-technology used to improve the disadvantages of natural products. All of these studies showed the great potential of natural products in cancer immunotherapy.

Fundamentos de elección terapéutica: osteonecrosis maxilar asociada a drogas antirresortivas (MRONJ) / Fundamentals of therapeutic choice: anti-resorptive drug-related maxillary osteonecrosis (MRONJ)

La acción terapéutica favorable que los antirresortivos (bifosfonatos BPs, denosumab DS) y drogas antiangiogénicas ocasionan en el tejido óseo en aquellos pacientes que presentan como causa etiológica cáncer o discrasias óseas incluyen hipercalcemias malignas o ­si requieren el consumo de dicha droga a baja concentración­ como ser: osteoporosis, osteopenia, enfermedad de Paget, displasia fibrosa, Osteogénesis Imperfecta. (1) La presente actualización pretende relacionar el tratamiento odontológico con prescripción crónica y drogas antirresortivas, para lo cual American Association of Oral and Maxillofacial Surgeons AAOMS: define el concepto de Osteonecrosis Maxilar Asociada a drogas Antirresortivas (MRONJ) como: «Área ósea necrótica expuesta al medio bucal con más de ocho semanas de permanencia, en presencia de tratamiento crónico con bifosfonatos en ausencia de radioterapia en cabeza y cuello¼. La AAOMS estableció los siguientes grupos de acuerdo con sus características clínicas en 4 estadios (0, 1 ,2 y 3) de acuerdo con el aspecto clínico y radiológico de la lesión osteonecrótica. Estadío 0: lesión osteonecrótica sin evidencia de hueso necrótico en pacientes bajo consumo de drogas antirresortivas. Estadío 1: lesión osteonecrótica con signos clínicos y ausencia de sintomatología clínica. Estadío 2: lesión osteonecrótica con signo y sintomatología clínica evidente. Estadío 3: lesión osteonecrótica con signo y sintomatología evidente que compromete a estructuras nobles: fracturas patológicas, anestesia del nervio dentario inferior, comunicación buco-nasal, comunicación buco-sinusal, fístulas cutáneas (2) (AU)

It is known the favourable action which antiresorptive (Bisphosphonates BPs, Denosumab: DS) and Antiangiogenic drugs produce in bone tissue. High concentrations are primarily used as an effective treatment in the management of cancer-related disorders, including hypercalcemia of malignant. Besides, low concentrations are used for other metabolic bone diseases including Osteoporosis, Osteopenia, Paget's Disease, Fibrous Dysplasia, Imperfect Osteogenesis. (1) The update relate relationship between dentistry and chronic treatment with antiresorptive drugs. According to the American Association of Oral and Maxillofacial Surgeons (AAOMS), MRONJ is defined as exposed or necrotic bone in the maxillofacial region that has persisted for more than 8 weeks in association with current or previous BPs or DS therapy and with a lack of head and neck radiotherapy. AAOMS divided the MRONJ into 4 stages (0,1, 2 and 3) according to the clinical and radiological aspect of the osteonecrotic lesion: Stage 0: osteonecrotic lesion without sign-pathognomonic evidence of osteonecrosis. Stage 1: osteonecrotic lesion with clinical signs and absence of clinical symptoms. Stage 2: osteonecrotic lesion with sign and evident clinical symptoms. Stage 3: osteonecrotic lesion with signs and evident symptoms that involve noble structures: pathological fractures, anaesthesia of the lower dental nerve, oral-nasal communication, oral-sinus communication, skin fistulas (2) (AU)

Knowledge and Attitude towards Board of Pharmacy Specialties (BPS) Certification among Pharmacists and Pharmacy Students: A Cross Sectional Survey

Background: For decades, the American Board of Pharmacy Specialties (BPS) has provided specialty certification programs for pharmacists. As pharmacists become involved in more advanced patient care services, board certification becomes an essential component to ensuring quality care. The aim of this study was to measure the self-reported knowledge and attitude towards the BPS certification. Methods: A cross sectional study included all pharmacy students and pharmacists at King Saud bin Abdulaziz University for Health Sciences (KSAU-HS) and King Abdulaziz Medical City (KAMC), respectively. However, the administrative pharmacy staff was not included. This is a manually distributed survey was adopted from previous published observational study. The survey included 6 demographic, 12 knowledge and 15 attitude questions where the participant rank from 1 to 5 (1: very poor, 2: poor, 3: Average, 4: good and 5: very good). This study is approved by IRB. Descriptive statistics were primarily used to analyze data. Categorical responses were compared using Chi-square tests. Result: In total of 221 participants agreed to participate in the study based on convenient sampling, there were more female participants (134, 60.6%) than male (87, 39.4%). More number of participants (191, 86.4%) were under the age-group ≤ 30 years. The overall mean age was found to be 25.20 ± 5.86 (20-60) years. Among 221 participants, 118 (53.4%) were students and 103 (46.6%) were employees. The current study found that 55.2% of respondents have a good knowledge about BPS certification. However, only 48.4% of participants reported their interest in pursuing board certification in their future career. Conclusion: Many respondents were aware of BPS certification, learning the most through didactic and experiential activities, and many indicated they are considering pursuing BPS certification. College of pharmacy and professional organizations can help provide educational session regarding board certification and professional development opportunities.

Validation of the Brazilian version of Behavioral Pain Scale in adult sedated and mechanically ventilated patients / Validação da versão Brasileira da Escala Comportamental de Dor (Behavioral Pain Scale) em adultos sedados e sob ventilação mecânica

Abstract Background and objectives: The Behavioral Pain Scale is a pain assessment tool for uncommunicative and sedated Intensive Care Unit patients. The lack of a Brazilian scale for pain assessment in adults mechanically ventilated justifies the relevance of this study that aimed to validate the Brazilian version of Behavioral Pain Scale as well as to correlate its scores with the records of physiological parameters, sedation level and severity of disease. Methods: Twenty-five Intensive Care Unit adult patients were included in this study. The Brazilian Behavioral Pain Scale version (previously translated and culturally adapted) and the recording of physiological parameters were performed by two investigators simultaneously during rest, during eye cleaning (non-painful stimulus) and during endotracheal suctioning (painful stimulus). Results: High values of responsiveness coefficient (coefficient = 3.22) were observed. The Cronbach's alpha of total Behavioral Pain Scale score at eye cleaning and endotracheal suctioning was 0.8. The intraclass correlation coefficient of total Behavioral Pain Scale score was ≥ 0.8 at eye cleaning and endotracheal suctioning. There was a significant highest Behavioral Pain Scale score during application of painful procedure when compared with rest period (p ≤ 0.0001). However, no correlations were observed between pain and hemodynamic parameters, sedation level, and severity of disease. Conclusions: This pioneer validation study of Brazilian Behavioral Pain Scale exhibits satisfactory index of internal consistency, interrater reliability, responsiveness and validity. Therefore, the Brazilian Behavioral Pain Scale version was considered a valid instrument for being used in adult sedated and mechanically ventilated patients in Brazil.

Resumo Justificativa e objetivos: A Escala Comportamental de Dor (Behavioral Pain Scale) é uma ferramenta de avaliação da dor para pacientes não-comunicativos e sedados em unidade de tratamento intensivo (UTI). A falta de uma escala brasileira para a avaliação da dor em adultos sob ventilação mecânica justifica a relevância deste estudo que teve por objetivo validar a versão brasileira da Escala Comportamental de Dor (ECD), bem como correlacionar seus escores com os registros de parâmetros fisiológicos, nível de sedação e gravidade da doença. Métodos: Vinte e cinco pacientes adultos internados em UTI foram incluídos neste estudo. A versão brasileira da ECD (previamente traduzida e adaptada culturalmente) e os registros dos parâmetros fisiológicos foram realizados simultaneamente por dois avaliadores durante o repouso, durante a limpeza dos olhos (estímulo não doloroso) e durante a aspiração endotraqueal (estímulo doloroso). Resultados: Valores elevados do coeficiente de coeficiente de responsividade (coeficiente = 3,22) foram observados. O coeficiente alfa de Cronbach do escore total da ECD durante a limpeza dos olhos e aspiração endotraqueal foi de 0,8. O coeficiente de correlação intraclasse do escore total da ECD foi ≥ 0,8 durante a limpeza dos olhos e aspiração endotraqueal. Houve um escore significativamente mais alto na ECD durante a aplicação do estímulo doloroso em comparação com o período de descanso (p ≤ 0,0001). No entanto, não foram observadas correlações entre dor e parâmetros hemodinâmicos, nível de sedação e gravidade da doença. Conclusões: Este estudo pioneiro de validação da ECD brasileira apresenta índices satisfatórios de consistência interna, confiabilidade entre avaliadores, responsividade e validade. Portanto, a versão da ECD brasileira foi considerada um instrumento válido para ser usado em pacientes adultos sedados e ventilados mecanicamente no Brasil.

The clinical effectiveness of detrusor combined triangle injection of Botulinum toxin type A plus hydrodistention in treating interstitial cystitis/bladder pain syndrome / 中华泌尿外科杂志

Objective To evaluate the effectiveness and security of Botulinum toxin type A (BTX-A) in treating interstitial cystitis /bladder pain syndrome,and also the effect of different site injection.Methods Sixty-nine consecutive BPS/IC patients from October 2011 to February 2016 were divided into three groups randomly,including control group (group A) and treatment group (group B and group C).There were 5 males and 64 females,with age from 23 to 66 years old (average 44.5 years old).Twentythree patients (1 male and 22 females,aged from 23 to 69 years old,with mean age of 44.6 years old) in control group (group A) underwent hydrodistention.Twenty-four patients (2 males and 22 females,aged from 27 to 65 years old,with mean age of 42.8 years old) in group B underwent BTX-A detrusor combined triangle injection plus hydrodistention.Twenty-two patients (2 males and 20 females,aged from 30 to 68 years old,with mean age of 44.3 years old) in group C underwent BTX-A triangle injection alone plus hydrodistention.The parameters such as daytime frequency,nocturia,visual analogue scale/score (VAS),functional cystemetric volume (FCV),post-void residual volume (PVR),QOL score,maximal bladder capacity (MBC),interstitial cystitis symtom index (ICSI),interstitial cystitisproblem index (ICPI),Qmax,and Hamilton anxiey scale (HAMA) score between pre-treatment and 1,3,6 and 9 months after therapy in the three groups were compared.Results There were no serious complications observed in the three groups.All parameters 1 month after therapy were obviously superior to that of pretreatment.The efficacy in control group decreased significantly 3 months after treatment except nocturia (3.0 vs.5.0),daytime frequency(7.0 vs.14.0)and Q (14.0 ml/s vs.13.0 ml/s).However,all parameters in research groups except PVR were still obviously superior to pretherapy.The parameters except Q and nocturia in group B had statistically significant difference from contemporaneous group A (all P ＜ 0.05).However,the parameters except Q nocturia and somatic anxiety score in group C had statistically significant difference from contemporaneous group A (all P ＜ 0.05).VAS (2.0 vs.3.0) and somatic anxiety score (6.0 vs.10.0) in group B were superior to group C (all P ＜ 0.05).When it came to 6 months after therapy,urinary frequence and urgency and pain symptoms were the same to pretherapy and all parameters had no statistically significant difference between pretherapy and after therapy in group A(all P ＞ 0.05).But all parameters except PVR in research group was still superior to pretherapy.the parameters except PVR,Q and QOL in group B had statistically significant difference from contemporaneous group A (all P ＜ 0.05).However,The parameters except PVR,Q MBC,ICSI and QOL in group C had statistically significant difference from contemporaneous group A (all P ＜ 0.05).Meanwhile,efficacy in group B was better than group C in term of ICPI (6.0 vs.8.0) and somatic anxiety score (7.0 vs.10.0) (all P ＜ 0.05).The efficacy decreased significantly 9 months after treatment in both group B and C,with no statistically significant difference compared with that of pretreatment.ICSI(10.0 vs.13.0),ICPI(9.0 vs.13.0),QOL(5.0 vs.6.0)in group B,and QOL(5.0 vs.6.0)in group C had statistically significant difference compared with the contemporary parameters in group A.ICSI(10.0 vs.12.0),MBC(285.0 ml vs.237.5 ml) in group B was better than that in group C (P ＜ 0.05).Conclusions Symptoms in IC/BPS patients can be alleviated significantly by detrusor BTX-A injection plus hydrodistention.Quality of life can be improved remarkably and HAMA scores can be reduced significantly after treatment.Thus,it's an effective therapeutic mnethod for IC/BPS,and detrusor combined triangle injection can provide a better effect than single triangle injection.

Charge-reversal nanoparticles: novel targeted drug delivery carriers

Spurred by significant progress in materials chemistry and drug delivery, charge-reversal nanocarriers are being developed to deliver anticancer formulations in spatial-, temporal- and dosage-controlled approaches. Charge-reversal nanoparticles can release their drug payload in response to specific stimuli that alter the charge on their surface. They can elude clearance from the circulation and be activated by protonation, enzymatic cleavage, or a molecular conformational change. In this review, we discuss the physiological basis for, and recent advances in the design of charge-reversal nanoparticles that are able to control drug biodistribution in response to specific stimuli, endogenous factors (changes in pH, redox gradients, or enzyme concentration) or exogenous factors (light or thermos-stimulation).

Development of a C3c-based ELISA method for the determination of anti-complementary potency of Bupleurum polysaccharides

Traditionally, determination of inhibitory potency of complement inhibitors is performed by the hemolytic assay. However, this assay is not applicable to the lectin pathway, thus impeding the understanding of complement inhibitors against the overall function of the complement system. The main objective of our study was to develop a specific enzyme-linked immunosorbent assay (ELISA) as an alternative method to assess the anti-complement activity, particularly against the lectin pathway. By using respective coating substrates against different activation pathways, followed by capturing the stable C3c fragments, our ELISA method can be used to screen complement inhibitors against the classical pathway and the lectin pathway. The inhibitory effect of suramin on the classical pathway, as measured by our hemolytic assay is consistent with previous reports. Further assessment of suramin and Bupleurum polysaccharides against the lectin pathway showed a good reproducibility of the method. Comparison of the lectin pathway IC50 between Bupleurum smithii var. parvifolium polysaccharides (1.055 mg/mL) and Bupleurum chinense polysaccharides (0.98 mg/mL) showed that, similar to the classical and alterative pathway, these two Bupleurum polysaccharides had comparable anti-complementary properties against the lectin pathway. The results demonstrate that the described ELISA assay can compensate for the shortcomings of the hemolytic assay in lectin pathway.

Expression of Insulin-like Growth Factor I (IGF-I) and Its Binding Proteins in Rat Tissues / 대한소아내분비학회지

covered with liguid nitrozen and pulverized with a pestle. To the powered tissue 5ml of 3.3M formic acid/0.5% Tween 20 was added and centrifuged at 40,000*g for 10 min. An aliquot of supernate was put into C18 sepak minicolumn to eliminates IGF-BPs. Measurement of IGF-I in rat tissues was done by RIA with anti-hIGF-I antibody and hIGF-I(PSIII) standard which was prepared by Drs. L. E. Underwood and J. J. Van Wyk UNC at Chapel Hill, NC, USA and distributed through the National Hormone and Pituitary Distribution Program. Distribution of IGF-I in rat tissue was seen by SDS-PAGE and ligand blotting method. A cDNA library in lambda gt11 of rat liver was used to isolate the cDNA of IGF-I. Phage containing inserts encoding rat IGF-I were identified by hybridization with biotin labeled synthesized oligomer which was the sequence from 1 to 8 aminoacids of known rat IGF-I. The EcoRI inserts were subcloned into PBluescript SK. The nucleotide sequence of both strands was determined by the dideoxy chain termination method. RESULTS: 1)IGF-BPs in tissue extract which could compete with antibody for IGF-I in measureing the IGF-I were eluted at 50Kdalton molecular weight marker using Protein-pak 300SW column. Using C18-sepak minicolumn, IGF-BPs were completely eliminated from tissue extract as much as possible, using Protein-pak 300SW column. 2)The amount of IGF-I in tissues was as folows: liver 575+/-41.6ng/g, lung 552.0+/-40.8ng/g. kidney 503+/-30.8ng/g, heart 449.0+/-30.4ng/g, testis 225+/-18.8ng/g, spleen 146+/-26.4ng/g, muscle 92+/-7.6ng/g and brain 49.0+/-5.8ng/g. The amount of IGF-I in blood was 1403+/-60.8ng/ml. 3)Banding patterns of IGF-BPs in rat tissues extract were obtained using ligand blotting. IGF-BP3 bands at 50 Kdalton molecular weight marker were strongly shown in testis, heart, and lung extracts but not in brain and muscle. IGF-BP1 and 2 band at 30Kdalton molecular weight marker was strongly shown in liver, kidney, spleen, testis, heart and lung. IGF-BP4 band at 21 Kdalton molecular weight marker was weakly shown only in spleen and muscle. 4) The nucleotide sequence of cloned cDNA of rat IGF-I is as follows. 5 10 15 5'----- CC CTT TGC GGG GCT GAG CTG GTG GAC GCT CTT CAG TTC GTG TGT 20 25 30 -GGA CCA AGG GGC TTT TAC TTC AAC AAG CCC ACA GGC TAT GGC- 35 40 45 -TCC AGC ATT CGG AGG GCA CCA CAG ACG GGC ATT GTG GAT GAG------3 CONCLUSION: This study suggests that tissue extraction method for IGF-I from tissues and elimination of IGF-BPs using C18 sepak minicolumn is suitable for measuring in large numbers of samples. Expression of IGF-I and IGF-BPs in multiple tissues suggests some phsiologic function at each tissue level. Subcloning of cDNA of exon 3 and 4 of IGF-I was useful for studying regulation of IGF-IA and IB mRNA in rat tissue.