Adverse drug and device reactions in the oral cavity: Surveillance and reporting

BackgroundAccording to the U.S. Centers for Disease Control and Prevention, 48 percent of Americans (roughly 144 million people) used at least one prescribed medication in the preceding month; 11 percent used five or more. The authors describe the U.S. Food and Drug Administration's (FDA's) MedWatch program, the safety surveillance system for drugs and devices in the United States, and the dentist's role with regard to voluntary reporting of adverse effects (AEs). They also identify the most frequent AEs in the oral cavity as reported in the FDA Adverse Event Reporting System (FAERS).MethodsThe authors reviewed the literature regarding MedWatch, and they mined data in the FAERS public database for the 100 most commonly prescribed medications and their associated AEs.ResultsPharyngitis was the most common AE. Cough, dysgeusia and dysphagia also were common.ConclusionThe MedWatch program and its related databases contain useful information about AEs of pharmaceuticals and devices manifested in the oral cavity. Increased participation in the reporting of suspected adverse reactions will improve the national surveillance system and ultimately will protect patients' safety.Practical ImplicationsAs pharmaceutical consumption increases exponentially for a growing segment of the population, and as innovation in dental technology and devices flourishes, dentists have a distinct role in safeguarding patients' well-being. Promptly reporting AEs in the oral cavity improves quality of care and protects patients' well-being.     

Should IFN-γ, IL-17 and IL-2 be considered predictive biomarkers of acute rejection in liver and kidney transplant? Results of a multicentric study

Acute rejection (AR) remains a major challenge in organ transplantation, and there is a need for predictive biomarkers. In the present multicenter study, we prospectively examined a series of biomarkers in liver and kidney recipients. Intracellular expression of IFN-γ, IL-17 and IL-2 and IL-17 soluble production were evaluated both pre-transplantation and post-transplantation (1st and 2nd week, 1st, 2nd and 3rd month). 142 transplant patients (63 liver/79 kidney) were included in the study. Twenty-eight recipients (14 liver/14 kidney) developed AR. Pre- and post-transplantation intracellular expression of %IFN-γ⁺ in CD4⁺CD69⁺ and in CD8⁺CD69⁺ and soluble IL17 identified liver and kidney transplant patients at high risk of AR. Pre-transplantation, %IL-2⁺ in CD8⁺CD69⁺ also identified kidney patients at high risk. We constructed pre- and post-transplantation risk prediction models, based on a composite panel of biomarkers, which could provide the basis for future studies and will be a useful tool for the selection and adjustment of immunosuppressive treatments.     

Auditory neural myelination is associated with early childhood language development in premature infants

Background

Auditory neural myelination (ANM) as evaluated by auditory brainstem evoked response (ABR) during the neonatal period has been used as a surrogate outcome for long-term neurodevelopment. The validity of ANM as a surrogate outcome for long-term neurodevelopment has not been well studied.

Aim

Evaluate the association of ABR I–V interpeak latency (IPL), an index of ANM, at 35 week postmenstrual age (PMA) with language outcome at 3 years of age.

Design

Prospective study.

Subjects

24–33 week gestational age (GA) infants were eligible if they did not meet exclusion criteria: craniofacial malformation, chromosomal disorders, deafness, auditory dys-synchrony, TORCH infection, or non-English speaking parents. Infants with malignancy, head injury, encephalopathy, meningitis, blindness, or who died or relocated were also excluded.

Outcome measures

ABRs were performed at 35 week PMA using 80 dB nHL and I–V IPL (ms) measured. Auditory Comprehension (AC) and Expressive Communication (EC) were evaluated by a speech-language pathologist at 3 years of age using Preschool Language Scale.

Results

Eighty infants were studied. The mean GA and birth weight of infants were 29.2 weeks and 1336 g, respectively. There was association of worse ear I–V IPL and better ear I–V IPL with AC (Coefficient − 5.4, 95% CI: − 9.8 to − 0.9 and Coefficient − 5.5, 95% CI: − 10  to−0.9, respectively) and EC (Coefficient − 5.6, 95% CI: − 9.5  to−1.8 and Coefficient − 6.7, 95% CI: − 10.6  to−2.7, respectively) after controlling for confounders.

Conclusion

The neonatal I–V IPL is a predictor of language development at 3 years of age in preterms.     

Mast cells derived from human induced pluripotent stem cells are useful for allergen tests

Background

Several methods have been developed to detect allergen-specific IgE in sera. The passive IgE sensitization assay using human IgE receptor-expressing rat cell line RBL-2H3 is a powerful tool to detect biologically active allergen-specific IgE in serum samples. However, one disadvantage is that RBL-2H3 cells are vulnerable to high concentrations of human sera. Only a few human cultured cell lines are easily applicable to the passive IgE sensitization assay. However, the use of human induced pluripotent stem cells (iPSCs) to generate human mast cells (MCs) has not yet been reported.

Intercellular communication via gap junctions in activated rat hepatic stellate cells

BACKGROUND AND AIMS: Gap junctional communication was studied in quiescent and activated hepatic stellate cells. METHODS: Connexin expression and intercellular dye transfer were studied in rat hepatic stellate cells in culture and in vivo. RESULTS: Protein expression of connexin 43 was up-regulated in activated hepatic stellate cells in vivo and in vitro and was mainly localized on the cell surface, whereas connexin 26 was found intracellularly. In contrast to hepatocytes, hepatic stellate cells do not express connexin 32. Confluent hepatic stellate cells in culture communicate via gap junctions, resulting in lucifer yellow transfer and propagation of intracellular calcium signals. Phorbol ester induces a protein kinase C-dependent hyperphosphorylation and degradation of connexin 43 and inhibits intercellular communication on a short-term time scale. At the long-term level, vitamin D(3) , lipopolysaccharide, thyroid hormone T(3), dexamethasone, platelet-derived growth factor, endothelin 1, and interleukin 1beta up-regulate connexin 43 protein and messenger RNA expression and enhance intercellular communication. Slight down-regulation of connexin 43 is observed in response to vitamin A. Connexin 43 induction by endothelin 1 is inhibited by both endothelin A and endothelin B receptor antagonists. In coculture systems, hepatic stellate cells communicate with each other, which is suggestive of a syncytial organization, but no communication was found between hepatic stellate cells and other liver cell types. As shown by immunohistochemistry and electron microscopy, gap junctions are formed between activated hepatic stellate cells in vivo. CONCLUSIONS: Gap junctional communication occurs between hepatic stellate cells, is enhanced after activation, and underlies complex regulation by cytokines, hormones, and vitamins.     

佛波酯对人胃癌细胞Ha-ras基因启动子及启动子结合蛋白的影响

目的探讨佛波酯（PMA）对人胃癌细胞BGC-823 Ha—ras基因启动子活性及启动子结合蛋白活性的影响。方法通过RT-PCR和运用自行构建的真核表达载体prasEYFP转染细胞进行荧光细胞检测,并应用凝胶电泳移动检测、Southwestern blotting等方法检测PMA（100μg／L）处理BGC-823细胞72和96h后,对Ha—ras基因表达水平、Ha—ras基因启动子活性以及对Ha—ras启动子结合蛋白的影响。结果经PMA（100μg／L）处理72和96h,与未处理细胞相比,BGC-823细胞中Ha—ras基因表达显著降低,Ha—ras基因启动子活性分别被抑制65．2％和71．8％;同时两个Ha-ras启动子结合蛋白活性也显著降低,经检测,其分子量分别约为18kD,35kD。结论PMA长期处理通过降低人胃癌细胞中Ha—ras启动子结合蛋白活性使Ha—ras启动子活性被抑制,从而在转录水平上调节Ha—ras基因表达。     

热休克、PMA对体外培养人角朊细胞表达ENA的影响

ENA在角朊细胞膜表达被认为与 LE的发病有关。为了探讨热休克和 PMA对 ENA表达的影响 ,我们用加热和 PMA刺激体外培养角朊细胞 ,用间接免疫荧光法观察了角朊细胞 ENA的表达。结果 ,4 2℃、4 5℃热休克 90 min后 ,分别可使 9.1± 1.2 %、2 0 .0± 4 .7%的细胞出现 ENA膜表达 ;5μg/ L、10 μg/ L PMA刺激 2 h后 ,2 2 .6± 7.6%、2 3.1± 4 .9%的角朊细胞膜出现 ENA表达。提示 ENA在角朊细胞膜的表达与热刺激和蛋白激酶 C传导路径有关。