Pharmacotherapeutic strategies for treating hypertension in patients with obesity

Introduction: Hypertension and obesity are important health challenges that independently increase cardiovascular morbidity and mortality. There is a lack of randomized controlled trials to clearly inform on preferred drug choices to be adopted in clinical practice for the treatment of obesity-related hypertension (OHT). Adequate differentiation of drug classes for preferential use in obesity or the metabolic syndrome aimed at avoiding adverse effects on body weight and the metabolic profile is neglected in this population, at least in part due to the lack of specific pharmacologic recommendations in hypertension guidelines.

Areas covered: The authors summarize and suggest pharmacotherapeutic strategies based on pathophysiologic rationale to achieve blood pressure (BP) control and avoid adverse metabolic consequences in OHT.

Expert opinion: Combinations of various pharmacologic antihypertensive approaches are required in the management of OHT. It is recommended that targeting sympathetic overactivity with a centrally acting sympatholytic agent such as moxonidine should be considered as a preferred second line treatment choice in combination with renin angiotensin system (RAS) blockade, the current first line choice. Though not all obese subjects have sympathetic overdrive, this approach is likely to provide effective control of blood pressure and improve the metabolic profile of patients with OHT along with positive implications for cardiovascular risk reduction.     

Graphene oxide regulates cox2 in human embryonic kidney 293T cells via epigenetic mechanisms: dynamic chromosomal interactions

To extend the applications of engineered nanomaterials, such as graphene oxide (GO), it is necessary to minimize cytotoxicity. However, the mechanisms underlying this cytotoxicity are unclear. Dynamic chromosomal interactions have been used to illustrate the molecular bases of gene expression, which offers a more sensitive and cutting-edge technology to elucidate complex biological processes associated with epigenetic regulations. In this study, the role of GO-triggered chromatin interactions in the activation of cox2, a hallmark of inflammation, was investigated in normal human cells. Using chromosome conformation capture technology, we showed that GO triggers physical interactions between the downstream enhancer and the cox2 promoter in human embryonic kidney 293T (293T) via p65 and p300 complex-mediated dynamic chromatin looping, which was required for high cox2 expression. Moreover, tumor necrosis factor-α (TNF-α), located upstream of the p65 signaling pathway, contributed to the regulation of cox2 activation through dynamic chromatin architecture. Compared with pristine GO and aminated GO (GO-NH₂), poly (acrylic acid)-functionalized GO (GO-PAA) induced a weaker inflammatory response and a weaker effect on chromatin architecture. Our results mechanistically link GO-mediated chromatin interactions with the regulation of cox2 and suggest that GO derivatives may minimize toxicity in practical applications.     

The principal–agent problem and owner‐managers: An instrumental variables application to nursing home quality

The literature on provider ownership has primarily focused broadly on for‐profits compared with nonprofits and chains versus nonchains. However, the understanding of more nuanced ownership arrangements within individual facilities is limited. Utilizing the principal–agent and managerial control frameworks, we study the role of managerial ownership and its relationship to quality among for‐profit nursing homes (NHs). We identify NH administrators with more than 5% ownership (owner‐manager) from Ohio Medicaid Cost Reports (2005–2010) and link these data to long‐stay resident records in the Minimum Data Set. Using differential distance to the nearest NHs with a salaried manager relative to an owner‐manager, we address the differential selection into these two types of NHs. After instrumenting for admissions to owner‐managed NHs, quality among long‐stay residents at owner‐managed NHs is generally better than NHs with salaried managers. We find suggestive evidence that the magnitudes of quality difference are larger when the principal–agent problem is likely more pronounced, such as when NHs that are part of a multifacility chain and located in more concentrated markets.     

Skeletal effects of bite jumping therapy on the mandible - removable vs. fixed functional appliances

AUTHORS: Shen G, Hagg U, Darendeliler MA. OBJECTIVE: Based on an extensive review of the literature, the aim of this study was to explore the mainstream consensus on the controversial topic of whether the bite jumping treatment could enhance mandibular growth. DESIGN: The data for removable and fixed functional appliances were respectively comprehended and analyzed with regard to their attributes in mandibular growth modification. Furthermore, numerous reported findings were assessed by relating them to some important factors influencing the effects of bite jumping, such as treatment timing, treatment duration and post-treatment follow-up, to allow for a more objective and accurate evaluation. RESULTS: The key differences between removable and fixed appliances are working hours (intermittent vs. continuous), length of treatment time (long vs. short), optimal treatment timing (before puberty growth vs. at or after puberty spurt), and mode of bite-jumping (considerable vertical opening vs. limited vertical opening). These different features lead to different treatment effects on mandibular and TMJ growth, such as the intensity of possibly increased growth (clinically less significant vs. significant), the direction of enhanced growth (vertical vs. horizontal), and the stability of treatment changes (unstable vs. stable). The short-term or long-term post-treatment relapse mainly relates to the rebound of dental position. CONCLUSION: The immediate effects of bite jumping functional appliances on the mandibular growth enhancement are convincing during actual treatment. This extra gain of growth might be sustainable during the short-term and long-term post-treatment period.     

Biocompatibility of resin-based materials used as pulp-capping agents

AIM: To evaluate and compare the response of pulps of rats capped with resin-modified glass-ionomer cement (RMGIC) or self-etching adhesive system. METHODOLOGY: Class I cavities were prepared on the occlusal surface of 54 maxillary first molars of 27 rats. Pulp exposure was performed on the cavity floor. The following resin-based materials were applied as pulp-capping agents: G1, Clearfil Liner Bond 2V (CLB 2V; Kuraray Co., Japan); G2, Vitrebond (VIT; 3M/ESPE, USA). In group 3 (control group), a calcium hydroxide/saline paste (CH; Labsynth, Brazil) was used. The cavities were restored with amalgam. After 7, 30 and 60 days, the animals were sacrificed and the jaws were processed for microscopic evaluation. RESULTS: Despite the inflammatory response caused by the experimental and the control materials at 7 days, pulpal healing associated with calcified barrier formation was observed at 60 days following the pulp therapy. Both resin-based materials promoted a large zone of cell-rich fibrodentine matrix deposition on the pulp horn related to the pulp exposure site, which was larger to VIT than to CLB 2V specimens. Tertiary dentine underneath the fibrodentine matrix was deposited by a layer of elongated pulpal cells. The remaining pulpal tissue exhibited normal histological characteristics. In the control group, healing and dentine-bridge formation was observed at 30 days. Pulpal breakdown occurred only when bacterial infection occurred. CONCLUSION: Both experimental pulp-capping agents allowed pulpal healing characterized by cell-rich fibrodentine and tertiary dentine deposition as well as calcified barrier formation.     

In vitro antimicrobial and resistance-modifying activities of aqueous crude khat extracts against oral microorganisms

OBJECTIVES: To assess antimicrobial activities of aqueous crude khat (Catha edulis) extracts against a panel of oral microorganisms and to test their ability to modify bacterial resistance to tetracycline and penicillin in vitro. DESIGN: Lyophilized aqueous extracts were prepared from three khat cultivars. The agar dilution method of the NCCLS was used to test the extracts, at concentrations of 20-1.25 mg/ml, against 33 oral strains. MIC was defined as the lowest concentration at which there was no visible growth. Slight growth was defined as marked growth reduction (MGR). The E-test was used to determine the MICs of tetracycline and penicillin-G for three resistant strains in absence and presence of a sub-MIC of the khat extracts (5mg/ml). RESULTS: Eighteen strains (55%) were sensitive to the extracts (MICs 5-20 mg/ml). Most of these were periodontal pathogens with Porphyromonas gingivalis and Tannerella forsythensis being the most susceptible (MIC 5-10mg/ml). Veillonella parvula, Actinomyces israelii and some streptococci were not sensitive. Except for Lactobacillus acidophilus that showed MGR at 1mg/ml, cariogenic species were neither sensitive. The extracts were active against Streptococcus pyogenes (MIC 10-20 mg/ml) but not against Candida albicans and Staphylococcus aureus. The presence of the khat extracts at a sub-MIC resulted in a 2-4-fold potentiation of the tested antibiotics against the resistant strains. CONCLUSIONS: Khat has water-soluble constituents possessing selective antibacterial activity against oral bacteria. There is preliminary evidence for presence of an antibiotic resistance-modifying component. Further investigation is needed to identify the active components and assess their clinical relevance.     

三种陶瓷酸蚀剂对Cerinate瓷和树脂粘结强度的影响

目的 :比较三种陶瓷酸蚀剂及不同酸蚀时间对Cerinate瓷与树脂粘结强度的影响。方法 :将Cerinate瓷试件分为 4组 ,一组不使用酸蚀剂 ,其余三组分别使用自制A型 (含 2 .5 %氢氟酸 )、B型 (含 6%氢氟酸 )及C型(含 10 %氢氟酸 )陶瓷酸蚀剂 ,分别酸蚀 3 0s～ 180s ,每 3 0s为一间隔 ,与树脂粘结后测试剪切强度。结果 :C配方陶瓷酸蚀剂在 3 0s时粘结强度最大 ,达 2 7.64MPa ,相应瓷表面形态最适于粘结。结论 :C配方 (含 10 %氢氟酸 )陶瓷酸蚀剂具有较好的临床应用价值。