Roger D. Gibb

Gingival Transcriptome Patterns During Induction and Resolution of Experimental Gingivitis in Humans

BACKGROUND To our knowledge, changes in the patterns of whole-transcriptome gene expression that occur during the induction and resolution of experimental gingivitis in humans were not previously explored using bioinformatic tools. METHODS Gingival biopsy samples collected from 14 subjects during a 28-day stent-induced experimental gingivitis model, followed by treatment, and resolution at days 28 through 35 were analyzed using gene-expression arrays. Biopsy samples were collected at different sites within each subject at baseline (day 0), at the peak of gingivitis (day 28), and at resolution (day 35) and processed using whole-transcriptome gene-expression arrays. Gene-expression data were analyzed to identify biologic themes and pathways associated with changes in gene-expression profiles that occur during the induction and resolution of experimental gingivitis using bioinformatic tools. RESULTS During disease induction and resolution, the dominant expression pathway was the immune response, with 131 immune response genes significantly up- or downregulated during induction, during resolution, or during both at P <0.05. During induction, there was significant transient increase in the expression of inflammatory and oxidative stress mediators, including interleukin (IL)-1 alpha (IL1A), IL-1 beta (IL1B), IL8, RANTES, colony stimulating factor 3 (CSF3), and superoxide dismutase 2 (SOD2), and a decreased expression of IP10, interferon inducible T-cell alpha chemoattractant (ITAC), matrix metalloproteinase 10 (MMP10), and beta 4 defensin (DEFB4). These genes reversed expression patterns upon resolution in parallel with the reversal of gingival inflammation. CONCLUSIONS A relatively small subset (11.9%) of the immune response genes analyzed by array was transiently activated in response to biofilm overgrowth, suggesting a degree of specificity in the transcriptome-expression response. The fact that this same subset demonstrates a reversal in expression patterns during clinical resolution implicates these genes as being critical for maintaining tissue homeostasis at the biofilm-gingival interface. In addition to the immune response pathway as the dominant response theme, new candidate genes and pathways were identified as being selectively modulated in experimental gingivitis, including neural processes, epithelial defenses, angiogenesis, and wound healing.

Fecal excretion of Bifidobacterium infantis 35624 and changes in fecal microbiota after eight weeks of oral supplementation with encapsulated probiotic

Certain randomized, placebo-controlled trials of oral supplementation with B. infantis 35624 have demonstrated the amelioration of symptoms of irritable bowel syndrome. Potential GI colonization by B. infantis 35624 or effects of supplementation on resident GI microbiota may pertain to these clinical observations. In this study, fecal excretion of B. infantis 35624 before, during and after 8 weeks of daily treatment was compared in subjects with IBS who received either the encapsulated oral supplement (n = 39) or placebo (n = 37) and in healthy subjects who received the supplement (n = 41). Secondarily, changes in assessed fecal microbiota and IBS symptoms were determined. Supplementation significantly increased fecal B. infantis 35624 excretion vs. placebo in IBS subjects; excretion in healthy subjects receiving supplement was quantitatively similar. Fecal levels of the probiotic declined and approached baseline once dosing ceased, documenting that colonization is transient. Although supplementation increased numbers of B infantis 35624 within the GI tract, limited changes in 10 other fecal taxa were observed either in healthy subjects or those with IBS. No impact on IBS symptoms was observed. Detection of bacterial DNA in fecal samples suggests that the probiotic is able to survive transit through the GI tract, although strain selective culture techniques were not performed to confirm viability of B. infantis 35624 in the feces. Continuous probiotic administration was necessary to maintain steady-state transit. Given the complex spectrum of GI microbiota, however, monitoring perturbations in selected taxa may not be not a useful indicator of probiotic function.

Psyllium fiber improves glycemic control proportional to loss of glycemic control: a meta-analysis of data in euglycemic subjects, patients at risk of type 2 diabetes mellitus, and patients being treated for type 2 diabetes mellitus

BACKGROUND A number of health benefits are associated with intake of soluble, viscous, gel-forming fibers, including reduced serum cholesterol and the attenuation of postprandial glucose excursions. OBJECTIVE We assess the effects of psyllium, which is a soluble, gel-forming, nonfermented fiber supplement, on glycemic control in patients who were being treated for type 2 diabetes mellitus (T2DM) and in patients who were at risk of developing T2DM. DESIGN A comprehensive search was performed of available published literature (Scopus scientific database) and clinical records stored by Procter & Gamble with the use of key search terms to identify clinical studies that assessed the glycemic effects of psyllium in nondiabetic, pre-T2DM, and T2DM patients. RESULTS We identified 35 randomized, controlled, clinical studies that spanned 3 decades and 3 continents. These data were assessed in 8 meta-analyses. In patients with T2DM, multiweek studies (psyllium dosed before meals) showed significant improvement in both the fasting blood glucose (FBG) concentration (-37.0 mg/dL; P < 0.001) and glycated hemoglobin (HbA1c) [-0.97% (-10.6 mmol/mol); P = 0.048]. Glycemic effects were proportional to baseline FBG; no significant glucose lowering was observed in euglycemic subjects, a modest improvement was observed in subjects with pre-T2DM, and the greatest improvement was observed in subjects who were being treated for T2DM. CONCLUSIONS These data indicate that psyllium would be an effective addition to a lifestyle-intervention program. The degree of psylliums glycemic benefit was commensurate with the loss of glycemic control. Because the greatest effect was seen in patients who were being treated for T2DM, additional studies are needed to determine how best to incorporate psyllium into existing prevention and treatment algorithms with concomitant hypoglycemic medications.

Doxylamine pharmacokinetics following single dose oral administration in children ages 2–17 years†

To characterize doxylamine pharmacokinetics in children. This study was conducted in 41 subjects, ages 2–17 years. Doxylamine succinate doses based on age/weight ranged from 3.125 to 12.5 mg. A single oral dose was administered with 2 to 4 oz. of water or decaffeinated beverages ∼2 hours after a light breakfast. Plasma samples were obtained before and for 72 hours after dosing and analyzed for doxylamine using HPLC MS/MS. Pharmacokinetic parameters were estimated using non‐compartmental methods and relationships with age were assessed using linear regression. Over the fourfold dose range, Cmax was similar while AUC increased only 60%, although not statistically significant (P‐value = 0.0517). As expected due to increasing body size, CLo and Vz/F increased with age. Due to a similar increase with age for Clo and Vz/F, no age‐related differences in t1/2,z were observed (∼16 hours). Allometric scaling indicated no maturation related changes in CLo; although Vz/F remained age‐dependent, the predicted range decreased ∼70%. Overall, the single doses were well tolerated. Somnolence was the most common reported AE with no apparent differences in incidence noted with age. An age/weight dosing nomogram utilizing a fourfold range of doses achieves similar Cmax, whereas AUC increases only 60%.

Evidence‐based treatment of frequent heartburn: The benefits and limitations of over‐the‐counter medications

Purpose: This review summarizes the pharmacological effects of over‐the‐counter (OTC) heartburn drugs, and the implications for treating frequent heartburn. Data sources: PubMed and SCOPUS were searched across all years to identify well‐controlled, randomized clinical studies that assessed mechanism of action and efficacy. Conclusions: Antacids can transiently neutralize acid in the esophagus, but do not significantly affect gastric pH or prevent subsequent heartburn episodes. Histamine‐2 receptor antagonists (H2RAs) rapidly develop tolerance with repeat dosing, and exhibit an analgesic effect that may provide heartburn relief while leaving the esophagus exposed to acid. Proton pump inhibitors (PPIs) provide a sustained inhibition of gastric acid production, and are superior to antacids and H2RAs for control of gastric acid and treatment of frequent heartburn. Implications for practice: When recommending therapies for frequent heartburn, it is of particular importance to understand the strengths and weaknesses of available OTC medications. Antacids and H2RAs are not recommended for treatment of frequent heartburn, while OTC PPIs are both indicated for, and effective for, treatment of frequent heartburn. A PPI dose of 20 mg is optimal for empiric treatment of frequent heartburn, and consistent with the 2013 treatment guidelines established by the American College of Gastroenterology (ACG) for treatment with a minimum effective dose.

Omeprazole-Mg 20.6 mg is superior to lansoprazole 15 mg for control of gastric acid: a comparison of over-the-counter doses of proton pump inhibitors

Aliment Pharmacol Ther 31, 846–851

The impact of diaper design on mitigating known causes of diaper dermatitis

Diapers play a critical role in infant health. In addition to providing sanitary methods of disposing of urine and feces, they can also directly impact skin health. Prolonged exposure to wetness and fecal matter has been shown to be a key driver of diaper dermatitis. This study sought to evaluate how diaper construction can affect absorption of stool.

Improving Diaper Performance for Extremely Low-Birth-Weight Infants:

Background. Extremely low-birth-weight (ELBW) infants face significant diapering challenges compared with their full-term peers, due to immature musculature, nervous system, and skin development. Advances in medical care have increased an ELBW infant’s rate of survival, which creates a growing need for diapers to better serve these infants. Aim of research. The objective of this study was to identify and confirm the requirements for optimal diaper performance from the neonatal intensive care unit nurses’ perspective, as well as to assess in-hospital performance to determine if new features improved key developmental care parameters. Method. Two surveys were shared among nurses to address study objectives. Study 1 (N = 151) was designed for neonatal intensive care unit nurses to identify key requirements for ELBW diapers and rate the performance of existing ELBW diapers. Study 2 (N = 99) assessed in-hospital performance of the test diaper compared with the usual diaper, under normal usage conditions. Findings/results. The majority of nurses agreed that ELBW diapers must fit appropriately between the legs so that hips and legs are not spread apart and that ELBW diapers need to be flexible between the legs for positioning. Of the nurses-infant pair responses, 93% (P < .0001) preferred the test ELBW diaper over their usual diaper. Conclusion. Findings suggest that nurses should be included in the product design process to ensure both their needs and the needs of an infant are being met. Nurses are considering how diaper features may affect both acute and long-term medical outcomes and this information provides necessary guidance to diaper manufacturers and designers when developing better-performing diapers.

Psyllium Is Superior to Wheat Dextrin for Lowering Elevated Serum Cholesterol

The Dietary Reference Intakes for fiber are based on an association between a high-fiber diet and a reduced risk of cardiovascular disease. Only 5% of Americans consume the recommended levels of dietary fiber; most consume approximately half the recommended level. If a fiber supplement is used to achieve the recommended level, it is important that the isolated fiber has the requisite physical properties to reduce the risk of cardiovascular disease by lowering elevated serum low-density lipoprotein and total cholesterol. The current study was designed to directly assess the cholesterol-lowering effects of psyllium, a natural nonfermented viscous/gel-forming fiber, versus wheat dextrin, a semisynthetic, readily fermented nonviscous supplement. The study was a 3-month, randomized, parallel-group design (n = 20 enrolled) that assessed psyllium husk (3.4 g) and wheat dextrin (3.5 g) dosed 3 times a day before meals. The results showed that gel-forming psyllium significantly (P < .05) lowered both low-density lipoprotein cholesterol (−17%) and total cholesterol (−11%), without affecting high-density lipoprotein cholesterol, versus wheat dextrin. In conclusion, clinicians and consumers should be aware that the physical characteristics of a fiber supplement determine whether it will provide specific health benefits, and it is recommended to only take those fiber supplements with evidence of clinically meaningful health benefits from well-controlled clinical studies.