A biochemical approach to periodontal regeneration: Tetracycline treatment of dentin promotes fibroblast adhesion and growth

One objective of periodontal therapy after resolution of the infectious process is to facilitate a new connective tissue attachment to the root dentin surface. Here we report that a selective advantage for attachment and growth can be conferred on human gingival fibroblasts by biochemical manipulation of the dentin surface. Tetracycline HCL treatment of the dentin surface increases binding of fibronectin. The adsorbed fibronectin stimulates fibroblast attachment and growth, while suppressing epithelial cell attachment and growth. This biochemical manipulation may provide a useful approach for the treatment of periodontally involved teeth.     

Antimicrobial properties of a chitosan dextran-based hydrogel for surgical use

A chitosan dextran-based (CD) hydrogel, developed for use in endoscopic sinus surgery, was tested for antimicrobial activity in vitro against a range of pathogenic microorganisms. The microdilution technique was used to determine minimum inhibitory, minimum bactericidal, and minimum fungicidal concentrations. In addition, the time-kill efficacy of CD hydrogel was determined for two bacterial species. Scanning and transmission electron microscopy were carried out to elucidate the antimicrobial mechanism of this compound. CD hydrogel was found to be effective against Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, and Clostridium perfringens at its surgical concentration of 50,000 mg/liter. Minimum bactericidal concentrations ranged from 2,000 to 50,000 mg/liter. Dextran aldehyde (DA) was found to be the antimicrobial component of the CD hydrogel with MBC ranging from 2,000 to 32,000 mg/liter. S. aureus appeared to be killed at a slightly faster rate than E. coli. Candida albicans and Pseudomonas aeruginosa were more resistant to CD hydrogel and DA. Scanning and transmission electron microscopy of E. coli and S. aureus incubated with CD hydrogel and DA alone revealed morphological damage, disrupted cell walls, and loss of cytosolic contents, compatible with the proposed mode of action involving binding to cell wall proteins and disruption of peptide bonds. Motility and chemotaxis tests showed E. coli to be inhibited when incubated with DA. The antibacterial activity of CD hydrogel may make it a useful postsurgical aid at other body sites, especially where there is a risk of Gram-positive infections.     

Maternal Early Life Factors Associated with Hormone Levels and the Risk of Having a Child with an Autism Spectrum Disorder in the Nurses Health Study II

It is not known whether reproductive factors early in the mother’s life influence risk of autism spectrum disorders (ASD). We assessed maternal age at menarche, menstrual cycle characteristics during adolescence, oral contraceptive use prior to first birth, body shape, and body mass index (BMI) in association with ASD using binomial regression in a cohort study of 61,596 women, including 743 cases. Overall, early life factors were not associated with ASD, though early age at menarche (RR for age 10 or less = 1.54, 95% CI 1.18, 2.02, p = 0.0002) and BMI at age 18 of ≥30 (RR 2.03, 95% CI 1.34, 3.08, p = 0.0008) were significantly associated with increased risk of ASD. Further work should investigate the potential influence of these factors.     

Cystatin C: influence of perfusion and myocardial injury on early (<24 h) renal function after pediatric cardiac surgery

Background: Cardiopulmonary bypass (CPB)‐associated renal dysfunction following cardiac surgery is well recognized. In patients with renal disease, cystatin C has emerged as a new biomarker which in contrast to creatinine (Cr) is sensitive to minor changes in glomerular filtration rate (GFR). Aim: We utilized cystatin C to investigate the association of CPB perfusion parameters with acute renal injury after pediatric cardiac surgery. Methods: Twenty children, aged 4–58 months (AVSD, n = 7; VSD, n = 9; and ASD, n = 4), were prospectively studied. Glomerular filtration rate was quantified postoperatively by creatinine clearance (first and second 12‐h periods; CrCl_0–12 and CrCl_12–24). Serum cystatin C and Cr were measured preoperatively and on days 0–3. Recorded CPB parameters included bypass duration (BP), perfusion pressure (PP), lowest pump flow (Q_min), lowest hematocrit, and corresponding lowest oxygen delivery (DO_{2 min}). Myocardial injury was determined by troponin‐I. Results: Postoperatively, GFR remained unchanged (CrCl_0–12 63.6 ± 37.0 vs CrCl_12–24 65.1 ± 27.5; P = 0.51) and only correlated with cystatin C (CrCl_0–12 vs cystatin C_Day0 [r = 0.58, P = 0.018] and Cr_Day0 [r = 0.09, P = 0.735]). Cr and cystatin C increased postoperatively to peak on days 2 and 3, respectively (Cr_PreOp 31 ± 6.9 vs Cr_Day2 36.9 ± 12.2, P = 0.03; cystatin C_Day0 0.83 ± 0.27 vs cystatin C_Day3 1.45 ± 0.53, P = 0.02). Increased cystatin C was significantly associated with BP (P = 0.001), mean PP (P = 0.029), Q_min (P = 0.005), troponin‐I (P < 0.001), and DO_2min <300 ml·min^?1·m^?2 (P = 0.007). Receiver–operator cutoff >1.044 mg·l^?1 for cystatin C exhibited 100% sensitivity and 67% specificity for detecting renal dysfunction, defined as GFR <55 ml·min^?1·1.73 m^?2. Conclusions: Cystatin C is a sensitive marker of early renal dysfunction following pediatric heart surgery. Variations in bypass parameters, myocardial injury, and ultimately critical oxygen delivery are significantly associated with the degree of renal impairment.     

A new horizon into the pathobiology, etiology and treatment of migraine

Sexual dimorphism in the prevalence of migraine (70% women 30% men) suggests the involvement of reproductive hormones in a women’s life. Excessive estrogen during menstruation directly stimulate estrogen receptor alpha thickly populated in trigeminal ganglia and periaqueductal gray which manifest as menstrual migraine. In contrast increased progesterone during pregnancy evokes progesterone receptors A/B, which coexist with ERs, providing complete remission from migraine episodes. Moreover, estrogen also increases nociception through extracellularly signal-regulated kinase (ERK) stimulation and down-regulating antinociceptive GABA, IL-R1 and Zn-fingers.Hormones may provoke migraine indirectly by disrupting mineral homeostasis. Estrogen enhances the absorption and half-life of copper which in turn inhibits the absorption of zinc. Zinc is required for the synthesis of melatonin and CoQ10 essential for growing women. Excess of copper exacerbates the deficiency of zinc, melatonin and CoQ10 typically low in migraineurs. Melatonin is an antioxidant, free radical scavenger and activates antioxidant enzymes like CuZn-superoxide dismutase, catalase, glutathione peroxidase (a Se-enzyme) and glutathione reductase. Zinc deficiency reduces activity of CuZn-SOD. Magnesium and vitamin B6 modulates the level of NO in the cell, both of which are deficient in migraineurs. Magnesium is essential for the removal of trapped NO from within the cell which does not occur under low magnesium levels, which reacts with superoxide generating dangerous peroxynitrite. Iron stimulates nitric oxide synthase producing more NO which is inhibited by zinc, thus, antagonizing peroxynitrite generation. Female hormones lowers magnesium but increase calcium levels which enhance migraine ubiquitousness. Accumulation of copper and iron in deep areas of brain and peripheral nerves typically catalyses the oxidation of catecholamines and generate free radicals involved in lipid-peroxidation, demyelination, denudation of axons and neurodegeneration in specific areas exposing hyperalgesic axons provoking Classical migraine. Furthermore, zinc is an essential component of Zn-fingers (Krox20 and Krox24) which play a pivotal role in the differentiation of Schwann cells-the mainstay for the myelination/remyelination of peripheral nerves.Taken together, conceptually and logically, 30 migraineurs were administered 75 mg of zinc sulfate orally in water daily for 6 weeks + one capsule of vitamin B-complex + one capsule of vitamin A or E (first 10 days) which almost cured all of them. Placebo controlled trials with incremental doses of zinc sulfate along with magnesium and selenium are proposed to augment recovery involving large population of migraineurs. Monitoring of hair and blood mineral analysis for rational therapy is recommended.