Antioxidant effect of omega-3 fatty acids on exercise-induced oxidative stress in rats.

OBJECTIVE: The aim of this study is to examine the effects of omega-3 supplementation on Catalase (CAT) activity, Malondialdehyde (MDA), advanced oxidation protein products (AOPP) and reduced glutathione (GSH) levels in long-term aerobic exercises in rats. MATERIALS AND METHODS: 28 male Wistar albino rats (8 weeks old, 220-350 g body weight) were included in the study. The rats were given treadmill exercise for 20 minutes at an average speed of 15 cm/s, 5 days a week, for 8 weeks. The experiment was terminated at the end of the eighth week. Blood samples were taken. CAT, MDA, AOPP and GSH analyses were performed. SPSS v. 21 package program was used in the analysis of the data. The distribution of the data was examined with the normality homogeneity test, and it was determined that it was a normal distribution. As a result, the One-Way ANOVA test, one of the parametric tests, was used. Tukey test was used to determine the difference between groups. Significance levels were evaluated as (p < 0.05). RESULTS: Statistical analysis showed a statistically significant difference between groups in CAT, MDA and GSH levels (p < 0.05), while there were no differences between the groups in AOPP levels (p > 0.05). CONCLUSIONS: In the conclusion of the study, it was determined that omega-3 supplementation caused a decrease in MDA level, an increase in CAT activity and GSH level in rats exposed to chronic long-term exercise. Thus, it can be said that omega-3 supplementation in chronic long-term exercise will provide antioxidant protection against potential oxidative damage.

Efficiency and clinical results of bleomycin injection in the treatment of lymphatic malformations.

Background: Lymphatic malformations (LMs) are rare congenital anomalies. The traditional treatment is surgical excision, but intralesional sclerosing agent injection is also preferred as the first-choice treatment because of postoperative frequent recurrences, poor cosmetic results, and high complication rate. We aimed to evaluate the efficacy of sclerosing agent injection used in the treatment of LMs in children. Materials and Methods: We retrospectively analyzed the children who were treated for LM between January 2011 and January 2022. The lesion sizes of the patients who were injected with sclerosant (Bleomycin) under sedation anesthesia, measured by ultrasound before and after the treatment, were recorded, and the difference between them was statistically evaluated. Results: Fifteen patients were retrospectively analyzed. The mean age was 45.2 ± 14.1 months. Of these, ten (66.6%) were male and five (33.3%) were female (F/M = 1/2). The mean age of male patients was 55 ± 20.1 months; the mean age of female patients was 25.8 ± 11. Seven patients had a single dose, two had twice, and six had three and more. The mean measurable size of macrocystic lesions before treatment was 55.2 ± 28.4 mm; after treatment, it was 23.8 ± 18.2 mm. Although no measurable shrinkage was detected in microcystic lesions, it was observed that the lesion shrank to allow surgical resection. With the statistical analysis, it was seen that there was a statistically significant difference between the dimensions before and after the treatment (P < 0.05) and the sclerosant injection had a great effect on the treatment (R: 0.89). Conclusion: Intralesional injection of bleomycin is less effective for microcystic or mixed-type LMs, but provides an effective reduction for a safe surgical procedure. It is an effective treatment for macrocystic lesions.

Disease course and treatment outcomes of Crohn's disease patients with early or late surgery - A Danish nationwide cohort study from 1997 to 2015.

BACKGROUND: Studies on early surgery among Crohn's disease patients are few and focus on ileocolonic resections. AIM: The aim of this nationwide cohort study was to investigate the disease course in all Crohn's disease patients who underwent early and late major abdominal surgery. METHODS: In a Danish nationwide cohort of Crohn's disease patients from 1997 to 2015 we included 493 patients (group 1) resected within 29 days, 472 patients (group 2) resected between 30 and 180 days, and 1,518 patients (group 3) resected after 180 days of diagnosis. Re-operation, hospitalisations and medications were analysed. RESULTS: The cumulative risk of re-operation was lower among patients from group 1 (five-year risk: 16.5% vs. group 2: 18.2% and group 3: 21.2%, p = 0.004). Fewer patients from group 2 and 3 required hospitalisations (269 (56.5%) and 803 (52.8%) vs. group 1: 329 (66.8%) p<0.001). Patients from group 3 had a higher cumulative use of immunomodulators in the first three years after initial surgery (one-year risk: 24.6% vs. group 1: 19.4% and group 2: 17.0%, p<0.001). CONCLUSION: Crohn's disease patients resected within 29 days of diagnosis had a lower cumulative risk of re-operation and a lower cumulative exposure to immunomodulators in the initial years after surgery.

Three-dimensional control of alluvial fans by rock uplift in an extensional regime: Aydin Range, Aegean extensional province.

Tectonics imparts a first-order control on the overall morphology of alluvial fan systems in extensional settings by influencing sediment flux and accommodation space, while other factors such as climate, catchment lithology, and fault footwall characteristics are secondary. Previous alluvial fan modeling studies have focused on the link between the three-dimensional development of alluvial fans and rock uplift, however, despite the potential influence of tectonics on the overall three-dimensional morphology of alluvial fans, the controlling mechanisms, as well as their relative importance, remain largely unquantified in a natural setting with a targeted source-to-sink approach. Here, we examine 45 alluvial fans and their catchments along the southern mountain front of the Aydin Range, delimited by segmented normal faults in the western Anatolia Extensional Province, to quantify the role of rock uplift. We quantify river incision rates and catchment-wide erosion rates together with a series of topographic analyses across the southern flank of the Aydin Range as a proxy for rock uplift. Our results indicate that the spatial distribution of thicker and steeper alluvial fans fit well with higher rock uplift rates along the strike of the mountain front. In contrast, a lower uplift rate is responsible for prograding alluvial fans with decreasing thickness and gradients. Also, our data shows that alluvial fan thickness compared to other alluvial fan metrics strongly associated with the pattern of the rock uplift. This study demonstrates a field-based, quantitative linkage between three-dimensional alluvial fan morphology and rock uplift which has significant implications for improving alluvial fan models and understanding how alluvial fans respond to tectonics in extensional regions.

Effects of curcumin administration on Nesfatin-1 levels in blood, brain and fat tissues of diabetic rats.

OBJECTIVE: We evaluated the efficacy of curcumin administration on blood glucose levels and its relationship with nesfatin-1 levels in blood brain and adipose tissue of streptozotocin-induced diabetic rats. MATERIALS AND METHODS: A total of 28 male rats were divided into four groups: control group, type 2 diabetes mellitus (DM) group, control plus curcumin group and type 2DM plus curcumin group. After fifteen days, blood samples were collected from sacrificed rats. Nesftain-1 levels were analysed from blood, brain, and fat tissues of rats in all groups. RESULTS: Nesfatin-1 level was found to be significantly lower in blood, brain and fat tissues of type 2 DM rats compared to the control group. A significant decrease in fasting blood glucose levels was observed in the curcumin administration group compared to type 2 DM group. Improvement of fasting blood glucose level was accompanied by improvement of nesfatin-1 levels in blood, brain, and fat tissues. CONCLUSIONS: As expected, curcumin administration caused significant improvement in fasting blood glucose levels. However, for the first time, we found marked improvements in nesfatin-1 levels in blood, brain, and fat tissues of type 2 DM rats. Thus, considering the crucial role of nesfatin-1 in regulation of glucose metabolism, it is logical to expect an interactive relationship between curcumin and nesfatin-1.

Early Caries in an In Vivo Model: Structural and Nanomechanical Characterization.

The utilization of rat models in cariology research has made substantial contributions to decipher mechanisms of caries formation and to develop preventive treatments. The existing rat models still have potential for improvement toward establishing a more accurate standard caries protocol to utilize in testing and/or developing new dental technologies. The current caries-scoring methods rely on optical microscopy-based techniques, which necessitates formation of highly advanced lesions. Moreover, models that facilitate the implementation of cariogenic bacteria by shifting the balance of oral flora through desalivation and/or antibiotic treatment create a nonnatural environment. Furthermore, there is a paucity of detailed structural and mechanical characterization on the resulting carious lesions. The purpose of this study was to develop a rat model that induces formation of mild carious lesions and to provide comprehensive structural and mechanical characterization. With this aim in mind, an in vivo model promoting progression of mild lesions was established with specific pathogen-free Sprague-Dawley rats. Cariogenic bacteria, Streptococcus mutans, was implemented into the oral flora without the use of antibiotics or desalivation surgery. During caries formation, progression of the infection was monitored by quantifying the relative abundance of S. mutans in oral flora with quantitative real-time polymerase chain reaction. A significant increase in colonization efficacy of S. mutans was detected during cariogenic challenge ( P < 0.01). The resulting carious lesions were analyzed by conventional light optical and scanning electron microscopy. A detailed structural and morphological characterization on fissure caries with different degrees of severity was provided. The changes in the morphology and demineralization state of the sound and carious tissues were quantified by energy-dispersive X-ray spectroscopy, and local mechanical properties were acquired with nanoindentation. The principles laid out in this work can be utilized in cariology research and developed into a standard protocol for future studies.

Comparison of Intermittent Fasting Versus Caloric Restriction in Obese Subjects: A Two Year Follow-Up.

OBJECTIVE: Caloric restriction (CR) is proven to be effective in increasing life span and it is well known that, nutritional habits, sleeping pattern and meal frequency have profound effects on human health. In Ramadan some Muslims fast during the day-light hours for a month, providing us a unique model of intermittent fasting (IF) in humans. In the present study, we have investigated the effects of IF versus CR on the same non-diabetic obese subjects who were followed for two years according to the growth hormone (GH)/Insulin like growth factor (IGF)-1 axis and insulin resistance. DESIGN: Single-arm Interventional Human Study. PARTICIPANTS: 23 female subjects (Body Mass Index (BMI) 29-39, aged between 28-42years). SETTING: Follow-up is designed as 12 months of CR, after which there was a month of IF and 11 months of CR again, to be totally 24 months. Subjects' daily diets were aligned as low calorie diet during CR and during the IF period, the same subjects fasted for 15 hours in a day for a month and there was no daily calorie restriction. Nutritional pattern was changed as 1 meal in the evening and a late supper before sleeping and no eating and drinking during the day light hours in the IF model. Subjects made brisk walking twice a day during the whole follow-up including both CR and IF periods. BMI, Blood glucose, insulin, TSH, GH, HbA1c, IGF-1, Homa-IR and urinary acetoacetate levels were monitored once in three months and twice in the fasting month. MEASUREMENTS AND RESULTS: While subjects lost 1250 ± 372g monthly during the CR, in the IF period, weight loss was decreased to 473 ± 146 g. BMI of all subjects decreased gradually and as the BMI decreased, glucose, HbA1c, insulin, Homa-IR and TSH levels were decreased. GH levels were at baseline at the beginning, increased in the first six months and stayed steady during the CR and IF period than began decreasing after the IF period, while IGF-I increased gradually during the CR period and beginning with the 7th day of IF period, it decreased and kept on decreasing till the end of the follow-up. Urinary acetoacetate levels were higher during the IF period suggesting a constant lipid catabolism. CONCLUSION: Our results suggest that, CR affects metabolic parameters positively which will help especially pre-diabetic and insulin resistant patients without any pharmacological approach. In addition IF without calorie restriction can enhance health and cellular resistance to disease without losing weight and those effects may be attributed to different signalling pathways and circulating ketones during IF. Changes observed during IF are probably due to the changes in eating and sleeping pattern and thus changes in metabolic rhythm.

Soluble Klotho levels in diabetic nephropathy: relationship with arterial stiffness.

OBJECTIVE: In this cross-sectional study, we investigate the relationship between soluble Klotho (s-Klotho) levels, markers of bone mineral metabolism and arterial stiffness in 109 diabetic nephropathy patients (median age 61.00± 9.77 years) and 32 healthy controls (median age 49.23 ± 7.32 years). PATIENTS AND METHODS: Blood samples were collected to measure the levels of s-Klotho, and FGF23, serum creatinine, Calcium (Ca), Phosphorus (P), 25-hydroxyvitamin D3 (25hD) and parathyroid hormone (PTH). Pulse wave velocity (PWV) and blood pressure were also measured using a combined monitor. RESULTS: s-Klotho, FGF23 and PTH levels were significantly higher and 25hD was significantly lower in the patients than in controls (p < 0.001). Systolic blood pressure, pulse pressure and PWV were also significantly higher in the patients (p < 0.001). s-Klotho, FGF23 and 25hD levels significantly varied between sub-groups according to CKD stages, defined according to the CKD epidemiology collaboration equation. A strong positive correlation was found between s-Klotho and FGF23 (r = 0.768, p = 0.001) levels, but not with other bone mineral metabolism, blood pressure or arterial stiffness parameters. Creatinine levels significantly differed (p = 0.009) between three s-Klotho-level sub-groups, with the high creatinine levels in the sub-group with the lowest s-Klotho levels and estimated glomerular filtration rate (eGFR). CONCLUSIONS: There was no correlation between eGFR and s-Klotho levels. Arterial stiffness increased in CKD but was not related to s-Klotho or FGF23 levels. Among all parameters, FGF23 levels had the greatest effect on s-Klotho levels.

Increased oxidative stress in diabetic nephropathy and its relationship with soluble Klotho levels.

BACKGROUND: In the present study, we aimed to assess the relationship between the levels of soluble Klotho (s-Klotho) and oxidative stress markers in diabetic nephropathy patients with different stages of chronic kidney disease (CKD) and albuminuria levels. METHODS: We enrolled 109 patients with type 2 diabetes (mean age, 61.63 ± 9.77 years) and 32 healthy controls (mean age, 49.53 ± 7.32 years) between January and June 2014.  Patients were classified into three groups based on their urinary albumin/creatinine ratio (UACR). Blood samples were collected to measure the levels of s-Klotho, serum creatinine, calcium, phosphorus, 25-hydroxyvitamin D3, and parathyroid hormone (PTH). We used the total oxidant status (TOS), total antioxidant status (TAS), ischemia-modified albumin (IMA), and ischemia-modified albumin ratio (IMAR) values to measure the oxidative status. Moreover, the oxidative stress index (OSI) was estimated as the percentage ratio of TOS/TAS values. RESULTS: The TOS, TAS, and OSI values were significantly greater in the diabetic nephropathy patients compared to controls (p <0.001). When patients were classified based on their UACR, we noted that the TOS, OSI, and IMA values did not significantly differ, although the TAS (p <0.001), and IMAR (p =0.002) values significantly differed between the groups. The s-Klotho levels also significantly differed (p =0.031) between the groups. These s-Klotho levels exhibited a significant positive correlation with TOS (r =0.186, p =0.034) and OSI (r =0.207 p =0.018), but showed no correlation with the estimated glomerular filtration rate; UACR; HbA1c, calcium, phosphorus, and PTH levels; and TAS, IMA, and IMAR values. CONCLUSION: Oxidative stress is greater in patients with diabetic nephropathy, and the TOS was positively correlated with s-Klotho levels in diabetic patients. The therapeutic reduction of oxidative stress in patients with diabetic nephropathy could improve the renal and cardiovascular outcomes. Hippokratia 2016, 20(3): 198-203.

The antioxidant effect of Echinacea angustifolia and Echinacea purpurea in rat colitis model induced by acetic acid.

BACKGROUND: Ulcerative colitis is a chronic inflammatory condition of the colon, and reactive oxidative metabolites (ROMs) play an important role in its pathogenesis. Alternative therapies such as herbal remedies are increasingly being used in the treatment of ulcerative colitis for better clinical outcome of ulcerative colitis and less adverse effects. Echinacea has many features including antioxidant and wound-healing properties. Hence, the present study was undertaken to evaluate the protective effect of Echinacea spp. on experimental colitis model induced by acetic acid in Wistar albino rats. METHODS: Acute colitis was induced by intrarectal administration of acetic acid. Rats were divided into four groups, namely control, Echinacea-administered, Echinacea-administered-colitis and colitis. Malondialdehyde and total antioxidant status were assayed in tissue samples. Histopathological evaluation was also performed. RESULTS: Macroscopic and microscopic scores were significantly higher in colitis group compared to control, Echinacea and Echinacea-colitis groups (p < 0.001). There was no significant differences in respect of macroscopic and microscopic scores between control, Echinacea and Echinacea-colitis groups (p > 0.3, p > 0.22). Malondialdehyde levels were elevated in colitis group compared to other groups (p < 0.001). Total antioxidant status was significantly higher in Echinacea group compared with other groups and also significantly higher in Echinacea-colitis group compared with colitis group (p < 0.001, p < 0.001, respectively). CONCLUSION: Echinacea may possibly have some therapeutic usefulness in the management of ulcerative colitis (Tab. 2, Fig. 4, Ref. 35).

Favourable effect of Eugenol on liver histology in acute cholestasis in rats after bile duct ligation.

BACKGROUND: Eugenol an essential oil found in clove was previously shown to have some anti-inflammatory properties. It also was shown to be linked to hepatoprotective effect. In this regard, we aimed to reveal the effect of eugenol on cholestatic liver disease. METHOD: Cholestatic liver disease model was established in 20 rats via bile duct ligation. Eugenol was administered and cytokine levels and liver histology after sacrifice were evaluated. RESULTS: Biliary ductular proliferation and neutropil infiltration were lower in eugenol-administered rats. CONCLUSION: Eugenol has a promising effect on liver histology in cholestatic liver disease (Tab. 1, Fig. 2, Ref. 16).

Ghrelin prevents the development of dermal fibrosis in bleomycin-induced scleroderma.

BACKGROUND: Scleroderma is a chronic inflammatory disease characterized by widespread fibrosis of the skin and the internal organs. Ghrelin is a polypeptide hormone produced by various tissues and inflammatory cells. In experimental studies, ghrelin has been shown to have anti-inflammatory and antioxidant effects, in addition to its metabolic actions. AIM: To evaluate the potential preventive effects of ghrelin on a mouse model of bleomycin (BLM)-induced scleroderma. METHODS: This study involved five groups of BALB/c mice (n = 7 in each group). Mice in the control group received 100 µL/day of phosphate-buffered saline (PBS) subcutaneously, while the other four groups were given 100 µg/day of BLM (dissolved in 100 µL PBS) subcutaneously. Three of the BLM-treated groups received intraperitoneal doses (10 ng/kg/day) of acylated, nonacylated or total ghrelin. Animals were killed at the end of the fourth week, and blood and tissue samples were collected for further analysis. Dermal thickness, serum levels of transforming growth factor-ß1, numbers of inflammatory cells on the dermal layer and numbers of α-smooth muscle actin-positive cells were determined. RESULTS: BLM increased dermal thickness, numbers of inflammatory cells on the dermal layer and activity of the myofibroblastic cells. Application of acylated, nonacylated and total ghrelin decreased the infiltration of inflammatory cells and the activity of the myofibroblastic cells, and reduced dermal fibrosis. CONCLUSIONS: Based on these results, it appears that ghrelin has an antifibrotic action, in addition to the anti-inflammatory and antioxidant effects that have been documented previously. The pathogenic and therapeutic roles of ghrelin in scleroderma should be evaluated by further studies.

Biological response on a titanium implant-grade surface functionalized with modular peptides.

Titanium (Ti) and its alloys are among the most successful implantable materials for dental and orthopedic applications. The combination of excellent mechanical and corrosion resistance properties makes them highly desirable as endosseous implants that can withstand a demanding biomechanical environment. Yet, the success of the implant depends on its osteointegration, which is modulated by the biological reactions occurring at the interface of the implant. A recent development for improving biological responses on the Ti-implant surface has been the realization that bifunctional peptides can impart material binding specificity not only because of their molecular recognition of the inorganic material surface, but also through their self-assembly and ease of biological conjugation properties. To assess peptide-based functionalization on bioactivity, the present authors generated a set of peptides for implant-grade Ti, using cell surface display methods. Out of 60 unique peptides selected by this method, two of the strongest titanium binding peptides, TiBP1 and TiBP2, were further characterized for molecular structure and adsorption properties. These two peptides demonstrated unique, but similar molecular conformations different from that of a weak binder peptide, TiBP60. Adsorption measurements on a Ti surface revealed that their disassociation constants were 15-fold less than TiBP60. Their flexible and modular use in biological surface functionalization were demonstrated by conjugating them with an integrin recognizing peptide motif, RGDS. The functionalization of the Ti surface by the selected peptides significantly enhanced the bioactivity of osteoblast and fibroblast cells on implant-grade materials.

Structure and mechanical properties of Ank/Ank mutant mouse dental tissues--an animal model for studying periodontal regeneration.

Enamel, dentine and cementum are dental tissues with distinct functional properties associated with their unique hierarchical structures. Some potential ways to repair or regenerate lost tooth structures have been revealed in our studies focused on examining teeth obtained from mice with mutations at the mouse progressive ankylosis (ank) locus. Previous studies have shown that mice with such mutations have decreased levels of extracellular inorganic pyrophosphate (PP(i)) at local sites resulting in ectopic calcification in joint areas and in formation of a significantly thicker cementum layer when compared with age-matched wild-type (WT) tissue [Ho AM, Johnson MD, Kingsley DM. Role of the mouse ank gene in control of tissue calcification and arthritis. Science 2000;289:265-70; Nociti Jr FH, Berry JE, Foster BL, Gurley KA, Kingsley DM, Takata T, et al. Cementum: a phosphate-sensitive tissue. J Dent Res 2002;81:817-21]. As a next step, to determine the quality of the cementum tissue formed in mice with a mutation in the ank gene (ank/ank), we compared the microstructure and mechanical properties of cementum and other dental tissues in mature ank/ank vs. age-matched WT mice. Backscattered scanning electron microscopy (SEM) imaging and transmission electron microscopy (TEM) analyses on mineralized tissues revealed no decrease in the extent of mineralization between ank/ank cementum vs. WT controls. Atomic-force-microscopy-based nanoindentation performed on enamel, dentine or cementum of ank/ank vs. age-matched WT molars revealed no significant difference in any of the tested tissues in terms of hardness and elastic modulus. These results indicate that the tissue quality was not compromised in ank/ank mice despite faster rate of formation and more abundant cementum when compared with age-matched WT mice. In conclusion, these data suggest that this animal model can be utilized for studies focused on defining mechanisms to promote cementum formation without loss of mechanical integrity.

Controlled failure mechanisms toughen the dentino-enamel junction zone.

STATEMENT OF PROBLEM: The dentino-enamel junction (DEJ) durably unites dissimilar hard brittle enamel and tough flexible dentin. In contrast to artificial bonds between restorations and dentin, the DEJ rarely fails except when it is affected by inherited disorders. Knowledge of DEJ toughening mechanisms is important in understanding inherited disorders, in biomimetic engineering of junctions between artificial restorations and teeth, and in tissue-engineering a DEJ. PURPOSE: The purpose of this study was to identify specific DEJ-zone failure mechanisms and to survey the fracture toughness of the human DEJ zone. MATERIAL AND METHODS: Fracture toughness indentations were made at 3 sites across the DEJ zone of 10 human incisor teeth. Failure modes identified using optical microscopy and fracture toughness (MPa.m(1/2)) were calculated following Vickers microindentation. Site mean values were then calculated and compared using 1-way analysis of variance (alpha=.05). RESULTS: The DEJ did not undergo catastrophic interfacial delamination; instead, damage was distributed over a broad zone. The primary damage mode involved cracking and damage dispersion in the specialized first-formed enamel close to the DEJ. Multiple, somewhat convoluted and sometimes branching, cracks spread and diffused damage over a wide area of adjacent enamel rather than producing catastrophic interfacial failure. Other secondary mechanisms included short microcracks in the DEJ adjacent dentin with possible cracked bridging, as well as plastic deformation of the DEJ without delamination. A DEJ-zone fracture toughness of approximately 0.8 to 0.9 MPa.m(1/2) was calculated. CONCLUSION: DEJ-zone damage occurred primarily within the adjacent layer of specialized first-formed enamel, and the optical DEJ interface resisted delamination.

Background subtraction for low-loss transmission electron energy-loss spectroscopy.

We present a technique for removing the zero-loss background from electron energy-loss spectra at very low energies (down to approximately 2eV), generating results that are superior in a number of ways to the results of standard Fourier deconvolution techniques. Our technique is based on a separately measured background spectrum which is spline-interpolated and matched to the zero-loss peak in the low-loss spectrum using curve-fit techniques. The data points are weighted with the use of a semi-empirical model of the random error in the data produced by a spectrometer. We demonstrate in tests on real-world data that this model accounts for the random error within the energy range of interest. We discuss practical details of implementation and present detailed comparisons of the results of various algorithms on a piece of test data obtained from a carbon nanotube sample. Compared to the standard techniques, our algorithm tends to be more consistent, less dependent on arbitrary parameters, and better able to quantify spectral features with small signal-to-noise ratios, particularly those at very low energies.

Regulated gene expression dictates enamel structure and tooth function.

Enamel is a complex bioceramic tissue. In its final form, enamel is a reflection of the unique molecular and cellular activities occurring during organogenesis. From the ectodermal origins of ameloblasts, their gene activity and protein expression profiles exist for the sole purpose of producing a mineralized shell, almost entirely devoid of protein, deposited over the 'bone-like' dentine. The interface between enamel and dentine is referred to as the dentine enamel junction and it is also unique in its biology. This review article is narrow in its scope. We restrict our review to selected advances in our understanding of the genetic, molecular and structural aspects of enamel biology. We present a model of enamel formation that relates gene expression to the assembly of an extracellular protein matrix that in turn controls the structural hierarchy and mechanical aspects of enamel and the tooth organ.