Axenfeld-Rieger syndrome: report on dental and craniofacial findings

Axenfeld-Rieger syndrome is a rare autosomal dominant disorder characterized by various ocular and extraocular malformations. Dental abnormalities are considered as definitive features for the diagnosis and differentiation of Rieger syndrome from other anterior chamber of the eye malformations. A case of Rieger syndrome with distinct dental and craniofacial anomalies is described. Significant cranio-dento-facial findings that have been observed are, teeth with short and dilacerated roots, hyperplastic frenums and underdeveloped maxilla. There was an anterior crossbite, bilateral posterior open-bite and moderate to severe anterior crowding.     

Considerations in the management of transposed teeth

AIM: To review the management of transposed teeth, and to illustrate the treatment options with four case reports. METHODS: The aetiology and management of transposed teeth are reviewed. Three management options are discussed: correcting the order of transposed teeth, maintaining the order of transposed teeth, and extraction of one of the transposed teeth. Methods of camouflaging transposed teeth are described in detail. The treatment options are illustrated with case reports.     

Inhibition of markers of hepatic stellate cell activation by the hormone relaxin

Hepatic fibrosis results from excess extracellular matrix produced primarily by hepatic stellate cells (HSC). In response to injury, HSC differentiate to a myofibroblastic phenotype expressing smooth muscle actin and fibrillar collagens. Relaxin is a polypeptide hormone shown to have antifibrotic effects in fibrosis models. In this study, activated HSC from rat liver were treated with relaxin to determine if relaxin can reverse markers of HSC activation. Relaxin treatment resulted in a decrease in the expression of smooth muscle actin, but had no effect on cell proliferation rate. The levels of total collagen and type I collagen were reduced, while the synthesis of new collagen was inhibited. Furthermore, relaxin caused an increase in the expression and secretion of rodent interstitial collagenase (MMP-13), but there was no effect on the gelatinases MMP-2 or MMP-9. Relaxin also increased secretion of TIMP-1 and TIMP-2. The effective concentration of relaxin to induce these effects was consistent with action through the relaxin receptor. In conclusion, relaxin reversed markers of the activated phenotype of HSC including the production of fibrillar collagen. At the same time, the activity of a fibrillar collagenase was increased. These data suggest that relaxin not only inhibits HSC properties that contribute to the progression of hepatic fibrosis, but also promotes the clearance of fibrillar collagen. Therefore, relaxin may be a useful approach in the treatment of hepatic fibrosis.     

Effects of granulocyte-macrophage colony-stimulating factor on 3'-azido-3'-deoxythymidine uptake, phosphorylation and nucleotide retention in human U-937 cells

Previous studies have demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) both increases and decreases levels of 3'-azido-3'-deoxythymidine (AZT) nucleotides in certain human myeloid cells. The present studies have examined the effects of GM-CSF on AZT metabolism in U-937 cells. The results demonstrate that GM-CSF stimulated AZT nucleotide formation in these cells. This stimulation was detectable during concurrent exposure to GM-CSF and AZT or as a result of pretreatment with GM-CSF. The GM-CSF-induced enhancement in AZT nucleotide formation was associated with a 4-fold increase in AZT uptake. The finding that uptake of AZT into U-937 cells was only partially sensitive to 6-[(4-nitrobenzyl)thio]-9-beta-D-ribofuranosylpurine (NBMPR) suggested a process primarily involving nonfacilitated diffusion. The results also demonstrate that treatment of U-937 cells with GM-CSF was associated with nearly a 2-fold increase in thymidine kinase activity. Moreover, the findings indicate that retention of AZT-MP and AZP-TP was prolonged significantly (P less than 0.05 and P less than 0.01 respectively) in association with GM-CSF treatment. Taken together, these results suggest that GM-CSF enhances the formation of AZT nucleotides by increasing AZT uptake and phosphorylation, as well as increasing retention of phosphorylated derivatives.     

Role of elevated S-adenosylhomocysteine in rat hepatocyte apoptosis: protection by betaine

Previous studies from our laboratory have shown that ethanol consumption results in an increase in hepatocellular S-adenosylhomocysteine levels. Because S-adenosylhomocysteine is a potent inhibitor of methylation reactions, we propose that increased intracellular S-adenosylhomocysteine levels could be a major contributor to ethanol-induced pathologies. To test this hypothesis, hepatocytes isolated from rat livers were grown on collagen-coated plates in Williams’ medium E containing 5% FCS and exposed to varying concentrations of adenosine in order to increase intracellular S-adenosylhomocysteine levels. We observed increases in caspase-3 activity following exposure to adenosine. This increase in caspase activity correlated with increases in intracellular S-adenosylhomocysteine levels and DNA hypoploidy. The adenosine-induced changes could be significantly attenuated by betaine administration. The mechanism of betaine action appeared to be via the methylation reaction catalyzed by betaine-homocysteine-methyltransferase. To conclude, our results indicate that the elevation of S-adenosylhomocysteine levels in the liver by ethanol is a major factor in altering methylation reactions and in increasing apoptosis in the liver. We conclude that ethanol-induced alteration in methionine metabolic pathways may play a crucial role in the pathologies associated with alcoholic liver injury and that betaine administration may have beneficial therapeutic effects.     

Changes in Tdap and MCV4 Vaccine Coverage Following Enactment of a Statewide Requirement of Tdap Vaccination for Entry Into Sixth Grade

Objectives. We evaluated changes in tetanus toxoid, reduced diptheria toxoid, acellular pertussis (Tdap), and tetravalen meningococcal (MCV4) vaccine coverage following enactment of a New York State mandate requiring Tdap before entering sixth grade.Methods. Using data from a hospital-based immunization registry, we measured Tdap and MCV4 coverage among youths aged 11 to 14 years in New York City at 3 time points: premandate, mandate year 1, and mandate year 2.Results. Among overlapping cohorts of 4316 (premandate), 4131 (mandate year 1), and 3639 (mandate year 2) youths, Tdap coverage increased steadily over time (29%, 58%, and 83%, respectively). Increases were observed among all ages. Across the same time points, MCV4 coverage also increased (10%, 30%, and 60%, respectively). Most adolescents did not receive MCV4 during the same visit they received Tdap.Conclusions. A Tdap school-entry mandate was associated with substantial increases in immunization coverage, even in age groups not directly affected by the mandate. At the postmandate time points, MCV4 coverage remained lower than Tdap coverage. Provider education should emphasize the importance of reviewing vaccine records and administering all recommended vaccines at every clinical encounter.In recent years, new vaccines against pertussis¹ and meningitis² have been introduced to the routine immunization schedule for children and adolescents. Both are recommended for youths aged 11 to 12 years, with catch-up vaccination for older adolescents. Pertussis is a highly contagious infection, often causing school or community outbreaks. Among healthy adolescents, pertussis is usually a self-limited illness characterized by a prolonged cough. However, secondary complications can occur, and adolescents serve as an important reservoir for transmission to infants, for whom infection can lead to pneumonia, respiratory failure, apnea, and even death.³ The tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine has been shown to be 92% effective in preventing culture-confirmed pertussis.⁴Adolescents, and specifically those in crowded living conditions, have been shown to be at increased risk for N. meningitides infection.⁵ N. meningitides is highly contagious and can cause meningitis, septicemia, and death. The tetravalent meningococcal polysaccharide-protein conjugate (MCV4) vaccine has been shown to be safe and highly immunogenic in protecting against N. meningitides infection.⁶Although the Tdap and MCV4 vaccines hold great promise, achieving high immunization coverage among adolescents remains a challenge. Barriers to adolescent immunization include failure to present for medical services, missed immunization opportunities, and scattered immunization records.⁷ Few adolescents report the receipt of annual preventive health visits,⁸ so reviewing immunization status and immunizing at every clinical encounter is key to increasing vaccine coverage in this population. Results of the 2008 National Immunization Survey–Teen indicate that among adolescents aged 13 to 17 years, nationwide coverage for Tdap and MCV4 remains low (41% and 42%, respectively).⁹Mandates requiring immunization prior to school entry have been highly effective in increasing immunization coverage.^10–14 In 1 study, hepatitis B immunization rates increased from 13% to 71% following implementation of a middle school mandate.¹⁵ Mandates were initially used to promote the uptake of vaccines for highly contagious infectious diseases and thus to prevent school-based outbreaks, but today many states mandate vaccines for diseases that are not communicable (tetanus) or that are communicable primarily through sexual or blood exposures (hepatitis B). Recent controversy regarding mandates for the human papillomavirus vaccine has resulted in significant backlash against mandates,^16–18 highlighting the need for states to be judicious in their decisions to implement new mandates.Although mandates are known to rapidly increase vaccine coverage in their target population, there is little evidence of any carryover benefits. No studies to date have evaluated whether a new mandate will result in improved vaccine coverage for nonmandated age groups or for other nonmandated, age-appropriate vaccines. In the fall of 2007, New York State became one of the first states to require Tdap prior to entering sixth grade. This situation provided a unique opportunity to observe postmandate changes in coverage for Tdap (the mandated vaccine) and MCV4 (a nonmandated, recommended vaccine) across multiple age groups.     

Pupillodynamics and corneal spherical aberrations in a set of Indian cataract patients and its implications for aberrometric customisation of intraocular lenses

Purpose:Assessment of pupil diameter in various light conditions and the corresponding corneal spherical aberrations in a cohort of Indian eyes with bilateral senile cataracts and the possible use of this data in aberrometric customization of intraocular lenses (IOLs).Methods:In this prospective observational study done at a tertiary eye care centre in India, the selected patients were subjected to measurement of their pupil diameters in scotopic, mesopic, and photopic conditions as well as the corresponding corneal spherical aberrations, using the Sirius Topographer (Costruzione Strumenti Oftalmici, Florence, Italy). Shapiro–Wilk test, Independent t-test, ANOVA with Bonferroni correction on post-hoc testing were used for statistical analysis.Results:104 eyes of 52 patients were enrolled for the study. The mean age was 53 ± 11.88 years. The mean scotopic, mesopic, and photopic pupil sizes were 4.37 mm (4.11–4.63 mm), 3.92 mm (3.71 mm–4.15 mm), and 3.37 mm (3.18–3.67 mm), respectively. There was a statistically significant difference (P = <0.001) in the mean corneal spherical aberration measured at the 6 mm zone (0.23 ± 0.02 microns) and at the 4 mm zone (0.06 ± 0.01 microns).Conclusion:The mean corneal spherical aberration corresponding to the average mesopic pupil size of our patient population was substantially lower than that of the scotopic pupil size and also less than the amount corrected by most of the negative aspheric IOLs. This perhaps indicates the need for customising IOLs based on the spherical aberrations of cornea at the zone corresponding to the mesopic pupil diameter for optimal residual total postoperative spherical aberrations.     

Novel Piperine Derivatives with Antidiabetic Effect as PPAR‐γ Agonists

Piperine is an alkaloid responsible for the pungency of black pepper. In this study, piperine isolated from Piper nigrum L. was hydrolyzed under basic condition to obtain piperic acid and was used as precursor to carry out the synthesis of twenty piperine derivatives containing benzothiazole moiety. All the benzothiazole derivatives were evaluated for their antidiabetic potential by OGT test followed by assessment of active derivatives on STZ‐induced diabetic model. It was observed that nine of twenty novel piperine analogues ( 5b, 6a‐h) , showed significantly higher antidiabetic activity in comparison with rosiglitazone (standard). Furthermore, these active derivatives were evaluated for their action as PPAR‐γ agonists demonstrating their mechanism of action. The effects on body weight, lipid peroxidation, and hepatotoxicity after administration with active derivatives were also studied to further establish these derivatives as lead molecules for treatment of diabetes with lesser side‐effects.