In vivo optimization of 2,3-diaminopyrazine Rho Kinase inhibitors for the treatment of glaucoma.

A series of 2,3,6-pyrazine Rho Kinase inhibitors were optimized for in vivo activity for topical ocular dosing. Modifications of the 2-(piperazin-1-yl)pyrazine derivatives produced compounds with improved solubility and physicochemical properties. Modifications of the 6-pyrazine substituent led to improvements in in vitro potency. Compound 9 had the best in vitro and in vivo potency of EC50=260 nM with a 30% reduction of IOP in a non-human primate model at a dose of 0.33%.

Health-related quality of life of intellectually disabled children attending a special school in Puducherry-A cross-sectional study.

Introduction: Health-related quality of life (HRQOL) is a measure of an individual's psychosocial, emotional, and physical well-being. Around 1 in 20 children are less than 15 years of age and are living with a moderate-to-severe form of disability. Thus, our study aims to determine the HRQOL of intellectual disabled (ID) children attending a special school in Puducherry and to determine the socio-demographic factors influencing the level of HRQOL. Methodology: A cross-sectional analytical study was conducted among 350 ID children attending a selected special school in Puducherry over 1 year. By the universal sampling method, all the caregivers of ID children were recruited and the parent proxy form of Pediatric Quality of life Inventory scale version 4.0 (PedsQL ver 4.0) was used to assess the level of HRQOL of ID children. The data were analyzed using the Statistical Package for Social Science version 16.0 (SPSS ver. 16.0) and the statistical significance was set at P value <0.05. Results: Among the 350 respondents, a majority of the caregivers were mothers (78.9%) and 65.7% were homemakers by occupation. Most of the respondents were from the nuclear family (77.7%) and 55.1% were from urban areas. The mean age of ID children was 12 (±3.8) years; 61.2% were males and 40.8% of the children had a moderate form of ID. Conclusion: The HRQOL of ID children is found to be lower. The factors influencing the lower HRQOL were age, the intelligent quotient (IQ) of ID children, and type of marriage of the caregivers.

2,3-Diaminopyrazines as Rho kinase inhibitors.

Inhibition of rho kinase (ROCK) has been recognized as an important target for a number of diseases, including glaucoma. Herein we report SAR development around two hits from a kinase library that led to the discovery of the ROCK inhibitor compound 38. In vitro and in vivo analysis of this compound, including its effects in a monkey model of glaucoma will be discussed.

Plasmonic quasicrystals with broadband transmission enhancement.

Plasmonic quasicrystals (PlQCs), by integrating the properties of quasicrystals (rotational symmetry and long range ordering but lack translational symmetry) and surface plasmon polariton mediated effects, offer several advantages over plasmonic crystals (PlCs). For example, in PlQCs one could have broadband, polarization independent response. However, large area patterning by electron beam lithography requires precise lattice coordinates as well as a practical way to design the structures for specific spectral response. We demonstrate design and fabrication of large area quasicrystal air hole patterns of π/5 symmetry in metal film in which broadband, polarization and launch angle independent transmission enhancement is observed. We demonstrate bi-grating quasicrystals to show that designable transmission response is possible over visible to near infrared wavelength regions with about 15 times enhancement. These would be useful in many applications like energy harvesting, nonlinear optics and quantum plasmonics.

Laparoscopic management of persistent mullerian duct syndrome.

Persistent mullerian duct syndrome (PMDS), characterized by the presence of mullerian structures in a virilized male, frequently presents as undescended testis, either intraabdominal or within a hernial sac. We describe a 10-month-old infant with PMDS successfully managed by the laparoscopic approach. At the age of 1.5 months, the patient presented with a left inguinal hernia and bilateral nonpalpable gonads in another center and underwent left inguinal exploration. The uterus and a gonadlike structure along with the hernia sac were found in the inguinal canal. Left inguinal herniotomy was performed after reduction of the uterus and gonadlike structure. No gonadal biopsy was obtained. The patient was further investigated in the same center. His karyotype was 46,XY. Magnetic resonance imaging of the abdomen and pelvis revealed a uterinelike structure posterior to the urinary bladder, but neither testis nor ovaries were visualized. At 10 months of age, he was referred to our department for further management. A laparoscopic single-stage orchiopexy was performed. Both testes were identified and brought to the scrotum by splitting the uterus in the midline and then bringing the testes with the vas and attached uterine tissue into the scrotum. The aim of placement of well-vascularized testes in the scrotum was achieved as confirmed on follow-up color Doppler ultrasound study 6 months postoperatively, which showed normal vascularity. Laparoscopic surgical techniques for this condition are also discussed.