Application of 3D-QSAR techniques in anti-HIV-1 drug design--an overview

Despite the availability of several classes of drugs against acquired immunodeficiency syndrome (AIDS) caused by human immunodeficiency virus type 1(HIV-1), this deadly disease showing very little sign of containment, especially in Sub-Saharan Africa and South-East Asia. More than 20 million people died since the first diagnosis of AIDS more than twenty years ago and almost 40 million people are currently living with HIV/AIDS. Structure-based drug design effort was immensely successful in identifying several drugs that are currently available for the treatment of HIV-1. Many applications have been reported on the use of quantitative structure-activity relationship (QSAR) studies to understand the drug-receptor interactions and help in the design of more effective analogs. Extensive application was also reported on the application of 3D-QSAR techniques, such as, Comparative Molecular Field Analysis (CoMFA), Comparative Molecular Similarity Analysis (CoMSIA), pharmacophore generation using Catalyst/HypoGen, free-energy binding analysis, GRID/GOLPE, HINT-based techniques, etc. in anti-HIV-1 drug discovery programs in academia and industry. We have attempted to put together a comprehensive overview on the 3D-QSAR applications in anti-HIV-1 drug design reported in the literature during the last decade.     

Vestibular gaze stabilization: different behavioral strategies for arboreal and terrestrial avians

In birds, it is thought that head movements play a major role in the reflexive stabilization of gaze and vision. In this study, we investigated the contributions of the eye and head to gaze stabilization during rotations under both head-fixed [vestibuloocular (VOR)] and head-free conditions in two avian species: pigeons and quails. These two species differ both in ocular anatomy (the pigeon has 2 distinct foveal regions), as well as in behavioral repertoires. Pigeons are arboreal, fly extended distances, and can navigate. Quails are primarily engrossed in terrestrial niches and fly only short distances. Unlike the head-fixed VOR gains that were under-compensatory for both species, gaze gains under head-free conditions were completely compensatory at high frequencies. This compensation was achieved primarily with head movements in pigeons, but with combined head and eye-in-head contributions in the quail. In contrast, eye-in-head motion, which was significantly reduced for head-free compared with head-fixed conditions, contributed very little to overall gaze stability in pigeons. These results suggest that disparity between the stabilization strategies employed by these two birds may be attributed to differences in species-specific behavior and anatomy.     

Effect of thermal energy produced by drilling on the facial nerve: histopathologic evaluation in guinea pigs

The effect of thermal energy due to drilling around the facial nerve canal on the facial nerve was histopathologically evaluated in four guinea pigs. The bony canal of the facial nerve was drilled using a 3 mm diamond burr for one minute. The temperature changes on the facial nerve canal were noted before and after dissection. The temporal bones of the animals were histopathologically examined under light microscopy using haematoxylin & eosin (H&E) and solochrome cyanine staining for myelin, and immunohistochemical staining for neuronal nitric oxide synthase (nNOS). Compared to the control group, it was observed with H&E staining that there was oedema among the axonal fibres and with solochrome cyanine staining that the thickness of the myelin fibres was decreased, and that the severity and extent of nNOS activity was decreased in the axonal fibres. It was concluded that a temperature increase on the facial canal may potentially lead to inflammation of the nerve, and may also cause deterioration of nerve conduction to some extent.     

Considerations of isolated destruction of the short process of the incus in a case of cholesteatoma

Cholesteatoma occurs frequently with the destruction of the ossicles. The most commonly eroded ossicle has been reported to be the incus. Many studies report destruction of the long process and body of the incus. However, isolated erosion of the short process of the incus is an unusual finding. We present such a case with a slight conductive hearing loss that remained unchanged at 2 1/2 years postoperatively. The short process of the incus may contribute to hearing up to 10–15 dB. It is also possible that it plays a role in epitympanic aeration by supplying an attachment surface to the incudal folds.     

Behavioral pattern continuity from prenatal to postnatal life--a study by four-dimensional (4D) ultrasonography

AIM: To investigate whether the same behavioral patterns were present pre- and postnatally, and whether there were any differences in the frequency of movements observed in fetal and in early neonatal life. SUBJECTS AND METHODS: Ten out of 37 pregnant women in the third trimester of pregnancy (median gestational age 34 weeks, range 33 to 35 weeks) in the two-month period (from November 1st to December 31st, 2003) were enrolled in the investigation. Ten term, appropriate for gestational age newborns (seven born vaginally, three by elective SC, six girls, six first-born) and were enrolled in the study. All 4D examinations were performed on Voluson 730 (Kretztechnik, Zipt, Austria) and Acuvix (Medison, Korea) with transabdominal 5 MHz transducer. After standard assessment in 2D B-mode ultrasound, a 4D mode was switched on and live 3D image was reconstructed by selecting the ideal representative 2D image placed in the region of interest (ROI). The recordings of neonatal behavior were made on the Sony P-612 OHMPL videotape by video camera (Sony Camcoder CC DTRV 318 Hv8) and reviewed on the videocassette recorder (Sony VHS SLV-N 900). The median of newborns' age at the moment of recording was 49 hours (range 4 to 112). During the examination, newborns were lying in the bed, separated from other infants in the nursery, dressed, and lying on their backs in a supine position with unrestrained hands. The temperature in the room was 22 to 24 degrees C. The video recording was performed mainly while the children were actively awake or during alert inactivity. RESULTS: There were no movements observed in fetal life that were not present in neonatal life, while the Moro reflex was present only in neonates. The most frequent fetal and neonatal movements were scowling, eye and mouth opening, and hand to face, hand to eye and hand to head movements. Isolated blinking, mouth to eyelid movement, yawning, tongue expulsion and scowling were more frequent in neonates than in fetuses, although the difference was not statistically significant. Hand to mouth movements were more frequent in neonatal than in fetal life while all other hand movements were less frequent in neonates than in fetuses, although the differences did not reach statistical significance. Spearman rank order correlation reached statistical significance in smiling (R=0.71; t=2.91; P=0.02) and in hand to ear movement (R = 0.80; t= 3.86; P = 0.005), and was almost statistically significant in isolated eye blinking (R=0.61; t=2.17; P =0.06), while the correlations between the rest of the movements were not statistically significant. CONCLUSIONS: 4D ultrasonography is a powerful tool in the assessment of fetal behavior, and our study showed that there is a continuity from fetal to neonatal behavior, especially in terms of isolated eye blinking movements, mouth and eyelid opening, yawning, tongue expulsion, smiling, scowling and hand movements directed to other parts of the face.     

Morphometry of the anterior third ventricle region as a guide for the transcallosal-interforniceal approach

The transcallosal-interforniceal approach is the most appropriate approach to localize and totally remove space-occupying lesions around the anterior third ventricle region such as craniopharyngiomas and gliomas. This study examined the microsurgical anatomy of the normal anterior third ventricle region in 81 adult cadaver hemispheres. The central sulcus was identified and surface landmarks determined as the points 5 cm (P5) and 7 cm anterior to the central sulcus (P7). The distances between P5 and P7 and the upper margin of the interventricular foramen, which delineate the surgical corridor chosen to avoid disturbance of important neural structures, were 46.26-60.96 (54.09 +/- 3.35) mm and 48.00-62.00 (54.94 +/- 3.09) mm, respectively. The distances between the upper margin of the hemisphere and the cingulate sulcus, especially important for avoiding damage to the cingulate gyrus and other mesiolimbic structures, were 13.54-30.00 (21.28 +/- 3.89) mm and 12.22-29.52 (21.12 +/- 3.90) mm at the level of P5 and P7. The distances between the upper margin of the hemisphere and the callosal cistern containing the pericallosal artery were 28.34-40.50 (33.94 +/- 2.84) mm and 28.16-40.26 (33.50 +/- 2.61) mm, respectively. Normative morphometric data of the structures involved in the surgical procedure are necessary for planning and performance of the transcallosal-interforniceal approaches. This study of a large series of specimens shows that these measurements have large individual variations.