Phase Diagrams Map the Properties of Antiviral Agents Directed against Hepatitis B Virus Core Assembly

Assembly effectors are small molecules that induce inappropriate virus capsid assembly to antiviral effect. To identify attributes of hepatitis B virus (HBV) assembly effectors, assembly reaction products (normal capsid, noncapsid polymer, intermediates, and free dimeric core protein) were quantified in the presence of three experimental effectors: HAP12, HAP13, and AT-130. Effectors bound stoichiometrically to capsid protein polymers, but not free protein. Thermodynamic and kinetic effects, not aberrant assembly, correlate with maximal antiviral activity.     

Modulatory influence of stimulus parameters on optokinetic head-tracking response

Optokinetic testing is a non-invasive technique, widely used for visual functional evaluation in rodents. The modulatory influence of optokinetic stimulus parameters such as contrast level and grating speed on head-tracking response in normal and retinal degenerate (RD) mice (rd10) and rats (S334ter-line-3) was evaluated using a computer-based testing apparatus. In normal (non-RD) mice and rats, specific stripe width and grating speed was found to evoke maximum optokinetic head-tracking response. In line-3 RD rats, the contrast sensitivity loss was slow and remained close to the baseline (normal control) level until very late in the disease, whereas, in rd10 mice the progression of the contrast sensitivity loss was more rapid. Observed differences between rd10 mice and line-3 RD rats in the progression of contrast sensitivity loss may not be directly related to the degree of photoreceptor loss. In young RD mice, the modulatory influence of stimulus parameters on optokinetic head-tracking response was similar to normal control animals. During later stages, slower grating speed was required to evoke the maximum optokinetic response. Grating speed had lesser apparent influence on the response properties of line-3 RD rats. Discrepancies between the two RD models in the modulatory influence of optokinetic stimulus parameters can be the manifestation of fundamental species differences and/or differences in the degeneration pattern. This study highlights the importance of careful selection of appropriate stimulus parameters for testing optokinetic head-tracking response in RD animals.     

Congenital midline cervical cleft with an underlying bronchogenic like cyst

Congenital midline cervical cleft (CMCC) is an uncommon malformation. We report a case of a baby girl aged 3 days with a CMCC associated with a cyst reported as a bronchogenic cyst (BC). The pathology is not specific. The association of BC and CMCC is extremely rare and only five cases have been found in the literature. We report our case and review the relevant literature.     

Refractive error in children in a rural population in India

PURPOSE: To assess the prevalence of refractive error and related visual impairment in school-aged children in the rural population of the Mahabubnagar district in the southern Indian state of Andhra Pradesh. METHODS: Random selection of village-based clusters was used to identify a sample of children 7 to 15 years of age. From April 2000 through February 2001, children in the 25 selected clusters were enumerated in a door-to-door survey and examined at a rural eye center in the district. The examination included visual acuity measurements, ocular motility evaluation, retinoscopy and autorefraction under cycloplegia, and examination of the anterior segment, media, and fundus. Myopia was defined as spherical equivalent refractive error of at least -0.50 D and hyperopia as +2.00 D or more. Children with reduced vision and a sample of those with normal vision underwent independent replicate examinations for quality assurance in seven clusters. RESULTS: A total of 4414 children from 4876 households was enumerated, and 4074 (92.3%) were examined. The prevalence of uncorrected, baseline (presenting), and best corrected visual acuity of 20/40 or worse in the better eye was 2.7%, 2.6%, and 0.78%, respectively. Refractive error was the cause in 61% of eyes with vision impairment, amblyopia in 12%, other causes in 15%, and unexplained causes in the remaining 13%. A gradual shift toward less-positive values of refractive error occurred with increasing age in both boys and girls. Myopia in one or both eyes was present in 4.1% of the children. Myopia risk was associated with female gender and having a father with a higher level of schooling. Higher risk of myopia in children of older age was of borderline statistical significance (P = 0.069). Hyperopia in at least one eye was present in 0.8% of children, with no significant predictors. CONCLUSIONS: Refractive error was the main cause of visual impairment in children aged between 7 and 15 years in rural India. There was a benefit of spectacles in 70% of those who had visual acuity of 20/40 or worse in the better eye at baseline examination. Because visual impairment can have a significant impact on a child's life in terms of education and development, it is important that effective strategies be developed to eliminate this easily treated cause of visual impairment.     

Moderate visual impairment in India: the Andhra Pradesh Eye Disease Study

AIM: To assess the prevalence and demographic associations of moderate visual impairment in the population of the southern Indian state of Andhra Pradesh. METHODS: From 94 clusters in one urban and three rural areas of Andhra Pradesh, 11 786 people of all ages were sampled using a stratified, random, cluster, systematic sampling strategy. The eligible people were invited for interview and detailed dilated eye examination by trained professionals. Moderate visual impairment was defined as presenting distance visual acuity less than 6/18 to 6/60 or equivalent visual field loss in the better eye. RESULTS: Of those sampled, 10,293 (87.3%) people participated in the study. In addition to the previously reported 1.84% prevalence of blindness (presenting distance visual acuity less than 6/60 or central visual field less than 20 degrees in the better eye) in this sample, 1237 people had moderate visual impairment, an adjusted prevalence of 8.09% (95% CI 6.89 to 9.30%). The majority of this moderate visual impairment was caused by refractive error (45.8%) and cataract (39.9%). Increasing age, female sex, decreasing socioeconomic status, and rural area of residence had significantly higher odds of being associated with moderate visual impairment. CONCLUSIONS: These data suggest that there is a significant burden of moderate visual impairment in this population in addition to blindness. Extrapolation of these data to the population of India suggests that there were 82 million people with moderate visual impairment in the year 2000, and this number is likely to be 139 million by the year 2020 if the current trend continues. This impending large burden of moderate visual impairment, the majority of which is due to the relatively easily treatable refractive error and cataract, would have to be taken into account while estimating the eye care needs in India, in addition to dealing with blindness. Specific strategies targeting the elderly population, people with low socioeconomic status, those living in the rural areas, and females would have to be implemented in the long term to reduce moderate visual impairment.     

Lysosomal Ca(2+) stores in bovine corneal endothelium

PURPOSE: Acidic organelles, including Golgi bodies and lysosomes, are known to operate as Ca(2+) storage sites in many cell types. This study demonstrates the presence of Ca(2+) stores in lysosomes of bovine corneal endothelial cells (BCECs) and examines their interaction with Ins(1,4,5)P(3)-sensitive Ca(2+) stores. METHODS: Glycyl-L-phenylalanine-beta-naphthylamide (GPN) was used to release Ca(2+) from lysosomes by inducing their selective osmotic swelling. Ca(2+) released into the cytoplasm was measured with fura-2 or fura-PE3 fluorescent dyes. Fluorescence of acridine orange (AO), which selectively sequesters into acidic organelles, was used to establish swelling of lysosomes in response to GPN. RESULTS: Exposure to GPN (100-200 microM) in cultured BCECs produced an increase in free cytosolic Ca(2+) ([Ca(2+)](i)) equivalent to approximately 79% of the peak response to uridine triphosphate (UTP), a P2Y agonist (n = 19). The endothelium of the freshly isolated cornea also produced [Ca(2+)](i) transients similar to those in cultured BCECs; however, the peak [Ca(2+)](i) increase was smaller ( approximately 43% of the peak response to UTP; n = 13). In cultured BCECs, the response to UTP was unaffected by pretreatment with GPN with extracellular calcium ([Ca(2+)](o)) at 0 and 1.2 mM (n = 10). Neither pretreatment with thapsigargin (5 microM) nor with U73122 (a phospholipase C inhibitor; 10 microM) blocked the peak GPN response (n = 6). Exposure to 20 microM monensin produced a [Ca(2+)](i) increase with [Ca(2+)](o) at 0 and 1.2 mM and also reduced the subsequent peak response to GPN (n = 6). CONCLUSIONS: GPN-sensitive lysosomal Ca(2+) stores, distinct from Ins(1,4,5)P(3)-sensitive Ca(2+) stores, are found in both cultured cells and fresh tissue. These stores are susceptible to depletion by the loss of the pH gradient across lysosomes and P2 agonists. The latter occurs through mechanisms independent of phospholipase C (PLC) activation or Ins(1,4,5)P(3). The GPN stores also induce [Ca(2+)](o) influx in response to their depletion.     

Terson's syndrome presenting as an ophthalmic emergency

PURPOSE: To report an unusual case of Terson's syndrome caused by a ruptured intracranial aneurysm presenting as an ophthalmic emergency with visual loss, without any neurological features at the time of presentation. METHODS: Case report. A 38-year-old man was referred to the eye emergency department with sudden loss of vision in both eyes. Vitreous haemorrhage was noted in both eyes. There was no history of loss of consciousness or headaches and no signs of meningeal irritation at presentation. The patient subsequently developed progressive neck stiffness and headache. RESULTS: Neuro-imaging studies revealed a subarachnoid haemorrhage resulting from a ruptured carotid-ophthalmic artery aneurysm. CONCLUSIONS: It is important to consider Terson's syndrome, a potentially life-threatening condition, in any patient presenting with bilateral vitreous haemorrhage. Some patients may not show any headache, neurological deficits or signs of meningeal irritation at presentation but may develop them later on.     

Synthesis and alpha 1-adrenoceptor antagonistic activity of some 4-amino-5,7-dimethyl-2-(substituted) aminopyrido (2,3-d) pyrimidines

A series of new 4-amino-5,7-dimethyl-2- (substituted)aminopyrido(2,3-d)pyrimidines (5) have been synthesized and tested for selective alpha 1-adrenoreceptor antagonistic activity. Some of the compounds were found to antagonize alpha 1-adrenoreceptor in a competitive and reversible manner. When screened on rat anococcygeus muscle some of the compounds exhibited significant alpha 1-adrenoreceptor antagonistic activity (pA2 values in the range of 5.2-7.8). The most potent compound (5j) was evaluated by an in vivo method and was found to reduce the systolic and diastolic blood pressure of spontaneously hypertensive rats. The percentage reduction in blood pressure by test compound 5j was found to be higher than that of the standard drug prazosin (CAS 19216-56-9) at the same dose level (1 mg/kg p.o.). Chemically, prazosin is a 4-aminoquinazolin derivative. Pyridopyrimidine is a known bioisostere of quinazoline. The study revealed that isosteric replacement of the benzene ring of prazosin by a pyridine ring increases the potency.