Radiation responses of Sf9, a highly radioresistant lepidopteran insect cell line

PURPOSE: Lepidopteran insect cells are known to exhibit very high radioresistance. Although very effective DNA excision-repair has been proposed as a contributing factor, a detailed understanding of insect cell radiation responses has not yet been obtained. Therefore, the study was carried out to understand the in vitro radiation responses of Sf9 lepidopteran cells. MATERIALS AND METHODS: Exponentially growing asynchronous Sf9 cells (derived from ovaries of Spodoptera frugiperda) were exposed to gamma-radiation doses of 2-200 Gy. Cell survival, growth inhibition, cell cycle progression delay, alterations in cell morphology as well as induction of DNA damage, micronuclei and apoptosis were studied at various post-irradiation time intervals. RESULTS: Biphasic survival response curves were obtained with D0 rising from 20 Gy (at doses < or = 60 Gy) to 85 Gy (between 60 and 200 Gy), corroborating earlier reports on lepidopteran cells. An additional downward deviation at 2 Gy indicated a hypersensitive response. Dose-dependent growth inhibition with a transient G2 delay starting 12 h and extending up to 48-96 h was observed at doses of 10-200 Gy, while a brief G1/S transition delay was observed only at higher doses (> or = 100 Gy). Significant DNA damage was detected only at 20 Gy and higher doses, in contrast with human cells that showed similar damage at 2 Gy. Interestingly, micronuclei were not induced at any of the doses tested, although spontaneous micronucleation was evident in <1% of cells. Lack of micronucleus induction even at doses that induced significant DNA damage and a transient G2 block (20-50 Gy) strongly indicated a role of holocentric lepidopteran chromosomes. Apoptosis was detected only in a small proportion of cells (3%) exposed to 200 Gy, and cell/nucleus size and granularity increased by 72-96 h post-irradiation in a dose-dependent manner. Sf9 nucleoids extracted at 2 M NaCl showed higher compactness than the nucleoids prepared from human cells. CONCLUSIONS: It is clearly shown that lepidopteran cells are highly resistant to the induction of DNA damage and micronuclei, and display very low induction of apoptosis at doses up to 200 Gy. While the lack of micronucleus induction seems to be primarily due to the holocentric nature of their chromosomes, certain unique signalling pathways might be responsible for the low induction of apoptosis. Factors causing protection of Sf9 cellular DNA from radiation-induced damage are presently being investigated.     

Health sector policy in the first decade of Nepal's multiparty democracy. Does clear enunciation of health priorities matter?

Nepal experienced a significant political regime shift in 1990 from the partyless Panchyat system to the present multiparty form of democracy. While political instability existed in the decade of the 1990s, reflected in the approximately one government per year, there had been continued enunciation of health policy priorities toward the rural sector, as reflected in the Nepal National Health Policy, 1991 (NHP (1991)) and subsequent plans. The objective of the paper is to assess whether clear enunciation of health priorities have translated into beneficial health outcomes, reflected in reduction of the child death rate, child morality rate, infant mortality rate and increase in the life expectancy rate. This question is assessed empirically over the 10-year period of fiscal year 1989/1990 to 1999/2000 using mainly secondary data published by His Majesty's Government of Nepal (HMG/N), through the perspectives of input-output model and extension of health services, along with an indicative regression of a Nepalese health production function. The results (i.e. empirical observations) suggest that while there have been clear enunciation of health priorities, there have not been significant positive effects on health sector outcomes. The paper ends with a number of recommendations and concludes with the necessity for effective and appropriate implementation.     

Household headship and child death: Evidence from Nepal

Background  

Nepal has seen substantial improvements in its reproductive health outcomes, but infant and child mortality are still high. This study attempts to examine the prevalence and factors influencing the experience of child death of mothers who have given birth during a five-year period. More specifically, this paper aims to investigate whether household headship has an impact on child death in Nepal.     

Visual defects in Nepalese children with Down syndrome

Background: Down syndrome (DS) is a common chromosomal anomaly. People with this syndrome have recognisable physical characteristics and limited intellectual abilities. The aim of this study was to determine visual defects, especially refractive error and binocular anomalies, in a sample of Nepalese children with DS. Methods: Thirty‐six children with DS (19 boys and 17 girls) from the Kathmandu valley, aged from four months to 18 years, underwent detailed optometric examination. Cycloplegic refraction was performed on all subjects. Vision on presentation of all the children was assessed with preferential looking cards, the Kay picture cards, the Bailey‐Lovie logMAR chart or the Snellen chart. Binocular function was assessed with cover test, Hirschberg or Bruckner test. Results: Cycloplegic refraction of the children revealed that 80 per cent of the children had significant refractive error. Most of them had hyperopia (55 per cent), followed by astigmatism (44 per cent), myopia (25 per cent) and anisometropia (19 per cent). Only two (5.6 per cent) children were strabismic and both of them were alternating esotropes. Nystagmus was present in 10 (28 per cent). Other ocular findings were upward slanting palpebral fissures, blepharitis, congenital nasolacrimal duct obstruction, blepharoconjunctivitis, chalazion and lenticular opacities. Conclusion: Nepalese children with DS have a high prevalence of refractive error and nystagmus. Regular eye examinations are indicated for these children to enable early diagnosis and appropriate management of ocular disorders to improve their vision and quality of life.     

New 6-bromoimidazo[1,2-a]pyridine-2-carbohydrazide derivatives: synthesis and anticonvulsant studies

In the present work, we report the facile synthesis and anticonvulsant study of new imidazo[1,2-a]pyridines carrying biologically active hydrazone functionality (3a–3e) and suitably substituted 1,2,4-triazole moieties (4, 5a–5d, 6, and 7a–7d). The newly synthesized intermediates and final compounds were characterized by various spectral techniques such as FTIR, ¹H NMR, ¹³C NMR, and mass spectral and elemental analysis studies. The in vivo anticonvulsant study of the target compounds were carried out following maximal electroshock seizure and subcutaneous pentylene tetrazole methods, while their toxicity study was performed following rotarod method by taking 20, 40, and 100 mg/kg dose levels. Most of the new compounds displayed remarkable anticonvulsant properties at these doses. Particularly, compounds 3b and 4 carrying hydrogen bond donor groups, viz. hydroxyl and amine moieties respectively, exhibited complete protection against seizure and their results are comparable to that of standard drug diazepam. Further, the motor impairment study revealed that all the compounds are nontoxic upto 100 mg/kg.     

Socio-Demographic Correlates of Injection Drug Use Among Male Drug Users: A Cross Sectional Study in Nepal

Drug abuse is one of the major public health problems in Nepal. The objective of this study is to explore the factors responsible for the injecting drug use in Nepal. A cross sectional study was conducted among drug users in Pokhara sub metropolitan city in Nepal. Taking prevalence of 20 % at 95 % confidence interval and 20 % non-response rate, 448 samples were calculated for face to face interviews. Most of the study participants were >24 year’s age. Sixty-one percentage of the participants were unemployed. The largest percentage belonged to Gurung/Rai/Pun (37 %) ethnic groups, and had completed secondary level of education (47.5 %). In the logistic regression analysis occupation, motivating factors for drug use, ever been to custody, age at first drug use, age at first sex, money spent on drugs, ever been rehabilitated and age of the respondents showed a statistically significant association with injecting drug use status. The respondents having business [Adjusted Odds ratio (aOR) 4.506, 95 % CI (1.677–12.104)], service [aOR 2.698, 95 % CI (a1.146-6.355], having tragedy/turmoil [aOR 3.867, 95 % CI (1.596–9.367)], family problem [aOR 2.010, 95 % CI (2.010–53.496)], had sex at >19 years [aOR 1.683, 95 % CI (1.017–2.785)], rehabilitated >2 times [aOR 4.699, 95 % CI (1.401–15.763)], >24 years age group [aOR 1.741, 95 % CI (1.025–2.957)] had higher odds of having injecting habits. Having money spent on drugs >3,000 NRs (300 USD) [aOR 0.489, 95 %CI (0.274–0.870), not been to custody (aOR 0.330, 95 %CI (0.203–0.537)] and having curiosity for drug use [aOR 0.147, 95 % CI (0.029–0.737)] were found to be protective for injecting drug use. This study recommends the harm reduction program specifically focused on drug users of occupational groups like business, service and the youths through public health actions to stop transiting them to injecting drug use.