Saree on Fireside: Fatal Burn in an Elderly Nepalese Female.

As winter approaches, people in the land of rural Himalayas commonly use fire as the source of heat. Many accidents occur in the process, and mostly the victims are among unattended children and the elderlies. We present a case from rural Nepal where an elderly female sustained fatal burn injuries. Advanced age, greater surface area, and secondary infection were the complicating factors. In the present case, the victim's clad cloth (Saree) was the harbinger to death. Prevention of infection following burn and control of sepsis still remains the mainstay of treatment in burn victims.

Effect of Planting into a Green Winter Cereal Rye Cover Crop on Growth and Development, Seedling Disease, and Yield of Corn.

Terminating winter cereal rye (Secale cereale L.) cover crops ≥10 days before planting (DBP) corn is recommended to minimize seedling disease and potential yield loss. In Iowa, cold temperatures and frequent precipitation can prevent farmers from following that recommendation and sometimes force them to plant corn while the rye plants are still green, referred to as "planting green" (PG). A field trial was established to evaluate the effect of rye termination shortly before or after corn planting on growth, seedling root disease, and yield of corn. A rye cover crop was terminated 17 and 3 DBP and 6 and 12 days after planting (DAP) corn; corn planted following no rye was included as a control. Rye biomass, C/N ratio, and N accumulation increased when terminated 6 or 12 DAP corn compared with rye terminated 17 or 3 DBP corn. Corn seedlings were taller from the PG treatments. More radicle root rot was observed when rye was terminated 3 DBP, 6 DAP, and 12 DAP corn than for the 17 DBP treatment and the no-rye control. Generally, greater Pythium clade B populations were detected on radicles and seminal roots of corn from the PG treatments. Corn populations, ears, or barren plants were not affected by the treatments. In both years, the no-rye control had the greatest corn yield and the 12 DAP treatment had the lowest yield. Our results suggest that PG increased corn seedling root disease and contributed to reduced corn yield.

Prevalence of Loss of Smell and/or Taste and other Otorhinolaryngology Symptoms in COVID-19 Patients.

Background Loss of smell and/or taste have been described in COVID-19 patients. Studies have not been conducted to evaluate the loss of smell and/or taste in the context of Nepal. Objective To investigate the prevalence of Ear, Nose and Throat related symptoms and assess smell and taste disorders in laboratory-confirmed SARS-CoV-2 patients. Method This prospective cross-sectional study evaluated patients from September 2020 to March 2021 with preceding COVID-19 diagnosis from a tertiary centre in Kathmandu. COVID-19 positive patients visiting out-patient department, quarantined or admitted were included. Patients were given questionnaire consisting of demographic data, history of smoking and evaluation of presenting symptoms. Loss of smell and taste were subjectively tested and followed up via telephone for ten weeks to evaluate for recovery time and degree of recovery. Result A total of 226 patients participated in the study, 18-92 years old (mean age, 36.77 ± 15.23 years; 53.5% males, 69% non-smokers). Majority of the patients had Myalgia (n = 128, 56.6%) as their presenting symptoms followed by fever (n = 122, 53.9%), loss of smell (n = 117, 51.7%), cough (n = 107, 47.34) and sore throat (n = 102, 45.1%). Loss of sense of smell and taste was reported in 51.8% and 42% respectively. The association between loss of sense of smell and taste was statistically significant (p < .001). All patients had some degree of recovery with 64.1% recovery of smell and 64.2% recovery of taste within 14 days of onset of symptoms. The mean recovery time for sense of smell and taste was 14.34 ± 9.82 days and 15.03 ± 10.06 days, respectively. Conclusion Olfactory and gustatory dysfunctions are cardinal features of COVID-19. They recover spontaneously along with other symptoms within few weeks. The absence of smell or taste in times of pandemic can be suggestive of potential COVID-19 infection and be used as a screening tool for early diagnosis and reduce transmission of the infection.

Improved Glioma Grading Using Deep Convolutional Neural Networks.

BACKGROUND AND PURPOSE: Accurate determination of glioma grade leads to improved treatment planning. The criterion standard for glioma grading is invasive tissue sampling. Recently, radiomic features have shown excellent potential in glioma-grade prediction. These features may not fully exploit the underlying information in MR images. The objective of this study was to investigate the performance of features learned by a convolutional neural network compared with standard radiomic features for grade prediction. MATERIALS AND METHODS: A total of 237 patients with gliomas were included in this study. All images were resampled, registered, skull-stripped, and segmented to extract the tumors. The learned features from the trained convolutional neural network were used for grade prediction. The performance of the proposed method was compared with standard machine learning approaches, support vector machine, random forests, and gradient boosting trained with radiomic features. RESULTS: The experimental results demonstrate that using learned features extracted from the convolutional neural network achieves an average accuracy of 87%, outperforming the methods considering radiomic features alone. The top-performing machine learning model is gradient boosting with an average accuracy of 64%. Thus, there is a 23% improvement in accuracy, and it is an efficient technique for grade prediction. CONCLUSIONS: Convolutional neural networks are able to learn discriminating features automatically, and these features provide added value for grading gliomas. The proposed framework may provide substantial improvement in glioma-grade prediction; however, further validation is needed.

Effect of 6-Methoxy-2-Benzoxazolinone (MBOA) on Pythium Species and Corn Seedling Growth and Disease.

Corn yield reduction following a cereal rye cover crop has been attributed to, among other factors, allelochemicals released from decomposing cereal rye residue. The allelopathic effect of 6-methoxy-2-benzoxazolinone (MBOA) was evaluated on corn seedling growth, mycelial growth of seven pathogenic species of Pythium, and root rot of corn seedlings caused by Pythium spp. at 13, 16, and 22 to 23°C (room temperature) using a plate assay. Mycelial growth of all Pythium spp. tested was slower with MBOA at 0.25 mg/ml compared with MBOA at 0.125 and 0.0625 mg/ml and the check (4% V8 juice medium containing neomycin sulfate and chloramphenicol with 0.5% dimethyl sulfoxide). Therefore, no further tests were done with MBOA at 0.25 mg/ml. In general, MBOA reduced corn radicle length and did not cause root rot across all temperatures. However, greater root rot severity in corn was observed on corn seedlings grown in the presence of Pythium lutarium and P. oopapillum on media amended with MBOA compared with the check at all temperatures. Similarly, more root rot caused by P. torulosum and P. spinosum was observed when MBOA was present at 16°C compared with the check with no MBOA. These data suggest that corn seedling disease caused by Pythium spp. could be more severe when corn is planted following a cover crop of winter cereal rye due to the presence of allelochemicals that are released from the cover crop.

Increased Notching of the Corpus Callosum in Fetal Alcohol Spectrum Disorder: A Callosal Misunderstanding?

BACKGROUND AND PURPOSE: In the medicolegal literature, notching of the corpus callosum has been reported to be associated with fetal alcohol spectrum disorders. Our purpose was to analyze the prevalence of notching of the corpus callosum in a fetal alcohol spectrum disorders group and a healthy population to determine whether notching occurs with increased frequency in the fetal alcohol spectrum disorders population. MATERIALS AND METHODS: We performed a multicenter search for cases of fetal alcohol spectrum disorders and included all patients who had a sagittal T1-weighted brain MR imaging. Patients with concomitant intracranial pathology were excluded. The corpus callosum was examined for notches using previously published methods. A χ2 test was used to compare the fetal alcohol spectrum disorders and healthy groups. RESULTS: Thirty-three of 59 patients with fetal alcohol spectrum disorders (0-44 years of age) identified across all centers had corpus callosum notching. Of these, 8 had an anterior corpus callosum notch (prevalence, 13.6%), 23 had a posterior corpus callosum notch (prevalence, 39%), and 2 patients demonstrated undulated morphology (prevalence, 3.4%). In the healthy population, the anterior notch prevalence was 139/875 (15.8%), posterior notch prevalence was 378/875 (43.2%), and undulating prevalence was 37/875 (4.2%). There was no significant difference among the anterior (P = .635), posterior (P = .526), and undulating (P = .755) notch prevalence in the fetal alcohol spectrum disorders and healthy groups. CONCLUSIONS: There was no significant difference in notching of the corpus callosum between patients with fetal alcohol spectrum disorders and the healthy population. Although reported to be a marker of fetal alcohol spectrum disorders, notching of the corpus callosum should not be viewed as a specific finding associated with fetal alcohol spectrum disorders.

Sampling and analyses of surfaces contaminated with chemical warfare agents by using a newly developed triple layered composite wipe.

A three-layered composite wipe was fabricated by laminating individual layers of non-woven polypropylene, activated carbon fabric (ACF) and aramid fabric for the sampling and investigation of chemical warfare agents (CWA)-contaminated urban porous and non-porous surfaces. The material of main ACF layer was characterized to ascertain its suitability to act as an efficient adsorbent for the surface wipe sampling. The performance of ACF-based composite wipe was determined by evaluating its extraction efficiency, wiping efficacy and adsorption capacity for the sampling of blister and nerve agent class of CWA-contaminated surfaces using gas chromatography-mass spectrometry (GC-MS). Parameters like amount of wipe required, solvent selection, amount of solvent, time of extraction etc. were optimized to achieve the maximum recovery of contaminating analytes required for the forensic investigations. Overall recoveries of contaminating analytes after sampling and extraction were found to be in the range of 45-85% for all types of surfaces. No breakthrough in wiping process was noticed up to contamination density (CD) 1.6 mg/cm2 for non-porous surface and 3.2 mg/cm2 for porous surfaces. ACF-based wipe was found capable to significantly reduce the vapour hazards from liquid sulphur mustard (HD) and sarin (GB). Contamination from surfaces could be preserved within the wipe up to 15 days for the extended forensic investigation purposes. Limit of detections (LOD) of contaminants was determined in the range of 0.8-6.8 ng/cm2 while limit of quantitation (LOQ) was achieved up to the range of 2.4-14.4 ng/cm2 for wipe sampling of different surfaces. Graphical abstract.

Magnesium Aluminate Nanoparticles for Chemical Detoxification of Sarin and Soman.

The solutions of Mg(NO3)2, Al(NO3)3, and (NH4)2CO3 were mixed at pH 8 and then heated at 95 °C for 4 h, aged at room temperature for 16 h, and calcined at 650 °C for 4 h to obtain magnesium aluminate nanoparticles. The obtained materials exhibited spinel structure with the particle size being 6 to 26 nm. The nanoparticles demonstrated type IV nitrogen adsorption isotherm, typical of mesoporosity with a surface area of 325 m²/g. They were utilized for studies on chemical detoxification of deadly chemical warfare agents such as sarin and soman. Our results showed that the magnesium aluminate nanoparticles effectively decontaminated more than 99% of sarin and soman within 8-10 min when used at a ratio of 1:50-60% w/w.

Normalized Transfer Entropy as a Tool to Identify Multisource Functional Epileptic Networks.

Epilepsy is a major health problem worldwide. A significant proportion of patients develop medication-refractory epilepsy (MRE); they are of ten evaluated for possible surgery where the focus of epileptogenic zones (EZ) are removed from the brain. Hence, prior to epilepsy surgery, insertion of depth electrodes into the brain is necessary to identify the EZs. These depth electrodes have multiple contacts that monitor the neuronal activity in multiple locations within the brain along each electrode trajectory. In the present study, we show that normalized transfer entropy measurements demonstrate functional connectivity across multiple sites within the brain of an MRE patient who did not demonstrate a clear EZ using conventional EEG criteria. Interestingly, linear measures of functional connectivity were not predictive of such an epileptic network. Our results suggest that routine evaluation of both linear and non-linear functional connectivity including normalized transfer entropy from depth electrode recordings may be useful to identify multisource epileptogenic networks in MRE patients. Identification of networks that contribute to epilepsy in such patients could potentially allow the clinician to avoid resective surgery and adopt alternate therapies such as vagal nerve stimulation or other emergent alternatives.

Comparative evaluation of antidotal efficacy of 2-PAM and HNK-102 oximes during inhalation of sarin vapor in Swiss albino mice.

Efficacy of two oximes treatments evaluated during inhalation of sarin vapor (LCt50, 755.9 mg/min/m3) in simulated real scenario in vivo. Majority of mice either became moribund or died within 1-2 min during exposure to multifold-lethal concentrations of sarin vapor. Protection indices were determined by exposing to sarin vapor in two sessions, 1 min exposure followed by treatments with or without HNK-102 (56.56 mg/kg, im) or 2-PAM (30 mg/kg, im) and atropine (10 mg/kg, ip), and again exposed for remaining 14 min. Protection offered by HNK-102 was found to be four folds higher compared to 2-PAM in the same toxic environment. Secondly, sub-lethal concentration of sarin vapor (0.8 × LCt50 or 605 mg/min/m3), 24 h post investigations revealed that the oximes could not reactivate brain and serum acetylcholinesterase (AChE) activity. The treatments prevented increase in protein concentration (p < .05) and macrophages infiltration compared to sarin alone group in broncho-alveolar lavage fluid. Lung histopathology showed intense peribronchial infiltration and edema with desquamating epithelial lining and mild to moderate alveolar septal infiltration in sarin and atropine groups, respectively. Noticeable peeling-off observed in epithelial lining and sporadic mild infiltration of epithelial cells at bronchiolar region in 2-PAM and HNK-102 groups, respectively. The oximes failed to reactivate AChE activity; however, the mice survived up to 6.0 × LCt50, proved involvement of non-AChE targets in sarin toxicity. Atropine alone treatment was found to be either ineffective or increased the toxicity. HNK-102, exhibited better survivability with lung protection, can be considered as a better replacement for 2-PAM to treat sarin inhalation induced poisoning.

Neuroprotective Effects of Galantamine on Nerve Agent-Induced Neuroglial and Biochemical Changes.

Neuroprotection from nerve agent such as soman-induced neural damage is a major challenge for existing drugs. Nerve agent exposure can cause many neural effects in survivors arising mainly due to acetylcholinesterase (AChE) inhibition or death within minutes. Unraveling the mechanisms underlying the nerve agent-induced multiple neurological effects is useful to develop better and safe drugs. The present study aimed to understand the molecular response during soman exposure and to evaluate the neuroprotective efficacy of galantamine on nerve agent-induced neurotoxic changes. mRNA expression studies using quantitative real-time PCR revealed significant changes in S-100ß, Gfap, c-fos, and Bdnf in the hippocampus and piriform cortex after soman (90 µg/kg, s.c) exposure. Immunoblot analysis showed acute soman exposure significantly increased the protein levels of neuroglial markers (S100-ß and GFAP); c-Fos and protein oxidation in discrete rat brain areas indicate their role in nerve agent-induced neurotoxicity. Induction of BDNF levels during soman exposure may indicate the recovery mechanisms activation. AChE was inhibited in the blood and brain up to 82% after soman exposure. Antidotal treatment with galantamine alone (3 mg/kg) and galantamine plus atropine (10 mg/kg) has protected animals from nerve agent-induced intoxication, death, and soman-inhibited AChE up to 45% in the blood and brain. Animal received galantamine displayed increased levels of neuroprotective genes (nAChRα-7, Bcl-2, and Bdnf) in the brain suggest the neuroprotective value of galantamine. Neuroglial changes, c-Fos, and protein oxidation levels significantly reduced after galantamine and galantamine plus atropine treatment indicate their potential antidotal value in nerve agent treatment.

Complications of Radiotherapy and Radiosurgery in the Brain and Spine.

Radiation therapy is an integral part of the standard of care for many patients with brain and spine tumors. Stereotactic radiation surgery is increasingly being used as an adjuvant therapy as well as a sole treatment. However, despite newer and more focused techniques, radiation therapy still causes significant neurotoxicity. In this article, we reviewed the scientific literature, presented cases of patients who had developed different complications related to conventional radiation therapy or radiosurgery (gamma knife), demonstrated the imaging findings, and discussed the relevant clinical information for the correct diagnoses. Radiation therapy can cause injury in different ways: directly damaging the structures included in the radiation portal, indirectly affecting the blood vessels, and increasing the chance of tumor development. We also divided radiation complications according to the time of occurrence: acute (0 to 4 weeks), early delayed (4 weeks to months), and late delayed (months to years). With the increasing application of radiation therapy for the treatment of CNS tumors, it is important for the neuroradiologist to recognize the many possible complications of radiation therapy. Although this may cause significant diagnostic challenges, understanding the pathophysiology, time course of onset, and imaging features may help institute early therapy and prevent possible deleterious outcomes. Learning Objectives: To recognize the main complications of radiation therapy and stereotactic radiosurgery in the brain and spine, and to highlight the imaging findings to improve the diagnostic process and treatment planning.

Approximation of Height of an Individual Using Somatometry of Human Male Skull.

INTRODUCTION: Numerous population specific studies conducted on skeletal remains have aimed to standardize the identification process. Known for ethnic and sexual variations, skull bone can also assist the identification process by estimating stature of the individual. The present study focuses on estimation of stature from skull bone using uni-variate and multi-variate regression models in south Indian population. METHODS: Stature and maximum cranial length, maximum cranial breadth, bi-pterion breadth, parietal cord and upper facial breadth were measured in wet skulls of 113 males, autopsied at Government Hospital of Kudla, Karnataka. RESULTS: All five measurements showed significant correlation with stature (P value <0.001). MCL showed the highest (r=0.77) and UFB the lowest (r=0.42) degree of correlation. Standard error of estimate was lowest for MCL (4.90 cm) in the derived uni-variate regression models. In the regression model obtained from the multi-variate analysis using all five skull measurements the ß-coefficients were significant (P value <0.001) and the Standard Error of Estimation of the model was observed to be 4.45 cm. Bland-Altman analysis was conducted to explore the agreement between the actual length and the estimated lengths from the multivariate regression model. The mean of difference was 0.105 with a standard deviation of 4.3 and the upper and lower limits of agreement were 8.5 and -8.3 respectively. CONCLUSIONS: The study concludes that stature can be estimated from skull measurements with reasonable accuracy, observations of multi-variate regression models being more precise than the uni-variate regression models. Data collected from South India was compared with data available for Nepalese population and validates the use of data of Indian population for extrapolation in Nepalese population.

In vivo protection studies of bis-quaternary 2-(hydroxyimino)- N-(pyridin-3-yl) acetamide derivatives (HNK oximes) against tabun and soman poisoning in Swiss albino mice.

The study reports antidotal efficacy of three HNK [ bis quaternary 2-(hydroxyimino)-N-(pyridin-3yl) acetamide derivatives] and pralidoxime (2-PAM), against soman and tabun poisoning in Swiss albino mice. Protection index (PI) was determined (treatment doses: HNK oximes, ×0.20 of their median lethal dose (LD50) and 2-PAM, 30 mg/kg, intramuscularly (im)) together with atropine (10 mg/kg, intraperitoneally). Probit log doses with difference of 0.301 log of LD50 of the nerve agents administered and inhibition of acetylcholinesterase (AChE) activity by 50% (IC50) was calculated at optimized time in brain and serum. Using various doses of tabun and soman (subcutaneously (sc)), in multiples of their IC50, AChE reactivation ability of the oximes was studied. Besides, acute toxicity (0.8× LD50, im, 24 h postexposure) of HNK-102 and 2-PAM was also compared by determining biochemical, hematological variables and making histopathological observations. Protection offered by HNK-102 against tabun poisoning was found to be four times higher compared to 2-PAM. However, nearly equal protection was noted with all the four oximes against soman poisoning. HNK-102 reactivated brain AChE activity by 1.5 times more than 2-PAM at IC50 dose of soman and tabun. Acute toxicity studies of HNK-102 and 2-PAM showed sporadic changes in urea, uric acid, aspartate aminotransferase, and so on compared to control group, however, not supported by histopathological investigations. The present investigation showed superiority of newly synthesized HNK-102 oxime over standard 2-PAM, as a better antidote, against acute poisoning of tabun (4.00 times) and soman (1.04 times), in Swiss albino mice.

CT Angiography of the Head in Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation is an artificial cardiopulmonary bypass technique used to support patients with severe pulmonary failure or both pulmonary and cardiac failure. The hemodynamic changes produced by extracorporeal membrane oxygenation affect the appearance of CTA of the head images, often confounding interpretation if the correct history and understanding of extracorporeal membrane oxygenation are not known. This technical report describes the principles of extracorporeal membrane oxygenation, techniques to optimize intracranial CTA imaging, and pitfalls.

Time Interval Between Cover Crop Termination and Planting Influences Corn Seedling Disease, Plant Growth, and Yield.

Experiments were established in a controlled-growth chamber and in the field to evaluate the effect of the length of time intervals between winter rye cover crop termination and corn planting on corn seedling disease, corn growth, and grain yield in 2014 and 2015. Rye termination dates ranged from 25 days before planting (DBP) to 2 days after planting (DAP) corn in the field and from 21 DBP to 1 DAP in controlled studies. Results were similar in both environments. In general, shorter intervals increased seedling disease and reduced corn emergence, shoot growth, and grain yield of corn following winter rye compared with corn planted 10 or more days after rye termination or without rye. Incidence of Pythium spp. increased with shorter intervals (less than 8 DBP); incidence of Fusarium spp. was not consistent between runs and experiments. In 2014, in the 1-DAP treatment, number of ears and grain yield were reduced (P = 0.05 and 0.02, respectively). In 2015, all termination intervals reduced plant population, number of ears, and yield (P = 0.01), with the 2-DBP treatment causing the biggest decrease. A 10- to 14-day interval between rye termination and corn planting should be followed to improve corn yield following a rye cover crop.

Scrub Typhus: An Emerging Neglected Tropical Disease in Nepal.

BACKGROUND: Scrub typhus is a neglected tropical disease and is under reported from Nepal. The objective of this study was to investigate the sero-epidemiology of scrub typhus in patients suffering from acute febrile illness. METHODS: A total of 434 specimens collected from July to November 2015 at National Public Health Laboratory (NPHL) were investigated for detection of immunoglobulin M (IgM) antibody to Orientiatsutsugamushi.The Scrub Typhus Detect TM kit (InBios, USA) was used to detect the antibodies to O.tsutsugamushi in human serum. Randomly selected 10% positive specimens were used for confirmation by dot- enzyme-linked immunosorbent assay and indirect immunofluorescence assay. RESULTS: Of the total, 175 (40.3%) were positive for IgM antibodies to O. tsutsugamushi. Positive results of scrub typhus were highest among female in 11-20 year followed by males in 41-50 years age group. The IgM antibodies to O. tsutusugamushi were positive in specimens of various geographical regions including 30 districts of Nepal. Positive cases were found in various ecological regions of Nepal. CONCLUSIONS: Scrub typhus is one of the neglected tropical diseases in Nepal. Patients with acute febrile illness should be investigated for scrub typhus with high priority. There is an urgent need of reliable and affordable diagnostic tests at all level of health facilities of Nepal. Surveillance and public health awareness about the disease transmission and preventive measures needs to be initiated.

Minimizing Radiation Exposure in Evaluation of Pediatric Head Trauma: Use of Rapid MR Imaging.

BACKGROUND AND PURPOSE: With >473,000 annual emergency department visits for children with traumatic brain injuries in the United States, the risk of ionizing radiation exposure during CT examinations is a real concern. The purpose of this study was to assess the validity of rapid MR imaging to replace CT in the follow-up imaging of patients with head trauma. MATERIALS AND METHODS: A retrospective review of 103 pediatric patients who underwent initial head CT and subsequent follow-up rapid MR imaging between January 2010 and July 2013 was performed. Patients had minor head injuries (Glasgow Coma Scale, >13) that required imaging. Initial head CT was performed, with follow-up rapid MR imaging completed within 48 hours. A board-certified neuroradiologist, blinded to patient information and scan parameters, then independently interpreted the randomized cases. RESULTS: There was almost perfect agreement in the ability to detect extra-axial hemorrhage on rapid MR imaging and CT (κ = 0.84, P < .001). Evaluation of hemorrhagic contusion/intraparenchymal hemorrhage demonstrated a moderate level of agreement between MR imaging and CT (κ = 0.61, P < .001). The ability of MR imaging to detect a skull fracture also showed a substantial level of agreement with CT (κ = 0.71, P < .001). Detection of diffuse axonal injury demonstrated a slight level of agreement between MR imaging and CT (κ = 0.154, P = .04). However, the overall predictive agreement for the detection of an axonal injury was 91%. CONCLUSIONS: Rapid MR imaging is a valid technique for detecting traumatic cranial injuries and an adequate examination for follow-up imaging in lieu of repeat CT.

Development and Structural Modifications of Cholinesterase Reactivators against Chemical Warfare Agents in Last Decade: A Review.

Organophosphate (OP) pesticides and nerve agents are responsible for suicidal and accidental poisonings. The acute toxicity of nerve agents leads to progressive inhibition of the enzyme acetylcholinesterase (AChE) by phosphylation of serine residue at the active site of gorge. The recent massive destruction of Syrian civilians by nerve gas sarin, has again renewed the research attention of global science fraternity towards nerve agents, their mode of action and most prominently their therapeutic treatment. This review is principally focused on nerve agent intoxication. The common approach to deal with OP-intoxication is, application of antimuscarinic drug (atropine), anticonvulsant drug (diazepam) and clinically used oximes (pralidoxime, trimedoxime, obidoxime and asoxime). However, the existing therapeutic approach is arguable and has several failings to cure all kinds of nerve agent poisonings. Considering this issue, numerous oximes have been synthesized and screened through various in-vitro and in-vivo studies in last decade to overcome the downsides. At present, only a few oximes (bis pyridinum-oximes) exhibit sound efficacy against selective OPs. In spite of extensive efforts, till date no oxime is available as a universal antidote against all the classes of OPs. This review is centered on the recent developments and structural modification of AChE reactivators against nerve agent toxicity. In particular, a deeper look has been taken into chemical modifications of the reactivators by incorporation of different structural moieties targeted towards the increased reactivation affinity and improved blood brain barrier (BBB) penetration.

In vivo protection of diisopropylphosphorofluoridate (DFP) poisoning by three bis-quaternary 2 -(hydroxyimino) -N -(pyridin-3-yl) acetamide derivatives in Swiss mice.

This study reports efficacy of three bis pyridinium derivatives of 2-(hydroxyimino)- N-(pyridine-3-yl) acetamide in terms of survival, reactivation of brain and serum acetylcholinesterase (AChE) activity in diisopropylphosphorofluoridate (DFP) intoxicated Swiss albino male mice. LD50 of DFP (3.9 mg/kg, s.c.) and new oximes, HNK-102, HNK-106, HNK-111, (282.8, 35.0 and 35.0 mg/kg respectively, i.m.) was determined. Various doses of DFP and oximes as treatment doses with atropine (10 mg/kg, i.p.) were used to determine protection index (PI). For time dependent maximum AChE inhibition, two doses of DFP (0.20 and 2.0 LD50) were chosen. At optimized time i.e. Sixty minutes, IC50 value was calculated as 0.249 and 0.017 LD50 of brain and serum AChE, respectively. Shift of DFP induced brain AChE IC50 curves to right was observed at 0.20 LD50 treatment dose of oximes with respect to 2-PAM. These findings propose that new HNK series of oximes are effective antidote, compared to that of 2-PAM in vivo.