PubMed Health⌕ Search

Biomedical subjects

A K Chaturvedi

Publications and source records attributed to A K Chaturvedi.

At least 19 recordsLinked to original sources

A novel dodecapeptide from a combinatorial synthetic library exhibits potent antifungal activity and synergy with standard antimycotic agents.

There has been a marked expansion in the discovery of new antifungal peptides. This paper describes a novel dodecapeptide, H-Arg-Trp-Trp-Arg-D-Trp-D-Phe-Ile-D-Phe-His-Trp-Arg-Trp-NH(2), derived from a previously described nonapeptide and synthesized by the combinatorial approach. Further, interaction of this peptide with antifungals such as amphotericin B, flucytosine and fluconazole was studied by checkerboard analysis and time-kill assay to obtain the dynamic picture with respect to time. The best synergistic activity was observed with a combination of peptide and fluconazole, followed by peptide and flucytosine.

Amino Acid Sequence↗

Synthesis of 4-hydroxy-1-methylindole and benzo[b]thiophen-4-ol based unnatural flavonoids as new class of antimicrobial agents.

Synthesis of nitrogen and sulfur heterocyclic mimics of furanoflavonoids have been achieved for the first time. Synthesized flavonoid alkaloids and thiophenyl flavonoids have been screened for antifungal and antibacterial activities. All the test compounds barring 25 exhibited antifungal activity. The compound 19 was the best and showed comparable MICs to the known compound karanjin. Compounds 5, 12, 14 and 22 also showed comparable MIC to karanjin.

Flavonoids↗

Immunolocalization of secretory proteins of Aspergillus fumigatus using monospecific polyclonal antibodies in a murine model.

The incidence of life-threatening mycoses caused by opportunistic fungi has increased dramatically in recent years with members of the genera Candida and Aspergillus being the most commonly encountered species. Prompt initiation of antifungal therapy for good prognosis of such cases is highly dependent on accurate diagnosis. The potential of metabolic antigens in the diagnosis of aspergillosis was investigated in the present study. Two proteins of 18 and 70 kDa were identified with success rate of 35% and 60% respectively based on their reactivity with patient sera of clinically diagnosed cases of aspergillosis. The antibodies raised against 70 and 18 kDa proteins in rabbits were found to be useful in detection of A. fumigatus in the kidneys of a mouse model of aspergillosis.

Animals↗

Synthesis of galactopyranosyl amino alcohols as a new class of antitubercular and antifungal agents.

The galactopyranosyl amino alcohols (3-16) were synthesised by regioselective oxirane ring opening of compound 2 with variety of amines and screened for antitubercular and antifungal activities. One of the compounds (16) showed potent activity against Mycobacterium tuberculosis H37 Rv in vitro and also displayed activity in MDR TB. The compound (16) was found to be superior to ethambutol clinically used anti TB drug in in vitro screen.

Amino Alcohols↗

A fatality caused by accidental production of hydrogen sulfide.

A 55-year-old male Caucasian truck driver was dead at the scene after breathing hydrogen sulfide (H(2)S) produced by an accidental transfer of sodium hydrogen sulfide (NaHS) from a tanker truck to a tank containing 4% sulfuric acid (H(2)SO(4)) and iron(II) sulfate (FeSO(4)). Autopsy of the decedent's body revealed pulmonary edema and passive congestion in lungs, spleen, kidneys, and adrenal glands. Postmortem biological samples were analyzed for carbon monoxide, cyanide, ethanol, and drugs. Since a potential exposure to H(2)S was involved, blood was also analyzed for sulfide (S(2-)). The analysis entailed isolating S(2-) from blood as H(2)S using 0.5M H(3)PO(4), trapping the gas in 0.1M NaOH, and determining the electromotive force using a sulfide ion specific electrode. Acetaminophen at a concentration of 14.3 microg/ml was found in blood, and metoprolol was detected in the blood, liver, and kidney samples. The blood S(2-) level was determined to be 1.68 microg/ml. It is concluded that the cause of death was H(2)S poisoning associated with a hazardous material accident in an industrial situation.

Accidents, Occupational↗

Blood carbon monoxide and hydrogen cyanide concentrations in the fatalities of fire and non-fire associated civil aviation accidents, 1991-1998.

Blood samples submitted to the Civil Aeromedical Institute (CAMI) from aviation accident fatalities are analyzed for carbon monoxide (CO), as carboxyhemoglobin (COHb), and hydrogen cyanide, as cyanide (CN(-)). These analyses are performed to establish possible exposure of victims to smoke from in-flight/post-crash fires or to CO from faulty exhaust/heating systems. The presence of both gases in blood would suggest that the victim was alive and inhaled smoke. If only COHb is elevated, the accident (or a death) could be the result of CO contamination of the interior. Information pertaining to blood levels of these gases in aviation fatalities, in relation to the associated accidents, is scattered or not available, particularly with regard to toxicity. Therefore, considering that COHb> or =10% and CN(-)> or =0.25 microg/ml are sufficient to produce some degree of toxicological effects, the necessary information was extracted from the CAMI database. Samples from 3857 fatalities of 2837 aviation accidents, occurring during 1991-1998, were received; 1012 accidents, encompassing 1571 (41%) fatalities, were fire associated, whereas 1820 accidents were non-fire related. The remaining five accidents were of unknown fire status. There were fewer fire related fatalities and associated accidents in the (COHb> or =10% and CN(-)> or =0.25 microg/ml) category than that in the (COHb<10% and CN(-)<0.25 microg/ml) category. No in-flight fire was documented in the former category, but in-flight fires were reported in 14 accidents (18 fatalities) in the latter category. No non-fire accident fatality was found wherein levels of both gases were determined to be at or above the stated levels. There were 15 non-fire accidents with 17 fatalities wherein only COHb (10-69%) was elevated. The present study suggests that aviation fire accidents/fatalities were fewer than aviation non-fire accidents/fatalities and confirms that aviation accidents related to in-flight fires and CO-contaminated interiors are rare.

Accidents, Aviation↗

Abnormal glucose levels found in transportation accidents.

BACKGROUND: The Federal Aviation Administration's Office of Aerospace Medicine is responsible for the certification of pilots with diabetic conditions. The present study evaluated the use of postmortem vitreous humor and urine glucose levels in transportation accident fatalities as indicators of potentially incapacitating medical conditions or performance impairment. METHODS: Vitreous humor and/or urine from 192 accident fatalities were analyzed for glucose using a hexokinase method. Cases with values below the lower limit of detection (10 mg x dl(-1)) and above 3 standard deviations (SD) from the mean were not included in the final statistics. All cases more than 5 SD above the mean were deemed abnormal and a full case history was evaluated based on the available medical history. RESULTS: The mean vitreous humor glucose concentration was 30+/-21 mg x dl(-1) (N=98), while it was 27+/-16 mg x dl(-1) in urine (N=127). Of the 192 cases, 9 were identified as having abnormal glucose levels. Abnormal glucose levels were found in 5 of the 8 cases with a known diabetic condition. Glycosuria or low renal threshold was reported in 2 fatal pilots; 1 of these pilots had an abnormal glucose level. CONCLUSIONS: Hyperglycemia can be established from the vitreous humor and urine glucose levels. All of the abnormal glucose cases detected were previously identified during the medical certification process or had a medical reason for the abnormal level. Elevated vitreous humor and urine glucose levels have proven useful in identifying individuals with a pre-existing diabetic condition that might have been a factor in the accident.

Accidents, Aviation↗

The FAA's postmortem forensic toxicology self-evaluated proficiency test program: the first seven years.

Existing proficiency-testing (PT) programs do not address the complexity of postmortem forensic toxicology. These programs do not include decomposed samples and solid tissues. Therefore, the Federal Aviation Administration in July 1991 started such a needed PT program. This program is used to: (i) professionally develop and maintain technical currency on a voluntary, interlaboratory, and self-evaluation basis, and (ii) quantifiably assess methods in the absence and presence of interfering substances. There are currently about 30 laboratories in the program. Functioning under various governmental/non-governmental agencies and academic institutions, these laboratories represent a broad cross-section of the country. PT samples are distributed quarterly, and result summaries are sent to the participants, while maintaining their anonymity. Since the inception of the program, 28 PT samples encompassing whole blood, plasma, urine, kidney, or liver, with (or without) drugs, metabolites, and common chemicals (nicotine, caffeine, beta-phenylethylamine, etc.) have been analyzed by the participants. Analytical findings were generally consistent with the anticipated values, but they were dependent on the nature and conditions of the specimens and types of the added analytes. Some incidences of false positives of concern were noted, as well. This PT program is one of the few programs recommended by the American Board of Forensic Toxicology in which laboratories may participate for their accreditation by the Board. It is anticipated that this PT program will continue to play a critical part in supporting the quality assurance/quality control (QA/QC) component of forensic toxicology, thereby enhancing operational performance.

Accidents, Aviation↗

Formation of an interfering substance, 3,4-dimethyl-5-phenyl-1,3-oxazolidine, during a pseudoephedrine urinalysis.

During fatal aviation accident investigations, biosamples from the victims are submitted to the FAA Civil Aeromedical Institute (CAMI) for drug analysis. In the process of one such analysis by CAMI, an unknown substance was found in a urine sample. Simultaneous screening by thin layer chromatography (TLC) and gas chromatography/FID (GC/FID) suggested the presence of pseudoephedrine. A subsequent routine confirmation analysis of a separate urine aliquot by GC Fourier transform infrared (GC/FTIR) and GC mass spectrometry (GC/MS) indicated that the retention times of the unknown substance matched with those of pseudoephedrine. However, its infrared and mass spectra were different--the -OH and -NH groups were missing, a C-O-C group was present, and the molar mass was 12 atomic mass units (amu) more than that of pseudoephedrine. A subsequent literature search suggested that ephedrine-like amines react with aldehydes to form oxazolidines. Therefore, the 12-amu increase could be accounted for by condensation of pseudoephedrine with formaldehyde. Since this aldehyde is present in various grades of methanol and ethyl acetate, and these solvents were used during the solid-phase extraction, 3,4-dimethyl-5-phenyl-1,3-oxazolidine was synthesized by using (+)-pseudoephedrine HCl and formaldehyde. The analytical findings of the synthesized compound were consistent with those of the unknown interfering substance, confirming that it was the oxazolidine. Aldehyde contaminants in solvents or specimens can transform drugs of interest and may result in misidentification of a compound originally present in specimens. Therefore, chemicals used in analyses should be of the highest available purity, and a multi-analytical approach should be adopted to maintain a high degree of quality assurance.

Accidents, Aviation↗

Aspiration vs nonaspiration technique of cytodiagnosis--a critical evaluation in 160 cases.

The two sampling techniques were studied in 160 randomly selected cases of superficial swellings in various sites of the body. They were sampled by fine needle aspiration (FNA) and by non-aspiration (NA) (a needle without application of aspiration pressure). Cell samples were cytologically assessed and critically evaluated using five objective parameters. Contamination with blood was more in lymphnode, thyroid and liver lesions in aspiration smears than NA smears and values were statistically significant. Similarly when compared for the degree of cellular trauma and cellular degeneration statistically significant better results were obtained by nonaspiration technique for lymphnode lesions. Regarding amount of cellular material obtained by FNA, statistical significant better results were found for breast lesions only. Statistically significant better maintenance of architecture was observed only for thyroid lesions by NA technique. Better average scores were observed by NA technique for lymphnode and thyroid only. Categorizing all the smears obtained by FNA & NA on the basis of their scores according to predetermined criteria, greater number of diagnostically adequate specimens were obtained by FNA than by NA but the number of diagnostically superior specimens obtained by NA technique was found to be more than that by FNA. The difference was found to be statistically significant. However the number of inadequate smears was also more by NA technique than by FNA technique.

Biopsy, Needle↗

Prevalence of chlorpheniramine in aviation accident pilot fatalities, 1991-1996.

BACKGROUND: Chlorpheniramine is known to cause drowsiness, and this side effect has a potential to impair performance and could be a factor in accidents. METHODS: Therefore, to establish the prevalence of this drug in pilot fatalities of aviation accidents, a postmortem toxicology database--maintained at the Civil Aeromedical Institute--was examined for the presence of chlorpheniramine in the fatalities, occurred during 1991-1996. RESULTS: There were 47 (2.2%) accidents involving chlorpheniramine. Of these, 16 had only chlorpheniramine at 109 ng.ml-1 (n = 4) in blood and 1412 ng.g-1 (n = 12) in liver. Other drugs were also present in the remaining 31 cases, wherein chlorpheniramine concentrations were 93 ng.ml-1 (n = 18) in blood and 747 ng.g-1 (n = 12) in liver. Ninety-five percent of all quantitated blood values were at or above the therapeutic level (10 ng.ml-1), giving a 100 ng.ml-1 (n = 21) mean blood value. The drug's mean liver concentration from all cases was 1080 ng.g-1 (n = 24). The average blood value was approximately 10 times higher than the therapeutic value. CONCLUSIONS: The presence of other drugs did not appear to significantly alter the blood chlorpheniramine level, but no such correlation could be established with the hepatic value. The approximate 10-fold increase in the liver concentration was consistent with the general trend of drug distribution in the hepatic compartment. However, the contribution of postmortem redistribution of the drug to alter its concentration cannot be entirely ruled out. This study suggests that chlorpheniramine was present in some aviation fatalities at levels higher than therapeutic levels.

Accidents, Aviation↗

Genotyping for DQA1 and PM loci in urine using PCR-based amplification: effects of sample volume, storage temperature, preservatives, and aging on DNA extraction and typing.

Urine is often the sample of choice for drug screening in aviation/general forensic toxicology and in workplace drug testing. In some instances, the origin of the submitted samples may be challenged because of the medicolegal and socioeconomic consequences of a positive drug test. Methods for individualization of biological samples have reached a new boundary with the application of the polymerase chain reaction (PCR) in DNA profiling, but a successful characterization of the urine specimens depends on the quantity and quality of DNA present in the samples. Therefore, the present study investigated the influence of storage conditions, sample volume, concentration modes, extraction procedures, and chemical preservations on the quantity of DNA recovered, as well as the success rate of PCR-based genotyping for DQA1 and PM loci in urine. Urine specimens from male and female volunteers were divided and stored at various temperatures for up to 30 days. The results suggested that sample purification by dialfiltration, using 3000-100,000 molecular weight cut-off filters, did not enhance DNA recovery and typing rate as compared with simple centrifugation procedures. Extraction of urinary DNA by the organic method and by the resin method gave comparable typing results. Larger sample volume yielded a higher amount of DNA, but the typing rates were not affected for sample volumes between 1 and 5 ml. The quantifiable amounts of DNA present were found to be greater in female (14-200 ng/ml) than in male (4-60 ng/ml) samples and decreased with the elapsed time under both room temperature (RT) and frozen storage. Typing of the male samples also demonstrated that RT storage samples produced significantly higher success rates than that of frozen samples, while there was only marginal difference in the DNA typing rates among the conditions tested using female samples. Successful assignment of DQA1 + PM genotype was achieved for all samples of fresh urine, independent of gender, starting sample volume, or concentration method. Preservation by 0.25% sodium azide was acceptable for sample storage at 4 degrees C during a period of 30 days. For longer storage duration, freezing at -70 degrees C may be more appropriate. Thus, the applicability of the DQA1 + PM typing was clearly demonstrated for individualization of urine samples.

DNA↗

Preparation of carboxyhemoglobin standards and calculation of spectrophotometric quantitation constants.

A method was developed for the preparation of carboxyhemoglobin (COHB) standards, which were stable for more than four months with the prepared control remaining within acceptable limits during this time. A mathematical equation was developed to more accurately determine the constants A and B used in the equation COHB% = 100[(C - B)/(A - B)], where B = 0% COHB peak ratio at 540 nm and 579 nm; A = 100% COHB peak ratio at 540 nm and 579 nm; and C = the peak ratio at 540 nm and 579 nm for the blood being analyzed. The following equations were developed to calculate A and B: B = Pavg - (P) [(Pavg - Navg)/(P - N)]; A = B + (Pavg - Navg)/(P - N), Pavg = average peak ratio 540/579 for the positive standard run on the spectrophotometer; P = average decimal concentration measured on the CO-OXIMETER for the positive standard; Navg = average peak ratio 540/579 for the negative standard; N = average decimal concentration measured on the CO-OXIMETER for the negative standard. The new equations provided results consistent with those obtained from a CO-OXIMETER.

Carboxyhemoglobin↗

PCR-based identification of postmortem microbial contaminants--a preliminary study.

Investigation of postmortem blood can reveal the presence of significant ethanol levels. However, in some instances it cannot easily be determined if the source of ethanol is from ingestion or from postmortem endogenous fermentation by contaminating microbes. Described here is a robust polymerase chain reaction (PCR)-based method for detecting the presence of common ethanol producing microbial contaminants in human blood. A set of DNA primers were designed for use in PCR to amplify and detect the genomic DNA from humans and three test microorganisms Escherichia coli, Proteus vulgaris, and Candida albicans. A rapid and reproducible protocol was developed for isolating genomic DNA from mixed human blood-microorganism samples that yields a suitable template for PCR. The organism-specific primer pairs can detect the presence of the target microorganisms in human blood at concentrations as low as 10 colony forming units/mL. The PCR products readily can be detected after agarose gel electrophoresis. This method provides an additional means of rapidly identifying microbial contaminants in postmortem blood samples.

Candida albicans↗

DNA typing as a strategy for resolving issues relevant to forensic toxicology.

To investigate aircraft accidents, multiple postmortem biological samples of victims are submitted to the Civil Aeromedical Institute for toxicological evaluation. However, depending upon the nature of a particular accident, their body components are often scattered, disintegrated, commingled, contaminated, and/or putrefied. These factors impose difficulties with victim identification, tissue matching, and consequently authentic sample analysis and result interpretation. Nevertheless, these limitations can be overpowered by DNA typing. In this regard, three situations are hereby exemplified where DNA analysis was instrumental in resolving a tissue mismatching/commingling issue, pinpointing an accessioning/analytical error, and interpreting an unusual analytical result. Biological samples from these cases were examined for six independently inherited genetic loci using polymerase chain reaction (PCR) suitable for analyzing degraded DNA generally encountered in putrefied/contaminated samples. In the first situation, three of five specimen bags from one accident were labeled with two different names. DNA analysis revealed that one of these bags actually had commingled specimens, originating from two different individuals. Therefore, the sample was excluded from the final toxicological evaluation. In the second situation, an unacceptable blind control result was reported in a cyanide batch analysis. By comparing DNA profiles of the batch samples with those of the known positive and negative blind controls, it was concluded that the error had occurred during the analysis instead of accessioning. Accordingly, preventive measures were taken at the analytical level. The third situation was related to the presence of atropine at toxic concentrations in the blood (318 ng/mL) and lung (727 ng/g) with its absence in the liver, spleen, and brain. DNA analysis of the blood and liver samples exhibited their common identity, ensuring that the submitted samples had indeed originated from one individual. The selective presence of atropine was attributed to its possible administration into the thoracic cavity by the emergency medical personnel at the accident site for resuscitation, but circulatory failure prevented its further distribution. These examples clearly demonstrate the applicability of the PCR-based DNA typing to enhance the effectiveness of forensic toxicology operation.

Accidents, Aviation↗

Stereochemical determination of selegiline metabolites in postmortem biological specimens.

In this study, findings related to an aircraft accident are reported. Biological specimens collected at autopsy from the pilot of the fatal accident and two types of tablets found at the accident scene were submitted for toxicological evaluation. It was determined that the pilot was dead at the crash site and the cause of death was multiple traumatic injuries. The tablets were identified as selegiline and levodopa, commonly prescribed for the treatment of Parkinson's disease. Selegiline, a stereospecific compound, is biotransformed into (-)-N-desmethylselegiline, (-)-methamphetamine, and (-)-amphetamine. The latter two levorotatory metabolites cannot be easily distinguished by routine analysis from their dextrorotatory isomers, which are controlled substances. It was, therefore, prudent to differentiate these isomers to determine if they resulted from the ingestion of a controlled substance, (+)-methamphetamine. Initial immunoassay drug screenings revealed the presence of amphetamine class drugs (867 ng/mL) in urine, amphetamine/methamphetamine (261 ng/mL) in urine, and methamphetamine (46 ng/mL) in blood. The gas chromatography-mass spectrometry (GC/MS) results revealed the presence of methamphetamine in the concentrations of 76 ng/mL of blood and 685 ng/mL of urine. The concentration of amphetamine was 52 ng/mL in blood and 320 ng/mL in urine. To determine the stereospecificity of these amines, the isolated amines from the biosamples were derivatized by a stereospecific agent, (S)-(-)-N-(trifluoroacetyl)-prolyl chloride, and characterized by a GC/MS method to be levorotatory. The 2.14 ratio of (-)-methamphetamine to (-)-amphetamine concentrations in the urine was consistent with a selegiline study in the recent literature. The stereospecific analysis, in conjunction with the history of the pilot being on Parkinson's medications, suggests that the source of these amines was selegiline. This conclusion substantiates the importance of the identification of enantiomers in evaluating and interpreting related analytical results for accident investigations.

Accidents, Aviation↗

Role of metabolites in aviation forensic toxicology.

In aviation accident investigations, specimens from fatal aircraft victims are analyzed for drugs. The presence of drugs suggests possible associated medical conditions for which they might have been taken. As drugs are mostly present in therapeutic to subtherapeutic levels in aviation forensic toxicology cases, determination of parent drugs and their metabolites in multispecimens is of significance. Although chemically reactive metabolites are difficult to detect, physiologically active and inactive metabolites can be analyzed. Selective and sensitive techniques are available, but unavailability of metabolite reference standards, endogenous substance interference, and low tissue metabolite levels limit the analyses. However, the majority of primary metabolites can be effectively characterized/quantitated. Demonstrating the presence of drug (e.g., terfenadine, cocaine, THC) metabolites provides a compelling evidence for exposure to the parent drug and facilitates interpretation of results, particularly when the metabolites are active. Such analyses are not as helpful if the metabolites are also available as drugs (e.g., diazepam, temazepam, oxazepam).

Accidents, Aviation↗

Aircraft fires, smoke toxicity, and survival.

In-flight fires in modern aircraft are rare, but post-crash fires do occur. Cabin occupants frequently survive initial forces of such crashes but are incapacitated from smoke inhalation. According to an international study, there were 95 fire-related civil passenger aircraft accidents worldwide over a 26-yr period, claiming approximately 2400 lives. Between 1985 and 1991, about 16% (32 accidents) of all U.S. transport aircraft accidents involved fire and 22% (140 fatalities) of the deaths in these accidents resulted from fire/smoke toxicity. Our laboratory analyses of postmortem blood samples (1967-93) indicate that 360 individuals in 134 fatal fire-related civil aircraft (air carrier and general aviation) accidents had carboxyhemoglobin saturation levels (> or = 20%), with or without blood cyanide, high enough to impair performance. Combustion toxicology is now moving from a descriptive to a mechanistic phase. Methods for gas analyses have been developed and combustion/animal-exposure assemblies have been constructed. Material/fire-retardant toxicity and interactions between smoke gases are being studied. Relationships between gas exposure concentrations, blood levels, and incapacitation onset are being established in animal models. Continuing basic research in smoke toxicity will be necessary to understand its complexities, and thus enhance aviation safety and fire survival chances.

Accidents, Aviation↗