Determination of mycophenolic acid in human plasma by high-performance liquid chromatography.

The development, validation and evaluation of high-performance liquid chromatography (HPLC) method for quantifying mycophenolic acid in human plasma is described. The method involved protein precipitation using acetonitrile, after addition of terazosin as an internal standard. Separation was achieved with a reversed-phase C18 column (250 mm x 4.6 mm) employing UV detection at 215 nm. The mobile phase consisted of 0.02 M potassium dihydrogenphosphate solution adjusted to pH 6.9 with 2 M potassium hydroxide solution-acetonitrile (80:20 (v/v)) at a flow rate of 1.5 ml/min. The total run time was 21.0 min. The assay was linear from 0.2 to 25 microg/ml with goodness of fit (r2) greater than 0.99 observed with three precision and accuracy batches during validation. The observed mean recoveries were 89.3 and 98.0% for drug and internal standard, respectively. The applicability of this method to pharmacokinetic studies was established after successful application during a 34-subject bioavailability study. The method was found to be precise, accurate and specific during the study.

Simultaneous determination of itraconazole and hydroxyitraconazole in human plasma by high-performance liquid chromatography.

The development and validation of a high-performance liquid chromatography (HPLC) method for the simultaneous determination of itraconazole and its metabolite, hydroxyitraconazole, in human plasma is described. The method involved liquid-phase extraction of itraconazole and hydroxyitraconazole using a hexane-dichloromethane (70:30) mixture, after addition of loratidine as an internal standard (IS). Separation was achieved with a reversed-phase C18 column (250 mm x 4.6 mm) employing fluorescence detection (excitation: 264 nm, emission: 380 nm). The mobile phase consisted of [0.01% triethylamine solution adjusted to pH 2.8 with orthophosphoric acid-acetonitrile (46:54)]-isopropanol (90:10, v/v) at a flow rate of 1.0 ml/min. For both the drug and metabolite, the standard curve was linear from 5.0 to 500 ng/ml with goodness of fit (r2) greater than 0.98 observed with four precision and accuracy batches during validation. An observed recovery was more than 70% for drug, metabolite and internal standard. The applicability of this method to pharmacokinetic studies was established after successful application during 35 subjects bioavailibity study. The method was found to be precise, accurate and specific during the study.

The possible role of surface charge in membrane organization in an acidophile.

Thiobacillus ferrooxidans, an obligate acidophile, possesses an electron transport chain that uses oxidation of ferrous iron to generate proton motive force. The cells possess an efficient machinery for inter-conversion of the two components of the free energy, namely pH gradient and membrane potential. Incidentally, unlike most of the naturally occurring membranes, surface in T. ferrooxidans appears to be positively charged at or near its physiological pH. Independent estimate of such charge was obtained from binding studies with anionic optical and fluorescent probes. When the external pH is lowered below a critical value the inter-conversion of the two components of the proton motive force was no longer operative. A surface charge mediated phase separation of membrane is suggested as one of the possible mechanisms for the failure of such inter-conversion process.

Post-traumatic epilepsy: its complications and impact on occupational rehabilitation--an epidemiological study from India.

The objective of this study was to assess the prevalence of seizure disorder, neuropsychiatric disorders and reproductive outcome of employees with post-traumatic epilepsy (PTE) and their effect on occupational rehabilitation. A case-comparison group study design was used to compare 30 subjects with PTE with (1) 129 non-PTE and (2) 55 non-PTE matched control employees. The 55 non-PTE matched controls were selected from the 129 non-PTE employees on the basis of age, age at onset of seizure, age at marriage and length of employment. The PTE group had a lower fertility rate than the controls and more neuropsychiatric disorders and seizure disability. PTE employees were more occupationally rehabilitated than non-PTE employees (p = 0.033). Of the 30 PTE subjects, thirteen who were rehabilitated by placement had more seizure disability (p = 0.007) and a higher fertility rate (p = 0.018). High prevalence of seizure disability and increased fertility rate among the placed PTE employees suggested that there might be some association between severity of seizures and increased production of live offspring and work placement. Work suitability or placement should not be judged on clinical assessment only but psychosocial seizure assessment, disability evaluation and other psychometric tests which are of equal importance.

Epilepsy and employability: a comparative evaluation of epileptic employees working in the steel plants of India.

Information on seizures and provoking factors, occupational status, shift work, overtime, home and work place adjustment was obtained from 176 epileptic employees working in hazardous, less and non-hazardous areas of steel plants in India. Accidents at work and sickness absence were also assessed in 44 epileptics. An overall comparison was made between Group A hazardous (63) and Group B less/non-hazardous (76) of the total of 139 epileptic employees over a three year period. Group A performed better than Group B. When compared with 77 employees with occupational dermatoses, 139 epileptics did more fixed shifts and had less promotion.

Effects of vibration on the hand-arm system of miners in India.

Sixty-six Jackhammer drillers and 35 blasters from two mines were clinically screened for hand-arm vibration syndrome (HAVS). The screening consisted of questionnaire-based information, clinical examination including measurement of phalangeal circumferences of fingers (FCT) and motor nerve conduction (MCV) studies. In a warm environment, the prevalence of symptom complexes suggested the existence of peripheral neuropathy and musculoskeletal abnormalities rather than any peripheral circulatory disorders. Clinical examination revealed soft tissue wasting in the hands (26 cases), ulnar nerve impairment (23 cases), median nerve impairment (16 cases) and Dupuytren's contracture (4 cases). Mean motor nerve conduction velocities of 59 out of 66 drillers who volunteered for this assessment were not significantly different from those of the 35 blasters. The results of their correlation coefficients varied considerably for MCVs when age and years of vibration exposure underwent regression analysis. However, comparison of MCV and FCT of 30 drillers with 30 matched blasters revealed that the mean MCV of the right median nerve in the vibration exposed group was significantly decreased (p < 0.01) and for the mean FCT, the proximal phalanxes of the right index finger, left thumb and left ring fingers were thinner in the vibration exposed group (p < 0.05).

Multilamellar vesicular clusters of phosphatidylcholine and their sensitivity to spectrin: a study by fractal analysis.

The cluster patterns of multilamellar vesicles (MLV) of dimyristoylphosphatidylcholine (DMPC) were analyzed using a combination of fractal analysis and lattice simulation. Self-assembly of DMPC MLVs resulted in two types of microscopically observable clusters. The clusters were classified on the basis of their mass fractal dimension, two-dimensional porosity, and the light scattering properties. Spectrin, a cytoskeletal protein, well known for its role in determining the cellular morphology, was used to perturb such spontaneously formed clusters. The fragmentation of the clusters by hydrodynamic perturbation followed a power law, implying again a fractal behavior. A lattice-based simulation was performed generating different class of cluster patterns. The observed correspondence between the cluster patterns and their stability was discussed in the framework of the proposed lattice simulation.

Epilepsy in the British Steel Corporation: an evaluation of sickness, accident, and work records.

Information relating to sickness, accident, and work records in 45 people with epilepsy employed in the British Steel Corporation was obtained and compared with 38 matched control subjects. Fewer people with epilepsy were prepared to do shift work compared with controls, and prolonged absence from work due to sickness was more frequent in the epileptic group. There was no difference between the two groups in four out of five factors relating to job performance. Those in the epileptic group who had an associated personality disorder had significantly poorer job performance ratings.

The performance of the ICEROSS prostheses amongst transtibial amputees with a special reference to the workplace--a preliminary study. Icelandic Roll on Silicone Socket.

A clinical trial was conducted to evaluate the efficiency of ICEROSS on randomly selected 46 male transtibial amputees. After rejection, only 27 (58.69%) amputees volunteered for various stages of the ICEROSS trial. All 27 were categorized into Group A-persons in employment (n = 16) and Group B-persons out of employment or economically inactive (n = 11). The study was conducted on the basis of questionnaire information, clinical examination and objective tests. The pre- and post-ICEROSS status were compared between the groups. Group A was younger and did better. Trauma was the main cause of amputation. There were certain changes of the stump before and after ICEROSS. The amputees with ICEROSS suspension performed better and had improved mobility in Group A. At the workplace, dynamic activities were less than the static activities (p < 0.001) and there were overall improvements in comfort and performance of amputees with ICEROSS.

Metoclopramide on rat phrenic hemidiaphragm.

The effect of metoclopramide on skeletal muscle and its neurotransmission was studied employing innervated and denervated rat diaphragm. Metoclopramide, at concentrations from 0.035 to 0.14 mM, inhibited the twitch contractions of rat diaphragm stimulated either directly or indirectly. Inhibition was greater in indirectly stimulated preparations, at a given concentration of metoclopramide, than in directly stimulated preparations. Inhibition of indirect twitch by metoclopramide could be intensified by raising the concentration of magnesium chloride, but was unaffected by physostigmine or d-tubocurarine. Metoclopramide also inhibited the submaximal contractures of denervated diaphragm elicited by potassium chloride and acetylcholine. In calcium-free physiological solution, metoclopramide inhibited the caffeine-induced contractures of denervated diaphragm as a function of its concentration. It is suggested that metoclopramide possesses a calcium antagonistic action in the rat diaphragm.