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At least 613 records · Page 34Linked to original sources

High-performance thin-layer chromatography for the determination of cetirizine in human plasma and its use in pharmacokinetic studies.

A rapid and sensitive high-performance thin-layer chromatography (HPTLC) assay has been developed for the measurement of cetirizine in human plasma and its utility for pharmacokinetic study has been evaluated. In the proposed HPTLC method, protein-bound cetirizine was freed by proteolysis of plasma proteins by incubating the plasma with 0.35% pepsin and then extracting with 2 mL pH 5.0 phosphate buffer, followed by 4 mL chilled chloroform. The chloroform layer was separated and concentrated. An aliquot of the extract was then spotted on precoated silica-gel 60 F254 plates using a Camag Linomat IV autosampler. Quantification was with the help of a dual-wavelength TLC scanner. The proposed method had a recovery of 98% and the lowest amount of cetirizine that could be detected was 50 ng. The method was applied for the determination of the plasma levels and pharmacokinetic parameters of cetirizine after oral administration of two marketed preparations in healthy volunteers and the pharmacokinetic parameters determined by the proposed method were in agreement with previously reported values.

Adult↗

High-performance thin-layer chromatography for the determination of nimesulide in human plasma, and its use in pharmacokinetic studies.

A rapid and sensitive high-performance thin-layer chromatographic assay has been developed for the measurement of nimesulide in human plasma. Its use for pharmacokinetic studies has been evaluated. The method includes a single-stage extraction procedure without the use of an internal standard. Analysis was performed on plasma containing known amounts of the drug, on drug-free plasma, and on plasma containing an unknown quantity of the drug. Known amounts of extract and nimesulide (100 and 200 ng, as external standard) were spotted on precoated silica-gel 60F254 plates by means of a Camag Linomat IV autosampler. Quantification was achieved using a Camag TLC scanner 3. The recovery of the method was 97.10 +/- 2.22%. The method was applied for the determination of plasma levels and pharmacokinetic parameters of nimesulide after oral administration of two formulations (100 mg) in healthy volunteers. The method is a sensitive, economical, rapid and specific assay for nimesulide in human plasma, and is suitable for pharmacokinetic studies after therapeutic doses.

Administration, Oral↗

Protein S deficiency in HIV associated ischaemic stroke: an epiphenomenon of HIV infection.

The purpose of the study was to determine the relevance of protein S deficiency in HIV infected patients with ischaemic stroke. In total, 33 HIV positive patients with ischaemic stroke, previously described by us, were prospectively compared with control groups for occurrence of protein S deficiency. The control groups comprised an equal number of consecutive matched HIV positive and negative patients without and with stroke respectively. Data were analysed in contingency tables using Fisher's exact test. Protein S deficiency occurred significantly more frequently in HIV positive compared with HIV negative stroke patients (p < 0.001). However, by including HIV positive patients without stroke as a control group and comparing this group with the HIV positive stroke group we found that protein S deficiency is statistically related to HIV infection and not stroke occurrence. Our data indicate that the presence of protein S deficiency in HIV positive patients with stroke is an epiphenomenon of HIV infection.

Adult↗

Human immunodeficiency virus associated intracranial aneurysms: report of three adult patients with an overview of the literature.

BACKGROUND AND PURPOSE: Aneurysms have been described in HIV infected patients. These involve predominantly extracranial blood vessels with specific histological and clinical features. Intracranial aneurysms are rare and have been identified mainly in children. METHODS: Case reports and literature review. RESULTS: Three black South African HIV positive adult patients with intracranial aneurysms were identified. The clinical, laboratory and radiological features are described. CONCLUSIONS: Intracranial aneurysms occur in both adults and children infected with HIV. More information is required on this association. The frequency in terms of numbers of cases indicates that it is an uncommon association or manifestation of HIV. The characteristics of the aneurysms suggest that they are distinctive and not a chance or coincidental co-occurrence of congenital or arteriosclerotic aneurysms.

Adult↗

Demyelinating disorder of the central nervous system occurring in black South Africans.

OBJECTIVES: To investigate the nature and cause in eight black South African patients of a recurrent (multiphasic), remitting, and relapsing demyelinating disease of the CNS. METHODS: The clinical and laboratory investigations and radiological manifestations of these patients were documented. RESULTS: Each patient had two or more acute attacks of demyelinating disease affecting the CNS. The clinical presentations of the patients were predominantly those of multiphasic neuromyelitis optica (NMO). Brain MRI in these patients showed features consistent with those described for acute disseminated encephalomyelitis (ADEM), as well as lesions that are described in multiple sclerosis. There was involvement of the corpus callosum in addition to typical ADEM lesions. Laboratory investigations excluded all other known causes of multiphasic CNS demyelination. Oligoclonal antibodies were not detected in these patients at any time. The patients were all from a population with a low risk for MS (black South Africans). CONCLUSION: The patients described here represent a new phenotypic expression of a recurrent (multiphasic), steroid sensitive, inflammatory demyelinating disorder of the CNS occurring in black South Africans. The disorder is either a distinct inflammatory demyelinating disorder of the CNS of as yet unknown aetiology, or a varied form of MS (ADEM/NMO) occurring in a population with a low risk (where the genetic trait and environmental risk factors for MS do not exist) for MS.

Adult↗

Genetic diversity and molecular mechanisms in hypertrophic cardiomyopathy: toward personalized therapy.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac muscle disorder, yet contemporary genomic and mechanistic research still lacks a cohesive model explaining how diverse genetic architectures give rise to heterogeneous phenotypes. This review synthesizes advances across sarcomeric and nonsarcomeric mutations, including intermediate-effect variants, polygenic modifiers, and ancestry-dependent sources of variant misclassification to elucidate how these factors govern disease penetrance and clinical expression. It critically evaluates how genetic diversity intersects with key molecular pathways, including sarcomeric hypercontractility, calcium dysregulation, mitochondrial energy deficiency, and transforming growth factor-&#x3b2; (TGF-&#x3b2;) and protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling, to drive hypertrophic and fibrotic remodeling. Emerging mechanism-based therapies, such as myosin inhibition, allele-specific silencing, clustered regularly interspaced short palindromic repeats (CRISPR)-based correction, and metabolic modulation, are examined with respect to their capacity to modify upstream molecular drivers rather than downstream hemodynamic consequences. Persistent challenges, including variants of uncertain significance classification, ancestry-biased databases, inequitable access to genetic testing, and unresolved safety concerns for gene-based therapies, are critically assessed as major barriers to precision-medicine integration. By linking genetic architecture, molecular pathogenesis, and targeted interventions, this review advances a contemporary, mechanistically grounded framework that informs both individualized management and future research directions. Future research should prioritize pathway-specific therapeutics, functional and mechanistic validation of emerging variants, deeper physiologic phenotyping to refine disease modeling, and accelerate translation throughout the continuum of HCM pathophysiology.

Humans↗

Stroke in black South African HIV-positive patients: a prospective analysis.

BACKGROUND AND PURPOSE: Stroke associated with HIV infection is poorly characterized. In this study we analyze the association in a black African population. METHODS: The clinical, laboratory, and radiological characteristics of 35 hospital-based black South African, heterosexual, HIV-infected patients who did not abuse intravenous drugs and presented with strokes were prospectively studied. The patients were antiretroviral therapy naive. Patients with other intracranial space-occupying lesions were excluded from the study. RESULTS: The age range was 20 to 61 years (mean, 32.1 years). There were 21 female and 14 male patients, with a female to male ratio of 1.5:1. Cerebral infarction occurred in 33 patients (94%) and intracerebral hemorrhage in 2 patients (6%). Underlying causes were identified in 30 of the 35 patients (86%) and included coagulopathies, meningitis, cardioembolism, and hypertension. The most common coagulopathy was protein S deficiency. No cause was found in 5 patients (14%). CONCLUSIONS: The results are similar to data from studies on young black African stroke patients who are HIV negative.

Adult↗

New-onset seizures associated with HIV infection.

The authors studied new-onset seizures in 60 heterosexual black South African HIV-infected patients who had not used IV drugs. An intracranial space-occupying lesion was identified in 53% of patients, meningitis in 22%, and no additional cause in 25%. Of the patients with an identifiable cause, 64% had probable tuberculosis (tuberculoma or tuberculous meningitis). The majority of patients had late-stage HIV infection (CD4 counts <200/mm(3)).

Adult↗

Pharmacokinetics of topically applied sparfloxacin in rabbits.

PURPOSE: Fluoroquinolones are antimicrobial agents that have a broad spectrum of activity and are widely used against many of the ocular pathogens, responsible for conjunctivitis, blepharitis, corneal ulcers etc. The aim of our study was to evaluate the ocular pharmacokinetics of sparfloxacin (0.3% w/v) in the aqueous humour of rabbits. MATERIALS AND METHODS: Pharmacokinetics of topically administered sparfloxacin were determined after a single application of 50 microl topically. The aqueous humour samples were collected at 0, 0.25, 0.5, 1, 2, 3, 4, 5 or 6 hours after instillation. High Performance Thin Layer Chromatographic method was used to analyse the drug concentration in the aqueous humour samples. RESULTS: Fifteen minutes after the instillation of 50 microl of sparfloxacin 0.3% solution, the mean concentration in aqueous humour was found to be 1.4 microg/ml, which reaches the peak level of 3.7 microg/ml after 1.3 hours. At 6 hours, the sparfloxacin aqueous levels were 0.562 microg/ml. The clinical efficacy was predicted based on the Maximum Concentration (Cmax): Minimum Inhibitory Concentration (MIC) and Area Under the Concentration-time curve (AUC):MIC ratios. CONCLUSION: The sparfloxacin levels in aqueous humour of rabbits are sufficiently high up to the 6 hours after instillation in the conjunctival sac to provide bactericidal effect against most of the ocular pathogens. Both Cmax:MIC and AUC:MIC ratios are high enough to provide bactericidal effect against most of the ocular pathogens. Sparfloxacin (0.3%) ophthalmic preparation has excellent penetration through cornea.

Animals↗

Plasma analysis of celiprolol by HPTLC: a useful technique for pharmacokinetic studies.

A rapid and sensitive high performance, thin-layer chromatographic (HPTLC) method has been developed for the measurement of celiprolol in human plasma and its use in pharmacokinetic studies has been evaluated. Detection and quantitation were performed without using an internal standard. A simple extraction procedure was followed for extracting celiprolol from plasma and a known amount of the extract was spotted on precoated silica gel 60 F254 plates using a Camag Linomat IV autosampler. Celiprolol was quantitated using a Camag TLC Scanner 3. The average recovery of authentic analytes (20 to 200 ng/mL) added to plasma was 72.06 +/- 2.8% and the lowest amount of celiprolol that could be detected was 10 ng/mL. The method provides a direct estimate of the amount of celiprolol present in plasma. Pharmacokinetic parameters of 2 marketed preparations have also been determined after oral administration to 12 healthy human volunteers.

Adrenergic beta-Antagonists↗

Damage to the plasma membrane in Escherichia coli K-12 induced by far-ultraviolet radiation and its repair.

Escherichia coli cells treated with low fluences of far-uv radiation (up to 90 J/m2) showed repairable damage to the plasma membrane. The loss of the ability of the cells to exclude citrate was evident from the respiratory stimulation of irradiated cells when citrate was provided exogenously. This loss of a barrier was a result of a structural disorganization of the plasma membrane as seen by freeze-etching electron microscopy. Analysis of the plasma membrane proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed a characteristic loss of certain membrane proteins. When irradiated cells were incubated in glucose minimal medium at 37 degrees C for various times, a gradual recovery of membrane structure and function was observed. The recovery process was inhibited in the absence of an energy source as well as protein synthesis. The majority of the recovery occurred in the initial 1 h of the postirradiation holding. These results demonstrated that far-uv radiation at a fluence less than the D10 value had a direct or indirect effect on plasma membrane proteins, causing their release from the membrane bilayer. The lost proteins were subsequently regained by de novo protein synthesis.

Cell Membrane↗

Cognitive and physiologic correlates of subclinical structural brain disease in elderly healthy control subjects.

CONTEXT: Healthy elderly persons commonly show 4 types of change in brain structure-cortical atrophy, central atrophy, deep white-matter hyperintensities, and periventricular hyperintensities-as forms of subclinical structural brain disease (SSBD). OBJECTIVES: To characterize the volumes of SSBD present with aging and to determine the associations of SSBD, physiology, and cognitive function. DESIGN: Cross-sectional study. SETTING: University of California, Los Angeles, Neuropsychiatric Institute. SUBJECTS: Forty-three community-dwelling healthy control subjects, aged 60 through 93 years. MAIN OUTCOME MEASURES: Volumetric magnetic resonance imaging, neuropsychological testing, and quantitative electroencephalographic coherence (functional connectivity) between brain regions. RESULTS: Regression models demonstrated significant relationships between SSBD volumes, age, cognitive performance, and connectivity. Cortical and central atrophy and periventricular hyperintensities had significant associations with age while deep white-matter hyperintensities did not. Posterior atrophy showed stronger associations with age than did anterior atrophy. Only a subset of subjects at older ages showed large SSBD volumes; older subjects primarily showed increasing variance of SSBD. Although all subjects scored within the normal range on cognitive testing, SSBD volume was inversely related to performance, most notably on the Trail-Making Test part B and the Shipley-Hartford Abstract Reasoning test. Coherence had significant associations with SSBD. Path analysis supported mediation of the effects of deep white-matter hyperintensities and periventricular hyperintensities on cognition by altered connectivity. For several measures, cognitive performance was best explained by coherence, and only secondarily by SSBD. CONCLUSIONS: Modest volumes of SSBD were associated with decrements in cognitive performance within the normal range in healthy subjects. Lower coherence was associated with greater volumes of SSBD and increasing age. Path analysis models suggest that brain functional connectivity mediates some effects of SSBD on cognition.

Aged↗