PARTAKE Survey of Public Knowledge and Perceptions of Clinical Research in India

Background

A public that is an informed partner in clinical research is important for ethical, methodological, and operational reasons. There are indications that the public is unaware or misinformed, and not sufficiently engaged in clinical research but studies on the topic are lacking. PARTAKE – Public Awareness of Research for Therapeutic Advancements through Knowledge and Empowerment is a program aimed at increasing public awareness and partnership in clinical research. The PARTAKE Survey is a component of the program.

Objective

To study public knowledge and perceptions of clinical research.

Methods

A 40-item questionnaire combining multiple-choice and open-ended questions was administered to 175 English- or Hindi-speaking individuals in 8 public locations representing various socioeconomic strata in New Delhi, India.

Results

Interviewees were 18–84 old (mean: 39.6, SD±16.6), 23.6% female, 68.6% employed, 7.3% illiterate, 26.3% had heard of research, 2.9% had participated and 58.9% expressed willingness to participate in clinical research. The following perceptions were reported (% true/% false/% not aware): ‘research benefits society’ (94.1%/3.5%/2.3%), ‘the government protects against unethical clinical research’ (56.7%/26.3%/16.9%), ‘research hospitals provide better care’ (67.2%/8.7%/23.9%), ‘confidentiality is adequately protected’ (54.1%/12.3%/33.5%), ‘participation in research is voluntary’ (85.3%/5.8%/8.7%); ‘participants treated like ‘guinea pigs’’ (20.7%/53.2%/26.0%), and ‘compensation for participation is adequate’ (24.7%/12.9%/62.3%).

Conclusions

Results suggest the Indian public is aware of some key features of clinical research (e.g., purpose, value, voluntary nature of participation), and supports clinical research in general but is unaware of other key features (e.g., compensation, confidentiality, protection of human participants) and exhibits some distrust in the conduct and reporting of clinical trials. Larger, cross-cultural surveys are required to inform educational programs addressing these issues.     

Use of the SOS-chromotest spot assay as a screening system for detecting genotoxic compounds in crude plant extracts

An SOS-chromotest spot assay was used to detect genotoxic compounds in crude plant extracts. The method allows simultaneous testing of extracts from different species in either a liquid or a solid crystalline form. Extracts from two species of the genus Senna, native to the state of Morelos, Mexico, were assayed. Four genotoxic compounds were isolated, and were identified as quercetin and rutin from S. wislizeni, and 5,7-di- O-methylrutin and 5,7-di-O-methylquercetin from S. skinneri. The SOS-chromotest spot assay proved to be useful for activity- guided fractionation at the beginning of screening for genotoxic compounds in crude plant extracts.     

Prostaglandins modulate baroreflex-induced changes in blood pressure and myocardial function in anesthetized dogs

The purpose of our study was to investigate the role of prostaglandins in the changes in myocardial function and peripheral and coronary vascular resistance which accompany a generalized increase in sympathetic tone caused by carotid baroreflex unloading in the anesthetized dog. Bilateral carotid artery occlusion (BCO) with heart rate held constant by electrical pacing (150 beats/min) resulted in increases in systolic, (33%) diastolic (40%), and mean (35%) arterial pressures, LV systolic pressure (33%) and left ventricular (LV) dP/dt (37%). After blockade of prostaglandin synthesis with indomethacin (N = 11) or meclofenamate (N = 6) the increases in systolic (41%), diastolic (45%), and mean (41%) arterial pressures, LV systolic pressure (39%), LV dP/dt (52%), and cardiac work caused by BCO were significantly greater, in spite of the initially higher baseline values (11-18%) following the administration of the drugs. In contrast, the changes in circumflex coronary blood flow and coronary vascular resistance to BCO were essentially the same before and after inhibition of prostaglandin synthesis. Systemic prostaglandin synthesis may, therefore, play a significant role in the control of systemic arterial pressure and myocardial function, most probably by modulating the release of norepinephrine from adrenergic nerve terminals, without adversely affecting coronary blood flow regulation.     

Homozygous disruption of Pctp modulates atherosclerosis in apolipoprotein E-deficient mice

Phosphatidylcholine transfer protein (PC-TP) is a cytosolic phospholipid binding protein and a member of the steroidogenic acute regulatory-related transfer domain superfamily. Its tissue distribution includes liver and macrophages. PC-TP regulates hepatic lipid metabolism, and its absence in cholesterol-loaded macrophages is associated with reduced ATP binding cassette transporter A1-mediated lipid efflux and increased susceptibility to apoptosis induced by unesterified cholesterol. To explore a role for PC-TP in atherosclerosis, we prepared PC-TP-deficient/apolipoprotein E-deficient (Pctp(-/-)/Apoe(-/-)) mice and littermate Apoe(-/-) controls. At 16 weeks, atherosclerosis was increased in chow-fed male, but not female, Pctp(-/-)/Apoe(-/-) mice. This effect was associated with increases in plasma lipid concentrations. By contrast, no differences in atherosclerosis were observed between male or female Pctp(-/-)/Apoe(-/-) mice and Apoe(-/-) controls fed a Western-type diet for 16 weeks. At 24 weeks, atherosclerosis in chow-fed male Pctp(-/-)/Apoe(-/-) mice tended to be reduced in proportion to plasma cholesterol. The attenuation of atherosclerosis in female Pctp(-/-)/Apoe(-/-) mice fed chow or the Western-type diet for 24 weeks was not attributable to changes in plasma cholesterol or triglyceride concentrations. These findings suggest that PC-TP modulates the development of atherosclerosis, in part by regulating plasma lipid concentrations.     

Driving forces enable high-titer anaerobic 1-butanol synthesis in Escherichia coli

1-Butanol, an important chemical feedstock and advanced biofuel, is produced by Clostridium species. Various efforts have been made to transfer the clostridial 1-butanol pathway into other microorganisms. However, in contrast to similar compounds, only limited titers of 1-butanol were attained. In this work, we constructed a modified clostridial 1-butanol pathway in Escherichia coli to provide an irreversible reaction catalyzed by trans-enoyl-coenzyme A (CoA) reductase (Ter) and created NADH and acetyl-CoA driving forces to direct the flux. We achieved high-titer (30 g/liter) and high-yield (70 to 88% of the theoretical) production of 1-butanol anaerobically, comparable to or exceeding the levels demonstrated by native producers. Without the NADH and acetyl-CoA driving forces, the Ter reaction alone only achieved about 1/10 the level of production. The engineered host platform also enables the selection of essential enzymes with better catalytic efficiency or expression by anaerobic growth rescue. These results demonstrate the importance of driving forces in the efficient production of nonnative products.     

Large scale preparation of the mammalian high mobility group protein A2 for biophysical studies

Due to asymmetrical charge distribution of the mammalian high mobility group protein A2 (HMGA2), which makes HMGA2 bind to both cation- and anion-exchange columns, we developed a rapid procedure for purifying HMGA2 in the milligram range. This purification procedure greatly facilitated biophysical studies, which require large amounts of the protein.     

Folding kinetic pathway of phosphofructokinase-2 from Escherichia coli: a homodimeric enzyme with a complex domain organization

Phosphofructokinase-2 is a 66 kD homodimer whose subunits are associated by means of a bimolecular domain, the β-clasp, which is linked to the larger portion of each subunit by a reentrant chain topology. To investigate how this structural organization determines the folding pathway of Pfk-2, unfolding and folding kinetic experiments were performed. The folding pathway shows an unstructured monomeric intermediate and that most part of the dimer structure is reached as a slow concerted folding/association step with a quite folded transition state in terms of solvent exposure. Unfolding kinetics show a transient intermediate, probably a partially unfolded dimer. We propose that these characteristics arise by a mutual constrain between the large domain and the β-clasp domain imposed by their interrupted chain connectivity.