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Pharmaceutical drug promotion: how it is being practiced in India?

The pharmaceutical industries (PI) throughout the World are heavily involved in aggressive drug promotions, with a clear aim to change the prescribing habits of physicians and to encourage the self-medication of patients. Broadly, drug promotion refers to all the informational and persuasive activities of the PI, the effect of which is to induce prescription, supply, purchase, and use of medicinal drugs. It includes the activities of medical representatives, drug advertisements to physicians, provision of gifts and samples, drug package inserts, direct-to-consumer advertisements, periodicals, telemarketing, holding of conferences, symposium and scientific meetings, sponsoring of medical education and conduct of promotional trials. The PI has the right to promote its products, but it should do so in a fair, accurate, and ethical manner. The promotional claims need to be reliable, truthful, informative, balanced, up-to-date, and capable of substantiation in good taste. However, now a days, whilst the promotional methods have become very sophisticated and effective, it was found that while promoting their products, the PI does not adhere to these ethical principles. Hence, in most situations, these lead to irrational use of drugs. This unfortunate situation could be tackled only by the multiple prong strategy involving government, PI, doctors, medical associations and consumers. The government is required to formulate some guidelines in addition to developing their own code. The doctors and consumers are required to be educated on the promotional practices and abuses committed by the PI and different ways to tackle those. Various medical and consumer groups should also intervene to improve the scenario of promotion.

Advertising↗

Repeated sodium depletion affects gustatory neural responses in the nucleus of the solitary tract of rats.

Furosemide sodium depletions were induced repeatedly to determine the effects on gustatory neural responses in the nucleus of the solitary tract (NST) of chronically prepared, but lightly anesthetized, rats. Sodium-replete and sodium-deplete conditions were alternated four times in each rat. When rats were under depleted conditions, the responses to NaCl were significantly greater than in sodium-replete conditions. This effect was attributable primarily to an increase in the magnitude of response of those neurons that responded better to NaCl than to the other standard stimuli (sucrose, citric acid, and quinine hydrochloride). In addition, the largest change in responsiveness of the NaCl-best neurons occurred during the third and fourth sodium depletions. These results are essentially opposite to those reported for NST neurons when sodium appetite is induced by dietary sodium restriction. This suggests that the coding of intensity in the gustatory system is dependent not only on the animal's deprivation condition, but also the method through which the deprivation is produced.

Animals↗

Identification of processed Japanese green tea based on polymorphisms generated by STS-RFLP analysis.

In Japan, tea is generally sold blended, though 90% of the total production is clonal. Due to the increasingly strict consumer need and taste, however, more and more Japanese green teas are being sold under their particular cultivar name. Moreover, tea made from Yabukita, a much appreciated cultivar originally developed in Japan, has recently been produced and imported from a neighboring country. This paper describes a simple and inexpensive methodology capable of identifying fresh and processed Japanese green teas to discourage its fraudulent commercialization. The study was based on 46 main tea cultivars, and polymorphism detected through STS-RFLP analysis of the coding and noncoding DNA regions of three genes, namely phenylalanine ammonia-lyase, chalcone synthase, and dihydroflavonol 4-reductase, for which nucleotide information was available. All 46 tea cultivars analyzed could be easily distinguished using a combination of codominant DNA markers. Yabukita displayed a unique profile when PAL intron was digested with DdeI, thus allowing its rapid authentication at low cost.

Acyltransferases↗

Candidate codes in the gustatory system of caterpillars.

Larvae of tobacco hornworms offer unique opportunities to relate the electrophysiological output of identified chemosensory neurons to specific behavioral responses. Larvae can discriminate among three preferred plants with only eight functioning gustatory receptors. They can be induced to prefer any one of the plants, and these preferences can be reversed. All eight neurons respond to each plant sap. Two fire too infrequently to permit detailed analysis. Analyses of the remaining six show that all electrophysiological responses consist of phasic and tonic components. Only the "salt best" cell fires during the phasic period. Temporal analysis of the spike train during this period shows that tomato and tobacco could be distinguished from Jerusalem cherry but not from each other by a rate code. Measurements of behavioral response times together with the nonspecificity of this with respect of food plants, unacceptable plants, and sodium chloride eliminate a phasic period rate code as a probable mechanism for complex discrimination. Events occurring in the tonic period, when all cells are firing, suggest a major role for this period. Analyses of variance in the interval frequencies of the large and medium spikes suggest that a variance code could allow discrimination among the three plants as long as both cells were firing at the same time. Evidence has been found for temporal patterning in the tonic response of the "salt best" cell to Jerusalem cherry but is absent elsewhere. The most likely basis for coding the difference between each of the three plants is across-fiber patterning in which the relative rates of firing and the variances of all the sensory neurons in the tonic phase are critical.

Action Potentials↗

Neural ensemble coding of satiety states.

The motivation to start or terminate a meal involves the continual updating of information on current body status by central gustatory and reward systems. Previous electrophysiological and neuroimaging investigations revealed region-specific decreases in activity as the subject's state transitions from hunger to satiety. By implanting bundles of microelectrodes in the lateral hypothalamus, orbitofrontal cortex, insular cortex, and amygdala of hungry rats that voluntarily eat to satiety, we have measured the behavior of neuronal populations through the different phases of a complete feeding cycle (hunger-satiety-hunger). Our data show that while most satiety-sensitive units preferentially responded to a unique hunger phase within a cycle, neuronal populations integrated single-unit information in order to reflect the animal's motivational state across the entire cycle, with higher activity levels during the hunger phases. This distributed population code might constitute a neural mechanism underlying meal initiation under different metabolic states.

Action Potentials↗

Cloning, characterization, and chromosomal localization of rec1.3, a member of the G-protein-coupled receptor family highly expressed in brain.

During a project to identify G-protein-coupled receptors (GPCR) expressed within taste buds, we have isolated a novel receptor-like sequence. The full length sequence of this receptor (rec1.3) has been obtained in both cow and mouse. Rec1.3 bears little sequence similarity to any GPCR whose ligand is known: the closest identity (33%) is to the orphan receptor edg-1. In cow, rec1.3 is expressed most prominently in the brain, with moderate expression in testis and tongue; in the mouse the expression is more widespread. No specific binding for a range of ligands was detected when the mouse coding sequence was expressed in eukaryotic cells. In situ hybridization showed that rec1.3 is widely expressed throughout the mouse brain and is highly expressed in localized regions of the hindbrain, midbrain and hypothalamus. The rec1.3 gene was localized to the centromeric region of chromosome 4 in mouse, a region associated with neonatal seizures.

Amino Acid Sequence↗

Definitions of healthy eating among university students.

PURPOSE: To identify definitions of healthy eating in terms of food characteristics, eating behaviours, barriers, and benefits in university students. METHODS: Four focus groups were conducted; verbatim transcripts were analyzed and coded using qualitative methods. Participants were nine students of dietetics and six students of other subjects. All were females in their third or fourth year at the University of British Columbia (UBC). RESULTS: Participants often described healthy eating as consuming all food groups of Canada's Food Guide to Healthy Eating, with the associated notions of moderation and balance. Benefits of healthy eating were cited as a healthy weight, good physical appearance, feeling better, preventing disease, and achieving personal satisfaction. Barriers to healthy eating included lack of time, choice, taste preferences, and finances. There was some discrepancy between what the dietetics students perceived as barriers for clients (e.g., lack of information), and barriers the potential clients (other students) perceived for themselves. CONCLUSIONS: As dietitians, we must try to understand our clients' definitions of healthy eating and their barriers to achieving it, which likely differ from our own.

Adult↗

Do the diminishing efficacy and increasing toxicity of sodium stibogluconate in the treatment of visceral leishmaniasis in Bihar, India, justify its continued use as a first-line drug? An observational study of 80 cases.

Eighty parasitologically confirmed cases of visceral leishmaniasis (kala-azar) in Bihar, India, were treated daily with 20 mg sodium stibogluconate/kg for 30 days, to assess the current efficacy and toxicity of this 30-day regimen. Clinical and parasitological cure was obtained in 48 (60%) of the patients. However, 26 (33%) patients did not respond to the first course of treatment (primary unresponsiveness), two relapsed after initial clinical and parasitological cure, and two were withdrawn from the study (one on day 6 of treatment because of cardiotoxicity in the form of supraventricular tachycardia and the other on day 24 because of severe loss of appetite). All 30 patients who were not entirely cured with sodium stibogluconate were successfully treated with amphotericin B. Electrocardiographic changes occurred in many of the patients as the result of treatment with sodium stibogluconate. Diminution in the height of the T wave was seen in 32 (40%), inversion of the T wave (Minnesota code 5-1, 5-2) in seven (9%), elevation of the ST segment (Minnesota code 4-1) in three (4%), prolonged QT interval (compared with baseline findings) in six (8%), and diminution in the height of the P, R and T waves in two (3%). Cardiac arrhythmia occurred in five patients (6%), supraventricular arrhythmia (coarse atrial fibrillation) occurred in one patient and ventricular tachycardia, ventricular fibrillation, torsade de pointes and multifocal ventricular ectopics occurred in the four patients (5%) who died of cardiotoxicity. Minor side-effects, such as pain at the site of injection (two cases), mild diminution in appetite (12 cases), metallic taste in mouth (six cases), and joint pain (two cases), were also observed. It was concluded that the efficacy of sodium stibogluconate in the study area has declined over the years and that its toxicity has increased. A more efficacious, safer and cheaper, alternative drug is required as the first line of treatment of kala-azar.

Adolescent↗

Optimization in development of acetaminophen syrup formulation.

Formulation of acetaminophen syrup could be developed by an optimization technique to reduce the time and cost of study. Cosolvents were used in the formulation because of the low solubility of acetaminophen in water. They were composed of polyethylene glycol 4000, propylene glycol, sorbitol solution, and glycerin. Their effects on the solubility of acetaminophen and the pH of formulations were investigated. Effects on taste and price were calculated based on their properties. Simulation study of the effect of cosolvents upon the formulation scores was performed, using an algorithm based upon a simulated annealing concept to achieve the global optima and heuristic optimization concept to accelerate convergence. The program written as a Visual Basic module within Microsoft Access 97 was used to simulate and assess the optimal cosolvent amounts to achieve the most desirable formulations automatically according to the specified criteria. Formulators could customize the optimal formulation according to their needs and cost constraints by redefining the desirable outcomes in the source code of the program.

Acetaminophen↗

Qualitative research methods in otorhinolaryngology.

OBJECTIVE: Qualitative research methods explore the character and meaning of human phenomena. The methodology is unfamiliar to most clinicians, not only because of the different techniques and the type of studied issues, but also because of important differences regarding terminology and criteria for evaluating qualitative studies. This paper aims at discussing the potential contribution of qualitative methods to otorhinolaryngological research in general, and to describe a specific method with an otologic application in detail. METHOD: In order to explore different disturbing sound phenomena and coping strategies in patients with manifest tympanic membrane retractions, individual semi-structured interviews were performed. The transcripts were systematically analyzed by coding, categorizing, and interpreting the content of the text. The extracted themes, categories, and patterns were summarized. RESULTS: The method proved useful when exploring empirically known but non-measurable sound disturbances. Moreover, the findings provided further support for an alternative pathogenic theory suggesting the patient's playing an active role in the development of tympanic membrane retractions. CONCLUSIONS: Used as a complement to quantitative methods, qualitative methods offer a means for exploring the patient's experiences and role in the development, therapy, and prevention of disease. Otorhinolaryngology involves disorders of sensory functions such as hearing, equilibrium, smell and taste, as well as the vital functions of breathing and eating. The related symptoms might be experienced and coped with very differently depending on individual interpretations, fear of severe disease, etc. Furthermore, the clinician's and the patient's perspectives of symptoms and expectations regarding treatment may differ, which has implications for information, planning of therapy, and quality assessment in health care. There is no lack of study questions, but rather a lack of experience of alternative and pertinent methods.

Auditory Perception↗

Effects of GPD1 overexpression in Saccharomyces cerevisiae commercial wine yeast strains lacking ALD6 genes.

The utilization of Saccharomyces cerevisiae strains overproducing glycerol and with a reduced ethanol yield is a potentially valuable strategy for producing wine with decreased ethanol content. However, glycerol overproduction is accompanied by acetate accumulation. In this study, we evaluated the effects of the overexpression of GPD1, coding for glycerol-3-phosphate dehydrogenase, in three commercial wine yeast strains in which the two copies of ALD6 encoding the NADP+-dependent Mg2+-activated cytosolic acetaldehyde dehydrogenase have been deleted. Under wine fermentation conditions, the engineered industrial strains exhibit fermentation performance and growth properties similar to those of the wild type. Acetate was produced at concentrations similar to that of the wild-type strains, whereas sugar was efficiently diverted to glycerol. The ethanol yield of the GPD1 ald6 industrial strains was 15 to 20% lower than that in the controls. However, these strains accumulated acetoin at considerable levels due to inefficient reduction to 2,3-butanediol. Due to the low taste and odor thresholds of acetoin and its negative sensorial impact on wine, novel engineering strategies will be required for a proper adjustment of the metabolites at the acetaldehyde branch point.

Acetates↗

Diterpene synthesis in Stevia rebaudiana: recruitment and up-regulation of key enzymes from the gibberellin biosynthetic pathway.

Stevia rebaudiana Bertoni leaves accumulate a mixture of at least eight different glycosides derived from the tetracyclic diterpene steviol. These natural products taste intensely sweet and have similar biosynthetic origins to those of gibberellic acid (GA). The initial steps leading to the formation of GA result from the two-step cyclization of geranylgeranyl diphosphate (GGDP) to (-)-kaurene via the action of two terpene cyclases (-)-copalyl diphosphate synthase (CPS) and (-)-kaurene synthase (KS). Steviol biosynthesis probably uses the same mechanism although the genes and enzymes from S. rebaudiana that are involved in the cyclization of GGDP have not been characterized. We have isolated both the CPS and KS genes from S. rebaudiana and found that recombinant CPS and KS were catalytically active, suggesting that the CPS and KS genes participate in steviol biosynthesis. The genes coding for CPS and KS are usually present in single copies in most plant species and their expression is normally low and limited to rapidly growing tissues. The KS gene has been duplicated in the S. rebaudiana genome and both the KS and CPS genes are highly expressed in mature leaves, a pattern opposite to that found with GA biosynthesis. This pattern may, at least in part, lead to temporal and spatial separation of GA and steviol biosynthesis and probably helps to prevent over-expression from interfering with normal GA metabolism. Our results show that CPS and KS are part of the steviol glycoside biosynthetic pathway and that Stevia rebaudiana has recruited two genes to secondary metabolism from a highly regulated pathway involved in hormone biosynthesis.

Alkyl and Aryl Transferases↗

Amine fluoride/stannous fluoride and chlorhexidine mouthwashes as adjuncts to single-stage dental implants: a comparative study.

BACKGROUND: The growing popularity of non-submerged dental implants in recent years requires a greater emphasis on microbial plaque control. Chlorhexidine (CHX), the most commonly used mouthwash in implant surgery, is sometimes associated with tooth staining and alteration in taste perception. Amine fluoride/stannous fluoride (AmF/SnF2) mouthwash has been shown to have anti-infective properties; however, it has not been tested as an adjunct anti-infective means in non-submerged dental implants. The purpose of this trial was to compare AmF/SnF2 and CHX mouthwashes as adjuncts to single-stage dental implants. METHODS: Thirty-three patients aged 34 to 79 (mean 54.30 +/- 8.69 SD) requiring dental implants were accepted into the study. Following comprehensive periodontal therapy patients received one to three non-submerged dental implants (maxilla: 17; mandible: 45; anterior: 3, posterior: 59). After surgery patients were given analgesics and antibiotics as well as 2,400 ml of coded mouthwash bottles previously randomized between the two above mentioned formulations. Clinical and radiographic parameters were recorded at baseline and 3 and 12 months post-surgery. RESULTS: Twelve-month survival rates were 100% and 92.9% for the AmF/SnF2 and CHX groups, respectively. Compliance was slightly higher in the AmF/SnF2 group (84.35% +/- 3.39% versus 78.15% +/- 4.59% SE) but statistically similar. There was no statistically significant difference between the AmF/SnF2 and CHX groups in staining index at 3 months (1.519 +/- 0.22 versus 1.457 +/- 0.24 SE) and patient subjective evaluation of the mouthwashes. Radiographic bone loss was 0.79 +/- 0.23 and 1 +/- 0.13 SE at 3 months and 1.06 +/- 0.13 and 1.27 +/- 0.25 at 12 months for the CHX and AmF/SnF2 groups, respectively; the difference was statistically insignificant (P = 0.388 and 0.504, respectively). CONCLUSION: Both CHX and AmF/SnF2 mouthwashes can be used post-surgically after one-stage implant surgery.

Adult↗

Australian parents' views on their 5-6-year-old children's food choices.

The home food environment is central to the development of healthy eating behaviours, but associations between the home food environment and children's food choices are not yet fully understood. The aims of this study were to explore parents' views regarding factors that influence children's food choices and parents' decision-making regarding the food they provide to their children. In-depth one-on-one interviews were conducted using a semi-structured interview schedule. Key concepts and themes were coded independently by two investigators. Participants include seventeen parents (16 mothers and 1 father) of children in their first year of formal schooling (aged 5-6 years). Five main themes emerged from the interviews: food marketing, food availability/food exposure, feeding strategies, modelling of eating and opportunities for food involvement. Parents believed that food marketing influenced their child's food preferences but differed in the ways they managed these influences. The food made available to children was also seen to influence what a child ate. Yet, although some parents believed it was the parents' role to determine what foods were made available to their child, others offered food on the basis of the child's tastes or preferences. The use of food as a reward was a feeding strategy employed by many parents. Family mealtimes were seen as an important opportunity for modelling of eating behaviour by parents. Peers were also seen to influence children's food preferences and eating behaviour. Finally, many parents believed that involving children in the preparation of food had a positive impact on children's food choices. Associations between the home food environment and children's food choices are complex and involve multiple mediators. Parents' views on the promoters and reinforcers of their decision-making regarding food and their child's food choices provide useful insights into these mediating factors. Increased understanding of these relationships is likely to enhance obesity prevention efforts.

Adult↗

Neural coding of aversive and appetitive gustatory stimuli: interactions in the hamster brain stem.

There is increasing evidence, both electrophysiological and behavioral, that bitter and sweet stimuli drive parallel pathways in the gustatory brainstem. Here we report two lines of investigation that suggest significant interactions among these parallel systems. First, responses recorded from single cells in the hamster's parabrachial nuclei (PbN) show that quinine hydrochloride (QHCl) produces a substantial suppression (> 40%) of the responses of PbN cells to sucrose. Sucrose stimulation has a reciprocal suppressive effect on the response to QHCl. These results imply that aversive and appetitive stimuli produce mutual inhibition in the gustatory system; studies of the chorda tympani nerve response suggest that this inhibition likely arises within the brainstem. A second line of investigation, using both an in vitro brainstem slice preparation and in vivo pharmacological manipulations of cells in the hamster NST, has demonstrated an inhibitory network within the rostral NST that plays a role in the modulation of taste activity. Patch-clamp and extracellular recording studies in vitro show that cells within the rostral central subdivision of the NST are inhibited by gamma-aminobutyric acid (GABA); this mediation is largely through the GABAA receptor subtype. Here we show that responses to taste stimulation recorded extracellularly from NST cells in vivo can be inhibited by local microinjections of GABA; this inhibition is blocked by the GABAA receptor antagonist bicuculline methiodide. Responses to sucrose are significantly more inhibited than those to NaCl or KCl. These combined lines of evidence show that appetitive and aversive stimuli activate mutually inhibitory systems within the brainstem and suggest that the basis for this interaction is a GABAergic inhibitory network within the NST.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

BDNF gene replacement reveals multiple mechanisms for establishing neurotrophin specificity during sensory nervous system development.

Neurotrophins have multiple functions during peripheral nervous system development such as controlling neuronal survival, target innervation and synaptogenesis. Neurotrophin specificity has been attributed to the selective expression of the Trk tyrosine kinase receptors in different neuronal subpopulations. However, despite overlapping expression of TrkB and TrkC in many sensory ganglia, brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) null mutant mice display selective losses in neuronal subpopulations. In the present study we have replaced the coding part of the BDNF gene in mice with that of NT3 (BDNF(NT3/NT3)) to analyse the specificity and selective roles of BDNF and NT3 during development. Analysis of BDNF(NT3/NT3) mice showed striking differences in the ability of NT3 to promote survival, short-range innervation and synaptogenesis in different sensory systems. In the cochlea, specificity is achieved by a tightly controlled spatial and temporal ligand expression. In the vestibular system TrkB or TrkC activation is sufficient to promote vestibular ganglion neuron survival, while TrkB activation is required to promote proper innervation and synaptogenesis. In the gustatory system, NT3 is unable to replace the actions of BDNF possibly because of a temporally selective expression of TrkB in taste neurons. We conclude that there is no general mechanism by which neurotrophin specificity is attained and that specificity is achieved by (i) a tightly controlled spatial and temporal expression of ligands, (ii) different Trk receptors playing distinct roles within the same neuronal subpopulation, or (iii) selective receptor expression in sensory neuron subpopulations.

Animals↗

Determination of acceptability of flavored oat bran frankfurters by older adults.

The US population is aging rapidly and, within the next 25 years, 20-25% will be over age 60. This creates a vast new market for age-specific products and increases the responsibility of food scientists and nutritionists to provide appropriate foods for older adults. Many older individuals are energy deficient and need to be encouraged to consume more food in order to maintain body weight and health, but need to decrease the calories from fat in their diets. Many of these older individuals are not inclined to eat foods that they enjoy for fear that these foods may be detrimental to their health (de Castro, 1993), or they have lost their gustational abilities to the degree that these foods are no longer enjoyable. This research looks at a possible solution to both problems by replacing fat in a favorite food of older adults and adjusting the flavor levels of this product. Frankfurters were made from mechanically deboned poultry meat in which standard commercial formulation was compared to three flavoring treatments using oat bran as a fat replacer (6% oat bran, 30% H2O). Mixed spices (traditional saucisson) were added to two of these treatments in standard and double proportions. Participants were 71 individuals over the age of 65 in varying levels of health from four regional care facilities. Seven gram, three-digit-coded samples were evaluated at 60 degrees C, and scored on a nine-point hedonic scale. A significant (alpha = 0.0004) preference was shown for the double-spiced frank. No differences by sex or race were found. Research concluded that addition of flavoring aids in the increased acceptability of products by older adults.

Aged↗

Processing of gustatory information by spiking local interneurons in the locust.

Despite the importance of gustation, little is known of the central pathways responsible for the processing and coding of different chemical stimuli. Here I have analyzed the responses of a population of spiking local interneurons, with somata at the ventral midline of the metathoracic ganglion, during stimulation of chemo- and mechanoreceptors on the legs of locusts. Volatile acidic stimuli were used to selectively activate the chemosensory neurons. Different members of the population of local interneurons received depolarizing or hyperpolarizing inputs during chemosensory stimulation. Many of the same interneurons that received chemosensory input also received mechanosensory inputs from tactile hairs on the leg, but others received exclusively mechanosensory inputs. Chemosensory inputs occurred with a short and constant latency, typical of monosynaptic connections. The chemosensory receptive fields of the spiking local interneurons mapped the surface of a hind leg so that spatial information relating to the location of a taste receptor was preserved. The amplitude of potentials in interneurons during chemosensory stimulation varied in a graded manner along the long axis of the leg, thus creating gradients in the chemosensory receptive fields of interneurons. Some interneurons were depolarized to a greater extent by chemical stimuli applied to basiconic sensilla on distal parts of the leg, whereas others were depolarized more by chemical stimulation of more proximal sensilla.

Animals↗