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Biomedical subjects

P K Rangachari

Publications and source records attributed to P K Rangachari.

At least 19 recordsLinked to original sources
PubMed2006

Low doses of ionizing radiation can prevent radiation-induced colonic epithelial hyporesponsiveness to muscarinic agonists.

PURPOSE: Colonic epithelium hyporesponsiveness to different secretagogues occurs after exposure to ionizing radiation, increasing susceptibility to bacterial translocation and intraluminal toxins. Growing evidence suggests that the biological effects of radiation might be hormetic in nature. We investigated if exposure to low doses of ionizing radiation (LDR) can prevent colon hyposecretion due to subsequent larger doses. METHODS: Rats were exposed to LDR (0.05 Gy) 24 h prior to 6 Gy, high dose radiation (HDR). The cyclic adenosine monophosphate (cAMP)-mediated pathway was explored using forskolin (FSK) and the intracellular Ca2+-mediated pathway through cholinergic stimulation. Changes in the colonic epithelium at the ultrastructural level were also explored. RESULTS: Maximal short circuit current (Isc) response to carbachol was significantly reduced in the group exposed to 6 Gy HDR and this was completely prevented by prior exposure to LDR. Responses to both FSK and electrical field stimulation (EFS) were significantly reduced after HDR but they were not prevented by prior adaption of LDR. Hyposecretion was not prevented by the inducible nitric oxide synthase (iNOS) inhibitor L-N6-(l-iminoethyl)lysine (L-NIL) ruling out a role for iNOS-derived nitric oxide (NO) in the colonic hyposecretion associated with whole body radiation. Prior exposure to LDR diminished the deleterious effect of full HDR on the ultrastructure of colonic epithelium as colonocytes vacuolization, microvilli lost and separation between neighboring cells were less evident. CONCLUSIONS: Previous exposure to LDR can prevent intracellular Ca2+-mediated colonic hyposecretion associated with exposure to HDR but fails to modify cAMP-mediated hyposecretion. Morphological damage at the ultrastructural level is less evident after prior LDR.

Animals↗
PubMed2006

Promoting self-directed learning using a menu of assessment options: the investment model.

Undergraduate science students took an Inquiry course in their second (sophomore) year. The course was designed to explore the social life of scientific knowledge. They were given a set of eight assessment options: personal logs, targeted oral examinations, commentaries, mini-lectures, individual explorations, research proposals, book reviews, and problem-solving exercises. Each option had a specific maximum mark (percentage or grade point) associated with it. Students were permitted to select any set of options to obtain their total grade for the course. From the student's perspective, the course provided a valuable learning experience and enabled them to recognize the complexities involved in the process of generating scientific information and making it useful and relevant to the public. The opportunity given to select their own assessment options enhanced their learning. For me, as the sole instructor managing 51 students, the experience was rewarding.

Educational Measurement↗
PubMed2004

Phenotypic differences in cholinergic responses of distal colonic epithelium.

The Flinders sensitive line (FSL) rats exhibit an increased cholinergic responsiveness in vivo when compared to their counterparts, the Flinders resistant line (FRL) rats. The functional consequences of this phenotypic difference on colonic mucosal function are not known. We sought to determine whether isolated distal colonic mucosa from the two strains exhibit differential responses to cholinergic agonists. The responses of the distal colonic mucosa from two lines of rats to carbachol were compared by recording changes in short-circuit current. The ion movements associated with these changes were assessed by flux analysis of the radiotracers, 22Na and 36Cl. The anticipated hyper-responsiveness to cholinergic stimulation in FSL rats was not seen. Carbachol responses were significantly enhanced by indomethacin pretreatment only in FRL rats. Tetrodotoxin (TTX) pretreatment significantly reduced responses to carbachol in FSL rats at all concentrations tested, though this was only seen with lower concentrations in FRL rats. Flux analysis indicated that both lines absorbed Na+ and Cl- under basal conditions and that a significant residual flux was present. Stimulation with carbachol led to significant reductions in net Na+ and Cl- fluxes in both lines. The changes in net Na+ and Cl- flux in both lines stem largely from a decrease in mucosal to serosal fluxes of both ions with an increase in serosal to mucosal flux of Cl-. The striking difference is the significant reduction in residual flux seen only in FRL rats. Indomethacin pretreatment abolished the changes in residual flux seen in FRL rats. Thus the responses to carbachol in these rats had at least three components: (a) a direct effect on the transporting colonocyte, (b) an indirect effect mediated by an arachidonic acid metabolite, and (c) another indirect effect involving a neurotransmitter. The relative contributions of each of these components were different in the two lines.

Animals↗
PubMed2004

Exploring the context of drug use: a problem-based learning course in pharmacoepidemiology for undergraduate science students.

The teaching of pharmacoepidemiology has been largely confined to health care professionals and graduate students. This paper reports an attempt to use problem-based learning (PBL) to teach the elements of that discipline to undergraduate science students. Carefully sequenced problems led students to consider the following issues: the terms used in epidemiology, merits and demerits of different epidemiological study designs, pharmacovigilance, the nature of evidence in law and science, economic evaluation of drugs and the use of drugs in different cultures. The 12-week course was taken by students in their final term prior to graduation. Multiple evaluation procedures were used: specific forms for assessing tutorial participation, individual explorations assessed usually by written essays and problem-solving exercises. The course has received high ratings from the students. The observations over a 10-year period suggest that PBL is a feasible approach to teach the social dimensions of drug use.

Biology↗
PubMed2004

Ascaridole-less infusions of Chenopodium ambrosioides contain a nematocide(s) that is(are) not toxic to mammalian smooth muscle.

Infusions of Chenopodium ambrosioides (L.) have been used for centuries in the Americas as a popular remedy against intestinal worm infections. The essential oil of Chenopodium ambrosioides contains high levels of ascaridole, which is a potent anthelmintic, but which has also been responsible for human fatalities, leading to its disuse. Almost 90% of the nematocidal activity of Chenopodium ambrosioides infusions was due to a hydrophilic component different from ascaridole. Synthetic ascaridole and the ascaridole from infusions, extracted into hexane, caused a reduction of carbachol-induced contractions in rat gastrointestinal smooth muscle at concentrations required to kill Caenorhabditis elegans (L.). The herbal infusion and the ascaridole-free hexane-extracted aqueous residue of the above infusion, at nematocidal concentrations, had no detectable effect on smooth muscle contraction in the above system. It would appear that the traditional form of usage of Chenopodium ambrosioides infusions as a vermifuge is safer than the use of the herb's essential oil.

Animals↗
PubMed2004

The targeted oral.

An oral examination for assessing senior undergraduate students is described. The examinations were conducted in a room with a one-way mirror so that all students could learn from each other. This procedure was much appreciated by the participants.

Biomedical Research↗
PubMed2003

Isoprostanes: more than just mere markers.

Isoprostanes are members of a family of prostaglandin isomers that are produced by free radical-catalysed mechanisms. They have become well-recognized indicators of oxidant-induced cell damage in a variety of pathophysiological conditions. Several isoprostanes have been shown to possess biological activity in whole-animal, isolated tissue and cell-based systems. Their actions include vasoconstriction, platelet aggregation and cardiac hypertrophy. Current evidence suggests that these effects are mediated by prostanoid receptors through a complex set of interactions that involve agonism, partial agonism, desensitization and co-operative behaviors. It is likely that other mechanisms of action are waiting to be discovered. Based on a consideration of these biological effects, we argue that isoprostanes are more than mere markers and may serve as active participants in promoting and exaggerating pathophysiological changes. To tease out their roles requires considerable more work and a willingness to suspend disbelief based on limited evidence.

Animals↗
PubMed2002

Student-designed clinical trials: evaluating self-directed learning in pharmacology.

An evaluation exercise was developed for a third-year undergraduate problem-based course in pharmacology for science students. They were asked to design a clinical trial to evaluate a novel drug for an existing condition or an established drug for a novel condition. The exercise was assessed on both required elements (provision of a clear rationale, clear definition of outcome measures, patient inclusion/exclusion criteria, statistical analysis and critical assessment of available information) as well as on aesthetic elements (imagination, flair and readability). To promote self-directed learning, students were given minimal instructions and received no formal lectures on the subject of clinical trials. The exercise has been rated very highly by the students.

Clinical Trials as Topic↗
PubMed2002

Calcium-stimulated short-circuit currents in the canine proximal colonic epithelium: effects of DK-PGD2, a metabolite of prostaglandin D2.

Prostaglandin D2 (PGD2) has marked inhibitory effects on the canine proximal colonic epithelium set up in Ussing chambers. These effects involved a receptor that is pharmacologically distinct from the classical DP, presumably the recently identified CRTH2/DP2 variety. The mechanism underlying these effects was studied using 13,14-dihydro-15-keto-PGD2 (DK-PGD2), a stable metabolite of the parent prostanoid. The metabolite quickly reversed short circuit currents (I(sc)) stimulated by diverse agonists. Greater inhibitory effects were seen with stimulants such as carbachol and cyclopiazonic acid (CPA) rather than with forskolin or protein kinase A activators. Since the same stimulants were differentially affected by removal and replacement of serosal Ca2+, we tested the possibility that the prostanoid inhibited basolateral Ca2+ entry. In the absence of serosal Ca2+, tissues primed with CPA demonstrated concentration-dependent increases in I(sc), to cumulative additions of Ca2+ or Sr2+, though the former was more potent. Cl- removal and pretreatment with bumetanide virtually abolished responses, suggesting that the increase in I(sc) reflected Ca2+ dependent Cl- secretion. Though responses were insensitive to the L-type channel antagonist, verapamil, a marked inhibition was seen in the presence of metal cations (Gd3+, Cd2+, and La3+). Pretreatment with DK-PGD2 inhibited responses to Ca2+ in CPA-primed tissues. Thus, basolateral Ca2+ entry via store-operated Ca2+ channels may be the locus for the inhibitory effects of PGD2 in this tissue. These results could indicate a potential transduction mechanism for the novel DP receptor variously called CRTH2 or DP2.

Animals↗
PubMed2001

Effects of isoprostanes and prostanoids on porcine small intestine.

The isoprostanes are prostaglandin (PG)-like compounds formed in vivo by free-radical-catalyzed peroxidation of polyunsaturated fatty acids and are synthesized independent of cyclooxygenase. It has been debated whether the biological effects of the isoprostanes are exerted on prostanoid receptors [thromboxane A2 (TP) receptors and prostanoid E (EP) receptors] or on a "unique" isoprostane receptor. We sought to define the receptors involved in the actions of isoprostanes on the porcine small intestine. Stripped intestinal sheets were mounted in Ussing chambers, and bioelectrical parameters were recorded. Serosal application of 8-iso-PGE2 (pEC(50) = 5.71), PGE2 (pEC(50) = 6.45 and pEC(50) = 5.04), and PGF2alpha (pEC(50) = 5.07) elicited concentration-dependent increases in the short-circuit current (I(SC)). No responses were seen with 8-iso-PGF2alpha. The TP receptor agonist U46619 induced transient increase in I(SC), and the tissue responded to a further challenge to PGE2. Pretreatment with U46619 did not alter responses to a subsequent addition of either PGE2 or 8-iso-PGE2. The TP receptor antagonist SQ29,548 significantly reduced responses to the TP agonist, U46619, but did not antagonize responses to 8-iso-PGE2. Homologous and heterologous desensitization between 8-iso-PGE2, PGE2, and PGF2alpha suggested the involvement of prostanoid EP and prostanoid F (FP) receptors in the response elicited to 8-iso-PGE2. The effects of 8-iso-PGE2 were not inhibited by tetrodotoxin. Pretreatment of the tissues with bumetanide significantly reduced the increase in I(SC). The results indicate that 8-iso-PGE2 induces a Cl- secretion, and the effects involve prostanoid EP and FP receptors but not TP receptors in the porcine small intestine.

Algorithms↗
PubMed2000

Exploring the context of biomedical research through a problem-based course for undergraduate students.

Students in an interdisciplinary program explored the manufacture of biomedical knowledge in a problem-based course. Because the class size was two to three times larger than the normal tutorial group, suitable modifications were made (formation of floating groups around defined learning tasks, formal presentations, written reports, and evaluations by students and tutor). A variety of problems and/or cases drawn from research papers, newspapers, biographies, or web pages permitted students to appreciate the complex interactions between ideals, individuals, institutions, and investments that comprise modern biomedical research.

Curriculum↗
PubMed1999

Probing the "active site" of diamine oxidase: structure-activity relations for histamine potentiation by O-alkylhydroxylamines on colonic epithelium.

The responses of the canine colonic epithelium to histamine are potentiated by O-alkylhydroxylamines. A study of a series of such compounds suggested that active compounds had the structure R-O-NH2, substitution of a nitrogen led to total loss of activity. The locus of the potentiation effect was traced to the inhibition of diamine oxidase. A new series of aliphatic and aromatic O-alkylhydroxylamines were synthesized to explore further the structure-activity relations of this effect. The potentiating effects of these compounds were determined by examining the changes in short circuit current (Isc) produced by histamine and from the activity of a soluble preparation of diamine oxidase. We found that 1) branched compounds are less active than their straight chain counterparts, 2) greater steric bulk of the aliphatic substituent decreased activity, 3) the presence of a double bond had no significant effect though a triple bond reduced activity, 4) longer straight chain compounds were less active than the shorter chain derivatives and 5) all benzylic compounds were less active than the straight chain aliphatics. O-1-benzyl was inactive however the meta or para oxygen substituted compounds as well as the O-(1-E-Cinnamyl) derivative were active. A current model for the action of diamine oxidase proposes a crucial role for a trihydroxyphenylalanine quinone cofactor as part of the active site together with a copper atom. Using molecular modeling based on our inhibition data we are able to define the region of space that is just beyond the reactive carbonyl of the trihydroxyphenylalanine residue at the active site of diamine oxidase. We suggest that a negatively charged species, such as an aspartate or a glutamate, resides in a trough about 7 to 8 A from the trihydroxyphenylalanine carbonyl carbon and this species aids in the strong selective binding of substrates such as putrescine and histamine.

Amine Oxidase (Copper-Containing)↗
PubMed1997

Intestinal effects of isoprostanes: evidence for the involvement of prostanoid EP and TP receptors.

The isoprostanes, which differ from prostaglandins by the cis orientation of their side chains, are believed to exert their biological effects on either a prostanoid TP receptor or a "unique" isoprostane receptor. Preliminary experiments suggested that canine colonic epithelium possessed no prostanoid TP receptor activity, in contrast to the muscularis mucosae, which responds well to the selective prostanoid TP receptor agonist U46619. To define the receptors involved, the in vitro responses of the epithelium and muscularis mucosae from the canine proximal colon to both 8-iso-PGE2 and 8-iso-PGF2alpha were compared. The epithelium responded to 8-iso-PGE2 but not to 8-iso-PGF2alpha. Under basal conditions, 8-iso-PGE2 produced concentration-dependent increases in short circuit current (pEC50 = 6.4 +/- 0.1) that were not antagonized by the selective prostanoid TP receptor antagonist SQ29548 (10(-6) M). Cross-desensitization experiments suggested that the stimulant effects involved a prostanoid EP receptor. Desensitization of the epithelium to PGE2 resulted in unexpected decreases in short circuit current in response to 8-iso-PGE2 (10(-6) M). This effect was mimicked by the selective prostanoid TP receptor agonist U46619 (10(-5) M), and antagonized by three structurally different prostanoid TP receptor antagonists: L670596 (10(-6) M), SQ29548 (10(-6) M) and GR32191 (10(-6) M). 8-Iso-PGE2, 8-iso-PGF2alpha and U46619 caused concentration-dependent increases in the force of contraction of the muscularis mucosae strips. These responses were antagonized by selective prostanoid TP receptor antagonists, arguing for the involvement of prostanoid TP receptors. Thus, the effects of isoprostanes on the canine colon involve both prostanoid TP and EP receptors.

Animals↗
PubMed1995

A checklist to help students analyze published articles in basic medical sciences.

Because critical analysis of published information is an essential component of scientific life, it is important that students be trained in its practice. Undergraduate students who are more accustomed to reading textbooks and taking lecture notes find it difficult to appreciate primary publications. To help such students, we have developed a checklist that helps them analyze different components of a research article in basic biomedical sciences. Students used the checklist to analyze critically a published article. The students were assigned an article and asked to write a paper (maximum 2 pages of single-spaced type) assessing it. This assignment has been found useful to both undergraduate and graduate students in pharmacology and physiology. Student responses to a questionnaire were highly favorable; students thought the exercise provided them with some of the essential skills for life-long learning.

Education, Medical, Undergraduate↗
PubMed1995

Active learning: in context.

Active learning has become trendy, particularly in health care education. It has been noted that active learning is an attitude, not a method. Promotion of active learning requires willing students, sympathetic teachers, and an institution willing to promote interactions between them. The essence is to shift the locus of control from the teacher to the student. This essay draws attention to books and articles discussing such issues.

Humans↗