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Biomedical subjects

R Radhakrishnan

Publications and source records attributed to R Radhakrishnan.

At least 19 recordsLinked to original sources
PubMed2006

Joint mobilization reduces hyperalgesia associated with chronic muscle and joint inflammation in rats.

UNLABELLED: Joint mobilization is a common treatment used by healthcare professions for management of a variety of painful conditions, including inflammatory joint and muscle pain. We hypothesized that joint mobilization would reduce the bilateral hyperalgesia induced by muscle and joint inflammation. Mechanical hyperalgesia was measured by examining the mechanical withdrawal threshold of the rat's paw before and after induction of inflammation with 3% carrageenan (gastrocnemius muscle) or 3% kaolin/carrageenan (knee joint), and for 1 hour after knee joint mobilization. The mobilization consisted of rhythmically flexing and extending the knee joint to the end of range of extension while the tibia was simultaneously moved in an anterior to posterior direction. A bilateral decrease in mechanical withdrawal thresholds occurred 1, 2, and 4 weeks after inflammation of the knee joint or muscle. In animals with muscle inflammation, mobilization of the knee joint increased the mechanical withdrawal threshold bilaterally when given 1, 2, or 4 weeks after inflammation. However, in animals with knee joint inflammation, mobilization of the knee joint at 4 weeks increased the mechanical withdrawal threshold but had no effect when administered 1 or 2 weeks after inflammation. Therefore, joint mobilization reduces hyperalgesia induced by chronic inflammation of muscle and joint. PERSPECTIVE: This article shows that unilateral joint mobilization reduces bilateral hyperalgesia induced by chronic muscle or joint inflammation. Understanding the pain conditions in which mobilization produces an analgesic effect should assist the clinician in selecting appropriate treatment techniques. The bilateral effect suggests that central mechanisms could mediate the analgesia.

Animals↗
PubMed2004

Efficient control of the energy exchange due to the Manakov vector-soliton collision.

By examining the concept of energy exchange among the orthogonally polarized components of each of two colliding (Manakov-like) vector solitons it is observed that a maximum or an efficient energy-exchange process is possible only for an appropriate choice of the initial physical parameters (namely, frequency separation, polarizations, time delay, and pulse-width separation between the colliding solitons) for which L(W) (walk-off length) >>L(NL) (nonlinear length). However, in this case only, the amount of energy-exchange can be considerably increased or decreased by appropriately changing the phases of colliding solitons without altering the walk-off length and the initial energy distributions between the soliton components. Moreover we observe that during the collision between two closely placed vector solitons of the practically interesting integrable Manakov model, nonuniform pulse broadening takes place in each of their components. Such an effect has not yet been reported in any (1+1) dimensional integrable soliton systems so far. In addition, the relation between walk-off length, polarization, and pulse width is briefly discussed.

Journal Article↗
PubMed2004

Influence of aqueous extract from Neurada procumbens L. on blood pressure of rats.

Neurada procumbens is a desert plant in the Arabian Peninsula. It has been considered edible by Bedouin and has been used traditionally as a medicinal herb. During a screening test of Arabian plants, the aqueous extract of Neurada procumbens increased the blood pressure of anaesthetized normotensive rats when it was administered orally. Further studies proved it elevated the blood pressure of conscious SHR, and produced vasoconstriction on the aortic strips of rats in vitro, which was reduced partially by phentolamine. This study demonstrates that the aqueous extract of the plant has an effect of increasing blood pressure that might be mediated through alpha-adrenergic receptors. Though more investigations are needed to prove its effect in humans, the present study warns that Neurada procumbens might not be so safe as it has been considered, and people, especially those with cardiovascular diseases, should be careful when they use the plant.

Animals↗
PubMed2003

Spinal muscarinic receptors are activated during low or high frequency TENS-induced antihyperalgesia in rats.

Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacological modality used clinically to relieve pain. Central involvement of serotonin and endogenous opioids are implicated in TENS-induced analgesia. Activation of spinal cholinergic receptors is antinociceptive and these receptors interact with opioid and serotonin receptors. In the current study, the possible involvement of spinal cholinergic receptors in TENS analgesia was investigated in rats. Hyperalgesia was induced by inflaming one knee joint with 3% kaolin-carrageenan and assessed by measuring paw withdrawal latency (PWL) to heat before and 4 h after injection. The non-selective nicotinic antagonist mecamylamine (50 microg), non-selective muscarinic antagonist atropine (30 microg) or one of the muscarinic subtype antagonists: pirenzepine (M1, 10 microg), methoctramine (M2, 10 microg), 4-DAMP (M3, 10 microg), or saline was administered intrathecally just prior to TENS treatment. Low or high frequency TENS was then applied to the inflamed knee and PWL was determined again. Atropine, pirenzepine and 4-DAMP significantly attenuated the antihyperalgesic effects of low and high frequency TENS while mecamylamine and methoctramine had no effects, compared to saline control. The results show that TENS-induced antihyperalgesia is mediated partially by activation of spinal muscarinic receptors but not spinal nicotinic receptors. Further, the results also indicate that spinal M1 and M3 muscarinic receptor subtypes mediate the muscarinic component of TENS antihyperalgesia.

Animals↗
PubMed2003

Joint manipulation reduces hyperalgesia by activation of monoamine receptors but not opioid or GABA receptors in the spinal cord.

Joint manipulation has long been used for pain relief. However, the underlying mechanisms for manipulation-related pain relief remain largely unexplored. The purpose of the current study was to determine which spinal neurotransmitter receptors mediate manipulation-induced antihyperalgesia. Rats were injected with capsaicin (50 microl, 0.2%) into one ankle joint and mechanical withdrawal threshold measured before and after injection. The mechanical withdrawal threshold decreases 2 h after capsaicin injection. Two hours after capsaicin injection, the following drugs were administered intrathecally: bicuculline, blocks gamma-aminobutyric acid (GABAA) receptors; naloxone, blocks opioid receptors; yohimbine blocks, alpha2-adrenergic receptors; and methysergide, blocks 5-HT(1/2) receptors. In addition, NAN-190, ketanserin, and MDL-72222 were administered to selectively block 5-HT1A, 5-HT2A, and 5-HT3 receptors, respectively. Knee joint manipulation was performed 15 min after administration of drug. The knee joint was flexed and extended to end range of extension while the tibia was simultaneously translated in an anterior to posterior direction. The treatment group received three applications of manipulation, each 3 min in duration separated by 1 min of rest. Knee joint manipulation after capsaicin injection into the ankle joint significantly increases the mechanical withdrawal threshold for 45 min after treatment. Spinal blockade of 5-HT(1/2) receptors with methysergide prevented, while blockade of alpha2-adrenergic receptors attenuated, the manipulation-induced antihyperalgesia. NAN-190 also blocked manipulation-induced antihyperalgesia suggesting that effects of methysergide are mediated by 5-HT1A receptor blockade. However, spinal blockade of opioid or GABAA receptors had no effect on manipulation induced-antihyperalgesia. Thus, the antihyperalgesia produced by joint manipulation appears to involve descending inhibitory mechanisms that utilize serotonin and noradrenaline.

Adrenergic alpha-Antagonists↗
PubMed2001

Anti-inflammatory and anti-ulcer activity of Calligonum comosum in rats.

The 10% ethanol extract of the aerial parts of Calligonum comosum (50--400 mg/kg, i.p.) significantly reduced the increase in hind paw oedema induced by carrageenan in rats. Following sub-acute oral administration of the extract (50 and 100 mg/kg, daily for 14 days), a significant anti-inflammatory activity in the cotton pellet model was observed. Pre-treatment with the extract (100, 200 and 400 mg/kg) produced a significant and dose-dependent inhibition to the acute gastric ulcers induced by phenylbutazone, indomethacin, 0.2 N NaOH and 80% ethanol.

Animals↗
PubMed2001

Anti-nociceptive and anti-inflammatory properties of Caralluma arabica.

In the present study, a 10% ethanolic extract of Caralluma arabica at the doses of 200 and 400 mg/kg was evaluated for the antinociceptive activity using the hot plate and acetic acid induced abdominal constrictions in mice and tail flick method in rats. Oral and topical application of C. arabica extract was assessed in the present study for anti-inflammatory properties using carrageenan-induced rat paw oedema. Anti-inflammatory activity was also evaluated using cotton pellet granuloma method. C. arabica extract showed significant Anti-nociceptive properties in all the models studied. C. arabica extract significantly reduced the increase in hind paw volume induced by carrageenan injection when used orally or topically. Results of the present study confirm the use of C. arabica traditionally for the treatment of painful and inflammatory conditions and indicate transdermal absorption of the plant extract.

Administration, Oral↗
PubMed2001

Neuropharmacological actions of Portulaca oleraceae L v. sativa (Hawk).

Portulaca oleracea L v. sativa (family: Portulacaceae) is a warm-climate annual, cultivated in the Arabian peninsula and used traditionally for alleviating pain and swelling. It was observed that a 10% ethanolic extract of this plant produced restriction of movement in animals during the routine screening studies. Therefore the effects of the extract on the locomotor activity, threshold to noxious stimulus, anti-convulsant activity and relaxant effects on the skeletal muscle were studied. The extract, on intraperitoneal administration, showed a significant reduction in the locomotor activity in mice, anti-nociceptive activity in rats using Tail Flick Method, an increase in the onset time of pentylenetetrazole-induced convulsions in mice and muscle relaxant activity in in vitro (rat hemidiaphragm) and in vivo (grip strength) experiments. The anti-nociceptive activity of the extract in rats was attenuated by naloxone pre-treatment indicating the involvement of opioid receptors in its anti-nociceptive effects. It is indicated from the results of the present study that P. oleracea v. sativa possesses varied effects on both the central and peripheral nervous system and the plant should be exhaustively studied for other neuropharmacological effects.

Analgesics↗
PubMed2000

The analgesic and anti-inflammatory effects of Portulaca oleracea L. subsp. Sativa (Haw.) Celak.

Many ethnic groups have used different species of Portulaca oleracea L., a member of the Family Portulacaceae, as vegetable and also herbal medicine against several diseases for many centuries. A review of the records in both folkloric and scientific literature indicates that Portulaca has many medicinal uses. After our previous preliminary screening of three species of the family for analgesic and anti-inflammatory properties, Portulaca oleracea L. subsp. sativa (Haw.) Celak. (a cultivar) was chosen for further work due to its abundant availability from reliable sources. The 10% ethanolic extract of the aerial parts (dried leaves and stem) showed significant anti-inflammatory and analgesic after intraperitoneal and topical but not oral administration when compared with the synthetic drug, diclofenac sodium as the active control. Results indicate this cultivar species of Portulaca also possesses some of the claimed traditional uses of the wild species in the relief of pain and inflammation.

Analgesics↗
PubMed1999

Crystal structure of ovine interferon-tau at 2.1 A resolution.

Ovine interferon-tau (ovIFN-tau) is a pregnancy recognition hormone required for normal embryonic development in sheep. In addition to its novel role in reproductive physiology, ovIFN-tau displays antiviral and antiproliferative activities similar to the IFN-alpha subtypes. To probe the structural basis for its unique activity profile, the crystal structure of ovIFN-tau has been determined at 2.1 A resolution. The fold of ovIFN-tau is similar to the previously determined crystal structures of human IFN-alpha2b and human and murine IFN-beta, which each contain five alpha-helices. Comparison of ovIFN-tau with huIFN-alpha2b, huIFN-beta, and muIFN-beta reveals unexpected structural differences that occur in regions of considerable sequence identity. Specifically, main-chain differences up to 11 A occur for residues in helix A, the AB loop, helix B, and the BC loop. Furthermore, these regions are known to be important for receptor binding and biological activity. Of particular interest, a buried ion pair is observed in ovIFN-tau between Glu71 and Arg145 which displaces a conserved tryptophan residue (Trp77) from the helical bundle core. This ion pair represents a major change in the core of ovIFN-tau compared to huIFN-alpha2b. Based on amino acid sequence comparisons, these ovIFN-tau structural features may be conserved in several human IFN-alpha subtypes and IFN-omega. The structure identifies potential problems in interpreting site-directed mutagenesis data on the human IFN-alpha family that consists of 12 proteins.

Amino Acid Sequence↗
PubMed1999

Cholangiopathy associated with portal hypertension: diagnostic evaluation and clinical implications.

BACKGROUND: There are few studies of biliary changes due to portal hypertension. We ascertained the incidence of such changes on endoscopic retrograde cholangiography and determined the reliability of biochemistry, ultrasonography (US) and hepatobiliary radionuclide scan in detecting this type of cholangiopathy. METHODS: Forty-two patients with portal hypertension were studied. RESULTS: Cholangiopathy was detected by cholangiography in 17 of 20 patients with extrahepatic portal venous obstruction. Abnormalities (mainly strictures and caliber irregularity) were seen in the common bile duct (5) and common hepatic duct (7) and in the right (8) and left (11) hepatic ducts (mainly dilatation). One of 11 patients with noncirrhotic portal fibrosis had a dilated right hepatic duct. Three of 11 patients with cirrhosis had pruned intrahepatic ducts. Eight patients with portal venous obstruction had elevated alkaline phosphatase levels; two had elevated bilirubin levels. US detected gallbladder varices (11) and choledochal varices (9) in patients with extrahepatic portal venous obstruction. Biliary abnormalities were detected on hepatobiliary scintigraphy in 16 of 17 patients. CONCLUSIONS: Cholangiopathy associated with portal hypertension occurs exclusively in patients with extrahepatic portal venous obstruction. It rarely leads to functional obstruction; jaundice does not occur in the absence of functional blockage. Elevated alkaline phosphatase level (after excluding bile duct calculi), presence of gallbladder varices on US, and abnormal radionuclide scans are reliable in detecting these lesions.

Adult↗
PubMed1999

Suppression and enhancement of soliton switching during interaction in periodically twisted birefringent fibers.

Soliton interaction in periodically twisted birefringent optical fibers has been analyzed analytically with reference to soliton switching. For this purpose we construct the exact general two-soliton solution of the associated coupled system and investigate its asymptotic behavior. Using the results of our analytical approach we point out that the interaction can be used as a switch to suppress or to enhance soliton switching dynamics, if one injects a multisoliton as an input pulse in the periodically twisted birefringent fiber.

Journal Article↗
PubMed1999

Coupled nonlinear Schrödinger equations with cubic-quintic nonlinearity: Integrability and soliton interaction in non-Kerr media.

We propose an integrable system of coupled nonlinear Schrödinger equations with cubic-quintic terms describing the effects of quintic nonlinearity on the ultrashort optical soliton pulse propagation in non-Kerr media. Lax pairs, conserved quantities and exact soliton solutions for the proposed integrable model are given. The explicit form of two solitons are used to study soliton interaction showing many intriguing features including inelastic (shape changing or intensity redistribution) scattering. Another system of coupled equations with fifth-degree nonlinearity is derived, which represents vector generalization of the known chiral-soliton bearing system.

Journal Article↗
PubMed1998

Purification, characterization, and kinetic mechanism of cyclin D1. CDK4, a major target for cell cycle regulation.

The cyclin D1.CDK4-pRb (retinoblastoma protein) pathway plays a central role in the cell cycle, and its deregulation is correlated with many types of cancers. As a major drug target, we purified dimeric cyclin D1.CDK4 complex to near-homogeneity by a four-step procedure from a recombinant baculovirus-infected insect culture. We optimized the kinase activity and stability and developed a reproducible assay. We examined several catalytic and kinetic properties of the complex and, via steady-state kinetics, derived a kinetic mechanism with a peptide (RbING) and subsequently investigated the mechanistic implications with a physiologically relevant protein (Rb21) as the phosphoacceptor. The complex bound ATP 130-fold tighter when Rb21 instead of RbING was used as the phosphoacceptor. By using staurosporine and ADP as inhibitors, the kinetic mechanism of the complex appeared to be a "single displacement or Bi-Bi" with Mg2+.ATP as the leading substrate and phosphorylated RbING as the last product released. In addition, we purified a cyclin D1-CDK4 fusion protein to homogeneity by a three-step protocol from another recombinant baculovirus culture and observed similar kinetic properties and mechanisms as those from the complex. We attempted to model staurosporine in the ATP-binding site of CDK4 according to our kinetic data. Our biochemical and modeling data provide validation of both the complex and fusion protein as highly active kinases and their usefulness in antiproliferative inhibitor discovery.

Adenosine Triphosphate↗
PubMed1998

Lipitoids--novel cationic lipids for cellular delivery of plasmid DNA in vitro.

BACKGROUND: Although synthetic nonviral vectors hold promise for the delivery of plasmid DNA, their gene-transfer efficiencies are far from matching those of viruses. To systematically investigate the structure-activity relationship of cationic lipids, a small library of cationic lipid-peptoid conjugates (lipitoids) was synthesized. The compounds were evaluated for their ability to form complexes with plasmid DNA and to mediate DNA transfer in vitro. RESULTS: Lipid-peptoid conjugates were conveniently prepared in high yield using solid-phase synthesis. Several lipitoids condensed plasmid DNA into 100 nm spherical particles and protected the DNA and DNase digestion. A subset of lipitoids with a repeated (aminoethyl, neutral, neutral) sidechain trimer motif conjugated with dimyristoyl phosphatidyl-ethanolamine (DMPE) mediated DNA transfer with high efficiency. CONCLUSIONS: Automated solid-phase synthesis of cationic lipids allowed the rapid synthesis of a diverse set of transfection reagents. The most active compound DMPE-(Nae-Nmpe-Nmpe)3 (Nae, N-aminoethyl glycine; Nmpe, N-p-methoxyphenethyl-glycine) is more efficient than lipofectin or DMRIE-C (two commercial cationic lipid transfection reagents) and is active in the presence and absence of serum. The activity in the presence of serum suggests potential for applications in vivo.

3T3 Cells↗
PubMed1997

Reduction of serum cholesterol in postmenopausal women with previous myocardial infarction and cholesterol malabsorption induced by dietary sitostanol ester margarine: women and dietary sitostanol.

BACKGROUND: Reduction of serum cholesterol decreases mortality in primary and especially in secondary prevention. We investigated how effectively postmenopausal women with a previous myocardial infarction reduced their serum cholesterol with dietary means by using sitostanol ester rapeseed oil margarine, alone and in combination with statins, and to what extent cholesterol metabolism was affected. METHODS AND RESULTS: The first study group consisted of 22 randomly chosen women with angiographically documented coronary artery disease. Baseline studies on home diet were followed by double-blind, randomized, cross-over studies on margarine without and with sitostanol (3 g/d) ester for 7 weeks in random order. A second group of 10 women on simvastatin consumed sitostanol ester margarine for 12 weeks. Sitostanol ester margarine lowered serum total cholesterol by 13% (P<.05) and LDL cholesterol by 20% (P<.01). Sitostanol ester margarine reduced total cholesterol in all patients, LDL cholesterol <2.6 mmol/L (<100 mg/dL) in 32%, and <3.4 mmol/L (<133 mg/dL) in 73% versus none and 27% during the home diet (P<.01 for both). Combined with simvastatin, sitostanol still reduced total and LDL cholesterol by 11+/-3% and 16+/-5% (P<.01 for both). Sitostanol reduced absorption (-45%), increased fecal elimination (+45% as neutral sterols), and stimulated synthesis (+39%) of cholesterol. High cholestanol and plant sterol (high cholesterol absorption) and low baseline precursor sterol proportions (low cholesterol synthesis) predicted high decreases in serum cholesterol. CONCLUSIONS: Dietary use of sitostanol ester margarine normalizes LDL cholesterol in about one third of women with previous myocardial infarction, especially in those with high baseline absorption and low synthesis of cholesterol, and in combination with statins reduces the needed drug dose.

Absorption↗