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S Suresh

Publications and source records attributed to S Suresh.

At least 55 records · Page 3Linked to original sources
PubMed1999

Solubility behaviour of haloperidol in individual solvents determination of partial solubility parameters.

The solubility behaviour of haloperidol in individual solvents ranging from non-polar to highly polar solvents was studied. Extended Hansen's method was used to analyze the solubility data and obtain partial solubility parameters of haloperidol. Flory-Huggin's size connection term 'B' was found to further improve the prediction of solubility. A four parameter extended Hansen's approach involving proton-donor and proton-acceptor parameters was also used in fitting the solubility data to a theoretical model. The term Wh, used as an empirical measure of solute-solvent interaction due to hydrogen bonding was used in calculating B. Different approaches were thus used in fitting the experimental solubility data to obtain regression equations which aim to provide a reasonable prediction of solubility of haloperidol in untested solvents. Solubility parameter was calculated from the partial solubility parameter values obtained from the different methods of data analysis, and compared with the theoretically obtained values. Solubility parameter of haloperidol is fixed at 10.58 H.

Haloperidol↗
PubMed1999

Subtype-selective expression of the five somatostatin receptors (hSSTR1-5) in human pancreatic islet cells: a quantitative double-label immunohistochemical analysis.

We have developed a panel of rabbit polyclonal antipeptide antibodies against the five human somatostatin receptor subtypes (hSSTR1-5) and used them to analyze the pattern of expression of hSSTR1-5 in normal human islet cells by quantitative double-label confocal fluorescence immunocytochemistry. All five hSSTR subtypes were variably expressed in islets. The number of SSTR immunopositive cells showed a rank order of SSTR1 > SSTR5 > SSTR2 > SSTR3 > SSTR4. SSTR1 was strongly colocalized with insulin in all beta-cells. SSTR5 was also an abundant isotype, being colocalized in 87% of beta-cells. SSTR2 was found in 46% of beta-cells, whereas SSTR3 and SSTR4 were relatively poorly expressed. SSTR2 was strongly colocalized with glucagon in 89% of alpha-cells, whereas SSTR5 and SSTR1 colocalized with glucagon in 35 and 26% of alpha-cells, respectively. SSTR3 was detected in occasional alpha-cells, and SSTR4 was absent. SSTR5 was preferentially expressed in 75% of SST-positive cells and was the principal delta-cell SSTR subtype, whereas SSTR1-3 were colocalized in only a few delta-cells, and SSTR4 was absent. These studies reveal predominant expression of SSTR1, SSTR2, and SSTR5 in human islets. Beta-cells, alpha-cells, and delta-cells each express multiple SSTR isoforms, beta-cells being rich in SSTR1 and SSTR5, alpha-cells in SSTR2, and delta-cells in SSTR5. Although there is no absolute specificity of any SSTR for an islet cell type, SSTR1 is beta-cell selective, and SSTR2 is alpha-cell selective. SSTR5 is well expressed in beta-cells and delta-cells and moderately well expressed in alpha-cells, and thereby it lacks the islet cell selectivity displayed by SSTR1 and SSTR2. Subtype-selective SSTR expression in islet cells could be the basis for preferential insulin suppression by SSTR1-specific ligands and of glucagon inhibition by SSTR2-selective compounds.

Animals↗
PubMed1998

Opioid tolerance in neonates: mechanisms, diagnosis, assessment, and management.

Opioid tolerance and withdrawal have been challenges for decades. The neurochemical mechanisms of tolerance and dependence are clinically important only because they can affect weaning schedules and the adjustment of doses for neonates. Analgesic effects are characterized by an increased depolarization threshold for the neuron, shorter duration of the action potential generated, and reduced release of neurotransmitters. Tolerance and withdrawal are associated with the reversal of these cellular effects. Adverse clinical effects associated with the use of opioids in neonates include respiratory depression, chest wall rigidity, urinary retention, and decreased gastrointestinal motility. The physiological systems most prominently affected by opioid withdrawal include the central nervous system, gastrointestinal system, and the autonomic nervous system. Opioid withdrawal symptoms in neonates can be assessed by using easily available scoring systems, although these need to be validated for different populations. Management of opioid withdrawal includes the use of other opioids, benzodiazepines and alpha-2 adrenergic receptor antagonist, clonidine. Careful titration of opioids with attention given to appropriate weaning schedules can reduce the incidence of withdrawal in neonates.

Drug Tolerance↗
PubMed1998

Cellular cholesterol storage in the Niemann-Pick disease type C mouse is associated with increased expression and defective processing of apolipoprotein D.

Apolipoprotein D (apoD), a member of the lipocalin superfamily of ligand transporters, has been implicated in the transport of several small hydrophobic molecules including sterols and steroid hormones. We have previously established that apoD is a secreted protein from cultured mouse astrocytes and that treatment with the oxysterol 25-hydroxycholesterol markedly stimulates apoD release. Here, we have investigated expression and cellular processing of apoD in the Niemann-Pick type C (NPC) mouse, an animal model of human NPC, which is a genetic disorder affecting cellular cholesterol transport. NPC is phenotypically characterized by symptoms of chronic progressive neurodegeneration. ApoD gene expression was up-regulated in cultured NPC astrocytes and in NPC brain. ApoD protein levels were also increased in NPC brain with up to 30-fold higher apoD content in the NPC cerebellum compared with control mice. Subcellular fractionation of NPC brain homogenates revealed that most of the apoD was associated with the myelin fraction. ApoD was found to be a secreted protein from cultured normal astrocytes and treatment with the oxysterol, 25-hydroxycholesterol, markedly stimulated apoD release (by five- to 10-fold). By contrast, secretion of apoD from NPC astrocytes was markedly reduced and could not be stimulated by oxysterol treatment. Secretion of apoE, another apolipoprotein normally produced by astrocytes, was similar in NPC and control cells. Furthermore, apoE secretion was not potentiated by oxysterol treatment in either cell type. Plasma levels of apoD were sixfold higher in NPC, whereas hepatic levels were substantially reduced compared with controls, possibly reflecting reduced hepatic clearance of the circulating protein. These results reveal hitherto unrecognized defects in apoD metabolism in NPC that appear to be linked to the known defects in cholesterol homeostasis in this disorder.

Animals↗
PubMed1998

Ultrasonic characterisation of malignant melanoma of choroid.

An in-vitro study of wave spectral analysis in 8 enucleated eyes was conducted in order to differentiate histological subtypes of malignant melanoma. To obtain the backscattering coefficient for the tissues, we used a broadband focussed transducer with a frequency range of 7-12 MHz and a centre frequency of 10 MHz. Experimental measurement of backscattering coefficient and attenuation coefficient at various frequencies was done by substitution techniques. The backscattering coefficient, scatterer size, and root mean square velocity fluctuation were derived by the numerical method, while the attenuation coefficient at 1 MHz was derived from attenuation coefficient at different frequencies. This study revealed that backscattering coefficient and attenuation coefficient, over a frequency range of 7-12 MHz, show an increase in the spindle cell type compared to the mixed cell type of malignant melanoma. Particularly, the scatterer size was significantly higher in the spindle cell group (p = 0.013) in contrast to the mixed cell type. Spindle cells have uniform and compact histological pattern which contributes to an increase in scatterer size and root mean square velocity fluctuation. The ultrasonically obtained parameters have been shown to have a good correlation with the histology of malignant melanoma.

Choroid Neoplasms↗
PubMed1997

Homology between jacalin and artocarpin from jackfruit (Artocarpus integrifolia) seeds. Partial sequence and preliminary crystallographic studies of artocarpin.

Jacalin and artocarpin, the two lectins from jackfruit (Artocarpus integrifolia) seeds, have different physicochemical properties and carbohydrate-binding specificities. However, comparison of the partial amino-acid sequence of artocarpin with the known sequence of jacalin indicates close to 50% sequence identity. Artocarpin crystallizes in two forms, both monoclinic P2(1), with one and two tetramic molecules, respectively, in the asymmetric units of form I (a = 69.9, b = 73.7, c = 60.6 A and beta = 95.1 degrees ) and form II (a = 87.6, b = 72.2, c = 92.6 A and beta = 101.1 degrees ). Both the crystal structures have been solved by the molecular replacement method using the known structure of jacalin as the search model and one of them partially refined, confirming that the two lectins are indeed homologous.

Journal Article↗
PubMed1997

Differential expression of apolipoprotein D and apolipoprotein E in the kainic acid-lesioned rat hippocampus.

Expression of apolipoprotein D, a member of the lipocalin superfamily of transporter proteins, was investigated in the kainic acid-lesioned rat hippocampus. Using an anti-rat apolipoprotein D antibody and biotin avidin-enhanced immunocytochemistry, in the normal rat hippocampus there was little apolipoprotein D expression, that was restricted mainly to scattered astrocytes. By contrast, kainic acid-injected rats showed apolipoprotein D immunoreactivity in the pyramidal neurons of the affected CA fields 24-48 h after injection of the excitotoxin, at a time when there was no histological evidence of cell death. Apolipoprotein D immunoreactivity peaked by day 3, coincident with neuronal cell death, and declined thereafter, reaching very low levels by day 7. Besides pyramidal neurons, apolipoprotein D immunoreactivity was also observed in a small number of reactive glial cells in the affected CA fields, but not in the vascular compartments at any time-point. In contrast to the neuronal expression of apolipoprotein D, apolipoprotein E immunoreactivity was observed predominantly in degenerating astrocytes. In conclusion, following excitotoxic injury with kainic acid, apolipoprotein D is expressed in hippocampal pyramidal neurons destined for subsequent cell death.

Animals↗
PubMed1997

A randomized multicenter study of remifentanil compared with alfentanil, isoflurane, or propofol in anesthetized pediatric patients undergoing elective strabismus surgery.

Remifentanil hydrochloride is a new, ultrashort-acting opioid metabolized by nonspecific plasma and tissue esterases. We conducted this multicenter study to examine the hemodynamic response and recovery profile of premedicated children undergoing strabismus repair who were randomly assigned to receive one of four treatment drugs (remifentanil, alfentanil, isoflurane, or propofol) along with nitrous oxide and oxygen for maintenance of anesthesia. Induction of anesthesia was by nitrous oxide, oxygen, and halothane or nitrous oxide, oxygen, and propofol. Anesthesia was then maintained with remifentanil 1.0 microgram/kg over 30-60 s, followed by a constant infusion of 1.0 microgram.kg-1.min-1, alfentanil 100 micrograms/kg bolus followed by a constant infusion of 2.5 micrograms.kg-1.min-1, propofol 2.5 mg/kg bolus followed by a constant infusion of 200 micrograms.kg-1.min-1, or isoflurane 1.0 minimum alveolar anesthetic concentration. The infusions of the anesthetics and the administration of the inhaled gases were adjusted clinically by predetermined protocols. Elapsed time intervals from the end of surgery to the time the patients were tracheally extubated and displayed purposeful movement, as well as the time the patients met the postanesthesia care unit (PACU) and hospital discharge times, were recorded. Heart rate and systolic and diastolic blood pressure were measured at fixed intervals. In addition, cardiovascular side effects (bradycardia, hypotension, and hypertension) as well as vomiting, pruritus, agitation, and postoperative hypoxemia were also noted. There were no significant differences in patient demographics among the treatment groups. There was no difference in the early recovery variables (times to extubation and purposeful movement) or the times to PACU and hospital discharge among groups. There were significant differences in side effects among the groups. Patients who received remifentanil had higher PACU objective pain-discomfort scores than those who received alfentanil and propofol. Patients anesthetized with alfentanil had a greater incidence in the use of naloxone and a greater incidence of postoperative hypoxemia compared with those anesthetized with remifentanil. The incidence of postoperative hypoxemia was the same for remifentanil, propofol, and isoflurane groups. There were no significant differences in the incidence of emesis among the four groups, and all four groups had similar hemodynamic profiles. We conclude that remifentanil appears to be an effective drug for anesthesia. Its hemodynamic and recovery profile appear similar to other comparable drugs. Based on previous pharmacokinetic studies, the 1.0 microgram.kg-1.min-1 infusion may be twice the 50% effective dose observed in adults. In this study, the relative "overdose" of remifentanil was well tolerated and did not prolong recovery.

Alfentanil↗
PubMed1997

Ultrasonographic diagnosis of subclinical filariasis.

Asymptomatic persons with lymphatic filariasis may harbor microfiliariae in the circulation, and despite the lack of symptoms, these patients may have occult pathologic lesions and renal abnormalities. Earlier investigators have shown that it is possible to detect live adult filarial worms and dilation of lymphatic channels with ultrasonography. It is also possible to assess response to therapy. Using sonography, we detected twirling motions in dilated lymph channels and characteristic sonographic findings associated with presence of adult filariae. On follow-up examination we also found evidence of loss of worm activity after chemotherapy.

Animals↗
PubMed1996

Application of artificial neural networks for the classification of liver lesions by image texture parameters.

Ultrasound imaging is a powerful tool for characterizing the state of soft tissues; however, in some cases, where only subtle differences in images are seen as in certain liver lesions such as hemangioma and malignancy, existing B-scan methods are inadequate. More detailed analyses of image texture parameters along with artificial neural networks can be utilized to enhance differentiation. From B-scan ultrasound images, 11 texture parameters comprising of first, second and run length statistics have been obtained for normal, hemangioma and malignant livers. Tissue characterization was then performed using a multilayered backpropagation neural network. The results for 113 cases have been compared with a classification based on discriminant analysis. For linear discriminant analysis, classification accuracy is 79.6% and with neural networks the accuracy is 100%. The present results show that neural networks classify better than discriminant analysis, demonstrating a much potential for clinical application.

Diagnosis, Differential↗
PubMed1996

X-ray studies on crystalline complexes involving amino acids and peptides. XXXI. Effect of chirality on ionization state, stoichiometry and aggregation in the complexes of oxalic acid with L- and DL-histidine.

Crystals of the oxalic acid complex of L-histidine (orthorhombic P2(1)2(1)2(1); a = 5.535(4), b = 6.809(4), c = 26.878(3) A; R = 3.6% for 1188 observed reflections) contain histidine molecules and semi-oxalate ions in the 1:1 ratio, while the ratio is 1:2 in the crystals of the DL-histidine complex (monoclinic P2(1)lc; a = 6.750(7), b = 10.139(2), c = 19.352(2) A, beta = 90.8 degrees; R = 3.7% for 3176 observed reflections). The histidine molecule in the latter has an unusual ionization state with positively charged amino and imidazole groups and a neutral carboxyl group. The molecule has the sterically least favourable allowed conformation with the side chain imidazole ring staggered between the alpha-amino and the alpha- carboxyl (carboxylate) groups, in both the structures. The unlike molecules aggregate into separate alternating layers in both of them. There are elements of similarity in the aggregation patterns in the semi-oxalate layers in the two complexes, but the patterns in the amino acid layers are entirely different. Interestingly, the crystal structure of L-histidine semi-oxalate has broad similarities with that of DL-histidine = glycolate, demonstrating how broad features of aggregation could be retained inspite of changes in chirality and composition. The unusual ionization state of the amino acid molecule in the DL-histidine complex is reflected in a hitherto unobserved aggregation pattern in its crystal structure.

Crystallography, X-Ray↗
PubMed1996

NMR and X-ray crystallographic studies on cyclic tetrapeptide, cyclo (D-Phe-Pro-Sar-Gly).

The conformation of the synthetic cyclic tetrapeptide cyclo(D-Phe-Pro-Sar-Gly) has been determined in solution using the nuclear magnetic resonance technique and in the crystal state by X-ray crystallography. Results showed that the peptide exhibited two different conformations in solution, conformer 1 having cis-trans-cis-trans peptide bonds and conformer 2 having trans-cis-trans-cis peptide bonds. No intramolecular hydrogen bonds were observed in the structures. The X-ray diffraction studies showed the crystals to be orthorhombic with space group P2(1)2(1)2(1) with unit-cell dimensions, a = 5.790, b = 10.344, c = 31.446 A, Z = 4, R = 0.104 for 2301 observed reflections. The crystal structure showed only one type of conformer having cis-trans-cis-trans peptide bonds similar to the conformer 1 in solution.

Crystallography, X-Ray↗
PubMed1996

Chronic pain in cystic fibrosis.

OBJECTIVE: The objective of this study was to examine the incidence and therapy of chronic pain in a group of older patients with cystic fibrosis (CF). PATIENTS: We identified two groups of patients followed at the CF Center at Children's Hospital (Boston); the first group consisted of all patients above the age of 5 years who died between 1984 and 1993, and the second was a cohort of 23 additional CF patients who had been referred to the Pain Treatment Service. DESIGN: Medical charts were reviewed for the etiology and therapy of all pain episodes requiring medical intervention. RESULTS: The incidence of chronic pain in this population increased sharply in the last 6 months of life. Headaches (55% of patients) and chest pain (65%) were frequently reported, although back pain (19%), abdominal pain (19%), and limb pain (16%) were also reported. In patients with headache, the main etiologies were hypercarbia or hypoxia, migraine, and sinusitis. The majority of chest pain was musculoskeletal, with pleuritis, pneumothorax, and rib fracture also reported as the cause of chest pain. INTERVENTIONS: A variety of nonpharmacological and pharmacological therapies were reported. Forty-one patients (53%) had pain severe enough to require opioid treatment, and 10 patients (13%) received opioids for more than 3 months. In eight patients with more severe pain, regional analgesia was found to be particularly effective. CONCLUSIONS: Chronic pain is a common problem in CF, particularly as the patient population ages. When administered with caution, opioids have proven to be effective and safe in this population; regional anesthesia can be used to preserve pulmonary toilet while adequately treating severe pain.

Adolescent↗
PubMed1995

Astrocytes synthesize and secrete the lipophilic ligand carrier apolipoprotein D.

Expression of the lipophilic ligand transporter, apolipoprotein D (apoD) by primary astrocyte cultures derived from neonatal mouse brain was investigated. Western blot analysis of cell lysates and media showed that apoD is constitutively secreted by astrocytes with little intracellular storage. The secreted apoD floated primarily at density 1.063-1.21 g ml-1 upon sequential ultracentrifugation indicating its association with lipids. Treatment of astrocytes with the carboxylic ionophore, monensin, resulted in intracellular retention and decreased secretion of apoD that was of slightly reduced M(r). Progesterone, a steroid hormone that binds to apoD with high affinity (10(-6) mol l-1) and the oxysterol, 25-hydroxycholesterol which is a potent regulator of cellular cholesterol homeostasis in mammalian cells, differentially stimulated apoD, but not apoE secretion. These results show that astrocytes synthesize and constitutively secrete apoD and suggest a physiologic role for this lipocalin in cholesterol metabolism in the nervous system.

Animals↗
PubMed1995

Cyclic compressive loading results in fatigue cracks in ultra high molecular weight polyethylene.

Wear damage to the articulating surfaces of total joint components made of ultra high molecular weight polyethylene is associated with a fatigue fracture mechanism, despite the fact that these surfaces are subjected to primarily compressive and compressive-tensile cyclic stresses. The question arises as to whether fatigue cracks will form under such loading conditions. In this study, we experimentally demonstrated that fatigue cracks could be initiated and propagated in notched ultra high molecular weight polyethylene specimens subjected to fully compressive and compressive-tensile cyclic loading. Under these loading conditions, growth of fatigue cracks was limited: the cracks arrested without catastrophic failure of the test specimens. The final length of the crack was dependent on the load ratio of the fatigue cycle; fatigue cracks propagated to greater lengths as the load ratio was increased.

Knee Prosthesis↗