Biomedical subjects

A Sharma

Publications and source records attributed to A Sharma.

At least 451 records · Page 25Linked to original sources

PubMed1997

Synergistic effect of retinoic acid on Sn-PP mediated suppression of heme oxygenase activity in vivo in rats.

The present investigation is designed to probe the influence of excess retinoic acid (50,000 I.U.) and Sn-protoporphyrin (50 mumol/kg bw) along with retinoic acid on the activity patterns of the rate-limiting enzyme, heme oxygenase, of the heme catabolic pathway in the liver, spleen, kidney, brain, heart, and lung of male Wistar rats. Our results are noteworthy as SnPP is being used for the amelioration and management of hyperbilirubinemia, and they emphasize that the combined dosing of retinoic acid and SnPP attenuates the suppression of the activity of HMOX, thereby decreasing plasma bilirubin levels. The features of action of retinoic acid and SnPP together in vivo, i.e., a substantial suppression of the formation of a potentially neurotoxic metabolite, bilirubin, and the enhancement of disposal of the untransformed substrate (heme) of the enzyme that is inhibited, define some of the prerequisites of a therapeutically useful formulation.

Administration, Oral↗

PubMed1997

Activity of paclitaxel liposome formulations against human ovarian tumor xenografts.

Although the current clinical formulation of paclitaxel (Taxol) is an important new anti-cancer agent, it has significant side effects, some of which are related to its formulation in Cremophor/ethanol. Paclitaxel is difficult to formulate for i.v. administration because of its poor aqueous solubility. Here, we report the therapeutic effects of 2 liposome formulations of paclitaxel against human ovarian A121 tumor growing as an s.c. xenograft in athymic nude mice. The liposome formulations used were ETL and TTL, which have I or 3 lipid components, respectively. TTL was used as a reconstituted lyophilate or as a stable aqueous suspension. ETL was used as a reconstituted lyophilate only. Both paclitaxel-liposome formulations were much better tolerated than Taxol after i.v. or i.p. administration. The acute reactions seen after Taxol administration did not occur when paclitaxel-liposome formulations were administered. All ETL and TTL preparations significantly delayed A121 tumor growth similarly to Taxol at equivalent doses and schedules. Based on pharmacokinetic data, it is possible that paclitaxel rapidly dissociates from ETL or TTL after i.v. administration and distributes in a manner similarly to Taxol. ETL and TTL formulations may be useful clinically not only for eliminating toxic effects of the Cremophor/ethanol vehicle but also for allowing alterations in route and schedule of drug administration.

Animals↗

PubMed1997

Mapping of the extracellular binding regions of the human interleukin-8 type B receptor.

This study was undertaken to define the regions of the human interleukin-8 type B receptor (IL8RB) which are critical for binding the ligands interleukin-8, NAP-2 and GRO alpha. Peptides corresponding to the N-terminus region and the first extracellular loop of the receptor demonstrated statistically significant (p = 0.001) inhibition of IL-8 control binding levels (inhibition levels of 73.0 +/- 5.1% and 89.9 +/- 2.2% respectively). In contrast, NAP-2 binding was inhibited only by the peptide representing the first extracellular loop (63.2 +/- 2.3%), while GRO alpha binding was inhibited by portions of the N-terminus (49.7 +/- 14.9% and 41.8 +/- 14.9%), but not the first extracellular loop. We suggest that: a) the chemokine receptor IL8RB, known to bind three related ligands with high affinity, seems to do so via distinct contact points and b.) the first extracellular loop is significant in the binding event.

Amino Acid Sequence↗

PubMed1997

CD28 ligation prevents bacterial toxin-induced septic shock in mice by inducing IL-10 expression.

The pathogenesis of septic shock is due mainly to bacterial toxin stimulation of the immune system, resulting in an excessive production of proinflammatory cytokines. TNF-alpha has been implicated as a major mediator in septic shock. Coinjection of D-galactosamine and LPS or staphylococcal enterotoxin B induced a rapid-onset, low-dose form of septic shock syndrome and ultimately led to death. We found that both the septic shock syndrome and death could be prevented by administration of anti-CD28 Ab. The protection induced by anti-CD28 Ab was associated with a decrease in TNF-alpha levels in the circulation. In addition, serum from anti-CD28 Ab-treated mice was capable of inhibiting the production of TNF-alpha by bone marrow-derived macrophages following treatment with LPS, indicating that anti-CD28 Ab induced production of soluble factors that subsequently inhibited the production of TNF-alpha. We confirmed that one of the factors present in serum was IL-10, because anti-CD28 Ab treatment stimulated the expression of IL-10, both in splenocytes and in T cell lines. Furthermore, injection of anti-IL-10 Abs could abolish the protective effect of anti-CD28 Ab on septic shock. Anti-IL-10 Ab could also suppress the anti-CD28 Ab-induced inhibition of TNF-alpha production, either in vivo or in vitro. Thus, we conclude that ligation of CD28 induces expression of IL-10, which in turn suppresses TNF-alpha production and prevents septic shock.

Animals↗

PubMed1997

Apolar, Polar, and Electrostatic Interactions of Spherical Particles in Cylindrical Pores

A new Surface Element Integration (SEI) technique is developed for determination of the interaction energy of a spherical particle in a cylindrical pore based on the knowledge of the corresponding interaction energy per unit area between plane-parallel half spaces. Like the celebrated Deryaguin's approximation, the SEI can be used for any component of the interaction energy (e.g., apolar Lifshitz-van der Waals, electrostatic, polar) whenever interaction between corresponding half-spaces is known theoretically or experimentally. Accuracy of the SEI is assessed based on its comparison with the exact results for the van der Waals interaction energy. Results of the SEI are also compared with the approximate series solution for the electrostatic interaction in the Debye-Huckel approximation. While Deryaguin's approximation fails for the particle-pore geometry for small pores (<10 nm), the SEI is accurate for all realistic combinations of particle and pore radii, radial position of the particle, and decay length of interactions. Based on the SEI, the role of polar repulsion (hydration pressure) on the partitioning behavior of macromolecules across small pores is also studied. The hydration force in aqueous hydrophilic systems can lead to a significant lowering of the distribution coefficient in small pores characteristic of ultrafiltration.

Journal Article↗

PubMed1997

A comparison of masticatory function in patients with or without reconstruction of the mandible.

BACKGROUND: The functional benefits of mandibular reconstruction following a composite resection remain unclear. Although microvascular surgical techniques have dramatically increased the predictability of bone and soft-tissue reconstruction towards presurgical anatomic norms, the specific factors responsible for improved function remain controversial. Objective measures of masticatory function need to be more clearly determined before the predictability and efficacy of reconstructive approaches is established. METHODS: We evaluated objective measures of oral function and patient reports of function in 10 reconstructed mandibulectomy patients, 10 without reconstruction, and 10 controls. Measures of oral function included bite force assessed at the first molar and incisal edge, a measure of tongue and cheek function, and patient reports of food they could eat. RESULTS: Both reconstructed and nonreconstructed patients presented decreased biting force, a more restricted diet, and compromised cheek and tongue function as compared with normals. However, reconstructed patients had significantly better measures of tongue function and ability to eat a varied diet than did nonreconstructed patients. Of the objective measures used to measure masticatory performance, bite force was poorly correlated, whereas measures of tongue function strongly correlated with successful mastication. CONCLUSION: Both reconstructed and nonreconstructed patients presented with a significant functional deficit when compared with normals, with reconstructed patients having better overall function than nonreconstructed patients.

Aged↗

PubMed1997

The cystic fibrosis delta F508 gene mutation and cancer.

Following the observation that relatives of cystic fibrosis (CF) patients have an increased mortality due to leukaemia, a study was initiated to determine whether leukaemia patients had an increased prevalence of the delta F508 CF mutation. No increase in carriers were found among leukaemias; however the carrier frequency of the delta F508 mutation appeared to be reduced in patients with malignant melanoma analysed as a control group compared to the normal population. This paper extends our previous study and investigates several other common human tumours, including those of the colon, breast, and lymphoma tissue. Fewer than expected carriers remained among the melanoma group from South Wales. There were fewer than expected carriers among patients with colon cancer compared to the normal population. The prevalence of the delta F508 mutation was normal in lymphomas and leukaemias.

Alleles↗

PubMed1997

Distribution of the 5-hydroxytryptamine2C receptor protein in adult rat brain and spinal cord determined using a receptor-directed antibody: effect of 5,7-dihydroxytryptamine.

A synthetic peptide, corresponding to the N-terminal decapeptide (+Y11C12) of the rat 5-hydroxytryptamine2C (5-HT2C) receptor protein was used to produce a sheep polyclonal antiserum. Western blot analysis showed that the resultant antibody G241 recognised two membrane proteins, one (55 kDa) approximating the molecular mass of the 5-HT2C receptor (52 kDa) and a second (63 kDa), which may be a glycosylated form of the receptor protein. HEK 293 cells transfected with human 5-HT2C cDNA displayed intense cell surface immunoreactivity with the 5-HT2C antiserum, which was completely prevented by incubating the antibody with the synthetic 5-HT2C peptide (10 microM), whilst neither non-immune serum nor untransfected cells displayed any immunoreactivity. A radioimmunoassay was developed to quantify the regional distribution of 5-HT2C-like immunoreactivity (LI) in the adult rat brain. The choroid plexus contained five-fold higher levels of 5-HT2C-LI than any brain region but high levels were found in the frontal cortex, septum, hypothalamus, and striatum, intermediate levels in the thalamus and midbrain, and lower levels in brainstem, cerebellum, and spinal cord. In rat cortical membranes, the B(max) value from [3H]-mesulergine binding was ten-fold lower than 5-HT2C-LI levels determined by radioimmunoassay, which may reflect measurement of internalised receptor protein by radioimmunoassay which is not detected with conventional 5-HT2C ligands. Ten days after depletion of 5-HT with the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT), there was a significant increase in 5-HT2C-LI in the choroid plexus and the ventral cervical spinal cord, suggesting that receptors therein are located post-synaptic to destroyed serotonergic nerve terminals. In contrast, the significant reduction in 5-HT2C-LI observed in the midbrain, brainstem, and dorsal thoracic spinal cord following 5,7-DHT implies that 5-HT2C receptors may be located on 5-HT nerve terminals in these regions.

5,7-Dihydroxytryptamine↗

PubMed1997

Effect of amiloride A Na+/H+ exchange inhibitor on cardioprotective effect of ischaemic preconditioning: possible involvement of resident cardiac mast cells.

The present study was designed to investigate the effect of amiloride, a Na+/H+ exchange inhibitor on cardioprotective effect of ischaemic preconditioning in isolated rat heart. Four episodes of ischaemic preconditioning and amiloride (174 microM) treatment markedly decreased the release of lactate dehydrogenase (LDH) and creatine kinase (CK) in coronary effluent and infarct size in hearts subjected to 30 min of global ischaemia followed by 120 min of reperfusion. Amiloride (174 microM) administered during ischaemic preconditioning (Amiloride in Ischaemic Preconditioning), produced no marked effect on LDH and CK release and infarct size. Ischaemic preconditioning and amiloride treatment significantly reduced ischaemia/reperfusion induced release of mast cell peroxidase (MPO). Four episodes of pH (20 mm of ammonium chloride) preconditioning also produced cardioprotection and decreased ischaemia/reperfusion induced release of MPO. It is interesting to note that a significant increase in release of MPO was observed immediately after ischaemic preconditioning and the release was inhibited by amiloride. Moreover, similar increase in MPO release was noted immediately after pH preconditioning. These findings tentatively suggest that ischaemic preconditioning and pH preconditioning produced cardioprotective effect by activating Na+/H+ exchange and consequent degranulation of resident cardiac mast cells. Amiloride administered during ischaemic preconditioning attenuated the cardioprotective effect of ischaemic preconditioning.

Amiloride↗

PubMed1997

Characterization of Streptomyces sp. strain DRS-1 and its ampicillin transformation product.

Incubation of ampicillin with whole cells of Streptomyces sp. DRS-1 resulted in accumulation of four compounds different from ampicillin. One of them was isolated, purified and partially characterized. On the basis of spectroscopic characteristics, RF value and antibacterial activity the compound was identified as cephalexin. It could also be obtained from ampicillin by using crude protein extract of the strain.

Ampicillin↗

PubMed1997

Positional MRI: a technique for confirming the site of leakage in cerebrospinal fluid rhinorrhoea.

We report confirmation of the site of leakage in two patients with spontaneous cerebrospinal fluid (CSF) rhinorrhoea by demonstrating CSF leaking on MRI. Both patients had midline anterior cranial fossa floor (cribriform plate/fovea ethmoidalis) dural-bone defects with arachnoid herniation with or without brain herniation into the upper part of the nasal cavity on MRI, which was subsequently confirmed surgically. Corresponding to the history of postural induction or aggravation of the rhinorrhoea, the CSF leak was demonstrated by the appearance of or increase in the sinonasal fluid collection by imaging the patient in the position of maximum leakage following initial images in the supine position.

Cerebrospinal Fluid Rhinorrhea↗

PubMed1997

Levamisole therapy in corticosteroid-dependent nephrotic syndrome.

The effect of prolonged treatment with levamisole was examined in 43 patients (30 boys) with steroid-dependent nephrotic syndrome (SDNS). The mean age at institution of treatment was 4.0 +/- 2.0 years. Fourteen patients had previously received cyclophosphamide with an ensuing remission of 8.5 +/- 10 months. Following induction of remission with prednisolone, levamisole was administered at a dose of 2.5 mg/kg body weight on alternate days. Prednisolone was tapered by 2.5-5 mg every 4 weeks to 0.5 mg/kg on alternate days. The duration of levamisole therapy ranged from 6 to 31 months (mean 17.4 +/- 8.4 months); 15 patients received levamisole for more than 18 months and 10 for more than 24 months. Prednisolone was discontinued in 18 patients after a mean duration of 11.7 +/- 7.1 months, whereas in 21 patients its dose was reduced to 0.2-0.4 mg/kg on alternate days. The mean relapse rate prior to levamisole therapy was 3.0 +/- 1.5 relapses/year, which reduced to 0.9 +/- 0.7 relapses/year during levamisole treatment (P < 0.001). A comparison of the response in 14 patients who had previously received cyclophosphamide with the other 29 patients did not show any significant difference. There were no side effects of levamisole therapy. Our findings suggest that prolonged treatment with levamisole is beneficial and safe in SDNS, with a marked steroid-sparing effect. A significant proportion of these patients can be kept in remission on levamisole alone.

Adjuvants, Immunologic↗

PubMed1997

Transcription factor abnormalities as a cause of beta cell dysfunction in diabetes: a hypothesis.

Well-characterized defects in insulin secretion, most notably a loss of glucose-induced insulin secretion, are found in virtually all forms of NIDDM, as well as in early IDDM. Similar abnormalities have been found in all animal models of diabetes in which they have been studied. A novel hypothesis is being proposed to explain the mechanisms responsible for these alterations. Many abnormalities in the various steps of glucose-induced insulin secretion have been identified in rodent models of diabetes, but none by itself seems sufficient to explain the defects. These include a loss of GLUT2, glycogen accumulation, glucose recycling, abnormal glucokinase or hexokinase, altered mitochondrial glycerol phosphate dehydrogenase (mGPDH) activity, abnormal ion channel function and beta cell degranulation. We propose that optimal secretory function is dependent upon the unique differentiation of beta cells that is maintained by a set of transcription factors and that this control is disrupted by the diabetic state. Therefore, we propose that key transcription factors are affected even when beta cells are stressed by insulin resistance in very earliest stages of diabetes and that the abnormality becomes more severe as full-blown diabetes develops, which leads to loss of beta cell differentiation and a resultant derangement of insulin secretion.

Animals↗

PubMed1997

Tracheal ligation: the dark side of in utero congenital diaphragmatic hernia treatment.

Currently there are two in utero procedures that have been proposed for the treatment of Congenital diaphragmatic hernia (CDH); reduction of the herniated viscera with repair of the diaphragmatic defect (CDH repair) and stimulation of lung growth by ligation of the fetal trachea (CDH + TL). Recent studies have shown that CDH + TL may result in a significant surfactant deficiency. The aim of this study was to compare the postnatal lung function of these two interventions using the fetal lamb model of CDH. CDH was created in 14 lambs at 78 days' gestation. At 110 days, seven lambs had their trachea ligated through a transverse neck incision and seven had repair of their diaphragmatic defect via a left subcostal incision. At term the lambs were instrumented with the umbilical circulation intact, then delivered and ventilated to a standard protocol for 4 hours. Pulmonary hemodynamics and blood gas levels were measured and compared every 30 minutes. Four lambs in the CDH repair group and five lambs in the CDH + TL group survived to be studied. After the initial data were analyzed, a further group of CDH + TL lambs (n = 4) were studied. In this group a replacement dose of surfactant (Infasurf, Ony Inc, Buffalo, NY) was administered. These initial results cast doubt on tracheal ligation as an in utero therapy for CDH, and indicate that the lung produced by this intervention is not physiologically normal as previously thought. However, the function of these lungs can be normalized if the surfactant deficiency is corrected. If this improvement can be maintained and there is recovery of the endogenous surfactant system, then in utero tracheal ligation may become a viable treatment for fetal CDH.

Analysis of Variance↗

PubMed1997

Developmental changes in P1 and N1 central auditory responses elicited by consonant-vowel syllables.

Normal maturation and functioning of the central auditory system affects the development of speech perception and oral language capabilities. This study examined maturation of central auditory pathways as reflected by age-related changes in the P1/N1 components of the auditory evoked potential (AEP). A synthesized consonant-vowel syllable (ba) was used to elicit cortical AEPs in 86 normal children ranging in age from 6 to 15 years and ten normal adults. Distinct age-related changes were observed in the morphology of the AEP waveform. The adult response consists of a prominent negativity (N1) at about 100 ms, preceded by a smaller P1 component at about 50 ms. In contrast, the child response is characterized by a large P1 response at about 100 ms. This wave decreases significantly in latency and amplitude up to about 20 years of age. In children, P1 is followed by a broad negativity at about 200 ms which we term N1b. Many subjects (especially older children) also show an earlier negativity (N1a). Both N1a and N1b latencies decrease significantly with age. Amplitudes of N1a and N1b do not show significant age-related changes. All children have the N1b; however, the frequency of occurrence of N1a increases with age. Data indicate that the child P1 develops systematically into the adult response; however, the relationship of N1a and N1b to the adult N1 is unclear. These results indicate that maturational changes in the central auditory system are complex and extend well into the second decade of life.

Acoustic Stimulation↗

PubMed1997

Effects of dietary consumption of black tea infusion alone and in combination with known clastogens on mouse bone marrow chromosomes in vivo.

Black tea infusion in water, in concentrations simulating human consumption, was administered by gavage daily to male Swiss mice for 7 days. One set was given tea once daily and the other twice daily. The mice were then exposed to two known clastogens: chromium (VI) as potassium dichromate and mitomycin C on day 7, and killed after 24 hr. Chromosome damage was studied in preparations made from bone marrow following colchine injection of all mice, and examination of the cells after pretreatment in hypotonic solution, fixation, air drying one and staining with Giemsa solution. No effect was observed in mice given tea once daily. In mice administered tea twice daily, the frequencies of chromosomal aberrations and damaged cells were increased as compared with those of the control in distilled water. Administration of tea twice daily for 7 days could not reduce the clastogenic effects of mitomycin C significantly. The damage due to potassium dichromate was reduced significantly, almost to the level of distilled water. Dietary administration of black tea infusion could therefore significantly protect against clastogenic activity of chromium compounds though it was itself mildly clastogenic.

Analysis of Variance↗

PubMed1997

Secondary capsule-supported intraocular lens implantation in children.

PURPOSE: To evaluate surgical problems, postoperative complications, and visual results of secondary posterior chamber intraocular lens (IOL) implantation in children. SETTING: L.V. Prasad Eye Institute, Hyderabad, India. METHODS: A retrospective study was done of secondary IOL implantation in 27 children (35 eyes) who were not satisfied with aphakic glasses and were intolerant of or reluctant to use contact lenses. The extent of posterior capsular support was assessed prior to surgery. Additional surgical procedures were posterior synechiolysis (11 eyes), anterior vitrectomy (8 eyes), pupilloplasty (2 eyes), and membranectomy (2 eyes). RESULTS: Postoperative complications included wound leak (1 eye), uveitis (5 eyes), peripheral anterior synechias (2 eyes), and retinal detachment (1 eye). Visual acuity improved or remained at the preoperative level in 34 eyes. CONCLUSION: Secondary posterior chamber IOL implantation is an effective optical modality for managing pediatric aphakia. Observation must continue to determine the long-term safety of the procedure.

Adolescent↗

PubMed1997

Traumatic brain injury in a child psychiatry inpatient population: a controlled study.

OBJECTIVE: To extend our findings from child psychiatry outpatients to child psychiatry inpatients regarding the similarity of children with a history of traumatic brain injury (TBI), particularly mild TBI, to matched children without such a history. METHOD: This is a chart review of patients consecutively admitted to a child psychiatry inpatient unit over a 5-year period. Children with TBI were matched by age, sex, race, and social class to children with no history of TBI. Axis I and II diagnoses and diagnostic clusters and use of special education services and IQ scores were compared. RESULTS: Fifty-six (8.1%) of 694 consecutive patients admitted had a definite TBI. Not one of more than 50 variables compared between TBI and control subjects was significantly different. CONCLUSION: In a child psychiatry inpatient unit, patients with a history of TBI were virtually indistinguishable from matched children without TBI. Caution should be exercised before attributing the child's problems, especially long-term problems, to the TBI unless the injury was severe or the child is exhibiting related phobic or posttraumatic stress symptomatology.

Adolescent↗