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Biomedical subjects

Israel Rubinstein

Publications and source records attributed to Israel Rubinstein.

At least 37 records · Page 2Linked to original sources
PubMed2003

VIP grafted sterically stabilized liposomes for targeted imaging of breast cancer: in vivo studies.

Targeted delivery of radionuclides and therapeutic agents to specific biomarkers of breast cancer has important implications for the diagnosis and therapy of breast cancer. Vasoactive intestinal peptide receptors (VIP-R) are approximately five times more expressed in human breast cancer, compared to normal breast tissue. We have used VIP, a 28 amino acid mammalian neuropeptide, as a breast cancer targeting moiety for targeted imaging of breast cancer. VIP was covalently attached to the surface of sterically stabilized liposomes (SSL) that encapsulated a radionuclide, Tc99m-HMPAO. Rats with n-methyl nitrosourea (MNU)-induced in situ breast cancers were used to test this targeted liposomal imaging agent. Specifically, the pharmacokinetics and biodistribution of Tc99m-HMPAO encapsulating SSL with and without VIP were determined together with their ability to image breast cancer. The presence of VIP did not alter the size and Tc99m-HMPAO encapsulation ability of SSL. It also did not alter the pharmacokinetic profile of SSL. Long-circulating liposomes with and without VIP on their surface accumulated at significantly higher quantities in breast cancer when compared to normal breast, indicating passive targeting of these constructs to cancer tissues. Importantly, in breast cancer, Tc99m-HMPAO encapsulating SSL with VIP showed significantly more accumulation than SSL without VIP. The tumor to non-tumor ratio was also significantly higher for Tc99m-HMPAO encapsulating VIP-SSL than Tc99m-HMPAO encapsulating SSL without VIP, suggesting active targeting of VIP-SSL to breast cancer. Collectively, these data showed that Tc99m-HMPAO encapsulating VIP-SSL can be successfully used for the targeted imaging of breast cancer.

Animals↗
PubMed2003

Preparation of graded materials by laterally controlled template synthesis.

A novel scheme is presented for the synthesis of graded materials by electrodeposition in porous insulating templates. Lateral control of copper electrodeposition in nanoporous alumina membranes is achieved by application of a lateral potential gradient on a thin Au film evaporated on the membrane, used as the cathode. Formation of metal gradients in the membranes is shown to occur under conditions where essentially no gradient is formed on similar bare electrodes. This is attributed to the permanent resistivity of the thin Au film between the pores, which does not disappear upon Cu deposition, allowing a potential gradient to be maintained. Formation of a copper gradient in porous alumina membranes by uniform deposition followed by gradient dissolution is also demonstrated. These results establish the feasibility of controlled electrodeposition and gradient formation in nanoporous insulating templates.

Journal Article↗
PubMed2003

Aldehydes in exhaled breath condensate of patients with chronic obstructive pulmonary disease.

The aims of the present study were (1) to evaluate whether individual aldehydes resulting from lipid peroxidation can be measured in exhaled breath condensate, (2) to assess the influence of sampling procedures on aldehyde concentrations, and (3) to compare aldehyde levels of patients with stable, moderate to severe, chronic obstructive pulmonary disease with those of smoking and nonsmoking control subjects. Aldehydes (malondialdehyde, hexanal, heptanal, and nonanal) were measured by liquid chromatography-tandem mass spectrometry in all samples and overlapping results were obtained by different sampling procedures. Malondialdehyde (57.2 +/- 2.4 nmol/L), hexanal (63.5 +/- 4.4 nmol/L), and heptanal (26.6 +/- 3.9 nmol/L) were increased in patients as compared with nonsmoking control subjects (17.7 +/- 5.5 nmol/L, p < 0.0001; 14.2 +/- 3.5 nmol/L, p = 0.004; and 18.7 +/- 0.9 nmol/L, p = 0.002, respectively). Only malondialdehyde was increased in patients compared with smoking control subjects (35.6 +/- 4.0 nmol/L, p = 0.0007). In conclusion, different classes of aldehydes were identified in exhaled breath condensate of humans. Whereas all aldehydes but nonanal were lower in control subjects as compared with other groups, only malondialdehyde distinguished smoking control subjects from patients with chronic obstructive pulmonary disease and could be envisaged as a biomarker potentially useful to monitor the disease and its response to therapy.

Adult↗
PubMed2003

Human galanin expresses amphipathic properties that modulate its vasoreactivity in vivo.

The purpose of this study was to determine whether human galanin, a pleiotropic 30-amino acid neuropeptide, expresses amphipathic properties in vitro and, if so, whether these properties modulate its vasoactive effects in the intact peripheral microcirculation. We found that human galanin aggregates in an aqueous solution and forms micelles with a critical micellar concentration (CMC) of 0.4 microM. In addition, the peptide interacted with model membrane as indicated by long and significant increase of the surface pressure of the biomimetic monolayer membrane in vitro. Interactions of human galanin with sterically stabilized phospholipid micelles (SMM) were not associated with a significant change in peptide conformation. Using intravital microscopy, we found that suffusion of human galanin alone elicited significant concentration-dependent vasoconstriction in the intact hamster cheek pouch. This response was amplified when human galanin in SSM was suffused onto the cheek pouch. The effects of human galanin alone and in SSM were mediated by galanin receptors because galantide, a galanin receptor antagonist, abrogated galanin-induced vasoconstriction. Collectively, these data show that human galanin expresses amphipathic properties in the presence of phospholipids which in turn amplifies its vasoactive effects in the intact peripheral microcirculation.

Animals↗
PubMed2003

Interactions of VIP with rigid phospholipid bilayers: implications for vasoreactivity.

The purpose of this study was to determine whether vasoactive intestinal peptide (VIP), a pleiotropic amphipathic peptide, interacts with rigid liposomes composed of gel phase phospholipids. We found that incubation of VIP with small unilamellar gel phase liposomes composed of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) and egg phosphatidylglycerol (ePG) for 2h at room temperature had no significant effects on VIP secondary structure. Moreover, suffusion of VIP (0.01, 0.1 and 1.0nmol) incubated in saline or with DPPC/ePG liposomes (size, 30 and 100nm) for 2h at room temperature or 4 degrees C onto the intact hamster cheek pouch microcirculation elicited a similar concentration-dependent vasodilation except for 0.01nmol VIP (P<0.05). By contrast, incubation of VIP with gel phase liposomes overnight at 4 degrees C significantly potentiated vasodilation evoked by all three concentrations of the peptide in comparison to aqueous VIP (P<0.05). VIP-induced vasodilation was liposome size-independent. The ratio of VIP to phospholipids in DPPC/ePG liposomes was concentration-independent. Collectively, these data indicate that short-term interactions of VIP with rigid phospholipid bilayers are limited resulting in only modest effects on VIP vasoreactivity in vivo.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2003

Conformation-dependent effects of VIP on nociception in rats.

The purpose of this study was to determine whether intrathecal injection of aqueous (random coil) vasoactive intestinal peptide (VIP) and VIP self-associated with sterically stabilized phospholipid micelles (alpha-helix VIP) at the lower lumbar vertebral level modulates foot withdrawal latency to low and high rate noxious radiant skin heating in anesthetized rats. We found that intrathecal random coil VIP evoked a significant bimodal, concentration-dependent response, early potent antinociception followed by hyperalgesia, during exposure to low and high rates of skin heating (P<0.05). Intrathecal alpha-helix VIP elicited a qualitatively similar response to that of random coil VIP except that the rate of decay of antinociception was faster and slower at low and high rates of skin heating, respectively. In addition, a low concentration of alpha-helix VIP evoked a potent late antinociception not observed with random coil VIP. Taken together, these data indicate that VIP modulates somatosensory processing in the lumbosacral spinal cord of rats in a complex fashion, and that this response is dependent, in part, on the conformation of VIP in the vicinity of target cells in the peripheral nervous system.

Animals↗
PubMed2003

Sterically stabilized phospholipid mixed micelles: in vitro evaluation as a novel carrier for water-insoluble drugs.

PURPOSE: Sterically stabilized phospholipid micelles (SSMs) composed of poly(ethylene glycol-2000)-grafted distearoyl phosphatidylethanolamine (PEG(2000)-DSPE) are new and promising lipid-based carriers for water-insoluble drugs. This study investigates and compares sterically stabilized mixed micelles (SSMM), composed of (PEG(2000)-DSPE) plus egg-phosphatidylcholine, with SSM as a novel delivery system for improved solubilization of water-insoluble drugs using paclitaxel as a model. METHODS: Paclitaxel was solubilized in SSM (P-SSM) and SSMM (P-SSMM) by coprecipitation and rehydration with isotonic 0.01M HEPES buffer, pH 7.4. After separation of excess drug by centrifugation, mean particle size and morphology of particles in the supernatant were determined by quasi-elastic light scattering and transmission electron microscopy. The solubilization potentials of SSMM and SSM for paclitaxel were determined by reverse phase high pressure liquid chromatography (RP-HPLC). Cytotoxic activity of paclitaxel in SSMM. SSM, and dimethyl sulfoxide (10% DMSO) was determined against human breast cancer cells (MCF-7). RESULTS: Mean hydrodynamic diameter of P-SSMM and P-SSM were 13.1 +/- 1.1 nm and 15 +/- 1 nm (n = 3), respectively. SSMM solubilized 1.5 times more paclitaxel than SSM for the same total lipid concentration. Solubilized paclitaxel amount increased linearly with an increase in lipid concentration. A therapeutically relevant lipid concentration (15 mM) of SSMM solubilized 1,321 +/- 48 microg/ml of paclitaxel. Paclitaxel in the absence of sufficient SSM aggregated to form lipid-coated crystals. P-SSMM, P-SSM. and paclitaxel in DMSO had comparable cytotoxic activities against MCF-7 cells. CONCLUSIONS: SSMM showed increased solubilization potential compared with SSM while retaining all of its own advantages. Therefore, it can be used as an improved lipid-based carrier for water-insoluble drugs.

Dose-Response Relationship, Drug↗
PubMed2003

Tissue reparative effects of macrolide antibiotics in chronic inflammatory sinopulmonary diseases.

It is well established that macrolide antibiotics are efficacious in treating sinopulmonary infections in humans. However, a growing body of experimental and clinical evidence indicates that they also express distinct salutary effects that promote and sustain the reparative process in the chronically inflamed upper and lower respiratory tract. Unlike the anti-infective properties, these distinct effects are manifested at lower doses, usually after a relatively prolonged period (weeks) of treatment, and in the absence of an identifiable, viable pathogen. Long-term, low-dose administration of macrolide antibiotics has been used most commonly for sinusitis, diffuse panbronchiolitis, asthma, bronchiectasis, and cystic fibrosis. It is associated with down-regulation of nonspecific host inflammatory response to injury and promotion of tissue repair. Although large-scale trials are lacking, the prolonged use of these drugs has not been associated with emergence of clinically significant bacterial resistance or immunosuppression. Long-term, low-dose administration of 14- and 15-membered ring macrolide antibiotics may represent an important adjunct in the treatment of chronic inflammatory sinopulmonary diseases in humans.

Anti-Bacterial Agents↗
PubMed2002

Transmission surface-plasmon resonance (T-SPR) measurements for monitoring adsorption on ultrathin gold island films.

Evaporation of ultrathin (1.3-10 nm nominal thickness) gold films onto quartz or mica leads to the formation of a layer of rather uniform gold islands on the transparent support. The morphology of ultrathin gold island films of various thicknesses was studied by using atomic force microscopy (AFM) and scanning electron microscopy (SEM) imaging. The surface plasmon (SP) absorption characteristic of such films is highly sensitive to the surrounding medium, with the plasmon band changing in intensity and wavelength upon binding of various molecules to the surface. The binding process can be monitored quantitatively by measuring the changes in the gold SP absorption, by using transmission UV/Vis spectroscopy. The method, termed transmission surface plasmon resonance (T-SPR) spectroscopy, is shown to be applicable to both chemically and physically adsorbed molecules, in liquid or gas phase, with measurements carried out either ex situ or in situ (real-time measurements) using a variety of molecular probes. Binding to a preformed molecular layer on the Au surface produces a similar response, suggesting the possible use of T-SPR for selective sensing. The sensitivity of T-SPR spectroscopy in detecting molecular binding to the gold depends strongly on the film preparation conditions, and may be comparable to that obtained in surface plasmon resonance (SPR) sensing.

Journal Article↗
PubMed2002

Secretin self-assembles and interacts spontaneously with phospholipids in vitro.

Secretin, a 27-amino acid neuropeptide, is a member of the secretin/glucagon/vasoactive intestinal polypeptide (VIP) superfamily of amphipathic peptides. The peptide modulates gastrointestinal and neuronal function and is currently being evaluated for the treatment of autism. However, as most peptides, it has a short circulation half-life. Previously, we have shown that VIP self-assembles in aqueous environment and interacts with a biomimetic phospholipid membrane. These in vitro characteristics increase VIP half-life and bioactivity in vivo. The purpose of this study was to investigate whether secretin exhibits similar properties in vitro by forming micelles in aqueous solution and interacting with phospholipids. Results of this study demonstrated that secretin self-assembles to form micelles in HEPES buffer at 25 degrees C above approximately 0.4 microM. Additionally, secretin interacts with a biomimetic phospholipid membrane as indicated from a significant increase in membrane surface pressure (from 25.5 +/- 1.3 to 32.5 +/- 3.0, P < 0.05). Importantly, the peptide undergoes conformational transition from predominantly random coil in saline to alpha-helix in the presence of phospholipid, distearoyl-phosphatidylcholine-poly(ethylene) glycol (mol mass 2000) micelles. We suggest that these distinct biophysical attributes could modulate secretin bioactivity in vivo.

Circular Dichroism↗
PubMed2002

Interactions of human secretin with sterically stabilized phospholipid micelles amplify peptide-induced vasodilation in vivo.

Secretin, a 27-amino acid neuropeptide, is a member of the glucagon/secretin/vasoactive intestinal polypeptide (VIP) superfamily of amphipathic peptides that elicits transient vasodilation in vivo. The purpose of this study was to determine whether association of human secretin with sterically stabilized phospholipid micelles (SSM) amplifies the vasorelaxant effects of the peptide in the peripheral microcirculation in vivo. We found that secretin in saline evoked significant concentration-dependent vasodilation in the intact hamster cheek pouch microcirculation (P < 0.05). This response was potentiated and prolonged significantly when secretin was associated with SSM (P < 0.05). Vasodilation evoked by secretin in saline and secretin in SSM was abrogated by VIP(10-28), a VIP receptor antagonist, but not by PACAP(6-38), a PACAP receptor antagonist, or Hoe140, a selective bradykinin B(2) receptor antagonist. Collectively, these data indicate that self-association of human secretin with SSM significantly amplifies peptide vasoreactivity in the intact peripheral microcirculation through activation of VIP receptors. We suggest that the vasoactive effects of human secretin in vivo are, in part, phospholipid-dependent.

Animals↗
PubMed2002

Effects of quinupristin/dalfopristin on vasomotor tone in the intact peripheral microcirculation.

The purpose of this study was to determine whether quinupristin/dalfopristin modulates vasomotor tone in the intact peripheral microcirculation. Using intravital microscopy, we found that superfusion of quinupristin/dalfopristin (120 mg/L) on the intact hamster cheek pouch microcirculation had no significant effects on arteriolar diameter. In addition, superfusion of quinupristin/dalfopristin (120 mg/L) had no significant effects on vasodilation evoked by bradykinin and acetylcholine, two endothelium-dependent agonists, or by vasoactive intestinal peptide, an endothelium-independent agonist, on to the cheek pouch. Collectively, these data indicate that quinupristin/dalfopristin has no significant effects on vasomotor tone in the intact peripheral microcirculation.

Animals↗
PubMed2002

Bacillus species are present in chewing tobacco sold in the United States and evoke plasma exudation from the oral mucosa.

Five Bacillus species, predominantly Bacillus megaterium and Bacillus pumilus, were isolated from two popular brands of commercially available chewing tobacco [(5.0 +/- 1) x 10(6) CFU/ml of supernatant; results for four experiments]. Moreover, the supernatant of the Bacillus culture evoked plasma exudation from postcapillary venules in the intact hamster cheek pouch, exudation that was mediated by the kallikrein/kinin metabolic pathway. Taken together, these data indicate that Bacillus species contaminate chewing tobacco commercially available in the United States and elaborate a potent exogenous virulence factor(s) that injures the oral mucosa.

Bacillus megaterium↗