Bioreducible cross-linked core polymer micelles enhance in vitro activity of methotrexate in breast cancer cells

Polymer micelles have emerged as promising carriers for controlled release applications, however, several limitations of micelle-based drug delivery have also been reported. To address these issues, we have synthesized a functional biodegradable and cytocompatible block copolymer based on methoxypoly(ethyleneglycol)-b-poly(?-caprolactone-co-?-azido-?-caprolactone) (mPEG-b-poly(?CL-co-?N3?CL)) as a precursor of reduction sensitive core-crosslinked micelles. The synthesized polymer was formulated as micelles using a dialysis method and loaded with the anti-inflammatory and anti-cancer drug methotrexate (MTX). The micellar cores were subsequently crosslinked at their pendant azides by a redox-responsive bis(alkyne). The size distributions and morphology of the polymer micelles were assessed using dynamic light scattering (DLS) and transmission electron microscopy, and drug release assays were performed under simplified (serum free) physiological and reductive conditions. Cellular uptake studies in human breast cancer cells were performed using Oregon-green loaded core-crosslinked micelles. The MTX-loaded core-crosslinked micelles were assessed for their effects on metabolic activity in human breast cancer (MCF-7) cells by evaluating the reduction of the dye MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. The apoptosis inducing potential of MTX-loaded core-crosslinked micelles was analysed using Hoechst/propidium iodide (PI) and annexin-V/PI assays. The data from these experiments indicated that drug release from these cross-linked micelles can be controlled and that the redox-responsive micelles are more effective carriers for MTX than non-crosslinked analogues and the free drug in the cell-lines tested

Asymmetric universal entangling machine

We give a definition of asymmetric universal entangling machine which entangles a system in an unknown state to a specially prepared ancilla. The machine produces a fixed state-independent amount of entanglement in exchange to a fixed degradation of the system state fidelity. We describe explicitly such a machine for any quantum system having $d$ levels and prove its optimality. We show that a $d^2$-dimensional ancilla is sufficient for reaching optimality. The introduced machine is a generalization to a number of widely investigated universal quantum devices such as the symmetric and asymmetric quantum cloners, the symmetric quantum entangler, the quantum information distributor and the universal-NOT gate.Comment: 28 pages, 3 figure

Neuronal anomalies and normal muscle morphology at the hypomotile ileocecocolonic region of patients affected by idiopathic chronic constipation

Patients suffering from idiopathic slowtransit chronic constipation have a delayed colonic transit referable to a decrease or loss of propagating contractions. Myogenic andlor neural mechanisms have been implicated in the pathophysiology of this dysfunction and neuronal abnormalities have been described at the ascending, descending and sigmoid colon. The morphology and motile behaviour of the ileocecocolonic region, which in healthy subjects regulates cecum filling and emptying, have never been investigated in such disease. Therefore, we endoscopically ascertained whether a motility impairment was present at these junctional areas and neither spontaneous nor provoked occlusive contractions were found at the cecocolonic junction. Light and electron microscope examination of the entire colon revealed apparently normal features of neurons, smooth muscle cells and interstitial cells of Cajal, while immunohistochemistry and quantitative analysis demonstrated neuronal anomalies at the junctional areas. These anomalies consisted of low total neuron density and significantly few VIP-immunoreactive neurons at the two enteric plexuses, significantly few NOS-immunoreactive neurons at t h e myenteric plexus and significantly more NOS-immunoreactive neurons at the submucous plexus. These findings exclude a myopathy and demonstrate the existence of a neuropathy. In particular, the presence at the ileocecocolonic region of few VIP- and NO-producing neurons suggests that there might be a reduced VIP and NO production which may result in a compromised relaxation andlor onset of propagating contractions, slowing down bolus transit. The presence at the proximal colon of such an abnormality might explain why left colectomy andlor cecorectal anastomosis are unsuccessful in patients with this disease

The cytoskeleton of the myenteric neurons during murine embryonic life

The organization of the cytoskeleton has been studied during mouse differentiation in cells of the myenteric neuronal lineage. The entire gut was examined starting from day 12.5 of embryonic life (E12.5) until birth (P0). Immunocytochemistry was performed to evaluate the expression of five of the most represented neurofilaments proteins (the low, NF-L, medium, NF-M, and heavy, NF-H, molecular weight subunits, alpha-internexin and peripherin) and of two of the microtubule-associated proteins (MAPI and MAP2a+2b). In parallel, the appearance in the differentiating myenteric neurons of filamentous and microtubular structures and their intracytoplasmatic distribution were observed under the electron microscope. A differential immunohistochemical expression of the structural proteins was found. Immature cells expressed alpha-internexin, peripherin, NF-M and MAP1 by day E12.5; alpha-internexin expression was strong in these cells, but gradually decreased with age and was practically absent in adulthood. Conversely, the expression of the other three proteins increased with cell differentiation and was still present in adulthood. NF-L and NF-H expression appeared later, by day E16.5, and was weak for the entire pre- and postnatal life. MAP2a+2b was never expressed. Under the electron microscope, at day E12.5 the cytoskeleton was already organized in filamentous and microtubular structures. At this age neurofilaments were few and mainly located in the cell processes, and microtubules were numerous and mainly assembled in the neuritic growth cones, together with synaptic vesicles. With ageing, neurofilaments and microtubules were ubiquitous in the neuron. Data obtained demonstrate that cytoskeletal proteins gradually accumulate in the cells of the neuronal lineage in parallel with the organization of the cytoskeletal structures, which in turn mediate important neural events by the earliest stages of murine embryonic life, including growth of nerve processes and initiation of axonal transport

Comparison of Resistant and Susceptible Strains of Trichomons vaginalis to Metronidazole Using PCR Method

Background: Metronidazole is drug of choice recommended by WHO for treatment of trichomoniasis, however, some reports claims drug resistance in Trichomonas vaginalis isolates recently. The objective of this study was to determine the minimum lethal concentration (MLC) of metronidazole in resistant and sensitive strains, as well as genetic patterns of these stains by PCR method. Methods: From February 2006 to March 2007, in a cross sectional study, clinical and wet mount examination of vaginal smear along with culture were performed on 683 women attending to public and private outpatient clinics in Hamadan. Trichomoniasis marked based on major clinical symptoms. Diagnosis confirmed using wet mount microscopically and culture in Diamond medium. A serial concentration of metronidazole was provided and all isolated Trichomonas strains (resistant and sensitive) tested by standard method. Finally, all sensitive and resistant strains examined by PCR technique. Results: Only 15/683, (2.2%) of patients clinically diagnosed trichomonal vaginitis were positive for T. vaginalis by wet smear and culture. The minimum lethal concentration (MLC) for clinically sensitive isolates was 25 µg/ml; however, this concentration for resistant isolates was 200 µg/ml after 24 h and 100 µg/ml after 50 h. The results of PCR examination of DNA from sensitive and resistant isolates had same pattern. The lanes appeared by two primers were 98 bp and 261 bp for both clinically sensitive and resistant strains. Conclusion: Resistance to metronidazole in T. vaginalis has not relation to genetic variations and might be related to some physiologic pathways of organism

Acute complications of diabetes mellitus in patients hospitalized in Shahid Beheshti Hospital, Kashan, 1991-99

Background: With respect to the prevalence of diabetes mellitus, its known complications, the impact of epidemiological features on prognosis and in order to determine the acute complications of diabetes mellitus and its related mortality and morbidity, the present study was conducted in Shaheed Beheshti University hospital in Kashan, during an 8-year period (1991-99). Materials and Methods: It was an existing data type study. Demographic characteristics as well disease profile were all recorded. Then descriptive statistics was used. Results: 114 patients with 144 acute complications were included. Diabetic ketoacidosis, hyperosmolar syndrome and hypoglycemia were reported in 54 (37.5), 9 (6.3) and 81 (56.2), respectively. Diabetic ketoacidosis was more obvious in 12-20-year-old individuals (21 cases). The mortality rare was 11.1, 66.6 and 6.2, respectively.Conclusion: Hypoglycemia was by far the most common complication. Diabetic ketoacidosis was found more common among 12-20-year-old individuals. Whereas hyperosmolar syndrome and hypoglycemia were more prevalent after 60. Mortality had occurred among these patients. Thus an experimental study is strongly recommended