Ultrathin films of charged polysaccharides assembled alternately with linear polyions

As a means of preparation of biocompatible molecular surfaces, an alternate assembly of charged polysaccharides and oppositely-charged synthetic polymers was conducted. Cationic chitosan was assembled alternately with anionic poly(sodium styrenesulfonate) (PSS) at pH 4. Regular film growth and its dependence on ionic strength were detected by the quartz crystal microbalance (QCM) method. Averaged film thicknesses for the chitosanCPSS layer were 15, 31, 46, and 69 A° , respectively, when 0, 0.25, 0.5, and 1 M of NaCl was contained in aqueous chitosan. Adsorption of chitosan did not reach saturation in 20 min at 0 M NaCl, while the adsorption became saturated within 6 min with 0.25 M NaCl. Anionic sodium chondroitin sulfate was also assembled in alternation with cationic poly(dimethyldiallylammonium chloride) (PDDA) at pH 6.5. The adsorption of chondroitin sulfate was less sensitive to ionic strength. Surface morphology of chitosan–PSS films was investigated by non-contact atomic force microscopy (AFM) observation. Maximum height difference and Ra value for a 1000 × 1000 nm area were 11 and 0.69 nm, respectively, indicating the formation of a molecularly flat surface by alternate layer-by-layer adsorption.     

Contribution of pulmonary hemodynamics on manifestation of allergic asthma in patients with congenital heart disease

The purpose of this study was to determine whether pulmonary hemodynamic abnormalities relate to manifestations of allergic asthma. In 448 patients with congenital heart disease the relationships between asthma and age or pulmonary arterial blood (PA) flow were studied. Asthma (allergic and non-allergic) was more common in 39 (19%) of 201 patients with high PA flow, compared with the incidence in those with normal PA flow (6/117, 5%; P < 0.001) and reduced PA flow (1/130, 1%; P < 0.05). In the high PA flow group, the frequency of asthma declined significantly (P < 0.01) with age, from 25–26% in the 6 month-5 year patient group to 5% in the 6–12 year old patients. The frequency of asthma, including allergic type, was significantly (P < 0.01) greater in patients with pulmonary hypertension (15/24, 63%) than in those without (10/77, 13%) at the age of 6 months to 1 year. Asthma in the high PA flow group was associated with other allergic diseases in 30 (77%) of 39 patients, including food allergy in nine (23%), atopic dermatitis in 14 (36%), allergic rhinitis in seven (18%) and abnormally high total IgE levels in 14 (36%). These findings suggest that high pulmonary flow or pulmonary hypertension enhances the manifestation of allergic disease, particularly asthma.     

Intraspinal Metastasis of Neuroblastoma -- Report of a Case Detected at Autopsy --

Metastasis to the brain or spinal cord parenchyma is extremelyrare in cases of neuroblastoma. We present a 3-year-7-month-old boy with neuroblastoma, stageIV, with intraspinal metastasis. He had no neurologic manifestationexcept incontinentia urinae and ataxia at the terminal stage.His cranial computed tomography scan showed high density areasin both cerebellar hemispheres which seemed to be distant metastaticmasses. At autopsy, the metastases in the cerebellum were foundto be due to dural infiltration but in the spinal cord parenchymaof the lumbar spine metastases were detected macroscopically.There were multiple distant metastatic areas near the roots,anterior and posterior. The neuroblastoma seemed to have spreadalong the roots by direct invasion from the meninges. In the future, the number of patients with metastasis into thebrain or spinal cord parenchyma will increase because patientswith progressive disease could live for a long time as a resultof intensive chemotherapy. Observation of these cases will behelpful to clarify the routes of metastasis to these areas.     

Vanoxerine: Cellular Mechanism of a New Antiarrhythmic

Cellular Electrophysiology of Vanoxerine. Introduction: There remains an unmet need for safe and effective antiarrhythmic drugs, especially for the treatment of atrial fibrillation. Vanoxerine is a drug that is free of adverse cardiac events in normal volunteers, yet is a potent blocker of the hERG (hK_v11.1) cardiac potassium channel. Consequently,we hypothesized that vanoxerine might also be a potent blocker of cardiac calcium (Ca) and sodium (Na) currents, and would not affect transmural dispersion of repolarization. Methods: The whole cell patch clamp technique was used to measure currents from cloned ion channels overexpressed in stable cell lines and single ventricular myocytes. We measured intracellular action potentials from canine ventricular wedges and Purkinje fibers using sharp microelectrode technique. Results: We found that vanoxerine was a potent hK_v11.1 blocker, and at submicromolar concentrations, it blocked Ca and Na currents in a strongly frequency‐dependent manner. In the canine ventricular wedge preparation vanoxerine did not significantly affect transmural action potential waveforms, QT interval or transmural dispersion of repolarization. Conclusions: Vanoxerine (1) is a potent blocker of cardiac hERG, Na and Ca channels; (2) block is strongly frequency‐dependent especially for Na and Ca channels; and (3) transmural dispersion of ventricular repolarization is unaffected. The multichannel block and repolarization uniformity resemble the effects of amiodarone, the exemplar atrial fibrillation drug. Vanoxerine is a completely different chemical and has none of amiodarone's toxic effects. Vanoxerine has characteristics of a potentially effective and safe antiarrhythmic. (J Cardiovasc Electrophysiol, Vol. 21, pp. 301–310, March 2010)     

Substance P derivatives with photoactivatable labels in the N-terminal part of the molecule

Photoactivatable substance P (SP) derivatives containing the p-benzoylbenzoic moiety at the N-terminal α-amino group of Arg 1 or at the ε-amino group of Lys 3 were prepared. Both derivatives also had a p-hydroxyphenylpropionyl group for radioiodination. To obtain the analogue with the photolabel at Arg 1, SP was first reacted with N-hydroxysuccinimide p-hydroxyphenylpropionate, the Lys 3-modified derivative was isolated by reversed-phase high-performance liquid chromatography (HPLC), reacted with N-hydroxysuccinimide p-benzoylbenzoate and purified by HPLC. To place the photolabel at Lys 3, the order of the reactions was reversed. The structure of the derivatives obtained was confirmed by mass spectrometry. The interaction of the derivatives obtained and of their ¹²⁵I-labeled forms with the NK-1 neurokinin receptor from the rat brain, as well as with the nicotinic acetylcholine receptor from Torpedo electrocytes was analyzed. The results obtained supported by the data from the literature indicate that benzoylbenzoic acid derivatives should not be considered as universal photolabels, which ensure in all cases a high level of photo-cross-linking.     

An effective organic solvent system for the dissolution of amino acids

Dimethylformamide containing strong acids (CF₃ COOH, HBF₄. TosOH, etc.) and an excess of tertiary base with p^K≤6 is an effective solvent system for the dissolution of amino acids and their derivatives. The preferable base is pyridine, which forms a system with an apparent pH of 5.3. Amino acids dissolved in this solvent system readily interact with acylating reagents (BOC₂O, ZOSu, Fmoc-OSu and activated derivatives of N-protected amino acids). A number of BOC-, Z-, Fmoc-amino acids, as well as several dipeptides, were synthesized using this solvent system with 80-99%) yields. © Munksgaard 1996.     

Spinal muscular atrophy in trizygotic triplets

The clinical, electrophysiological, pathological and genetic findings in trizygotic triplets with spina muscular atrophy (SMA) are reported. The first child was clinically affected shortly after birth and the third one first showed symptoms at 1 month of age. Electromyography and a muscle biopsy provided evidence of lower motor neuron disease. The second child remains clinically normal, but electromyography showed fibrillation potentials and regular spontaneous motor unit activity at rest. Genetic linkage analysis revealed that the two siblings with typical type 1 SMA had the same chromosome 5q haplotype, and that the second child had a different haplotype. It is considered that in this family there is a link to SMA 5q and there is little possibility that the second child is affected. These data emphasize the need to adhere to strict clinical criteria for the diagnosis of chromosome 5q SMA.     

Detection of apoptosis in keloids and a comparative study on apoptosis between keloids, hypertrophic scars, normal healed flat scars, and dermatofibroma

Recent studies have suggested that the regulation of apoptosis during wound healing is important in scar establishment and the development of pathological scarring. In this study, we demonstrate that keloid fibroblasts can be identified as apoptotic cells because of their highly condensed chromatin and discrete nuclear fragments. To further reveal the phenomenon of apoptosis, we quantified the number of terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells in surgically resected tissues of keloids (N = 10), hypertrophic scars (N = 10), normal healed flat scars (N = 10), and dermatofibroma (N = 10). The number of TUNEL-positive cells was relatively low, but was significantly higher for the keloid group compared with the normally healed flat scar group (p = 0.004), suggesting reduced cell survival and increased apoptotic cell death in a subpopulation of keloid fibroblasts. Furthermore, the number of TUNEL-positive cells was significantly higher for the keloid group compared with the dermatofibroma group (p = 0.044), suggesting that a subpopulation of keloid fibroblasts may suppress tumorgenicity at a greater rate than dermatofibroma by undergoing cell death. Hypertrophic scars had significantly higher levels of apoptosis than normally healed flat scars (p = 0.033). Therefore, these results suggest that selected fibroblasts in keloids and hypertrophic scars undergo apoptosis, which may play a role in the process of pathological scarring.     

Structure and correlates of alcohol dependence in clinical samples in the United States and Russia

Using items from the Composite International Diagnostic Interview, dimensionality of the alcohol dependence syndrome was assessed in clinical samples in the United States and Russia. In both groups, a single-factor model provided a high degree of goodness of fit thus demonstrating cross-cultural coherence of the construct. The item dealing with narrowing of the drinking repertoire is most disparate in each sample. Seventy of alcohol consequences was moderately related to alcohol dependence in both samples. Demographic variables, however, correlated less with severity of consequences. After the effects of severity of dependence and demographics were removed, quantity/frequency of recent alcohol consumption did not contribute to severity of consequences. Country, however, remained a significant, but small, predictor of severity of alcohol consequences.