Platelet deposition on stainless steel, spiral, and braided polylactide stents. A comparative study

Platelets play a key role in (sub)acute thrombotic occlusion after stenting. We examined the possible differences between biodegradable polylactide (PLA) and stainless steel (SS) stents in platelet attachment and morphology after whole blood perfusion. PLA stents of different configurations (spiral/braided) and polycaprolactone-polylactide (PCL-PLA)-coatings, or SS stents were implanted into a PVC tube (? 3.2 mm), with or without precoating of the tube with type-I collagen. PPACK (30 microM)-anticoagulated blood with (3)H-serotonin prelabeled platelets was perfused (flow rate: 30 ml/min, 90 s) over the stents. Platelet deposition was assessed by scintillation counting and morphology by scanning electron microscopy (SEM). To examine coagulation activation, plasma prothrombin fragments (F1 + 2) were measured before and after the perfusion. Protein deposition on PLA/SS stents was assessed at augmented shear forces mimicking coronary flow (rate: 60 ml/min, 60 s) under minimal anticoagulation (PPACK 1 microM). More platelets deposited on PLA stents than on SS stents under all study conditions (p < 0.03). Under anticoagulation (PPACK 30 microM) the generation of F1 + 2 remained unaltered. Under higher flow rate and limited anticoagulation SS stents accumulated 3.27 +/- 0.75 microg and PLA stents 5.25 +/- 1.74 microg of protein (Mean +/- SD, p <0.95). Among all biodegradable stents, the braided PLA stent coated with PCL-PLA-heparin accumulated the fewest platelets (p < 0.02). In SEM, signs of platelet activation on braided heparin-coated PLA stents, when compared with uncoated braided PLA/SS stents, appeared modest. In conclusion, PCL-PLAheparin coating of biodegradable stents may enhance their hemocompatibility, expressed by less platelet deposition. Nevertheless, materials, design, and coating techniques of biodegradable stents must be further developed.     

Abnormal imitation-related cortical activation sequences in Asperger's syndrome

Subjects with Asperger's syndrome (AS) are impaired in social interaction and imitation, but the underlying brain mechanisms are poorly understood. Because the mirror-neuron system (MNS) that matches observed and executed actions has been suggested to play an important role in imitation and in reading of other people's intentions, we assessed MNS functions in 8 adult AS subjects and in 10 healthy control subjects during imitation of still pictures of lip forms. In the control subjects, cortical activation progressed in 30 to 80-millisecond steps from the occipital cortex to the superior temporal sulcus, to the inferior parietal lobe, and to the inferior frontal lobe, and finally, 75 to 90 milliseconds later, to the primary motor cortex of both hemispheres. Similar activation sites were found in AS subjects but with slightly larger scatter. Activation of the inferior frontal lobe was delayed by 45 to 60 milliseconds and activations in the inferior frontal lobe and in the primary motor cortex were weaker than in control subjects. The observed abnormal premotor and motor processing could account for a part of imitation and social impairments in subjects with AS.     

Electrostimulation at sensory level improves function of the upper extremities in children with cerebral palsy: a pilot study

The aim of this study was to evaluate the effect of electrical stimulation (ES) on the function of the upper extremities in children with cerebral palsy (CP). The participants were 12 children (seven females and five males) with spastic hemiplegia (mean age 5 years 7 months, SD 3 years 9 months). Indications were weak wrist dorsiflexion and elbow extension. The ES was given at sensory level (20–40 minutes) on the infraspinatus muscle and on the wrist dorsiflexors during 12 regularly scheduled physical and occupational therapy sessions (during 4–5 weeks). The Goal Attainment Scale, the Zancolli classification of hand function, muscle testing according to Daniels and Worthington, and King hypertonicity scale were used for evaluation. Assessments were made twice before (between 4 weeks) and twice after (between 12 weeks) the stimulation period except the King hypertonicity scale, which was used once before and 3 months after the stimulation period. Active elbow extension, wrist dorsiflexion, and forearm supination with the elbow flexed and extended improved when the results of assessments before ES were compared with those made immediately before (p < 0.001) and three months after (p < 0.01) this treatment. Results of this pilot uncontrolled study suggest that ES at sensory level can be used as an adjunct to physiotherapy and/or occupational therapy in children with spastic hemiplegia. These results will be used as basis for further research.     

Expression of the thioredoxin system in interstitial lung disease

The thioredoxin system containing thioredoxin (Trx) and thioredoxin reductase (TrxR) has profound effects on cell proliferation and protection against exogenous oxidants. The significance of the Trx system in human lung and lung diseases is, however, largely unresolved. Altogether, 66 specimens of human lung were investigated by immunohistochemistry for their expression of Trx and TrxR. The diseases included interstitial pneumonias such as usual interstitial pneumonia (UIP), desquamative interstitial pneumonia (DIP), and UIP associated with collagen vascular diseases (CVD-ILD), and granulomatous diseases such as sarcoidosis and allergic alveolitis. The ultrastructural localization of Trx and TrxR was analysed by immunoelectron microscopy. In healthy lung, Trx and TrxR were expressed in bronchial epithelium and alveolar macrophages. Trx and TrxR were highly concentrated in areas of metaplastic epithelium in UIP and in alveolar macrophages in DIP, though fibrotic areas in UIP were mainly negative. The expression of both enzymes was clearly weaker in CVD-ILD than in UIP. Granulomas of sarcoidosis showed moderate to intense Trx immunoreactivity. Ultrastructurally, Trx and TrxR were expressed diffusely in the cytosolic compartment and plasma membrane of metaplastic type II pneumocytes, macrophages, and bronchial epithelial cells. This study highlights the importance of Trx and TrxR in primary defence in bronchial epithelium, alveolar epithelium, and macrophages in human lung, but also indicates that elevated expression of these proteins may serve as markers of ongoing cell regeneration and inflammation.     

The effects of transdermal estrogen therapy on bone mass and turnover in early postmenopausal smokers: a prospective, controlled study

OBJECTIVE: The purpose of this study was to investigate whether smoking reduces the effects of transdermal estrogen replacement therapy on bone. STUDY DESIGN: One hundred forty-eight women (0.5-5 years after menopause, aged 46-58 years) completed the study. Smokers were assigned randomly to receive either 1.0 mg (n=32 women) or 1.5 mg (n=31 women) of transdermal estradiol in gel daily, and nonsmokers (n=46 women) were assigned to receive 1.0 mg of transdermal estradiol for 2 years. The control group consisted of 17 smokers and 22 nonsmokers. Bone mineral density was measured by dual-energy x-ray absorptiometry. Bone turnover was assessed by measurements of urinary aminoterminal telopeptide of type I collagen and serum aminoterminal propeptide of type I procollagen. RESULTS: Lumbar spine bone mineral density increased similarly in smoking (+3.6%) and nonsmoking (+2.6%) estrogen users (P<.0001 to a decrease of 2.5% in the control group). Femoral neck bone mineral density increased 2.2% to 2.4% in smoking and nonsmoking estrogen users but decreased 0.2% in control subjects (P<.05). Urinary aminoterminal telopeptide of type I collagen decreased similarly in all estrogen-using groups (P<.05 to control group), but serum aminoterminal propeptide of type I procollagen decreased more in smoking than in nonsmoking estrogen users (P=.006). Serum 25-hydroxyvitamin D was 20% lower (P=.004) in smokers than in nonsmokers. CONCLUSION: Transdermal estrogen treatment protects smoking women as effectively as nonsmokers from osteoporosis. Smoking worsens the vitamin D state of postmenopausal women.     

Sex hormone metabolism in prostate cancer cells during transition to an androgen-independent state

The progression of prostate cancer during androgen deprivation therapy is a serious clinical problem. Little is known, however, about the mechanisms behind the transition of the disease to an androgen-independent stage. In the present report, we provide evidence of substantial changes in both estrogen and androgen metabolism during the transition of cultured prostate cancer LNCaP (lymph node carcinoma of the prostate) cells. The results of enzyme activity measurements performed using HPLC suggest that, related to the transition, there exists a remarkable decrease in the oxidative 17 beta-hydroxysteroid dehydrogenase (17HSD) activity, whereas the reductive 17HSD activity seems to increase. Relative quantitative RT-PCR revealed that the decrease in oxidative activity largely coincided with the remarkable decrease in the expression of the HSD17B2 gene. Furthermore, the present data suggest that the observed increasing activity of 17HSD type 7 could lead to the increased intracellular production of 17 beta-estradiol during disease progression. This was supported by the cDNA microarray screening results, which showed a considerable overexpression of several estrogen up-regulated genes in the LNCaP cell line variant that represents progressive prostate cancer. Because 17HSDs critically contribute to the control of bioavailability of active sex steroid hormones locally in the prostate, the observed variation in intraprostatic 17HSD activity might be predicted to be crucially involved in the regulation of growth and function of the organ.     

Treatment of lymphangiomas with OK-432 (Picibanil)

Purpose: To determine the efficacy of OK-432 sclerotherapy in the treatment of lymphangiomas. Methods: The treatment was begun for 14 patients with lymphangioma. The age range of the patients at the time of the first injection was from 10 months to 42 years. Eleven of the lesions involved the head and neck region, two the thorax and one was localized in the extremity. Prior to treatment all patients were investigated with either magnetic resonance imaging, computed tomography, ultrasound or a combination of these modalities. The injections were performed with ultrasound and/or fluoroscopic guidance. Eight patients received OK-432 as first-line treatment; five were treated after surgery and one after medical therapy. On average, 2.2 intracystic injections were performed per patient. Nine of the lesions were macrocystic and five were mixed lesions. Results: Eleven patients showed complete or marked response to the OK-432 sclerotherapy, two patients had moderate shrinkage of their lesions and only one patient showed no response to therapy. Macrocystic lesions showed the best response to therapy. Those patients who received OK-432 as first-line treatment showed complete or marked response. Conclusion: It was found that treatment of lymphangiomas with OK-432 was safe and effective.     

Cortical effects of shifting letter position in letter strings of varying length

Neuroimaging and lesion studies suggest that occipito-temporal brain areas play a necessary role in recognizing a wide variety of objects, be they faces, letters, numbers, or household items. However, many questions remain regarding the details of exactly what kinds of information are processed by the occipito-temporal cortex. Here, we address this question with respect to reading. Ten healthy adult subjects performed a single word reading task. We used whole-head magnetoencephalography to measure the spatio-temporal dynamics of brain responses, and investigated their sensitivity to: (1) lexicality (defined here as the difference between words and consonant strings), (2) word length, and (3) variation in letter position. Analysis revealed that midline occipital activity around 100 msec, consistent with low-level visual feature analysis, was insensitive to lexicality and variation in letter position, but was slightly affected by string length. Bilateral occipito-temporal activations around 150 msec were insensitive to lexicality and reacted to word length only in the timing (and not strength) of activation. However, vertical shifts in letter position revealed a hemispheric imbalance: The right hemisphere activation increased with the shifts, whereas the opposite pattern was evident in the left hemisphere. The results are discussed in the light of Caramazza and Hillis's (1990) model of early reading.     

Hemispheric balance in processing attended and non-attended vowels and complex tones

We compared cortical processing of attended and non-attended vowels and complex tones, using a whole-head neuromagnetometer, to test for possible hemispheric differences. Stimuli included vowels [a] and [i], spoken by two female Finnish speakers, and two complex tones, each with two pure tone components corresponding to the first and second formant frequencies (F1-F2) of the vowels spoken by speaker 1. Sequences including both vowels and complex tones were presented to eight Finnish males during passive and active (phoneme/speaker/complex tone identification) listening. Sequences including only vowels were presented to five of the subjects during passive listening and during a phoneme identification task. The vowel [i] spoken by speaker 1 and the corresponding complex tone were frequent, non-target stimuli. Responses evoked by these frequent stimuli were analyzed. Cortical activation at approximately 100 ms was stronger for the complex tone than the vowel in the right hemisphere (RH). Responses were similar during active and passive listening. Hemispheric balance remained the same when the vowel was presented in sequences including only vowels. The reduction of RH activation for vowels as compared with complex tones indicates a relative increase of left hemisphere involvement, possibly reflecting a shift towards more language-specific processing.     

Chromatin condensation during glutamate-induced excitotoxicity of cerebellar [correction of celebellar] granule neurons precedes disintegration of nuclear DNA into high molecular weight DNA fragments

The disturbance of the intracellular ionic homeostasis after activation of channel-associated membrane receptors by the excitatory neurotransmitters represents a principle event that triggers excitotoxic cell death of neurons. Here we demonstrate that glutamate-induced excitotoxicity of cerebellar granule neurons was accompanied by apoptosis-like nuclear shrinkage, chromatin condensation, and disintegration of nuclear DNA into high molecular weight DNA fragments, but was neither associated with activation of caspase 1, -2, -3, -9, nor was protected by a pan-caspase inhibitor, zVAD-fmk. We further demonstrate that chromatin condensation took place at the early stages of excitotoxicity and preceded nuclear DNA fragmentation. The results suggest that fragmentation of nuclear DNA and condensation of chromatin are uncoupled events during neuronal cell death