How cosmetic tightening products modulate the biomechanics and morphology of human skin.

The active and passive mechanical behavior of a cosmetic tightening product for skin anti-aging is investigated based on a wide range of in vivo and in vitro measurements. The experimental data are used to inform a numerical model of the attained cosmetic effect, which is then implemented in a commercial finite-element framework and used to analyze the mechanisms that regulate the biomechanical interaction between the native tissue and the tightening film. Such a film reduces wrinkles and enhances skin consistency by increasing its stiffness by 48-107% and reducing inelastic, non-recoverable deformations (-47%). The substrate deformability influences both the extent of tightening and the reduction of wrinkle amplitude. The present findings allow, for the first time, to rationalize the mechanisms of action of cosmetic products with a tightening action and provide quantitative evidence for further optimization of this fascinating class of biomaterials.

In peripheral nerve regeneration environment enriched with activity stimulating factors improves functional recovery.

Enriched environment stimulates brain plasticity processes after brain lesion. Less is known about the influence of enriched environment with activity stimulating factors as determinants of functional outcome after peripheral nerve repair. BDNF (brain-derived neurotrophic factor) plays a role in activity-dependent neuronal plasticity and changes in motor cortex in rats learning complex motor skills. Our study aimed to elucidate if enriched environment influences functional results after peripheral nerve repair. The results in this rat sciatic nerve transection and repair model showed that environment enriched with activity stimulating factors can improve functional results.

Nerve regeneration using tubular scaffolds from biodegradable polyurethane.

INTRODUCTION: In severe nerve lesion, nerve defects and in brachial plexus reconstruction, autologous nerve grafting is the golden standard. Although, nerve grafting technique is the best available approach a major disadvantages exists: there is a limited source of autologous nerve grafts. This study presents data on the use of tubular scaffolds with uniaxial pore orientation from experimental biodegradable polyurethanes coated with fibrin sealant to regenerate a 8 mm resected segment of rat sciatic nerve. METHODS: Tubular scaffolds: prepared by extrusion of the polymer solution in DMF into water coagulation bath. The polymer used for the preparation of tubular scaffolds was a biodegradable polyurethane based on hexamethylene diisocyanate, poly(epsilon-caprolactone) and dianhydro-D-sorbitol. EXPERIMENTAL MODEL: Eighteen Sprague Dawley rats underwent mid-thigh sciatic nerve transection and were randomly assigned to two experimental groups with immediate repair: (1) tubular scaffold, (2) 180 degrees rotated sciatic nerve segment (control). Serial functional measurements (toe spread test, placing tests) were performed weekly from 3rd to 12th week after nerve repair. On week 12, electrophysiological assessment was performed. Sciatic nerve and scaffold/nerve grafts were harvested for histomorphometric analysis. Collagenic connective tissue, Schwann cells and axons were evaluated in the proximal nerve stump, the scaffold/nerve graft and the distal nerve stump. The implants have uniaxially-oriented pore structure with a pore size in the range of 2 micorm (the pore wall) and 75 x 700 microm (elongated pores in the implant lumen). The skin of the tubular implants was nonporous. Animals which underwent repair with tubular scaffolds of biodegradable polyurethanes coated with diluted fibrin sealant had no significant functional differences compared with the nerve graft group. Control group resulted in a trend-wise better electrophysiological recovery but did not show statistically significant differences. There was a higher level of collagenic connective tissue within the scaffold and within the distal nerve stump. Schwann cells migrated into the polyurethane scaffold. There was no statistical difference to the nerve graft group although Schwann cell counts were lower especially within the middle of the polyurethane scaffold. Axon counts showed a trend-wise decrease within the scaffold. CONCLUSION: These results suggest that biodegradable polyurethane tubular scaffolds coated with diluted fibrin sealant support peripheral nerve regeneration in a standard gap model in the rat up to 3 months. Three months after surgery no sign of degradation could be seen.

Synergistic terminal motor end-to-side nerve graft repair: investigation in a non-human primate model.

End-to-side nerve repair has re-emerged in the literature in recent years but clinical applications for this technique are not yet fully defined and clinical reports are rare and controversial. Hypothetically, there might be useful functional results performing peripheral end-to-side nerve graft repair using synergistic terminal branches with defined motor function. An end-to-side nerve graft repair bridging from the terminal motor branch of deep branch of the ulnar nerve to the thenar motor branch of the median nerve was performed in non-human primates. The results in this non-human primate model demonstrate the efficacy of end-to-side nerve graft repair at the level of peripheral terminal motor branches. End-to-side neurorrhaphy may present a viable alternative in conditions of unsuitable end-to-end coaptation and inappropriate nerve grafting procedures.

Enhanced sensory re-learning after nerve repair using 3D audio-visual signals and kinaesthesia--preliminary results.

Sensory re-learning methods and basics on cortical reorganization after peripheral nerve lesion are well documented. The aim of enhanced sensory re-learning using 3D audio-visual signals and kinaesthetic training is the augmentation of cognitive memory (visual and acoustic sensory memory) and cognitive function for the improvement of cerebral plasticity processes and starts as soon as possible after nerve repair. Preliminary results are shown.

Experimental and theoretical analyses of the age-dependent large-strain behavior of Sylgard 184 (10:1) silicone elastomer.

The commercial polydimethysiloxane elastomer Sylgard(®) 184 with mixing ratio 10:1 is in wide use for biomedical research or fundamental studies of mechanobiology. In this paper, a comprehensive study of the large strain mechanical behavior of this material under multiaxial monotonic and cyclic loads, and its change during the first 26 days after preparation is reported. The equibiaxial stress response studied in inflation experiments reveals a much stiffer and more nonlinear response compared to the uniaxial and pure shear characteristics. The polymer revealed remarkably elastic behavior, in particular, very little dependence on strain rates between 0.3%/s and 11%/s, and on the strain history in cyclic experiments. On the other hand, both the small-strain and large strain nonlinear mechanical characteristics of the elastomer are changing with sample age and the results suggest that this process has not ceased after 26 days. A recent re-interpretation of the well-known Ogden model for incompressible rubber-like materials was applied to rationalize the results and accurate agreement was obtained with the experimental data over all testing configurations and testing times. The change of a single parameter in this model is shown to govern the evolution of the nonlinear material characteristics with sample age, attributed to a continuation of the cross-linking process. Based on a kinetic relation to account for this process over time, the model provided successful predictions of the material behavior even after more than one year.

Cardiovascular effects, pharmacokinetics, and converting enzyme inhibition of enalapril after morning versus evening administration.

The cardiovascular effects and pharmacokinetics of once-daily enalapril were studied after single-dose and subchronic treatment in eight patients with hypertension by use of ambulatory blood pressure monitoring. Enalapril, 10 mg, was given at either 7 AM or 7 PM in a randomized crossover design. In addition, inhibition of serum converting enzyme was studied. Subchronic treatment at 7 AM significantly reduced blood pressure during the day but was less effective at night. Subchronic dosing at 7 PM significantly further decreased nighttime blood pressure followed by a slow increase during the day, with no effect on elevated afternoon values. Peak concentrations of enalaprilat were found 3.5 hours (morning) and 5.6 hours (evening) after drug intake (p < 0.05), whereas peak effects occurred 7.4 hours (morning) and 12 hours (evening) after drug administration. In conclusion, 24-hour blood pressure profiles in patients with hypertension were significantly influenced by the time of enalapril dosing. Differences in effect profiles could not be attributed to similar changes in pharmacokinetics or to different time courses of angiotensin converting enzyme inhibition.

Ambulatory blood pressure profiles in essential hypertensives after treatment with a new once daily nifedipine formulation.

The antihypertensive efficacy of a new controlled-release preparation of nifedipine developed for once daily administration was investigated in comparison with a standard therapy with sustained-release nifedipine given twice daily in a randomised, open crossover trial. Twenty-two patients with mild to moderate essential hypertension were enrolled. Ambulatory blood pressure monitoring (ABPM) was performed after a wash-out period and after a 3 weeks treatment with 40 mg controlled-release nifedipine once daily and 20 mg sustained-release nifedipine twice daily, respectively. ABPM data were evaluated by conventional linear analysis and by rhythm analysis. Both once daily and twice daily administration of nifedipine significantly reduced systolic blood pressure during the daytime and during the night when compared with baseline. The 24-h diastolic blood pressure was significantly decreased by both treatments, but only the once daily regimen significantly lowered both diastolic daytime and night-time means. Comparing systolic and diastolic blood pressures after both treatments, however, no significant differences were obtained. Both nifedipine treatments did neither greatly modify the circadian blood pressure pattern nor reflexly increase heart rate. In conclusion, once daily application of the controlled-release formulation of nifedipine resulted in a consistent and significant blood pressure reduction. Once daily and twice daily medications of nifedipine were about equally effective in lowering the elevated blood pressures.

Convulsive seizures following subdural application of fibrin sealant containing tranexamic acid in a rat model.

OBJECTIVES: Tranexamic acid (t-AMCA) has been shown to cause severe convulsions in humans and cats when applied topically to the central nervous system. We wanted to determine whether pure t-AMCA or fibrin sealant (FS) containing t-AMCA would induce similar effects when applied to the spinal cord in a rat model. METHODS: Following low-thoracic laminectomy, the dura was incised to expose the dorsal surface of the lumbar enlargement. Rats were allocated to one of the following treatments: 1) t-AMCA (10 mg/ml), 2) vehicle (phosphate buffered saline), 3) FS containing t-AMCA, 4) FS containing aprotinin. The response of the rats was evaluated based on neurological and behavioral observations. Additionally, motor function was scored in the rats that had received FS. RESULTS: Application of either 10 mg/ml t-AMCA or FS containing t-AMCA caused severe hind limb spasms that developed into spontaneous generalized convulsions. Two of the three rats that had received FS containing t-AMCA died of respiratory failure. In contrast, application of vehicle or FS containing aprotinin did not cause any abnormal conditions of the animals. CONCLUSION: Tranexamic acid may cause severe complications when used in the central nervous system. Thus, fibrin sealants containing t-AMCA should not be used in neurosurgery.

[Radiological heart volume determination--a new method carried out in the sitting position (author's transl)]. / Röntgenologische Herzvolumenbestimmung. Beschreibung einer neuen Methode mit Durchführung im Sitzen.

A method is described for the determination of cardiac volume with the subject in a sitting position. The results correspond with those of other accepted methods, but there are several significant advantages: 1. The position is easily maintained by the subject and the method is therefore acceptable for patients with cardiac disease. 2. The risks connected with a Valsalva effect are reduced. 3. There is no need to change the position of the x-ray tube during the examination. 4. Contrary to the traditional technique, the x-ray room does not require a very high ceiling. 5. Because of even blood distribution, the cardiac volume determinations also provide information regarding the lungs.

A noninvasive functional evaluation following peripheral nerve repair with electromyography in a rat model.

A new bipolar surface electrode array was designed and constructed for a noninvasive "closed" functional evaluation with electromyography following sciatic nerve transection in a rat model. This "closed" method was compared with a conventional one-shot "open" measurement. Nerve conduction velocity and distal latency were calculated. Data obtained from the recordings from different animals as well as from the same animal at different points in time yielded excellent reproducibilities. There is no difference in the mean values whether nerve conduction velocity and distal latency are obtained by "closed" or "open" measurements. Correlation was significant (p < 0.01; rNCV = 0.77, rDL = 0.63) between these two methods. The results lead to the conclusion that the noninvasive functional evaluation with the parameters of nerve conduction velocity and distal latency introduced in the present study could be employed as a reliable method for serial functional evaluations following nerve transection in a long-term study in a rat model.

Persisting effect of Ca(2+)-channel blockers on left ventricular function in hypertrophic cardiomyopathy after 14 years' treatment.

Ca(2+)-channel blockers of the verapamil type have been reported to exert a beneficial effect on clinical symptoms and survival rates in hypertrophic cardiomyopathy. The effects of verapamil have been attributed predominantly to an improved diastolic filling. It is unknown whether an effect on diastolic filling persists in these patients after long-term treatment. Fourteen patients (12 men, 2 women, median age fifty-one [thirty-two to fifty-five] years) with hypertrophic cardiomyopathy were included in the study. Patients had been treated with verapamil 240-480 mg/d or gallopamil 150-200 mg/d for fourteen (seven to seventeen) years. The effect of a withdrawal of Ca(2+)-channel blockers on parameters of left ventricular diastolic function was evaluated at rest and during exercise in patients with hypertrophic cardiomyopathy after long-term therapy. Investigations were performed at rest and during supine ergometric exercise during ongoing Ca(2+)-channel blocking therapy and after five (four to nine) days' withdrawal (control). Pulsed Doppler echocardiography was used to record diastolic mitral flow profiles from an apical four-chamber view. Withdrawal of Ca(2+)-channel blockers of the phenylalkylamine type after long-term treatment of hypertrophic cardiomyopathy resulted in a significant reduction of early diastolic inflow velocity at rest and during exercise. In conclusion, these results indicate a persistent improvement of early diastolic filling by Ca(2+)-channel blockers even after long-term treatment.

[Piretanide in chronic and acute decompensated heart failure. Effect on hemodynamics and vasoactive hormones]. / Piretanid bei chronischer und akut dekompensierter Herzinsuffizienz. Einfluss auf Hämodynamik und vasoaktive Hormone.

Eight patients with chronic heart failure classified as NYHA class II to III (group 1) and nine patients with acute decompensated heart failure classified as NYHA class IV (group 2) were treated with piretanide at a dosage of 12 mg administered intravenously. In both groups the level of prostaglandine PGE2 as well as plasma renine activity significantly increased prior to the onset of diuresis. The percentage increase was more pronounced in group 1 which had lower baseline values. With a time-lag, the norepinephrine plasma level also increased significantly. During the first 30 minutes there was only little effect on blood pressure, pulmonary artery pressure and cardiac output in patients with chronic heart failure (group 1). Only after 60 minutes there was a significant decrease in mean pulmonary artery pressure (from 39 +/- 17 to 33 +/- 18 mm Hg; p less than 0.05). In patients with acute decompensated heart failure (group 2) piretanide led to a significant reduction in mean pulmonary artery pressure (from 42 +/- 13 to 37 +/- 12 mm Hg; p less than 0.05) within 15 minutes after administration, i.e. even prior to the onset of diuresis. Thus, the administration of piretanide had a positive effect on hemodynamics in patients with chronic as well as in patients with acute decompensated heart failure. Significant improvement prior to diuresis onset, however, was only found in patients with acute decompensated heart failure. These effects may be explained by a stimulation of prostaglandines which promote vasodilation. They are increased by the diuresis.(ABSTRACT TRUNCATED AT 250 WORDS)

[Disturbed sleep caused by sleep apnea. To the sleep laboratory for diagnosis?]. / Gestörte Nachtruhe durch Schlafapnoe. Zur Diagnostik ins Schlaflabor?

Since it was shown that numerous neurological, psychiatric and internal illnesses have characteristics manifested during, or influenced by sleep, somnology has been playing a clinically more and more important role. Among the 88 diagnoses listed by ICD, not only insomnia, but also sleep-related respiratory disorders, in particular the obstructive sleep apnea syndrome, are of special importance. Sleep apnea is associated with coronary heart disease, myocardial insufficiency and other pathological conditions. Already in the doctor's office, a carefully taken history (nocturnal apnea alternating with irregular snoring, and diurnal sleepiness) can arouse an appropriate suspicion. This can be confirmed by an ambulatory polygraphic exploration. The definitive diagnosis is then established with the aid of polysomnography in the sleep lab where specific treatment is also initiated.

NON-activated protein C as post-treatment after spinal cord compression injury in rats.

BACKGROUND: Neuroprotective effects of recombinant human activated Protein C (rhAPC) in models of Spinal Cord Injury (SCI) and ischemic stroke have been reported in rodents. To rule out immunogenicity of rhAPC and to possibly maintain the physiological PC/thrombin balance the use of zymogen PC in SCI might be preferable. Although activation of Protein C (PC) has been demonstrated in rats, the efficacy and drug safety of NON activated PC has not been previously tested in experimental SCI. METHODS: Twelve rats were subjected to 40 g compression of the spinal cord at TH11 for 20 minutes and randomly allocated to either the NON activated PC (25 IU/kg) or the Placebo group (saline).Results. 25 IU treatment yielded improved recovery from SCI compared to placebo and the triple fold dose of PC (75 IU/kg) was subsequently tested to detect treatment associated complications (TAC). Treatment was administered as a single shot via the right vena jugularis forty minutes after onset of compression. The observation period was 5 weeks in 25 IU treated and 1 week in the 75 IU treated rats. Improvement of motor function recovery was measured with behaviour tests and electrophysiology. FINDINGS: Single shot treatment with 25 IU/kg of NON activated PC led to improved recovery in terms of behaviour and electrophysiology. TACs neither occurred in the 25 IU nor in the 75 IU group within one week. CONCLUSION: NON activated PC is a potent and safe drug in experimental SCI and should be considered for treatment in neurotrauma.

Effects of nifedipine and propranolol combined therapy in patients with hypertrophic cardiomyopathy.

Fifteen (14 male and one female) patients with hypertrophic cardiomyopathy, ranging from 22 to 67 (mean: 45.5) years of age were treated with oral nifedipine and propranolol for 6 to 24 (mean:18) months. Twelve of the patients had been pretreated with a mean oral dose of 560 mg verapamil for 60 up to 93 (mean: 78.5) months, showing slight subjective and objective improvement. Treatment with nifedipine-propranolol was terminated in five cases due to deterioration or side effects after 6 and 12 months, respectively. During combined therapy, two patients reported subjective improvement, but in five cases there was no change and eight patients reported deterioration. The mean Sokolow-index showed no change. The radiologically determined heart volume increased in 11/15 patients and significantly in the mean of all patients from 887 +/- 239 to 947 +/- 246 ml/m2. In addition, echocardiographic measurements showed a significant increase in left atrial diameter from 40.0 +/- 9 to 42.1 +/- 9 mm, whereas ventricular wall thickness remained unchanged. Thus, high dose verapamil therapy seems superior to nifedipine-propranolol therapy in most patients with hypertrophic cardiomyopathy.

10-year results and survival of patients with hypertrophic cardiomyopathy treated with calcium antagonists.

Hypertrophic cardiomyopathy is characterized by progredient myocardial hypertrophy causing ventricular systolic and diastolic dysfunction. Long-term results of beta-blocker therapy have been disappointing. Neither the impaired ventricular filling or the prognosis are improved. In contrast, calcium antagonists mainly influence diastolic ventricular dynamics, but also have beneficial effects on systolic function. The results of long-term therapy with calcium antagonists, including patients treated for more than 10 years, are presented here. A total of 84 consecutive patients (mean age 43 years; 20 female and 64 male) with confirmed hypertrophic cardiomyopathy were treated with high doses of calcium antagonists (mean doses of 515 mg verapamil or 158 mg gallopamil per day). In the course of therapy with a mean duration of 52 months, heart size--assessed by X-ray technique--and Sokolow-index in the ECG decreased significantly (heart volume: from 947 to 885 ml/1.73 m2 body surface; Sokolow-index: from 5.0 to 4.5 mV). The echocardiogram showed a significant decrease in left atrial diameter, whereas wall thickness only tended to decrease. Hemodynamic control investigations confirmed an improvement in systolic as well as in diastolic ventricular function (mean follow-up period was 31 months). According to these findings the condition and stress tolerance improved in 84% of the patients. Therapy with calcium antagonists also improved prognosis: without treatment or following treatment with beta-blocking agents, annual mortality is approximately 3.5%, whereas in the described patient population mortality dropped to less than 2%. Thus, a calcium antagonist is the medication of first choice for patients with hypertrophic cardiomyopathy.

Management of hypertrophic cardiomyopathy.

Therapy of hypertrophic cardiomyopathy aspires to reduce symptoms, increase exercise tolerance, retard or prevent disease progression, and improve prognosis. Medical treatment with calcium antagonists and suppression of rhythm disturbances with amiodarone seem to be most effective. In patients who show no improvement, surgical treatment must be considered.