Comparative study of lignins isolated from Alfa grass (Stipa tenacissima L.).

Soda lignin, dioxane lignin and milled lignin were isolated from Alfa grass (Stipatenacissima L.). The physico-chemical characterization of three different lignins: one industrial lignin precipitated from soda spent liquor and two lignin preparations isolated under laboratory conditions from Alfa grass (also know as Esparto grass) was performed. The structures of lignins were studied by three non-destructive (FT-IR, solid state (13)C NMR and UV/visible spectroscopy) and two destructive (nitrobenzene oxidation and thermogravimetric analysis) methods. Elemental analysis and the methoxyl content determination were performed in order to determine the C(9) formulae for the studied lignins. The total antioxidant capacity of the studied lignins has been determined and compared to commercial antioxidants commonly used in thermoplastic industry.

[Diabetic coma and hypoglycemia in children. What to do when in an emergency]. / Diabetes-komplikationen bei Kindern. Nach dem Fussballspiel: Insulinbedarf falsch eingeschätzt.

With a few very rare exceptions, hypoglycemia and diabetic coma almost always occur in patients with diabetes mellitus, and are among the most common emergencies in children. For the emergency physician, it is important, on the basis of a specific history-taking and information from, for example, family members, supplemented by a clinical examination done in the light of knowledge of the typical symptoms of each of the entities, to determine whether hypoglycemia or diabetic coma is presenting. The most important technical examination is the measurement of blood glucose. In the event of hypoglycemia, the first therapeutic measure is the administration of sugar--in the case of a comatose patient via a venous line. The s.c. or i.m. administration of glucagon to achieve short-term improvement might be considered. In the event of a diabetic coma, abundant electrolyte solution is initially needed, followed by i.v. insulin. Referral to hospital is mandatory.

Features of gastritis predisposing to gastric adenoma and early gastric cancer.

BACKGROUND/AIMS: Helicobacter pylori gastritis is a risk factor for the development of gastric cancer. The results of several studies indicate that gastric adenomas, which are considered premalignant lesions, may also be associated with H pylori gastritis. However, it is not clear whether there are different patterns of gastritis in these patients compared with patients with gastric cancer or patients with H pylori gastritis alone. Therefore, this study was designed to investigate the patterns of gastritis in these three groups of patients. METHODS: The histological features of gastric mucosa at a distance from the tumour were analysed prospectively in 118 patients with gastric adenoma (mean age, 71.8; female to male ratio, 6 : 4). In addition, for every patient with H pylori associated gastric adenoma an age and sex matched control patient with either H pylori associated early gastric cancer of the intestinal type or H pylori gastritis only was investigated. RESULTS: Only 60 patients (50.9%) with gastric adenoma were infected with H pylori. In the remaining patients, complete atrophic gastritis predominated. In those patients with adenoma and H pylori infection, the gastritis was similar to that seen in patients with early gastric cancer (median score, 2 for activity and degree of gastritis in the antrum and corpus); intestinal metaplasia was common to both groups. These two groups differed significantly from patients with H pylori gastritis only (median grade and activity of gastritis, 1 in antrum and corpus), in whom intestinal metaplasia was rare. CONCLUSIONS: It appears that gastric adenomas and gastric intestinal cancer arise by analogous mechanisms. However, owing to severe atrophic gastritis and a lower incidence of H pylori, adenomas do not appear to be definite precursor lesions for gastric cancer.

Chest sonography in the diagnosis of pulmonary embolism: a comparison with MRI angiography and ventilation perfusion scintigraphy.

AIM: To compare the diagnostic performance of chest sonography, MRI angiography and ventilation/perfusion intigraphy in pulmonary embolism (PE). METHOD: In a prospective clinical study, 55 patients (41 women, 14 men, age 23 - 91 years) with clinical signs of PE were investigated within 48 hours of the onset of symptoms. The final diagnosis was made by MRI angiography (reference method). RESULTS: PE was diagnosed in a total of 36 patients. Chest sonography revealed rounded or wedge-shaped hypoechoic lesions in 30 patients. On ventilation/perfusion (V/P) scintigraphy, 41 patients had positive V/P scans, but only 23 were of high probability. Chest ultrasound had a positive predictive value of 97 % to diagnose PE. The sensitivity, specificity, the negative predictive value and accuracy were 81 %, 84 %, 84 % and 82 %, respectively. As 18 patients had inconclusive scans, the diagnostic performance of ventilation/perfusion scintigraphy was poor. The positive predictive value, sensitivity and specificity were 58 %, 42 % and 91 %, respectively. Patients in whom PE was excluded mainly suffered from congestive heart failure, bronchopulmonary infections or pulmonary hypertension. CONCLUSION: A negative sonographic study cannot rule out PE with certainty. However, a chest sonography is of acceptable diagnostic value in patients with suspected PE and may be used as an adjunct or guide to more established methods.

Autonomic failure after stroke--is it indicative for pathophysiology of complex regional pain syndrome?

In order to find pieces of evidence for a central origin of autonomic failure in complex regional pain syndrome I (CRPS I), the pattern of autonomic symptoms in CRPS I patients was compared to patients a few days after stroke. Autonomic failure in the latter group is assumed to represent definite CNS origin. Seventeen stroke patients, 21 patients in the acute and late stage of CRPS I and a control group of 23 healthy subjects were investigated. Detailed neurological examination was performed, sweating was induced centrally (thermoregulatory sweating, TST) and peripherally by carbachol iontophoresis (QSART) and quantified by evaporation hygrometry. Skin temperature was assessed by infrared thermography. The incidence of motor-sensory dysfunction (without pain) and the incidence of edema was strikingly similar in stroke and CRPS patients. Furthermore, stroke patients had increased TST but not QSART responses on the contralesional limb (P < 0.05) and skin temperature was decreased (P < 0.001). The same pattern of autonomic failure was found in late CRPS (TST: P < 0.02, skin temperature: P < 0.01) whereas in acute CRPS additional, presumably peripheral mechanisms, contribute to sympathetic symptoms. In conclusion, our investigation suggests that many clinical symptoms and the main features of sympathetic dysfunction in CRPS could be explained by a CNS pathophysiology.

Discovery of a new class of p38 kinase inhibitors.

The MAP kinase p38 has been implicated in cytokine signaling, and its inhibitors are potentially useful for the treatment of arthritis and osteoporosis. Novel small-molecule inhibitors of p38 kinase were derived from a combinatorial chemistry effort and exhibit activity in the nanomolar range. Very steep structure-activity relationships are observed within this class.

1-Phenyl-5-pyrazolyl ureas: potent and selective p38 kinase inhibitors.

Inhibitors of the MAP kinase p38 are potentially useful for the treatment of arthritis and osteoporosis. Several 2,3-dichlorophenyl ureas were identified as small-molecule inhibitors of p38 by a combinatorial chemistry effort. Optimization for cellular potency led to the discovery of a new class of potent and selective p38 kinase inhibitors, exemplified by the 1-phenyl-5-pyrazolyl urea 7 (IC50 = 13 nM).

Experimental tissue acidosis leads to increased pain in complex regional pain syndrome (CRPS).

The aim of this study was to investigate the role of local acidosis in the generation of pain in complex regional pain syndrome (CRPS). We investigated ten patients with CRPS of the upper extremity with a mean duration of the disease of 43 weeks (range 4-280 weeks) and ten control subjects for sensitivity to infusion of fluids with low pH (pH 6.1). Another group of five CRPS patients and three healthy controls was investigated using the same protocol but neutral infusion fluid (pH 7.4). A motorized syringe pump was installed for a constant infusion of synthetic interstitial fluid (SIF, either acidified (pH 6.1) or neutral) into the skin at the back of the hands and, thereafter, into the interosseus I muscle on both sides. A flow rate of 30 ml/h was chosen for intradermal and 7.5 ml/h for intramuscular infusion over a period of 10 min. The magnitude of pain was rated on an electronic visual analogue scale. Patients were requested to give their ratings every 10 s during the whole stimulation period. The ratings were normalized as fractions of individual grand mean values. We found significantly increased pain perception during infusion of acidified SIF on the affected side in CRPS patients. Low pH fluid into the skin was significantly more painful between 4 and 6 min (ipsi 1.27 normalized rating (NR) (0. 19-1.94), contra 0.31 NR (0.03-0.51), P<0.02) and between 8 and 10 min (ipsi 1.38 NR (0.19-1.94), contra 0.08 NR (0-0.27), P<0.03) on the affected side, while analysis over the whole stimulation period just failed to reach statistical significance (ipsi 281 area under the curve (AUC) (187-834), contra 87 AUC (28-293), P=0.059). Low pH infusion into the muscle was significantly more painful on the affected side during the whole infusion time (ipsi 861 AUC (308-1377), contra 190 AUC (96-528), P<0.01). The quality of the deep pain during infusion into the muscle was described by the patients as very similar to the CRPS-related pain. In controls we found no side differences of pain intensity during low pH stimulation. Neutral SIF evoked no pain at all, neither in CRPS patients (ipsi 0 AUC, contra 0 AUC) nor in healthy controls. Our results suggest that hyperalgesia to protons is present in patients with CRPS. Further, we could demonstrate that pain is not only restricted to the skin but is also generated in deep somatic tissue of the affected limb.

Neurological findings in complex regional pain syndromes--analysis of 145 cases.

Early diagnosis is a prerequisite for a successful treatment of complex regional pain syndrome (CRPS). In order to describe neurological symptoms which characterize CRPS, we evaluated 145 patients prospectively. Two-thirds of these were women, the mean age at time of investigation was 50.4 years. CRPS followed limb trauma, surgery and nerve lesion. Employing the current IASP criteria 122 patients were classified as CRPS I and 23 as CRPS II. All patients were assessed clinically pain was quantified using the McGill pain questionnaire, skin temperature was measured by an infrared thermometer and a subgroup of 57 patients was retested in order to determine thermal thresholds (QST). Of our patients 42% reported stressful life events in a close relationship to the onset of CRPS and 41% had a history of chronic pain before CRPS. The latter group of patients gave a higher rating of CRPS pain (P<0.05). The major symptoms were pain at rest in 77% and hyperalgesia in 94%. Typical pain was deep in the limb having a tearing character. Patients getting physical therapy had significantly less pain than those without (P<0.04). Autonomic signs were frequent (98%) and often changed with the duration of CRPS. Skin temperature was warmer in acute and colder in chronic stages (P<0.001). Likewise edema had a higher incidence in acute stages (P<0.001). We found no correlation between pain and autonomic dysfunction. Motor dysfunction (present in 97%) included weakness, tremor, exaggerated tendon reflexes, dystonia or myoclonic jerks. QST revealed increased warm perception thresholds (P<0.02) and decreased cold pain thresholds (P<0.03) of the affected limb. The detailed knowledge of clinical features of CRPS could help physicians early to recognize the disease and thus to improve therapy outcome.

Synthesis and cytostatic activities of didemnin derivatives.

The highly cytostatic didemnins contain a 23-membered cyclopeptolide with a side chain attached to the backbone through the amine group of threonine. Thirty-six derivatives varying the side chain were prepared, but only compounds with D-MeLeu attached to threonine show remarkable biological activities. To protect the macrocycle from degradation by lipases the two ester bonds were replaced successively by amide bonds. Although these variations have a major effect on the conformation and rigidity of the ring, the compound which contains exclusively amide bonds is highly active, equivalent to acetyl-didemnin A.

[The assessment of sudomotor function for diagnosis of autonomic diseases. Principles and methods]. / Die Schweissmessung zur Diagnostik autonomer Störungen. Grundlagen und Methoden.

Thermoregulatory and emotional sweating can be distinguished in humans. While the first is organized via feed back mechanisms involving thermoreceptors, thermoregulatory centers in the brain and the effector system (sympathetic nervous system and sweat glands), the latter is generated directly by cortical and limbic mechanisms without any feed back. Sweat glands on the hairy skin can be stimulated by thermoregulatory mechanisms (rising body temperature), the emotional sweating on the glabrous skin as a result of an arousal reaction and they can be stimulated by peripheral acting cholinergic agents, which initiate direct or axon reflex mediated sweating. To evaluate sweating there are qualitative methods that visualize the sweat response or indirect methods like the registration of skin potentials. Alternatively sweat output can be quantified by evaporative measurement. For best results these methods should be combined. In this way autonomic dysfunction e.g. after nerve lesions, in polyneuropathies, central lesions and certain pain disorders can be assessed. The sudomotor function tests complete the conventional electrophysiological methods.

[Complex regional pain syndrome. Clinical and autonomic disorders during acute and chronic illness stages]. / Komplexes regionales Schmerzsyndrom. Klinik und autonome Störung während akuter und chronischer Krankheitsstadien.

In order to describe autonomic dysfunction and clinical outcome in complex regional pain syndrome (CRPS) 20 patients were followed-up. First investigation was performed in the acute stage of CRPS and the second investigation two years later after therapy (individual, not standardized). Skin temperature and sudomotor function (thermoregulatory sweating (TST) and quantitative sudomotor axon reflex (QSART)) were assessed, and a clinical follow-up was performed carefully. Skin temperature was warmer on the affected side at first investigation (p < 0.001) and colder at follow-up (p < 0.02). Sudomotor output was enhanced on the affected side both after TST (p < 0.005) and QSART (p < 0.05) at first investigation. At follow-up, however, while thermoregulatory sweating was still increased (p < 0.04) QSART was not different. While autonomic failure improves as assessed by clinical examination, therapy failed to alleviate pain significantly. But patients' self-assesment of therapy was mostly positive (16 of 20, p < 0.001). The present study has shown that the autonomic failure may be probably the result of central disturbances of thermoregulation, but secondary peripheral mechanisms also contribute to our findings. Individual based therapy seems to be efficacious for long term treatment, but for final judge controlled studies are required.

Patterns of hyperalgesia in complex regional pain syndrome.

Complex regional pain syndrome (CRPS) is characterized by a triad of sensory, motor and autonomic dysfunctions, with long-standing pain and temperature differences of the affected and contralateral limb as predominant symptoms. The pathogenesis of the disorder still remains unclear. Among the main hypotheses of an underlying pathophysiology we find inflammatory processes and dysfunction of the sympathetic nervous system. Whether the main site of dysfunction is found centrally or peripherally is not known. With psychophysical methods we studied patterns of hyperalgesia to obtain a better understanding of the neuropathic pain component in CRPS. Forty patients in an acute phase of CRPS and a median duration of the disease of 10 weeks, were included in the study. Hyperalgesia to heat was tested with a thermode providing feedback-controlled temperature increases. Two forms of mechanical hyperalgesia were examined: phasic mechanical stimuli by using a custom-made impact stimulator for the determination of individual pain thresholds, tonic mechanical stimuli were applied using a pinch-device. Additionally a 'wind-up' paradigm was used to study a pain phenomenon of presumed central origin: a defined impact stimulus was given once and five times in repetition. A subpopulation of patients was reevaluated for mechanical hyperalgesia after i.v. injection of 500 mg acetyl-salicylic acid. Hyperalgesia to heat was insignificant. We found, however, a marked mechanical hyperalgesia to phasic impact stimuli (P < 0.005), whereas, static stimulation (squeezing skin folds) results were insignificant again. Wind-up related pain was also significantly enhanced in the affected limb (P < 0.02). The anti-inflammatory agent had no effect. These results indicate a non-inflammatory pathogenesis in CRPS presumably central in origin.

Contribution to the synthesis of aureobasidin A. Synthesis of cyclopeptolides containing the sequence leucyl-N-methyl-beta-hydroxyvalyl-(2R)-oxy-(3R)-methyl-pentanoi c acid.

The efficient antimycotic agent aureobasidin A, isolated from the culture broth of Aureobasidium pullulans R 106, and the [(R)-Pro9]-aureobasidin A were prepared starting from benzyl N-Boc-N-methyl-(S)-beta-triethylsiloxyvalinate, the synthesis of which is described here. The easy accessibility of the tripeptolide benzyl Boc-leucyl-N-methyl-beta-hydroxyvalyl-(2R)-oxy-(3R)-methylpentanoa te [Boc-Leu-HOMeVal-(R)-HMP-OBn] facilitates the construction of the cyclopeptolides 28, 34, 45 and 47. The peptide bonds of the N-methylamino acids were formed with the help of O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophophate. The rings of [(R)-Pro9]-aureobasidin A and of cyclopeptolides 28, 34, 45 and 47 were closed by way of pentafluorophenyl esters. The ring of aureobasidin A could only be formed with bromo-tris-pyrrolidinophosphonium hexafluorophosphate.