Melatonin and aging: relevance for clinical approach?
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Action Potentials↗
Biomedical subjects
H Hoffmann
Publications and source records attributed to H Hoffmann.
Formation and Properties of Lamellar Phases in Systems of Cationic Surfactants and Hydroxy-Naphthoate.
We investigated the phase behavior and the phase transitions in aqueous solutions of 100 mM cetyltrimethylammonium hydroxide (CTAOH) with 3-hydroxy-2-naphthoic acid (HNC) and of 100 mM cetyltrimethylammonium bromide (CTAB) with sodium-3-hydroxy-2-naphthoate (SHNC). The naphthoate/surfactant ratio has been varied. As previously observed by the groups of C. Manohar and J. Candau we observed for the second system two viscoelastic gel-like regions, two liquid crystalline regions, and a precipitate region. For the CTAOH/HNC system one finds with increasing concentration of HNC a low viscous solution, a viscoelastic gel, and a viscoelastic liquid crystalline Lalpha-phase. In both surfactant systems the lamellar phase is formed around an equimolar ratio of cationic surfactant and naphthoate. The lamellar phases have been examined by polarization microscopy and freeze-fracture electron microscopy. The Lalpha-phase in the system CTAOH/HNC consists of densely packed multilamellar vesicles while the lamellar phase in the system CTAB/SHNC contains vesicles, as well as stacked bilayers and tubuli. Corresponding to their different microstructures the lamellar phases in the system, CTAOH/HNC and CTAB/SHNC have different rheological properties. The vesicular phase is highly viscoelastic and has a yield stress value while the bilayer phase has a much lower viscosity and no yield stress value. The transition from the micellar to the vesicle phase occurs for CTAOH/HNC over a two-phase region, where micelles and vesicles coexist. In the case of CTAB/SHNC the transition from the micellar to the lamellar phase occurs over a three-phase region, where a surfactant-poor phase coexists with a lamellar and a coacervate phase. In mixtures of CTAB and SHNC a thick precipitate is formed at an equimolar ratio of CTAB and SHNC. This precipitate consists of condensed multilamellar vesicles that contain little water and stick together, as the vesicles collapse due to the shielding of the repulsive forces by NaBr from an unbinding to a binding state. The precipitate can be retransformed to a swollen lamellar phase by charging the vesicles with an excess of ionic surfactant, by adding electrolyte in high concentrations, or by increasing the temperature. As predicted by C. Manohar et al. the vesicle phases show a phase transition at a critical temperature Tc of 46 degreesC. This transition was detected by us for the first time by DSC and by conductivity measurements. It occurs within a narrow temperature range of 2-3 degrees with an enthalpy change of 0.5 kJ/mol. The transition is observed both in the swollen and in the precipitated vesicle phase. It is well separated from the vesicle/rod transition at higher temperatures (>70 degreesC) and the liquid crystalline/crystalline transition at lower temperatures (25-30 degreesC) that has a melting enthalpy of 55 kJ/mol. It is conceivable that the observed transition at 46 degreesC is due to the melting of a two-dimensional solid-like lattice of the HNC-counterions on the vesicle interface. Copyright 1998 Academic Press.
Journal Article↗
Structural Changes in the Isotropic Phase of the Ternary Surfactant System: Tetradecyldimethylamine Oxide/Benzyl Alcohol/Water.
The surfactant system tetradecyldimethylamine oxide (TDMAO)/benzyl alcohol/water has been studied. In the phase diagram of this ternary system a large isotropic region is encountered that connects the water corner to the benzyl alcohol corner. This isotropic phase has been investigated in some detail by means of electric conductivity, viscosity, electric birefringence, and small-angle neutron scattering (SANS) measurements. From these experiments it can be concluded that for roughly equal amounts of alcohol and water a bicontinuous structure is present, similar to that typically observed for bicontinuous microemulsions. The structural units present become continuously smaller with increasing alcohol content, and at very high alcohol content only small reverse aggregates are present. The formation of this bicontinuous phase can be understood by the fact that the presence of the benzyl alcohol reduces the stiffness of the surfactant film, and therefore such a "sponge"-type structure is favored. With increasing surfactant concentration the amphiphilic film becomes stiffer again, which leads to the formation of a lamellar phase. The corresponding phase boundary is exactly related to the amphiphilicity factor as it can be deduced from the scattering experiments. Copyright 1998 Academic Press.
Journal Article↗
[Technique and rationale of lymph node dissection in bronchial carcinoma].
Any operation for lung cancer that is planned as curative includes dissection of the lymph nodes in the mediastinum in order to allow correct staging of the disease. It is well known that ipsilateral lymph node metastases (N2) mean a poor prognosis. Since most patients with this finding die from metastatic tumor progression within 3 years after the operation, it can be assumed that positive findings in the mediastinal lymph nodes represent generalization of the cancer. Therefore, the probability of a therapeutic effect from more radical removal of lymph nodes in the mediastinum is rather low. On the other hand, it is justified to apply and evaluate additional systemic treatment in these tumor stages.
Carcinoma, Bronchogenic↗
Approaches to the replacement of ethinylestradiol by natural 17beta-estradiol in combined oral contraceptives.
The strong hepatic estrogenic actions of ethinylestradiol (EE) are very likely to be the cause of the cardiovascular morbidity related to the use of combined oral contraceptives (COCs). This survey presents results of EE replacement in COCs with natural 17beta-estradiol (E2) in the following stages: reduction of EE to daily doses of 0.01 mg and concomitant replacement with E2 (as valerate, EV), complete replacement of EE with E2 using a novel multiphasic combination containing EV and the progestin dienogest (DNG), and the use of natural E2 to develop estrogen sulfamates (J 995) showing sufficient dissociation of uterine from liver estrogenicity. Recent data from preclinical and clinical studies show that these approaches seem to be promising.
Animals↗
Predicting schizophrenic outpatients' behavior by symptomatology and social skills.
Though social skills have been identified as an independent construct, recent studies have revealed that schizophrenic symptomatology and social skills are interrelated. The nature and extent of this relationship, however, are far from clear. To address this issue, we examined 33 schizophrenic outpatients participating in a rehabilitation program for an average of 10 months. The object of this study was to investigate to what extent behavior can be predicted by symptomatology and social skills, and whether social skills have a significant effect on outpatients' behavior independently of schizophrenic symptoms and vice versa. Regression analyses revealed good prediction of outpatients' behavior by conceptual disorganization and disorder of relating from the PANSS and, to a lesser degree, social skills. After having eliminated the influence of psychopathology on social skills and behavior, social skills variables still had significant predictive value for social competence, social interest, and irritability. These findings imply specific contributions of both symptomatology and social skills to future behavior of chronic schizophrenic outpatients.
Ambulatory Care↗
Pentoxifylline decreases the incidence of multiple organ failure in patients after major cardio-thoracic surgery.
We assessed the safety and efficacy of intravenous pentoxifylline [3,7-dimethyl-1-(5-oxohexyl)-xanthine] in patients at risk for developing multiple organ failure after major cardio-thoracic surgery in a single-center, randomized, placebo-controlled study. Of 816 consecutive patients who underwent major cardio-thoracic surgery, 40 who had Acute Physiology and Chronic Health Evaluation II score values > or = 19 at the first postoperative day after the surgery were included. Patients were randomized to receive either placebo (control; n = 25) or intravenous pentoxifylline treatment (pentoxifylline; n = 15) at a dosage of 1.5 mg/kg/h as an adjunct to standard supportive therapy. Main outcome measurements were duration of required ventilator support, intensive care unit stay, and incidence of renal failure. Thirty-seven patients were eligible for evaluation. No significant adverse events related to pentoxifylline treatment were observed. The duration of mechanical ventilation was significantly greater for control patients (8.3 +/- 3.1 days) compared with pentoxifylline-treated patients (3.1 +/- .9 days; p < .05). Patients treated with pentoxifylline experienced fewer days on hemofiltration (1.2 +/- .8 vs. 6.8 +/- 3.3; p < .05) and a shorter intensive care unit stay (5.2 +/- 1.1 vs. 11.4 +/- 3.1 days). There were no intergroup differences in mortality. Mortality was 33% in the pentoxifylline group and 36% among control group patients. In conclusion, supplemental pentoxifylline treatment may decrease the incidence of multiple organ failure in patients at risk of systemic inflammatory response syndrome after cardiac surgery. Additional studies are required to determine the validity of the observed effects.
APACHE↗
Evaluation of an oral pulsatile delivery system for melatonin in humans.
Using melatonin (MT) as a circadian synchroniser in humans to treat a variety of rhythm disorders, it is desirable to develop controlled-release dosage forms that deliver MT in accordance with its endogenous secretory pattern as well as preparations that release MT in a pulsatile way. In this paper we describe two oral pulsatile dosage forms containing 10 mg MT each (capsules B and C) and a fast-release form containing 5 mg MT (capsule A) studied in a randomised single-dose, threefold cross-over study in 15 healthy male volunteers. The concentrations of both MT in serum and its main metabolite 6-sulfatoxymelatonin (aMT6s) in urine were analysed by means of specific radioimmunoassays up to 10 h p.a. of the MT preparations. Mean peak concentrations of MT in serum were reached between 0.5 h and 0.75 h (Cmax[1] pmol/ml): 20.7 (A), 16.4 (B), 9.7 (C). The capsules B and C released a second MT pulse after about 3.5 h with Cmax[2] of 13.0 and 17.5 pmol/ml, respectively. Dose proportionality for the MT preparations studied was calculated by determining the AUC0-infinity (pmol/ml.h): 18.4 (A), 36.1 (B), 42.4 (C). The terminal serum half-lives of MT ranged between 0.64 and 0.84 h. The time course of the renally excreted aMT6s correlated with that of changes in MT serum concentrations.
Adult↗
[Lung metastases: tumor reduction as an oncologic concept].
The principle of surgery for lung metastases is the removal of all lesions in the lung that are either visible or detectable by palpation. This may be combined with complete dissection of all ipsilateral lymph nodes. Therefore, "tumor reduction" rather than "complete" or "radical resection" may be an adequate description of this surgical approach. Since the dissemination of--macroscopically not detectable--tumor cells represents the major mannerism of every metastatic disease, any local therapy appears to be a discrepancy. However, in most cases the rationale of surgery for lung metastases is the lack of effective systemic therapy and the low morbidity of surgery, along with up to 60% 5-year survival rates.
Combined Modality Therapy↗
Delayed treatment with desulfato-hirudin prevents fibrin formation in lipopolysaccharide-induced shock.
Previous work has shown that pre-treatment with the thrombin inhibitor recombinant desulfato-hirudin prevented fibrin formation and respiratory dysfunction in porcine lipopolysaccharide shock. We examined the effects of delayed administration of recombinant desulfato-hirudin in bacterial lipopolysaccharide shock. Miniature pigs were studied under anaesthesia and ventilation, and received a bacterial lipopolysaccharide infusion (2 microg/kg/h) for 7 h; recombinant desulfato-hirudin was started 1 h after bacterial lipopolysaccharide in 10 animals (bolus 12.9 nmol/kg; continuous infusion 6.5 nmol/ kg/h); 10 randomised control animals received saline instead of recombinant desulfato-hirudin. Fibrin and thrombin-antithrombin complex levels in plasma were significantly lower in bacterial lipopolysaccharide+recombinant desulfato-hirudin animals than in controls. Both groups displayed a similar rise in pulmonary vascular resistance and other parameters of lung dysfunction; only lung tissue wet/dry ratio was lower in recombinant desulfato-hirudin-treated than in control animals. Both groups had similar circulatory alterations. Recombinant desulfato-hirudin interrupted coagulation activation during ongoing bacterial lipopolysaccharide-induced shock in pigs even when administered with a delay of one hour after start of the bacterial lipopolysaccharide infusion. A protective effect of delayed recombinant desulfato-hirudin administration on bacterial lipopolysaccharide-induced acute lung injury and alterations in the systemic circulation could not be demonstrated in this experiment.
Animals↗
Presynaptic exocytosis regulates NR2A mRNA expression in cultured neocortical neurones.
N-methyl-D-aspartate (NMDA) receptors are hetero-oligomeric receptor-channel complexes composed of NR1 and NR2 subunits. Subunit composition determines the properties of NMDA receptor subtypes. However, the molecular mechanisms regulating their subunit composition are unknown. Using reverse transcription (RT)-competitive PCR we studied the expression of NR2A and NR2B mRNA in neocortical neurones differentiating in culture. We found a developmental increase in NR2A mRNA expression in relation to NR2B mRNA expression. This increase was inhibited by addition of tetanus toxin to the culture medium and by chronic pharmacological blockade of postsynaptic, ionotropic glutamate receptors. These results suggest that presynaptic exocytosis regulates NR2A mRNA expression. This mechanism might influence NMDA receptor properties and thus developmental changes in long-term synaptic plasticity.
Animals↗
Hypothermic storage alone in lung preservation for transplantation: a metabolic, light microscopic, and functional analysis after 18 hours of preservation.
BACKGROUND: Current lung preservation consists of flushing of the donor organs, with successive hypothermic storage in an inflated state. Recently, hypothermic storage alone was reported to be superior in terms of functional recovery. This study was designed to investigate the metabolic, morphologic, and functional consequences of hypothermic storage alone, in experimental lung preservation. METHODS: Orthotopic left-sided lung transplantation was performed in pigs. Donor lungs were flushed with Euro-Collins solution (n=6) or simply explanted (n=6) and stored for 18 hr at 4 degrees C. After this, left-sided single lung transplantation was performed. Sham-operated animals (n=6) served as control. Morphology and metabolism were analyzed in normal lungs, after ischemia and at the end of reperfusion. Gas exchange and pulmonary hemodynamics of the transplanted organs were measured, after exclusion of the native lung from perfusion and ventilation. RESULTS: Metabolic and morphologic evaluation did not show a significant difference between the groups at the end of ischemia. Lungs preserved by hypothermia alone showed a functional recovery close to sham-operated animals and superior to flushed organs. CONCLUSIONS: Hypothermia alone is a sufficient means of preservation for explanted lungs for at least 18 hr.
Animals↗
Relationships between social competence, psychopathology and work performance and their predictive value for vocational rehabilitation of schizophrenic outpatients.
Earlier studies suggest that social competence has a higher predictive value for vocational outcome than psychopathology. These studies, however, show methodological shortcomings, including the fact that the instruments used for assessing social competence, psychopathology and work performance are strongly interrelated. The present study, involving a population of 34 chronically schizophrenic outpatients enrolled in a vocational rehabilitation program, was conducted in order to determine: (1) how closely the Role Play Test, the Positive and Negative Syndrome Scale and the Work Behavior Assessment Scale are related to each other; and (2) whether social competence is a better predictor of work performance and outcome of vocational rehabilitation than psychopathology. Factor analysis has revealed that the instruments are interrelated, mainly in the dimensions of negative symptoms, social relationships, non-verbal measures of social competence and conceptual disorganization. In backward regression analyses, psychopathological indicators proved to be the best predictors of work performance both cross-sectionally as well as in the longterm course. In the traditional two-syndrome model of schizophrenic psychopathology only negative symptoms were left in the regression model. In a four-dimension model the disorder of relating and the conceptual disorganization dimension were the best predictors. Differences between disorder of relating and social competence, assessed by the Role Play Test, are discussed here as well as the implications of this study for rehabilitation.
Adult↗
Strategies to avoid virus transmissions by biopharmaceutic products.
The use of biopharmaceutical products offers an opportunity for the treatment of many diseases. Biotechnical manufacturing using recombinant mammalian cell lines is the most appropriate method today for the production of biopharmaceutical protein drugs for the treatment of human and animal diseases. However, mammalian cell line derived products have a potential risk for virus transmission to patients who are treated with these biopharmaceutical products. The reliability that biological products are free of any viruses requires a combination of several strategies: The use of well-characterized cell bank systems and, if feasible, the avoidance of biological raw materials for the cultivation of these mammalian cell lines and the production of biopharmaceuticals. Further on, the purification process for biopharmaceuticals has to be validated for its ability to efficiently remove and inactivate any potential virus contamination and, where applicable, also unconventional transmissible agents, such as BSE. In addition, the biopharmaceutical product itself can be tested for the presence of viruses. Like other manufacturing processes, biotechnical production processes have to be performed in compliance with current Good Manufacturing Practices (cGMP).
Animals↗
[Incomplete resections in bronchial carcinoma: morbidity and prognosis].
Residual tumor (R1) was proven at the proximal bronchial resection margin in 88 (3.6%) of 2464 cases of lung cancer following lung resection and standard lymph node dissection. Postoperative complications (8%) were: fistula of the bronchial suture line (n = 7), bleeding (n = 2) and heart luxation (n = 1). The in-hospital mortality was 16.6%. Causes of death were: bronchial fistula (n = 7), erosion of the pulmonary artery (n = 4), respiratory failure (n = 1), and empyema (n = 1). Forty-three patients received postoperative radiation therapy. Median survival of all patients following incomplete resection was 16 months, compared to 37 months following complete resection (P < 0.001). Length of survival was independent of tumor stage, histology, site of infiltration and postoperative radiation. In conclusion, in resection for lung cancer clear margins should be verified by intraoperative frozen section. In the case of residual tumor at the bronchial resection margin, wider resection is mandatory in stage I and II if the patient meets the functional criteria. Even in stage III a and III b prognosis is significantly better after complete resection than R1-resection; the difference, however, is smaller than in lower stages.
Adult↗
In vivo and in vitro studies on the sonographical detection of Ascaris lumbricoides.
Intestinal ultrasound, a frequently applied diagnostic tool in industrialized nations, has recently also been introduced in tropical regions. This study attempts to describe the anatomical and sonographical features of Ascaris lumbricoides in the human intestine. In the course of a schistosomiasis morbidity study in Madagascar, 581 inhabitants of a rice-farming village on the high plateau of the island had their stools examined by means of a modified Kato-Katz thick smear technique (four slides per sample); 53% had eggs of Ascaris lumbricoides in their stools. Twenty-two individuals underwent intestinal ultrasound examination and, in six cases, Ascaris lumbricoides was visualized. All six patients showed eggs upon stool examination. At ultrasound, the parasite was seen as a large, curved echogenic strip (4-6 mm in diameter) with an inner, anechoic, longitudinal canal. The image resembled a winding highway, the central structure representing the pseudocoel of the parasite. Patients were treated with mebendazole. The excreted worms of one patient were scanned under water, showing the same characteristics as in vivo. We conclude that Ascaris lumbricoides has a characteristic sonographical appearance and should not be a confounding factor in studies using intestinal ultrasound.
Aged↗
Reduced lipid peroxidation and ischemia-reperfusion injury after lung transplantation using low-potassium dextran solution for lung preservation.
Ischemia-reperfusion injury is one of the significant problems in clinical lung transplantation. We investigated the effect of lung preservation with Euro-Collins solution (EC group) or low-potassium dextran solution (LPD group) on lipid peroxidation and ischemia-reperfusion injury in a pig model of lung allotransplantation. The donor lungs were preserved at 4 degrees C for 18 h. Left-sided single lung transplantation was performed, followed by 6 h of reperfusion. Lipid peroxidation was measured as thiobarbituric acid-reactive materials (TBARM) in bronchoalveolar lavage (BAL) fluid and effluent solutions from pulmonary artery (Effluent). After 18 h of ischemia, the LPD group showed lower TBARM in BAL and Effluent than the EC group (p < 0.05). After ischemia plus reperfusion, lung wetto-dry weight ratios and TBARM levels in BAL in the LPD group were lower than those of the EC group (p < 0.05). Lung wet-to-dry weight ratios correlated with TBARM levels in BAL (p < 0.05, r = 0.50). We conclude lipid peroxidation in BAL and Effluent may reflect the degree of ischemia-reperfusion injury, and lung preservation with LPD can reduce lipid peroxidation and lung injury as compared with EC.
Animals↗
Transport of Ions through Vesicle Bilayers
Stopped flow measurements to determine the permeability of vesicles are presented. The kinetics of the reaction between FeSCN2+ and F- ions is used to monitor the permeability of vesicles. Samples with vesicles that have been equilibrated with the iron complex are mixed with F- solutions. The reaction is followed by UV/VIS absorption. The influence of temperature and surfactant concentration on the membrane permeability of large unilamellar phospholipid vesicles was studied. A dramatic increase of the permeability of the LUVs is observed when 30 to 40 mol% of the surfactant OP-10 (main component of Triton X-100) is added to the lipid. It is assumed that the increased permeability is due to the stabilization of transient defects in the bilayers of the vesicles as shown previously by other groups. Furthermore, a strong binding of the iron (III) thiocyanate complex to the phospholipid is observed by UV/VIS spectroscopy and zeta-potential measurements. Additional experiments with vesicles from a fluorocarbon surfactant show a much higher permeability than the phospholipid system. Models for the diffusion of either the iron (III) complex or the fluoride ions through the vesicles bilayer are discussed for LUV as well as for vesicles from a fluorocarbon surfactant. The results indicate that the rate-determining step is the diffusion of the iron complex through the membrane.
Journal Article↗