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1.
S Lombardi Borgia M Regehly R Sivaramakrishnan W Mehnert H C Korting K Danker B R?der K D Kramer M Sch?fer-Korting 《Journal of controlled release》2005,110(1):151-163
With topical treatment of skin diseases, the requirement of a high and reproducible drug uptake often still is not met. Moreover, drug targeting to specific skin strata may improve the use of agents which are prone to cause local unwanted effects. Recent investigations have indicated that improved uptake and skin targeting may become feasible by means of nanoparticular systems such as solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and nanoemulsions (NE). Here we describe techniques to characterize drug loading to carrier systems and skin penetration profiles by using the lipophilic dye nile red as a model agent. Since the mode of drug association with the particle matrix may strongly influence the efficiency of skin targeting, parelectric spectroscopy (PS) was used to differentiate between matrix incorporation and attachment to the particle surface and fluorescence spectroscopy (FS) to solve dye distribution within NLC particles. Nile red was incorporated into the lipid matrix or the covering tensed shell, respectively, of SLN and NLC with all the lipids studied (Compritol, Precirol, oleic acid, Miglyol). In NLC, the dye was enriched in the liquid phase. Next, nile red concentrations were followed by image analysis of vertical sections of pigskin treated with dye-loaded nanoparticular dispersions and an oil-in-water cream for 4 and 8 h in vitro. Following the SLN dispersions, dye penetration increased about fourfold over the uptake obtained following the cream. NLC turned out less potent (相似文献
2.
In a randomized cross-over study the antihypertensive effects of nifedipine and the combination of co-dergocrine and nifedipine (Pontuc) respectively as well as the influence of both preparations on the glucose metabolism was tested in 22 hypertensive patients with diabetes type II over a period of 4 weeks. During treatment with the combination a significantly more pronounced blood pressure reduction was achieved compared to monotherapy with nifedipine, whereas the heart rate was significantly increased only by nifedipine. Both drugs--nifedipine and co-dergocrine/nifedipine--did not change the concentrations of glucose in the blood or urine or of HbA1. 相似文献
3.
4.
H. Mehnert F. Dittmar G. Schäfer H. Förster und D. Ennemoser 《Journal of molecular medicine (Berlin, Germany)》1966,44(4):219-220
Zusammenfassung Bei Wöchnerinnen wurden vor und nach oraler Belastung mit 100 g Glucose Bestimmungen der Seruminsulinspiegel durchgeführt. Dabei zeigte sich, daß Frauen, die von Kindern mit einem durchschnittlichen Geburtsgewicht von 4300 g entbunden worden waren, mit einem verzögerten und signifikant höheren Anstieg der Werte des freien (mit Antiserum unterdrückbaren) Insulins und der gesamten insulinähnlichen Aktivität reagierten als Mütter von normalgewichtigen Kindern (Durchschnittsgewicht 3300g). Da die Glucosetoleranz bei allen Probandinnen normal war, kann dieser Befund neben dem erhöhten Geburtsgewicht als prädiabetisches Symptom angesehen werden.
Summary Investigations of antibody-suppressible and non-suppressible ILA have been performed in two groups of women during an oral glucose tolerance test (100 g Glucose per os). Group 1: Women 3–6 days after the delivery of a baby with normal weight (about 3300 g); group 2: Women 3–6 days after the delivery of a big baby (weight about 4300 g). Inspite of a normal glucose tolerance in all subjects it could be demonstrated that the women of group 2 showed a delayed and significantly higher increase of the fat pad ILA and the suppressible ILA, particularly. This behaviour of the insulin secretion seems to be a prediabetic symptom.相似文献
5.
6.
Mehnert P Malchaire J Kampmann B Piette A Griefahn B Gebhardt H 《European journal of applied physiology》2000,82(1-2):52-60
The prediction of the mean skin temperature used for the Required Sweat Rate index was criticised for not being valid in
conditions with high radiation and high humidity. Based on a large database provided by 9 institutes, 1999 data points obtained
using steady-state conditions, from 1399 experiments and involving 377 male subjects, were used for the development of a new
prediction model. The observed mean skin temperatures ranged from 30.7 °C to 38.6 °C. Experimental conditions included air
temperatures (T
a) between 20 and 55 °C, mean radiant temperatures (T
r) up to 145 °C, partial vapour pressures (P
a) from 0.2 to 5.3 kPa, air velocities (v
a) between 0.1 and 2 m/s, and metabolic rates (M) from 102 to 620 W. Rectal temperature (T
re) was included in the models to increase the accuracy of prediction. Separate models were derived for nude (clothing insulation,
Icl, ≤0.2 clo, where 1 clo=0.155 m2 · °C · W−1, which is equivalent to the thermal insulation of clothing necessary to maintain a resting subject in comfort in a normally
ventilated room, air movement=10 cm/s, at a temperature of 21 °C and a humidity of less than 50%) and clothed (0.6 ≤ Icl ≤ 1.0 clo) subjects using a multiple linear regression technique with re-sampling (non-parametric bootstrap). The following
expressions were obtained for nude and clothed subjects, respectively: T
sk=7.19 + 0.064T
a + 0.061T
r + 0.198P
a− 0.348v
a + 0.616T
re and T
sk=12.17 + 0.020T
a + 0.044T
r + 0.194P
a − 0.253v
a + 0.0029M + 0.513T
re. For the nude and clothed subjects, 83.3% and 81.8%, respectively, of the predicted skin temperatures were within the range
of ±1 °C of the observed skin temperatures. It is concluded that the proposed models for the prediction of the mean skin temperature
are valid for a wide range of warm and hot ambient conditions in steady-state conditions, including those of high radiation
and high humidity.
Accepted: 7 February 2000 相似文献
7.
Matthias Wicklmayr Günther Dietze Bernulf Günther Richard Schifmann Ingolf Böttger Reinhard Geiger Hans Fritz Hellmut Mehnert 《Inflammation research》1980,10(4):339-343
The influence of synthetic bradykinin (BK) on disturbed protein and carbohydrate metabolism was studied in chemical and manifest maturity-onset diabetics, in surgical patients and in alloxan diabetic rats. BK,mixed with insulin and injected subcutaneously twice daily in alloxan diabetic rats lowered the morning blood glucose concentration in a dose-dependent way, whereas in a control group treated with insulin only no decrease was seen. Accelerated local blood flow or enhanced vascular permeability as a cause of increased glucose uptake could be ruled out by control experiments using papaverine and eledoisin. Better metabolic control in the BK/insulin-treated group was also indicated by lower arterial levels of free fatty acids and of -hydroxybutyrate, normalized hepatic glycogen content and better growth of body weight. In healthy man an intravenous infusion of BK (80 g/h) did not influence normal fasting blood glucose concentrations, whereas elevated glucose levels in maturity-onset diabetics were continuously reduced within 100 min by 12.2±1.4%. A comparable diabetic group receiving saline alone showed no spontaneous drop of blood glucose concentration. An improvement of pathological carbohydrate metabolism by infusion of BK i.v. could also be demonstrated using the intravenous glucose tolerance test in chemical and manifest maturity-onset diabetics and in surgical patients: in all groupsk values of the glucose tolerance test were significantly increased by BK. This effect was neither due to stimulated insulin release nor to changed glucose pool or to increased renal glucose loss, which was even reduced by BK. Interestingly, normalk values in healthy volunteers were not further improved by BK. A stimulated protein breakdown, which occurs after surgery due to peripheral insulin resistance, can also be restricted by intravenous infusion of BK: in surgical patients urinary nitrogen excretion was reduced by 50% during infusion of BK and was accelerated again after cessation of the infusion. These results indicate that BK can improve the efficacy of exogenous insulin in insulin-deficient animals and depressed insulin sensitivity in maturity-onset diabetics and surgical patients. 相似文献
8.
9.
N. Lotz W. Bachmann T. Ladik H. Mehnert 《Journal of molecular medicine (Berlin, Germany)》1988,66(21):1079-1084
Summary In type 2 diabetes with secondary failure of sulfonylurea therapy good metabolic control can seldom be achieved by insulin therapy even with high insulin doses. Hyperinsulinemia however is a possible risk factor of cardiovascular disease in type 2 diabetes. Maintaining the effects of sulfonylurea action insulin should be added in as small amounts as possible to avoid hyperinsulinemia and to ameliorate hyperglycemia.16 type 2 diabetics with secondary failure were treated either with insulin alone (group A;n=8) or with 3.5 mg b.i.d glibenclamide plus small amounts of intermediate insulin (group B;n=8) in a randomised order. After the inpatient period outpatient control was performed monthly up to six months, later on four times a year up to two years.Both groups were comparable with regard to age, duration of diabetes, body weight and metabolic control. The daily insulin dose was 14±2 IU
after one month and 19±2 IU after two years in group B. In contrast 30±3 IU and 43±5 IU respectively were needed in group A (p<0.001). All patients B were treated with one daily injection, all patients A needed two injections. Resulting in nearly identical metabolic control in group A basal insulin levels exceeded those in group B after two years significantly (28.6±3.7 vs. 18.6±1.6 mcU/ml;p<0.01). Endogenous C-peptide response was suppressed in group A compared to group B after inpatient period and after one month (0.12±0.01 vs. 0.49±0.15 and 0.09±0.04 vs. 0.13±0.08 pmol/ml;p<0.05). The combined therapy of insulin and sulfonylureas demonstrates the benefit of a prolonged sulfonylurea administration in the treatment of type 2 diabetes with secondary failure.As compared to common insulin therapy a small amount of exogenous insulin by one daily injection additionally to glibenclamide shows similar improvement in metabolic control. Hyperinsulinemia as a risk factor of macroangiopathy is markedly reduced in patients treated with combined therapy compared to those with insulin alone.
Herrn Professor Dr. N. Zöllner zum 65. Geburtstag gewidmet 相似文献
10.
Solid lipid nanoparticles (SLN) are a colloidal carrier system for controlled drug delivery. The lipophilic model drugs tetracaine and etomidate were incorporated to study the maximum drug loading, entrapment efficacy, effect of drug incorporation on SLN size, zeta potential (charge) and long-term physical stability. Drug loads of up to 10% could be achieved whilst simultaneously maintaining a physically stable nanoparticle dispersion. Incorporation of drugs showed no or little effect on particle size and zeta potential compared to drug-free SLN. The optimized production parameters previously established for drug-free SLN dispersions can therefore be transferred to drug-loaded systems to facilitate product development. 相似文献