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Biomedical subjects

M Brandl

Publications and source records attributed to M Brandl.

At least 19 recordsLinked to original sources
PubMed1995

Racemization of ketorolac in aqueous solution.

The racemization of ketorolac was studied in aqueous buffered solution at 25 and 80 degrees C and analyzed in detail with respect to the catalytic species in solution. The reaction has a U shaped pH rate profile at 80 degrees C with the pH of maximum stability occurring in the region of pH 3.0-7.5. A T90 value of 8 months was observed for a 1.5% (R)-ketorolac tromethamine solution at pH 7.4 and 25 degrees C. Additionally, the data shows that alternative salt forms are necessary in order to prepare a stable single isomer formulation. Alternative buffers, in particular phosphate buffer, provide formulations exhibiting a T90 greater than 2 years.

Catalysis↗
PubMed1995

Quantitative NMR microscopy of multicellular tumor spheroids and confrontation cultures.

In cancer research, tumor spheroids are a well established system to study tumor metabolism resembling the situation in vivo more closely cell monolayers. Spherical aggregates of malignant melanoma cells (MV3) and their invasion into rat brain aggregates have been investigated by quantitative NMR microscopy. Relaxation times (T1, T2) and diffusion parameter images were acquired with an in-plane resolution of 14 x 14 microns2. The authors were able to demonstrate that the morphology of the spheroids can be visualized on these NMR maps. The contrast was mainly manifested in relaxation maps, where average relaxation times T1 = 1.94 +/- 0.17 s and T2 = 42.8 +/- 6.3 ms were obtained for proliferating cells, and T1 = 2.49 +/- 0.31 s and T2 = 104.3 +/- 29.4 ms for the necrobiotic center. The mean diffusion coefficients were 0.59 +/- 0.12 micron2/ms and 0.85 +/- 0.14 micron2/ms, respectively. The authors could follow the dynamic process of tumor cell invasion in the investigated co-culture system. Knowledge about tumor cell migration and tumor cell invasion is essential for the understanding of cancer and its therapy. Quantitative NMR microscopy can study this dynamic process noninvasively and therefore may help to assess the influence of therapy on the micromilieu of these spheroids.

Animals↗
PubMed1995

Acute toxicity and depression of phagocytosis in vivo by liposomes: influence of lysophosphatidylcholine.

Small unilamellar phospholipid vesicles (liposomes), intended as drug carriers, have recently been demonstrated to reversibly depress phagocytic activity in rats when injected in a single high dose (2g of lipid per kg body weight) as revealed by the carbon clearance test. Depression of the phagocytic function was found to vary widely depending on the lipid used [M. Brandl et al., Pharm. Pharmacol. Lett., 4 (1) 1-4, 1994]. This study has now been extended in two directions: Firstly, liposomes made of the same type of lipid but different batches of raw material were compared in terms of their influence on phagocytosis as well as for their contents of impurities. The test revealed great variability of RES suppression between different batches of hydrogenated soy PC, whereas the reproducibility of the carbon clearance test was satisfactory with liposomes made of a single batch of raw material. Thin layer chromatographic analyses of the used phosphatidylcholines (PCs) and limulus tests on lipopolysaccharides revealed lysophosphatidylcholine (lysoPC) as the only impurity which showed parallels with the observed differences in phagocytosis. Secondly by "spiking" phosphatidylcholine with increasing amounts of lysoPC the latter could be proven to enhance RES depression by liposomes in a dose-dependent manner. At the same time a strong and dose-limiting increase in acute toxicity of PC vesicles was observed with increasing contents of lysoPC. However, in cholesterol-containing vesicles lysoPC-spiking did not significantly alter their behaviour, for lysoPC contents of up to 10%. Only PC/cholesterol-vesicles containing lysoPC contents as high as 15% provoked enhanced RES depression and toxicity compared to lysoPC-free vesicles. LysoPC and cholesterol in liposomes are known to play a destabilizing and stabilizing role respectively within liposomal bilayers which might influence recognition and uptake of vesicles by macrophages and thus modulation of phagocytosis.

Animals↗
PubMed1994

Entrapment of haemoglobin into liposomes by the dehydration-rehydration method: vesicle characterization and in vivo behaviour.

Haemoglobin (Hb) was isolated from human erythrocytes under conditions which maintained NADH-cytochrome-b5 reductase activity and suppressed oxidation of Hb during storage at 4 degrees C (methaemoglobin values < 3% after 29 days). Hb was entrapped into liposomes composed of hydrogenated egg phosphatidylcholine and equimolar cholesterol according to the dehydration/rehydration procedure of Kirby and Gregoriadis ((1984) Biotechnology 2, 979). However, encapsulation of Hb in its intact form was poor (< 5%) as a result of its oxidation and denaturation during freeze-drying. The addition of cryoprotectants and the use of both, higher initial concentrations of Hb and very small void vesicles resulted in Hb-rich dehydration/rehydration vesicles (phospholipid/Hb molar ratio of about 200:1) of the preferred size of 110 nm (mean). Highly homogeneous and small void vesicles as starting material were prepared using the one-step method of Brandl et al. ((1990) Drug Dev. Ind. Pharm. 16, 2167). The cryoprotectants were chosen with respect to their sufficient protection of Hb without affecting its loading into vesicles during freeze-drying and rehydration. 51Cr-labelling of Hb was used for the in vivo monitoring of the fate of Hb-containing vesicles rather than 125I-labelling since the latter induced strong interactions of Hb with liposomes. Upon intravenous administration into rats, liposomal 51Cr-Hb showed greater blood levels and prolonged circulation times in the blood compared to free Hb. The present approach provides high yield entrapment of labile molecules into vesicles of small size known to exhibit long circulation time.

Animals↗
PubMed1991

[Role of the anesthetist in the recovery stage].

Surveillance of the patient in the particularly critical phase immediately following operation and anaesthetic must be considered a purely anaesthesiological task. Today, it is no longer considered sufficient merely to keep the patient under observation until his protective reflexes have returnded; rather, appropriate postoperative therapeutic measures must be initiated already during the recovery phase to enable the patient to be returned to the nursing ward with his or her vital functions optimal and stabilised. The tasks of the anaesthetist in the recovery phase are as follows: safeguarding of the transportation phase of the patient from the operating room to the recovery unit; hand-over of the patient to the recovery staff; monitoring for possible complications in the recovery phase, collection of suitable diagnostic parameters to determine the current state of the patient; initiation of optimised treatment as dictated by the state of the patient; documentation of all findings as well as all therapeutic measures instituted, and deciding on the further transfer of the patient.

Anesthesia Recovery Period↗
PubMed1990

High-performance liquid chromatographic (HPLC) and HPLC-mass spectrometric (MS) analysis of the degradation of the luteinizing hormone-releasing hormone (LH-RH) antagonist RS-26306 in aqueous solution.

The kinetics of the degradation of an LH-RH antagonist, RS-26306,1, in aqueous solution from pH 1 to pH 11 were studied by reverse-phase HPLC. The pH-rate profiles at 50, 60, and 80 degrees C were U-shaped with the rate law of kobs = kHaH + kw + kOHaOH. The predicted 25 degrees C shelf life at the pH of maximum stability, pH approximately 5, is greater than 10 years. The products from the degradation were analyzed by HPLC-MS using thermospray ionization. Below pH 3, the primary product, 2, forms from the acid-catalyzed deamidation of the C-terminal amide. Above pH 7, epimerization of the individual amino acids is the principal reaction. Between pH 4 and pH 6, intramolecular serine-catalyzed peptide hydrolysis becomes important, yielding a tripeptide, 3, and a heptapeptide, 4. At the pH of maximum stability all three pathways for degradation are observed.

Chemical Phenomena↗
PubMed1990

Plasma level changes of fentanyl and midazolam after release of a prolonged thigh tourniquet.

In 14 elderly orthopedic patients undergoing total knee joint replacement, the influence of complete arterial occlusion of the limb on the course of plasma levels of fentanyl and midazolam was examined. The patients were premedicated with midazolam intramuscularly (0.05 mg/kg) and were then given neurolept anesthesia in dosages of 0.1 mg/kg midazolam and 0.01 mg/kg fentanyl intravenously prior to the placement of the tourniquet. Up to 4 h after the tourniquet was released, plasma levels of fentanyl and midazolam as well as pH value, PaCO2 and plasma lactate levels were measured. In 12 patients there was an increase in fentanyl and in 10 patients an increase in midazolam plasma levels after tourniquet release. The maximum increase varied between 1 min and 2 h after release. The plasma levels of midazolam after removal of the tourniquet varied greatly between individuals. Especially patients older than 70 years showed excessively high concentrations of midazolam. These results would indicate that there can be a clinically significant increase of fentanyl and midazolam levels due to initial reperfusion of the lower extremity following prolonged ischemia. Therefore a correspondingly extended period of postoperative surveillance is advisable.

Aged↗
PubMed1989

Nitrogen absorption in pancreatectomized patients: protein versus protein hydrolysate as substrate.

To investigate nitrogen absorption in the absence of the pancreas, six patients with total pancreatectomy, all in stable nutritional and metabolic condition, underwent two periods of enteral nutrition identical in all respects except for the nitrogen source. Nitrogen source was either lactalbumin or its hydrolysate. The quantity and quality of calories infused simulated the patient's usual diet, which was a high-protein diet (2.0 +/- 0.4 gm/kg body weight). Pancreatic enzyme replacement therapy was discontinued during each period of enteral nutrition. All patients had greater nitrogen absorption during the enteral nutrition with lactalbumin hydrolysate than that with lactalbumin (91% +/- 2% vs 61% +/- 6% of nitrogen intake, p less than 0.02). Despite this difference in absorption, nitrogen balances during the two periods of enteral nutrition were not significantly different. This appeared to be caused by a urea production rate that was greater during the enteral nutrition with lactalbumin hydrolysate than the rate during that with lactalbumin (26 +/- 1 gm/24 hr vs 16 +/- 3 gm/24 hr, p less than 0.05). Plasma concentrations of amino acids and proteins did not differ significantly during the two treatments. In conclusion, the data suggest that (1) the intestine plays a significant role in protein digestion and that (2) enteral feeding with a protein hydrolysate could eliminate the need for a high-protein diet in patients with pancreatic insufficiency.

Absorption↗
PubMed1989

Protein-restricted diets in chronic renal failure: a four year follow-up shows limited indications.

Several retrospective and prospective studies confirmed the beneficial effect of dietary protein restriction (DPR) on the downhill course of renal function in chronic kidney disease. The long-term results of this therapeutic modality may be different than the short-term effects. In our nephrology outpatient department, a prospective randomized trial has been in progress since April, 1982. In 1984, we reported a general beneficial effect of our diet after two years of follow-up. Two hundred and forty-eight patients with initial creatinine clearances between 10 and 60 ml/min entered the trial. Patients were stratified for sex, age and degree of renal insufficiency. One hundred and twenty-nine patients were randomly assigned to a DPR-group (0.4 to 0.6 g/kg/day); 118 patients to a control group. Patients on DPR visited the dietitian every three months during the first 24 months of the study; thereafter, as with the controls, the dietitian visits were only for specific needs. Urea excretion decreased significantly in DPR patients as a sign of good compliance and stayed at that level, even without frequent visits to the dietitian. Biochemical parameters showed no signs of malnutrition. Amino acid profiles were related to the degree of renal failure. The diet appeared to have a selective effect on the progression rate of renal failure: only patients with primary glomerular disease responded to the diet. Furthermore, there were striking intersex differences. Males showed a more rapid decline towards end-stage renal failure, but responded in a positive way to the diet, whereas female patients did not benefit from the dietary manipulation at all.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Biochemical and hormonal parameters in patients with multiple trauma.

We measured amount, course and duration of different parameters in order to assess metabolic-endocrine changes in patients with multiple trauma and the final outcome. Injures were initially quantified according to the Injury Severity Score. Serum levels of lactate, creatinine, bilirubin, somatomedin and thyroid hormons were measured in 51 patients (39 survivors, 12 deceased patients) for six days following the injury. In addition, neopterin levels were measured in 26 patients (19 survivors, 7 deceased patients). The patients were devided into two groups (survivors vs non-survivors). Global Index Scores and Septic Severity Scores were significantly different at the 1% and 5% level (p less than 0.05 to p less than 0.01). The same statistical differences were shown for lactate, somatomedin, neopterin and thyroid hormones.

Biomarkers↗
PubMed1988

Plasma amino and keto acids in chronic renal failure.

During both early and late stages of chronic renal insufficiency the response of BCKA to the disease state, as indicated by plasma levels, differs from that of BCAA. Val is the only BCAA whose concentration changes under the conditions of our study, and this only during the more advanced stages of disease. In contrast, all three BCKA declined, KIVA and KICA even in mild renal failure, showing that already during the early stages of the disease these BCKA levels are decreased. BCKA are more sensitive parameters than the corresponding amino acids with regard to the metabolic dysfunctions characteristic of this disease. Modern analytical methods allow more exact and reliable knowledge of these indicators and thus a better understanding of biochemical mechanisms, possibly resulting in better therapy.

Amino Acids↗
PubMed1988

Metabolites of microorganisms. 247. Phenazines from Streptomyces antibioticus, strain Tü 2706.

From a strain of Streptomyces antibioticus seven yellow phenazines were isolated. The antibacterially most active antibiotic was identified as (-)-saphenamycin, a second one with compound DC-86-Y (saphenic acid). Three compounds were new: Saphenic acid methyl ether, 6-acetylphenazine-1-carboxylic acid and an inseparable mixture of fatty acid esters of saphenic acid. Two simple phenazines were phenazine-1-carboxylic acid (tubermycin B) and unsubstituted phenazine, which was isolated for the first time from a microorganism.

Microbial Sensitivity Tests↗
PubMed1988

Metabolites of microorganisms. 248. Synthetic analogs of saphenamycin.

A synthesis of racemie saphenic acid is described. From this acid 9 ester derivatives of saphenamycin were prepared. Those with aromatic acid components showed high activity against many Gram-positive and some Gram-negative bacteria. Of the esters with aliphatic acid moieties only the acetate and, to a lesser extent, the butyrate showed considerable anti-bacterial activities, whereas esters with higher fatty acids showed strongly reduced, if any, activities against some test organisms. Similar results were obtained with ID50 values against the eucaryotic tumor cell line CCRF/CEM. The salicylate, which is structurally similar to saphenamycin, was most active.

Anti-Bacterial Agents↗