Micro-algae as a source of protein.

About five decades ago, the mass production of certain protein-rich micro-algae was considered as a possibility to close the predicted so called "protein gap". Comprehensive analyses and nutritional studies have demonstrated that these algal proteins are of high quality and comparable to conventional vegetable proteins. However, due to high production costs as well as technical difficulties to incorporate the algal material into palatable food preparations, the propagation of algal protein is still in its infancy. To date, the majority of micro-algal preparations are marketed as health food, as cosmetics or as animal feed.

Safety aspects of a coumarin-troxerutin combination regarding liver function in a double-blind placebo-controlled study.

OBJECTIVE: Coumarin is reported to elevate liver function tests (LFT) values. In a prospective, placebo-controlled, clinical trial, efficacy and safety of a coumarin-containing combination (SB-LOT) were evaluated in the treatment of chronic venous insufficiency. Here, we report on the drug safety of coumarin with special respect to liver reaction. METHODS: 114 patients were treated with SB-LOT (30 mg coumarin and 180 mg troxerutin t.i.d.) and 117 with placebo during a period of 16 weeks. LFT values (ALT, AST, AP and gamma-GT) were monitored at baseline, 4, 6, 8, 12 and 16 weeks of therapy. Adverse drug reactions were assessed regarding causality. Additionally, lymphocyte proliferation test was used to identify allergic reactions. Logistic regression analysis was performed to identify possible risk factors. RESULTS: No serious adverse drug reactions occurred. Elevations of LFT were assessed as biochemical abnormality. Specific clinical symptoms such as jaundice did not occur. Only 1 patient reported fatigue and exhaustion. Logistic regression estimated a basic risk for elevation of LFT of 4.9% under SB-LOT and 2.1% under placebo. Hepatitis in the history and diseases of the liver were identified as risk factors. CONCLUSION: This evaluation contributes to safety data of SB-LOT in man. LFT elevation is transient and the low risk of the SB-LOT therapy to increase LFT value can be limited when risk factors are considered.

Immunomodulatory properties of rumalon, a glycosaminoglycan peptide complex, in patients with osteoarthritis: activation of T helper cell type 2 cytokines and antigen-specific IgG4 antigen-specific igG4 antibodies.

OBJECTIVE: To assess the immunogenic properties of the glycosaminoglycan peptide complex Rumalon, an aqueous extract of bovine cartilage and bone marrow frequently used in patients with osteoarthritis (OA). METHODS: Sera from 31 patients with OA who had received several series of Rumalon injections (Group 1, n = 17: before therapy and after one injection series; Group 2, n = 6: after 2-3 injection series; Group 3, n = 4: after 4-8 injection series; Group 4, n = 4: after 9-18 injection series) were tested by ELISA for antibodies against Rumalon and its components as well as by a double sandwich ELISA for type 1 [interferon-gamma, interleukin 2 (IL-2)] and type 2 cytokines (IL-4, IL-5, IL-10, IL-13). RESULTS: After the first injection series antibodies to Rumalon were induced in 7 of the 17 patients that were all negative before therapy. The antibodies were preferentially of the IgG4 type. IgG4 levels were increased during therapy (ELISA optical density x 1000 in Group 1: 73.9 +/- 209.5; Group 4: 1354.5 +/- 307.6), and in Group 4 all patients had developed these antibodies. Upon analysis of cytokine levels, there was a significant increase in IL-5 (Group 1 before therapy 407.4 +/- 257.1 pg/ml, Groups 3 and 4: 1409.4 +/- 963.1 pg/ml; p < 0.001) and to a lesser extent of IL-10 during therapy (Group 1 before therapy 950.2 +/- 867.8 pg/ml, Groups 3 and 4: 2817.8 +/- 3127.3 pg/ml; p < 0.05), while type 1 cytokines were not affected. CONCLUSION: Rumalon appears to have immunomodulatory properties and preferentially stimulates IgG4 antibodies via the activation of type 2 cytokines in vivo. Whether these phenomena can be correlated with the postulated therapeutic effect of Rumalon in patients with OA remains to be seen, but pain relief via release of endorphins by Th2 cells could be one explanation.

Kinetic equilibrium of forces and molecular events in muscle contraction.

In biomolecular systems, the mechanical transfer of free energy occurs with both high efficiency and high speed. It is shown here that such a transfer can be achieved only if the participating free-energy-storing elements exhibit opposing relationships between their content of free energy and the force they exert in the transfer direction. A kinetic equilibrium of forces (KEF) results, in which the transfer of free energy is mediated essentially by thermal molecular motion. On the basis of present evidence, KEF is used as a guiding principle in developing a mechanical model of the crossbridge cycle in muscle contraction. The model allows the basic features of molecular events to be visualized in terms of plausible structures. Real understanding of the process will require identification of the elements that perform the functions described here. Besides chemomechanical energy transduction, KEF may have a role in other biomolecular processes in which free energy is transferred mechanically over large distances.

[Incidence and clinical relevance of antibodies to phospholipids, serotonin and ganglioside in patients with sudden deafness and progressive inner ear hearing loss]. / Häufigkeit und klinische Relevanz von Antikörpern gegen Phospholipide, Serotonin und Ganglioside bei Patienten mit Hörsturz und progredienter Innenohrschwerhörigkeit.

Immunoserological assays of patients with sudden deafness and progressive hearing losses have revealed the presence of different antibodies, leading to the assumption that immunological processes may be involved. Recent investigations have demonstrated that these patients have phospholipid antibodies that can cause venous or arterial vasculopathies. In the present study we analyzed the incidence of these antibodies in patients with inner ear disorders. Sera of 55 patients with sudden deafness and 80 patients with progressive hearing loss were tested. Phospholipid antibodies were demonstrable in 49% of the patients with sudden hearing loss and 50% of the patients with progressive hearing loss. Serotonin and ganglioside antibodies were found in 53% of the patients with sudden hearing loss and 63% of the patients with progressive hearing loss. Since these three antibodies are also frequently found in patients with fibromyalgia syndrome (FMS) and chronic fatigue syndrome (CFS), 28 of the patients studied displayed symptoms typical for these disorders, including fatigue, myalgia, arthralgia, depressions, sicca symptoms and diarrhea. We now recommend questioning patients suffering from inner ear disorders for symptoms typical for FMS or CFS, since these diseases are often closely related to inner ear disorders. If symptoms are present, antibodies should be tested against phospholipids, serotonin and gangliosides. If present, the antibodies are diagnostic for each syndrome. Additionally these immunologic and serologic findings show that these antibodies may play a role in the etiology of hearing loss disorders.

Effects of clozapine on in vitro immune parameters: a longitudinal study in clozapine-treated schizophrenic patients.

Clozapine is an atypical antipsychotic agent with immunomodulatory properties. We hypothesized that in vitro immune parameters of peripheral blood mononuclear cells (PBMC) are affected in the course of clozapine treatment and that clozapine per se, added in vitro to PBMC cultures of clozapine-treated patients, exerts differential effects in the timecourse of treatment in vivo. We measured proliferation and cytokine secretion of PBMC, serum autoantibodies, and immunoglobulin levels in 17 patients before and during the first 6 weeks of clozapine treatment. Independent of clozapine dosage and rectal temperature, clozapine treatment in vivo suppressed proliferation and shedding of sIL-2r by PBMC, and the addition of clozapine in vitro induced, relative to unstimulated conditions, PBMC proliferation and secretion of IL-6 and sIL-2r. Serum IgG levels were increased; whereas, autoantibody pattern was unaffected. Thus, clozapine treatment and the addition of clozapine in vitro exert differential effects on various in vitro immune parameters independent of clozapine dosage and rectal temperature in the course of treatment.

California residential air exchange rates and residence volumes.

UNLABELLED: Air exchange rate data from two residential indoor air quality studies are presented. In the first investigation, over 500 residences in Southern California were sampled for three one-week periods from 1984 to 1985. Those data provided seasonal information for a broad range of residential characteristics in a large metropolitan area. In the second study, a probability sample of nearly 300 residences were sampled for a two-day period during the winter of 1991-1992 throughout the state of California. Air exchange rate is summarized by season, geographic area, and appliance type. Residence volumes are presented by cooking and heating appliance. The data approximately followed lognormal distributions. IMPLICATIONS: Indoor air quality and human exposure models often require estimates of air exchange rate and residence volumes. Application of those models to California residences can be improved by using the data distributions provided in this manuscript. Data distributions presented for heating and cooking appliances are useful for modeling the impact of indoor sources specific for those appliance types. Measured air exchange rate is also useful for modeling energy use for heating and cooling in residences.

[Trimethoprim-sulfamethoxazole-induced cholestatic hepatitis. Clinico-immunological demonstration of its allergic origin]. / Trimethoprim-Sulfamethoxazol-induzierte cholestatische Hepatitis. Klinisch-immunologischer Nachweis der allergischen Genese.

HISTORY AND CLINICAL FINDINGS: A 22-year-old woman was given trimethoprim plus sulphamethoxazole for a urinary infection (160 and 800 mg, respectively, daily), drugs she had not previously taken. After 2 weeks she noticed a rash of small spots on her trunk. In addition she had nausea and vomiting. The rash faded within 2 days of stopping the drug, but progressive jaundice developed. INVESTIGATIONS: SGPT and SGOT concentrations rose to maximally 328 and 83 U/l, total bilirubin to maximally 5.9 mg/dl. There was no evidence for viral hepatitis (B or C, cytomegalovirus, Epstein-Barr), autoimmune hepatitis or primary biliary hepatitis. Liver biopsy showed central acinar cholestasis, which suggested drug-induced liver damage. COURSE: The patient's symptoms regressed over several weeks without any specific treatment and 8 weeks after onset of the rash the laboratory tests also became normal. The allergic cause of the cholestatic hepatitis was confirmed by a lymphocyte transformation test. CONCLUSION: Clinical suspicion of drug allergy as cause of a cholestatic hepatitis can be confirmed reliably and without any risk to the patient with the lymphocyte transformation test.

Replacement value of blue-green alga (Spirulina platensis) for fishmeal and a vitamin-mineral premix for broiler chicks.

1. The effect of sun-dried Spirulina platensis in poultry diets was studied in a 12-week feeding trial by replacing either fishmeal (FM) or groundnut cake (GC) in a commercial diet with algae at isonitrogenous concentrations of 140 g/kg and 170 g/kg respectively. Additional vitamins/minerals were omitted from the algal diets because Spirulina is rich in them. 2. Efficiency of food utilisation, protein efficiency ratio and dressing percentage indicated that substitution of FM or GC by alga did not affect the performance of broilers. 3. None of the diets affected the weights, compositions and histopathology of the various organs of the chicks. 4. Meat quality remained unchanged except for a more intense colour in the case of birds fed on the alga-containing diets.

[Allergic vasculitis caused by Vigabatrin]. / Allergische Vaskulitis durch Vigabatrin.

A patient with focal epilepsy that was resistant to medical treatment received add-on therapy with vigabatrin. Six months after commencement of vigabatrin therapy, allergic vasculitis caused by vigabatrin was diagnosed. The patient displayed unilateral anterior ischaemic optic neuropathy with impairment of vision and concentric loss of visual field. The diagnosis was based on the lymphocyte transformation test and the clinical course. The allergic vasculitis was healed by cortisone therapy.

Biomechanical model of the P-type ion pumps of the cell.

The mechanisms of the Na/K pump and of the primary Ca pumps of the cell have not yet been clarified. A biomechanical model of these so-called p-type ion pumps is proposed here. It is based on the assumption that the Na+ and Ca2+ ions are occluded by a contracting protein chain cooperating with the ATPase section of the pump. After transfer of the chain into the region of high Na+ or Ca2+ concentrations, the ions are released through stretching of the chain by the ATPase. In the backward transfer of the chain, a retrograde transport of Na+ ions is prevented through occlusion of K+ ions by another region of the same chain. In the case of Ca2+ ions, a similar effect is expected from hydrated Mg2+ ions. The two sections of the chain discriminate between the electrical field strength at the surface and the polarizability of the ions. The most likely mechanism for the transfer of the ion-binding chain is considered to involve a thermally induced transition of a pump dimer between two almost equivalent stable orientations in the membrane.

Distribution of the PBC-specific- (M2) and the naturally-occurring mitochondrial antigen- (NOMAg) systems in plants.

In previous studies it was demonstrated that antibodies in sera from patients with primary biliary cirrhosis (PBC) and their relatives can recognize two different antigen systems in the ATPase fraction prepared from beef heart mitochondria, namely the PBC-related M2- and the naturally occurring mitochondrial antigen (NOMAg)-related epitopes. Since separation of these two antigen systems could not be achieved using mammalian mitochondria, mitochondria from a wide spectrum of plants were analysed with respect to the presence of mitochondrial antigens. Mitochondria from 29 species of plants were prepared and tested by ELISA and Western blot using marker sera from patients with PBC reacting in the Western blot with M2a,b,c,d (alpha-ketoacid-dehydrogenase complex) and NOMAg-specific sera recognizing the three major epitopes epsilon, zeta, and eta at 65, 61 and 58 kD. Naturally occurring mitochondrial antibody (NOMA)-positive marker sera reacted in the ELISA with mitochondria from all plants, and the zeta/eta positive sera gave also a positive reaction at 61/58 kD in the Western blot while the epsilon epitope could not be visualized by this method. In contrast, the M2 antigen was detected preferentially in lower plants such as algae, fungi, and ferns. Analysing these data with respect to the evolution of proteins one would have to assume that the M2 antigen was lost in most higher plants or underwent some structural alterations. Furthermore, considering the fact that the M2- and the NOMAg-related epitopes could be only partially separated, i.e. there were no plant mitochondria showing only M2 but no NOMAg, one could speculate that anti-M2 antibodies are derived from the pool of naturally occurring antibodies.

[The analysis of a severe side effect of a cartilage-protective agent by immunological studies]. / Analyse einer schweren Nebenwirkung auf ein Chondroprotektivum mit Hilfe immunologischer Untersuchungen.

After 18 intramuscular injections of Arumalon, a 62-year-old woman with degenerative hip-joint changes developed a severe illness with fever up to 39 degrees C, swellings of the finger, hand and knee joints, as well as a local skin rash and changes in the blood (WBC 1900/microliters, platelets 113,000/microliters), and increase in liver enzymes (GOT 83 U/l, GPT 93 U/l, lactate dehydrogenase 693 U/l). Arumalon, a glucosaminoglycan-peptide complex containing a watery extract of bovine cartilage and bone marrow, is used as a cartilage-protecting medication. The close temporal relationship between the injections and the symptoms suggested that the illness was drug-induced. This view was supported by a positive lymphocyte transformation test with Arumalon and its constituents, as well as by the demonstration of Arumalon-specific antibodies in the cultured lymphocyte fluid while the serum was negative for the antibodies. The illness took a protracted course. The patient became completely free of symptoms only after a year on a maintenance dose of prednisone, 15 mg daily. As a local inflammatory reaction was noted at the very start of the Arumalon injections, presensitization against the foreign proteins in Arumalon cannot be excluded. This is also supported by the fact that the specific lymphocyte proliferation was essentially unchanged even after nine months. This case illustrates the importance of careful assessment of increased and repeated manifestations of local reaction during Arumalon treatment, in particular in view of the risk of systemic side effects.

Dynamics and kinetics of enzymes. Kinetic equilibrium of forces in biochemistry.

To explain the high specificity, high reaction rate, and high thermodynamic efficiency in enzymatic processes, cooperation of the enzyme with a molecular transfer unit is assumed. A "kinetic equilibrium of forces" is suggested, which enables high reaction rates to occur under equilibrium conditions and a thorough examination of the substrate to be made without consumption of free energy. In case of ATPases, ion-binding proteins are the most probable transfer units. By analyzing the elementary effect in muscle contraction it is shown that the new theorem may be of substantial value in elucidating biochemical processes.

[Recurrent agranulocytosis after taking calcium dobesilate]. / Wiederholte Agranulozytose nach Einnahme von Calciumdobesilat.

A 64-year-old woman fell ill with generalized pyoderma and fever up to 40 degrees C. White cell count was 600/microliters, with 96% lymphocytes. Granulopoiesis in the bone marrow was markedly diminished. After treatment with cefotaxime, 2 g twice daily for one week, the blood count returned to normal. 8 months later generalized pyoderma, fever and agranulocytosis (white cell count 700/microliters) recurred. Once again the findings improved on ofloxacin 200 mg twice daily for 9 days. On repeat questioning about previous drug intake the patient stated that each time before the onset of the agranulocytosis she had taken calcium dobesilate, 500 mg twice daily for the preceding 15 and 3 weeks, respectively. Thereupon a lymphocyte transformation test was performed which revealed significant stimulation by calcium dobesilate 4, 8 and 14 weeks after the second episode of agranulocytosis. -Allergic side effects of calcium dobesilate have repeatedly been reported, but there has been no previously published report of agranulocytosis induced by this drug.