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PubMed1994

Product differentiation among health maintenance organizations: causes and consequences of offering open-ended products.

Open-ended products that allow an HMO enrollee to use providers who are not affiliated with the HMO have become an important component of the Clinton administration's health reform proposal, because these products maintain consumer freedom of choice of any provider. However, little is known about the consequences of offering an open-ended product from an organizational standpoint. This paper uses a theory of "spatial competition" to examine the decisions of health maintenance organizations to offer an open-ended product and the effect of offering an open-ended product on their enrollment.

Community Participation↗
PubMed2000

Metabolism of citric acid production by Aspergillus niger: model definition, steady-state analysis and constrained optimization of citric acid production rate.

In an attempt to provide a rational basis for the optimization of citric acid production by A. niger, we developed a mathematical model of the metabolism of this filamentous fungus when in conditions of citric acid accumulation. The present model is based in a previous one, but extended with the inclusion of new metabolic processes and updated with currently available kinetic data. Among the different alternatives to represent the system behavior we have chosen the S-system representation within power-law formalism. This type of representation allows us to verify not only the ability of the model to exhibit a stable steady state of the integrated system but also the robustness and quality of the representation. The model analysis is shown to be self-consistent, with a stable steady state, and in good agreement with experimental evidence. Moreover, the model representation is sufficiently robust, as indicated by sensitivity and steady-state and dynamic analyses. From the steady-state results we concluded that the range of accuracy of the S-system representation is wide enough to model realistic deviations from the nominal steady state. The dynamic analysis indicated a reasonable response time, which provided further indication that the model is adequate. The extensive assessment of the reliability and quality of the model put us in a position to address questions of optimization of the system with respect to increased citrate production. We carried out the constrained optimization of A. niger metabolism with the goal of predicting an enzyme activity profile yielding the maximum rate of citrate production, while, at the same time, keeping all enzyme activities within predetermined, physiologically acceptable ranges. The optimization is based on a method described and tested elsewhere that utilizes the fact that the S-system representation of a metabolic system becomes linear at steady state, which allows application of linear programming techniques. Our results show that: (i) while the present profile of enzyme activities in A. niger at idiophase steady state yields high rates of citric acid production, it still leaves room for changes and suggests possible optimization of the activity profile to over five times the basal rate synthesis; (ii) when the total enzyme concentration is allowed to double its basal value, the citric acid production rate can be increased by more than 12-fold, and even larger values can be attained if the total enzyme concentration is allowed to increase even more (up to 50-fold when the total enzyme concentration may rise up to 10-fold the basal value); and (iii) the systematic search of the best combination of subsets of enzymes shows that, under all conditions assayed, a minimum of 13 enzymes need be modified if significant increases in citric acid are to be obtained. This implies that improvements by single enzyme modulation are unlikely, which is in agreement with the findings of some investigators in this and other fields.

Aspergillus niger↗
PubMed2005

Association of the risk of osteoarthritis with high innate production of interleukin-1beta and low innate production of interleukin-10 ex vivo, upon lipopolysaccharide stimulation.

OBJECTIVE: In a sibpair study of osteoarthritis (OA) patients, we investigated whether, upon stimulation with lipopolysaccharide (LPS), variations in the innate ex vivo production of interleukin-1beta (IL-1beta), IL-1 receptor antagonist (IL-1Ra), IL-10, and tumor necrosis factor alpha (TNFalpha) in whole-blood assays contribute to the risk of OA. METHODS: Data from 305 patients with OA at multiple sites (hand, knee, hip, and spine), whose median age was 60 years (range 43-79 years), were compared with those from 137 controls. OA was defined in accordance with the American College of Rheumatology criteria. Whole-blood samples were stimulated with LPS (10 ng/ml). In the supernatants, cytokines were measured by enzyme-linked immunosorbent assay. Odds ratios (ORs) were used as measures of the relative risk of OA in relation to quartiles of IL-1beta, IL-1Ra, TNFalpha, and IL-10 production. The ORs were adjusted for sex and age, and 95% confidence intervals (95% CIs) were computed using robust standard errors to take into account the intrafamily effect. RESULTS: Subjects in the highest quartile of IL-1beta and IL-1Ra had an increased risk of OA (OR 3.3, 95% CI 1.4-7.9 and OR 8.0, 95% CI 3.7-17.4, respectively), while subjects in the lowest quartile of IL-10 had a 3-fold increased risk of OA (OR 3.1, 95% CI 1.5-6.5). High innate ex vivo production of TNFalpha was not associated with an increased risk of OA. CONCLUSION: Subjects with a high innate ex vivo production of IL-1beta and IL-1Ra and low innate ex vivo production of IL-10 have an increased risk of OA. These results suggest that a proportion of the genetic susceptibility to OA may be encoded for by variations in innate cytokine activity.

Adult↗
PubMed2003

Substrate and product inhibition of hydrogen production by the extreme thermophile, Caldicellulosiruptor saccharolyticus.

Substrate and product inhibition of hydrogen production during sucrose fermentation by the extremely thermophilic bacterium Caldicellulosiruptor saccharolyticus was studied. The inhibition kinetics were analyzed with a noncompetitive, nonlinear inhibition model. Hydrogen was the most severe inhibitor when allowed to accumulate in the culture. Concentrations of 5-10 mM H(2) in the gas phase (identical with partial hydrogen pressure (pH(2)) of (1-2) x 10(4) Pa) initiated a metabolic shift to lactate formation. The extent of inhibition by hydrogen was dependent on the density of the culture. The highest tolerance for hydrogen was found at low volumetric hydrogen production rates, as occurred in cultures with low cell densities. Under those conditions the critical hydrogen concentration in the gas phase was 27.7 mM H(2) (identical with pH(2) of 5.6 x 10(4) Pa); above this value hydrogen production ceased completely. With an efficient removal of hydrogen sucrose fermentation was mainly inhibited by sodium acetate. The critical concentrations of sucrose and acetate, at which growth and hydrogen production was completely inhibited (at neutral pH and 70 degrees C), were 292 and 365 mM, respectively. Inorganic salts, such as sodium chloride, mimicked the effect of sodium acetate, implying that ionic strength was responsible for inhibition. Undissociated acetate did not contribute to inhibition of cultures at neutral or slightly acidic pH. Exposure of exponentially growing cultures to concentrations of sodium acetate or sodium chloride higher than ca. 175 mM caused cell lysis, probably due to activation of autolysins.

Archaea↗
PubMed1979

Production of interferon in the murine mixed lymphocyte culture. II. Interferon production is a T cell-dependent function, independent of proliferation.

Interferon production occurs after two days of culture in murine mixed lymphocyte cultures (MLC). This was demonstrated in various combinations of mouse spleen cells differing at the major histocompatibility (H-2) locus. Interferon production could be demonstrated in one-way MLC when F1/parent combinations were used and in reactions in which one partner was treated by puromycin. After treatment of both cell populations with mitomycin C, interferon production occurred in the absence of lymphoproliferation. Interferon production in response to alloantigen did not occur in spleen cell cultures of nude mice and in cultures treated by anti-theta antiserum plus complement indicating that interferon production is a T cell-dependent function.

Animals↗
PubMed2004

Enforced Bcl-2 expression in B lymphocytes induces rheumatoid factor and anti-DNA production, but the Yaa mutation promotes only anti-DNA production.

The presence of rheumatoid factors (RF) is a characteristic feature of patients with rheumatoid arthritis, but not systemic lupus erythematosus. In this study, we have explored the role of the anti-apoptotic Bcl-2 protein and the Y-linked autoimmune acceleration (Yaa) mutation in the production of IgG RF in comparison with IgG anti-DNA autoimmune responses. Analysis in C57BL/6 mice, in their F1 hybrids with lupus-prone NZW mice, and in bone marrow chimeras containing mixtures of C57BL/6 bcl-2-transgenic and BXSB non-transgenic cells demonstrated that an enforced Bcl-2 expression in B cells promoted the induction of IgG anti-DNA production in these mice, while significant IgG RF responses were observed only in mice developing high levels of gp70-anti-gp70 immune complexes and lethal glomerulonephritis. Moreover, in contrast to a synergistic interaction between the Yaa mutation and Bcl-2 overexpression on IgG anti-DNA production, the Yaa mutation failed to enhance the production of IgG RF induced in bcl-2-transgenic mice. Our results reveal that defects in the regulation of B cell apoptosis play a critical role in the production of IgG RF, and that the Yaa mutation differentially modulates RF and anti-DNA autoimmune responses, likely related to the nature of autoantigens involved in each autoimmune response.

Animals↗
PubMed1995

Chromium-induced production of reactive oxygen species, DNA single-strand breaks, nitric oxide production, and lactate dehydrogenase leakage in J774A.1 cell cultures.

The involvement of oxidative stress in the toxicity of chromium (VI) and chromium (III) has been proposed. We have therefore examined the effects of these cations on the production of superoxide anion, nitric oxide (NO), and DNA single strand breaks (SSB) in J774A.1 macrophage cells in culture as well as the effects on lactate dehydrogenase (LDH) leakage and cell viability. Following a 48 hour incubation, over twofold increases in superoxide anion and NO production were observed at concentrations of approximately 0.30 and 50 microM for Cr (VI) and Cr (III), respectively. The patterns of cell viability and LDH leakage paralleled superoxide anion and NO production for Cr (VI) and Cr (III). A 50% decrease in viability was observed at approximately the concentrations that produced a twofold increase in superoxide and NO production. Concentration-dependent increases in DNA-SSB were observed after incubation with Cr (III) with maximum increases occurring at a concentration of approximately 60 microM. Cr (VI) had no effect on the incidence of DNA-SSB at any of the tested concentrations. The results indicate that Cr (VI) and Cr (III) are toxic to the J774A.1 cell line, and the toxicity may be due at least in part to an oxidative stress induced by the production of reactive oxygen species.

Cell Line↗
PubMed2003

Cyclic tensile stretch modulates proteoglycan production by intervertebral disc annulus fibrosus cells through production of nitrite oxide.

Degeneration of the intervertebral disc is the main pathophysiological process implicated in low back pain and is a prerequisite to disc herniation. Clinically, mechanical forces are important modulators of the degeneration, but the underlying molecular mechanism is not known and needs investigation to identify the biological target. The aim of this work was to study, at the molecular level, the effects of cyclic tensile stretch (CTS) on the production of proteoglycan by intervertebral disc annulus fibrosus cells since proteoglycans seem to be implicated in the dynamic process of intervertebral disc degeneration. Such cells of rabbit were cultured at high density on plates with a flexible bottom. CTS was applied with use of a pressure-operated instrument to deform the plates. With CTS at 1% elongation (1 Hz frequency), the level of (35)S-labeled neosynthesized proteoglycans that accumulated in the cellular pool or were secreted in the culture medium did not change, but at 5% elongation, the level was significantly reduced after 8 h of stimulation (30 and 21%, respectively) and further reduced at 24 h (43 and 41%, respectively). Introducing the protein synthesis inhibitor cycloheximide had no effect on this result. Neither aggrecan and biglycan expression nor proteoglycan physical properties were modified. The level of nitrite oxide production significantly increased by 3.5 times after 8 h of 5% elongation. Introducing the nitric oxide synthase (NOS) inhibitors N(G)-methyl-l-arginine or N-omega nitro-l-arginine diminished the effects of CTS on the production of nitrite oxide and proteoglycans. By contrast, introducing N-iminoethyl-l-lysine (a more specific inhibitor of inductible NOS [iNOS]) had little or no effect. Taken together, these results suggest that cNOS activation seems to be more implicated in the 5% CTS modulation of proteoglycan production than iNOS activation. These results suggest that CTS can help regulate the intervertebral disc matrix by decreasing proteoglycan production through a post-translational regulation involving nitrite oxide. This result could be of interest in the development of local therapeutic strategies aimed at controlling intervertebral disc degeneration.

Animals↗
PubMed2004

Fragmentation study of short-chain products derived from oxidation of diacylphosphatidylcholines by electrospray tandem mass spectrometry: identification of novel short-chain products.

Lineloyl-palmitoyl (PLPC) and arachidonoyl-palmitoyl (PAPC) phosphatidylcholine were oxidized under Fenton reaction conditions (H2O2 and Fe2+), and the short-chain products formed were identified by electrospray ionization mass spectrometry (ESI-MS). The short-chain products resulted from beta-cleavage of oxygen-centered radicals and comprised aldehydes, hydroxyaldehydes and dicarboxylic acids that yielded both [MH]+ and [MNa]+ ions. The fragmentation of the [MH]+ and [MNa]+ ions of the peroxidation products was studied by tandem mass spectrometry (MS/MS). The MS/MS spectra of both ions showed ions resulting from characteristic losses of glycerophosphatidylcholine. Other product ions, resulting from C-C cleavages occurring in the vicinity of the functional group, and fragmentations involving the hydroxy groups, were the most informative since they allowed us to obtain structural information relating to the sn-2 acyl residue. Both fragmentation pathways are due to charge-remote fragmentation occurring by a 1,4-hydrogen elimination mechanism and/or by homolytic cleavage. Furthermore, the fragmentation pathway of some ions observed in the ESI-MS spectrum was not consistent with the fragmentation behavior expected for some of the short-chain species identified in the literature and allowed the reassignment of the ions as different structures. Isobaric ions were observed in the ESI-MS spectra of both oxidized phospholipids, and were differentiated based on distinct fragmentation. The detailed knowledge of lipid peroxidation degradation products is of major importance and should be very valuable in providing new markers for oxidative stress signaling and for disease states monitoring.

Aldehydes↗
PubMed1994

Nitric oxide production depends on preceding tetrahydrobiopterin synthesis by endothelial cells: selective suppression of induced nitric oxide production by sepiapterin reductase inhibitors.

Using murine vascular endothelial cells expressing both constitutive and inducible nitric oxide synthases (cNOS and iNOS), we explored the feasibility of suppressing cytokine-induced nitric oxide (NO) production without affecting constitutive NO production by inhibition of the tetrahydrobiopterin (BH4) biosynthesis. We show in this study that in endothelial cells cytokine/endotoxin-activated BH4 synthesis precedes the induction of NO generation. Using the sepiapterin reductase inhibitors phenprocoumon or dicumarol as BH4 synthesis inhibitors, we achieved a pronounced and selective suppression of induced NO production in cytokine-activated endothelial cells. Addition of exogenous BH4, but not sepiapterin, restored NO production in the presence of the inhibitors. Despite profound inhibition of the BH4 biosynthesis, constitutive NO synthesis was not affected, thereby demonstrating the selectivity and specificity of the inhibitors. Suppression of enhanced NO production by sepiapterin reductase inhibitors such as cumaroles could provide pharmacologic means for therapeutic interventions in NO-mediated pathophysiologic events.

Alcohol Oxidoreductases↗
PubMed1996

The regulation of tumor necrosis factor-alpha production in murine mast cells: pentoxifylline or dexamethasone inhibits IgE-dependent production of TNF-alpha by distinct mechanisms.

Mast cells activated via high-affinity receptors for IgE can produce a variety of multifunctional cytokines, including TNF-alpha, which is thought to be involved in the pathophysiology of allergic diseases and other inflammatory disorders. We investigated the regulation of Fc Fc epsilon RI-dependent TNF-alpha production by mouse mast cells using dexamethasone and pentoxifylline, pharmacological agents which are known to suppress TNF-alpha production by macrophages. We now report that either dexamethasone or pentoxifylline can inhibit IgE-dependent mouse mast cell production of TNF-alpha; however, the major site of action of these agents was different. Pentoxifylline inhibited mast cell TNF-alpha gene transcription, while dexamethasone inhibited TNF-alpha production predominantly by a post-transcriptional mechanism. These results demonstrate that the synthesis of mast cell TNF-alpha can be regulated pharmacologically at either the transcriptional or the translational level and that pentoxifylline and dexamethasone, two agents that are used to treat inflammatory disorders, can modulate mast cell TNF-alpha production at different points in the synthetic pathway of this cytokine.

Animals↗
PubMed1998

Adrenal hormone modulation of type 1 and type 2 cytokine production by spleen cells: dexamethasone and dehydroepiandrosterone suppress interleukin-2, interleukin-4, and interferon-gamma production in vitro.

Our previous work has documented that physical or psychological stress can alter interleukin (IL)-2, IL-4, and interferon (IFN)-gamma production by spleen or lymph node cells in vitro. To determine if adrenal hormones might be mediating these stress-induced changes in type 1 and type 2 cytokines and immune effector functions, we cultured spleen cells in vitro with either the synthetic glucocorticoid dexamethasone (DEX) or the putative restorative hormone dehydroepiandrosterone (DHEA). Spleen cells were obtained from either young (5-6 weeks old) or mature (7-8 months old) BALB/c mice that were either unimmunized or immunized with the T-cell-dependent antigen keyhole limpet hemocyanin (KLH). We determined that DEX suppressed production of all three cytokines examined. DHEA was not associated with any enhancement of cytokine production. These data challenge the hypothesis that glucocorticoids can differentially regulate Th1-like versus Th2-like cytokine production. Further, they suggest that in stress paradigms in which differential regulation of cytokine production and effector function has been observed, other neuroendocrine factors in addition to glucocorticoids must be relevant.

Animals↗
PubMed1984

Enhanced production of prostaglandins and plasminogen activator during activation of human articular chondrocytes by products of mononuclear cells.

We have examined the way in which products of cultured human blood mononuclear cells activate human articular chondrocytes. Conditioned medium from mononuclear cells enhanced the production of prostaglandin E by cultured human chondrocytes and also stimulated fibrinolytic activity in these cultures. These two effects may be interrelated, since the increased fibrinolysis in response to products of mononuclear cells was partially inhibited by indomethacin, an inhibitor of prostaglandin biosynthesis. The increased fibrinolysis is probably attributable to plasminogen activator, since it was strongly dependent on the presence of plasminogen. Increased amounts of PGE and chondroitin sulphate were also released from intact fragments of cartilage exposed to medium from cultured mononuclear cells. The time course and dose dependence of these effects were studied. The addition of exogenous arachidonic acid markedly enhanced production of PGE2. Ultrogel AcA54 was used to fractionate medium from cultured mononuclear cells and the chondrocyte-stimulating activity eluted with an apparent molecular weight between 12 000 and 25 000 daltons. Adherent and non-adherent mononuclear blood cells were also partially separated and conditioned medium from each was assayed for chondrocyte-stimulating factors. Both populations released factor(s) which increased the production of prostaglandin E by chondrocytes, but more activity came from the adherent mononuclear cells. The possible interrelationship between the chondrocyte activating factor studied here and others described in the literature is discussed.

Arachidonic Acid↗
PubMed1977

[The behavior of polyphosphates during production and storage of long keeping milk products (author's transl)].

Polyphosphates added as stabilizers in the production process if liquid sterilized milk products are completely hydrolyzed to mono- and diphosphates. The diphosphate is further hydrolyzed during storage of the products. The extent of hydrolysis of diphosphate depends upon the processing conditions and may vary from production to production. During spray-drying of milk, the polyphosphates added are only partially hydrolyzed; further degradation of the polyphosphates takes place during storage.

Animals↗
PubMed2005

The inhibitory effects of roflumilast on lipopolysaccharide-induced nitric oxide production in RAW264.7 cells are mediated by heme oxygenase-1 and its product carbon monoxide.

OBJECTIVES: Heme oxygenase-1 (HO-1) is an enzyme that degrades heme into biliverdin, free iron, and carbon monoxide (CO). This enzyme is known to have cytoprotective and anti-inflammatory effects. In this study, we investigated whether roflumilast, a newly developed specific phosphodiesterase 4 (PDE4) inhibitor, mediates some of its anti-inflammatory effects by blocking nitric oxide (NO) and tumor necrosis factor alpha (TNF-alpha) via the induction of HO-1 expression in macrophages. METHODS: The expression of iNOS and HO-1 was analyzed by western blot analysis. The production of NO and TNF-alpha was assayed by Greiss and ELISA, respectively. RESULTS: Roflumilast markedly suppressed LPS-induced NO and TNF-alpha production and these phenomena were correlated with the induction of HO-1 protein levels. Moreover, the inhibitory effects of roflumilast on NO production were abrogated by a HO-1 inhibitor and a CO scavenger. Tricarbonyldichlrororuthenium(II) dimer, a CO releasing molecule significantly suppressed NO production. CONCLUSIONS: These results suggested that roflumilast exerts its anti-inflammatory effects in macrophages through a novel mechanism that involves the action of HO-1 and its product, CO.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1999

Alternative schemes of butyrate production in Butyrivibrio fibrisolvens and their relationship to acetate utilization, lactate production, and phylogeny.

Butyrivibrio fibrisolvens strains D1 and A38 produced little lactate, but strain 49 converted as much as 75% of its glucose to lactate. Strain 49 had tenfold more lactate dehydrogenase activity than strains D1 or A38, this activity was stimulated by fructose 1,6-bisphosphate, and had a pH optimum of 6.25. A role for fructose 1,6-bisphosphate or pH regulation of lactate production in strain 49 was, however, contradicted by the observations that very low concentrations (< 0.2 mM) of fructose 1,6-bisphosphate gave maximal activity, and continuous cultures did not produce additional lactate when the pH was decreased. The lactate production of strain 49 was clearly inhibited by the presence of acetate in the growth medium. When strain 49 was supplemented with as little as 5 mM acetate, lactate production decreased dramatically, and most of the glucose was converted to butyrate. Strain 49 did not possess butyrate kinase activity, but it had a butyryl-CoA/acetate CoA transferase that converted butyryl-CoA directly to butyrate, using acetate as an acceptor. The transferase had a low affinity for acetate (K(m) of 5 mM), and this characteristic explained the acetate stimulation of growth and butyrate formation. Strains D1 and A38 had butyrate kinase but not butyryl-CoA/acetate CoA transferase, and it appeared that this difference could explain the lack of acetate stimulation and lactate production. Based on these results, it is unlikely that B. fibrisolvens would ever contribute significantly to the pool of ruminal lactate. Since relatives of strain 49 (strains Nor37, PI-7, VV1, and OB156, based on 16S rRNA sequence analysis) all had the same method of butyrate production, it appeared that butyryl-CoA/acetate CoA transferase might be a phylogenetic characteristic. We obtained a culture of strain B835 (NCDO 2398) that produced large amounts of lactate and had butyryl-CoA/acetate CoA transferase activity, but this strain had previously been grouped with strains A38 and D1 based on 16S rRNA sequence analysis. Our strain B835 had a 16S rRNA sequence unique from the one currently deposited in GenBank, and had high sequence similarity with strains 49 and Nor37 rather than with strains A38 or D1.

Acetates↗
PubMed2005

Food-drug interactions in the summary of product characteristics of proprietary medicinal products.

BACKGROUND: Food-drug interactions can produce negative effects in the safety and efficacy of drug therapy, as well as in the nutritional status of the patient. However, the data commonly provided to the prescriber about possible nutrient-pharmacological compound interactions and the recommendations for their prevention are often scarce. The summary of product characteristics (SmPC) of a proprietary medicinal product, as authorised by the health authorities in Europe, is usually the main source of information for the health professional. Therefore, the SmPC can be a useful tool to prevent or reduce food-drug interactions and, as a consequence, improve the therapeutical approach. OBJECTIVE: The aim of this study was to assess the information about food-drug interactions with potential clinical relevance as it is described in the SmPCs of the authorised medicinal products in a European Union country (Spain). METHODS: A bibliographical search of food-drug interactions, including nutrients and alcohol, was carried out. The adequate information to be included in the SmPC was defined in accordance with the European Recommendations in this field. The SmPCs of the medicinal products containing selected active substances were examined with emphasis on food-drug interactions. RESULTS: It was found that, frequently, the information concerning food-drug interactions as is mentioned in the SmPC of the authorised medicinal products in Spain does not fulfil the current recommendations, both in quantity and quality. Indeed, the available data reveal that the food-drug information is only mentioned in 72.7% of all SmPC where it should be and it was only found in the specific section for interactions in 36.0% of all cases. The description and agreement with recommendations for each SmPC item ranged between 4.2% and 36.0% and between 31.8% and 49.0%, respectively. Some related factors, such as the clinical relevance of the interaction, the existence of an authorised SmPC and the registration procedure followed, influence the information characteristics concerning food-drug interactions. CONCLUSION: The SmPC is a suboptimal source of information for food-drug interactions.

Beverages↗
PubMed1996

Lantibiotic nisin Z fermentative production by Lactococcus lactis IO-1: relationship between production of the lantibiotic and lactate and cell growth.

The influence of several parameters on the fermentative production of nisin Z by Lactococcus lactis IO-1 was studied. Considerable attention has been focused on the relationship between the primary metabolite production of bacteriocin and lactate and cell growth, which has so far not been clarified in detail. Production of nisin Z was optimal at 30 degrees C and in the pH range 5.0-5.5. The addition of Ca2+ to the medium showed a stimulating effect on the production of nisin Z. A maximum activity of 3150 IU/ml was obtained during pH-controlled batch fermentation in the medium supplemented with 0.1 M CaCl2. It was about three times higher than that obtained under the optimal conditions for cell growth and lactic acid production.

Anti-Bacterial Agents↗