In vitro evaluation of Bifidobacterium strains of human origin for potential use in probiotic functional foods.

The present study investigated some in vitro properties for probiotic use of four strains of bifidobacteria isolated from faeces of healthy children (Bifidobacterium longum 51A, Bifidobacterium breve 1101A, Bifidobacterium pseudolongum 1191A and Bifidobacterium bifidum 1622A). In vitro tests were carried out to compare growth rate, aerotolerance, antagonistic activity against pathogens, antimicrobial susceptibility profile and cell wall hydrophobicity. Mean doubling time of B. longum 51A was shorter compared to the other strains. All strains were aerotolerant up to 72 h of exposure to oxygen. In vitro antagonism showed that B. longum 51A and B. pseudolongum 1191A were able to produce inhibitory diffusible compounds against all pathogenic bacteria tested, but not against Candida albicans. B. longum 51A was sensitive to all the antimicrobials tested, except neomycin. The hydrophobic property of the cell wall was highest for B. bifidum 1622A. Based on these parameters, B. longum 51A showed the best potential for probiotic use among the tested strains, presenting the greatest sensitivity to antimicrobials, the best growth rate and the highest capacity to produce antagonistic substances against various pathogenic microorganisms.

Sensing glucose concentrations at GHz frequencies with a fully embedded Biomicro-electromechanical system (BioMEMS).

The progressive scaling in semiconductor technology allows for advanced miniaturization of intelligent systems like implantable biosensors for low-molecular weight analytes. A most relevant application would be the monitoring of glucose in diabetic patients, since no commercial solution is available yet for the continuous and drift-free monitoring of blood sugar levels. We report on a biosensor chip that operates via the binding competition of glucose and dextran to concanavalin A. The sensor is prepared as a fully embedded micro-electromechanical system and operates at GHz frequencies. Glucose concentrations derive from the assay viscosity as determined by the deflection of a 50 nm TiN actuator beam excited by quasi-electrostatic attraction. The GHz detection scheme does not rely on the resonant oscillation of the actuator and safely operates in fluidic environments. This property favorably combines with additional characteristics-(i) measurement times of less than a second, (ii) usage of biocompatible TiN for bio-milieu exposed parts, and (iii) small volume of less than 1 mm3-to qualify the sensor chip as key component in a continuous glucose monitor for the interstitial tissue.

Levels of parotid and submandibular/sublingual salivary immunoglobulin A in response to experimental gingivitis in humans.

Salivary secretory IgA (s-IgA) is considered to act as an important first line of defense mechanism in the oral cavity. It has therefore been suggested that an increased antigenic load would induce an increase in salivary IgA production. This study investigated the pure glandular levels of salivary IgA in parotid and submandibular/sublingual (SM/SL) saliva during plaque accumulation leading to experimental gingivitis. Starting from regular oral hygiene, 14 healthy, nonsmoking men refrained from all oral hygiene measures for 12 days. On days -2, 0, 3, 6, and 12 a plaque index, a bleeding index, and unstimulated and stimulated saliva from the parotid and the SM/SL glands were measured. Salivary IgA was quantified using a sandwich ELISA. All subjects developed gingivitis as measured by a bleeding index. Compared to baseline the salivary flow rate was increased on day 12. Regarding the secretion rate of IgA there was a statistically significant increase in stimulated parotid saliva but not SM/SL saliva compared to baseline after 6 and 12 days without oral hygiene. No significant changes were observed for the concentration of IgA during the trial. Thus, in healthy subjects with regular oral hygiene the development of plaque induced gingivitis is associated with increased salivary gland output and increased total IgA output levels in stimulated parotid saliva but not in SM/SL saliva.

Quo vadis, biotech? (Part 2).

Those following the financial markets and the valuation of biotechnology companies recently might find themselves perplexed. Towards the end of 1999, during which the availability of capital for biotech initial public offerings and for private investment rounds seemingly withered, the markets suddenly turned around and gave the biotechnology industry its biggest bonanza ever.

[Mycotic aneurysms--A retrospective analysis]. / Mykotische Aneurysmen - Eine retrospektive Analyse.

12 patients (10 males and 2 females, average age 53 years) were operated upon in our hospital between 1994 and 1999 for mycotic aneurysms. The aneurysms were located in 7 patients in the aorto-iliac segment, 5 patients were treated for peripheral or visceral aneurysms. Two of these patients suffered from multiple aneurysms. When peripheral arteries were affected, a pulsatile tumour was felt. Most of these tumours developed in a relatively short period of time and sometimes a perivascular inflammation occurred. This was not the case when central arteries were attacked. A septic process or an infection, for example salmonella-enteritis, often preceded shortly the development of a mycotic aneurysm. In the case of an aneurysm of the aorto-iliac section we consider an in situ reconstruction with alloplastic material in combination with a perivascular debridement, lavage and omentum majus plastic as the treatment of choice. In peripheral arteries reconstruction should be performed with autologous vessels. Depending on the local findings, a perivascular debridement should also be performed in these cases. The reconstruction always should be combined with a calculated antibiotic therapy. Two of our patients died perioperatively. During follow up, 8 patients showed patent reconstructions and no signs of infection. The urgency of surgery depends on the level of inflammation and the existence of any secondary complications.

Quo vadis, biotech? (Part 1).

The recent increase in the capitalization value of the biotechnology industry appears to be sustainable. The phenomenon is interpreted as an acknowledgement by the markets that this industry has become the main source of innovation for the pharmaceutical industry. In addition, biotechnology is beginning to impact on other industries. However, from a methodological and strategic point of view, the biotechnology industry is still too fragmented. Consolidation along the lines of value generation in drug research and development, however, will occur. Over the next 5 to 10 years, the biotechnology industry will remain the fastest growing industry in the health care arena.

Drug discovery: a historical perspective.

Driven by chemistry but increasingly guided by pharmacology and the clinical sciences, drug research has contributed more to the progress of medicine during the past century than any other scientific factor. The advent of molecular biology and, in particular, of genomic sciences is having a deep impact on drug discovery. Recombinant proteins and monoclonal antibodies have greatly enriched our therapeutic armamentarium. Genome sciences, combined with bioinformatic tools, allow us to dissect the genetic basis of multifactorial diseases and to determine the most suitable points of attack for future medicines, thereby increasing the number of treatment options. The dramatic increase in the complexity of drug research is enforcing changes in the institutional basis of this interdisciplinary endeavor. The biotech industry is establishing itself as the discovery arm of the pharmaceutical industry. In bridging the gap between academia and large pharmaceutical companies, the biotech firms have been effective instruments of technology transfer.

The 6 volt battery for implantable cardioverter/defibrillators.

The usage of a 6 V lithium manganese dioxide battery results in a significant reduction of capacitor loading time within implantable defibrillators/cardioverters. In order to provide ERI indication a new cathode formulation has been developed. The battery shows no voltage delays, a low self-discharge and fulfilled all requirements to an energy source for an implantable device.

Intent and coincidence in pharmaceutical discovery. The impact of biotechnology.

Drug research developed around a purpose: the cure of diseases. This intent to cure, however, offered no clue to the understanding of diseases and to their treatment. Instead such guidance had to come from scientific disciplines which laid the foundations for drug research and offered specific opportunities for the solution of therapeutic problems. In the sequence of their appearance, these scientific disciplines were: chemistry, pharmacology/physiology, microbiology, biochemistry and molecular biology. It can be shown that new therapeutic classes of drugs like muscle relaxants, diuretics, L-dopa, antibiotics, recombinant proteins, monoclonal antibodies and others were generated on the basis of scientific opportunities rather than therapeutic need. All of these drugs were created within the confines of a chemical paradigm of medicine and drug therapy. We are now witnessing the entry of a new informational paradigm into medicine which is most prominently represented by genomic sciences. This paradigm will bring two important changes to the therapy of diseases. First, molecular biology has matured to such a degree that it can now study complex genomes and their functionality in complex organisms such as humans. Therefore, results from these studies no longer have to be translated into the context of medicine: they are already within this context. Secondly, drug therapy which used to be largely symptomatic, will now aim at targets which are closer to the causes of diseases than previously. Therapeutic progress, which used to be indirect, conjectural and coincidental, is about to become more directed, definitive and intentional. At least from the limited and utilitarian perspective of medicine, drug discovery will be more often based on intent rather than coincidence. But industry and, for that matter, society as a whole should not forget that this situation has come about through the evolution of science which was not, and can never be, predictable.

Medicine and genetic engineering: just another method or a new paradigm?

Scientific and technical developments have influenced medicine in a more profound way than any other cultural forces. In our days, molecular biology appears to be the major scientific factor which forms medicine. To those who practise medicine in the clinical environment, this statement may come as a surprise; however, if one looks at therapeutic and diagnostic research, the magnitude of change becomes evident. Most of these changes can still be interpreted in the context of known categories. In the analysis of the human genome, as well as in somatic gene therapy, however, a new principle emerges which will change our understanding of disease in a profound way. The scientific interpretation of disease as well as of diagnosis and therapy was first based on a morphological paradigm, which can be traced back to R. Virchow as well as to his contemporaries and successors. This powerful paradigm was later complemented by a chemical or biochemical paradigm which turned out to be extremely useful: modern diagnostics based on clinical chemistry as well as drug therapy are direct consequences of this influence. The new understanding of disease, diagnosis and treatment, which molecular biology is affording, is centered around the concept of genetic information. Diseases can be interpreted as informational deficits, as manifestations of faulty, inadequate or surplus information. While disease was previously interpreted on the basis of alterations in form and function it can now be seen as a derangement of the flow of information within cells, between cells, and between organs. The consequences for strategies of diagnosis and treatment will be profound.(ABSTRACT TRUNCATED AT 250 WORDS)

Gene technology and the drugs of tomorrow.

The progress of pharmaceutical research depends on three factors: on the evolution of medical needs, on societal attitudes, and on scientific and technical feasibility. Among the factors which are 'internal' to science, molecular biology seems to be the most important driving force, at least for the foreseeable future. The influence of molecular biology on pharmaceutical research is occurring in several distinct phases. The first phase was characterized by the use of gene technology as a production instrument for known proteins. In the second phase, gene technology is instrumental in the identification of novel proteins and in the elucidation of their gene structure and physiological function. A great number of proteins which have therapeutic potential will eventually emerge from this phase, with the more important ones like the hematopoietic factors yet to come. During the third phase, gene technology will provide proteins that can serve as pharmacological tools: receptors, ligands, enzymes, cytokines and other proteins provided by gene technology will enable us to open up new fields of pharmacology from which novel drugs, often low molecular weight chemical entities, will emerge. Finally the fourth phase will be characterized by a knowledge of gene structure and regulation extensive enough to develop a pharmacology of gene regulation and to establish somatic gene therapy. New drugs that can be expected to emerge from the interaction of molecular biology and pharmaceutical research within the next ten to twelve years are discussed. It is expected that pharmaceutical research will in the end be transformed into a discipline in which molecular biology and structural chemistry play dominating roles while synthetic chemistry will be reduced to the role of an important tool.

Balance performance among noninstitutionalized elderly women.

Descriptive data were collected regarding static standing balance of 71 noninstitutionalized elderly women as they performed two timed balance tests. All subjects performed the sharpened Romberg test and the one-legged stance test on each foot in four test conditions: 1) eyes open, 2) eyes closed, 3) shoes on, and 4) shoes off. Subjects were grouped and analyzed according to the following age ranges: 1) 60 to 64 years, 2) 65 to 69 years, 3) 70 to 74 years, 4) 75 to 79 years, and 5) 80 to 86 years. The best time of three trials was used for data analysis. The maximum balance time for the sharpened Romberg test was 60 seconds. For the one-legged stance test, a maximum balance time was 30 seconds. No significant difference was found between right and left or dominant and nondominant limbs while performing the one-legged stance test. No significant difference was found in mean balance time between subjects who had fallen versus those who had not fallen, nor between shoes-on and shoes-off test performance. Subjects' performance on the eyes-open test was consistently superior to their eyes-closed test performance (p less than .0001). The one-legged stance test mean balance time decreased significantly as age increased. More subjects reached the maximum balance time on the sharpened Romberg test than on the one-legged stance test. The results of this study indicate that additional research is needed in the area of balance maintenance among the elderly population.