Development of consumer probiotics for the US market

Curiosity about probiotic bacteria is high. This is not surprising given the rapid growth of the natural products market in the USA, which was 22% in 1995 (New Hope Natural Media, Boulder, CO). Although probiotic cultures are only one component of that market, this trend shows that consumers in the USA are increasingly taking a pro-active stance towards their health and are purchasing products not only to eliminate what is perceived as dietary negatives but to increase the levels of dietary positives (Wrick, 1995). This shift in consumer attitude bodes well for the development of the American probiotic market. This article describes the composition, promotion and labelling of probiotic-containing products, discusses attributes of commercial probiotic bacteria, and estimates the size of the probiotic market in the USA. This market information was obtained from several published (Anon, 1996a,b) and unpublished but commercially available (SPINS Information Services, San Francisco, CA and New Hope Natural Media, Boulder, CO) sources.     

Dependence of muscle VO2 on blood flow dynamics at onset of forearm exercise

The hypothesis that the rate of increase in muscle O2 uptake (VO2mus) at the onset of exercise is influenced by muscle blood flow was tested during forearm exercise with the arm either above or below heart level to modify perfusion pressure. Ten young men exercised at a power of approximately 2.2 W, and five of these subjects also worked at 1.4 W. Blood flow to the forearm was calculated from the product of blood velocity and cross-sectional area obtained with Doppler techniques. Venous blood was sampled from a deep forearm vein to determine O2 extraction. The rate of increase in VO2mus and blood flow was assessed from the mean response time (MRT), which is the time to achieve approximately 63% increase from baseline to steady state. In the arm below heart position during the 2.2-W exercise, blood flow and VO2mus both increased, with a MRT of approximately 30 s. With the arm above the heart at this power, the MRTs for blood flow [79.8 +/- 15.7 (SE)s] and VO2mus (50.2 +/- 4.0 s) were both significantly slower. Consistent with these findings were the greater increases in venous plasma lactate concentration over resting valued in the above heart position (2.8 +/- 0.4 mmol/l) than in the below heart position (0.9 +/- mmol/l). At the lower power, both blood flow and VO2mus also increased more rapidly with the arm below compared with above the heart. These data support the hypothesis that changes in blood flow at the onset of exercise have a direct effect on oxidative metabolism through alterations in O2 transport.     

Principal axes and surface fitting methods for three-dimensional image registration

We evaluated the effect of the image acquisition parameters on the accuracy of the principal axes and surface-fitting techniques for three-dimensional image registration. Using two types of phantom objects, MR brain image and a mathematically defined ellipsoid, we simulated pairs of scans with known acquisition parameters, including longitudinal coverage, magnitude of mis-registration, number of sections and section thickness. Both methods are sensitive to the systematic deformation of contours. The principal axes method is also sensitive to incomplete scan coverage and to the x-axis and y-axis misangulation. Both methods are insensitive to the number of sections, section thickness and the number of points per section. Surface fitting performed well without user supervision. There is no need for routine inclusion of the scaling factors as search parameters. The results confirm the feasibility of three-dimensional multimodality registration of brain scans with accuracy 1-2 mm, with surface fitting being the method of choice.     

Phase I/II study of a short course of weekly cisplatin in patients with advanced solid tumours

Twenty-five patients with advanced solid tumours were entered in a phase I/II study of six, weekly cycles of cisplatin. Nineteen patients were chemonaive and six were previously treated. The starting dose was 50 mg m-2 week-1. This dose could be escalated without major toxicity to 70 mg m-2 week-1. At a dose of 80 mg m-2 myelosuppression grade 3 occurred as well as grade 1 nephro- and neurotoxicity. The maximum tolerated dose was 85 mg m-2 with dose limiting thrombocytopenia. Hypertonic saline was effective in preventing nephrotoxicity. Ondansetron was a very effective antiemetic in the first weeks of treatment but its efficacy waned later on. Responses were observed in head and neck cancer, melanoma and mesothelioma. At the dose level of 80 mg m-2 the optimal dose intensity was reached. This schedule will be tested further in phase II studies.     

Dual immunodetection and hybridisation in situ of opsin mRNA and rhodopsin protein in retinal sections

We describe a simple method for combining in situ hybridisation and immunohistochemistry on the same retinal section. The technique was developed using a radiolabelled cDNA probe for opsin and an antibody (ROS1F4) against rhodopsin. This method retains the antigenic sites if immunocytochemistry is performed prior to in situ hybridisation. Opsin mRNA was found in the photoreceptor inner segment with rhodopsin immunolocalised to the photoreceptor outer segments. The technique should be applicable to numerous situations including analysis of the sequence of events in the expression and synthesis of the various opsins during retinal development and degeneration.     

Preliminary irradiation test results from the Yankee Atomic Electric Company reactor vessel test irradiation program

The Yankee Atomic Electric Company test irradiation program was implemented to characterize the irradiation response of representative Yankee Rowe reactor vessel beltline plate materials and to remove uncertainties in the analysis of existing irradiation data on the Yankee Rowe reactor vessel steel. Plate materials each containing 0·24 w/o copper, but different nickel contents at 0·63 w/o and 0·19 w/o, were heat treated to simulate the Yankee vessel heat treatment (austenitized at 982°C (1800°F)) and to simulate Regulatory Guide 1·99 database materials (austenitized at 871°C (1600°F)). These heat treatments produced different microstructures so the effect of microstructure on irradiation damage sensitivity could be tested. Because the nickel content of the test plates varied and the copper level was constant, the effect of nickel on irradiation embrittlement was also tested. Correlation monitor material, HSST-02, was included in the program to benchmark the Ford Nuclear Reactor (University of Michigan Test Reactor) which had never been used before for this type of irradiation program. Materials taken from plate surface locations (versus 1/4T) were included to test whether or not the improved toughness properties of the plate surface layer, resulting from the rapid quench, are maintained after irradiation. If the improved properties are maintained, pressurized thermal shock calculations could utilize this margin. Finally, for one experiment, irradiations were conducted at two irradiation temperatures (260°C and 288°C) to determine the effect of irradiation temperature on embrittlement. The preliminary results of the irradiation program show an average temperature effect of 38°C for a 28°C difference in irradiation temperature. The results suggest that for nickel bearing steels, the superior toughness of plate surface material is maintained after irradiation and for the copper content tested, nickel has little effect on irradiation response. No apparent microstructure effect on irradiation response was noted and the HSST-02 material's response to irradiation was similar to results from power reactor and other test reactor tests, thus qualifying the Ford Test Reactor for irradiation experiments such as those conducted for the Yankee Atomic program.     

The pattern of inflammation in rat sepsis due to enterotoxin-producing Staphylococcus aureus: a comparison with ischemia-reperfusion injury

Sepsis and trauma have similarities in their immunopathologic profiles. Both conditions can result in multi-system organ failure which is sometimes associated with cytokine generation and inflammatory cell activation. Furthermore, decreases in peripheral blood monocyte expression of HLA-DR have been noted in both human sepsis and trauma. However, the magnitude, onset, and time course of such stimuli are often difficult to ascertain in human studies. Thus, to study a more detailed in vivo immunologic profile in these conditions, rat models were employed. Our aim was to describe and analyze cytokine and peripheral blood immunophenotype patterns in bacterially induced rat sepsis and to compare this to rat ischemia-reperfusion injury. Sprague-Dawley rats underwent either bacterial injection with enterotoxin producing Staphylococcus aureus or hind limb ischemia/ reperfusion. Two bacterial doses which were either lethal or sublethal at 24-48 hours were utilized. Peripheral blood neutrophils and B-lymphocytes were studied for expression of beta-integrins (CD11b and CD11b/c) and I-A, respectively, using flow cytometry. Corresponding plasma levels of TNF alpha and interferon gamma were measured by ELISA. At 24 hr, a lethal bacterial lethal bacterial dose injection resulted in significantly higher levels of neutrophil CD11b/c expression (p < 0.005) compared with ischemia-reperfusion treatment. B-cell I-A expression was also higher in lethal sepsis. Gamma interferon levels were significantly higher in lethal sepsis compared with ischemia-reperfusion (p = 0.005). Studies over time showed that CD11b expression and interferon gamma were both more marked at 6 hr than at 24 hr in lethal sepsis. This pattern was not observed in sublethal sepsis or in ischemia-reperfusion. CD11b/c expression on the other hand remained elevated at comparable levels at 6 and 24 hr in lethal sepsis. B-cell I-A expression in ischemia-reperfusion and sublethal sepsis decreased at 24 hr compared with baseline. Lethal sepsis in rats injected with enterotoxin producing staphylococcus results in phasic alterations in neutrophil CD11b and plasma interferon levels prior to death. In analogy to the findings of monocyte decreases in DR expression observed in human trauma and sepsis, rat B-cell I-A expression showed decreases in sublethal sepsis as well as in ischemia-reperfusion injury. However, this was not observed in lethal sepsis. These findings have implications in understanding the immunologic/inflammatory changes observed in human sepsis and trauma.