Structural features determining the antibiotic potencies of natural and synthetic hop bitter resins, their precursors and derivatives

Twenty-six hop bitter resins, some hitherto not investigated, were tested for antimicrobial activities. Gram-positive bacteria were much more sensitive than Gram-negative ones. The inhibitory effect against Bacillus subtilis 168 was measured by several methods and the general rule could be established that the antibiotic properties are mainly dependent on the hydrophobic parts of the molecules. Thus the acyl-lupuphenones (2-acyl-3,5-4,4',6-tri(3-methyl-2-butenyl)-cyclohexane-triones (1, 3, 5) having three prenyl and one acyl side chain are the most active substances. Their minimum inhibitory concentration (MIC) increases from the capro (0.5 muM) to the aceto derivative (11 muM). Any substitution with hydrophilic functions or loss of hydrophobic groups causes reductions in biological activity. This is most evident with the corresponding acyl-phloroglucine precursors (2-acyl-1,3,5-trihydroxybenzenes) which lack the three prenyl side chains (MIC, 110 to 5050 muM respectively). Conversion of the central six-membered ring structure into a five-membered one results in additional losses of antimicrobial activity. These findings support the proposal that the lipophilic region of the cell membrane represents the target site for the hop bitter resins.     

A technique for identifying the subgroup membership of certain misarticulating children

Cluster analysis was used to identify two homogeneous clusters of 8-9 1/2-year-old children who misarticulated /s/, /r/, or both. The analysis was based on the children's scores on 40 measures of language, reading, auditory processing, and other variables. Discriminant function analysis was then used to identify a subset of five measures and a means of computing classification scores. These measures and the classification scores can be used to identify the cluster membership of new subjects. The use of classification scores for identifying cluster membership was cross-validated against cluster analysis of a second group of children. The two clusters are described in terms of their performance on language and reading measures.     

Heated-air drying of oilseeds

This paper describes experimental work on the drying of oilseeds. Resistance to air flow and drying rates, parameters needed for oilseed drier design, were measured. Safe drying temperatures were deter,ined in a small batch fluidized bed. Some sealed tube heating tests were also perforrned for comparison. Quality assessment was based on the effect of drying conditions on the germination of the seed and on the free fatty acid content and peroxide value of the extracted oil. Colour of the oil was also measured before and after a heat bleach test using a photometric method.Quality results indicate that germination is affected by heat above a critical drying air and seed temperature. For sunflower seed, safe drying air temperatures of 65, 60 and 55°C were obtained for initial moisture contents of 12, 14 and 16% respectively. For rapeseed, an inlet air temperature of 60°C caused no loss of germination for each initial moisture content. However, sealed tube heating of 16% m.c. sunflower and rapeseed at 60°C for 4 hr completely killed the seeds. Free fatty acid content and peroxide value were not significantly changed by the heat treatments in all cases, and oil colour after heat bleaching generally showed some improvement up to an air temperature of 70°C. At 80°C, however, substantial darkening of sunflower oil was observed.     

Converging and diverging flow in narrow conical passages

Summary This paper deals with sink and source flows developed in cones with small apex angles and in narrow gaps formed by two concentric cones. Numerical and approximate analytical solutions to these flows are presented. An exact solution for the creeping flow in conical gaps in terms of Legendre polynomials is derived. The analytical solutions to the flow in cones, includes the linearized inertia terms in the momentum equations, and are given using Gauss' hypergeometric series. For low Reynolds numbers, both converging and diverging flows are shown to coincide and are similar to Poiseuille's flow. However, when inertia effects are included, these are found to be radically different. For a sink flow, the radial velocity flattens in the neighborhood of the mid-angle and, as Re increases, the plateau expands out towards the conical walls, tending to the inviscid flat profile throughout the entire flow field. Contrary to the accelerating flow, the maximum velocity of the decelerating flow is shown to increase with Re. As a first critical Reynolds number is approached, the shear stress reduces to zero on the cone walls or, for a conical gap, on the outer cone walls. A further increase in Re above this first critical value, is found to produce a flow reversal either near the wall or, for the case of a conical gap, in the proximity of the outer cone. Thus, when Re exceeds this second value, purely decelerating flow cannot exist. The results for accelerating (sink) flow indicate that the approximate analytic solution is an excellent representation of this flow, whereas, for decelerating (source) flows particularly near separation, the results indicate that the numerical approach is needed to properly capture all flow features.     

Amifostine protects normal tissues from paclitaxel toxicity while cytotoxicity against tumour cells is maintained

The objectives of this study were to evaluate the protective effects of amifostine against paclitaxel-induced toxicity to normal and malignant human tissues. Haematopoietic progenitor colony assays were used to establish the number of CFU-GEMM and BFU-E colonies after incubation with WR-1065 alone, Amifostine alone, paclitaxel (2.5 or 5 microM) +/- WR-1065 or amifostine. MTT and alkaline elution assays evaluated the in vitro growth inhibitory and DNA damaging effects, respectively, of paclitaxel with or without amifostine against normal human fibroblasts and human non-small cell lung cancer (NSCLC) cells. This combination was also evaluated in vivo using severe combined immune deficient (scid) mouse models of early (non-palpable tumours) and advanced (palpable tumours) human ovarian cancer. Human 2780 ovarian cancer cells were inoculated subcutaneously while paclitaxel and amifostine were administered intraperitoneally. A brief exposure (15 min) to amifostine not only protected human haematopoietic progenitor colonies from paclitaxel toxicity, but stimulated the growth of CFU-GEMM and BFU-E beyond control values. Amifostine protected normal human lung fibroblasts from paclitaxel-induced cytotoxicity and DNA single-strand breaks. However, paclitaxel cytotoxicity and DNA single-strand breaks were actually enhanced by pretreatment with amifostine in the NSCLC model. Importantly, amifostine did not interfere with paclitaxel antitumour activity even with prolonged exposure (24.5 h) of the lung cancer cells to high concentrations (1.2 mM) in vitro or following five repetitive high doses (200 mg/kg) given to scid mice with human ovarian cancer xenografts. Indeed, under certain circumstances, amifostine resulted in sensitisation of tumour cells to paclitaxel. Our results confirm previous reports of the ability of amifostine to protect normal tissues from the toxic effects of chemotherapy drugs and now extend these observations to paclitaxel.     

Personalities and alimentary behaviors in obese patients

The ability of lonidamine (LND), an energolytic derivative of indazole-carboxylic acid, to modulate the cytotoxic activity of cisplatin (CDDP) and epidoxorubicin (EPI), singly or in combination, was investigated in two human breast cancer cell lines (MCF7 and T47D). A 72-hr post-incubation with a non-cytotoxic concentration of LND (75 microM) increased the activity of a 1-hr CDDP treatment as well as that of a 1 to 16-hr EPI treatment. A different pattern of interaction among the drugs and modulator was observed as a function of the sequence of drug treatment. Specifically, supra-additive or additive effects of the combination were obtained in the two cell lines according to the different treatment schemes. In particular, the maximum potentiation was observed in MCF7 cells simultaneously exposed to CDDP, EPI and LND for 1 hr and then post-incubated with LND for 72 hr, and in T47 first exposed to EPI and LND, then to CDDP and LND, and finally post-incubated with LND. Flow cytometric analysis of MCF7 cell distribution in the different cycle phases showed that combined treatment with EPI/CDDP/LND was able to stabilize cell cycle perturbations (mainly G2M accumulation) induced by individual agents. The ability of LND to potentiate CDDP and EPI cytotoxicity, and the consideration that LND causes side effects different from those caused by alkylating agents and anthracyclines, make this compound an attractive candidate for multidrug combination therapy in breast cancer.     

Relation of endothelium, thrombogenesis, and hemorheology in systemic hypertension to ethnicity and left ventricular hypertrophy

Although the arterial tree is exposed to increased pressure in hypertensive patients, paradoxically, the complications of hypertension (heart attacks, stroke) are mainly thrombotic rather than hemorrhagic. Patients with left ventricular (LV) hypertrophy are at high risk of the complications of hypertension. We performed a cross-sectional study of 178 patients attending a hypertension clinic in a city center teaching hospital, and measured plasma levels of the soluble adhesion molecule P-selectin (associated with platelet activity/function and atherosclerosis), the von Willebrand factor (vWf; a marker of endothelial dysfunction), fibrin D-dimer (an index of thrombogenesis), plasminogen activator inhibitor (PAI, an index of fibrinolysis), lipoprotein(a) (Lp(a), associated with thrombogenesis and atherogenesis) and hemorheological indexes (fibrinogen, hematocrit, plasma viscosity, hemoglobin) in patients with essential hypertension, in whom the LV mass and LV mass index were determined using echocardiography. The 178 patients (86 men, mean age 54 +/- 15 years) were compared with 47 normotensive healthy controls (aged 56 +/- 20 years). Hypertensive patients had higher P-selectin, PAI, vWf, fibrin D-dimer, Lp(a), plasma fibrinogen, and plasma viscosity when compared with controls. Black hypertensive patients had higher Lp(a) levels and LV septal and posterior wall thickness on echocardiography, but lower plasma PAI levels. Patients with LV hypertrophy (defined as a LV mass index > 134 g/m2 in men or > 110 g/m2 in women) had higher plasma fibrinogen compared with those without LV hypertrophy. Systolic blood pressures were significantly correlated to age, plasma viscosity, plasma fibrinogen, and vWf. Diastolic blood pressures were significantly correlated with age and plasma fibrinogen. Fibrinogen levels were correlated with LV mass, LV mass index, left atrial size, plasma viscosity, and vWf. Fibrin D-dimer levels were significantly correlated with vWf and fibrinogen levels. Thus, hypertensive patients have high plasma fibrinogen levels, thrombogenesis, and impaired fibrinolysis (as indicated by high D-dimer and PAI levels, respectively), platelet activation (raised soluble P-selectin), and endothelial dysfunction (high vWF). The high plasma fibrinogen levels were related to blood pressures, LV mass index (and LV hypertrophy), and left atrial size. These abnormalities in hemorheologic factors and markers of thrombogenesis and endothelial function may act synergistically to increase the risk of thrombogenesis and atherosclerosis in hypertensive patients.