Homogenisation and oxygen transfer rates in large agitated and sparged animal cell bioreactors: Some implications for growth and production

Because of concern for cell damage, very low agitation energy inputs have been used in industrial animal cell bioreactors, typical values being two orders of magnitude less than those found in bacterial fermentations. Aeration rates are also very small. As a result, such bioreactors might be both poorly mixed and also unable to provide the higher oxygen up-take rates demanded by more intensive operation. This paper reports experimental studies both of K _L a and of mixing (via pH measurements) in bioreactors up to 8 m³ at Wellcome and of scaled down models of such reactors at Birmingham. Alongside these physical measurements, sensitivity of certain cell lines to continuously controlled dO₂ has been studied and the oxygen up-take rates measured in representative growth conditions. An analysis of characteristic times and mixing theory, together with other recent work showing that more vigorous agitation and aeration can be used especially in the presence of Pluronic F-68, indicates ways of improving their performance. pH gradients offer a special challenge.     

Minocycline induced autoimmune hepatitis and systemic lupus erythematosus-like syndrome.

Monocycline is the most widely prescribed systemic antibiotic for acne largely because it needs to be given only once or twice a day and seems not to induce resistance. Up to April 1994 11 cases of minocycline induced systemic lupus erythematosus and 16 cases of hepatitis had been reported to the Committee on Safety of Medicines. An analysis of these cases together with seven other cases shows the severity of some of these reactions. Two patients died while taking the drug for acne and a further patient needed a liver transplant. Acne itself can induce arthritis and is often seen in association with autoimmine liver disease, but the clinical and biochemical resolution seen after withdrawal of the drug, despite deterioration of the acne, suggests a drug reaction. In five cases re-exposure led to recurrence. Because reactions may be severe early recognition is important to aid recovery and also to avoid invasive investigations and treatments such as corticosteroids and immunosuppresants. Safer alternatives should be considered for treating acne.     

Cell cycle and cell size dependence of susceptibility to hydrodynamic forces

Exposure of animal cells to intense hydrodynamic forces exerted in turbulent capillary flow, and by controiled agitation and aeration, resulted in preferential destruction of S and G(2) cells and the extent of destruction of these cells was dependent upon the intensity of the action. The loss of these cells was possibly due to their larger size. However, the appearance of large numbers of membrane-bound vesicular structures similar to apoptotic bodies as well as cells with low DNA stainability (in a sub-G(1) peak) suggested that the action of adverse hydrodynamic forces on these large cells may at least in part be to induce an apoptotic response. (c) 1995 John Wiley & Sons, Inc.     

Ventilation inhomogeneity in oleic acid-induced pulmonary edema

Tsang, John Y. C., Michael J. Emery, and Michael P. Hlastala. Ventilation inhomogeneity in oleic acid-inducedpulmonary edema. J. Appl. Physiol.82(4): 1040-1045, 1997.Oleic acid causes permeability pulmonaryedema in the lung, resulting in impairment of gas-exchange andventilation-perfusion heterogeneity and mismatch. Previous studies haveshown that by using the multiple-breath helium washout (MBHW)technique, ventilation inhomogeneity (VI) can be quantitativelypartitioned into two components, i.e., convective-dependent inhomogeneity (cdi) and diffusive-convective-dependent inhomogeneity (dcdi). Changes in VI, as represented by the normalized slope of thephase III alveolar plateau, were studied for 120 min in fiveanesthetized mongrel dogs that were ventilated under paralysis by aconstant-flow linear motor ventilator. These animals received oleicacid (0.1 mg/kg) infusion into the right atrium att = 0. MBHWs were done induplicate for 18 breaths every 40 min afterward. Three other dogs thatreceived only normal saline served as controls. The data show that,after oleic acid infusion, dcdi, which represents VI in peripheralairways, is responsible for the increasing total VI as lung wateraccumulates progressively over time. The cdi, which represents VIbetween larger conductive airways, remains relatively constantthroughout. This observation can be explained by increases in theheterogeneity of tissue compliance in the periphery, distal airwayclosure, or by decreases in ventilation through collateral channels.

     

A new monoclonal antibody (3D3) generated with human respiratory mucins and directed against Lewis determinants

We have prepared a monoclonal antibody (MAb), 3D3, raised againstpurified human respiratory mucins. This antibody recognizedmucins and proteolytically derived glycopeptides. The epitoperecognized by the antibody was destroyed by -L-fucosidase, indicatingthat it was present on the carbohydrate moieties. Structuralspecificity was determined by adsorption on a variety of synthetic,insolubilized oligosaccharides. Several lines of evidence indicatethat the 3D3 MAb reacted strongly with the Lewis (Le^b) antigen,but also recognized Le^a and Le^y determinants. This antibodymight be useful to study mucin secretion. human bronchial mucins Lewis b     

A new genus and two new species of gobiid fishes (Perciformes) from the Chagos Archipelago,Central Indian Ocean

Synopsis A recent (1979) expedition to the Chagos Archipelago resulted in the collection of about 40 new taxa of fishes. A new genus,Trimmatom, and two new species,T. nanus andT. offucius, are described here. The new genus is characterized by having all pelvic-fin rays simple (unbranched), a scaleless body, no head pores, a wide gill opening extending anteroventrally to below the eye, and hypurals 1 and 2 fused to the complex formed by the fusion of the ural centrum and hypurals 3 and 4.T. nanuss andT. offucius are differentiated on the basis of fin ray counts and colour pattern.T. nanus is the smallest vertebrate yet to be described. Mature females with ovaries full of eggs are 8–10 mm in standard length.