Fatty Acids Released from Milk Fat by Lipoprotein Lipase and Lipolytic Psychrotrophs

ABSTRACT: The ability of 13 different strains of psychrotrophs to release free fatty acids in milk was evaluated by using GC analysis. The 13 strains could be categorized into 3 groups: Group 1 consisted of bacteria that grew well and released large quantities of free fatty acids, group 2 consisted of bacteria that grew well but released low amounts of free fatty acids, and group 3 consisted of bacteria that did not grow well nor released large quantities of fatty acids. In group 1, 3 strains were determined to be highly lipolytic, releasing short‐chain fatty acids in amounts greater than reported threshold values. Group 3 consisted of 2 strains, which did not grow well in heat‐treated milk, and the subsequent release of free fatty acids was minor during the 10‐d monitoring time. The other 8 strains tested showed no specific pattern of fatty acid release and quantities of short‐chain fatty acids were not large, despite the ability to grow to high numbers in the treated milk. This work indicates that the lipolytic activity of psychrotrophs common in raw milk is specific to the species and a general prediction of free fatty acid release may not be possible.     

Prodrugs for targeting hypoxic tissues: regiospecific elimination of aspirin from reduced indolequinones

We report the cases of three patients with anorexia nervosa (AN) who each recovered rapidly after experiencing a life-threatening episode with severe thrombocytopenia. All three cases were the typical restricting-type of AN, occurring in adolescence. They refused to be admitted to a hospital until their general condition had been severely deteriorated. Their lowest platelet counts were 2.9, 4.6, and 2.3 x 10(4)/mm3, respectively. Apparent hemorrhagic tendencies, such as purpura, gingival and nasal bleeding, and gastrointestinal bleeding were observed. The bone marrow examination showed apparent hypoplasia in two patients. No evidence of disseminated intravascular coagulation or autoantibody to platelets was detected. The platelet counts recovered rapidly by water and nutritional supplementation. The recovery from the AN itself was excellent in all three patients without specific psychotherapy.     

Calcium-dependent and -independent binding of the pentraxin serum amyloid P component to glycosaminoglycans and amyloid proteins: enhanced binding at slightly acid pH

It has been found that sphingosine and sphingosylphosphorylcholine (amphiphilic cations) have a stimulatory, and cholesterol 3-sulfate (an amphiphilic anion), an inhibitory, effect on [14C]serine incorporation into phosphatidylserine in glioma C6 and rat liver microsomes. In glioma intact cells sphingosine stimulates phosphatidylserine synthesis in a process independent of protein kinase C, but suppressed by thapsigargin. We suggest that the stimulation of the enzyme occurs by the interaction of amphiphilic cations with the membrane cosubstrate phospholipids, leading to a charge redistribution on their phosphate groups, and hence facilitating the enzyme action. A new hypothesis concerning the mechanism of the serine base exchange reaction is discussed.     

Enzymology of the reduction of the novel fused pyrazine mono-n-oxide bioreductive drug, RB90740 roles for P450 reductase and cytochrome b5 reductase

RB90740 is the lead compound in a series of fused pyrazine mono-N-oxide bioreductive drugs. Theses agents have potential application in cancer therapy, since they are more toxic to hypoxic than to aerobic cells as a consequence of their bioactivation by cellular reductase enzymes within the hypoxic regions of a tumour. In this study, mouse liver microsomes have been used to characterise the enzymology of the reductive activation of RB90740. Under hypoxic conditions, the reduction of RB90740 to its stable 2-electron reduced product RB92815 was supported by both NADH and NADPH, the former supporting a rate approximately 80% of the latter. Combining the two cofactors had no additive effect. Neither carbon monoxide nor metyrapone inhibited reduction of RB90740, indicating that P450 isozymes were not involved in the reduction of this compound. 2' AMP, and inhibitor of P450 reductase, did not inhibit formation of RB92815, whereas DPIC, another inhibitor but with a different mode of action, inhibited both the NADH, and NADPH-dependent reduction of RB90740. Similarly, two selective inhibitors of NADH: cytochrome b5 reductase, pHMB and PTU, completely inhibited both NADH and NADPH-dependent reduction of RB90740. Our findings implicate P450 reductase, cytochrome b5 reductase, and cytochrome b5 in the activation of the compound. However, there is no clear relationship between the intracellular levels of P450 reductase and cytochrome b5 reductase and the hypoxic toxicity of RB90740, which implies that other factors, in addition to drug activation, play a major role in controlling the toxicity of this particular bioreductive drug.     

A new tool for studying the molecular architecture of the fungal cell wall: one-step purification of recombinant trichoderma beta-(1-6)-glucanase expressed in Pichia pastoris

We assessed the anesthetic properties of helium and neon at hyperbaric pressures by testing their capacity to decrease anesthetic requirement for desflurane using electrical stimulation of the tail as the anesthetic endpoint (i.e., the minimum alveolar anesthetic concentration [MAC]) in rats. Partial pressures of helium or neon near those predicted to produce anesthesia by the Meyer-Overton hypothesis (approximately 80-90 atm), tended to increase desflurane MAC, and these partial pressures of helium and neon produced convulsions when administered alone. In contrast, the noble gases argon, krypton, and xenon were anesthetic with mean MAC values of (+/- SD) of 27.0 +/- 2.6, 7.31 +/- 0.54, and 1.61 +/- 0.17 atm, respectively. Because the lethal partial pressures of nitrogen and sulfur hexafluoride overlapped their anesthetic partial pressures, MAC values were determined for these gases by additivity studies with desflurane. Nitrogen and sulfur hexafluoride MAC values were estimated to be 110 and 14.6 atm, respectively. Of the gases with anesthetic properties, nitrogen deviated the most from the Meyer-Overton hypothesis. Implications: It has been thought that the high pressures of helium and neon that might be needed to produce anesthesia antagonize their anesthetic properties (pressure reversal of anesthesia). We propose an alternative explanation: like other compounds with a low affinity to water, helium and neon are intrinsically without anesthetic effect.     

Bispectral EEG index during nitrous oxide administration

Recent reports suggest an increased incidence of cytomegalovirus (CMV) infection in recipients of unrelated donor (UD) bone marrow transplantation (BMT). In this study we have collated the incidence of CMV infection and disease in sequential UD (n = 119) and related donor (RD; n = 79) BMT performed in a single institution over a 7-year period. Low-risk patients (CMV seronegative recipient and donor) accounted for 51% of UD BMT (n = 61) and 62% of RD BMT (n=49), with CMV excretion documented in one RD BMT only. The remaining high-risk patients received identical prophylaxis regimens with aciclovir and intravenous immunoglobulin (IVIG). Two groups consisting of 58 UD BMT (median age 9.0 years, range 0.7-45.3 years) and 30 RD BMT (median age 13.6 years. range 1.6-47.6 years) were analysed. CMV reactivation/re-infection was documented in 15 UD BMT (26%) and 10 RD BMT (33%) (P = 0.72), and CMV disease in four UD BMT (8%) and four RD BMT (13%) (P = 0.533). In this series the risk of CMV excretion and disease following UD BMT was similar to that following RD BMT.     

Cardiac involvement in neuromuscular diseases

Many neuromuscular disorders involve the heart, occasionally with overt clinical disease. Muscular dystrophies (dystrophinopathies, limb girdle muscular dystrophy, Emery-Dreifuss muscular dystrophy, Steinert's myotonic dystrophy), congenital myopathies, inflammatory myopathies and metabolic diseases (glycogenosis, periodic paralysis, mitochondrial diseases) may produce dilated or hypertrophic cardiomyopathy and heart rhythm or conduction disturbances. Furthermore the heart is commonly involved in some hereditary and degenerative diseases (Friedreich's ataxia and Kugelberg-Welander syndrome) and acquired (Guillain-Barré syndrome) or inherited (Refsum's disease and Charcot-Marie-Tooth syndrome) polyneuropathies. A cardiologist's high clinical suspicion and a simple but systematic skeletal muscle and peripheral nerve investigation, including muscle enzymes quantification, neurophysiological study and muscle biopsy, are necessary for an accurate diagnosis. In selected patients, more sophisticated biochemical and genetic analysis will be necessary. In most cases, endomyocardial biopsy is not essential for the diagnosis.