The pyrimido-pyrimidine derivative RA-642 protects from brain injury in a combined model of permanent focal ischemia and global ischemia reperfusion

The effects of pyrimido-pyrimidine derivatives (dipyridamole, RA-642 and mopydamole) on lipid peroxidation (inhibition of the production of malondialdehyde, MDA) in different regions of the rat brain were studied. Ferrous sulfate and ascorbic acid (FeAs) were used to induce lipid peroxidation via the formation of hydroxyl anions. The antiperoxidative effect of RA-642 (in the μM range) was 10 times more potent than that of dipyridamole. Mopydamole did not exert any inhibitory effect on MDA production. In a model of ischemia reperfusion with bilateral occlusion of the common carotid arteries for 1 h and restoration of circulation for a period of 2 h, dipyridamole inhibited FeAs-induced MDA production but did not protect from postischemic brain tissue damage (measured by mitochondrial reduction of tetraphenyl tetrazolium). RA-642 inhibited FeAs-induced MDA production and showed 50–67% protection from tissue damage as compared with untreated animals, while mopydamole did not inhibit MDA production and showed 30–48% protection. No correlation was found between inhibition of lipid peroxidation and protection from brain tissue damage.     

Human neutrophil-specific granule deficiency: a model to assess the role of neutrophil-specific granules in the evolution of the inflammatory response

It has been suggested that neutrophil (PMN) specific granules are important in cell aggregation, locomotion, hydroxyl radical formation, and in extracellular functions such as the generation of complement- related inflammatory mediators (C5a) and the feedback regulation of myelopoiesis. In the current studies, a 9-yr-old boy with a history of recurrent infections and specific granule deficiency (absent lactoferrin, B-12 binding proteins, and characteristic specific granules on sucrose gradient centrifugation of cell homogenates) was studied to assess some of these concepts. In vivo, the patient had decreased PMN and monocyte accumulation into Rebuck skin windows but an expected febrile episode with an associated neutropenia (PMN margination) and neutrophilia (mobilization of marrow reserves) in response to intravenous endotoxin. In vitro, the patient's resting PMN showed increased ruffling, increased surface-to-volume ratio, and increased numbers of centriole-associated microtubules. His PMN showed a significant decrease in cell negative surface charge (which may relate to aggregation) in response to several stimuli and adhered better than normally to plastic. In addition, his PMN aggregated normally in response to the chemoattractant f-met-leu-phe, although the subsequent disaggregation normally seen with PMN did not occur with the patient's cells. Chemotaxis of the patient's PMN to several stimuli was abnormal, and specific saturable and displaceable binding of the chemoattractant f-met-leu-[3H]phe was decreased. Similarly, following incubation with secretagogues, there was a less than normal increase in f-met-leu-[3H]phe binding and an absence of the normal increases in PMN surface area. The patient's PMN bactericidal activity, stimulated oxygen metabolism (cytochrome-c reduction, chemiluminescence, and NBT reduction), and elicited changes in membrane potential were also abnormal. Studies assessing the mechanism for the abnormal monocyte accumulation into skin windows indicated the patient's monocyte chemotaxis was better than normal in vitro. However, the patient's PMN homogenates lacked a stimulus of monocyte locomotion and did not generate chemotactic activity normally from serum. Thus, the data indicate that specific granule constituents are not required for neutrophil margination in vivo or aggregation in vitro. However, the data support the concept that PMN-specific granules are important for PMN locomotion and oxidative metabolism. In addition, extracellular release of specific granule constituents appears to be important for amplification of the initial and subsequent phases of the inflammatory response.     

Direct and indirect maximum oxygen consumption in sedentary subjects living at a moderate altitude

In order to compare 1) predicted values of aerobic capacity (VO2Max) and, 2) direct VO2Max reported in the literature for sedentary subjects, direct VO2Max was measured in 27 sedentary males (18-25 years old), residents at 2240 meters (588.5 +/- 1.0 mmHg). To get direct VO2Max, ventilation and expired gases were measured while the subjects performed maximal exercise on a motor treadmill. Predicted VO2Max was estimated from the Astrand and Ryhming nomogram by measuring submaximal heart rate (HR) during a step test protocol. The mean results from the maximal protocol were: HR 194.9 +/- 5.4 beats/min, direct VO2Max 3.15 +/- 0.46 L/min and 47.67 +/- 5.07 ml/min/Kg, absolute and relative to body weight, respectively. From the submaximal protocol, mean HR was 171 +/- 8.3 beats/min and predicted VO2Max 2.50 +/- 0.39 L/min. In spite of a good correlation (r = 0.79) between predicted and direct VO2Max, the predicted values underestimated 20.3 +/- 7.2% direct measurements. Our data point out that 1) indirect measuring of aerobic capacity from the Astrand and Ryhming nomogram is discouraged in sedentary subjects living at moderate altitudes and, 2) in contrast to other author's suggestions, aerobic capacity is not diminished by chronic exposure to moderate hypoxia.     

Effects of low concentrations of arachidonic acid derived mediators on the membrane potential and respiratory burst responses of human neutrophils as assessed by flow cytometry

Hypaque-Ficoll purified (95%) neutrophils (PMN) from normal healthy subjects were assessed for FMLP-elicited membrane potential (delta psi) responses and dichlorofluorescein (DCF) fluorescence (a measure of intracellular hydrogen peroxide production) using flow cytometry and appropriate fluorescent probes. Superoxide (O2) production was measured spectrophotometrically as the superoxide dismutase-inhibitable reduction of cytochrome C. The modulatory effects of dilute solutions of the arachidonic acid-derived inflammatory mediators LTB4, LTC4, LTD4, PGE1, PGE2 and PGF2 alpha (10(-9)-10(-5) M) were assessed in these systems. While LTB4 enhanced the proportion of cells depolarizing to the chemoattractant N-formyl-methionyl-leucyl-phenylalanine (FMLP) 2-3x with a maximum effect in the 10(-9)-10(-8) M range, LTC4 and LTD4 showed no such enhancement except at high concentrations (10(-6) M). Unlike LTB4, LTC4 and LTD4 were unable to enhance FMLP mediated PMN O2 or DCF responses at any concentration tested, implying a divergence between the effects of the leukotrienes on membrane potential and oxidant responses. Pre-incubation of PMN with prostaglandins E1 or E2 led to a dose dependent inhibition of the proportion of depolarizing PMN in response to FMLP; PGF2 alpha did not show such an effect. The present data indicate that LTB4, in addition to being a powerful direct neutrophil activator, may act in a priming capacity by increasing the proportion of subsequently FMLP responsive cells, while PGE's inhibit. These modulatory effects appear relatively specific for LTB4 and the E-series prostaglandins.     

Lymphangiomas or cystic hygromas of the oral cavity

Limphangioma or cystic higroms is a benign tumour constituted by capillar or cavernous limpha channels, which are uncommon in oral cavity. A worldwide bibliographic revision was done to unified opinions and a case which was treated at Specialities Hospital of Medical Center la Raza, Mexican Social Security Institute, is shown in this article.     

Reversal by hypotonic medium of the antiviral state induced by lymphoblastoid interferon in human HeLa cells

The induction kinetics of the antiviral state in HeLa cells treated with human lymphoblastoid interferon (IFN) was studied. In cells treated with 4-200 U/ml IFN, the antiviral state was fully established in 7-9 h. Inhibition of virus multiplication was more rapid if the concentration of IFN was increased to 1,000 U/ml. This antiviral state gradually disappeared during the 48 h after IFN removal. Several compounds known to act on the cell membrane or on the cytoskeleton were tested for their influence on the establishment and reversal of the antiviral state. None of them were found to influence these two parameters to a significant extent. In contrast, placing HeLa cells in medium lacking NaCl partially reversed the blockade to virus multiplication induced by IFN treatment. Cells treated with IFN and later placed in hypotonic medium synthesized virus proteins after encephalomyocarditis virus infection, although at a reduced level compared to cells that had not been treated with IFN.