Cardiovascular Response and Anesthetic Recovery in Electroconvulsive Therapy with Propofol or Thiopental

Propofol provokes a slight hypotensive effect that could mitigate the cardiovascular response to electroconvulsive therapy (ECT). In this study we compared the effects of propofol and thiopental for ECT anesthesia in seven women (22-67 years of age). Anesthesia was induced with either thiopental or propofol, and with atropine and suxamethonium for each treatment. The first anesthesia was assigned to thiopental or propofol at random; the next anesthesia was induced with the other drug, and alternated thereafter. Systolic blood pressure, diastolic blood pressure (DBP), and heart rate (HR) were recorded before anesthesia, after anesthetic induction, and 1 and 5 min after ECT. ECT-induced increases in DBP and HR were less marked with propofol than with thiopental. Seizure durations were decreased with propofol compared with thiopental.     

Results of treatment of acute myocardial infarction with thrombolytic therapy. Experiences in 437 patients in the coronary care unit of the National Institute of Cardiology "Ignacio Chavez"]

OBJECTIVE: To review the results and complications of thrombolysis in patients with acute myocardial infarction (AMI) and its complications. METHODS: Since june 1989 to august 1994 we studied patients with AMI, who underwent thrombolysis. Clinical characteristics, complications and angiographic results are described. RESULTS: Of the total population 86.3% patients received Streptokinase (SK) and 13.7% recombinant tissue plasminogen activator (rt-PA). In 20 patients the age was under 40 years, 373 between 40-70 years, and 80 patients over 70 years. 84% were men and 16% women. 72% had smoking habit; 21% diabetes mellitus, 43% hypertension, 54% had previous angina and previous AMI in 22%. The location of AMI was anterior in 234 patients and 239 inferior. In 63% enzyme washout was observed, and rapid electrocardiographic evolution in 81%. Postthrombolisis arrhythmias was observed in 64.7%. Major bleeding in 11.8% and central nervous system hemorrhage in 0.4% only with rt-PA. Postinfarction angina in 22%, and re-infarction in 4%. Cardiac rupture in 1.4%, with shock and death. Mitral insufficiency in 2.1% demonstrated by echocardiogram. Coronary angiography was done in 373 patients (80%), of which 50.7% was made in the first 5 days. The culprit artery was anterior descending in 273 patients and right coronary in 95. Left ventricular dysfunction was seen in 23% in patients with anterior AMI, and 5% with inferior AMI. Cardiogenic shock was seen in 7%. Coronary artery bypass grafting was undertaken in 106 patients and coronary angioplasty in 67. The ten days mortality was 8.8%, principally due to cardiogenic shock, ventricular arrhythmias and ventricular rupture. CONCLUSIONS: The usefull permeability in the culprit artery was obtained in 40%, who had coronary angiography done 145 hours posthrombolysis. Mortality was under 10% in this study.     

Interaction between theophylline and oestrogen in the rat uterus

Theophylline alone or in the presence of 0.001, 0.01, 0.1 or 1 microgram oestradiol-17 beta/100 g body wt increase uterine RNA and protein content 6 h after administration. Uterine oedema induced by physiological doses of oestradiol-17 beta was increased further in the presence of theophylline. Theophylline decreased the number of eosinophils in the blood and concurrently decreased oestrogen-induced uterine oesinophilia at doses of 0.01, 0.1, 1, 10 or 30 micrograms oestradiol-17 beta/100 g body wt. Oestrogen binding by uterine eosinophils in vitro increased in the presence of theophylline. This effect of theophylline could explain the increase of oestrogen-induced uterine oedema in vivo.     

Identification of an oncogenic form of the thrombopoietin receptor MPL using retrovirus-mediated gene transfer

Thrombopoietin and its receptor (MPL) are important regulators of megakaryopoiesis. We have identified an activating mutation of MPL using a combination of a retrovirus-mediated gene transfer and polymerase chain reaction-driven random mutagenesis. This point mutation causes a single amino acid substitution from Ser498 to Asn498 in the transmembrane region and abrogates factor-dependency of all interleukin-3-dependent cell lines tested. Murine interleukin-3- dependent Ba/F3 cells expressing the mutated but not the normal form of MPL were tumorigenic when transduced into syngeneic mice. Analysis of intracellular signaling pathways indicated that the mutant MPL protein constitutively activated two distinct signaling pathways, SHC-Raf-MAPK and JAK2-STAT3/STAT5.     

Involvement of lysosomal cathepsins in the cleavage of DNA topoisomerase I during necrotic cell death

OBJECTIVE: Autoantibodies to DNA topoisomerase I (topo I) are associated with diffuse systemic sclerosis (SSc), appear to be antigen driven, and may be triggered by cryptic epitopes exposed during in vivo topo I fragmentation. These autoantibodies recognize topo I and fragments of this autoantigen generated during apoptosis and necrosis. We undertook this study to determine whether lysosomal cathepsins are involved in topo I fragmentation during necrosis. METHODS: Topo I cleavage during necrosis was assessed by immunoblotting of lysates from L929 fibroblasts exposed to tumor necrosis factor alpha (TNFalpha) and the broad caspase inhibitor Z-VAD-FMK, and by immunoblotting of lysates from endothelial cells treated with HgCl2. Purified topo I and L929 nuclei were incubated with cathepsins B, D, G, H, and L, and topo I cleavage was detected by immunoblotting. The intracellular localization of cathepsin L activity and topo I in necrotic cells was examined using fluorescence microscopy. RESULTS: Treatment of L929 cells with TNFalpha and Z-VAD-FMK induced caspase-independent cell death with necrotic morphology. This cell death involved topo I cleavage into fragments of approximately 70 kd and 45 kd. This cleavage profile was reproduced in vitro by cathepsins L and H and was inhibited by the cathepsin L inhibitor Z-FY-CHO. During necrosis, cathepsin L activity diffused from lysosomes into the cytoplasm and nucleus, whereas topo I partially relocalized to the cytoplasm. Z-FY-CHO delayed necrosis and partially blocked topo I cleavage. The topo I cleavage fragments were also detected in necrotic endothelial cells and recognized by SSc sera containing anti-topo I antibodies. CONCLUSION: These results implicate cathepsins, particularly cathepsin L, in the cleavage of topo I during necrosis. This cleavage may generate potentially immunogenic fragments that could trigger anti-topo I immune responses in SSc.     

Targeting the Dopaminergic System in Autoimmunity

Journal of Neuroimmune Pharmacology - Dopamine has emerged as a fundamental regulator of inflammation. In this regard, it has been shown that dopaminergic signalling pathways are key players...     

Transient neonatal diabetes due to a missense mutation (E227K) in the gene encoding the ATP‐sensitive potassium channel (KCNJ11)

Neonatal diabetes is a monogenic form of diabetes. Herein, we report on a newborn presenting diabetic ketoacidosis at 17 days of life . A KCNJ11 mutation was identified. In such cases, insulin can be replaced by sulfonylurea with a successful metabolic control, as an example of how molecular diagnosis may influence the clinical management of the disorder.     

Description and molecular characterization of Haemoproteus macrovacuolatus n. sp. (Haemosporida,Haemoproteidae), a morphologically unique blood parasite of black-bellied whistling duck (Dendrocygna autumnalis) from South America

During a surveillance programme on avian influenza in wild birds in the east of Colombia, 42 % of examined wild black-bellied whistling ducks (Dendrocygna autumnalis) were infected with undescribed Haemoproteus sp., which macrogametocytes possess one or several huge (2.5 μm in largest diameter) conspicuous roundish vacuoles, a unique character of avian haemoproteids. This parasite is named Haemoproteus (Parahaemoproteus) macrovacuolatus and described here using data on the morphology of its gametocytes, host cells and sequences of the complete mitochondrial genome and cytochrome b fragments. Illustrations of blood stages of the new species and DNA sequence information are provided. The phylogenetic analysis identified a closely related lineage C033, reported in South Asian ducks belonging to Dendrocygna. We also found that all Haemoproteus lineages from Passeriformes conformed a monophyletic group. Whereas we cannot exclude that this pattern could be an artefact of the limited taxonomic sampling in non-passeriform birds, thus this finding is worthy of attention. This study adds to our knowledge of the phylogenetic relationships among species of avian haemoproteids and describes a new haemoparasite in a non-passerine host.     

Fatty acid profiles in Leishmania spp. isolates with natural resistance to nitric oxide and trivalent antimony

Fatty acids, especially those from phospholipids (PLFA), are essential membrane components that are present in relatively constant proportions in biological membranes under natural conditions. However, under harmful growth conditions, such as diseases, environmental changes, and chemical exposure, the fatty acid proportions might vary. If such changes could be identified and revealed to be specific for adverse situations, they could be used as biomarkers. Such biomarkers could facilitate the identification of virulence and resistance mechanisms to particular chemotherapeutic agents. Therefore, specific biomarkers could lead to better therapeutic decisions that would, in turn, enhance treatment effectiveness. The objective of this study was to compare the fatty acid profiles of trivalent antimony and nitric oxide (NO)-resistant and -sensitive Leishmania chagasi and Leishmania amazonensis isolates. Fatty acid methyl esters (FAMEs) were obtained from total lipids (MIDI), ester-linked lipids (ELFA), and ester-linked phospholipids (PLFA). FAMEs were analyzed by chromatography and mass spectrometry. Species- or resistance-associated differences in FAME profiles were assessed by nonmetric multidimensional scaling, multiresponse permutation procedures, and indicator species analyses. The isolate groups had different MIDI-FAME profiles. However, neither the ELFA nor PLFA profiles differed between the sensitive and resistant isolates. Levels of the fatty acid 18:1 Δ9c were increased in sensitive isolates (p?<?0,001), whereas the fatty acid 20:4 Δ5,8,11,14 showed the opposite trend (p?<?0.01). We conclude that these two fatty acids are potential biomarkers for NO and antimony resistance in L. chagasi and L. amazonensis and that they could be helpful in therapeutic diagnoses.