Extramedullary hematopoiesis in the liver in sudden infant death syndrome

Liver extramedullary hematopoiesis was examined in 54 victims of sudden infant death syndrome and in 21 infants who died of other causes in an attempt to confirm Naeye's findings of increased extramedullary hematopoiesis in cases of sudden infant death syndrome. Our data showed greater extramedullary hematopoiesis in victims of sudden infant death syndrome (F = 23.52), supporting Naeye's hypothesis that victims of sudden infant death syndrome have suffered a subtle, chronic hypoxemic condition before death.     

A randomized trial of intravenous tissue plasminogen activator for acute myocardial infarction with subsequent randomization to elective coronary angioplasty

Patients presenting within four hours of the onset of acute myocardial infarction were randomly assigned to receive 80 to 100 mg of recombinant human-tissue plasminogen activator (t-PA) intravenously over a period of three hours (n = 72) or placebo (n = 66). Administration of the study drug was followed by coronary arteriography, and candidates for percutaneous transluminal coronary angioplasty were randomly assigned either to undergo angioplasty on the third hospital day (n = 42) or not to undergo angioplasty during the 10-day study period (n = 43). The patency rates of the infarct-related arteries were 66 percent in the t-PA group and 24 percent in the placebo group. No fatal or intracerebral hemorrhages occurred, and episodes of bleeding requiring transfusion were observed in 7.6 percent of the placebo group and 9.8 percent of the t-PA group. As compared with the use of placebo, administration of t-PA was associated with a higher mean (+/- SEM) ejection fraction on the 10th hospital day (53.2 +/- 2.0 vs. 46.4 +/- 2.0 percent, P less than 0.02), an improved ejection fraction during the study period (+3.6 +/- 1.3 vs. -4.7 +/- 1.3 percentage points, P less than 0.0001), and a reduction in the prevalence of congestive heart failure from 33 to 14 percent (P less than 0.01). Angioplasty improved the response of the ejection fraction to exercise (+8.1 +/- 1.4 vs. +1.2 +/- 2.2 percentage points, P less than 0.02) and reduced the incidence of postinfarction angina from 19 to 5 percent (P less than 0.05), but did not influence the ejection fraction at rest. These data support an approach to the treatment of acute myocardial infarction that includes early intravenous administration of t-PA and deferred cardiac catheterization and coronary angioplasty.     

Effect of gossypol in association with chromium protoporphyrin on heme metabolic enzymes

Gossypol prevents the liberation of oxygen from oxyhemoglobin and exerts a hemolytic effect on erythrocytes. In excessive dosages of gossypol, an extreme burden is placed upon the respiratory and circulatory organs owing to the reduced oxygen carrying capacity of blood. Chromium protoporphyrin (CrPP) has been shown to either competitively suppress or to significantly ameliorate a variety of naturally occurring or experimentally induced forms of jaundice in animals and man. In this communication, a novel tissue dependent response to gossypol (50 micromol/kg bw) and gossypol in association with CrPP (50 micromol/kg bw) is described. Our results revealed that gossypol stimulated the hepatic, splenic, and renal delta-aminolevulinic acid synthase (ALA-S) activity, the heme biosynthetic enzyme, and simultaneous administration of CrPP and gossypol synergized the gossypol-mediated increase of ALA-S activity. Gossypol was found to be a potent stimulator of heme oxygenase (HMOX) activity in rat liver and kidney to varying degrees. This tissue response contrasted with that of the spleen, where gossypol decreased the activity of the enzyme. In consonance with the increased hepatic and renal HMOX activity, a marked increase was observed in total serum bilirubin concentration in gossypol treated rats. When rats were given CrPP simultaneously with gossypol, the gossypol mediated increase in hepatic and renal HMOX activity was effectively blocked. Furthermore, the increase in enzymatic activity was accomplished by a decline in the total microsomal protein content on gossypol administration. These findings emphasize the toxic effect of gossypol in eliciting increased heme degradation by stimulating HMOX activity in the liver and the kidney and the potential usefulness of CrPP in experimental and perhaps clinical conditions in which hyperbilirubinemia occurs.     

Mechanism of fluconazole resistance in Candida albicans biofilms: phase-specific role of efflux pumps and membrane sterols

Candida albicans biofilms are formed through three distinct developmental phases and are associated with high fluconazole (FLU) resistance. In the present study, we used a set of isogenic Candida strains lacking one or more of the drug efflux pumps Cdr1p, Cdr2p, and Mdr1p to determine their role in FLU resistance of biofilms. Additionally, variation in sterol profile as a possible mechanism of drug resistance was investigated. Our results indicate that parent and mutant strains formed similar biofilms. However, biofilms formed by double and triple mutants were more susceptible to FLU at 6 h (MIC = 64 and 16 microg/ml, respectively) than the wild-type strain (MIC > 256 microg/ml). At later time points (12 and 48 h), all the strains became resistant to this azole (MIC > or = 256 microg/ml), indicating lack of involvement of efflux pumps in resistance at late stages of biofilm formation. Northern blot analyses revealed that Candida biofilms expressed CDR and MDR1 genes in all the developmental phases, while planktonic cells expressed these genes only at the 12- and 48-h time points. Functionality of efflux pumps was assayed by rhodamine (Rh123) efflux assays, which revealed significant differences in Rh123 retention between biofilm and planktonic cells at the early phase (P = 0.0006) but not at later stages (12 and 48 h). Sterol analyses showed that ergosterol levels were significantly decreased (P < 0.001) at intermediate and mature phases, compared to those in early-phase biofilms. These studies suggest that multicomponent, phase-specific mechanisms are operative in antifungal resistance of fungal biofilms.     

Stroke-prone rats exhibit prolonged behavioral deficits without increased brain injury: an indication of disrupted post-stroke brain recovery of function

Stroke-prone rat strains exhibit an increased stroke risk and sensitivity, and reduced endogenous mechanisms of ischemic brain tolerance. This experiment provides a comparative, serial evaluation of neurological deficits and brain injury following middle cerebral artery occlusion/permanent focal stroke in this high-risk strain. Stroke-prone spontaneously hypertensive (SHR-SP), spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats were evaluated over 28 days using magnetic resonance imaging (MRI), histopathology, and neurobehavioral testing. T2- and diffusion weighted-MRI was performed after 1, 10 and 28 days to measure the degree of stroke-induced brain injury. Normotensive WKY rats receiving the same stroke and other SHR-SP rats receiving sham surgery were used for control comparisons. Functional deficits were scored after 1, 4, 11, 18 and 28 days. The degree of brain infarction/injury was practically identical in hypertensive and stroke-prone rats. WKY rats exhibited significantly smaller infarcts (P<0.05), with neurological function recovering quickly to normal by day 11 in this strain. Functional deficits persisted longer in hypertensive rats, with function recovering to normal by day 18 (P<0.05). Functional deficits in SHR-SP rats persisted the longest, and were observed even after 28 days (P<0.05). This increased and prolonged neurologic dysfunction exhibited by SHR-SP compared to SHR rats, while exhibiting practically identical degrees of brain injury/infarction, reflects the increased stroke risk and sensitivity of this strain and suggests a reduced SHR-SP brain plasticity following injury. Therefore, the stroke-prone rat provides an enhanced and prolonged functional deficit model that can be used to elucidate those mechanisms/novel targets critical to longitudinal neurobehavioral recovery post-stroke.     

Molecular characterization of a strain of cucumber mosaic virus based on coat protein and movement protein genes

Cucumber mosaic virus (CMV) A strain (CMV-A) isolated from Amaranthus tricolor was partially characterized at molecular level. Complete coat protein (CP) and movement protein (MP) ORFs were cloned and sequenced. The 657 bp region of CP gene and the 840 bp region of MP gene encode 218 and 276 amino acids, respectively. CP, at nucleotide level, showed 90-98% sequence identity with the CMV subgroup I and less than 80% with the CMV subgroup II, it showed at amino acid level 92-96% identity with the subgroup I and 74-87% with the subgroup II. The nucleotide and amino acid sequence identities of MP ranged in 91-94% and 92-96%, respectively with the subgroup I but in 81-83% with the subgroup II. Phylogenetic trees generated from nucleotide and amino acid sequences of both CP and MP genes identified the virus strain as a member of the subgroup IB. CMV-A CP also displayed a remarkably higher homology with Indian strains of CMV than with other CMV strains and formed a separate cluster within the subgroup IB.     

Use of cuprous ion and metallic copper as initiators of aqueous vinyl polymerization

Cuprous chloride and copper powder (in acid media) initiate the aqueous polymerization of certain vinyl monomers such as methyl methacrylate, ethyl methacrylate, methacrylic acid and styrene but it fails in case of acrylonitrile, methyl acrylate, and acrylic acid under identical conditions. Catalyst exponent of this initiator (in acid aqueous media) with respect to methyl methacrylate is 0.38. Quantitative determination of end-groups by dye techniques of the polymers obtained shows that about 2 hydroxyl end-groups per chain are present under acidic conditions in presence of slight traces of oxygen but in rigorous absence of oxygen, very little OH end-groups are found incorporated. The mechanism of initiation under different experimental condition is discussed.