Superior efficacy of liposomal amphotericin B with prolonged circulation in blood in the treatment of severe candidiasis in leukopenic mice

In leukopenic mice with severe systemic candidiasis, single-dose treatment (5 mg of amphotericin B [AMB]/kg of body weight) with long-circulating polyethylene glycol-coated AMB liposomes (PEG-AMB-LIP) resulted in zero mortality and a significant reduction in the number of viable Candida albicans in the kidney, whereas 70% mortality was seen in mice treated with five daily doses of AmBisome (5 mg of AMB/kg . day). When the first of five daily doses of AmBisome was combined with a single low dose of Fungizone (0.1 mg of AMB/kg), the efficacy was equal to that of PEG-AMB-LIP.     

Regulated spacing of synapses and presynaptic active zones at larval neuromuscular junctions in different genotypes of the flies Drosophila and Sarcophaga

Synapses at larval neuromuscular junctions of the flies Drosophila melanogaster and Sarcophaga bullata are not distributed randomly. They have been studied in serial electron micrographs of two identified axons (axons 1 and 2) that innervate ventral longitudinal muscles 6 and 7 of the larval body wall. The following fly larvae were examined: axon 1--wild-type Sarcophaga and Drosophila and Drosophila mutants dunce(m14) and fasII(e76), a hypomorphic allele of the fasciclin II gene; and axon 2--drosophila wild-type, dunce(m14), and fasII(e76). These lines were selected to provide a wide range of nerve terminal phenotypes in which to study the distribution and spacing of synapses. Each terminal varicosity is applied closely to the underlying subsynaptic reticulum of the muscle fiber and has 15-40 synapses. Each synapse usually bears one or more active zones, characterized by dense bodies that are T-shaped in cross section; they are located at the presumed sites of transmitter release. The distribution of synapses was characterized from the center-to-center distance of each synapse to its nearest neighbor. The mean spacing between nearest-neighbor pairs ranged from 0.84 microm to 1.05 microm for axon 1, showing no significant difference regardless of genotype. The corresponding values for axon 2, 0.58 microm to 0.75 microm, were also statistically indistinguishable from one another in terminals of different genotype but differed significantly from the values for axon 1. Thus, the functional class of the axon provides a clear prediction of the spacing of its synapses, suggesting that spacing may be determined by the functional properties of transmission at the two types of terminals. Individual dense bodies were situated mostly at least 0.4 microm away from one another, suggesting that an interaction between neighboring active zones could prevent their final positions from being located more closely.     

Bone marrow cellular composition in Listeria monocytogenes infected mice detected using ER-MP12 and ER-MP20 antibodies: a flow cytometric alternative to differential counting

We examined whether apoptosis is involved in hypoxic cell death using primary cultures of rat cortical neurons and whether the cell death is associated with changes in Bcl-2 and Bax expressions and activities of caspases. Hypoxic insult accelerates apoptosis, as shown by apoptotic nuclei and by chromatin degradation of internucleosomal fragments. This apoptotic process is accompanied by a rapid and sustained down-regulation of Bcl-2, whereas levels of Bax are unchanged. Furthermore, hypoxic insult activates sequentially caspase-1-like and caspase-3-like proteases, following down-regulation of Bcl-2 expression. Peptide inhibitors of either caspase-1 or caspase-3 protect against neuronal death, although they do not prevent hypoxia-induced down-regulation of Bcl-2. Furthermore, treatment of cortical neurons with either insulin-like growth factor-1 (IGF-1) or basic fibroblast growth factor (bFGF), growth factors which are implicated to prevent neuronal loss in ischemic brain, partly prevented neuronal death accompanied by inhibition of alterations in Bcl-2 protein levels and caspase-3-like activities. These results suggest that hypoxia induces neuronal death by down-regulation of Bcl-2 protein levels followed by sequential activation of the caspases, and the protection from neuronal cell death of these growth factors under hypoxic conditions derives at least partly from their capability to prevent down-regulation of the anti-apoptotic protein levels.     

The changes of lipids, lipoproteins and apolipoproteins in plasma in ischemic stroke

Contents of lipids (cholesterol CS, triglycerides) as well as levels of CS of lipoproteins of different density and of apolipoproteins A1 and B were measured in blood serum of 31 patients in different periods after of ischemic stroke. The majority of the indices studied were significantly decreased in men in acute periods of the stroke, especially in 8-21 days after the stroke development. Meanwhile, the levels of lipids, CS lipoproteins of both low and very low densities were increased later. Contents of CS of antiatherogenic lipoproteins of high density (HDLP) was low in different periods after the development of disorders of cerebral circulation. This confirms the concept that low level of HDLP is one of the risk factors of ischemic stroke. Decrease of the levels of both lipids and CS of lipoproteins of different density was more pronounced in patients with more severe atherosclerotic damages of the main cerebral arteries. Disorders of metabolism of lipoproteins in ischemic disorders of cerebral circulation are discussed with reference to literary data taking into consideration their heterogeneity. Genetically determined pathology of certain apolipoproteins plays a key role factor in the development of early atherosclerosis and in the elucidation of biochemical markers of the primary damages of cerebral vessels.     

Acute tumor lysis syndrome after transcatheter chemoembolization of hepatocellular carcinoma

PURPOSE: Thromboprophylaxis with heparins after total joint replacement is well accepted. The aim of this prospective randomized study was to evaluate the thrombo-prophylactical efficiency of an ankle joint moving device (Artroflow) after total knee arthroplasty. METHOD: In this prospective study 160 patients were examined who had undergone total knee arthroplasty (TKA). All of the 160 patients received Enoxaparin 1 x 40 mg subcutaneously per day. In addition to this, 90 patients received Artroflow three times a day for 30 minutes. The passive movements of the ankle joint lead to an emptying of the foot and calf veins. Except for the daily routine, we performed physical examination and ultrasound in colour, compression and duplex technique one day before surgery and at the 7th and 14th day after surgery. If a thrombosis was suspected, an ascending phlebography was carried through. RESULTS: The overall thrombosis rate was 6.3% (n = 10). 11.4% (n = 70) deep vein thromboses (DVT) could be observed in the group without Artroflow. Thrombosis occurred in the group with Artroflow in 2 cases (2.2%, n = 90). A statistical difference was found between the two patient groups (p < 0.05, Chi-Square-test). One patient was excluded from the study because of pain in the ankle joint at the fourth day of treatment. CONCLUSION: In addition to heparins, this ankle joint moving device can be recommended as a physical way to prevent DVTs in the thromboprophylaxis of total knee arthroplasty.     

Analysis of longitudinal data within accelerated longitudinal designs.

Using latent growth curve methodology and combining information from 4 different overlapping age cohorts, each measured at 1-yr intervals over a 3-yr period, a single developmental trajectory for adolescent alcohol use was formed spanning 12–17 years of age (n?=?461). At the same time, data collected from the same study sample on a single cohort (n?=?81) over 6 annual assessments (ages 12–17) was examined to determine whether the accelerated design adequately approximated the developmental trend within a true longitudinal design observed over 6 yrs of data collection. Comparison of separate models and a combined multisample model revealed no significant differences between the 2 designs in their representation of initial status and growth, as well as similar effects for the covariates of gender, deviance, and parent alcohol use on initial status and growth. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Multilocus linkage identifies two new loci for a mendelian form of stroke, cerebral cavernous malformation, at 7p15-13 and 3q25.2-27

Cerebral cavernous malformation (CCM) is a Mendelian model of stroke, characterized by focal abnormalities in small intracranial blood vessels leading to hemorrhage and consequent strokes and/or seizures. A significant fraction of cases is inherited as an autosomal dominant trait with incomplete penetrance. Among Hispanic Americans, virtually all CCM is attributable to a founder mutation localized to 7q ( CCM1 ). Recent analysis of non-Hispanic Caucasian kindreds, however, has excluded linkage to 7q in some, indicating at least one additional CCM locus. We now report analysis of linkage in 20 non-Hispanic Caucasian kindreds with familial CCM. In addition to linkage to CCM1, analysis of linkage demonstrates linkage to two new loci, CCM2 at 7p13-15 and CCM3 at 3q25.2-27. Multilocus analysis yields a maximum lod score of 14.11, with 40% of kindreds linked to CCM1, 20% linked to CCM2 and 40% linked to CCM3, with highly significant evidence for linkage to three loci (linkage to three loci supported with an odds ratio of 2.6 x 10(5):1 over linkage to two loci and 1.6 x 10(9):1 over linkage to one locus). Multipoint analysis among families with high posterior probabilities of linkage to each locus refines the locations of CCM2 and CCM3 to approximately 22 cM intervals. Linkage to these three loci can account for inheritance of CCM in all kindreds studied. Significant locus-specific differences in penetrance are identified. These findings have implications for genetic testing of this disorder and represent an important step toward identification of the molecular basis of this disease.     

Ozone therapy of diffuse peritonitis in the early postoperative period

The functional status of the oxidative-antioxidative system was studied in 72 patients after vast cancer operations. Traditional surgical treatment and its combination with intraoperative irradiation were shown to lead to tense antioxidative defense and to suppressed T-cell immunity and to call for antioxidative and immunomodulating therapy. High intraoperative blood loss complicated by hemorrhagic shock injured the oxidative-antioxidative system greatly. The magnitude of this damage correlated with the rate of prehypoxia. Addition of the potent antioxidant Ceruloplasmin to the drug regimen normalized a recovery period, helped to correct posthypoxic multiorgan insufficiency, to recover oxidative-antioxidative balance, and to decrease the incidence of pyoinflammatory complications. Patients with endogenous intoxication showed activated lipid peroxidation, decreased functional activity of antioxidative defense components and of T-cell immunity in homeostasis. The use of Ceruloplasmin and Laprot had pronounced antiinflammatory and detoxifying effects on the patient's body and activated its antioxidative defense.