Neuritogenesis: polarization of constitutive exocytosis by effectors of Rho-family GTPases?

The sprouting of neurites from a neuron represents a highly specialized form of cellular morphogenesis that must involve coordinated changes in two major cellular processes at two membrane locations: reorganization of the cytoskeleton and redirection of membrane traffic from the trans-Golgi network to the plasma membrane of the growth tip. How exactly are these two processes linked and how is spatial and temporal coordination achieved at the first instance of neurite sprouting? Recent advances may have already revealed some, if not most of the pieces in the puzzle. We discuss below, with some extrapolations, of what has recently come to light, and what more is needed to construct a coherent picture.     

Effects of zopiclone on blood glucose level, serum lipid concentration and clot lysis time in normoglycemic and normolipidemic rats

In normoglycemic and normolipidemic rats the i.p. injection of zopiclone induced an acceleration of fibrinolysis in a dose-dependent bell shaped manner and various changes of the blood glucose level. Total lipids, total cholesterol and triglyceride serum levels remained unaffected by doses of 1.25, 2.5 and 15.0 mg/kg, with the exception of the medium dose (5.0 mg/kg) and the next dose (10.0 mg/kg) which lowered them very significantly.     

Survival of bird schistosomes in mammalian lungs

Bird schistosome cercariae have a low specificity to vertebrate skin and, thus, they are also able to penetrate into mammals. As a consequence, a hypersensitive skin response-cercarial dermatitis-develops. It was thought that the parasites die in the skin soon after penetration. Our results on Trichobilharzia szidati and Bilharziella polonica in the non-specific murine host confirm that some of the penetrating bird schistosomes may fully transform to schistosomula and migrate to the lungs. They persist there for up to 10days post exposure. In a duck, the worms grow and feed rapidly, but in a mouse the lung schistosomula seem to be inhibited in their development. However, TEM results show that there is no damage to the tegument of these larvae and no immune effector cells attack the parasites. These results suggest that the parasite's failure in the murine host might be caused by some immunologically unrelated factors.     

Differences in genotypes of Helicobacter pylori from different human populations

DNA motifs at several informative loci in more than 500 strains of Helicobacter pylori from five continents were studied by PCR and sequencing to gain insights into the evolution of this gastric pathogen. Five types of deletion, insertion, and substitution motifs were found at the right end of the H. pylori cag pathogenicity island. Of the three most common motifs, type I predominated in Spaniards, native Peruvians, and Guatemalan Ladinos (mixed Amerindian-European ancestry) and also in native Africans and U.S. residents; type II predominated among Japanese and Chinese; and type III predominated in Indians from Calcutta. Sequences in the cagA gene and in vacAm1 type alleles of the vacuolating cytotoxin gene (vacA) of strains from native Peruvians were also more like those from Spaniards than those from Asians. These indications of relatedness of Latin American and Spanish strains, despite the closer genetic relatedness of Amerindian and Asian people themselves, lead us to suggest that H. pylori may have been brought to the New World by European conquerors and colonists about 500 years ago. This thinking, in turn, suggests that H. pylori infection might have become widespread in people quite recently in human evolution.     

Mechanism of high susceptibility of iron-overloaded mouse to Vibrio vulnificus infection

Vibrio vulnificus produces fulminant septicemia in humans with underlying conditions, particularly those with diseases that elevate the iron level. The effect of a high iron level on the virulence of V. vulnificus was therefore investigated in mice treated with iron dextran. The mice loaded with iron became highly susceptible to V. vulnificus infection, the LD50 (50% lethal dose) decreased five logs when infected per peritoneum. However, when infected via the oral route, the LD50 was affected little unless the mouse was treated with an additional drug such as cyclophosphamide or D-galactosamine. Mice with or without iron-overloading died when the bacterial concentration in the blood reached 10(5) cfu/ml or above. Iron increased the growth rate of the bacteria, both inside and outside of the animal, quickly reaching a lethal concentration in the iron-overloaded mouse. V. vulnificus, grown with or without the addition of iron, showed strong cytotoxicity on the isolated cells or within the animal at high bacterial concentration. Iron overload stimulated the production of tumor necrosis factor alpha (TNF-alpha), a major factor of septic shock, in mice upon infection with the bacteria, probably caused by the endotoxin; however, the neutrophils, whose migration is effected by TNF-alpha, appeared to be less active. Taken together, the major virulence factor of V. vulnificus appeared to be the accelerated growth of bacteria to quickly reach the lethal level and the lower activity of immune cells including neutrophil as a result of iron-overloading. These two effects manifest other virulence factors, the host's as well as bacterial. Such factors, other than TNF-alpha stimulated by the endotoxin, enhanced cytotoxicity, which kills the host cells including the host's immune cells.     

Familial defective apolipoprotein B-100: a lesson from homozygous and heterozygous patients

Familial defective apolipoprotein B-100 (FDB) is a genetic disorder caused by a substitution of glutamine for arginine at residue 3500 of the apolipoprotein B-100 molecule. We have identified 23 heterozygotes and one homozygote for FDB (frequency 1:20) in a group of 510 patients with hypercholesterolemia. Mean age of the patients (18 females and 6 males) was 46 years. The diagnosis of FDB was based on point mutation PCR analysis of exon 26 of the apo B gene. Plasma lipids in heterozygous patients were: total cholesterol 8.76+/-1.2 mmol/l, triglycerides 1.42+/-0.5 mmol/l, HDL-cholesterol 1.43+/-0.3 mmol/l, LDL-cholesterol 6.69+/-1.2 mmol/l, apoB 1.69+/-0.4 g/l, Lp(a) 0.26+/-0.2 g/l. The most frequent apoE genotype was 3/3 (19 patients), apoE 3/4 genotype was found in 3 patients and one person had apoE 2/3. Xanthelasma palpebrarum was present in 4 patients and tendon xanthomas in 3 patients including the homozygote. Premature manifestation of coronary heart disease was revealed in 3 patients. Sixteen patients were treated with statins, a combination of statin and resin was used in 2 patients (including the homozygote), whereas six patients were treated with the diet only. We conclude that although the plasma lipid levels of total and LDL cholesterol in FDB patients are lower than in patients with familial hypercholesterolemia, the patients with FDB suffer from premature atherosclerosis. The therapeutic approach to FDB individuals and patients with familial hypercholesterolemia is very similar.     

Effect of Blood Vessel Segmentation on the Outcome of Electroporation-Based Treatments of Liver Tumors

Electroporation-based treatments rely on increasing the permeability of the cell membrane by high voltage electric pulses applied to tissue via electrodes. To ensure that the whole tumor is covered with sufficiently high electric field, accurate numerical models are built based on individual patient anatomy. Extraction of patient''s anatomy through segmentation of medical images inevitably produces some errors. In order to ensure the robustness of treatment planning, it is necessary to evaluate the potential effect of such errors on the electric field distribution. In this work we focus on determining the effect of errors in automatic segmentation of hepatic vessels on the electric field distribution in electroporation-based treatments in the liver. First, a numerical analysis was performed on a simple ''sphere and cylinder'' model for tumors and vessels of different sizes and relative positions. Second, an analysis of two models extracted from medical images of real patients in which we introduced variations of an error of the automatic vessel segmentation method was performed. The results obtained from a simple model indicate that ignoring the vessels when calculating the electric field distribution can cause insufficient coverage of the tumor with electric fields. Results of this study indicate that this effect happens for small (10 mm) and medium-sized (30 mm) tumors, especially in the absence of a central electrode inserted in the tumor. The results obtained from the real-case models also show higher negative impact of automatic vessel segmentation errors on the electric field distribution when the central electrode is absent. However, the average error of the automatic vessel segmentation did not have an impact on the electric field distribution if the central electrode was present. This suggests the algorithm is robust enough to be used in creating a model for treatment parameter optimization, but with a central electrode.