Amphotericin B: a novel class of antiscrapie drugs

Amphotericin B (AmB) has been able to lengthen the incubation period of intracerebrally (ic) scrapie-injected hamsters to 45 d. This article reports a linear relationship between AmB doses and the duration of the incubation periods of ic-treated animals compared with controls, a greater effect of AmB treatment administered 2 w before or the same day of ic scrapie incubation, and the ineffectiveness of mepartricin, an AmB analogue, in prolonging the incubation period of ic scrapie-injected hamsters. The beneficial effect of AmB appears due to a delay in the replication of the scrapie agent in the brain of infected hamsters. Moreover, AmB suppresses scrapie replication in the spleen of treated animals. Three hypotheses may explain these results: (1) AmB alters a hypothetical scrapie receptor, preventing the entry of the agent into central nervous system (CNS) target cells; (2) AmB interferes with mechanisms involved in scrapie replication; (3) AmB prevents the formation and accumulation of a scrapie-specific amyloid protein responsible for the disease. Whatever the mechanism of action, AmB is the only currently available drug to modify experimental CNS scrapie infection, so AmB is proposed as a novel class of antiscrapie drugs.     

Micronuclei frequencies in hospital workers occupationally exposed to low levels of ionizing radiation: influence of smoking status and other factors

In the context of a medical surveillance program aimed at preventing cancer risk from exposure to ionizing radiation, we investigated chromosomal damage in peripheral lymphocytes from 37 hospital workers exposed to low levels of ionizing radiation and 37 controls. The micronuleus (MN) assay was used as a biomarker of genetic damage. The influence of confounding factors like smoking status, age and gender was investigated by multiple regression analysis. The results indicated that, overall, MN frequency was higher in exposed workers than in controls, although the difference was not statistically significant. Interestingly, smoking status significantly raised MN frequency among the exposed workers but not among controls. This suggests that smoking can influence chromosomal damage induced in humans by ionizing radiation. Among both exposed workers and controls, MN frequency was found to increase with age. Female gender influenced the increase in MN frequency in the exposed group. Our results suggest that the effect of cigarette smoking should be carefully factored into genetic monitoring studies assessing the risks associated with low level radiation exposure.     

S-100 protein in white preadipocytes: An lmmunoelectronmicroscopic study

Differentiation of adipocytes from their precursor cells (preadipocytes) is an important problem in the study of the pathogenesis of obesity. Unfortunately, among the immature stages of adipocytes, only relatively differentiated forms can be identified by their fine structure; because early preadipocytes cannot be distinguished from fibroblasts solely on the basis of their morphology, it is impossible to assess the size of the preadipocyte population. S-100 protein has been identified in various mammalian tissues and recently mature adipocytes have been shown to be positive for this protein. Because fibroblasts are negative for S-100 protein, the present study tested the S-100 immunoreactivity of preadipocytes by the peroxidase-antiperoxidase (PAP) preembedding method at the ultrastructural level both in vivo and in culture. Mature adipocytes and early preadipocytes, including fibroblast-like cells devoid of lipid droplets, were positive both in vivo and in culture. Endothelial cells and pericytes were negative; but flattened, lipid-free, fibroblast-like cells surrounding the pericytes were positive. True fibroblasts both in vivo and in culture were negative. Therefore, S-100 protein can be a useful biochemical marker in distinguishing fibroblasts from early preadipocytes.     

Transfection and cloning of genes for membrane antigens using the FACS

In order to facilitate cloning of genes for cell surface molecules, we cotransfected LTK^? mouse fibroblasts with thymidine kinase (TK) genes and total human or mouse DNA. TK⁺ cells, selected by growth in HAT medium, were stained with fluorochrome conjugated monoclonal antibodies or other fluorescent ligands which bind to one or another membrane differentiation antigen or receptor. We isolated fluorescent transfectants expressing these molecules using a fluorescence activated cell sorter (FACS). For some antigens, spontaneous gene amplification occurred. By repeated cycles of FACS sorting and regrowth we obtained high expressing clones. We then isolatedcDNA and genomic clones using selectedcDNA probes to screen phage withcDNA inserts. DNA from virtually any tissue source transfected equally well for the various molecules except for DNA from a trophoblast derived choriocarcinoma cell line which did not transfect for Leu-2.     

Cross-Sectional Serosurvey of Companion Animals Housed with SARS-CoV-2–Infected Owners,Italy

We conducted a serologic survey among dogs and cats in Italy to detect antibodies against severe acute respiratory syndrome virus 2 (SARS-CoV-2). We found that SARS-CoV-2 seroprevalence was higher among cats (16.2%) than dogs (2.3%). In addition, seroprevalence was higher among animals living in close contact with SARS-CoV-2–positive owners.     

Increased brain synthesis of prostaglandin E2 and F2-isoprostane in human and experimental transmissible spongiform encephalopathies

The levels of 2 arachidonic acid metabolites formed either by enzymatic activity of cyclooxygenase, i.e. prostaglandin E2 (PGE2), or by free radical-catalyzed peroxidation, i.e. F2-isoprostane 8-epi-prostaglandin F2alpha (8-epi-PGF2alpha), were measured in the CSF of subjects with sporadic and familial Creutzfeldt-Jakob disease (CJD) and in brain homogenates of scrapie-infected mice. The CSF levels of both metabolites were increased in sporadic CJD (n = 52) and familial CJD (n = 10) patients when compared with a group of patients with noninflammatory disorders. Similarly, PGE2 and 8-epi-PGF2alpha levels were higher in brain homogenates obtained from C57BL/6J mice infected with the ME7 scrapie strain than in brain homogenates from control animals. As PGE2 is 1 of the most abundant prostaglandins released during inflammation and 8-epi-PGF2alpha is a quantitative marker of lipid peroxidation, our results provide in vivo biochemical evidence for the occurrence of inflammation and oxidative stress in human and experimental transmissible spongiform encephalopathies (TSEs), a concept so far based mainly on histopathological and in vitro evidence. Interestingly, in sporadic CJD patients, high CSF levels of PGE2, but not 8-epi-PGF2alpha, correlated with short survival time, suggesting that the inflammatory response correlates with the clinical duration of disease.     

Clinical outcomes of primary arterial embolization in severe hepatic trauma: A systematic review

Purpose

This purpose of this systematic review was to determine the safety and efficacy of arterial embolization as the primary treatment for grade III-V liver trauma, excluding the postoperative use of arterial embolization.

Effects of resynchronization therapy on sympathetic activity in patients with depressed ejection fraction and intraventricular conduction delay due to ischemic or idiopathic dilated cardiomyopathy

This study assesses the effect of biventricular pacing on sympathetic nerve activity (SNA) in patients with depressed ejection fraction and intraventricular conduction delay (IVCD). Biventricular pacing has been shown to result in hemodynamic improvement in patients with depressed ejection fraction and IVCD. The effect of biventricular pacing on SNA, however, remains unclear. A total of 15 men with a mean ejection fraction of 25 +/- 4% were enrolled. Arterial pressure, central venous pressure and SNA were recorded during 3 minutes of right atrial (RA) pacing and RA-biventricular pacing. Pacing was performed at a rate 5 to 10 beats faster than sinus rhythm, with an atrioventricular interval equal to 100 ms during RA-biventricular pacing. RA-biventricular pacing resulted in greater arterial pressures (p <0.05) than RA pacing (146 +/- 15/83 +/- 11 vs 141 +/- 15/80 +/- 10 mm Hg). There were no differences in central venous pressures between the 2 pacing modes (p = 0.76). SNA was significantly less during RA-biventricular pacing (727 +/- 242 U) than during RA pacing (833 +/- 332 U) (p <0.02). Furthermore, there was a positive correlation between baseline QRS duration and the decrease in SNA noted with RA-biventricular pacing (r = 0.58, p = 0.03). Biventricular pacing results in improved hemodynamics and a decrease in SNA compared with intrinsic conduction in patients with left ventricular dysfunction and IVCD. If the current findings are also present with chronic biventricular pacing, then this form of therapy may have a positive impact on mortality.