Liposomal hamycin in the control of experimental aspergillosis in mice: effect of phosphatidic acid with and without cholesterol

Hamycin incorporated into liposomes containing phosphatidylcholine (SPC) and phosphatidic acid (PA) had reduced toxicity and an enhanced antifungal activity in experimental aspergillosis in balb/c mice. Incorporation of cholesterol into liposomes led to a dose dependent decrease in the toxicity of hamycin. The LD50 (mg/kg) of hamycin contained in SPC/cholesterol/PA (molar ratio 4:5:1) liposomes was 2.8 whereas that in SPC/PA liposomes (molar ratio 9:1) was 0.35. Although the free drug had little or no protective effect on the animals, those administered liposomal hamycin at an equivalent dose (0.1 mg/kg) in the absence of cholesterol (SPC/PA; molar ratio 9:1) showed 90% survival after seven days of therapy. On the other hand the presence of cholesterol in the carrier phosphatidic acid liposomes (SPC/cholesterol/PA; molar ratio 4:5:1) at a similar dose (0.1 mg/kg) led to a 60% survival over the same time period. Hamycin incorporation in phosphatidic acid liposomes both in the presence or absence of cholesterol was found to be effective in reducing the fungal load in lung, liver, spleen and kidney. Studies with distribution of hamycin in various tissues by HPLC showed a significant reduction in the concentration of the liposomal drug in circulation as compared to those seem after administration of free drug.     

The preferential mobilisation of C20 and C22 polyunsaturated fatty acids from the adipose tissue of the chick embryo: potential implications regarding the provision of essential fatty acids for neural development

The effects of 10 day clenbuterol administration on cardiac and skeletal muscle capillarities were studied, particularly in terms of the distribution of arteriolar and venular capillaries and their capillary density, in young (10-week-old) and middle-aged (37-week-old) male Wistar rats. Rats of the treated groups were fed a diet containing 2 mg kg-1 clenbuterol hydrochloride. In both young and middle aged rats, clenbuterol treatment increased the body wt and the weights of the heart and hindlimb muscles. The mean fibre cross-sectional area was significantly increased after the treatment in the left ventricle, soleus, plantaris and both deep and superficial portions of gastrocnemius (P < 0.01). In the left ventricle, the total capillary density and the density of venular capillaries were decreased after the treatment in both young (9 and 13%, respectively) and middle-aged rats (10 and 11%, respectively). A decrease in total capillary density was also observed in all skeletal muscles examined. In both young and middle-aged rats, the capillary-to-fibre (C:F) ratio and the proportion of each capillary did not change after the treatment in both the left ventricle and skeletal muscles. Clenbuterol significantly decreased the activity of succinate dehydrogenase in all skeletal muscles examined (P < 0.01). These results suggest that clenbuterol increased the diffusion distance for oxygen in the left ventricle and skeletal muscles. These changes may reduce the oxygen supply to tissues and increase muscle fatigability.     

Peritraumatic dissociation and posttraumatic stress in male Vietnam theater veterans

OBJECTIVE: The aim of this study was to determine the reliability and validity of a proposed measure of peritraumatic dissociation and, as part of that effort, to determine the relationship between dissociative experiences during disturbing combat trauma and the subsequent development of posttraumatic stress disorder (PTSD). METHOD: A total of 251 male Vietnam theater veterans from the Clinical Examination Component of the National Vietnam Veterans Readjustment Study were examined to determine the relationship of war zone stress exposure, retrospective reports of dissociation during the most disturbing combat trauma events, and general dissociative tendencies with PTSD case determination. RESULTS: The total score on the Peritraumatic Dissociation Experiences Questionnaire--Rater Version was strongly associated with level of posttraumatic stress symptoms, level of stress exposure, and general dissociative tendencies and weakly associated with general psychopathology scales from the MMPI-2. Logistic regression analyses supported the incremental value of dissociation during trauma, over and above the contributions of level of war zone stress exposure and general dissociative tendencies, in accounting for PTSD case determination. CONCLUSIONS: These results provide support for the reliability and validity of the Peritraumatic Dissociation Experiences Questionnaire--Rater Version and for a trauma-dissociation linkage hypothesis: the greater the dissociation during traumatic stress exposure, the greater the likelihood of meeting criteria for current PTSD.     

The block to HIV-1 envelope glycoprotein-mediated membrane fusion in animal cells expressing human CD4 can be overcome by a human cell component(s)

Membrane fusion mediated by interaction of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein with the human CD4 molecule generally requires that the CD4 be expressed on a human cell. The failure of murine or simian cells expressing human CD4 to form syncytia upon mixing with cells expressing envelope glycoprotein could not be corrected by expression of both molecules at extremely high surface levels using vaccinia virus expression vectors. Video fluorescence microscopic analysis of fluorescent dye transfer between fusing cells indicated that the block occurred at the level of membrane fusion between individual pairs of cells. To gain insight into the basis for this fusion block, we tested the ability of fluorescent probe cells expressing envelope glycoprotein to fuse with transient animal x human hybrid giant cells expressing human CD4. The hybrid giant cells were generated either by low-pH-induced fusion of vaccinia-infected cells or by CD4/HIV-1 envelope glycoprotein-mediated cell fusion. We observed that envelope glycoprotein-expressing probe cells efficiently fused with CD4-expressing animal x human hybrid giant cells, independent of whether the CD4 was originally expressed on the animal or on the human cell. Fusion did not occur with CD4-expressing giant cells derived from animal cells alone. These results indicate that the fusion block is not due to dominant inhibitory components in the animal cell. Rather, they suggest that human cells contain an additional component(s) which, when transferred to the CD4-bearing animal cell, confers the ability to undergo membrane fusion mediated by the HIV-1 envelope glycoprotein.     

The effectiveness of modified ingram therapy compared with severity of psoriasis

PURPOSE: This study investigated the pathogenesis of tractional retinal detachment associated with proliferative vitreoretinopathy in an experimental model, using immunohistochemical staining. METHODS: To produce tractional retinal detachment in rabbit eyes, homologous cultured fibroblasts obtained from the gluteal muscle fascia were injected intravitreously. Right eyes of 20 rabbits in the study group, and 7 rabbits in the control group were followed for 26 days at weekly intervals with indirect ophthalmoscopy and fundus photographs. RESULTS: During the follow-up period grade III tractional retinal detachment developed in 11 eyes, grade II in six, and grade 1 in three eyes. The spindle-shaped cells contributed predominantly to the development of epiretinal membrane, and a smaller number of round small and large cells. In 10/17 grade II and III eyes, spindle-shaped cells had vimentin, 7/10 had actin, 5/17 had GFAP, 4/17 had S-100 protein immunoreactivity. Round small and large cells expressed S-100 protein, GFAP and actin in 5/17 eyes. Epiretinal membrane appeared to be formed by spindle-shaped fibroblast-like cells and small and large round glia-like cells. Actin positivity of spindle-shaped and round cells was taken as a marker of contractile elements of the cells and their locomotional features. CONCLUSIONS: These features are believed to be involved in contraction of the membrane and retinal detachment.     

The effects of instructional match and content overlap on generalized reading performance

This study examined the effects of instructional match and content overlap on students' ability to generalize from passage reading instruction. Four students with mild disabilities served as participants. Using a multielement design, students were instructed with passages at two levels of text difficulty (instructionally matched vs. instructionally mismatched), and generalization was assessed with passages at two levels of similarity to those instructed (low vs. high content overlap). Results indicated that students' oral reading accuracy and fluency showed the greatest degree of generalization when instructional materials were matched to the students' skill level and assessment materials were similar to those used during instruction. Moreover, these results were maintained at 1-month follow-up. The implications of these findings for classroom reading instruction and the assessment of students' reading skills are discussed.