Schistosoma mansoni: structural damage and tegumental repair after in vivo treatment with praziquantel

Parasitology ◽  
1987 ◽  
Vol 94 (2) ◽  
pp. 243-254 ◽  
Author(s):  
M. K. Shaw ◽  
D. A. Erasmus

SUMMARYThe long-term, in vivo effects of a single, subcurative dose (200 mg/kg body weight of mouse) of praziquantel on the structure of adult Schistosoma mansoni and on the process and speed of tegumental repair are described. In both male and female worms praziquantel caused often extensive damage to the tegument, in the form of surface blebbings, swellings and lesions, and vacuolization and disruption of the subtegumental tissues. Repair of the drug-induced tegumental damage occurred slowly with partial and, more rarely, complete repair only being seen after 65 days post-treatment (p.t.), although signs of damage were still observed, particularly in male worms, at 100 days p.t. In contrast, repair of damage to the subtegumental/parenchymal tissues including the tegumental perikarya occurred relatively quickly, with the majority of worms examined appearing normal by 8–12 days p.t. The possible role(s) of the host immune response in relation to the speed of tegumental repair in vivo is discussed.

Parasitology ◽  
1990 ◽  
Vol 100 (1) ◽  
pp. 65-72 ◽  
Author(s):  
M. K. Shaw

SummaryThe in vivo effects of a single, subcurative dose (200 mg/kg body wt of mouse) of praziquantel on the structure of the tegument and subtegumental tissues of juvenile (21-, 26- and 30-day-old) and adult Schistosoma mansoni are described. In juvenile worms praziquantel caused only moderate damage to both the tegument and subtegumental tissues although the degree of drug-induced damage was related to both the sex of the worms and to the developmental status of each individual worm. In general, male worms exhibited more extensive and longer lasting surface damage than females. However, the level and extent of the changes increased as the worms became more developmentally advanced with adult worms showing extensive damage to the tegument and vacuolization and disruption of the subtegumental tissues. The possible correlation between the stage-dependent changes in susceptibility to praziquantel and age-related changes, particularly in the phospholipid composition of the outer tegumental membrane is discussed.


2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Peter Nordbeck ◽  
Leoni Bönhof ◽  
Karl-Heinz Hiller ◽  
Sabine Voll ◽  
Paula Arias ◽  
...  

Background: Surgical procedures in small animal models of heart disease, such as artificial ligation of the coronary arteries for experimental myocardial infarction, can evoke alterations in cardiac morphology and function. Such alterations might induce artificial early or long term effects in vivo that might account for a significant bias in basic cardiovascular research, and, therefore, could potentially question the meaning of respective studies in small animal models of heart disease. Methods: Female Wistar rats were matched for weight and distributed to sham left coronary artery ligation or untreated control. Cardiac parameters were then investigated in vivo by high-field MRI over time after the surgical procedure, determining left and right ventricular morphology and function. Additionally, the time course of several metabolic and inflammatory blood parameters was determined. Results: Rats after sham surgery showed a lower body weight for up to 8 weeks after the intervention compared to healthy controls. Left and right ventricular morphology and function were not different in absolute measures in both groups 1 week after surgery. However, there was a confined difference in several cardiac parameters normalized to the body weight (bw), such as myocardial mass (2.19±0.30/0.83±0.13 vs. 1.85±0.22/0.70±0.07 mg left/right per g bw, p<0.05), or enddiastolic ventricular volume (1.31±0.36/1.21±0.31 vs. 1.14±0.20/1.07±0.17 µl left/right per g bw, p<0.05). Vice versa, after 8 weeks, cardiac masses, volumes, and output showed a trend for lower values in the sham operated rats compared to the controls in absolute measures (782.2±57.2/260.2±33.2 vs. 805.9±84.8/310.4±48.5 mg, p<0.05 for left/right ventricular mass), but not normalized to body weight. Matching these findings, blood testing revealed prolonged metabolic and inflammatory changes after surgery not related to cardiac disease. Conclusion: There is a small distinct impact of cardio-thoracic surgical procedures on the global integrity of the organism, which in the long term also includes circumscribed repercussions on cardiac morphology and function. This impact has to be considered when analyzing data from respective studies and transferring the findings to conditions in patients.


Parasitology ◽  
2006 ◽  
Vol 133 (4) ◽  
pp. 421-432 ◽  
Author(s):  
P. M. BARTLEY ◽  
S. WRIGHT ◽  
J. SALES ◽  
F. CHIANINI ◽  
D. BUXTON ◽  
...  

To determine whether prolonged in vitro passage would result in attenuation of virulence in vivo, Neospora caninum tachyzoites were passaged for different lengths of time in vitro and compared for their ability to cause disease in mice. Groups of Balb/c mice were inoculated intraperitoneally with 5×106 or 1×107 of low-passage or high-passage N. caninum tachyzoites. The mice were monitored for changes in their demeanour and body weight, and were culled when severe clinical symptoms of murine neosporosis were observed. Mice inoculated with the high-passage parasites survived longer (P<0·05), and showed fewer clinical symptoms of murine neosporosis, compared to the mice receiving the low-passage parasites. The parasite was detected in the brains of inoculated mice using immunohistochemistry and ITS1 PCR. Tissue cysts containing parasites were seen in mice inoculated with both low-passage and high-passage parasites. When the in vitro growth rates of the parasites were compared, the high-passage parasites initially multiplied more rapidly (P<0·001) than the low-passage parasites, suggesting that the high-passage parasites had become more adapted to tissue culture. These results would suggest that it is possible to attenuate the virulence of N. caninum tachyzoites in mice through prolonged in vitro passage.


2007 ◽  
Vol 73 (16) ◽  
pp. 5300-5307 ◽  
Author(s):  
Luis G. Bermúdez-Humarán ◽  
Sébastien Nouaille ◽  
Vladimir Zilberfarb ◽  
Gérard Corthier ◽  
Alexandra Gruss ◽  
...  

ABSTRACT Leptin is an adipocyte-derived pleiotropic hormone that modulates a large number of physiological functions, including control of body weight and regulation of the immune system. In this work, we show that a recombinant strain of the food-grade lactic acid bacterium Lactococcus lactis (LL-lep) can produce and efficiently secrete human leptin. The secreted leptin is a fully biologically active hormone, as demonstrated by its capacity to stimulate a STAT3 reporter gene in HEK293 cells transfected with the Ob-Rb leptin receptor. The immunomodulatory activity of leptin-secreting L. lactis was evaluated in vivo by coexpression with the human papillomavirus type 16 E7 protein. In C57BL/6 mice immunized intranasally with a recombinant L. lactis strain coproducing leptin and E7 antigen, the adaptive immune response was significantly higher than in mice immunized with recombinant L. lactis producing only E7 antigen, demonstrating adjuvanticity of leptin. We then analyzed the effects of intranasally administered LL-lep in obese ob/ob mice. We observed that daily administration of LL-lep to these mice significantly reduced body weight gain and food intake. These results demonstrate that leptin can be produced and secreted in an active form by L. lactis and that leptin-producing L. lactis regulates in vivo antigen-specific immune responses, as well as body weight and food consumption.


Blood ◽  
2000 ◽  
Vol 95 (10) ◽  
pp. 3078-3084 ◽  
Author(s):  
Brian M. Davis ◽  
Omer N. Koç ◽  
Stanton L. Gerson

Abstract The limited efficacy of hematopoietic gene therapy can be improved by in vivo selection for transduced long-term repopulating cells (LTRC). We selected for G156A MGMT (▵MGMT) transduced LTRC present in 5 × 104 to 100 × 104 marrow cells infused into nonmyeloablated mice by the administration of O6-benzylguanine (BG) and BCNU every 3 to 4 weeks. To facilitate engraftment, mice were given a nonablative dose of BG and BCNU before infusion. Without selection, ▵MGMT was not detected in any hematopoietic colony-forming units (CFU) 24 to 30 weeks after infusion. After BG and BCNU, ▵MGMT+ CFU were frequently detected, and their proportions increased with each treatment cycle. After 2 to 3 cycles of BG and BCNU, many mice were stably reconstituted with 75% to 100% ▵MGMT+ CFU for at least 6 months, representing up to 940-fold enrichment. Thus, BG and BCNU stem cell toxicity allows ▵MGMT-transduced LTRC to repopulate the bone marrow. This degree of selection pressure in nonmyeloablated mice is far greater than that observed in previous drug-resistance gene transfer studies. These data support our approved clinical trial to select for drug-resistant, transduced hematopoietic cells, potentially decreasing cumulative drug-induced myelosuppression in patients with cancer. These data also suggest that ▵MGMT may be a potent, dominant, selectable marker for use in dual gene therapy.


2014 ◽  
Vol 9 (10) ◽  
pp. 973-981
Author(s):  
Yordanka Gluhcheva ◽  
Vasil Atanasov ◽  
Juliana Ivanova ◽  
Ekaterina Pavlova

AbstractAn in vivo experimental model for testing the effects of long-term chronic treatment with cobalt(II) compounds — cobalt chloride (CoCl2) and cobalt-EDTA (Co-EDTA) on mice at different stages of development was optimized. Pregnant mice and their progeny were treated with daily doses of 75 or 125 mg kg−1 body weight until postnatal day 90. The compounds were dissolved in regular tap water. Mice were sacrificed on days 18, 25, 30, 45, 60 and 90 after birth, which correspond to different stages of their development. Altered organ weight indices (calculated as a ratio of organ weight to body weight) of spleen, liver and kidneys, were found depending on the type of compound used, dose, duration of treatment, and the age of the animals. The results also showed significant accumulation of cobalt ions in blood plasma, spleen, liver and kidneys of the exposed mice. More Co(II) was measured in the organs of the immature mice (day 18, 25 and 30 pnd) indicating that they were more sensitive to treatment.


2004 ◽  
Vol 10 (5) ◽  
pp. 584-594 ◽  
Author(s):  
Teresa Casanovas-Taltavull ◽  
M. Guadalupe Ercilla ◽  
Cecilia P. Gonzalez ◽  
Elias Gil ◽  
Odette Viñas ◽  
...  

1984 ◽  
Vol 58 (1) ◽  
pp. 59-68 ◽  
Author(s):  
Johanna Clarkson ◽  
D. A. Erasmus

AbstractThe effects of Astiban, Lucanthone, Hycanthone and Niridazole on autophagic activities in the gastrodermis of Schistosoma mansoni were determined in vivo, using different dosage levels and dosage times. With Astiban, high levels of autophagy were observed in the gastrodermis 2 hours after an injection of the drug into the mouse, and this response had declined by 20 hours, marking a recovery by the parasite from the drug. Hycanthone and Lucanthone produced an autophagic response several days after the onset of treatment, and no recovery was observed in the morphology of the gastrodermis after the drug was discontinued. The effects of Niridazole on the gastrodermis were to produce the most dramatic ultrastructural changes after high doses and over several days of treatment. With all the drugs examined, gastrodermal autophagy was characterized by the formation of vacuoles containing cell components, lipid droplets and sometimes hydrolytic enzyme reaction product. The autophagic vacuoles appeared to be formed by the sequestration of cytoplasmic material by the basal membrane infoldings, and the transfer of enzymes into the vacuole from within the limiting membrane. The residues from intracellular digestion appeared to be emptied into the caecal lumen.


2020 ◽  
Author(s):  
Ariane C. Scheuren ◽  
Gisela A. Kuhn ◽  
Ralph Müller

AbstractIn vivo micro-CT has already been used to monitor microstructural changes of bone in mice of different ages and in models of age-related diseases such as osteoporosis. However, as aging is accompanied by frailty and subsequent increased sensitivity to external stimuli such as handling and anesthesia, the extent to which longitudinal imaging can be applied in aging studies remains unclear. Consequently, the potential of monitoring individual mice during the entire aging process – from healthy to frail status – has not yet been exploited. In this study, we assessed the effects of long-term in vivo micro-CT imaging - consisting of 11 imaging sessions over 20 weeks - on hallmarks of aging both on a local (i.e., static and dynamic bone morphometry) and systemic (i.e., frailty index (FI) and body weight) level at various stages of the aging process. Furthermore, using a premature aging model (PolgA(D257A/D257A)), we assessed whether these effects differ between genotypes.The 6th caudal vertebrae of 4 groups of mice (PolgA(D257A/D257A) and PolgA(+/+)) were monitored by in vivo micro-CT every 2 weeks. One group was subjected to 11 scans between weeks 20 and 40 of age, whereas the other groups were subjected to 5 scans between weeks 26-34, 32-40 and 40-46, respectively. The long-term monitoring approach showed small but significant changes in the static bone morphometric parameters compared to the other groups. However, no interaction effect between groups and genotype was found, suggesting that PolgA mutation does not render bone more or less susceptible to long-term micro-CT imaging. The differences between groups observed in the static morphometric parameters were less pronounced in the dynamic morphometric parameters. Moreover, the body weight and FI were not affected by more frequent imaging sessions. Finally, we observed that longitudinal designs including baseline measurements at young adult age are more powerful at detecting effects of in vivo micro-CT imaging on hallmarks of aging than cross-sectional comparisons between multiple groups of aged mice subjected to fewer imaging sessions.


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