Effect of wide spectrum anti-helminthic drugs upon Schistosoma mansoni experimentally infected mice

An important issue of concern for drug analysis in hair is the change in the drug concentration induced by the cosmetic treatment of hair. The products used for this treatment are strong bases and they are expected to cause hair damage. As a result drugs may be lost from the hair matrix or, under conditions of environmental contamination, be more easily incorporated into the hair matrix. We investigated the effects of cosmetic treatment in vivo by analysing hair samples selected from people who had treated their hair by bleaching or dyeing before sample collection. All of the subjects admitted a similar drug consumption during the time period for which the strands were analysed. Samples were viewed under a microscope to establish the degree of hair damage. Treated and untreated portions from each lock of hair were then selected, separated and analysed by standard detection procedures for cocaine, opiates, cannabinoids and nicotine. In all cases the drug content in hair that had undergone cosmetic treatment decreased in comparison to untreated hair. The majority of the mean differences were in the range of 40%-60% (cocaine, benzoylecgonine, codeine, 6-acetylmorphine and THC-COOH). For morphine the mean difference was higher than 60%, and two cases (THC and nicotine) differed by approx. 30%. These differences depended not only on the type of cosmetic treatment, as bleaching produced higher decreases than dyeing, but also on the degree of hair damage i.e. the more damaged the hair, the larger the differences in the concentration levels of drugs.     

Pairing of Schistosoma mansoni males in infected Syrian hamsters

Pairing of male schistosomes in the liver of infected hamsters was recorded with Egyptians S. mansoni strain. The homospecific male pairs never carried each other in the gynaecophoric duct, but they being closed in either central or hepatic veins. Other perfused males and females en copula showed normal mating behaviour. The paired males were more or less in the same size. The random sexed miracidia used resulted in obtaining 1:2.1 female/male ratio. It is concluded that the random increase of male schistosomes may create the male pairing behaviour. Also, the migration of female against the blood stream to the mesenteric plexus of the host and the failure of male to catch them may lead to this homosexual pairing. The black haemozoin-like substance seen in mature females was also observed in the pairing males and this probably reflects the effect of scarcity or migration of females to the mesenteric plexus.     

Involvement of regional lymph nodes after penetration of Schistosoma mansoni cercariae in naive and infected mice

The very low density lipoprotein receptor (VLDL-r) is a cell-surface molecule specialized for the internalization of multiple diverse ligands, including apolipoprotein E (apoE)-containing lipoprotein particles, via clathrin-coated pits. Its structure is similar to the low-density lipoprotein receptor (LDL-r), although the two have substantially different systemic distributions and regulatory pathways. The present work examines the distribution of VLDL-r in the central nervous system (CNS) and in relation to senile plaques in Alzheimer disease (AD). VLDL-r is present on resting and activated microglia, particularly those associated with senile plaques (SPs). VLDL-r immunoreactivity is also found in cortical neurons. Two exons of VLDL-r mRNA are differentially spliced in the mature receptor mRNA. One set of splice forms gives rise to receptors containing (or lacking) an extracellular O-linked glycosylation domain near the transmembrane portion of the molecule. The other set of splice forms appears to be brain-specific, and is responsible for the presence or absence of one of the cysteine-rich repeat regions in the binding region of the molecule. Ratios of the receptor variants generated from these splice forms do not differ substantially across different cortical areas or in AD. We hypothesize that VLDL-r might contribute to metabolism of apoE and apoE/A beta complexes in the brain. Further characterizations of apoE receptors in Alzheimer brain may help lay the groundwork for understanding the role of apoE in the CNS and in the pathophysiology of AD.     

Features of Schistosoma mansoni infection in SCID mice

Features of Schistosoma mansoni infection in SCID mice, which lack functional T- and B-lymphocytes, were investigated. The retarded development of parasites as well as reduction of liver egg recovery in SCID mice was significantly lower than those in congenic counterpart C.B-17 mice. Furthermore, the rate of parasite recovery from SCID mice with primary infection was always lower than that from C.B-17 mice by 20%, showing the innate resistance to S. mansoni infection. SCID mice vaccinated with UV-attenuated S. mansoni cercariae did not show protective immunity against a homologous challenge infection. The present innate resistance exhibited in SCID mice is discussed in relation to cell mediated immunity of macrophage activation by IFN-gamma which would not involve T-lymphocytes but is initiated by IL-12 and TNF-alpha cytokines. SCID mice may provide novel information on the host-parasite relationship in schistosome infections.     

Protection of mice against Schistosoma mansoni infection by passive transfer of sera from infected rabbits

Twelve patients with bilateral comparable gingival recessions were treated using a split mouth design, to compare the relative success of root coverage by two regenerative procedures. The areas of recession treated were Class I or II according to Miller's classification and caused either an esthetic problem and/or root sensitivity. The symmetrical defects, on the maxillary canines, 4 mm or deeper, were randomly assigned in each patient to surgical procedures with either a bioresorbable matrix barrier (test) or a non-resorbable expanded polytetrafluoroethylene membrane (control). Gingival recession, clinical attachment level, probing depth, and extension of keratinized tissue were measured at baseline and at 6 months postsurgically. Both procedures resulted in significant root coverage (P < 0.0001) and attachment gain (P < 0.0001). The gingival recession decreased from 4.75 +/- 0.22 mm to 0.83 +/- 0.24 mm and from 4.75 +/- 0.22 mm to 0.75 +/- 0.22 mm, corresponding to a mean root coverage of 82.4% and 83.2%, at the test and control sites respectively. The average clinical attachment gain was 4.33 +/- 0.44 mm at the test sites compared to 4.42 +/- 0.48 mm for the non-resorbable barrier. No significant changes were found for probing depth and keratinized tissue. Data analysis did not demonstrate any significant difference between the two procedures for any of the variables included. However, a questionnaire given to each patient revealed the single-step surgery to be the patients' choice.     

Tegument changes of Schistosoma japonicum and Schistosoma mansoni in mice treated with artemether

AIM: To study the effect of artemether (Art) on the tegument of schistosomes. METHODS: Mice infected with S japonicum cercariae for 7 and 35 d, or with S mansoni cercariae for 49 d were treated intragastrically with Art 200-300 mg.kg-1.d-1 for 2 d. Schistosomes were collected in groups of 2 mice at various intervals after medication for scanning electron microscopic observation. RESULTS: The tegumental changes induced by Art appeared to be similar in S japonicum and S mansoni: swelling and fusion of tegumental surfaces, vesicle formation and collapse of discoid-like sensory structures. In S japonicum the emergence of tegumental alterations was earlier in 7-d-old schistosomulae than that in 35-d-old adult worms. CONCLUSION: Art injured the teguments of S japonicum and S mansoni.     

Susceptibility to chemotherapeutic agents of Schistosoma mansoni isolates from patients treated with oxamniquine and praziquantel and not cured

Ten inhabitants of Itaquara, Bahia, Brazil treated with oxamniquine and subsequently praziquantel were not cured. Schistosoma mansoni isolates derived from these patients were studied. Snails were infected with miracidia derived from the feces of these patients and the cercariae produced used to infect albino mice. The animals were then treated with a single oral dose of oxamniquine (25, 50 and 100mg/kg) or praziquantel (100, 200 and 400 mg/kg). The response to chemotherapy was significantly different in some of the isolates although it was not possible to characterize any of them as resistant. In addition, DNA analysis of the isolates by means of "Random Amplified Polymorphic DNA" indicated a low degree of variability as compared with a laboratory strain, LE. Thus, it was not possible to characterize these organisms at a genetic level as a distinct strain.     

Modification of the lung recovery assay for schistosomula and correlations with worm burdens in mice infected with Schistosoma mansoni

The kinetics of recovery of schistosomula from the lungs of previously-unexposed CF1 mice were studied following infection with Schistosoma mansoni cercariae. Lung tissue fragments were incubated from 3 to 48 hr and the completeness of recovery of viable schistosomula was determined. The recovery of schistosomula from the lungs was shown to correlate closely with 7-week worm recoveries. With the additional incubation described, the lung recovery assay may provide a more defined indicator of protective immunity. Based on the data generated by these analyses, it is predicted that under these conditions schistosomula arrive in the lungs from 3 to 7 days after infection, and that they sojourn there for a 3-day period.     

Anti-schistosomal IgE and its relation to gastrointestinal allergy in breast-fed infants of Schistosoma mansoni infected mothers

To study the relationship between presence of gastrointestinal allergic manifestations in breast-fed infants and presence of IgE against Schistosoma mansoni antigens, sixty breast-fed infants of S. mansoni infected mothers were selected. Of them, thirty infants were suffering from manifestations of gastrointestinal allergy (patients) and the other thirty were not suffering from such manifestations (controls). Levels of IgE against S. mansoni adult worm antigen (AWA), soluble egg antigen (SEA) and cercarial antigen (CA) were determined, by ELISA, in sera of these infants. There was significant association between presence of allergic manifestations and presence of IgE against AWA (P = 0.018), SEA (P < 0.001) and CA (P = 0.002). Also, concentration of IgE against AWA was significantly higher in patients group than the control group (P = 0.024). IgE against AWA showed significant negative correlation with haemoglobin concentration (P = 0.009) and serum albumin level (P = 021) and significant positive correlation with absolute eosinophilic count (P = 0.005). Also, IgE against CA showed significant negative correlation with haemoglobin concentration (p = 0.047) and serum albumin level (0 = 0.036). It was concluded that gastrointestinal allergy in breast-fed infants of S. mansoni infected mothers may be due to hypersensitivity of Schistosoma mansoni antigens present in mothers' milk. Schistosoma mansoni should be investigated and treated in mothers from endemic localities when their breast-fed infants are suffering from manifestations suggestive of gastrointestinal allergy.     

Eosinophil-enriched inflammatory response to schistosomula in the skin of mice immune to Schistosoma mansoni

Exposure of the mouse skin to Schistosoma mansoni cercariae gives rise to acute, exudative inflammation in both normal and immune mice, but the immune response is anamnestically accelerated and is oesinophil-enriched, thereby enhancing opportunities for tegumental contact of schistosomula with host leukocytes, particularly with eosinophils. Many of the inflammatory changes occurring within the first 48 hours after exposure are due to cercarial products, e.g., "penetration tracts," but some remain demonstrable when schistosomula metamorphosed in vitro are injected intradermally and are therefore directed against the schistosomula themselves, such as the leukocyte "streaming patterns" seen in their pathways. In contrast to earlier observations in primates, cellular responses to schistosomula in the mouse lung 4 days after penetration are minimal in either normal or immune mice. Thus, immune cellular responses to schistosomula in mice are limited to an early time period after cercarial penetration and are morphologically suggestive of an antibody-mediated response rather than of delayed hypersensitivity. Our observations complement earlier evidence suggesting that antibody-mediated host leukocyte contact with schistosomula initiates the killing of challenge parasites in immune mice, with the eosinophil probably playing a crucial role.     

Biology and pathology of Schistosoma mansoni and Schistosoma japonicum infections in several strains of nude mice

Schistosoma mansoni and S. japonicum infections in nude mice (nu/nu) were compared with infections in nu/+ heterozygotes or intact mice. Seven to 12 weeks after exposure to S. mansoni, the responses of Swiss NCR, C3H, BALB/c and C57B1/6 nude mice did not differ substantially. Nude mice of all these strains showed minute granulomas around eggs in the liver and minimal hepatic fibrosis. Microvesicular and necrotizing changes in hepatocytes were similar in all mouse strains, and S. mansoni infections were frequently lethal to nude, but not to intact mice between the seventh and ninth weeks of infection. Nude mice that survived the ninth week of infection generally lived until the 12th week. The number of eggs per mature worm pair in the tissues of S. mansoni-infected nude mice was similar to the number in intact mice, but nude mice passed fewer eggs in the feces. Nude mice that received serum from infected intact mice excreted eggs in the stool in numbers equivalent to intact mice, but continued to form minute granulomas around S. mansoni eggs. Reconstitution with fetal thymus or with splenocytes from normal or S. mansoni-infected mice partially or completely restored hepatic granuloma size, granuloma eosinophils, hepatic fibrosis, and excretion of eggs in the feces. In contrast to S. mansoni infection, S. japonicum infections in nude mice did not cause necrosis of hepatocytes or excessive mortality, and S. japonicum eggs were passed in the feces in numbers equivalent to those passed by infected intact mice.     

Detection of Schistosoma mansoni M antigen in circulating immune-complexes and in kidneys of infected hamsters

Circulating M antigen (CMA) of Schistosoma mansoni was found in the trichloroacetic acid (TCA) soluble fraction of a polyethylene glycol precipitate of serum from infected hamsters. It was also found as a TCA-soluble component in an immunoglobulin-containing fraction eluted from infected hamster kidneys. It was not found in similarly treated control sera nor in the products of acid dissociation of circulating immune complexes (CIC) from infected hamster sera. CMA was not detected in the kidneys of normal hamsters. Precipitating anti-M antigen antibodies were present in one of 10 sera from infected hamsters, but not in the eluates of hamster kidneys. These results indicate that CMA is present in circulating immune complexes in infected hamsters. The presence of CMA in kidneys from the same hamsters suggests a possible role for circulating antigens in immune-complexed form in the aetiology of glomerulonephritis in S. mansoni infection.     

Fc epsilon receptor-positive cells are a major source of antigen-induced interleukin-4 in spleens of mice infected with Schistosoma mansoni

When cultured in vitro with either mitogen or parasite antigens, spleen cells from mice infected with Schistosoma mansoni produce significantly higher levels of IL-4 than splenocytes from control animals. Previous studies suggested that this increase in IL-4 production occurs because of a selective expansion of T helper type 2 (Th2) cells in infected mice. However, these experiments employed unfractionated spleen populations rather than purified T lymphocytes. Here we demonstrate that T-depleted spleen cells from infected animals synthesize high levels of interleukin-4 (IL-4), but no IL-5 when stimulated with parasite antigen in vitro. Nevertheless, when purified by sorting, T cells and non-B, non-T (NBNT) populations produced similar amounts of IL-4 in response to parasite antigen. The IL-4 producing NBNT cells were found to belong to an Fc epsilon receptor (Fc epsilon R)-positive population which after sort purification produced high levels of IL-4 (between 1000 and 2000 U of per 5 x 10(3) cells). FACS analysis revealed that these Fc epsilon R+ cells make up 0.53% of splenic NBNT cells in control animals while in 8-9-week-infected animals they increase to 3.8% of that population. In contrast, in mice with 8-week unisexual worm infections these cells comprise only 1.71% of NBNT cells, indicating that eggs are a major stimulus of the response. The expansion of Fc epsilon R+ cells and their production of IL-4 could be an important factor regulating the selection and induction of different CD4+ subsets in schistosome-infected hosts.     

An ultrasonographic study of liver fibrosis in patients infected with Schistosoma mansoni in north-east Brazil

Between August 1988 and July 1990, 176 patients with Schistosoma mansoni infection attending the University Hospital, Recife, Brazil received a complete clinical examination including stool examination for intestinal parasites, liver function tests, and ultrasonography. The majority were also examined by upper digestive tract endoscopy. The clinical distribution of their disease was as follows: 26.7% intestinal, 13.6% hepato-intestinal, 53.4% compensated hepatosplenic and 6.3% decompensated hepatosplenic. Infection intensity was high, with a median of 360 eggs/g of faeces. Ultrasonography showed a good correlation between the degree of hepatic periportal fibrosis and the clinical stage of disease (P < 0.0001). Of the patients with the intestinal form of schistosomiasis, 12.8% had grade I fibrosis and the others had no fibrosis; 33.3% of patients with hepatointestinal schistosomiasis had grade I fibrosis, 8.3% had grade II fibrosis, and 58.4% had no fibrosis; all the patients with hepatosplenic disease had grade II or grade III fibrosis. The degree of liver fibrosis detected by ultrasonography correlated with the degree of oesophageal varices detected by endoscopy (P = 0.0001). The degree of oesophageal varices also correlated with the presence of haemorrhage (P < 0.0001). Ultrasonography is considered superior to liver biopsy, permitting a dynamic approach to the study of schistosomiasis morbidity with precise diagnosis and simple sequential follow-up of post-treatment results.     

Immunological response of major histocompatibility complex class II-deficient (Abeta(o)) mice infected by the parasite Schistosoma mansoni

This study investigated changes in autonomic nervous activities due to psychological stress in Type A females. Eight Type A and eight Type B females performed a psychomotor task for 30 minutes. Power spectral analysis of heart rate variability (HRV) was used to examine the autonomic nervous activities. Results showed the low frequency (LF) component and LF/HF ratio in Type A females increased after the onset of the task. There were no significant differences in task performance between Type A and Type B females. The subjective mental workload increased gradually in Type A females during the tasks, whereas in Type B females this parameter did not change in a consistent manner. The results suggest that the sympathetic nervous system in Type A females was more stimulated by the task and Type A females felt a greater subjective mental workload than did Type B females.     

Biodistribution study of the anaesthetic sodium phenobarbital labelled with technetium-99m in Swiss mice infected with Schistosoma mansoni Sambon, 1907

The surgical treatment of transsphenoidal cephaloceles in children is controversial. Reduction and repair via a transcranial approach are associated with high postoperative rates of morbidity, mortality, and hypothalamic dysfunction. In this study, four patients, aged 3 to 35 months at surgery, underwent successful transpalatal repair of two encephaloceles and two meningoceles. Two patients presented with nasal obstruction in infancy, one presented with unexplained meningitis, and in one patient the lesion was found incidentally during evaluation for seizures. Two children had median cleft face syndrome, another had an associated Arnold-Chiari type I malformation, and the fourth had no other cranial abnormalities. All patients underwent preoperative evaluation including magnetic resonance (MR) imaging. Auditory, ophthalmological, genetic, endocrinological, or other evaluation was undertaken as indicated. Lesions were approached through the median raphe of the hard and soft palates. All cephaloceles were easily visualized and dissected after division of the nasal palatal mucosa. The dural sac and its contents were reduced by surface coagulation after division and dissection of the overlying mucosa. Once reduced, the bone defect was obliterated in three of four patients. The dura was not opened and anomalous neural elements were not resected. At follow-up evaluation, all patients demonstrated resolution of preoperative symptoms without evidence of infection or lasting morbidity. Follow-up MR imaging showed reduction in all cases. The authors conclude that this transpalatal approach is safe and reliable for the treatment of transsphenoidal cephaloceles in young children.