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Biomedical subjects

J El-On

Publications and source records attributed to J El-On.

At least 19 recordsLinked to original sources

Pathological developments mediated by cyclophosphamide in rats infected with Trypanosoma lewisi.

Trypanosoma lewisi is an obligatory, flagellated parasite of the rat. Despite the fact that naturally the rats overcome the disease, a lethal infection can be induced by the administration of an immunosuppressive agent, i.e. cyclophosphamide (Cy). In the Cy treated infected rats (CyI) the severity of the trypanosome infection was demonstrated in the internal organs, in the following order: lungs>liver>heart>spleen>kidney. The parasites were not detected in the brain. The accumulation of the parasites in the lungs led to the development of hemorrhagic inflammatory foci. The rupture of blood vessels was accompanied by lymphocyte infiltrations into the damaged tissues and multiple foci of edema around the blood vessels. In most cases the lungs were dark brown in color due to intra-alveolar hemorrhages. The spleen of the CyI rats showed general deformation of the tissue's architecture, migration of macrophages and cell depletion due to the Cy action. The liver showed inflammatory hemorrhagic foci associated with massive destruction of the parenchyma. In spite of the heavy parasitemia (>50%) developed in the CyI rats the brain remained free of parasites, which might explain the non-virulent character of this parasite compared to the African trypanosomes.

Animals↗

The flow-cytometry-based evaluation of cellular immunity in cases of cutaneous leishmaniasis and healthy controls from the endemic area in southern Israel.

Only limited data are available on the early immunological events associated with human cutaneous leishmaniasis (CL). In this study, peripheral-blood mononuclear cells were obtained from 66 individuals (34 patients with cutaneous lesions and 32 apparently healthy controls) who had each spent no more than 3 months in the endemic region of Qetzioth, in southern Israel. These cells' responses to Leishmania major antigen were then explored, by the flow-cytometry-based evaluation of blast transformation (BT). The lymphocytes from 17 (50%) of the patients but only one (3%) of the controls displayed BT. When, in an ELISA, most (52) of the subjects were checked for anti-L. major antibodies, none of the 22 controls investigated but 19 (63%) of the 30 patients were found seropositive. Although 14 (47%) of the 30 patients who were checked for antibodies were BT-positive, the seropositive patients were not significantly more or less likely to be BT-positive than the seronegative patients (P<0.919). These data indicate that, in CL, the hosts' cellular and humoral responses develop independently within the first 3 months post-infection, but further investigation is required to confirm this hypothesis.

Animals↗

Prevalence of cystic echinococcosis among Muslim and Jewish populations in southern Israel.

Following a review of records at the Soroka University Medical Center (SUMC) showing a recent increase in the annual incidence of hydatidosis among the Bedouin population of southern Israel, a seroepidemiological survey was conducted. A total of 1439 blood samples were collected from Bedouins and Jews living in the Negev area in southern Israel. An enzyme-linked immunosorbent assay (ELISA) for immunoglobulin G, indirect haemagglutination (IHA) and immunoelectrophoresis (IEP) were used to detect anti-Echinococcus granulosus antibodies. The seroprevalence in the Bedouin group was 0.68% (7/1026), including two children under the age of 10. Among Jews, a seroprevalence of 0.5% was recorded in patients over 60 years of age only. A high rate of infection was shown in goats and sheep slaughtered in abattoirs in Bedouin localities. The results indicate that echinococcosis is a common disease in the Muslim communities of southern Israel.

Adolescent↗

Interleukin 1alpha activity of peritoneal and bone marrow macrophages infected with Leishmania major and Leishmania donovani in vitro.

In this study, the pattern of interleukin-1alpha (IL-1alpha) production by both peritoneal (PM) and bone marrow macrophages (BMM) from resistant (C3H/HeJ) and susceptible (BALB/c) mice was investigated, using a bioassay and an IL-1alpha-specific ELISA kit. PM from normal uninfected mice showed either an initial high (C3H/HeJ) or a neglected (BALB/c) level of IL-1alpha activity, respectively, probably due to thioglycollate stimulation. Infection with Leishmania major induced only a marginal effect on IL-1 production by both cells. Normal, uninfected and unstimulated BMM from both mice did not produce IL-1alpha over a 7-day period of cultivation in vitro. Upon stimulation with either lipopolysaccharide (LPS) (BALB/c) or concanavalin A (Con A) (C3H/HeJ), both cell types produced IL-1alpha that peaked within the first 12-24 h following stimulation. BMM from C3H/HeJ and BALB/c mice failed to produce IL-1alpha when infected in vitro with L. major or L. donovani promastigotes. However, infection with these two parasites did not interfere with the capability of the host cell to produce IL-1alpha when stimulated with LPS or Con A. The level of IL-1alpha production was independent of the degree of parasitization of the macrophages. Similar results were observed with IL-1beta and IL-6 production by BMM, even though their levels were generally slightly higher than those obtained with IL-1alpha.

Animals↗

Giardia lamblia carriage in Israeli Bedouin infants: risk factors and consequences.

Giardiasis is a common protozoan infection, with varying clinical manifestations. We investigated the associations between Giardia lamblia carriage and environmental, family, illness, and growth characteristics. Bedouin infants (n=234) were followed from birth to age 18-23 months. At monthly home visits, stool samples were obtained, history of illness was determined, and an environmental assessment was done. The comparisons presented are between 4 groups defined by length of carriage of G. lamblia. Study children had a mean+/-SD of 4.1+/-2.9 diarrhea episodes. No illness, environmental, or family characteristics were associated with length of carriage. Significant differences were found in weight-for-age and weight-for-height z scores between the never-positive-for-G. lamblia group and all other carriage groups combined. Faltering growth was shown to be subsequent to G. lamblia infection rather than preceding it. Our findings confirm that G. lamblia carriage is not associated with diarrhea. However, the effect on growth deserves further investigation.

Adolescent↗

Natural history of Giardia lamblia and Cryptosporidium infections in a cohort of Israeli Bedouin infants: a study of a population in transition.

The natural history of Giardia lamblia and Cryptosporidium infections were determined in a cohort of 164 Bedouin children, from a population not previously studied, which is in transition from nomadism to a settled life style. Stools were sampled monthly from birth to two years of age and at all diarrhea episodes. The risk of infection with G. lamblia and Cryptosporidium infection by age two was 91.5% and 48.8%, respectively. Cryptosporidium prevalence was 3-4% at all ages, whereas G. lamblia prevalence was > 30% after age one. Giardia lamblia and Cryptosporidium asymptomatic detection rates were high, 28.5% and 1.6%, respectively. Detection of G. lamblia was higher in diarrhea episode samples obtained before six months of age, but after that age and overall, the detection was lower than in nondiarrhea samples (odds ratio [OR] = 0.8, 95% confidence interval [CI] = 0.7-0.9, P < 0.05). Detection rates of C. parvum were higher in episode-related samples in all age groups (OR = 2.8, 95% CI = 1.9-4.2, P < 0.05) and infections in boys were more frequently symptomatic than in girls. While G. lamblia does not appear to be a consistent pathogen in this population where it is hyperendemic, Cryptosporidium has been shown to be an important cause of diarrhea in young children in the community.

Adolescent↗

Cellular and humoral immune responses of hydatidosis patients to Echinococcus granulosus purified antigens.

The cellular and humoral immune responses of 41 hydatidosis patients, 12 healthy uninfected individuals, and seven patients with other parasitic diseases were determined using serologic and lymphoproliferative assays (LPAs), respectively. Echinococcal antigens were obtained by gel filtration of crude hydatid cyst fluid (HCF) on a Sephadex G-200 column. The fractions contained either a mixture of antigens A plus B or antigen B alone that was further enriched by boiling. All the hydatidosis patients responded positively by LPA to either crude or purified echinococcal antigens: 95% of them responded to either crude HCF, or a mixture of antigens A plus B and 83% to antigen B alone. The degree of the response to crude HCF (mean stimulation index [SI] = 75.3) was higher than that of purified antigens (SI = 39.1 for a mixture of antigens A plus B and SI = 36.9 for antigen B alone). No positive LPA response was obtained with the control groups. Serologic examinations showed that 78% of cases were positive by immunoblot, 73% by indirect hemagglutination, and 46% by immunoelectrophoresis. No correlation between the degree of cellular and humoral responsiveness to both crude and purified echinococcal antigens was observed. Nine of the 41 patients examined who were serologically negative also developed a high lymphoproliferative (LP) response to either crude or purified echinococcal antigens. The LP response remained positive over a long period after successful treatment. No relationship was observed between the results of treatment and the LP response. The present study indicates that the LPA could be used as an additional tool for the diagnosis of hydatid disease, particularly in seronegative cases, although it is unsuitable for effective monitoring treatment/surgery.

Adolescent↗

Evaluation of an enzyme immunoassay for the detection of Cryptosporidium spp. in stool specimens from infants and young children in field studies.

Diagnosis of Cryptosporidium is made by the identification of oocysts in stool specimens. Screening in field studies relies mainly on acid-fast staining followed by microscopic examination. The more sensitive immunofluorescent antibody (IFA) staining method is time-consuming, may involve technical difficulties, and is extremely costly as a screening procedure in field studies. We evaluated the diagnostic utility of a commercially available enzyme immunoassay (EIA), which detects Cryptosporidium-specific antigen, in 204 unprocessed stool specimens obtained from patients less than three years of age from a field study in southern Israel. When compared with the routine screening procedure applied in this field study (screening by acid-fast staining and microscopy after concentration, and confirmation of positive results by IFA), both the sensitivity and specificity were 98%. Of 139 specimens negative by microscopy, 13 (9.3%) were positive by the EIA. Eleven of these were confirmed by inhibition with antibody to Cryptosporidia-specific antigen. The EIA is an important tool for identifying Cryptosporidium in fecal specimens in field studies since it is sensitive, specific, simple to use, and unaffected by the presence of a preservative.

Animals↗

Leishmania major: histopathological responses before and after topical treatment in experimental animals.

The cellular response in the cutaneous leishmaniasis lesion (CL), of BALB/c mice treated topically with an ointment composed of 15% paromomycin and 12% methylbenzethonium chloride (PR-ointment) was studied. In the infected, untreated control group, the lesion showed progressive necrosis with an increase in the number of parasites, macrophages, lymphocytes, and polymorphonuclear cells over a period of 18 weeks. In the PR ointment-treated group, complete healing of the lesion was observed 4 weeks after termination of treatment, but total elimination of the parasites from the lesion was observed only 2 weeks later. A marked reduction in the number of macrophages and polymorphonuclear cells was observed during the healing process. A similar phenomenon was observed with mice inoculated intraperitoneally with paromomycin alone, although total elimination of the parasites from the lesions of these mice was not demonstrated over a period of 18 weeks. Neither L3T4 helper T cells nor Ly2 cytotoxic suppressor T cells were detected in the CL lesion, either before or after treatment.

Administration, Topical↗

Topical treatment of cutaneous leishmaniasis.

Sixty-seven patients, 19 females and 48 males, 4-66 years old, suffering from lesions of cutaneous leishmaniasis were treated topically with an ointment comprising 15% paromomycin sulfate and 12% methylbenzethonium chloride in white soft paraffin (P-ointment, U.K. patent GB117237A). After 10 days of treatment, twice daily, the lesions in 72% of the treated patients were free of parasites, 15% became free within an additional 20 days, without further treatment, and 13% failed to respond. Pigmentation developed in 18% of the treated lesions and inflammation of varying degree was associated with the treatment. These developments did not affect the clinical healing process which was generally completed in a period of 10-30 days after termination of treatment. In addition, 94% of the treated lesions healed with little or no scarring. No adverse clinical or laboratory side effects were observed except for a burning sensation at the site of treatment. Parasites isolated from patients who failed to respond to topical treatment were found to be susceptible to PR-MBCl in both in vitro infected macrophages and in vivo in experimentally infected BALB/c mice.

Administration, Topical↗

Protection of guinea pigs against cutaneous leishmaniasis by combined infection and chemotherapy.

A paromomycin and methylbenzethonium chloride ointment cured Leishmania enriettii infections in guinea pigs. Amastigotes were totally eliminated from the treated lesion after 10 days of treatment. A delayed effect also occurred on untreated lesions in the same animals. Lesions treated at various times after infection permitted protective immunity to develop, and 90% of treated animals were refractory to reinfection.

Animals↗

Leishmania major: antileishmanial activity of methylbenzethonium chloride.

Methylbenzethonium chloride (MBCl) decreased the growth of Leishmania major promastigotes and amastigotes in vitro. This decrease occurred during 4 days of exposure to the drug at concentrations of 0.1 to 2.5 micrograms ml-1. MBCl at 2 micrograms ml-1 killed almost 100% of the free living promastigotes and 87% of amastigotes within 4 days of treatment. Electron microscopy studies showed marked swelling of mitochondria in treated parasites. A possible additional effect on the parasite surface membrane is discussed.

Benzethonium↗

Leishmania major: excreted factor, calcium ions, and the survival of amastigotes.

Mouse macrophages infected with amastigotes of Leishmania major contain about 40% more intracellular exchangeable calcium than control macrophages. Similar elevation of intracellular exchangeable calcium was observed in macrophages engulfing red blood cells coated with purified excreted factor from L. major. The rate of cytolysis of red blood cells coated with excreted factor was significantly lower than that of uncoated controls. Excreted factor strongly binds calcium; thus, the possible role of a microenvironment rich in calcium bound to excreted factor within the phagolysosome in protecting the amastigotes may be considered.

Animals↗