The immunomodulatory activity of Chenopodium ambrosioides reduces the parasite burden and hepatic granulomatous inflammation in Schistosoma mansoni-infection.

ETHNOPHARMACOLOGICAL RELEVANCE: Folk medicine reports have described the use of Chenopodium ambrosioides as an anti-inflammatory, analgesic, and anthelmintic herb. These effects, including its activity against intestinal worms, are already scientifically observed. However, the immunological mechanisms of this species in the treatment of Schistosoma mansoni infection are unknown. AIM OF THE STUDY: To evaluate the immunological and anti-Schistosoma mansoni effects of a crude Chenopodium ambrosioides hydro-alcoholic extract (HCE). MATERIALS AND METHODS: For the in vitro analysis, cercariae and adult worms were exposed to different concentrations (0 to 10,000 µg/mL) of the HCE. For the in vivo evaluation, Swiss mice were infected with 50 cercariae of S. mansoni and separated into groups according to treatment as follows: a negative control (without treatment), a positive control (treated with Praziquantel®), HCE1 Group (treated with HCE during the cutaneous phase), HCE2 Group (treated with HCE during the lung phase), HCE3 Group (treated with HCE during the young worm phase), and HCE4 Group (treated with HCE during the adult worm phase). The animals treated with HCE received daily doses of 50 mg/kg, by gavage, for seven days, corresponding to the different developmental stages of S. mansoni. For comparison, a clean control group (uninfected and untreated) was also included. All animals were euthanized 60 days post-infection to allow the following assessments to be performed: a complete blood cells count, counts of eggs in the feces and liver, the quantification of cytokines and IgE levels, histopathological evaluations of the livers, and the analysis of inflammatory mediators. RESULTS: HCE treatment increased the mortality of cercariae and adult worms in vitro. The HCE treatment in vivo reduced the eggs in feces and liver. The number and area of liver granulomas, independent of the phase of treatment, were also reduced. The treatment with HCE reduced the percentage of circulating eosinophils, IgE, IFN-γ, TNF-α, and IL-4. In contrast, the treatment with the HCE, dependent on the phase, increased IL-10 levels and the number of peritoneal and bone marrow cells, mainly of T lymphocytes, B lymphocytes, and macrophages. This effect could be due to secondary compounds presents in this extract, such as kaempferol, quercetin and derivatives. CONCLUSIONS: This study demonstrates that Chenopodium ambrosioides has antiparasitic and immunomodulatory activity against the different phases of schistosomiasis, reducing the granulomatous inflammatory profile caused by the infection and, consequently, improving the disease prognosis.

Diagnosis efficacy of CEUS for hepatic inflammatory lesions.

PURPOSE: In this study, the efficacy of US/CEUS and clinicopathologic parameters in differential diagnosis of hepatic inflammatory lesions were evaluated. METHODS: This was a retrospective study in which CEUS imaging was performed on 182 patients. Among these patients, 44 patients had hepatic inflammatory lesions and 138 patients had malignant lesions. The ultrasound (US), CEUS, and clinicopathologic parameters with respect to differential diagnosis of hepatic inflammatory lesions were analyzed. RESULTS: Irregular lesion shape and unclear margin were commonly seen in hepatic inflammatory lesions by US/CEUS examination. Hypoenhancement in arterial phase (AP) and portal venous phase (PVP), and isoenhancement in delayed phase (DP) were more commonly found in inflammatory lesions rather than malignant lesions [9% (4/44), 68% (30/44), and 16% (7/44) vs 2% (3/138), 11% (15/138), 1% (1/138), respectively; P < .05]. The enhancement coverage was also a significant indicator for the differentiation of inflammatory lesions and malignant lesions (P < .05). History of hepatitis or cirrhosis, and higher serum alpha-fetoprotein (AFP) level were indicators for malignant lesions, while liver parasites and higher body temperature were indicators for inflammatory lesions. When the US/CEUS findings were combined with clinicopathologic parameters, the diagnostic accuracy of inflammatory lesions could reach 93.3%, with sensitivity, specificity, positive predictive value, and negative predictive value of 63.64%, 96.03%, 84.85%, and 88.32%, respectively. CONCLUSION: The US/CEUS findings combined with clinical characteristics can accurately differentiate hepatic inflammatory lesions and malignant lesions. The results of study will improve the diagnostic confidence for hepatic inflammatory lesions.

Treatment with Lycopodium clavatum 200dH Intensifies Kidney and Liver Injury in Mice Infected with Toxoplasma gondii.

The effects of infection with Toxoplasma gondii vary from asymptomatic to the development of alterations in various organs (including the liver and kidneys) which may be irreversible, and lead to the death of the host. Whereas homeopathy is an alternative and effective method for treating various diseases, including those caused by protozoa, we questioned the effect of using Lycopodium clavatum in mice infected with T. gondii. One hundred male Swiss mice, 60 days old, were divided into four groups (n = 25/group): NIC (uninfected and untreated control), IC (infected and treated with un-dynamized 7% alcohol solution [vehicle]), G48 (infected and treated 48 h before infection and treated three more times; at 2, 4, and 6 days post-infection (dpi) with L. clavatum 200dH), and G72 (infected and treated for 3 consecutive days before infection with L. clavatum 200dH). In this study, physiological, histopathological, and immunological parameters were evaluated. The L. clavatum 200dH intensified renal damage in mice infected with T. gondii from 7 dpi, causing severe and progressive alterations during this period, such as various degrees of inflammation, edema, atrophy, and tubular cystic dilation, degenerated tubules with intra-cytoplasmic vacuoles and coalescing spots, severe vascular lesions, glomerulonephritis, and peri-glomerular congestion. In the G72 animals, which received L. clavatum 200dH, more severe cortex damage was observed (91.66-96.66%) as compared to the IC group (55-80%) and more renal corpuscle, and renal tubule injury was observed (80 ± 5 to 96.7% ± 2.89 of the total area) during all periods, as compared to the IC group (p < 0.05). Both groups presented high liver enzyme levels, and the highest values for AST were observable at 60 dpi. We observed significant increases of type I and III collagen, as well as high levels of TGF-ß1 in both organs of the treated animals, the main factor involved in fibrosis in areas damaged by the process. L. clavatum 200dH intensifies kidney and liver alterations in mice infected with T. gondii. Our results reinforce caution when indicating administration schemes and dosages for ultra-diluted drugs.

Comparative effects of Herba Cox®, a commercial herbal extract, on rabbits (Oryctolagus cuniculus) experimentally infected with Eimeria stiedae.

The objective of this study was to evaluate the efficacy of Herba Cox®, a commercial herbal compound containing extracts from Bombax malabaricum, Aegle marmelos, Anethum foeniculum, Resina salvia, Ferula asafoetida and Papaver somniferum, for the treatment of rabbit hepatic coccidiosis. Thirty rabbits were allocated into three groups (10 × 3), the G1 group served as a negative control group, G2 group (positive control group) was infected with 5 × 104 sporulated E. stiedaeoocysts and served as infected-untreated group, and G3 group was infected with 5 × 104 sporulated E. stiedaeoocysts and treated with Herba Cox®, 1 ml/liter of drinking water, starting 7 days before infection and continuing for 4 weeks post-infection. When compared to the infected group (G2), body weight and weight gain were significantly (P ≤ 0.05) increased, the feed conversion rate was improved and no mortality was detected in infected treated group (G3) and similar to negative control group (G1). In addition, faecal oocyst output and liver enzymes were significantly decreased. Malondialdehyde, nitric oxide, and glutathione concentrations observed in G3 were similar to those in G1. In infected-untreated rabbits (G2), the haemoglobin, lymphocytes, and CD4+/ CD8+ ratio were significantly decreased, while the total leukocyte count, percentage of heterophils, and heterophil/lymphocyte ratio were increased. Significantly more severe histopathological hepatic lesions were observed in G2 when compared to G1 and G3. In conclusion, the obtained results showed that Herba Cox® should be considered a safe and novel effective compound for the treatment of E. stiedae infection in rabbits.

Syphilis-Associated Acute Renal Failure and Hepatitis in the Setting of Human Immunodeficiency Virus Coinfection.

Two individuals with human immunodeficiency virus presented in acute renal failure with nephrotic range proteinuria and were diagnosed with secondary syphilis. One of them also had elevated transaminases. Kidney biopsies revealed membranous nephropathy, a rare complication of secondary syphilis, in both cases. Normal hepatic and renal function were restored after treatment with penicillin.

Acute liver failure due to visceral leishmaniasis in Barcelona: a case report.

BACKGROUND: Leishmaniasis is an emerging infectious disease. Due to human migration and tourism, visceral leishmaniasis may become more common in non-endemic areas. In the Mediterranean basin, visceral leishmaniasis typically occurs in rural regions. CASE PRESENTATION: We present an unusual urban case of acute liver failure due to visceral leishmaniasis, following a prolonged fever of unknown origin. After obtaining negative results from the bone marrow aspirate, we performed a liver biopsy that elucidated the diagnosis. The liver involvement in visceral leishmaniasis may appear as chronic granulomatous hepatitis. However diffuse hepatitis process, a necro-inflammatory pattern, without forming granulomas were observed in the liver biopsy specimens in this case. Intracytoplasmic Leishmania amastigotes were observed in the liver biopsy specimens and a polymerase chain reaction confirmed the diagnosis. Only five pathological confirmed cases of acute hepatitis due to visceral leishmaniasis have been described so far, just two in adults and both from Barcelona. A revision of the literature is performed. CONCLUSIONS: Acute hepatitis is an uncommon debut of visceral leishmaniasis in immunocompetent patients. Furthermore there are only few cases in the literature that describe the histopathological changes that we found in this patient. In conclusion, in case of acute hepatitis leading to liver failure, leishmaniasis should be considered a differential diagnosis (even in non-endemic countries and without clear epidemiological exposure) and liver biopsy can elucidate the diagnosis.

Anti-Toxoplasma activity of silver nanoparticles green synthesized with Phoenix dactylifera and Ziziphus spina-christi extracts which inhibits inflammation through liver regulation of cytokines in Balb/c mice.

Toxoplasmosis constitutes a global infection caused by oblige intracellular apicomplexan protozoan parasite Toxoplasma gondii Although often asymptomatic, infection can result in more severe, potentially life threatening symptoms particularly in immunocompromised individuals. The present study evaluated the anti-Toxoplasma effects in experimental animals of silver nanoparticles synthesized in combination with extracts of natural plants (Phoenix dactylifera and Ziziphus spina-christi) as an alternative method to standard sulfadiazine drug therapy. Liver functions estimated by and AST and ALT were significantly increased in T. gondii-infected mice compared with the control group as well as hepatic nitric oxide (NO), lipid peroxidation (LPO) levels and caused significant decrease in superoxide dismutase (SOD), catalase (CAT) and glutathione activities in the liver homogenates. Nanoparticles pretreatment prevented liver damage as determined by enzyme activity inhibition, in addition to significant inhibition of hepatic NO levels and significant elevation in liver SOD and CAT activities. Moreover, nanoparticle treatment significantly decreased hepatic LPO and NO concentrations and proinflammatory cytokines but significantly boosted the antioxidant enzyme activity of liver homogenate. In addition, histological examinations showed distinct alterations in the infected compared with untreated control groups. Conversely, nanoparticles pretreatment showed improvement in the histological features indicated by slight infiltration and fibrosis, minimal pleomorphism and less hepatocyte and degeneration. Furthermore, nanoparticles treatment induced a reduction in immunoreactivity to TGF-ß and NF-κB in hepatic tissues. Therefore, the present study provides new insights into various natural plants that are used traditionally for the treatment of toxoplasmosis and other parasitic infections, which may be useful as alternative treatment option for T. gondii infections.

First case report of Toxoplasma gondii-induced abortions and stillbirths in sheep in Argentina.

The aim of this study is to report an episode of reproductive losses due to toxoplasmosis in a sheep flock in Argentina. A total of 15 abortions and 9 stillbirths were recorded in a flock of 190 Texel ewes. The affected ewes were more likely to be seropositive for Toxoplasma gondii (15/24) than ewes that delivered normal lambs (5/34, OR=9.6, 95%CI=2.7-34.0, p=0.0004). A pair of aborted twins was recovered for diagnostic investigation. One of these fetuses and its dam were seropositive for T. gondii. Histological examination of the two fetuses revealed non-suppurative myocarditis and epicarditis, portal hepatitis and multifocal necrotizing encephalitis with protozoal cysts in the brain. T. gondii was detected intralesionally by immunohistochemistry in one fetus and by PCR in both. Further investigations are necessary to evaluate the economic losses due to T. gondii in the Argentinean ovine industry.

Severe Toxoplasmic Hepatitis in an Immunocompetent Patient.

Acute Toxoplasma gondii infection causes different clinical courses in 10-20% of cases. In immunocompetent patients, toxoplasmosis most often presents as asymptomatic cervical lymphadenopathy. Clinical manifestations such as pneumonia, myocarditis, hepatitis, and encephalitis are rarely reported. We present the case of an immunocompetent patient with a serious and complicated clinical course of toxoplasmic hepatitis with a maculopapular rash. The diagnosis was confirmed by serology and identification of bradyzoites in liver biopsy samples.

[Acute hepatitis in infectious diseases].

Hepatitis A, B, C, D, E, G are the most common causes of acute hepatitis, however, there are many infectious diseases affecting liver and with fever, early diagnostics of which is very important for the clinic of internal diseases. This review presents infections, causing fever and hepatitis, but not necessarily accompanied by jaundice. Leptospirosis, yellow fever have been considered, in which liver damage determines the clinic and the prognosis of the disease. In other cases, such as infectious mononucleosis, cytomegalovirus and herpetic hepatitis, typho-para-typhoid infections, typhoid, pneumonia, some viral diseases, malaria, Legionnaire's disease, hepatitis do not have their independent status and represent one of the important syndromes of a common disease. Modern methods of diagnostics and treatment of these diseases have been described.

Mice lacking inducible nitric oxide synthase develop exacerbated hepatic inflammatory responses induced by Plasmodium berghei NK65 infection.

Infection of mice with Plasmodium berghei NK65 represents a well-recognized malaria model in which infection is accompanied by an intense hepatic inflammatory response. Enzyme-inducible nitric oxide synthase is an important regulator of inflammation and leukocyte recruitment in microvessels, but these functions have yet to be evaluated in experimental malaria. In this study, we assessed the involvement of inducible nitric oxide synthase in inflammatory responses to murine experimental malaria induced by P. berghei NK65. We observed that wild type (WT) and nitric oxide synthase (iNOS)-deficient mice (iNOS(-/-)) mice showed similar levels of parasitemia following P. berghei NK65 infection, although infected iNOS(-/-) mice presented early mortality. Inducible nitric oxide synthase deficiency led to increased leukocyte rolling and adhesion to the liver in iNOS(-/-) mice relative to the WT animals, as observed via intravital microscopy. Infected iNOS(-/-) mice also exhibited increased hepatic leukocyte migration and subsequent liver damage, which was associated with high serum levels of the cytokines TNF-α, IL-6 and IL-10. Our data suggest potential role for the iNOS enzyme as a regulator of hepatic inflammatory response induced by P. berghei NK65-infection, and its absence leads to exacerbated inflammation and sequential associated-hepatic damage in the animals.

Hepatic stellate cells increase in Toxoplasma gondii infection in mice.

BACKGROUND: Toxoplasma gondii is a ubiquitous protozoan parasite that can infect humans and animals. The severity of toxoplasmosis varies according to the immune status of the individual, parasite strain, and host species. In mammalian species, it has been observed that severe lesions of acute toxoplasmosis form in visceral organs such as the liver, lung, and spleen. Some epidemiological studies have reported an association of T. gondii infection with liver cirrhosis. METHODS: Acute infection was induced in fifteen 30-day-old normal Swiss albino mice. The mice were infected by intraperitoneal inoculation of 5000 T. gondii RH strain tachyzoites. The mice were sacrificed in groups of 5 at 2, 4, and 6 days after inoculation. Another group of 5 mice were used as the controls. Anti-glial fibrillary acidic protein (GFAP) and anti-T. gondii antibodies were used to compare GFAP-immunoreactive cells and anti-T. gondii-immunopositive areas in the liver between the T. gondii-infected groups and the healthy controls, respectively. RESULTS: There was a significant correlation between the numbers of GFAP-positive hepatic stellate cells (HSCs) when they were compared with T. gondii antigen immunostaining (p < 0.05). The amount of T. gondii immunostaining increased significantly with the increase in the number of HSCs. CONCLUSIONS: There is a significant relationship between the number of HSCs and T. gondii antigens, which may represent an active role of HSCs in liver pathology and the pathobiology of T. gondii-related hepatitis.

[Tropical malaria in children in the Republic of Tajikistan].

The complications of tropical malaria were noted in 25 (9.4%) of 196 pediatric patients followed up. These included cerebral malaria in 8 (3%), severe hemolytic anemia in 15 (5.7%), hemoglobinuric fever in 1 (0.37%), and malarial hepatitis in 1 (0.37%). The occurrence of complications was associated with the late referral of patients to a health care facility and untimely treatment, as well as with preliminary misdiagnoses (acute respiratory viral infection, typhoid-parathyphoid fever, meningitis, acute enteric infection, viral hepatitis, sepsis). The main reasons for late diagnosis were the absence of malarial paroxysm at the onset of disease in infants and the wrong type of a temperature curve.

Adenocarcinoma of gallbladder: an immunohistochemical profile and comparison with cholangiocarcinoma.

AIM: Cholangiocarcinomas display intestinal and pyloric gland metaplasia-cell phenotypes. Those that arise in chronically inflamed (fluke infested) bile ducts more frequently express the intestinal metaplasia-cell phenotype and p53 than sporadic cholangiocarcinomas. We wished to determine if adenocarcinomas of the gallbladder display a similar profile. METHODS: Adenocarcinoma, adenoma, and dysplastic and metaplastic epithelia were studied in 55 gallbladders. Serial paraffin sections were stained for five foregut antigens characteristically present in pyloric gland metaplasia, three intestinal-specific antigens and p53. Antigen expression was compared with that shown by 65 fluke-associated and 47 sporadic cholangiocarcinomas. RESULTS: Pyloric gland metaplasia in gallbladders with chronic cholecystitis invariably displayed the five foregut antigens. The frequency of expression of these five antigens by the gallbladder cancers and cholangiocarcinomas did not differ significantly. An intestinal goblet-cell marker and p53 were more frequently expressed by gallbladder carcinoma (59% and 45%, respectively) and fluke-associated cholangiocarcinoma (45% and 46%) than by sporadic cholangiocarcinoma (17% and 23%). K20 was more frequently expressed by gallbladder carcinoma (52%) than either fluke-associated (21%) or sporadic (17%) cholangiocarcinoma. Dysplastic epithelium and adenomas also displayed the pyloric gland and intestinal metaplasia-cell phenotypes. Cells staining for pyloric gland metaplasia-cell phenotypes were distinct from the intestinal metaplasia-cell phenotypes when present together in a gallbladder carcinoma, cholangiocarcinoma, dysplastic epithelium or adenoma. CONCLUSIONS: Adenocarcinomas of gallbladder generally arise from a foregut cell lineage via a metaplasia-dysplasia-carcinoma sequence. A background of chronic inflammation increases the frequency of expression of an intestinal goblet-cell phenotype and p53 in the cancers.

Liver response of rabbits to Eimeria coecicola infections.

Intestinal coccidiosis of rabbits induced by E. coecicola causes enormous economic losses in rabbit farms. Here, we investigate the effect of E. coecicola on the liver of the rabbit Oryctolagus cuniculus. On day 7 p.i., fecal expulsion of E. coecicola oocysts is maximal and rabbits have lost approximately 25% of their weight. The liver, though not targeted by parasites, exhibits several signs of moderate inflammations, i.e., inflammatory cellular infiltrations around the central vein, dilatated blood sinusoids, increase in vacuolated hepatocytes, hypertrophic Kupffer cells, and lipid peroxidation as well as decreases in catalase and superoxide dismutase activities. Liver injuries are also indicated by an increase in blood plasma, by an increase in liver enzymes such as alanine transaminase, aspartate transaminase, alkaline phosphatase, and gamma glutamyl transferase, and a decrease in total protein and albumin. Circulating neutrophils have increased from 61% on day 0 p.i. to 71.3% on day 7 p.i., while lymphocytes are decreased from 37% to 26%. Agilent two-color oligo microarray technology, in combination with quantitative PCR, reveals that the expressions of 56 genes are upregulated and that of 22 genes are downregulated in the liver. The genes are largely involved in metabolism, calcium homeostasis, transport, and diverse signaling processes in the liver. In addition, numerous genes encoding for different regions of T-cell receptor as well as IgM, IgG, and IgA antibodies are both up- and downregulated in the liver by E. coecicola infections. The latter data suggest that the liver is not only 'passively' inflamed by intestinal infections with E. coecicola but rather is actively involved in the host defense against the intestinal Eimeria parasites.