Focus: Zoonotic Disease: Zoonotic Ocular Onchocercosis by Onchocerca lupi

The parasitic filarioid Onchocerca lupi causes ocular disease characterized by conjunctivitis and nodular lesions. This nematode was first described in 1967 in a wolf from Georgia, and since then cases of infection from dogs and cats with ocular onchocercosis and sporadically from humans also with subcutaneous and cervical lesions caused by O. lupi have been reported from the Middle East, Europe, and North America. Due to its zoonotic potential, this parasitic infection has gained attention in the past 20 years. Phylogenetic studies have highlighted the recent divergence of O. lupi from other Onchocerca spp. and the importance of domestication in the evolutionary history of this worm. Moreover, the finding of an O. lupi genotype associated with subclinical and mild infection in the Iberian Peninsula, raises important questions about the pathogenicity of this presently enigmatic parasite.     

Disseminated staphylococcal disease in laboratory rabbits (Oryctolagus cuniculus).

The pathologic findings in 13 cases of staphylococcal disease in New Zealand white rabbits were described. Subcutaneous abscesses and embolic pyemic abscesses in kidney, heart, brain, and lung were found. Conjunctivitis, rhinitis, otitis media, and fibrinous pneumonia also occurred. One rabbit had a valvular endocarditis. Staphylococcus aureus, coagulase-positive, and fermenting mannitol were isolated from the lesions described. Staphylococcal disease was diagnosed in 13 of the 171 (7.6%) rabbits necropsied during a 3-yr period. Disseminated staphylococcal lesions were observed only in rabbits during this time.     

In-Line Phase Contrast Imaging of Hepatic Portal Vein Embolization with Radiolucent Embolic Agents in Mice: A Preliminary Study

It is crucial to understand the distribution of embolic agents inside target liver during and after the hepatic portal vein embolization (PVE) procedure. For a long time, the problem has not been well solved due to the radiolucency of embolic agents and the resolution limitation of conventional radiography. In this study, we first reported use of fluorescent carboxyl microspheres (FCM) as radiolucent embolic agents for embolizing hepatic portal veins. The fluorescent characteristic of FCM could help to determine their approximate location easily. Additionally, the microspheres were found to be fairly good embolizing agents for PVE. After the livers were excised and fixed, they were imaged by in-line phase contrast imaging (PCI), which greatly improved the detection of the radiolucent embolic agents as compared to absorption contrast imaging (ACI). The preliminary study has for the first time shown that PCI has great potential in the pre-clinical investigation of PVE with radiolucent embolic agents.     

Oxidative stress and inflammation: liver responses and adaptations to acute and regular exercise

The liver is remarkably important during exercise outcomes due to its contribution to detoxification, synthesis, and release of biomolecules, and energy supply to the exercising muscles. Recently, liver has been also shown to play an important role in redox status and inflammatory modulation during exercise. However, while several studies have described the adaptations of skeletal muscles to acute and chronic exercise, hepatic changes are still scarcely investigated. Indeed, acute intense exercise challenges the liver with increased reactive oxygen species (ROS) and inflammation onset, whereas regular training induces hepatic antioxidant and anti-inflammatory improvements. Acute and regular exercise protocols in combination with antioxidant and anti-inflammatory supplementation have been also tested to verify hepatic adaptations to exercise. Although positive results have been reported in some acute models, several studies have shown an increased exercise-related stress upon liver. A similar trend has been observed during training: while synergistic effects of training and antioxidant/anti-inflammatory supplementations have been occasionally found, others reported a blunting of relevant adaptations to exercise, following the patterns described in skeletal muscles. This review discusses current data regarding liver responses and adaptation to acute and regular exercise protocols alone or combined with antioxidant and anti-inflammatory supplementation. The understanding of the mechanisms behind these modulations is of interest for both exercise-related health and performance outcomes.     

Factors influencing the etiology of cribra orbitalia in prehistoric Nubia

The present research represents an attempt to explain the occurrence of cribra orbitalia in Nubian skeletal remains associated with Meroitic, X-Group and Christian cultural horizons. The distribution of cribra orbitalia among 285 crania examined revealed a concentration of lesions among infants and aged individuals. While earlier studies have suggested cribra orbitalia may reflect the occurrence of abnormal hemoglobins such as sickle cell anemia or thalassemia, a consideration of the environmental context in which the lesions occurred makes an alternative hypothesis more likely. Particularly in Nubia (past and present), where parasitic infection is high, the diet is poor in iron, weanling diarrhea is frequent and multiparity is the norm, chronic iron deficiency anemia is a more likely causal factor. This interpretation is also compatable with clinical observations of cribra orbitalia among modern individuals suffering from chronic iron deficiency anemia.     

肝囊型包虫病非手术治疗方法的研究进展

肝囊型包虫病(简称肝包虫病)是一种由细粒棘球蚴感染肝脏引起的人兽共患寄生虫病,严重危害人类以及家畜的健康。近年来,由于该病术后复发率较高且易出现并发症,非手术治疗方法如介入技术、放射治疗以及药物治疗均得到了不断的发展。介入技术对于肝包虫病的治疗是一种比较新颖的方法,其临床应用时间较短,主要包括经皮穿刺治疗、射频消融、门静脉栓塞,以经皮穿刺治疗最为常见。放射治疗肝包虫病尚处于研究阶段,效果尚不完全明确。苯并咪唑类药物及其新剂型、非苯并咪唑类药物如地塞米松等及中草药治疗肝包虫病也均具有各自的优缺点。本文主要对上述非手术治疗方法及优缺点进行了综述。     

The hepato-renal syndrome in cultured turbot (Scophthalmus maximus L.)

The histopathology of biliary hyperplasia and renal calcinosis, associated with infections of two parasites, Myxidium incurvatum and Rhabdospora thelohani , is described in turbot, Scophthalmus maximus (L.), from Scottish marine fish farms and wild populations. Liver and kidney lesions were divided into four, and parasite infections into five grades of severity. A few of the fish examined were not parasitized, but every one showed some evidence of pathological change, even the apparently normal individuals from all populations. Although there is a positive association between the parasitic and pathological data, parasitism is not considered to be the principal cause of either the hepatic or renal lesion; the evidence suggests rather a secondary opportunist role for the parasites. The general severity of the condition in captive stocks suggests that the cause may lie in the fundamentals of present techniques of turbot husbandry, but no specific agent has been identified. A case is put forward for considering Rhabdospora to be a parasite rather than a specialized host cell.     

Four cases of gastric submucosal mass suspected as anisakiasis

Anisakiasis is a parasitic disease caused by ingestion of raw fish infected with anisakid larvae. Endoscopic changing patterns of submucosal lesions in chronic gastric anisakiasis have not been known yet. Here we report 4 cases of suspected gastric anisakiasis which were improved during follow-up periods without surgical treatment. The patients presented with abdominal pain, nausea and vomiting after consuming raw marine fish, and visited our gastroenterology outpatient department. Their endoscopic findings showed firm and yellowish submucosal masses accompanied with eccentric erosions. Histologic findings showed severe eosinophilic infiltrations. In blood tests, peripheral eosinophil counts and total IgE levels were elevated. We believed that all cases were caused by larval anisakid infections. The submucosal mass lesions disappeared during the follow-up periods of 2 to 4 mo.     

Trypanosoma cruzi Infection Is a Potent Risk Factor for Non-alcoholic Steatohepatitis Enhancing Local and Systemic Inflammation Associated with Strong Oxidative Stress and Metabolic Disorders

Background

The immune mechanisms underlying experimental non-alcoholic steatohepatitis (NASH), and more interestingly, the effect of T. cruzi chronic infection on the pathogenesis of this metabolic disorder are not completely understood.

Methodology/Principal Findings

We evaluated immunological parameters in male C57BL/6 wild type and TLR4 deficient mice fed with a standard, low fat diet, LFD (3% fat) as control group, or a medium fat diet, MFD (14% fat) in order to induce NASH, or mice infected intraperitoneally with 100 blood-derived trypomastigotes of Tulahuen strain and also fed with LFD (I+LFD) or MFD (I+MFD) for 24 weeks. We demonstrated that MFD by itself was able to induce NASH in WT mice and that parasitic infection induced marked metabolic changes with reduction of body weight and steatosis revealed by histological studies. The I+MFD group also improved insulin resistance, demonstrated by homeostasis model assessment of insulin resistance (HOMA-IR) analysis; although parasitic infection increased the triglycerides and cholesterol plasma levels. In addition, hepatic M1 inflammatory macrophages and cytotoxic T cells showed intracellular inflammatory cytokines which were associated with high levels of IL6, IFNγ and IL17 plasmatic cytokines and CCL2 chemokine. These findings correlated with an increase in hepatic parasite load in I+MFD group demonstrated by qPCR assays. The recruitment of hepatic B lymphocytes, NK and dendritic cells was enhanced by MFD, and it was intensified by parasitic infection. These results were TLR4 signaling dependent. Flow cytometry and confocal microscopy analysis demonstrated that the reactive oxygen species and peroxinitrites produced by liver inflammatory leukocytes of MFD group were also exacerbated by parasitic infection in our NASH model.

Conclusions

We highlight that a medium fat diet by itself is able to induce steatohepatitis. Our results also suggest a synergic effect between damage associated with molecular patterns generated during NASH and parasitic infection, revealing an intense cross-talk between metabolically active tissues, such as the liver, and the immune system. Thus, T. cruzi infection must be considered as an additional risk factor since exacerbates the inflammation and accelerates the development of hepatic injury.     

Experimental thioacetamide-induced cirrhosis of the liver.

Hepatic cirrhosis is a complex disease in which several biological, biochemical and chemical alterations are combined, none of these alone being sufficient for diagnosis. The morphological characteristics of the final stages of cirrhosis are well known, but the initial lesions and intermediate stages still have not been fully clarified. An experimental model of hepatic cirrhosis by chronic administration over 30 weeks of thioacetamide (50 mg/kg twice weekly) to female Wistar rats has been produced. In a macroscopic, microscopic and ultrastructural study. The different lesions that appeared were evaluated according to the dose of the toxic agent administered up, until hepatic cirrhosis was finally installed; this was after 60 doses of the toxic agent (30 weeks). Discussion is made of the different types of administration and the doses employed to obtain a suitable survival rate for these cases; in our experiments this was 95%. It has been demonstrated in both human and experimental pathology that once the disease itself has been installed, currently there is no rational or useful treatment for it. A beneficial effect has been demonstrated for certain substances, improving the initial and intermediate lesions, so we conclude by stating that it is necessary to further study the hepatic lesions preceeding cirrhosis. Knowledge of these lesions could form the basis for establishing a useful and rational therapy for such cases.     

Do Antenatal Parasite Infections Devalue Childhood Vaccination?

On a global basis, both potent vaccine efficacy and high vaccine coverage are necessary to control and eliminate vaccine-preventable diseases. Emerging evidence from animal and human studies suggest that neglected tropical diseases (NTDs) significantly impair response to standard childhood immunizations. A review of efficacy and effectiveness studies of vaccination among individuals with chronic parasitic infections was conducted, using PUBMED database searches and analysis of data from the authors'' published and unpublished studies. Both animal models and human studies suggest that chronic trematode, nematode, and protozoan infections can result in decreased vaccine efficacy. Among pregnant women, who in developing countries are often infected with multiple parasites, soluble parasite antigens have been shown to cross the placenta and prime or tolerize fetal immune responses. As a result, antenatal infections can have a significant impact on later vaccine responses. Acquired childhood parasitic infections, most commonly malaria, can also affect subsequent immune response to vaccination. Additional data suggest that antiparasite therapy can improve the effectiveness of several human vaccines. Emerging evidence demonstrates that both antenatal and childhood parasitic infections alter levels of protective immune response to routine vaccinations. Successful antiparasite treatment may prevent immunomodulation caused by parasitic antigens during pregnancy and early childhood and may improve vaccine efficacy. Future research should highlight the varied effects that different parasites (alone and in combination) can have on human vaccine-related immunity. To optimize vaccine effectiveness in developing countries, better control of chronic NTDs may prove imperative.     

"No-reflow" phenomenon during percutaneous carotid angioplasty in a scleroderma patient

Atherosclerosis remains the most common etiology of carotid artery stenosis, but other systemic diseases can also cause this disease. Percutaneous carotid angioplasty and stenting (CAS) with and without distal embolic protection devices is gaining acceptance as the treatment of choice. No-reflow phenomenon due to distal embolization has been previously described mainly during percutaneous intervention of degenerated saphenous vein graft. We describe a patient with systemic sclerosis who underwent CAS with distal embolic protection device with occurrence of no-reflow phenomenon during the procedure that resolved after retrieval of the filter device.     

Lung function in diaphragm pacing.

Electric stimulation of the diaphragm via the phrenic nerve to induce ventilation has recently been used for the long-term management of chronic ventilatory insufficiency. Since 1973 three patients with inadequate alveolar ventilation have been treated with diaphragm pacing at the Toronto Western Hospital. Two, who had quadriplegia due to lesions of the spinal cord in the upper cervical region and a severe restrictive ventilatory defect, were treated with continuous diaphragm pacing. The third patient required assisted nocturnal ventilation because of primary alveolar hypoventilation. All three patients tolerated the diaphragm pacing well, and pulmonary function tests showed satisfactory gas exchange with the patients breathing room air. This form of therapy seems to be a practical clinical method of managing chronic ventilatory failure in patients with lesions of the upper cervical cord or primary alveolar hypoventilation.     

Shifting patterns of nitrogen excretion and amino acid catabolism capacity during the life cycle of the sea lamprey (Petromyzon marinus)

The jawless fish, the sea lamprey (Petromyzon marinus), spends part of its life as a burrow-dwelling, suspension-feeding larva (ammocoete) before undergoing a metamorphosis into a free swimming, parasitic juvenile that feeds on the blood of fishes. We predicted that animals in this juvenile, parasitic stage have a great capacity for catabolizing amino acids when large quantities of protein-rich blood are ingested. The sixfold to 20-fold greater ammonia excretion rates (J(Amm)) in postmetamorphic (nonfeeding) and parasitic lampreys compared with ammocoetes suggested that basal rates of amino acid catabolism increased following metamorphosis. This was likely due to a greater basal amino acid catabolizing capacity in which there was a sixfold higher hepatic glutamate dehydrogenase (GDH) activity in parasitic lampreys compared with ammocoetes. Immunoblotting also revealed that GDH quantity was 10-fold and threefold greater in parasitic lampreys than in ammocoetes and upstream migrant lampreys, respectively. Higher hepatic alanine and aspartate aminotransferase activities in the parasitic lampreys also suggested an enhanced amino acid catabolizing capacity in this life stage. In contrast to parasitic lampreys, the twofold larger free amino acid pool in the muscle of upstream migrant lampreys confirmed that this period of natural starvation is accompanied by a prominent proteolysis. Carbamoyl phosphate synthetase III was detected at low levels in the liver of parasitic and upstream migrant lampreys, but there was no evidence of extrahepatic (muscle, intestine) urea production via the ornithine urea cycle. However, detection of arginase activity and high concentrations of arginine in the liver at all life stages examined infers that arginine hydrolysis is an important source of urea. We conclude that metamorphosis is accompanied by a metabolic reorganization that increases the capacity of parasitic sea lampreys to catabolize intermittently large amino acid loads arising from the ingestion of protein rich blood from their prey/hosts. The subsequent generation of energy-rich carbon skeletons can then be oxidized or retained for glycogen and fatty acid synthesis, which are essential fuels for the upstream migratory and spawning phases of the sea lamprey's life cycle.     

Cuban parasitology in review: a revolutionary triumph

Although the population of Hispaniola, Cuba's most similar neighbour in the Caribbean, continues to be threatened by parasitic diseases (including malaria), many tropical parasitic infections in Cuba have been eliminated or controlled. However, some parasitic infections remain important in the Cuban population, and the occurrence of vectors and the high possibility of introduction of parasites mean that Cuban diagnosticians must remain alert. Some key aspects of human parasitology in Cuba are reviewed here, including historical information, comparative data from Hispaniola and Jamaica, and how Cuba strives to maintain and improve its control against parasitic infections. Data from recent key novel parasitology research conducted in Cuba are also described.     

Clan CD cysteine peptidases of parasitic protozoa

Parasitic protozoa contain an abundance of cysteine peptidases that are crucial for a range of important biological processes. The most studied cysteine peptidases of parasitic protozoa belong to the group of papain-like enzymes known as clan CA. However, several more recently identified cysteine peptidases differ fundamentally from the clan CA enzymes and have been included together in clan CD. Enzymes of this clan have now been identified in parasitic protozoa. Many have important roles and also differ significantly from known mammalian counterparts. The main characteristics of clan CD enzymes are outlined here, in particular glycosylphosphatidylinositol (GPI):protein transamidase, metacaspase and separase, and their differences from the clan CA enzymes are described.     

Adaptive immune stimulation is required to obtain high protection with fatty acid binding protein vaccine candidate against Fasciola hepatica in Balb/C mice

Fascioliasis is a parasitic disease that mainly affects cattle and sheep, causing significant economic losses with a great impact in developing countries. Human fascioliasis is becoming more important with the high endemicity in some countries of the world. Previous studies have shown the importance of Fasciola hepatica fatty acid binding proteins (FABP) as protective molecules against fascioliasis in various animal models including mice, rabbits, and sheep. Our studies have shown the protective efficacy of recombinant FABP (rFh15) when the protein is formulated in the adjuvant adaptation system (ADAD), using either natural or synthetic immunomodulators. The ADAD system is most effective when it is used 5 days before each dose of specific vaccine antigen. The results showed survival rates of up to 50% with less severe hepatic lesions and high levels of IgG2a or IFNγ in immunized mice, using the ADAD system, compared to survival rates of 13% with no hepatic lesion reduction and high levels of IgG1 and IL-4 in those mice immunized with the simplified mode (ADADs).     

Mass Spectrometry-Based Metabolite Profiling in the Mouse Liver following Exposure to Ultraviolet B Radiation

Although many studies have been performed on the effects of ultraviolet (UV) radiation on the skin, only a limited number of reports have investigated these effects on non-skin tissue. This study aimed to describe the metabolite changes in the liver of hairless mice following chronic exposure to UVB radiation. We did not observe significant macroscopic changes or alterations in hepatic cholesterol and triglyceride levels in the liver of UVB-irradiated mice, compared with those for normal mice. In this study, we detected hepatic metabolite changes by UVB exposure and identified several amino acids, fatty acids, nucleosides, carbohydrates, phospholipids, lysophospholipids, and taurine-conjugated cholic acids as candidate biomarkers in response to UVB radiation in the mouse liver by using various mass spectrometry (MS)-based metabolite profiling including ultra-performance liquid chromatography-quadrupole time-of-flight (TOF)-MS, gas chromatography-TOF-MS and nanomate LTQ-MS. Glutamine exhibited the most dramatic change with a 5-fold increase in quantity. The results from altering several types of metabolites suggest that chronic UVB irradiation may impact significantly on major hepatic metabolism processes, despite the fact that the liver is not directly exposed to UVB radiation. MS-based metabolomic approach for determining regulatory hepatic metabolites following UV irradiation will provide a better understanding of the relationship between internal organs and UV light.