Safety of Intravenous Thrombolysis for Acute Ischemic Stroke in Patients Taking Warfarin with Subtherapeutic INR.

INTRODUCTION: Current guidelines allow the administration of intravenous recombinant tissue plasminogen activator (IV r-tPA) to warfarin-treated patients with acute ischemic stroke (AIS) who have an international normalized ratio (INR) of ≤1.7. However, concerns remain about the safety of using IV r-tPA in this situation due to a conceivable risk of symptomatic intracranial hemorrhage (sICH), lack of dedicated randomized controlled trials and the conflicts in the available data. We aimed to determine the risk of sICH in warfarin-treated patients with subtherapeutic INR who received IV r-tPA for AIS in our large volume comprehensive center. METHODS: Patients who had received IV r-tPA for AIS in a 9.6-year period were retrospectively investigated (n = 834). Patients taking warfarin prior to presentation were identified (n = 55). One patient was excluded due to elevated INR beyond the acceptable range for IV r-tPA treatment. Because of the significant difference in the sample size (54 vs 779), warfarin group was matched with 54 non-warfarin patients adjusted for independent risk factors for sICH (age, admission NIHSS, history of diabetes). Good outcome was defined as mRS of 0-2 on discharge and sICH was defined as an ICH causing increase in NIHSS ≥4 or death. Warfarin-treated group was further dichotomized based on INR (1-1.3 vs 1.3-1.7) and safety and outcome measures were compared between resultant groups. RESULTS: No significant difference was found between warfarin-treated and the non-warfarin groups in terms of chance of good outcome on discharge (27.8% in warfarin group vs 26.4% in non-warfarin group; p-value >0.05), or the rate of occurrence of sICH (3.7% in warfarin group vs 11.1% in non-warfarin group; p-value >0.05). Furthermore, rate of sICH (5.1% in patients with INR <1.3 versus 0.0% in patients with INR 1.3-1.7; p-value >0.05) or chance of good outcome on discharge (28.2% of patients with INR <1.3 versus 26.7% in patients with INR 1.3-1.7; p-value >0.05) were not found to be different after the warfarin-treated group was dichotomized. CONCLUSION: Administration of IV r-tPA for AIS in warfarin-treated patients with subtherapeutic INR <1.7 does not increase the risk of sICH.

In vitro and in vivo activity of cinnamaldehyde against Eimeria kofoidi in chukar partridge (Alectoris chukar).

One hundred and twenty one-day-old chukar partridges were randomly divided into eight groups which received diets with different supplementations. There were four unchallenged groups. One group received salinomycin (50 ppm), two groups received cinnamaldehyde (CINN) (100 and 200 mg/kg of diet), and another one received only the basal diet from the 1st to the 31st day. There were also four corresponding groups orally challenged by 3 × 105Eimeria kofoidi sporulated oocysts at the 21st day. Three samplings were done at the 24th, 26th, and 31st days of rearing for pathological and biochemical assessments. Fecal samples were daily taken to check the pattern of oocyst shedding from the 26th to 31st day. The body weight of birds was measured at 21st and 31st days. Along with the in vivo experiment, an in vitro sporulation inhibition test was carried out. The in vitro results showed that CINN decreased sporulation rate at 1 and 0.5 mg/ml. In vivo, it was found that CINN did not prevent the oocyst shedding. Furthermore, the histopathological findings revealed that CINN and salinomycin had no effect on infection establishment. However, our findings showed that CINN (200 mg/kg of diet) could enhance the body weight and improve antioxidant status. Although our results did not support the in vivo anticoccidial activity of CINN, it had a promising potential to improve antioxidant status and body weight in the chukar partridge.

GD2-targeted immunotherapy and potential value of circulating microRNAs in neuroblastoma.

Neuroblastoma (NB) with various clinical presentation is a known childhood malignancy. Despite significant progress in treatment of NB afflicted patients, high risk disease is usually associated with poor outcome, resulting in long-term survival of less that 50%. Known as a disease most commonly originated form the nerve roots, the variants involved in NB imitation and progression remain to be elucidated. The outcome of low to intermediate risk disease is favorable whereas the high risk NB disease with dismal prognosis, positing the necessity of novel approaches for early detection and prognostication of advanced disease. Tailored immunotherapy approaches have shown significant improvement in high-risk NB patients. It has found a link between Gangliosides and progression of NB. The vast majority of neuroblastoma tumors express elevated levels of GD2, opening new insight into using anti-GD2 drugs as potential treatments for NBs. Implication of anti-GD2 monoclonal antibodies for treatment of high risk NBs triggers further investigation to unearth novel biomarkers as prognostic and response biomarker to guide additional multimodal tailored treatment approaches. A growing body of evidence supports the usefulness of miRNAs to evaluate high risk NBs response to anti-GD2 drugs and further prevent drug-related toxicities in refractory or recurrent NBs. miRNAs and circulating proteins in body fluids (plasma and serum) present as potential biomarkers in early detection of NBs. Here, we summarize various biomarkers involved in diagnosis, prognosis and response to treatment in patients with NB. We further attempted to overview prognostic biomarkers in response to treatment with anti-GD2 drugs.

Curcumin: A promising treatment for Cryptosporidium parvum infection in immunosuppressed BALB/c mice.

Members of the genus Cryptosporidium are frequent protozoan pathogens in humans and a wide range of animals. There is no consistently effective treatment against cryptosporidiosis, especially in immunodeficient patients. The present study was carried out to study the therapeutic effects of curcumin against cryptosporidiosis in immunosuppressed BALB/c mice. Mice were divided into five groups and immunosuppressed by dexamethasone. Three groups were inoculated with C. parvum oocysts, administered with curcumin, paromomycin, and without treatment. The reminders were regarded as controls. The oocysts in the fecal smear were counted daily. At days 0, 3, 7, and 11 post-treatment, the mice were sacrificed, and the efficacy of drugs was evaluated by comparing the histopathological alterations in jejunum and ileum, measuring the total antioxidant capacity, and malondialdehyde in the affected tissues. The infection was completely eliminated in the curcumin-treated group, and oocyst shedding stopped with no recurrence after drug withdrawal. On the contrary, paromomycin was unable to eliminate C. parvum infection completely, and oocyst shedding continued even 10 days after the drug withdrawal. Based on these findings, curcumin can be a trustworthy compound for the elimination of infection in immunosuppressed hosts. Further evaluation to find its accurate mechanism of action should be considered.

Anticoccidial effects of Artemisia annua ethanolic extract: prevention, simultaneous challenge-medication, and treatment.

The effect of Artemisia annua ethanolic extract (AE) as a potential source of herbal anticoccidial activity was investigated on experimental coccidiosis in chicken. One hundred ninety-two one-day-old chicks were divided in to 8 groups (n = 24) including AE prevention group, AE-treated group, simultaneously challenged AE-medicated group, challenged-untreated group (positive control), unchallenged-untreated group (negative control), salinomycine prevention group, salinomycine-treated group, and simultaneously challenged salinomycine-medicated group, in a completely randomized design. Oral challenge carried out by a suspension containing a mixture of 200,000 oocysts Eimeria acervulina, 30,000 oocysts Eimeria necatrix, and 20,000 oocysts Eimeria tenella on day 21 of age. Weight gain in AE prevention group significantly increased compared to positive control group (p < 0.05). Unlike salinomycine prevention group, the food conversion ratio (FCR) of AE prevention group was not significantly higher than negative control. Oocyst per gram (OPG) in simultaneously challenged AE-medicated group had no significant difference, while for 38% of the days, in simultaneously challenged salinomycine-medicated group significantly decreased (p < 0.05). The food intake of AE-treated group had no significant difference with salinomycine-treated group (p > 0.05). In half of the days of OPGs sampling, AE-treated group was reduced significantly compared to positive control group (p < 0.05). Collectively, the in vivo study of anticoccidial effects of AE in the prevention section was more effective than the treatment section, while the treatment section was more effective than the simultaneous section. We concluded that AE has a potential value to use as an herbal medicine for preventive measure in chicken coccidiosis.

Dynamic Patterns of Systemic Innate Immunity and Inflammatory Associated Factors in Experimental Caprine Coccidiosis.

The present study was designed to assess the dynamic patterns of pro-inflammatory cytokines, including IFN-γ, TNF-α, IL-4, IL-6, acute phase protein (α1-acid-glycoprotein, AGP), and an inflammation associated factor (adenosine deaminase; ADA) following experimental caprine coccidiosis. Ten kids aging from 2 to 4 months were infected orally with 5×104 sporulated oocysts and 10 animals served as controls. Blood samples were collected in both groups before infection and at days 3, 7, 14, 21, 28, and 35 post-infection (PI), and the levels of above-mentioned factors were measured. IFN-γ, TNF-α, IL-4, IL-6, AGP, and ADA activities were significantly higher in infected animals from day 7 PI (P<0.05). In conclusion, the circulatory levels of most systemic inflammatory markers, including pro-inflammatory cytokines (IFN-γ, TNF-α, IL-4, IL-6), AGP, and ADA increased significantly starting from day 3 to day 7 PI in caprine coccidiosis.

γ-Glutamyl transferase 7 is a novel regulator of glioblastoma growth.

BACKGROUND: Glioblastoma (GBM) is the most malignant primary brain tumor in adults, with a median survival time of one and a half years. Traditional treatments, including radiation, chemotherapy, and surgery, are not curative, making it imperative to find more effective treatments for this lethal disease. γ-Glutamyl transferase (GGT) is a family of enzymes that was shown to control crucial redox-sensitive functions and to regulate the balance between proliferation and apoptosis. GGT7 is a novel GGT family member that is highly expressed in brain and was previously shown to have decreased expression in gliomas. Since other members of the GGT family were found to be altered in a variety of cancers, we hypothesized that GGT7 could regulate GBM growth and formation. METHODS: To determine if GGT7 is involved in GBM tumorigenesis, we modulated GGT7 expression in two GBM cell lines (U87-MG and U138) and monitored changes in tumorigenicity in vitro and in vivo. RESULTS: We demonstrated for the first time that GBM patients with low GGT7 expression had a worse prognosis and that 87% (7/8) of primary GBM tissue samples showed a 2-fold decrease in GGT7 expression compared to normal brain samples. Exogenous expression of GGT7 resulted in a 2- to 3-fold reduction in proliferation and anchorage-independent growth under minimal growth conditions (1% serum). Decreasing GGT7 expression using either short interfering RNA or short hairpin RNA consistently increased proliferation 1.5- to 2-fold. In addition, intracranial injections of U87-MG cells with reduced GGT7 expression increased tumor growth in mice approximately 2-fold, and decreased mouse survival. To elucidate the mechanism by which GGT7 regulates GBM growth, we analyzed reactive oxygen species (ROS) levels in GBM cells with modulated GGT7 expression. We found that enhanced GGT7 expression reduced ROS levels by 11-33%. CONCLUSION: Our study demonstrates that GGT7 is a novel player in GBM growth and that GGT7 can play a critical role in tumorigenesis by regulating anti-oxidative damage. Loss of GGT7 may increase the cellular ROS levels, inducing GBM occurrence and growth. Our findings suggest that GGT7 can be a promising biomarker and a potential therapeutic target for GBM.

Glioblastoma antigen discovery--foundations for immunotherapy.

Prognosis for patients with glioblastoma (GBM), the most common high-grade primary central nervous system (CNS) tumor, remains discouraging despite multiple discoveries and clinical advances. Immunotherapy has emerged as a promising approach to GBM therapy as the idea the human CNS is immunoprivileged is being challenged. Early clinical studies of vaccine-based approaches have been encouraging, but further investigation is required before these therapies become clinically meaningful. A key challenge in immunotherapy involves identification of target antigens that are specific and sensitive for GBM. Here we discuss tumor-associated antigens that have been targeted for GBM therapy, strategies for discovery of novel antigens, and the theory of epitope spreading as it applies to GBM immunotherapy.

The field efficacy of Lepidium latifolium and Zataria multiflora methanolic extracts against Varroa destructor.

Varroa destructor is the most serious pest of honeybee (Apis mellifera), causing high economic losses in the beekeeping industry worldwide. The intensive utilization of many chemical substances against the mites resulted in resistance development. One of the applicable and alternative treatments being used for their control is plant-derived products (PDSS). The aim of this study was to evaluate the acaricidal activity of Lepidium latifolium and Zataria multiflora leaf extracts on V. destructor in field conditions. Four different concentrations (100, 200, 400, and 500 ppm) of the methanolic extracts were sprayed to treat each colony. The efficacy and side effects on adult bees were compared to Apistan chemical strips (ACSS). The acaricidal activity was the highest (100%) for L. latifolium extract at 500 ppm after 12 days and 86.26% for Z. multiflora. The infestation rate was decreased to 0.0% with L. latifolium and to 13.74% with Z. multiflora. The highest reduction was observed with L. latifolium followed by Z. multiflora extract at 500 ppm concentration. Both of the extracts showed negligible effect on bees, and it can be concluded that these PDSS as biodegradable agents could be used for V. destructor control in honeybee colonies.

A study on the status of inflammatory systems in camels naturally infected with Toxoplasma gondii.

Toxoplasma gondii is a unique intracellular parasite with a worldwide distribution. This parasite infects a variety of cells in a wide range of animal species such as dromedary camels (Camelus dromedarius). In order to evaluate the pattern of possible changes in the blood level of some inflammatory mediators and antioxidant enzymes in camels infected with T. gondii, blood samples were taken from a total of 493 dromedary camels and serum concentrations of inflammatory mediators, acute phase proteins and antioxidant enzymes were measured. According to serological data, no seropositivity was found for anti-T. gondii IgM in serum samples; however, 49 camels (9.93 %) showed positive titrations for anti-Toxoplasma IgG. The analyses of data in seropositive animals showed significant increases (P < 0.05) in the serum level of IL-1ß and adenosine deaminase activity; however, IFN-γ and TNF-α demonstrated no significant changes in serum samples of the infected camels. In addition, while major acute phase proteins (haptoglobin (Hp) and serum amyloid A (SAA)) were markedly elevated in infected camels, the activity of antioxidant enzymes (SOD and GPX) was remarkably decreased in the blood samples of infected animals. Thus, during the chronic infection in camels, T. gondii can promote significant rises in concentrations of some cytokines (such as IL-1ß), acute phase proteins and adenosine deaminase.

Herbal-based compounds: A review on treatments of cryptosporidiosis.

Cryptosporidium, a monoxenous apicomplexan coccidia, is a prevalent diarrhetic and an opportunistic agent, mainly in immunocompromised individuals. As there are few chemotherapeutic compounds that have limited efficacy, we need to identify new compounds or specific parasite targets for designing more potent drugs to treat cryptosporidiosis. Herbal products with low toxicity, environmental compatibility, wide therapeutic potential, and abundant resources can be considered alternatives for treatment. The current review tried to summarize the studies on plants or herbal bioactive constituents with anti-cryptosporidial activities. Based on constituents, plants act via different mechanisms, and further investigations are needed to clarify the exact mechanisms by which they act on the developmental stages of the parasite or host-parasite relationships.

A review on acute phase response in parasitic blood diseases of ruminants.

Parasitic blood diseases (theileriosis, babesiosis, anaplasmosis, and trypanosomiasis) are common in regions where the distributions of the hosts, parasites, and vectors are convergent. They endanger animal production, and a few are also harmful to public health. The acute phase reaction (APR) is a complex, non-specific reaction that occurs in various events, including surgical trauma, infection, stress, inflammation, and neoplasia. To understand pathogenesis, we must study APR effects and acute phase proteins (APPs) alterations in naturally occurring and experimental infections. The elevation of haptoglobin (Hp), Serum amyloid A (SAA), and fibrinogen concentrations was markedly significant in bovine and ovine theileriosis. Hp, SAA, ceruloplasmin, and fibrinogen concentrations in anaplasmosis were dramatically elevated. A significant increase in SAA was observed in bovine babesiosis, while ovine babesiosis showed a significant rise in sialic acid levels. In cases of trypanosomiasis caused by T. vivax, there have been reports of elevated levels of Hp, complement C3, and antitrypsin. Improving our understanding of APR could result in more effective methods for diagnosis, treatment, control, and eradication of diseases. The article provides an overview of APPs alterations and other inflammation-related parameters (some cytokines, adenosine deaminase, and sialic acids) in parasitic blood diseases of ruminants.

Host oxidative stress in piroplasmosis: A review in domestic animals.

Piroplasmida is an order of economically important blood parasites, including Babesia, Theileria, and Cytauxzoon, transmitted to mammals by ticks. Oxidative stress is a state in which the balance between oxidants and antioxidants is disturbed so that antioxidants cannot compensate for the harmful effects of oxidants. Due to the high concentration of oxygen and hemoglobin in red blood cells (RBCs), these are among the first cells exposed to oxidative damage. When RBCs are exposed to oxidative stress, their hemoglobin is oxidized, and lipid peroxidation leads to membrane instability, deformation, hemolysis, and anemia. Oxidative stress has a fundamental role in the pathogenesis of these parasites. In the present review article, we collected studies on the oxidative stress caused by Piroplasmida in domestic animals. What is obtained from the total review of studies conducted on piroplasmosis revealed that in these infections, the host faces oxidative stress, and the resultant oxidative injury plays a fundamental role in their pathogenicity. Further studies are needed to be carried out on the more precise role of oxidative stress, the use of more sensitive diagnostic biomarkers, and the possible therapeutic role of antioxidant agents in piroplasmosis.

Molecular characterization and phylogenetic analysis of Linguatula serrata isolated from camels, sheep and goats in Iran.

Linguatula serrata is an important zoonotic parasite with worldwide distribution. The objective of the present study was to investigate the molecular characterization and phylogenetic analysis of nymphal stage of L. serrata from camels, goats and sheep in Iran. The mesenteric lymph nodes were collected from various ruminants including goats, sheep and camels at Isfahan and Shiraz slaughterhouses and the nymphs were identified using morphological characteristics. After DNA extraction, the 18 S rRNA and Cox1 genes were amplified by polymerase chain reaction. The sequencing of the genes was conducted using specific primers and a capillary DNA analyzer. The comparison of amplified sequences with existing data confirmed the presence of L. serrata with 99.6-100% nucleotide sequence similarity. Based on 18 S rRNA and Cox1 sequences, two isolates collected from sheep revealed 100% and 99.9% sequence identity, respectively. Also, three isolates from camel had 99.64-100% and 99.7-100% homology. Two isolates from sheep had 100% identity in their 18SrRNA gene and were categorized together, but showed 99.9% similarity in the Cox1 gene, not clustering together. Phylogenetic analysis of the Cox1 gene classified nearly all the isolates into L. arctica clade. It can be concluded that 18 S rRNA and Cox1 genes sequencing can be a proper method for the analysis of phylogenetic relationships of L. serrata among different hosts in different parts of Iran, possibly helpful for infection control and prevention.

Basilar artery recanalization by proximal balloon occlusion and aspiration in a single vessel vertebrobasilar system: A case report.

The authors present a case of a patient with a hypoplastic right vertebral artery (VA) ending in the posterior inferior cerebellar artery who sustained an acute onset basilar artery occlusion. A balloon-guided catheter was used to proximally occlude the dominant left VA, and aspiration was applied until reversal of flow was achieved in the basilar artery. Thus, basilar artery reperfusion was achieved without the need for stent-retrieval thrombectomy. We believe this represents the first described case of successful thrombectomy in the vertebrobasilar system using only proximal artery occlusion and aspiration. This novel technique may decrease the time to recanalization and improve outcomes for patients with acute basilar artery occlusion in the setting of a hypoplastic contralateral VA.

Rescue Intracranial Balloon Angioplasty with or without Stent Placement in Acute Strokes with Intracranial Atherosclerotic Disease.

BACKGROUND: Optimal management of acute ischemic stroke (AIS) secondary to intracranial atherosclerotic disease (ICAD) refractory to conventional mechanical thrombectomy remains unclear. We aimed to investigate the clinical outcome of patients undergoing rescue intracranial balloon angioplasty with or without stent placement in the setting of AIS in our institution. METHODS: This is a retrospective single-arm observational study to evaluate the efficacy and safety of rescue balloon angioplasty with or without stent placement in emergent large vessel occlusion (EVLO) strokes with underlying ICAD. We included all patients undergoing such rescue intervention within 24 hours of AIS presentation with EVLO between 2017 and 2021. We further evaluated stent or vessel reocclusion. RESULTS: Of 20 patients undergoing rescue intervention, 3 cases achieved adequate recanalization of artery using balloon angioplasty alone. Seventeen patients required stent placement. Fourteen (70%) procedures resulted in National Institutes of Health Stroke Scale improvement in postprocedure and upon discharge. Among 6 (30%) procedures with worsening neurological measures, 3 had reoccluded stent 24-48 hours after procedure, 2 had symptomatic hemorrhagic conversion, and 1 had perforator occlusion. Nine patients (45%) had favorable functional outcome (modified Rankin Scale ≤2) at discharge, unchanged or improved at 3-month follow-up. The median modified Rankin Scale score was 4 (Interquartile range: 1.75-4) at discharge, improving to 3 (Interquartile range: 0-4) at 3-month follow-up. Two patients (10%) died during hospital stay. CONCLUSIONS: Rescue angioplasty with or without stenting can lead to significant clinical improvement in patients with ICAD presenting with ELVO and refractory to thrombectomy; however, this procedure is associated with a high rate of morbidity in acute setting.

In Vitro and In Vivo Anti-Toxoplasma Activities of Dracocephalum kotschyi Extract in Experimental Models of Acute Toxoplasmosis.

BACKGROUND: The problem of resistance to antiparasitic drugs, associated with their side effects, suggest exploring other alternatives, including medicinal plants. Dracocephalum kotschyi (D. kotschyi), for example, from Lamiaceae family, is a plant widely used in Iran and in many countries, and to which interesting pharmacological properties have been attributed. This study aimed to investigate in vitro and in vivo anti-Toxoplasma activities of D. kotschyi extract in experimental models of acute toxoplasmosis. METHODS: Anti-Toxoplasma activity of the extracts in vitro was performed on Vero Cell, using the MTT test. Vero cell were infected with (3 × 105 tachyzoites/well) following treatment with Dichloromethane (F1), dichloromethane: methanol (F2), methanol (F3), methanol: water (F4), and deionized water (F5) extracts of D. kotschyi, and pyrimethamine and sulfadiazine (positive control). MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) was used to measure cell viability. Effects of extracts on tachyzoites viability were evaluated by trypan blue exclusion method, followed by light microscopy. For in vivo test, 18 groups of 8-10-week-old Inbred Balb/c mice weighing 18-20 g, were intraperitoneally infected with 2 × 103 tachyzoites and then treated with sterile PBS (negative control), pyrimethamine (25 mg/kg) and sulfadiazine (500 mg/kg) as positive controls, and F1 to F5 extracts (at doses 50, 100 and 200 mg/kg). RESULTS: The 50% Inhibitory Concentration of F1 extract, F2 extract, Sulfadiazine (Positive control) and Pyrimethamine (Positive control) were 8.77 µg, 7.1 µg 391.18 µg, and 84.20 µg, respectively, while the selectivity indices were 15.667, 30.197, 1.552 and 4.064, respectively. In vivo anti-Toxoplasma activity test showed that Methanol: water (F-4) 50 extract was more active than the positive control. CONCLUSIONS: Indeed, the extract allowed a survival rate of 10% of the mice, compared to 0% for all the other groups. D. kotschyi has the potential to be valorized in the management of toxoplasmosis.

Targeting the CTLA-4/B7 axes in glioblastoma: preclinical evidence and clinical interventions.

INTRODUCTION: Glioblastoma Multiforme (GBM) is one of the fatal cancers of the Central Nervous System (CNS). A variety of reasons exist for why previous immunotherapy strategies, especially Immune Checkpoint Blockers (ICBs), did not work in treating GBM patients. The cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a key immune checkpoint receptor. Its overexpression in cancer and immune cells causes tumor cell progression. CTLA-4 suppresses anti-tumor responses inside the GBM tumor-immune microenvironment. AREAS COVERED: It has been attempted to explain the immunobiology of CTLA-4 as well as its interaction with different immune cells and cancer cells that lead to GBM progression. Additionally, CTLA-4 targeting studies have been reviewed and CTLA-4 combination therapy, as a promising therapeutic target and strategy for GBM immunotherapy, is recommended. EXPERT OPINION: CTLA-4 could be a possible supplement for future cancer immunotherapies of GBM. However, many challenges remain such as the high toxicity of CTLA-4 blockers, and the unresponsiveness of most patients to immunotherapy. For the future clinical success of CTLA-4 blocker therapy, combination approaches with other targeted treatments would be a potentially effective strategy. Going forward, predictive biomarkers can be used to reduce trial timelines and increase the chance of success.

Changing patterns of acute phase proteins and inflammatory mediators in experimental caprine coccidiosis.

This experiment was conducted to assess the changing patterns and relative values of acute phase proteins and inflammatory cytokines in experimental caprine coccidiosis. Eighteen newborn kids were allocated to 3 equal groups. Two groups, A and B, were inoculated with a single dose of 1×10(3) and1×10(5) sporulated oocysts of Eimeria arloingi, respectively. The third group, C, received distilled water as the control. Blood samples were collected from the jugular vein of each kid in both groups before inoculation and at days 7, 14, 21, 28, 35, and 42 post-inoculation (PI), and the levels of haptoglobin (Hp), serum amyloid A (SAA), TNF-α, and IFN-γ were measured. For histopathological examinations, 2 kids were selected from each group, euthanized, and necropsied on day 42 PI. Mean Hp concentrations in groups A and B (0.34 and 0.68 g/L) at day 7 PI were 3.2 and 6.3 times higher than the levels before inoculation. The mean SAA concentrations in groups A and B (25.6 and 83.5 µg/ml) at day 7 PI were 4.2 and 13.7 times higher than the levels before inoculation. The magnitude and duration of the Hp and SAA responses correlated well with the inoculation doses and the severity of the clinical signs and diarrhea in kids. These results were consistent with the histopathological features, which showed advanced widespread lesions in group B. In both groups, significant correlations were observed for TNF-α and IFN-γ with SAA and Hp, respectively. In conclusion, Hp and SAA can be useful non-specific diagnostic indicators in caprine coccidiosis.

In vitro and in vivo Anti-Toxoplasma activity of Dracocephalum kotschyi essential oil.

Toxoplasma gondii is a zoonotic parasite of worldwide importance, responsible for toxoplasmosis in homeotherms. Although treatment options are readily available, most drugs often cause serious side effects. Extracts of Dracocephalum kotschyi (D. kotschyi) have shown significant pharmacological activity against various parasites, viruses, and bacteria. In this study, we evaluated the anti-T. gondii activity in vitro and in vivo of D. kotschyi essential oil. The thiazolyl blue tetrazolium bromide (MTT) method was used to assess the anti-T. gondii activity and cytotoxicity of the essential oil. The presence of T. gondii was observed by Giemsa staining, and the viability was evaluated by the trypan blue staining method. Furthermore, the survival rate of acutely infected mice was evaluated by intraperitoneal injecting of the essential oil (50, 100, and 200 mg kg-1 day-1) for five days after infection with 2 × 104 tachyzoites. Essential oil, negative, and positive controls that showed the best toxoplasmacidal activity were assayed in triplicate at each concentration. The essential oil exhibited the highest anti-Toxoplasma activity with a half-maximal inhibitory concentration (IC50) of 9.94 ± 0.38 µg, with a selectivity index of 2.463. On Vero cells, the CC50 of the oil was 24.49 ± 0.96 µg and exhibited a significant anti-Toxoplasma activity. Moreover, the treatment by essential oil significantly increased the survival rate compared to untreated infected control. In conclusion, the essential oil might be a useful compound, and with more testing, it may be an excellent alternative to standard chemical drugs in the treatment of toxoplasmosis.