Role of Vital Trace Elements in Nanocurcumin-Centered Formulation: A Novel Approach to Resuscitate the Immune System.

The present paper described the immunomodulatory potential of novel nanocurcumin-based formulation enriched with trace elements and vitamins on cyclophosphamide-induced immunosuppression in rat model. Major immune-related assays were monitored such as hemagglutination assay, delayed-type hypersensitivity (DTH) reaction, cellular immune response, IgG, IgE, IgM, cerebrospinal fluid biomarkers, hematological study, antioxidant profile, and lipid biomarkers. Chemical characterization of novel formulation showed retention time (R t ) 18.98 of curcumin, while LC-MS data revealed the presence of the curcumin mass at m/z 369.01 [M + H]+ (calculated for C21H21O6+, 369.13). This novel formulation exhibited significantly (p ≤ 0.001) increased primary and secondary antibody titer by 72.41% and 33.25%, respectively, while DTH response being improved by 87.50% (p ≤ 0.01). However, CD4+, CD8+, and CD28+ counts were significantly (p ≤ 0.05) increased by 76.46%, 68.21%, and 19.29%, respectively, while the concentrations of IgE, IgM, and IgG were significantly (p ≤ 0.05) increased by 40%, 28.43%, and 38.75%, respectively. CSF biomarkers analysis showed a decreased level of corticosterone, dopamine, serotonin, and tau protein by 29.38%, 51.73%, 29.93%, and 4.87%, respectively. Antioxidant enzymes such as CAT, GPx, and SOD were increased by 43.74%, 49.00%, and 40.84%, respectively, and non-enzymatic component, GSH, was increased by 55.52%. Similarly, free radical LPO was significantly (p ≤ 0.05) decreased by 40.37%, and acute inflammatory marker, MPO concentration, was reduced by 31.14%, compared with the disease control group. In addition, supportive hematology and lipid profile analysis showed promising results with improved overall animal profile. Thus, trace elements in novel formulation can be used in the various pharmacological activities and as dietary supplement due to its wide properties.

Evaluation of cysticercus-specific IgG (total and subclasses) and IgE antibody responses in cerebrospinal fluid samples from patients with neurocysticercosis showing intrathecal production of specific IgG antibodies / Avaliação das respostas de anticorpos anti-cisticercos IgG (total e subclasses) e IgE em amostras de líquido cefalorraquidiano de pacientes com neurocisticercose apresentando produção intratecal de anticorpos específicos IgG

In the present study, an enzyme-linked immunosorbent assay (ELISA) standardized with vesicular fluid of Taenia solium cysticerci was used to screen for IgG (total and subclasses) and IgE antibodies in cerebrospinal fluid (CSF) samples from patients with neurocysticercosis showing intrathecal production of specific IgG antibodies and patients with other neurological disorders. The following results were obtained: IgG-ELISA: 100% sensitivity (median of the ELISA absorbances (MEA)=1.17) and 100% specificity; IgG1-ELISA: 72.7% sensitivity (MEA=0.49) and 100% specificity; IgG2-ELISA: 81.8% sensitivity (MEA=0.46) and 100% specificity; IgG3-ELISA: 63.6% sensitivity (MEA=0.12) and 100% specificity; IgG4-ELISA: 90.9% sensitivity (MEA=0.85) and 100% specificity; IgE-ELISA 93.8% sensitivity (MEA=0.60) and 100% specificity. There were no significant differences between the sensitivities and specificities in the detection of IgG-ELISA and IgE-ELISA, although in CSF samples from patients with neurocysticercosis the MEA of the IgG-ELISA was significantly higher than that of the IgE-ELISA. The sensitivity and MEA values of the IgG4-ELISA were higher than the corresponding values for the other IgG subclasses. Future studies should address the contribution of IgG4 and IgE antibodies to the physiopathology of neurocysticercosis.

No presente estudo, uma reação imunoenzimática (ELISA) padronizada com o fluido vesicular de cisticercos de Taenia solium foi utilizada para avaliar as respostas de anticorpos anti-cisticercos IgG (total e subclasses) e IgE em amostras de líquido cefalorraquidiano (LCR) de pacientes com neurocisticercose apresentando produção intratecal de anticorpos específicos IgG e pacientes com outras desordens neurológicas. Os seguintes resultados foram obtidos: ELISA-IgG: 100% de sensibilidade (mediana das absorbâncias das reações ELISA (MAE)=1,17) e especificidade 100%; ELISA-IgG1: sensibilidade 72,7% (MAE=0,49) e especificidade 100%; ELISA-IgG2: sensibilidade 81,8% (MAE=0,46) e especificidade 100%; ELISA-IgG3: sensibilidade 63,6% (MAE=0,12) e especificidade 100%; ELISA-IgG4: sensibilidade 90,9% (MAE=0,85) e especificidade 100%; ELISA-IgE: sensibilidade 93,8% (MAE=0,60) e especificidade 100%. Não foram encontradas diferenças significativas entre as sensibilidades e especificidades das reações ELISA-IgG e ELISA-IgE, embora a MAE da reação ELISA-IgG em amostras de LCR de pacientes com neurocisticercose tenha sido significativamente maior que a obtida com ELISA-IgE. Os valores de sensibilidade e MAE da reação ELISA-IgG4 foram maiores que os valores correspondentes para as outras subclasses da IgG. Estudos futuros deverão abordar a contribuição dos anticorpos IgG4 e IgE na fisiopatologia da neurocisticercose.

Evaluation of cysticercus-specific IgG (total and subclasses) and IgE antibody responses in cerebrospinal fluid samples from patients with neurocysticercosis showing intrathecal production of specific IgG antibodies.

In the present study, an enzyme-linked immunosorbent assay (ELISA) standardized with vesicular fluid of Taenia solium cysticerci was used to screen for IgG (total and subclasses) and IgE antibodies in cerebrospinal fluid (CSF) samples from patients with neurocysticercosis showing intrathecal production of specific IgG antibodies and patients with other neurological disorders. The following results were obtained: IgG-ELISA: 100% sensitivity (median of the ELISA absorbances (MEA)=1.17) and 100% specificity; IgG1-ELISA: 72.7% sensitivity (MEA=0.49) and 100% specificity; IgG2-ELISA: 81.8% sensitivity (MEA=0.46) and 100% specificity; IgG3-ELISA: 63.6% sensitivity (MEA=0.12) and 100% specificity; IgG4-ELISA: 90.9% sensitivity (MEA=0.85) and 100% specificity; IgE-ELISA 93.8% sensitivity (MEA=0.60) and 100% specificity. There were no significant differences between the sensitivities and specificities in the detection of IgG-ELISA and IgE-ELISA, although in CSF samples from patients with neurocysticercosis the MEA of the IgG-ELISA was significantly higher than that of the IgE-ELISA. The sensitivity and MEA values of the IgG4-ELISA were higher than the corresponding values for the other IgG subclasses. Future studies should address the contribution of IgG4 and IgE antibodies to the physiopathology of neurocysticercosis.

[Toxocara canis cerebral vasculitis revealed by iterative strokes]. / Vascularite cérébrale àToxocara canis révélée par des AVC itératifs.

INTRODUCTION: Cerebral vasculitis is a rare and severe condition, posing problems for diagnosis and treatment. Toxocara canis cerebral vasculitis is exceptionally rare, with only 4 cases having been reported. We report an additional case revealed by iterative strokes. OBSERVATION: A 49-years-old Laotian man presented with right ACA infarction associated with contrast enhancement of cerebrospinal fluid, and multiple segmental stenoses in small and medium caliber encephalic arteries, in a context of hypereosinophilia and chronic headaches. Laboratory tests showed lymphocytic meningitis and T. canis antibody IgE in the blood and CSF. The diagnosis of T. canis cerebral vasculitis was retained. During follow-up, the patient presented again with left pontine hemorrhagic stroke. Conventional cerebral angiography confirmed progression of vasculitis despite treatment. CONCLUSION: This case-report illustrates the diagnostic and therapeutic difficulties associated with vasculitis.

Atopic myelitis in a European woman residing in Japan.

Nearly 100 cases of atopic myelitis have been reported in Japan. However, it has only been described in two non-Japanese patients, both from Western Europe. We report a European individual who developed cervical myelitis while resident in Japan. This showed a partial response to corticosteroids. There was no clinical or radiological dissemination for over 5 years, at which time she had a brainstem relapse caused by a new lesion in the medulla oblongata. The patient had high serum total IgE with evidence of allergy to several antigens, including house dust mite and soya. It is possible that the incidence of atopic myelitis may be underestimated where it is not standard practice to measure serum IgE levels in patients with myelopathy. Such cases will instead be subsumed into the diagnostic category of clinically isolated syndrome. However, it remains uncertain whether atopic myelitis is a distinct disease or falls within the spectrum of demyelinating diseases. Further studies are required to fully elucidate the relationship between atopy and the incidence and severity of CNS inflammatory disorders.

[Peculiarities of meningoencephalitis caused by Angiostrongylus cantonensis in America]. / Peculiaridades de la meningoencefalitis por Angiostrongylus cantonensis en América.

INTRODUCTION: 25 years ago was first reported in Cuba and in the western hemisphere an emergent disease: eosinophilic meningoencephalitis due to Angiostrongylus cantonensis larvae. AIM: To collect in a summary form the accumulated experience and the findings of the study of this parasitosis during the period in the Western hemisphere. DEVELOPMENT AND CONCLUSIONS: There have been collected the first evidences, the parasitological and malacological findings, the experimental and molecular studies on immunology and neuroimmunology, the clinic-pathological findings in children and adults with the particularities of this diseases in our environment with special emphasis in the never-before scientific findings reported. It has been documented the testimony, the main findings among the malacological studies, the role of the immunoglobulin E and the mechanism involved in the central nervous system, the intrathecal synthesis patterns of immunoglobulins and the clinical elements in children and adults.

Neurological manifestation of tick-borne encephalitis in North-Eastern Italy.

Tick-borne encephalitis (TBE) is an infectious zoonotic disease, moving from Central Europe to other countries and still rare in Italy. The disease, produced by the European subtype virus, typically takes a biphasic course with neurological disorders of different severity during its second phase. We report the first three TBE cases in Friuli Venezia Giulia (FVG), characterised by extremely variable clinical features. Knowledge of these different presentations will assist physicians in increasing their level of attention to TBE also in this region, where no cases of TBE had been reported in the past, despite the fact that it borders countries with high prevalence of the infection.

IgG1,IgG2 and IgE intrathecal synthesis in Angiostrongylus cantonensis meningoencephalitis.

INTRODUCTION: Angiostrongylus cantonensis meningoencephalitis is an emergent zoonotic disease in the Caribbean basin, characterized by the presence of eosinophils and third stage larva of the helmint. OBJECTIVE: To analyze the IgG subclasses and IgE intrathecal synthesis patterns obtained by reibergrams in pediatric patients suffering from eosinophilic meningoencephalitis due to A. cantonensis. PATIENTS AND METHODS: 20 pediatric patients with the disease were studied. During the first diagnostic lumbar puncture an eosinophilic pleocytosis was found. Simultaneously a serum sample was taken. Eight days later, a second lumbar and venous puncture was performed. IgA, IgM, IgG, albumin in serum and cerebrospinal fluid samples were quantified by immunodiffusion in addition to a differential cell count in cerebrospinal fluid. IgG subclasses were quantified in 10 patients by immunodiffusion and IgE in four patients by nephelometry. RESULTS: During the first diagnostic lumbar puncture, all the cases had a blood-cerebrospinal fluid barrier dysfunction with absence of immunoglobulins intrathecal synthesis, a mean of 450 cells/mul and an average of 48% of eosinophils. In the second lumbar puncture 40% of the patients had a dysfunction of the blood-cerebrospinal fluid barrier and an intrathecal synthesis pattern of IgA+IgM+IgG in 50% of the patients. Eight patients had an intrathecal IgA+IgG class response. The synthesis pattern of IgG subclasses was IgG1+IgG2 in six patients, IgG1+IgG2+IgG3 in one patient, IgG1+IgG2+IgG4 in one more patient. Two patients from the second lumbar puncture remained without intrathecal synthesis. IgE intrathecal synthesis was observed in the four analyzed patients in the first diagnostic lumbar puncture. CONCLUSIONS: The IgG1+IgG2 and IgE intrathecal synthesis pattern demonstrated the complexity of the antigenic mosaic of the helmint and it can contribute to diagnosis of eosinophilic meningoencephalitis due to A. cantonensis.

Myelitis with atopic diathesis: a nationwide survey of 79 cases in Japan.

We recently reported the occurrence of myelitis in patients with atopic disorders and its pathology to be eosinophilic inflammation. Because similar cases have been reported, we conducted a nationwide epidemiological survey (NES) of myelitis with atopy in Japan. We compared the clinicolaboratory features of the 30 NES cases with the 49 cases at Kyushu University Hospital (KU). Although the NES cases were distributed throughout Japan, the NES and KU cases shared common characteristics. We therefore combined all of the cases identified. The average onset age was 35.8+/-13.4 years, and the male/female ratio was 1:0.65. The onset mode was subacute/chronic in half the patients, and stepwise progression or symptom fluctuation was frequent (69.6%). The most common lesion site was determined clinically and by MRI to be the cervical cord, and paresthesia and/or dysesthesia were the most common symptoms initially (74.7%) and throughout the entire course (83.5%). Cerebrospinal fluid (CSF) abnormalities were infrequent and mild. These findings suggest that myelitis associated with atopy has mild but prolonged symptoms and occurs throughout Japan.

Enzyme linked immunosorbent assay (ELISA) for the detection of IgG, IgM, IgE and IgA against Cysticercus cellulosae in cerebrospinal fluid of patients with neurocysticercosis.

The objective of this study was to analyze different immunoglobulins classes (IgG, IgM, IgE and IgA) against Cysticercus cellulosae in the cerebrospinal fluid (CSF), through enzyme linked immunosorbent assay (ELISA), correlating them to clinical and tomographic profiles in patients with neurocysticercosis (NCC). Eighty-five specimens of CSF were obtained from 43 cases with NCC (26 with the active form and 17 with the inactive form) and from 42 patients with other neurological diseases. The inactive form of NCC presented a profile in CSF similar to the group without NCC. The active form of NCC presented elevation of specific immunoglobulins (IgG, IgM, IgE, and IgA) in decreasing order, with the highest values being detected among the cases with intraventricular cysts, or with inflammation signs in CSF or in those with multiple clinical manifestations. The highest sensitivity and specificity were obtained with ELISA-IgG (88.5% and 93.2%, respectively). This study confirmed the importance of ELISA in the immunologic diagnosis of NCC.

Immunoglobulin isotypes reveal a predominant role of type 1 immunity in multiple sclerosis.

IgG, its subclasses and IgE concentrations were measured in cerebrospinal fluid (CSF) and serum of multiple sclerosis (MS) patients and matched controls as surrogate markers for type 1 and type 2 immunity. IgE indices were significantly reduced in MS patients compared to controls. In contrast, IgG1 was elevated in CSF of MS patients and elevated indices indicated intrathecal synthesis. Because isotype switching to IgE and IgG4 is driven by type 2 immunity and occurrence of IgG1 has previously been found in type 1 immunity-dominated diseases, the results underscore a role of type 1 immunity in MS.

Total IgE detection in paired cerebrospinal fluid and serum samples from patients with neurocysticercosis.

Neurocysticercosis (NC), the presence of Taenia solium metacestodes in tissues, is the most frequent and severe parasitic infection of the central nervous system. We investigated the presence of total IgE by an automated chemiluminescence assay in 53 paired cerebrospinal fluid (CSF) and serum samples from patients with NC (P) and in 40 CSF samples from individuals with other neurological disorders as the control group (C). Total IgE concentration ranged from 1.2 to 6.6 IU/ml (mean = 1.4 IU/ml, standard deviation-sd = 1.1 IU/ml) in 28.3% of CSF samples from the P group, a value significantly higher than for the C group ( pound1.0 IU/ml). The serum samples from the P group showed concentrations ranging from 1. 0 to 2330.0 IU/ml (mean = 224.1 IU/ml, sd = 452.1 IU/ml), which were higher than the normal value cited by the manufacturer (<100.0 IU/ml) in 32.1% of the samples. A significant difference was observed in CSF samples from the P and C groups (p = 0.005) and in serum samples from the P group compared to the normal value (p = 0. 005), with sera showing more frequent abnormal results.

Total IgE detection in paired cerebrospinal fluid and serum samples from patients with neurocysticercosis

Neurocysticercosis (NC), the presence of Taenia solium metacestodes in tissues, is the most frequent and severe parasitic infection of the central nervous system. We investigated the presence of total IgE by an automated chemiluminescence assay in 53 paired cerebrospinal fluid (CSF) and serum samples from patients with NC (P) and in 40 CSF samples from individuals with other neurological disorders as the control group (C). Total IgE concentration ranged from 1.2 to 6.6 IU/ml (mean = 1.4 IU/ml, standard deviation-sd = 1.1 IU/ml) in 28.3 per cent of CSF samples from the P group, a value significantly higher than for the C group (< or = 1.0 IU/ml). The serum samples from the P group showed concentrations ranging from 1.0 to 2330.0 IU/ml (mean = 224.1 IU/ml, sd = 452.1 IU/ml), which were higher than the normal value cited by the manufacturer (<100.0 IU/ml) in 32.1 per cent of the samples. A significant difference was observed in CSF samples from the P and C groups (p = 0.005) and in serum samples from the P group compared to the normal value (p = 0.005), with sera showing more frequent abnormal results.

Human neurocysticercosis. IgE in cerebrospinal fluid.

The detection of IgE is technically difficult because of its reduced concentrations in serum, and even lower concentrations in cerebrospinal fluid (CSF). In the present investigation we studied 86 CSF samples using an immunoenzymatic method with an anti-IgE-alkaline phosphatase conjugate and a fluorigenic substrate. The samples were from three groups: A) 29 patients with neurocysticercosis (NC), B) 36 patients with different neurologic disorders (neurosyphilis, neurotuberculosis, meningitis, tumors, hemorrhage) and C) 21 discharged individuals who had been hospitalized for bacterial meningitis. The results obtained were: A) 0.05 to 3.00 IU/ml (0.76 +/- 0.79), B) 0.00 to 1.50 IU/ml (0.23 +/- 0.34) and C) 0.05 to 1.25 IU/ml (0.34 +/- 0.34). The present results suggest that IgE appears to play a role in the pathogeny of NC and that efforts should be made to standardize a test for the detection of specific IgE antibodies.

Human neurocysticercosis: IgE in cerebrospinal fluid

The detection of IgE is technically difficult because of its reduced concentrations in serum, and even lower concentrations in cerebrospinal fluid (CSF). In the present investigation we studied 86 CSF samples using animmunoenzymatic method with an anti-IgE-alkaline phosphatase conjugate and a fluorigenic substrate. The samples were from three groups: A) 29 patients with neurocysticercosis (NC), B) 36 patients with different neurologic disorders (neurosyphilis, neurotuberculosis, meningitis, tumors, hemorrhage) and C) 21 discharged individuals who had been hospitalized for bacterial meningitis. The results obtained were: A) 0.05 to 3.00 IU/ml (0.76 + 0.79), B) 0.00 to 1.50 IU/ml (0.23 + 0.34) and C) 0.05 to 1.25 IU/ml (0.34 + 0.34). The present results suggest that IgE appears to play a role in the pathogeny of NC and that efforts should be made to standardize a test for the detection of specific IgE antibodies.

Cerebrospinal fluid interleukin-6 and IgE in bacterial and viral meningitis.

The aim of the present study was to assess the significance of IgE and interleukin-6 (IL-6) in paired CSF and serum of patients with viral and bacterial infections of the central nervous system. The results suggest that the detection of IL-6 and IgE in CSF is an useful marker for monitoring course and prognosis of these patients.

Immunoglobulin E and G4 antibodies in cysticercosis.

The importance of immunoglobulin G (IgG) subclass responses in different infections has been elucidated for a number of organisms, but few parasitic organisms have been examined in this regard. In the current study, quantitative radioimmunoassays were used to examine the IgE and IgG4 subclass responses to larval Taenia solium. Patients were divided into clinically infected (CI) and probably uninfected (PU) groups. Unexposed normal subjects were used as controls. The CI group had elevated geometric mean levels of total IgE in serum (28.6 IU/ml) and specific IgG4 antibodies (438.8 arbitrary units [AU]/ml) compared with controls (8.3 IU/ml and 50.1 AU/ml, respectively). The CI group also had significantly elevated levels in cerebrospinal fluid of total IgG4 (18.6 micrograms/ml) and specific IgG4 antibodies (86.0 AU/ml) compared with the PU group (2.5 micrograms/ml and 1.6 AU/ml, respectively). There was no specific IgE antibody response detected in either the CI or PU patient group. The marked IgG4 response of CI patients to T. solium merits further investigation.

Total and specific IgE in serum and cerebrospinal fluid of rats and guinea pigs infected with Angiostrongylus cantonensis.

The total and specific IgE response to Angiostrongylus cantonensis infection was evaluated according to host permissiveness. Total IgE levels measured by a double antibody radioimmunoassay (RIA) increased slowly in the permissive host (the rat), reaching a maximum between 4 and 8 weeks after infection. This maximum was earlier but significantly lower in the non-permissive host (the guinea pig). IgE antibodies specific for adult worms or L1 or L3 larvae of A. cantonensis were measured by a radioallergosorbent test (RAST). In the case of adult worms and L1 antigens, specific IgE antibody levels showed large variations in relation to the duration of infection in rats. In contrast to total IgE levels, the specific IgE response to L3 larvae was lower in rats than in guinea pigs in both the serum and cerebrospinal fluid (CSF). These results suggest variations in the total vs specific IgE response according to host permissiveness or non-permissiveness to A. cantonensis infection. These results are discussed in the context of the possible participation of IgE antibodies in immune defence.