Cellular injury and neuroinflammation in children with chronic intractable epilepsy

<p>Abstract</p> <p>Objective</p> <p>To elucidate the presence and potential involvement of brain inflammation and cell death in neurological morbidity and intractable seizures in childhood epilepsy, we quantified cell death, astrocyte proliferation, microglial activation and cytokine release in brain tissue from patients who underwent epilepsy surgery.</p> <p>Methods</p> <p>Cortical tissue was collected from thirteen patients with intractable epilepsy due to focal cortical dysplasia (6), encephalomalacia (5), Rasmussen's encephalitis (1) or mesial temporal lobe epilepsy (1). Sections were processed for immunohistochemistry using markers for neuron, astrocyte, microglia or cellular injury. Cytokine assay was performed on frozen cortices. Controls were autopsy brains from eight patients without history of neurological diseases.</p> <p>Results</p> <p>Marked activation of microglia and astrocytes and diffuse cell death were observed in epileptogenic tissue. Numerous fibrillary astrocytes and their processes covered the entire cortex and converged on to blood vessels, neurons and microglia. An overwhelming number of neurons and astrocytes showed DNA fragmentation and its magnitude significantly correlated with seizure frequency. Majority of our patients with abundant cell death in the cortex have mental retardation. IL-1beta, IL-8, IL-12p70 and MIP-1beta were significantly increased in the epileptogenic cortex; IL-6 and MCP-1 were significantly higher in patients with family history of epilepsy.</p> <p>Conclusions</p> <p>Our results suggest that active neuroinflammation and marked cellular injury occur in pediatric epilepsy and may play a common pathogenic role or consequences in childhood epilepsy of diverse etiologies. Our findings support the concept that immunomodulation targeting activated microglia and astrocytes may be a novel therapeutic strategy to reduce neurological morbidity and prevent intractable epilepsy.</p

Bone mineral density and cytokine levels during interferon therapy in children with chronic hepatitis B: does interferon therapy prevent from osteoporosis?

BACKGROUND: Our aim was to determinate bone mineral density (BMD), levels of biochemical markers and cytokines in children with chronic hepatitis B treated with interferon (IFN)-alpha and to investigate effect of IFN-alpha therapy on these variables. To the best of our knowledge, this is first study carried out about BMD and cytokine levels in pediatric patients with chronic hepatitis B treated with IFN-alpha. METHODS: BMD, levels of parathyroid hormone (PTH), osteocalcin, C-terminal cross-linking telopeptide of type I collagen (CTX), calcium, alkaline phosphates (ALP), cytokines as TNF-alpha, interleukin (IL)-1(β), IL-2r, IL-6, and IL-8 were studied in 54 children with chronic hepatitis B (4–15 years old) treated with interferon alone (n = 19) or in combination with lamivudine (n = 35) for six months and as controls in 50 age-matched healthy children. RESULTS: There was no significant difference in respect to serum IL-1(β), TNF-α and osteocalcin levels while serum IL-2r (p = 0.002), IL-6 (p = 0.001), IL-8 (p = 0.013), PTH (p = 0.029), and CTX (p = 0.021) levels were higher in children with chronic hepatitis B than in healthy controls. BMD of femur neck (p = 0.012) and trochanter (p = 0.046) in patients were higher than in healthy controls. There was a statistically significant correlation between serum IL-1(β )and osteocalcin (r = -0.355, p < 0.01); between serum IL-8 and CTX levels (r = 0.372, p = 0.01), and ALP (r = 0.361, p = 0.01); between serum ALP and femur neck BMD (r = 0.303, p = 0.05), and trochanter BMD (r = 0.365, p = 0.01); between spine BMD and IL-2R (r = -0.330, p < 0.05). CONCLUSION: In conclusion, our study suggest that BMD of femur, serum IL-2r, IL-6, IL-8, PTH, and CTX levels were higher in children with chronic hepatitis B treated with IFN-alpha alone or combination with lamivudine than in healthy children. High femur BMD measurements found in patients may suggest that IFN-alpha therapy in children with chronic hepatitis B could contribute indirectly to prevent from hip osteoporosis. Additionally, further investigations on effects of IFN-alpha for bone structure in children should be performed in the future

Effect of dietary honey on intestinal microflora and toxicity of mycotoxins in mice

BACKGROUND: Bee honey is a functional food which has a unique composition, antimicrobial properties and bifidogenic effect. In order to assess whether honey can inhibit the toxic effect of mycotoxins, the present study was undertaken. METHODS: Production of biomass and toxins by Aspergillus parasiticus and Aspergillus ochraceus were followed in media without and with honey. Although aflatoxins and ochratoxin A. were administrated to male Swiss albino mice up to 1 μg and 10 ng/kg body weight/day respectively. The experimental animals were fed diets without our with 10% honey for two months. The changes in colonic probiotic bacteria, determintal colon enzyme glucuronidases, and genotoxicity were followed. RESULTS: Addition of 32% in its media increased the biomass of A parasiticus, while the biomass of A. ochraceus decreased and Ochratoxin A. was not produced. When the honey was added at the ratio of 32 and 48% in the medium. No relationship was found between mycelium weight and production of mycotoxins. Oral administration of aflatoxins (mixture of B(1), B(2), G(1) and G(2)) and Ochratoxin A. induced structural and numerical chromosomal aberrations in bone marrow and germ cells of male mice, whereas, honey treatment reduced the genotoxicity of mycotoxins. Also both toxins induced histopathological changes in liver and kidney. Feeding on diet supplemented with honey improved the histopathological changes in case of aflatoxin group, but not in the case of ochratoxin A. group (except of kidney in two cases). No significant differences were found in the activity of colon β-glucuronidase between group fed diet with or without honey. On the other hand, the colon bifido bacteria and lactobacilli counts were increased markedly in group receiving diet supplemented with honey. CONCLUSION: Substituting sugars with honey in processed food can inhibit the harmful and genotoxic effects of mycotoxins, and improve the gut microflora

The role of inflammation in epilepsy.

Epilepsy is the third most common chronic brain disorder, and is characterized by an enduring predisposition to generate seizures. Despite progress in pharmacological and surgical treatments of epilepsy, relatively little is known about the processes leading to the generation of individual seizures, and about the mechanisms whereby a healthy brain is rendered epileptic. These gaps in our knowledge hamper the development of better preventive treatments and cures for the approximately 30% of epilepsy cases that prove resistant to current therapies. Here, we focus on the rapidly growing body of evidence that supports the involvement of inflammatory mediators-released by brain cells and peripheral immune cells-in both the origin of individual seizures and the epileptogenic process. We first describe aspects of brain inflammation and immunity, before exploring the evidence from clinical and experimental studies for a relationship between inflammation and epilepsy. Subsequently, we discuss how seizures cause inflammation, and whether such inflammation, in turn, influences the occurrence and severity of seizures, and seizure-related neuronal death. Further insight into the complex role of inflammation in the generation and exacerbation of epilepsy should yield new molecular targets for the design of antiepileptic drugs, which might not only inhibit the symptoms of this disorder, but also prevent or abrogate disease pathogenesis

Evaluation of clinical and laboratory findings in the differential diagnosis of central precocious puberty and premature thelarche

Aim: In this study, it was aimed to examine the clinical and laboratory findings that can be used to predict central precocious puberty (CPP) in cases whose breast development started before the age of 8. Materials and Methods: The chronological age, anthropometric measurements, bone age (BA), hormone test results and pelvic ultrasonography findings of the cases were recorded. Those with a peak luteinizing hormone (LH) level of ≥5 IU/L in the gonadotropin-releasing hormone (GnRH) stimulation test were classified as CPP and those with a peak LH level of <5 IU/L were classified as prepubertal cases. A receiver operating characteristic (ROC) analysis was performed to determine the diagnostic accuracy of laboratory variables. Findings: A total of 297 female cases were included in the study. The age at the time of admission, height-standard deviation score (SDS), BA, the long axis of the uterus and the volumes of the right and left ovaries of the cases diagnosed with CPP were found to be significantly higher than those of the prepubertal group. The cut-off value providing the best sensitivity (99%) and specificity (99%) for the peak LH was found to be 4.55; the cut-off value providing the best sensitivity (94%) and specificity (85%) for the peak LH/follicle-stimulating hormone (FSH) ratio was found to be 0.32 and the cut-off value providing the best sensitivity (47%) and specificity (93%) for the basal LH was found to be 0.13. Conclusion: We believe that in female cases with early breast development, a peak LH level of ≥4.55 may possibly indicate CPP and a basal LH level of <0.13 can significantly rule out CPP

Combination therapy for children with chronic hepatitis B virus infection

WOS: 000177749200008PubMed ID: 12201869Background and Aim: To compare the therapeutic efficacy of two different interferon (INF)-alpha and lamivudine (LAM) combination therapy regimens in childhood chronic hepatitis B (CHB) infections. Methods: Thirty-two children with CHB infection were prospectively evaluated in two random groups. In the first group, patients received INF-alpha 10 MU/m(2) and LAM 4 mg/kg (max 100 mg) simultaneously for 6 months, and then LAM alone was continued for 6 months. In the second group, LAM was started alone for the first 2 months, then INF-alpha added to LAM for 6 months, after which INF-alpha was stopped, and LAM alone was continued for 4 months. The same doses of LAM and INF-alpha were used in both groups. Results: In the first group, the mean values of alanine aminotransferase (ALT) were 125 +/- 100 IU/L and 28 +/- 8 IU/L at the beginning of the treatment and at the end of the 12 months, respectively (P 0.05). After 6 months from completion of therapy, rates of seroconversion to anti-HBe were found to be 64% and 47% in group 1, and 53% and 46% in group 2, respectively ( P > 0.05). Hepatitis B virus (HBV) DNA was detectable by polymerase chain reaction in only one patient in group 1 at the end of therapy and 6 months after termination of therapy. Clearance of HBV DNA in group 2 was observed in all but one patient at the end of the therapy. However, two patients relapsed within 6 months of cessation of therapy. Complete response occurred in 47% and 40% of patients at the end of the therapy in group 1 and 2, respectively (P > 0.05). These ratios were changed to 47% and 46%, respectively, 6 months after discontinuation of drugs (P > 0.05). Conclusions: Comparison of our two different combination regimens disclosed similar results in the normalization of ALT, clearance of HBeAg and HBV DNA and seroconversion to anti-HBe. However, the most beneficial combination of LAM and INF-alpha treatment modalities needs to be further investigated. (C) 2002 Blackwell Publishing Asia Pty Ltd

MRI in CLN2 disease patients: Subtle features that support an early diagnosis

Neuronal ceroid lipofuscinosis type 2 (CLN2) disease is a rare, paediatric-onset, neurodegenerative disorder characterised in its early stages by language delay, seizures and loss of motor function. It is rapidly progressive and ultimately results in the premature death of patients. We aim to highlight common magnetic resonance imaging (MRI) features seen in early CLN2 disease and increase disease awareness among clinicians in order to facilitate early diagnosis and treatment of patients with disease-modifying enzyme replacement therapy. We obtained MRI scans from 12 Turkish children with CLN2 disease, at symptom onset or time of diagnosis, and at various times during disease progression. Patient details including age at onset of symptoms, age at diagnosis and clinical presentation were collected. MRIs were analysed to identify common features present in patients with CLN2 disease. The median diagnostic delay in this cohort was 2 years, highlighting the need for increased disease awareness among clinicians. Key MRI features suggestive of CLN2 disease that were identified included cerebellar atrophy in 11 patients, linear hyperintensity of central white matter in 10 patients, cerebral atrophy in 8 patients and thinning of the corpus callosum in 6 patients. Thalamic hypointensity was seen in 1 patient and may also indicate CLN2 disease. It is important to consider the presenting symptoms alongside clinical test results in order to support early diagnosis of CLN2 disease. Clinical suspicion of CLN2 disease accompanied by the detection of any of the above-mentioned features on MRI should encourage healthcare professionals to test for CLN2 disease. (c) 2020 The Authors. Published by Elsevier Ltd on behalf of European Paediatric Neurology Society

Comparison of treatments of chronic hepatitis B in children with lamivudine and alpha-interferon combination and alpha-interferon alone

WOS: 000177950500009PubMed ID: 12225552Background : The aim of this study was to compare the efficacy of the alpha-interferon treatment with treatment using alpha-interferon and lamivudine in combination for cases of childhood chronic hepatitis B infection. Methods : Patients were evaluated in two groups retrospectively. In group 1, 27 patients were simultaneously given alpha-interferon 2b 10 MU/m(2) , 3 days a week by s.c. injection plus lamivudine 4 mg/kg a day (maximum 100 mg) for 12 months. In group 2, there were 13 patients who only received the same dosage of alpha-interferon and no lamivudine over the same period of time. Results : In group 1 the initial mean value of alanine aminotransferase (ALT) was 121 +/- 66 IU/L and decreased to 27.8 +/- 11.5 IU/L; in group 2, initial mean values of ALT was 129 +/- 46 IU/L and decreased to 60 +/- 6 IU/L at the end of the twelfth month of the therapy (P 0.05). The number of patients with complete response was found to be 10 out of 27 (37%) in group 1 and four out of 13 cases (30.7%) in group 2, 6 months after the end of the therapy. There was no statistically significant difference between both groups (P > 0.05). Conclusion : alpha-Interferon and lamivudine combination therapy had a more beneficial effect than alpha-interferon monotherapy in normalization of ALT and clearance of HBV-DNA; however, the complete response rate at 6 months after the end of the therapy was not statistically significantly different between both groups