Valproate-Induced Hyperammonemic Encephalopathy Following Accidental Ingestion in a Toddler.

Clinical manifestations of valproic acid (VPA) toxicity can range from just mild confusion and drowsiness to serious encephalopathy, leading to depressed sensorium and even coma and death. The exact cause(s) of how VPA influences the integrity of brain function remains unknown. Nevertheless, several mechanisms have been postulated including a surge in the blood ammonia concentration. Valproic acid-induced hyperammonemic encephalopathy is a rare yet serious sequalae and that can lead to grave outcomes. We report a case of hyperammonemic encephalopathy with preserved liver function following a moderate VPA intoxication in a toddler, who was successfully managed conservatively. Additionally, we briefly discuss mechanistic basis of VPA toxicity and highlight some of the available potential therapies.

Investigating the awareness, behavior, and attitude toward epilepsy among university students in Benghazi, Libya.

OBJECTIVE: The aim of this study was to explore the level of knowledge regarding epilepsy and attitudes prevalent toward people with epilepsy (PWE) among Libyan university students in comparison with international data. METHODS: A self-administrated questionnaire on awareness regarding epilepsy and behaviors toward PWE was distributed among undergraduate students enrolled in the University of Benghazi. The collected data were analyzed against responses from an Italian survey that utilized a similar questionnaire to explore epilepsy-related knowledge and attitudes among Italian university students in Rome (Mecarelli et al., 2007). RESULTS: Out of the 500 interviewed students, 96% successfully completed the survey. Further, 96.6% asserted that they possessed some knowledge regarding epilepsy, gained mainly from their families (76.6%). A total of 57.5% considered epilepsy to be a psychiatric disorder while 11.6% recommended psychological tests for the diagnosis of epilepsy. Moreover, 37.5% believed in ancient superstitions, such as possession by evil forces, as the underlying cause of the condition, and 31.8% recommended traditional remedies to cure it. Further, 66.6% deemed epilepsy as a barrier for career prospects, 41% indicated that it presents an impediment in participation in sports, and 35% considered it as an obstacle in marriage. Additionally, epilepsy was perceived as a severe illness by 53.3% of the respondents and considered to be a moderately severe condition by 43.7%. The responses were found to be statistically significant (P<0.05) against the responses from the Italian study. CONCLUSION: There is a reasonable level of awareness regarding epilepsy among Libyan students, though a lack of accuracy in the acquired knowledge exists. The ancient misconceptions regarding the nature of epilepsy and negative attitudes toward PWE appear to be rather common among the Libyan students. Consequently, the discrepancies in the views between the two surveys concerning the ways in which epilepsy is perceived and PWE are treated were extremely evident, thus reflecting the already established view that epilepsy faces greater stigma as a health condition in developing countries in comparison with Western nations.

Enteral Nutrition in the Management of Crohn's Disease: Reviewing Mechanisms of Actions and Highlighting Potential Venues for Enhancing the Efficacy.

Crohn's disease (CD) is a chronic condition that affects the gut and has adverse effects on growth and development. There is a global increase in the incidence and prevalence rates, and several factors are believed to contribute to this rise, including dietary habits. In contrast, the use of enteral nutrition (EN) as an exclusive source of nutrition is increasingly becoming the preferred induction treatment of pediatric CD patients in part to address the nutrition complications. However, EN therapy is considered less effective in adults with CD. A better understanding of the molecular mechanisms of enteral therapy will help improve the clinical management of CD. It is increasingly becoming evident that the therapeutic utility of EN is in part due to the reversal of the microbial changes and the direct immunomodulatory effects. Moreover, there is a potential tendency for enhancing the efficacy of EN therapy by improving the palatability of the given formulas and, more important, by magnifying the anti-inflammatory properties. Recent observations have shown that the immunomodulatory effects of EN are mediated at least in part by blocking nuclear factor-κB. Furthermore, it is likely that several ingredients of EN contribute to this activity, in particular glutamine and arginine amino acids. In addition, manipulating the composition of EN therapy by altering concentrations of the key ingredients is found to have the potential for more efficient therapy. In this review, the underlying mechanisms of EN actions will be discussed further with a focus on the potential methods for enhancing the efficacy.

Exploring and Enhancing the Anti-Inflammatory Properties of Polymeric Formula.

BACKGROUND: Exclusive enteral nutrition (EEN) therapy using a polymeric formula (PF) can substantially attenuate intestinal inflammation in Crohn's disease (CD) patients. However, the mechanism(s) by which EEN suppresses inflammation are not yet fully understood. The aims were to examine cellular mechanism(s) through which EEN may suppress inflammation and investigate potential pathways to enhance anti-inflammatory properties of EEN. METHODS: Glutamine, arginine, vitamin D3, and α linolenic acid (ALA), present in PF, along with curcumin, were identified as immunoactive nutrient therapies. Tumor necrosis factor (TNF)-α-exposed HT-29 colonic epithelial cells were used to investigate the immunosuppressive activity of the nutrients by assessing their effect on cell viability, cell activity, chemokine response (interleukin-8 [IL-8]), nuclear factor (NF)-κB, P38 mitogen-activated protein kinase, IκB kinase (Iκκ), and nitric oxide (NO). RESULTS: Cellular viability and activity were maintained with all nutrient treatments. Glutamine, arginine, and vitamin D3, but not ALA, significantly attenuated IL-8 production. Glutamine and arginine led to phosphorylation blockade of the signaling components in NF-κB and P38 pathways, reduction in kinase activity, and enhancement in NO production. Combining glutamine, arginine, and curcumin at optimal concentrations completely abolished the IL-8 response. CONCLUSIONS: These data indicate that glutamine, arginine, and vitamin D3 can suppress inflammation at concentrations equivalent to those used in PF. The mechanisms of this action were mediated through influencing the NF-κB and P38 cascades. Glutamine and arginine-fortified PF with curcumin might be a promising option to enhance the effectiveness and expand the scope of EEN therapy in CD treatment.

Advancing nutritional therapy: A novel polymeric formulation attenuates intestinal inflammation in a murine colitis model and suppresses pro-inflammatory cytokine production in ex-vivo cultured inflamed colonic biopsies.

BACKGROUND & AIMS: Nutritional therapy is a viable therapeutic option for the treatment of Crohn disease (CD). Therefore improving nutritional therapy would greatly benefit CD patients. The aim of this study was to define the anti-inflammatory properties of a novel nutritional polymeric formula (PF) in comparison to a currently available standard PF. METHODS: Dextran sodium sulfate (DSS) was utilized to induce colitis in C57BL/6 mice with mice randomized to receive either standard PF or novel PF in addition to control groups. Changes in body weight were recorded and colonic damage was assessed histologically and biochemically. Additional experiments were also included where the cytokine response of colonic biopsies from pediatric CD patients was measured following exposure to standard PF or novel PF. RESULTS: DSS induced significant body weight loss, morphological changes in the colon, increased myeloperoxidase (MPO) activity and up-regulated colonic mRNA expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-12 and monocyte chemoattractant protein (MCP)-1, as well as associated histological changes. Other than histological damage, these inflammatory changes were reversed by both novel and standard PF. However, the novel PF, but not standard PF, completely suppressed TNF-α, IL-6 and IL-8 levels from cultured biopsies. CONCLUSIONS: Newly developed nutritional formula reproducibly ameliorated DSS-induced colitis in a murine model, although this response was not measurably different to standard PF. However, the novel PF was significantly superior in suppressing inflammatory cytokine release from cultured colonic biopsies. Collectively, these findings support a possible role for novel PF in advancing nutritional therapy for CD patients.

An overview of the bacterial contribution to Crohn disease pathogenesis.

Crohn disease (CD) is a chronic inflammatory condition primarily affecting the gastro-intestinal tract and is characterized by reduced bacterial diversity. The exact cause of disease is unknown; however, evidence suggests that several components, including microbiota, may contribute to the underlying pathology and disease development. Perturbation of the host-microbe commensal relationship is considered the main driving force of tissue destruction and pathological changes seen in CD. Several putative bacterial pathogens including species from Mycobacterium, Campylobacter and Helicobacter are postulated in the aetiology of CD. However, to date, no strong evidence supports a single bacterium contributing overall to CD pathogenesis. Alternatively, dysbiosis or bacterial imbalance is more widely accepted as a leading factor in the disrupted host-immune system cross-talk resulting in subsequent intestinal inflammation. Depletion of symbiont microbes including Firmicutes, Bifidobacterium and Clostridia, in conjunction with an increase in pathobiont microbes from Bacteroidetes and Enterobacteria, is a striking feature observed in CD. No single factor has been identified as driving this dysbiosis, although diet, antibiotic exposure and possible early life events in presence of underlying genetic susceptibility may contribute. The aim of this review is to highlight the current accumulating literature on the proposed role of bacteria in the pathogenesis of CD.

The major pathway by which polymeric formula reduces inflammation in intestinal epithelial cells: a microarray-based analysis.

Nutritional therapy is well established as a means to induce remission in active Crohn's disease (CD). Evidence indicates that exclusive enteral nutrition (EEN) therapy for CD both alters the intestinal microbiota and directly suppresses the inflammatory response in the intestinal mucosa. However, the pathway(s) through which EEN suppresses inflammation is still unknown. Therefore, the aim of the current study was to use microarray technology to investigate the major pathway by which polymeric formula (PF) alters inflammatory processes in epithelial cells in vitro. HT-29 cells were grown to confluence and then co-cultured with tumour necrosis factor (TNF)-α (100 ng/ml) for 5 h in the presence or absence of PF, as used for EEN. Following incubation, RNA was extracted and subjected to polymerase chain reaction (PCR) and microarray analysis. Enzyme-linked immunosorbent assays were employed to evaluate cytokine protein levels. Neither TNF-α nor PF had a toxic effect on cells over the experimental period. Microarray analysis showed that PF modulated the expression of genes specifically linked to nuclear factor (NF)-κB, resulting in downregulation of a number of genes in this pathway. These findings were further confirmed by real-time PCR of selected dysregulated genes as well as reduced expression of IL-6 and IL-8 proteins following PF treatment. The results arising from this study provide evidence that PF alters the inflammatory responses in intestinal epithelial cells through modulation of the NF-κB pathway.

An update of the role of nutritional therapy in the management of Crohn's disease.

Crohn's disease is an increasingly global health concern. Currently without a cure, it significantly alters the quality of life of Crohn's disease sufferers and places a heavy financial burden on the community. Recent reports show that the rising prevalence of Crohn's disease is no longer confined to Western countries, with considerable increases seen particularly in Asia. Nutritional problems are often associated with Crohn's disease, most notably in the paediatric population, with underweight and stunting commonly seen at presentation. In addition, linear growth retardation and pubertal delay can also manifest in these younger patients. Therefore, exclusive enteral nutrition has been used as a therapeutic option to treat Crohn's disease, in part to address the nutritional complications of the disease. Exclusive enteral nutrition can improve nutrition as well as induce remission at a rate equivalent to corticosteroids. It is safe particularly with long-term use and can induce mucosal healing, considered the gold standard for therapy, at a rate superior to corticosteroids. Exclusive enteral nutrition has thus become the preferred therapeutic option in many centres for the treatment of paediatric Crohn's disease. This review discusses the role of exclusive enteral nutrition as a therapeutic option for the treatment of Crohn's disease, as well as the latest findings into its mechanisms of action.