Prevalence and prediction of serious bacterial infection in febrile children: a role for cytokines?

BACKGROUND: To date, no consensus has been reached regarding the evaluation and management of young febrile children, and no single laboratory test has been shown to reliably identify young children at high or low risk of having serious bacterial illness. Knowing the local prevalence of SBI is essential in formulating management strategies because extrapolation from studies done elsewhere is difficult.AIMS: i) To determine the prevalence of SBI in young febrile children served by a paediatric hospital. Ii) To evaluate the role of cytokines in predicting SBI in these children.HYPOTHESIS: IL-6, IL-8 and sICAM-1 can accurately predict SBI in young febrile children.METHODOLOGY: The study population was children seen at the emergency department of the Edinburgh Royal Hospital for Sick Children. All children ≤5 years old with a temperature of ≥38.5°C were studied over a 12-month period. Demographic, clinical and laboratory data were collected prospectively. Serum IL-6, IL-8 and sICAM-1 were measured by ELISA. The performance characteristics of the cytokines in predicting SBI were compared to those of the traditional tests (WBC, ANC, CRP, ESR).RESULTS: 618 patients fulfilled the study criteria of age and temperature. 26.7% of the patients had a SBI. The commonest SBI was pneumonia. 2.7% of blood cultures were positive, over half were streptococcus pneumoniae. 40% of positive blood cultures were from patients discharged with an apparently benign illness. The modest gain in the posttest probability of SBI was comparable between the cytokines and the traditional tests. Serum IL-6 and IL-8 was elevated in all patients with bacteraemia or meningitis. A model based on the respiratory rate, CRP, and sICAM-1 correctly identified 70% of SBI.CONCLUSION: The prevalence of SBI, and bacteraemia, in young febrile children is still high in spite of the decline in immunizable diseases. Highly febrile young children should continue to be evaluated with a blood culture and close follow up, and UTI should be excluded in all infants. IL-6 and IL-8 appear to be sensitive markers for bacteraemia and meningitis and their role requires further evaluation

PREPARATION AND CHARACTERIZATION OF ITRACONAZOLE TRANSDERMAL PATCHES CONTAINING SINGLE-PHASE EMULGEL

Objective: Emulgel technique has attempts for preparation of itraconazole (ITZ) transdermal patches of reservoir type using a single-phase system with different polymers of Carbopol 934 and Carboxy methyl cellulose (CMC). Methods: The transdermal patches were prepared by using eudragit L30 as a polymer and propylene glycol (PG) as plasticizer has been made to predict the mechanism of drug release and absorption based on the order of release. The optimized transdermal patches were characterised as surface morphology, pH, viscosity, spreadability, folding endurance, drug permeation, assay, in vitro dissolution and stability for 3 mo. Results: The result of the study showed that the transdermal patches prepared with eudragit (8 %) showed 96.11±3.17 % drug release in 24 h and the optimised formulation F8, which had the highest concentration of span 20 and tween 20, displayed the highest percentage of drug penetration. The drug release kinetics was studied, including the Baker-Lonsdale model with in vitro drug permeation data was found that release from non-spherical matrices, the first-order model with non-fickian diffusion. Conclusion: ITZ administered transdermally might be avoided the number of drawbacks associated with oral delivery and perhaps maintain a relatively constant plasma level during a lengthy course of treatment

Prevention and treatment of murine experimental allergic encephalomyelitis with T cell receptor Vβ-specific antibodies

Experimental allergic encephalomyelitis (EAE) is a model system for T cell-mediated autoimmune disease. Symptoms of EAE are similar to those of multiple sclerosis (MS) in humans. EAE is induced in susceptible animal strains by immunization with myelin basic protein (MBP) and potent adjuvant. The major T cell response to MBP in B10.PL mice is directed towards an NH2-terminal epitope and involves T cells expressing either V beta 8.2 or V beta 13 gene segments. Animals treated with a TCR V beta 8-specific mAb have a reduced incidence of EAE. We report here that the in vivo administration of a combination of anti-V beta 8.2 and anti-V beta 13 mAbs results in a long-term elimination of T cells involved in the response to MBP. When given before MBP immunization, anti-TCR antibody treatment leads to nearly complete protection against EAE. Antibody treatment also results in a dramatic reversal of paralysis in diseased animals. Thus, treatment with a combination of V beta-specific antibodies is a very effective therapy for the prevention and treatment of EAE. It is hoped that the future characterization of TCR V gene usage in human autoimmune diseases may lead to similar strategies of immune intervention

Characterization of the T cell receptor repertoire causing collagen arthritis in mice

Collagen type II-induced arthritis (CIA) is generated in susceptible rodent strains by intradermal injections of homologous or heterologous native type II collagen in complete Freund's adjuvant. Symptoms of CIA are analogous to those of the human autoimmune disease, rheumatoid arthritis. CIA is a model system for T cell-mediated autoimmune disease. To study the T cell receptor (TCR) repertoire of bovine type II-specific T cells that may be involved in the pathogenesis of CIA in DBA/1Lac.J (H-2q) mice, 13 clonally distinct T cell hybridomas specific for bovine type II collagen have been established and the alpha and beta chains of their TCRs have been analyzed. These T cell hybridomas recognize epitopes that are shared by type II collagens from distinct species and not by type I collagens, and exhibit a highly restricted TCR-alpha/beta repertoire. The alpha chains of the TCRs employ three V alpha gene subfamilies (V alpha 11, V alpha 8, and V alpha 22) and four J alpha gene segments (J alpha 42, J alpha 24, J alpha 37, and J alpha 32). The V alpha 22 is a newly identified subfamily consisting of approximately four to six members, and exhibits a high degree of polymorphism among four mouse strains of distinct V alpha haplotypes. In addition, the beta chains of the TCRs employ three V beta gene subfamilies (V beta 8, V beta 1, and V beta 6), however the V beta 8.2 gene segment is preferentially utilized (58.3%). In contrast, the J beta gene segment usage is more heterogeneous. On the basis of the highly limited TCR-alpha/beta repertoire of the TCRs of the panel of bovine type II-specific T cell hybrid clones, a significant reduction (60%) of the incidence of arthritis in DBA/1Lac.J mice is accomplished by the use of anti-V beta 8.2 antibody therapy

DEVELOPMENT AND IN VITRO EVALUATION OF VALSARTAN-LOADED RESEALED ERYTHROCYTES

Objective: Resealed erythrocyte technique has attempts for preparation of valsartan loaded reservoir type using red blood cell as a carrier. Methods: The resealed erythrocytes were prepared by using glutaraldehyde as a cross-linking agent by Preswell dilution technique and sodium chloride as the medium has been made to predict mechanism of drug release and absorption based on the order of release. The prepared resealed erythrocytes was characterised as a percentage of cell recovery drug content, osmotic shock, turbulence fragility, osmotic fragility, in vitro drug release studies, and hemoglobin content study. Results: The result of the study showed that the resealed erythrocytes prepared with sodium chloride (9 %) showed biconcave shape, an assay of 6.5±0.4 %, osmotic shock (0.028±0.004 µg/ml), turbulence fragility of 0.228±0.046 µg/ml, and 44.38±5.54 % drug release in 8 h. The drug release kinetics was studied and found that release from spherical matrices, first-order model with non-fickian diffusion with and the dissolution occurs in planes that are parallel to the drug surface pattern. Conclusion: VaL administration could be avoided the number of drawbacks associated with systemic delivery and perhaps maintain a relatively constant plasma level during a lengthy course of treatment

TERMINALIA CHEBULA: AN EPHEMERAL GLANCE

Herbal drugs represent a major allocation of all the recognized systems of health in the world. Also, the medicinal plants have been regarded as valuable and cheap sources of various phytoconstituents which are used extensively in the development of drugs against various diseases. Terminalia chebula, commonly called as black myrobalan, ink tree, or chebulic myrobalan, is a deciduous tree belonging to the family Combretaceae, has been regarded as one of the most important medicinal plants used in medicines of ayurveda, siddha, unani and homeopathy. Numbers of phytochemical constituents have been found to be associated with the drug such as tannins, chebulinic acid, ellagic acid, gallic acid, punicalagin and flavonoids. Moreover, Terminalia chebula has been well reported to possess antioxidant, antidiabetic, antibacterial, antiviral, antifungal, anticancerous, antiulcer, antimutagenic and wound healing activities. In addition, Terminalia chebula has been used extensively in the preparation of many Ayurvedic formulations for infectious diseases like chronic ulcer, leucorrhoea, pyorrhoea and fungal infections of the skin. The present review article has been designed to elucidate data on phytochemistry, pharmacognostic characters and pharmacological activities associated with Terminali

Penetration enhancers in proniosomes as a new strategy for enhanced transdermal drug delivery

AbstractThe aim of this work is to investigate penetration enhancers in proniosomes as a transdermal delivery system for nisoldipine. This was performed with the goal of optimising the composition of proniosomes as transdermal drug delivery systems. Plain proniosomes comprising sorbitan monostearate, cholesterol, ethanol and a small quantity of water were initially prepared. Subsequently, proniosomes containing lecithin or skin penetration enhancers were prepared and evaluated for transdermal delivery of nisoldipine. The plain proniosomes significantly enhanced the transdermal flux of nisoldipine to reach 12.18μgcm−2h−1 compared with a saturated aqueous drug solution which delivered the drug at a rate of 0.46μgcm−2h−1. Incorporation of lecithin into such proniosomes increased the drug flux to reach a value of 28.51μgcm−2h−1. This increase can be attributed to the penetration enhancing effect of lecithin fatty acid components. Replacing lecithin oleic acid (OA) produced proniosomes of comparable efficacy to the lecithin containing system. The transdermal drug flux increased further after incorporation of propylene glycol into the OA based proniosomes. Similarly, incorporation of isopropyl myristate into plain proniosomes increased drug flux. The study introduced enhanced proniosomes as a promising transdermal delivery carrier and highlighted the role of penetration enhancing mechanisms in enhanced proniosomal skin delivery. The study opened the way for another line of optimisation of niosome proconcentrates

INTESTINAL ABSORPTION OF EPROSARTAN MESYLATE FROM SELF EMULSIFYING SYSTEM AND CYCLODEXTRIN COMPLEX

Objective: The aim of this work was to determine the intestinal membrane transport parameters of eprosartan mesylate (EM) and to investigate self-nano emulsifying drug delivery systems (SNEDDS) and inclusion complexation with hydroxypropyl b cyclodextrin (HPbCD) for enhanced intestinal absorption of eprosartan mesylate. Methods: The intestinal absorption was monitored using the in situ rabbit intestinal perfusion technique. SNEDDS was developed using labrafil, Lauroglycol with a tween in the presence of ethanol. Inclusion complexation was achieved by construction of phase solubility diagram in the presence of HPbCD. The prepared complex was evaluated using Fourier Transform Infrared Spectroscopy (FTIR) and differential scanning calorimetry (DSC). Results: The drug was found to be poorly absorbed from the jejuno-ileum and the colon with the absorption being mainly through paracellular pathway. An inclusion complex was developed between the drug and HPβCD. Perfusion of the drug in the nanoemulsion formulation or as an inclusion complex resulted in a significant increase in the intestinal absorption of the drug compared with the control.Conclusion: SNEDDS and inclusion complexation are promising strategies for enhanced intestinal absorption of eprosartan mesylate

Contemporary Onlay Incisional Hernia Repair: Review Article

Background: Abdominal procedures, whether open or laparoscopic are often complicated with an incisional abdominal hernia (IH). Approximately 15% - 20 % of all laparotomies and 1% to 5% of all laparoscopic surgeries are complicated by IHs. IH is a really bad situation for doctors and patients. Dissatisfaction, long-term malfunction, and limitations of activities and unsatisfying cosmetic appearance are just a few of the side effects that patients endure as a result of IH. For doctors; it is a challenging surgical issue associated with multiple risk factors, unclear etiology and different pathological changes, affecting different patients. Management of such a variable surgical issue necessitates a good understanding of the anatomical and physiological features of the abdominal wall by the hernia surgeon beside a wide armamentarium of surgical options to deal with complex variants to repair and restore abdominal wall integrity and function, many procedures have been utilized to repair IH and to restore abdominal wall integrity. Objective: To review the feasibility and safety of the abdominal wall component release with contemporary onlay mesh fixation procedure in the treatment of incisional abdominal hernias. Conclusion: Large incisional hernias that are difficult to close in the midline might benefit from the component separation approach. Repair of incisional hernias by abdominal wall omponent separation with contemporary onlay mesh fixation results in favorable outcomes and lower recurrence rates. It gives a more durable abdominal wall repair, a more physiological repair in cases of loss of domain, an affordable financial outlay, and a low incidence of complications