Overview: Japanese encephalitis

Japanese encephalitis (JE) is one of the most important endemic encephalitis in the world especially in Eastern and Southeastern Asia. JE affects over 50,000 patients and results in 15,000 deaths annually. JE virus is a single stranded positive sense RNA virus belonging to family flaviviridae. JE virus is transmitted through a zoonotic cycle between mosquitoes, pigs and water birds. Humans are accidentally infected and are a dead end host because of low level and transient viremia. In the northern region, large epidemics occur during summers whereas in the southern region JE tends to be endemic: cases occur throughout the year with a peak in the rainy season. Occurrence of JE is more closely related to temperature than to humidity. JE is regarded as a disease of children in the endemic areas but in the newly invaded areas, it affects both the adults and children because of the absence of protective antibodies. For every patient of JE, there are large numbers of subclinical cases (25–1000). Symptomatic JEV infection manifests with nonspecific febrile illness, aseptic meningitis or encephalitis. Encephalitis manifests with altered sensorium, seizures and focal neurological deficit. Acute flaccid paralysis may occur due to anterior horn cell involvement. A wide variety of movement disorders especially transient Parkinsonian features and dystonia (limb, axial, orofacial) are reported in 20–60% patients. JE mainly affects thalamus, corpus striatum, brainstem and spinal cord as revealed by MRI and on autopsy studies. Coinfection of JE and cysticercosis occurs because of the important role of pigs in the life cycle of both JEV and cysticercosis.     

A study of cytokines in tuberculous meningitis: Clinical and MRI correlation

There is paucity of studies on cytokines in tuberculous meningitis (TBM) and their relation with clinical and radiological changes; therefore this study was undertaken. 16 TBM patients diagnosed on the basis of clinical, CSF and radiological criteria were included. They were subjected to TNF-α, IL-6, IL-8, IL-10, IL-1β, and IL-12p70 estimation in CSF. The cytokine levels were also estimated in 10 controls. Initial clinical examination, stage of TBM and MRI findings (infarct, hydrocephalus, tuberculoma and exudates) were recorded. The patients were treated with 4 drugs antitubercular (RHZE) therapy and after 3 months clinical examination, cytokine levels, and radiological studies were repeated. Outcome was defined by Barthel index score at 3 months into poor, partial and complete recovery. The patient's age ranged between 10 and 50 years, 5 were females. At 3 months, all the patients were clinically followed up and 14 underwent repeat MRI. 10 patients improved, 1 remained stable and 5 deteriorated. There was worsening with respect to tuberculoma in 3, infarction in 2 and exudate in 1 patient. TNF-α was expressed in 32% patients, IL-6, IL-10, IL-1β and IL-8 were significantly expressed in patients and declined after 3 months following treatment. The cytokine levels did not correlate with stage of meningitis, outcome and radiological deterioration or improvement.     

Relationship of solvent to the photopolymerization process, properties, and structure in model dentin adhesives

The ratio of the double-bond content of monomer to polymer, i.e. degree of conversion (DC) has been used frequently as a convenient means of comparing the behavior and properties of dental composites and adhesives. The purpose of this investigation was to study the relationship of photopolymerization processes, bulk properties, and structure using model dentin adhesives cured in the presence of different ethanol content as an example. There was little difference in the DC of model BisGMA-based adhesives cured in the presence of ethanol concentrations ranging from 0 to 40 wt %, but there were substantial differences in the mechanical properties. Ultimate tensile strength (UTS) and modulus of elasticity decreased with an increase in ethanol content. Polymer structure was revealed by thermal behavior in the glass transition temperature (Tg) region; these measurements were obtained by modulated temperature differential scanning calorimetry (MTDSC) technology, which removes the competing irreversible effects associated with release of volatiles and residual curing. Glass transition temperature of model adhesives decreased substantially with an increase in ethanol content. The DC based on the quantity of remaining double bond has been used extensively to characterize and provide a relative assessment of the quality of dentin adhesives and dental composites. Since polymers differing in linearity, and therefore crosslink density, may have a similar degree of conversion, the measurement of monomer/polymer conversion does not necessarily provide complete representation of the quality or durability of the polymer structure.     

On the suitability of nanocrystalline ferrites as a magnetic carrier for drug delivery: functionalization, conjugation and drug release kinetics

Superparamagnetic nickel ferrite nanoparticles functionalized with polyvinyl alcohol, polyethylene oxide and polymethacrylic acid (PMAA) polymers and subsequently conjugated with doxorubicin anti-cancer drug are studied for their use as a magnetic carrier for drug delivery. Fourier transform infrared spectroscopy enabled examination of the ability of the nanoparticles to be functionalized with polymers and conjugated with doxorubicin drug. The functionalized polymer-coated nanocrystalline nickel ferrites retain the magnetic characteristics of non-functionalized nanocrystalline nickel ferrites (superparamagnetism, absence of hysteresis, remanence and coercivity at room temperature), encouraging their application as a magnetic carrier for drug delivery. The PMAA-coated nanoferrites are demonstrated as being a potentially superior magnetically targeted drug carrier based on FTIR results and drug release kinetics in the absence and presence of an external magnetic field.     

Intermediate monocytes are increased in enthesitis‐related arthritis,a category of juvenile idiopathic arthritis

Microarray of peripheral blood (PB) and synovial fluid mononuclear cells (PBMC, SFMC) of patients with juvenile idiopathic arthritis–enthesitis‐related arthritis (JIA‐ERA) has shown the involvement of monocytes. On the basis of CD14 and CD16 expression, monocytes are classified as classical, intermediate and non‐classical. In response to Toll‐like receptor (TLR) stimulation, intermediate monocytes produce proinflammatory cytokines and play a role in inflammatory diseases. Therefore, we have studied the microarray profile of monocytes, the frequency of their subsets and cytokine production. Monocyte‐specific microarray analysis was performed in six healthy controls' PBMC and six patients' PBMC and SFMC using Illumina chips WG12. Monocyte subsets were assessed in 46 patients with JIA‐ERA and 17 healthy controls and 17 disease controls by flow cytometry. Interleukin (IL)?23 and tumour necrosis factor (TNF) levels were measured in culture supernatants of eight controls and seven patients' PBMC/SFMC with/without lipopolysaccharide (LPS) stimulation. Cytokine‐producing intermediate monocytes were assessed by flow cytometry. Genes related to antigen presentation, cytokine signalling and TLR pathway were regulated differentially in PB and synovial monocytes of patients with JIA‐ERA. Key genes of intermediate monocytes, such as CLEC10A and MARCO, were expressed three‐ to fourfold more in JIA‐ERA. In PB, the frequency of intermediate monocytes was significantly higher in JIA‐ERA (4·90% ± 3·5) compared to controls (1·8% ± 1·06; P < 0·001). Patients' synovial cells also had more intermediate monocytes compared to PB (11·25% ± 11·32, 5·9% ± 4·8; P = 0.004). Intermediate monocytes are the major producers of IL‐23. Thus, intermediate monocytes may play an important role in JIA‐ERA, possibly by producing cytokines, and contribute to joint inflammation.     

Glatiramer acetate-specific antibody titres in patients with relapsing / remitting multiple sclerosis and in experimental autoimmune encephalomyelitis

Glatiramer acetate (GA) is an immunomodulatory drug approved for the treatment of clinically isolated syndrome (CIS) and relapsing/remitting multiple sclerosis (RRMS). As an antigen-based therapy, GA induces GA-specific antibodies in treated patients and animals. GA-specific antibodies do not neutralize therapeutic effects on relapses and disability. Rather, it has been suggested that GA-specific antibodies may be associated with improved clinical outcomes. We evaluated antibody responses in eight patients with RRMS treated with GA for 15 months and antibody responses in GA-treated C57BL/6 mice before and after induction of experimental autoimmune encephalomyelitis (EAE). There were no significant differences from pretreatment levels of total IgE or GA-specific IgE in patients with RRMS. Total IgG1, IgG3 and GA-specific IgG4 were significantly increased at 15 months of GA treatment. Antibody type and titre were not associated with clinical outcomes, i.e. expanded disability status scale (EDSS) score, disease burden on magnetic resonance images (MRI) or clinical relapses. In contrast, mice with EAE showed a marked increase in GA-specific IgE and GA-specific IgG1 antibody responses. GA-treated mice demonstrated improved clinical symptoms and lower mortality than untreated controls. Our results suggest that antibody responses to GA are heterogeneous among patients with RRMS, with no apparent association between antibody response and clinical outcomes. Clinical improvements in EAE-induced GA-treated mice suggest that GA-specific IgE and IgG1 may contribute to GA treatment effects in EAE.     

Structure-process-property relationship of the polar graphene oxide-mediated cellular response and stimulated growth of osteoblasts on hybrid chitosan network structure nanocomposite scaffolds

We here describe the structure-process-property relationship of graphene oxide-mediated proliferation and growth of osteoblasts in conjunction with the physico-chemical, mechanical, and structural properties. Chitosan-graphene network structure scaffolds were synthesized by covalent linkage of the carboxyl groups of graphene oxide with the amine groups of chitosan. The negatively charged graphene oxide in chitosan scaffolds was an important physico-chemical factor influencing cell-scaffold interactions. Furthermore, it was advantageous in enhancing the biocompatibility of the scaffolds and the degradation products of the scaffolds. The high water retention ability, hydrophilic nature, and high degree of interconnectivity of the porous structure of chitosan-graphene oxide scaffolds facilitated cell attachment and proliferation and improved the stability against enzymatic degradation. The cells infiltrated and colonized the pores of the scaffolds and established cell-cell interactions. The interconnectivity of the porous structure of the scaffolds helps the flow of medium throughout the scaffold for even cell adhesion. Moreover, the seeded cells were able to infiltrate inside the pores of chitosan-graphene oxide scaffolds, suggesting that the incorporation of polar graphene oxide in scaffolds is promising for bone tissue engineering.     

Sacrococcygeal teratoma

This retrospective study details our experience regarding 72 patients with sacrococcygeal teratoma treated over a period of 17 years. The sex incidence was nearly equal, but there was a high proportion of Altmann type IV tumors. A preliminary colostomy before combined abdominosacral excision of large type III and IV lesions reduced morbidity. Sixty-six percent of the patients presented beyond the neonatal period; 14 had been treated elsewhere for bowel/urinary obstruction. Imaging studies included radiography, abdominal ultrasound, computed tomography, and magnetic resonance imaging (after 1995). In 60 patients the tumor was excised via the sacral route, 11 had a preliminary colostomy, and 1 had a vesicostomy. Eight children (5 with malignant lesions) required abdominosacral excision. After 1990, serial estimation of serum alpha-fetoprotein (AFP) was used to monitor tumor recurrence. There were 34 male and 38 female patients (age range 3 days-12 years); 47 had benign tumors, of which 42 were excised through the sacral route. Three patients underwent a preliminary colostomy and abdominosacral excision of the tumor with subsequent colostomy closure. There were 4 deaths in this group; no recurrence was seen in the surviving children with benign tumors. Twenty-five patients had malignant teratomas. In 18 of these the tumor was excised via the sacral route and 5 underwent abdominal-sacral excision. Eight had a preliminary colostomy and chemotherapy followed by excision of the residual tumor and colostomy closure. None of the initial 14 patients with malignant lesions survived beyond 2 years. Of the latter 11 (who received cisplatinum-based chemotherapy), 10 were alive 1 year after surgery. One patient is currently on preoperative chemotherapy and another developed recurrence of the tumor. The overall follow-up ranged from 3 months to 8 years; there has been no complaint of functional neurological deficit in any of the patients. As intrapelvic tumors tend to have a delayed diagnosis, this can be avoided by performing a rectal examination. There should be no recurrence after excision of a benign teratoma. Cisplatinum-based chemotherapy has improved the survival of patients with malignant tumors.