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Multiple sclerosis (MS) is an immune-mediated inflammatory demyelinating disease of the central nervous system. It was previously shown that toll-like receptor (TLR)-2 signaling plays a key role in the murine experimental autoimmune encephalomyelitis (EAE) model of MS, and that TLR2-stimulation of regulatory T cells (Tregs) promotes their conversion to T helper 17 (Th17) cells. Here, we sought potential sources of TLR2 stimulation and evidence of TLR2 activity in MS patient clinical samples. Soluble TLR2 (sTLR2) was found to be significantly elevated in sera of MS patients (n = 21), in both relapse and remission, compared to healthy controls (HC) (n = 24). This was not associated with the acute phase reaction (APR) as measured by serum C-reactive protein (CRP) level, which was similarly increased in MS patients compared to controls. An independent validation cohort from a different ethnic background showed a similar upward trend in mean sTLR2 values in relapsing-remitting MS (RRMS) patients, and significant differences in sTLR2 values between patients and HC were preserved when the data from the two cohorts were pooled together (n = 41 RRMS and 44 HC, P = 0.0006). TLR2-stimulants, measured using a human embryonic kidney (HEK)-293 cells transfectant reporter assay, were significantly higher in urine of MS patients than HC. A screen of several common urinary tract infections (UTI)-related organisms showed strong induction of TLR2-signaling in the same assay. Taken together, these results indicate that two different markers of TLR2-activity—urinary TLR2-stimulants and serum sTLR2 levels—are significantly elevated in MS patients compared to HC.

A sandwich immunosensor was successfully developed for monitoring of interleukin-1β (IL-1β) in rat whole blood.

Aquatic plants are generally considered as breeding grounds for mosquitoes and other harmful vectors of diseases. However, in recent years, some research has been carried out to test their significance as sources of antimicrobial lead molecules. The aim of this research was to study the phytochemical composition of local aquatic plant species and test their antimicrobial effect against selected bacterial strains. Three different aquatic plant samples were collected from a large water body near Dhaka. Ethanol and ethyl acetate extracts of the plant species: Eichhornia crassipes, Pistia stratiotes, and Spirodela polyrrhiza were tested against Staphylococcus aureus, Salmonella typhi, and Lactobacillus spp. Out of the eight different extracts, only the ethyl acetate extracts prepared from Eichhornia crassipes showed significant anti-microbial activity against Staphylococcus aureus and Salmonella typhi. In disk diffusion tests, zone of inhibitions of ethyl acetate extracts of Eichhornia crassipes leaves and stems were 8.00 ± 0.5 mm and 7.83 ± .29 mm respectively. In well diffusion tests, zone of inhibitions of ethyl acetate extracts of Eichhornia crassipes leaves and stems were 18.00 mm and 20.00 mm respectively. Zones of inhibition of ethyl acetate extracts of Eichhornia crassipes stems against Staphylococcus aureus were 7.67 ± 0.29 mm and 12.00 mm respectively in disk and well diffusion tests. Zone of inhibition of ethyl acetate extracts of Spirodela polyrrhiza was 8.17 ± 0.29 mm against Staphylococcus aureus in disk diffusion tests. No extracts showed any antimicrobial potential against Lactobacillus. Phytochemical composition analysis showed the presence of alkaloids, flavonoids, steroids, phenolics, tannins, glycosides, and cardiac glycosides in the different ethanol and ethyl acetate extracts. Tannins were absent in all extracts and saponins were absent in all ethyl acetate extracts. Bangladesh J Microbiol, Volume 35 Number 1 June 2018, pp 7-11

Peripheral neuropathy (PN) is a debilitating complication of diabetes that affects >50% of patients. Recent evidence suggests that obesity and metabolic disease, which often precede diabetes diagnosis, may influence PN onset and severity. We examined this in a translationally relevant model of prediabetes induced by a cafeteria (CAF) diet in Sprague–Dawley rats (n = 15 CAF versus n = 15 control). Neuropathy phenotyping included nerve conduction, tactile sensitivity, intraepidermal nerve fiber density (IENFD) and nerve excitability testing, an in vivo measure of ion channel function and membrane potential. Metabolic phenotyping included body composition, blood glucose and lipids, plasma hormones and inflammatory cytokines. After 13 weeks diet, CAF-fed rats demonstrated prediabetes with significantly elevated fasting blood glucose, insulin and impaired glucose tolerance as well as obesity and dyslipidemia. Nerve conduction, tactile sensitivity and IENFD did not differ; however, superexcitability was significantly increased in CAF-fed rats. Mathematical modeling demonstrated this was consistent with a reduction in sodium–potassium pump current. Moreover, superexcitability correlated positively with insulin resistance and adiposity, and negatively with fasting high-density lipoprotein cholesterol. In conclusion, prediabetic rats over-consuming processed, palatable foods demonstrated altered nerve function that preceded overt PN. This work provides a relevant model for pathophysiological investigation of diabetic complications.

Experimental autoimmune encephalomyelitis (EAE) is the most relevant and commonly used animal model to study autoimmune demyelinating diseases like Multiple Sclerosis (MS). In EAE, the activation of CD4+ T-cells is considered to be the main trigger leading to inflammation and central nervous system (CNS) demyelination. Toll-like receptors (TLRs) are the most important and first class of pattern recognition receptors (PRRs) in innate immune system and play critical roles in initiating inflammatory responses and promoting adaptive immune responses due to their ability to recognize a wide range of pathogen associated molecular patterns (PAMPs) and being expressed in a wide range of cell types both in the innate and adaptive immune systems. Upon TLR stimulation by appropriate ligand, innate immune cells produce pro-inflammatory cytokines and can serve as antigen-presenting cells (APCs) to prime naïve T cells to recognize antigens. Thus, TLRs play an important role in linking the innate to the adaptive immune response. To date, large numbers of studies have been done to investigate the role of adaptive immunity in both EAE and MS but delineating the role of innate immunity in EAE received very little focus and appreciation taking into account that it might contribute to both the initiation and progression of the disease. Moreover, EAE is not only a model to study inflammatory demyelination in the CNS; it is in general a model to study cell-mediated organ-specific autoimmune conditions. Roles of different TLRs were studied in relation to EAE and MS. More recently, some studies demonstrated the immune adjuvant properties of certain TLR ligands including TLR2, TLR4, and TLR9 in EAE. This chapter outlines different methods employed in our labs to investigate the role of TLRs in EAE model.

Background: Diabetes mellitus is a non-communicable disease with increasing prevalence worldwide. The present study was done to identify the modifiable factors that were associated with the poor glycemic control in Bangladeshi type 2 diabetic patients attending in a tertiary care hospital.Methods: This cross-sectional study was conducted in the Department of Medicine, Sir Salimullah Medical College & Mitford Hospital (SSMC & MH), Dhaka from July 2014 to June 2015. A total of 140 adult type 2 diabetes mellitus patients were included in this study. Of them 70 patients had uncontrolled diabetes mellitus with glycated haemoglobin ³ 7% (group 1) and 70 patients with controlled diabetes mellitus (HbA1c< 7%) (group 2).Results: The present study demonstrated statistically significant difference regarding the mean age of both group 1 and group 2 [59.26±12.88 years and 55.24±11.52 years respectively (p <0.05)] and mean duration of diabetes [10.44±8.46 years and 5.96±6.39 years (p=0.0006) respectively]. Moderate physical activity was significantly (p=0.018) associated with good glycaemic control (group 1= 15.7% and group 2= 32.9%). Mean body mass index (BMI) of both group 1 and group 2 were almost equal (23.73±4.72 Kg/ m2 and 23.87±4.86 Kg/ m2 respectively) with no statistical significance and waist hip ratio was 0.98±0.07 and 0.95±0.09 respectively which was statistically significant (p=0.013). Poor economic conditions were significantly associated with uncontrolled blood glucose (p <0.05). Poor glycemic control was also significantly associated with smoking (p=0.00038) and frequent visit with specialist physician (p=0.011). Proper counseling was frequently associated with poor glycaemic control. Most of the patients in group 1 were irregular in dietary habit (58.6%) and exercise (67.1%) and intake of refined sugar (60%) were major contributory factors of poor glycaemic control.Conclusions: Low socioeconomic condition, smoking and intake of refined sugar were the significant modifiable factors that contributed to poor glycaemic control of diabetes. Irregular dietary habits and exercise and proper follow up with specialist physician were more frequent with poor blood glucose control. Proper counseling about diabetes and its management was another modifiable factor. Central obesity and longer duration of diabetes were predisposed to uncontrolled diabetes.Birdem Med J 2018; 8(3): 229-234

Diabetic peripheral neuropathy (DPN) affects over half of type 2 diabetes mellitus (T2DM) patients, with an urgent need for effective pharmacotherapies. While many rat and mouse models of T2DM exist, the phenotyping of DPN has been challenging with inconsistencies across laboratories. To better characterize DPN in rodents, a consensus guideline was published in 2014 to accelerate the translation of preclinical findings. Here we review DPN phenotyping in rat models of T2DM against the ‘Neurodiab’ criteria to identify uptake of the guidelines and discuss how DPN phenotypes differ between models and according to diabetes duration and sex. A search of PubMed, Scopus and Web of Science databases identified 125 studies, categorised as either diet and/or chemically induced models or transgenic/spontaneous models of T2DM. The use of diet and chemically induced T2DM models has exceeded that of transgenic models in recent years, and the introduction of the Neurodiab guidelines has not appreciably increased the number of studies assessing all key DPN endpoints. Combined high-fat diet and low dose streptozotocin rat models are the most frequently used and well characterised. Overall, we recommend adherence to Neurodiab guidelines for creating better animal models of DPN to accelerate translation and drug development.