Recombinant single-chain anti-idiotypic antibody: an effective fungal beta-1,3-glucan synthase inhibitor

Recombinant single-chain fragment variable anti-idiotypic antibodies were produced to represent the internal image of HM-1 killer toxin and were used as novel and effective antifungal agents to inhibit in vitro beta-1,3-glucan synthase and cell growth. The mechanism of cytocidal activity of anti-idiotypic antibodies was investigated and was compared with the actions of aculeacin A and papulacandin B, the most common antibiotics acting as beta-1,3-glucan synthase inhibitors. The degree of inhibition of beta-1,3-glucan synthase by both antibodies and antibiotics were examined for yeasts Saccharomyces cerevisiae A451, Cryptococcus albidus NBRC 0612 and Candida albicans IFM 40215. Although the mechanism of actions of the anti-idiotypic antibodies and antibiotics seems identical, the IC(50) values for the various yeasts used in this study confirmed that anti-idiotypic antibodies could be used as more effective fungal beta-1,3-glucan synthase inhibitors than those of antibiotics.     

Prevalence and risk factors for diabetic retinopathy--a study of 217 patients from University of Malaya Medical Centre

Two hundred and seventeen diabetic patients attending the eye clinic were examined to determine the prevalence of retinal changes, and the association between diabetic retinopathy and risk factors. A detailed fundus examination was done, after dilating the pupils, using 90 D lens and slitlamp biomicroscope. Diabetic retinopathy was detected in 112 patients (51.6%). Background retinopathy was seen in 40 out of 217 (18.4%), pre-proliferative retinopathy in 11 (5.1%), proliferative retinopathy in 61 (28.1%) and maculopathy in 58 (26.7%) patients. Factors significantly associated with occurrence of retinopathy were duration of diabetes, presence of hypertension and presence of systemic complications (diabetic foot ulcer, lower limb amputation, nephropathy, and peripheral neuropathy).     

Microcystins (cyanobacterial toxins) in surface waters of rural Bangladesh: pilot study

In Bangladesh the exposure of millions of inhabitants to water from (shallow) tube wells contaminated with high geogenic loads of arsenic is a major concern. As an alternative to the costly drilling of deep wells, the return to the use of surface water as a source of drinking water is considered. In addition to the well-known hazards of water borne infectious diseases associated with the use of surface water, recently the potential public health implications of toxic cyanobacteria have been recognized. As a first step towards a risk assessment for cyanotoxins in Bangladesh surface waters, seston samples of 79 ponds were analysed in late summer 2002 for the presence of cyanobacteria and microcystins (MCYST), the most frequently detected cyanobacterial toxins worldwide. Microcystins could be detected in 39 ponds, mostly together with varying abundance of potentially microcystin-producing genera such as Microcystis, Planktothrix and Anabaena. Total microcystin concentrations ranged between <0.1 and > 1,000 microg l(-1), and more than half of the positive samples contained high concentrations of more than 10 microg l(-1). The results clearly show that concentrations of microcystins well above the provisional WHO guideline value of 1 microg l(-1) MCYST-LR can be frequently detected in Bangladesh ponds. Thus, an increasing use of surface water for human consumption introduces a risk of replacing one health hazard by another and therefore needs to be accompanied by cyanotoxin hazard assessments.     

Diagnostic value of a group of biochemical markers of liver fibrosis in patients with non‐alcoholic steatohepatitis

OBJECTIVE:  The objectives of this study were to investigate the use of non‐invasive biochemical markers to evaluate the severity of liver fibrosis in patients with non‐alcoholic steatohepatitis (NASH). METHODS:  This was a cross‐sectional study of patients with histopathologically confirmed NASH between January 2005 and December 2006. The patients’ characteristics were recorded and the body mass index was calculated for each patient. All patients underwent ultrasound‐guided liver biopsy and a fibrosis assessment was performed using the Brunt criteria. The non‐invasive laboratory markers measured were insulin resistance, tumor necrosis factor (TNF‐α), type IV collagen and hyaluronic acid (HA). RESULTS:  Thirty patients were recruited, of whom 18 (60%) were men. Their mean age was 45 ± 13.9 (18–71) years. About 83% of patients had fibrosis stage 1–2. In bivariate analysis, age, TNF‐α and type IV collagen concentrations showed a weak but significant correlation with the fibrosis stage. When the patients were grouped into mild fibrosis (stages 1–2) and advanced fibrosis (stages 3–4), the mean concentrations of HA and type IV collagen were significantly higher in those with advanced fibrosis than those with mild fibrosis (180.8 ± 49.63 vs 543.6 ± 360.45 ng/mL; for HA; P = 0.026 and 125.3 ± 32.11 vs 288.0 ± 171.22 ng/mL for type IV collagen; P = 0.010). CONCLUSION:  Our study showed that the degree of liver fibrosis was significantly correlated with age, TNF‐α and type IV collagen concentrations. The level of HA and type IV collagen could differentiate between mild (F1–2) and advanced fibrosis (F3–4).     

Potent α-glucosidase and protein tyrosine phosphatase 1B inhibitors from Artemisia capillaris

As a part of our ongoing effort to identify anti-diabetic constituents from natural sources, we examined the inhibitory activity of the methanol extracts of 12 species of the genus Artemisia, against α-glucosidase and protein tyrosine phosphatase 1B (PTP1B). The methanol extracts of different species exhibited promising α-glucosidase and PTP1B inhibitory activities. Since the methanol extract of Artemisia capillaris exhibited the highest α-glucosidase inhibitory activity together with significant PTP1B inhibitory activity, it was selected for further investigation. Repeated column chromatography based on bioactivity guided fractionation yielded 10 coumarins (esculetin, esculin, scopolin, isoscopolin, daphnetin, umbelliferone, 7-methoxy coumarin, scoparone, scopoletin, 6-methoxy artemicapin C), 8 flavonoids (hyperoside, quercetin, isorhamnetin, cirsilineol, arcapillin, isorhamnetin 3-robinobioside, linarin, isorhamnetin 3-glucoiside), 6 phenolic compounds (1,5-dicaffeoylquinic acid, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid methyl ester, 4,5-dicaffeoylquinic acid, 3-caffeoylquinic acid), and one chromone (capillarisin). Among these compounds, esculetin, scopoletin, quercetin, hyperoside, isorhamnetin, 3,5-dicaffeoylquinic acid methyl ester, 3,4-dicaffeoylquinic acid, and 1,5-dicaffeoylquinic acid exhibited potent α-glucosidase inhibitory activity when compared to the positive control acarbose. In addition, esculetin and 6-methoxy artemicapin C displayed PTP1B inhibitory activity. Interestingly, all isolated dicaffeoylquinic acids showed significant PTP1B inhibitory activity. Therefore, the results of the present study clearly demonstrate the potential of the A. capillaris extract to inhibit α-glucosidase and PTP1B. These inhibitory properties can be largely attributed to a combination of different chemical structures, including coumarins, flavonoids, and dicaffeoylquinic acids, which could be further explored to develop therapeutic or preventive agents for the treatment of diabetes.     

Suppression of c-Fos Protein and mRNA Expression in Pentylenetetrazole-Induced Kindled Mouse Brain by Isoxylitones

An early immediate gene c-fos has been proposed as the gene responsible for turning on molecular events that might underlie the long-term neural changes occurring during kindling. We have evaluated the effects of novel anticonvulsant isomeric compounds isoxylitones [(E/Z)-2-propanone-1,3,5,5-trimethyl-2-cyclohexen-1-ylidine] on the c-Fos protein and mRNA expression in the brain samples of kindled mice and compared it with the normal and untreated kindled groups. Kindling was induced in male NMRI mice by repeated administration of sub-convulsive dose (50 mg/kg) of pentylenetetrazole (PTZ) until a seizure score of 4-5 was achieved. The c-Fos expression was quantified by combination of immunohistochemistry and RT-PCR protocols. Both the immunohistochemical and RT-PCR analysis revealed a marked increase in the expression of c-fos mRNA and protein in the brain regions tested in case of PTZ-kindled control group compared to normal control. In contrast, the isoxylitone (30 mg/kg)-treated group demonstrated significant reduction of c-Fos expression compared to PTZ-kindled control animals. However, low expression of c-fos mRNA was only detected in the thalamus of the isoxylitone-treated brain samples. Based on these observations, we suggest that isoxylitones may have the capacity to control the seizure pattern by mechanism such as the suppression of c-Fos protein and mRNA levels in different regions of the brain. Further investigations to explore the mechanism of action of these compounds are under process.     

Insights into the p-nitrophenol adsorption by amidoxime-modified poly(acrylonitrile-co-acrylic acid): characterization,kinetics, isotherm,thermodynamic, regeneration and mechanism study

This study performs an appraisal of the adsorptive capacity of amidoxime-modified poly(acrylonitrile-co-acrylic acid) or abbreviated as (AO-modified poly(AN-co-AA)) for the p-nitrophenol (PNP) adsorption, from aquatic environments via batch system. The AO-modified poly(AN-co-AA) polymer was developed with redox polymerization, and then altered by using hydroxylamine hydrochloride (HH). Tools used to describe the physicochemical and morphological characteristics of the AO-modified poly(AN-co-AA) were Fourier transform infrared (FTIR) spectroscopy, CHN elemental analysis, X-ray diffraction analysis (XRD) and scanning electron microscopy (SEM). The adsorption kinetics were examined by pseudo-first order, pseudo-second order, Elovich and intraparticle diffusion kinetic models. Meanwhile, the isotherms were investigated by Langmuir, Freundlich, Temkin and Redlich–Peterson models. It was found that the adsorption was best fitted with pseudo-second order, and agreed with both Langmuir and Freundlich isotherm models. It was described best with the Freundlich isotherm due to highest R² (0.999). The maximum adsorption capacity was 143.06 mg g⁻¹ at 298 K, and thermodynamic functions showed that the adsorption process was exothermic. Also, following five regeneration cycles, the adsorbent recorded 71.7% regeneration efficiency. The finding in this study indicates that the AO-modified poly(AN-co-AA) is an effective adsorbent to remove PNP from an aqueous solution.

This study performs an appraisal of the adsorptive capacity of amidoxime-modified poly(acrylonitrile-co-acrylic acid) for the p-nitrophenol (PNP) adsorption, from aqueous solutions.     

Non-tuberculous mycobacterium bacteraemia in a pregnant systemic lupus erythematosus (SLE) patient: a case review and pooled case analysis

Clinical Rheumatology - Non-tuberculous mycobacteria (NTM) are recognized as an important cause of human diseases and infections. It is commonly known to cause infections of the skin, soft tissue...