Inflammatory stress exacerbates hepatic cholesterol accumulation via disrupting cellular cholesterol export

Background and Aim: Both inflammation and cholesterol accumulation play important roles in the development of non‐alcoholic fatty liver disease. This study was undertaken to investigate whether inflammation aggravated cholesterol accumulation via disrupting hepatic cholesterol export and we explored the underlying mechanisms. Methods: We used casein injection in C57BL/6J mice, and tumor necrosis factor alpha (TNF‐α) stimulation in human hepatoblastoma cell line (HepG2) cells to induce inflammation. Intracellular cholesterol level was examined by Oil Red O staining and quantitative analysis. Bile acid level was quantified by colorimetric analysis. ³[H] cholesterol assay by scintillation counting was performed to evaluate the cholesterol efflux. The mRNA and protein expression was examined by real‐time polymerase chain reaction and Western blot. Results: Inflammation increased cholesterol accumulation in livers of C57BL/6J mice and in HepG2 cells. High‐fat diet in mice and low‐density lipoprotein (LDL) loading in HepG2 cells increased bile acid synthesis and cholesterol efflux, enhanced the mRNA and protein expression of liver X receptor α (LXRα), peroxisome proliferator‐activated receptors (PPARα, γ), cholesterol 7α‐hydroxylase (CYP7A1) and ATP‐binding cassette transporter A1 (ABCA1). However, inflammation reduced bile acid synthesis and cholesterol efflux even in high‐fat‐diet‐fed mice and HepG2 cells in the presence of LDL loading. The enhanced effects of these genes and proteins expression due to high‐fat diet and LDL loading were inhibited by inflammation both in vivo and in vitro. Conclusions: Inflammation disrupted PPAR‐LXR‐CYP7A1/ABCA1‐mediated bile acid synthesis and cholesterol efflux resulting in exacerbated cholesterol accumulation in livers of C57BL/6J mice and HepG2 cells.     

Biologic risk factors for low birthweight in Al Ain,United Arab Emirates

A prospective study of biological factors for low birthweight (LBW) among UAE nationals in the Al Ain Medical District was undertaken from 15 January 1992 to 14 January 1993, using a case control method. All 293 mothers of LBW infants and an equal number of mothers of the next normal weight infants born after the LBW infant were studied. Of the 3,485 live births, 293 (8.4%) were LBW (less than 2,500 g). Maternal age less than 25 years, lighter weight at booking, nulliparity, first cousin marriage and short interpregnancy interval (IPI) of 3 months or less significantly increased the risk of LBW in this population. After adjusting for other biologic confounders, only low maternal weight and short IPI significantly increased the risk of LBW. Modification of these biologic risk factors would help to reduce the incidence of LBW among the UAE population. © 1996 Wiley-Liss, Inc.     

Blue-emissive two-component supergelator with aggregation-induced enhanced emission

Two-component organogels offer several advantages over one-component gels, but their design is highly challenging. Hence, it is extremely important to design new approaches for the crafting of two-component organogels with interesting optical and mechanical properties. Herein, we report the design of a new class of two-component supergelators obtained from the assembly between acid functionalized tetraphenylethylene (TPE)-based dendrons and alkylated melamine. No gelation behaviour is observed for the individual components, but interestingly, remarkable gelation behaviour is observed for their hydrogen-bonded complex. The primary driving force responsible for the gelation is the strong π–π stacking interaction of TPE units. Because of the strong π-stacking of TPEs in the gel state, the C(sp²)–C(sp²) bond rotation of the TPE segment is completely arrested in the gel state, which results in intense fluorescence emission of the gels. Furthermore, excellent elastic response is observed for the gels as evident from their high storage modulus compared to loss modulus values. Our results clearly demonstrate that by the appropriate selection of the molecular components, this approach can be applied for the creation of functional nanomaterials with emergent properties absent in the individual blocks.

Design of a novel class of two-component, highly emissive, low molecular weight supergelator is reported.     

Evaluation of Matrix-assisted laser desorption/ionization Time-of flight Mass spectrometry (MALDI TOF MS) and VITEK 2 in routine microbial identification

BacgroundMicrobial Identification was done by phenotypic methods. VITEK-2 and Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) are now being increasingly used in laboratories.ObjectivesTo compare and evaluate the usefulness of MALDI-TOF MS and VITEK-2 in routine microbial identification.MethodsThe performances of MALDI-TOF MS and VITEK 2 were compared for identifying microorganisms.ResultsMALDI- TOF MS and VITEK-2 correctly identified 96 % (96/100) and 97% (97/100) of the isolates upto the genus level.ConclusionMALDI TOF MS and VITEK -2 gave comparable identification and error rates. The rapid reduction in turnaround time with MALDI TOF is a significant game-changer in the field of clinical microbiology.FundingState Board of Medical Research (SBMR).     

Pegylated interferon alfa-2b plus ribavirin for treatment of chronic hepatitis C

AIM: To study the safety and efficacy of pegylated interferon alfa-2b, indigenously developed in India, plus ribavirin in treatment of hepatitis C virus(HCV). METHODS: One-hundred HCV patients were enrolled in an open-label, multicenter trial. Patients were treated with pegylated interferon alfa-2b 1.5 μg/kg per week subcutaneously plus oral ribavirin 800 mg/d for patients with genotypes 2 and 3 for 24 wk. The same dose of peginterferon plus weight-based ribavirin(800 mg/d for ≤ 65 kg; 1000 mg/d for 65-85 kg; 1200 mg/d for 85-105 kg; 1400 mg/d for 105 kg body weight) was administered for 48 wk for patients with genotypes 1 and 4. Serological and biochemical responses of patients were assessed.RESULTS: Eighty-two patients(35 in genotypes 1 and 4 and 47 in 2 and 3), completed the study. In genotype 1, 25.9% of patients achieved rapid virologic response(RVR): while the figures were 74.1% for early virologic response(EVR) and 44.4% for sustained virologic response(SVR). For genotypes 2 and 3, all patients bar one belonged to genotype 3, and of those, 71.4%, 87.5%, and 64.3% achieved RVR, EVR, and SVR, respectively. In genotype 4, 58.8%, 88.2%, and 52.9% of patients achieved RVR, EVR, and SVR, respectively. The majority of patients attained normal levels of alanine aminotransferase by 4-12 wk of therapy. Most patients showed a good tolerance for the treatment, although mild-to-moderate adverse events were exhibited; only two patients discontinued the study medication due to serious adverse events(SAEs). Eleven SAEs were observed in nine patients; however, only four SAEs were related to study medication.CONCLUSION: Peginterferon alfa-2b, which was developed in India, in combination with ribavirin, is a safe and effective drug in the treatment of HCV.     

Electrophysiological and behavioural study of localisation in presence of noise

Objective: The ability to determine the location of the sound source is often important for effective communication. However, it is not clear how the localisation is affected by background noise. In the current study, localisation in quiet versus noise was evaluated in adults both behaviourally, and using MMN and P3b.

Design: The speech token/da/was presented in a multi-deviant oddball paradigm in quiet and in presence of speech babble at +5?dB SNR. The deviants were presented at locations that differed from the standard by 30°, 60° and 90°.

Study sample: Sixteen normal hearing adults between the age range of 18–35?years participated in the study.

Results: The results showed that participants were significantly faster and more accurate at identifying deviants presented at 60° and 90° as compared to 30°. Neither reaction times nor electrophysiological measures (MMN/P3b) were affected by the background noise. The deviance magnitude (30°, 60° and 90°) did not affect the MMN amplitude, but the smaller deviant (30°) generated P3b with smaller amplitude.

Conclusions: Under the stimulus paradigm and measures employed in this study, localisation ability as effectively sampled appeared resistant to speech babble interference.     

Sinonasal organising haematoma – a little known entity

IntroductionSinonasal organising haematoma is a recently described, rare, benign inflammatory condition, which closely resembles malignancy in its clinical presentation.ObjectiveTo describe the clinical features of organising haematoma and to review the evolution of surgical options successfully used.MethodsA retrospective review of charts of all patients with a histopathological diagnosis of sinonasal organising haematoma was performed.ResultsSix (60%) of the 10 patients were male with a mean age of 47.4 years. All patients had unilateral disease with recurrent epistaxis as the presenting symptom. Maxillary sinus was the most commonly involved sinus. There was no history of trauma in any of the patients. Hypertension (80%) was the most commonly associated comorbidity. Contrast-enhanced CT scan of the paranasal sinuses showed heterogeneous sinus opacification with/without bone erosion. Histopathological examination was diagnostic. Complete endoscopic excision was done in all patients resulting in resolution of the disease.ConclusionAwareness of this relatively new clinical entity and its evaluation and treatment is important for otolaryngologists, maxillofacial surgeons and pathologists alike. Despite the clinical picture of malignancy, histopathological features of benign disease can safely dispel such a diagnosis.     

Light and electron microscopic studies on the synovial membrane in reiter's syndrome.

Studies by light microscopy on synovium obtained from 11 patients with Reiter's syndrome during the first month of an episode showed proliferation of synovial lining cells, polymorphonuclear neutrophils among the synovial lining cells, increased surface fibrin, and vascular congestion. Biopsy specimens taken later showed vascular congestion and still proliferated synovial lining cells, fewer polymorphonuclear neutrophils in some, and a tendency toward increased infiltration with lymphocytes and plasma cells. Electron microscopy of samples from 8 patients during the first month of disease activity showed occlusion of vessels by platelets in 4, and fibrin or dense granular material in the vessel walls in 4. Five of the patients with arthritis of less than 4 weeks duration had unidentified intracellular and extracellular particles; some of these were highly suggestive of Chlamydia. No such particles were noted in samples from patients with more chronic cases. Using an antibody to Chlamydia trachomatis and the peroxidase-antiperoxidase technique, immunocytochemistry showed reaction product in synovial macrophages in 2 patients with arthritis of less than 4 weeks duration, but not in the 1 patient studied who had more chronic disease. These studies provide support for dramatic synovial vascular injury consistent with that caused by endotoxin and the presence of chlamydial antigen in synovial macrophages, at least in the early phases of synovitis.