An echo-cardiographic (M-mode & 2D) analysis of thalassaemia major

25 cases of thalassaemia major were studied by 2D and M-mode echocardiography. A significantly increased (p less than 0.001) mean value (100.8 +/- 27.37 msec, range 80 to 140 msec) of A2-E (early relaxation period) interval on M-mode was observed in thalassemia in comparison to mean level (82.6 +/- 5.7, range 60 to 100 msec) of control population. No significant differences were noted in FS % (fractional shortening) and EF% (ejection fraction) when compared to corresponding normal values respectively. Mean serum iron concentration (142.2 +/- 29.1 micrograms/dl, range 102 to 192 micrograms/dl) was significantly higher in thalassaemia as compared to normal population (mean 106.3 +/- 11.4 micrograms/dl, range 75 to 120 micrograms/dl). There was also a direct correlation between serum iron concentration and A2-E interval. 11 patients (44%) showed abnormal A2-E interval but only 3 patients (12%) showed abnormal percentage of FS and EF. It is therefore concluded that A2-E interval will help to detect early left ventricular dysfunction much before overt and irreversible heart failure becomes manifest and which will also help to optimise transfusion and chelation therapy.     

The genetic effect of the apoprotein AV gene on the serum triglyceride level in Japanese

The newly identified apoprotein AV (apoAV) gene was suggested to have a significant effect on triglyceride (TG) metabolism in Caucasians. We studied the genetic effect of this gene on serum TG in a Japanese population. Participants (481 male and 412 female) were recruited at a health examination. A T/C single nucleotide polymorphism called SNP3 in the 5'-region of the apoAV gene was genotyped as described previously. The frequency of the C allele was much greater in Japanese than in Caucasians (0.34 vs. 0.08). The serum TG level in subjects with the TT genotype was significantly lower than the level in those with TC/CC (1.10, 1.25 and 1.21 mmol/l for TT, TC and CC, respectively, P=0.0003 by ANOVA), while there were no significant differences either in the serum total cholesterol or the low- and high-density lipoprotein cholesterol levels among the three genotypes. Multiple regression analysis indicated that SNP3 had a significant independent effect on the serum TG level in Japanese (P<0.0001). This result indicates that polymorphism in the apoAV gene influence serum TG in populations of different ethnicities.     

Histological observations on the anterior olfactory nucleus in human

Aim: Localization of isolated clusters of anterior olfactory nucleus (AON) in a human olfactory bulb and tract. Materials and methods: This investigation was done on human olfactory bulbs and their tracts, collected from the freshly donated cadavers, before embalming, in the Department of Anatomy, IPGMER, Kolkata. H&E stained histological slides were prepared along the whole length of specimens and examined under a Leica DM 2000 microscope and with a Leica Quin image analyzer. Results: The anterior olfactory nucleus was detected in the form of a major cluster and in two smaller clusters of neurons. The major cluster was located at the caudal pole of the bulb and was composed of medium-sized triangular cells which had an average diameter of 13.92 ± 3.43 μm. Out of the two minor clusters, one was detected at the beginning and another at the middle of the olfactory tract. Here neurons were little larger in size and their diameter ranged approximately 15–17 μm. Olfactory striae also accommodated some neurons in a scattered manner. Conclusion: This observation will be helpful in exploration of the complex role of AON in the organization and function of the olfactory system and its clinical significance in human.     

Determination of the safety and efficacy of therapeutic neutralization of tumor necrosis factor-α (TNF-α) using AZD9773, an anti-TNF-α immune Fab, in murine CLP sepsis

Objective and design

TNF-α neutralization is associated with increased mortality in mouse cecal ligation puncture (CLP) models. AZD9773 is an ovine polyclonal human TNF-α immune Fab, with pharmacological properties that differ from previously studied anti-TNF-α agents. We explored the safety and efficacy of therapeutically administered AZD9773 in mouse CLP sepsis.

Methods

A moderate/severe-grade CLP model resulting in 20–30 % 5-day survival and a mild-grade CLP model resulting in ~70 % 5-day survival were established in human TNF-α transgene/murine TNF null (Tg1278/?/?) mice.

Treatment

Mice received saline resuscitation and imipenem administration every 12 h (0–72 h post-CLP). AZD9773 (or DigiFab control) was dosed 24, 36, 48 and 60 h post-CLP.

Results

Therapeutic dosing of AZD9773 in moderate/severe-grade CLP resulted in significantly increased survival (>70 %) compared with DigiFab (27 %, P < 0.05). Therapeutic dosing of AZD9773 in mild-grade CLP did not significantly affect survival outcome compared with DigiFab or imipenem alone (~60–70 % survival).

Conclusions

These data demonstrate that TNF-α neutralization can improve survival in moderate/severe CLP sepsis. TNF-α suppression in mild-grade models was not associated with survival benefit and did not increase 5-day mortality. These findings suggest that therapeutic benefit following TNF-α attenuation in models of sepsis may depend on model severity.     

Low Concentration of a Dioxin (2, 3, 7, 8 TCDD) Affects the Glycosidases and Acid Phosphatase Activity in Mice Hepatocytes

Present communication reports the effects of environmentally available, low doses of tetra chloro di benzo-p-dioxin (2,3,7,8 TCDD) to lysosomal enzymes in mice liver. The study tests the hypothesis, in vivo exposure of low dose TCDD provokes dose and duration dependent toxic effects to key lysosomal enzymes and thereby causes cellular apoptotic changes. Three groups of female Swiss albino mice were subjected to two doses of TCDD (0.004 mg/kg bw/d, 0.04 mg/kg bw/d) for 2, 4 and 6 days of exposure durations. The results indicated significant exposure duration dependent effects of TCDD in mice liver cells. The results suggested that TCDD possibly induced an increase in intracellular ions or ROS which in turn altered different physiological activities by affecting different metabolic pathway of the liver cells. The altered functions of key lysosomal enzymes by TCDD may also evoke the process of cellular apoptosis.     

Andrographolide inhibits human serum albumin fibril formations through site-specific molecular interactions

Protein misfolding and fibrillation are the fundamental traits in degenerative diseases like Alzheimer''s, Parkinsonism, and diabetes mellitus. Bioactives such as flavonoids and terpenoids from plant sources are known to express protective effects against an array of diseases including diabetes, Alzheimer''s and obesity. Andrographolide (AG), a labdane diterpenoid is prescribed widely in the Indian and Chinese health care systems for classical efficacy against a number of degenerative diseases. This work presents an in depth study on the effects of AG on protein fibrillating pathophysiology. Thioflavin T fluorescence spectroscopy and DLS results indicated concentration dependent inhibition of human serum albumin (HSA) fibrillation. The results were confirmed by electron microscopy studies. HSA fibril formations were markedly reduced in the presence of AG. Fluorescence studies and UV-Vis experiments confirmed further that AG molecularly interacts with HSA at site. In silico molecular docking studies revealed hydrogen bonding and hydrophobic interactions with HSA in the native state. Thus AG interacts with HSA, stabilizes the native protein structure and inhibits fibrillation. The results demonstrated that the compound possesses anti-amyloidogenic properties and can be promising against some human degenerative diseases.

Andrographolide inhibited HSA protein fibrillation through site specific interactions.     

Purification and Characterization of Alkaline Protease from Bacillus sp. HD292

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Proteolytic enzymes form a very significant group of enzymes which are used for a variety of purposes...