First evidence of comparative responses of Toll-like receptor 22 (TLR22) to relatively resistant and susceptible Indian farmed carps to Argulus siamensis infection

Toll-like receptor 22 (TLR22) is present in teleost but not in mammals. Among Indian farmed carps, Catla catla is relatively more resistant than Labeo rohita to Argulus siamensis lice infection. TLR22 is believed to be associated with innate immunity against ectoparasite infection. To investigate the TLR22 mediated immunity against argulosis, we have cloned and characterized TLR22 genes of L. rohita (rTLR22) and C. catla (cTLR22). The full-length cDNAs of rTLR22 and cTLR22 contained an open reading frame of 2838 and 2841 nucleotides, respectively; bearing the typical structural features. Phylogenetically rTLR22/cTLR22 was most closely related to Cyprinus carpio (common carp) counterpart, having highest sequence identity of 86.0%. The TIR domain remained highly conserved with 90% identity within freshwater fishes. The sequence information of cDNA and genomic DNA together revealed that the rTLR22/cTLR22 genes are encoded by uninterrupted exons. The co-habitation challenge study with A. siamensis infection confirmed that C. catla is comparatively more resistant than L. rohita. Further, comparative mRNA expression profile in immune relevant tissues also suggested about the participatory role of TLR22 during lice infection. However, TLR22 might not solely be involved in conferring relative resistance among carp species against argulosis.     

Oro-nasal fistula of infective origin and alveolar necrosis in a 13 year old boy.

An unusual case of oronasal fistulla of infective origin in a patient with a previous history of aplastic anemia and cancrum oris is discussed here in this report. As the general condition of the patient was not favouring the surgical closure, an obturator was fabricated and inserted to relieve the problems of regurgitation of food and fluids into the nasal cavity.     

Neuroprotective effect of Tinospora cordifolia ethanol extract on 6-hydroxy dopamine induced Parkinsonism

Objective:

The present study investigates the neuroprotective activity of ethanol extract of Tinospora cordifolia aerial parts against 6-hydroxy dopamine (6-OHDA) lesion rat model of Parkinson''s disease (PD).

Materials and Methods:

T. cordifolia ethanol extract (TCEE) was standardized with high performance thin layer chromatography using berberine. Experimental PD was induced by intracerebral injection of 6-OHDA (8 μg). Animals were divided into five groups: sham operated, negative control, positive control (levodopa 6 mg/kg) and two experimental groups (n = 6/group). Experimental groups received 200 and 400 mg/kg of TCEE once daily for 30 days by oral gavage. Biochemical parameters including dopamine level, oxidative stress, complex I activity and brain iron asymmetry ratio and locomotor activity including skeletal muscle co-ordination and degree of catatonia were assessed.

Results:

TCEE exhibited significant neuroprotection by increasing the dopamine levels (1.96 ± 0.20 and 2.45 ± 0.40 ng/mg of protein) and complex I activity (77.14 ± 0.89 and 78.50 ± 0.96 nmol/min/mg of protein) at 200 and 400 mg/kg respectively when compared with negative control group. Iron asymmetry ratio was also significantly attenuated by TCEE at 200 (1.57 ± 0.18) and 400 mg/kg (1.11 ± 0.15) when compared with negative control group. Neuroprotection by TCEE was further supported by reduced oxidative stress and restored locomotor activity in treatment groups.

Conclusion:

Results show that TCEE possess significant neuroprotection in 6-OHDA induced PD by protecting dopaminergic neurons and reducing the iron accumulation.KEY WORDS: Complex I activity, dopamine, iron asymmetry, levodopa, neurodegeneration     

Administration of a tumor necrosis factor inhibitor at the time of myocardial infarction attenuates subsequent ventricular remodeling.

BACKGROUND: Tumor necrosis factor (TNF) causes myocardial extracellular matrix remodeling and fibrosis in myocardial infarction and chronic heart failure models. Pre-clinical and clinical trials of TNF inhibition in chronic heart failure have shown conflicting results. This study examined the effects of the administration of a TNF inhibitor immediately after myocardial infarction on the development of heart failure. METHODS: Lewis rats underwent coronary artery ligation and then received either intravenous etanercept (n = 14), a soluble dimerized TNF receptor that inhibits TNF, or saline as control (n = 13). Leukocyte infiltration into the infarct borderzone was evaluated 4 days post-ligation in 7 animals (etanercept = 4, control = 3). After 6 weeks, the following parameters were evaluated in the remaining animals: cardiac function with a pressure-volume conductance catheter, left ventricular (LV) geometry, and borderzone collagenase activity. RESULTS: Etanercept rats had significantly less borderzone leukocyte infiltration 4 days post-infarction than controls (10.7 +/- 0.5 vs 18.0, +/-2.0 cells/high power field; p < 0.05). At 6 weeks, TNF inhibition resulted in significantly reduced borderzone collagenase activity (110 +/- 30 vs 470 +/- 140 activity units; p < 0.05) and increased LV wall thickness (2.1 +/- 0.1 vs 1.8 +/- 0.1 mm, p < 0.05). Etanercept rats had better systolic function as measured by maximum LV pressure (84 +/- 3 mm Hg vs 68 +/- 5 mm Hg, p < 0.05) and the maximum change in left ventricular pressure over time (maximum dP/dt) (3,110 +/- 230 vs 2,260 +/- 190 mm Hg/sec, p < 0.05), and better diastolic function as measured by minimum dP/dt (-3,060 +/- 240 vs -1,860 +/- 230 mm Hg/sec; p < 0.05) and the relaxation time constant (14.6 +/- 0.6 vs 17.9 +/- 1.2 msec; p < 0.05). CONCLUSIONS: TNF inhibition after infarction reduced leukocyte infiltration and extracellular matrix turnover and preserved cardiac function.     

Biochemical and histochemical changes pertaining to active and healed cutaneous tuberculosis

BACKGROUND: Fibrosis is one of the major causes of post-treatment morbidity in tuberculosis. The molecular basis of fibrosis in active and healed tuberculous lesions is yet to be fully characterized. OBJECTIVES: To measure the tissue levels of collagen, elastin, fibronectin, transforming growth factor-beta (TGF-beta) and zinc in active and healed lesions of cutaneous tuberculosis. PATIENTS AND METHODS: Biopsy lesions obtained from 17 patients with active cutaneous tuberculosis and 12 patients after a 6-month regimen of antituberculous chemotherapy were examined. Collagen, elastin and zinc were estimated biochemically. In addition, the presence of collagen IV, TGF-beta and fibronectin were determined immunohistochemically. RESULTS: It was found that collagen, elastin, fibronectin and TGF-beta levels were higher in the active lesions. The levels of zinc were similar in both active and healed lesions. Clinically, scar tissue or keloid formation was not seen in any of the healed lesions. CONCLUSIONS: Effective antituberculous chemotherapy will lead to a substantial reduction of fibrosis and the consequent disability that can arise in patients with tuberculosis.     

Nitrogen laser irradiation (337 nm) causes temporary inactivation of clinical isolates of <Emphasis Type="Italic">Mycobacterium tuberculosis</Emphasis>

We have investigated the effect of nitrogen laser irradiation (337 nm) on viability of clinical isolates of Mycobacterium tuberculosis. Bacteria were exposed to a nitrogen laser (average power 2.0 mW) in vitro at power density of 70 ± 0.7 W/m² for 0–30 min, and the cell viability was determined by luciferase reporter phage (LRP) assay. Immediately after laser exposure, all the clinical isolates investigated showed a dose-dependent decrease in cell viability. However, when the laser-exposed isolates were incubated in broth medium for 3 days, most of these showed significant recovery from laser-induced damage. Addition of 5.0 g/ml acriflavine (a DNA repair inhibitor) in the incubation medium had no significant effect on recovery. This suggests that DNA damage may not be involved in the cell inactivation. Electron paramagnetic resonance (EPR) studies using 5-doxyl strearic acid (5-DS) as a probe suggest alterations in lipid regions of the cell wall. Implications of these results for understanding therapeutic effect of nitrogen laser on drug-resistant tuberculosis are discussed.Abbreviations 5-DS 5-Doxyl strearic acid - INH Isoniazid - LRP Luciferase reporter phage - M.tb Mycobacterium tuberculosis - RLU Relative light unit - RMP Rifampicin     

Effect of Crude Extract of Eugenia jambolana Lam. on Human Cytochrome P450 Enzymes

The fruit of Eugenia jambolana Lam. is very popular for its anti‐diabetic property. Previous studies on the crude extract of E. jambolana (EJE) have successfully explored the scientific basis for some of its traditional medicinal uses. Considering its wide use and consumption as a seasonal fruit, the present study investigates the ability of E. jambolana to interact with cytochrome P450 enzymes. The standardized EJE was incubated with pooled human liver microsomes to assess the CYP2C9‐, CYP2D6‐, and CYP3A4‐mediated metabolism of diclofenac, dextromethorphan, and testosterone, respectively. The metabolites formed after the enzymatic reactions were quantified by high performance liquid chromatography. EJE showed differential effect on cytochrome P450 activities with an order of inhibitory potential as CYP2C9 > CYP3A4 > CYP2D6 having IC₅₀ of 76.69, 359.02, and 493.05 µg/mL, respectively. The selectivity of EJE for CYP2C9 rather than CYP3A4 and CYP2D6 led to perform the enzyme kinetics to explicate the mechanism underlying the inhibition of CYP2C9‐mediated diclofenac 4′‐hydroxylation. EJE was notably potent in inhibiting the reaction in a non‐competitive manner with K_i of 84.85 ± 5.27 µg/mL. The results revealed the CYP2C9 inhibitory potential of EJE with lower K_i value suggesting that EJE should be examined for its potential pharmacokinetic and pharmacodynamic interactions when concomitantly administered with other drugs. Copyright © 2014 John Wiley & Sons, Ltd.     

Endoprosthetic reconstruction using total femoral custom mega prosthesis in malignant bone tumours

We analysed 17 patients with primary malignant bone tumour of the femur who underwent limb salvage surgery with the total femoral custom mega prosthesis during the period 1994–2008. The patients were in the age group of 12–73 years, with a mean age of 30.94 years. There were 14 males. The most common diagnosis was osteosarcoma. The average follow-up period was 54.05 months with the longest being 168 months. The average Musculoskeletal Tumour Society (MSTS) functional score was 66.6%. The two- to 14-year overall survival was 82.4%. Three patients died of disease and one patient required amputation. Complications encountered were deep infection and dislocation of the prosthesis.     

Targeted overexpression of growth hormone by adenoviral gene transfer preserves myocardial function and ventricular geometry in ischemic cardiomyopathy

BACKGROUND: Post-infarction heart failure is characterized by progressive left ventricular dilatation and wall thinning, with both systolic and diastolic cardiac dysfunction. Human growth hormone (GH) stimulates cardiac hypertrophy when secreted in excess and directly enhances cardiomyocyte contractile function. We hypothesized that local myocardial overexpression of GH could prevent ventricular remodeling and heart failure following myocardial infarction (MI) in rats. METHODS AND RESULTS: Rats underwent ligation of the left anterior descending coronary artery with direct intramyocardial injection of adenovirus encoding human GH (n = 8) or null virus as control (n = 8). Six weeks following MI, Adeno-GH treated animals had significant preservation of both systolic and diastolic cardiac function compared to Null animals (maximum dP/dt GH 2927 +/- 83 vs Null 1622 +/- 159 mmHg/sec, p < 0.001; minimum dP/dt -2409 +/- 82 vs -1195 +/- 179 mmHg/sec, p < 0.01). GH animals had improved ventricular geometry with decreased chamber dilatation (13.2 +/- 0.13 vs 14.4+/-0.15 mm, p < 0.001) and increased wall thickness (2.02 +/- 0.10 vs 1.28 +/- 0.07 mm, p < 0.001), and this was associated with advantageous myocardial hypertrophy with increased cardiomyocyte fiber size. Local myocardial overexpression of GH protein was seen in Adeno-GH animals, while serum levels of human GH were undetectable after 6 weeks. CONCLUSIONS: Treatment with Adeno-GH following MI resulted in reduced ventricular dilatation, increased local myocardial hypertrophy, and preservation of both systolic and diastolic cardiac function. No significant systemic exposure to growth hormone transgene was observed. The induction of regional hypertrophy is a novel approach to treating heart failure, and may be useful to treat or prevent post-infarction ischemic cardiomyopathy.     

Taxonomic and Biochemical Composition and Digestive Enzyme Activity of Periphyton and Plankton: A Comparative Study

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Periphyton grown on sugarcane bundles was analyzed for major digestive enzymes in order to quantify their...