Scrutinizing the therapeutic response of Phyllanthus exmblica's different doses to restore the immunomodulation potential in immunosuppressed female albino rats.

OBJECTIVE: Immunosuppression and microbial resistance are the major drawbacks in conventional pharmaceutics. The present research work was planned to screen and characterize phytochemical constituents present in Phyllanthus emblica and to explore the immunomodulation potential of P. emblica by evaluating stress markers and different biochemical parameters in animals. MATERIALS AND METHODS: The phytochemical analysis explored the presence of antioxidant profiles and revealed the radical scavenging activities. In the second phase, an animal trial was performed using female albino rats. Female rats (n=18) were administered three different doses of P. emblica (low dose 100 mg/kg, intermediate 200 mg/kg, and high dose 300 mg/kg) for three weeks. After a significant change (p<0.05) in antioxidant status i.e., TOS and TAS, hematological, biochemical parameters, and immunoregulation i.e., IgM and IgG were elevated. Statistical analysis (ANOVA) illustrates that these selected plants have a great impact on microbial resistance and immunosuppression and have shown highly significant results. RESULTS: The results of all in vitro and in vivo assays conducted as part of the recent research work offer considerable evidence that the chosen medicinal plant has the ability to induce specific hormone release and boost the immune system. CONCLUSIONS: Based on our findings, it is proposed that medicinal herbs may be isolated using cutting-edge approaches to tackle the issues of immunosuppression and microbial resistance.

A High-Throughput Assay for In Vitro Determination of Release Factor-Dependent Peptide Release from a Pretermination Complex by Fluorescence Anisotropy-Application to Nonsense Suppressor Screening and Mechanistic Studies.

Premature termination codons (PTCs) account for ~12% of all human disease mutations. Translation readthrough-inducing drugs (TRIDs) are prominent among the several therapeutic approaches being used to overcome PTCs. Ataluren is the only TRID that has been approved for treating patients suffering from a PTC disease, Duchenne muscular dystrophy, but it gives variable readthrough results in cells isolated from patients suffering from other PTC diseases. We recently elucidated ataluren's mechanism of action as a competitive inhibitor of release factor complex (RFC) catalysis of premature termination and identified ataluren's binding sites on the ribosome responsible for such an inhibition. These results suggest the possibility of discovering new TRIDs, which would retain ataluren's low toxicity while displaying greater potency and generality in stimulating readthrough via the inhibition of termination. Here we present a detailed description of a new in vitro plate reader assay that we are using both to screen small compound libraries for the inhibition of RFC-dependent peptide release and to better understand the influence of termination codon identity and sequence context on RFC activity.

Early Postmarket Results with EmboTrap II Stent Retriever for Mechanical Thrombectomy: A Multicenter Experience.

BACKGROUND AND PURPOSE: EmboTrap II is a novel stent retriever with a dual-layer design and distal mesh designed for acute ischemic stroke emergent large-vessel occlusions. We present the first postmarket prospective multicenter experience with the EmboTrap II stent retriever. MATERIALS AND METHODS: A prospective registry of patients treated with EmboTrap II at 7 centers following FDA approval was maintained with baseline patient characteristics, treatment details, and clinical/radiographic follow-up. RESULTS: Seventy patients were treated with EmboTrap II (mean age, 69.9 years; 48.6% women). Intravenous thrombolysis was given in 34.3%, and emergent large-vessel occlusions were located in the ICA (n = 18), M1 (n = 38), M2 or M3 (n = 13), and basilar artery (n = 1). The 5 × 33 mm device was used in 88% of cases. TICI ≥ 2b recanalization was achieved in 95.7% (82.3% in EmboTrap II-only cases), and first-pass efficacy was achieved in 35.7%. The NIHSS score improved from a preoperative average of 16.3 to 12.1 postprocedure and to 10.5 at discharge. An average of 2.5 [SD, 1.8] passes was recorded per treatment, including non-EmboTrap attempts. Definitive treatment was performed with an alternative device (aspiration or stent retriever) in 9 cases (12.9%). Some hemorrhagic conversion was noted in 22.9% of cases, of which 4.3% were symptomatic. There were no device-related complications. CONCLUSIONS: Initial postmarket results with the EmboTrap II stent retriever are favorable and comparable with those of other commercially available stent retrievers. Compared with EmboTrap II, the first-generation EmboTrap may have a higher first-pass efficacy; however, data are limited by retrospective case analysis, incomplete clinical follow-up, and small sample size, necessitating future trials.

Oscillations of the bandgap with size in armchair and zigzag graphene quantum dots.

We determine here the evolution of the bandgap energy with size in graphene quantum dots (GQDs). We find oscillatory behaviour of the bandgap and explain its origin in terms of armchair and zigzag edges. The electronic energy spectra of GQDs are computed using both the tight binding model and ab initio density functional methods. The results of the tight binding model are analyzed by dividing zigzag graphene quantum dots into concentric rings. For each ring, the energy spectra, the wave functions and the bandgap are obtained analytically. The effect of inter-ring tunneling on the energy gap is determined. The growth of zigzag terminated GQD into armchair GQD is shown to be associated with the addition of a one-dimensional Lieb lattice of carbon atoms with a shell of energy levels in the middle of the energy gap of the inner zigzag terminated GQD. This introduces a different structure of the energy levels at the bottom of the conduction and top of the valence band in zigzag and armchair GQD which manifests itself in the oscillation of the energy gap with increasing size. The evolution of the bandgap with the number of carbon atoms is compared with the notion of confined Dirac Fermions and tested against ab initio calculations of Kohn-Sham and TD-DFT energy gaps.

Elucidation of binding mode and three dimensional quantitative structure-activity relationship studies of a novel series of protein kinase B/Akt inhibitors.

Protein kinase B (PKB; also known as Akt kinase) is located downstream in the PI-3 kinase pathway. Overexpression and constitutive activation of PKB/Akt leads to human prostate, breast and ovarian carcinomas. A series of 69 PKB/Akt inhibitors were examined to explore their binding modes using FlexX, and three-dimensional quantitative structure-activity relationship (3D-QSAR) studies based on comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed to provide structural insights into these compounds. CoMFA produced statistically significant results, with cross-validated q ( 2 ) and non-cross validated correlation r(2) coefficients of 0.53 and 0.95, respectively. For CoMSIA, steric, hydrophobic and hydrogen bond acceptor fields jointly yielded 'leave one out' q(2) = 0.51 and r(2) = 0.84. The predictive power of CoMFA and CoMSIA was determined using a test set of 13 molecules, which gave correlation coefficients, r(2)(predictive) of 0.58 and 0.62, respectively. Molecular docking revealed that the binding modes of these molecules in the ATP binding sites of the Akt kinase domain were very similar to those of the co-crystallized ligand. The information obtained from 3D contour maps will allow the design of more potent and selective Akt kinase inhibitors.

Role of otoacoustic emission in children with middle-ear effusion and grommets.

OBJECTIVE: To evaluate the role of otoacoustic emission in children with middle-ear effusion and grommets. MATERIALS AND METHODS: A prospective study was carried out on a total of 90 ears. All children listed for grommet insertion had a pre-operative and post-operative (three to six months after grommet insertion) pure tone audiometry, tympanometry and otoacoustic emission recorded. A comparison was made between pure tone audiometry and otoacoustic emission both pre-operatively and post-operatively. RESULTS: Pre-operatively, 63 ears had an abnormal pure tone audiometry of which 59 had absent otoacoustic emission. Therefore the sensitivity of otoacoustic emission in detecting a conductive loss was 59/63 = 94 per cent (95 per cent confidence interval 85 to 98 per cent). All 27 ears with normal hearing pre-operatively had normal otoacoustic emission. The specificity of otoacoustic emission was 27/27 = 100 per cent, (95 per cent confidence interval, 88 to 100 per cent). The positive predictive value was 59/59 = 100 per cent (95 per cent confidence interval, 94 to 100 per cent). After three to six months all post-operative patients with grommets had a normal pure tone audiometry and otoacoustic emission. So both pure tone audiometry and otoacoustic emission were strongly related both in patients with middle-ear effusion and in patients with grommets. CONCLUSION: As the demonstration of hearing in young and difficult-to-test children can be problematic and time-consuming, we suggest that otoacoustic emission can be used as an alternative to pure tone audiometry in patients with middle-ear effusion and grommets.

Epidermoid cyst of the submandibular gland.

Primary epidermoid cyst of the salivary gland is extremely rare and has only been reported once in the parotid gland A case of epidermoid cyst of the submandibular gland is presented, which required excisional biopsy for the diagnosis. Such excision is also curative.

Spindle-cell variant of intralingual lipoma--report of a case with literature review.

A true lipoma is a rare lesion in the oral cavity. A histologically distinct variant is the spindle-cell variety, which is an innocuous lesion that can simulate a myxoid liposarcoma. We report a case of intra-oral spindle-cell lipoma in a 42-year-old female and have reviewed the literature pertaining to this unusual histopathological entity. Awareness of the condition is essential for both clinicians and pathologists to avoid any misinterpretation of the benign nature of this condition.

Decreased adenosine deaminase activity in peripheral lymphocytes of patients suffering from amebic liver abscess.

Amebic liver abscess (ALA) is associated with a state of transient suppression of cell-mediated immunity (CMI). T4 helper-inducer cell number is reported to be reduced. However, little is known of the reason for such reduction. Adenosine deaminase (ADA), an enzyme of salvage pathway in purine metabolism, is reported to be essential for the normal growth, differentiation and proliferation of T-lymphoid cells. In a pilot study we estimated the ADA levels in the peripheral lymphocytes of ALA patients. It was observed that the mean enzyme level in patients was 223.98 +/- 51.81 as against 405 +/- 38.12 in controls. The significantly low levels (p < 0.05) of enzyme in patients' lymphocytes may possibly explain the reduction of T4 helper-inducer cells reported in these cases. This parameter, if further evaluated, can serve as a differentiation marker between helper and suppressor T-cell subsets.

Detergent dissection of membrane proteins of Entamoeba histolytica and its effect on lymphokine release in in vitro.

Fifty-two amoebic liver abscess cases were assessed for the release of lymphokines (LMIF) using detergent dissected membrane proteins (DDMP) of axenic Entamoeba histolytica (NIH:200) obtained with sodium deoxycholate treatment. Lymphokines release by T lymphocytes in response to both DDMP and whole amoebic lysate (WAL) was tested by leukocyte migration inhibition test on blood samples from amoebic liver abscess cases. A significant increase was noted in the release of LMIF and 100% positivity was observed with DDMP compared to whole amoebic extract with a positivity of 73%. The difference between means of the above two with regards to release of LMIF was found to be highly significant (P less than 0.005). This shows the patients had high degree of leukocyte sensitization to surface antigens of E. histolytica compared to the whole amoebic lysate. These findings suggest that the antigens shed might have important role as a potent antigen in elicitation of CMI response in amoebic liver abscess cases.

Immunogenicity of detergent membrane proteins of Entamoeba histolytica.

The lymphokine release and antibody production were assessed in the peripheral blood of 52 and 48 cases of amoebic liver abscess respectively, by employing detergent dissected membrane proteins (DDMP) of axenic Entamoeba histolytica (NIH:200). Lymphokine release by T lymphocytes in response to both DDMP and whole amoebic lysate (WAL) was performed by leukocyte migration inhibition test. A highly increased release of LMIF and 100 per cent positivity was observed with DDMP where as the same for whole amoebic extract, was only 73 per cent. The difference between the means of the above two values with regards to release of LMIF, was found to be highly significant (P less than 0.005). Antibodies production in response to both DDMP and whole amoebic lysate was performed by indirect haemagglutination assay on blood samples from amoebic liver abscess cases. A 53 folds increased titres of IHA and cent percent positivity was observed with DDMP compared to WAL. The difference between mean titres of the above two with regards to detection of antibodies, was found to be highly significant (P less than 0.001). This shows that the patients, had high degree of leukocyte sensitization and production of antibodies which will not be assessed simply with WAL. These findings suggest that the shed material might have important role as a potent antigen in elicitation cell mediated and humoral immune response in amoebic liver abscess cases.

Study of duodenal ulcer disease in 100 families using total serum pepsinogen as a genetic marker.

Although various markers have been used in attempts to elucidate the mode of inheritance of duodenal ulcer, they have not significantly contributed to a clear understanding of the problem. In the present study total serum pepsinogen was used as a genetic marker and its concentrations were estimated in 100 ulcer patients and their family members up to three generations. Eighty three per cent of the ulcer patients had hyperpepsinogenaemia on a familial basis, and it followed an autosomal dominant mode of inheritance. Thus a large majority of ulcer patients have associated hyperpepsinogenaemia which forms a genetic basis of their disease. The remaining 17% ulcer patients did not have associated hyperpepsinogenaemia nor was the ulcer inherited by the family. Based on these observations we wish to suggest that duodenal ulcer associated with hyperpepsinogenaemia may be considered a genetic disease. This type may be termed 'primary duodenal ulcer'. In the remaining patients without hyperpepsinogenaemia or affected relatives the ulcer may be called 'secondary duodenal ulcer'. Thus total serum pepsinogen may be considered a reliable genetic marker in helping to delineate the genetic disorder from the non-genetic, thereby improving the predictive ability in duodenal ulcer.

AMP deaminase, 5'-nucleotidase and adenosine deaminase in rat myocardial tissue in myocardial infarction and hypothermia.

AMP deaminase, 5'-nucleotidase and adenosine deaminase have been estimated in skeletal muscle and myocardial tissue in normal rats and in rats subjected to experimental myocardial infarction or hypothermia. A difference in the enzyme distribution was found between the right and left ventricles in the normal rat. A decrease in the activity of 5'-nucleotidase and an increase in the activity of adenosine deaminase were observed in infarcted myocardial tissue. The activity of all 3 enzymes was found to be depressed in the myocardium in rats subjected to hypothermia. These results are discussed in relation to adenosine production and its beneficial effects.