Age-dependent changes in the hippocampal antioxidant ability of EL mice

Electron spin resonance (ESR) spectroscopy combined with in vivo microdialysis was used to analyze the antioxidant ability in the hippocampus of mice in an interictal state of EL mice utilizing decay ratio of an exogenously applied nitroxide radical (3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (PCAM)). In EL mice with a history of frequent seizures, the half-life of the electron paramagnetism of PCAM in the hippocampus was prolonged. These results revealed decreased antioxidant ability, suggesting vulnerability against oxidative stress. Our data suggest that epileptogenesis in EL mice with chronic seizures is associated with functional failure due to the oxidized redox state and revealed that the decreased hippocampal antioxidant ability is related to the regional vulnerability to oxidative stress in the limbic system of EL mice during epileptogenesis.     

Pharmacological interventions for stress ulcer prophylaxis in critically ill patients: a mixed treatment comparison network meta-analysis and a recursive cumulative meta-analysis

Background: Proton pump inhibitors (PPI), histamine-2 receptor antagonists (H2RA), sucralfate and antacids are the commonly administered agents for stress ulcer prophylaxis (SUP) in critically ill patients. The authors of this paper have conducted a network meta-analysis to compare the efficacy of these agents in SUP.

Methods: Electronic databases were searched for randomized controlled trials, cohort studies and conference abstracts for studies comparing a SUP agent in critically ill patients to another active SUP agent or placebo. Overt, occult and clinically significant upper gastro-intestinal (UGI) bleeding, all-cause mortality, pneumonia, gastric colonization and ICU length of stay were considered as the outcome measures. A random effects model was used to generate pooled estimates.

Results: A total of 53 studies (4258 participants) were included. The pooled estimates were in favor of PPI and sucralfate for the overt UGI bleeding. PPI and H2RA bolus were associated with increased risk of gastric colonization and pneumonia.

Conclusions: SUP in critically ill patients was not associated with any benefit with regard to clinically significant bleeding episodes. However, PPI and sucralfate significantly reduces overt UGI bleeding. On the contrary, PPI and H2RA bolus are associated with an increased risk of gastric colonization and pneumonia.     

Efficacy and safety of iron chelators in thalassemia and sickle cell disease: a multiple treatment comparison network meta-analysis and trial sequential analysis

Background: To compare the efficacy and safety of desferrioxamine (DFO), deferiprone (DFP), deferasirox (DFX) and silymarin in patients with either thalassemia or sickle cell disorder through network meta-analysis.

Methods: Electronic databases were searched for appropriate randomized clinical trials comparing iron chelators in patients with iron overload. Random effects model was used to generate direct, indirect and mixed treatment comparison pooled estimates for the following outcomes: serum ferritin, liver iron concentration (LIC), changes in serum ferritin, mortality, urine iron excretion, adverse events, neutropenia, agranulocytosis and number of patients withdrawing the chelating therapy.

Results: Thirty-two clinical trials were included in the meta-analysis. DFX/DFO was associated with better serum ferritin levels compared to DFO, DFX, DFO/Silymarin and DFP/DFO. DFX/DFO also lower LIC significantly compared to DFO. DFP/DFO was associated with higher LVEF, low risk of adverse events and reduced end of serum ferritin compared to DFO. Combination of silymarin with either DFP or DFX was observed with reduced end of treatment serum ferritin compared to using either of the drugs alone. DFP was observed with better effects in sickle cell disease. The strength of evidence was very low for most of the comparisons.

Conclusion: Relative estimates between the individual iron chelators have been established. However, this evidence should be considered preliminary and may change with the results of future head-to-head clinical trials.     

Ligand-conjugated mesoporous silica nanorattles based on enzyme targeted prodrug delivery system for effective lung cancer therapy

Epidermal growth factor receptor antibody (EGFRAb) conjugated silica nanorattles (SNs) were synthesized and used to develop receptor mediated endocytosis for targeted drug delivery strategies for cancer therapy. The present study determined that the rate of internalization of silica nanorattles was found to be high in lung cancer cells when compared with the normal lung cells. EGFRAb can specifically bind to EGFR, a receptor that is highly expressed in lung cancer cells, but is expressed at low levels in other normal cells. Furthermore, in vitro studies clearly substantiated that the cPLA₂α activity, arachidonic acid release and cell proliferation were considerably reduced by pyrrolidine-2 loaded EGFRAb-SN in H460 cells. The cytotoxicity, cell cycle arrest and apoptosis were significantly induced by the treatment of pyrrolidine-2 loaded EGFRAb-SN when compared with free pyrrolidine-2 and pyrrolidine-2 loaded SNs in human non-small cell lung cancer cells. An in vivo toxicity assessment showed that silica nanorattles and EGFRAb-SN-pyrrolidine-2 exhibited low systemic toxicity in healthy Balb/c mice. The EGFRAb-SN-pyrrolidine-2 showed a much better antitumor activity (38%) with enhanced tumor inhibition rate than the pyrrolidine-2 on the non-small cell lung carcinoma subcutaneous model. Thus, the present findings validated the low toxicity and high therapeutic potentials of EGFRAb-SN-pyrrolidine-2, which may provide a convincing evidence of the silica nanorattles as new potential carriers for targeted drug delivery systems.     

Study on the Prevalence of Leptospirosis among Fever Cases Reported from Private Clinics in the Urban areas of Villupuram District,Tamil Nadu,India

Objectives

To know the prevalence of leptospirosis cases reported in private clinics among fever cases in Villupuram District, Tamil Nadu, India to know its real magnitude of the problem and to diagnose Leptospirosis among fever cases from differential diagnosis.

Methods

1502 Blood serum samples collected from three urban towns namely Kallakurichi (Latitude: 11° 73′ N; Longitude: 78° 97′ E), Villupuram (Latitude: 11° 75′ N; Longitude: 79° 92′ E) and Thindivanam (Latitude: 12° 25′ N; Longitude: 79° 65′ E) in fifteen clinics based on case definition of leptospirosis delineated by the National Vector Borne Disease Control Programme (NVBDCP), Government of India. Samples were tested in the laboratory of the Zonal Entomological Team (ZET), Cuddalore with Macroscopic Slide Agglutination Test (MSAT) and Ig-M ELISA.

Result

There were 65 positive cases detected from 1502 blood serum samples in both MSAT and Ig-M ELISA. It could be known that there was 4% cases contributed from private clinics among fever cases. From this study, further it was known that all age groups of people affected irrespective of sexes based on their living condition associated with the environment prevailed of the disease.

Conclusion

From this study, it was quantified that 4% of cases reported in private clinics among fever cases and its findings ascertained both the importance of differential diagnosis as well as reports that should be included to the Government for knowing its real magnitude for planning.     

Argyrophilic nucleolar organizer regions in the evaluation of tumour progression in the oral mucosa: correlation with tissue pathology

The present study has analysed the numbers of argyrophilic nucleolar organizer regions (AgNOR) in normal tissues and in premalignant and malignant lesions of the oral mucosa in order to assess their potential as a biological marker for tumour progression. On comparison of AgNOR numbers in different lesions, carcinomas showed the highest number (4.65±0.98) compared to leukoplakias (2.38±0.47) and normal tissues (1.53±0.39). Spindle cell carcinomas and poorly differentiated squamous cell carcinomas had higher AgNOR counts than well-differentiated carcinomas. In various clinically different types of oral leukoplakia, the lowest AgNOR counts were observed in homogenous leukoplakia and the highest in speckled leukoplakia. No significant difference in AgNOR number was observed between non-dysplastic and dysplastic leukoplakia, although a significant difference was evident between dysplastic leukoplakia and normal oral mucosa. Correlating the AgNOR count and tumour progression, a significantly high positive correlation coefficient (r=0.7969,P=0.0000) was observed.     

Role of retrograde dilatation in the management of pharyngo-esophageal corrosive strictures

Pharyngo-esophageal corrosive stricture is a complex clinical scenario. If an esophageal opening cannot be found orally through endoscopy, a retrograde approach with a mini-laparotomy and gastrostomy should be attempted. This study primarily aimed at defining the role of preoperative retrograde dilatation of pharyngo-esophageal corrosive strictures. A retrospective analysis of 51 cases of pharyngo-esophageal corrosive strictures identified between 1997-2005 was performed. The demographic details were analyzed. The details of the injury to the pharynx either in isolation or in combination were noted and the management details were recorded. In 21 patients preoperative retrograde dilatation was considered and the technique was successful in 14 (Group I). In seven the technique failed (Group II) and these patients underwent transhiatal resection and gastric pull-through and/or retrosternal pharyngocoloplasty. In Group I patients the postoperative stay was significantly less than in Group II (12 +/- 2.03 days vs. 18 +/- 4.32 days; p = 0.001) Recurrent aspiration, respiratory tract infections, choking sensation and the need for tracheostomy were less frequent in Group I. The overall functional assessment was good in Group I. For treatment of pharyngo-esophageal obstruction, if antegrade dilatation is not possible due to technical reasons, retrograde dilatation is a viable option before opting for organ replacement/bypass procedures. There is no best replacement of the native organ to maintain quality of life.     

Perturbations in the erythroid marrow progenitor cell pools may play a role in the augmentation of HbF by 5-azacytidine

In vivo observations on the kinetics of F cells and of fetal hemoglobin (HbF) synthesis and in vitro studies of erythroid progenitors, their number, and the gamma-gene expression in their progeny were carried out in baboons (Papio cynocephalus) treated with 5-azacytidine. Maximum effect on the increase of HbF production in vivo was observed only when an expanded erythroid marrow population was present. In these animals, as well as in normal animals, treatment resulted in a significant reduction of the late erythroid progenitor cell pools (erythroid clusters and erythroid colony-forming units, CFU-E) in the marrow. This reduction was more pronounced among those progenitors grown in the absence of added erythropoietin, and it was followed by a rebound a few days after treatment cessation, reflecting the accumulation of regenerating progenitors. An early increase in the in vitro synthesis of HbF in erythroid clusters and CFU-E colonies was observed. This increase was further documented at the cellular level, with immunofluorescent labeling of colonies with monoclonal anti-gamma- globin chain antibodies. In contrast to the findings in late progenitors, the number of erythroid burst-forming unit (BFU-E) colonies and the synthesis of HbF in these colonies was not influenced significantly by 5-azacytidine treatment. It is proposed that the toxic effects of 5-azacytidine on late progenitors, leading to faster mobilization of earlier progenitors to the next more mature compartment, play a role in the in vivo augmentation of HbF synthesis by this drug. This perturbation in the progenitor cell population kinetics and the presumed hypomethylation of the surviving differentiating cells may act synergistically to produce a maximum HbF response after 5-azacytidine treatment.