Polymorphism study of rhoptry associated membrane antigen (RAMA) gene of Plasmodium falciparum--a putative vaccine candidate

The antigenic diversity of Plasmodium falciparum is one of the major obstacles to antimalarial vaccine development. Thus, it becomes obvious to search for a protein that is fairly conserved and is necessary for the parasite to survive in the host cell. Rhoptry associated membrane antigen (RAMA) plays a potential role in parasite biology and invasion. The C-terminal end of RAMA is shown to have protective immune responses and binds to the erythrocyte membrane. In this work, we have studied the polymorphism of RAMA gene in the C-terminal end from 1525 to 3196 nucleotide (nt) in 230 samples. The presence of few variants suggests RAMA to be under a balancing selection. The above criterion of restricted antigenic diversity and a protective immune response towards the C-terminal end makes RAMA a strong vaccine candidate.     

Relating pulmonary oxygen uptake to muscle oxygen consumption at exercise onset: in vivo and in silico studies

Assessment of the rate of muscle oxygen consumption, UO_2m, in vivo during exercise involving a large muscle mass is critical for investigating mechanisms regulating energy metabolism at exercise onset. While UO_2m is technically difficult to obtain under these circumstances, pulmonary oxygen uptake, VO_2p, can be readily measured and used as a proxy to UO_2m. However, the quantitative relationship between VO_2p and UO_2m during the nonsteady phase of exercise in humans, needs to be established. A computational model of oxygen transport and utilization—based on dynamic mass balances in blood and tissue cells—was applied to quantify the dynamic relationship between model-simulated UO_2m and measured VO_2p during moderate (M), heavy (H), and very heavy (V) intensity exercise. In seven human subjects, VO_2p and muscle oxygen saturation, StO_2m, were measured with indirect calorimetry and near infrared spectroscopy (NIRS), respectively. The dynamic responses of VO_2p and StO_2m at each intensity were in agreement with previously published data. The response time of muscle oxygen consumption, estimated by direct comparison between model results and measurements of StO_2m was significantly faster (P < 0.001) than that of pulmonary oxygen uptake, (M: 13 ± 4 vs. 65 ± 7 s; H: 13 ± 4 vs. 100 ± 24 s; V: 15 ± 5 vs. 82 ± 31 s). Thus, by taking into account the dynamics of oxygen stores in blood and tissue and determining muscle oxygen consumption from muscle oxygenation measurements, this study demonstrates a significant temporal dissociation between UO_2m and VO_2p at exercise onset.     

Cobalt oxide nanoparticles induced oxidative stress linked to activation of TNF‐α/caspase‐8/p38‐MAPK signaling in human leukemia cells

The purpose of this study was to determine the intracellular signaling transduction pathways involved in oxidative stress induced by nanoparticles in cancer cells. Activation of reactive oxygen species (ROS) has some therapeutic benefits in arresting the growth of cancer cells. Cobalt oxide nanoparticles (CoO NPs) are an interesting compound for oxidative cancer therapy. Our results showed that CoO NPs elicited a significant (P <0.05) amount of ROS in cancer cells. Co‐treatment with N‐aceyltine cystine (an inhibitor of ROS) had a protective role in cancer cell death induced by CoO NPs. In cultured cells, the elevated level of tumor necrosis factor‐alpha (TNF‐α) was noted after CoO NPs treatment. This TNF‐α persuaded activation of caspase‐8 followed by phosphorylation of p38 mitogen‐activated protein kinase and induced cell death. This study showed that CoO NPs induced oxidative stress and activated the signaling pathway of TNF‐α‐Caspase‐8‐p38‐Caspase‐3 to cancer cells. Copyright © 2015 John Wiley & Sons, Ltd.     

Lumbar spine: postoperative MR imaging with Gd-DTPA

Thirty patients with failed back surgery syndrome were studied to evaluate the effectiveness of magnetic resonance (MR) imaging with gadolinium-diethylenetriaminepentaacetic acid/dimeglumine (Gd-DTPA) in differentiating postoperative epidural fibrosis (scar) from recurrent disk herniation. Pre- and postcontrast MR images were interpreted without access to other diagnostic, surgical, or pathologic findings. Seventeen patients had surgical and pathologic correlation of the MR findings at 19 disk levels. The precontrast studies had a sensitivity, specificity, and accuracy of 100%, 71%, and 89%, respectively. The enhanced MR studies correctly depicted the character of abnormal epidural soft tissue in 17 patients at all 19 levels. Scar showed heterogeneous enhancement on the early T1-weighted spin-echo images obtained within 10 minutes after contrast material administration. Herniated disk did not show significant enhancement on the early studies but showed variable degrees of enhancement on delayed images in nine of 12 cases. Other criteria were found to be less useful than the pattern of enhancement. Results indicate that precontrast and early postcontrast T1-weighted spin-echo studies are highly accurate in separating epidural fibrosis from herniated disk.     

Quantitative imaging of arsenic and its species in goat following long term oral exposure

Severity of arsenic toxicity was reported to vary depending on its species. The present study reflects the status of different species of arsenic in goat following long-term exposure of arsenic leading to hepatic damage. The experiment was conducted with six black Bengal goats, which were administered with sodium arsenite orally at a dose rate of 2 mg kg⁻¹ daily for 84 days. Faeces, urine, hair and blood samples were collected from those animals at 14 days interval. Excretion of total arsenic was reduced from 56 days onwards through both faeces and urine indicating higher accumulation of arsenic in body. The speciation study revealed that urinary arsenic was mainly of organic type, whereas hair accumulated almost equal proportion of arsenite, arsenate and organo arsenicals. Goats excreted high proportion of organo arsenicals through faeces possibly due to hepatobiliary secretion of organo arsenic into the gut. Significantly elevated serum alanine aminotransferase and aspartate aminotransferase activities (p < 0.05) alongwith histopathological changes in liver indicated hepatotoxicity. The arsenite fraction increased and organic proportion decreased in urine as the time progressed, which indicates that arsenite gets methylated in liver of goat. The study thus alluded that the toxicity of arsenic would aggravate if the animals were exposed for long time as the hepatotoxicity progressed resulting in decreased methylation and formation of organo arsenicals and decreased excretions through urine.     

<Emphasis Type=Italic>Vivax</Emphasis> malaria presenting with cerebral malaria and convulsions

A patient was admitted with fever, vomiting, restlessness and convulsions. He was febrile and unconscious. Laboratory tests showed a low platelet count and ruled out enteric fever and dengue. His peripheral blood smear was positive for Plasmodium vivax. The presence of P. vivax monoinfection was confirmed by polymerase chain reaction and DNA sequencing. The report highlights the importance of considering the possibility of complications even in P. vivax malaria and formulation of strategies accordingly.     

Efficacy of female <Emphasis Type="Italic">Culex quinquefasciatus</Emphasis> with entomopathogenic fungus <Emphasis Type="Italic">Fusarium pallidoroseum</Emphasis>

This study was conducted to isolate and identify natural entomopathogenic fungi from female Culex quinquefasciatus and to test their adulticidal activity. Field-collected female C. quinquefasciatus died early and were placed on a Saboraud’s dextrose agar plates for growth and isolation of natural entomopathogenic fungi. The plates were maintained in an incubator at 24 ± 2°C for 3 days. Four fungal species were isolated in two genera namely, Aspergillus and Fusarium. The identified fungal species were A. niger, A. flavus, A. nidulans var acristatus (ITCC-6327.04), and F. pallidoroseum (ITCC-6324.06). Adult bioassays were carried out using spore-impregnated paper in WHO-holding tubes. F. pallidoroseum was found to be more effective than the others. Exposure of C. quinquefasciatus to spores of A. flavus and A. niger for 4 h caused 5.53% and 5.51% mortality in the mosquitoes within a week, respectively. All the female C. quinquefasciatus were killed within 4 days of exposure to F. pallidoroseum at a concentration of 1.11 × 10¹⁰ conidia per m². Significant difference of longevity was observed between the F. pallidoroseum-treated C. quinquefasciatus and control mosquitoes. The LT₅₀ of F. pallidoroseum was 2.08 days for 4 h exposure to C. quinquefasciatus. Results of the present study confirm that F. pallidoroseum is one of the alternative biological control agents of adult mosquitoes.     

An audit of the presurgical evaluation and patient selection for extratemporal resective epilepsy surgery in a resource-poor country

PurposeThe selection of ideal candidates for extratemporal resective epilepsy surgery is a challenge in resource-poor countries because of the limited presurgical diagnostic facilities and their affordability. To audit the presurgical evaluation strategy and selection for extratemporal resective epilepsy surgery in a resource-poor region.MethodsFrom the prospective database maintained at an epilepsy surgery center in southern India, we reviewed the data of consecutive patients who underwent presurgical evaluation from January 2005 through December 2008 for antiepileptic drug-resistant focal epilepsies emanating from the frontal, parietal and occipital lobes. Out of 285 patients, only 71 (24.9%) underwent resective surgery; the remaining 214 (75.1%) patients could not be selected for surgery. We inquired the reasons for their exclusion from surgery.ResultsThe difference in the rates of seizure-free outcome between surgical and non-surgical groups was highly significant (73.2% vs. 7.7%, P < 0.0005). The major reasons for exclusion from surgery were normal MRI in 107 (50%), inability to afford invasive EEG monitoring in 40 (18.7%) and lesion location adjacent to eloquent cortical areas in 27 (12.6%) patients. While clustering of seizures and presence of preoperative neurological deficits favored surgical selection, the presence of secondary generalized seizures and discordant interictal epileptiform abnormalities were associated with exclusion from surgery.ConclusionsWe conclude that, in a resource-poor country, ideal candidates for extratemporal resective epilepsy surgery are those with well-circumscribed lesions not adjoining eloquent cortical areas. In such patients, concordant EEG findings and absence of preoperative secondary generalized seizures reinforce selection for surgery.