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[en] The recent availability of extremely intense, femtosecond X-ray free-electron laser (XFEL) sources has spurred the development of serial femtosecond nanocrystallography (SFX). Here, SFX is used to analyze nanoscale crystals of β-hematin, the synthetic form of hemozoin which is a waste by-product of the malaria parasite. This analysis reveals significant differences in β-hematin data collected during SFX and synchrotron crystallography experiments. To interpret these differences two possibilities are considered: structural differences between the nanocrystal and larger crystalline forms of β-hematin, and radiation damage. Simulation studies show that structural inhomogeneity appears at present to provide a better fit to the experimental data. If confirmed, these observations will have implications for designing compounds that inhibit hemozoin formation and suggest that, for some systems at least, additional information may be gained by comparing structures obtained from nanocrystals and macroscopic crystals of the same molecule.
[en] Malaria has protean clinical manifestations and renal complications, particularly acute renal failure that could be life threatening. To evaluate the incidence, clinical profile, ou come and predictors of mortality in patients with malarial acute renal failure, we retrospectively studied the last two years records of malaria induced acute renal failure in patients with peripheral smear positive for malarial parasites. One hundred (10.4%) (63 males, 37 females) malaria induced acute renal failure amongst 958 cases of acute renal failure were evaluated. Plasmodium (P). falciparum was reported in 85%, P. vivax in 2%, and both in 13% patients. The mean serum creatinine was 9.2 ± 4.2 mg%, and oligo/anuria was present in 82%; 78% of the patients required hemodialysis. Sixty four percent of the patients recovered completely, 10% incompletely, and 5% developed chronic kidney failure; mortality occurred in 21% of the patients. Low hemoglobin, oligo/anuria on admission, hyperbilirubinemia, cerebral malaria, disseminated intravascular coagulation, and high serum creatinine were the main predictors of mortality. We conclude that malaria is associated with acute renal failure, which occurs most commonly in plasmodium falciparum infected patients. Early diagnosis and prompt dialysis with supportive management can reduce morality and enhance recovery of renal function (Author).
[en] To assess the abnormalities of haemotological parameters associates to different types of malaria. Design: Observational study. Study Setting and Duration: Present study was carried out in the medicine department, of (LUH) Liaquat University Objective: To assess the abnormalities of haemotological parameters associates to different types of malaria. Design: Observational study. Study Setting and Duration: Present study was carried out in the medicine department, of (LUH) University of Medical and Health Sciences Hospital Hyderabad / Jamshoro from March 2013 to august 2013. Method: All the cases after diagnosis having, tuberculosis, hepatitis, typhoid, dengue fever, pregnancy and diagnosis of meningitis excluded from the present study. Blood sample of the patients for CBC were sent to the diagnostic and research laboratory of liaquat medical University Hospital Hyderabad. After reports all the hematological abnormalities was documented. Results: Total 200 patients were selected in this study, and mean age was found as; Mean +- SD 32.4 +- 5.6. Female were found in the majority 58%. Vivax was found most common in the cases with percentage of 68%. According to the haematological abnormalities, in the vivax infected patients abnormal Hb (g/dl) was found in (24.2%) cases and thrombocytopenia was found with the (20.4%) cases in the cases, while Falciparum infected patients mostly abnormal H,b (g/dl) was found in 27 (20.4%) and thrombocytopenia found most common 31 (45.5%) respectively. Conclusion: In the conclusion of this study, there are a big haematological disturbance are evaluated in the malarial affected patients, mostly thrombocytopenia and anemia. (author)
[en] Plasmodium gallinaceum-infected blood which received up to 24 krad during exposure to gamma-rays from a cobalt-60 source produced infections of normal course and duration when injected into chickens. The prepatent period advanced with increasing exposure of infected blood to radiation, suggesting some degree of attenuation. At 26, 28 and 30 krad, the infections were transient and the parasites were morphologically abnormal. It is thought that the amount of radiation required to render the parasites non-viable is about 45 krad for an inoculum of 106 parasites. There is evidence that exoerythrocytic stages may be more susceptible to gamma-rays than are blood parasites. Chickens were inoculated three times, over a period of four weeks, with vaccines prepared from gamma-irradiated infected blood and brain tissue. Half the birds which had been inoculated with attenuated parasitized blood exhibited mild infections during vaccination, and they were the only birds to show at challenge immunity to both homologous blood and exoerythrocytic parasites. (author)
[en] The present study was conducted to evaluate the synthesized 4-(4?-Bromophenyl)-4-hydroxy piperdine derivatives for plasmepsin inhibition (antimalarial activity) and analgesic response to develop excellent moiety to work in malaria. The plasmepsin II and cathepsin D (Biodesign International, USA) assays were measured using a fluorescence resonance energy transfer (FRET) method. The inhibition of enzyme was done (in triplicates) in 96 well plate format and response were obtained on a Perkin Elmer LS55 Fluorescence spectrometer with an excitation and emission wavelengths of 336 and 490 nm, respectively and analgesic activity of synthesized derivatives of 4-(4-Bromophenyl)-4-hydroxy piperidine was conducted by Eddy's hot plate method in albino mice by providing standard colony conditions using Pethidine as standard drug. These novel compounds having the parent moiety 4-(4-Bromophenyl)-4-hydroxy piperdine were found to prove strong inhibition towards plasmepsin enzyme with 8-10 IC50 in micro M and highly significant analgesic response in albino mice. The current studies suggest that the designed molecules were found to work both on cellular level and also on the symptoms of disease as the headache, fever and muscle aches are the very common and initial symptoms associated with malaria and hence the molecules discovered as excellent analgesics. (author)
[en] Background: Cerebral malaria is a major health hazard, with a high incidence of mortality. The disease is endemic in many developing countries, but with a greater increase in tourism, occasional cases may be detected in countries where the disease in not prevalent. Early diagnosis and evaluation of cerebral involvement in malaria utilizing modern imaging modalities have an impact on the treatment and clinical outcome. Purpose: To evaluate the magnetic resonance (MR) features of patients with cerebral malaria presenting with altered sensorium. Material and Methods: We present the findings in three patients with cerebral malaria presenting with altered sensorium. MR imaging using a 1.5-Tesla unit was carried out. The sequences performed were 5-mm-thick T1-weighted, T2-weighted, fluid-attenuated inversion-recovery (FLAIR), and T2-weighted gradient-echo axial sequences, and sagittal and coronal FLAIR. Diffusion-weighted imaging was performed with b values of 0 and 1000 s/mm2, and apparent diffusion coefficient (ADC) maps were obtained. Results: Focal hyperintensities in the bilateral periventricular white matter, corpus callosum, occipital subcortex, and bilateral thalami were noticed on T2-weighted and FLAIR sequences. The lesions were more marked in the splenium of the corpus callosum. No enhancement on postcontrast T1-weighted MR images was observed. There was no evidence of restricted diffusion on the diffusion-weighted sequence and ADC map. Conclusion: MR is a sensitive imaging modality, with a role in the assessment of cerebral lesions in malaria. Focal white matter and corpus callosal lesions without any restricted diffusion were the key findings in our patients
[en] Highlights: ► Is it evident that the residues position are relevant regarding of φ angular value. ► The geometry considered for detailing the alterations undergone by HABPs. ► The inter planar interactions ruled by clashes between the atoms making them up. -- Abstract: Conserved Plasmodium falciparum high activity binding peptides’ (HABPs) most relevant proteins involved in malaria parasite invasion are immunologically silent; critical binding residues must therefore be specifically replaced to render them highly immunogenic and protection-inducing. Such changes have a tremendous impact on these peptides’ steric–electronic effects, such as modifications to peptide length peptide bonds and electronic orbitals’ disposition, to allow a better fit into immune system MHCII molecules and better interaction with the TCR which might account for the final immunological outcome.