Mechanism of hypochlorous acid-mediated heme destruction and free iron release

Here, we show that hypochlorous acid (HOCl), a potent neutrophil-generated oxidant, can mediate destruction of free heme (Ht) and the heme precursor, protoporphyrin IX (PPIX). Ht displays a broad Soret absorbance peak centered at 365 and 394 nm, indicative of the presence of monomer and μ-oxo-dimer. Oxidation of Ht by HOCl was accompanied by a marked decrease in the Soret absorption peak and release of free iron. Kinetic measurements showed that the Ht-HOCl reaction was triphasic. The first two phases were HOCl concentration dependent and attributable to HOCl binding to the monomeric and dimeric forms. The third phase was HOCl concentration independent and attributed to Ht destruction with the release of free iron. HPLC and LC-ESI-MS analyses of the Ht-HOCl reaction revealed the formation of a number of degradation products, resulting from the cleavage or modification of one or more carbon-methene bridges of the porphyrin ring. Similar studies with PPIX showed that HOCl also mediated tetrapyrrole ring destruction. Collectively, this work demonstrates the ability of HOCl to modulate destruction of heme, through a process that occurs independent of the iron molecule that resides in the porphyrin center. This phenomenon may play a role in HOCl-mediated oxidative injury in pathological conditions.     

Soil-transmitted helminthiasis: a critical but neglected factor influencing school participation of Aboriginal children in rural Malaysia

Soil-transmitted helminthiasis (STH), among the most common neglected tropical diseases, is a major public health problem in Malaysia with a possible impact on the nutritional status and school participation of rural children. This study was carried out among Aboriginal schoolchildren, living in an endemic area for STH in Malaysia, to determine the possible relationship between intestinal helminthiasis and school absenteeism. We also evaluated whether successful treatment of the infection will affect school attendance among the subjects. Stool analysis revealed that more than 90% of the subjects were infected with at least 1 helminth species, with Ascaris lumbricoides and Trichuris trichiura infections being most prevalent. Infection of moderate-to-heavy worm burdens, low level of fathers' education and anaemia were identified as the significant predictors of high absenteeism among the subjects (P<0·05). Following treatment of the infected children, it was found that school absenteeism was reduced significantly (P<0·01). In conclusion, STH continues to have significant impacts on public health, particularly in rural communities with a negatively significant effect on the school participation of Aboriginal children. A school-based de-worming programme should be introduced and incorporated in the current educational assistance targeted towards the Aboriginal communities, under the auspices of the government.     

The Menace of Schistosomiasis in Nigeria: Knowledge,Attitude, and Practices Regarding Schistosomiasis among Rural Communities in Kano State

Background

Schistosomiasis is one of the most common neglected tropical diseases, especially in the developing countries in Africa, Asia and South America, with Nigeria having the greatest number of cases of schistosomiasis worldwide. This community-based study aims to evaluate the knowledge, attitude and practices (KAP) regarding schistosomiasis among rural Hausa communities in Kano State, Nigeria.

Methods

A cross-sectional study was carried out among 551 participants from Hausa communities in five local government areas in Kano State, North Central Nigeria. Demographic, socioeconomic and environmental information as well as KAP data were collected using a pre-tested questionnaire. Moreover, faecal and urine samples were collected and examined for the presence of Schistosoma mansoni and S. haematobium eggs respectively.

Results

The overall prevalence of schistosomiasis was 17.8%, with 8.9% and 8.3% infected with S. mansoni and S. haematobium respectively, and 0.5% had co-infection of both species. Moreover, 74.5% of the participants had prior knowledge about schistosomiasis with 67.0% of them how it is transmitted and 63.8% having no idea about the preventive measures. Three-quarters of the respondents considered schistosomiasis a serious disease while their practices to prevent infections were still inadequate, with only 34.7% of them seeking treatment from clinics/hospitals. Significant associations between the KAP and age, gender, education and employment status were reported. Multiple logistic regression analysis revealed that age, gender, history of infection and educational level of the respondents were the most important factors significantly associated with the KAP on schistosomiasis among this population.

Conclusions

Schistosomiasis is still prevalent among Hausa communities in Nigeria and participants’ knowledge about the disease was poor. Mass drug administration, community mobilization and health education regarding the cause, transmission and prevention of schistosomiasis and education about good personal and sanitary hygiene practices should be considered in order to significantly reduce the prevalence and morbidity of infection within these communities.     

Comparison of Two New Robust Parameter Estimation Methods for the Power Function Distribution

Estimation of any probability distribution parameters is vital because imprecise and biased estimates can be misleading. In this study, we investigate a flexible power function distribution and introduced new two methods such as, probability weighted moments, and generalized probability weighted methods for its parameters. We compare their results with L-moments, trimmed L-moments by a simulation study and a real data example based on performance measures such as, mean square error and total deviation. We concluded that all the methods perform well in the case of large sample size (n>30), however, the generalized probability weighted moment method performs better for small sample size.     

‘Variations in phenological and functional traits in Thapsia garganica populations in Al Jebel Al Akhdar,Libya’

Thapsia garganica is a herbaceous perennial in the Apiaceae, distributed around the Mediterranean and traditionally used in North Africa as a remedy for arthritis, herpes, hair-fall, hypertension, rheumatic, eczema and scabies. T. garganica is the source of thapsigargin: known for killing cancer cells. Seven populations were studied in sites differing in aspect and elevation within Al Jebel Al Akhdar in Libya. We studied the within-population size distribution of individuals, the timing of the phenological events, and vegetative and reproductive traits.Thapsia garganica showed high flexibility of functional traits and shifts in the timing of phenological events in response to elevation and aspect (north- or south-facing slopes). Local soil properties, together with effects due to altitude and aspect, could be direct causes of the observed differences in terms of population size and phenological traits. The phenological patterns detected also provide insights into the species response to climate change. Despite this phenotypic flexibility, and good growth in sites at 300–700 m a. s. l. on south-facing slopes, most sites in this study have an unstable size-structure, with few small individuals. This raises concerns about the long-term persistence of the other populations of this species in Al Jebel Al Akhdar.     

Potential role of tryptophan and chloride in the inhibition of human myeloperoxidase

Myeloperoxidase (MPO) binds H2O2 in the absence and presence of chloride (Cl-) and catalyzes the formation of potent oxidants through 1e(-) and 2e(-) oxidation pathways. These potent oxidants have been implicated in the pathogenesis of various diseases including atherosclerosis, asthma, arthritis, and cancer. Thus, inhibition of MPO and its by-products may have a wide application in biological systems. Using direct rapid kinetic measurements and H2O2-selective electrodes, we show that tryptophan (Trp), an essential amino acid, is linked kinetically to the inhibition of MPO catalysis under physiological conditions. Trp inactivated MPO in the absence and presence of plasma levels of Cl(-), to various degrees, through binding to MPO, forming the inactive complexes Trp-MPO and Trp-MPO-Cl, and accelerating formation of MPO Compound II, an inactive form of MPO. Inactivation of MPO was mirrored by the direct conversion of MPO-Fe(III) to MPO Compound II without any sign of Compound I accumulation. This behavior indicates that Trp binding modulates the formation of MPO intermediates and their decay rates. Importantly, Trp is a poor substrate for MPO Compound II and has no role in destabilizing complex formation. Thus, the overall MPO catalytic activity will be limited by: (1) the dissociation of Trp from Trp-MPO and Trp-MPO-Cl complexes, (2) the affinity of MPO Compound I toward Cl(-) versus Trp, and (3) the slow conversion of MPO Compound II to MPO-Fe(III). Importantly, Trp-dependent inhibition of MPO occurred at a wide range of concentrations that span various physiological and supplemental ranges.