Mitochondrial dysfunction and human immunodeficiency virus infection

Human immunodeficiency virus (HIV) infection and the pharmacological treatment thereof have both been shown to affect mitochondrial function in a number of tissues, and each may cause specific organ pathology through specific mitochondrial pathways. HIV has been shown to kill various tissue cells by activation of mitochondrial apoptosis. Nucleoside analogues, used extensively to treat HIV infection, are known to influence a number of steps affecting mitochondrial DNA integrity. This review describes the basic physiology, pharmacology and pathophysiology of HIV infection and the nucleoside analogues regarding mitochondrial function and discusses the progress made in this field with respect to the measurement of these effects and the prediction of potential drug toxicity.Keywords: highly active antiretroviral treatment, HIV, nucleoside reverse transcriptase inhibitor, mitochondrial DNA, mitochondrial toxicit

“...But the Poor Opted for the Evangelicals!”– Evangelicals, Poverty and Prosperity

This article discusses developments in the historical discourse on evangelicalism, poverty and prosperity. Have the global evangelical celebrations of 2010 bridged the dichotomy between social responsibility (Ecumenicals) and the proclamation of salvation (Evangelicals)? The article focuses on the rapid growth of a specific brand of evangelicalism, namely “prosperity faith” as predisposition within the neo-Pentecostal churches, especially throughout sub-Saharan Africa. In an appreciative, but critical enquiry, this article reflects on the radical claim of dispensing “health and wealth” to the desperately poor. Are proponents of prosperity faith putting forward a credible answer to poverty, a new entrepreneurial and creative evangelical response to the call for social responsibility? Or will the poor ultimately be disillusioned? What challenges are posed to Evangelicals

I am the bread of life. Imagery in John 6:32-51

John 6 is one of the most discussed chapters in the Gospel according to John, because of the Eucharistic nature of the language in 6:51c-59. The complex nature of the metaphors and imagery used in these verses, as well as the richness and power of the ensuing communication, are often overlooked. This article explores the literary nature of the text and focuses on the dynamics of metaphor, the interaction between the figurative and literal sections in the text, as well as the strong influence of the socio-religious context of the text on its interpretation and understanding.Acta Theologica Vol. 2 2007: pp. 186-20

The identity of the recipients of the Fourth Gospel in the light of the purpose of the Gospel

The purpose of this article is to explore the identity of the recipients at the time of the completion of the Gospel. An effort is made to determine to whom John wrote this Gospel and how he adapted his theological message to reach this aim. It will be argued that John did not only focus on a specific group of people, but had a wide variety of people (i.e., Jews, Hellenists, Samaritans) in mind, which leads to the conclusion that the Fourth Gospel was written with both evangelistic and didactic aims

Hoe is Jesus gekruisig?

The way in which Jesus was crucified After an overview of various forms of crucifixion in the ancient world, the available archaeological data and artistic renderings of different means of crucifixion are discussed. The New Testament information concerning the crucifixion of Jesus is then discussed and evaluated. It is concluded that, in the view of the absence of convincing literary evidence, the statue representing the 'crucofixion of Marsyas in the Hermitage museum provides a contemporary example of a possible manner in which Jesus could haye been crucified

Plasma sarcosine does not distinguish early and advanced stages of prostate cancer

Introduction. Diagnosis of prostate cancer by prostate specific antigen (PSA) is error-prone and cannot distinguish benign prostatic hyperplasia (BPH) from malignant disease, nor identify aggressive and indolent types. Methods. We determined serum sarcosine (N-methylglycine) in 328 cancer patients by gas chromatography (GC)/mass spectroscopy (MS) and searched for correlations with early (stage T1/T2) and advanced (stage T3/T4) disease. Results. Serum sarcosine of male control patients ranged from 1.7 µmol/l to 4.8 µmol/l. In prostate cancer patients, sarcosine ranged from 2.8 µmol/l to 20.1 µmol/l. Expressed as the sarcosine/alanine ratio, serum control values were 9.4±5.5x10-3 (mean±SD) compared with 21.6±9.0; 28.5±16.6; 22.7±7.7 and 22.2±11.0 for patients diagnosed with T1, T2, T3 and T4 prostate tumours, respectively. The small differences between T1, T2, T3 and T4 patients were not statistically significant (p=0.51). However, the conventional PSA marker significantly correlated with T stage in these patients (r=0.63;

Residual allergenicity of amino acid-based and extensively hydrolysed cow’s milk formulas

Background. Criteria for labelling infant feeds as suitable for the dietary management of cow’s milk protein allergy (CMPA) rely on proving the hypoallergenicity of such feeds or clinical studies showing that the feeds are tolerated by 90% of children with proven CMPA. South African (SA) labelling legislation does not indicate what testing is necessary to prove hypoallergenicity.Objectives. To evaluate all extensively hydrolysed cow’s milk formulas and amino acid-based formulas available in SA for residual allergen content, protein size and amino-acid content.Results. All amino-acid and extensively hydrolysed formulas were found to be similar in composition, with no residual cow’s milk allergens detectable by enzyme-linked immunosorbent assay. Furthermore, proteins were absent and only small molecules in the size range of amino acids and possibly of very small oligopeptides were detected.Conclusions. These findings indicate that the formulas are extremely likely to be compliant with the definition of hypoallergenicity as tolerance in 90% of proven sufferers from cow’s milk allergy. The formulas may therefore be labelled as suitable for the dietary management of infants with CMPA

Clinical, biochemical, and genetic spectrum of MADD in a South African cohort: an ICGNMD study

\ua9 2024, The Author(s).Background: Multiple acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive disorder resulting from pathogenic variants in three distinct genes, with most of the variants occurring in the electron transfer flavoprotein-ubiquinone oxidoreductase gene (ETFDH). Recent evidence of potential founder variants for MADD in the South African (SA) population, initiated this extensive investigation. As part of the International Centre for Genomic Medicine in Neuromuscular Diseases study, we recruited a cohort of patients diagnosed with MADD from academic medical centres across SA over a three-year period. The aim was to extensively profile the clinical, biochemical, and genomic characteristics of MADD in this understudied population. Methods: Clinical evaluations and whole exome sequencing were conducted on each patient. Metabolic profiling was performed before and after treatment, where possible. The recessive inheritance and phase of the variants were established via segregation analyses using Sanger sequencing. Lastly, the haplotype and allele frequencies were determined for the two main variants in the four largest SA populations. Results: Twelve unrelated families (ten of White SA and two of mixed ethnicity) with clinically heterogeneous presentations in 14 affected individuals were observed, and five pathogenic ETFDH variants were identified. Based on disease severity and treatment response, three distinct groups emerged. The most severe and fatal presentations were associated with the homozygous c.[1067G > A];c.[1067G > A] and compound heterozygous c.[976G > C];c.[1067G > A] genotypes, causing MADD types I and I/II, respectively. These, along with three less severe compound heterozygous genotypes (c.[1067G > A];c.[1448C > T], c.[740G > T];c.[1448C > T], and c.[287dupA*];c.[1448C > T]), resulting in MADD types II/III, presented before the age of five years, depending on the time and maintenance of intervention. By contrast, the homozygous c.[1448C > T];c.[1448C > T] genotype, which causes MADD type III, presented later in life. Except for the type I, I/II and II cases, urinary metabolic markers for MADD improved/normalised following treatment with riboflavin and L-carnitine. Furthermore, genetic analyses of the most frequent variants (c.[1067G > A] and c.[1448C > T]) revealed a shared haplotype in the region of ETFDH, with SA population-specific allele frequencies of < 0.00067–0.00084%. Conclusions: This study reveals the first extensive genotype–phenotype profile of a MADD patient cohort from the diverse and understudied SA population. The pathogenic variants and associated variable phenotypes were characterised, which will enable early screening, genetic counselling, and patient-specific treatment of MADD in this population

Formaldehyde Densitometry of Galactic Star-Forming Regions Using the H2CO 3(12)-3(13) and 4(13)-4(14) Transitions

We present Green Bank Telescope (GBT) observations of the 3(12)-3(13) (29 GHz) and 4(13)-4(14) (48 GHz) transitions of the H2CO molecule toward a sample of 23 well-studied star-forming regions. Analysis of the relative intensities of these transitions can be used to reliably measure the densities of molecular cores. Adopting kinetic temperatures from the literature, we have employed a Large Velocity Gradient (LVG) model to derive the average hydrogen number density [n(H2)] within a 16 arcsecond beam toward each source. Densities in the range of 10^{5.5}--10^{6.5} cm^{-3} and ortho-formaldehyde column densities per unit line width between 10^{13.5} and 10^{14.5} cm^{-2} (km s^{-1})^{-1} are found for most objects, in general agreement with existing measurements. A detailed analysis of the advantages and limitations to this densitometry technique is also presented. We find that H2CO 3(12)-3(13)/4(13)-4(14) densitometry proves to be best suited to objects with T_K >~ 100 K, above which the H2CO LVG models become relatively independent of kinetic temperature. This study represents the first detection of these H2CO K-doublet transitions in all but one object in our sample. The ease with which these transitions were detected, coupled with their unique sensitivity to spatial density, make them excellent monitors of density in molecular clouds for future experiments. We also report the detection of the 9_2--8_1 A^- (29 GHz) transition of CH3OH toward 6 sources.Comment: 17 pages; 6 figures; Accepted by Ap