Pediatric HIV/AIDS in sub-Saharan Africa: emerging issues and way forward

Background

Sub-Saharan Africa has the largest burden of pediatric HIV in the world. Global target has been set for eradication of pediatric HIV by 2015 but there are still so many complex issues facing HIV infected and affected children in the sub-continent.

Objective

To review the current and emerging challenges facing pediatric HIV care in sub-Saharan Africa; and proffer solutions that could help in tackling these challenges.

Method

A Medline literature search of recent publications was performed to identify articles on “pediatric HIV”, “HIV and children”, “HIV and infants”, “HIV and adolescents” in sub-Saharan Africa.

Result

There are a number of challenges and emerging complex issues facing children infected and affected by HIV in sub-Saharan Africa. These include late presentation, limited access to pediatric HIV services, delayed diagnosis, infant feeding choices, malnutrition, limited and complex drug regimen, disclosure, treatment failure and reproductive health concerns. A holistic cost effective preventive, diagnostic and treatment strategies are required in order to eliminate pediatric HIV in SSA.

Conclusion

HIV infected children and their families in sub-Saharan Africa face myriad of complex medical and psychosocial issues. A holistic health promotional approach is being advocated as the required step for eradication of pediatric HIV in Africa.     

Antimicrobial and antispasmodic activity of leaf extract and fractions of Stachytarpheta cayennensis

ObjectiveTo investigate the antimicrobial activity of the methanol leaf extract (ME), n-hexane fraction (HF), ethylacetate fraction (EF) and methanol fraction (MF), of Stachytarpheta cayennensis C. Rich (verbenaceae) as well as to ascertain the antispasmodic effects of the ME and the various fractions (HF, EF and MF) on acetylcholine (Ach) and histamine (H) induced contractions on isolated guinea pig ileum.MethodsThe in vitro agar well diffusion method was used for the antimicrobial studies while the isolated tissue method was employed for the antispasmodic test. Organisms used were all clinical isolates of Bacillus subtilis, Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella paratyphi, Candida albicans and Aspergillus niger.ResultsThe extract and fractions exhibited dose dependent inhibition against all the bacteria tested and also exhibited insignificant antifungal activity against Candida albicans and Aspergillus niger. The minimum inhibitory concentration (MIC) of the extract and fractions (mg/mL) on Bacillus subtilis, Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella paratyphi respectively were ME 5.62, 14.12, 22.38, 2.11; EF 1.25, 6.30, 9.40, 9.40 and MF 3.98, 8.81, 39.80, 21.13. The n-hexane fraction exhibited MIC of 1.07 mg/mL against only Bacillus subtilis. The extract and fractions exhibited significant (P< 0.05) dose dependent attenuation of contractions induced by acetylcholine and histamine on isolated guinea pig ileum. Concentrations of the extract and fractions (μg/mL) which evoked 50% inhibition of maximal response exhibited by Ach were ME 0.64, HF 0.16, EF 0.08 and MF 0.15, while that of histamine included ME 5.12, HF 0.16, EF 0.04 and MF 0.64. Preliminary phytochemical studies on the extract and fractions indicated the presence of carbohydrates, alkaloids, saponins, flavonoids, steroids and terpenoids.ConclusionsThe extract and fractions of Stachytarpheta cayennensis possessed both antibacterial and antispasmodic effects confirming the claimed use in folkloric medicine for wound healing and gastrointestinal ulceration.     

Dental status of Portuguese HIV+ patients and related variables: a multivariate analysis

Oral Diseases (2010) 16 , 176–184 Objective: The aim of this cross‐sectional study was to evaluate the dental status of 101 Portuguese HIV+ subjects aged 22–71 years (mean = 39) and its association with clinical, socioeconomic, and behavioral variables. Materials and Methods: A calibrated dentist performed clinical examination and collected data on dental caries, periodontal status, dental plaque levels, prosthetic conditions, and need. The volunteers completed questionnaires on socioeconomic and behavioral variables as well as the Oral Health Impact Profile (OHIP‐14) questionnaire. Univariate and multiple logistic regression (MLR) analyses were performed. Results: The mean number of decayed, missing or filled teeth index (DMFT index) was 16.44, standard deviation (s.d.) = 8.42. MLR demonstrated that salaried employee and those with OHIP‐14 ≤4.22, or any/no dental plaque were less prone to have DMFT > median (=17). As regards prosthetic status, 28.8% of the examined individuals used dental prosthesis. MLR demonstrated that HIV+ with DMFT >17 or those who knew they were HIV‐positive for longer than 5 years were more prone to need dental prostheses. The mean OHIP‐14 index was 5.83 (s.d. = 7.79). Conclusions: The dental health status of HIV‐infected Portuguese patients was unsatisfactory and related to clinical, socioeconomic, and behavioral variables.     

The effectiveness of the McKenzie method in addition to first-line care for acute low back pain: a randomized controlled trial

Background  

Low back pain is a highly prevalent and disabling condition worldwide. Clinical guidelines for the management of patients with acute low back pain recommend first-line treatment consisting of advice, reassurance and simple analgesics. Exercise is also commonly prescribed to these patients. The primary aim of this study was to evaluate the short-term effect of adding the McKenzie method to the first-line care of patients with acute low back pain.     

Tachykinin receptor modulation of cyclooxygenase-2 expression in human polymorphonuclear leucocytes

Background and purpose:

We investigated the ability of natural and synthetic selective NK receptors agonists and antagonists to modulate cyclooxygenase-2 (COX-2) expression in human polymorphonuclear leucocytes (PMNs).

Experimental approach:

The presence of all three tachykinin in PMNs was assessed by Western blot and PCR techniques. Natural and synthetic ligands selective for the tachykinin receptors were used to modulate COX-2 protein (measured with Western blotting) and activity [as prostaglandin E₂ (PGE₂) output]. Effects of substance P (SP) on phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) activation were studied to analyse the signalling pathway involved in COX-2 up-regulation mediated by SP.

Key results:

Stimulation of NK receptors with the natural ligands SP, neurokinin A (NKA) and neurokinin B, in the pmol·L⁻¹-µmol·L⁻¹ concentration range, modulated COX-2 expression and PGE₂ release in a concentration- and time-dependent manner. Experiments with synthetic selective agonists [Sar⁹, Met(O₂)¹¹]SP, [β-Ala⁸] NKA(4-10), senktide or selective antagonists L703,606, SR48,968 or SR142801, confirmed that COX-2 up-regulation was mediated by NK receptors. We found that mainly p38, p42 and p46 MAPKs were phosphorylated by SP and SB202190, PD98059 and SP600125, which are selective inhibitors of these kinases, blocked SP-induced COX-2 expression. SP also induced nuclear translocation of NF-κB concentration-dependently, with a maximum effect at 1 nmol·L⁻¹.

Conclusions and implications:

Human PMNs possess functional NK₁, NK₂ and NK₃ receptors, which mediate the induction of COX-2 expression and NF-κB activation by SP.     

Increased endothelin-1 reactivity and endothelial dysfunction in carotid arteries from rats with hyperhomocysteinemia

Background and purpose:

There are interactions between endothelin-1 (ET-1) and endothelial vascular injury in hyperhomocysteinemia (HHcy), but the underlying mechanisms are poorly understood. Here we evaluated the effects of HHcy on the endothelin system in rat carotid arteries.

Experimental approach:

Vascular reactivity to ET-1 and ET_A and ET_B receptor antagonists was assessed in rings of carotid arteries from normal rats and those with HHcy. ET_A and ET_B receptor expression was assessed by mRNA (RT-PCR), immunohistochemistry and binding of [¹²⁵I]-ET-1.

Key results:

HHcy enhanced ET-1-induced contractions of carotid rings with intact endothelium. Selective antagonism of ET_A or ET_B receptors produced concentration-dependent rightward displacements of ET-1 concentration response curves. Antagonism of ET_A but not of ET_B receptors abolished enhancement in HHcy tissues. ET_A and ET_B receptor gene expressions were not up-regulated. ET_A receptor expression in the arterial media was higher in HHcy arteries. Contractions to big ET-1 served as indicators of endothelin-converting enzyme activity, which was decreased by HHcy, without reduction of ET-1 levels. ET-1-induced Rho-kinase activity, calcium release and influx were increased by HHcy. Pre-treatment with indomethacin reversed enhanced responses to ET-1 in HHcy tissues, which were reduced also by a thromboxane A₂ receptor antagonist. Induced relaxation was reduced by BQ788, absent in endothelium-denuded arteries and was decreased in HHcy due to reduced bioavailability of NO.

Conclusions and implications:

Increased ET_A receptor density plays a fundamental role in endothelial injury induced by HHcy. ET-1 activation of ET_A receptors in HHcy changed the balance between endothelium-derived relaxing and contracting factors, favouring enhanced contractility.British Journal of Pharmacology (2009) 157, 568–580; doi:10.1111/j.1476-5381.2009.00165.x; published online 9 April 2009This article is part of a themed section on Endothelium in Pharmacology. For a list of all articles in this section see the end of this paper, or visit: http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009     

Gadolinium-enhanced cardiovascular magnetic resonance: administered dose in relationship to united states food and drug administration (FDA) guidelines

Purpose

Myocardial late gadolinium enhancement was originally validated using higher than label-recommended doses of gadolinium chelate. The objective of this study was to evaluate available evidence for various gadolinium dosing regimens used for CMR. The relationship of gadolinium dose warnings (due to nephrogenic systemic fibrosis) announced in 2008 to gadolinium dosing regimens was also examined.

Methods

We conducted a meta-analysis of peer reviewed publications from January, 2004 to December, 2010. Major subject search headings (MeSh) terms from the National Library of Medicine''s PubMed were: contrast media, gadolinium, heart, magnetic resonance imaging; searches were limited to human studies with abstracts published in English. Case reports, review articles, editorials, MRA related papers and all reports that did not indicate gadolinium type or weight-based dose were excluded. For all included references, full text was available to determine the total administered gadolinium dose on a per kg basis. Average and median dose values were weighted by the number of subjects in each study.

Results

399 publications were identified in PubMed; 233 studies matched the inclusion criteria, encompassing 19,934 patients with mean age 54.2 ± 11.4 (range 9.3 to 76 years). 34 trials were related to perfusion testing and 199 to myocardial late gadolinium enhancement. In 2004, the weighted-median and weighted-mean contrast dose were 0.15 and 0.16 ± 0.06 mmol/kg, respectively. Median contrast doses for 2005-2010 were: 0.2 mmol/kg for all years, respectively. Mean contrast doses for the years 2005-2010 were: 0.19 ± 0.03, 0.18 ± 0.04, 0.18 ± 0.10, 0.18 ± 0.03, 0.18 ± 0.04 and 0.18 ± 0.04 mmol/kg, respectively (p for trend, NS). Gadopentetate dimeglumine was the most frequent gadolinium type [114 (48.9%) studies]. No change in mean gadolinium dose was present before, versus after the Food and Drug Administration (FDA) black box warning (p > 0.05). Three multi-center dose ranging trials have been published for cardiac MRI applications.

Conclusion

CMR studies in the peer-reviewed published literature routinely use higher gadolinium doses than regulatory agencies indicated in the package leaflet. Clinical trials should be supported to determine the appropriate doses of gadolinium for CMR studies.     

Evaluation of antiplasmodial activity of ethanolic seed extract of Picralima nitida

The in vivo antiplasmodial activity of the ethanol seed extract of Picralima nitida grown particularly for the leaf and seed in Niger Delta region of Nigeria was evaluated in Plasmodium berghei berghei infected mice. Picralima nitida (35-115 mg/kg day) exhibited significant (P<0.05) blood schizonticidal activity both in 4-day early infection test and in established infection with a considerable mean survival time though not comparable to that of the standard drug, chloroquine, 5 mg/kg day. The seed extract possesses significant (P<0.05) antiplasmodial activity which correlate with it reported in vitro activity.