An Overview of the Potential Use of Ethno-Medicinal Plants Targeting the Renin-Angiotensin System in the Treatment of Hypertension.

The development of risk factors associated with cardiovascular disorders present a major public health challenge in both developed countries and countries with emerging economies. Hypertension and associated complications including stroke and myocardial infarction have reached pandemic levels. Current management strategies of hypertension predominantly include the utilization of pharmaceutical drugs which are often associated with undesirable side effects. Moreover, the drugs are often too expensive for populations from resource-limited Southern African rural, and some urban, communities. As a result, most patients rely on ethno-medicinal plants for the treatment of a variety of diseases including cardiovascular and metabolic disorders. The effectiveness of these plants in managing several cardiovascular diseases has been attributed to the presence of bioactive phytochemical constituents. In this review, the treatment options that target the renin-angiotensin system (RAS) in the management of hypertension were summarized, with special emphasis on ethno-medicinal plants and their influence on the ACE1 RAS pathway. The dearth of knowledge regarding the effect of ethno-medicinal plants on the ACE2 pathway was also highlighted.

Heart Rate Variability and Academic Performance of First-Year University Students.

BACKGROUND: Heart rate variability (HRV) measures have been shown to be positively associated with cognitive processing, while a positive association between cognitive processing and academic performance has been demonstrated. OBJECTIVES: To determine whether resting HRV or HRV marker response to either a cognitive or an orthostatic challenge is significantly associated with a first-year university student's academic performance. METHOD: HRV markers used in the study included total power (TP) as a measure of overall HRV and the root mean square of successive differences (RMSSD) as a measure of parasympathetic influence on the heart. Academic performance was determined by standardized general mean scores. RESULTS: Greater supine overall HRV (TP) was significantly associated with greater academic performance predominantly in females. Vagal (RMSSD) measures were not shown to be associated with academic performance. CONCLUSIONS: This, to our knowledge, is the first study to show that overall HRV has a significant positive association with academic performance of a first-year university student.

Validity of Commonly Used Heart Rate Variability Markers of Autonomic Nervous System Function.

BACKGROUND: Despite strong reservations regarding the validity of a number of heart rate variability (HRV) measures, these are still being used in recent studies. AIMS: We aimed to compare the reactivity of ostensible sympathetic HRV markers (low and very low frequency [LF and VLF]) to that of electrodermal activity (EDA), an exclusively sympathetic marker, in response to cognitive and orthostatic stress, investigate the possibility of LF as a vagal-mediated marker of baroreflex modulation, and compare the ability of HRV markers of parasympathetic function (root mean square of successive differences [RMSSD] and high frequency [HF]) to quantify vagal reactivity to cognitive and orthostatic stress. RESULTS: None of the purported sympathetic HRV markers displayed a reactivity that correlated with electrodermal reactivity. LF (ms2) reactivity correlated with the reactivity of both RMSSD and HF during baroreflex modulation. RMSSD and HF indexed the reactivity of the parasympathetic nervous system under conditions of normal breathing; however, RMSSD performed better as a marker of vagal activity when the task required breathing changes. CONCLUSIONS: Neither LF (in ms2 or normalized units [nu]) nor VLF represent cardiac sympathetic modulation of the heart. LF (ms2) may reflect vagally mediated baroreflex cardiac effects. HRV linear analysis therefore appears to be restricted to the determination of vagal influences on heart rate. With regard to HRV parasympathetic markers, this study supports the suggestion that HRV frequency domain analyses, such as HF, should not be used as an index of vagal activity in study tasks where verbal responses are required, as these responses may induce respiratory changes great enough to distort HF power.

Comparison between plasma neopterin and the urine neopterin:creatinine ratio as inflammatory biomarkers.

BACKGROUND: Neopterin, a product of cell-mediated immunity, is a non-specific biomarker of inflammation. Plasma/serum is generally the body fluid of choice for neopterin assessment, but urine is often used as it does away with venepuncture. Analysis of urine neopterin is based on collection of a single urine sample and expressed as µmol neopterin/mol creatinine. OBJECTIVES: To examine published correlations between plasma neopterin levels and urine neopterin:creatinine ratios and to determine whether they are in diagnostic agreement. METHODS: Literature search was performed by databases and by hand. Databases included Academic Search Complete; Africa-Wide Information; AHFS Consumer Medication Information; eBook Collection (EBSCOhost); Family & Society Studies Worldwide; MasterFILE Premier; MEDLINE; TOC Premier. RESULTS: Positive correlations of varying statistical significance generally exist between plasma neopterin and urine neopterin: creatinine ratios. With a decline in renal clearance, plasma neopterin over-estimates inflammatory activity. With immune-complex renal disease, urine neopterin:creatinine ratios over-estimate systemic inflammation. The two biomarkers can differ in diagnostic validity. CONCLUSION: Correlations between plasma neopterin and urine neopterin:creatinine ratios suggest both as suitable biomarkers. However, since correlations reflect equality of means and not individual values, significant correlations, do not necessarily imply diagnostic agreement. Therefore, plasma and urine cannot summarily be assumed interchangeable for diagnostic/prognostic purposes.

EEG Brain Wave Activity at Rest and during Evoked Attention in Children with Attention-Deficit/Hyperactivity Disorder and Effects of Methylphenidate.

OBJECTIVE: The aim of this study was to assess baseline EEG brain wave activity in children with attention-deficit/hyperactivity disorder (ADHD) and to examine the effects of evoked attention and methylphenidate on this activity. METHOD: Children with ADHD (n = 19) were tested while they were stimulant free and during a period in which they were on stimulant (methylphenidate) medication. Control subjects (n = 18) were tested once. EEG brain wave activity was tested both at baseline and during focussed attention. Attention was evoked and EEG brain wave activity was determined by means of the BioGraph Infiniti biofeedback apparatus. RESULTS: The main finding of this study was that control subjects and stimulant-free children with ADHD exhibited the expected reactivity in high alpha-wave activity (11-12 Hz) from baseline to focussed attention; however, methylphenidate appeared to abolish this reactivity. CONCLUSION: Methylphenidate attenuates the normal cortical response to a cognitive challenge.

Production, characterization, and antigen specificity of recombinant 62-71-3, a candidate monoclonal antibody for rabies prophylaxis in humans.

Rabies kills many people throughout the developing world every year. The murine monoclonal antibody (mAb) 62-71-3 was recently identified for its potential application in rabies postexposure prophylaxis (PEP). The purpose here was to establish a plant-based production system for a chimeric mouse-human version of mAb 62-71-3, to characterize the recombinant antibody and investigate at a molecular level its interaction with rabies virus glycoprotein. Chimeric 62-71-3 was successfully expressed in Nicotiana benthamiana. Glycosylation was analyzed by mass spectroscopy; functionality was confirmed by antigen ELISA, as well as rabies and pseudotype virus neutralization. Epitope characterization was performed using pseudotype virus expressing mutagenized rabies glycoproteins. Purified mAb demonstrated potent viral neutralization at 500 IU/mg. A critical role for antigenic site I of the glycoprotein, as well as for two specific amino acid residues (K226 and G229) within site I, was identified with regard to mAb 62-71-3 neutralization. Pseudotype viruses expressing glycoprotein from lyssaviruses known not to be neutralized by this antibody were the controls. The results provide the molecular rationale for developing 62-71-3 mAb for rabies PEP; they also establish the basis for developing an inexpensive plant-based antibody product to benefit low-income families in developing countries.

Potent and broad neutralization of HIV-1 by a llama antibody elicited by immunization.

Llamas (Lama glama) naturally produce heavy chain-only antibodies (Abs) in addition to conventional Abs. The variable regions (VHH) in these heavy chain-only Abs demonstrate comparable affinity and specificity for antigens to conventional immunoglobulins despite their much smaller size. To date, immunizations in humans and animal models have yielded only Abs with limited ability to neutralize HIV-1. In this study, a VHH phagemid library generated from a llama that was multiply immunized with recombinant trimeric HIV-1 envelope proteins (Envs) was screened directly for HIV-1 neutralization. One VHH, L8CJ3 (J3), neutralized 96 of 100 tested HIV-1 strains, encompassing subtypes A, B, C, D, BC, AE, AG, AC, ACD, CD, and G. J3 also potently neutralized chimeric simian-HIV strains with HIV subtypes B and C Env. The sequence of J3 is highly divergent from previous anti-HIV-1 VHH and its own germline sequence. J3 achieves broad and potent neutralization of HIV-1 via interaction with the CD4-binding site of HIV-1 Env. This study may represent a new benchmark for immunogens to be included in B cell-based vaccines and supports the development of VHH as anti-HIV-1 microbicides.