Does the taste matter? Taste and medicinal perceptions associated with five selected herbal drugs among three ethnic groups in West Yorkshire, Northern England

In recent years, diverse scholars have addressed the issue of the chemosensory perceptions associated with traditional medicines, nevertheless there is still a distinct lack of studies grounded in the social sciences and conducted from a cross-cultural, comparative perspective. In this urban ethnobotanical field study, 254 informants belonging to the Gujarati, Kashmiri and English ethnic groups and living in Western Yorkshire in Northern England were interviewed about the relationship between taste and medicinal perceptions of five herbal drugs, which were selected during a preliminary study. The herbal drugs included cinnamon (the dried bark of Cinnamomum verum, Lauraceae), mint (the leaves of Mentha spp., Lamiaceae), garlic (the bulbs of Allium sativum, Alliaceae), ginger (the rhizome of Zingiber officinale, Zingiberaceae), and cloves (the dried flower buds of Syzygium aromaticum, Myrtaceae). The main cross-cultural differences in taste perceptions regarded the perception the perception of the spicy taste of ginger, garlic, and cinnamon, of the bitter taste of ginger, the sweet taste of mint, and of the sour taste of garlic. The part of the study of how the five selected herbal drugs are perceived medicinally showed that TK (Traditional Knowledge) is widespread among Kashmiris, but not so prevalent among the Gujarati and especially the English samples. Among Kashmiris, ginger was frequently considered to be helpful for healing infections and muscular-skeletal and digestive disorders, mint was chosen for healing digestive and respiratory troubles, garlic for blood system disorders, and cinnamon was perceived to be efficacious for infectious diseases. Among the Gujarati and Kashmiri groups there was evidence of a strong link between the bitter and spicy tastes of ginger, garlic, cloves, and cinnamon and their perceived medicinal properties, whereas there was a far less obvious link between the sweet taste of mint and cinnamon and their perceived medicinal properties, although the link did exist among some members of the Gujarati group. Data presented in this study show how that links between taste perceptions and medicinal uses of herbal drugs may be understood as bio-cultural phenomena rooted in human physiology, but also constructed through individual experiences and culture, and that these links can therefore be quite different across diverse cultures

Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis

INTRODUCTION: Despite the advent of biological therapies for the treatment of rheumatoid arthritis, there is a compelling need to develop alternative therapeutic targets for nonresponders to existing treatments. Soluble receptors occur naturally in vivo, such as the splice variant of the cell surface receptor for vascular endothelial growth factor (VEGF)--a key regulator of angiogenesis in rheumatoid arthritis. Bioinformatics analyses predict that the majority of human genes undergo alternative splicing, generating proteins--many of which may have regulatory functions. The objective of the present study was to identify alternative splice variants (ASV) from cell surface receptor genes, and to determine whether the novel proteins encoded exert therapeutic activity in an in vivo model of arthritis. METHODS: To identify novel splice variants, we performed RT-PCR using an mRNA pool representing major human tissue types and tumors. Novel ASV were identified by alignment of each cloned sequence to its respective genomic sequence in comparison with full-length transcripts. To test whether these ASV have biologic activity, we characterized a subset of them for ligand binding, and for efficacy in an animal model of arthritis. The in vivo study was accomplished using adenoviruses expressing secreted ASV. RESULTS: We cloned 60 novel human ASV from 21 genes, encoding cell surface receptors--many of which are known to be important in the regulation of angiogenesis. The ASV were characterized by exon extension, intron retention and alternative exon utilization. Efficient expression and secretion of selected ASV--corresponding to VEGF receptor type 1, VEGF receptor type 2, VEGF receptor type 3, angiopoietin receptor Tie1, Met (receptor for hepatocyte growth factor), colony-stimulating factor 1 receptor, platelet-derived growth factor receptor beta, fibroblast growth factor receptor 1, Kit, and RAGE--was demonstrated, together with binding to their cognate ligands. Importantly, ASV derived from VEGF receptor type 1 and Tie1, and to a lesser extent from VEGF receptor type 2 and fibroblast growth factor receptor 1, reduced clinical signs of arthritis in vivo. The reduction was paralleled by decreased joint inflammation and destruction. CONCLUSION: The present study shows that unique ASV derived from receptors that play key roles in angiogenesis--namely, VEGF receptor type 1 and, for the first time, Tie1--can markedly reduce arthritis severity. More broadly, our results demonstrate that ASV are a source of novel proteins with therapeutic potential in diseases in which angiogenesis and cellular hyperplasia play a central role, such as rheumatoid arthritis

Multilayer scaffolds in orthopaedic tissue engineering

Abstract Purpose The purpose of this study was to summarize the recent developments in the field of tissue engineering as they relate to multilayer scaffold designs in musculoskeletal regeneration. Methods Clinical and basic research studies that highlight the current knowledge and potential future applications of the multilayer scaffolds in orthopaedic tissue engineering were evaluated and the best evidence collected. Studies were divided into three main categories based on tissue types and interfaces for which multilayer scaffolds were used to regenerate: bone, osteochondral junction and tendon-to-bone interfaces. Results In vitro and in vivo studies indicate that the use of stratified scaffolds composed of multiple layers with distinct compositions for regeneration of distinct tissue types within the same scaffold and anatomic location is feasible. This emerging tissue engineering approach has potential applications in regeneration of bone defects, osteochondral lesions and tendon-to-bone interfaces with successful basic research findings that encourage clinical applications. Conclusions Present data supporting the advantages of the use of multilayer scaffolds as an emerging strategy in musculoskeletal tissue engineering are promising, however, still limited. Positive impacts of the use of next generation scaffolds in orthopaedic tissue engineering can be expected in terms of decreasing the invasiveness of current grafting techniques used for reconstruction of bone and osteochondral defects, and tendon-to-bone interfaces in near future

Friday Convocation

Program listing performers and works performe

Infected Cell Killing by HIV-1 Protease Promotes NF-κB Dependent HIV-1 Replication

Acute HIV-1 infection of CD4 T cells often results in apoptotic death of infected cells, yet it is unclear what evolutionary advantage this offers to HIV-1. Given the independent observations that acute T cell HIV-1 infection results in (1) NF-κB activation, (2) caspase 8 dependent apoptosis, and that (3) caspase 8 directly activates NF-κB, we questioned whether these three events might be interrelated. We first show that HIV-1 infected T cell apoptosis, NF-κB activation, and caspase 8 cleavage by HIV-1 protease are coincident. Next we show that HIV-1 protease not only cleaves procaspase 8, producing Casp8p41, but also independently stimulates NF-κB activity. Finally, we demonstrate that the HIV protease cleavage of caspase 8 is necessary for optimal NF-κB activation and that the HIV-1 protease specific cleavage fragment Casp8p41 is sufficient to stimulate HIV-1 replication through NF-κB dependent HIV-LTR activation both in vitro as well as in cells from HIV infected donors. Consequently, the molecular events which promote death of HIV-1 infected T cells function dually to promote HIV-1 replication, thereby favoring the propagation and survival of HIV-1

Focal Distribution of Hepatitis C Virus RNA in Infected Livers

Background: Hepatitis C virus (HCV) is a plus-strand RNA virus that replicates by amplification of genomic RNA from minus strands leading to accumulation of almost one thousand copies per cell under in vitro cell culture conditions. In contrast, HCV RNA copy numbers in livers of infected patients appear to be much lower, estimated at a few copies per cell. Methodology/Principal Findings: To gain insights into mechanisms that control HCV replication in vivo, we analyzed HCV RNA levels as well as expression of interferon beta (IFNb) and several interferon stimulated genes (ISGs) from whole liver sections and micro-dissected subpopulations of hepatocytes in biopsy samples from 21 HCV-infected patients. The results showed that intrahepatic HCV RNA levels range form less than one copy per hepatocyte to a maximum of about eight. A correlation existed between viral RNA levels and IFNb expression, but not between viral RNA and ISG levels. Also, IFNb expression did not correlate with ISGs levels. Replication of HCV RNA occurred in focal areas in the liver in the presence of a general induction of ISGs. Conclusion/Significance: The low average levels of HCV RNA in biopsy samples can be explained by focal distribution of infected hepatocytes. HCV replication directly induces IFNb, which then activates ISGs. The apparent lack of a correlation between levels of IFNb and ISG expression indicates that control of the innate immune response during HCV infection

HIV gp120 Induces, NF-κB Dependent, HIV Replication that Requires Procaspase 8

HIV envelope glycoprotein gp120 causes cellular activation resulting in anergy, apoptosis, proinflammatory cytokine production, and through an unknown mechanism, enhanced HIV replication.We describe that the signals which promote apoptosis are also responsible for the enhanced HIV replication. Specifically, we demonstrate that the caspase 8 cleavage fragment Caspase8p43, activates p50/p65 Nuclear Factor kappaB (NF-kappaB), in a manner which is inhibited by dominant negative IkappaBalpha. This caspase 8 dependent NF-kappaB activation occurs following stimulation with gp120, TNF, or CD3/CD28 crosslinking, but these treatments do not activate NF-kappaB in cells deficient in caspase 8. The Casp8p43 cleavage fragment also transactivates the HIV LTR through NF-kappaB, and the absence of caspase 8 following HIV infection greatly inhibits HIV replication.Gp120 induced caspase 8 dependent NF-kappaB activation is a novel pathway of HIV replication which increases understanding of the biology of T-cell death, as well as having implications for understanding treatment and prevention of HIV infection

Rule-Based Categorization Deficits in Focal Basal Ganglia Lesion and Parkinson’s Disease Patients

Patients with basal ganglia (BG) pathology are consistently found to be impaired on rule-based category learning tasks in which learning is thought to depend upon the use of an explicit, hypothesis-guided strategy. The factors that influence this impairment remain unclear. Moreover, it remains unknown if the impairments observed in patients with degenerative disorders such as Parkinson’s disease (PD) are also observed in those with focal BG lesions. In the present study, we tested patients with either focal BG lesions or PD on two categorization tasks that varied in terms of their demands on selective attention and working memory. Individuals with focal BG lesions were impaired on the task in which working memory demand was high and performed similarly to healthy controls on the task in which selective-attention demand was high. In contrast, individuals with PD were impaired on both tasks, and accuracy rates did not differ between on and off medication states for a subset of patients who were also tested after abstaining from dopaminergic medication. Quantitative, model-based analyses attributed the performance deficit for both groups in the task with high working memory demand to the utilization of suboptimal strategies, whereas the PD-specific impairment on the task with high selective-attention demand was driven by the inconsistent use of an optimal strategy. These data suggest that the demands on selective attention and working memory affect the presence of impairment in patients with focal BG lesions and the nature of the impairment in patients with PD

Disease concepts and treatment by tribal healers of an Amazonian forest culture

<p>Abstract</p> <p>Background</p> <p>The extensive medicinal plant knowledge of Amazonian tribal peoples is widely recognized in the scientific literature and celebrated in popular lore. Despite this broad interest, the ethnomedical systems and knowledge of disease which guide indigenous utilization of botanical diversity for healing remain poorly characterized and understood. No study, to our knowledge, has attempted to directly examine patterns of actual disease recognition and treatment by healers of an Amazonian indigenous culture.</p> <p>Methods</p> <p>The establishment of traditional medicine clinics, operated and directed by elder tribal shamans in two remote Trio villages of the Suriname rainforest, presented a unique investigational opportunity. Quantitative analysis of clinic records from both villages permitted examination of diseases treated over a continuous period of four years. Cross-cultural comparative translations were articulated of recorded disease conditions through ethnographic interviews of elder Trio shamans and a comprehensive atlas of indigenous anatomical nomenclature was developed.</p> <p>Results</p> <p>20,337 patient visits within the period 2000 to 2004 were analyzed. 75 disease conditions and 127 anatomical terms are presented. Trio concepts of disease and medical practices are broadly examined within the present and historical state of their culture.</p> <p>Conclusion</p> <p>The findings of this investigation support the presence of a comprehensive and highly formalized ethnomedical institution within Trio culture with attendant health policy and conservation implications.</p