Results-based monitoring and evaluation for organizations working in agricultural development: a guide for practitioners

The purpose of this guide for practitioners is to contribute to the development of RBM&E capacity and to facilitate its institutionalization in organizations dealing with agricultural development. The target audiences of the guide include the staff in planning, monitoring and evaluation departments/units of public organizations and non-governmental organizations dealing with agricultural development at federal, regional, zonal or district levels. Staff of the agricultural research and higher learning institutes may also find the guide useful. It is assumed that users of the guide would have some basic knowledge of project/program/policy planning and implementation. The guide is based on an extensive review of M&E literature and the experiences of the RBM&E activities of the IPMS (Improving Productivity and Market Success) of Ethiopian farmers project.1 As part of its overall approach to market-oriented agricultural development, the IPMS project is working to facilitate the use and institutionalization of RBM&E system. The guide is organized as follows. Section two deals with basic concepts of RBM&E. Section three presents the relationships between the concepts and practices of M&E. Section four deals with the concepts and applications of participatory monitoring and evaluation. Sections five and six present the practices and processes of the selection of results to monitor and evaluate, and the selection of key performance indicators, respectively. Section seven discusses the methods of setting baseline data and targets, and section eight deals with data collection and analysis. While section nine deals with reporting and using M&E information, section ten discusses issues, approaches and requirements for institutionalizing and sustaining the RBM&E system

p38 MAP kinase mediated proteoglycan synthesis as a target for the prevention of atherosclerosis

The major underlying pathology of most cardiovascular disease is the chronic inflammatory disease of atherosclerosis. Type 2 diabetes, also recognised as an inflammatory condition, accelerates the development of atherosclerosis. Current therapies for atherosclerosis target risk factors such as elevated blood lipids and hypertension and are of strong but limited efficacy. The "response to retention" hypothesis states that atherosclerosis is initiated by the accumulation of lipids through binding to extracellular matrix, and this is specifically the glycosaminoglycan (GAG) chains on proteoglycans. Many vasoactive agonists stimulate changes in the structure of the GAGs which increase lipid binding and the relevant signalling pathways are a potential therapeutic target. It has recently been demonstrated that the actions of transforming growth factor b; on vascular smooth muscle proteoglycan synthesis involves signalling through p38 MAP kinase and inhibition of this pathway reduces binding of lipids. Inhibition of p38 MAP kinase will elicit a wide spread antiinflammatory response which may alleviate some of the deleterious processes in cardiovascular tissues. This article explores the potential for the actions of p38 MAP kinase inhibitors directed at proteoglycan synthesis in vascular smooth muscle to contribute to the beneficial outcomes from targeting p38 MAP kinase for the prevention of cardiovascular disease

Platelet-derived growth factor-stimulated versican synthesis but not glycosaminoglycan elongation in vascular smooth muscle is mediated via Akt phosphorylation

Proteoglycans are associated with the initiation of atherosclerosis due to their binding of apolipoproteins on lipid particles leading to retention in the vessel wall. The signaling pathways through which growth factors regulate the synthesis and structure of proteoglycans are potential therapeutic targets. Platelet-derived growth factor (PDGF) is present in atherosclerotic plaques and activates phosphorylation of the serine/threonine kinase Akt. We have investigated the role of Akt in the signaling pathways for proteoglycan core protein expression and elongation of glycosaminoglycan chains on proteoglycans secreted by human vascular smooth muscle cells. The pharmacological inhibitor of Akt phosphorylation, SN30978, blocked PDGF stimulated phosphorylation of Akt. SN30978 caused concentration dependent inhibition of PDGF stimulated radiosulfate incorporation into secreted proteoglycans and the response was blocked by the PDGF receptor antagonists Ki11502 and imatinib. Analysis of the size of the biglycan molecules by SDS-PAGE showed that PDGF increased the apparent size of biglycan but this effect on glycosaminoglycan chain elongation was blocked by Ki11502 but not by SN30978. PDGF also stimulated total protein core protein synthesis assessed as 35S-methionine/cysteine incorporation and specifically the expression of versican mRNA. Both of these responses were blocked by SN30978. This data shows that PDGF-stimulated proteoglycan core protein synthesis but not glycosaminoglycan chain elongation is mediated via Akt phosphorylation. These data identify potential pathways for the development of agents which can pharmacologically regulate individual components of the synthesis of proteoglycans

Smad2-dependent glycosaminoglycan elongation in aortic valve interstitial cells enhances binding of LDL to proteoglycans

Calcific aortic valve disease is a progressive condition that shares some common pathogenic features with atherosclerosis. Transforming growth factor-ß1 is a recognized mediator of atherosclerosis and is expressed in aortic valve lesions. Transforming growth factor-ß1 stimulates glycosaminoglycan elongation of proteoglycans that is associated with increased lipid binding. We investigated the presence of transforming growth factor-ß1 and downstream signaling intermediates in diseased human aortic valves and the effects of activated transforming growth factor-ß1 receptor signaling on aortic valve interstitial cell proteoglycan synthesis and lipid binding as a possible mechanism for the initiation of the early lesion of calcific aortic valve disease

TGF-β stimulates biglycan core protein synthesis but not glycosaminoglycan chain elongation via Akt phosphorylation in vascular smooth muscle

Transforming growth factor-b (TGF-b) can mediate proteoglycan synthesis via Smad and non-Smad signalling pathways in vascular smooth muscle (VSM). We investigated whether TGF-b-mediated proteoglycan synthesis is via PI3K/Akt. TGF-b induced a rapid phosphorylation of Akt that continued upto 4 h. Akt phosphorylation was blocked by Akt1/2 inhibitor SN30978; however, it did not block Smad2 phosphorylation at either the carboxy or linker regions indicating that TGF-bmediated Akt phosphorylation is independent of Smad2 signalling. The role of Akt in TGF-b-mediated proteoglycan synthesis was investigated. Treatment with SN30978 showed a concentration-dependent decrease in TGF-b-mediated [35S]- sulphate and [35S]-Met/Cys incorporation into secreted proteoglycans; however, SDS-PAGE showed no change in biglycan size. In TGF-b-treated cells, biglycan mRNA levels increased by 40-100% in 24 h and was significantly blocked by SN30978. Our findings demonstrate that Akt is a downstream signalling component of TGF-b-mediated biglycan core protein synthesis but not glycosaminoglycan chain hyper-elongation in VSM

CB1 Receptors Regulate Alcohol-Seeking Behavior and Alcohol Self-administration of Female Alcohol-Preferring (P) Rats

Rationale The endogenous cannabinoid (CB) system mediates a number of behaviors associated with drug-seeking and drug self-administration. In this study the effects of CB1 receptor manipulations on operant ethanol (EtOH) responding during EtOH-seeking, EtOH- relapse as well as on-going EtOH self-administration were determined. Methods Alcohol-preferring (P) rats were trained in 2-lever operant chambers to self-administer 15% EtOH (v/v) and water on a concurrent fixed-ratio 5 – fixed-ratio 1 (FR5-FR1) schedule of reinforcement in daily 1-hr sessions. After 10 weeks, rats underwent 7 extinction sessions, followed by 2 weeks in their home cages without access to EtOH or operant chambers. Rats were then returned to the operant chambers for testing of EtOH-seeking behavior (no EtOH present) for 4 sessions. After a week in their home cages following the EtOH-seeking test, rats were returned to the operant chambers with access to EtOH and water (relapse). Rats were then maintained in the operant chambers for daily 1-hr sessions with access to 15% EtOH and water for several weeks. Results The CB1 receptor antagonist (SR141716A), at doses of 1 and 2 mg/kg, i.p. reduced EtOH-seeking and transiently reduced EtOH self-administration during relapse and maintenance. Conversely, treatment with the CB1 receptor agonist CP, 55-940, at doses of 1 and 10 μg/kg i.p., increased EtOH-seeking and EtOH self-administration during relapse. Conclusions The results of this study demonstrate that activation of CB1 receptors are involved in regulating EtOH-seeking as well as the reinforcing effects of EtOH under relapse and on-going self-administration conditions

Genistein inhibits PDGF-stimulated proteoglycan synthesis in vascular smooth muscle without blocking PDGFß receptor phosphorylation

The signaling pathways that regulate the synthesis and structure of proteoglycans secreted by vascular smooth muscle cells are potential therapeutic targets for preventing lipid deposition in the early stage of atherosclerosis. PDGF stimulates both core protein expression and elongation of glycosaminoglycan (GAG) chains on proteoglycans. In this study we investigated the effects of the tyrosine kinase inhibitor genistein on PDGF mediated receptor phosphorylation and proteoglycan synthesis in human vascular smooth muscle cell

Atherogenic, fibrotic and glucose utilising actions of glucokinase activators on vascular endothelium and smooth muscle

Pharmaceutical interventions for diabetes aim to control glycaemia and to prevent the development of complications, such as cardiovascular diseases. Some anti-hyperglycaemic drugs have been found to have adverse cardiovascular effects in their own right, limiting their therapeutic role. Glucokinase activity in the pancreas is critical in enhancing insulin release in response to hyperglycaemia. Glucokinase activators (GKAs) are novel agents for diabetes which act by enhancing the formation of glucose-6-phosphate leading to increased insulin production and subsequent suppression of blood glucose. Little, however, is known about the direct effects of GKAs on cardiovascular cells.Methods: The effect of the GKAs RO28-1675 and Compound A on glucose utilisation in bovine aortic endothelial cells (BAEC) and rat MIN6 was observed by culturing the cells at high and low glucose concentration in the presence and absence of the GKAs and measuring glucose consumption. The effect of RO28-1675 at various concentrations on glucose-dependent signalling in BAEC was observed by measuring Smad2 phosphorylation by Western blotting. The effect of RO28-1675 on TGF-ß stimulated proteoglycan synthesis was measured by 35S-SO4 incorporation and assessment of proteoglycan size by SDS-PAGE. The effects of RO28-1675 on TGF-ß mediated Smad2C phosphorylation in BAEC was observed by measurement of pSmad2C levels. The direct actions of RO28-1675 on vascular reactivity were observed by measuring arteriole tone and lumen diameter