In silico analysis of κ-theraphotoxin-Cg2a from Chilobrachys guangxiensis

κ-theraphotoxin-Cg2a is a 29- residue polypeptide extracted from the venomous glands of the Chinese earth tiger tarantula Chilobrachys guangxiensis. Plethoras of cancers are being associated with irregular functions of potassium ion channels. An extensive understanding of the toxin’s interaction with the voltage-gated potassium channels is of utmost necessity for it to be screened as a potential pharmacological molecule which may perhaps serve as toxin-based therapy to manage various cancer channelopathies. Physicochemical properties were studied, the evolutionary analysis was done to visualize the conserved domain among different toxins of tarantula family, docking studies between κ-theraphotoxin-Cg2a and a voltage-gated potassium ion channel was done by ClusPro 2.0. The presence of signal peptide was observed using PSIPRED. Cysteine – disulfide bonds present in the amino acid sequence was predicted by DiANNA server. Multiple sequence alignment illustrated conserved residues with other families of tarantula’s toxin. The docking of κ-theraphotoxin-Cg2a with the voltage-gated potassium channel was found to be interactive. The presence of cysteine –disulfide bonds were observed potentially playing a crucial role in the docking process. The interaction between the receptor and the ligand was found to be interactive which could turn out to help develop strategies to assist in creating potential pharmacological drug-based therapies

Using health markets to improve access to medicines: three case studies

This editorial introduces a series of case studies that together highlight the use of health market interventions to improve access to medicines in low-and-middle income countries (LMICs). It underscores the added value of using a systems approach for a holistic understanding of how these interventions interact with the rest of the health system and the intended and unintended consequences that result. It goes on to summarize key findings from each of the studies and concludes with lessons for decision-makers on the design and implementation of market based interventions in LMIC health system

Cardiovascular Outcomes in Action to Control Cardiovascular Risk in Diabetes: Impact of Blood Pressure Level and Presence of Kidney Disease.

BACKGROUND: Persons with chronic kidney disease (CKD) represent a population prone to cardiovascular disease (CVD) but vulnerable to adverse medication effects. We assessed the impact of intensive antihypertensive therapy on the cerebrovascular and other CVD outcomes in high-risk patients with type 2 diabetes and baseline CKD. METHODS: Using current guideline criteria, 1,726 (36.9%) of 4,678 participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) blood pressure (BP) arm had mild to moderate CKD (CKD1-3B) at baseline. Participants of this study were randomized to intensive (systolic <120 mm Hg) or standard (systolic <140 mm Hg) BP goals. Fatal and non-fatal stroke were pre-specified secondary outcomes of the ACCORD study. RESULTS: Total cerebrovascular events were significantly higher in participants with baseline CKD (0.66%/year) compared with participants free of CKD (0.28%/year). A significantly higher rate of events was observed in CKD participants. Intensive antihypertensive therapy in participants without CKD at baseline resulted in a 55% significant reduction of any stroke (hazard ratio 0.447; 95% CI 0.227-0.880) and a 50% reduction of non-fatal stroke (hazard ratio 0.498; 95% CI 0.250-0.993). In participants with CKD at baseline, the occurrence of any stroke was reduced by 38% (hazard ratio 0.623; 95% CI 0.361-1.074) and non-fatal stroke by 36% (hazard ratio 0.642; 95% CI 0.361-1.142). Test for interaction was NS between the 2 groups. Changes in other CVD outcomes did not reach statistical significance. CONCLUSIONS: These findings suggest that intensive antihypertensive therapy offers significant cerebrovascular protection in diabetic participants without CKD at baseline, but significant benefit to patients with CKD cannot be excluded