10 research outputs found
Canagliflozin and renal outcomes in type 2 diabetes and nephropathy
BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years
A Comprehensive Study of Extended Tetrathiafulvalene Cruciform Molecules for Molecular Electronics: Synthesis and Electrical Transport Measurements
Cruciform-like
molecules with two orthogonally placed π-conjugated
systems have in recent years attracted significant interest for their
potential use as molecular wires in molecular electronics. Here we
present synthetic protocols for a large selection of cruciform molecules
based on oligoÂ(phenyleneethynylene) (OPE) and tetrathiafulvalene (TTF)
scaffolds, end-capped with acetyl-protected thiolates as electrode
anchoring groups. The molecules were subjected to a comprehensive
study of their conducting properties as well as their photophysical
and electrochemical properties in solution. The complex nature of
the molecules and their possible binding in different configurations
in junctions called for different techniques of conductance measurements:
(1) conducting-probe atomic force microscopy (CP-AFM) measurements
on self-assembled monolayers (SAMs), (2) mechanically controlled break-junction
(MCBJ) measurements, and (3) scanning tunneling microscopy break-junction
(STM-BJ) measurements. The CP-AFM measurements showed structure–property
relationships from SAMs of series of OPE3 and OPE5 cruciform molecules;
the conductance of the SAM increased with the number of dithiafulvene
(DTF) units (0, 1, 2) along the wire, and it increased when substituting
two arylethynyl end groups of the OPE3 backbone with two DTF units.
The MCBJ and STM-BJ studies on single molecules both showed that DTFs
decreased the junction formation probability, but, in contrast, no
significant influence on the single-molecule conductance was observed.
We suggest that the origins of the difference between SAM and single-molecule
measurements lie in the nature of the molecule–electrode interface
as well as in effects arising from molecular packing in the SAMs.
This comprehensive study shows that for complex molecules care should
be taken when directly comparing single-molecule measurements and
measurements of SAMs and solid-state devices thereof
A Comprehensive Study of Extended Tetrathiafulvalene Cruciform Molecules for Molecular Electronics: Synthesis and Electrical Transport Measurements
Cruciform-like
molecules with two orthogonally placed π-conjugated
systems have in recent years attracted significant interest for their
potential use as molecular wires in molecular electronics. Here we
present synthetic protocols for a large selection of cruciform molecules
based on oligoÂ(phenyleneethynylene) (OPE) and tetrathiafulvalene (TTF)
scaffolds, end-capped with acetyl-protected thiolates as electrode
anchoring groups. The molecules were subjected to a comprehensive
study of their conducting properties as well as their photophysical
and electrochemical properties in solution. The complex nature of
the molecules and their possible binding in different configurations
in junctions called for different techniques of conductance measurements:
(1) conducting-probe atomic force microscopy (CP-AFM) measurements
on self-assembled monolayers (SAMs), (2) mechanically controlled break-junction
(MCBJ) measurements, and (3) scanning tunneling microscopy break-junction
(STM-BJ) measurements. The CP-AFM measurements showed structure–property
relationships from SAMs of series of OPE3 and OPE5 cruciform molecules;
the conductance of the SAM increased with the number of dithiafulvene
(DTF) units (0, 1, 2) along the wire, and it increased when substituting
two arylethynyl end groups of the OPE3 backbone with two DTF units.
The MCBJ and STM-BJ studies on single molecules both showed that DTFs
decreased the junction formation probability, but, in contrast, no
significant influence on the single-molecule conductance was observed.
We suggest that the origins of the difference between SAM and single-molecule
measurements lie in the nature of the molecule–electrode interface
as well as in effects arising from molecular packing in the SAMs.
This comprehensive study shows that for complex molecules care should
be taken when directly comparing single-molecule measurements and
measurements of SAMs and solid-state devices thereof