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Query: EC:6.2.1.1 (
ACS
)
78,556
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
To determine the prevalence of concomitant microvascular and macrovascular complications of diabetic nephropathy we retrospectively reviewed the medical records of all 1,952 type 2 diabetic patients followed-up at Security Forces Hospital, Riyadh, Saudi Arabia from January 1989 to December 2004. There were 626 (32.1%) patients (294 (47%) were males) who developed diabetic nephropathy. Their mean age was 66.9 +/- 11.4 years, mean duration of diabetes was 15.4 +/- 7.5 years, mean age at the onset of nephropathy was 61.5 +/- 12.4 years, and mean duration of nephropathy was 3.9 +/- 3.8 years. Concomitant diabetic complications included cataract (38.2%), acute coronary syndrome (36.1%), peripheral neuropathy (24.9%), myocardial infarction (24.1%), background retinopathy (22.4%), stroke (17.6%), proliferative
retinopathy
(11.7%), foot infection (7.3%), limb amputation (3.7%) and blindness (3%). Hypertension was documented in 577 (92.2%) patients, dyslipidemia in 266 (42.5%) and mortality from all causes in 86 (13.7%). There were 148 (23.6%) patients with one complication, 81 (12.9%) with two, 83 (13.3%) with three, and 61 (9.7%) with four or more. Deterioration of glomerular filtration rate was observed in 464 (74%) patients and doubling of serum creatinine in 250 (39.9%), while 95 (15.2%) developed end-stage renal disease (ESRD) at the end of study and 79 (12.6%) required dialysis. Complications were significantly more prevalent among males with greater number reaching ESRD level than females (P< 0.05). Relative risks of developing complications were significant after the onset of nephropathy;
ACS
(1.41), MI (1.49), stroke (1.48), diabetic foot (1.6), amputation (1.58) and death (1.93). We conclude that complications of diabetes are aggressive and progressive including high prevalence of diabetic nephropathy. Careful monitoring and proper institution of management protocols should be implemented to identify diabetic patients at high risk for complications and mitigate progression into ESRD.
...
PMID:Concomitant macro and microvascular complications in diabetic nephropathy. 1941 42
Cone photoreceptor cyclic-nucleotide gated channels (CNG) are tetrameric proteins composed of subunits from
CNGA3
and
CNGB3
. These channels transduce light information into electrical signals carried by both Na
+
and Ca
2+
ions. More than 100 mutations in the
CNGA3
gene are associated with the inherited
retinal disorder
, achromatopsia 2 (ACHM2), which results in attenuation or loss of color vision, daylight blindness, and reduced visual acuity. Classical techniques to measure CNG channel function utilize patch clamp electrophysiology measuring Na currents in the absence of divalent cations, yet intracellular Ca
2+
regulates both light and dark adaptation in photoreceptors. We developed a fluorescence-based, high-throughput Ca
2+
flux assay using yellow fluorescent protein (YFP) tagged CNGA3 channels expressed in HEK293 cells which allow monitoring for folding defects in mutant channels. The cell permeant cGMP analog, 8-(4-chlorophenylthio)-cGMP (CPT-cGMP), was used to activate Ca
2+
flux. The assay was validated using wild-type CNGA3 homomeric and heteromeric channels and ACHM2-associated homomeric mutant CNG channels, CNGA3-R427C, CNGA3-E590K, and CNGA3-L633P. Additionally, we examined two naturally occurring canine mutations causing day-blindness previously studied by patch clamp. We compared the CPT-cGMP
K
0.5
values of the channels with patch clamp values from previous studies. The assay provides a screen for modulation of gating and/or rescue of trafficking and/or misfolding defects in ACHM2-associated CNG channels. Importantly, the calcium flux assay is advantageous compared to patch clamp as it allows the ability to monitor CNG channel activity in the presence of calcium.
ACS
Chem Neurosci 2019 08 21
PMID:High-Throughput Ca
2+
Flux Assay To Monitor Cyclic Nucleotide-Gated Channel Activity and Characterize Achromatopsia Mutant Channel Function. 3129 Jun 51
