Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new potassium research articles will be listed here shortly after becoming available to us.
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Medical research on potassium
Renal senescence in 2008: progress and challenges.
Int Urol Nephrol. 2008 Jun 27;
Zhou XJ, Saxena R, Liu Z, Vaziri ND, Silva FG
Kidneys are significantly affected by profound anatomic and functional changes with senescence. These changes lead to decline in glomerular filtration rate, decreased urinary concentrating and diluting ability, diminished urinary acidification, and impaired potassium clearance, to list a few. Such changes make the elderly prone to drug toxicity and serious fluid and electrolyte imbalance. While the entire mystery of aging is far from being clear, the role of oxidative stress, telomere length, Klotho gene expression, and the renin angiotensin system seem to be the key mechanisms involved in aging. Aging, being a complex process, involves an array of intertwined molecular pathways. Simultaneous study of multiple molecular pathways in parallel could provide invaluable information in understanding the clinical course of kidney aging and elucidating mechanisms that play key roles in the aging process. A better understanding of these mechanisms may help to preserve renal function, improve morbidity and mortality, and hopefully reduce healthcare costs for the aging population.
Potentiometric platform for the quantification of cellular potassium efflux.
Lab Chip. 2008 Jul; 8(7): 1210-5
Generelli S, Jacquemart R, de Rooij NF, Jolicoeur M, Koudelka-Hep M, Guenat OT
Renewed interest in the measurement of cellular K(+) effluxes has been prompted by the observation that potassium plays an active and important role in numerous key cellular events, in particular cell necrosis and apoptosis. Although necrosis and apoptosis follow different pathways, both induce intracellular potassium effluxes. Here, we report the use of potassium-selective microelectrodes located in a microfluidic platform for cell culture to monitor and quantify such effluxes in real time. Using this platform, we observed and measured the early signs of cell lysis induced by a modification of the extracellular osmolarity. Furthermore, we were able to quantify the number of dying cells by evaluating the extracellular potassium concentration. A comparison between the potentiometric measurement with a fluoresecent live-dead assay performed under similar conditions revealed the delay between potassium effluxes and cell necrosis. These results suggest that such platforms may be exploited for applications, such as cytotoxicological screening assays or tumor cell proliferation assays, by using extracellular K(+) as cell death marker.
Indian J Dermatol Venereol Leprol. 2008 May-Jun; 74(3): 226-9
Shenoy MM, Teerthanath S, Karnaker VK, Girisha BS, Krishna Prasad MS, Pinto J
Background: Onychomycosis is a common problem noticed in clinical practice. Currently available standard laboratory methods show inconsistent sensitivity; hence there is a need for newer methods of detection. Aims: This study involves comparison of standard laboratory tests in the diagnosis of onychomycosis, namely, potassium hydroxide mount (KOH mount) and mycological culture, with histopathologic examination using periodic acid-Schiff (PAS) staining of the nail clippings. Methods: A total of 101 patients with clinically suspected onychomycosis were selected. Nail scrapings and clippings were subjected to KOH mount for direct microscopic examination, culture using Sabouraud's dextrose agar (with and without antibiotics) and histopathologic examination with PAS staining (HP/PAS). Statistical analysis was done by McNemar's test. Results: Direct microscopy with KOH mount, mycological culture, and HP/PAS showed positive results in 54 (53%), 35 (35%), and 76 (75%) patients respectively. Laboratory evidence of fungal infection was obtained in 84 samples by at least one of these three methods. Using this as the denominator, HP/PAS had a sensitivity of 90%, which was significantly higher compared to that of KOH mount (64%) or mycological culture (42%). Conclusions: Histopathologic diagnosis with PAS staining of nail clippings was the most sensitive among the tests. It was easy to perform, rapid, and gave significantly higher rates of detection of onychomycosis compared to the standard methods, namely KOH mount and mycological culture.
Ann Clin Biochem. 2008 Jul; 45(Pt 4): 375-9
Tanner M, Kent N, Smith B, Fletcher S, Lewer M
BACKGROUND: Blood samples collected in rural and remote areas of Australasia are often exposed to a range of environmental conditions prior to analysis in a laboratory. The aim of this study was to determine analyte stability of venous blood specimens in serum gel tubes exposed to a range of storage temperatures and times prior to centrifugation. METHODS: Thirty healthy adult volunteers were enrolled in the study. Blood was collected into 11 serum gel separator tubes. All samples were allowed to clot at room temperature for 30 min. Two samples were centrifuged and analysed as controls. Nine samples were stored at 15, 25 or 35 degrees C for 4, 8 or 24 h, respectively, before centrifugation. Thirty-five biochemical analytes were measured on each sample. RESULTS: Most analytes remained stable in all storage conditions including sodium, total protein, albumin, bilirubin, alanine transferase, aspartate aminotransferase, alkaline phosphatase, gamma glutamyl transferase, creatinine kinase, lipase, cholesterol, triglycerides, transferrin, urate, C-reactive protein, vitamin B(12), thyroid-stimulating hormone, free thyroxine, free triiodothyronine, follicle-stimulating hormone, oestradiol, prostate-specific antigen, cortisol and vitamin D. Potassium, glucose, phosphate, creatinine, urea, ferritin, iron, lactate dehydrogenase, magnesium and calcium were not stable in at least one of the storage conditions. CONCLUSIONS: These results can be used to determine which analytes produce valid results despite exposure to variable storage conditions for up to 24 h prior to centrifugation. The majority of analytes were unaffected by a delay in centrifugation at a variety of temperatures, however, some important analytes were significantly affected.
Multimeric nature of voltage-gated proton channels.
Proc Natl Acad Sci U S A. 2008 Jun 26;
Koch HP, Kurokawa T, Okochi Y, Sasaki M, Okamura Y, Larsson HP
Voltage-gated potassium channels are comprised of four subunits, and each subunit has a pore domain and a voltage-sensing domain (VSD). The four pore domains assemble to form one single central pore, and the four individual VSDs control the gate of the pore. Recently, a family of voltage-gated proton channels, such as H(V) or voltage sensor only protein (VSOP), was discovered that contain a single VSD but no pore domain. It has been assumed that VSOP channels are monomeric and contain a single VSD that functions as both the VSD and the pore domain. It remains unclear, however, how a protein that contains only a VSD and no pore domain can conduct ions. Using fluorescence measurements and immunoprecipitation techniques, we show here that VSOP channels are expressed as multimeric channels. Further, FRET experiments on constructs with covalently linked subunits show that VSOP channels are dimers. Truncation of the cytoplasmic regions of VSOP reduced the dimerization, suggesting that the dimerization is caused mainly by cytoplasmic protein-protein interactions. However, these N terminus- and C terminus-deleted channels displayed large proton currents. Therefore, we conclude that even though VSOP channels are expressed mainly as dimers in the cell membrane, single VSOP subunits could function independently as proton channels.
Bioorg Med Chem Lett. 2008 Jun 10;
Das BC, Madhukumar AV, Anguiano J, Kim S, Sinz M, Zvyaga TA, Power EC, Ganellin CR, Mani S
PXR, pregnane X receptor, in its activated state, is a validated target for controlling certain drug-drug interactions in humans. In this context, there is a paucity of inhibitors directed toward activated PXR. Using prior observations with ketoconazole as a PXR inhibitor, the target compound 3 was synthesized from (s)-glycidol with overall 56% yield. (+)-Glycidol was reacted with 4-bromophenol and potassium carbonate in DMF to yield the ring opened compound 6. This was then heated to reflux in benzene along with 2', 4'-difluoroacetophenone and catalytic amount of para-toluene sulfonic acid to yield 8. The resultant acetal 8 was then functionalized using Palladium chemistry to yield the target compound 3. The activity of the compound was compared with ketoconazole and UCL2158H. However, in contrast with ketoconazole (IC(50) approximately 0.020muM; approximately 100% inhibition), 3 has negligible effects on inhibition of microsomal CYP450 (maximum approximately 20% inhibition) at concentrations >40muM. In vitro, micromolar concentration of ketoconazole is toxic to passaged human cell lines, while 3 does not exhibit cytotoxicity up to concentrations approximately 100muM (viability >85%). This is the first demonstration of a chemical analog of a PXR inhibitor that retains activity against activated PXR. Furthermore, in contrast with ketoconazole, 3 is less toxic in human cell lines and has negligible CYP450 activity.
Injury. 2008 Jun 24;
Singh Mangat K, Mehra A, Yunas I, Nightingale P, Porter K
AIM: Comparison of renal function in patients who died within 30 days of surgery for hip fractures with surviving patients matched for age, type of surgery, type of anaesthesia and clinical assessment of fitness for surgery. MATERIALS & METHODS: A retrospective case-control study of 80 patients was performed. Pre- and post-operative urea, creatinine, estimated glomerular filtration rate (eGFR), sodium and potassium of 40 patients who died within 30 days post-surgery (cases) were compared with 40 patients who survived matched for age, sex, surgical procedure and pre-operative ASA grade (controls). Statistical analysis involved univariable analysis by paired t-test and logistic conditional regression analysis. RESULTS: Pre- and post-operative mean serum creatinine were significantly higher in patients who died compared with surviving controls (pre-op 108.2 vs. 90.2mumol/l [p=0.002], post-op 103.9 vs. 87.1mumol/l [p=0.003]). However, mean creatinine values for both groups were still within normal laboratory reference ranges. Mean serum urea was also higher in patients who died (pre-op 8.81 vs. 6.75mmol/l [p=0.010] and post-op 9.30 vs. 6.63mmol/l [p=0.004], respectively). Pre- and post-operative eGFR was significantly lower in those patients who died within 30 days of hip fracture surgery (pre-op 61.75 vs. 68.78ml/min per 1.73m(2) [p=0.011], post-op 63.03 vs. 76.03ml/min per 1.73m(2) [p=0.009]). The mean eGFR values for survivors and non-survivors fell in the chronic kidney disease mild renal impairment category. There were no significant differences in mean serum sodium or potassium concentration between groups. Stepwise conditional logistic regression analysis, showed that after allowing for creatinine, urea was no longer significantly related to mortality. CONCLUSION: These results suggest that when allowance is made for demography, fitness for surgery and surgical procedure, subtle reductions in eGFR are still associated with mortality risk. However, these are of questionable clinical use.
Eur J Pharmacol. 2008 Jun 12;
Sahlholm K, Nilsson J, Marcellino D, Fuxe K, Arhem P
The recently cloned histamine H(4) receptor is expressed predominantly in haematopoietic cells and has been found to modulate the function of mast cells, eosinophils, dendritic cells and T lymphocytes. It represents an attractive target for pharmacological interventions against a number of inflammatory and autoimmune disorders. In the present work we used two-electrode voltage-clamp to demonstrate histamine H(4) receptor modulation of G protein-coupled inward rectifier potassium (GIRK) channels heterologously expressed in Xenopus oocytes. In accordance with earlier findings in other effector systems, full agonism by histamine and (R)-alpha-methylhistamine, partial agonism by clobenpropit and inverse agonism by thioperamide were observed. Furthermore, in oocytes injected with low amounts of receptor cRNA, clobenpropit apparently acted as a neutral antagonist. We also used the high temporal resolution afforded by this system to study the differential time courses of response deactivation upon ligand washout for clobenpropit and (R)-alpha-methylhistamine. GIRK channels represent a novel effector system for histamine H(4) receptor modulation, which may be of physiological relevance and prove useful in the development of compounds targeting this receptor.
Biochim Biophys Acta. 2008 Jun 3;
Bisset D, Chung SH
Blockade of the KcsA potassium channel by externally applied tetraethylammonium is investigated using molecular dynamics calculations and Brownian dynamics simulations. In KcsA, the aromatic rings of four tyrosine residues located just external to the selectivity filter create an attractive energy well or a binding cage for a tetraethylammonium molecule. We first investigate the effects of re-orienting the four tyrosine residues such that the centers of the aromatic rings face the tetraethylammonium molecule directly. Then, we systematically move the residues inward in both orientations so that the radius of the binding cage formed by them becomes smaller. For each configuration, we construct a one-dimensional free energy profile by bringing in a tetraethylammonium molecule from the external reservoir toward the selectivity filter. The free energy profile is then converted to a one-dimensional potential energy profile, taking the available space between the tyrosine residues and the tetraethylammonium molecule into account. Incorporating this potential energy profile into the Brownian dynamics algorithm, we determine the conductance properties of the channel under various conditions, construct the current-tetraethylammonium-concentration curve and compare it with the experimentally determined inhibitory constant k(i) for externally applied tetraethylammonium. We show that the experimentally determined binding affinity for externally applied tetraethylammonium can be replicated when each of the four tyrosine residues is moved inward by about 0.7 A, irrespective of orientation of their aromatic rings.
Gitelman's syndrome: report of one case.
Acta Paediatr Taiwan. 2008 Jan-Feb; 49(1): 31-4
Chan CF, Mu SC, Lau BH, Chang CJ, Lin SH
Gitelman's syndrome (GS) is a rare autosomal recessive renal tubular disorder characterized by hypokalemia, metabolic alkalosis, hypomagnesemia, and hypocalciuria. It is primarily caused by inactivating mutations of the SLC12A3 gene encoding the thiazide-sensitive Na-Cl cotransporter (NCC) on the apical membrane of distal convoluted tubule. We report an eight-year-old girl with incidental hypokalemia prior to appendectomy. All biochemical studies were consistent with GS. Genetic analysis of the NCC gene revealed two novel mutations (N442K and IVS6-1G > A). With regular potassium and magnesium supplementation, the patient has remained normal growth and development during two years of follow-up.