Substituent effects in cation-π interactions revisited: a general approach based on intrinsic properties of the arenes.

The controversial proposal that substituent effects in cation-π interactions can be attributed mainly to electrostatic effects between the ion and local dipoles has been theoretically studied by analyzing 171 aromatics interacting with Na(+). Our results stress the importance of both electrostatic and π-polarization effects to properly describe cation-π interactions.

The power of desktop scanning electron microscopy with elemental analysis for analyzing urinary stones.

The aim of this paper is to present a protocol for the routine morphocompositional study of kidney stones in a clinical setting, and to demonstrate that it is a simple and useful approach that can reliably determine the etiology of all types of kidney stones. Our routine study of kidney stones consists of a combination of stereoscopic microscopy, scanning electron microscopy, and infrared spectroscopy. The usefulness of such a procedure is demonstrated by its application to several illustrating examples. The protocol applied here is reliable and fast, and does not require multiple infrared spectroscopic analyses for most non-homogeneous samples. It also provides the identification of components that are present in very small proportions, the characteristics of internal and external structures, and information about areas with biological structures, such as renal tubules. It should be noted that results are obtained in a relatively short time and with high reliability. The detailed morphocompositional study of a urinary calculus is essential for establishing the diagnosis and etiology and for initiating the treatment of a patient with renal lithiasis, because there is a relationship between the specific characteristics of a stone and the specific etiology of the disease. The increasing number of treatments available for patients with different types of renal calculi makes improvements in diagnosis and determination of stone etiology, such as the procedure described here, more important now than ever.

Urinary pH and renal lithiasis.

Formation of calcium oxalate crystals, either as monohydrate or dihydrate, is apparently unrelated to urinary pH because the solubilities of these salts are practically unaltered at physiologic urinary pH values. However, a urinary pH <5.5 or >6.0 may induce uric acid or calcium phosphate crystals formation, respectively, which under appropriate conditions may induce the development of the calcium oxalate calculi. We assessed the relationship between the urinary pH and the formation of different types of calculi. A retrospective study in 1,478 patients was done. We determined the composition, macrostructure, and microstructure of the calculi and the urinary pH, 50.9% of calcium oxalate monohydrate unattached calculi were present in patients with urinary pH <5.5. We found that 34.1 and 41.5% of calcium oxalate dihydrate calculi were present in patients with urinary pH <5.5 and >6.0, respectively. Infectious calculi were found primarily in patients with urinary pH >6.0 (50.7%). Only calcium oxalate monohydrate papillary calculi were associated with urinary pH between 5.5 and 6.0 (43.1%). Urine of pH <5.5 shows an increased capacity to develop uric acid crystals, which can act as a heterogeneous nuclei of calcium oxalate crystals. In contrast, urine of pH >6.0 has an increased capacity to develop calcium phosphate crystals, which can act as a heterogeneous nuclei of calcium oxalate crystals. Oxalate monohydrate papillary calculi were associated to pH between 5.5 and 6.0 because the injured papilla acts as a heterogeneous nucleant. Consequently, measurement of urinary pH may be used to evaluate the lithogen risk of given urine.

Anticalculus effect of a triclosan mouthwash containing phytate: a double-blind, randomized, three-period crossover trial.

BACKGROUND AND OBJECTIVE: Dental calculus occurs as a consequence of supersaturation of saliva with respect to calcium phosphates. This mineralization of dental plaque can be delayed by the presence of crystallization inhibitors, such as pyrophosphate or bisphosphonates. Phytate inhibits brushite and hydroxyapatite crystallization and has the potential to prevent dental calculi formation. The aim of the present study was to examine the effects of phytate and zinc, administered in a mouthwash solution, to prevent the formation of dental calculus. MATERIAL AND METHODS: Healthy dental plaque-forming volunteers (n = 25) took part in a randomized, double-blind, three-period crossover clinical study to assess the efficacy of a phytate-containing mouthwash in relation to control and placebo effects. Subjects rinsed their mouths for 1 min, twice each day, with 20 mL of the test solution, without ingestion. Mouthwash efficacy was assessed through quantification of the amounts of calcium, phosphorus and magnesium present in the residues obtained by dental cleaning, performed by a single trained examiner. RESULTS: A good correlation was found among total calcium, magnesium and phosphorus in calcified dental plaque residues, indicating that any of these variables is adequate for evaluating the reduction of plaque crystallization as calcium phosphate. A statistically significant decrease in total calcium, magnesium and phosphorus was found in the phytate-treatment period compared with control and placebo periods, demonstrating the efficacy of the proposed treatment in reducing dental calculus formation. CONCLUSION: The high efficacy of phytate in reducing dental calculus formation suggests that this substance may be an effective treatment for preventing the development of calculus deposits.

Pemphigus-like lesions induced by imiquimod.

Imiquimod is an immunomodifier recently approved for the treatment of superficial basal cell carcinomas (sBCC). Although local adverse events (AEs) are the most commonly reported, systemic AEs have also been described. We present the case of a 60-year-old woman who, after the application of two sachets of imiquimod cream per day for 5 days/week to two large sBCCs, developed pemphigus-like lesions both at and distant from the application site. Histological examination of a skin biopsy found intraepidermal acantholytic blistering but results of direct immunofluorescence examination were negative. The lesions resolved after cessation of imiquimod. Two previous cases of imiquimod-induced pemphigus have been reported, but this is the first case with lesions distant from the site of application. We suggest that systemic absorption of the drug or greatly increased synthesis of cytokines could explain this reaction and recommend the use of low doses of imiquimod in the treatment of large or multiple sBCCs.

Intake of myo-inositol hexaphosphate and urinary excretion of inositol phosphates in Wistar rats: Gavage vs. oral administration with sugar.

OBJECTIVE: To evaluate the urinary levels of inositol phosphates (InsPs) in rats that received different salts of myo-inositol hexaphosphate (InsP6) by gavage or by oral administration. METHODS: Thirty rats received AIN-76A diet (in which InsPs are undetectable) for 15 days. Then, 12 rats received InsP6 by gavage as a Na salt or a Ca/Mg salt; after 4 days, the Na or Ca/Mg InsP6 was administered with water containing 15 g/L sucrose and urine samples were collected. The other 18 rats received oral InsP6, in which 0.5 g of sugar was combined with InsP6 as a Na salt, a Ca/Mg salt, or a Na salt with CaCO3; daily urine samples were collected. Urine levels of InsPs were determined using a nonspecific method and a specific method (polyacrylamide gel electrophoresis, PAGE), and different InsPs were identified by mass spectroscopy (MS). RESULTS: After 15 days of the InsP6-free diet, the non-specific method detected no urinary InsPs, and MS detected only InsP2. After administration of Na-InsP6 by gavage, the non-specific method indicated more urinary InsPs than the amount of InsP6 determined by PAGE. MS indicated the presence of urinary InsP2, InsP3, InsP4, InsP5, and InsP6 in these rats, with notable variations among animals. Use of the same treatment to administer Ca/Mg-InsP6 led to a lower overall content of urinary InsPs and a lower level of InsP6. Oral administration of InsP6 as a sugar pill led to lower urinary levels of InsPs than administration of InsP6 by gavage, and administration as a Ca/Mg pill or a Ca/Mg pill with CaCO3 led to lower levels than administration as a Na pill. CONCLUSION: Administration of InsP6 to rats leads to the excretion of a mixture of different InsPs. Rats more effectively absorb InsP6 when supplied without dietary components that interfere with its uptake, such as the Ca ion and sugar.

Evaluation of inositol phosphates in urine after topical administration of myo-inositol hexaphosphate to female Wistar rats.

AIMS: Previous studies demonstrated a remarkable increase of urinary InsP6 by topical administration. However, the methodology used for InsP6 analysis was not specific. The aim of this paper is to measure urinary inositol phosphates InsPs using more advanced methodologies and to compare the results with those obtained by the non-specific method. MATERIALS AND METHODS: We fed 12 female rats with a diet without InsP6 for 16days. Then, we administered a topical InsP6 gel at high doses for 7days (50mgInsP6/day) or at low doses for 28days (20mgInsP6/day). We measured urine levels InsPs using a nonspecific method (based on the ability of InsPs to complex Al3+) and levels of InsP6 by a specific method (using polyacrylamide gel electrophoresis). Identification of different InsPs was performed by MS. KEY FINDINGS: At baseline, after dietary deprivation of InsP6, rats only excreted InsP2 in their urine, and there was no detectable InsP6 or other InsPs. Rats given the high dose treatment for 7days had abundant urinary InsP6, but also had other InsPs in their urine; cessation of InsP6 administration led to decreased levels of urinary InsPs. Rats given the low dose treatment for 28days had increasing levels of urinary InsPs over time. The maximum urinary InsP6 was at 21days, after which InsPs excretion decreased. SIGNIFICANCE: We conclude that the skin can absorb InsP6 from a topical gel, and that InsP6 is excreted in the urine, along with other InsPs (InsP5, InsP4, InsP3, and InsP2).

Structural features of three ureterocele calculi.

Ureterocele calculi are developed in cavities with urinary retention but far from the upper renal cavities. The structural features of three ureterocele calcium oxalate stones were observed by scanning electron microscope coupled with X ray microanalysis. The urinary parameters of the three patients were also determined. The stone A consisted of loose structure of large calcium oxalate dihydrate crystals and small spheres of hydroxyapatite. The interior contains disorganized plate-like calcium oxalate monohydrate crystals. The stone B was formed by a compact outer layer of calcium oxalate monohydrate columnar crystals. The structure of stone interior was similar to the stone A. The stone C was formed by concentric layers composed of either calcium oxalate monohydrate columnar crystals or hydroxyapatite. The core consisted of agglomerated calcium oxalate monohydrate crystals, hydroxyapatite and organic matter. From the urinary biochemical data it was deduced that two ureterocele patients (who formed A and B stones) were hypercalciuric (calcium > 300 mg/24 h), being 6.5 the urinary pH value of the patient that formed the A stone, and 7.0 the urinary pH of the patient that formed the C stone. The rest of urinary parameters for the three patients were normal. Thus, one of the requisite conditions for unattached stone development is the existence of a place inside the urinary tract where the solid particles that act as calculus initiator of the stone can be retained enough time to exert this action.

Carbodiphosphorane mediated synthesis of a triflyloxyphosphonium dication and its reactivity towards nucleophiles.

A carbodiphosphorane ((Ph3P)2C) mediated synthesis of the first triflyloxyphosphonium dication (12+) bearing two electrophilic sites is presented. Depending on the nucleophile, 12+ reacts selectively either at the sulfur atom of the triflyloxy moiety or at the directly attached phosphorus atom. In substitution reactions at the phosphorus atom the triflyloxy moiety serves as a leaving group and enables the synthesis of rare examples of pseudo-halophosphonium dications.

Donor-acceptor interactions in tri(phosphonio)methanide dications [(Ph3P)2CP(X)Ph2]2+ (X = H, Me, CN, NCS, OH, Cl, OTf, F).

The impact of the strongly electron donating carbodiphosphorane moiety in the series of tri(phosphonio)methanide dications as triflate salts [(Ph3P)2CP(X)Ph2][OTf]2 (X = H, Me, CN, NCS, OH, Cl, OTf, F) deriving from [(Ph3P)2CPPh2][OTf] (19[OTf]) is presented. The influence of the introduced substituents X on the electronic structures of these dications is investigated by means of detailed NBO analysis, NMR spectroscopy and X-ray analysis.

Factors affecting calcium oxalate dihydrate fragmented calculi regrowth.

BACKGROUND: The use of extracorporeal shock wave lithotripsy (ESWL) to treat calcium oxalate dihydrate (COD) renal calculi gives excellent fragmentation results. However, the retention of post-ESWL fragments within the kidney remains an important health problem. This study examined the effect of various urinary conditions and crystallization inhibitors on the regrowth of spontaneously-passed post-ESWL COD calculi fragments. METHODS: Post-ESWL COD calculi fragments were incubated in chambers containing synthetic urine varying in pH and calcium concentration: pH = 5.5 normocalciuria (3.75 mM), pH = 5.5 hypercalciuria (6.25 mM), pH = 6.5 normocalciuria (3.75 mM) or pH = 6.5 hypercalciuria (6.25 mM). Fragment growth was evaluated by measuring increases in weight. Fragment growth was standardized by calculating the relative mass increase. RESULTS: Calcium oxalate monohydrate (COM) crystals formed on COD renal calculi fragments under all conditions. Under pH = 5.5 normocalciuria conditions, only COM crystals formed (growth rate = 0.22 +/- 0.04 microg/mg x h). Under pH = 5.5 hypercalciuria and under pH = 6.5 normocalciuria conditions, COM crystals and a small number of new COD crystals formed (growth rate = 0.32 +/- 0.03 microg/mg x h and 0.35 +/- 0.05 microg/mg x h, respectively). Under pH = 6.5 hypercalciuria conditions, large amounts of COD, COM, hydroxyapatite and brushite crystals formed (growth rate = 3.87 +/- 0. 34 microg/mg x h). A study of three crystallization inhibitors demonstrated that phytate completely inhibited fragment growth (2.27 microM at pH = 5.5 and 4.55 microM at pH = 6.5, both under hypercalciuria conditions), while 69.0 microM pyrophosphate caused an 87% reduction in mass under pH = 6.5 hypercalciuria conditions. In contrast, 5.29 mM citrate did not inhibit fragment mass increase under pH = 6.5 hypercalciuria conditions. CONCLUSION: The growth rate of COD calculi fragments under pH = 6.5 hypercalciuria conditions was approximately ten times that observed under the other three conditions. This observation suggests COD calculi residual fragments in the kidneys together with hypercalciuria and high urinary pH values may be a risk factor for stone growth. The study also showed the effectiveness of specific crystallization inhibitors in slowing calculi fragment growth.

Influence of concomitant food intake on the excretion of orally administered myo-inositol hexaphosphate in humans.

myo-Inositol hexaphosphate (InsP6) widely occurs in plant seeds. At present, some important benefits of InsP6 for human health have been described. The purpose of this study was to find the best condition for the optimum absorption of orally administered InsP6, evaluated by InsP6 urinary excretion. The influence of different stomach conditions (empty, empty with an alkalinizing agent, and full stomach) on the effects of oral administration of InsP6 and its urinary excretion was investigated in six healthy subjects on an InsP6-poor diet, given 400 mg of calcium/magnesium salt of InsP6 as a single dose. The basal urinary excretion of InsP6 on an InsP6-poor diet (50.91 +/- 15.09 microg) was significantly lower than that found when an InsP6-normal diet was consumed (100.09 +/- 26.42 microg) (P < .05). No differences were observed in the areas under the curve of accumulated excretion at 8 hours among the three different stomach conditions studied, suggesting that the overall InsP6 absorption took place independently of the stomach state (full or fasted) and indicating that the InsP6 absorption also takes place during the intestinal transit. Thus, if InsP6 supplements of vegetal origin are consumed to maintain the optimum InsP6 levels needed for a healthy status, these supplements can be consumed either during or between meals with the same efficacy.

Absorption of myo-inositol hexakisphosphate (InsP6) through the skin in humans.

In this paper, we present a pilot study of the absorption of myo-inositol hexakisphosphate (InsP6) through the skin in humans. We found that, after topical treatment with a 4% InsP6 rich gel, InsP6 urinary excretion increased 54% compared to the control situation (participants submitted to an InsP6-poor diet for 15 days, n = 6), clearly demonstrating that InsP6 is absorbed through the skin of humans. These results demonstrate the topical application as a suitable administration route of InsP6 in humans.

Approach to Management of Eyes with no Light Perception after Open Globe Injury.

Loss of light perception (LP) after open globe injury (OGI) does not necessarily mean the patient will have permanent complete visual loss. Findings that seem to be associated reliably with permanent profound vision loss after OGI include optic nerve avulsion, optic nerve transection, and profound loss of intraocular contents, which can be identified with CT/MRI imaging albeit with varying degrees of confidence. Eyes with NLP after OGI that undergo successful primary repair with intact optic nerves may be considered for additional surgery, particularly if there is: (1) recovery of LP on the first day after primary repair; (2) treatable pathology underlying NLP status (e.g., extensive choroidal hemorrhage, dense vitreous and subretinal hemorrhage); (3) NLP in the fellow eye. We counsel patients that the chance of recovering ambulatory vision under these circumstances is very low (~5%).