Renal Transplantation in Second-Level Private Hospitals in the State of Mexico.

BACKGROUND: Kidney transplantation (KT) is the replacement therapy of choice in patients with end-stage renal disease (ESRD). Here we show a cohort of kidney transplant recipients from the period of May 1994 to May 2016 in 2 2nd-level private hospitals from the city of Toluca in the state of Mexico. METHODS: We checked the clinical files of all the patients that received KT in the period of study. RESULTS: We report 25 KT: 23 performed in Sanatorio Toluca and 2 in Sanatorio Florencia; 16 (64%) male and 9 (26%) female; mean age 36.03 ± 15.9 years (range, 10-66); 19 (76%) hemodialysis and 9 (24%) continuous ambulatory peritoneal dialysis before KT; ESRD etiology unknown in 16 (64%), diabetes in 5 (20%), IgA nephropathy in 2 (8%), and other in 2 (8%); living donors in 13 (52%) and deceased donors in 12 (48%); blood group 0+ in 18 (72%), A+ in 5 (20%), and B+ in 2 (8%); 21 (84%) with 0 and 4 (16%) with 1 HLA mismatch; and delayed graft function in 8 (32%), of which 7 were from deceased donors and 1 from a living donor. All 25 (100%) had a functional kidney at 1 year of follow-up. Immunosuppression regime consisted of multitarget maintenance therapy in all 25 (100%): cyclosporine in 18 (72%) and tacrolimus in 7 (28%). We used only methylprednisolone (MTP) as induction therapy. There were only 2 cases (8%) of acute rejection during the 1st 6 months of follow-up, and both responded to treatment with MTP. CONCLUSIONS: KT is the treatment of choice for patients with ESRD. The obtained results using only an MTP induction regime are satisfactory, with graft and patient survivals of 100% in the 1st year of follow-up.

Evidences of Polymorphism Associated with Circadian System and Risk of Pathologies: A Review of the Literature.

The circadian system is a supraphysiological system that modulates different biological functions such as metabolism, sleep-wake, cellular proliferation, and body temperature. Different chronodisruptors have been identified, such as shift work, feeding time, long days, and stress. The environmental changes and our modern lifestyle can alter the circadian system and increase the risk of developing pathologies such as cancer, preeclampsia, diabetes, and mood disorder. This system is organized by transcriptional/tranductional feedback loops of clock genes Clock, Bmal1, Per1-3, and Cry1-2. How molecular components of the clock are able to influence the development of diseases and their risk relation with genetic components of polymorphism of clock genes is unknown. This research describes different genetic variations in the population and how these are associated with risk of cancer, metabolic diseases such as diabetes, obesity, and dyslipidemias, and also mood disorders such as depression, bipolar disease, excessive alcohol intake, and infertility. Finally, these findings will need to be implemented and evaluated at the level of genetic interaction and how the environment factors trigger the expression of these pathologies will be examined.

Circadian System and Melatonin Hormone: Risk Factors for Complications during Pregnancy.

Pregnancy is a complex and well-regulated temporal event in which several steps are finely orchestrated including implantation, decidualization, placentation, and partum and any temporary alteration has serious effects on fetal and maternal health. Interestingly, alterations of circadian rhythms (i.e., shiftwork) have been correlated with increased risk of preterm delivery, intrauterine growth restriction, and preeclampsia. In the last few years evidence is accumulating that the placenta may have a functional circadian system and express the clock genes Bmal1, Per1-2, and Clock. On the other hand, there is evidence that the human placenta synthesizes melatonin, hormone involved in the regulation of the circadian system in other tissues. Moreover, is unknown the role of this local production of melatonin and whether this production have a circadian pattern. Available information indicates that melatonin induces in placenta the expression of antioxidant enzymes catalase and superoxide dismutase, prevents the injury produced by oxidative stress, and inhibits the expression of vascular endothelial growth factor (VEGF) a gene that in other tissues is controlled by clock genes. In this review we aim to analyze available information regarding clock genes and clock genes controlled genes such as VEGF and the possible role of melatonin synthesis in the placenta.

Flexible probe for in vivo quantification of corneal epithelium permeability through non-invasive tetrapolar impedance measurements.

Studies concerning the functional status of the corneal epithelium are of special interest due to its key role in preventing ocular surface disease and corneal infections. In particular, quantitative measurements of the epithelium permeability translayer electrical resistance (TER) have been proven as a sensitive in vitro test for evaluation of the corneal barrier function. In a recent work from the authors (Guimera et al. Biosens. Bioelectron. 31:55-61, 2012), a novel method to non-invasively assess the corneal epithelial permeability by using tetrapolar impedance measurements, based on the same TER theoretical principles, was presented and validated using a rigid sensing device. In this work, the usability of this method has been dramatically improved by using SU-8 photoresist as a substrate material. The flexibility of this novel sensing device makes no need to apply pressure on the cornea to ensure the electrical contact between the electrodes and the corneal surface. The feasibility of this flexible sensor has been evaluated in vivo by increasing the permeability of rabbit corneal epithelium. For that, different concentrations of benzalkonium chloride (BAC) solution were instilled on different rabbit corneas. The obtained results have been compared with measurements of the permeability to sodium fluorescein of different excised corneas, a well-known method used to evaluate the corneal barrier function, to demonstrate the feasibility of this novel flexible sensor for quantifying the corneal epithelium permeability in vivo in a non-invasive way.

In vivo and in vitro pharmacological characterization of SVT-40776, a novel M3 muscarinic receptor antagonist, for the treatment of overactive bladder.

BACKGROUND AND PURPOSE: Highly selective M(3) muscarinic receptor antagonists may represent a better treatment for overactive bladder syndrome, diminishing side effects. Cardiac side effects of non-selective antimuscarinics have been associated with activity at M(2) receptors as these receptors are mainly responsible for muscarinic receptor-dependent bradycardia. We have investigated a novel antimuscarinic, SVT-40776, highly selective for M(3) over M(2) receptors (Ki = 0.19 nmol.L(-1) for M(3) receptor affinity). This study reports the functional activity of SVT-40776 in the bladder, relative to its activity in atria. EXPERIMENTAL APPROACH: In vitro and ex vivo (oral dosing) inhibition of mouse detrusor and atrial contractile responses to carbachol were used to study the functional activity of SVT-40776. The in vivo efficacy of SVT-40776 was characterized by suppression of isovolumetric spontaneous bladder contractions in anaesthetized guinea pigs after intravenous administration. KEY RESULTS: SVT-40776 was the most potent in inhibiting carbachol-induced bladder contractions of the anti-cholinergic agents tested, without affecting atrial contractions over the same range of concentrations. SVT-40776 exhibited the highest urinary versus cardiac selectivity (199-fold). In the guinea pig in vivo model, SVT-40776 inhibited 25% of spontaneous bladder contractions at a very low dose (6.97 microg.kg(-1) i.v), without affecting arterial blood pressure. CONCLUSIONS AND IMPLICATIONS: SVT-40776 is a potent inhibitor of M(3) receptor-related detrusor contractile activity. The absence of effects on isolated atria preparations represents an interesting characteristic and suggests that SVT-40776 may lack unwanted cardiac effects; a feature especially relevant in a compound intended to treat mainly elderly patients.

Synthesis and biological evaluation of 1,3,4-triaryl-3-pyrrolin-2-ones, a new class of selective cyclooxygenase-2 inhibitors.

The synthesis and structure activity relationships (SAR) of a series of novel selective COX-2 inhibitors are reported. The results show that some of the 1,3,4-triaryl-3-pyrrolin-2-ones 1 are more potent as COX-2 inhibitors than celecoxib, and that lactam Id has the same selectivity.

In vitro susceptibilities of clinical yeast isolates to the new antifungal eberconazole compared with their susceptibilities to clotrimazole and ketoconazole.

The antifungal activity of eberconazole, a new imidazole derivative, against 124 clinical isolates of Candida comprising eight different species and to 34 isolates of Cryptococcus neoformans was compared to those of clotrimazole and ketoconazole. MICs of eberconazole, determined by the National Committee for Clinical Laboratory Standards standardized microbroth method, were equal to or lower than those of other azoles, especially for Candida krusei and Candida glabrata, which are usually resistant to triazoles.

Effects of linoleic and oleic acid anilides on prostacyclin synthesis and fibrinolytic profile of human endothelial cells in culture: relevance to the toxic oil syndrome.

We evaluated the effects of fatty-acid anilides (FAA) on prostacyclin (PGI2) synthesis and on the fibrinolytic properties of human umbilical vein endothelial cells. Preincubation of endothelial cells with oleic- and linoleic-anilides (OAA and LAA, respectively) resulted in a time- and concentration-dependent inhibition of ionophore A23187- and thrombin-induced PGI2 synthesis. However, no significant effects of FAA on arachidonic acid-induced PGI2 synthesis were found, except with 1000 microM LAA which inhibited cyclooxygenase activity after 24 h. In general terms, OAA showed similar inhibitory effects on PGI2 production as did LAA, but with a shifted time course, since the production of PGI2 at 24 h for OAA was similar to that observed for LAA at 2 h. The release of labeled arachidonic acid from cell membranes was significantly reduced (75-85%), after 24 h, with both FAA. The effect of 100 microM LAA on thrombin-induced PGI2 production was rapid (within 15 min) and irreversible after 60 min. The recovery of PGI2 synthesis after LAA treatment was blocked by cycloheximide, suggesting a decrease of phospholipase(s) activity or cessation of enzyme synthesis. Moreover, this reduced PGI2 synthesis was not associated with [3H]adenine release. Our data indicate that FAA induce a significant impairment of stimulated PGI2 synthesis and arachidonic acid release in endothelial cells, acting primarily as inhibitors of phospholipase(s) rather than of cyclooxygenase. Finally, both LAA and OAA induce an anti-fibrinolytic activity in these cells where major changes are observed in the plasminogen activator inhibitor and the urine-type plasminogen activator.

Influence of fatty acid anilides present in toxic oils on the metabolism of exogenous arachidonic acid in cultured human endothelial cells.

The effect of fatty acid anilides (FAA) on the exogenous arachidonic acid (AA) metabolism and toxicity of isolated human endothelial cells was studied to clarify their possible role in the etiology of toxic oil syndrome. Confluent cells were incubated with and without linoleic acid anilide (LAA), oleic acid anilide (OAA) and two unrelated samples for 2-24 h prior to the addition of [l-14C]AA alone or with calcium ionophore A-23187. The eicosanoids produced were analyzed by RP-HPLC. A dual stimulatory and inhibitory effect on the conversion of exogenous AA as a function of preincubation time with anilides (100 and 1000 microM) was observed. Treated cells significantly increased (1-3-fold) the production of the main cyclooxygenase-derived prostanoids (6-keto-PGF1 alpha and PGF2 alpha) formed by these cells, with a maximum stimulatory effect after 2-3 h, only when AA was used alone. However, afterwards a time- and dose-dependent decrease in prostanoid formation was observed with LAA (P < 0.05 at 24 h), either in the absence or presence of ionophore A-23187 in the incubation mixture. This inhibitory effect on cyclooxygenase was not observed with OAA, which still stimulate after 24 h of treatment. The changes in prostanoid synthesis were not followed with a parallel release in the lactate dehydrogenase activity in the medium (except with unrelated samples). Moreover, anilide treatment increased the appearance of cytosolic lipid droplets or vacuoles after 2 and 5 h of contact with LAA and OAA, respectively. From these results, it was suggested that anilides impair prostanoid synthesis in endothelial cells; their stimulatory effect could be explained by an unspecific effect on cell membrane, not related to cell toxicity and the inhibitory effect by an inhibition of the cyclooxygenase activity. These observations further contribute to our understanding of the possible role of anilides in the etiology of the toxic oil syndrome.

Cyclotron production of NCA 99mTc and 99Mo. An alternative non-reactor supply source of instant 99mTc and 99Mo----99mTc generators.

The direct production of no-carrier-added (NCA) 6.02 h 99mTc and of 66 h 99mMo using proton beams of natural Mo targets was investigated. The major objective of this work was to evaluate the potential of utilizing high-intensity proton accelerators as a supply source of 99mTc and 99Mo for use in diagnostic nuclear medicine. The excitation functions for the production of the directly-made 99mTc via the 100Mo(p, 2n)99mTc (Q = -7.85 MeV) reaction, and of its parent 99Mo via the 100Mo(p, pn) 99Mo (Q = -8.30 MeV) and 100Mo(p, 2p)99mNb(15 s)----99Mo (Q = -11.14 MeV) reactions, were measured in the 68-8 MeV energy range. Single and cumulative yields for 99mTc and 99Mo, and for other Tc, Mo, Zr, Nb and Y radiocontaminants were also determined. The prospects of integrating the use of enriched 100Mo targets with high-intensity, dual beam, H- accelerators was analyzed. The potential of this combined method to replace or complement the current reactor-based supply sources of 99Mo----99mTc generators, is also discussed. Finally, a brief analysis is made on the potential use of this combined technology to support the anticipated expansion of nuclear medicine in developing nations.

[Kinetics of eicosanoid formation in human epidermal cells in suspension]. / Estudio de la cinética de formación de eicosanoides en células epidérmicas humanas en suspensión.

Increased levels of eicosanoids in lesions of psoriasis suggest activation of arachidonic acid metabolism in different cell types play a physiopathologic role. The contribution of each cell type present in psoriasis has been the subject of some controversy, which has led us to study the metabolism of arachidonic acid in human epidermal cells suspensions. 12-HETE was found to be the main product, followed by PGE2 and PGF2 alpha; no 5-lypoxygenase products were found. Thus epidermal cell contribution to LTB4 levels present in plaques of psoriasis appears to be irrelevant. Conversely, increased levels of 12-HETE probably do result from arachidonic acid metabolism by epidermal cells.