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Boyer L.V.,University of Arizona | Chase P.B.,University of Arizona | Degan J.A.,University of Arizona | Figge G.,Northwest Hospital | And 3 more authors.
Toxicon | Year: 2013

Background: Envenomation by pit vipers is associated with coagulation disorders including hypofibrinogenemia and thrombocytopenia. These abnormalities correct following antivenom treatment during the acute phase of the disease. Delayed or recurrent coagulation abnormalities have been reported following use of Fab antivenom, resulting in risk of hemorrhage or death. Methods: We hypothesized that the longer plasma persistence of F(ab')2 antivenom, relative to Fab, in patients at risk of coagulopathy would result in decreased venonemia and coagulopathy one week after treatment. We conducted a Phase 2, randomized comparative clinical trial of rattlesnake bitten adults presenting for care in Tucson, Arizona, USA. Patients were randomly assigned to receive either Fab or F(ab')2 antivenom using a predefined treatment schedule. Endpoints included platelet counts, fibrinogen levels, and venom and antivenom ELISAs. Measurements were conducted at baseline and at various times over the following two weeks. Results: Twelve patients were studied, with 6 randomly assigned to each treatment group. Early response of platelet counts, fibrinogen, and venom levels to acute treatment was similar in the two groups. One week following treatment, platelet counts and fibrinogen levels were lower in the Fab group than in the F(ab')2 group, following a characteristic pattern that reached its lowest point approximately one week after initial treatment. Venom levels dropped below detection limits in all patients following initial treatment but subsequently rebounded into the measurable range in 4 of 6 Fab cases. F(ab')2 antivenom levels demonstrated a longer plasma persistence than Fab levels, with a less rapid drop during the two days following treatment. Two patients in the Fab group had significant adverse events involving coagulation abnormalities, for which additional antivenom was administered following the initial treatment period. Conclusions: Following the acute phase of presentation and treatment for pit viper envenomation, there appears to be a roughly 2-week subacute phase of the disease during which ongoing presence of venom may result in serious delayed or recurrent coagulation defects. Late hypofibrinogenemia and thrombocytopenia are associated with recurrent venonemia and drop in antivenom levels. This pattern was apparent in patients treated with Fab antivenom but was not seen among F(ab')2 recipients in this Phase 2 study, consistent with pharmacokinetic differences between the two products. Improved understanding of Fab pharmacokinetics is important for the management of coagulopathy-prone pit viper envenomation. Use of F(ab')2 antivenom may prevent recurrent venom effects, but larger studies are necessary for statistical confirmation of this observation. © 2013 Elsevier Ltd.


Guzman-Brambila C.,University of Guadalajara | Quintero-Fabian S.,University of Guadalajara | Gonzalez-Castillo C.,University of Guadalajara | Gonzalez-Castillo C.,S.A. de C.V | And 6 more authors.
Research in Veterinary Science | Year: 2012

Bovine respiratory disease (BRD) complex is a major cause of economic losses for the cattle backgrounding and feedlot industries. Mannheimia haemolytica is considered the most important pathogen associated with this disease. Vaccines against M. haemolytica have been prepared and used for many decades, but traditional bacterins have failed to demonstrate effective protection and their use has often exacerbated disease in vaccinated animals. Thus, the BRD complex continues to exert a strong adverse effect on the health and wellbeing of stocker and feeder cattle. Therefore, generation of recombinant proteins has been helpful in formulating enhanced vaccines against M. haemolytica, which could confer better protection against BRD. In the present study, we formulated a vaccine preparation enriched with recombinant small fragments of leukotoxin A (LKTA) and outer-membrane lipoprotein (PlpE) proteins, and demonstrated its ability to generate high antibody titers in rabbits and sheep, which protected against M. haemolytica bacterial challenge in mice. © 2012 Elsevier Ltd.


Solari L.A.,National Autonomous University of Mexico | Gonzalez-Leon C.M.,National Autonomous University of Mexico | Ortega-Obregon C.,National Autonomous University of Mexico | Valencia-Moreno M.,National Autonomous University of Mexico | Rascon-Heimpel M.A.,S.A de C.V.
International Journal of Earth Sciences | Year: 2017

Several Proterozoic basement units crop out in the Sonora State of NW Mexico, and the same can be correlated with crustal provinces of southern Laurentia in the neighboring southwestern USA. Zircon U–Pb and Hf isotopic determinations in more than 300 grains separated from igneous and metaigneous rocks from these units indicate that the crystalline basement in Sonora is made up of different components, which are from west to east: (1) The Caborca–Mojave province to the west, characterized by the so-called Bámori Complex, have U–Pb ages between 1696 and 1772 Ma, with moderately juvenile to slightly evolved εHf values, yielding TDM ages of ca. 2.1–2.4 Ga; (2) in the intermediate area, east of Hermosillo, the Palofierral and La Ramada orthogneiss units yield an age of 1640 and 1703 Ma, respectively, both having juvenile εHf with the Palofierral overlapping the depleted mantle curve at ca. 1.65 Ga; and (3) in the northeastern Sonora, samples from the southern extension of the Mazatzal province, represented by the Pinal Schist, yielded ages between 1674 and 1694 Ma, with moderately juvenile to juvenile εHf values and a TDM age of ca. 1.9 Ga. In addition, a suite of post-tectonic granites was also studied in Caborca (San Luis granite) as well as in northeastern Sonora (Cananea granite), both yielding ages of ca. 1.44 Ga with moderately juvenile εHf values ranging from −1 to +8 and TDM dates of ca. 1.8–1.9 Ga and 1.6–1.7 Ga, respectively. These two isotopically contrasting provinces may imply the existence of a Proterozoic paleo-suture. However, if the Palofierral gneiss, of which the Hf signature straddles the depleted mantle array, is taken as the source for the 1.44 Ga Cananea granite, then the location of such a suture zone should lay farther south than the proposed trace of the Mojave–Sonora megashear. © 2017 Springer-Verlag GmbH Germany


Stern J.M.,Yeshiva University | Kibanov Solomonov V.V.,S.A. de C.V | Sazykina E.,S.A. de C.V | Schwartz J.A.,Nanospectra Biosciences, Inc. | And 2 more authors.
International Journal of Toxicology | Year: 2016

To evaluate the clinical safety profile for the use of gold nanoshells in patients with human prostate cancer. This follows on the nonclinical safety assessment of the AuroShell particles reported previously. Twenty-two patients, with biopsy diagnosed prostate cancer, underwent nanoshell infusion and subsequent radical prostatectomy (RRP). Fifteen of these patients had prostates that were additionally irradiated by a single-fiber laser ablation in each prostate hemisphere prior to RRP. Patients in the study were assessed at 9 time points through 6 months postinfusion. Adverse events were recorded as reported by the patients and from clinical observation. Blood and urine samples were collected at each patient visit and subjected to chemical (16 tests), hematological (23 tests), immunological (3 tests, including total PSA), and urinalysis (8 tests) evaluation. Temperature of the anterior rectal wall at the level of the prostate was measured. The study, recorded 2 adverse events that were judged attributable to the nanoparticle infusion: (1) an allergic reaction resulting in itching, which resolved with intravenous antihistamines, and (2) in a separate patient, a transient burning sensation in the epigastrium. blood/hematology/urinalysis assays indicated no device-related changes. No change in temperature of the anterior rectal wall was recorded in any of the patients. The clinical safety profile of AuroShell particles is excellent, matching nonclinical findings. A recent consensus statement suggested that the published literature does not support a preference for any ablation technique over another.1 Now that clinical safety has been confirmed, treatment efficacy of the combined infusion plus laser ablation in prostate will be evaluated in future studies using imaging modalities directing the laser against identified prostate tumors. © The Author(s) 2015.


Aidrete-Velasco J.,SA de CV | Lopez-Garcia R.,University Del Estado Of Louisiana | Zuniga-Guajardo S.,Autonomous University of Nuevo León | Riobo-Servan P.,Hospital Fundacioniimenez Diaz idc salud | And 8 more authors.
Medicina Interna de Mexico | Year: 2017

Non-caloric sweeteners are a good alternative to replace the sweet flavors without the physiological response generated by the consumption of sugars. Alone they are not tools for weight control. Its intake must be accompanied by a proper diet and a healthy lifestyle that includes physical activity. Its usefulness lies in providing a pleasant sweet taste without the energy intake. The safety of each of the compounds is tested and approved and constantly reassessed to take into account the results of new studies. Since there is no perfect sweetener, variety helps that more and more pleasing to the consumer products are developed. This work is the result of a comprehensive review of the literature and discussions of a panel of experts from various specialties: toxicology, obstetrics and gynecology, pediatrics, endocrinology, nutrition, internal medicine, public health and preventive medicine, where literature was widely analyzed reviewing a variety of scientific papers that address the questions that usually are made by health professionals on safety in different age groups and with specific diseases, acceptable daily intake, etc.


Herrera I.,National Autonomous University of Mexico | Herrera I.,S.A. de C.V | Yates R.A.,National Autonomous University of Mexico | Yates R.A.,S.A. de C.V
Numerical Methods for Partial Differential Equations | Year: 2011

The most commonly used nonoverlapping domain decomposition algorithms, such as the FETI-DP and BDDC, require the introduction of discontinuous vector spaces. Most of the works on such methods are based on approaches that originated in Lagrange multipliers formulations. Using a theory of partial differential equations formulated in discontinuous piecewise-defined functions, introduced and developed by Herrera and his collaborators through a long time span, recently the authors have developed an approach to domain decomposition methods in which general problems with prescribed jumps are treated at the discrete level. This yields an elegant and general direct framework that permits analyzing the problems in greater detail. The algorithms derived using it have properties similar to those of well-established methods such as FETI-DP, but, in our experience, they are easier to implement. Also, they yield explicit matrix formulas that unify the different methods. Furthermore, this multipliers-free framework has permitted us to extend such formulas to make them applicable to nonsymmetric matrices. The extension of the unifying matrix formulas to nonsymmetric matrices is the subject matter of the present article. A conspicuous result is that in numerical experiments in 2D and 3D, the MF-DP algorithms for nonsymmetric matrices exhibit an efficiency of the same order as state-of-the-art algorithms for symmetric matrices, such as BDDC, FETI-DP, and MF-DP. © 2010 Wiley Periodicals, Inc.

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