Association of obesity, diabetes, and hypertension with arsenic in drinking water in the Comarca Lagunera province (north-central Mexico).

Chronic endemic regional hydroarsenicism (CERHA) is a global issue that affects over 200 million people exposed to arsenic (As) in drinking water. This includes 1.75 million individuals residing in La Comarca Lagunera, a region in north-central Mexico. Arsenic levels in this region typically exceeds the WHO guideline of 10 µg L-1. Biochemical alterations related to the human As metabolism may increase the risk of overweight and obesity (O&O), type 2 diabetes (T2D), and hypertension (AHT). In our study, we investigated the role of As in drinking water as a risk factor for these metabolic diseases. We focused on populations with historically moderate (San Pedro) and low (Lerdo) drinking water As levels and people with no historical evidence of As water contamination. The exposure assessment to As was based on measurements of the drinking water (medians 67.2, 21.0, 4.3 µg L-1) and urinary As concentrations in women (9.4, 5.3, 0.8 µg L-1) and men (18.1, 4.8, 1.0 µg L-1). A significant correlation between As in drinking water and urine evidenced the As exposure in the population (R2 = 0.72). Adjusted odds ratios with 95% confidence intervals evidenced higher chances of being diagnosed with T2D (1.7, 1.2-2.0) and AHT (1.8, 1.7-1.9) in individuals living in San Pedro than those in Lerdo. Still, there was no significant association with obesity. Individuals living in CERHA towns were found to have a higher risk of obesity (1.3-1.9), T2D (1.5 to 3.3), and AHT (1.4 to 2.4) compared to those residing in non-CERHA towns. Finally, obesity is more probable in women [inverse of OR and 95%CI 0.4 (0.2-0.7)] compared to men, while men is more likely to be diagnosed with T2D [OR = 2.0 (1.4-2.3)] and AHT [OR = 2.0 (1.5-2.3)] than women, independently of the municipality.

High-pressure homogenization of raw and pasteurized milk modifies the yield, composition, and texture of queso fresco cheese.

High-pressure homogenization (HPH) of milk was studied as an alternative processing operation in the manufacturing of queso fresco cheese. Raw and pasteurized (65°C for 30 min) milks were subjected to HPH at 0, 100, 200, and 300 MPa and then used to manufacture queso fresco. The cheeses were evaluated for yield, moisture content, titratable acidity, nitrogen content, whey protein content, yield force, yield strain, and tactile texture by instrumental or trained panel analyses. The combination of HPH and thermal processing of milk resulted in cheeses with increased yield and moisture content. The net amount of protein transferred to the cheese per kilogram of milk remained constant for all treatments except raw milk processed at 300 MPa. The highest cheese yield, moisture content, and crumbliness were obtained for thermally processed milk subjected to HPH at 300 MPa. The principal component analysis of all measured variables showed that the variables yield, moisture content, and crumbliness were strongly correlated to each other and negatively correlated to the variables yield strain, protein content (wet basis), and sensory cohesiveness. It is suggested that the combination of thermal processing and HPH promotes thermally induced denaturation of whey protein, together with homogenization-induced dissociation of casein micelles. The combined effect results in queso fresco containing a thin casein-whey matrix that is able to better retain sweet whey. These results indicate that HPH has a strong potential for the manufacture of queso fresco with excellent yield and textural properties.

Effects of a functional food supplemented with probiotics on biological factors related to dental caries in children: a pilot study.

PURPOSE: The aim of this study was to evaluate the effects of a functional food supplemented with probiotics on biological factors related to dental caries in children aged 3-5 years. METHODS: A repeated measures pilot study was conducted with children who have consumed a commercial milk containing two lactic acid bacteria as probiotics (WP milk) for a period of 3 months and another period of 3 months consuming a milk without probiotics (NP milk). Salivary pH, plaque index, pH variation before and after a sugar rinse, quantification of Streptococcus mutans in saliva and demineralisation of the carious lesions were determined at the beginning and at the end of both milk ingestion periods. RESULTS: Regarding WP milk, a non-significant decrease in terms of the concentration of S. mutans and pH variation (p > 0.05), a significant decrease (i.e. acidification) in salivary pH (p < 0.01) and a remineralisation of 39.4% of the caries were found. On the other hand, for NP milk, a non-significant increase in terms of the concentration of S. mutans, pH variation, salivary pH (p > 0.05) and a remineralisation of 64.2% were found. CONCLUSIONS: Lactic acid probiotics can contribute to the decrease in the number of cariogenic microorganisms. However, the appropriate selection of the bacteria type with regard to its acidogenicity is fundamental to avoid the generation of an effect contrary to that expected, e.g. a significant decrease in salivary pH.

Phase I clinical trial in healthy adults of a nasal vaccine candidate containing recombinant hepatitis B surface and core antigens.

BACKGROUND: The nasal vaccine candidate (NASVAC), comprising hepatitis B virus (HBV) surface (HBsAg) and core antigens (HBcAg), has been shown to be highly immunogenic in animal models. METHODS: A phase I double-blinded, placebo-controlled randomized clinical trial was carried out in 19 healthy male adults with no serologic markers of immunity/infection to HBV. This study was aimed at exploring the safety and immunogenic profile of nasal co-administration of both HBV recombinant antigens. The trial was performed according to Good Clinical Practice guidelines. Participants ranged in age from 18 to 45 years and were randomly allocated to receive a mixture of 50 microg HBsAg and 50 microg HBcAg or 0.9% physiologic saline solution, as a placebo, via nasal spray in a five-dose schedule at 0, 7, 15, 30, and 60 days. A total volume of 0.5 ml was administered in two dosages of 125 microl per nostril. Adverse events were actively recorded 1 h, 6 h, 12 h, 24 h, 48 h, 72 h, 7 days and 30 days after each dose. Anti-HBs and anti-HBc titers were evaluated using corresponding ELISA kits at days 30 and 90. RESULTS: The vaccine candidate was safe and well tolerated. Adverse reactions included sneezing (34.1%), rhinorrhea (12.2%), nasal stuffiness (9.8%), palate itching (9.8%), headache (9.8%), and general malaise (7.3%). These reactions were all self-limiting and mild in intensity. No severe or unexpected events were recorded during the trial. The vaccine elicited anti-HBc seroconversion in 100% of subjects as early as day 30 of the immunization schedule, while a seroprotective anti-HBs titer (>or=10 IU/l) was at a maximum at day 90 (75%). All subjects in the placebo group remained seronegative during the trial. CONCLUSION: The HBsAg-HBcAg vaccine candidate was safe, well tolerated and immunogenic in this phase I study in healthy adults. To our knowledge, this is the first demonstration of safety and immunogenicity for a nasal vaccine candidate comprising HBV antigens.

[Factors associated with delayed hospital treatment for patients with acute cerebrovascular disease]. / Factores asociados a la demora del tratamiento hospitalario de los pacientes con enfermedad cerebrovascular aguda.

INTRODUCTION: Cerebrovascular diseases are an important cause of morbidity and mortality in the world and the effectiveness of thrombolytic therapy depends on early intervention. AIMS: To determine the time taken for patients with acute cerebrovascular events to reach hospital and to observe the variables associated to a longer delay. PATIENTS AND METHODS: We conducted a retrospective, descriptive study of 151 patients treated for acute cerebrovascular events between September 2003 and September 2004 at the Hospital Nacional Cayetano Heredia (Lima, Peru). We searched the records for the time taken to reach hospital, demographic variables and cerebrovascular risk factors, and we observed whether they exerted a significant effect on the arrival time. RESULTS: It was found that 29.8% of patients with an acute cerebrovascular event go to hospital within the first three hours; the mean arrival time is 51.11 hours. In contrast, 51% of patients go to hospital after more than 12 hours. Taking three and six hours as the cut-off points, uni and multivariate analyses showed ischemic stroke to be linked to a longer delay; a diagnosis of atrial fibrillation is associated to a shorter delay in arrival time in the multivariate analysis if a cut-off time of three hours is taken into account. CONCLUSIONS: Despite the high percentage of patients who take a long time to visit hospital following a cerebrovascular event, approximately a third of the patients would benefit from early treatment with thrombolytic therapy.

The impact of malnutrition on morbidity, mortality and length of hospital stay in trauma patients.

BACKGROUND AND AIM: To asses the nutritional status of hospitalised trauma patients and the repercussion on the clinical follow up. METHODS: In a prospective way 161 adult patients admitted to the units of Intensive Care (ICU), General Surgery, Maxillofacial Surgery and Orthopedics of the Centro de Emergencias Médicas in Asunción, Paraguay, from March 2002 to March 2004 were evaluated at admission by using the Subjective Global Assessment (SGA). Patients were followed to determine length of hospital stay, complications and in-hospital mortality. RESULTS: From the trauma patients median age was 27 (14-92) years and 94% were males. Most patients (74%) were from the countryside. The most frequent anatomic sites of trauma were: head 25%, thorax 16.6%, limbs 15.4%, abdomen 14%. The median Injury Severity Score (ISS) was 20 (1-39). From this population of patients, 40% were malnourished or at risk of malnutrition according to the SGA. Multivariate analysis identified as significant risk factors for mortality: malnutrition according to the SGA (p = 0.04, RR = 4 (1-15), and admission to the ICU (p = 0.0001, RR 53 (12-234). Risk factors for complications were malnutrition according to the SGA (p = 0.003, RR 2.9 (1.4-5.8) and ISS over 20 (p = 0.001, RR = 8.4 (2.3-29.9). The risk factors for length of stay were malnutrition according to the Subjective Global Assesment (p = 0.01, RR = 2.3 (1.2-4.7) and Injury Severity Score over 20, p = 0.03, RR = 2.8 (1-7.3). CONCLUSIONS: In the conditions of this study, malnutrition is frequent on admission in trauma patients, and is an independent risk factor for morbidity, mortality, and prolongs the length of hospitalisation. Efforts should be made to quickly assess the nutritional status of these patients and early start nutritional intervention.

The role of intracellular acidification in calcium mobilization in human neutrophils.

Propionic acid induces a calcium mobilization in human neutrophils which is prevented by pretreatment with phorbol ester or pertussis toxin. The effect is reminiscent of that of chemotactic factors and leukotriene B4 and was attributed to cytoplasmic acidification (Naccache, P.H. et al. (1988) J. Cell. Physiol. 136, 118-124). We show there that other weak acids also induced cytoplasmic alkalinization and calcium mobilization. However, addition of trimethylamine together with propionic acid prevented the cytoplasmic acidification without modifying the calcium mobilization. Propionic acid increased the production of inositol phosphates but this effect was largely prevented by the joint addition of trimethylamine. The ionophores nigericin and monensin can both be forced to produce either cytoplasmic acidification or alkalinization by manipulating the extracellular concentrations of Na+, K+ or H+. Both ionophores produced calcium mobilization in all the cases, irrespective of the direction of the cytoplasmic pH shift. The ionophores were documented to collapse existing pH gradients among the cytoplasm and intracellular compartments. We conclude that the calcium-mobilizing effect of propionic acid and other weak acids is not due to the acidification of the cytoplasm. Our results are consistent, however, with calcium mobilization induced by weak acids and ionophores arising from acidification of an alkaline intracellular compartment.

[Multiple sclerosis in Peru. A clinical-epidemiological description of a series of patients]. / Esclerosis múltiple en Perú. Descripción clinicoepidemiológica de una serie de pacientes.

INTRODUCTION: In Peru up to recent years multiple sclerosis (MS) was considered a very rare disorder. AIM. To report clinical, epidemiological and ancillary test results of an MS cases series. PATIENTS AND METHODS: Description of a retrospective cohort of 55 patients studied in HNCH and a private neurological center in Lima between 1993-2004. Clinical records, laboratory and MRI tests were reviewed with Mc Donald's criteria. RESULTS: There were 55 cases (36 women). Mean age was forty. 65% were born in Lima, 27% have foreign ancestor up to third generation. 42 cases were definite MS and 13 possible MS. The most frequent form of MS was RRMS (49.1%). Early symptoms were optic neuritis, motor and sensitive complaints; in the follow up cerebelar symptoms, increase of motor compromise and sphincteric disturbance were showed. Brain and spine MRI were positive in 27 cases and 17 cases respectively. VEP were abnormal in 53% of cases, just one case had cerebrospinal fluid (CSF) compatible with MS. Mode of EDSS was 6.5. Immunomodulators were used in 30% of cases. Survival at 10 and 20 years of disease were 87% and 45% respectively. CONCLUSION: Our study shows than optic neuritis is an important early symptom and CSF study is commonly negative in patients with MS. Survival is shorter than other reports. Other features resembled previous international reports. To have foreign ancestors could be a risk factor for MS in this group.

Sall2 is required for proapoptotic Noxa expression and genotoxic stress-induced apoptosis by doxorubicin.

The Sall2 transcription factor is deregulated in several cancers; however, little is known about its cellular functions, including its target genes. Recently, we demonstrated that p53 directly regulates Sall2 expression under genotoxic stress. Here, we investigated the role of Sall2 in the context of cellular response to genotoxic stress. In addition, we further examined the Sall2-p53 relationship during genotoxic stress in primary mouse embryo fibroblasts (MEFs), which are derived from Sall2 knockout mice separately, or in combination with the p53ERTAM knock-in mice. We found that the levels of Sall2 mRNA and protein are dynamically modulated in response to doxorubicin. At early times of stress, Sall2 is downregulated, but increases under extension of the stress in a p53-independent manner. Based on caspase-3/7 activities, expression of cleaved poly (ADP-ribose) polymerase, expression of cleaved caspase-3 and induction of proapoptotic proteins, Sall2 expression was correlated with cellular apoptosis. Consequently, Sall2-/- MEFs have decreased apoptosis, which relates with increased cell viability in response to doxorubicin. Importantly, Sall2 was required for apoptosis even in the presence of fully activated p53. Searching for putative Sall2 targets that could mediate its role in apoptosis, we identified proapoptotic NOXA/PMAIP1 (phorbol-12-myristate-13-acetate-induced protein 1). We demonstrated that Sall2 positively regulates Noxa promoter activity. Conserved putative Sall2-binding sites at the NOXA promoter were validated in vitro by electrophoretic mobility shift assay and in vivo by ChIP experiments, identifying NOXA as a novel Sall2 target. In agreement, induction of Noxa protein and mRNA in response to doxorubicin was significantly decreased in Sall2-/- MEFs. In addition, studies in leukemia Jurkat T cells support the existence of the Sall2/Noxa axis, and the significance of this axis on the apoptotic response to doxorubicin in cancer cells. Our study highlights the relevance of Sall2 in the apoptotic response to extended genotoxic stress, which is important for understanding its role in normal physiology and disease.

Enhanced tumor metastases upon drug delivery in cross-linked albumin beads.

Growth of the murine hepatoma H6 was significantly suppressed by amiloride, a sodium influx inhibitor. Primary tumor growth inhibition was augmented by loading the drug into cross-linked albumin carriers, but lung metastases were enhanced. These results emphasize the importance of using metastatic tumor models when testing new drugs and/or alternative modes of drug delivery.

The beta-endorphin-induced secretion of growth hormone but not of prolactin is inhibited by an endogenous opioid antagonist.

The naturally occurring peptide human beta-endorphin-(1-27) (h beta-EP-(1-27) has been shown to antagonize beta-endorphin (h beta-EP)-induced analgesia. We have evaluated the effects of the fragment on h beta-EP-induced growth hormone (GH) and prolactin (PRL) release. It inhibited beta-EP-induced GH release in a dose-related way but left beta-EP-induced PRL stimulation unchanged.

Using Airborne Digital Imagery for Detecting Oak Wilt Disease.

Color-infrared (CIR) digital imagery was evaluated as a remote sensing tool for detecting oak wilt disease in live oak (Quercus fusiformis). Aerial CIR digital imagery and CIR photography were obtained concurrently of a live oak forested area in south-central Texas affected by oak wilt. Dead, diseased, and healthy live oak trees could generally be delineated as well in the digital imagery as in the CIR photography. Light reflectance measurements obtained in the field showed that dead, diseased, and healthy trees had different visible and near-infrared reflectance values.

Effect of RotyIenchulus reniformis on reflectance of cotton plant leaves.

Differences between light reflectance from leaves of cotton (Gossypiurn hirsutum) plants grown with a low- or no-nematode (Rotylenchulus reniformis) population (nonstressed), and from leaves grown with a high nematode population (stressed) were measured in field and greenhouse experiments. Reflectance was measured spectrophotometrically in the laboratory on single leaves and spectroradiometrically in the field on plant canopies. Nematode-stressed cotton plants were stunted with fewer, smaller, and darker-green leaves than nonstressed plants. Over the 0.5- to 2.5-/microm waveband, stressed leaves had lower reflectance than nonstressed leaves of the same chronological age for both field- and greenhouse-grown plants. Reflectance differences between stressed and nonstressed leaves in the visible (0.5 to 0.75 microm), near-infrared (0.75 to 1.35 mum) and infrared water absorption (1.35 to 2.5 microm) regions were primarily caused by differences in leaf chlorophyll concentration, mesophyll structure, and water content, respectively. Results indicate the potential for remotely sensing nematode-infested plants to distinguish them from normal plants.

[Chemical disinfection. An alternative to sterilization in the treatment of cure instruments]. / Desinfección quimíca. Una alternativa a la esterilización en el tratamiento del instrumental de curas.

UNLABELLED: Sterilization is the reference method recommended to ensure the asepsia of an instrument used to perform cures. Chemical disinfection has shown itself to be highly effective in this process for endoscope equipment without there being definitive references about its efficiency on instruments used for cures. OBJECTIVE: Evaluate the efficiency of chemical disinfection on instruments used for cures, with the reference method being sterilization. METHODS: Prospective study in which the efficiency of glutaraldehyde-phenolate is compared to sterilization on 9 sets of instruments used for cures, each one having a dissection clamp and a Kocher clamp, used in 122 cures carried out in different wards at the León Hospital. Their efficiency was evaluated by means of microbiological studies after cures were performed and after disinfection or sterilization occurred. RESULTS: There were no positive cultures after either the disinfection or the sterilization. The existence of positive cultures after cures was related to the type of wound treated, clean wounds were always negative while dirty wounds were frequently positive (p < 0.05). CONCLUSION: Chemical disinfection with glutaraldehyde-phenolate is as efficient as sterilization in assuring the asepsia of instruments, while offering some clear advantages compared to sterilization since this chemical disinfection has a low cost, its use avoids the need to have duplicate instrument sets, it provides a longer life for these instruments and does not require moving instruments from their work site, thus preventing their loss.

An hypothesis on pressure transmission from anterior chamber to optic nerve.

Few studies have characterized how pressure in the anterior chamber (AC) of the eye is transmitted via the vitreous to the vitreous-ganglion cell interface. We are aware of only one study that simultaneously measured the pressures in the AC and vitreous humor; and of only one study that simultaneously measured the pressures in the AC and the suprachoroidal space (SCS). The pressure in the AC is defined as the intraocular pressure (IOP), which when elevated beyond statistically normal limits is a recognized risk factor for glaucoma, a malady best described as an optic neuropathy with degeneration and eventual death of the retinal ganglion cells (GC's) and highly characteristic changes in the optic nerve head (ONH). Most investigators currently believe that the prevalent risk factor for GC apoptosis is ocular hypertension, but no one has demonstrated how an increase in IOP in the AC is transmitted to the GC's. In patients with primary open angle glaucoma, the pressure in the AC increases due to an increase in the resistance of the trabecular meshwork (TM) outflow pathway. We questioned how such increased pressure in the AC would be transmitted to the GC to produce the changes in the ONH seen in glaucoma. Based on our preliminary data and purview of the literature, we hypothesize that a pressure increase originating in the AC is likely transmitted via both the SCS and the vitreous, with transmission via the former pathway probably most efficient in affecting the GC. Independently of the mechanism that produces GC apoptosis, the ones that are first affected, as repeatedly shown by visual field tests, are the most peripheral ones; i.e., those whose axons are the most external as they form the ONH and enter the lamina cribrosa. There are no published reports explaining this peculiarity. The dogma is that the pressure transmitted via the vitreous is higher at the periphery because it is transmitted across a shorter distance, since the vitreous acts as a buffer that absorbs part of the pressure being transmitted. We propose that IOP is not only transmitted via the vitreous but also via the SCS. Increases in IOP could be efficiently applied via the SCS to the most external axons of the ONH as they leave the eye. Our hypothesis can also explain low-tension glaucoma in which the most peripheral GC's are also affected first, because pressure is transmitted without decay due to a reduced uveoscleral (UVS) flow.

Causa infrecuente de obstrucción intestinal / Unusual cause of bowel obstruction

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Volume change of the ocular lens during accommodation.

During accommodation, mammalian lenses change shape from a rounder configuration (near focusing) to a flatter one (distance focusing). Thus the lens must have the capacity to change its volume, capsular surface area, or both. Because lens topology is similar to a torus, we developed an approach that allows volume determination from the lens cross-sectional area (CSA). The CSA was obtained from photographs taken perpendicularly to the lenticular anterior-posterior (A-P) axis and computed with software. We calculated the volume of isolated bovine lenses in conditions simulating accommodation by forcing shape changes with a custom-built stretching device in which the ciliary body-zonulae-lens complex (CB-Z-L) was placed. Two measurements were taken (CSA and center of mass) to calculate volume. Mechanically stretching the CB-Z-L increased the equatorial length and decreased the A-P length, CSA, and lens volume. The control parameters were restored when the lenses were stretched and relaxed in an aqueous physiological solution, but not when submerged in oil, a condition with which fluid leaves the lens and does not reenter. This suggests that changes in lens CSA previously observed in humans could have resulted from fluid movement out of the lens. Thus accommodation may involve changes not only in capsular surface but also in volume. Furthermore, we calculated theoretical volume changes during accommodation in models of human lenses using published structural parameters. In conclusion, we suggest that impediments to fluid flow between the aquaporin-rich lens fibers and the lens surface could contribute to the aging-related loss of accommodative power.

Hipertermia maligna / Malignant hypertermia

La hipertermia maligna es un trastorno muscular hereditario que se manifiesta como un estado hipermetabólico desencadenado después de que individuos susceptibles reciben anestésicos volátiles y/o relajantes musculares depolarizantes. La susceptibilidad se basa en una alteración en la regulación del calcio dentro de la fibra del músculo esquelético causada por un defecto en canales de calcio en el retículo sarcoplásmico. Una vez que la crisis de hipertermia maligna se desencadena, se inicia una liberación anormalmente alta de calcio en el retículo sarcoplásmico, dando lugar a un estado hipermetabólico, con signos clínicos típicos tales como taquicardia, rigidez muscular, hipercapnia e hipertermia. Debido a que la hipertermia maligna es potencialmente letal, es relevante establecer los conceptos de manejo de cuidados perioperatorios durante la crisis inesperada y en los pacientes susceptibles que se someten a cirugía. El objetivo de esta revisión es presentar los conocimientos actuales sobre la fisiopatología y los factores desencadenantes de la hipertermia maligna, así como conceptos para el manejo seguro de la anestesia de estos pacientes.

Malignant hyperthermia is an inherited muscle disorder characterized by hypermetabolism and is usually triggered after susceptible individuals are given volatile anesthetics and/or depolarizing muscle relaxants. Susceptibility is based on an altered regulation of calcium within the skeletal muscle fibre caused by a defective calcium release channel at the sarcoplasmic reticulum. Once malignant hyperthermia is triggered an abnormally high release of calcium from the sarcoplasmic reticulum is initiated resulting in a hypermetabolic state, leading to typicalclinical signs, such as tachycardia, muscle rigidity, hypercapnia as well as hyperthermia. Because malignant hyperthermia is potentially lethal, it is relevant to establish management concepts for perioperative care during unexpected crisis and susceptible patients who require surgery. The aim of this review is to present current knowledge about pathophysiology and triggers of malignant hyperthermia as well as concepts for safe anaesthesiological management of these patients.