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Aims: This subanalysis of the SoliMix trial assessed the efficacy and safety of advancing basal insulin (BI) therapy with iGlarLixi versus BIAsp 30 in people with type 2 diabetes (T2D) living in Latin American (LATAM) countries, i.e. Argentina and Mexico (N = 160)., Materials and Methods: SoliMix (EudraCT: 2017-003370-13) was a 26-week, open-label, multicentre study, where adults with T2D suboptimally controlled with BI plus one or two oral glucose-lowering drugs and glycated haemoglobin (HbA1c) ≥7.5% to ≤10% were randomized to once-daily iGlarLixi or twice-daily BIAsp 30. Primary efficacy endpoints were non-inferiority in HbA1c reduction (margin 0.3%) or superiority in body weight change for iGlarLixi versus BIAsp 30., Results: Both primary efficacy endpoints were met in the LATAM region. After 26 weeks, HbA1c was reduced by 1.8% with iGlarLixi and 1.4% with BIAsp 30, meeting non-inferiority [least squares mean difference -0.47% (95% confidence interval: -0.82, -0.11); p < .001]. iGlarLixi was superior to BIAsp 30 for body weight change [least squares mean difference -1.27% (95% confidence interval: -2.41, -0.14); p = .028]. iGlarLixi was also superior to BIAsp 30 for HbA1c reduction (p = .010). A greater proportion of participants achieved HbA1c <7% without weight gain and HbA1c <7% without weight gain and without hypoglycaemia with iGlarLixi versus BIAsp 30. Incidence and rates of American Diabetes Association Level 1 and 2 hypoglycaemia were lower with iGlarLixi versus BIAsp 30., Conclusions: Once-daily iGlarLixi provided better glycaemic control with weight benefit and less hypoglycaemia than twice-daily premix BIAsp 30. iGlarLixi may be a favourable alternative to premix BIAsp 30 in people with suboptimally controlled T2D to advance BI therapy in the LATAM region., (© 2023 Sanofi Group and The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Evidence suggests that schizophrenia (SCZ), schizoaffective disorder (SAD) and bipolar disorder (BPD) share genetic risk variants. ZNF804A gene has been associated with these disorders in different populations. GWAS and candidate gene studies have reported association between the rs1344706 A allele with SCZ, SAD and BPD in European and Asian populations. In Mexican patients, no studies have specifically analyzed ZNF804A gene variants with these disorders. The aim of the study was to analyze the rs1344706 and identify common and rare variants in a targeted region of the ZNF804A gene in Mexican patients with SCZ, BPD and SAD compared with a control group., Methods: We genotyped the rs1344706 in 228 Mexican patients diagnosed with SCZ, SAD and BPD, and 295 controls. Also, an additional sample of 167 patients with these disorders and 170 controls was analyzed to identify rare and common variants using the Sanger-sequence analysis of a targeted region of ZNF804A gene., Results: Association analysis of rs1344706 observed a higher frequency of A allele in the patients compared with the control group; however, did not show statistical differences after Bonferronís correction (χ2 = 5.3, p = 0.0208). In the sequence analysis, we did not identify rare variants; however, we identified three common variants: rs3046266, rs1366842 and rs12477430. A comparison of the three identified variants between patients and controls did not show statistical differences (p > 0.0125). Finally, haplotype analysis did not show statistical differences between SCZ, SAD and BPD and controls., Conclusions: Our findings did not support the evidence suggesting that ZNF804A gene participates in the etiology of SCZ, SAD and BPD. Future studies are needed in a larger sample size to identify the effect of this gene in psychiatric disorders., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Progression of CKD in type 2 diabetes, despite dual inhibition of sodium-glucose transporter-2 and the renin-angiotensin system, remains a concern. Bromoindirubin-3'-oxime (BIO), previously reported to promote podocyte survival and regeneration, is a candidate additional drug to elicit renoprotective effects beyond therapy with metformin, ramipril, and empagliflozin (MRE). Evaluating a drug with standard therapeutics more closely mimics the clinical setting than evaluating the drug alone., Methods: Uninephrectomized BKS- Lepr -/- (db/db) mice treated with or without MRE served as a model of progressive CKD in type 2 diabetes. Mice on or off MRE were randomized to only 4 weeks of add-on BIO or vehicle. The primary end point was slope of GFR ( Δ GFR)., Results: Four weeks of MRE treatment alone did not affect Δ GFR, but significantly attenuated hyperglycemia, albuminuria, and glomerulosclerosis and increased podocyte filtration slit density, as assessed by STED super-resolution microscopy upon tissue clearing. BIO alone improved albuminuria, podocyte density in superficial and juxtamedullary nephrons, and podocyte filtration slit density. MRE+BIO combination therapy had additive protective effects on Δ GFR, glomerulosclerosis, podocyte density in juxtamedullary nephrons, and filtration slit density., Conclusions: Add-on treatment with BIO for only 4 weeks attenuates progression of CKD beyond MRE therapy in mice with type 2 diabetes. Additional drug combinations may help to further delay ESKD in type 2 diabetes., (Copyright © 2020 by the American Society of Nephrology.)

Purpose of Review: Crescents are classical histopathological lesions found in severe forms of rapidly progressive glomerulonephritis, also referred to as crescentic glomerulonephritis (CGN). Crescent formation is a consequence of diverse upstream pathomechanisms and unraveling these mechanisms is of great interest for improving the management of patients affected by CGN. Thus, in this review, we provide an update on the latest insight into the understanding on how crescents develop and how they resolve., Recent Findings: Cellular crescents develop from activated parietal epithelial cells (PECs) residing along Bowman's capsule and their formation has as a consequence the decline in glomerular filtration rate (GFR). Cellular crescents can be reversible, but when multilevel growth of PECs associate with an epithelial--mesenchymal transition-like change in cell phenotype, fibrous crescents form, and crescents become irreversible also in terms of GFR recovery. Different molecular pathways trigger the activation of PECs and are a prime therapeutics target in CGN. First, crescent formation requires also vascular injury causing ruptures in the glomerular basement membrane that trigger plasmatic coagulation within Bowman's space. This vascular necrosis can be triggered by different upstream mechanisms, such as small vessel vasculitides, immune complex glomerulonephritis, anti-GBM disease, and C3 glomerulonephritis, that all share complement activation but involve diverse upstream immune mechanisms outside the kidney accessible for therapeutic intervention., Summary: Knowing the upstream mechanisms that triggered crescent formation provides a tool for the development of therapeutic interventions for CGN.

Objectives: The authors sought to evaluate cardiac activity of angiotensin-converting enzyme (ACE) and ACE2 after heart transplantation (HT) and its relation with acute rejection (AR) and chronic allograft vasculopathy (CAV)., Background: The renin-angiotensin system is altered in heart failure and HT. However, ACE and ACE2 activities in post-HT acute and chronic rejection have not been previously studied., Methods: HT patients (n = 45) were included when appropriate serial endomyocardial biopsies (EMB) and coronary angiography were available for analysis. In 21 patients, three post-HT time points were selected for CAV study in EMB tissue: basal (0-3 wks), second (2-3 months) and third (4-5 months). At 10 years post-HT, CAV was evaluated by coronary angiography (CA) and patients were grouped by degree of CAV: 0-1, non-CAV (n = 15) and 2-3, CAV (n = 6). For the AR study, 28 HT patients with evidence of one EMB rejection at grade 3 and two EMB grade 1A and/or 1B rejections were selected., Results: Post-HT, ACE2 activity was increased in the CAV group, compared to non-CAV. Patients with AR showed increased ACE, but not ACE2, activity., Conclusions: Our results suggest that early post-HT cardiac ACE2 activity may have an important role in CAV development. In contrast, ACE activity was increased in AR. The renin-angiotensin system seems to be altered after HT and strategies to balance the system may be useful., (Copyright © 2018. Published by Elsevier B.V.)

Flooding is one of the most frequent and costly natural disasters affecting mankind. However, implementing Internet of Things (IoT) technology to monitor river behavior may help mitigate or prevent future disasters. This article outlines the hardware development of an IoT system (RiverCore) and defines an application scenario in a specific hydrological region of the state of Colima (Mexico), highlighting the characteristics of data acquisition and data processing used. Both fixed position and moving drifter node systems are described along with web-based data acquisition platform developments integrated with IoT techniques to retrieve data through 3G cellular networks. The developed architecture uses the Message Queuing Telemetry Transport (MQTT) protocol, along with encryption and security mechanisms, to send real-time data packages from fixed nodes to a server that stores retrieved data in a non-relational database. From this, data can be accessed and displayed through different customizable queries and graphical representations, allowing future use in flood analysis and prediction systems. All of these features are presented along with graphical evidence of the deployment of the different devices and of several cellular communication and on-site data acquisition tests.

The long pentraxin 3 (PTX3) exerts a variety of regulatory functions in acute and chronic tissue inflammation. In particular, PTX3 acts as an opsonin for a variety of pathogens and endogenous particles. We hypothesized that PTX3 would exhibit opsonin-like functions toward calcium oxalate crystals, too, and inhibit crystal growth. This process is fundamental in kidney stone disease as well as in hyperoxaluria-related nephrocalcinosis, the paradigmatic cause of chronic kidney disease (CKD) in children with primary hyperoxaluria type I due to genetic defects in oxalate metabolism. Direct effects of PTX3 on calcium oxalate crystals were investigated in chemico by adding recombinant PTX3 to supersaturated calcium and oxalate solutions. PTX3, but not isomolar concentrations of albumin, dose-dependently inhibited crystal growth. In vivo , the PTX3 protein was undetectable in tubular epithelial cells and urine of wild-type mice under physiological conditions. However, its levels increased within 3 weeks of feeding an oxalate-rich diet, an exposure inducing hyperoxaluria-related nephrocalcinosis and CKD in selected mouse strains (male and female C57BL/6N and male Balb/c mice) but not in others (male and female 129SV and CD-1, male and female Balb/c mice). Genetic ablation of ptx3 in nephrocalcinosis un-susceptible B6;129 mice was sufficient to raise the oxalate nephropathy phenotype observed in susceptible strains. We conclude that PTX3 is an endogenous inhibitor of calcium oxalate crystal growth. This mechanism limits hyperoxaluria-related nephrocalcinosis, e.g., in primary or secondary hyperoxaluria, and potentially also in the more prevalent kidney stone disease.

Angiotensin-converting enzyme (ACE) and ACE2 play a critical role in the renin-angiotensin system (RAS) by altering angiotensin II (ANGII) levels, thus governing its deleterious effects. Both enzymes are altered by sex and diabetes, and play an important role in the development of diabetic nephropathy (DN). Importantly, previous evidence in diabetic and ACE2-deficient (ACE2KO) males suggest a sex-dependent crosstalk between renal ACE and ACE2. In the present work, we aimed to study the sex-specific susceptibility to diabetes and direct infusion of ANGII in kidney disease progression, with a special focus on its link to ACE2 and ACE. In our mouse model, ANGII promoted hypertension, albuminuria, reduced glomerular filtration, and glomerular histological alterations. ANGII adverse effects were accentuated by diabetes and ACE2 deficiency, in a sex-dependent fashion: ACE2 deficiency accentuated ANGII-induced hypertension, albuminuria, and glomerular hypertrophy in diabetic females, whereas in diabetic males exacerbated ANGII-mediated glomerular hypertrophy, mesangial expansion, and podocyte loss. At the molecular level, ANGII downregulated renal ACE gene and enzymatic activity levels, as well as renin gene expression in ACE2KO mice. Interestingly, male sex and diabetes accentuated this effect. Here we show sex dimorphism in the severity of diabetes- and ANGII-related renal lesions, and demonstrate that ACE2- and ACE-related compensatory mechanisms are sex-specific. Supporting our previous findings, the modulation and ANGII-mediated crosstalk between ACE2 and ACE in DN progression was more evident in males. This work increases the understanding of the sex-specific role of ACE2 and ACE in DN, reinforcing the necessity of more personalized treatments targeting RAS.

Background and Aims: Circulating Angiotensin Converting Enzyme 2 (ACE2) activity in chronic kidney disease (CKD) patients without previous history of cardiovascular disease (CVD) has been associated with classical risk factors (older age, diabetes and male gender). Furthermore, silent atherosclerosis has been described as a pathological link between CKD and CVD. We analyzed baseline ACE2 activity in non-dialysis CKD stages 3-5 (CKD3-5) patients as a biomarker of renal progression, silent atherosclerosis and CV events after 2 years of follow-up., Methods: Prospective study of 1458 CKD3-5 subjects without any previous CV event included in the Spanish multicenter NEFRONA study. Association between baseline circulating ACE2 activity and renal parameters, carotid/femoral echography, atheromatous disease, ankle-brachial index, intima-media thickness, need of renal replacement therapy, cardiovascular events and mortality at 24 months of follow-up were analyzed., Results: Patients with an increase in the number of territories with plaques at 24 months showed significantly higher levels of baseline ACE2 activity as compared to stable patients (29.6 (20.6-47.6)RFU/μL/h versus 35.7 (24.5-56), p < 0.001). Multivariate linear regression analysis showed that male gender, pathological ankle-brachial index and progressive silent atherosclerosis defined as an increased number of territories with plaques at 24 months were associated with increased baseline ACE2 activity. Male gender, older age, diabetes, smoking and increased baseline circulating ACE2 were independent predictors of atherosclerosis at 24 months of follow-up., Conclusions: In CKD3-5 patients, higher circulating ACE2 activity at baseline is associated with higher risk for silent atherosclerosis, suggesting that ACE2 may serve as a biomarker to predict CV risk before CVD is established., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Circulating and renal activity of angiotensin-converting enzyme 2 (ACE2) is increased in non-obese diabetic (NOD) mice. Because paricalcitol has been reported to protect against diabetic nephropathy, we investigated the role of paricalcitol in modulating ACE2 in these mice. In addition, renal ADAM17, a metalloprotease implied in ACE2 shedding, was assessed. NOD female and non-diabetic control mice were studied for 21 days after diabetes onset and divided into various treatment groups. Diabetic animals received either vehicle; 0.4 or 0.8 μg/kg paricalcitol, aliskiren, or a combination of paricalcitol and aliskiren. We then studied the effect of paricalcitol on ACE2 expression in proximal tubular epithelial cells. Paricalcitol alone or in combination with aliskiren resulted in significantly reduced circulating ACE2 activity in NOD mice but there were no changes in urinary albumin excretion. Serum renin activity was significantly decreased in mice that received aliskiren but no effect was found when paricalcitol was used alone. Renal content of ADAM17 was significantly decreased in animals that received a high dose of paricalcitol. Renal and circulating oxidative stress (quantified by plasma H2O2 levels and immunolocalization of nitrotyrosine) were reduced in high-dose paricalcitol-treated mice compared with non-treated diabetic mice. In culture, paricalcitol incubation resulted in a significant increase in ACE2 expression compared with nontreated cells. In NOD mice with type 1 diabetes, paricalcitol modulates ACE2 activity, ADAM17, and oxidative stress renal content independently from the glycemic profile and urinary albumin excretion. In tubular cells, paricalcitol may modulate ACE2 by blocking its shedding. In the early stage of diabetic nephropathy, paricalcitol treatment counterbalances the effect of diabetes on circulating ACE2 activity. Our results suggest that additional use of paricalcitol may be beneficial in treating patients with diabetes under standard therapeutic strategies., (Copyright © 2016 the American Physiological Society.)

Background: Patients with cardiovascular (CV) disease have an increased circulating angiotensin-converting enzyme 2 (ACE2) activity, but there is little information about changes in ACE2 in chronic kidney disease (CKD) patients without history of CV disease. We examined circulating ACE2 activity in CKD patients at stages 3-5 (CKD3-5) and in dialysis (CKD5D) without any history of CV disease., Methods: Circulating ACE2 activity was measured in human ethylenediamine-tetraacetic acid (EDTA)-plasma samples from the NEFRONA study (n = 2572): control group (CONT) (n = 568), CKD3-5 (n = 1458) and CKD5D (n = 546). Different clinical and analytical variables such as gender; age; history of diabetes mellitus (DM), dyslipidemia and hypertension; glycaemic, renal, lipid and anaemia profiles; vitamin D analogues treatment and antihypertensive treatments (angiotensin-converting enzyme inhibitor and angiotensin receptor blockade) were analysed. Circulating ACE2 and ACE activities were measured using modified fluorimetric assay for EDTA-plasma samples, where zinc chloride was added to recover enzymatic activity., Results: In CKD3-5 and CKD5D, significant decrease in circulating ACE2 activity was observed when compared with CONT, but no differences were found between CKD3-5 and CKD5 when performing paired case-control studies. By multivariate linear regression analysis, male gender and advanced age were identified as independent predictors of ACE2 activity in all groups. Diabetes was identified as independent predictor of ACE2 activity in CKD3-5. Significant increase in the activity of circulating ACE was found in CKD3-5 and CKD5D when compared with CONT and in CKD5D when compared with CKD3-5. By multiple regression analysis, female gender and younger age were identified as independent predictors of ACE activity in CONT and CKD3-5. Diabetes was also identified as an independent predictor of ACE activity in CKD3-5 patients., Conclusions: Circulating ACE2 and ACE activities can be measured in human EDTA-plasma samples with zinc added to recover enzymatic activity. In a CKD population without previous history of CV disease, ACE2 activity from human EDTA-plasma samples directly correlated with the classical CV risk factors namely older age, diabetes and male gender. Our data suggest that circulating ACE2 is altered in CKD patients at risk for CV event., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

The seroepidemiology of Entamoeba histolytica infection in Tepehuanos population in Mexico is largely unknown. This study aimed to study the seroprevalence and correlates of E. histolytica antibodies in Tepehuanos in Durango, Mexico. Through a cross-sectional study, we determined the frequency of E. histolytica IgG antibodies in 156 Tepehuanos people in Durango, Mexico using an enzyme-linked immunoassay. Furthermore, we studied the association of E. histolytica seroprevalence with the socio-demographic, clinical, and behavioral characteristics of the Tepehuanos studied. Forty-four (28.2%) Tepehuanos with mean age of 31.03 ± 16.71 years old had anti- E. histolytica IgG antibodies. Multivariate analysis showed that E. histolytica exposure was positively associated with laborer occupation (Odds ratio=2.77; 95% CI: 1.15, 6.66; p=0.02), and history of lymphadenopathy (Odds ratio=4.97; 95% CI: 1.74, 14.13; p=0.002), and negatively associated with soil contact (Odds ratio=0.13; 95% CI: 0.03, 0.53; p=0.004). Other behavioral characteristics including drinking untreated water or unpasteurized milk, and consumption of unwashed raw vegetables or fruits were not associated with E. histolytica exposure. The seroprevalence of E. histolytica infection in Tepehuanos in Durango is higher thanseroprevalences reported in national surveys. The factors associated with E. histolytica seropositivity reported in the present study might aid for the planning and implementation of effective measures against E. histolytica infection.

Diabetic kidney disease (DKD) remains the most common cause of chronic kidney disease and multiple therapeutic agents, primarily targeted at the renin-angiotensin system, have been assessed. Their only partial effectiveness in slowing down progression to end-stage renal disease, points out an evident need for additional effective therapies. In the context of diabetes, endothelin-1 (ET-1) has been implicated in vasoconstriction, renal injury, mesangial proliferation, glomerulosclerosis, fibrosis and inflammation, largely through activation of its endothelin A (ETA) receptor. Therefore, endothelin receptor antagonists have been proposed as potential drug targets. In experimental models of DKD, endothelin receptor antagonists have been described to improve renal injury and fibrosis, whereas clinical trials in DKD patients have shown an antiproteinuric effect. Currently, its renoprotective effect in a long-time clinical trial is being tested. This review focuses on the localization of endothelin receptors (ETA and ETB) within the kidney, as well as the ET-1 functions through them. In addition, we summarize the therapeutic benefit of endothelin receptor antagonists in experimental and human studies and the adverse effects that have been described.

Through a cross-sectional study design, 326 women with a history of miscarriage were examined for anti-Toxoplasma gondii IgG and IgM antibodies in Durango City, Mexico. Prevalence association with sociodemographic, clinical, and behavioral characteristics in women with miscarriage was also investigated. Twenty-two (6.7%) of the 326 women studied had anti-T. gondii IgG antibodies and two (0.6%) were also positive for anti-T. gondii IgM antibodies. Seroprevalence of T. gondii infection was not influenced by age, birth place, occupation, educational level, or socioeconomic status. In contrast, logistic regression showed that T. gondii exposure was associated with consumption of raw or undercooked meat (OR = 6.84; 95% CI: 1.04-44.95; P = 0.04) and consumption of chicken brains (OR = 18.48; 95% CI: 1.26-269.43; P = 0.03). This is the first study on the seroepidemiology of T. gondii infection in women with a history of miscarriage in Northern Mexico. Of interest, we also observed an association of T. gondii exposure with consumption of chicken brains. Contributing factors for T. gondii exposure found in the present study should be taken into consideration for public health measures to avoid infection with T. gondii and its sequelae.

Purpose: The seroprevalence of infection with the parasite Toxoplasma gondii and the association with risk factors has not been determined in inmates. Through a case-control study, 166 inmates from a state correctional facility in Durango City, Mexico and 166 age- and gender-matched non-incarcerated subjects were examined for the presence of anti-T. gondii IgG and IgM antibodies using enzyme-linked immunoassays., Results: Seroprevalence of anti-T. gondii IgG antibodies was higher in inmates (35, 21.1%) than in controls (14, 8.4%) (OR = 2.90; 95% CI: 1.43-5.94; P = 0.001). Anti-T. gondii IgM antibodies were detected in two (1.2%) inmates and in seven (4.2%) controls (P = 0.17). Multivariate analysis of socio-demographic, incarceration, and behavioral characteristics of inmates revealed that T. gondii seropositivity was associated with being born out of Durango State (OR = 3.91; 95% CI: 1.29-11.79; P = 0.01). In addition, T. gondii seroprevalence was higher (P = 0.03) in inmates that had suffered from injuries (17/56: 30.4%) than those without such history (18/110: 16.4%)., Conclusions: The seroprevalence of T. gondii infection in inmates in Durango City is higher than the seroprevalences found in the general population in the same city, indicating that inmates may represent a new risk group for T. gondii infection. Further research on T. gondii infection in inmates is needed.

Background: Cancer survivors have a higher suicide rate than the general population. Oncology nurses need to have knowledge and skills in assessing risk for suicide in this population., Objective: This study aimed to conduct a literature review on risk factors for and incidence of suicide in patients with cancer and to identify potential screening tools., Methods: PubMed, CINAHL, and PsycINFO databases were searched to identify research articles in peer-reviewed journals from 1999 to 2009. The variables under study included suicide rate, cancer type, demographic characteristics, and signs and symptoms associated with suicide. In addition, articles focused on suicide risk assessment tools were also included., Results: Twenty-four articles met the inclusion criteria. As in the general population, suicide risk was higher among men with cancer as compared with women with cancer. Patients aged 65 years or older with cancer have a higher rate of suicide compared with those younger than 65 years, with rates highest among men 80 years or older. Specific diagnoses associated with higher suicide rates include prostate, lung, pancreatic, and head and neck cancers. The first year after diagnosis carries a higher risk for completed suicide. Multiple risk assessment tools have been developed and are effective in identifying patients with depression or hopelessness, factors associated with higher risk for suicide. However, no tools exist that sensitively and specifically predict suicide., Conclusion: The incidence of suicide in someone with a cancer diagnosis is approximately double the incidence of suicide in the general population. Early detection of depression in special cancer populations, such as older male patients, may help identify those at greatest suicide risk., Implications for Practice: Oncology nurses should be aware of cancer patients considered at higher risk for suicide. Systematic screening for suicidal ideation and behavior may identify cancer patients at high risk and facilitate appropriate mental health evaluation and treatment.

Virus-like particles (VLPs) are biological nanoparticles identical to the natural virions, but without genetic material. VLPs are suitable for the analysis of viral infection mechanisms, vaccine production, tissue-specific drug delivery, and as biological nanomaterials. Human parvovirus B19 (B19) infects humans; therefore VLPs derived from this virus have enormous potential in medicine and diagnostics. Current production of self-assembled VLPs derived from B19 is typically carried out in eukaryotic expression systems. However many applications of VLPs require access to its internal core. Consequently, the processes of disassembly and further reassembly of VLPs are critical both for purification of viral proteins, and for encapsulation purposes. Herein we report the in vitro self-assembly of B19 VLPs derived from the recombinant VP2 protein expressed in Escherichia coli and the effects of pH and ionic strength on the assembly process. Our results demonstrate that VP2 is able to form VLPs completely in vitro. At neutral pH, homogeneous VLPs assemble, while at acidic and basic pHs, with low ionic strength, the major assemblies are small intermediates. The in vitro self-assembled VLPs are highly stable at 37°C, and a significant fraction of particles remain assembled after 30min at 80°C., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Background: Azinphos-methyl is the main insecticide used to control codling moth on apple and pears in Northern Patagonia. The aim of this study was to evaluate the toxicological and biochemical response of diapausing larvae of codling moth in orchards subjected to different insecticide selection pressure., Results: Dose-mortality assays with azinphos-methyl in diapausing larvae of Cydia pomonella L. showed significant differences between the LD(95) from a population collected in one untreated orchard (2.52 microg moth(-1)) compared with that in a laboratory-susceptible population (0.33 microg moth(-1)). Toxicity to azinphos-methyl in field populations of diapausing larvae collected during 2003-2005 was evaluated by topical application of a discriminating dose (2.5 microg moth(-1)) that was obtained from larvae collected in the untreated orchard (field reference strain). Significantly lower mortality (37.71-84.21%) was observed in three out of eight field populations compared with that in the field reference strain. Most of the field populations showed higher esterase activity than that determined in both the laboratory susceptible and the field reference strains. Moreover, there was a high association between esterase activity and mortality (R(2)=0.64) among the field populations. On the other hand, a poor correlation was observed between glutathione S-transferase activity and mortality (R(2)=0.33) among larvae collected from different orchards., Conclusions: All the field populations evaluated exhibited some degree of azinphos-methyl tolerance in relation to the laboratory susceptible strain. Biochemical results demonstrated that esterases are at least one of the principal mechanisms involved in tolerance to this insecticide.

Amphibians may be critically challenged by aquatic contaminants during their embryonic development. Many classes of compounds, including organophosphorus pesticides, are able to cause oxidative stress that affects the delicate cellular redox balance regulating tissue modeling. We determined the progression of antioxidant defenses during the embryonic development of the South American common toad, Bufo arenarum. Superoxide dismutase (SOD) and catalase (CAT) activities were high in the unfertilized eggs, and remained constant during the first stages of development. SOD showed a significant increase when the gills were completely active and opercular folds began to form. Reductase (GR) activity was low in the oocytes and increased significantly when gills and mouth were entirely developed and the embryos presented a higher exposure to pro-oxidant conditions suggesting an environmental control. Reduced glutathione (GSH) content was also initially low, and rose continuously pointing out an increasing participation of GSH-related enzymes in the control of oxidative stress. GSH peroxidases and GSH-S-transferases showed relatively high and constant activities, probably related to lipid peroxide control. B. arenarum embryos have plenty of yolk platelets containing lipids, which provide the energy and are actively transferred to the newly synthesized membranes during the early embryonic development. Exposure to the pro-oxidant pesticide malathion during 48 h did not significantly affect the activity of antioxidant enzymes in early embryos, but decreased the activities of CAT, GR, and the pool of GSH in larvae. Previous work indicated that lipid peroxide levels were kept low in malathion-exposed larvae, thus we conclude that oxidative stress is overcome by the antioxidant defenses. The increase in the antioxidant metabolism observed in the posthatching phase of development of B. arenarum embryo, thus constitutes a defense against natural and human-generated pro-oxidants present in the aquatic environment.

In order to establish if there is a mutual regulation between COX and NOS in vascular and renal tissue during pregnancy, we measured the protein expression of COX-1, COX-2 and NOSIII by Western blot comparing the thoracic and abdominal aorta and the renal cortex and medulla of non pregnant and pregnant (21st day) Wistar rats. We found there was no difference in the quantity of protein of any of the two isoforms of COX between the two segments of the aorta of non pregnant animals while an increased expression of both COX-1 And COX-2 was found in the abdominal compared to the thoracic segment of the pregnant rats. An increased expression of NOS III was found in the abdominal segment of the aorta form pregnant rats. No changes were found between pregnant and no pregnant animals in the expression of COX-1 and COX-2 in the renal cortex or medulla while an increased expression of NOS III was found in the cortex from pregnant compared to non pregnant animals. These results suggest the influence of pregnancy is not homogeneous along the aorta and also that a balance between prostaglandins and nitric oxide is responsible of the blunted vascular reactivity during pregnancy in the rat.

Peripheral vascular resistance and sensitivity to circulating pressor and vasoconstrictor agents are blunted during pregnancy. This has been mainly attributed to an increased production of endothelium-derived mediators. The objective of this work was to evaluate if pregnancy changes the relative participation of nitric oxide (NO) and prostaglandins (PG) in respect to the modulation of the increases in renal perfusion pressure induced by phenylephrine (Phe). Dose-response curves were made with gradually increasing doses of Phe using an isolated kidney preparation in the presence of a NO synthase (NOS) inhibitor (L-NAME, 1 microM), a PG-synthesis inhibitor (indomethacin, 1 microM), both, or neither. Also, renal cyclooxygenase (COX-1 and COX-2) and endothelial NOS (eNOS) expression was determined using PCR. The experiments were done in kidneys from nonpregnant and pregnant rats. Our results showed that the relative participation of renal vasoactive mediators seems to change during pregnancy. We found the presence of a COX-1-dependent vasoconstrictor in the middle of pregnancy that was not found in nonpregnant rats. Our results also suggest that there is increased participation of another renal vasodilator substance, the effect of which is observed when NO or PG synthesis is inhibited during late pregnancy. In addition, an apparent interaction between renal eNOS and COX-1 expression was observed: eNOS expression was diminished, while COX-1 was increased during the 2nd week of pregnancy. In contrast, in kidneys from the 3rd week of pregnancy, the expression of these two enzymes was similar.

Background: The Helicobacter pylori (Hp) is found in patients with gastritis and peptic ulcer approximately in up to 80 percent. The eradication rates of 80 to 90 percent are achievable with some regimens., Aims: Evaluate two regimens for H pylori eradication in gastritis and peptic ulcer., Methods: Patients more than 20 years old with gastritis, gastric and duodenal ulcer disease and H pylori positive entered the study. We investigated prior history of peptic ulcer and hemorrhage, NSAID's use, smoking, alcoholism and epigastric pain. Endoscopy was performed before and at the end of the 8-12 weeks treatment, biopsies were taken from the antrum for Hp histological detection. Patients were randomly assigned to receive bismuth-metronidazole-tetracycline-ranitidine or bismuth-metronidazole-amoxicillin-ranitidine during two weeks., Statistical Analysis: chi square and multivariate analysis., Results: One hundred and eighteen patients were included in this study, 52% male and 48% female with mean age of 47 +/- 16 years. History of peptic ulcer and bleeding was present in 79% and 62% respectively. NSAID's, and tobacco use among all patients was 49%, and 30%. Epigastric pain, melena and hematemesis was present in 90%, 47% and 24% respectively. H pylori eradication treatment was successful in 70% in both regimens (pNS). Was no related to age, tobacco and alcohol for Hp eradication (pNS), and NSAID's use was inversely related to Hp eradication (p < 0.05). Persistent peptic ulcer was seen in 23%., Conclusions: Eradication treatment was successful in 70% (p NS). Peptic ulcer refractory in 23% of patients and NSAID's use was inversely related to Hp eradication (p 0.05).

The objective of this report was to assess the sensitivity and specificity of Pap smear and to evaluate if routine colposcopy can improve cervical screening. One hundred and fifty patients undergoing routine cervical cytologic screening in our outpatient clinic were randomly selected. All patients were evaluated by colposcopy and cervical punch biopsy. Pap smears and biopsies specimens were interpreted independently. Colposcopy was performed and interpreted without knowledge of cytologic or histologic findings. The statistical analysis was carried out with a chi square (chi 2) test. A P value of less than 0.05 was considered significant. Twenty three patients (15.3%) who had biopsy proved to have cervical pathology. Pap smear identified only 4/23 (17%) of these patients. Colposcopy noted atypical transformation zones in 20/23 (97%), P < 0.001). Fifteen of 27 patients (55.5%) with negative Pap smears had colposcopic anormalities and histologically proved cervical intraepithelial neoplasia (CIN). We concluded that it is necessary to improve sensitivity and that colposcopy may enhance cervical screening particularly in women with otherwise negative Papapnicolaou smears.