An experimental vaccine against American dermal leishmaniasis: experience in the State of Espírito Santo, Brazil

A vaccine prepared from killed and sonicated promastigotes of five Brazilian strains of Leishmania was used during an epidemic of American dermal leishmaniasis that occurred in Viana county, State of Espírito Santo, Brazil. Initially, all of the participants in the vaccination programme had negative reactions to Montenegro antigen. Forty days after the last dose of vaccine had been given, 87.6% of the 216 vaccinated individuals had become Montenegro-positive whereas the 266 unvaccinated persons remained Montenegro-negative. The study area had an unstable population and details are given about the human population changes that occurred during the two-year study period. Taking into account population movements, 1.5% of those vaccinated and 6.4% of the unvaccinated group developed dermal leishmanial lesions by the end of the first year. At the end of the second year, 1.7% of those vaccinated and 8.9% of the unvaccinated group had become infected. The difference in infection rates of the two groups is statistically significant at both the end of the first and second years of observation. Diagnosis of the disease(s) was based on the clinical appearance of lesions combined with parasitological and/or immunological evidence and subsequent responses to treatment. The experience gained in Viana also provided information about the storage and administration of the experimental vaccine which have been used in mounting a randomized clinical trial.     

Effects of polyunsaturated fatty acids (PUFAs) in the treatment of experimental chronic renal failure

Purpose

A diet with polyunsaturated fatty acid (PUFA) supplementation has been reported to reduce renal and cardiac diseases. This study sought to elucidate whether PUFAs derived from plant or marine oils could have beneficial effects on the progression of experimental chronic renal failure (CRF).

Methods

Experimental CRF was achieved by a 5/6 nephrectomy model. Male Wistar rats were divided into groups and given daily supplements of fish oil (group FO), flaxseed oil (group FXO), or soybean oil (control?Cgroup SO) for 30?days. Serum creatinine (sCr), 24-h proteinuria, total cholesterol, triglycerides, and creatinine clearance (CLcr) were measured at day 0 and 30?days after surgery when the rats were euthanized for histological analysis of the remnant kidney.

Results

After 30?days, we observed lower levels of sCr in the groups supplemented with PUFA when compared with the control group (FO: 0.92?±?0.13; FXO: 1.06?±?0.28; SO: 1.32?±?0.47?mg/dL) and significantly slower variations of sCr (??sCr) in the groups treated with PUFAs (FO?=?0.35?±?0.16; FXO?=?0.47?±?0.31; OS?=?0.72?±?0.43; mg/dL, P?=?0.041). Similarly, the CLcr of both of the groups that received PUFAs was significantly slower than the rats in the control group (FO: 0.45?±?0.15; FXO: 0.60?±?0.09; SO: 0.28?±?0.06?mL/min/day; P?=?0.01). The rats that received PUFA supplements also presented significantly less histological lesions compared with the control group.

Conclusions

These results suggest a beneficial effect of dietary supplementation with flaxseed or fish oil in rats with CRF.     

Clinical impact of drug-eluting stents in changing referral practices for coronary surgical revascularization in a tertiary care center

BACKGROUND: The long-term benefits of angioplasty are limited by the occurrence of restenosis. Drug-eluting stents with a projected restenosis rate of close to 0% are soon to become available. The short- and long-term consequences of this advance to the cardiac surgical volume remain unclear. METHODS: A total of 196 consecutive coronary angiograms and medical records of patients referred for coronary bypass surgery were reviewed. Considering the hypothetical premise of having drug-eluting stents with a near zero restenosis rate, we reviewed each case to determine if surgical revascularization was still the preferred option for revascularization. RESULTS: The mean age was 60 (+/-10.6) years. Seventy-two percent of patients were male. Considering the availability of drug-eluting stents 154 (79%) would still have been sent to surgery, representing a 21% decrease in the number of surgical revascularizations. Angiographic characteristics predicting coronary bypass revascularization were the presence of chronic total occlusion (odds ratio [OR]: 9.1; confidence interval [CI]: 2.1 to 39), left main coronary artery stenosis (OR: 9.6; CI: 1.27 to 73), and need for valvular surgery (OR: 7.38; CI: 1.3 to 157). The most common predictors of a change in clinical management from surgical to percutaneous revascularization if drug-eluting stents were available were diffuse coronary narrowing (OR: 15.78), restenotic lesions (OR: 27.86), and small coronary arteries (OR: 26). CONCLUSIONS: Drug-eluting stents may have a significant impact on cardiac surgery volume (approximately a 21% decrease in our center). It may also direct patients with small vessels, diffuse narrowing, or restenotic lesions and diabetic patients to percutaneous therapy.     

A molecular view of liver regeneration

The purpose of this review was to carry out an analysis of the liver regenerative process focusing on the molecular interactions involved in this process. The authors undertook a review of scientific publications with a focus on the liver regeneration. The cellular processes involved in liver regeneration require multiple systematic actions related to cytokines and growth factors. These interactions result in the initiation of mitogenic potential of the hepatocytes. The action of these modulators in the regenerative process require a processing in the extra-cellular matrix. Serines and metal proteins are responsible for the bio availability of cytokines and growth factors so that they can interact as receptors in the cellular membrane generating signaling events for the beginning and end of the liver regenerative process. The exact mechanism of interaction between cells, cytokines and growth factors is not well established yet. A series of ordered events that result in the hepatic tissue regeneration has been described. The better understanding of these interactions should provide a new approach of the treatment for liver diseases, aiming at inducing the regenerative process.     

Inhibition of Epithelial-Mesenchymal Transition and Metastasis by Combined TGFbeta Knockdown and Metformin Treatment in a Canine Mammary Cancer Xenograft Model

Epithelial mesenchymal transition (EMT) is a process by which epithelial cells acquire mesenchymal properties, generating metastases. Transforming growth factor beta (TGF-β) is associated with this malignancy by having the ability to induce EMT. Metformin, has been shown to inhibit EMT in breast cancer cells. Based on this evidence we hypothesize that treatment with metformin and the silencing of TGF-β, inhibits the EMT in cancer cells. Canine metastatic mammary tumor cell line CF41 was stably transduced with a shRNA-lentivirus, reducing expression level of TGF-β1. This was combined with metformin treatment, to look at effects on cell migration and the expression of EMT markers. For in vivo study, unmodified or TGF-β1sh cells were injected in the inguinal region of nude athymic female mice followed by metformin treatment. The mice’s lungs were collected and metastatic nodules were subsequently assessed for EMT markers expression. The migration rate was lower in TGF-β1sh cells and when combined with metformin treatment. Metformin treatment reduced N-cadherin and increased E-cadherin expression in both CF41 and TGF-β1sh cells. Was demonstrated that metformin treatment reduced the number of lung metastases in animals bearing TGF-β1sh tumors. This paralleled a decreased N-cadherin and vimentin expression, and increased E-cadherin and claudin-7 expression in lung metastases. This study confirms the benefits of TGF-β1 silencing in addition to metformin as potential therapeutic agents for breast cancer patients, by blocking EMT process. To the best of our knowledge, we are the first to report metformin treatment in cells with TGF-β1 silencing and their effect on EMT.     

Active surveillance is superior to radical nephrectomy and equivalent to partial nephrectomy for preserving renal function in patients with small renal masses: Results from the DISSRM registry

Purpose

We compared renal function outcomes among patients in the surveillance and intervention arms of the DISSRM registry.

Heterologous Immune Responses to Influenza Vaccine in Kidney Transplant Recipients

Influenza vaccine is known to have suboptimal immunogenicity in transplant recipients. Despite this, influenza vaccine may have the added benefit of inducing a cross‐reactive immune response to viral strains not found in the vaccine. This is termed “heterologous immunity” and has not been assessed previously in transplant patients. Pre‐ and postvaccination sera from kidney transplant recipients (n = 60) immunized with the 2012–2013 adjuvanted or nonadjuvanted influenza vaccine underwent testing by hemagglutination inhibition assay for strains not present in vaccine: A/New Caledonia/20/99 (H1N1), A/Texas/50/2012 (H3N2) and B/Brisbane/60/2008. The geometric mean titer of antibody to heterologous strains increased after vaccine (H1N1: 80.0 to 136.1, p < 0.001; H3N2: 23.3 to 77.3, p < 0.001; B: 13.3 to 19.5, p < 0.001). Seroconversion rates were 16.7%, 41.7%, and 13.3%, respectively. No differences in heterologous response were seen in the adjuvanted versus nonadjuvanted groups. Patients were more likely to seroconvert for a cross‐reactive antigen if they seroconverted for the specific vaccine antigen. Seroconversion to heterologous A/H3N2, for example, was 84.0% for homologous H3N2 seroconverters versus 11.4% for nonseroconverters (p < 0.001). This study provides novel evidence that transplant recipients are able to mount significant cross‐protective responses to influenza vaccine that may be an additional, previously unknown benefit of immunization.     

COL1A1 Sp1-binding site polymorphism as a risk factor for genital prolapse

The objective of this study was to verify the possible association between the Sp1-binding site polymorphism and genital prolapse. A case–control study was conducted in 107 patients with stages III and IV genital prolapse. The control group included 209 women with stages 0 and I. The polymorphism of type I collagen Sp1-binding site was identified by amplification of the first intron of the COL1A1 gene. We did not find differences in the prevalence of the GT and TT genotypes between the groups (p = 0.34), even when we grouped patients with at least one polymorphic allele (GT and TT) and compared them with patients without the polymorphic allele (GG; p = 0.17) The presence of at least one vaginal delivery, family history for prolapse, and macrosomatic fetus were independent risk factors for prolapse. In conclusion, the COL1A1 Sp1-binding site was not significantly associated with genital prolapse among our study subjects.     

Hepatitis C Virus Infection After Renal Transplantation

Hepatitis C virus (HCV) infection is the main cause of liver disease after renal transplantation. Most patients have seroconverted on dialysis to positive RNA. The viral load increases during immunosuppressive therapy. The risk of developing chronic liver disease is related to the histopathologic findings, duration and severity of the disease, immunosuppression, and transplantation time. Hepatitis C virus infection can predict onset, of proteinuria and diabetes. We studied 868 patients who received renal transplants between (1987 and 2006), of whom 18.7% were seropositive for HCV. We observed a higher rate of HCV-seropositive patients related to the duration of hemodialysis therapy. Of the HCV seropositive patients, 77% had received renal allografts before 1998. There was no difference between the sexes; however, the HCV positive patients were younger. Polymerase chain reaction tests results were positive in 91.6% of the patients with HCV antibodies. The prevalence of diabetes was greater among HCV positive patients, as was as the persistence of proteinuria. Cryoglobulins were positive in 30.8%. The incidence of acute rejection episodes in the first year was similar between groups. Of the HCV-positive patients, 80.2% were treated with cyclosporine, most patients continued this therapy throughout the study. We observed no significant difference in mortality end graft survival rate between the two groups. However, renal function differed significantly at some points during the evolution of the clinical course. Renal transplantation is still the best treatment option in patients with chronic renal disease.     

Remifentanil for sedation and analgesia in a preterm neonate with respiratory distress syndrome

We present the efficacy and safety of the use of remifentanil for intubation, sedation and analgesia in a preterm infant during mechanical ventilation for respiratory distress syndrome. A 34-week-old baby, born by cesarean delivery that developed respiratory distress, required intubation and ventilatory support. For intubation, the baby was given midazolam (0.2 mg.kg(-1)) and remifentanil (1 microg.kg(-1)). The intubation conditions were assessed and classified as excellent. The remifentanil infusion was started at dose 0.75 microg.kg(-1).min(-1) and the dose adjustments were made depending on the neonatal infant pain scale (NIPS), hemodynamic and respiratory changes or the presence of spontaneous movements. Pulse oximetry, respiratory rate, ECG and invasive blood pressure were continuously monitored. He was given surfactant within 2.5 h of life after which ventilator parameters could be progressively decreased. Three hours later, the remifentanil infusion was decreased to 0.5 microg.kg(-1).min(-1), and he remained sedated (NIPS < 2). Six hour after surfactant administration, blood gases and chest X ray were normal. The remifentanil infusion was then discontinued and 30 min later the baby was awake and extubated with success. There were no side effects after intubation or during the continuous infusion. The profile of remifentanil allowing a rapid recovery, the absence of side effects and a good level of sedation and analgesia support the choice of this opioid for sedation in the NICU.