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.     

Left ventricular thrombi diagnosed by echocardiography in patients with acute myocardial infarction treated with intracoronary streptokinase followed by intravenous heparin

Thirty patients with acute myocardial infarction (AMI) treated with intracoronary streptokinase (7 X 10(5) +/- 3 X 10(5) IU) followed by 10 days of intravenous heparin (800 to 1,500 IU/hour) therapy were prospectively studied by serial 2-dimensional echocardiography for left ventricular (LV) thrombus. Within the first 24 hours, evidence of a thrombolytic state appeared as indicated by fibrin and fibrinogen degradation products (123 +/- 45 mg/dl at 24 hours). Throughout the course of this study partial thromboplastin times were maintained within therapeutic range (40 to 100 seconds). Apical LV thrombus developed in 8 of 30 patients (27%). Apical thrombus developed within 24 hours in 3 patients with anterior AMI and persisted through day 10. By day 10, apical thrombus developed in 3 additional patients with anterior AMI and 2 patients with inferior AMI. In these patients, anterior AMI and apical dysfunction were significant (p less than 0.01 for both) determinants of LV thrombus formation. Hence, the incidence of LV thrombus in patients treated with streptokinase/heparin is similar to that reported earlier in comparable patients not receiving thrombolytic therapy.     

Treatment of critical defects produced in calvaria of mice with mesenchymal stem cells

Mesenchymal stem cells (MSC) are present in specialized niches in perivascular regions of adult tissues and are able to differentiate into various cell types, such as those committed to repairing. Bone marrow derived MSC from eight young mice C57BL/ 6 gfp+ were expanded in culture for repairing critical defects in calvarial bone produced in twenty-four young isogenic adult C57BL/6 mice. The animals were subjected to a cranial defect of 6.0mm diameter and divided into two equal experimental groups. Control group did not receive any treatment and the treated group received a MSC pellet containing 1.0 x 10(7) cells/mL into the defects. The group treated with MSC showed increased angiogenesis and amount of new bone deposited on the defect limits than that observed in the control group. The results demonstrated that transplantation of bone marrow-derived MSC of C57BL/6 gfp+ mice to bone critical defects produced in mice calvarial contributes positively to the bone repair process. MSC presets ability to influence the correct functioning of osteoblasts, increases the amount of mobilized cells for the repairing process, speeds up growth, and increases deposition of bone matrix.     

Nephropathy associated with heroin abuse in Caucasian patients.

BACKGROUND: Renal disease is a complication of heroin addiction. Using renal biopsies in Caucasian patients, we studied the types of nephropathy associated with heroin abuse. METHODS: Nineteen renal biopsies were performed on heroin addicts between January 1993 and December 2001. The indications for renal biopsy included proteinuria with or without renal insufficiency. RESULTS: All 19 patients had serological evidence of hepatitis C virus (HCV) infection, one had hepatitis B virus surface antigen and three were HIV positive. Thirteen patients (68.4%) were found to have membranoproliferative glomerulonephritis (MPGN), 12 with type I and one with type III. Of the remaining patients, two had chronic interstitial nephritis, two had acute proliferative glomerulonephritis, one had amyloidosis and one had granulomatous glomerulonephritis with interstitial nephritis. No apparent decline in the incidence of renal disease was observed. CONCLUSIONS: In this cohort of male Caucasian heroin addicts, HCV-associated MPGN was the most frequent pattern of nephropathy, showing that the nephropathy associated with heroin abuse in Caucasians is not of the focal and segmental glomerulosclerosis type, in contrast to previous reports on African-Americans. This aspect may have important implications for patient management and prognosis.     

Feasibility of supraomohyoid neck dissection in N1 and N2a oral cancer patients

BACKGROUND: The use of selective neck dissection in a positive neck is still controversial. The object of this study was to ascertain the possibility of doing this procedure in oral cavity carcinoma with a single clinically metastatic lymph node smaller than 6 cm (N1 and N2a). PATIENTS AND METHODS: From 1970 to 1994, we analyzed 164 oral cavity cancer patients with clinically N1 or N2a stage cancer submitted to radical neck dissection. RESULTS: The histologic findings did not confirm a metastatic lymph node in 69 (42.1%) cases (pN0) and showed multiple lymph nodes in 19 (11.6%) cases. Moreover, just one patient (0.6%) had a metastatic lymph node at level IV (one case with multiple lymph nodes) and none at level V. CONCLUSIONS: Because we did not find a single metastatic lymph node at levels IV and V and there was a high incidence of pN0 (57.4%) in patients with clinical N1 stage at level I, these patients could be candidates for a supraomohyoid neck dissection (extended or not to level IV) instead of radical neck dissection.     

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.     

Effects of doxorubicin administration on bone strength and quality in sedentary and physically active Wistar rats

Summary

Doxorubicin (DOX) is used in pediatric cancer treatment. This study assessed the effects of 7 weeks of DOX and 10-week recovery on bone quality and biomechanical properties in sedentary and exercised Wistar rats. DOX decreases femur diaphysis radial growth and biomechanical properties. Some of these DOX effects were aggravated by exercise.

Introduction

Bone growth in pre-pubertal years critically influences adult fracture risk. DOX is widely used in the treatment of pediatric cancers, but there is limited evidence on its potential negative effects on bone growth. Exercise improves bone growth in children, but there is no evidence if it protects against DOX-induced bone toxicity. This study investigates the early and intermediate effects of a 7-week course of DOX on bone histomorphometry and strength in sedentary and exercised growing animal models.

Methods

Sixty-eight male Wistar rats (8 weeks) were treated with DOX (2 mg kg^?1) or vehicle for 7 weeks and afterward housed in standard cages or in cages with a running wheel and killed 2 or 10 weeks after last DOX administration. Femurs and blood were collected for assaying geometry, trabecular microarchitecture (histology), biomechanical properties (three-point bending and shearing of the femoral neck), bone calcium content and density (atomic absorption spectroscopy), and bone turnover markers (ELISA).

Results

DOX treatment reduced the femur diaphysis radial growth, with DOX-treated animals having a lower tissue area, cortical area, cortical thickness, and moment of inertia. DOX also decreased distal femur trabecular bone volume and trabecular number and increased trabecular separation. Femur diaphysis stiffness and maximum load were also reduced in past DOX-treated animals. Exercise was shown to worsen the effects of past DOX treatment on the femur diaphysis mechanical properties.

Conclusion

DOX negatively affects bone geometry, trabecular microarchitecture, and femur mechanical properties in growing Wistar rats. Exercise further aggravates the detrimental effects of past DOX treatment on bone mechanical properties.

     

Hetastarch co-loading is as effective as pre-loading for the prevention of hypotension following spinal anesthesia for cesarean delivery

BackgroundPre-loading with hetastarch decreases the incidence and severity of hypotension after spinal anesthesia for cesarean delivery. However, pharmacokinetic studies with crystalloid predict that fluid loading should be more efficacious if rapidly administered immediately after induction of spinal anesthesia. The aim of this study was to compare pre- and co-loading of hetastarch for the prevention of hypotension following spinal anesthesia for cesarean delivery.MethodsForty-six healthy term parturients scheduled for cesarean delivery were randomized to receive 500 mL of 6% hetastarch intravenously, either slowly before spinal anesthesia (pre-loading) or as quickly as possible immediately after spinal anesthesia (co-loading). Systolic blood pressure was maintained at or above 90% of baseline with intravenous vasopressor boluses (ephedrine 5 mg/mL + phenylephrine 25 μg/mL). The primary outcome was the volume of vasopressor mix required. Secondary outcomes included blood pressure and heart rate changes, time to first vasopressor use, nausea or vomiting, and neonatal outcomes (umbilical artery and vein pH, Apgar scores).ResultsThe pre-loading group used 3.5 ± 2 mL (mean ± SD) of vasopressor mixture compared with 3.2 ± 3 mL in the co-loading group (P = 0.6). There were no differences in any important maternal hemodynamic or neonatal outcome values between the two study groups.ConclusionHetastarch co-loading is as effective as pre-loading for the prevention of hypotension after spinal anesthesia for cesarean delivery. Surgery need not be delayed to allow a predetermined pre-load to be administered before induction of spinal anesthesia.     

GLP-1 and Adiponectin: Effect of Weight Loss After Dietary Restriction and Gastric Bypass in Morbidly Obese Patients with Normal and Abnormal Glucose Metabolism

Background  It has been proposed that there is improvement in glucose and insulin metabolism after weight loss in patients who underwent diet restriction and bariatric surgery. Methods  Eleven normal glucose tolerant (NGT) morbidly obese patients [body mass index (BMI), 46.1 ± 2.27 g/m²] and eight abnormal glucose metabolism (AGM) obese patients (BMI, 51.20 kg/m²) were submitted to diet-restriction and bariatric surgery. Prospective study on weight loss changes, over the glucose, insulin metabolism, glucagon-like peptide-1 (GLP-1), and adiponectin levels were evaluated by oral glucose tolerance test during three periods: T1 (first evaluation), T2 (pre-surgery), and T3 (9 months after surgery). Results  Insulin levels improved after surgery. T1 was 131.1 ± 17.60 pmol/l in the NGT group and 197.57 ± 57.94 pmol/l in the AGM group, and T3 was 72.48 ± 3.67 pmol/l in the NGT group and 61.2 ± 9.33 pmol/l in the AGM group. The major reduction was at the first hour of the glucose load as well as fasting levels. At 9 months after surgery (T3), GLP-1 levels at 30 and 60 min had significantly increased in both groups. It was observed that the AGM group had higher levels of GLP-1 at 30 min (34.06 ± 6.18 pmol/l) when compared to the NGT group (22.69 ± 4.04 pmol/l). Homeostasis model assessment of insulin resistance from the NGT and AGM groups had a significant reduction at periods T3 in relation to T1 and T2. Adiponectin levels had increased concentration in both groups before and after surgical weight loss. However, it did not have any statistical difference between periods T1 vs. T2. Conclusions  Weight loss by surgery leads to improvement in the metabolism of carbohydrates in relation to sensitivity to the insulin, contributing to the reduction of type 2 diabetes incidence. This improvement also was expressed by the improvement of the levels of adiponectin and GLP-1.