Gremlin promotes vascular smooth muscle cell proliferation and migration

Recent reports highlight the importance of BMP in the vasculature. We investigated the expression pattern and role of the BMP antagonist gremlin in VSMC. We detected gremlin mRNA constitutive expression in adult and embryonic rat aortic VSMC, and in rat carotids. In vitro analysis demonstrated that angiotensin II, TGF-β1 and PDGF induced significant changes in gremlin mRNA expression. Gremlin stable overexpression in A7r5 cells blocked BMP signaling. BMP-induced reduction in VSMC DNA synthesis was markedly inhibited by gremlin overexpression. In fact, gremlin overexpression increased DNA synthesis and cell counts, and accelerated cell cycle progression of VSMC, through mechanisms that include p27^kip1 down-regulation. Gremlin also led to marked increments in VSMC migration. In addition, gremlin gene silencing promoted a significant blockade on cell proliferation and migration. In vivo studies disclosed increased gremlin protein expression in the neointima of balloon-injured carotid arteries. In summary, the BMP antagonist gremlin is constitutively expressed in the normal vasculature. Gremlin induces VSMC proliferation and migration and is significantly regulated by growth factors and injury. We postulate that gremlin plays a part in the development of pathological phenotypic changes of adult VSMC.     

Hypokalemia and hyperkalemia in patients on peritoneal dialysis: incidence and associated factors

International Urology and Nephrology - Hypokalemia is a well-described electrolyte disturbance in patients on peritoneal dialysis (PD). Hyperkalemia, however, is still overlooked, although it also...     

Peritoneal dialysis outcomes in a modern cohort of overweight patients

Background

The incidence of obesity is increasing both in the general population and in incident dialysis patients. While there is evidence that being overweight is associated with good outcomes in hemodialysis, the evidence in peritoneal dialysis (PD) patients is not very clear. We studied a modern cohort of PD patients to examine outcomes in large patients.

Methods

Forty-three patients who started PD, who weighed more than 90 kg at dialysis initiation, between January/2000 and June/2010 were matched with 43 control patients who weighed less than 90 kg. Detailed review of the charts was undertaken.

Results

The mean weight and body mass index of the wt < 90 kg group were 69.3 ± 11.3 kg and 25.0 ± 3.9 kg/m². The number of peritonitis episodes per year was 0.33 ± 0.6 (wt < 90 kg) and 0.82 ± 1.7 (wt ≥ 90 kg) (p = 0.26). The median time to first peritonitis showed a trend toward earlier peritonitis in larger patients [9.5 (4.3, 27) months in wt ≥ 90 kg, 19.1(7.9, 30.8) months in wt < 90 kg] but did not reach statistical significance (p = 0.12). Surprisingly, hernias and leaks were more common in the weight <90 kg group (44 vs. 18.6 % p = 0.02). There was no difference in total number of hospitalizations or the number of days hospitalized. Kaplan–Meier analysis of survival on PD showed no differences between the two groups (logrank p = 0.99). Cox regression analysis using age, race, cause of ESRD due to diabetes and Charlson comorbidity index as the covariates did not show weight to be associated with survival on PD.

Conclusions

Large patients tend to do just as well on PD, with survival on PD being no different compared to individuals with lower weight and body mass index.     

knowledge level about of American tegumentary leishmaniasis (ATL) and use of alternative therapies in an endemic area in the Amazon Region in the State of Maranhão, Brazil

The level of knowledge concerning American tegumentary leishmaniasis (ATL) and use of alternative therapies was evaluated in five rural communities in Buriticupu, Maranh?o State, Brazil. The study lasted from September 1997 to January 1998. Local inhabitants answered an interview on housing conditions, epidemiological aspects, prevention, standard clinical treatment, and alternative therapies. The study population was 378 (19%) out of a total of 1,980 inhabitants, from Sexta Vicinal (35), Quinta Vicinal (63), Trilha 410 (96), Vila Uni?o (85), and Buritizinho (99). Of the interviewees, 72% had little knowledge of ATL transmission, 96% had heard something about the disease from friends, and 60.7% knew ATL by the local term "lésh". Glucantime was the most familiar drug for treatment, while 29.6% referred to use of herbal remedies on the ulcers. Citrus limon (lemon) was the plant most frequently used, and 15.4% of the interviewees used it as a powder spread on the wound. We conclude that the population had little correct knowledge of ATL in the five areas studied, especially with regard to prevention and treatment.     

Effects of simvastatin on bone regeneration in the mandibles of ovariectomized rats and on blood cholesterol levels

The purpose of this study was to evaluate the effects of simvastatin on guided bone regeneration in the mandibles of ovariectomized rats, and to observe their blood cholesterol levels. Seventy female rats were divided into two groups: control and treated, both groups containing normal and ovariectomized rats. A month after ovariectomy a bone defect was created in the mandible, and was covered by a polytetrafluoroethylene membrane. The treated groups received simvastatin orally for 15 or 30 days. The rats were sacrificed 15, 30 or 60 days after surgery, at which time a blood sample was extracted for blood cholesterol level analysis and the mandible was extracted for densitometric, histological and morphometric analysis. All specimens underwent analysis of variance. The ovariectomized animals had higher cholesterol levels than the treated normal animals, and no significant difference was found between the different treatment periods and the sacrifice times. The densitometric, histological and morphometric analysis showed that the treated ovariectomized animals developed more new bone than the control ovariectomized rats, but no significant difference was observed between the treatment periods. It can be concluded that the deficiency of estrogen increased the level of blood cholesterol and that the simvastatin aided new bone formation in the ovariectomized animals.     

The unexpected presence of iron in bone biopsies of hemodialysis patients

Purpose

Bone biopsy defines classical diseases that constitute the renal osteodystrophy. There is a recent concern regarding other histological findings that are not appreciated by using the turnover, mineralization, and volume (TMV) classification. Iron (Fe) overload has been considered a new challenge and the real significance of the presence of this metal in bones is not completely elucidated. Therefore, the main goal of the current study was to not only to identify bone Fe, but also correlate its presence with demographic, and biochemical characteristics.

Methods

This is a cross-sectional analysis of bone biopsies performed in 604 patients on dialysis from 2010 to 2014 in a tertiary academic Hospital.

Results

Histomorphometric findings revealed the presence of Fe in 29.1%. Fe was associated with higher levels of serum ferritin and serum calcium. No TMV status was related to Fe bone overload.

Conclusion

Our study has highlighted that the presence of Fe in one-third of bone samples has unknown clinical significance. The lack of other contemporary bone biopsy study reporting Fe prevents us from comparison. The findings presented here should be specifically addressed in a future research and will require attention prior to implementation of any clinical guideline. If any proposed treatment, however, would change the bone Fe-related morbidity is undetermined.

     

Lantana macrophylla Schauer (Verbenaceae) ethanolic extract induces activation of ERK1/2 and p38 MAPKs pathway and Ca2+ imbalance in human trophoblasts derived cell lines

Lantana macrophylla Schauer (Verbenaceae) a medicinal plant used to treat menstrual and respiratory disorders was investigated. The ethanolic extract from leaves was subjected to phytochemical and biological analysis. BeWo and JEG-3 cells were used to evaluate human chorionic gonadotropin hormone (hCG) production, syncytial formation, Ca2+ uptake and Ca2+ handling protein expression. The cAMP production and the mitogen-activated protein kinases (MAPKs) phosphorylation were also investigated. Phytochemical analysis yield three triterpenes: oleanolic, ursolic and latonolic acid. Viability assay showed no significant cytotoxic effect. A significant decrease in hCG production but not a disturbance on BeWo cell fusion were observed. The cAMP pathway was not affected by L. macrophylla extract alone; although the cAMP production inducted by forskolin was diminished. Both ERK1/2 and p38 MAPKs pathways were activated. Increased intracellular Ca2+ concentration ([Ca2+]i) was observed after 24 h treatment in a time and dose dependent manner; however only L. macrophylla at 10 μg/mL induced increased [Ca2+]i after 10 min treatment. CaBP28K and PMCA1/4 were modulated at protein and mRNA levels, respectively. This study showed for the first time the effect of triterpenoids from L. macrophylla leaves on trophoblasts-like cells and indicates a potential toxic effect of this plant in the placental development and fetal growth.     

Role of inflammation in oral carcinogenesis (Part I): Histological grading of malignancy using a binary system

The aim of the present study was to assess the suppressant role of the inflammatory infiltrate in oral carcinogenesis through the immunohistochemical expression of CD8 and FOXP3 and to discuss how representative this expression proved, as well as other parameters considered to be of prognostic value. A total of 20 cases of oral epithelial dysplasia and 40 cases of oral squamous cell carcinoma were selected. The criteria suggested by the World Health Organization were used for the histological grading of dysplasia. For carcinoma, a binary method was developed for the present study using parameters such as type of invasion, maturity, presence of epithelial masses and dysmorphism of the masses. Immunohistochemical analysis was performed for assessment of the expression of anti-CD8 and anti-FOXP3 in cases of dysplasia and carcinoma. Although the inflammatory infiltrate was more intense in the majority of carcinomas, it exercised a protective role in the dysplasia cases, as CD8 expression was significantly greater. Although a correlation was found between CD8 and the intensity of the inflammatory infiltrate in the carcinoma cases, CD8 demonstrated >5% expression in only 32.5% of the cases, compared to 80% of the dysplasia cases. Thus, we suggest that the inflammatory infiltrate should not be used as a parameter in routine examinations, as it plays different roles in the various stages of carcinogenesis. The histological grading system for malignancy employed in the present study is indicated for the assessment of oral squamous cell carcinoma.     

Cinnamaldehyde induces changes in the protein profile of Salmonella Typhimurium biofilm

The effect of cinnamaldehyde against biofilm cells of Salmonella Typhimurium ATCC 14028 was evaluated. We also assessed differential protein patterns that were expressed by biofilms compared with planktonic cells and protein expression by cinnamaldehyde-treated biofilms cells. This compound decreased biofilm biomass and metabolic activity of biofilms at both concentrations tested. Cinnamaldehyde treatment reduced the number of attached cells in polypropylene, reflected by colony count and scanning electron microscopy. The proteomic analysis of biofilms compared with planktonic cells indicated that several proteins were upregulated or downregulated, especially proteins that are involved in energy metabolism. Peroxiredoxin, ATP synthase alpha chain protein, conjugal transfer nickase/helicase TraI and elongation factor G were upregulated in untreated-biofilm cells, and their expression decreased as a function of cinnamaldehyde treatment. Cinnamaldehyde had antibiofilm activity, and several differentially expressed proteins identified provide potential and interesting targets to explore new control strategies for S. Typhimurium biofilms.