Antiobesity,hypolipidemic, antioxidant and hepatoprotective effects of Achyranthes aspera seed saponins in high cholesterol fed albino rats

Introduction

Numerous herbal medicines have been recommended for the treatment of different diseases. Achyranthes aspera, Linn. (Family: Amaranthaceae), popularly known as Charchitta or Pitpapra, is commonly used by traditional healers for the treatment of fever, malaria, dysentery, asthma, arterial hypertension, pneumonia, and diabetes. The root extract is well reputed for its insect molting hormonal activity. This investigation was conducted to evaluate the effects of saponins from Achyranthes aspera seeds on the serum lipid profile of albino rats fed a high cholesterol diet.

Material and methods

Hypolipidemic, antioxidant and hepatoprotective activities of these saponins were tested as described previously. To determine the mechanism underlying the observed effects, serum antioxidant status was assessed according to ABTS (2,2’-azino-bis-3-ethylbenzo-thiazoline-6-sulfonic acid), superoxide dismutase and ferric ion reducing antioxidant power (FRAP) assays in saponin-treated hyperlipidemic animals. Liver enzyme levels were determined to reveal any possible hepatotoxicity.

Results

Four-week oral administration of A. aspera seed saponins produced a significant (p < 0.05) decrease of total cholesterol, total triglycerides and LDL-C and a significant increase of HDL-C level in hyperlipidemic rats. Treatment with A. aspera seed saponins also showed a significant (p < 0.01) improvement of serum antioxidant status in tested animals. No significant hepatotoxicity was produced by such treatment as the serum liver enzyme activity remained unaltered.

Conclusions

Saponins from A. aspera seeds possess antihyperlipidemic and antioxidant properties which might lead to improvement of serum lipid profile and blood antioxidant status. Our findings support the folkloric use of this indigenous plant in the treatment of hyperlipidemia. However, its exact mechanism of action remains to be elucidated.     

P2Y12 Platelet Receptors: Importance in Percutaneous Coronary Intervention

Apart from their role in hemostasis and thrombosis, platelets are involved in manyother biological processes such as wound healing and angiogenesis. Percutaneouscoronary intervention is a highly thrombogenic procedure inducing platelets andmonocytes activation through endothelial trauma and contact activation byintravascular devices. Platelet P2Y₁₂ receptor activation by adenosinediphosphate facilitates non-ADP agonist-mediated platelet aggregation, dense granulesecretion, procoagulant activity, and the phosphorylation of several intraplateletproteins, making it an ideal drug target. However, not all compounds that target theP2Y₁₂ receptor have similar efficacy and safety profiles. Despitetargeting the same receptor, the unique pharmacologic properties of each of theseP2Y₁₂ receptor-directed compounds can lead to very different clinicaleffects.     

Effectiveness of diaphragmatic stimulation with single-channel electrodes in rabbits

Every year, a large number of individuals become dependent on mechanicalventilation because of a loss of diaphragm function. The most common causes arecervical spinal trauma and neuromuscular diseases. We have developed anexperimental model to evaluate the performance of electrical stimulation of thediaphragm in rabbits using single-channel electrodes implanted directly into themuscle. Various current intensities (10, 16, 20, and 26 mA) produced tidalvolumes above the baseline value, showing that this model is effective for thestudy of diaphragm performance at different levels of electrical stimulation     

Lung function in post-poliomyelitis syndrome: a cross-sectional study

OBJECTIVE:

To compare lung function between patients with post-poliomyelitis syndrome and those with sequelae of paralytic poliomyelitis (without any signs or symptoms of post-poliomyelitis syndrome), as well as between patients with post-poliomyelitis syndrome and healthy controls.

METHODS:

Twenty-nine male participants were assigned to one of three groups: control; poliomyelitis (comprising patients who had had paralytic poliomyelitis but had not developed post-poliomyelitis syndrome); and post-poliomyelitis syndrome. Volunteers underwent lung function measurements (spirometry and respiratory muscle strength assessment).

RESULTS:

The results of the spirometric assessment revealed no significant differences among the groups except for an approximately 27% lower mean maximal voluntary ventilation in the post-poliomyelitis syndrome group when compared with the control group (p = 0.0127). Nevertheless, the maximal voluntary ventilation values for the post-poliomyelitis group were compared with those for the Brazilian population and were found to be normal. No significant differences were observed in respiratory muscle strength among the groups.

CONCLUSIONS:

With the exception of lower maximal voluntary ventilation, there was no significant lung function impairment in outpatients diagnosed with post-poliomyelitis syndrome when compared with healthy subjects and with patients with sequelae of poliomyelitis without post-poliomyelitis syndrome. This is an important clinical finding because it shows that patients with post-poliomyelitis syndrome can have preserved lung function.     

Immunogenicity of Recombinant Proteins Consisting of Plasmodium vivax Circumsporozoite Protein Allelic Variant-Derived Epitopes Fused with Salmonella enterica Serovar Typhimurium Flagellin

A Plasmodium falciparum circumsporozoite protein (CSP)-based recombinant fusion vaccine is the first malaria vaccine to reach phase III clinical trials. Resistance to infection correlated with the production of antibodies to the immunodominant central repeat region of the CSP. In contrast to P. falciparum, vaccine development against the CSP of Plasmodium vivax malaria is far behind. Based on this gap in our knowledge, we generated a recombinant chimeric protein containing the immunodominant central repeat regions of the P. vivax CSP fused to Salmonella enterica serovar Typhimurium-derived flagellin (FliC) to activate the innate immune system. The recombinant proteins that were generated contained repeat regions derived from each of the 3 different allelic variants of the P. vivax CSP or a fusion of regions derived from each of the 3 allelic forms. Mice were subcutaneously immunized with the fusion proteins alone or in combination with the Toll-like receptor 3 (TLR-3) agonist poly(I·C), and the anti-CSP serum IgG response was measured. Immunization with a mixture of the 3 recombinant proteins, each containing immunodominant epitopes derived from a single allelic variant, rather than a single recombinant protein carrying a fusion of regions derived from each of 3 allelic forms elicited a stronger immune response. This response was independent of TLR-4 but required TLR-5/MyD88 activation. Antibody titers significantly increased when poly(I·C) was used as an adjuvant with a mixture of the 3 recombinant proteins. These recombinant fusion proteins are novel candidates for the development of an effective malaria vaccine against P. vivax.     

Determination of the HER2 amplification status by in situ fluorescent hybridization and concordance with immunohistochemistry for breast cancer samples in Colombia

Objectives:

To determine the status of the HER2 amplification in Breast cancer performed in peripheral laboratories in Colombia by immunohistochemistry and its comparison with central laboratories and the FISH status.

Methods:

Four thousand one hundred and five cases referred for the determination of the HER2 status by FISH and/or IHQ to the Department of Pathology of the Fundacion Santa Fe were studied. The analysis included correlation between the IHQ HER2 score submitted by the peripheral laboratory (PL), the HER2 score emitted in the CL and the FISH studies performed in the central laboratory (CL).

Results:

Two thousand five hundred and eight HER2 IHQ studies were performed in the (CL), using the Dako Herceptest. With the following results: 68.2 % negative (0-1+); 16,4% indeterminate (2+); 15.3% 3+ and 2.3 % not adequate. 1360/ 1719 cases studied by FISH came from the (PL), and 329 (19.1%) from the (CL). Comparing the IHQ score emitted by the PL and the positive FISH status showed: 6/28 0+ were positive (21. 4%); 7/31 1+ (22. 5%); 397/1240 2+ (32.8%) and 74/91 3+ (81. 3%). In the CL the results were 1/9 0+ (11.1%); 3/18 1+ (16.7%); 154/292 2+ (53%); and 9/9 3+ (100%). Only 1/4 negative cases (0/1+) was in house.

Conclusion:

The false negative rate (22%), and false positive results (18.7%), of the HER2 status performed by IHQ in peripheral laboratories in Colombia is unacceptable high as well as the inadequacy of tissue indicating that pre-analytical factors have to be improved in Colombia in order to get optimal results.     

Prevalence of sphincter of Oddi dysfunction in patients referred to endoscopic retrograde cholangiopancreatography

BACKGROUND: Sphincter of Oddi manometry is the gold-standard method for sphincter of Oddi dysfunction. The prevalence of sphincter of Oddi dysfunction among patients referred to endoscopic retrograde cholangiopancreatography is largely unknown. AIM: To evaluate prospectively the prevalence of biliary sphincter of Oddi dysfunction (B-SOD) among Brazilian patients referred to endoscopic retrograde cholangiopancreatography and to study the safety of sphincter of Oddi manometry in this setting. METHODS: Biliary sphincter of Oddi manometry was intended in 110 patients referred to endoscopic retrograde cholangiopancreatography. The number of attempts to obtain deep cannulation with the manometry catheter was recorded and patients were divided into two groups: up to 5 (easy cannulation) and >5 attempts (difficult cannulation). RESULTS: Sphincter of Oddi manometry was successful in 71/110 patients (64.5%). Sphincter of Oddi dysfunction was found in 18/71 patients (25%). Endoscopic retrograde cholangiopancreatography findings were: normal in 16, biliary stones in 39, malignant biliary strictures in 9 and benign biliary strictures in 7. There was no statistical difference in sphincter of Oddi dysfunction prevalence regarding disease, gender or difficulty of cannulation. Only 2/71 patients developed post-procedure mild pancreatitis. CONCLUSIONS: We have found a high prevalence of sphincter of Oddi dysfunction in patients referred to endoscopic retrograde cholangiopancreatography. Gender, nature of disease or difficulty of cannulation did not influence the prevalence of sphincter of Oddi dysfunction among these patients. Sphincter of Oddi manometry is a safe procedure for the evaluation of sphincter of Oddi dysfunction in patients referred to endoscopic retrograde cholangiopancreatography.     

Increased prevalence of antimitochondrial antibodies in first-degree relatives of patients with primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disorder that can progress to cirrhosis, shortening life expectancy. PBC patients are often asymptomatic, present with biochemical cholestasis, and test positive (>or=90%) for antimitochondrial antibodies (AMAs) in serum. Although AMA positivity without biochemical cholestasis may indicate increased risk of future PBC development, the contribution of these antibodies to pathogenesis remains enigmatic. Environmental risks and genetic determinants are likely implicated in PBC etiology. Given the familial aggregation of PBC, we hypothesized that AMAs also aggregate among relatives of PBC probands. We investigated the prevalence of AMAs in first-degree relatives (FDRs) of PBC probands to examine whether AMAs aggregate in such pedigrees. Using a PBC family registry, we prospectively screened for AMAs in the serum of 306 FDRs in 145 pedigrees, 350 PBC probands, and 196 controls who were age-matched, sex-matched, race-matched, and residence-matched to probands. The prevalence of AMA in FDRs and controls was 13.1% and 1%, respectively. Greater prevalence of AMA was found in female FDRs of PBC probands [sisters (20.7%), mothers (15.1%), and daughters (9.8%)] than in male FDRs [brothers (7.8%), fathers (3.7%), and sons (0%)]. CONCLUSIONS: AMAs aggregate among FDRs of PBC probands. Our data have clinical implications for FDRs of PBC probands because AMA positivity may suggest susceptibility to PBC. Thus, the identification and follow-up of these relatives may lead to earlier disease diagnosis and treatment. Furthermore, if AMA development is heritable, this trait will provide a basis to dissect the genetic predisposition to PBC.     

Curcumin-loaded into PLGA nanoparticles

The incorporation of the curcumin into poly(lactic-co-glycolic)acid (PLGA) nanospheres by the nanoprecipitation technique, the characterization of the nanoparticles and the schistosomicidal activity of the curcumin-loaded into PLGA nanospheres were reported. The incorporation process occurred with high efficiency and the images of field-emission scanning electron microscopy (FESEM) revealed the production of spherically shaped particles. According to the dynamic light scattering measurements, the particles are nanometric and monodisperse. The curcumin-loaded PLGA nanoparticles (50 and 100 μM) caused the death of all worms and a separation between 50% and 100% of Schistosoma mansoni couples at concentrations from 30 μM. Moreover, the curcumin-loaded PLGA nanoparticles also decreased the motor activity and caused partial alterations in the tegument of adult worms. This study marks the first time that schistosomicidal activity has been reported for curcumin-loaded PLGA nanoparticles.