Effect of tetrahydrocurcumin on lipid peroxidation and lipids in streptozotocin-nicotinamide-induced diabetic rats

Hyperlipidaemia is an associated complication of diabetes mellitus. We recently reported that tetrahydrocurcumin lowered the blood glucose in diabetic rats. In the present study, we have investigated the effect of tetrahydrocurcumin, one of the active metabolites of curcumin on lipid profile and lipid peroxidation in streptozotocin-nicotinamide-induced diabetic rats. Tetrahydrocurcumin 80 mg/kg body weight was administered orally to diabetic rats for 45 days, resulted a significant reduction in blood glucose and significant increase in plasma insulin in diabetic rats, which proved its antidiabetic effect. Tetrahydrocurcumin also caused a significant reduction in lipid peroxidation (thiobarbituric acid reactive substances and hydroperoxides) and lipids (cholesterol, triglycerides, free fatty acids and phospholipids) in serum and tissues, suggesting its role in protection against lipid peroxidation and its antihyperlipidemic effect. Tetrahydrocurcumin showed a better effect when compared with curcumin. Results of the present study indicate that tetrahydrocurcumin showed antihyperlipidaemic effect in addition to its antidiabetic effect in type 2 diabetic rats.     

Heart surgery in infants with hemophilia

We describe 2 infants with hemophilia A who had heart surgery under cardiopulmonary bypass with factor VIII replacement therapy, and we recommend a guideline for factor VIII support for cardiac surgery. One child had repair of total anomalous pulmonary venous connection. The second had cardiac catheterization followed by repair of ventricular septal defect and total anomalous pulmonary venous connection. Close collaboration between hematologist, laboratory, cardiologist, and cardiac surgeon is crucial in successful management of coagulation abnormalities during and after surgery.     

Plasma CRP level predicts left ventricular function and exercise capacity in patients with acute myocardial infarction

BACKGROUND: C-reactive protein estimation can help in predicting short- and long-term prognosis after acute myocardial infarction. High plasma C-reactive protein level in the acute phase strongly indicates a poor clinical outcome of the patients with myocardial infarction. METHODS AND RESULTS: One hundred consecutive patients admitted with ST elevation myocardial infarction in the intensive coronary care unit in our hospital who were able to do symptom-limited treadmill test during early recovery phase were studied. Plasma C-reactive protein was measured at the time of admission by immunoturbidity method. The normal value of the C-reactive protein was taken as 0.8 mg/dl. Echocardiographic study was done on day three of admission and ejection fraction was estimated by modified Simpson's method. Symptom-limited treadmill exercise test was done in all the patients. Patients were classified into two groups based on level of C-reactive protein: those with low C-reactive protein level (1.26 +/- 0.91 mg/dl, n=40) and those with high C-reactive protein level (6.52 +/- 3.97 mg/dl, n=60). Ejection fraction was lower in high C-reactive protein group (46.7 +/- 11.9%) compared to low C-reactive protein group (56.9 +/- 7.7%) (p = 0.011). Exercise capacity was lower in high C-reactive protein group (2.8 +/- 1.4 METs) compared to low C-reactive protein group (5.5 +/- 2.5 METs) p = 0.027). CONCLUSIONS: C-reactive protein levels are an index of the severity of myocardial necrosis which translate to worse left ventricular function. Higher the C-reactive protein level, lower the ejection fraction and worse may be the prognosis.     

In vivo tumor imaging using polo-box domain of polo-like kinase 1 targeted peptide

Polo-like kinase 1 (Plk1) is a regulator of cell cycle progression during mitosis; it is overexpressed in many different tumors and has been implicated as a potential antimitotic target. Plks are characterized by the presence of a highly conserved C-terminal polo-box domain (PBD) that is involved in regulating kinase activity. The phosphopeptide Pro-Leu-His-Ser-p-Thr (PLHSpT) is a potent selective inhibitor of the PBD of human plk1 that acts by inducing mitotic arrest and apoptotic cell death in cancer cells. We synthesized cRGDyK-S-S-CPLHSpT to exploit the drug delivery and molecular imaging using positron emission tomography (PET). The peptide was blocked dramatically proliferation of tumor in?vitro and in?vivo. It was attempted to develop and show a tumor PET image with the radiolabeled-peptide. Here we showed the peptide is promising not only as an anticancer drug, but also as a radioligand for tumor diagnosis with PET. We expect that our contribution will provide new insights into the design of Plk1 peptide inhibitors and have significant implications for anticancer therapy and tumor diagnosis.     

Synthesis of silver nanoparticles using leaves of Catharanthus roseus Linn. G. Don and their antiplasmodial activities

Objective

To develop a novel approach for the green synthesis of silver nanoparticles using aqueous leaves extracts of Catharanthus roseus (C. roseus) Linn. G. Don which has been proven active against malaria parasite Plasmodium falciparum (P. falciparum).

Methods

Characterizations were determined by using ultraviolet-visible (UV-Vis) spectrophotometry, scanning electron microscopy (SEM), energy dispersive X-ray and X-ray diffraction.

Results

SEM showed the formation of silver nanoparticles with an average size of 35–55 nm. X-ray diffraction analysis showed that the particles were crystalline in nature with face centred cubic structure of the bulk silver with the broad peaks at 32.4, 46.4 and 28.0.

Conclusions

It can be concluded that the leaves of C. roseus can be good source for synthesis of silver nanoparticle which shows antiplasmodial activity against P. falciparum. The important outcome of the study will be the development of value added products from medicinal plants C. roseus for biomedical and nanotechnology based industries.     

Plasma neutrophil gelatinase-associated lipocalin predicts recovery from acute kidney injury following community-acquired pneumonia

Although plasma neutrophil gelatinase-associated lipocalin (NGAL) is a promising biomarker for early detection of acute kidney injury, its ability to predict recovery is unknown. Using RIFLE criteria to define kidney injury, we tested whether higher plasma NGAL concentrations on the first day of RIFLE-F would predict failure to recover in a post hoc analysis of a multicenter, prospective, cohort study of patients with community-acquired pneumonia. Recovery was defined as alive and not requiring renal replacement therapy during hospitalization or having a persistent RIFLE-F classification at hospital discharge. Median plasma NGAL concentrations were significantly lower among the 93 of 181 patients who recovered. Plasma NGAL alone predicted failure to recover with an area under the receiver operating characteristic curve of 0.74. A clinical model using age, serum creatinine, pneumonia severity, and nonrenal organ failure predicted failure to recover with area under the curve of 0.78. Combining this clinical model with plasma NGAL concentrations did not improve prediction. The reclassification of risk of renal recovery, however, significantly improved by 17% when plasma NGAL was combined with the clinical model. Thus, in this cohort of patients with pneumonia-induced severe acute kidney injury, plasma NGAL appears to be a useful biomarker for predicting renal recovery.     

A rare cause of intermittent dysphagia: giant fibrovascular polyp of the proximal esophagus

Fibrovascular polyps account for only 0.5-1% of all benign esophageal tumors and causes intermittent dysphagia. The patient was a 63-year-old gentleman with gradually progressive intermittent dysphagia of 40 days duration. Investigations revealed a submucosal tumor of the proximal esophagus causing luminal compromise. Excision was performed through a cervical esophagotomy and specimen was subject to histopathological examination. Postoperative recovery was uneventful and he was completely relieved of his symptoms.     

Superoxide radical scavenging and antibacterial activities of different fractions of ethanol extract of Mentha spicata (L.)

Mentha spicata is a well-known spice that has a variety of biological properties and is abundantly available throughout the world. This study was designed to investigate the superoxide radical scavenging and antibacterial properties of different fractions (hexane, chloroform, ethyl acetate, and aqueous) of the ethanol extract of Mentha spicata. In addition, xanthine oxidase generated uric acid inhibition, reducing potential and iron chelating activity, also was investigated. Ethyl acetate fraction exhibited the highest (≤84%) superoxide radical scavenging and inhibition of uric acid formation at 40 μg/ml compared with the standard quercetin (≤81%) at 30 μg/ml. The highest reducing potential also is observed in ethyl acetate and aqueous fractions, which were comparable to the reducing potential of quercetin and ascorbic acid. Iron chelating activity of solvent fractions was found to be better than standard of EDTA (79% at 3 mg/ml). In addition, all fractions showed effective antibacterial activity against five human pathogenic bacteria among the ten samples used. However, aqueous fraction showed maximum growth inhibition zone (≤36 mm diameter at 6 μg/per disc) against Shigella boydii. Hence, we conclude that the ethyl acetate and aqueous fractions of ethanol extract of Mentha spicata exhibited higher superoxide radical scavenging and antibacterial activities.     

Boldine improves endothelial function in diabetic db/db mice through inhibition of angiotensin II-mediated BMP4-oxidative stress cascade

BACKGROUND AND PURPOSE

Boldine is a potent natural antioxidant present in the leaves and bark of the Chilean boldo tree. Here we assessed the protective effects of boldine on endothelium in a range of models of diabetes, ex vivo and in vitro.

EXPERIMENTAL APPROACH

Vascular reactivity was studied in mouse aortas from db/db diabetic and normal mice. Reactive oxygen species (ROS) production, angiotensin AT₁ receptor localization and protein expression of oxidative stress markers in the vascular wall were evaluated by dihydroethidium fluorescence, lucigenin enhanced-chemiluminescence, immunohistochemistry and Western blot respectively. Primary cultures of mouse aortic endothelial cells, exposed to high concentrations of glucose (30 mmol L⁻¹) were also used.

KEY RESULTS

Oral treatment (20 mg kg⁻¹day⁻¹, 7 days) or incubation in vitro with boldine (1 μmol L⁻¹, 12 h) enhanced endothelium-dependent aortic relaxations of db/db mice. Boldine reversed impaired relaxations induced by high glucose or angiotensin II (Ang II) in non-diabetic mouse aortas while it reduced the overproduction of ROS and increased phosphorylation of eNOS in db/db mouse aortas. Elevated expression of oxidative stress markers (bone morphogenic protein 4 (BMP4), nitrotyrosine and AT₁ receptors) were reduced in boldine-treated db/db mouse aortas. Ang II-stimulated BMP4 expression was inhibited by boldine, tempol, noggin or losartan. Boldine inhibited high glucose-stimulated ROS production and restored the decreased phosphorylation of eNOS in mouse aortic endothelial cells in culture.

CONCLUSIONS AND IMPLICATIONS

Boldine reduced oxidative stress and improved endothelium-dependent relaxation in aortas of diabetic mice largely through inhibiting ROS overproduction associated with Ang II-mediated BMP4-dependent mechanisms.