Effect of Ocimum sanctum, ascorbic acid, and verapamil on macrophage function and oxidative stress in mice exposed to cocaine

Objective:

To investigate the effect of Ocimum sanctum, ascorbic acid, and verapamil on macrophage function and oxidative stress in experimental animals exposed to cocaine.

Materials and Methods:

Mice were used in this study and were divided randomly into different groups of six animals each. They were either treated with intraperitoneal injection of saline or cocaine hydrochloride or an oral feeding of oil of Ocimum sanctum, ascorbic acid or verapamil, or both (ascorbic acid and verapamil), and were evaluated for a respiratory burst of macrophages, superoxide and nitric oxide (NO) production, estimation of TNF-α in the serum and supernatant of cultured macrophages, estimation of lipid peroxidation (malondialdehyde- MDA) in the serum, and superoxide dismutase activity in the erythrocytes.

Results:

Unstimulated respiratory burst as well as superoxide production was enhanced on treatment with cocaine and all the three drugs were found to attenuate this enhancement. The bactericidal capacity of macrophages decreased significantly on chronic cocaine exposure, as it was associated with decreased respiratory burst and superoxide production. There was a significant decrease in NO production by macrophages on chronic cocaine exposure and all the test drugs were found to restore nitrite formation to a normal level. There was an increase in the malonylodialdehyde (MDA) level and decrease in the superoxide dismutase level on chronic cocaine exposure, and all the three drugs effectively decreased the MDA level and increased superoxide dismutase level. There was an increase in serum TNF-α on chronic cocaine exposure, which was decreased significantly by ascorbic acid and verapamil.

Conclusion:

O. sanctum, ascorbic acid, and verapamil were equally effective in improving the macrophage function and reducing oxidative stress. These findings suggested that O. sanctum, ascorbic acid, and verapamil attenuated acute and chronic cocaine-mediated effects.     

The Biology and Clinical Features of Non–small Cell Lung Cancers with EML4-ALK Translocation

The anaplastic lymphoma kinase (ALK) acts as a dominant oncogenic driver following chromosomal rearrangements in certain cancers including non–small cell lung cancer (NSCLC). NSCLC with ALK translocation occurs in a specific subset of patients and results in unique clinical features. Crizotinib is a small molecule inhibitor of ALK kinase that has recently been approved by the FDA for the treatment of patients with ALK-positive NSCLC. Treatment with crizotinib results in clinical benefit rate of 85%–90% and a median progression-free survival of 9–10 months for this molecular subset of patients. Ongoing studies will define the impact of crizotinib on overall survival and provide insights into the resistance mechanisms and potential activation of alternate pathways. Heat shock protein 90 inhibitors also appear promising in the treatment of ALK-positive NSCLC patients, based on early results. This article reviews the characteristics, treatment, and ongoing research in patients with ALK-positive NSCLC.     

紫山姜体外抗氧化及抗癌活性研究(英文)

AIM:Ethylacetate extract of Alpinia purpurata was evaluated for its potential in vitro antioxidant and antican-cer activity.METHODS:The antioxidant activity was evaluated by 1,1-diphenyl-2-picrylhydrazyl(DPPH) free radical scav-enging method,hydroxyl radical activity,superoxide radical scavenging activity,nitric oxide radical scavenging activity,hy-drogen peroxide radical scavenging activity and reducing power activity.The viability of OAW42 cells was evaluated by MTT assay.RESULTS:A.purpurata exhibited potential antioxidant activity with a concentration-dependent manner.The extract showed potential anticancer activity at the 48th hour with IC50 of 130.20 μg·mL·1 and exhibited a dose-dependent decrease in cell count for all the concentrations tested.CONCLUSION:The results suggested that long term consumption of A.purpurata exhibited antioxidant and anticancer activity and could be further exploited for their anticancer properties.     

Expression of the IAP protein family is dysregulated in pancreatic cancer cells and is important for resistance to chemotherapy

Pancreatic cancer is one of the most aggressive human tumors with a 5-year survival rate of only 3% and a striking resistance to chemotherapy and radiotherapy. The search for new therapeutic approaches includes strategies exploiting the deregulation of apoptotic pathways commonly found in cancer cells. The IAP proteins are inhibitors of apoptosis that have altered activity in numerous cancer types and are implicated in resistance to chemotherapy, and therefore are potentially interesting as therapeutic targets. We investigated alterations in the expression of IAPs and their inhibitors in pancreatic adenocarcinoma by using real-time PCR, in situ hybridization and immunohistochemistry. We found differential expression of various IAPs in this malignancy, and particularly we observed overexpression of cIAP-2, survivin, livin and XIAP. We also looked for correlations between the expression of IAPs and resistance to paclitaxel, doxorubicin, CDDP and 5-fluorouracil, and found that resistance to these drugs correlates most significantly with expression of cIAP-2. Using RNAi to downregulate these proteins we further confirmed that the levels of cIAP-2 and XIAP influence the response to the anti-cancer drugs, although only marginally for 5-FU. We conclude that anti-tumor strategies based on the inhibition of particular IAPs can be useful in targeting pancreatic adenocarcinoma.     

Routine evaluation of left ventricular diastolic function by cardiovascular magnetic resonance: A practical approach

Background

Cardiovascular magnetic resonance (CMR) has excellent capabilities to assess ventricular systolic function. Current clinical scenarios warrant routine evaluation of ventricular diastolic function for complete evaluation, especially in congestive heart failure patients. To our knowledge, no systematic assessment of diastolic function over a range of lusitropy has been performed using CMR.

Methods and Results

Left ventricular diastolic function was assessed in 31 subjects (10 controls) who underwent CMR and compared with Transthoracic echocardiogram (TTE) evaluation of mitral valve (MV) and pulmonary vein (PV) blood flow. Blood flow in the MV and PV were successfully imaged by CMR for all cases (31/31,100%) while TTE evaluated flow in all MV (31/31,100%) but only 21/31 PV (68%) cases. Velocities of MV flow (E and A) measured by CMR correlated well with TTE (r = 0.81, p < 0.001), but demonstrated a systematic underestimation by CMR compared to TTE (slope = 0.77). Bland-Altman analysis of the E:A ratio and deceleration time (DT) calculated from each modality showed excellent agreement (bias -0.29, and -10.3 ms for E:A and DT, respectively). When assessing morphology using TTE, CMR correctly identified patients as having normal or abnormal inflow conditions.

Conclusion

We have shown that there is homology between CMR and TTE for the assessment of diastolic inflow over a wide range of conditions, including normal, impaired relaxation and restrictive. There is excellent agreement of quantitative velocity measurements between CMR and TTE. Diastolic blood flow assessment by CMR can be performed in a single scan, with times ranging from 20 sec to 3 min, and we show that there is good indication for applying CMR to assess diastolic conditions, either as an adjunctive test when evaluating systolic function, or even as a primary test when TTE data cannot be obtained.     

Efficacy of fixed low-dose isotretinoin (20 mg, alternate days) with topical clindamycin gel in moderately severe acne vulgaris

Background  In view of the potentially serious side-effects of standard isotretinoin (0.5–1.0 mg/kg per day) therapy for acne, we studied the safety and efficacy of low-fixed dose isotretinoin plus topical 1%clindamycin gel in the treatment of moderate grade of acne.
Methods  In this prospective, non-comparative study, 320 adult patients, with moderately severe acne were enrolled and treated with fixed-dose isotretinoin at 20 mg every alternate day (approximately 0.15 mg/kg/day to 0.28 mg/kg/day) for 6 months along with topical clindamycin gel. All female patients were assessed for polycystic ovarian disease. Patients were followed up for 6 months.
Results  A total of 305 patients completed the study. Overall, patients received a mean of 38.4 mg/kg cumulative dose of isotretinoin, and very good results were observed in 208 (68.20%), while good response was seen in 59 (19.34%) of patients. Failure of the treatment occurred in 38 (12.46%), while relapses occurred in 50 (16.39%) of patients. Relapses were commoner in females, and 37 of 43 (86.04%) patients had polycystic ovarian disease. Though mild chelitis (91%) and xerosis (43%) were common, laboratory abnormalities in the form of elevated hepatic enzymes (5%) and elevated serum lipids (6%) were rare.
Conclusion  Six months of treatment with fixed-dose, alternate-day isotretinoin (20 mg) plus topical 1%clindamycin gel was found to be effective in the treatment of moderate acne in adult patients, with a low incidence of side-effects.

Conflicts of interest

None declared     

Effect of liver disease on maternal and fetal outcome--a prospective study.

BACKGROUND: Liver disease in pregnancy can have serious consequences. Its prevalence, profile and effect on outcome of pregnancy have not been documented systematically in India. We prospectively determined the frequency, causes and outcome of liver disease in pregnant women. SETTING: Tertiary-care teaching hospital. METHODS: Consecutive pregnant women with liver disease attending the inpatient or outpatient services of the Departments of Gastro-enterology and Obstetrics and Gynecology between December 2002 and October 2004 were evaluated and followed up till 2 weeks postpartum or death. RESULTS: Liver disease was found in 107 (0.9%) of 12,061 pregnancies. Of these, fifty six (52.3%) had pregnancy-specific liver disorders (pregnancy-induced hypertension [PIH]-associated liver dysfunction 36--including HELLP syndrome 22 and pre-eclamptic liver dysfunction 14; intrahepatic cholestasis of pregnancy 10; hyperemesis gravidarum 7; acute fatty liver of pregnancy 3). Liver disorders not specific to pregnancy included hepatitis E (16), hepatitis B, non A-E hepatitis and chronic liver disease (5 each) and others (14); in 6 patients no cause could be found. Ninety-six patients completed follow up. Overall maternal and perinatal mortality rates were 19.7% and 35.4%, respectively. CONCLUSIONS: PIH-associated liver dysfunction was the most common cause of liver disease in pregnancy. This is associated with significant maternal and perinatal morbidity and mortality.     

Can cardiovascular MRI be used to more definitively characterize cardiac masses initially identified using echocardiography?

In diagnosing cardiac and paracardiac masses, cardiac MRI (CMR) has gained acceptance as the gold standard. CMR has been observed to be superior to echocardiography in characterizing soft‐tissue structures and, specifically, in classifying cardiac masses. The aim of our study was to evaluate the association between mortality and cardiac or paracardiac masses initially identified by echocardiography (ECHO) and confirmed by CMR. Between January 2002 and August 2007, a total of 158 patients underwent both ECHO and CMR for the evaluation of cardiac masses that were equivocal or undefined by ECHO. The primary study endpoints were 5‐year all‐cause mortality and 5‐year cardiac mortality. Causes of death as of April 1, 2015 were obtained from medical records or the National Death Index. Patients were analyzed according to mass type determined by CMR using the Kruskal–Wallis test, Kaplan–Meier curves, and the log‐rank test. Over a mean duration of follow‐up of 10.4 ± 2.9 years (range: 0.01–12 years) post‐CMR, the overall all‐cause mortality rate was 25.9% (41/158). Median age at death was 76 years and there were 21 females (51.2%). Mortality rates in the different classifications of cardiac masses by CMR were as follows: 20% (1/5) in patients with a Nondiagnostic CMR; 20% (1/5) in Other Diagnoses; 17.9% (7/39) in No Masses (includes Normal Anatomical Variants); 16.7% (3/18) in Benign Masses; 23.8% (15/63) in Fat; 50% (5/10) in Thrombus; and 61.5% (8/13) in Malignant Mass. The mean survival time in patients with No Mass (n = 39) was not significantly longer than patients with any type of cardiac mass (n = 114) (P = .16). No significant difference was found in age at death between patients when grouped by CMR classification (P = .40). However, among CMR‐confirmed masses, there were some significant differences by mass classification type (P = .006). During the follow‐up period, 26% (41/158) of patients died and 22% (9/41) of the deaths were cardiovascular related; there was no significant difference in mean survival times with respect to cause of mortality (P = .23). In patients with cardiac masses, dually confirmed by ECHO and CMR, significant differences in survival time were observed based upon CMR classified type of mass while CMR was instrumental in obviating invasive biopsy.