Screening the antiangiogenic activity of medicinal plants grown and sold in Jordan

Angiogenesis is essential for the growth, invasion, and metastasis of most solid tumors and has become a valuable pharmacological target for cancer prevention and treatment. This study was performed to assess the antiangiogenic activity of 31 medicinal plants grown and sold in Jordan. The antiangiogenic activity was assessed using the rat aortic ring assay. Out of 31 extracts, 15 extracts showed more than 50?% inhibition of the blood vessels outgrowth from the primary tissue explants (p?=?0.000). Three of these 15 extracts showed a potential cytotoxic effect on normal fibroblast cells. Four extracts shared antiangiogenic and antiproliferative activity towards MCF7 breast cancer cell lines. Eight extracts demonstrated selective antiangiogenic activity. This is the first report demonstrating the potential antiangiogenic activity of Artemisia judaica, Aloysia citriodora, Salvia egyptiaca, and Calendula arvensis. Some extracts with antiangiogenic activity exhibited selectivity against the endothelial cells proliferation, demonstrating a direct inhibitory activity against the key step in tumor angiogenesis.     

Impairment of left and right ventricular longitudinal strain in asymptomatic children with type 1 diabetes

AimThe relationship between type 1 diabetes (T1DM) and cardiac function in children is not well established. The purpose of this study was to investigate whether children and adolescents with T1DM present early asymptomatic abnormalities of left ventricular (LV) and right ventricular (RV) function. In addition, we evaluated the relationship of any such abnormalities with glycemic control and diabetes duration.MethodsThis was a prospective study. Standard echocardiography, tissue Doppler imaging, and two-dimensional strain analysis were performed prospectively in 52 children with T1DM. The results were compared with those from 52 healthy children matched for age and sex.ResultsThere were no significant differences between the two groups in LV ejection fraction or RV systolic function. There was a difference between the two study groups in transtricuspid flow: the E-wave and A-wave velocities were significantly higher in the diabetic group. Left ventricular global longitudinal strain (LV GLS) was significantly lower in children with T1DM (?20.01 ± 1.86% vs. ?22.99 ± 0.98%, respectively; P < .001), as was RV free-wall longitudinal strain (RV FWLS) (?29.13 ± 1.85% vs. ?30.22 ± 1.53%, respectively; P = .002). LV GLS was correlated with diabetes duration (r = 0.444, P < .001) and glycated hemoglobin (HbA1c) (r = 0.683, P < .001); however, no correlation was found between RV FWLS and HbA1c or diabetes duration.ConclusionsOur findings suggest that LV GLS and RV FWLS are impaired in children with T1DM and that the decrease in LV GLS is correlated with diabetes duration and HbA1c levels.     

The use of the EEG in measuring therapeutic drug action: focus on depression and antidepressants

A major issue in proof of concept studies and early clinical trials of novel therapeutic agents is that the active drugs can often have a relatively small additional effect compared with placebo. This is especially the case in psychiatry when we usually have no direct method of measuring the pathology underlying the disorder being studied but, rather, have to rely on the subjective assessment of psychiatric symptoms. The use of the electroencephalogram (EEG) offers two potential major means of addressing this problem. First it is able to provide direct data relating to neural activity that may be abnormal in certain disorders. As such there are opportunities for utilizing the EEG in a variety of ways as an objective outcome measure. Second there is growing evidence that in certain circumstances the EEG can be used to predict which patients are likely to respond to treatment, thus potentially increasing the power of studies by decreasing non-response rates and increasing mean changes in outcome measure. Both of these uses of the EEG are illustrated in reference to the study of mood disorders and in particular depression and its treatment with antidepressants.     

Effects of cortisol on the laterality of the neural correlates of episodic memory

Alterations in the laterality of cortical activity have been shown in depressive illnesses. One possible pathophysiological mechanism for this is an effect of corticosteroids. We have previously demonstrated that endogenous cortisol concentrations correlate with the asymmetry of cortical activity related to episodic memory in healthy subjects and depressed patients. To further-examine whether this is due to a causal effect of cortisol on the laterality of episodic memory, we studied the effect of exogenous administration of cortisol in healthy subjects. Twenty-three right-handed healthy male volunteers were tested in a double-blind cross-over study. Event-related potentials (ERPs) were recorded during an episodic memory task following a four-day course of 160mg/day cortisol or placebo. Low-resolution brain electromagnetic tomography (LORETA) was used to identify brain regions involved in the neurocognitive task. Cortisol levels were measured in saliva samples. ERP and LORETA analysis following placebo demonstrated significant left parahippocampal activation associated with successful retrieval. Cortisol led to a decrease in the mean early frontal ERP voltage and an increase in the late right ERP voltage. LORETA suggested this to be due to a significant increased late activation of the right superior frontal gyrus. There was no significant effect of cortisol on episodic memory performance. This study suggests that exogenous cortisol leads to more positive-going waveforms over the right than the left hemisphere, possibly due to increased monitoring of the products of retrieval. The results support the hypothesis of causal effects of cortisol on the laterality of cortical activity occurring during an episodic memory task.     

Central glucocorticoid receptor-mediated effects of the antidepressant, citalopram, in humans: a study using EEG and cognitive testing

Our previous work in cellular and animal models has shown that antidepressants activate glucocorticoid receptor (GR) translocation, induce GR down-regulation, and decrease GR-mediated effects in the presence of GR agonists. However, whether these effects can be extrapolated to the human brain is still unclear. In this study, the effects of four days of treatment with the antidepressant, citalopram (20 mg/day), or placebo, were assessed in a double-blind, placebo-controlled, cross-over study. Central GR-mediated effects were examined by the effects of a single dose of cortisol (30 mg, orally) on two measures known to be sensitive to glucocorticoid administration: EEG alpha power and working memory function. Twenty healthy male subjects aged between 18 and 33 years participated to the study. The results suggest that GR activation by antidepressants, and the subsequent decrease in GR-mediated effects in the presence of GR agonists, indeed occurs in the human brain. Specifically, pre-treatment with citalopram decreased the well-known ability of cortisol to increase EEG alpha power and to impair working memory: cortisol-induced increase in EEG alpha power was (anteriorly) +15 to +20% (p=0.01) after placebo and +5 to +8% (p>0.5) after citalopram; and cortisol-induced increase in working memory errors was (at level 12, on average) 2.50 vs. 4.55 (p<0.05) after placebo and 4.10 vs. 3.35 (p>0.05) after citalopram. No effects were detected on alerting. These results are consistent with the notion that citalopram treatment activates GR translocation and inhibits the functional consequences of the subsequent cortisol administration. Our study further emphasizes the importance of the GR as a target for antidepressant action in humans.     

Combretastatin A4-camptothecin micelles as combination therapy for effective anticancer activity

Cancer is a major worldwide health problem, for which chemotherapy is a common treatment option. However drug toxicity and the development of resistance to chemotherapy are two main challenges associated with the traditional anticancer drugs. Combined pharmacological therapy based on different mechanisms might be an effective strategy in cancer treatment, and could exhibit a synergistic therapeutic efficacy. Herein, we aim to combine combretastatin A4 (CA4) and camptothecin (Cpt) chemically into a codrug through two hydrophilic linkers utilizing click chemistry to improve their water solubility and anticancer activity. The synthesized amphiphilic structure could self-assemble into a micelle structure as confirmed by atomic force microscopy (AFM) and dynamic light scattering (DLS), which showed a high stability and improved water solubility at pH 7.4, with a low critical micelle concentration (CMC) value of 0.9 mM. Moreover, in vitro hydrolysis was observed upon incubation of the hybrid compound with an esterase enzyme, which suggested a complete disassembly into the starting active drugs. Finally, cytotoxicity studies on HeLa cancer cells showed that the codrug demonstrated an enhanced (five fold) cytotoxicity as compared with the free drugs. In addition the combination index (CI) was <1, which suggests a synergistic activity for the codrug. Moreover, the tested concentrations of the codrug were not significantly cytotoxic to a noncancerous fibroblast cell line. The imaging of HeLa cells treated with FITC-loaded micelles showed a rapid internalization. In conclusion, the codrug of CA4 and Cpt might be a potential novel anticancer drug as it demonstrated a synergistic cytotoxic activity that might spare noncancerous cells.

Novel CA4-TEG-triazole-TEG-Cpt (codrug 9) was synthesized and self-assembled into a micelle structure that showed a great synergistic anticancer activity on HeLa cancer cells without affecting the viability of 3T3 normal cells.     

The association between micronutrient status and sleep quality in patients with depression: a case-control study

Sleep and Breathing - Few previous studies estimated the association between micronutrient status and sleep quality; no previous work was done in patients with depression compared with healthy...     

The effects of fasting on heart rate variability in hypertensive patients

ABSTRACT

Heart rate variability (HRV) is an independent indicator of increased mortality in patients with myocardial infarction and congestive heart failure. The effects of fasting on the HRV are not known in hypertensive patients. Therefore, studying the effects of Ramadan fasting on hypertensive patients’ HRV seems reasonable to address.

We conducted a prospective study including 20 hypertensive patients with sinus rhythm. HRV was determined twice by ambulatory 24-hour Holter recordings at fasting during and after Ramadan.

Subjects mean age was 55 ± 11.8 years. Sex-ratio was 1.5. When two groups compared, statistically significant differences were found in terms of SDNN (113 ± 71 vs 140 ± 38, p = 0.001), SDANN (109.7 ± 45 vs 134.8 ± 48.3, p = 0.008), T power (2368.7 ± 121.3 vs 3660.5 ± 170.9, p = 0.03) and LF (552.2 ± 31.3 vs 903.7 ± 48.9, p < 0.0001) values.

HRV parameters were found to be decreased in Ramadan. Thus, Ramadan fasting enhances the activity of the sympathetic system in hypertensive patients.     

Association between polymorphisms in apoptotic genes and susceptibility for developing breast cancer in Syrian women

Apoptosis is a major protective mechanism against cancer. The tumor suppressor protein p53 is the central protein in the apoptotic pathway and was shown to harbor mutations in a considerable fraction of breast cancer tumors. The NQO1 was shown to act as a p53 stabilizer and was suggested to play an important role in the protection against carcinogenic catechol estrogens. Functional polymorphisms in TP53 and NQO1 were investigated in relation to breast cancer susceptibility in several studies, primarily involving Asian and Caucasian populations. The aim of the present study was to investigate TP53 and NQO1 polymorphisms and their combined effects with respect to breast cancer susceptibility in a Syrian study cohort. The study cohort consisted of 122 cases and 139 controls. The tetra-primer ARMS-PCR method was used to genotype three TP53 polymorphisms; namely, exon 4 G>C Arg72Pro, IVS3 16 bp Del/Ins, and MspI IVS6+62A>G, and NQO1 C609T (Pro187Ser) polymorphism. Association was tested under six genetic models. We found a significant association for the heterozygous Arg/Pro genotype when combined with heterozygosity for IVS3 16 bp Del/Ins and MspI IVS6+62A>G (OR = 2.05 (1.22–3.47), P = 0.006). No significant association was found for NQO1 C609T or its combinations with TP53 polymorphisms. Our results support an association for TP53 polymorphisms with breast cancer susceptibility in the Syrian population.