Metabolomics combined to chemometrics reveals the putative α-glucosidase and α-amylase inhibitory metabolites of ground cherry (Physalis pruinosa L.).

In this work, metabolic profiling of the different parts of ground cherry (P. pruinosa) including fruits, calyces, leaves, stems and roots using UPLC-MS/MS analysis combined to chemometric analysis was attempted. A total of 82 chromatographic peaks belonging to different metabolite classes were identified including terpenes, flavonoids genin and glycosides, withanolides, physalins, sucrose esters, fatty acids and other miscellaneous compounds with withanolides being the most predominant class. Roots extracts possessed the highest relative content of the identified 5ß,6ß-epoxy withanolides and intermediate withanolides, while sucrose esters and flavonoidal glycosides were found in a great abundance in calyces extracts. Moreover, physalins were found in all extracts except for roots extracts. Studying the coefficients plots revealed that terpenes and physalins (physanicantriol, loliolide, physalisitin C) were responsible for discrimination of fruits extracts. Calyces, leaves and stems extracts were found to possess antioxidant activity and higher inhibition of α-glucosidase activity. In an attempt to identify the compounds responsible for the hypoglycemic activity using both α-amylase and α-glucosidase inhibition assays, OPLS models coefficient plots were constructed which indicated that physangulide B, physaperuvin G, neophysalin A, and acylsucroses were positively correlated to α-glucosidase inhibition, while guaiacyl-primeveroside, phyperunolide C, physalactone, physalolactone C and perulactone, were positively correlated to α-amylase inhibitory activity.

Chemical constituents, Antibacterial and Acetylcholine esterase inhibitory activity of Cupressus macrocarpa leaves.

The chemical constituents of Cupressus macrocarpa were investigated. A new neolignan glycoside (1) in addition to nine known compounds were isolated. The acetylcholinesterase (AChE) inhibitory activity and antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) of different fractions and isolates of C. macrocarpa were evaluated. The light petroleum fraction showed the highest activity in both assays with IC50 value of 88.79 µg/ml and 152.58 µg/ml for the AChE inhibitory activity and MRSA antibacterial activities, respectively. Weak to moderate activity were detected for the isolated compounds.

Promoter Methylation Status of Breast Cancer Susceptibility Gene 1 and 17 Beta Hydroxysteroid Dehydrogenase Type 1 Gene in Sporadic Breast Cancer Patients.

Epigenetic modifications are involved in breast carcinogenesis. Identifying genes that are epigenetically silenced via methylation could select target patients for diagnostic as well as therapeutic potential. We assessed promoter methylation of breast cancer susceptibility gene 1 (BRCA1) and 17 Beta Hydroxysteroid Dehydrogenase Type 1 (17ßHSD-1) in normal and cancer breast tissues of forty sporadic breast cancer (BC) cases using restriction enzyme based methylation-specific PCR (REMS-PCR). In cancerous tissues, BRCA1 and 17ßHSD-1 were methylated in 42.5% and 97.5%, respectively, while normal tissues had 35% and 95% methylation, respectively. BRCA1 methylation in normal tissues was 12.2-fold more likely to associate with methylation in cancer tissues (p < 0.001). It correlated significantly with increased age at menopause, mitosis, the negative status of Her2, and the molecular subtype "luminal A" (p = 0.048, p = 0.042, p = 0.007, and p = 0.049, resp.). Methylation of BRCA1 and 17ßHSD-1 related to luminal A subtype of breast cancer. Since a small proportion of normal breast epithelial cells had BRCA1 methylation, our preliminary findings suggest that methylation of BRCA1 may be involved in breast tumors initiation and progression; therefore, it could be used as a biomarker for the early detection of sporadic breast cancer. Methylation of 17ßHSD-1 in normal and cancer tissue could save patients the long term use of adjuvant antiestrogen therapies.

Efficacy of modified constraint-induced movement therapy in acute stroke.

BACKGROUND: Modified constraint induced movement therapy (m-CIMT) discourages the use of the unaffected extremity and encourages the active use of the hemiplegic arm in order to restore the motor function. AIM: The aim was to assess the efficacy of m-CIMT on functional recovery of upper extremity (UE) in acute stroke patients, as compared to conventional rehabilitation therapy. DESIGN: This is a prospective comparative study. SETTING: This study included sixty patients with acute stroke recruited from neurology department. METHODS: This study included sixty acute stroke patients. Inclusion criteria were: patients within two weeks from the onset of stroke, persistent hemiparesis leading to impaired upper extremity function, evidence of preserved cognitive function, and a minimum of 10 degrees of active finger extension and 20 degrees of active wrist extension. Exclusion criteria were: intra-cerebral hemorrhage, previous stroke on the same side, presence of neglect or a degree of aphasia impeding understanding of instructions, and conditions that limit the use of the upper limb before the stroke. Patients were assessed by Fugl-Meyer motor assessment (FMA), action research arm test (ARAT) and motor evoked potentials (MEPs), recorded from the abductor pollicis brevis (APB) of the affected hand. The clinical and neurophysiological tests were performed pre and postrehabilitation. The patients were divided into two groups: Conventional rehabilitation program group (CRP) included 30 patients who were given a conventional rehabilitation program for two weeks. CIMT group included 30 patients who were subjected to modified CIMT for two consecutive weeks. Total treatment time was the same in both groups. RESULTS: CRP group showed a non-significant improvement in FMA and ARAT. CIMT group showed a significant improvement in clinical scores on all tests (P<0.05). When comparing both groups using FMA and ARAT tests pre- and post- therapy, a significant difference (P<0.05) was found between both groups with CIMT group showing greater improvement. When comparing MEPs in CRP group, pre and postrehabilitation, a non-significant improvement was found for resting motor threshold (RMT), central motor conduction time (CMCT) and amplitude of MEPs. In contrast, each of the MEP parameters exhibited a significant improvement in CIMT group (P<0.05). CONCLUSION: In contrast to conventional rehabilitation therapy, modified CIMT revealed a significant functional and MEP improvement in acute stroke patients indicating that m-CIMT might be a more efficient treatment strategy. CLINICAL REHABILITATION IMPACT: It is advised to use modified constraint movement therapy in rehabilitation of cerebrovascular stroke during acute stage.

Chemical composition, antimicrobial and insecticidal activities of the essential oils of Conyza linifolia and Chenopodium ambrosioides.

Two essential oil-containing plants growing wildly in Egypt: Conyza linifolia (Willd.) Täckh. (Asteraceae) and Chenopodium ambrosioides L. (Chenopodiaceae) were subjected to essential oil analysis and biological investigation. The essential oils from both plants were prepared by hydrodistillation, and GC/MS was employed for volatiles profiling. This study is the first to perform GC/MS analysis of C. linifolia essential oil growing in Egypt. C. linifolia essential oil contained mainly sesquiterpenes, while that of C. ambrosioides was rich in monoterpenes. Ascaridole, previously identified as the major component of the latter, was found at much lower levels. In addition, the oils were investigated for their antimicrobial activity against two Gram positive and two Gram negative bacteria, and one fungus. The insecticidal activities of both oils, including mosquitocidal and pesticidal potentials, were also evaluated. The results of biological activities encourage further investigation of the two oils as antimicrobial and insecticidal agents of natural origin.

Chemical constituents from Tribulus terrestris and screening of their antioxidant activity.

Two oligosaccharides (1,2) and a stereoisomer of di-p-coumaroylquinic acid (3) were isolated from the aerial parts of Tribulus terrestris along with five known compounds (4-8). The structures of the compounds were established as O-ß-D-fructofuranosyl-(2→6)-α-D-glucopyranosyl-(1→6)-ß-D-fructofuranosyl-(2→6)-ß-D-fructofuranosyl-(2→1)-α-D-glucopyranosyl-(6→2)-ß-D-fructofuranoside (1), O-α-D-glucopyranosyl-(1→4)-α-D-glucopyranosyl-(1→4)-α-D-glucopyranosyl-(1→2)-ß-D-fructofuranoside (2), 4,5-di-p-cis-coumaroylquinic acid (3) by different spectroscopic methods including 1D NMR ((1)H, (13)C and DEPT) and 2D NMR (COSY, TOCSY, HMQC and HMBC) experiments as well as ESI-MS analysis. This is the first report for the complete NMR spectral data of the known 4,5-di-p-trans-coumaroylquinic acid (4). The antioxidant activity represented as DPPH free radical scavenging activity was investigated revealing that the di-p-coumaroylquinic acid derivatives possess potent antioxidant activity so considered the major constituents contributing to the antioxidant effect of the plant.

Incessant ovulation and ovarian cancer - a hypothesis re-visited.

Ovarian cancer continues to be a silent killer. Most women have advanced disease at the time of diagnosis. Intensive efforts to develop effective screening strategies have not so far met with success. There is a need to re-visit the potential of prevention strategies. In 1971, the author submitted a hypothesis for a possible relationship between incessant ovulation and development of epithelial ovarian cancer. Subsequent research from different disciplines opened new frontiers to be explored for prevention in the general population and in high-risk groups, and for opportunistic interventions. The protective effect of oral contraceptive pills has been well documented. Widespread use of the pill in the past several decades is credited with a fall in the incidence of ovarian cancer in the general population, countering the effect of low parity. Removing the barriers against contraceptive access and satisfying the still unmet contraceptive need could expand the protective coverage. Enhanced understanding of the biological mechanisms involved in process of ovulation offers the promise of non-hormonal pharmacologic suppression of follicle rupture for women who have risk factors and do not need contraception. The evidence for a possible origin of epithelial cancer in the fimbria of the Fallopian tube presents an opportunity for preventive intervention, during hysterectomy, where salpingectomy alone may provide protection while one or both ovaries are conserved. Finally, the incessant ovulator egg-laying hen has demonstrated its potential as an experimental model for chemoprevention of epithelial ovarian cancer.

Antihyperglycaemic and hypolipidaemic effects of the methanolic extract of Caralluma tuberculata in streptozotocin-induced diabetic rats.

The antihyperglycaemic and hypolipidaemic effects of the methanolic extract of Caralluma tuberculata were investigated in streptozotocin (STZ)-induced diabetic rats. The antihyperglycaemic activity was assessed by the reduction in fasting blood glucose (54% at 4th week) and the peak of blood glucose at 120?min of an oral glucose tolerance test in diabetic rats. Further, the tested extract also increased plasma insulin by 206.8%. The hypolipidaemic action of the extract was evident by the significant decrease in the levels of total cholesterol, triglycerides and LDL-cholesterol by 41.5%, 36.7% and 49.1%, respectively, compared to diabetic rat values. Interestingly, the extract increased the cardio-protective lipid HDL-cholesterol by 147.97% as compared to diabetic rat value. The present data suggests that the methanolic extract of C. tuberculata has both antihyperglycaemic and hypolipidaemic effects in STZ-induced diabetic rats that may need further studies to be used in the management of diabetes and associated hyperlipedaemia.

Antihepatotoxic effect of marrubium vulgare and withania somnifera extracts on carbon tetrachloride-induced hepatotoxicity in rats.

Marrubium vulgare and Withania somnifera are used in folk medicine of several countries. Many researches showed that they are used for the treatment of variety of diseases due to their antioxidant effects. The present aim of this study was to evaluate the antihepatotoxic and antioxidant activities of the both extracts against carbon tetrachloride (CCl4)-induced hepatic damage in rats. Both extracts were given orally in a dose of 500 mg/kg/day for 4 weeks along with CCl4 started at the 7th week of induction of hepatotoxicity. The antihepatotoxic activity was assessed by measuring aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), reduced glutathione (GSH), tissue content and malondialdehyde (MDA) as well as histopathological examination. Both extracts showed a significant antihepatotoxic effect by reducing significantly the levels of AST, ALT and LDH. However, ALP levels were decreased non-significantly. Regarding the antioxidant activity, they exhibited significant effects by increasing the GPx, GR and GST activities with increased GSH tissue contents and decreased production of MDA level. Furthermore, both extracts alleviated histopathological changes in rats' liver treated with CCl4. M. vulgare and W. somnifera protect the rats' liver against CCl4-induced hepatotoxicity. This effect may be attributed, at least in part, to the antioxidant activities of these extracts.

Chemical composition, insecticidal and insect repellent activity of Schinus molle L. leaf and fruit essential oils against Trogoderma granarium and Tribolium castaneum.

Fruit and leaf essential oils of Schinus molle showed insect repellent and insecticidal activity against Trogoderma granarium and Tribolium castaneum. In these oils, 65 components were identified by GC-MS analysis. Hydrocarbons dominated the oil composition with monoterpenes occurring in the largest amounts in fruits and leaves, 80.43 and 74.84%, respectively. p-Cymene was identified as a major component in both oils. The high yield and efficacy of S. molle essential oil against T. granarium and T. castaneum suggest that it may provide leads for active insecticidal agents.

Iridoid glycosides from Barleria trispinosa.

A new iridoid glycoside and three known iridoid glycosides were isolated from the aerial parts of Barleria trispinosa. The structure of the new compound was determined as 6-alpha-L-rhamnopyranosyl-8-O-acetylshanzihiside methyl ester. The known compounds were identified as 6,8-O,O-diacetylshanhiside methyl ester (acetyl barlerin), 8-O-acetylshanzhiside methyl ester (barlerin) and shanzhiside methyl ester, which were isolated from the plant for the first time. The structures of the isolated compounds were elucidated by spectroscopic evidence, mainly one- and two-dimensional proton and carbon-13 NMR spectroscopy.

Antiplasmodial and antitrypanosomal activity of plants from the Kingdom of Saudi Arabia.

The antiplasmodial and antitrypanosomal activity of the methanol extracts of 42 plants collected from the Kingdom of Saudi Arabia and some fractions obtained thereof were evaluated. The antiplasmodial activity was tested in vitro against chloroquine-resistant strain (K1) and sensitive strain (FCR3), and the antitrypanosomal activity was tested in vitro against Trypanosoma brucei brucei GUTat 3.1 strain. For host cells, the cytotoxicity of the active extracts was also evaluated against the MRC5 human cell line. Only extracts of three samples demonstrated good antiplasmodial activity (IC(50) < 12.5 and > 1.56 microg/ml, score 2), the methanol extracts of Lycium shawii, Heliotropium zeylanicum and the petroleum ether-soluble fraction of the methanol extract of Caralluma tuberculata, while extracts of the remaining 42 plants were inactive (IC(50) > 12.5 microg/ml, score 1). As for the antitrypanosomal activity, the methanol extract of Solanum schimperianum demonstrated the highest activity (IC(50) 0.061 microg/ml), followed by the petroleum ether-soluble fraction of the methanol extract of C. tuberculata (IC(50) 0.5 microg/ml). The chloroform-soluble fraction of the methanol extract of C. tuberculata was moderately active (IC(50) 3.5 microg/ml), with low cytotoxicity (IC(50) 62.6 microg/ml) and moderate selectivity index (SI 17.9). The methanolic extracts of 34 plants showed good activity with score 2 (IC(50) < 12.5 and > 1.56 microg/ml), while the extracts of seven plants were inactive (IC(50) > 12.5 microg/ml, score 1).

Acylated pregnane glycosides from Caralluma tuberculata and their antiparasitic activity.

Five pregnane glycosides were isolated from Caralluma tuberculata (1-5), in addition to a known one (russelioside E, 6). The structures of the isolated compounds were elucidated by the analysis of NMR data and FAB-MS experiments. All the isolated compounds were tested for their antimalarial and antitrypanosomal activities as well as their cytotoxicity against human diploid embryonic cell line (MRC5).

Relation between hypercholesterolaemia and vascular endothelial microinflammation.

We investigated the correlation between hypercholesterolaemia and oxidative stress and P-selectin and interleukin-6 (IL-6) as markers for endothelial status. We studied 40 Egyptian adults with asymptomatic hypercholesterolaemia and 20 age- and sex-matched controls. Lipid peroxidation was significantly higher (P < 0.001) in the study group and positively correlated with cholesterol (P < 0.001) and low-density lipoprotein (LDL) (P < 0.002). Glutathione peroxidase activity was also significantly higher (P < 0.001) with positive correlation with cholesterol (P < 0.001) and LDL (P < 0.001). Markers for endothelial cell function were significantly higher in the study group (P < 0.001) with a positive correlation with cholesterol (P < 0.001) and LDL (P < 0.001). Hypercholesterolaemia causes endothelial microinflammation, and P-selectin and IL-6 may also be risk factors for cardiovascular disease.

Laparoscopically assisted balloon vaginoplasty for management of vaginal aplasia.

OBJECTIVE: To report the intra-operative and post-operative results of laparoscopically assisted balloon vaginoplasty, a new technique for management of vaginal aplasia. METHODS: Eight women with vaginal aplasia due to Mullerian agenesis who were referred for apareunia, dyspareunia. All had a poor penetration score and sexual satisfaction score. A Foley's catheter was laparoscopically inserted in the space between the urethra and rectum. Gradual traction and distension were used to create a neovagina. Outcomes measured were intra-operative complications, post-operative complications, length of the neovagina and post-operative complications and sexual satisfaction score in both partners. RESULTS: Mean operative time was 25.5+/-5.5 min. No operative complications were recorded. Pain scores ranged from zero to 30 points at rest and from 30 to 60 points during dressing, traction and distension. Penetration and satisfaction scores increased significantly after the operation. CONCLUSIONS: Balloon vaginoplasty is a simple, safe and satisfactory technique for management of blind vagina.

Use of the non-pneumatic anti-shock garment (NASG) to reduce blood loss and time to recovery from shock for women with obstetric haemorrhage in Egypt.

Obstetric haemorrhage is one of the leading causes of maternal mortality. In many low-resource settings, delays in transport to referral facilities and in obtaining lifesaving treatment, contribute to maternal deaths. The non-pneumatic anti-shock garment (NASG) is a low-technology pressure device that decreases blood loss, restores vital signs, and has the potential to improve adverse outcomes by helping women survive delays in receiving adequate emergency obstetric care. With brief training, even individuals without medical backgrounds can apply this first-aid device. In this secondary analysis of hospital data from a pre-post intervention study in Egypt (N=364 women with obstetric haemorrhage and shock), 158 received standard care, while 206 received standard care plus the NASG. The NASG significantly reduced blood loss, time to recovery from shock, and, for those with postpartum haemorrhage due to uterine atony who received oxytocin, the NASG had a significant effect on blood loss independent of oxytocin. These results indicate that the NASG may be a valuable innovation for reducing maternal mortality in low-resource settings. Testing at community and household levels will be necessary in order to determine whether the NASG can help women survive the longest delays.