Human umbilical cord Wharton's jelly stem cells and its conditioned medium support hematopoietic stem cell expansion ex vivo.

Bone marrow mesenchymal stromal cells (BMMSCs) have been used as feeder support for the ex vivo expansion of hematopoietic stem cells (HSCs) but have the limitations of painful harvest, morbidity, and risk of infection to the patient. This prompted us to explore the use of human umbilical cord Wharton's jelly MSCs (hWJSCs) and its conditioned medium (hWJSC-CM) for ex vivo expansion of HSCs in allogeneic and autologous settings because hWJSCs can be harvested in abundance painlessly, are proliferative, hypoimmunogenic, and secrete a variety of unique proteins. In the presence of hWJSCs and hWJSC-CM, HSCs put out pseudopodia-like outgrowths and became highly motile. Time lapse imaging showed that the outgrowths helped them to migrate towards and attach to the upper surfaces of hWJSCs and undergo proliferation. After 9 days of culture in the presence of hWJSCs and hWJSC-CM, MTT, and Trypan blue assays showed significant increases in HSC numbers, and FACS analysis generated significantly greater numbers of CD34(+) cells compared to controls. hWJSC-CM produced the highest number of colonies (CFU assay) and all six classifications of colony morphology typical of hematopoiesis were observed. Proteomic analysis of hWJSC-CM showed significantly greater levels of interleukins (IL-1a, IL-6, IL-7, and IL-8), SCF, HGF, and ICAM-1 compared to controls suggesting that they may be involved in the HSC multiplication. We propose that cord blood banks freeze autologous hWJSCs and umbilical cord blood (UCB) from the same umbilical cord at the same time for the patient for future ex vivo HSC expansion and cell-based therapies.

Growth factors in relation to obesity, food habits, and microbiota among healthy Saudis: preliminary results.

OBJECTIVE: Obesity is a serious problem among Saudis because of the country's affluent lifestyle. Obesity is associated with various metabolic disorders and characterized by low-grade inflammation that leads to the release of pro-inflammatory cytokines, human growth factors (GFs), lipids, aberrant adipokines, and other chemokines from adipose tissue. The objective of this study is to delineate the effects of GFs on microbiota and their relationship to body mass index (BMI) and food habits. SUBJECTS AND METHODS: In a cross-sectional study, 32 randomly selected participants (16 males and 16 females) were enrolled in a survey covering their sociodemographic information, medical history, lifestyle, and dietary practices. The information on diet, health condition, food and drink intake habits were examined under four distinct BMI categories: normal, underweight, overweight, and obese. The participants' serum samples were analyzed for the various GFs using a human magnetic 30-plex panel multiplex assay. Bioinformatics analysis was performed to investigate which bacterial taxa are enriched and to predict the functional profiles of the samples. RESULTS: Correlational studies revealed sex-based differences between GFs and microbiota. Females exhibited a significant correlation between epidermal GF (EGF) and Proteobacteria, whereas males showed a significant correlation between fibroblast GF-basic and Actinobacteria. Interestingly, a combined analysis of both sexes showed a significant correlation between EGF and vascular endothelial GF with Firmicutes. The data in the underweight group revealed a correlation between granulocyte colony-stimulating factor (G-CSF) and hepatocyte GF with Firmicutes. In the obese group, a correlation was found between G-CSF and Actinobacteria. CONCLUSIONS: Our results identified links between GFs, microbiota, and BMI in a Saudi cohort. The insights from this preliminary study will contribute to the predictive diagnosis of obesity. However, further research involving a larger cohort will be necessary to understand the mechanistic aspects of these GFs to provide biomarkers of potential obesity.

A systematic review of different type of tuberculosis.

Tuberculosis (TB) is still a leading cause of death worldwide. Almost a third of the world's population is infected with TB bacilli, and each year approximately 8 million people develop active tuberculosis and 2 million die as a result. However, there are few studies of long-term TB treatment outcomes from Directly Observed Therapy, Short-course (DOTS) programs in high-burden settings and particularly settings of high drug resistance. This study is a systematic review to evidence the incidence and prevalence of latent TB infection (LTBI) and disease and to evaluate the impact of various preventive strategies that have been attempted. To identify relevant studies, we searched electronic databases and journals, and contacted experts in the field. This review demonstrates that, various types of tuberculosis have different imaging findings, and typical computed tomography (CT) and magnetic resonance (MG) findings can suggest the diagnosis. Available evidence reinforces the need to design and implement simple, effective, and affordable tuberculosis infection-control programs in health-care facilities in our countries. With the revision of all the data's, we are able to conclude that the controlling of tuberculosis by human beings is yet not achieved. So, there is an urgency to develop awareness amongst the individuals and also a new drugs regimen for the proper treatment of tuberculosis.

Protective effect of propyl gallate against myocardial oxidative stress-induced injury in rat.

This study was designed to investigate the effect of chronic administration of propyl gallate on myocardial oxidative stress-induced injury. Propyl gallate was administered orally to Wistar albino rats (150-200 g) in three different doses, by gastric gavage (250 mg kg(-1) (P1), 500 mg kg(-1) (P2) and 750 mg kg(-1) (P3)), 6 days a week for 5 weeks. At the end of this period, all the rats, except the normal untreated rats that served as the control group, were administered isoproterenol (ISO), 85 mg kg(-1) subcutaneously, for 2 consecutive days to induce myocardial injury. After 48 h, rats (n = 6 per group) were anaesthetized with anaesthetic ether, sacrificed and the hearts were harvested for the estimation of thiobarbituric acid reactive substances (TBARS), endogenous antioxidants (reduced glutathione (GSH), superoxide dismutase (SOD) and catalase) and for the assessment of histological changes. In the P2 BL group (BL = baseline), there was a significant (P < 0.001) rise in baseline TBARS and SOD when compared with the saline-treated group, while no such changes were observed in the other baseline-treated groups. However, there was a significant (P < 0.001) increase in TBARS and endogenous anti-oxidants (GSH, SOD and catalase) in the P2 ISO and P3 ISO groups, when the hearts were subjected to in-vivo myocardial oxidative stress-induced injury. We observed no such changes in the P1 ISO group. This study showed that propyl gallate modulates the levels of endogenous antioxidants present at the myocardial site. Whether these modifications are a result of direct interference at this site or a remote effect is not immediately clear. In conclusion, from the results it could be stated that chronic administration of 500 mg kg(-1) of propyl gallate offers significant protection against myocardial oxidative stress-induced injury.

Effect of Tribulus terrestris on nicotinamide adenine dinucleotide phosphate-diaphorase activity and androgen receptors in rat brain.

Tribulus terrestris L. (Zygophyllaceae) have been used as an aphrodisiac both in the Indian and Chinese traditional systems of medicine. Administration of Tribulus terrestris extract (TT) increased sexual behaviour and intracavernous pressure both in normal and castrated rats and these effects were probably due to the androgen increasing property of TT. The objective of the present study is to evaluate the effect of TT on nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) activity and androgen receptor (AR) immunoreactivity in rat brain. Twenty-four adult male Sprague-Dawley rats were divided into two groups of twelve each. Group I was treated with distilled water and Group II was treated with TT at the dose of 5mg/kg body weight orally, once daily for 8 weeks. Following treatment transcardiac perfusion was done with Ringer lactate, 4% paraformaldehyde and 30% sucrose. The brain tissue was removed and sections of the paraventricular (PVN) area of hypothalamus were taken for NADPH-d and AR immunostaining. There was an increase in both NADPH-d (67%) and AR immunoreactivity (58%) in TT treated group and these results were statistically significant compared to the control. Chronic treatment of TT in rats increases the NADPH-d positive neurons and AR immunoreactivity in the PVN region. Androgens are known to increase both AR and NADPH-d positive neurons either directly or by its conversion to oestrogen. The mechanism for the observed increase in AR and NADPH-d positive neurons in the present study is probably due to the androgen increasing property of TT. The findings from the present study add further support to the aphrodisiac claims of TT.

Terminalia arjuna (Roxb.) protects rabbit heart against ischemic-reperfusion injury: role of antioxidant enzymes and heat shock protein.

The bark of Terminalia arjuna Roxb. (TA) is widely recommended for the treatment of ischemic heart disease (IHD) in Indian system of medicine. Oral administration of TA for 12 weeks in rabbits caused augmentation of myocardial antioxidants; superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) along with induction of heat shock protein72 (HSP72). In vivo ischemic-reperfusion injury induced oxidative stress, tissue injury of heart and haemodynamic effects were prevented in the TA treated rabbit hearts. The study provides scientific basis for the putative therapeutic effect of TA in ischemic heart disease.

Aphrodisiac properties of Tribulus Terrestris extract (Protodioscin) in normal and castrated rats.

Tribulus terrestris (TT) has long been used in the traditional Chinese and Indian systems of medicine for the treatment of various ailments and is popularly claimed to improve sexual functions in man. Sexual behaviour and intracavernous pressure (ICP) were studied in both normal and castrated rats to further understand the role of TT containing protodioscin (PTN) as an aphrodisiac. Adult Sprague-Dawley rats were divided into five groups of 8 each that included distilled water treated (normal and castrated), testosterone treated (normal and castrated, 10 mg/kg body weight, subcutaneously, bi-weekly) and TT treated (castrated, 5 mg/kg body weight, orally once daily). Decreases in body weight, prostate weight and ICP were observed among the castrated groups of rats compared to the intact group. There was an overall reduction in the sexual behaviour parameters in the castrated groups of rats as reflected by decrease in mount and intromission frequencies (MF and IF) and increase in mount, intromission, ejaculation latencies (ML, IL, EL) as well as post-ejaculatory interval (PEI). Compared to the castrated control, treatment of castrated rats (with either testosterone or TT extract) showed increase in prostate weight and ICP that were statistically significant. There was also a mild to moderate improvement of the sexual behaviour parameters as evidenced by increase in MF and IF; decrease in ML, IL and PEI. These results were statistically significant. It is concluded that TT extract appears to possess aphrodisiac activity probably due to androgen increasing property of TT (observed in our earlier study on primates).

Cardioprotective effect of the alcoholic extract of Terminalia arjuna bark in an in vivo model of myocardial ischemic reperfusion injury.

The present study was designed to investigate the effects of chronic administration of the alcoholic extract of Terminalia arjuna (TAAE) bark on isoproterenol induced myocardial injury. The TAAE was administered orally to Wistar albino rats (150-200 g) in three different doses, by gastric gavage [3.4 mg/kg: (T1), 6.75 mg/kg: (T2) and 9.75 mg/kg: (T3)] 6 days/week for 4 weeks. At the end of this period, all the animals, except the normal untreated rats that served as the control group, were administered isoproterenol (ISO) 85 mg/kg, S.C., for two consecutive days to induce in vivo myocardial injury. After 48 hours rats were anaesthetized with anaesthetic ether, then sacrificed and the hearts were harvested for biochemical and histological studies. A significant rise in myocardial thiobarbituric acid reactive substances (TBARS) and loss of reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (suggestive of increased oxidative stress) occurred in the hearts subjected to in vivo myocardial ischemic reperfusion injury. The 6.75 mg/kg TAAE treatment group (baseline) shows a significant increase in myocardial TBARS as well as endogenous antioxidants (GSH, SOD, and catalase), but not in the other treatment groups. In in vivo ischemic reperfusion injury of the TAAE treated rats there was a significant decrease in TBARS in all the groups. In 6.75 mg/kg treatment group, a significant rise in the levels of GSH, SOD and catalase were observed, and it shows better recovery profile than the other groups subjected to in vivo ischemic reperfusion injury. In histological studies, all the groups, except the isoproterenol treated group, showed preserved myocardium. The present study demonstrates that the 6.75 mg/kg TAAE augments endogenous antioxidant compounds of the rat heart and also prevents the myocardium from isoproterenol induced myocardial ischemic reperfusion injury.

Effect of chronic treatment with bark of Terminalia arjuna: a study on the isolated ischemic-reperfused rat heart.

Dried pulverized bark of Terminalia arjuna Linn (TA) was administered orally to Wistar albino rats (120-150 g) in two doses [500 and 750 mg/kg in 2% carboxy methyl cellulose (CMC)], 6 days per week for 12 weeks. Thereafter, rats were sacrificed either for determination of baseline changes in cardiac endogenous antioxidant compounds [superoxide dismutase (SOD), reduced glutathione (GSH) and catalase (CAT)] or the hearts were subjected to oxidative stress associated with in vitro ischemic-reperfusion injury (IRI). There was significant increase in the baseline contents of thiobarbituric acid reactive substance (TBARS) (a measure of lipid peroxidation) with both doses of TA. However, only in the 500 mg/kg treated group, this was accompanied by a simultaneous increase in SOD, GSH and CAT levels, but not in the 750 mg/kg treated group, where only CAT was raised. Significant rise in myocardial TBARS and loss of SOD, CAT and GSH (suggestive of increased oxidative stress) occurred in the vehicle-treated hearts subjected to in vitro IRI. Only hearts, harvested from the 500 mg/kg rats treated rats, were significantly protected from oxidative stress, when subjected to in vitro IRI. The results suggest that crude bark of TA augments endogenous antioxidant compounds of rat heart and also prevents oxidative stress associated with IRI of the heart.

Proerectile pharmacological effects of Tribulus terrestris extract on the rabbit corpus cavernosum.

INTRODUCTION: The objective of the present study was to investigate the effect of oral treatment of Tribulus terrestris (TT) extract on the isolated corpus cavernosal tissue of New Zealand white (NZW) rabbits and to determine the mechanism by which protodioscin (PTN), a constituent of the TT, exerts its pharmacological effects. MATERIALS AND METHODS: Twenty-four NZW rabbits were randomly assigned to 4 experimental groups of 6 each. Group I served as control. Groups II to IV were treated with the extract at different dose levels, i.e. 2.5 mg/kg, 5 mg/kg and 10 mg/kg body weight, respectively. The TT extract was administered orally, once daily, for a period of 8 weeks. The rabbits were then sacrificed and their penile tissue isolated to evaluate the responses to both contracting and relaxing pharmacological agents and electrical field stimulation (EFS). RESULTS: PTN on its own had no effect on the isolated corpus cavernosal strips. The relaxant responses to EFS, acetylcholine and nitroglycerin in noradrenaline precontracted tissues from treated groups showed an increase in relaxation of a concentration dependent nature compared to that of the tissues from control group. However, the contractile, anti-erectile response of corpus cavernosal tissue to noradrenaline and histamine showed no significant change between the treatment and the control groups. CONCLUSIONS: The relaxant responses to acetylcholine, nitroglycerin and EFS by more than 10%, 24% and 10% respectively compared to their control values and the lack of such effect on the contractile response to noradrenaline and histamine indicate that PTN has a proerectile activity. The enhanced relaxant effect observed is probably due to increase in the release of nitric oxide from the endothelium and nitrergic nerve endings, which may account for its claims as an aphrodisiac. However, further study is needed to clarify the precise mechanism of its action.

ACE inhibitors - angiotensin II receptor antagonists: A useful combination therapy for ischemic heart disease.

Morbidity and mortality from cardiovascular diseases are still high, even with the use of the best available therapies. There is mounting evidence that excessive renin-angiotensin system activation triggers much of the damaging and progressive nature of cardiovascular and kidney diseases through expression of angiotensin II. Moreover, angiotensin II play a major role in the development of end organ damage through a variety of inflammatory mechanisms. Today, angiotensins-converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists have clearly demonstrated their efficacy in preventing target organ damage and in reducing cardiovascular morbidity and mortality in ischemic heart disease (IHD). Moreover, the development of angiotensin II receptor antagonists has enabled a large gain in tolerability and safety. Several clinical trials have firmly established that these drugs act on the renin-angiotensin system, reducing the incidence of coronary events with monotherapy and combination therapy. In this review we summarize the role mono- and combined therapy of ACE inhibitors and angiotensin II receptor antagonists play in ischemic heart disease. In this respect the review will improve ideas for developing new formulations with combinations of these drugs in the future.

Dronedarone in the management of atrial fibrillation.

Atrial fibrillation is the most common type of tachyarrhythmia caused by multiple re-entrant wave forms within the atria and bombarding the atrioventricular node several times making it beat in a rapid, disorganized fashion termed "fibrillation". In atrial fibrillation, atria beat more than 300 times per minute. The arrhythmatous condition needs to be controlled, as humans cannot withstand this rapid and chaotic beating of the heart. New investigational drugs like Dronedarone(®) are being used. Dronedarone is the most recent antiarrhythmic drugs. It was approved by US-FDA on July 2nd 2009 and is available in the USA as Multaq tablets (400 mg). Dronedarone falls under the category of multiple ion channel blocker. It mainly targets the repolarization currents, making them less active and hence prolonging the action potential duration (APD). Dronedarone also exhibits antiadrenergic activity, thus reducing the pace of the pacemaker. Dronedarone has been proven to be a safer and efficacious AAD, evidenced by both animal and human studies. These studies showed that there was prolongation of the APD and absence of QT interval prolongation with long term administration of the drug. Also there was reduced thyroid hormone receptor expression. Dronedarone is significantly safer and effective in maintaining the sinus rhythm and reducing the ventricular proarrhythmias, justifying it for the long term treatment of atrial fibrillation compared to other antiarrhythmic drugs.

Statins inhibit the growth of variant human embryonic stem cells and cancer cells in vitro but not normal human embryonic stem cells.

BACKGROUND AND PURPOSE: Statins inhibit proliferation of various human cancer cell lines in vitro. As human embryonic stem cells (hESCs) possess neoplastic-like properties we have evaluated the role of various statins on karyotypically normal hESCs (HES3 and BG01), abnormal hESCs (BG01V) and breast adenocarcinoma cells (MCF-7) to evaluate whether the mode of action of the statins was via a stemness pathway. EXPERIMENTAL APPROACH: All cell lines were treated with simvastatin, pravastatin, lovastatin and mevastatin (1 micromol x L(-1) to 20 micromol x L(-1)) up to 7 days and their effects on cell proliferation, cell cycle, apoptosis and pluripotency studied. KEY RESULTS: All four statins did not inhibit HES3 and BG01 proliferation, but BG01V and MCF-7 were inhibited by simvastatin, lovastatin and mevastatin. These inhibitory effects were reversed by the endogenous isoprenoids, farnesylpyrophosphate and geranylgeranylpyrophosphate. Terminal deoxynucleotidyl transferase biotin-dUTP nick end labelling and cell cycle assay confirmed apoptosis in BG01V and MCF-7. Stem cell surface markers [stage-specific embryonic antigen-4, tumour rejection antigen-1-81, octamer-4 (OCT-4)] were expressed in HES3 and BG01, but not in BG01V cells, even after prolonged treatment with simvastatin. In BG01V and MCF-7, the pro-apoptotic Bcl-2-associated X protein genes were up-regulated, while the antiapoptotic BCL2 and SURVIVIN genes were down-regulated. Expression of the stemness-related genes namely, the growth differentiation factor-3, NANOG and OCT-4 was decreased in BG01V compared with BG01 and HES3. CONCLUSIONS AND IMPLICATIONS: Normal hESCs were resistant to prolonged exposure to statins over a range of doses, compared with BG01V and MCF-7, probably because of genetic and behavioural differences. The statins not only have anti-cancer properties but can suppress abnormal hESCs thus promoting growth of normal hESCs in vitro.

In vitro and in vivo analysis of co-electrospun scaffolds made of medical grade poly(epsilon-caprolactone) and porcine collagen.

In this study, a nanofiber mesh made by co-electrospinning medical grade poly(epsilon-caprolactone) and collagen (mPCL/Col) was fabricated and studied. Its mechanical properties and characteristics were analyzed and compared to mPCL meshes. mPCL/Col meshes showed a reduction in strength but an increase in ductility when compared to PCL meshes. In vitro assays revealed that mPCL/Col supported the attachment and proliferation of smooth muscle cells on both sides of the mesh. In vivo studies in the corpus cavernosa of rabbits revealed that the mPCL/Col scaffold used in conjunction with autologous smooth muscle cells resulted in better integration with host tissue when compared to cell free scaffolds. On a cellular level preseeded scaffolds showed a minimized foreign body reaction.