Biomedical subjects

Angelo A Izzo

Publications and source records attributed to Angelo A Izzo.

At least 37 records · Page 2Linked to original sources

PubMed2005

Effectiveness and safety of ginger in the treatment of pregnancy-induced nausea and vomiting.

OBJECTIVE: Conventional antiemetics are burdened with the potential of teratogenic effects during the critical embryogenic period of pregnancy. Thus, a safe and effective medication would be a welcome addition to the therapeutic repertoire. This systematic review was aimed at assessing the evidence for or against the efficacy and safety of ginger (Zingiber officinale) therapy for nausea and vomiting during pregnancy. DATA SOURCES: Systematic literature searches were conducted in 3 computerized databases (MEDLINE, EMBASE, and Cochrane Library), and the reference lists of all papers located were checked for further relevant publications. METHODS OF STUDY SELECTION: For the evaluation of efficacy, only double-blind, randomized controlled trials (RCTs) were included. All retrieved clinical data, including uncontrolled trials, case reports, observational studies, and RCTs, were included in the review of safety. TABULATION, INTEGRATION, AND RESULTS: Six double-blind RCTs with a total of 675 participants and a prospective observational cohort study (n = 187) met all inclusion criteria. The methodological quality of 4 of 5 RCTs was high. Four of the 6 RCTs (n = 246) showed superiority of ginger over placebo; the other 2 RCTs (n = 429) indicated that ginger was as effective as the reference drug (vitamin B6) in relieving the severity of nausea and vomiting episodes. The observational study retrieved and RCTs (including follow-up periods) showed the absence of significant side effects or adverse effects on pregnancy outcomes. There were no spontaneous or case reports of adverse events during ginger treatment in pregnancy. CONCLUSION: Ginger may be an effective treatment for nausea and vomiting in pregnancy. However, more observational studies, with a larger sample size, are needed to confirm the encouraging preliminary data on ginger safety. LEVEL OF EVIDENCE: I.

Administration, Oral↗

PubMed2005

Effects of the antidepressant St. John's wort (Hypericum perforatum) on rat and human vas deferens contractility.

PURPOSE: Since sexual dysfunction related to vas deferens smooth muscle contractility is a possible side effect of St. John's wort (SJW) (Hypericum perforatum) we evaluated the effect of this herbal antidepressant on rat and human vas deferens contractility. MATERIALS AND METHODS: The effect of SJW was evaluated on contractions induced by electrical field stimulation or exogenous agonists (alpha,beta-methylene adenosine triphosphate and phenylephrine) in isolated rat and human vas deferens. RESULTS: SJW (1 to 300 microM) decreased in a concentration dependent manner the amplitude of electrical field stimulation and agonist induced contractions with the same potency, suggesting direct inhibition of rat vas deferens smooth muscle. Of the chemical constituents of SJW tested hyperforin but not hypericin or the flavonoids quercitrin, rutin and kaempferol inhibited phenylephrine induced contractions. SJW and hyperforin also inhibited phenylephrine induced contractions in human vas deferens CONCLUSIONS: The results of our study demonstrate that SJW directly inhibits rat and human vas deferens contractility. If confirmed in vivo, these results suggest that SJW might affect sexual function in humans. These results might explain delayed ejaculation described in patients receiving SJW.

Animals↗

PubMed2005

Herb-drug interactions: an overview of the clinical evidence.

Herbal medicines are mixtures of more than one active ingredient. The multitude of pharmacologically active compounds obviously increases the likelihood of interactions taking place. Hence, the likelihood of herb-drug interactions is theoretically higher than drug-drug interactions, if only because synthetic drugs usually contain single chemical entities. Case reports and clinical studies have highlighted the existence of a number of clinically important interactions, although cause-and-effect relationships have not always been established. Herbs and drugs may interact either pharmacokinetically or pharmacodynamically. Through induction of cytochrome P450 enzymes and/or P-glycoprotein, some herbal products (e.g. St John's wort) have been shown to lower the plasma concentration (and/or the pharmacological effect) of a number of conventional drugs, including cyclosporine, indinavir, irinotecan, nevirapine, oral contraceptives and digoxin. The majority of such interactions involves medicines that require regular monitoring of blood levels. To date there is less evidence relating to the pharmacodynamic interaction. However, for many of the interactions discussed here, the understanding of the mechanisms involved is incomplete. Taking herbal agents may represent a potential risk to patients under conventional pharmacotherapy.

Anti-Allergic Agents↗

PubMed2005

Memory T lymphocytes generated by Mycobacterium bovis BCG vaccination reside within a CD4 CD44lo CD62 ligand(hi) population.

In the lungs of mice vaccinated with Mycobacterium bovis BCG, there was an accumulation of CD4 cells expressing the activated effector phenotype CD44hi CD62 ligandlo) (CD62Llo) which were capable of secreting gamma interferon. Upon cell transfer, however, cells expressing a resting/naïve phenotype (CD44lo CD62Lhi) were capable of protecting the recipients from a virulent challenge infection, suggesting the emergence of T-cell memory from within this subset.

Activated-Leukocyte Cell Adhesion Molecule↗

PubMed2005

Tracking antigen-specific CD8 T lymphocytes in the lungs of mice vaccinated with the Mtb72F polyprotein.

This study used a major histocompatibility complex class I tetramer reagent to track antigen-specific CD8 T cells in the lungs of mice immunized with the tuberculosis vaccine candidate Mtb72F. The results show that CD8 T cells recognizing an immunodominant Mtb32-specific epitope could be detected in significant numbers over the course of infection in mice exposed to low-dose aerosol challenge with Mycobacterium tuberculosis and that prior vaccination substantially increased the numbers of these cells early in the lungs. The effector phenotype of the cells was shown by the demonstration that many secreted gamma interferon, but very few contained granzyme B. As the course of the infection progressed, many activated CD8 T cells down-regulated expression of CD45RB and upregulated expression of the interleukin-7 receptor alpha chain, indicating a transition of these cells to a state of memory. These data support the hypothesis that M. tuberculosis-specific CD8 T cells can be targeted by vaccination with the Mtb72F polyprotein.

Animals↗

PubMed2004

Cannabinoids and intestinal motility: welcome to CB2 receptors.

Delta(9)-tetrahydrocannabinol (the active ingredient of marijuana), as well as endogenous and synthetic cannabinoids, exert many biological functions by activating two types of cannabinoid receptors, CB(1) receptors (expressed by central and peripheral neurons) and CB(2) receptors (that occur mainly in immune cells). Convincing evidence has accumulated in recent years that cannabinoids inhibit gastric and intestinal motility through activation of enteric CB(1) receptors. However, a report in this issue of British Journal of Pharmacology has highlighted the possibility that CB(2) receptors in the rat intestine could contribute to reducing the increase of intestinal motility induced by an endotoxic inflammation. By minimizing the adverse psychotropic effects associated with brain cannabinoid receptors, the CB(2) receptor represents a new molecular target for the treatment of motility disorders associated with intestinal inflammation.

Animals↗

PubMed2004

Inhibitory effect of ginger (Zingiber officinale) on rat ileal motility in vitro.

Ginger (Zingiber officinale rhizome) is a widespread herbal medicine mainly used for the treatment of gastrointestinal diseases, including dyspepsia, nausea and diarrhoea. In the present study we evaluated the effect of this herbal remedy on the contractions induced by electrical stimulation (EFS) or acetylcholine in the isolated rat ileum. Ginger (0.01-1000 microg/ml) inhibited both EFS- and acetylcholine-evoked contractions, being more potent in inhibiting the contractions induced by EFS. The depressant effect of ginger on EFS-induced contractions was reduced by the vanilloid receptor antagonist capsazepine (10(-5) M), but unaffected by the alpha(2)-adrenergic antagonist yohimbine (10(-7) M), the CB(1) receptor antagonist SR141716A (10(-6) M), the opioid antagonist naloxone (10(-6) M) or by the NO synthase inhibitor L-NAME (3 x 10(-4) M). Zingerone (up to 3 x 10(-4) M), one of the active ingredients of ginger, did not possess inhibitory effects. It is concluded that ginger possesses both prejunctional and postjunctional inhibitory effects on ileal contractility; the prejunctional inhibitory effect of ginger on enteric excitatory transmission could involve a capsazepine-sensible site (possibly vanilloid receptors).

Acetylcholine↗

PubMed2004

The gastrointestinal pharmacology of cannabinoids: an update.

Recent work in the field of gastrointestinal pharmacology of cannabinoids has focused on enteric endocannabinoid and endovanilloid systems and their modulation in pathophysiological conditions. CB(1) receptor immunoreactivity was detected on enteric cholinergic neurones and vasoactive intestinal peptide-containing submucosal ganglion cells, on discrete nuclei of the dorsovagal complex (involved in emesis) and on central and peripheral vagal terminals, thus controlling gastroesophageal reflux and gastrointestinal motility. CB(1) receptor activation by endocannabinoids inhibited induced fluid secretion and inflammation in animal models and reduced proliferation of cultured colorectal cancer cells. Endocannabinoids also activate cannabinoid CB(2) and vanilloid VR1 receptors in certain inflammatory states. Thus endocannabinoid metabolism could provide a useful therapeutic target for many gastrointestinal disorders.

Animals↗

PubMed2004

Inhibitory effect of the antidepressant St. John's wort (hypericum perforatum) on rat bladder contractility in vitro.

OBJECTIVES: To evaluate the effect of St. John's wort (SJW), an effective and safe herbal antidepressant, on rat bladder contractility. Recent data have suggested a strong association between depression and urinary incontinence. METHODS: Strips were cut from the bladder body and placed in organ baths containing Krebs solution. Contractions were induced by electrical field stimulation (EFS) and, in some experiments, by exogenous alpha,beta (alpha,beta)-methylene adenosine triphosphate. RESULTS: St. John's wort was significantly more active in inhibiting the EFS-induced contractions than the alpha,beta-methylene adenosine triphosphate-induced contractions, suggesting both a presynaptic site of action and a direct inhibition of bladder smooth muscle. The inhibitory effect of SJW on EFS-induced contractions was unaffected by methysergide, haloperidol, phentolamine plus propranolol (antagonists that block the action of the neurotransmitters 5-hydroxytriptamine, dopamine, and noradrenaline on their own receptors), the L-type calcium channel antagonist verapamil, capsazepine (which blocks the vanilloid receptor), or cannabinoid CB1 receptor antagonist SR141716A. However, the opioid receptor antagonist naloxone significantly reduced the inhibitory effect of SJW on EFS-induced contractions. Among the chemical constituents of SJW tested, hyperforin and, to a lesser extent, the flavonoid kaempferol showed inhibitory effects. CONCLUSIONS: The results of our study demonstrated that SJW inhibits excitatory transmission of the rat urinary bladder and also directly inhibits smooth muscle contractility. The inhibitory effect on excitatory transmission could involve, at least in part, opioid receptors. SJW may be evaluated for its possible use in treating urinary incontinence in depressed patients.

Acetylcholine↗

PubMed2004

A secoisopimarane diterpenoid from Salvia cinnabarina inhibits rat urinary bladder contractility in vitro.

We have evaluated the effect of 3,4-secoisopimar-4(18),7,15-triene-3-oic acid (compound 1), isolated from the aerial parts of Salvia cinnabarina, on the contractile response elicited by electrical field stimulation (EFS) in the rat isolated urinary bladder. Compound 1 (10 ( - 7) - 10 ( - 4) M) produced a concentration-dependent inhibition of the EFS contractile response without modifying the contractions produced by exogenous acetylcholine (10 ( - 6) M). A number of antagonists/inhibitors including a combination of atropine (10 ( - 6) M), phentolamine (10 ( - 6) M), propranolol (10 ( - 6) M) and hexamethonium (10 ( - 4) M), the NK (1) receptor antagonist SR140333 (10 ( - 7) M) plus the NK (2) receptor antagonist SR48968 (10 ( - 6) M), naloxone (10 ( - 6) M), verapamil (10 ( - 7) M), capsazepine (10 ( - 5) M) and the CB (1) receptor antagonist SR141716A (10 ( - 6) M) did not modify the inhibitory effect of compound 1. However, the nitric oxide (NO) synthase inhibitor L-NAME (3 x 10 ( - 4) M), significantly reduced the inhibitory effect of compound 1. It is concluded that compound 1 inhibits rat bladder contractility with a mechanism involving, at least in part, NO production.

Acetylcholine↗

PubMed2004

A diterpenoid from Salvia cinnabarina inhibits mouse intestinal motility in vivo.

This study was aimed to investigate the effect of 3,4 secoisopimara-4(18),7,15-trien-3-oic acid (compound 1) isolated from the aerial parts of Salvia cinnabarina, on upper gastrointestinal transit in mice in vivo. Compound 1 (10 - 100 mg/kg, i. p.) dose-dependently delayed gastrointestinal motility. Pretreatment ( i. p.) of mice with hexamethonium (10 mg/kg), naloxone (2 mg/kg), N(G)-nitro- L-arginine-methyl ester ( L-NAME) (25 mg/kg) or yohimbine (1 mg/kg) did not modify the inhibitory effect of compound 1 (50 mg/kg). However, the L-type Ca (2+) channel verapamil (5 mg/kg, i. p.) significantly reduced the antimotility effect of compound 1 (50 mg/kg). These results suggest that compound 1 inhibits gastrointestinal motility in mice. The effect could involve, at least in part, L-type Ca (2+) channels.

Animals↗

PubMed2004

New sesquiterpenes with intestinal relaxant effect from Celastrus paniculatus.

The seed oil obtained from Celastrus paniculatus has been used in Ayurvedic medicine for the treatment of several complaints including intestinal disorders. The muscle relaxing activity of C. paniculatus has been studied in vitro on isolated preparations of rat intestine. C. paniculatus seeds extract (0.001 - 100 microg/mL) produced a concentration-related relaxation of the rat ileum [IC (50) (95 % c. l.) 0.24 (0.13 - 0.45) microg/mL]. Among the four fractions ( n-hexane, CCl (4), CHCl (3), n-BuOH) obtained from the methanolic extract of C. paniculatus, only the carbon tetrachloride fraction (0.01 - 10 000 ng/mL) induced a significant relaxation of the intestinal muscle [IC (50) (95 % c. l.): 1.9 (1.38 - 2.87) ng/mL]. Three new sesquiterpene polyol esters have been isolated from the carbon tetrachloride fraction. These new metabolites, characterised as 1alpha,8beta,14-triacetoxy-9beta-furoyloxydihydro-beta-agarofuran ( 1), 1alpha, 6beta,8beta,14-tetraacetoxy-9beta-benzoyloxydihydro-beta-agarofuran ( 2) and 1alpha,8beta-diacetoxy-9beta-benzoyloxydihydro-beta-agarofuran ( 3), at the concentration of 1 microg/mL produced a relaxant effect of 30.6 +/- 12.2 %, 26.9 +/- 4.7 % and 7.27 +/- 1.7 %, respectively.

Animals↗

PubMed2004

Neuroprotective effect of cannabidiol, a non-psychoactive component from Cannabis sativa, on beta-amyloid-induced toxicity in PC12 cells.

Abstract Alzheimer's disease is widely held to be associated with oxidative stress due, in part, to the membrane action of beta-amyloid peptide aggregates. Here, we studied the effect of cannabidiol, a major non-psychoactive component of the marijuana plant (Cannabis sativa) on beta-amyloid peptide-induced toxicity in cultured rat pheocromocytoma PC12 cells. Following exposure of cells to beta-amyloid peptide (1 micro g/mL), a marked reduction in cell survival was observed. This effect was associated with increased reactive oxygen species (ROS) production and lipid peroxidation, as well as caspase 3 (a key enzyme in the apoptosis cell-signalling cascade) appearance, DNA fragmentation and increased intracellular calcium. Treatment of the cells with cannabidiol (10(-7)-10(-4)m) prior to beta-amyloid peptide exposure significantly elevated cell survival while it decreased ROS production, lipid peroxidation, caspase 3 levels, DNA fragmentation and intracellular calcium. Our results indicate that cannabidiol exerts a combination of neuroprotective, anti-oxidative and anti-apoptotic effects against beta-amyloid peptide toxicity, and that inhibition of caspase 3 appearance from its inactive precursor, pro-caspase 3, by cannabidiol is involved in the signalling pathway for this neuroprotection.

Amyloid beta-Peptides↗

PubMed2004

Magnetic resonance imaging of pulmonary lesions in guinea pigs infected with Mycobacterium tuberculosis.

We utilized magnetic resonance imaging to visualize lesions in the lungs of guinea pigs infected by low-dose aerosol exposure to Mycobacterium tuberculosis. Lesions were prominent in such images, and colorized three-dimensional reconstructions of images revealed a very uniform distribution in the lungs. Lesion numbers after 1 month were approximately similar to the aerosol exposure algorithm, suggesting that each was established by a single bacterium. Numbers of lesions in unprotected and vaccinated animals were similar over the first month but increased thereafter in the control animals, indicating secondary lesion development. Whereas lesion sizes increased progressively in control guinea pigs, lesions remained small in BCG-vaccinated animals. A prominent feature of the disease pathology in unprotected animals was rapid and severe lymphadenopathy of the mediastinal lymph node cluster, which is paradoxical given the strong state of cellular immunity at this time. Further development of this technical approach could be very useful in tracking lesion size, number, and progression in the search for new tuberculosis vaccines.

Animals↗

PubMed2004

The protective effect of the Mycobacterium bovis BCG vaccine is increased by coadministration with the Mycobacterium tuberculosis 72-kilodalton fusion polyprotein Mtb72F in M. tuberculosis-infected guinea pigs.

A tuberculosis vaccine candidate consisting of a 72-kDa polyprotein or fusion protein based upon the Mtb32 and Mtb39 antigens of Mycobacterium tuberculosis and designated Mtb72F was tested for its protective capacity as a potential adjunct to the Mycobacterium bovis BCG vaccine in the mouse and guinea pig models of this disease. Formulation of recombinant Mtb72F (rMtb72F) in an AS02A adjuvant enhanced the Th1 response to BCG in mice but did not further reduce the bacterial load in the lungs after aerosol challenge infection. In the more stringent guinea pig disease model, rMtb72F delivered by coadministration with BCG vaccination significantly improved the survival of these animals compared to BCG alone, with some animals still alive and healthy in their appearance at >100 weeks post-aerosol challenge. A similar trend was observed with guinea pigs in which BCG vaccination was boosted by DNA vaccination, although this increase was not statistically significant due to excellent protection conferred by BCG alone. Histological examination of the lungs of test animals indicated that while BCG controls eventually died from overwhelming lung consolidation, the majority of guinea pigs receiving BCG mixed with rMtb72F or boosted twice with Mtb72F DNA had mostly clear lungs with minimal granulomatous lesions. Lesions were still prominent in guinea pigs receiving BCG and the Mtb72F DNA boost, but there was considerable evidence of lesion healing and airway remodeling and reestablishment. These data support the hypothesis that the coadministration or boosting of BCG vaccination with Mtb72F may limit the lung consolidation seen with BCG alone and may promote lesion resolution and healing. Collectively, these data suggest that enhancing BCG is a valid vaccination strategy for tuberculosis that is worthy of clinical evaluation.

Animals↗

PubMed2003

Induction of nitric oxide synthase expression by Withania somnifera in macrophages.

Withania somnifera (ashwagandha, Indian ginseng) is an immunostimulant herbal medicine used to improve overall health and prevent diseases, particularly in the elderly. However, the mechanisms underlying its immunostimulant effect is poorly understood. To elucidate the mechanism of Withania somnifera, we investigated the effect of a methanolic extract from the root of Withania somnifera (WS) on nitric oxide (NO) production in J774 macrophages. We found that WS (1-256 microg/ml) produced a significant and concentration-dependent increase in NO production, an effect which was abolished by N(G)nitro-L-arginine methyl ester (L-NAME, 3-300 microM), a non-selective inhibitor of NO synthase (NOS), dexamethasone (10 microM), an inhibitor of protein synthesis and N(alpha-p)-tosyl-L-lysine chloromethyl ketone (TLCK, 0.01-10 microM), an inhibitor of nuclear factor-kappaB (NF-kappaB) activation. Dexamethasone did not have any effect on NO production once NOS had been induced (i.e. 12 h after WS). Moreover, western blot analysis showed that WS increased, in a concentration-dependent fashion, inducible NOS protein expression. These results demonstrate that WS may induce the synthesis of inducible NOS expression likely by acting at transcriptional level. The increased NO production by macrophages could account, at least in part, for the immunostimulant properties of Withania somnifera.

Animals↗

PubMed2003

Free radical scavenging capacity and protective effect of Bacopa monniera L. on DNA damage.

Bacopa monniera L. (family Scrophulariaceae) (BM) is an Ayurvedic medicine, clinically used for memory enhancing, epilepsy, insomnia and as a mild sedative. In this work, the free radical scavenging capacity of a methanol extract of BM and the effect on DNA cleavage induced by H2O2 UV-photolysis was investigated. In addition, we examined whether this plant extract is capable of reducing the hydrogen peroxide-induced cytotoxicity and DNA damage in human non-immortalized fibroblasts. It showed a dose-dependent free radical scavenging capacity and a protective effect on DNA cleavage. These results were confirmed by a significant protective effect on H2O2-induced cytoxicity and DNA damage in human non-immortalized fibroblasts. The antioxidant capacity of BM may explain, at least in part, the reported antistress, immunomodulatory, cognition-facilitating, antiinflammatory and antiaging effects produced by it in experimental animals and in clinical situations and may justify further investigation of its other beneficial properties. Moreover, this experimental evidence suggests that because of its antioxidant activity, this Ayurvedic drug may be useful in the treatment of human pathologies in which free radical production plays a key role.

Bacopa↗

PubMed2003

An endogenous cannabinoid tone attenuates cholera toxin-induced fluid accumulation in mice.

BACKGROUND & AIMS: Cholera toxin (CT) is the most recognizable enterotoxin causing secretory diarrhea, a major cause of infant morbidity and mortality throughout the world. In this study, we investigated the role of the endogenous cannabinoid system (i.e., the cannabinoid receptors and their endogenous ligands) in CT-induced fluid accumulation in the mouse small intestine. METHODS: Fluid accumulation was evaluated by enteropooling; endocannabinoid levels were measured by isotope-dilution gas chromatography mass spectrometry; CB(1) receptors were localized by immunohistochemistry and their messenger RNA (mRNA) levels were quantified by reverse-transcription polymerase chain reaction (PCR). RESULTS: Oral administration of CT to mice resulted in an increase in fluid accumulation in the small intestine and in increased levels of the endogenous cannabinoid, anandamide, and increased expression of the cannabinoid CB(1) receptor mRNA. The cannabinoid receptor agonist CP55,940 and the selective cannabinoid CB(1) receptor agonist arachidonoyl-chloro-ethanolamide inhibited CT-induced fluid accumulation, and this effect was counteracted by the CB(1) receptor antagonist SR141716A, but not by the CB(2) receptor antagonist SR144528. SR141716A, per se, but not the vanilloid VR1 receptor antagonist capsazepine, enhanced fluid accumulation induced by CT, whereas the selective inhibitor of anandamide cellular uptake, VDM11, prevented CT-induced fluid accumulation. CONCLUSIONS: These results indicate that CT, along with enhanced intestinal secretion, causes overstimulation of endocannabinoid signaling with an antisecretory role in the small intestine.

Amides↗