Abstracts on Herbal Medicine

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Jagtap AG; Shirke SS; Phadke AS | Effect of polyherbal

formulation on experimental models of inflammatory bowel

diseases. | Journal of Ethnopharmacology 90, (2-3), February

2004, 195-204 | Email: sarikashirke; Department

of Pharmacology, Bombay College of Pharmacy, Kalina, Santacruz

(E), Mumbai, 400 098, India | A polyherbal ayurvedic formulation

from an ancient authentic classical text of ayurveda was evaluated

for its activity against inflammatory bowel disease (IBD). The

polyherbal formulation contained four different drugs viz., Bilwa

(Aegle marmeloes), Dhanyak (Coriandrum sativun), Musta

(Cyperus rotundus) and Vala (Vetiveria zinzanioids). The

formulation has been tried before in clinical practice and was found

to be useful in certain number of cases of IBD (ulcerative colitis),

so was tried in the same form i.e., decoction (aqueous extract) in

experimental animals to revalidate the claims of the same. The

formulation was tried on two different experimental animal models

of inflammatory bowel disease, which are acetic acid-induced

colitis in mice and indomethacin-induced enterocolitis in rats.

Prednisolone was used as the standard drug for comparison. The

formulation showed significant inhibitory activity against

inflammatory bowel disease induced in these experimental animal

models. The activity was comparable with the standard drug

prednisolone. The results established the efficacy of this polyherbal

formulation against inflammatory bowel diseases.

 

Kim Bokyung; Kim Junghwan; Kim Aeran; Kim Yoon-Sun; Lee

Youn Ri; Bae Young Min; Cho Sungil; Rhyu Mee-Ra | Ligusticum

wallichi-induced vasorelaxation mediated by mitogen-activated

protein kinase in rat aortic smooth muscle. | Journal of

Ethnopharmacology 90, (2-3), February 2004, 397-401 | Email:

bkkim2; Department of Physiology, College of

Medicine, Konkuk University, Danwol-dong 322, Chungju, Choong-

Buk, 380-701, South Korea | Traditional herbal medicines have

been widely used for the treatment of cardiovascular disorders in

oriental countries. To determine the effects of Ch1LW, a chloroform

extract of Ligusticum wallichi, on the vascular system, we studied

changes in rat aortic smooth muscle in terms of magnitude of

contraction and the activity of mitogen-activated protein kinases

(MAPKs). Ch1LW inhibited the muscle contraction induced by

norepinephrine (NE) in aortic strips. Ch1LW also abolished Ca2+-

independent contraction evoked by 12-deoxyphorbol 13-isobutyrate

in Ca2+-free medium containing 1 mM EGTA. Furthermore,

western blotting analysis using phosphorylated MAPK antibodies

showed that NE increased the activity of both extracellular signal-

regulated kinase 1/2 (ERK1/2) and p38 MAPK, which were

inhibited by PD98059 and SB203580, blockers of ERK1/2 and p38

MAPK, respectively. Furthermore, treatment with Ch1LW

significantly abolished NE-mediated activation of ERK1/2, whereas

the activity of p38 MAPK was not affected by the extract. Ch1LW

induced vasorelaxation in rat aortic smooth muscle, which may be

mediated by the inhibition of ERK1/2 pathway, but not p38 MAPK.

 

Kim C; Ha H; Lee JH; Kim JS; Park SW et al | Herbal extract

prevents bone loss in ovariectomized | Archives of Pharmacal

Research (Korea) 26, (11), 2003, 917-924 | Korea Inst Oriental

Med, Drug Res & Dev Team, 129-11 Chungdam Dong, Seoul

135100, South Korea cskim | This research aims to

test a new drug candidate based on a traditional medicinal herb,

F1, an herbal extract obtained from Astragalus membranaceus and

its main ingredient, 1-monolinolein that may have fewer side effects

and less uterine hypertrophy. In vitro experiments, human

osteoblast-like cell lines, MG-63 and Saos-2, were analyzed by 3-

(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)

and an alkaline phosphatase (ALP) assays. Mouse osteoclasts

were induced through a calcium-deficient diet and inhibition effects

were measured. In vivo experiments were done using

ovariectomized (OVX) rats for 9 weeks. At necropsy, uterus

weights were measured, trabecular bone area (TBA) of tibia and

lumbar vertebra were measured bone histomorphology. In results,

cell proliferation and ALP activity in Saos-2 by ether F1 or 1-

monolinolein did not increased significantly compared to the

control. The F1 inhibited osteoclast development

(IC<INF>25</INF> = 3.37 x 10<SUP>-5</SUP> mg/mL) less than

17beta-estradiol. The OVX rats administered F1 (2 mg/kg/day and

10 mg/kg/day) showed an increase in TBA of the tibia significantly

(136.3 +/- 4.2% and 138.5 +/- 10.3% of control). In conclusions,

the herbal extract, F1 inhibited tibia and lumbar bone loss and did

not cause uterine hypertrophy. However, 1-monolinolein, the main

ingredient of the herbal extract, did not inhibit bone loss.

 

Kim Mi-Sun; Choi In-Young; Lee Si-Hyeong; Hong Seung-Heon;

Shin Taekyun; Kim Hyung-Min | The Oriental medicine 'Cool-Cool

(Cool-X-A)' inhibits inflammatory cytokine production and migration

in mast cells. | Biological & Pharmaceutical Bulletin 27, (1),

January 2004, 34-37 | Email: hmkim; Department of

Pharmacology, College of Oriental Medicine, Kyung Hee

University, 1 Hoegi-Dong, Dongdaemun-Gu, Seoul, 130-701, South

Korea | Plant medications have been applied to treat pains from

various types of arthritis in Korea. Rheumatoid arthritis (RA) is well

known to be a chronic autoimmune/inflammatory disease that

leads to progressive joint damage and cartilage destruction.

Accumulation and activation of mast cells have been demonstrated

in rheumatoid synovial tissue. Because infiltrated mast cells and

their mediators may contribute to the initiation and progression of

the inflammatory process and matrix degradation of RA, we tested

the inhibitory effects of 'Cool-Cool' (CC, Cool-X-A), an Oriental

medication, on the production and migration of major inflammatory

cytokines in mast cells. CC was treated in vitro before activation of

human mast cell line (HMC-1) with phorbol 12-myristate 13-

acetate, and the cytotoxicity of CC was assessed by 3-(4,5-

dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay. CC

had no cytotoxic effects on HMC-1 cell viability. The inhibitory

effects on cytokine production were monitored by enzyme-linked

immunosorbent assay and reverse transcriptase-polymerase chain

reaction (RT-PCR). CC inhibited not only the secretion but also the

expression of TNF-alpha and IL-8 in HMC-1 cells. CC also

suppressed migration of mast cells induced by stem cell factor.

These findings may help in understanding the mechanism of action

of this herbal medication, leading to the control of mast cells in

inflammatory conditions like RA.

 

Koo Hyan-Na; Lee Jai-Kyoo; Hong Seung-Heon; Kim Hyung-Min |

Herbkines increases physical stamina in mice. | Biological &

Pharmaceutical Bulletin 27, (1), January 2004, 117-119 | Email:

hmkim; Department of Pharmacology, College of

Oriental Medicine, Kyung Hee University, 1 Hoegi-Dong,

Dongdaemun-Gu, Seoul, 130-701, South Korea | Herbkines has

been used for the purpose of development of physical strength. In

the present study, we investigated the effect of Herbkines on

performance of the forced swimming test (FST) and on blood

biochemical parameters related to fatigue: blood urea nitrogen

(BUN), creatine kinase (CK), lactic dehydrogenase (LDH), glucose

(Glc), and total protein (TP). Herbkines were orally administered to

mice, 10 ml/kg, continuously once/day for 2 weeks using a feeding

atraumatic needle. After 2 d, on FST, the immobility time was

decreased in the Herbkines-fed group (178 +/- 8.2 s) in comparison

with the control group (189 +/- 22 s); however, the statistical

difference was very weak (p=0.596). After 2 weeks, the immobility

time was significantly decreased in the Herbkines-fed group (196 +/-

4.5 s) in comparison with the control group (221 +/- 6.2 s). In

addition, the content of BUN in the blood serum was significantly

decreased. However, the levels of CK, LDH, Glc, and TP did not

show a significant change. The results predict a potential benefit of

Herbkines as an anti-fatigue treatment and for improving physical

stamina.

 

Lee Mi-Hye; Yoon Sik; Moon Jeon-Ok | The flavonoid naringenin

inhibits dimethylnitrosamine-induced liver damage in rats. BIO 07-

14 PREV200400157314 NDN- 244-0279-4608-1 | Biological &

Pharmaceutical Bulletin 27, (1), January 2004, 72-76 | Email:

mjo; College of Pharmacy, Pusan National

University, Changjeon-dong, Kumjeong-gu, Pusan, 609-735, South

Korea | Naringenin, a phytoalexin found in grapefruits and

tomatoes, has been reported to exhibit a wide range of

pharmacological properties. In this study, we investigated the

protective effect of naringenin on hepatic injury induced by

dimethylnitrosamine (DMN) in rats. Oral administration of

naringenin (20 and 50 mg/kg daily for 4 weeks) remarkably

prevented the DMN-induced loss in body and liver weights and

inhibited the elevation of serum alanine transaminase, aspartate

transaminase, alkaline phosphatase, and bilirubin levels.

Naringenin also restored serum albumin and total protein levels,

and reduced the hepatic level of malondialdehyde. Furthermore,

DMN-induced collagen accumulation, as estimated by histological

analysis of liver tissue stained with Sirius red, was reduced in the

naringenin-treated rats. A reduction in hepatic stellate cell

activation, as assessed by alpha-smooth muscle actin staining,

was associated with naringenin treatment In conclusion, these

results demonstrate that naringenin exhibited in vivo

hepatoprotective and anti-fibrogenic effects against DMN-induced

liver injury. Naringenin may be useful in preventing the development

of hepatic fibrosis.

 

Miyata T | Novel approach to respiratory pharmacology -

Pharmacological basis of cough, sputum and airway clearance |

Journal of the Pharmaceutical Society of Japan (Japan)123, (12),

2003, 987-1006 | Kumamoto Univ, Grad Sch Med & Pharmaceut

Sci, 5-1 Oehonmachi, Kumamoto 8620973, Japan

tmiyata | The development of new

techniques has made it possible to identify and measure the

mucus components, measure the rheologic parameters more

accurately, and evaluate mucociliary clearance precisely in

animals and humans. Therefore, with modifications of methods, we

have investigated airway-cleansing drugs from various points of view

to reflect actions in inflammatory states for more than two

decades. Here, I introduce the methods we have used to study

many of the parameters involved in airway clearance, including

cough reflex, and describe some of the mucoactive-antitussive

drugs that we have studied recently. There is an increasing usage

of traditional Chinese herbal medicines in clinics and hospitals,

because they tend to have moderate side effects and sometimes

remarkable efficacy To renormalize overall defects in airway

disorders, Chinese medicines may be adequate, because they are

composed of various herbs with weak but ubiquitous pharmacologic

activities. We have been investigating Bakumondo-to. Bakumondo-

to has been used for the treatment of bronchitis and pharyngitis

accompanying severe dry cough. We found that unlike codeine

Bakumondo-to had a notable antitussive activity against the cough

associated with bronchitis and the cough increased by angiotensin-

converting enzyme inhibitors. Recently, we have found that, in

alveolar type II cells, Bakumondo-to attenuated phosphatidylcholine

secretion increased by oxygen radicals from activated PMNLS. In

addition, we found that Bakumondo-to itself stimulated

phosphatidylcholine secretion and increased beta-adrenoceptor

gene expression in rat alveolar type II cells. We studied the

mechanism of action and clarified that Bakumondo-to increased

glucocorticoid-sensitive promotor activity. The effect may contribute

to its ubiquitous effectiveness in the treatment of airway diseases.

Various parameters (chemical properties, physical properties,

mucus production, surfactant phospholipid production, and

mucociliary clearance) are considered to be important for the

dynamics and mobilization of airway secretions. Pharmacologic

investigation, with appropriate techniques, of the ability of an agent

to modify these parameters can provide useful information about its

mechanism of action. However, since these parameters are

interconnected, it is very complicated to elucidate the precise

mechanisms of action of mucoactive drugs. This means that the

goal of treatment cannot always be achieved by the modification of

a single parameter, but should, more realistically, be aimed at a

renormalization of several parameters. On the basis of this idea,

glucocorticoids are ideal mucoactive drugs because they exert

various pharmacologic effects in the lung. From a

polypharmacologic point of view, a traditional Chinese medicine

can be classified as a glucocorticoid-like drug because Chinese

medicines consist of many types of active components that have

various pharmacologic effects As one future course of research, we

believe that efforts to seek compatible actions between

glucocorticoids and Oriental medicines may lead to new

opportunities for development of ideal airway-cleansing drugs with

specific actions, i.e., suppression of gene expression.

 

Munemoto Yoshinori; Iida Yoshiro; Ohata Kou; Saito Hideo;

Fujisawa Katsunori; Kasahara Yoshiro; Mitsui Tsuyoshi; Asada

Yasuyuki; Miura Shoji | Significance of postoperative adjuvant

immunochemotherapy after curative resection of colorectal

cancers: Identification of responders incorporating the age factor. |

Oncology Reports 11, (3), March 2004, 623-635 | Email: y-

munemoto; Department of Surgery,

Prefecture of Saiseikai Fukui Hospital, 7-1 Funabashi, Wadanaka-

cho, Fukui, 918-8503, Japan | To identify responders when protein-

bound polysaccharide (PSK) is used in adjuvant

immunochemotherapy after curative resection of colorectal

cancers, we examined the host and tumor factors that affect the

prognosis incorporating the age factor. A total of 101 patients who

had undergone macroscopic curative resection of colorectal cancer

were treated with mitomycin C+fluoropyrimidine oral

antineoplastics+PSK (MFP therapy) for two years in principle.

These cases were divided into two age groups of <65 years (n=55;

54.8 +/- 8.3 years (mean +/- SD)) and >/=65 years (n=46; 69.1 +/-

3.3 years). Host factors including humoral factors (complement C3

and C4), immunosuppressive acidic protein (IAP), lymphocyte

transformation (cellular factors) induced by various mitogens

(phytohemagglutinin (PHA), pokeweed mitogen (PWM), and PSK),

and tumor markers (CEA, CA19-9) were measured. The cases

were divided by the cut-off value of each parameter into >/= cut-off

value and < cutoff value groups, and the 5-year survival rates were

compared. The cut-off values obtained for these parameters and the

tumor factor (Dukes class) were subjected to multivariate analysis

to identify the markers that affect prognosis. The 5-year mortality

rate was 74.5% in the <65 age group and 56.8% in the >/=65 age

group, with a tendency of better prognosis in the <65 age group

(p=0.1109). Compared to the <65 age group, the >/=65 age group

showed higher levels of C3 (2-way ANOVA: p=0.0582), C4

(p=0.0009) and IAP (p=0.0110) over time, but lower PSK-induced

stimulation index (SI) as an indicator of cellular immunity)

(p=0.0001) and PHA-induced SI (p=0.2650) over time. These

results indicated that compared to patients aged <65 years,

patients aged >/=65 years were characterized by lowered cellular

immunity in addition to augmented complement production and an

aggravated immunosuppressive state, suggesting the presence of

some differences in host immune function with aging. Using the

Cox proportional hazard model, the prognostic determinant was

found to be Dukes C in the <65 age group, and CEA level in the

>/=65 age group. The results suggested that analysis of prognostic

determinants of this therapy should take into account the age

factor. Especially in elderly subjects, responders to PSK may be

identified using the preoperative CEA value.

 

Raeth Karin; Taxis Katja; Walz Gitta; Gleiter Christoph H; Li Shu-

Ming; Heide Lutz | Pharmacokinetic study of artemisinin after oral

intake of a traditional preparation of Artemisia annua L. (Annual

Wormwood). | American Journal of Tropical Medicine and Hygiene

70, (2), February 2004, 128-132 | Email: heide;

Pharmazeutische Biologie, Pharmazeutisches Institut, Universitaet

Tuebingen, Auf der Morgenstelle 8, 72076, Tuebingen, Germany h |

Artemisia annua L. (annual wormwood) contains the antimalarial

artemisinin. Aqueous preparations of the dried herb are included in

the pharmacopoeia of the People's Republic of China for treatment

of fever and malaria. Fourteen healthy male volunteers received one

liter of tea prepared from nine grams of Artemisia annua leaves.

Blood samples were taken and artemisinin was detected by

reversed phase high-performance liquid chromatography. The mean

+/- SD maximum plasma concentration of artemisinin was 240 +/-

75 ng/mL and the mean +/- SD area under the plasma

concentration-time curve was 336 +/- 71 ng/mLXhr. Artemisinin

was absorbed faster from herbal tea preparations than from oral

solid dosage forms, but bioavailability was similar. One liter of an

aqueous preparation of nine grams of Artemisia annua contained

94.5 milligrams of artemisinin (approximately 19% of the usually

recommended daily dose). Artemisinin plasma concentrations after

intake of this herbal tea are sufficient for clinical effects, but

insufficient to recommend such preparations as equivalent

substitutes for modern artemisinin drugs in malaria therapy

 

Schoetz Karl | Quantification of allergenic urushiols in extracts of

Ginkgo biloba leaves, in simple one-step extracts and refined

manufactured material (EGb 761). | Phytochemical Analysis 15,

(1), January-February 2004, 1-8 DOCUMENT TYPE- Article ISSN-

0958-0344 | Email: karl.schoetz; Phytochemical

Department, Dr. Willmar Schwabe Arzneimittel, Willmar-Schwabe-

Str. 4, D-76227, Karlsruhe, Germany | Extracts of leaves of

Ginkgo biloba (family Ginkgoaceae), widely used in the treatment

of peripheral and cerebral circulatory disorders as well as for

dementia of different aetiology, contain long chain alkylphenols

(with allergenic, cytotoxic, mutagenic and tumour-promoting

properties) together with the extremely potent allergens, the

urushiols. Such hazardous compounds can be present only in very

low concentrations in phytopharmaceutical preparations and

hence, for the purposes of drug safety, techniques must be

available for the identification and quantification of these allergens

at extremely low levels in refined manufactured materials. GC-MS

analysis of samples collected at various stages during the

production process of a standardised extract of G. biloba (EGb

761) demonstrated that all alkylphenols present in the primary

acetone extracts were removed in parallel with the same efficiency

irrespective of their aromatic substitution pattern. Furthermore, in

the final product the content of urushiols was generally below the

detection limit of 0.03 ppm. Therefore, it is concluded that

demonstrating the absence of the predominant, and easily

quantifiable, ginkgolic acids provides a reliable means for the

control of pharmaceutical quality of the final product.

 

Storr M; Sibaev A; Marsicano G; Lutz B; Schusdziarra V;

Timmermans J-P; Allescher HD | Cannabinoid receptor type 1

modulates excitatory and inhibitory neurotransmission in mouse

colon. | American Journal of Physiology 286, (1), Part 1 January

2004, G110-G117 | Email: martin.storr; II. Med. Klinik

und Poliklinik, Technischen Universitaet Muenchen, Ismaningerstr.

22, 81675, Muenchen, Germany | The effects of cannabinoid

receptor agonists and antagonists on smooth muscle resting

membrane potentials and on membrane potentials following

electrical neuronal stimulation in a myenteric neuron/smooth

muscle preparation of wild-type and cannabinoid receptor type 1

(CB1)-deficient mice were investigated in vitro. Double staining for

CB1 and nitric oxide synthase (neuronal) was performed to identify

the myenteric CB1-expressing neurons. Focal electrical stimulation

of the myenteric plexus induced a fast (f) excitatory junction

potential (EJP) followed by a fast and a slow (s) inhibitory junction

potential (IJP). Treatment of wild-type mice with the endogenous

CB1 receptor agonist anandamide reduced EJP while not affecting

fIJP and sIJP. EJP was significantly higher in CB1-deficient mice

than in wild-type littermate controls, and anandamide induced no

effects in CB1-deficient mice. N-arachidonoyl ethanolamide

(anandamide), R-(2,3-dihydro-5-me- thyl-3-(4-morpholin-

ylmethyl)pyrrolo(1,2,3,-de)-1,4-benzoxazin-6-yl)-1-

naphtalenylmethanone, a synthetic CB1 receptor agonist, nearly

abolished EJP and significantly reduced the fIJP in wild-type mice.

N-piperidino-5-(4-c- hlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-3-

pyrazole-caroxamide (SR141716A), a CB1-specific receptor

antagonist, was able to reverse the agonist effects induced in wild-

type mice. SR141716A, when given alone, significantly increased

EJP in wild-type mice without affecting IJP in wild-type and EJP in

CB1-deficient mice. Interestingly, SR141716A reduced fIJP in CB1-

deficient mice. In the mouse colon, nitrergic myenteric neurons do

not express CB1, implying that CB1 is expressed in cholinergic

neurons, which is in line with the functional data. Finally, excitatory

and inhibitory neurotransmission in the mouse colon is modulated

by activation of CB1 receptors. The significant increase in EJP in

CB1-deficient mice strongly suggests a physiological involvement

of CB1 in excitatory cholinergic neurotransmission.

 

Yamaguchi Shuhei; Matsubara Miwa; Kobayashi Shotai | Event-

related brain potential changes after Choto-san administration in

stroke patients with mild cognitive impairments. |

Psychopharmacology 171, (3), January 2004, 241-249 | Email:

yamagu3n; Department of Internal Medicine

III, Shimane Medical University, 89-1 Enya-cho, 693-8501, Izumo,

Japan | Few drugs have been reported to be effective for the

treatment of vascular dementia. Chotosan is a herbal medicine

expected to be effectivein this condition, but it is unclear how this

drug modulates brain activities and cognitive functions. P3 event-

related brain potentials (ERP) provide reliable electrophysiological

indices for some aspects of cognitive functions. Objectives: We

measured P3 ERP to assess the effect of Chotosan administration

on stroke patients with mild cognitive impairments. Methods: Choto-

san was given for 12 weeks to ten chronic stroke patients. P3 ERP

were recorded before and after drug administration in a modified

auditory oddball paradigm including occasional novel sounds using

a high-density array EEG recording system. The reproducibility of

ERP was also assessed in other ten stroke patients with a 12-

week interval. Cognitive functions were assessed with the Mini

Mental State Examination (MMSE) and verbal fluency test. Results

: Twelve-week administration of Choto-san significantly improved

MMSE and verbal fluency test scores. The reproducibility of P3

latency and amplitude to target and novel sounds was excellent.

P3 latency to target sounds was shortened in association with

reduced reaction time to the sounds after drug administration.

Furthermore, P3 amplitude to novel sounds was enlarged and its

topography shifted from central to frontal sites. Choto-san improved

electrophysiological indices related to attention and decision

making, in addition to neuropsychological test scores in stroke

patients with mild cognitive impairments.

 

Yuste J; Fung DYC | Inactivation of Salmonella Typhimurium and

Escherichia coli O157:H7 in apple juice by a combination of nisin

and cinnamon. | Journal of Food Protection 67, (2), February 2004,

371-377 | Email: dfung; Department of Animal

Sciences and Industry, Kansas State University, Call Hall,

Manhattan, KS, 66506, USA | Pasteurized apple juice with nisin (0,

25, 50, 100, and 200 ppm, wt/vol) and cinnamon (0 and 0.3%,

wt/vol) was inoculated with Salmonella Typhimurium and

Escherichia coli O157:H7 at 104 CFU/ml and stored at 5 and

20DegC. Counts on tryptic soy agar (TSA), selective medium

(xylose lysine desoxycholate agar for Salmonella Typhimurium,

and MacConkey sorbitol agar for E. coli O157:H7), and thin agar

layer (TAL) were determined at 1 h and 1, 3, 7, and 14 days. The

TAL method (selective medium overlaid with TSA) was used for

recovery of sublethally injured cells. The pathogens were gradually

inactivated by the acidic pH of apple juice. Nisin and cinnamon

greatly contributed to the inactivation. The killing effect was more

marked at 20DegC, with counts in all treated samples being

undetectable by direct plating in 3 days for Salmonella

Typhimurium and 7 days for E. coli O157:H7. Thus, several factors

influenced the decrease in counts: low pH, addition of nisin and

cinnamon, and storage temperature. The TAL method was as

effective as TSA in recovering injured cells of the pathogens. The

combination of nisin and cinnamon accelerates death of

Salmonella Typhimurium and E. coli O157:H7 in apple juice and so

enhances the safety of the product.

 

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