Background: Cardiovascular disease (CVD) is one of the major causes of morbidity and mortality worldwide. Clinical guidelines, based on the results of randomised controlled trials, state that effective secondary prevention therapies should be prescribed following a diagnosis of particular CVD unless there are contraindications. Although evidence shows that use of evidence based pharmacotherapies after diagnosis of CVD reduces mortality and disease progression, many inequalities exist in prescribing practice. Many studies have documented that women and the elderly are less likely to receive evidence based therapies than men and the young, respectively. Greater socioeconomic deprivation has also been shown to be associated with lower rates of prescribing of therapies. However, prior studies have all focussed on one particular CVD or failed to adjust for confounders. Also, few studies have examined trends in the prescribing of evidence based pharmacotherapies over time and documented whether prescribing inequalities are static, narrowing or widening. This project aims to describe the pharmacotherapy received by patients with CVD in Scotland, and to describe the factors associated with prescribing of evidence based pharmacotherapy. Methods: In this retrospective cohort study I examined a linked database of primary care records (Continuous Morbidity Records) and secondary care records (Scottish Morbidity Records) covering 238064 individuals in Scotland (approximately 6% of the total population) from 1997 to 2005. Patients with a first diagnosis (defined as a first hospitalisation or first recording of the diagnosis in primary or secondary care) of myocardial infarction (MI), angina, and peripheral arterial disease (PAD) were identified. Patients who died within the first 30 days of diagnosis/first hospitalisation were excluded from further analysis. Data on prescribing of evidence based therapies (angiotensin converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARBs), β-blockers, statins and antiplatelet agents [aspirin or clopidogrel]) within 30 days of diagnosis was obtained from primary care database records. Multivariable logistic regression was conducted to examine the association between prescribing of evidence based pharmacotherapies and age, sex, socioeconomic status, comorbidities and year of diagnosis. Results: Between 1997 and 2005, 4305 (83.4%) patients with a first diagnosis of MI, 7210 (98.6%) with angina, and 3385 (95.8%) with PAD had survived to 30 days after their first diagnosis. Increasing age was associated with lower odds of being prescribed evidence based therapies. This association persisted after adjustment for sex, socioeconomic status, year of diagnosis, and comorbidities. In general, older patients ≥ 85 were significantly less commonly prescribed evidence based therapy (EBTs), however they were significantly prescribed nitrates (OR 1.29; 95% CI 1.05-1.59, P < 0.01) for angina. Generally men were more likely to be prescribed evidence based therapies than women. After adjustment, prescribing of evidence based therapies was significantly higher in men with a MI for β-blockers (OR 1.18; 95% CI1.04-1.33, P < 0.01), ACEI/ARBs (OR1.26; 95% CI1.05-1.47, P < 0.01) in angina, and statins in men (OR 1.39; 95% CI1.01-1.93, P < 0.04) with PAD and coronary heart disease (CHD). In contrast, men diagnosed with isolated PAD were significantly less commonly prescribed statins than women (OR 0.73; 95% CI0.59-0.91, P < 0.004). Prescribing of evidence based therapies varied negligibly between the most deprived and least deprived patients. These minor differences disappeared after adjustment except for β-blockers which were significantly less likely to be prescribed for patients who had been diagnosed with angina and were residing in quintile 9 compared to the least deprived area (OR 0.76, 95% CI 0.58-1.00, p= 0.05). Prescribing of evidence based therapies increased between 1997 and 2005, particularly for ACEIs/ARBs, β-blockers, statins and antiplatelet agents. Generally the presence of comorbidities was associated with lower odds of being prescribed evidence based therapies. When comparing prescribing rates between the different diagnoses, patients with a first MI were more likely to be prescribed ACEI/ARBs, β-blockers, statins, aspirin and clopidogrel compared to angina. All evidence based therapies were less likely to be prescribed for those with PAD compared to patients with a MI or angina. Conclusion: In conclusion, I have shown that prescribing of evidence based therapies has improved over time, though rates remain low. Prescribing evidence based therapies is inequitable, though not always significant, for age, sex, and socioeconomic status. Concomitant disease decreased the odds of being prescribed evidence based therapies. More studies are needed to identify the reasons for the prescribing inequalities and low rates observed. Further studies are needed to examine the existence of other inequalities in using evidence based therapies such as dosing and to find strategies to improve prescribing rates.

Introduction: In patients who present with ST-elevation myocardial infarction (STEMI), primary percutaneous coronary intervention and the administration of dual antiplatelet therapy (aspirin plus a P2Y12 inhibitor) are recommended. This thesis aimed to determine the extent to which oral P2Y12 inhibitors (clopidogrel/prasugrel/ticagrelor) exert their antiplatelet effect during the acute phase of a STEMI compared to non-ST elevation myocardial infarction (NSTEMI). Methods: The degree and time-course of platelet inhibition following oral administration of P2Y12 inhibitors was determined in 87 patients from their pharmacokinetic (plasma concentration) and pharmacodynamic (degree of platelet inhibition) profiles at 20 minutes, balloon inflation, 60 and 240 minutes using liquid chromatography/mass spectrometry, VerifyNow and VASP-phosphorylation assays. Results: In STEMI patients, oral P2Y12 inhibitors do not provide adequate levels of platelet inhibition at the time of angioplasty and have a limited effect at 240 minutes. The NSTEMI group displayed a marked and rapid antiplatelet effect at all time points. A significant difference in the acute efficacy of oral P2Y12 inhibitors in STEMI vs NSTEMI patients (p < 0.001) was seen. Conclusion: Oral P2Y12 inhibitors display delayed and attenuated antiplatelet effects in STEMI patients in the immediate period following administration of a loading dose when compared with NSTEMI patients.

The work described in this thesis is concerned with the design and evaluation of microsphere-based systems for drug delivery into the colon. In initial experiments, techniques were devised for the preparation of microspheres from two sustained-release acrylic polymers, Eudragits RL and RS, using emulsification-solvent evaporation techniques. For Eudragit RS microspheres containing the drug 5-aminosalicylic acid, the rate of drug release could be controlled by the type and concentration of surfactant used for preparation. Consequently, formulations could be produced which released encapsulated drug instantaneously or over many hours. The surfactants may have been altering the structure of the microsphere drug-polymer matrix. Two novel analytical techniques were employed to characterise Eudragit RS microspheres containing sulphasalazine. Fourier transform-Raman spectroscopy was successfully used as a non-destructive method for qualitative and quantitative microsphere characterisation. The technique provided good agreement with a UVspectrophotometric method in quantifying the amount of drug in microsphere samples. X-ray photoelectron spectroscopy was used to estimate the concentration of sulphasalazine at the microsphere surface for samples produced with or without the use of surfactant. Across a wide range of microsphere drug loadings, the surface drug content remained remarkably constant, but was consistently lower in the samples produced using surfactant. In a parallel programme of work, using gamma scintigraphy, the transit rate of different sizes of radiolabelled materials through the human colon was investigated to determine whether there was an optimal size to maximise colon residence. There was no clear evidence of any difference in the colon residence time of 0.2 mm particles, 5 mm tablets, or 8.4 mm tablets, under normal conditions and during accelerated transit. In healthy subjects, 50% of a dose of 0.2 mm particles resided in the ascending colon for an average of 11 hours. Finally, an in vivo biopharmaceutical evaluation of sulphapyridine-containing Eudragit RS microspheres in the human colon was undertaken. For this study, a neutron activation technique was developed for microsphere radiolabelling. Microspheres could be successfully radiolabelled by incorporation of samarium oxide followed by neutron irradiation. However, it was necessary to minimise the period of irradiation and the amount of incorporated samarium oxide, since high levels of both were found to adversely affect microsphere performance. The in vivo investigation revealed that the colonic bioavailability of sustained-release microencapsulated sulphapyridine was less than 50% of unencapsulated sulphapyridine powder. This shortfall was possibly due to an interaction of the drug with colonic bacteria or in vitro/in vivo differences in microsphere drug release characteristics.

The movement and concentration of water inside hydrophilic matrices and the bioadhesive bonds formed by them have been proposed as important factors in the bioadhesion of hydrophilic matrices (Smart et al, 1991, and Mortazavi and Smart, 1993). This thesis has developed a non-invasive magnetic resonance imaging (MRI) technique to spatially resolve the self-diffusion coefficient (SDC) and concentration profiles of water inside the bioadhesive bonds formed by dry and hydrated hydrophilic matrices. The bioadhesive interaction between mucin and adhesive may affect the network structure and diffusion retarding properties of either polymer. The mobility of solutes may be used as an indicator of such changes. This thesis has developed a fluorescence recovery after photobleaching (FRAP) technique to measure the mobility of fluorescently tagged dextrans in the mucin and adhesive polymer networks. These methods were combined with basic studies of liquid uptake kinetics and bond strength through detachment force testing to study the bioadhesive bonds formed between alginate matrices and pig gastric mucus. These studies provided evidence to suggest that the bioadhesion of dry and hydrated alginate matrices involved several underlying mechanisms. In the case of bioadhesive bonds formed by dry alginate matrices, the SDC profiles indicated that the hydration of alginate and the formation of a viscous gel layer may cause the localised dehydration of mucus directly adjacent to the alginate matrix. Furthermore, the work of adhesion (Wa) of bioadhesive bonds formed between pig gastric mucus and dry alginate matrices suggested that polymer interpenetration and secondary chemical bonding might also be involved. In the case of bonds formed by hydrated alginate matrices, similar studies indicated that the bioadhesion of hydrated alginate matrices might involve polymer interpenetration and secondary chemical bonding as well as mucus dehydration, although the latter phenomenon appeared to be dependent on the molecular weight of alginate.

Despite intensive research, cancer remains one of the major causes of worldwide morbidity. It is widely believed, however, that if currently available anti-cancer drugs could be delivered specifically to tumours then the disease would have been mastered. The delivery of prodrug converting enzymes by clostridial spores specifically to the anoxic centres of tumours is one potential delivery mechanism. This is due to the extreme selectivity of spores to germinate solely in the hypoxic regions of tumours. Once germinated, the expression of a prodrug converting enzyme converts a systemical1y administered prodrug to a highly toxic drug only in the tumour. Previous studies using Clostridium acetobutylicum and Clostridium beijerinckii as the delivery vehicle highlighted that prodrug converting enzyme expression is only found in tumours. However, no significant anti-tumour affect was observed. Two possible reasons were evolved. Firstly, expression of the prodrug converting enzyme may be low, and/or, secondly, the tumours may not be colonised sufficiently to promote an antitumour effect. Preliminary studies identified that Clostridium sporogenes NCIMB 10696 may represent a more suitable host. Higher spore titres could be prepared and, once administered, higher cell counts are found in the colonised tumours. Prodrug converting enzymes with improved kinetics over pre-existing enzymes have also been identified. Once effective gene transfer systems and expression systems had been developed, suitably high levels of several different prodrug converting enzymes, in particular nitroreductases, were obtained. Initial in vivo studies on one of the early recombinant strains identified a definite anti-tumour effect. Since those initial studies, further improvements to expression have been made. It is hoped that a more significant anti-tumour affect would result from using these improved strains. It is the ultimate aim of CDEPT to have the prodrug converting enzymes integrated into the host genome so as to negate the use of antibiotics. Towards this, studies on the use of both classical and novel integrative technologies have been investigated.

This thesis is concerned primarily with the practical implementation of Bayesian methodology within the context of the pharmaceutical industry. The implementation includes the development, where appropriate, of analytic approximations to the posterior distributions of interest and graphical methods for mapping prior assumptions to posterior inference. Two critical areas within pharmaceutical research, critical in the sense of the controversy which they have aroused, have been investigated. First, Bayesian methods for the analysis of two-treatment crossover designs which fell in to disfavour in the late 1970's and early 1980's because of the US Food and Drug Administration's published view that the two-treatment two-period design was not the design of first choice if unequivocal evidence of a treatment effect was required were developed. Each type of design considered and for which methods are developed are illustrated with examples from clinical trials which have already been reported in the medical literature. Second, a Bayesian method is developed whose purpose is to classify test compounds into one of several toxicity classes on the basis of an LD50 estimate. The method is generalised to deal with a non-standard LD50 problem related to the prediction of results from a future LD50 experiment. Both of these applications arose out of a practical consultancy session within the context of a statistics group in the chemical/pharmaceutical industry. As part of the methods required for carrying out these analyses the zeros and weights associated with some non-standard orthogonal polynomial are developed as a result of which a new asymptotic expansion of the Behrens-Fisher density is developed. Further applications of the polynomials orthogonal to t-kernels are developed including problems associated with prediction in clinical trials. A FORTRAN program which has been implemented at a laboratory level within the pharmaceutical toxicology department at CIBA-GEIGY in Switzerland is provided SAS programs for a variety of the analyses developed for the two-treatment crossover designs are provided as are SAS programs for determining the zeros and weights of a number of different classes of orthogonal polynomials.

To improve the outcomes of drug therapy, there is increasing interest in the community pharmacist providing medicines management services (MMS) (Department of Health, 2000b, 2003a). In 2001, the Department of Health funded the Community Pharmacy Medicines Management Project (CPMMP) to evaluate the introduction of a community pharmacy led MMS. This thesis set out to critically assess the views and experiences of community pharmacists and general practitioners (GPs) participating in the CPMMP; exploring how relationships and perceptions of each other could influence community pharmacists carrying out a MMS, from the viewpoint of both community pharmacists and GPs. This is a qualitative study whereby eight focus groups were conducted with thirty five community pharmacists, and semi-structured telephone interviews were carried out with twenty one GPs and twenty eight community pharmacists. Data was analysed using the broad principles of Grounded Theory (Glaser and Strauss, 1967). Almost all pharmacists and GPs stated they had a good working relationship with each other prior to the MMS commencing, although a number of attitudinal barriers were identified. These included professional hierarchy, GPs' lack of awareness of a pharmacist's training and role in health care, and concerns that commercial interests could potentially affect a community pharmacist's advice. However, these data suggested that where there was an established relationship between the two professions, the most positive feedback about the MMS was reported. These data also suggested that some GPs were not supportive for community pharmacists to undertake a MMS and were generally unwillingly for the community pharmacist to have full access to patients' medical records. There were also some concerns around boundary encroachment. The project had a limited impact on improving relationships between community pharmacists and GPs, with relationships and GPs' perceptions remaining unaltered in many instances. This piece of research has highlighted that attitudinal barriers need to be addressed in order to accomplish effective collaborative working between community pharmacists and GPs.

An analysis of judicial attitudes in the United States of America towards pharmacist responsibility has shown distinct patterns or trends. Early cases set the standards for pharmacists at a high professional level. The courts later restricted liability to technical inaccuracy in prescription processing. More recently, the judiciary is recognising the necessity to apply standards appropriate to the pharmacist’s new roles and functions. A legislative gloss to these developments has been provided in the United States of America by the enactment of legislation which seeks to recognise professional roles, enhance pharmacy practice standards and improve the outcome of drug therapy for patients, by bettering patient compliance with drug regimes. There is a current expectation, particularly on the part of the public, but also on the part of health care policy makers, that pharmacists have a responsibility to detect problems with prescribed medications, and that to fail in this responsibility is a direct threat to the public health. The new expectations of drug therapy and the parallel anticipation of the participants in drug therapy have created a new duty on the part of the pharmacist, to intervene and promote the patient’s best interests. In this thesis, it is argued that this perspective is a reasonable one. Pharmacists ought to detect and prevent problems with drug therapy. The public should be disappointed if a profession, a government-sanctioned monopoly, has the ability to improve the public health but fails to do so. In turn, courts (and a legislature) that refuse to recognise expanded responsibilities for pharmacists, and that fail to impose corresponding expanded liabilities for the failure to meet a responsibility, are perpetuating an outdated view of pharmacy practice based on an incomplete understanding of the medication use system. There are solid policy reasons for imposing a higher standard for pharmacists that includes, but goes beyond, mere technical accuracy in order processing. In turn, there are limits to what pharmacists can reasonably be expected to do, and a legal system exploring the subject of expanded pharmacist responsibility should be aware of those limits.

The prevalence of obesity worldwide has more than doubled since 1980. The World Health Organisation (WHO) estimates that more than one in ten adults in the global population is obese. Cardiovascular and metabolic health can be improved with moderate weight loss; losses of 5%–10% have been found to improve conditions such as diabetes, hypertension and cholesterol and low-density lipoprotein (LDL) levels. Within the UK, a number of weight management programmes that depend on lifestyle intervention (tier 2) and others that supplement this with drug therapy (tier 3) and surgery (tier 4) are available. The guidelines produced by the Scottish Intercollegiate Guideline Network (SIGN) advocate that weight management programmes address changes to diet, physical activity and behaviour. For patients with a body mass index (BMI) ≥30 kg/m2 or ≥28 kg/m2 in patients with comorbidities, orlistat can be considered as a drug intervention on a case-by-case basis following a full risk and benefit assessment. The objective of the Glasgow and Clyde Weight Management Service (GCWMS), a specialist weight-loss programme, is for patients to lose at least 5 kg. There are a number of metabolic disorders that are associated with obesity. One such disorder is type 2 diabetes mellitus, where weight loss is a standard recommendation to improve blood glucose control. Randomised controlled trials (RCTs) of orlistat indicate that the drug is effective in promoting weight loss and improving metabolic control for those patients with the comorbidity of type 2 diabetes and obesity. There are several different groups of anti-diabetic drugs that can be used to manage diabetes. The effects of the different medications on body weight are considerable. Some, such as biguanides (metformin), dipeptidyl peptidase-4 inhibitors (DPP-IV), Glucagon-like peptide-1 agonist (GLP-1) and sodium-glucose co-transporter-2 inhibitors (SGLT2), either have no effect on weight or can cause weight loss. Others, such as sulfonylureas (SUs) and thiazolidinediones (TZDs) can lead to weight gain. This thesis explores the impact of lifestyle interventions in weight management services, and the impact of drug interventions, on weight loss and glycaemic control. It is supported by the results of five complementary studies that reviewed the effect of orlistat on type 2 diabetes and assessed the impact of the prescription patterns of anti-diabetic drugs in addition to the effects of these pharmacological interventions on weight change in comorbid patients. The first aim of this thesis is to review the evidence of the effects of orlistat on diabetic outcomes. The second aim is to evaluate the lifestyle interventions, and phase 2 of the GCWMS. Finally, the third aim is to determine the prescribing patterns of anti-diabetic drugs, and to observe the association between anti-diabetic medications and weight change. This thesis addresses the following objectives: 1. To undertake a systematic review and meta-analysis of published studies in order to review the evidence of the effects of orlistat on weight loss, specifically concerning glycosylated haemoglobin (HbA1c) and fasting plasma glucose (FPG), using the Cochrane review methodology; 2. To investigate the proportion of patients losing 5 kg of weight, commencing from their entry into the GCWMS programme, until the end of the lifestyle phase of treatment, for individuals of different ages, genders, and socioeconomic groups; 3. To study the proportion of patients losing 5 kg of weight, commencing from their entry into the GCWMS programme, until the end of phase 2, with the three different interventions of orlistat, low-calorie diet (LDL), and further weight loss (FWL); 4. To investigate the proportion of patients referred to the GCWMS on weight-neutral, mixed, and weight-gaining anti-diabetic medications; 5. To investigate the effect of baseline anti-diabetic medications on weight change for patients within a weight management programme. Chapter 2 presents the first study, which was a systemic review that considered the evidence collected in RCTs on the efficacy of orlistat for type 2 diabetes and weight loss. The effects were considered at the biochemical level and included the levels of glycosylated haemoglobin (HbA1c) and fasting plasma glucose (FPG) in people with overweight and obesity. The results, collected from 2,802 participants in 12 trials, were combined into a meta-analysis. The overall finding was that a combination of orlistat and lifestyle intervention yielded superior results. When the results were compared, it was evident that patients who are overweight or obese who were subjected to combined lifestyle and drug intervention lost more weight and had better glycaemic control than patients who were subjected to lifestyle interventions only. Chapter 3 presents the second study which appraised the effectiveness of a real-life NHS lifestyle weight management intervention in reducing body weight by ≥5 kg. The study followed 23,650 patients referred to the GCWMS, of whom 7,329 attended at least two lifestyle intervention sessions. Those individuals had either a BMI of ≥30 kg/m2, with obesity-related comorbidities, or a BMI of ≥35 kg/m2 and were aged ≥18 years. The lifestyle interventions included a combination of a 600 kcal deficit diet, exercise, and behavioural changes. 30% of the overall group succeeded in losing ≥5 kg. Out of those who completed the programme, however, a considerably higher number (46%) lost ≥5 kg. The greatest losers were men, those aged ≥40 years, those with a BMI ≥50 kg/m2, and those from areas that are more affluent. Chapter 4 presents the third study which focused on patients who lost ≥5 kg in phase 2 of the treatment provided by GCWMS which comprised a low-calorie diet (LCD), orlistat 120 mg, three times a day, or further weight loss (FWL). Participants on LCD were prescribed a 1,200 or 1,500 calorie plan; however, those on FWL repeated the lifestyle phase. There were 3,262 participants who attended at least two sessions in phase 2; these were divided into three categories: 536 who took orlistat, 1,043 who followed a LCD and 1,683 who were selected FWL. By the end of phase 2, the levels of success in terms of weight loss across the groups varied from 31% of participants in the orlistat group to 22% of participants in the LCD group and 83% of participants in the FWL group who lost ≥5 kg. Chapter 5 presents the fourth study, which evaluated the pattern of anti-diabetic drug prescriptions for comorbid patients referred to the GCWMS. The study also looked at the proportion of patients who were referred prior to and after the publication of updated SIGN guidelines for the prescription of anti-diabetic medication. In total, the study enrolled 3,063 participants who received anti-diabetic medications, of whom 47.8% received weight-neutral medications, 39.4% had mixed-effect medications and 12.7% took weight-gaining drugs. Prior to the publication of the SIGN guidelines, 11.6% of participants were on weight-gaining drugs, a proportion that did not change significantly one year after the release of the guidelines. Weight-neutral drugs were more commonly prescribed to women, those with a higher BMI and young people. No relationship was observed between the Scottish Index of Multiple Deprivation (SIMD) and anti-diabetic drug prescriptions. Weight-gaining drugs such as SUs and TZDs were more commonly prescribed to older patients and those with lower BMIs. Chapter 6 presents the fifth and final study, which investigated the effect on body weight of anti-diabetic medications in 998 participants following the lifestyle phase of the GCWMS. By the end of the programme, patients who were on weight-neutral anti-diabetic drugs achieved a mean weight change of -3.3 kg (95% confidence interval [CI]: -3.8 to -2.9 kg) and those on weight-gaining drugs achieved a mean weight change of -2.5 kg (95% CI: -3.2 to -1.8 kg), p =0.05. / Among those who completed the programme, the difference was statistically significant (p =0.005). The association between weight change and anti-diabetic drug type was not explained by differences in sex, initial BMI or age. To conclude, there was a clinically and statistically significant change in weight, HbA1c and FPG in patients with obesity and type 2 diabetes who used orlistat. Of the patients following the GCWMS lifestyle phase, less than 50% succeeded in losing at least 5 kg, with patients who completed the programme being more successful. Participants who lost weight in the lifestyle phase were selected for FWL and experienced the greatest weight loss by the end of phase 2. Those who were unsuccessful in losing 5 kg through the lifestyle programme, were offered orlistat and LCD. The large sample size increased the precision of the results, while the stratification for potential confounding factors increased the study’s validity. A higher proportion of patients were prescribed weight-neutral medications, compared with mixed and weight-gaining anti-diabetic medications. The proportion of patients on weight-gaining diabetes drugs referred to the GCWMS did not alter appreciably following the release of the SIGN guidelines. By the end of the lifestyle treatment phase, patients receiving weight-neutral drugs (metformin, DPP-IV, GLP-1, and SGLT2) were more successful in losing weight than those receiving weight-gaining drugs (SUs, TZDs, and any combination including insulin). The main recommendation from this research are, that further studies are carried out to better establish the best timing of use of orlistat within a weight management programme, that the intensity of phase 2 of the GCWMS is increased, and that prescribers take account of a patient’s current BMI prior when prescribing anti-diabetic medication, especially when recommending weight loss and referring to a weight management programme.

Congenital heart defects are a leading cause of postnatal loss; they could genetically or environmentally induced. Herbal remedies are often used during the early stages of pregnancy, being considered ‘harmless’ and ‘natural'. To alleviate pregnancy-induced symptoms, women frequently use herbal medicines such as ginger to relieve nausea and vomiting - ‘morning sickness’, gingko biloba and ginseng as dietary supplements or tonics to boost body energy and blood circulation, particularly to the brain. Also, chamomile and holy basil are recommended to promote calmness and reduce stress, often related to planned or unplanned pregnancy. These easily available and accessible medicinal herbs could be possible causes of congenital malformations. Additionally, diabetes mellitus in gestation is a considerable medical challenge, since it is related to ‎augmented dangerous morbidity and mortality for both the fetus ‎and the pregnant woman. Two in vitro methods were utilised; chick embryonic heart micromass (MM) and mouse embryonic D3 stem cells (ESD3). The potential effects of the tested herbal components in both in vitro systems were evaluated by monitoring the alteration in several endpoints. These include contractile activity (morphological scoring system), cell activity, total protein content, ROS production, DNA damage, transmembrane proteins expression (connexin43, integrin β1) and stem cell migration. In MM, 6-gingerol decreased contractility, cell activity and protein content. It caused an increase in ROS production and DNA damage and a decrease in transmembrane protein expression (connexin43, integrin β1) at high concentrations. In ESD3, 6-gingerol severely affected differentiation into cardiomyocytes cell activity and protein content at both low and high concentrations. With regards to ginkgolide A and ginkgolide B, there were alterations for few endpoints in both systems at moderate to high concentrations. G-Rg1, from ginseng, decreased contractile activity, cell activity, protein content and elevated ROS production in both systems only at high concentrations. α-bisabolol (chamomile) showed no immediate effects on all end points at low concentrations, but several disturbances occurred at high concentrations. Eugenol (holy basil) at moderate to high concentrations, significantly decreased contractility, cell activity and protein content. The diabetic formula used showed an increase in DNA damage and a decline in cell migration in mouse embryonic stem cells. Molecular endpoints indicate a role for reactive oxygen species and changes in cell membrane proteins. To summarise, these data indicate that some herbal remedies used in the first trimester of pregnancy might not be safe for fetal development. Also care needs to be taken to ensure good glycaemic control in diabetic pregnancy.