M Gossell-Williams

Dietary intake of choline and plasma choline concentrations in pregnant women in Jamaica

Choline is an essential nutrient for humans and its availability during pregnancy is important for optimal fetal development. The Food and Nutrition Board of the Institute of Medicine in the United States of America has set the adequate choline intake during pregnancy at 450 mg/day. There is limited data available on normal plasma choline concentrations in pregnancy. Moreover, there are neither documented studies of choline intake among pregnant women in the Jamaican population nor of free plasma choline concentrations during pregnancy. Sixteen women presenting to the antenatal clinic of the University Hospital of the West Indies (UHWI) at 10-15 weeks of gestation were selected for this pilot study. A food frequency questionnaire was administered to estimate frequency of consumption of foods rich in choline. Fasting blood samples were collected by venepuncture and plasma assayed for choline using liquid chromatography electrospray ionization isotopic dilution mass spectrometry. Most of the women reported consumption of diets that delivered less than the recommended choline intake (mean +/- SEM, 278.5 +/- 28.9 mg). Mean plasma choline concentration was 8.4 +/- 0.4 micromol/L. This falls below the normal concentration (10 micromol/L) reported for individuals that are not pregnant and pregnant (14.5 micromol/L). The results of this study may be an indication that the choline included in the diet of pregnant women in Jamaica may not be adequate to meet both the needs of the mother and fetus and that further studies are warranted to determine clinical implications.

Supplementation with Pumpkin Seed Oil improves Plasma Lipid Profile and Cardiovascular Outcomes of Female Non-ovariectomized and Ovariectomized Sprague-Dawley Rats

Pumpkin (Cucurbita species) seed oil (PSO) is a rich source of phytoestrogens and the aim of this study was to examine the effect of PSO supplementation on the total cholesterol (TC), low density lipoprotein cholesterol (LDL‐C), triglycerides, high density lipoprotein cholesterol (HDL‐C), systolic and diastolic blood pressure in non‐ovariectomized and ovariectomized Sprague‐Dawley rats. Female rats weighing 220–300 g were divided into non‐ovariectomized rats for supplementation with corn oil (control CO; n = 6) or PSO (control PSO; n = 5) and ovariectomized rats for supplementation with corn oil (OVX/CO; n = 6) or PSO (OVX/PSO; n = 5) for 5 days per week for 12 weeks (corn oil 40 mg/kg or PSO 40 mg/kg given orally). Systolic and diastolic blood pressures were measured weekly. Blood was collected at the end of the period for plasma lipid assays. Control PSO had lower TC, LDL–C, triglycerides and higher HDL‐C than the control CO. The OVX/CO had higher TC, LDL–C, triglycerides and lower HDL‐C than the control CO and these changes were prevented in the OVX/PSO rats. PSO supplementation also resulted in lower systolic and diastolic blood pressures in both non‐ovariectomized and ovariectomized rats. It is concluded that PSO supplementation can prevent changes in plasma lipids and blood pressure associated with inadequate oestrogen availability. Copyright

The past and present use of plants for medicines

Evidence of the use of plants for medicinal purposes dates as far back as 60 000 years ago (1) in both western and eastern cultures; in both developed and undeveloped countries. For example, the pharmacopoeia of Emperor Shen Nung of China, around 2730–3000 BC, describes the medicinal use of plants such as Hemp, Aconite, Opium. The Egyptian Pharmacopoeia of Ebers Papyrus, written about 1500 BC, documents the medicinal use of plant extracts such as the poppy of Opium and oil of Castor beans (2, 3). Some of the plants commonly used today, such as peppermint (Mentha piperita), poppy (Papaver somniferum), mugwort (Artemisia vulgaris), sage (Horminum pyrenaicum), rosemary (Hyssopus officinalis), rue (Ruta graveolens) and verbena (Verbena officinalis) are well documented in the “Materia medica” of the great physician Hippocrates (about 460–370 BC) and in the several manuscripts written (around 160 AD) by Galen, a surgeon from Asia Minor. In early civilizations, illness was usually believed to be due to divine punishment. The Aztecs Indian of South America, for example, believed that particular diseases were linked to specific gods; thus their god Tlaloc was associated with diseases caused by water, such as oedema (4). Similarly, Greek physicians, such as Theoprastus, were generally followers of Asclepius, the god of Medicine. Thus the use of plants for healing became strongly associated with the gods. With the fall of the Roman Empire and the advancement of Christianity in western cultures, the use of plants for healing was discouraged. Ironically, although early Christians also saw disease and illness as divine (heaven-sent) punishment, they believed it could only be cured through repentance and prayer, not through the use of medicinal plants. Additionally, as Christianity only recognizes the power of one God, the strong association of many gods and plant medicines led to the value of plant medicines becoming clouded in myths. By the 1500s AD, the use of plants as medicine in western society became further mystified by the “Doctrine of Signatures”. Supporters of the doctrine believed that the physical attributes of plants were indications of their medicinal value. Thus, the holes in the leaves of St John’s wort (Hypericum perforatum) signified

Angiotensin converting enzyme inhibiting and anti‐dipsogenic activities of Euphorbia hirta extracts

The methanol extract obtained from the leaves and stems of Euphorbia hirta inhibited the activity of angiotensin converting enzyme (ACE) by 90% and 50% at 500u2009μg and 160u2009μg respectively using enzyme linked immunosorbent assay (ELISA). The effect of the extract on thirst was examined using Wistar rats. Intraperitoneal administration of 10u2009mg/100u2009mg body wt of the extract significantly (p <0.05) decreased the amount of water consumed by rats. This effect lasted for 2u2009h.

Improvement in HDL cholesterol in postmenopausal women supplemented with pumpkin seed oil: pilot study

ABSTRACT Objective Pumpkin seed oil is rich in phytoestrogens and animal studies suggest that there is some benefit to supplementation in low estrogen conditions. This study is the first to evaluate the benefit of pumpkin seed oil in postmenopausal women. Methods This pilot study was randomized, double-blinded and placebo-controlled. Study participants included 35 women who had undergone natural menopause or had iatrogenically entered the climacteric due to surgery for benign pathology. Wheat germ oil (placebo; n = 14) and pumpkin seed oil (n = 21) were administered to eligible participants over a 12-week period at a dose of 2 g per day. Serum lipids, fasting plasma glucose and blood pressure were measured and an 18-point questionnaire regarding menopausal symptoms was administered; the atherogenic index was also calculated. Differences between groups, as well as before and after the period of supplementation, were evaluated with Students t-test, Wilcoxon matched-pair signed-ranked test and Mann–Whitney test, as appropriate (Stata version 10.1). Results Women receiving pumpkin seed oil showed a significant increase in high density lipoprotein cholesterol concentrations (0.92 ± 0.23 mmol/l vs. 1.07 ± 0.27 mmol/l; p = 0.029) and decrease in diastolic blood pressure (81.1 ± 7.94 mmHg vs. 75.67 ± 11.93 mmHg; p < 0.046). There was also a significant improvement in the menopausal symptom scores (18.1 ± 9.0 vs. 13.2 ± 6.7; p < 0.030), with a decrease in severity of hot flushes, less headaches and less joint pains being the main contributors. Women in the group receiving wheat germ oil reported being more depressed and having more unloved feeling. Conclusion This pilot study showed pumpkin seed oil had some benefits for postmenopausal women and provided strong evidence to support further studies.

Synthesis, pharmacological studies and molecular modeling of some tetracyclic 1,3-diazepinium chlorides.

Seven new 1,3-diazepinium chlorides exhibiting some structural similarities to the 1,4-benzodiazepines were synthesized. In a Hippocratic screen using mice, three of these salts, 3-methoxy-6-oxo-7,13-dihydro-6H-benzofuro[2,3-e]pyrido[1,2-a][1,3]diazepin-12-ium chloride (8a), 3-methoxy-9-methyl-6-oxo-7,13-dihydro-6H-benzofuro[2,3-e]pyrido[1,2-a][1,3]diazepin-12-ium chloride (8c) and 3-methoxy-11-methyl-6-oxo-7,13-dihydro-6H-benzofuro[2,3-e]pyrido[1,2-a][1,3]diazepin-12-ium chloride (8e) were examined for their effect on the central nervous system, and their activities compared to that of diazepam. On their own, salts 8a, 8c and 8e solicited no sedative effects on the behaviour of the animals. However, they elicited significant effects in combination with diazepam on diazepam-induced activities such as decreased motor activity, ataxia and loss of righting reflex. Compounds 8a and 8c were fitted into the pharmacophore/receptor model developed by Cook et al. with interaction at the L(1), H(1) and A(2) sites indicating that they are potential inverse agonists of the Bz receptor. The compounds displayed some affinity for the alpha1 isoform of the GABA(A)/BzR (L(Di) interaction) but are non-selective for alpha5 (no L(2) interaction). Results of binding affinity studies showed that compound 8a is mildly selective for the alpha1 receptor although not very potent (K(i)=746.5nM). The significant potentiation of diazepam-induced ataxia and decreased motor activity by compounds 8a and 8c in the Hippocratic screen may be associated with alpha1 selectivity.

Monoclonal Antibodies in Cancer Therapy: Mechanisms, Successes and Limitations.

Rituximab was the first chemotherapeutic monoclonal antibody (CmAb) approved for clinical use in cancer therapeutics in 1997 and has significantly improved the clinical outcomes in non-Hodgkins lymphoma. Since then, numerous CmAbs have been developed and approved for the treatment of various haematologic and solid human cancers. In this review, the classification, efficacy and significantly reduced toxicity of CmAbs available for use in the United States of America are presented. Finally, the limitations of CmAbs and future considerations are explored.

A Review of Pharmacovigilance.

Pharmacovigilance supports safe and appropriate use of drugs. Spontaneous reporting of adverse drug reactions (ADRs) is an essential component of pharmacovigilance. However, there is significant underreporting of ADRs. Adverse drug reactions have become a major problem in developing countries. Knowledge of pharmacovigilance could form the basis for interventions aimed at improving reporting rates and decreasing ADRs.

Choline: are our university students eating enough?

Choline is an essential nutrient; dietary deficiency of choline is associated with impaired liver function, elevated blood concentrations of alanine aminotransferase, creatinine phosphokinase and homocysteine. There is also depletion of acetylcholine concentration in the brain, leading to deficit in memory function. The authors examined the dietary intake of choline in groups of students at the Mona Campus of the University of the West Indies. Sixty-two medical students (first and second years) and biochemistry students (final year) were recruited They were asked to (including amounts) record all foods and drinks consumed for three days (two weekdays and one weekend day). The sheets were collected and the amount of choline and betaine (a metabolite of choline) consumed were calculated Dietary intake of folate was also evaluated. The analysis revealed that 86.2% of the females and 90.9% of the males reported diets that delivered less daily choline than the adequate intake quoted by the Institute of Medicine of the National Academy of Sciences, USA (425-550 mg/day). The betaine consumption ranged between 25 to 620 mg/day (no adequate intake documented) and the folate consumed was more than the recommended daily allowance of folate (180-200 microg/day). The dietary intake of choline in the majority of students is below adequate intake. Although folate also serves similar functions to choline, it is unlikely that it can substitute for choline in all physiological aspects and therefore the implications of low dietary choline need further investigation.

Isolation of a muscarinic alkaloid with ocular hypotensive action from Trophis racemosa

A muscarinic alkaloid with a quaternary nitrogen was isolated from Trophis racemosa. Aqueous solutions (0.5%–2%) of the chloride salt of the alkaloid produced dose‐dependent reductions of intra‐ocular pressure ranging from 6.6u2005±u20050.7u2005mmHg to 15.7u2005±u20050.3u2005mmHg, (pu2005<u20050.001, nu2005=u20055) in dogs. Atropine (0.1u2005mL of a 1% solution) and pirenzepine at a non selective antagonist dose (0.1u2005mL of 0.5% solution) for M1 and M3 receptors blocked the reduction of intra‐ocular pressure, but alpha‐adrenoceptor blockade with phenoxybenzamine (0.1u2005mL of a 1% solution) did not block the reduction of intra‐ocular pressure. On the isolated guinea‐pig ileum and trachea, the alkaloid produced contractions which were inhibited by atropine (6u2005×u200510−7M or 0.4u2005µg/mL) and by pirenzepine at a non‐selective antagonist dose (3.1u2005×u200510−6M or 1.3u2005µg/mL) for M1 and M3 receptors. But neither selective blockade of M2 receptors with gallamine (1.7u2005×u200510−6M or 1.5u2005µg/mL) nor selective blockade of M1 receptors with pirenzepine (7u2005×u200510−9M or 3u2005ng/mL) inhibited the alkaloid‐induced contractions. There was also no inhibition of the alkaloid‐induced contractions in the presence of ganglionic nicotinic receptor blockade with pentolinium (5.6u2005×u200510−7M or 0.3u2005µg/mL) and hexamethonium (1.7u2005×u200510−6M or 0.6u2005µg/mL), but nicotine‐induced contractions were inhibited by these ganglionic blockers. These results suggest that a muscarinic alkaloid from Trophis racemosa produced ocular hypotension via M3 receptor stimulation in dogs. Copyright