The Effect of Natural Mulches on Crop Performance, Weed Suppression and Biochemical Constituents of Catnip and St. John's Wort.

Because of expanding markets for high-value niche crops, opportunities have increased for the production of medicinal herbs in the USA. An experiment was conducted in 2001 and 2002 near Gilbert, IA, to study crop performance, weed suppression, and environmental conditions associated with the use of several organic mulches in the production of two herbs, catnip (Nepeta cataria L.) and St. John's wort (Hypericum perforatum L. 'Helos'). Treatments were arranged in a completely randomized design and included a positive (hand-weeded) control, a negative (nonweeded) control, oat straw, a flax straw mat, and a nonwoven wool mat. Catnip plant height was significantly greater in the oat straw than the other treatments at 4 wk through 6 wk in 2001; at 4 to 8 wk in 2002, catnip plant height and width was significantly lower in the negative control compared with the other treatments. Catnip yield was significantly higher in the flax straw mat than all other treatments in 2001. In 2002, St. John's wort yields were not statistically different in any treatments. All weed management treatments had significantly fewer weeds than the non-weeded rows in 2002. Total weed density comparisons in each crop from 2 yr showed fewer weeds present in the flax straw and wool mat treatments compared with positive control plots. There was no significant weed management treatment effect on the concentration of the target compounds, nepetalactone in catnip and pseudohypericin-hypericin in St. John's wort, although there was a trend toward higher concentrations in the flax straw treatment.

Ghana: defining the African challenge.

In 1957, Ghana became the first African nation to achieve independence from its colonial ruler. But since then Ghana has suffered mixed political and economic fortunes. The health of Ghana's people and the country's progress in modernising its health-care system have fluctuated according to peaks and troughs in West African history. Some critics see Ghana's course since independence as a promise unfulfilled. Others view Ghana as a model for North-South cooperation, which could be rolled out across the whole of Africa. In November, 2001, I visited hospitals and health centres in both rural and urban settings to investigate the present state of Ghanaian medicine. The picture I saw was one of a country clear about what it wants to do but divided about how it should achieve its goals. If Ghana is to be a model for Africa, it is more a model of problems to be faced than solutions discovered.

gamma-glutamyltranspeptidase-deficient knockout mice as a model to study the relationship between glutathione status, mitochondrial function, and cellular function.

gamma-Glutamyltranspeptidase (GGT)-deficient mice (GGT(-/-)) display chronic glutathione (GSH) deficiency, growth retardation, and die at a young age (<20 weeks). Using livers from these mice, we investigated the relationship between GSH content, especially mitochondrial, and mitochondrial and cellular function. We found that the GSH content of isolated liver mitochondria was diminished by >/=50% in GGT(-/-) mice when compared with wild-type mice. Respiratory control ratios (RCRs) of GGT(-/-) mice liver mitochondria were /=40% in mitochondria obtained from GGT(-/-) mice. We observed a strong correlation between mitochondrial GSH content and RCRs. Even moderate decreases (<50%) correlated with adverse effects with respect to respiration. Electron microscopy revealed that livers from GGT(-/-) knockout mice were deprived of fat and glycogen, and swollen mitochondria were observed in animals that were severely deprived of GSH. Thus, GGT(-/-) mice exhibit a loss of GSH homeostasis and impaired oxidative phosphorylation, which may be related to the rate of adenosine triphosphate (ATP) formation and subsequently leads to progressive liver injury, which characterizes the diseased state. We also found that supplementation of GGT(-/-) mice with N-acetylcysteine (NAC) partially restored liver GSH, but fully restored mitochondrial GSH and respiratory function. Electron microscopy revealed that the livers of NAC-supplemented GGT(-/-) mice contained fat and glycogen; however, slightly enlarged mitochondria were found in some livers. NAC supplementation did not have any beneficial effect on the parameters examined in wild-type mice.

Lack of effect of St John's Wort on carbamazepine pharmacokinetics in healthy volunteers.

BACKGROUND: St John's Wort is a popular herbal product used by approximately 7% of patients with epilepsy. Previous reports have described reductions in concentrations of CYP3A4 substrates indinavir and cyclosporine (INN, ciclosporin) associated with St John's Wort. OBJECTIVE: Our objective was to determine the effect of St John's Wort on steady state carbamazepine and carbamazepine-10,11-epoxide pharmacokinetics. METHODS AND SUBJECTS: Eight healthy volunteers (5 men; age range, 24-43 years) participated in this unblinded study. Subjects received 100 mg of carbamazepine twice daily for 3 days, 200 mg twice daily for 3 days, and then 400 mg once daily for 14 days. Blood samples were collected before and 1, 2, 4, 6, 8, 10, 12, and 24 hours after the dose on day 21. The subjects then took 300 mg of St John's Wort (0.3% hypericin standardized tablet) 3 times daily with meals and with carbamazepine for 14 days. On day 35, blood sampling was repeated. Plasma samples were analyzed for carbamazepine and carbamazepine-10,11-epoxide with HPLC. We compared carbamazepine and carbamazepine-10,11-epoxide noncompartmental pharmacokinetic parameter values before and after St John's Wort with a paired Student t test. RESULTS: We found no significant differences before or after the administration of St John's Wort in carbamazepine peak concentration (7.2 +/- 1 mg/L before versus 7.6 +/- 1.3 mg/L after), trough concentration (4.8 +/- 0.5 mg/L before versus 4.3 +/- 0.8 mg/L after), area under the plasma concentration-time curve (142.4 +/- 12.9 mg x h/L before versus 143.8 +/- 27.2 mg x h/L after), or oral clearance (2.8 +/- 0.3 L/h before versus 2.9 +/- 0.6 L/h after). Similarly, no differences were found in peak concentration (2 +/- 0.5 mg/L before versus 2.1 +/- 0.4 mg/L after), trough concentration (1.3 +/- 0.3 mg/L before versus 1.4 +/- 0.3 mg/L after), and area under the plasma concentration-time curve (37.5 +/- 7.4 mg x h/L before versus 41.9 +/- 10.3 mg x h/L after) of carbamazepine-10,11-epoxide. CONCLUSIONS: The results suggest that treatment with St John's Wort for 14 days did not further induce the clearance of carbamazepine.

The influence of gender and age on neonatal rat hypothalamic 5-HT1A and 5-HT2A receptors.

1. Rat hypothalamic 5-hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) concentrations are transiently sexually differentiated in the second week postpartum (pp), with higher levels in the female. In this report we investigate the possibility that 5-HT receptors may also exhibit sexual dimorphism in the neonatal period. 2. 5-HT1A and 5-HT2A receptors were quantitated by radioligand binding of [3H]ketanserin and [3H]8-OH DPAT, respectively, in hypothalamus and amygdala from male and female rats at days 8-16 pp. 3. There was no sexual dimorphism or change in the density of 5-HT2A binding in hypothalamus or amygdala over days 8-16 pp. There was also no sexual dimorphism of 5-HT1A receptors. 4. There was an increase in 5-HT1A receptor density in both the hypothalamus and the amygdala. In the hypothalamus, but not the amygdala, this increase was interrupted on day 14 by a decrease in 5-HT1A receptors, which we suggest may be of physiological significance in modifying the eventual pattern of adult agonistic activity. 5. The results suggest that the sexual dimorphism in 5-HT turnover is predominantly presynaptic, relating to altered synthesis and/or release, and is not of sufficient magnitude or duration to produce adaptive responses in postsynaptic 5-HT1A or 5-HT2A receptors.

Procoagulant activity in cancer cells is dependent on tissue factor expression.

Procoagulant activity of pairs of cell lines, which were derived from the same original cell type but which possess different growth characteristics and metastatic properties, was examined. The following characteristics were considered suggestive of a greater likelihood of metastatic potential: high histological grade; establishment of the line from a metastatic rather than a nonmetastatic cancer; increased tumorigenicity in nude mice; and/or estrogen receptor-negative mammary cancer. Procoagulant activity was evaluated by a two stage clotting assay. Procoagulant activity was highly variable, with up to a 1,300-fold difference, among the cancer cell lines examined. The rate of clot formation was factor VII dependent and was totally inhibited by an anti tissue factor monoclonal antibody, indicating that tissue factor was the only significant procoagulant present in these cancer cells. Tissue factor antigen expression, evaluated by ELISA, correlated with procoagulant activity. In all pairs of cancer cell lines, those with characteristics of increased proliferative potential had increased tissue factor levels compared to cell lines that originated from the same cell type, but which possess less aggressive characteristics. Tissue factor activity in these cancer cells was increased by cell lysis or by exposure of intact cells to a calcium ionophore, similar to results previously obtained in fibroblasts. Tissue factor mRNA was evaluated by northern blot analysis using a specific probe complementary to tissue factor mRNA. The previously described predominant tissue factor mRNA species of 2.2 kb was identified in the majority of cancer cell lines examined, but tissue factor mRNA species of 3.2 to 3.4 kb were also identified.(ABSTRACT TRUNCATED AT 250 WORDS)

Excretion of lignocaine and its metabolite monoethylglycinexylidide in breast milk following its use in a dental procedure. A case report.

The excretion of lignocaine in breast milk has been documented in a 34-year-old woman following the injection of 20 mg lignocaine for a dental alloy restoration in the right upper quadrant. Lignocaine and its primary metabolite monoethylglycinexylidide in milk and plasma were quantified by high-performance liquid chromatography. The concentration of lignocaine in milk ranged from 44-66 micrograms l-1 while that for monoethylglycinexylidide ranged from 35-41 micrograms l-1. The milk: plasma ratios for lignocaine and monoethylglycinexylidide were 1.1 and 1.8, respectively. The calculated daily infant doses for the parent drug and metabolite were both less than 0.01 mg kg-1 day-1. With the exception of very rare allergic reactions, these levels of infant exposure are extremely low and of no toxicological significance. Nursing mothers receiving lignocaine for standard dental procedures can be advised that continuation of breast feeding is safe.

Brain beta-adrenoceptor binding sites in depressed suicide victims: effects of antidepressant treatment.

beta-Adrenoceptor binding sites were measured by saturation binding of [3H]CGP 12177 in nine brain regions from 13 suicides, with a firm retrospective diagnosis of depression, who had been receiving antidepressant drugs, and 11 matched controls. Significantly lower numbers of beta-adrenoceptor binding sites were found in thalamus and temporal cortex (Brodmann area 38), but not in other brain regions, of antidepressant-treated suicides compared to controls. The lower number of beta-adrenoceptor binding sites in thalamus appeared to be related to drug treatment, whereas lower numbers of beta-adrenoceptors in temporal cortex were also found in antidepressant-free suicides.

Morphine decreases LH secretion in ovariectomized ewes only after steroid priming and not by direct pituitary action.

To determine whether opiates directly modulate pituitary LH secretion in vivo, morphine was administered to hypothalamo-pituitary-disconnected (HPD) ewes which were receiving exogenous pulses of GnRH. To define the steroidal background which is permissive to a morphine-induced decrease in LH secretion, ovariectomized (OVX) ewes were treated as follows in groups of four: group 1, no implant; group 2, small 17 beta-estradiol (E2) (1 cm long x 0.33 diameter) and progesterone (P) implants; group 3, medium E2 (1 cm long x 0.46 diameter) and P implants, and group 4, medium E2 implants. Jugular blood samples were taken at 10-min intervals for 9 h, during which there was a 3-hour pretreatment period, a 3-hour treatment period when the sheep were given six intravenous injections of 10 mg morphine every 30 min, and a 3-hour run-off period. Morphine inhibited the mean plasma concentrations of LH and LH pulse frequency in group 3 only, and in 2/4 ewes in this group LH secretion was abolished and did not return to a pulsatile mode during the 3-hour run-off sampling period. In a second experiment designed to test the pituitary action of morphine, OVX-HPD ewes were primed with medium E2 and P implants and were given hourly pulses of 250 ng GnRH intravenously. Jugular blood samples were taken around each GnRH pulse over an 8-hour period. The first three pulses served as a control sampling period, after which the sheep were treated with morphine (six intravenous injections of 10 mg morphine every 30 min).(ABSTRACT TRUNCATED AT 250 WORDS)

5-HT2 receptor binding and 5-HT uptake in mouse brain: developmental changes and the relationship to audiogenic seizure susceptibility in DBA/2J mice.

Abnormal function of serotonergic neurones may be involved in the age-related susceptibility of DBA/2J mice to generalised convulsions induced by auditory stimulation. We have measured 5-HT2 receptor binding sites and synaptosomal 5-HT uptake in 5 brain regions of DBA/2J mice at ages before, during and after their maximal susceptibility to audiogenic seizures and in age-matched C57 B1/6 mice, a strain resistant to audiogenic seizures at all ages. The number of 5-HT2 binding sites was 20% higher in the cerebral cortex of DBA/2J than C57 B1/6 mice at the time of maximal susceptibility of DBA/2J mice to audiogenic seizures but did not differ at other ages. The number of 5-HT2 binding sites did not differ between the two strains at the ages studied in forebrain, mid-brain, hippocampus and pons-medulla. A marked reduction in the number of 5-HT2 binding sites was apparent in the mid-brain, hippocampus and pons-medulla of both strains of mice between 13-15 days of age and 21-23 days of age. Synaptosomal 5-HT uptake did not differ significantly between DBA/2J and C57 B1/6 in any of the brain regions at the ages studied. The higher density of cortical 5-HT2 binding sites in DBA/2J mice may contribute to their susceptibility to sound-induced seizures.

Brain GABAB binding sites in depressed suicide victims.

Binding sites for gamma-aminobutyric acid, type B (GABAB), were measured in post-mortem brain samples (frontal cortex, temporal cortex, and hippocampus) from a group of suicide victims and a group of sex- and age-matched controls. Retrospective psychiatric diagnosis was performed, and only suicide victims with clear evidence of depression in the absence of symptoms of other psychiatric or neurological disorders were studied. There were no significant differences between depressed suicides and controls in the number or affinity of GABAB binding sites in the frontal or temporal cortex and no difference in GABAB binding (measured at two concentrations) in the hippocampus. Thirteen of the depressed suicides had not been prescribed antidepressant drugs recently, and none were found in their blood at postmortem. The number of GABAB binding sites in the frontal and temporal cortex and GABAB binding in the hippocampus did not differ significantly between these drug-free suicides and matched controls. The Kd was higher, however, in the temporal cortex of the drug-free suicides than in the controls. A significant negative correlation was found between age and the number of GABAB binding sites in the temporal cortex (on the basis of pooled data from suicides and controls). These results indicate that GABAB binding sites are unaltered in the brains of depressed suicide victims.

Naloxone evokes large-amplitude GnRH pulses in luteal-phase ewes.

Ewes were sampled during the mid-late luteal phase of the oestrous cycle. Hypophysial portal and jugular venous blood samples were collected at 5-10 min intervals for a minimum of 3 h, before i.v. infusions of saline (12 ml/h; N = 6) or naloxone (40 mg/h; N = 6) for 2 h. During the 2-h saline infusion 2/6 sheep exhibited a GnRH/LH pulse; 3/6 saline infused ewes did not show a pulse during the 6-8-h portal blood sampling period. In contrast, large amplitude GnRH/LH pulses were observed during naloxone treatment in 5/6 ewes. The mean (+/- s.e.m.) amplitude of the LH secretory episodes during the naloxone infusion (1.07 +/- 0.11 ng/ml) was significantly (P less than 0.05) greater than that before the infusion in the same sheep (0.54 +/- 0.15 ng/ml). Naloxone significantly (P less than 0.005) increased the mean GnRH pulse amplitude in the 5/6 responding ewes from a pre-infusion value of 0.99 +/- 0.22 pg/min to 4.39 +/- 1.10 pg/min during infusion. This episodic GnRH secretory rate during naloxone treatment was also significantly (P less than 0.05) greater than in the saline-infused sheep (1.53 +/- 0.28 pg/min). Plasma FSH and prolactin concentrations did not change in response to the opiate antagonist. Perturbation of the endogenous opioid peptide system in the ewe by naloxone therefore increases the secretion of hypothalamic GnRH into the hypophysial portal vasculature. The response is characterized by a large-amplitude GnRH pulse which, in turn, causes a large-amplitude pulse of LH to be released by the pituitary gland.

Evidence that prostacyclin modulates the vascular actions of calcium in man.

Increases in extracellular calcium (Ca++) can alter vascular tone, and thus may result in increased blood pressure (Bp) and reduced renal blood flow (RBF). Ca++ can stimulate prostaglandin E2 (PGE2) and/or prostacyclin (PGI2) release in vitro, which may modulate Ca++ vascular effects. However, in man, the effect of Ca++ on PG release is not known. To study this, 14 volunteers received low-dose (2 mg/kg Ca++ gluconate) or high-dose (8 mg/kg) Ca++ infusions. The low-dose Ca++ infusion did not alter systemic or renal hemodynamics, but selectively stimulated PGI2, as reflected by the stable metabolite 6-keto-PGF1 alpha in urine (159 +/- 21-244 +/- 30 ng/g creatinine, P less than 0.02). The same Ca++ infusion given during cyclooxygenase blockade with indomethacin or ibuprofen was not associated with a rise in PGI2 and produced a rise in Bp and fall in RBF. However, sulindac, reported to be a weaker renal PG inhibitor, did not prevent the Ca++ -induced PGI2 stimulation (129 +/- 33-283 +/- 90, P less than 0.02), and RBF was maintained despite similar increases in Bp. The high-dose Ca++ infusion produced an increase in mean Bp without a change in cardiac output, and stimulated urinary 6-keto-PGF1 alpha to values greater than that produced by the 2-mg/kg Ca++ dose (330 +/- 45 vs. 244 +/- 30, P less than 0.05). In contrast, urinary PGE2 levels did not change. A Ca++ blocker, nifedipine, alone had no effect on Bp or urinary 6-keto-PGF1 alpha levels, but completely prevented the Ca++ -induced rise in Bp and 6-keto-PGF1 alpha excretion (158 +/- 30 vs. 182 +/- 38, P greater than 0.2). However, the rise in 6-keto-PGF1 alpha was not altered by the alpha 1 antagonist prazosin (159 +/- 21-258 +/- 23, P less than 0.02), suggesting that calcium entry and not alpha 1 receptor activation mediates Ca++ pressor and PGI2 stimulatory effects. These data indicate a new vascular regulatory system in which PGI2 modulates the systemic and renal vascular actions of calcium in man.