Regulatory mechanisms underlying agmatine homeostasis in humans

Regulation of agmatine homeostasis has so far only been poorly defined. In the present study, three mechanisms regulating human agmatine homeostasis were investigated. 1) Enzymatic regulation: expression of arginine decarboxylase, diamine oxidase, and ornithine decarboxylase in human colon neoplastic tissue was, at the mRNA level, about 75% and 50% lower and 150% higher, respectively, than in the adjacent normal tissue; expression of agmatinase was unchanged. 2) Bacteria-derived agmatine: ten representative bacteria strains of the human intestinal microbiota considerably differed in agmatine production and its efflux into their surrounding fluid, suggesting that the composition of the intestinal microbiota influences the agmatine availability in the gut lumen for absorption. 3) Regulation of blood plasma agmatine concentration by the human liver: at low concentrations in portal venous blood plasma, agmatine either slightly increased or further decreased in blood plasma through liver passage. Above a threshold of 14 ng/ml agmatine in the portal venous blood plasma, substantial hepatic agmatine removal from blood occurred. Taken together, a perturbation of agmatine homeostasis has been proven to be involved in the regulation of malignant cell proliferation. The amount of agmatine available for absorption, which is an important physiological source of agmatine in the human organism, should differ considerably depending on the composition of the bacterial flora in the chyme since the various species of intestinal bacteria largely differ in their ability to form agmatine. Finally, evidence has been presented that the liver plays a crucial physiological role in the maintenance of agmatine homeostasis in the human organism.     

Effect of interferon-beta and atorvastatin on Th1/Th2 cytokines in multiple sclerosis

Beneficial effects by both interferon-beta and statin treatment in patients with multiple sclerosis (MS) may be linked to interference with the Th1/Th2 cytokine balance. We determined patterns of Th1/Th2 cytokines (interleukin (IL)-1beta, IL-2, IL-6, IL-12p70, tumor-necrosis factor (TNF)-alpha and interferon-gamma, and IL-4, IL-5 and IL-10, respectively) in the serum of patients with relapsing-remitting MS treated with 250microg interferon-beta 1b or with interferon-beta plus 40mg atorvastatin. In treatment na?ve patients with MS, a trend for lower TNF-alpha serum levels compared to controls was detected (P=0.08). Interferon-beta treatment increased TNF-alpha levels, while a trend for lowering of IL-5 serum levels was found (P=0.07). Addition of atorvastatin raised IL-12p70 serum levels (P<0.05). Mean levels of two Th2 cytokines (IL-4, IL-10) showed a non-significant increase after addition of atorvastatin. We conclude that interferon-beta and atorvastatin exert divergent action on Th1/Th2 serum cytokines levels in MS. Supplemental atorvastatin might promote a Th1-type response by raising IL-12p70. Further studies are required to support a Th2 cytokine shift by atorvastatin in patients with MS.     

Functional diversity and mechanisms of action of the semaphorins

The second EMBO workshop on ;Semaphorin function and mechanisms of action', held in the gorgeous surroundings of the 12th Century Abbaye des Vaulx de Cernay near Paris, France this May, brought together a wide range of scientists working in diverse systems with a common interest: the semaphorins. Emerging new themes discussed at the meeting included the recognition of an increasingly complex way in which different cells regulate responsiveness, and the significance of considering semaphorins in the pathology of various diseases.     

Estrogen, medroxyprogesterone acetate, endothelial function, and biomarkers of cardiovascular risk in young women

Medroxyprogesterone acetate (MPA) is widely known for its use in combination hormone therapy for postmenopausal women. However, MPA is also commonly used in young women for contraception and treatment of a number of gynecological conditions. Despite its widespread use, the cardiovascular effects of MPA in young women are unclear. Therefore, the purpose of this study was to determine the acute effects of MPA when used in combination with estradiol on markers of cardiovascular risk in young women. We suppressed endogenous estrogens and progesterone in 10 premenopausal women using a gonadotropin-releasing hormone antagonist (GnRHa) for 10 days. On day 4 of GnRHa subjects received 0.1 mg of estradiol (GnRHa+E(2)), and on day 7 5 mg of MPA was added (GnRHa+E(2)+MPA). Endothelium-dependent vasodilation and endothelium-independent vasodilation of the brachial artery, lipids, homocysteine, high-sensitivity C-reactive protein, and endothelin-1 were assessed during treatment with GnRHa, GnRHa+E(2), and GnRHa+E(2)+MPA. Four additional subjects were tested to validate the efficacy of the GnRHa model and confirm the findings. Endothelium-dependent vasodilation was greater during GnRHa+E(2) than during GnRHa or GnRHa+E(2)+MPA (P = 0.006). Endothelin-1 was lower during GnRHa+E(2) than GnRHa alone (P = 0.039). Endothelin-1 increased with the addition of MPA and was not significantly different from GnRHa alone. There were no differences in the other markers of cardiovascular risk between hormone treatment days. These data suggest that acute MPA administration negates the beneficial effects of estradiol on endothelium-dependent vasodilation in young women. In addition, these data suggest that estradiol decreases endothelin-1 concentrations and the addition of MPA may counteract the effect of estradiol on endothelin-1.     

N-type Inactivation Features of Kv4.2 Channel Gating

We examined whether the N-terminus of Kv4.2 A-type channels (4.2NT) possesses an autoinhibitory N-terminal peptide domain, which, similar to the one of Shaker, mediates inactivation of the open state. We found that chimeric Kv2.1(4.2NT) channels, where the cytoplasmic Kv2.1 N-terminus had been replaced by corresponding Kv4.2 domains, inactivated relatively fast, with a mean time constant of 120 ms as compared to 3.4 s in Kv2.1 wild-type. Notably, Kv2.1(4.2NT) showed features typically observed for Shaker N-type inactivation: fast inactivation of Kv2.1(4.2NT) channels was slowed by intracellular tetraethylammonium and removed by N-terminal truncation (Δ40). Kv2.1(4.2NT) channels reopened during recovery from inactivation, and recovery was accelerated in high external K⁺. Moreover, the application of synthetic N-terminal Kv4.2 and ShB peptides to inside-out patches containing slowly inactivating Kv2.1 channels mimicked N-type inactivation. Kv4.2 channels, after fractional inactivation, mediated tail currents with biphasic decay, indicative of passage through the open state during recovery from inactivation. Biphasic tail current kinetics were less prominent in Kv4.2/KChIP2.1 channel complexes and virtually absent in Kv4.2Δ40 channels. N-type inactivation features of Kv4.2 open-state inactivation, which may be suppressed by KChIP association, were also revealed by the finding that application of Kv4.2 N-terminal peptide accelerated the decay kinetics of both Kv4.2Δ40 and Kv4.2/KChIP2.1 patch currents. However, double mutant cycle analysis of N-terminal inactivating and pore domains indicated differences in the energetics and structural determinants between Kv4.2 and Shaker N-type inactivation.     

Implications of troponin testing in clinical medicine

During the past decade considerable research has been conducted into the use of cardiac troponins, their diagnostic capability and their potential to allow risk stratification in patients with acute chest pain. Determination of risk in patients with suspected myocardial ischaemia is known to be as important as retrospective confirmation of a diagnosis of myocardial infarction (MI). Therefore, creatine kinase (CK)-MB - the former 'gold standard' in detecting myocardial necrosis - has been supplanted by new, more accurate biomarkers.Measurement of cardiac troponin levels constitute a substantial determinant in assessment of ischaemic heart disease, the presentations of which range from silent ischaemia to acute MI. Under these conditions, troponin release is regarded as surrogate marker of thrombus formation and peripheral embolization, and therefore new therapeutic strategies are focusing on potent antithrombotic regimens to improve long-term outcomes. Although elevated troponin levels are highly sensitive and specific indicators of myocardial damage, they are not always reflective of acute ischaemic coronary artery disease; other processes have been identified that cause elevations in these biomarkers. However, because prognosis appears to be related to the presence of troponins regardless of the mechanism of myocardial damage, clinicians increasingly rely on troponin assays when formulating individual therapeutic plans.     

Food, feed or medicine: The multiple functions of edible wild plants in Vietnam

Many of the edible wild plants that are included in local food baskets have both therapeutic and dietary functions. Such medicinal foods have been part of Eastern medicinal theories since ancient times and have recently received attention in the USA and Europe within the fields of functional foods, neutraceuticals and phyto-nutrients. This paper provides an example from Vietnam of the continued use of a multitude of edible wild vegetables. Vietnamese traditional medicine also holds an important position within the health care system and many of the plants that are used have both dietary and medicinal functions. Using a combination of qualitative and quantitative techniques (Rapid Rural Appraisal and Food Frequency Questionnaires), information on over 90 species of edible wild plants was obtained from 4 villages in the Mekong Delta and the Central Highlands. About a third of the plants also had therapeutic roles, forty percent were used also as livestock feeds and one fifth were used as food/livestock feed/ medicine. From a nutrition viewpoint it is important to pay attention to this group of traditional foods for several reasons. Their direct nutritional contribution is often significant but neglected. Very little is known about the health benefits of regular consumption of small quantities of medicinal foods and an important “medicinal role” of traditional plant medicines may be the contribution of small quantities of trace minerals and vitamins. The parallel functions as livestock feeds make animal products more accessible to poor households and help improve the quality of their diets.     

Vision and Eating Behavior

Objective: Eating behavior is influenced by internal and external factors. Vision is one part of the complex pattern of factors influencing the amount of food consumed during a meal. The aim of this study was to explore the impact of vision on the microstructure of eating behavior and the subjective motivation to eat. Research Methods and Procedures: Nine blind subjects and nine matched seeing control subjects consumed a standardized meal registered by VIKTOR, an eating monitor, measuring the microstructure of the eating behavior. The eating behavior of the control subjects was registered twice, with and without blindfold. Results: The eating behavior of the blind subjects did not differ from that of seeing control subjects. However, the eating behavior of seeing subjects eating with blindfold demonstrated a clear impact of vision on eating behavior. When blindfolded, subjects ate 22% less food (p < 0.05), had shorter meal durations (p < 0.05), and had less decelerated eating curves (p < 0.05). Despite a smaller amount of food consumed when blindfolded, the reported feeling of fullness was identical to that reported after the larger meal consumed without blindfold. Discussion: The importance of vision in regulating our eating behavior is further stressed in this study. Eating with a blindfold decreased the intake of food, without making subjects feel less full. Eating blindfolded, therefore, may force subjects to rely more on internal signals. These results might be used as an aid in the development of new treatment strategies for obese subjects.     

Implications of long‐distance movements of frugivorous rain forest hornbills

Long‐distance seed dispersal influences many critical ecological processes by improving chances of gene flow and maintaining genetic diversity among plant populations. Accordingly, large‐scale movements by frugivores may have important conservation implications as they provide an opportunity for long‐distance seed dispersal. We studied movement patterns, resource tracking, and potential long‐distance seed dispersal by two species of Ceratogymna hornbills, the black‐casqued hornbill C. atrata, and the white‐thighed hornbill C. cylindricus, in lowland tropical forests of Cameroon. We determined fruiting phenology of 24 tree species important in hornbill diet at monthly intervals and compared these patterns to monthly hornbill census data. After capture and radio‐tagging of 16 hornbills, we used radio telemetry by vehicle and fixed wing aircraft to determine the extent of long‐distance movements. Hornbills exhibited up to 20‐fold changes in numbers in response to fruit availability in our 25 km² study area. Also, hornbills made large‐scale movements up to 290 km, which are larger than any movement previously reported for large avian frugivores. Together, these observations provide direct evidence that hornbills are not resident and that hornbills track available fruit resources. Our results suggest that Ceratogymna hornbills embark on long‐distance movements, potentially dispersing seeds and contributing to rain forest regeneration and diversity.