An autocrine role for pituitary GABA: Activation of GABA-B receptors and regulation of growth hormone levels

There is increasing evidence suggesting that the neurotransmitter gamma-aminobutyric acid (GABA) is a local factor involved in the regulation of endocrine organs. Examples of such functions are documented in the pancreas, but recent results suggest that GABA may act in a similar way in the pituitary, in which GABA receptors are expressed and pituitary growth hormone (GH) cells provide a source of GABA. We hypothesised that GABA secreted in somatotropes may act as an autoregulatory signaling molecule. To test this hypothesis we first examined the nature of GABA receptors expressed by GH cells. RT-PCR analysis demonstrated that GABA-B receptor subunits R1 and R2 are present in the whole rat pituitary. Laser microdissection of immunostained GH cells, followed by RT-PCR as well as immunoelectron microscopy, showed that GABA-B receptors are expressed on somatotropes. To investigate GABA-B receptor function in somatotropes, we used rat GH3 adenoma cells, which, like pituitary GH cells, express GABA-B R1 and R2 (as assessed by RT-PCR and immunoelectron microscopy) and produce GABA (checked by high performance liquid chromatography). After inhibition of endogenous GABA synthesis, GH production was stimulated by baclofen, a chromatography). After inhibition of endogenous GABA synthesis, GH production was stimulated by bactofen, a GABA-B receptor agonist. By contrast, blocking GABA-B receptors by an antagonist, phaclofen, decreased GH levels. We conclude that in GH-producing cells, GABA acts as an autocrine factor via GABA-B receptors to control GH levels. Copyright (C) 2002 S. KargerAG, Basel

Sinc-Galerkin method for solving nonlinear boundary-value problems

AbstractThe sinc-Galerkin method is used to approximate solutions of nonlinear problems involving nonlinear second-, fourth-, and sixth-order differential equations with homogeneous and nonhomogeneous boundary conditions. The scheme is tested on four nonlinear problems. The results demonstrate the reliability and efficiency of the algorithm developed

The Role of Local Agency in Peacebuilding: The Case of the Bawku Inter-Ethnic Peace Committee

This article explores the failure of top-level interventions in the resolution of local conflicts and the role of local agency in peacebuilding. The article relied primarily on qualitative techniques and instruments to collect data to examine why top-level interventions by successive governments have failed to resolve the Bawku chieftaincy conflict. The article finds that top-level interventions have failed to resolve the conflict because they are introduced with little to no participation by local communities. These interventions are, therefore, unable to garner grassroot support and commitment. In contrast, the BIEPC led peace process has been more successful in the management of the conflict because it is a bottom-up approach with representatives from the various ethnic groups working together in an attempt to find common solutions to their differences. The adoption of indigenous conflict resolution mechanisms provides inclusion and participation by the wider community, and also serves to restore communal harmony and relationship among the people, their ancestors and the gods of the community. In spite of recent setbacks in the peace process, the BIEPC offers the most promising route to the resolution of the structural causes of the conflict

Evidence for a GABAergic system in rodent and human testis: Local GABA production and GABA receptors

The major neurotransmitter of the central nervous system, gamma-aminobutyric acid (GABA), exerts its actions through GABA(A), GABA(B) and GABA(C) receptors. GABA and GABA receptors are, however, also present in several non-neural tissues, including the endocrine organs pituitary, pancreas and testis. In the case of the rat testis, GABA appears to be linked to the regulation of steroid synthesis by Leydig cells via GABA(A) receptors, but neither testicular sources of GABA, nor the precise nature of testicular GABA receptors are fully known. We examined these points in rat, mouse, hamster and human testicular samples. RT-PCR followed by sequencing showed that the GABA-synthesizing enzymes glutamate decarboxylase (GAD) 65 and/or GAD67, as well as the vesicular GABA transporter vesicular inhibitory amino acid transporter (VIAAT/VGAT) are expressed. Testicular GAD in the rat was shown to be functionally active by using a GAD assay, and Western blot analysis confirmed the presence of GAD65 and GAD67. Interstitial cells, most of which are Leydig cells according to their location and morphological characteristics, showed positive immunoreaction for GAD and VIAAT/VGAT proteins. In addition, several GABA(A) receptor subunits (alpha1-3, beta1-3, gamma1-3), as well as GABAB receptor subunits R1 and R2, were detected by RT-PCR. Western blot analysis confirmed the results for GABA(A) receptor subunits beta2/3 in the rat, and immunohistochemistry identified interstitial Leydig cells to possess immunoreactive GABA(A) receptor subunits beta2/3 and alpha1. The presence of GABA(A) receptor subunit alpha1 mRNA in interstitial cells of the rat testis was further shown after laser microdissection followed by RT-PCR analysis. In summary, these results describe molecular details of the components of an intratesticular GABAergic system expressed in the endocrine compartment of rodent and human testes. While the physiological significance of this peripheral neuroendocrine system conserved throughout species remains to be elucidated, its mere presence in humans suggests the possibility that clinically used drugs might be able to interfere with testicular function. Copyright (C) 2003 S. Karger AG, Basel

Improved Quality of Color Sumatra Barb, Puntigrus Tetrazona (Bleeker, 1855) with Artificial Feed Enriched Red Spinach Flour (Amaranthus Tricolor L.)

Ikan sumatra albino (Puntigrus tetrazona) merupakan salah satu ikan hias asli Indonesia yang berasal dari pulau Sumatera. Budidaya ikan sumatra albino mengalami penurunan dalam kualitas warna karena spesies ini tidak dapat memproduksi karotenoid dalam tubuhnya. Guna mengatasi permasalahan ini, maka dibutuhkan sebuah alternatif berupa penambahan karotenoid dalam pakan. Penelitian ini bertujuan untuk mengkaji efektivitas dosis tepung bayam merah sebagai pakan terhadap kualitas warna ikan sumatra albino. Ikan hias sumatra albino dengan bobot 0,54 g dan panjang 3,50 cm dipelihara di dalam akuarium (30 cm x 20 cm x 20 cm).Penelitian ini menggunakan Rancangan Acak Lengkap (RAL) dengan empatperlakuan (A=0% (kontrol), B=2%, C=4%, dan D=6%) dan tiga ulangan. Parameter yang diamati meliputi nilai kualitas warna kulit ikan (L=lightness, C=chroma, dan H=hue) dan total karotenoid pada kulit, sirip,serta daging ikan sumatra albino. Ikan dipelihara selama 42 hari dan diberi pakan tigakali sehari. Hasil penelitian menunjukkan bahwapenambahantepung bayam merah pada dosis 6%dengan kandungan karotenoid 45,26 ppm pada pakan, 50,44 ppm pada sirip, 16,10 ppm pada kulit, dan 3,69 ppm pada daging, dapat meningkatkan kualitas warna ikan sumatra albino. Hal tersebut diindikasikan dengan menurunnya nilai L=60,83%, meningkatnya nilai C=20,57%, dan mempertahankan nilai H=87,09°

Low copper levels measured in the aortic wall of New Zealand patients with non-syndromic ascending thoracic aortic aneurysm

OBJECTIVES: Studies in animals have shown causal relationships between copper (Cu) deficiency and the development of thoracic aortic aneurysms (TAAs) [1, 2]. Cu deficiency is widespread in New Zealand (NZ) soils; the high soil pH from the use of lime fertilizers reduces the bioavailability of Cu for grazing animals and growing plants; this, in turn, reduces Cu availability in the NZ human food chain. Our study is a pilot study to explore associations between Cu and TAA. We measured Cu levels in aneurysmal aortic tissues in patients undergoing Bentall procedures and non-aneurysmal aortic tissue from coronary artery bypass graft patients. METHODS: Aortic samples were collected from 2 groups of patients during elective open-heart surgery over 4 months between November 2017 and February 2018. The groups were a TAA group, patients with non-syndromic aortic aneurysm and without the bicuspid aortic valve or known infectious or inflammatory condition (ANEURYSM; n = 13), and a control coronary artery bypass graft group (CONTROL; n = 44). Standardized digested dry tissue weighed samples were analysed from both groups. Tissue extraction of trace elements was carried out using HCl-H2O2 digestion and a highly sensitive analytical technique, inductively coupled plasma mass spectrometry-used to measure elemental concentrations. RESULTS: Cu concentration (mean ± SD) was significantly lower in ANEURYSM (3.34 ± 0.16 µg/g) when compared to the CONTROL group tissues (4.33 ± 0.20 µg/g) (dry weight; mean ± SD; Student's t-test, P < 0.05). Over 46% of the Aneurysm patients were Maori and live in a geographically Cu-deficient NZ territory. CONCLUSIONS: Cu deficiency may play a role in the development or progression of non-syndromic ascending aortic aneurysms in NZ. Maori patients are more at risk as they commonly live in rural NZ, dependent on locally grown nutritional sources. Further studies are required to confirm this exciting finding and to establish cause and effect relationship

Cholesterol Synthesis in the Intestine of Man: Regional Differences and Control Mechanisms

A B S T R A C T Cholesterol in the circulating serum pool is derived either from absorption of dietary cholesterol or from endogenous synthesis principally in the liver and gastrointestinal tract. While the control of intestinal cholesterogenesis has been elucidated in several lower animal species, no data currently are available in the case of man. In the present study using tissue specimens obtained by suction biopsy in 29 normal subjects, we have shown the rate of cholesterogenesis is low in the stomach (25 ±6 mumoles/g per 2 hr) and rectum (40 +8 mimoles/g per 2 hr); in the small bowel the rate progressively decreases in the proximal duodenum (90 +16 mnvmoles/g per 2 hr); distal duodenum (80 ±11 mymoles/g per 2 hr); and distal jejunum (35 ±5 mnmoles/g per 2 hr); but abruptly increases in the distal ileum (280 ±33 mnmoles/g per 2 hr). Indirect evidence is provided that the intestinal crypt epithelium is the main site of this sterol synthesis. Fasting for 48 hr suppressed the rate of cholesterogenesis in the distal duodenum from a control value of 80 ±+11 m/Amoles/g per 2 hr to 40 ±8 mumoles/g per 2 hr while cholesterol feeding for 7 days did not alter the rate of cholesterol synthesis (75 ±12 mymoles/g per 2 hr). This resistance to cholesterol feeding also was present in the distal ileum where control and cholesterol-fed subjects had comparable rates of cholesterogenesis (280 and 261 m/tmoles/g per 2 hr, respectively). Interruption of the enterohepatic circulation, in contrast, resulted in greatly enhanced sterol synthesis with a mean rate of 259 ±29 nvmoles/g per 2 hr being found in the duodenum of four patients with biliary obstruction as compared with the rate of 80 ±11 mnmoles/g per 2 hr in control subjects. These studies indicate that the mechanisms of control of cholesterol synthesis by the human intestine are similar to those described for the intestine of lower animals; this also appears to be true for the human liver. Thus, th

A system of ODEs for a Perturbation of a Minimal Mass Soliton

We study soliton solutions to a nonlinear Schrodinger equation with a saturated nonlinearity. Such nonlinearities are known to possess minimal mass soliton solutions. We consider a small perturbation of a minimal mass soliton, and identify a system of ODEs similar to those from Comech and Pelinovsky (2003), which model the behavior of the perturbation for short times. We then provide numerical evidence that under this system of ODEs there are two possible dynamical outcomes, which is in accord with the conclusions of Pelinovsky, Afanasjev, and Kivshar (1996). For initial data which supports a soliton structure, a generic initial perturbation oscillates around the stable family of solitons. For initial data which is expected to disperse, the finite dimensional dynamics follow the unstable portion of the soliton curve.Comment: Minor edit

Minimum follow-up time required for the estimation of statistical cure of cancer patients: verification using data from 42 cancer sites in the SEER database

BACKGROUND: The present commonly used five-year survival rates are not adequate to represent the statistical cure. In the present study, we established the minimum number of years required for follow-up to estimate statistical cure rate, by using a lognormal distribution of the survival time of those who died of their cancer. We introduced the term, threshold year, the follow-up time for patients dying from the specific cancer covers most of the survival data, leaving less than 2.25% uncovered. This is close enough to cure from that specific cancer. METHODS: Data from the Surveillance, Epidemiology and End Results (SEER) database were tested if the survival times of cancer patients who died of their disease followed the lognormal distribution using a minimum chi-square method. Patients diagnosed from 1973–1992 in the registries of Connecticut and Detroit were chosen so that a maximum of 27 years was allowed for follow-up to 1999. A total of 49 specific organ sites were tested. The parameters of those lognormal distributions were found for each cancer site. The cancer-specific survival rates at the threshold years were compared with the longest available Kaplan-Meier survival estimates. RESULTS: The characteristics of the cancer-specific survival times of cancer patients who died of their disease from 42 cancer sites out of 49 sites were verified to follow different lognormal distributions. The threshold years validated for statistical cure varied for different cancer sites, from 2.6 years for pancreas cancer to 25.2 years for cancer of salivary gland. At the threshold year, the statistical cure rates estimated for 40 cancer sites were found to match the actuarial long-term survival rates estimated by the Kaplan-Meier method within six percentage points. For two cancer sites: breast and thyroid, the threshold years were so long that the cancer-specific survival rates could yet not be obtained because the SEER data do not provide sufficiently long follow-up. CONCLUSION: The present study suggests a certain threshold year is required to wait before the statistical cure rate can be estimated for each cancer site. For some cancers, such as breast and thyroid, the 5- or 10-year survival rates inadequately reflect statistical cure rates, and highlight the need for long-term follow-up of these patients