Tetrahydrobiopterin metabolism in depression and senile dementia of Alzheimer type

Excretion of biopterin and the related pteridines neopterin and pterin was measured in urine samples from a group of 76 male and female unipolar and bipolar depressed outpatients receiving lithium therapy, and compared to 61 male and female control subjects. The ratio of neopterin to biopterin excreted (N/B) was significantly higher in the patients than the controls. The significant positive correlation between urinary neopterin and biopterin shown by the controls was absent in the patients, indicating disrupted biosynthesis of tetrahydrobiopterin.Urinary cortisol excretion in depressed patients was similar to controls, implying normal hypothalmus-pituitary-adrenal axis function in these patients, Serum folate was shown to correlate with urinary total biopterin excretion in female unipolar patients. Two groups of elderly females with senile dementia of Alzheimer type (SDAT) were examined for urinary pteridine excretion. In the first study of 10 patients, the N/B ratio was significantly higher than in 24 controls and the ratio B/B+ N significantly lower. A second study of 30 SDAT patients and 21 controls confirmed these findings. However, neopterin correlated with biopterin in both patients and controls, indicating that the alteration in tetrahydrobiopterin metabolism may be different to that shown in depression. Lithium had no effect in vivo or in vitro on Wistar rat brain or liver biosynthesis of tetrahydrobiopterin at a range of concentrations and duration of dosing period, showing that lithium was not responsible for the lowered biopterin excretion by depressed patients. No significant effects on tetrahydrobiopterin metabolism in the rat were shown by the tricyclic antidepressant imipramine, the anticonvulsant sodium valproate, the vitamin folic acid, the anticatecholaminergic agent amethylparatyrosine, the synthetic corticosteroid dexamethasone, or stimulation of natural cortisol by immobilisation stress. Scopolamine, an ant ichol inergic drug, lowered rat brain pterin which may relate to the tetrahydrobiopterin deficits shown in SDAT.

Refractive errors associated with tilted optic discs:a prospective study

Purpose: Tilted disc syndrome has been described to be associated with obliquely directed long axis of the disc, oblique direction of vessels, retinal pigment epithelial conus, hypoplasia of retina, visual field defects and myopic astigmatism. This prospective study looks at corneal astigmatism in eyes with a tilted optic disc. Refractive errors in these eyes were also analyzed. Methods: Patients with tilted optic discs were identified prospectively by clinical evaluation (BI, VK). All the patients with obliquely directed long axis of the disc, oblique direction of vessels and retinal pigment epithelial conus were included in the study. Best corrected visual acuity, slit-lamp examination, optic disc measurements, keratometry and refraction were recorded. Results: Twenty four patients (41 eyes) were recruited for the study. Eighteen (75%) patients had bilateral tilted optic discs. Eighteen patients (75%) were females and six (25%) were males. The mean age was 62 years(range 9 – 86 years). 76% of the patients were myopic and 24% hypermetropic. The mean spherical equivalent was –7.49 dioptres (SD 1.7D, range +6D to -17D). The mean corneal astigmatism was 1.09D (SD 0.9D, range 0.25D to 3.80D). The 6 patients who had unilateral, untilted discs were used as a control group to compare their mean corneal astigmatism (1.32 D) with the rest. Student "t" test was performed. ("p" = 0.49). Conclusions: In our study, tilted disc syndrome was found to be largely bilateral and more commonly seen in females. Myopia was the commonest refractive error associated with this clinical condition. However, 24% of patients in this series were hypermetropic. No correlation between the tilting of the optic disc and significant corneal astigmatism was noted as previously reported.

Acute and long-term effects of metformin on the function and insulin secretory responsiveness of clonal β-cells

Functional effects of acute and prolonged (48 h) exposure to the biguanide drug metformin were examined in the clonal pancreatic ß-cell line, BRIN-BD11. Effects of metformin on prolonged exposure to excessive increased concentrations of glucose and palmitic acid were also assessed. In acute 20-min incubations, 12.5-50 µm metformin did not alter basal (1.1 mm glucose) or glucose-stimulated (16.7 mm glucose) insulin secretion. However, higher concentrations of metformin (100-1000 µm) increased (1.3-1.5-fold; p

Bending and orientational characteristics of long period gratings written in D-shaped optical fiber

Long period gratings (LPGs) were written into a D-shaped single-mode fiber. These LPGs were subjected to a range of curvatures, and it was found that as curvature increased, there was increasingly strong coupling to certain higher order cladding modes without the usual splitting of the LPGs stopbands. A bend-induced stopband yielded a spectral sensitivity of 12.55 nm·m for curvature and 2.2×10-2 nm°C-1 for temperature. It was also found that the wavelength separation between adjacent bend-induced stopbands varied linearly as a function of curvature. Blue and red wavelength shifts of the stopbands were observed as the sensor was rotated around a fixed axis for a given curvature; thus, in principle, this sensor could be used to obtain bending and orientational information. The behavior of the stopbands was successfully modeled using a finite element approach.

Bending and orientational characteristics of long period gratings written in D-shaped optical fiber

Long period gratings (LPGs) were written into a D-shaped single-mode fiber. These LPGs were subjected to a range of curvatures, and it was found that as curvature increased, there was increasingly strong coupling to certain higher order cladding modes without the usual splitting of the LPGs stopbands. A bend-induced stopband yielded a spectral sensitivity of 12.55 nm · m for curvature and 2.2 × 10-2 nm°C-1 for temperature. It was also found that the wavelength separation between adjacent bend-induced stopbands varied linearly as a function of curvature. Blue and red wavelength shifts of the stopbands were observed as the sensor was rotated around a fixed axis for a given curvature; thus, in principle, this sensor could be used to obtain bending and orientational information. The behavior of the stopbands was successfully modeled using a finite element approach.

Acute and long-term effects of peroxisome proliferator-activated receptor-γ activation on the function and insulin secretory responsiveness of clonal beta-cells

Thiazolidinediones (TZDs) are used as antidiabetic therapy. The purpose of the present study was to examine whether the TZD rosiglitazone has direct actions on pancreatic beta-cells that contribute to its overall effects. Effects of acute and prolonged (48 h) exposure to rosiglitazone, as a model glitazone compound, were assessed in clonal pancreatic BRIN-BD11 beta-cells maintained in standard, glucotoxic and lipotoxic cultures. In acute 20-min incubations, rosiglitazone (0.2-100 M) did not alter basal or glucose-stimulated insulin secretion. However, rosiglitazone (6.25 M) enhanced (p

Application of long period gratings sensors to respiratory function monitoring

A series of in-line curvature sensors on a garment are used to monitor the thoracic and abdominal movements of a human during respiration. These results are used to obtain volumetric tidal changes of the human torso showing reasonable agreement with a spirometer used simultaneously to record the volume at the mouth during breathing. The curvature sensors are based upon long period gratings written in a progressive three layered fibre that are insensitive to refractive index changes. The sensor platform consists of the long period grating laid upon a carbon fibre ribbon, which is encapsulated in a low temperature curing silicone rubber. An array of sensors is also used to reconstruct the shape changes of a resuscitation manikin during simulated respiration. The data for reconstruction is obtained by two methods of multiplexing and interrogation: firstly using the transmission spectral profile of the LPG's attenuation bands measured using an optical spectrum analyser; secondly using a derivative spectroscopy technique.

The application of a long period grating array for respiratory function monitoring

In this paper, multiplexed sensor network capable of monitoring the shape changes of the torso for respiratory function monitoring is developed. As a demonstration, LPGs written into refractive index insensitive, progressive three layered fibre are embedded into supporting material is then placed on a resuscitation training manikin simulating respiration. A derivative spectroscopy interrogation technique is implemented and the bend sensitivity of the LPGs is used to reconstruct the shape of the manikin's torso. © 2003 IEEE.

Real-time detection of DNA interactions with long-period fiber-grating-based biosensor

Using an optical biosensor based on a dual-peak long-period fiber grating, we have demonstrated the detection of interactions between biomolecules in real time. Silanization of the grating surface was successfully realized for the covalent immobilization of probe DNA, which was subsequently hybridized with the complementary target DNA sequence. It is interesting to note that the DNA biosensor was reusable after being stripped off the hybridized target DNA from the grating surface, demonstrating a function of multiple usability.

Bending characteristics of fiber long-period gratings with cladding index modified by femtosecond laser

A femtosecond laser has been used to asymmetrically modify the cladding of fiber containing long-period gratings. Following modification, devices in single-mode fiber are shown to be capable of sensing the magnitude and direction of bending in one plane by producing blue and red wavelength shifts depending upon the orientation of the bend. The resulting curvature sensitivities were -1.62 and +3.82 nm&middotm. Devices have also been produced using an elliptical core fiber to study the effects of the cladding modification on the two polarization eigenstates. A cladding modification applied on the fast axis of the fiber is shown to affect the light in the fast axis much more significantly than the light in the orthogonal state; this behavior may ultimately lead to a sensor capable of detecting the direction of bending in two dimensions for applications in shape sensing.

Long-period fibre grating based biosensor for detection of DNA hybridisation

We implement an optical biosensor using long-period fibre grating immobilised with probe DNA. It has been used to detect hybridisation of target DNA, showing a high sensitivity and reusability function.

DNA hybridisation biosensor based on dual-peak long-period grating

Using an optical biosensor based on dual-peak long-period fibre grating, we demonstrate the detection of interactions between DNA biomolecules in real-time, showing a high sensitivity and reusability function.

An investigation of reading ability and visual function with eccentric visual field

This study investigated the detrimental effect of central field loss (CFL) on reading ability and general visual function. The aim was to improve the understanding of reading with eccentric retina in order that reading performances of individuals with CFL may be maximised. To improve visual ability of individuals with CFL, it is important to be able to accurately measure the outcome of any intervention. Various methods for determining visual function were therefore compared with perceived visual performance (as measured with a quality of life questionnaire) before and after surgical removal of choroidal new vessels (CNV) in macular disease patients. The results highlight the importance of low contrast measures (low contrast visual acuity and contrast sensitivity) when investigating perceived reading performance. Reading speed was found to be important for reflecting changes in general visual quality of life. Potential causes for reduced peripheral reading ability were investigated using both normally sighted and CFL subjects. For normally sighted subjects reading eccentrically with rapid serial visual presentation (RSVP) text, the inferior visual field was a better position (in terms of reading speed) for the presentation of the text. The size of the visual span was found to reduce with increasing eccentricity of fixation, providing a potential reason for reduced peripheral reading performances. The investigation of the ability to use context when reading with peripheral retina resulted in conflicting results. Studies in this thesis found both a reduction and no reduction in the ability of the peripheral retina to utilise context compared to the fovea. Individuals with long-term CFL showed no improvement in peripheral reading ability over that found for normally sighted subjects reading at the same eccentricity.

Sensing and control of adipocyte function

Obesity has become a global epidemic. Approximately 15% of the world population is either overweight or obese. This figure rises to 75% in many westernised countries including the United Kingdom. Health costs in the UK to treat obesity and associated disease are conservatively estimated at 6% of the National Health Service (NHS) budget equating to 3.33 billion Euros. Excess adiposity, especially in visceral depots, increases the risk of type 2 diabetes, cardiovascular disease, gall stones, hypertension and cancer. Type 2 diabetes mellitus accounts for >90% of all cases of diabetes of which the majority can be attributed to increased adiposity, and approximately 70% of cardiovascular disease has been attributed to obesity in the US. Weight loss reduces risk of these complications and in some cases can eliminate the condition. However, weight loss by conventional non-medicated methods is often unsuccessful or promptly followed by weight regain. This thesis has investigated adipocytes development and adipokine signalling with a view to enhance the understanding of tissue functionality and to identify possible targets or pathways for therapeutic intervention. Adipocyte isolation from human tissue samples was undertaken for these investigative studies, and the methodology was optimised. The resulting isolates of pre-adipocytes and mature adipocytes were characterised and evaluated. Major findings from these studies indicate that mature adipocytes undergo cell division post terminal differentiation. Gene studies indicated that subcutaneous adipose tissue exuded greater concentrations and fluctuations of adipokine levels than visceral adipose tissue, indicating an important adiposensing role of subcutaneous adipose tissue. It was subsequently postulated that the subcutaneous depot may provide the major focus for control of overall energy balance and by extension weight control. One potential therapeutic target, 11ß-hydrosteroid dehydrogenase (11ß-HSD1) was investigated, and prospective inhibitors of its action were considered (BVT1, BVT2 and AZ121). Selective reduction of adiposity of the visceral depot was desired due to its correlation with the detrimental effects of obesity. However, studies indicated that although the visceral depot tissue was not unaffected, the subcutaneous depot was more susceptible to therapeutic inhibition by these compounds. This was determined to be a potentially valuable therapeutic intervention in light of previous postulations regarding long-term energy control via the subcutaneous tissue depot.

Enhanced spectral sensitivity of fibre long period gratings to refractive index of aqueous solutions utilising copper patterned coatings

A set of long period grating devices have been fabricated in photosensitive single mode fibre coated with a series of copper rings (period of 380μm, 50% duty cycle and length of 4cm). The long period gratings were inscribed with a uniform UV-laser exposure across the entire length of the copper ring patterned coating. The devices ranged in copper thickness from 0.5μm to 1.5μm. In addition, a control long period grating was fabricated in the same type of fibre with the same period for comparison. The refractive index and temperature spectral sensitivity of these devices were investigated and it was found that the index and temperature sensitivity is a function of the thickness of the copper rings, as supported by theoretical modelling. Furthermore, the index sensitivity of these devices in the 1.333 index region is greater than the control long period grating. The patterned 0.5μm coated long period grating gave a sensitivity of Δλ/Δn = -74 nm leading to a resolution of 1.4×10-3 compared to the control which had a sensitivity of Δλ/Δn = -32 nm with a resolution of 3.2×10-3 in the index region of 1.320 to 1.380 (aqueous solution regime). This demonstrates a two fold increase in the sensitivity. This novel fibre long period grating device shows potential for increasing the resolution of measurements of the index of aqueous solutions.