Corneal epithelial barrier function after oxybuprocaine provocation in diabetics

Corneal epithelial permeability for fluorescein was determined after provocation by a local anesthetic in 18 non-insulin-dependent diabetes mellitus (NIDDM) patients, 23 insulin-dependent diabetes mellitus (IDDM) patients, and 22 healthy controls to evaluate the corneal epithelial barrier function in diabetes. All volunteers had Oxybuprocaine instilled into one eye and saline into the other eye. The epithelial permeability values were determined by fluorophotometry, and the ratio between both eyes was calculated for each individual. The mean permeability values of the saline-instilled eyes in the diabetic patients did not differ significantly from those in the healthy controls (P greater than 0.2). The individual ratios between Oxybuprocaine- and saline-instilled eyes in the NIDDM and IDDM patients differed significantly from those in the healthy controls (mean ratios: 2.6, 1.9, and 1.0, respectively; P less than 0.002). The permeability ratios and the percentage glycosylated hemoglobin (HbAlc) were linearly correlated in the NIDDM patients but not in the IDDM patients (r = 0.73, P less than 0.001, and r = 0.09, P greater than 0.68, respectively). The results showed that the corneal epithelial barrier function in the diabetic patients was not impaired compared with that in the healthy controls. After provocation by a local anesthetic, the barrier function was impaired in the diabetic patients only.     

A chimeric tyrosine/tryptophan hydroxylase

The neurotransmitter biosynthetic enzymes, tyrosine hydroxylase (TH), and tryptophan hydroxylase (TPH) are each composed of an amino-terminal regulatory domain and a carboxylterminal catalytic domain. A chimeric hydroxylase was generated by coupling the regulatory domain of TH (TH-R) to the catalytic domain of TPH (TPH-C) and expressing the recombinant enzyme in bacteria. The chimeric junction was created at proline 165 in TH and proline 106 in TPH because this residue is within a conserved five amino-acid span (ValProTrpPhePro) that defines the beginning of the highly homologous catalytic domains of TH and TPH. Radioenzymatic activity assays demonstrated that the TH-R/TPH-C chimera hydroxylates tryptophan, but not tyrosine. Therefore, the regulatory domain does not confer substrate specificity. Although the TH-R/TPH-C enzyme did serve as a substrate for protein kinase (PKA), activation was not observed following phosphorylation. Phosphorylation studies in combination with kinetic data provided evidence that TH-R does not exert a dominant influence on TPH-C. Stability assays revealed that, whereas TH exhibited a t_1/2 of 84 min at 37°C, TPH was much less stable (t _1/2=28.3 min). The stability profile of TH-R/TPH-C, however, was superimposable on that of TH. Removal of the regulatory domain (a deletion of 165 amino acids from the N-terminus) of TH rendered the catalytic domain highly unstable, as demonstrated by at _1/2 of 14 min. The authors conclude that the regulatory domain of TH functions as a stabilizer of enzyme activity. As a corollary, the well-characterized instability of TPH may be attributed to the inability of its regulatory domain to stabilize the catalytic domain.     

Keeping the arm in the limelight: advanced visual control of arm movements in neonates.

To test whether newborn babies have voluntary control over their limbs, spontaneous arm-waving movements were measured in the dark while the baby lay supine with its head turned to one side. A narrow beam of light was shone over the baby's nose or chest in such a way that the arm the baby was facing was only visible when the hand encountered the, otherwise, invisible beam of light. The results showed the babies were capable of precisely controlling the position, velocity, and deceleration of their arms so as to keep the hand visible in the light. The findings indicate that newborns can purposely control their arm movements to meet external demands and that the development of visual control of arm movement is underway soon after birth.     

Oral administration of methylergometrine shows a late and unpredictable effect on the non-pregnant human menstruating uterus

Objective: To study the pharmacodynamic and pharmacokinetic properties of oral and intravenous methylergometrine upon uterine motility during menstruation. Study-design: Intra-uterine pressure was measured in six volunteers with a fluid-filled sponge-tipped catheter during menstruation. Methylergometrine was given orally (0.5 mg) or intravenously (0.2 mg) in a cross-over design. Results: After intravenous administration, a fast increase of the frequency of uterine contractions and basal tone occurred with a decrease of amplitude, lasting at least 30 min. Oral administration had a late and less marked effect on uterine motility. An intravenous dose administered 24 h after an oral dose had no effect on uterine motility. Pharmacokinetic data, such as the maximum plasma concentration (C_max), the time at which C_max is reached (t_max) and the half-life of absorption (t_1/2abs) also demonstrated large individual variations after oral administration. Conclusion: Oral administration of methylergometrine had an unpredictable and late effect on uterine motility on the menstruating uterus, probably due to an unpredictable bioavailability, in contrast with the fast and predictable effect after intravenous administration.     

Are clinical differences between black and white stroke patients caused by variations in the atherosclerotic involvement of the arterial tree?

The differences in site and degree of atherosclerotic involvement of various vascular beds and their clinical significance are emphasised in a study of 304 black stroke patients. Detailed clinical examinations, computed tomography (CT), gated blood pool studies, echocardiography and ECG were performed and autopsy studies carried out. CT of the brain showed that non-haemorrhage, i.e. ischaemic lesions, accounted for 71.2% of strokes, a similar figure to that found in white stroke patients. However, carotid bruits (0.62%) and peripheral vascular disease (0.9%) followed by transient ischaemic attacks (1.9%) were found to be uncommon. Similarly, ischaemic heart disease (6.9%) appeared to be less common than the incidence in reported white stroke patients. In 30 patients who came to autopsy, the maximum degree of atherosclerotic stenosis of the extracranial carotid arteries was 21.7% of the lumen diameter. The differences in the site and degree of atherosclerosis in blacks not only give rise to differences in the clinical features of stroke patients but may have an important bearing on their investigation, management and prognosis.     

Rapid determination of benzalkonium chloride in pharmaceutical preparations with flow injection liquid-liquid extraction

Benzalkonium chloride was assayed by on-line extraction of the benzalkonium ion with picrate to chloroform. The absorbance of picrate was measured. The extractions were performed with a home-made flow injection extraction unit. Calibration curves (1.5-180 x 10(-4)% w/v) were straight lines (r = 0.9993) and the relative standard deviation of a series of injections was less than or equal to 2%. Pharmaceutical benzalkonium preparations, containing xylometazoline, timolol, phenylephrine or carbachol could also be assayed. The method was compared with a modified HPLC assay.     

Early morphogenesis of persistent hyperplastic tunica vasculosa lentis and primary vitreous. A transmission electron microscopic study

This report provides transmission electron microscopic observations on the early pathogenesis of persistent hyperplastic tunica vasculosa lentis/persistent hyperplastic primary vitreous (PHTVL/PHPV) in affected canine fetuses at days 28-44 postcoitum. The retrolental tissue by which this anomaly is characterized consists of loosely arranged fibroblasts in a randomly oriented meshwork of collagenous fibrils. Some of these cells contain melanosomes at day 44. In one day-44 eye, cells of neuroectodermal origin (Müller cells; fibrous astrocytes) were observed. From day 37 onward, the posterior subcapsular part of the lens contains rounded, increased intercellular spaces, resembling vacuoles, which deform the shape of the lens fibers. The posterior lens capsule develops normally until day 30. From day 35 onward the capsule has an amorphous ultrastructure, as opposed to the clearly laminated ultrastructure in reference eyes at day 35. In addition, the capsule's thickness increases until day 35, and, instead of growing thicker, decreases thereafter. Based on these results, it is hypothesized that a primary metabolic disorder in the lens fibers, subsequently leading to the formation of an abnormal posterior lens capsule, constitutes the primary defect in the sequence of events leading to PHTVL/PHPV.     

The Relationship Between Quantitative MRI and Neuropsychological Functioning in Temporal Lobe Epilepsy

Summary: Purpose: Quantitative MRI techniques provide an unparalleled opportunity to examine in vivo the relationship between the extent and laterality of hippocampal pathology and associated neuropsychological deficits. The purpose of this study was to examine the nature of the relationship between quantitative measures of hippocampal pathology and neuropsychological measures, using a multivariate approach. Methods: We examined the relationship between two MRI measures of hippocampal structure; hippocampal volumes (HCvol) and T2 relaxation times (HCT2), and memory performance, in 80 presurgical temporal lobe epilepsy patients. Results: As a group, patients with left hippocampal sclerosis (LHS) performed more poorly that those with right hippocampal sclerosis (RHS) on immediate and delayed prose recall. In the group as a whole, right hippocampal volume was significantly correlated with the delayed recall of a complex figure. None of the verbal memory test scores were significantly correlated with the right or left HCvol or HCT2 measures. However, stepwise multiple regression analyses indicated that up to a third of the variation in specific test scores could be explained by the quantitative MRI hippocampal measures in conjunction with chronological age, and age at onset of habitual epilepsy. Left hippocampal measures explained 24% of the variance in the story-recall tasks, while right hippocampal measures explained 18% of the variance in a design-learning task and 32% of the variance in a figure-recall task. Conclusions: Our results provide some support for the lateralised model of material specific memory deficits, but suggest that a number of demographic and epilepsy-related factors may interact with the extent and laterality of hippocampal pathology in shaping the nature of the associated neuropsychological deficit.