[The annual conference of the American Academy of Opthalmology (AAO) held in Orlando, Florida, 2002].
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Humans↗
Biomedical subjects
R Nesher
Publications and source records attributed to R Nesher.
Overcoming the language barrier in visual field testing.
PURPOSE: To evaluate the effect of using recorded instructions in patients' native language compared with interpreter-assisted instructions on the reliability and duration of the visual field test. PATIENTS AND METHODS: Sixty patients referred for visual field testing were included in the study. Thirty-five had limited or no knowledge of the Hebrew language, and 25 control patients were fluent in Hebrew, the native language. None had previous experience with automated perimetry. Patients were randomized to receive recorded instructions on the visual field test in their native language or translator-assisted instructions by the technician before performing the test. For each patient, the time required for instructions and test performance and the reliability indices were documented. RESULTS: The method of instruction (recorded or interpreter-assisted) did not affect the time required for patient instructions (66 +/- 24 seconds and 57 +/- 30 seconds, respectively), the time for test performance (7.2 +/- 1.5 minutes and 7.8 +/- 1.8 minutes, respectively), and test reliability as measured by the rate of fixation losses. Regardless of the method of explanation, the time required for instructions and for performing the test were significantly shorter for Hebrew speakers than for non-Hebrew speakers. CONCLUSION: The use of a recorded explanation in the patient's native language before visual field testing is an applicable method for patient instruction. Clinics in areas with multilingual populations may use this method to save technicians time, without adversely affecting the time required for performing the test and its reliability.
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Charles Bonnet syndrome in glaucoma patients with low vision.
PURPOSE: To characterize the nature and frequency of Charles Bonnet syndrome in glaucoma patients with low vision. PATIENTS AND METHODS: All patients attending the glaucoma clinic during a period of 10 months who had visual acuity of 20/80 or less in both eyes were included in this study. Each patient was questioned about the occurrence of visual hallucinations. Those who responded positively had a thorough interview relating to the characteristics of the hallucinations. Medical history and social history were taken, followed by a complete ocular examination. RESULTS: Eighty-nine patients met the inclusion criteria. Eleven patients (12.3%), eight men and three women, admitted to having experienced visual hallucinations. Except for one case, the patients did not disclose this experience previously. Eight patients had one repeatable hallucination, and three patients experienced more than one sight. The visions were usually sharp, and the figures were occasionally incomplete. Most hallucinations were chromatic. Frequency of hallucinations varied between daily and weekly, and duration was mostly a few minutes. In addition to glaucoma, nine of the eleven patients had other ocular findings that could have contributed to the reduction of vision. CONCLUSION: Visual hallucinations are not rare in glaucoma patients with low vision. Patients tend to conceal their experience of visual hallucinations, but a discussion of these phenomena with the patient and assurance of their harmless nature will reduce his or her anxiety and concerns.
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Defective stimulus-secretion coupling in islets of Psammomys obesus, an animal model for type 2 diabetes.
Psammomys obesus is a model of type 2 diabetes that displays resistance to insulin and deranged beta-cell response to glucose. We examined the major signaling pathways for insulin release in P. obesus islets. Islets from hyperglycemic animals utilized twice as much glucose as islets from normoglycemic diabetes-prone or diabetes-resistant controls but exhibited similar rates of glucose oxidation. Fractional oxidation of glucose was constant in control islets over a range of concentrations, whereas islets from hyperglycemic P. obesus showed a decline at high glucose. The mitochondrial substrates alpha-ketoisocaproate and monomethyl succinate had no effect on insulin secretion in P. obesus islets. Basal insulin release in islets from diabetes-resistant P. obesus was unaffected by glucagon-like peptide 1 (GLP-1) or forskolin, whereas that of islets of the diabetic line was augmented by the drugs. GLP-1 and forskolin potentiated the insulin response to maximal (11.1 mmol/l) glucose in islets from all groups. The phorbol ester phorbol myristic acid (PMA) potentiated basal insulin release in islets from prediabetic animals, but not those from hyperglycemic or diabetes-resistant P. obesus. At the maximal stimulatory glucose concentration, PMA potentiated insulin response in islets from normoglycemic prediabetic and diabetes-resistant P. obesus but had no effect on islets from hyperglycemic P. obesus. Maintenance of islets from hyperglycemic P. obesus for 18 h in low (3.3 mmol/l) glucose in the presence of diazoxide (375 pmol/l) dramatically improved the insulin response to glucose and restored the responsiveness to PMA. Immunohistochemical analysis indicated that hyperglycemia was associated with reduced expression of alpha-protein kinase C (PKC) and diminished translocation of lambda-PKC. In summary, we found that 1) P. obesus islets have low oxidative capacity, probably resulting in limited ability to generate ATP to initiate and drive the insulin secretion; 2) insulin response potentiated by cyclic AMP-dependent protein kinase is intact in P. obesus islets, and increased sensitivity to GLP-1 or forskolin in the diabetic line may be secondary to increased sensitivity to glucose; and 3) islets of hyperglycemic P. obesus display reduced expression of alpha-PKC and diminished translocation of lambda-PKC associated with impaired response to PMA. We conclude that low beta-cell oxidative capacity coupled with impaired PKC-dependent signaling may contribute to the animals' poor adaptation to a high-energy diet.
Animals↗
beta-cell glucotoxicity in the Psammomys obesus model of type 2 diabetes.
Deficient insulin secretion and relative hyperproinsulinemia are characteristic features of type 2 diabetes. The gerbil Psammomys obesus appears to be an ideal natural model of the human disease because it shows increased tendency to develop diet-induced diabetes, which is associated with moderate obesity. The disease is characterized by initial hyperinsulinemia, progressing to hypoinsulinemia associated with depleted pancreatic insulin stores and an increased proportion of insulin precursor molecules in the blood and islets. Although the proinsulin translational efficacy was found to be increased in hyperglycemic animals, insulin mRNA levels were not augmented and exhibited a gradual decrease with disease progression. The development of hyperglycemia was associated with a transient increase in beta-cell proliferative activity, as opposed to a prolonged increase in the rate of beta-cell death, culminating in disruption of islet architecture. The hypothesis that glucotoxicity is responsible in part for these in vivo changes was investigated in vitro in primary islet cultures. Islets from diabetes-prone P. obesus cultured at high glucose concentrations displayed changes in beta-cell function that mimic those observed in diabetic animals. These changes include deficient insulin secretion, depleted insulin content, an increased proportion of insulin precursor molecules, a progressive increase of DNA fragmentation, and a transient proliferative response. Furthermore, insulin mRNA was not increased by short-term exposure of P. obesus islets to elevated glucose in vitro. It is proposed that beta-cell glucotoxicity in P. obesus results from the inability of proinsulin biosynthesis to keep pace with chronic insulin hypersecretion. The resulting depletion of the insulin stores may be related to deficient glucose-regulated insulin gene transcription, possibly due to defective PDX-1 (pancreatic duodenal homeobox factor-1) expression in the adult P. obesus. An additional glucotoxic effect involves the loss of beta-cell mass in hyperglycemic P. obesus as a result of progressive beta-cell death without an adequate increase in the rate of beta-cell proliferation.
Animals↗
Visual hallucinations in giant cell arteritis: association with visual loss.
OBJECTIVE: To evaluate the frequency and characteristics of visual hallucinations (VH) in patients with giant cell arteritis (GCA) and to determine their relationship to other visual phenomena. METHODS: This prospective study included 31 consecutive patients with GCA. All were asked whether they had experienced recent visual phenomena. Patients with visual symptoms underwent a comprehensive ophthalmologic examination. When unusual visual phenomena were reported, patients were asked to describe their nature, duration, and frequency of occurrence. RESULTS: Visual symptoms occurred in 6 patients: permanent visual loss in 5 and amaurosis fugax in one. In 4 of the 5 patients with permanent visual loss, it was preceded by intermittent VH over a period of 1-10 days. Patients were aware of the unreal nature of the visions. Hallucinations disappeared within 2 weeks, but in one patient, recurred 6 months later in association with further visual deterioration. CONCLUSION: The occurrence of visual hallucinations in patients with GCA-associated visual loss is more common than previously appreciated. As hallucinations preceded permanent loss of vision, this phenomenon may serve as a harbinger of imminent visual loss.
Age Distribution↗
Recombinant thyroid-stimulating hormone in differentiated thyroid cancer.
Recombinant TSH is effective in providing exogenous TSH stimulation for patients with differentiated thyroid cancer on thyroid hormone-suppressive therapy. It allows for detection of thyroid remnant and metastases by radioiodine scan and by serum thyroglobulin determination. The sensitivity and image quality of the WBS are similar after rTSH and after THSH withdrawal in the majority of patients. The equivalent 100% sensitivity of rTSH- and withdrawal-stimulated serum thyroglobulin measurement alone in identifying patients with radioiodine uptake outside the thyroid bed [38] may eventually lead to more extensive use of serum thyroglobulin testing after rTSH, with more selective application of radioiodine WBS [39]. Currently, a phase IV trial is in progress to evaluate the efficacy of rTSH-stimulated thyroglobulin levels as the primary modality for long-term follow-up of low risk thyroid cancer patients. The use of rTSH prevents the morbidity, metabolic impairment and the risk of tumor progression associated with THST withdrawal, because of shorter exposure time to elevated TSH [38]. Furthermore, it decreases the radiation exposure of healthy tissues due to faster iodine clearance in euthyroidism. rTSH is well tolerated, with transient nausea in 10.5% and headache in 7.3% of patients. No antibodies specific to rTSH were documented, even after multiple courses of the drug. Currently, rTSH is suggested for patients who do not respond to hormone withdrawal or cannot tolerate hypothyroidism. For patients with low risk of tumor recurrence, rTSH-stimulated testing may be used at 6-12 months after postoperative I-131 ablation and with a repeat cycle of rTSH one year later, followed by testing every 3-5 years. In high risk patients, one set of negative I-131 scan and thyroglobulin test results after hormone withdrawal are recommended before using rTSH testing, because of a greater sensitivity of the withdrawal scan and because rTSH is not currently approved for subsequent I-131 therapy often indicated in these patients [24]. Subsequently, two cycles of rTSH testing are recommended at 6-12 month intervals, followed by testing every 1-3 years for at least the first decade after initial diagnosis. The cost of this commercially available form of rTSH has been considered a major impediment to its common use; however, this should be weighed against the loss of productivity of working hours related to withdrawal [40]. In the therapeutic setting, rTSH is the only acceptable option in a subgroup of patients with hypopituitarism, ischemic heart disease, a history of "myxedema madness," debilitation due to advanced disease, or inability to elicit TSH elevation due to continued production of thyroxine by thyroid remnant or metastatic tumor [33,38]. In conclusion, recombinant TSH facilitates the management of patients with differentiated thyroid carcinoma. It increases the sensitivity of thyroglobulin testing during thyroid hormone suppression therapy and enables radioiodine uptake for whole-body scan and occasionally for radioiodine therapy, without the need for prolonged THST withdrawal and its associated hypothyroidism, reduced quality of life and risk of tumor progression.
Animals↗
Interaction between genetic and dietary factors determines beta-cell function in Psammomys obesus, an animal model of type 2 diabetes.
The gerbil Psammomys obesus develops nutrition-dependent diabetes. We studied the interaction between diet and diabetic predisposition for beta-cell function. A 4-day high-energy (HE) diet induced a 3-, 4-, and 1.5-fold increase in serum glucose, insulin, and triglycerides, respectively, in diabetes-prone (DP) but not diabetes-resistant (DR) P. obesus. Hyperglycemia and concurrent 90% depletion of islet immunoreactive insulin stores were partially corrected by an 18-h fast. In vitro early insulin response to glucose was blunted in both DR and DP perifused islets. The HE diet augmented early and late insulin response in DR islets, whereas in DP islets, secretion progressively declined. Dose-response studies showed a species-related increase in islet glucose sensitivity, further augmented in DP P. obesus by a HE diet, concomitant with a decreased threshold for glucose and a 55% reduction in maximal response. These changes were associated with a fourfold increase in glucose phosphorylation capacity in DP islets. There were no differences in islet glucokinase (GK) and hexokinase (HK) Km; however, GK Vmax was 3.7- to 4.6-fold higher in DP islets, and HK Vmax was augmented 3.7-fold by the HE diet in DP islets. We conclude that the insulin-resistant P. obesus has an inherent deficiency in insulin release. In the genetically predisposed P. obesus (DP), augmented islet glucose phosphorylation ability and diet-induced reduction of the glucose threshold for secretion may lead to inadequate insulin secretion and depletion of insulin stores in the presence of caloric abundance. Thus, genetic predisposition and beta-cell maladaptation to nutritional load seem to determine together the progression to overt diabetes in this species. It is hypothesized that similar events may occur in obese type 2 diabetic patients.
Animal Nutritional Physiological Phenomena↗
Translocation inhibitors define specificity of protein kinase C isoenzymes in pancreatic beta-cells.
The protein kinase C (PKC) family consists of 11 isoenzymes. Following activation, each isoenzyme translocates and binds to a specific receptor for activated C kinase (RACK) (Mochly-Rosen, D. (1995) Science 268, 247-251) that provides an anchoring site in close proximity to the isoenzyme's specific substrate. Pancreatic islet cells contain at least six PKC isoenzymes (Knutson, K. L., and Hoenig, M. (1994) Endocrinology 135, 881-886). Although PKC activation enhances insulin release, the specific function of each isoenzyme is unknown. Here we show that following stimulation with glucose, alphaPKC and epsilonPKC translocate to the cell's periphery, while deltaPKC and zetaPKC translocate to perinuclear sites. betaC2-4, a peptide derived from the RACK1-binding site in the C2 domain of betaPKC, inhibits translocation of alphaPKC and reduces insulin response to glucose. Likewise, epsilonV1-2, an epsilonPKC-derived peptide containing the site for its specific RACK, inhibits translocation of epsilonPKC and reduces insulin response to glucose. Inhibition of islet-glucose metabolism with mannoheptulose blocks translocation of both alphaPKC and epsilonPKC and diminishes insulin response to glucose while calcium-free buffer inhibits translocation of alphaPKC but not epsilonPKC and lowers insulin response by 50%. These findings illustrate the unique ability of specific translocation inhibitors to elucidate the isoenzyme-specific functions of PKC in complex signal transduction pathways.
Animals↗
A comparative study of two dose regimens of latanoprost in patients with elevated intraocular pressure.
OBJECTIVE: The purpose of the study was to determine whether latanoprost (13,14-dihydro-17-phenyl-18,19,20-trinor PGF2a-isopropyl ester), a new prostaglandin analogue that has been found effective in reducing intraocular pressure (IOP) in humans, is equally effective at lower concentrations than those currently employed. DESIGN AND PARTICIPANTS: Fifty patients with glaucoma or ocular hypertension were treated in a randomized, crossover, double-masked fashion with 1 drop of latanoprost (50 microg/ml once daily and 15 microg/ml twice daily) in the affected eye(s) for 3 weeks on each concentration. Tonometry was obtained at 8:00, 13:00, and 17:00 hours at baseline (untreated) and after 3 weeks on each concentration. Placebo (a buffer solution of latanoprost eye drop) was administered for complete masking of the study. RESULTS: Mean baseline (untreated) diurnal IOP for the entire sample was 24.7 mmHg. Intraocular pressure was reduced by 6.1 mmHg with latanoprost 15 microg/ml twice daily, and by 7.5 mmHg with 50 microg/ml once daily. Results with both regimens were significant (P < 0.001 each, Student's t-test). However, the 50 microg/ml dose was significantly more effective than the 15 microg/ml dose, with a difference of 1.4 mmHg (P < 0.001, ANOVA). Both dose regimens were well tolerated, with little, predominantly mild, ocular discomfort. The higher dose did not cause more hyperemia at 3 weeks than the lower one, i.e., the lower dose yielded a slightly higher score (1.8 mm) on the visual analogue scale (P < 0.29, ANOVA). CONCLUSIONS: Latanoprost administered at a concentration of 50 microg/ml once daily effectively reduces IOP in patients with elevated IOP. Administration of a lower concentration (15 microg/ml) twice daily is less effective, but still significant.
Adult↗
Glucose- and GTP-dependent stimulation of the carboxyl methylation of CDC42 in rodent and human pancreatic islets and pure beta cells. Evidence for an essential role of GTP-binding proteins in nutrient-induced insulin secretion.
Several GTP-binding proteins (G-proteins) undergo post-translational modifications (isoprenylation and carboxyl methylation) in pancreatic beta cells. Herein, two of these were identified as CDC42 and rap 1, using Western blotting and immunoprecipitation. Confocal microscopic data indicated that CDC42 is localized only in islet endocrine cells but not in acinar cells of the pancreas. CDC42 undergoes a guanine nucleotide-specific membrane association and carboxyl methylation in normal rat islets, human islets, and pure beta (HIT or INS-1) cells. GTPgammaS-dependent carboxyl methylation of a 23-kD protein was also demonstrable in secretory granule fractions from normal islets or beta cells. AFC (a specific inhibitor of prenyl-cysteine carboxyl methyl transferases) blocked the carboxyl methylation of CDC42 in five types of insulin-secreting cells, without blocking GTPgammaS-induced translocation, implying that methylation is a consequence (not a cause) of transfer to membrane sites. High glucose (but not a depolarizing concentration of K+) induced the carboxyl methylation of CDC42 in intact cells, as assessed after specific immunoprecipitation. This effect was abrogated by GTP depletion using mycophenolic acid and was restored upon GTP repletion by coprovision of guanosine. In contrast, although rap 1 was also carboxyl methylated, it was not translocated to the particulate fraction by GTPgammaS; furthermore, its methylation was also stimulated by 40 mM K+ (suggesting a role which is not specific to nutrient stimulation). AFC also impeded nutrient-induced (but not K+-induced) insulin secretion from islets and beta cells under static or perifusion conditions, whereas an inactive structural analogue of AFC failed to inhibit insulin release. These effects were reproduced not only by S-adenosylhomocysteine (another methylation inhibitor), but also by GTP depletion. Thus, the glucose- and GTP-dependent carboxyl methylation of G-proteins such as CDC42 is an obligate step in the stimulus-secretion coupling of nutrient-induced insulin secretion, but not in the exocytotic event itself. Furthermore, AFC blocked glucose-activated phosphoinositide turnover, which may provide a partial biochemical explanation for its effect on secretion, and implies that certain G-proteins must be carboxyl methylated for their interaction with signaling effector molecules, a step which can be regulated by intracellular availability of GTP.
Acetylcysteine↗
Carboxylmethylation of the catalytic subunit of protein phosphatase 2A in insulin-secreting cells: evidence for functional consequences on enzyme activity and insulin secretion.
We report the carboxylmethylation of a 36-kDa protein in intact normal rat islets and clonal beta (INS-1) cells. This protein was predominantly cytosolic. Its carboxylmethylation, as assessed by vapor phase equilibration assay, was resistant to inhibition by N-acetyl-S-trans, trans-farnesyl-L-cysteine, a competitive substrate for cysteine methyl transferases. These data suggest that the methylated C-terminal amino acid is not cysteine. The methylated protein was identified as the catalytic subunit of protein phosphatase 2A (PP2Ac) by immunoblotting. The carboxylmethylation of the PP2Ac increased its catalytic activity, suggesting a key role in the functional regulation of PP2A. Therefore, we studied okadaic acid, a selective inhibitor of PP2A that acts by an unknown mechanism. Okadaic acid (but not 1-nor-okadaone, its inactive analog) inhibited (Ki = 10 nM) the carboxylmethylation of PP2Ac and phosphatase activity in the cytosolic fraction (from normal rat islets and clonal beta-cells) as well as in intact rat islets. Furthermore, methylated PP2Ac underwent rapid demethylation (t 1/2 = 40 min) catalyzed by a methyl esterase localized in islet homogenates. Ebelactone, a purported inhibitor of methyl esterases, significantly delayed (> 200 min) the demethylation of PP2Ac. Furthermore, ebelactone reversibly inhibited glucose- and ketoisocaproate-induced insulin secretion from normal rat islets. These data identify, for the first time, a methylation-demethylation cycle for PP2Ac in the beta-cell and suggest a key functional relationship between PP2A activity and the carboxylmethylation of its catalytic subunit. These findings thus suggest a negative modulatory role for PP2A in nutrient-induced insulin exocytosis.
Animals↗
Insulin secretion in obese and non-obese NIDDM.
Both the insulin response to glucose and the sensitivity to insulin show large variation in the normal population. Many subjects have either a markedly low insulin response or low sensitivity to insulin, with nevertheless normal glucose tolerance. For such subjects to become diabetic, insulin secretion or insulin action must further deteriorate with time, or other factors are added which tip the balance towards diabetes. Most evidence to date indicates that reduced beta-cell responsiveness and reduced insulin sensitivity co-exist in subjects prior to developing NIDDM. Both insulin secretion and insulin action are genetically controlled and influenced by intrauterine and neonatal factors. Insulin secretion and insulin action vary inversely in a closely linked manner; inability to fully compensate for changes in one variable may generate a functional deficit in glucose homeostasis. Subjects combining low functions would run a proportionately larger risk of decompensating the glucose tolerance and be more vulnerable, in terms of diabetes susceptibility, to factors that further reduce insulin output or insulin action. Careful analysis of existing data prompts us to ascribe a dominating role to the impairment of insulin secretion in the pathogenesis of IGT and NIDDM. Patients with NIDDM also exhibit increased proportions of proinsulin and proinsulin conversion intermediates. We used hyperinsulinaemic diabetic and non-diabetic Psammomys obesus to study the possible relationship between steady-state pancreatic insulin stores and the proportion of proinsulin-related peptides in the plasma and the pancreas. A marked increase in these peptides was associated with 90% reduction in insulin stores of the pancreas. After food deprivation, the depletion of pancreatic insulin in the diabetic animals was partially corrected, and the proinsulin/insulin ratio normalized. In contrast, non-diabetic psammomys showed only 50% reduction in pancreatic insulin stores under non-fasting conditions, with no change in proinsulin/insulin ratio. These findings suggest that in the diabetic Psammomys obesus, pancreatic capacity for storage/production of insulin is limited; the metabolic consequences of this limitation are amplified by increased secretory demand secondary to insulin resistance, thus facilitating the establishment of hyperglycaemia, which may in itself further exacerbate the pancreatic dysfunction.
Animals↗
Charles Bonnet syndrome in temporal arteritis.
An 87-year-old woman presented with Charles Bonnet syndrome--the occurrence of formed visual hallucinations in sane aged individuals. This was followed by headaches and unilateral visual loss, and the diagnosis of temporal arteritis (TA) was confirmed by biopsy. Steroid therapy resulted in disappearance of hallucinations, which recurred 7 mo later, responding to an increase in steroid dosage. Charles Bonnet syndrome may be an early sign of decreasing visual acuity in aged individuals; thus, diagnosis of TA or exacerbation of established TA should be considered in such patients.
Aged↗
The human pattern ERG: alteration of response properties with aging.
The influence of aging on both the amplitude and the latency of transient and steady-state pattern electroretinograms (PERG's) was studied in 80 healthy participants ranging from 25 to 77 years of age (mean age, 55.3 years). Responses to counterphasing checkerboard patterns were recorded for each of 7 test conditions in which the spatial (i.e., check sizes 0.25, 0.50, 1.00, and 2.00 degrees) and temporal characteristics (i.e., counterphasing at either 2, 4, 8, or 16 rps) of the stimuli were varied. For both the transient and steady-state PERG's amplitude was inversely related to age (p less than 0.05 for each test condition). In general, PERG latency directly correlated with age, but this effect was less robust (p less than 0.05 for one transient condition and three of the four steady-state conditions). The influence of age on the spatial tuning of the PERG was minimal; the decrease in PERG amplitude and the increase in PERG latency as a function of age were essentially the same for all test conditions. However, the magnitude of the age-related reduction in PERG amplitude was observed to vary with temporal frequency, being largest for the steady-state condition (16 rps). The results from an experiment in which young subjects were tested while wearing opaque contact lenses with 2-mm artificial pupils suggest that senile miosis is a significant factor contributing to the age-related PERG amplitude and latency changes, but it does not fully account for the observed changes.
Adult↗
The pattern electroretinogram in retinal and optic nerve disease. A quantitative comparison of the pattern of visual dysfunction.
A retrospective analysis was performed on the transient and steady-state pattern electroretinograms recorded from 42 patients with glaucoma, 13 patients with senile dementia of the Alzheimer's type, 58 patients with diabetes mellitus, and 92 control subjects to evaluate the pattern of electroretinographic changes associated with retinal and optic nerve disease. The amplitudes of both the initial positive component (N1 to P1) and the subsequent negative component (P1 to N2) of the transient (4 rps) responses were measured. From these measurements the (P1 to N2)/(N1 to P1) was derived. The N1 to P1 amplitude of the steady-state pattern electroretinogram also was measured. In the glaucoma patients all three amplitude measures, as well as the amplitude ratio of the components of the transient response, were reduced significantly compared with age-matched controls (p less than 0.05). A similar pattern was detected in the patients with Alzheimer's disease, but in this case the only statistically significant amplitude reduction was in the steady-state pattern electroretinogram. A different pattern was observed among the diabetic patients (both with and without retinopathy). Only minor reductions in the amplitude of the transient pattern electroretinogram, which were not statistically significant, were noted. In addition, the ratio of the amplitudes of the components of the transient response did not differ from age-matched controls. The amplitude of the steady-state pattern electroretinogram was reduced in diabetics, but this was significant only for those patients with retinopathy (p less than 0.01). These findings support the suggestion that an analysis of both the positive and negative components of the pattern electroretinogram may be useful for differentiating the contributions of retinal and optic nerve dysfunction to visual impairment. The results also indicate that in both retinal and optic nerve disease the steady-state pattern electroretinogram can be an earlier sign of dysfunction than the transient pattern electroretinogram.
Adult↗
Polymyxin B inhibits contraction-stimulated glucose uptake in rat skeletal muscle.
Glucose transport in muscle is activated by contractile activity, an effect that persists in the postexercise state. Polymyxin B, a cyclic decapeptide antibiotic, inhibits the stimulation of glucose uptake in isolated muscle by contractile activity but also decreases tension development in electrically stimulated muscle. The purpose of this study was to determine whether polymyxin B also inhibits contraction-stimulated glucose uptake after in vivo administration of the drug and to examine the relationship between the effects of polymyxin B on tension development and its effects on contraction-stimulated glucose uptake. When polymyxin B was administered to rats in vivo, glucose uptake in muscle after electrical stimulation was decreased, despite the same amount of tension developed as in control rats, indicating an effect of polymyxin B on glucose transport independent of tension development. Our results also indicate that the postexercise increase in glucose uptake is a function of the tension developed by prior contractions. When muscles were perfused with medium containing polymyxin B, this relationship was disrupted. These results provide evidence that polymyxin B causes a decrease in muscle glucose uptake independent of its effects on tension development. The extent to which its effects on glucose uptake are also the result of a diminution in contractile force is uncertain.
Animals↗
Corneal endothelial changes in ocular hypertensive individuals after long-term unilateral treatment with timolol.
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Aged↗