Caffeine inhibits cytoplasmic Ca2+ oscillations induced by carbachol and guanosine 5′-O-(3-thiotriphosphate) in hyperpolarized pancreatic ß-cells

The effects of caffeine on cytoplasmic Ca²⁺ oscillations induced by carbachol and guanosine 5-O-(3-thiotriphosphate) (GTP--S) were studied in individual mouse pancreatic ß-cells clamped at a hyperpolarized potential. Addition of 10 mM caffeine did not affect the cytoplasmic Ca²⁺ concentration ([Ca²⁺]₁) in ß-cells exposed to 20 mM glucose and hyperpolarized with diazoxide. Under similar conditions 100 M carbachol induced a typical response with a marked [Ca²⁺]_i peak followed by a lower sustained elevation. Irrespective of whether 10 mM caffeine was present, there were [Ca²⁺]_i transients with frequencies of 1–5/min superimposed on the sustained phase in 50–60% of the cells. In previously non-exposed cells the introduction of 10 mM caffeine caused temporary lowering of the sustained phase with disappearance of the transients. Subsequent omission of caffeine in the continued presence of carbachol caused a marked [Ca²⁺]_i peak followed by reappearance of the [Ca²⁺]_i, transients. However, in cells oscillating in the presence of caffeine its omission caused disappearance of the transients. In this case reintroduction of caffeine restored the transients.In cells kept at –70 mV by a patch pipette containing 100 M GTP--S and 3 mM Mg-ATP there were [Ca²⁺]_i transients with frequencies of 0.5–2.5/min. These transients were sufficiently pronounced to activate repetitively a K⁺ current. Addition of 10 mM caffeine caused disappearance of the [Ca²⁺]_i transients or reduction of their amplitudes and frequencies.The results indicate that caffeine does not activate Ca²⁺-induced Ca²⁺ release in hyperpolarized ß-cells but inhibits the Ca²⁺-mobilizing effect of inositol 1,4,5-trisphosphate. Correspondence to: E. Gylfe at the above address     

Simultaneous irradiation and imaging of blood vessels during pulsed laser delivery

BACKGROUND AND OBJECTIVE: Simultaneous irradiation and viewing of 10-120 microm cutaneous blood vessels were performed to investigate the effects of 2-micros 577-nm dye laser pulses. STUDY DESIGN/MATERIALS AND METHODS: A modified scanning laser confocal microscope recorded vessel response to different radiant exposures (J/cm2). Probit analysis determined the 50% probability ("threshold") radiant exposure necessary to cause embolized or partly occluding coagula, coagula causing complete blood flow stoppage, and hemorrhage. RESULTS: A statistically significant difference in the threshold radiant exposure existed for each damage category for blood vessels 10-30 microm in diameter, but not for larger vessels. For vessels over 60 microm, complete flow stoppage was unattainable; increasing laser pulse energy produced hemorrhage. In larger vessels, coagula often were attached to the superficial vessel wall while blood flowed underneath. Monte Carlo optical and finite difference thermal modeling confirmed experimental results. CONCLUSION: These results provide insight into the role of pulse duration and vessel diameter in the outcome of pulsed dye laser irradiation.     

Critical evaluation of medical, statistical, and occupational data sources in the Kola Peninsula of Russia pertinent to reproductive health studies

Background: The feasibility study described herein was prompted by a report in 1992 of possible reproductive and developmental health concerns among female workers in a Russian nickel refinery. Objective: The primary goal was to ascertain whether medical, statistical, and occupational data bases could be accessed for information about the pregnancy histories, occupational histories, and life-style factors of the women affected. Methods: The project was facilitated by construction of a registry of all births in three towns with a nickel refinery and verification of its contents against patients' records obtained from hospital delivery and gynecology departments and community polyclinics. Municipal Registration Board, Regional Health Statistics Board, and nickel company records were also reviewed. Results: Reproductive/developmental outcome information and workplace histories were acceptable. Sample-size calculations indicated that a cohort or cross-sectional study would be amenable and suitable for the detection of an excess risk for spontaneous abortion with adequate statistical significance and power. Such investigations would need to be supplemented by workplace environmental/biological monitoring assessments for evaluation of exposure to occupational hazardous factors and a worker's questionnaire to obtain information about life-style factors. A case-control design is recommended for the study of congenital defects. Conclusions: A well-designed, comprehensive epidemiology study is technically feasible because of the availability of a favorable pool of study subjects, reproductive/developmental outcome data, information to control for major confounders, and suitable occupational records. Received: 13 July 1998 / Accepted: 7 February 1999     

A model for the intracortical origin of orientation preference and tuning in macaque striate cortex.

We report results of numerical simulations for a model of generation of orientation selectivity in macaque striate cortex. In contrast to previous models, where the initial orientation bias is generated by convergent geniculate input to simple cells and subsequently sharpened by lateral circuits, our approach is based on anisotropic intracortical excitatory connections which provide both the initial orientation bias and its subsequent amplification. Our study shows that the emerging response properties are similar to the response properties that are observed experimentally, hence the hypothesis of an intracortical generation of orientation bias is a sensible alternative to the notion of an afferent bias by convergent geniculocortical projection patterns. In contrast to models based on an afferent orientation bias, however, the "intracortical hypothesis" predicts that orientation tuning gradually evolves from an initially nonoriented response and a complete loss of orientation tuning when the recurrent excitation is blocked, but new experiments must be designed to unambiguously decide between both hypotheses.     

Cardiac allograft vasculopathy: the green lane hospital experience 1987-1998

AIMS: To determine the prevalence of cardiac allograft vasculopathy in heart transplant recipients at Green Lane Hospital and to examine potential risk factors for vasculopathy. METHODS: We retrospectively reviewed the coronary angiograms of all cardiac transplant recipients. Angiography was usually performed one, two and five years after operation. The diagnosis of allograft vasculopathy was made if there was any evidence of coronary artery disease. Patients' medical records were reviewed for potential risk factors. RESULTS: Ninety-one patients underwent cardiac transplantation between December 1987 and March 1998. One year survival was 87%. Angiographic evidence of coronary disease was present in 30 patients and in three patients coronary lesions were first identified at post mortem. Vasculopathy was present in 25%, 35% and 61% of patients at one two and five years following transplant. Donor-acquired lesions could not be excluded as few patients had immediate postoperative angiograms for comparison. Five late deaths have been due to vasculopathy. Recipient age, race, donor age and ischaemic time were similar for those with and without vasculopathy. Frequency or severity of acute rejection episodes, cytomegalovirus infection, lipid profiles, diabetes and hypertension were not significantly different in patients with vasculopathy. CONCLUSION: Cardiac allograft vasculopathy is a common finding after heart transplantation. No definite risk factors were identified in this patient group.     

Planum temporale, planum parietale and dichotic listening in dyslexia

A reduction or reversal of the normal leftward asymmetry of the planum temporale (PT) has been claimed to be typical of dyslexia, although some recent studies have challenged this view. In a population-based study of 20 right-handed dyslexic boys and 20 matched controls, we have measured the PT and the adjacent planum parietale (PP) region in sagittal magnetic resonance images. For the PT, mean left and right areas and asymmetry coefficients were compared. Since a PP area often could not be identified in one or both hemispheres, a qualitative comparison was used for this region. The total planar area (sum of PT and PP) was also compared between the two groups. A dichotic listening (DL) test with consonant–vowel syllables was administered to assess functional asymmetry of language. The results showed a mean leftward PT asymmetry in both the dyslexic and the control group, with no significant difference for the degree of PT asymmetry. Planned comparisons revealed however, a trend towards smaller left PT in the dyslexic group. In control children, but not in the dyslexic children, a significant correlation between PT asymmetry and reading was observed. A mean leftward asymmetry was also found for the total planar area, with no difference between the groups for the degree of asymmetry. Significantly fewer dyslexic children than control children showed a rightward asymmetry for the PP region. Both groups showed a normal right ear advantage on the DL task, with no significant difference for DL asymmetry. No significant correlation was observed between PT asymmetry and DL asymmetry. The present population-based study adds to recent reports of normal PT asymmetry in dyslexia, but indicates that subtle morphological abnormalities in the left planar area may be present in this condition.     

Vitamin C intake and apoptosis in normal rectal epithelium.

Apoptosis, or programmed cell death, may lower the risk of neoplasia by removing genetically damaged or mutated cells. A high rate of apoptosis has been linked to a reduced risk of colorectal adenomas; therefore, it is important to understand factors that impact apoptosis. Antioxidants (e.g., vitamin C) protect cells from harmful oxidation processes but may interfere with apoptosis by protecting genetically damaged cells from reactive oxygen species-dependent cell death. The objective of this study was to evaluate the association between vitamin C intake and apoptosis in normal rectal mucosa. Study participants were part of a large, cross-sectional study, the Diet and Health Study III. Participants were recruited from consecutive, consenting patients who underwent colonoscopy at University of North Carolina Hospitals between August 1, 1998 and March 4, 2000. Vitamin C intake, obtained from a food frequency questionnaire, included both dietary sources and vitamin supplements. Apoptosis was measured by morphological evaluation of H&E-stained sections obtained from pinch biopsy samples of normal rectal mucosa in consenting participants (n = 503). The relationship between vitamin C and apoptosis varied by adenoma status. Among individuals with adenomas, there was an inverse linear association between apoptosis and total vitamin C intake. Similarly, individuals with adenomas in the highest quintile of total vitamin C intake were substantially less likely than those in the lowest quintile to have increased colonic apoptosis (odds ratio, 0.05; 95% confidence interval, 0.01-0.46). Vitamin C was not significantly associated with apoptosis in adenoma-free patients. High vitamin C intake was associated with reduced colorectal apoptosis among individuals with adenomas in this study population. Given that high apoptosis may lower colorectal cancer risk, vitamin C supplements may be contraindicated for patients with a history of adenomas.     

Changes in rapidly extracted auditory evoked potentials during tracheal intubation

BACKGROUND: One of the problems encountered in assessment of the hypnotic level during anesthesia is the extraction of a consistent and reliable measure online and close to real time. Hemodynamic parameters such as heart rate and blood pressure are not, at least with the traditional single parameter versus time presentation, adequate for ensuring an optimal level of anesthesia, especially when using neuromuscular blocking agents (NMBA). In the literature, it has been demonstrated that auditory evoked potentials (AEP) are able to provide two aspects relevant to determining level of anesthesia: firstly, they have identifiable anatomical significance and, secondly, their characteristics reflect the way the brain perceives a stimulus. METHODS: The aim of this study was to evaluate the AEP index based on a system identification model, the autoregressive model with exogenous input (ARX-model), and to compare it to the classical method, the moving time average (MTA). The ARX enables the extraction within 15-25 sweeps, depending on the signal-to-noise ratio (SNR), whereas MTA typically needs 250-500 sweeps. The hypothesis of the present study was that since the ARX-model extracts the AEP faster than the MTA-model, the former should be able to detect changes during the brief, intense stimulus of endotracheal intubation. Twelve female patients scheduled for gynecological surgery were included in the study. Anesthesia was initiated with thiopentone and maintained with isoflurane and alfentanil. The AEP was mapped into an index (AEP-index) normalized to 100 when the individual was awake and decreasing to an average of 25 during thiopentone induced anaesthesia. The results were compared to those obtained by MTA-extracted AEP. RESULTS: During tracheal intubation 9 patients showed an increase in the ARX-extracted AEP-index larger than 15, and 6 of these patients showed an increase larger than 25 (mean increase=33, SD=18). The MTA-extracted AEP-index showed only one patient with an increase larger than 15. The ARX-extracted AEP changed significantly faster than the MTA-extracted AEP. CONCLUSION: The ARX-extracted AEP-index increases during tracheal intubation. There is a significant difference between the ARX-extracted AEP and the traditional MTA-extracted AEP, in terms of response time. In order to trace short-lasting changes in the hypnotic level by AEP, the AEP should be extracted by a method with a fast response such as the ARX-model.