Non-contact tonometry synchronized with cardiac rhythm and its relationship with blood pressure

PURPOSE: The main objectives of this study were to determine the differences between non-synchronized intraocular pressure (IOP_N) and intraocular pressure readings synchronized with cardiac pulse and try to determine if these parameters are related to blood pressure values. METHODS: One hundred and sixty-five right eyes from 165 volunteers (107 females, 58 males) aged from 19 to 73 years (mean +/- S.D., 29.93 +/- 11.17) were examined with the Nidek NT-4000, a new non-contact tonometer that allows the measurement of IOP synchronized with the cardiac rhythm. IOP measurements in the four different modes of synchronization were taken in a randomized order. Three measures of each parameter were taken and then averaged. The blood pressure was determined three times with a portable manometer and mean values of systolic and diastolic pressure and the pulse rate were computed. Mean arterial pressure (MAP) was determined as being 1/3 of systolic plus 2/3 of diastolic blood pressure. RESULTS: The mean +/- S.D. values for the standard intraocular pressure (IOP_N: 14.76 +/- 2.86), intraocular pressure in the systolic instant or peak (IOP_P: 14.99 +/- 2.85), intraocular pressure in the middle instant between heartbeats or middle (IOP_M: 14.68 +/- 2.76), and intraocular pressure in the diastolic instant or bottom (IOP_B: 13.86 +/- 2.61) were obtained. The IOP_P was higher than the remaining values. A significant difference in mean IOP existed between IOP_B and the remaining modes of measuring (p < 0.05). Differences were statistically significant for all pair comparisons involving IOP_B. Arterial blood pressure values were systolic 125.5 +/- 14.22, diastolic 77.7 +/- 8.38 and MAP 93.64 +/- 9.44 mmHg. The pulse rate was 77.3 +/- 12.6 beats per minute. Except for the MAP (p = 0.025) there was no significant correlation between different IOP values and systolic or diastolic blood pressure, or pulse rate. CONCLUSIONS: NT-4000 is able to differentiate IOP values when synchronized with the cardiac rhythm and those differences are expected to be within a range of +/-2.5 to +/- 3.0 mmHg. IOP_B seems to be the parameter whose value differs from the non-synchronized and the remaining synchronized parameters in a significant way. Other than a weak association with MAP, no significant correlation between IOP and BP was found. The measurements of IOP readings for the three modes are consistent with timings during the cardiac cycle and IOP pulse cycle.     

Type 2 diabetes: assessment of endothelial lesion and fibrinolytic system markers.

This study aimed to investigate whether endothelial cells are damaged and to evaluate fibrinolytic system function in patients with type 2 diabetes. For this proposal, plasma levels of von Willebrand factor (an endothelial marker of injury), homocysteine (an inductor of endothelial injury), D-dimer (a marker of coagulation cascade activation) and plasminogen activator inhibitor-1 (a fibrinolysis marker) were measured in individuals with both type 2 diabetes and high blood pressure, with type 2 diabetes, with high blood pressure and in healthy control individuals. No significant differences among groups were observed for von Willebrand factor and homocysteine plasma levels. The type 2 diabetes and high blood pressure group presented a significant difference to the other groups for D-dimer and also presented high values for plasminogen activator inhibitor-1. The high blood pressure group and type 2 diabetes group presented separately higher values of plasminogen activator inhibitor-1 compared with the control group. High levels of D-dimer and plasminogen activator inhibitor-1 in patients with type 2 diabetes and high blood pressure with normoalbuminuria therefore indicate a state of hypercoagulability and hypofibrinolysis, despite no evident microvascular injury supported by normal levels of von Willebrand factor and homocysteine.     

The synthesis and antibacterial activities of quinolones containing five- and six-membered heterocyclic substituents at the 7-position

A series of 6-fluoro-7-substituted-1-ethyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acids were prepared. The substituents at the 7-position included five- and six-membered heterocyclic rings such as oxazoline and oxazine as well as five-membered heteroaromatic rings such as oxazoles and imidazoles. The structure--activity relationships (SAR) of these compounds indicated that oxazole substituents containing a 2-methyl group had the greatest in vitro potency. The compounds showed greater in vitro antibacterial activity against Gram-positive organisms than against Gram-negative organisms.     

Stimulation of nerve growth factor and substance P expression in the iris–trigeminal axis of diabetic rats—involvement of oxidative stress and effects of aldose reductase inhibition

In rats with streptozotocin-induced diabetes, we measured increased (by 61%; P<0.05) mRNA for nerve growth factor (NGF) in the iris together with increased (by 82%; P<0.05) mRNA for preprotachykinin (the substance P precursor) in the trigeminal ganglion, suggesting that increased NGF was driving increased substance P gene expression. In other diabetic rats, these changes were prevented by treatment with either an antioxidant (butylated hydroxytoluene; 1% by diet) or an aldose reductase inhibitor (ARI) (sorbinil; 25 mg/kg/day p.o.) and the sorbinil treatment was associated with significant inhibition of polyol pathway intermediates in both lens and sciatic nerve. This suggests that polyol pathway activity in the lens may translate to oxidative stress-driving stimulation of NGF gene expression in the iris. The change is selective for NGF, because expression of the analogous neurotrophin, neurotrophin-3 (NT-3), was unaltered in the same irises. These changes suggest that oxidative stress and/or inflammation can drive up NGF expression in diabetes—a mechanism that might participate in iritis.     

Selective aflatoxin B1-induced sister chromatid exchanges and cytotoxicity in differentiating B and T lymphocytes in vivo

The purpose of this study was to assess the genotoxic and cytotoxic effects of the fungal metabolite aflatoxin B1 (AfB1) on the developing immune system of the chick embryo, a model in vivo system. Of particular interest was the assessment of AfB1 -mediated selective toxicity toward developing B lymphocytes as compared to T lymphocytes. In vivo bromodeoxyuridine (BrdU) labelling of DNA was used to detect the induction of sister chromatid exchanges (SCE) in lymphocytes and to assess the progression of these cells through successive cell cycles. Cytotoxicity was also assessed by studying the entrance and maintenance of cells in mitosis (mitotic index). Graded doses of AfB1 (1.09–17.4 μ/g embryo) were applied to chick embryos of 18 days of incubation (Dl). Embryos also received two doses of BrdU at 3 mg/200 μ (3 hr apart) to provide continuous labelling of B and T lymphocyte replicating DNA. B and T lymphocytes were harvested 20 hr post-AfB1/BrdU exposure from the bursa and thymus, respectively, and were processed for cytogenetic analyses. AfB1 induced dose-related increases in SCE in B lymphocytes; this induction was 6- to 8-fold that of controls at the higher doses tested, AfB1 -mediated induction of SCE in T cells was just 2-fold that of controls at the highest dose tested. AfB1 reduced the progression of B cells and to a lesser extent T ceels through successive rounds of replication. Furthermore, AfB1 dramatically reduced the mitotic index of B cells but not of T cells. These data indicate both selective genotoxicity and cytotoxicity of AfB1 toward B cells in the late stage embryo. © 1993 Wiley-Liss, Inc.     

Cardiovascular and respiratory changes during acute pulmonary edema produced by nephrotoxic serum in the rat

The intravenous injection of rabbit anti-rat kidney serum in rats produces, with a latency of 30 to 60 seconds, the triad sinus bradycardia (or S-A blockade), systemic hypotension and apnea. Recordings of the intracardiac pressures showed a rise in the right and a simultaneous fall in the left ventricular pressure, 30 to 60 seconds after the serum injection. These initial effects were followed by pulmonary edema and death. Bilateral vagotomy prevented the bradycardia and apnea, but not the intracardiac changes, edema and death. Atropine also prevented the bradycardia, but not the apnea, edema and death. Experiments using alpha and beta adrenergic blocking agents seem to indicate that the edema is not caused by the release of catecholamines. It is suggested that the edema could be explained by a rise in the pulmonary capillary pressure, due to the antigen-antibody reaction. The triad bradycardia, systemic hypotension and apnea seems to be the first sign of the pulmonary edema, is reflex in nature, and is assumed to be due to stimulation of J receptors in the lungs, by a mechanical effect (edema). Phenylbutazone and acetylsalicylic acid give a partial protection against the pulmonary edema. Ultramorphological observations of lungs with edema were described.     

X-linked liver glycogenosis type II (XLG II) is caused by mutations in PHKA2, the gene encoding the liver alpha subunit of phosphorylase kinase

X-linked liver glycogenosis type II (XLG II) is a recently described X- linked liver glycogen storage disease, mainly characterized by enlarged liver and growth retardation. These clinical symptoms are very similar to those of XLG I. In contrast to XLG I patients, however, XLG II patients do not show an in vitro enzymatic deficiency of phosphorylase kinase (PHK). Recently, mutations were identified in the gene encoding the liver alpha subunit of PHK (PHKA2) in XLG I patients. We have now studied the PHKA2 gene of four unrelated XLG II patients and identified four different mutations in the open reading frame, including a deletion of three nucleotides, an insertion of six nucleotides and two missense mutations. These results indicate that XLG II is due to mutations in PHKA2. In contrast to XLG I, XLG II is caused by mutations that lead to minor structural abnormalities in the primary structure of the liver alpha subunit of PHK. These mutations are found in a conserved RXX(X)T motif, resembling known phosphorylation sites that might be involved in the regulation of PHK. These findings might explain why the in vitro PHK enzymatic activity is not deficient in XLG II, whereas it is in XLG I.      

Enhancement of murine IgE antibody detection by IgG removal

RATIONALE: Although animal models for the study of allergic reactions are desirable, the use of mice has been hindered by the lack of sufficiently sensitive in vitro immunoglobulin epsilon (IgE) antibody assays. The aim of this study was to enhance IgE antibody measurements by immunoglobulin gamma (IgG) depletion. METHODS: Seven- to eight-week-old female mice of four strains (C3H/HeJ, CBA/J, C57Bl/6J, and Balb/c) were immunized (20 mice/group) with shrimp or peanut extracts using Al(OH)(3) as adjuvant. Following immunization, animals were sacrificed by exsanguination and the sera of each group pooled. Initial measurements of IgE antibody levels by enzyme-linked immunosorbent assay (ELISA) were relatively low; IgG and IgE reactivity patterns by immunoblot were similar. Thus, sera from shrimp or peanut immunized mice were depleted of IgG (absorbed 3-6 times with immobilized protein G) and then tested for IgE antibody to shrimp or peanut allergen. RESULTS: A 3- to 5-fold increase in IgE antibody reactivity as measured by ELISA was demonstrated when >80-90% of the IgG was removed. This increase in detection of allergen-specific IgE occurred in sera from all mouse strains and to all allergens tested. In addition, reactivity of IgE antibodies to peanut or shrimp allergens by immunoblot increased visually approximately 4- to 10-fold. CONCLUSIONS: These studies indicate that allergen-specific IgG antibodies, which may be in more than 100-fold excess to IgE antibodies, interferes with detection of allergen-specific IgE, probably by competitive binding to allergenic epitopes. Substantial depletion of IgG antibodies (>80%) result in a significant increase in the sensitivity of the antibody measurements.     

Granulocyte precursors are the principal cells in bone marrow that stimulate allospecific cytolytic T-lymphocyte responses.

Mouse bone marrow cells were fractionated and enriched for functional activity as stimulators of allospecific cytolytic T-lymphocyte (CTL) responses in vitro. The relevant stimulator cells were enriched sequentially in the low-density fraction of bone marrow, its 2-hr adherent and 18-hr non-adherent fractions and in the FcR-negative fraction of 18-hr non-adherent cells. The functionally enriched cell population contained over 90% granulocyte precursors by ultrastructural analysis. The results indicate that granulocyte precursors are the principal cells in bone marrow that stimulate alloreactive T-cell responses.     

Dra/AfaE adhesin of uropathogenic Dr/Afa+ Escherichia coli mediates mortality in pregnant rats

Escherichia coli bearing adhesins of the Dr/Afa family frequently causes urogenital infections during pregnancy in humans and has been associated with mortality in pregnant rats. Two components of the adhesin, Dra/AfaE and Dra/AfaD, considered virulence factors, are responsible for bacterial binding and internalization. We hypothesize that gestational mortality caused by Dr/Afa⁺ E. coli is mediated by one of these two proteins, Dra/AfaE or Dra/AfaD. In this study, using afaE and/or afaD mutants, we investigated the role of the afaE and afaD genes in the mortality of pregnant rats from intrauterine infection. Sprague-Dawley rats, on the 17th day of pregnancy, were infected with the E. coli afaE⁺ afaD and afaE afaD⁺ mutants. The clinical E. coli strain (afaE⁺ afaD⁺) and the afaE afaD double mutant were used as positive and negative controls, respectively. The mortality rate was evaluated 24 h after infection. The highest maternal mortality was observed in the group infected with the afaE⁺ afaD⁺ strain, followed by the group infected with the afaE⁺ afaD strain. The mortality was dose dependent. The afaE afaD double mutant did not cause maternal mortality, even with the highest infection dose. The in vivo studies corresponded with the invasion assay, where the afaE⁺ strains were the most invasive (afaE⁺ afaD strain > afaE⁺ afaD⁺ strain), while the afaE mutant strains (afaE afaD⁺ and afaE afaD strains) seemed to be noninvasive. This study shows for the first time that the afaE gene coding for the AfaE subunit of Dr/Afa adhesin is involved in the lethal outcome of gestational infection in rats. This lethal effect associated with AfaE correlates with the invasiveness of afaE⁺ E. coli strains in vitro.