Interaction between cephaloridine and furosemide in man

The effect of intravenous somatostatin on basal and gastrin-stimulated human lower esophageal sphincter pressure (LESP) was examined with the rapid pull-through technique. In a group of 7 healthy volunteers LESP was not influenced under basal conditions, but there was an augmented response to pulse-doses of pentagastrin (0.6 mug/kg) during infusion of somatostatin (250 mug/kg-h). The physiological importance of these findings still has to be evaluated.     

Dehydroascorbate and dehydroascorbate reductase are phantom indicators of oxidative stress in plants

In many physiological studies dehydroascorbate (DHA) reductase is regarded as one of the chloroplast enzymes involved in the protection against oxidative stress. Here, evidence is presented that plant cells do not possess a specific DHA reductase. The DHA reductase activities measured in plant extracts are due to side reactions of proteins containing redox-active dicysteine sites. Native gel electrophoresis combined with specific activity staining revealed three different proteins with DHA reductase activity in leaf and chloroplast extracts. These proteins have been identified as thioredoxins and trypsin inhibitors (Kunitz type) by Western blot analysis. The essential regulatory functions of thioredoxins in chloroplast metabolism are strongly inhibited in the presence of as little as 50 microM DHA. Thus, the intracellular DHA concentration should be kept below 50 microM but not all proteins with DHA reductase activity are effective enough for this purpose. A specific DHA reductase is frequently demanded as part of the enzymatic equipment to avoid oxidative stress. We argue that this is not necessary because in chloroplasts DHA does not accumulate to any significant extent due to the high activities of monodehydroascorbate reductase and of reduced ferredoxin.     

A study of plasmalogen as an index of oxidative stress in patients with chronic renal failure. Evidence of increased oxidative stress in malnourished patients

BACKGROUND: The incidence of premature cardiovascular disease is high in patients with chronic renal failure (CRF). Free-radical-induced tissue damage is thought to play a major role in the pathogenesis of atherosclerosis and several reports indicate increased oxidative stress in patients with CRF. However, the cause of such stress in CRF is not exactly known. Plasmalogens, a group of phospholipids with a vinyl ether bond in the sn-1 position, are supposed to be sensitive markers of oxidative stress. METHODS: The fasting relative plasmalogen levels of erythrocyte membranes (DMA 16/C16:0 and DMA 18/C18:0), as well as of vitamin E and serum lipids, were determined in a cohort of 105 patients (mean age 51+/-2 years) with advanced CRF (creatinine clearance 9+/-1 ml/min) before starting dialysis treatment. Twenty-nine healthy controls (47+/-2 years) were also investigated. RESULTS: Significantly lower relative plasmalogen levels (DMA 16/C16:0 and DMA 18/C18:0) were found in erythrocytes of predialysis patients than in controls. When the patients were divided on the basis of subjective global assessment of nutritional status (SGA), the malnourished patients (SGA 2-4) had significantly (P<0.05) lower relative plasmalogen levels than the well-nourished predialysis patients (SGA 1). In the prospective part of the study, we found that a 12-month dialysis treatment in 38 patients was associated with significant increases in both erythrocyte DMA 16/C16:0 (P<0.001) and DMA18/C18:0 (P<0.05) ratios. CONCLUSION: The present results suggest that predialysis patients are exposed to an augmented oxidative stress which is partially reversed by 12 months of dialysis treatment. The present study also demonstrates lower relative plasmalogen levels in erythrocyte membranes in malnourished than in well-nourished predialysis patients. One could speculate that an increased oxidative stress may be a factor contributing to the high prevalence of cardiovascular disease documented in malnourished CRF patients.     

Urinary and kidney kallikrein in hypertensive rats

10 Patients with positive orthostatic dysregulation were investigated with regard to venous capacity, heart frequency and arterial blood pressure both lying down and sitting up. The venous capacity was reduced by 14% after dehydroergotamine (DHE) in the lying position, which is an expression of increased venous tone. There is no change in venous capacity following the administration of beta blockers in the lying position. Under orthostatic conditions beta blockers bring about an approximate normalization of the venous capacity reaction, whereas the abnormal response following placebo administration is only slightly altered by DHE.     

Hydrogen peroxide metabolism and oxidative stress in cortical, medullary and papillary zones of rat kidney

Piperonyl butoxide was administered to male mice from 5 to 12 weeks of age in the diet at levels of 0 (control), 0.15, 0.30, and 0.60%, and some behavioural parameters were measured. The animals performed three trials in multiple water T-maze at 10 weeks of age, and the number of errors was significantly decreased in treatment groups on the 3rd trial, while there was no biologically significant effect of piperonyl butoxide on maze learning. The motor activity of the exploratory behaviour was measured by ANIMATE AT-420 at 8 and 11 weeks of age. At 8 weeks of age, some parameters were increased in the 0.30% group, while there was no consistent compound- or dose-related effect. At 11 weeks of age, some parameters were different in treatment groups, and there were biologically consistent significant effects; i.e., number of movements, movement time, total distance, average speed, and number of turnings increased. From these results, piperonyl butoxide showed adverse effects on the motor activity of the exploratory behaviour in male mice.     

Blood and breath analyses as biological indicators of exposure to trihalomethanes in indoor swimming pools

The establishment of in vitro culture systems provides an accessible means to study events within the immune system. In contrast to either dispersed suspension or two-dimensional monolayer culture, the explantation of tissue fragments under organ culture conditions is, to date, the only method which allows essential three-dimensional cellular interactions to be maintained under conditions which permit controlled experimental manipulation in vitro. Recent modifications of explant technology, particularly within the area of fetal thymic organ culture, now allow the controlled reassociation of defined cellular subsets and manipulation of gene expression, under conditions where the functioning of both lymphoid and stromal cell types closely resembles that in vivo.     

Urinary oxalic acid excretion in chronic kidney failure and after kidney transplantation

In order to examine the use of helical computed tomography (CT) in lung cancer screening, we evaluated the effects of tube current and table feed speed on image quality. CT images of normal volunteers, which were scanned under various tube currents (150mA, 100mA, 50mA) and various table feed speeds (15mm/sec, 20mm/sec, 25mm/sec, 30mm/sec), were visually evaluated by experienced diagnostic radiologists. The images were not affected by decreasing the milliamperage. However, as table feed speed increased, images were evaluated as significantly worse. Particularly, since the degradation of the images scanned at greater than 25mm/sec was remarkable, they were judged to be unacceptable for detection of the abnormality. In conclusion, a tube current of less than 50mA and table feed speed of less than 20mm/sec are suitable in the application of helical CT for lung cancer screening.     

Urinary tract infection in the immunocompromised host. Lessons from kidney transplantation and the AIDS epidemic

The occurrence of urinary tract infection and its clinical impact is determined, as with any infectious disease, by the interaction between the virulence of the infecting organism and the host defense mechanisms that can be mobilized. In the case of urinary tract infections, an anatomically and functionally intact kidney and urinary tract are the primary host defenses, with phagocytic function and immune mechanisms coming into play to limit the consequences of those infections. Of all the categories of immunocompromised hosts, the renal transplant patient is the one most susceptible to the direct and indirect consequences of urinary tract infections. In the first 3 months post transplant, the incidence of urinary tract infection is greater than 30%, and there is a relatively high rate of bacteremia and overt pyelonephritis of the allograft. After this time period, unless anatomic or functional derangement of the urinary tract is present, the direct clinical manifestations are far more benign. In addition to the direct effects of urinary tract infection on these patients, indirect effects are also important. These include the activation of CMV by TNF released as a consequence of a urinary tract infection and the initiation of allograft injury. Fortunately, low-dose trimethoprim-sulfamethoxazole or fluoroquinolones are safe and effective prophylactic strategies for preventing the direct and indirect consequences of urinary tract infections. Although the pathogenetic mechanisms are incompletely understood, data are emerging that AIDS patients have both an increased incidence and severity of urinary tract infection. The risk for urinary tract infections seem to be correlated with the degree of immune compromise and, perhaps, the amount of malnutrition and wasting that are present. The best strategies for preventing urosepsis in AIDS patients remain to be defined.     

Hemolytic uremic syndrome as a clinical manifestation of oxidative stress

An examination was made of seventeen children having various stages of the hemolytic uremic syndrome: Stage 1 is the period of an expanded clinical picture of the disease, the patients' condition is grave (anuria, azotemia, severe hemolytic anemia and thrombocytopenia); Stage 2 is the period of recovery. The plasma levels of malonic dialdehyde, dienic conjugates, alpha-tocopherol at the first stage of the disease were considerably higher than the control ones, on recovery there were their reductions though their levels remained higher than the normal levels. The levels of malonic dialdehyde in the red blood cell membranes in ill children were also much higher than those in healthy donors, but at the second stage they decreased, but remained high. The activity of superoxide dismutase in the red blood cells of ill children in the acute period of the disease did not significantly differ from that of donors. At the second stage of the disease there was a significant fall in the activity of red blood cell superoxide dismutase. The activity of catalase in the red blood cells of ill children was thrice higher than in the controls; however, this index decreased during treatment and at the second stage it did not differ from that in the controls. There were no significant differences in the activity of red blood cell superoxide dismutase in donors and ill children. Mechanisms responsible for abnormal plasma and red blood cell peroxidation are considered in the hemolytic uremic syndrome. It is concluded that free radical reactions play a substantial role in the pathogenesis of this abnormality.     

Selenium intake as a modulator of responsiveness to oxidative stress

A deficiency in important components of the endogenous antioxidative defense system (AODS) against the production of reactive oxygen species, including free radicals, results in the accumulation of oxidative damage, inducing oxidative stress. A dietary deficiency in selenium (Se), an important part of AODS, can increase the sensitivity of a living system to oxidative stress. We investigated the effects of Se supplementation, in the form of Se-enriched yeast, on the AODS resistance of red blood cells (RBC) to experimentally induced oxidative stress. We analyzed the alterations in main components of the AODS, such as the amount of reduced (GSH) oxidized glutathione (GSSG), Se-dependent glutathione peroxidase (GSH-Px), Se content, catalase (CAT), and thiobarbituric acid reactive substances (TBARS), in RBC of male Wistar rats exposed to gamma rays and supplemented with Se-enriched yeast (SeY) in drinking water. The results suggested that the increased Se level generally exhibited a protective effect against whole body irradiation, reducing the expenditure of the AODS components in defense. These reductions differed depending on the time observed and the parameter investigated but, generally, SeY supplementation induced a faster restoration of the AODS after this kind of oxidative stress.     

Role of biological indicators in the therapeutic decision in breast carcinoma

Before planning therapeutic strategies for patients at different risks of relapse, it is essential to identify prognostic factors. In addition to important anatomo-pathological prognostic factors such as lymph node status and tumour size, certain biological indicators, such as receptor status and proliferative kinetics, are now regarded as useful tools for prognosis. Tumour cell kinetics is an important prognostic variable in different stages of breast cancer. It is also a useful index for identifying subjects of aggressive tumours in node-negative patients. As far as the relationship between TLI estrogen receptor status and tumor size is concerned, it has been observed that only TLI retains its prognostic significance as regards both time to relapse and overall survival. Lymph node status, receptor status, cell kinetics and c-erbB-2 expression were examined as predictive factors of response. It emerged that not all chemotherapeutic regimens have the same impact in a situation where the disease is evaluated exclusively on the basis of lymph node status. Moreover, receptor status and receptor level significantly condition the response to endocrine therapy. Response rates to chemotherapy increase in highly proliferating tumours, whereas endocrine therapy achieves a better response in ER+ tumours with a low TLI index. Further studies are needed to clarify the role of c-erbB-2 as a predictive factor of response.     

Iron-induced oxidative stress modulates olfactory learning and memory in honeybees.

Reactive oxygen species (ROS)-mediated oxidative stress tends to increase with environmental stress, aging, and age-related diseases resulting in progressive neuronal dysfunction. The purpose of the present study was to examine whether or not oxidative stress can be induced into the antennal lobes of the honeybee brain by injecting ferrous ammonium citrate (FAC). Proboscis Extension Reflex conditioning procedure was used to assay subjects' responses to odorants for evaluating the effect of oxidative stress on the olfactory learning and memory. FAC-induced inhibitory effect on olfactory learning and memory was dose-and time-dependent. Injections of reduced glutathione (GSH) into the antennal lobes before FAC treatment blocked oxidative stress-mediated inhibitory effect. Injections of VK-28 prior to FAC treatment overcame oxidative stress-mediated inhibitory response. However, injections of GSH into the antennal lobes prior to mianserin/dsRNA treatment did not reverse octopamine receptor disruption-mediated inhibitory response. These results indicate that normal cellular redox is crucial for olfactory processing, and chelation of iron prevents ROS-mediated oxidative stress. Furthermore, octopamine receptor disruption, and FAC-mediated oxidative stress confer two independent mechanisms that impair olfactory learning and memory in honeybees. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The oxidative stress in the cataract formation

The lens of the eye is an avascular tissue surrounded by fluids such as the aqueous humor and vitreous body, with one side facing toward the outside of the body. We investigated peroxidative reactions occurring in cataractous lenses, examining changes within the lens tissues as well as in the surrounding environment. 1. Peroxidative reactions in lenses. 1) Aging and peroxidative reactions. The activity of superoxide dismutase (SOD) began to decrease in the lenses of rats at six months of age. Moreover, the level of lipid peroxide increased significantly in the lenses of rats at 24 months of age. Lipoproteins became increasingly oxidized with age. The levels of Na+, K+, and Ca++, ions that are important to the maintenance of membrane function, also varied significantly with age. In the lenses of six-month-old Senescence Accelerated Mice (SAM), there was a marked decrease in the ability of scavenge active oxygen and a marked increase in the amount of lipid peroxide. In human lenses, the level of autofluorescence increased as the lens fiber structure changed with age. 2) Generation of free radicals inside the lens. We verified that HO. and ascorbic acid radicals were being generated inside cataractous lenses using electron spin resonance (ESR). 3) Changes in oxidation-related substances in cataractous lenses. Senile cataractous lenses and diabetic cataractous lenses were classified as four types, cortical, nuclear, posterior subcapsular, and mature. In cataractous lenses from all types of diabetic patients, the levels of glucose, glycated protein, and lipid peroxide were higher than in senile cataractous lenses. Among the four types of cataracts, the accumulation of peroxides was the greatest in the nuclear type both diabetic and senile cataractous lenses. 4) Transitional metals. Iron ions and copper ions existed in lens tissue. In particular, the subepithelial region of the lens stained strongly for copper ions. The increased level of copper ions in cataractous lenses is likely to be related to the increased peroxidation in this tissue. 5) Changes in membrane. Lowered levels of phospholipids and a higher degree of saturation of fatty acids were observed in senile cataractous lenses as compared with normal lenses. The increased saturation of fatty acids indicated that there was a damage to the membrane structure due to peroxidative reactions. The receptors for low density lipoprotein (LDL) were shown to exist on the epithelium of normal lenses. Acetyl-LDL, a denatured lipoprotein was incorporated into senile cataractous lenses but not into normal lenses, suggesting that the barrier function of the membrane deteriorates in cataractous lenses. Moreover, in diabetic cataractous lenses, the levels of very low density lipoprotein (VLDL) and LDL significantly increased. 2. Change in the environment surrounding the lens and peroxidative reactions. 1) Changes in the levels of oxidation-related substances in blood, aqueous humor, and vitreous body from diabetic patients: all had decreased levels of reduced glutathione and superoxide scavenging activity, and increased levels of lipid peroxide and glycated protein. This may have been due to a reduction in the anti-oxidative potential in the environment surrounding the lens due to the enhanced glycation. Changes in the level of oxidation related substances in the vitreous body in particular, will likely have a significant impact on the lens. 2) Changes in lenses as the surrounding environment deteriorates. Human lenses were cultured for three weeks under conditions similar to those found in vivo utilizing the culture system that we had originally designed and constructed. When protective activity against peroxidation was reduced, the amount of lipid peroxide increased significantly. In the presence of high levels of glucose, the levels of lipid peroxide increased and the amount and activity of SOD decreased. 3. Effects of changes in the external environment on peroxidative reactions.     

Ascorbic acid and dehydroascorbic acid as biomarkers of oxidative stress caused by smoking

Using a reliable, newly developed assay for ascorbic acid (reduced form) and dehydroascorbic acid (DHAA; the oxidized form) in plasma, we studied the influence of age, sex, and smoking on 219 healthy, age-stratified, and randomly selected subjects representing the Danish population. The mean (+/-SD) plasma total ascorbic acid (ascorbic acid + DHAA) concentration was lower in smokers (62.8 +/- 24.9 mumol/L) than in nonsmokers (74.9 +/- 23.6 mumol/L) (P < 0.001) and the DHAA content was 1.8 +/- 4.0% of the total ascorbic acid in smokers compared with 0.1 +/- 3.1% in nonsmokers (P < 0.001). A significant inverse correlation between the DHAA fraction and the total ascorbic acid concentration was found in smokers (P < 0.002) but not in smokers; the slopes of the linear regressions were significantly different in the two groups (P < 0.005). The mean plasma concentration of total ascorbic acid was higher in females than in males (P < 0.005); this difference persisted in multivariate analysis when smoking was adjusted for. No age dependence could be identified. The data show that smoking results in severe oxidative stress, depletion of the ascorbic acid pool, and insufficient reduction capacity to maintain ascorbic acid in the reduced form in plasma. We suggest that the additional analysis of DHAA allows further differentiation in the assessment of oxidative stress and may provide an objective way of determining vitamin C requirements in smokers. Preliminary findings suggest that a vitamin C dose that results in a plasma concentration of approximately 70 mumol/L or higher is required in smokers.     

Loneliness, social isolation, and behavioral and biological health indicators in older adults.

Objective: A number of mechanisms have been proposed through which social isolation and loneliness may affect health, including health-related behavioral and biological factors. However, it is unclear to what extent isolation and loneliness are independently associated with these pathways. The objective of the present analysis was to determine the impact of social isolation and loneliness, individually as well as simultaneously, on health-related behavioral and biological factors using data from the English Longitudinal Study of Ageing (ELSA). Method: Data on health behaviors (smoking and physical activity) were analyzed from 8,688 participants and data on blood pressure, cholesterol, and inflammatory markers were analyzed from over 5,000 of these participants who were eligible for a nurse visit and blood sampling. Loneliness was measured using the short form of the Revised UCLA scale and an index of social isolation was computed incorporating marital status; frequency of contact with friends, family, and children; and participation in social activities. Results: Fewer than 2% of participants reported being lonely all the time, while nearly 7% had the highest possible scores on social isolation. Both social isolation and loneliness were associated with a greater risk of being inactive, smoking, as well as reporting multiple health-risk behaviors. Social isolation was also positively associated with blood pressure, C-reactive protein, and fibrinogen levels. Conclusions: Loneliness and social isolation may affect health independently through their effects on health behaviors. In addition, social isolation may also affect health through biological processes associated with the development of cardiovascular disease. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Adolescent mothers' cognitions and behaviors as at-risk indicators.

Examined how qualities of adolescent mothers (AMs) are related to their child's socioemotional development and the relationship between maternal characteristics and the AM's ratings of her child's behavior. Ss included 39 AMs (mean age 17.9 yrs) and their children (aged 4–22 mo). Multiple measures of parental characteristics were used, including self-report measures of parenting expectations and mood orientation, and a qualitative behavioral measure of involvement. Analyses compared these measures with ratings of the child's coping behavior by trained observers and mothers' ratings of their child using the Parenting Stress Index (PSI). Findings indicate that parenting expectations had a unique and differential power in explaining both objective child observation ratings and the mothers' PSI ratings of their children. Interactions involving maternal positive behavior were related significantly to mothers' PSI ratings of the child's acceptability or reinforcement. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Urinary retinol excretion and kidney function in children with shigellosis

BACKGROUND: Acute infections, including diarrhea, are associated with an increased risk of vitamin A deficiency. Urinary retinol excretion during such infections may contribute to this risk. The mechanism accounting for urinary retinol loss has not been clearly defined. OBJECTIVE: This study attempted to determine whether urinary retinol loss in children with acute infection is associated with impaired kidney function, particularly impaired tubular protein reabsorption. DESIGN: Urinary retinol excretion and kidney function were examined in 66 hospitalized children 5 mo to 5 y of age with acute Shigella dysentery. RESULTS: Urinary retinol loss occurred in 59% of children and was substantial (>0.1 micromol/d) in 8% of them. Children with more severe disease excreted higher concentrations of urinary retinol; those with a body temperature > or =40 degrees C excreted a mean of 0.10 +/- 0.18 micromol/d compared with 0.005 +/- 0.008 micromol/d for other children (P < 0.0001). Children with more severe disease also had impaired tubular reabsorption of low-molecular-weight proteins beta2-microglobulin and retinol binding protein (RBP)], although other measures of tubular and glomerular function were not similarly impaired. In multiple regression analysis, severity of disease indicators were the best predictors of tubular reabsorption of beta2-microglobulin (R2 = 0.53) whereas tubular reabsorption of beta2-microglobulin and RBP were found to be the best predictors of urinary retinol loss (R2 = 0.69). CONCLUSIONS: A significant amount of retinol was excreted in the urine in children with shigellosis: 8% excreted >0.10 micromol/d (15% of the daily metabolic requirement). Impaired tubular reabsorption of low-molecular-weight proteins, such as RBP transporting retinol, appeared to be the cause of this urinary retinol loss.     

Role of mitochondria in oxidative stress and ageing

Mitochondria are deeply involved in the production of reactive oxygen species through one-electron carriers in the respiratory chain; mitochondrial structures are also very susceptible to oxidative stress as evidenced by massive information on lipid peroxidation, protein oxidation, and mitochondrial DNA (mtDNA) mutations. Oxidative stress can induce apoptotic death, and mitochondria have a central role in this and other types of apoptosis, since cytochrome c release in the cytoplasm and opening of the permeability transition pore are important events in the apoptotic cascade. The discovery that mtDNA mutations are at the basis of a number of human pathologies has profound implications: maternal inheritance of mtDNA is the basis of hereditary mitochondrial cytopathies; accumulation of somatic mutations of mtDNA with age has represented the basis of the mitochondrial theory of ageing, by which a vicious circle is established of mtDNA damage, altered oxidative phosphorylation and overproduction of reactive oxygen species. Experimental evidence of respiratory chain defects and of accumulation of multiple mtDNA deletions with ageing is in accordance with the mitochondrial theory, although some other experimental findings are not directly ascribable to its postulates.     

Role of oxidative stress in health and disease

BACKGROUND: Radiation therapy can cause corneal and conjunctival abnormalities that sometimes require surgical treatment. Corneal stem cell dysfunction is described, which recovered after the cessation of radiation. METHODS: A 44-year-old man developed a corneal epithelial abnormality associated with conjunctival and corneal inflammation following radiation therapy for maxillary cancer. He experienced ocular pain and loss of vision followed by conjunctival epithelialisation of the upper and lower parts of the cornea. RESULTS: Examination of brush cytology samples showed goblet cells in the upper and lower parts of the cornea, which showed increased fluorescein permeability, and intraepithelial lymphocytes. Impression cytology showed goblet cells in the same part of the cornea. Specular microscopy revealed spindle type epithelial cells. Patient follow up included artificial tears and an antibiotic ophthalmic ointment. The corneal abnormalities resolved after 4 months with improved visual acuity without any surgical intervention, but the disappearance of the palisades of Vogt did not recover at 1 year after radiation. CONCLUSION: Radiation therapy in this patient caused temporary stem cell dysfunction which resulted in conjunctivalisation in a part of the cornea. Although limbal stem cell function did not fully recover, this rare case suggested that medical options should be considered before surgery.