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Biomedical subjects

S Berger

Publications and source records attributed to S Berger.

At least 73 records · Page 4Linked to original sources

Genetic disruption of mineralocorticoid receptor leads to impaired neurogenesis and granule cell degeneration in the hippocampus of adult mice.

To dissect the effects of corticosteroids mediated by the mineralocorticoid (MR) and the glucocorticoid receptor (GR) in the central nervous system, we compared MR-/- mice, whose salt loss syndrome was corrected by exogenous NaCI administration, with GR-/- mice having a brain-specific disruption of the GR gene generated by the Cre/loxP-recombination system. Neuropathological analyses revealed a decreased density of granule cells in the hippocampus of adult MR-/- mice but not in mice with disruption of GR. Furthermore, adult MR-/- mice exhibited a significant reduction of granule cell neurogenesis to 65% of control levels, possibly mediated by GR due to elevated corticosterone plasma levels. Neurogenesis was unaltered in adult mice with disruption of GR. Thus, we could attribute long-term trophic effects of adrenal steroids on dentate granule cells to MR. These MR-related alterations may participate in the pathogenesis of hippocampal changes observed in ageing, chronic stress and affective disorders.

Animals↗

Effect of multiple-dose gatifloxacin or ciprofloxacin on glucose homeostasis and insulin production in patients with noninsulin-dependent diabetes mellitus maintained with diet and exercise.

STUDY OBJECTIVES: To compare the effects of gatifloxacin and ciprofloxacin on glucose homeostasis, including glucose tolerance test (GTT), pancreatic beta-cell function, and insulin production and secretion in patients with noninsulin-dependent (type 2) diabetes mellitus (NIDDM) maintained with diet and exercise; and to evaluate the pharmacokinetics, safety, and tolerability of gatifloxacin. DESIGN: Randomized, double-blind, placebo-controlled, multiple-dose study. SETTING: GFI Pharmaceutical Services, Inc., Evansville, Indiana; Chicago Center for Clinical Research, Chicago, Illinois; and New Orleans Center for Clinical Research, New Orleans, Louisiana, USA. PATIENTS: Forty-eight men and women with NIDDM. INTERVENTIONS: Patients were assigned sequentially at enrollment to receive gatifloxacin 400 mg/day orally, ciprofloxacin 500 mg twice/day orally, or placebo for 10 days. Oral GTTs were performed on specific days throughout the study, as well as measurements of serum glucose, serum insulin, and C-peptide levels. Physical examinations, electrocardiograms, spirometry, and clinical laboratory tests were performed before dosing and on selected dosing days. MEASUREMENTS AND MAIN RESULTS: Gatifloxacin had no significant effect on glucose tolerance and pancreatic beta-cell function, as shown by oral GTT results and insulin and C-peptide levels. Fasting glucose levels 0-6 hours after gatifloxacin administration on days 1 and 10 showed a downward trend, but it was not significant compared with placebo; results were similar with ciprofloxacin. Gatifloxacin also lacked a long-term effect on fasting insulin levels, but this was not shown for a short-term effect, suggesting a modest, transient effect on insulin release. On the other hand, ciprofloxacin had no short-term effect but produced a more sustained effect on insulin release and production. The pharmacokinetics of gatifloxacin in patients with NIDDM were similar to those in healthy subjects. Overall, subjects tolerated treatment well. All reported drug-related adverse events were mild to moderate in intensity. The frequency of adverse events was similar in gatifloxacin- and ciprofloxacin-treated patients, and only slightly higher than in placebo-treated patients. CONCLUSION: Gatifloxacin was well tolerated in patients with NIDDM controlled by diet and exercise. It had no significant effect on glucose homeostasis, beta-cell function, or long-term fasting serum glucose levels, but it did cause a brief increase in serum insulin levels.

Adult↗

Repaglinide/troglitazone combination therapy: improved glycemic control in type 2 diabetes.

OBJECTIVE: This multicenter open-label clinical trial compared the efficacy and safety of repaglinide/troglitazone combination therapy, repaglinide monotherapy, and troglitazone monotherapy in type 2 diabetes that had been inadequately controlled by sulfonylureas, acarbose, or metformin alone. RESEARCH DESIGN AND METHODS: Patients with type 2 diabetes (n = 256) who had inadequate glycemic control (HbA1c > or =7.0%) during previous monotherapy were randomly assigned to receive repaglinide (0.5-4.0 mg at meals), troglitazone (200-600 mg once daily), or a combination of repaglinide (1-4 mg at meals) and troglitazone (200-600 mg once daily). After a 4-6 week washout period, the trial assessed 22 weeks of treatment: 3 weeks (weeks 0-2) of forced titration, 11 weeks of fixed-dose treatment (weeks 3-13), and 8 weeks (weeks 14-21) of titration to maximum dose. Changes in HbA1c and fasting plasma glucose (FPG) values were measured. RESULTS: The combination therapy showed a significant reduction in mean HbA1c values (-1.7%) that was greater than with either type of monotherapy Repaglinide monotherapy resulted in a reduction of HbA1c values that was significantly greater than troglitazone (-0.8 vs. -0.4%) (P < 0.05). Combination therapy was more effective in reducing FPG values (-80 mg/dl) than either repaglinide (-43 mg/dl) or troglitazone (-46 mg/dl) monotherapies. Adverse events were similar in all groups. CONCLUSIONS: Combination therapy with repaglinide and troglitazone leads to better glycemic control than monotherapy with either agent alone. Repaglinide monotherapy was more effective in lowering HbA1c levels than troglitazone monotherapy Repaglinide/troglitazone combination therapy was effective and did not show unexpected adverse events.

Adult↗

The selection of homograph meaning: word association when context changes.

In a study of lexical ambiguity processing, responses to homographs were examined in a word association task. The context of repeated exposures of a homograph was manipulated by requiring a response to a word related to a meaning of the homograph on the trial prior to homograph presentation. A change of that relationship reduced the effectiveness of the contextual item as a prime on the second occurrence of the homograph. In response to a third unprimed occurrence of the homograph, associations were consistent with a conclusion that when semantic contexts are opposed, a "primacy effect" is obtained. The overall effects in the studies reported are seen as consistent with the theoretical view of Simpson and Kang (1994) that processing and responding to one meaning of a homograph result in the inhibition of alternative meanings. A mechanism to account for that inhibition is proposed.

Association↗

[Current nutrition supporting programs of the population in the USA].

In this work main programs of nutrition-supporting in the USA were presented as a part of national and local social and health policy. Following programs were reviewed namely: FSP (The Food Stamp Program), NSLP (The National School Lunch Program), SBP (School Breakfast Program), SMP (The Special Milk Program), WIC Program (The Special Supplemental Food For Women, Infants and Children), SFSP (The Summer Food Service Program). The level of monthly income per person (no more than 130% of poverty line) is the condition for participation in every program. Some programs (e.g. FSP) are addressed to all citizens, who are fulfilling income criteria, whereas other (e.g. WIC, SBP) are available to selected population groups only. Assistance within these programs may occur in various forms (e.g. food stamps for family, possibilities in using of low cost meals, free of cost milk for school children). Authors suggest to utilize some of US experience in nutrition-supporting programs also in Poland.

Health Promotion↗

Evidence of two enzymes performing the de-N-glycosylation of proteins in barley: expression during germination, localization within the grain and set-up during grain formation.

The occurrence of two enzymes performing de-N-glycosylation of glycoproteins, namely, endo-N-acetyl-beta-D-glucosaminidase (ENGase, EC 3.2.1.96) and peptide-N(4)-(N-acetyl-beta-D-glucosaminyl) asparagine amidase (PNGase, EC 3.5.1.52) was investigated in barley, cv. Plaisant (a winter six rowed variety). The dry grain showed both activities according to the HPLC detection of the hydrolysis of fluorescent resorufin-labelled substrates. However, PNGase activity was 16-fold higher than ENGase activity. During germination, both activities increased, PNGase by only 1.5-fold compared to nearly 4.8-fold for ENGase over the 4 d following imbibition. The localization of these activities within the grain showed that the major contribution of PNGase was due to the endosperm, typically representing over 90% of the whole grain activity. In contrast, ENGase activity was especially high in the embryo and, later, in the developing plantlet (10-fold higher than in the endosperm), particularly in the rootlets and scutellum. In developing spikes, PNGase activity was 5.6-fold higher than in the leaves, but similar ENGase activity was measured in both organs. During grain formation, PNGase activity followed dry matter increase together with endosperm development. In contrast, ENGase activity dropped by 66% at the beginning of grain filling before stabilizing until harvest. The occurrence of de-N-glycosylation-performing enzymes throughout the development of barley raises the question of the nature of their natural substrates. Moreover, the prevalence of one of these enzymes over the other depending on the organ and the developmental stage, could represent the first evidence of specific functions for each enzyme.

Amidohydrolases↗

[Health - oriented aspects in nutrition of children and adolescents].

The author underlines the necessity of recognition health-oriented aspects in nutrition of children and adolescents for both food producers as well as consumers. It is of great importance not only for growth and development of the young population but also for the health of adults. The author has presented the concept of interrelationship between factors aimed at achieving safe food and proper nutritional guidelines for consumer and the knowledge of genetic and environmental aspects. Educational programmes and research in the field of safe food and proper nutrition sciences should play a crucial role.

Adolescent↗

Rapid nongenomic effects of aldosterone in mineralocorticoid-receptor-knockout mice.

In addition to genomic effects of aldosterone, rapid nongenomic effects of steroids have been reported in various tissues that were clearly incompatible with a genomic action of aldosterone. Rapid effects of aldosterone involve second messengers such as calcium and cAMP. Specific high affinity binding sites for aldosterone have been characterized in membranes for different cells, which probably transmit those rapid steroid effects. To date, it is unclear if these binding sites are modified classical mineralocorticoid receptors (MR) or if they represent an unrelated receptor protein. The aim of the present study was to investigate whether rapid aldosterone action still occurs in the absence of the classical MR. For this purpose we used the model of MR knockout mice. Rapid effects were analyzed in skin cells, measuring intracellular calcium and cAMP levels after stimulation with aldosterone. We found that rapid effects are not only present in MR knockout mice, but that the effects are even larger than in wild-type mice cells. The results of the present study demonstrate that the classic MR is dispensable for rapid aldosterone action. The study, thus, proves that a receptor different from the classic intracellular receptor is involved in rapid aldosterone signaling.

Aldosterone↗

Evaluation of eating patterns with different methods: the Polish experience.

The implementation of a market economy at the beginning of the 1990s has changed Polish consumers. This paper describes results of different methods which are used to evaluate food consumption, including eating patterns, in this time of transition. Except for the significant decrease of dairy products and increase of vegetable oils the pattern of the menu in Poland remains very traditional. The differences between the previous and present situation are based on changes in the organization of shopping and the possibilities of preparing meals.

Diet Surveys↗

Expression and biotinylation of a mutant of the transcarboxylase carrier protein from Propioni shermanii.

A deletion mutant (residues 10 to 48 cut) of the biotinyl subunit (tcc) from the enzyme transcarboxylase (EC 2.1.3.1) of Propioni shermanii was overexpressed in Escherichia coli. Complete biotinylation of the protein was achieved by addition of exogenous biotin and coexpression of the biotin holoenzyme synthetase (EC 6.3. 4.15.) from E. coli. The transcription of both genes was put under control of different operators/promoters, thus achieving independent control of expression levels and optimized yields of the holo-tcc. Bacteria were grown in a biotin-supplemented minimal medium (M9) that contained [(13)C]glucose as the carbon source and [(15)N]NH(4)Cl as the sole nitrogen source. The target protein could be purified to homogeneity by ion-exchange chromatography and concentrated to NMR-suitable concentrations (2 mM) without aggregation.

Biotinylation↗

Injuries of the lateral collateral ligaments of the ankle: assessment with MR imaging.

The aim of this study was to evaluate the ability of MRI to display injuries of the lateral collateral ligamentous complex in patients with an acute ankle distorsion trauma. The MR examinations of 36 patients with ankle pain after ankle distorsion were evaluated retrospectively without knowledge of clinical history, outcome and/or operative findings. The examinations were performed on a 1. 5-T whole-body imager using a flexible surface coil. The signs for ligamentous abnormality were as follows: complete or partial discontinuity, increased signal within, and irregularity and waviness of the ligament. The results were compared with operative findings in 18 patients with subsequent surgical repair. Eighteen patients with conservative therapy had a follow-up MR examination after 3 months. There was 1 sprain, 3 partial and 32 complete tears of the anterior talofibular ligament, and 5 sprains, 5 partial, and 7 complete tears of the calcaneofibular ligament. There were no lesions of the posterior talofibular ligament. Compared with surgery, MRI demonstrated in 18 of 18 cases the exact extent of anterior talofibular ligament injuries and underestimated the extent in 2 of 8 cases of calcaneofibular ligament injury. In patients with follow-up MRI after conservative therapy, a thickened band-like structure was found along the course of the injured ligament in 17 of 18 cases. The absence of ligament repair after conservative treatment was confirmed during operative revision in one case. The MRI technique allows for grading of the extent of injury of the lateral collateral ligamentous complex after acute ankle strain. It seems to be suitable for monitoring the healing process after conservative-functional treatment of ligament tears.

Acute Disease↗

Rescue of the mineralocorticoid receptor knock-out mouse.

The mineralocorticoid receptor knock-out mouse (MR-/-), resembling inborn pseudohypoaldosteronism, dies 8-12 days after birth in circulatory failure with all the signs of terminal volume contraction. The present study aimed to examine the functional defects in the kidney and colon in detail and to attempt to rescue these mice. In neonatal (nn) MR-/- the amiloride-sensitive short-circuit current in the colon was reduced to approximately one-third compared to controls (MR+/+ and MR+/-). In isolated in vitro perfused collecting ducts the amiloride-induced hyperpolarization of the basolateral membrane (Vbl) of nn MR-/- was similar to that of controls, but urinary Na+ excretion was markedly increased to 4.3 micromol/day.g (BW). Based on this measured urinary Na+ loss we tried to rescue nn MR-/- mice by injecting NaCl twice daily (3.85 micromol/g BW), corresponding to 22 microliter of isotonic saline/g BW subcutaneously. This regimen was continued until the animals had reached a body mass of 8.5 g. Thereafter, in addition to normal chow and tap water, NaCl drinking water (333 mmol/l) and pellets soaked in 333 mmol/l NaCl were offered. Unlike the untreated nn MR-/- most of these mice survived. The adult animals were examined between days 27 and 41, some were used for breeding. When compared to age-matched controls the growth of MR-/- was delayed until day 20. Then their growth curve increased in slope and reached that of controls. MR-/- retained their Na+-losing defect. Amiloride's effect on urinary Na+ excretion was not significant in MR-/- mice and the effect on Vbl in isolated cortical collecting ducts was attenuated. The renin-producing cells were hypertrophic and hyperplastic. Plasma renin and aldosterone concentrations were significantly elevated in MR-/- mice. These data indicate that MR-/- can be rescued by timely and matched NaCl substitutions. This enables the animals to develop through a critical phase of life, after which they adapt their oral salt and water intake to match the elevated excretion rate; however, the renal salt-losing defect persists.

Absorption↗

Phenoxybenzamine improves systemic oxygen delivery after the Norwood procedure.

BACKGROUND: Achieving adequate systemic oxygen delivery after the Norwood procedure frequently is complicated by excessive pulmonary blood flow at the expense of systemic blood. We hypothesized that phenoxybenzamine could achieve a balanced circulation through reduction of systemic vascular resistance. METHODS: In this prospective, nonrandomized study, oximetric catheters were placed in the superior vena cava for continuous monitoring of systemic venous oxygen saturation. Postoperative hemodynamic variables were compared between 7 control patients and 8 patients who received phenoxybenzamine. RESULTS: The hospital survival rate was 93% (14 of 15 patients). Improvements in postoperative hemodynamics in the phenoxybenzamine group included a higher systemic venous oxygen saturation, a narrower arteriovenous oxygen content difference, a lower ratio of pulmonary to systemic flow, and a lower indexed systemic vascular resistance. In the phenoxybenzamine group, mean arterial blood pressure was related directly to systemic oxygen delivery, in contrast to the control group, where mean arterial pressure was related directly to indexed systemic vascular resistance and the ratio of pulmonary to systemic circulation. CONCLUSIONS: Continuous postoperative monitoring of systemic venous oxygen saturation in a patient who has undergone the Norwood procedure provides early identification of low systemic oxygen delivery and an elevated ratio of pulmonary to systemic circulation. In this pilot study, phenoxybenzamine appeared to improve systemic oxygen delivery during the early postoperative period after the Norwood procedure. Further studies are indicated to confirm these results.

Adrenergic alpha-Antagonists↗

Sudden cardiac death in infants, children, and adolescents.

Although SCD is relatively uncommon, its psychosocial impact is devastating. This article has reviewed the potential causes of SCD in infants, children, and adolescents. Many patients who die from SCD have identifiable cardiac disease and are known to have been at risk; however, the existence of other cardiac abnormalities, such as hypertrophic cardiomyopathy or long QT syndrome, may not be known, and SCD may be the first symptom. The authors' contention is that many of the patients in this latter group (e.g., patients who have hypertrophic cardiomyopathy or LQLTS but who have no symptoms) can be screened with a careful, accurate, and detailed history, including family history and review of systems, and physical examination. Any patient with a positive family history, positive review of systems, or positive physical examination should receive further in-depth evaluation, such as an ECG and echocardiogram. These studies permit the detection of most, if not all, of the entities potentially associated with SCD in the pediatric population.

Adolescent↗

Possibilities of fish oil application for food products enrichment with omega-3 PUFA.

Polyunsaturated fatty acids of omega-3 series (omega-3 or n-3 PUFA), especially long chain EPA and DHA, exert strong positive influence on human health. Intake of these fatty acids is however usually too low: that brings many unfavourable health effects to the whole populations. Therefore the increased consumption of omega-3 fatty acids is recommended. A good way to raise the omega-3 PUFA content in the diet, without radical changes of eating habits, seems to be the enrichment of frequent and common consumed food products. The target of this study was to explore the possibility of selected food products enrichment with omega-3 PUFA, using fish oil preparations in liquid (30% EPA and DHA) and powder-micro-encapsulated (10%) form, without significant taste deterioration of the enriched foods. These were designed as functional food, useful in prevention of many diseases. It was shown that food product palatability was affected very differently by enrichment. The highest inclusion level was obtained in the case of instant powder-milk-based formulae concentrates (up to 18% that provided 1.8% EPA, DHA), fats (up to 1.5% that provided 0.5% EPA, DHA), and products of high sweetness and flavours intensity, that mask unpleasant fishy taste and odour. Enriched salad oil retained good quality during 4 months of storage: also concentrates-during 6 months. Shelf-life prolongation of low pH, water-based products (fruit beverages), requires additional technological treatment to decrease oxidation. Enrichment at significant level (up than 0.1% that provides 0.03% EPA, DHA) of low-flavours intensity products (milk, vegetable juice), strongly decreases their palatability. As a final conclusion, authors suggest that frequent consumption of food products enriched at sensory acceptable levels may considerably increase EPA and DHA amount in the diet, improving its nutritional quality.

Animals↗