Peach extract induces systemic and local immune responses in an experimental food allergy model.

Peach allergy is among the most frequent food allergies in the Mediterranean area, often eliciting severe anaphylactic reactions in patients. Due to the risk of severe symptoms, studies in humans are limited, leading to a lack of therapeutic options. This study aimed to develop a peach allergy mouse model as a tool to better understand the pathomechanism and to allow preclinical investigations on the development of optimized strategies for immunotherapy. CBA/J mice were sensitized intraperitoneally with peach extract or PBS, using alum as adjuvant. Afterwards, extract was administered intragastrically to involve the intestinal tract. Allergen provocation was performed via intraperitoneal injection of extract, measuring drop of body temperature as main read out of anaphylaxis. The model induced allergy-related symptoms in mice, including decrease of body temperature. Antibody levels in serum and intestinal homogenates revealed a Th2 response with increased levels of mMCPT-1, peach- and Pru p 3-specific IgE, IgG1 and IgG2a as well as increased levels of IL-4 and IL-13. FACS analysis of small intestine lamina propria revealed increased amounts of T cells, neutrophils and DCs in peach allergic mice. These data suggest the successful establishment of a peach allergy mouse model, inducing systemic as well as local gastrointestinal reactions.

Calcium gluconate supplementation is effective to balance calcium homeostasis in patients with gastrectomy.

UNLABELLED: We demonstrate histological evidence for hyperparathyroidism in patients with gastrectomy. This is, at least in part, explained by impaired calcium absorption, resulting in mineralization defects and secondary hyperparathyroidism. Additionally, we demonstrate improved bone mineralization in patients with gastrectomy after gluconate therapy and showed the effectiveness of calcium gluconate over carbonate to balance impaired calcium hemostasis in mice. INTRODUCTION: Gastrectomy and hypochlorhydria due to long-term proton pump inhibitor therapy are associated with increased fracture risk because of intestinal calcium malabsorption. Hence, our objectives were to histologically investigate bone metabolism in patients with gastrectomy and to analyze the impact of calcium gluconate supplementation on skeletal integrity in the setting of impaired gastric acidification. METHODS: Undecalcified bone biopsies of 26 gastrectomized individuals were histologically analyzed. In the clinical setting, we retrospectively identified 5 gastrectomized patients with sufficient vitamin D level, who were additionally supplemented with calcium gluconate and had a real bone mineral density (aBMD) follow-up assessments. A mouse model of achlorhydria (ATP4b-/-) was used to compare the effect of calcium gluconate and calcium carbonate supplementation on bone metabolism. RESULTS: Biopsies from gastrectomized individuals showed significantly increased osteoid, osteoclast, and osteoblast indices and fibroosteoclasia (p < 0.05) as well as impaired calcium distribution in mineralized bone matrix compared to healthy controls. Five gastrectomized patients with sufficient vitamin D level demonstrated a significant increase in aBMD after a treatment with calcium gluconate alone for at least 6 months (p < 0.05). Calcium gluconate was superior to calcium carbonate in maintaining calcium metabolism in a mouse model of achlorhydria. CONCLUSION: Gastrectomy is associated with severe osteomalacia, marrow fibrosis, and impaired calcium distribution within the mineralized matrix. We show that calcium gluconate supplementation can increase bone mineral density in gastrectomized individuals and performs superior to calcium carbonate in restoring calcium/skeletal homoeostasis in a mouse model of achlorhydria.

The role of patient-mode high-resolution peripheral quantitative computed tomography indices in the prediction of failure strength of the elderly women's thoracic vertebral body.

UNLABELLED: The correlations between the failure load of 20 T12 vertebral bodies, their patient-mode high-resolution peripheral quantitative computed tomography (HR-pQCT) indices, and the L1 areal bone mineral density (aBMD) were investigated. For the prediction of the T12 vertebral failure load, the T12 HR-pQCT microarchitectural parameters added significant information to that of L1 aBMD and to that of cortical BMD, but not to that of T12 vertebral BMD and not to that of T12 trabecular BMD. INTRODUCTION: HR-pQCT is a new in vivo imaging technique for assessing the three-dimensional microarchitecture of cortical and trabecular bone at the distal radius and tibia. But little is known about this technique in the direct measurement of vertebral body. METHODS: Twenty female donors with the mean age of 80.1 (7.6) years were included in the study. Dual X-ray absorptiometry of the lumbar spine and femur was performed. The spinal specimens (T11/T12/L1) were dissected, scanned using HR-pQCT scanner, and mechanically tested under 4° wedge compression. The L1 aBMD, T12 patient-mode HR-pQCT indices, and T12 vertebral failure loads were analyzed. RESULTS: For the prediction of vertebral failure load, the inclusion of BV/TV into L1 aBMD was the best model (R (2) = 0.52), Tb.N and Tb.Sp added significant information to the L1 aBMD and to the cortical BMD, but none of the vertebral microarchitectural parameters yielded additional significant information to the trabecular BMD (or BV/TV) and to the vertebral BMD. CONCLUSION: Vertebral microarchitectural parameters obtained from the patient-mode HR-pQCT analysis provide significant information on bone strength complementary to that of aBMD and to that of cortical BMD, but not to that of vertebral BMD and not to that of trabecular BMD.

Avaliação da atividade antioxidante e alelopática do extrato etanólico e frações das cascas do caule de Zanthoxylum rhoifolium Lam., Rutaceae / Assessment of antioxidant and allelopathic activities of ethanolic extract and solvent fractions from stem bark of Zanthoxylum rhoifolium Lam. (Rutaceae)

The purpose of this study was to test for antioxidantand allelopathic activities in stem bark of Zanthoxylum rhoifolium Lam., Rutaceae, with the eventual aim of discovering biologically active substances. The plant material was subjected to ethanolic extraction and this extract was partitioned, yielding hexane, chloroform, ethyl acetate and hydroalcoholic fractions. Antioxidant activity was estimated by the reduction of phosphomolybdenum complex, of DPPH. and of thiobarbituric acid-reactive substances (TBARS). To detect allelopathy, the samples were tested, at four concentrations, on the germination and development of the radicle and hypocotyl of L. sativa seeds. The samples showed significant antioxidant activity against the reduction of the phosphomolybdenum complex, as compared to rutin, and reduction of TBARS, ascompared to BHT, as well as allelopathic activity, since they stimulated growth and seed germination. The chloroform and ethyl acetate fractions showed the best antioxidant potentials, with 204.17% and 127.11% compared to rutin, in the reduction of phosphomolybdenum complex, as did the crude ethanolic extract and hexane fraction, with 64.2% and 60.9% compared to BHT, in the TBARS method. In the allelopathic assay, the chloroform fraction stood out as the only sample that stimulated the growth of both the radicle and hypocotyl at most concentrations, ranging from 41 to 144%, while the ethyl acetate fraction achieved the greatest stimulus in this bioassay, increasing the growth of the hypocotyl by 274%. This is the first study that demonstrates the antioxidant and allelopathic activities of the species Z. rhoifolium...

Este trabalho teve como objetivo o estudo das atividades antioxidante e alelopática das cascas do caule de Zanthoxylum rhoifolium Lam., Rutaceae, de modo a conduzir à descoberta de substâncias biologicamente ativas. O material vegetal foi submetido à extração etanólica e este extrato foi fracionado obtendo as frações (hexano, clorofórmio, acetato de etila e hidroalcoólica). Para a avaliação da atividade antioxidante, empregaram-se os métodos de redução do complexo fosfomolibdênio, de redução do radical DPPH e das substâncias reativas ao acido tiobarbitúrico (TBARS). Quanto à alelopatia, as amostras foram testadas em quatro concentrações sobre a germinação e o desenvolvimento de radícula e hipocótilo das sementes de Lactuca sativa. As amostras evidenciaram atividade antioxidante significativa frente ao método de redução do complexo fosfomolibdênio quando comparada à rutina, e do TBARS quando comparado ao BHT, assim como a atividade alelopática, uma vez que estimularam tanto a germinação como o crescimento das sementes. A fração clorofórmica e acetato de etila demonstraram melhor potencial antioxidante com 204,17% e 127,11% em relação à rutina no método de formação do complexo fosfomolibdênio, e o extrato bruto e a fração hexano com 64,2% e 60,9%, em relação ao BHT, no método TBARS. No ensaio alelopático, destaca-se a fração clorofórmica, pois foi a única amostra que estimulou o crescimento do hipocótilo e radícula na maioria das concentrações, variando de 41 a 144%, e a fração acetato de etila que apresentou a maior porcentagem de estímulo nesse bioensaio, demonstrando estímulo de 274% do crescimento do hipocótilo. Este é o primeiro trabalho que demonstra a atividade antioxidante e alelopática de Z. rhoifolium...

Spontaneous osteonecrosis of the knee (SONK).

PURPOSE: Spontaneous osteonecrosis of the knee (SONK/Morbus Ahlback) mainly affects the medial condyle of elderly women. It is assumed that localized vascular insufficiency leads to necrosis of the subchondral bone with subsequent disruption of the nutrition supply to the cartilage above. The aetiology remains unclear in detail. Operative treatment procedures compete against non-operative strategies, whereas the outcome is unpredictable in many cases. METHOD: A consecutive case series of five patients suffering from SONK was analysed. All patients underwent a clinical examination, magnetic resonance imaging (MRI) and dual-energy X-ray absorptiometry scan, as well as laboratory analyses and visual analogue scale (VAS) evaluation. Our treatment regime is based on high-dose vitamin D administered orally and intravenous application of 3 mg ibandronate two times within 8 weeks. Another 8 weeks later, all patients were followed up including a follow-up MRI. RESULTS: Within 4 weeks, all patients were free of symptoms. The MRI follow-up showed remission of the bone marrow oedema in every case studied. VAS decreased significantly from 7.4 ± 1.0 pre-interventional to 0.8 ± 1.0 post-interventional. No allergic reactions or other side effects were documented. CONCLUSION: We showed that our treatment regime not only eliminated the pathological findings in the MRI of all cases studied, but also decreased the pain level and functional limitations within a short-time period. LEVEL OF EVIDENCE: IV.

Protective effect of hop beta-acids on microbial degradation of thick juice during storage.

AIMS: This study assessed the value of a commercial alkaline solution of hop beta-acids (HBA) for prevention of microbial degradation of thick juice, a concentrated intermediate product in the production of beet sugar. METHODS AND RESULTS: The antimicrobial effect of different concentrations of HBA against microbial degradation of thick juice was tested in a pilot-scale storage experiment. Chemical, biochemical and microbial parameters were monitored during thick juice storage. Thick juice degradation, indicated as a decrease in pH, was generally accompanied by an increase in the count of fastidious bacteria (FB) on Columbia Agar with Sheep Blood (CAwSB), which were mainly identified as Tetragenococcus halophilus. Addition of HBA delayed juice acidification and the development of FB in a concentration-dependent manner. The susceptibility of FB to HBA was determined by plating degraded thick juice (FB > 10(5) CFU ml(-1) on CAwSB plates with different concentrations of HBA (0-160 ppm). None of the HBA concentrations tested reduced the number of FB colonies formed, but increasing HBA concentrations extended the lag time of colony formation. CONCLUSIONS: HBA produce no measurable bactericidal effect, but retard the development of FB in thick juice. Moreover, HBA do not prevent the thick juice from deteriorating, but significantly delay its degradation. SIGNIFICANCE AND IMPACT OF THE STUDY: These results indicate that adding a commercially available HBA formulation can prolong the storage life of thick juice in the sugar industry, although degradation cannot be eliminated. Future research will focus on the detailed characterization of FB consistently isolated from degraded thick juice and on determining their role in thick juice degradation.

Facial expression recognition and subthalamic nucleus stimulation.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor signs in Parkinson's disease. However, clinical studies suggest that DBS of the STN may also affect cognitive and emotional functions. OBJECTIVE: To study the impact of STN stimulation in Parkinson's disease on perception of facial expressions. RESULTS: There was a selective reduction in recognition of angry faces, but not other expressions, during STN stimulation. CONCLUSIONS: The findings may have important implications for social adjustment in these patients.

High frequency stimulation of the basal ganglia for the treatment of movement disorders: current status and clinical results.

High frequency stimulation of the basal ganglia has gained much interest during the last years. Based on the reevaluation of the results of functional neurosurgery for movement disorders from Leksell's group, pallidotomy as lesional procedure was the first functional operation that underwent a renaissance for the treatment of movement disorders. The work by Benabid and Siegfried who carried out thalamic high frequency stimulation to suppress tremor, the knowledge about deep brain stimulation (DBS) for the treatment of chronic pain as well as better understanding in basal ganglia physiology and the development of reliable stimulation hardware led to an increasing number of centers worldwide who currently apply high frequency DBS for different movement disorders. In the present review the current status of DBS for movement disorders is presented and the results with high frequency stimulation targeted at different brain areas are summarized.

Cardiomyocyte-transistor-hybrids for sensor application.

An extracellular recording system has been designed for the detection of electrical cell signals using p-channel or n-channel field-effect transistor (FET) arrays with non-metallized gates. Signals from rat heart muscle cell were recorded by these devices and the results described on the basis of an equivalent circuit. This technique is sensitive enough to detect minute changes of the extracellular membrane voltage and has potential applications in drug screening. We show that known cardiac stimulants (isoproterenol, norepinephrine) and relaxants (verapamil, carbamylcholine) have characteristic effects on the heart cells in terms of the changes of beat frequencies in the absence or presence of corresponding agents.

Novel histamine H(3)-receptor antagonists with carbonyl-substituted 4-(3-(phenoxy)propyl)-1H-imidazole structures like ciproxifan and related compounds.

Novel histamine H(3)-receptor antagonists possessing a 4-(3-(phenoxy)propyl)-1H-imidazole structure generally substituted in the para-position of the phenyl ring have been synthesized according to Mitsunobu or S(N)Ar reactions. With in vitro and in vivo screening for H(3)-receptor antagonist potency, the carbonyl-substituted derivatives proved to be highly active compounds. A number of compounds showed in vitro affinities in the subnanomolar concentration range, and the 4-hexanoyl (10) and 4-acetyl-3-methyl (29) substituted derivatives showed in vivo antagonist potencies of about 0.1 mg/kg after po administration. Many proxifans were also tested for their affinities at other histamine receptor subtypes thereby demonstrating their pronounced H(3)-receptor subtype selectivity. Since the cyclopropyl ketone derivative 14 (ciproxifan) had high affinity in vitro as well as high potency in vivo, it was selected for further studies in monkeys. It showed good oral absorption and long-lasting, dose-dependent plasma levels making it a promising compound for drug development.

Comparison of analgesia and akinesia after retrobulbar injections at different speeds.

PURPOSE: To assess how the speed of injection of local anesthetic solutions affected pain of injection, bulbar akinesia and analgesia with retrobulbar anesthesia (RBA). METHODS: 70 patients undergoing RBA for cataract surgery were enrolled in a prospective masked trial. They were allocated randomly to receive 5 ml anesthetic solution injected either within 20 seconds (group A) or within 60 seconds (group B). Additionally, akinesia of the orbicularis muscle was created according to O'Brien's technique. The pain of injection was registered on an ordinal analogue scale immediately before and after RBA. The following data were collected before and 20 minutes after retrobulbar injection: eye motility (Kestenbaum test), and corneal sensitivity (0: no sensitivity; 1: sensitivity remaining). Data were also collected on age, sex, and bulbar length, and any side effects of the intervention. RESULTS: Injection pain did not differ in the two groups. After RBA horizontal and vertical eye motility was slightly lower in group A than group B. Persistent motility was found in 18 patients in group A and 16 in group B. Median horizontal and vertical motility was 0 mm in both groups. Four patients in group A and five in group B had corneal sensitivity persisting after RBA. CONCLUSIONS: This comparison of different injection velocities brought to light no significant differences regarding bulbar analgesia and akinesia after RBA.

Primary structure and expression analysis of human UDP-N-acetyl-glucosamine-2-epimerase/N-acetylmannosamine kinase, the bifunctional enzyme in neuraminic acid biosynthesis.

N-Acetylneuraminic acid is a main constituent of glycoproteins and gangliosides. In many membrane-bound receptors it is the target for external stimuli. The key enzyme for its biosynthesis is the bifunctional enzyme UDP-N-acetyl-glucosamine-2-epimerase/N-acetylmannosamine kinase, catalysing the first two steps of the biosynthesis in the cytosol. The rat enzyme was previously isolated and characterised. In this report we present the corresponding human cDNA sequence, compare it with the primary structure of the rodent enzyme, and report the analysis of its expression in different human tissues and cell lines.

Effect of therapeutic concentrations of nitric oxide on bacterial growth in vitro.

OBJECTIVES: Besides its vasodilative actions, nitric oxide (NO) is also involved in host defense on a cellular level. We studied the antimicrobial properties of NO in concentrations used with inhaled NO therapy for the treatment of pulmonary hypertension in neonates. DESIGN: In vitro study of bacterial growth of five species, with and without NO exposure. SETTING: Level IV neonatal intensive care unit at a university children's hospital. SUBJECTS: In vitro bacterial cultures. INTERVENTIONS: We tested ten different strains of five bacterial species (Staphylococcus aureus, Staphylococcus epidermidis, group B streptococcus [GBS/Streptococcus agalactiae], Escherichia coli, and Pseudomonas aeruginosa), derived from the tracheal isolates of ventilated premature and term infants. Cultures were exposed to three different concentrations of NO (40, 80, and 120 parts per million [ppm]) and bacterial growth was compared with the same strains incubated in ambient air for 24 hrs. After incubation (with or without NO), colony-forming units were counted. MEASUREMENTS AND MAIN RESULTS: Bacterial growth of S. aureus, E. coli, and P. aeruginosa was not reduced with the NO concentrations applied. The number of colony-forming units of S. aureus increased at 80 ppm of NO. Growth of S. epidermidis and GBS was significantly affected at 120 ppm, resulting in decreased numbers of colony-forming units as compared with controls exposed to ambient air. CONCLUSIONS: We conclude that NO has a selective bacteriostatic effect on some of those bacteria most commonly cultured in tracheal specimens of premature infants and neonates. This effect appears to be dose-dependent and occurs in the upper range of dosages used with inhaled NO therapy. However, in the range of dosages applied in ongoing controlled trials of inhaled NO in neonates and premature infants (1 to 80 ppm), a bacteriostatic effect of NO is not to be expected.

Effect of volume recruitment on response to surfactant treatment in rabbits with lung injury.

We determined if surfactant treatment effect can be enhanced by mechanical volume recruitment during surfactant administration by measuring functional residual capacity, tidal volume, the alveolar portion of tidal volume, dynamic compliance of the respiratory system, a/A ratio, and PaCO2 by measuring before and after surfactant administration to rabbits with lung injury induced by airway lavage. There was improvement in all lung function indices when surfactant was given with volume recruitment, but when surfactant was given without volume recruitment, the only index to show significant improvement was a/A ratio of oxygenation. These results support the hypothesis that mechanical recruitment of terminal airspaces from a previously unventilated compartment will enhance the effectiveness of surfactant replacement by facilitating the distribution of instilled surfactant to this compartment.

Does warming of anesthetic solutions improve analgesia and akinesia in retrobulbar anesthesia?

PURPOSE: The authors assess the effect of warming local anesthetic solutions on pain of injection and on bulbar akinesia and analgesia of retrobulbar anesthesia (RBA). METHODS: Seventy patients undergoing RBA for cataract surgery were enrolled in a prospective, double-blind trial. They were allocated randomly to receive 5 ml either warm (37 degrees C) or cold (20 degrees C) anesthetic solution for RBA. Additionally, O'Brien's method was used to create an akinesia of the orbicularis oculi muscle. The following data were collected before and 20 minutes after retrobulbar injection: pain of injection, eye motility (Kestenbaum test), and corneal sensitivity (0: no sensitivity; 1: sensitivity remaining) at four different sites. The pain of injection was registered using an ordinal analogous scale before and immediately after the injection. Furthermore, data acquisition included any possible side effects and the bulbar length, measured with ultrasound. RESULTS: The score for injection pain (4.5 +/- 2.3 points), horizontal eye motility (0.2 +/- 0.8 mm), vertical eye motility (0.9 +/- 2.1 mm) all were lower for the warm group in comparison to the cold group (average pain score: 5.2 +/- 2.6 points; horizontal eye motility: 0.7 +/- 1.6 mm; vertical eye motility: 1.2 +/- 2.0 mm). Two patients in the warm group and four patients in the cold group had remaining corneal sensitivity. None of the differences were significant. CONCLUSIONS: Data indicate no significant difference in bulbar analgesia and akinesia after RBA between injections of warm and cold anesthetic solutions.

Is the medial globus pallidus a site for stimulation or lesioning in the treatment of Parkinson's disease?

After the encouraging report on bilateral pallidal stimulation by Siegfried in 1994, we started this procedure in 1995 and will report our experience in 6 patients with a mean follow-up of 1 year. In contrast to the good results of pallidotomy reported in the literature improving the 'on' symptoms as dyskinesias as well as 'off' symptoms such as rigidity, bradykinesia and on-off fluctuations, our results indicate that pallidal stimulation improves the 'off' symptoms only to a minor extent and L-dopa-induced dyskinesias remain the main indication. Considering the overall functional outcome, the question arises whether the medial globus pallidus should be lesioned or stimulated.

[On carnitine requirements in full term and low birth weight neonates]. / W sprawie gospodarki karnityna u noworodków donoszonych i z mala masa ciala.

The concentration of total carnitine in the blood serum of 15 newborns between days 5-21 of life was determined. The concentration of carnitine in low-birth-weight newborns is decreased in comparison with normal weight newborns; this deficiency may increase as a consequence of lack of carnitine provided with food or concomitant infection. The authors suggest that supplementation with carnitine be provided to this group of patients so as to prevent possible metabolic and clinical consequences.

[Intensive care aspects in severe tropical malaria: clinical aspects, therapy and prognostic factors]. / Intensivmedizinische Aspekte bei schwerer Malaria tropica: Klinik, Therapie und prognostische Faktoren.

In a retrospective study we analyzed the clinical and blood chemical data of 12 patients with severe tropical malaria in the intensive care units of the University Hospital Zurich and the Stadtspital Triemli, Zurich, between 1991 and 1994. None of the 12 patients had been exposed to malaria before or had taken drugs for chemoprophylaxis. 7 patients survived, 5 died from complications of malaria. According to the criteria of severe tropical malaria defined by the WHO, the following pathological clinical and blood chemical parameters were noted on admission: cerebral coma (2/12); blood hemoglobin < 5 g/dl (0/12), < 8 g/dl (2/12); serum creatinine > 265 mumol/l (3/12); blood glucose < 2.2 mmol/l (0.12); circulatory collapse/shock (0/12); bleeding/signs of disseminated intravascular coagulation in laboratory tests (4/12); acidosis with pH < 7.25 (1/12). Further signs of severe tropical malaria were: hyperparasitemia > 5% (9/12); qualitative and quantitative disturbances of consciousness (6/12); thrombocytopenia < 30 x 10(9)/l (9/12); hyponatremia 125-135 mmol/l (9/12), < 125 mmol/l (2/12); rhabdomyolysis with creatine kinase > 1000 U/l (4/12). The basic treatment consisted of parenteral quinine hydrochloride in all patients; doxycycline was added in 8 cases, clindamycin in 3. Adjuvant therapy with desferrioxamin was given in 3 cases. 6 patients had exchange transfusions. Parasitemia cleared in all patients within 5 to 6 days. Later in the course, 5 patients developed acute respiratory distress syndrome, 6 required hemofiltration due to oliguria, and one became comatose.(ABSTRACT TRUNCATED AT 250 WORDS)