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1.
Eur Rev Med Pharmacol Sci ; 26(8): 2891-2899, 2022 04.
Article in English | MEDLINE | ID: mdl-35503635

ABSTRACT

OBJECTIVE: The objective of this study is to find a contrast-enhanced CT-radiomic signature to predict clinical incomplete response in patients affected by hepatocellular carcinoma who underwent locoregional treatments. PATIENTS AND METHODS: 190 patients affected by hepatocellular carcinoma treated using focal therapies (radiofrequency or microwave ablation) from September 2018 to October 2020 were retrospectively enrolled. Treatment response was evaluated on a per-target-nodule basis on the 6-months follow-up contrast-enhanced CT or MR imaging using the mRECIST criteria. Radiomics analysis was performed using an in-house developed open-source R library. Wilcoxon-Mann-Whitney test was applied for univariate analysis; features with a p-value lower than 0.05 were selected. Pearson correlation was applied to discard highly correlated features (cut-off=0.9). The remaining features were included in a logistic regression model and receiver operating characteristic curves; sensitivity, specificity, positive and negative predictive value were also computed. The model was validated performing 2000 bootstrap resampling. RESULTS: 56 treated lesions from 42 patients were selected. Treatment responses were: complete response for 26 lesions (46.4%), 18 partial responses (32.1%), 10 stable diseases (17.9%), 2 progression diseases (3.6%). Area-Under-Curve value was 0.667 (95% CI: 0.527-0.806); accuracy, sensitivity, specificity, positive and negative predictive values were respectively 0.66, 0.85, 0.50, 0.59 and 0.79. CONCLUSIONS: This contrast-enhanced CT-based model can be helpful to early identify poor responder's hepatocellular carcinoma patients and personalize treatments.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/therapy , Humans , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/pathology , Liver Neoplasms/therapy , Retrospective Studies , Tomography, X-Ray Computed/methods
2.
Mar Pollut Bull ; 167: 112308, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33866203

ABSTRACT

Seagrass ecosystems exist throughout Pacific Island Countries and Territories (PICTs). Despite this area covering nearly 8% of the global ocean, information on seagrass distribution, biogeography, and status remains largely absent from the scientific literature. We confirm 16 seagrass species occur across 17 of the 22 PICTs with the highest number in Melanesia, followed by Micronesia and Polynesia respectively. The greatest diversity of seagrass occurs in Papua New Guinea (13 species), and attenuates eastward across the Pacific to two species in French Polynesia. We conservatively estimate seagrass extent to be 1446.2 km2, with the greatest extent (84%) in Melanesia. We find seagrass condition in 65% of PICTs increasing or displaying no discernible trend since records began. Marine conservation across the region overwhelmingly focuses on coral reefs, with seagrass ecosystems marginalised in conservation legislation and policy. Traditional knowledge is playing a greater role in managing local seagrass resources and these approaches are having greater success than contemporary conservation approaches. In a world where the future of seagrass ecosystems is looking progressively dire, the Pacific Islands appears as a global bright spot, where pressures remain relatively low and seagrass more resilient.


Subject(s)
Ecosystem , Melanesia , Micronesia , Pacific Islands , Papua New Guinea , Polynesia
3.
Physiol Int ; 2021 Apr 08.
Article in English | MEDLINE | ID: mdl-33835941

ABSTRACT

Aging is a multifactorial process, which is considered as a decline over time. It is increasingly clear that there is a gender difference in aging and in the prevalence of age-related diseases as well. We aimed to examine the effects of the aging process in the colonic tissue of female Wistar rats aged 10 weeks (young) and 13 months (middle-aged) at an early stage, according to three main symptoms associated with aging: a decrease in the efficacy of the proteasome and muscle function and an increase in oxidative stress. The aging process was found to cause a significant decrease in ubiquitin C-terminal hydrolase ligase (UCHL-1) and a significant increase in 3-nitrotyrosine (3-NT), total glutathione (GSH), calcium (Ca2+), calcitonin gene-related peptide (CGRP) and superoxide dismutase (SOD) activity in middle-aged animals. In summary, it is suggested that the reduced activity of the proteasomal degradation system may be the result of the diminished expression of the UCHL-1 enzyme and the decreased levels of ubiquitin; furthermore, we found some key targets which may help to better understand the fundamental aging process.

4.
J Oncol ; 2019: 6153041, 2019.
Article in English | MEDLINE | ID: mdl-31781215

ABSTRACT

The term "artificial intelligence" (AI) includes computational algorithms that can perform tasks considered typical of human intelligence, with partial to complete autonomy, to produce new beneficial outputs from specific inputs. The development of AI is largely based on the introduction of artificial neural networks (ANN) that allowed the introduction of the concepts of "computational learning models," machine learning (ML) and deep learning (DL). AI applications appear promising for radiology scenarios potentially improving lesion detection, segmentation, and interpretation with a recent application also for interventional radiology (IR) practice, including the ability of AI to offer prognostic information to both patients and physicians about interventional oncology procedures. This article integrates evidence-reported literature and experience-based perceptions to assist not only residents and fellows who are training in interventional radiology but also practicing colleagues who are approaching to locoregional mini-invasive treatments.

5.
Eur Rev Med Pharmacol Sci ; 23(15): 6554-6561, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31378896

ABSTRACT

OBJECTIVE: To assess the safety and feasibility of computed tomography-guided radiofrequency ablation (CT-guided RFA) in unresectable lung neoplasms, using a new 15G monopolar internally cooled wet electrode. PATIENTS AND METHODS: 15 consecutive patients with lung neoplasms (< 4 cm), both primary and secondary, unsuitable for or refusing surgery, underwent percutaneous CT-guided RFA using a 15G electrode with a 3-cm exposed tip. The prevalence and grade of adverse events and technical success were evaluated, as well as the extension of the ablation zone, the complete response rates, and the time to progression, determined at CT examination performed 1, 6, and 12 months after the procedure. RESULTS: A total of 22 lung neoplasms were treated (mean diameter: 28 mm; range: 20-39 mm). Technical success was obtained in all patients, without major complications or intraprocedural deaths. Mild or moderate pneumothorax was registered in 46.7% of patients, while a perilesional hemorrhage was observed in 5/15 cases. During the follow-up period, a complete response was obtained in 19 out of 22 lesions (86.4%) with three partial response, two of them successfully retreated with the same technique. CONCLUSIONS: Percutaneous RFA using a 15G internally cooled wet electrode is a safe and feasible treatment for unresectable lung neoplasms, with high complete response rates.


Subject(s)
Carcinoma, Non-Small-Cell Lung/surgery , Catheter Ablation/instrumentation , Lung Neoplasms/surgery , Pneumothorax/epidemiology , Postoperative Hemorrhage/epidemiology , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/mortality , Catheter Ablation/adverse effects , Catheter Ablation/methods , Electrodes , Feasibility Studies , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Lung/diagnostic imaging , Lung/surgery , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/mortality , Male , Middle Aged , Pneumothorax/diagnosis , Pneumothorax/etiology , Postoperative Hemorrhage/diagnosis , Postoperative Hemorrhage/etiology , Prospective Studies , Radiography, Interventional , Severity of Illness Index , Tomography, X-Ray Computed , Treatment Outcome
6.
Physiol Int ; 106(2): 140-150, 2019 Jun 01.
Article in English | MEDLINE | ID: mdl-31282761

ABSTRACT

INTRODUCTION: The quality and function of movements undergo deterioration due to weight gain. Aerobic training normalizes body weight, improves the health status, and in addition, it is expected to improve the dynamics of movements. The aims of this study were to prove the beneficial effects of recreational physical activities on the movements. METHODS: Participants were divided into five different age categories: second childhood, adolescence, mature age I, mature age II, and aging. Squatting and vertical jumping of the participants were measured at the beginning and at the end of a 5-month training program. These movements simulated ordinary daily movements. Changes in the body were determined by InBody230. APAS 3D system was used for movement analysis. RESULTS: The results showed significant improvements in body weight, fat mass, muscle mass, fat mass-body weight ratio, muscle mass-body weight ratio, body mass index, body fat percentage, and waist-hip ratio. During jumping, the lifting and sinking of the center of gravity's (CG) position and its velocity and acceleration were improved. In case of squatting, the results showed significant improvements in the velocity and acceleration of dynamical characteristics of the CG. Other correlations were observed between changes in body composition and the dynamics of movements. DISCUSSION: The research proved that recreational training optimized body composition and improved the characteristics of CG's dynamics. The study suggests considerable connection between body composition and the characteristics of the movements' dynamics. From this point of view, our training program was the most effective in the working age groups.


Subject(s)
Exercise/physiology , Acceleration , Adolescent , Adult , Aged , Body Composition/physiology , Body Mass Index , Body Weight/physiology , Child , Female , Gravitation , Humans , Male , Middle Aged , Waist Circumference/physiology , Young Adult
7.
Homo ; 68(5): 398-409, 2017 Oct.
Article in English | MEDLINE | ID: mdl-29066093

ABSTRACT

Abdominal fat accumulation is a major risk factor for cardiometabolic morbidity and mortality. The purpose of the study is to assess the possibility of developing accurate estimation equations based on body measurements to determine total abdominal (TFA), subcutaneous (SFA) and visceral fat area (VFA). Hungarian volunteers (n=198) aged between 20 and 81 years were enrolled in the study, which was conducted between July and November 2014. All persons underwent anthropometric measurements and computer tomographic (CT) scanning. Sex-specific multiple linear regression analyses were conducted in a subgroup of 98 participants to generate estimation models, then Bland-Altman's analyses were applied in the cross-validation group to compare their predictive efficiency. The variables best predicting VFA were hip circumference, calf circumference and waist-to-hip ratio (WHR) for males (R2=0.713; SEE=5602.1mm2) and sagittal abdominal diameter (SAD), WHR, thigh circumference and triceps skinfold for females (R2=0.845; SEE=3835.6mm2). The SFA prediction equation included SAD, thigh circumference and abdominal skinfold for males (R2=0.848; SEE=4124.1mm2), body mass index and thigh circumference for females (R2=0.861; SEE=5049.7mm2). Prediction accuracy was the highest in the case of TFA: hip circumference and WHR for males (R2=0.910; SEE=5637.2mm2), SAD, thigh circumference and abdominal skinfold for females (R2=0.915; SEE=6197.5mm2) were used in the equations. The results suggested that deviations in the predictions were independent of the amount of adipose tissue. Estimation of abdominal fat depots based on anthropometric traits could provide a cheap, reliable method in epidemiologic research and public health screening to evaluate the risk of cardiometabolic events.


Subject(s)
Abdominal Fat/anatomy & histology , Adiposity , Anthropometry/methods , Abdominal Fat/diagnostic imaging , Adult , Aged , Aged, 80 and over , Biostatistics , Female , Humans , Male , Middle Aged , Obesity, Abdominal/diagnostic imaging , Obesity, Abdominal/pathology , Risk Factors , Tomography, X-Ray Computed , Waist-Hip Ratio , Young Adult
8.
Clin Neurol Neurosurg ; 155: 20-21, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28214652

ABSTRACT

BACKGROUND: Charcot-Marie-Tooth disease (CMT) type 1A is the most common form of CMT 1 and one of the autosomal dominant demyelinating hereditary motor and sensory neuropathies (HMSN). Cranial nerves may be frequently subclinically affected in CMT disease. However manifest clinical signs of cranial nerve involvement are rare. METHODS: This case comprise neurological, ophthalmological, internal medicine and ear-nose-throat investigation, motor and sensory nerve conduction velocity, auditory evoked potentials and orbicularis-oculi reflex measurements, lumbar puncture and blood examination, inclusive molecular genetic testing, as well as electrocardiogram and cranial imaging such as computer tomography and magnetic resonance imaging RESULTS: The present case shows a Charcot-Marie-Tooth (CMT) 1A patient with complete unilateral oculomotor palsy in combination with predominant ipsilateral subclinical trigeminal demyelination. A combined of third and fifth cranial nerves as in our patient has not been reported yet. CONCLUSIONS: This case shows cranial nerve involvement as an unusual leading symptom of CMT 1A. It may remind us that hereditary neuropathies have to be taken into consideration in patients with slowly progressing unilateral or asymmetric cranial neuropathies.


Subject(s)
Charcot-Marie-Tooth Disease/physiopathology , Cranial Nerves/physiopathology , Hereditary Sensory and Motor Neuropathy/physiopathology , Adult , Charcot-Marie-Tooth Disease/diagnosis , Charcot-Marie-Tooth Disease/genetics , Demyelinating Diseases/complications , Demyelinating Diseases/diagnosis , Demyelinating Diseases/physiopathology , Hereditary Sensory and Motor Neuropathy/diagnosis , Humans , Male , Phenotype , Reflex
9.
J Mol Neurosci ; 60(4): 525-530, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27752928

ABSTRACT

The effects of ghrelin on vasopressin and oxytocin secretion were studied in 13-14-day cell cultures of isolated rat neurohypophyseal tissue. The vasopressin and oxytocin contents of the supernatant were determined by radioimmunoassay after a 1- or 2-h incubation. Significantly increased levels of vasopressin and oxytocin production were detected in the cell culture media following ghrelin administration, depending on the ghrelin doses. The oxytocin level proved to be more elevated than that of vasopressin. The increase of vasopressin and oxytocin secretion could be totally blocked by previous administration of the ghrelin receptor antagonist ([D-Lys3]-growth hormone-releasing peptide-6). Application of the ghrelin receptor antagonist after ghrelin administration proved ineffective. The results indicate that vasopressin and oxytocin release is influenced directly by the ghrelin system, and the effects of ghrelin on vasopressin and oxytocin secretion from the neurohypophyseal tissue in rats can occur at the level of the posterior pituitary. Our observations lend support to the view that neurohypophysis contains ghrelin receptors.


Subject(s)
Exocytosis , Ghrelin/pharmacology , Hormones/pharmacology , Neuroendocrine Cells/metabolism , Oxytocin/metabolism , Pituitary Gland/cytology , Vasopressins/metabolism , Animals , Cell Line , Cells, Cultured , Male , Neuroendocrine Cells/drug effects , Oligopeptides/pharmacology , Pituitary Gland/metabolism , Rats , Rats, Wistar , Receptors, Ghrelin/antagonists & inhibitors , Receptors, Ghrelin/metabolism
10.
Versicherungsmedizin ; 69(2): 67-9, 2016 Jun 01.
Article in German | MEDLINE | ID: mdl-27483686

ABSTRACT

The case report involves a 38-year-old female patient with muscular atrophy, paresis and sensory deficits in the right upper limb following several vaccinations. A legal dispute ensued over whether medical malpractice could have caused the neurological deficits. Medical malpractice could not be confirmed. Even vaccinations administered correctly can lead to neurological impairment.


Subject(s)
Expert Testimony/methods , Malpractice/legislation & jurisprudence , Medical Errors/legislation & jurisprudence , Neuromuscular Diseases/diagnosis , Neuromuscular Diseases/etiology , Vaccination/adverse effects , Adult , Female , Germany , Humans , Medical Errors/classification
11.
Eur Rev Med Pharmacol Sci ; 20(13): 2872-7, 2016 07.
Article in English | MEDLINE | ID: mdl-27424988

ABSTRACT

OBJECTIVE: To assess safety, feasibility and effectiveness of transarterial chemoembolization with degradable-starch-microspheres (DSM-TACE) in the treatment of patients with advanced hepatocellular carcinoma (HCC) dismissing or ineligible for multikinase-inhibitor chemotherapy administration (Sorafenib) due to unbearable side effects or clinical contraindications. PATIENTS AND METHODS: Six consecutive advanced HCC patients dismissing Sorafenib because of unbearable side effects or worsened clinical conditions were enrolled in our prospective single-center pilot study. DSM-TACE was performed via a lobar approach, based on extent and distribution of the disease (1 treatment session for every lobe involved, with a 2-week interval in case of bilobar disease). Tumor response based on mRECIST criteria was evaluated on MD-CT performed at 1 month after "complete treatment" and every 3 months thereafter. RESULTS: Eleven treatments were performed, and technical success was achieved in all patients. No intra/peri-procedural death/major complications occurred. No signs of liver failure or systemic toxicity were detected. At one month follow-up, 5 partial responses (83.3%) and 1 progression disease (16.6%) with an overall disease control (ODC) of 83.3% were observed. In two patients with ODC and residual viable tumor higher than 50%, a repeated DSM-TACE treatment was performed. During the mean follow-up of 11 months (range: 4-14 months), an ODC of 66.6% was obtained. Progression-free survival was 5.5 months with a cumulative 6-month and 1-year overall survival rates of 83.3% and 66.6%, respectively. CONCLUSIONS: DSM-TACE seems to be a promising option for advanced HCC patients ineligible for Sorafenib administration or dismissing it due to progressive disease or unbearable side effects.


Subject(s)
Carcinoma, Hepatocellular/therapy , Chemoembolization, Therapeutic , Liver Neoplasms/therapy , Starch , Carcinoma, Hepatocellular/physiopathology , Complementary Therapies , Humans , Liver Neoplasms/physiopathology , Pilot Projects
12.
Tuberculosis (Edinb) ; 95 Suppl 1: S29-34, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25840822

ABSTRACT

The paleopathological analysis of a well-preserved young adult female skeleton from the AD 7-8th century (Avar Age) in Hungary revealed multiple lytic lesions in all of the thoracic and lumbar vertebral bodies. The lesions were characterized by smooth marginal zones and space-occupying mass appearance. The considerable loss of spongy bone in the thoracolumbar vertebrae resulted in angular deformity and fusion, characteristic of the healing stage of TB. Osteolytic lesions were also observed on the vertebral processes, ribs and sternum. On the endocranial surface, abnormal blood vessel impressions were revealed, indicating some kind of meningitis. The X-ray and CT analysis of the affected bones detected abnormal structures and cystic zones of destruction. The lesions were however not always bordered by areas of increased density, which is typical in cystic TB. Vertebral remains were also subjected to biomolecular analysis in two different laboratories, which attested the presence of Mycobacterium tuberculosis complex (MTBC) DNA and supported the paleopathological diagnosis of TB. Spoligotyping analysis confirmed the presence of MTBC DNA and more specifically an infection caused by bacteria belonging to the M. tuberculosis lineage. This case study provides new data for the paleoepidemiology of TB in this geographical area and historical period, and draws attention to the great variability of TB lesions in the human skeleton.


Subject(s)
Tuberculosis, Spinal/pathology , Adult , DNA, Bacterial/genetics , Female , History, Ancient , Humans , Hungary , Mycobacterium tuberculosis/genetics , Nucleic Acid Amplification Techniques , Paleopathology , Tomography, X-Ray Computed , Tuberculosis, Spinal/genetics , Tuberculosis, Spinal/history , Young Adult
13.
Acta Neurol Scand ; 132(3): 212-5, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25644365

ABSTRACT

BACKGROUND: Recently, new guidelines for the monitoring and the risk evaluation of monoclonal gammopathy with undetermined significance (MGUS) became available and the light chain MGUS subtype was defined. AIMS OF THE STUDY: To characterize the type, risk and diagnostic implications of MGUS in patients with amyotrophic lateral sclerosis. METHODS: We screened 97 consecutive patients with ALS and 97 age- and gender-matched controls for MGUS by serum electrophoresis and immunofixation and compared the characteristics of MGUS with population-based data. RESULTS: MGUS was identified in 8.2% of ALS patients and 6.2% of controls (mean age: 62.5 years both). Seven of eight ALS patients with MGUS had 'low-risk MGUS'. M-protein was moderately increased in one ALS patient. The immunoglobulin distribution in ALS patients with MGUS was IgG kappa (n = 2), IgM lambda (n = 1) and light chains of lambda type (n = 3). No differences in demographic and clinical parameters were found between patients with and without MGUS. CONCLUSIONS: The percentage of patients with MGUS is increased in ALS, but the immunoglobulin distribution is similar to that reported in the general population. MGUS in ALS mostly represents 'low-risk MGUS'; therefore, unnecessary diagnostic procedures should be avoided in ALS patients.


Subject(s)
Amyotrophic Lateral Sclerosis/complications , Monoclonal Gammopathy of Undetermined Significance/epidemiology , Adult , Aged , Female , Humans , Male , Middle Aged
14.
Klin Monbl Augenheilkd ; 231(1): 42-6, 2014 Jan.
Article in German | MEDLINE | ID: mdl-24014037

ABSTRACT

BACKGROUND: Dry eye is one of the most common eye surface disorders. Patients suffer in particular from annoying subjective symptoms that compromise quality of life. The aim of the study was to find out when patients consult ophthalmologists in Germany and what symptoms they present. PATIENTS/MATERIAL AND METHODS: 170 patients treated at ophthalmological practices in Bavaria, Saxony and Saxony-Anhalt with dry eye were surveyed regarding their symptoms. RESULTS: The majority of those questioned were 40 years of age or older (88 %) (average: 60), female (59 %) and described a variety of subjective symptoms (65 %). More than five different concurrent symptoms were named. There is a recognisable increase in cases - by more than 3.5 times - at the age of forty (in women) and fifty (in men). CONCLUSIONS: We hope to contribute with the data obtained to a more complete understanding of this highly complex pathological process. A further aim is to facilitate recognition of this mostly chronic condition in its early stages when the symptoms are still poorly defined. The data on the German population obtained here should become part of a comparative analysis within the international context. Despite considerable scientific effort, dry eye remains a difficult challenge for both patients and attending physicians.


Subject(s)
Dry Eye Syndromes/epidemiology , Dry Eye Syndromes/psychology , Quality of Life/psychology , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Female , Germany/epidemiology , Humans , Incidence , Male , Middle Aged , Risk Factors , Sex Distribution , Young Adult
15.
Mol Genet Metab Rep ; 1: 85-97, 2014.
Article in English | MEDLINE | ID: mdl-27896078

ABSTRACT

BACKGROUND: The risk of osteoporosis is known in myopathies requiring long-term steroid treatment and Pompe disease, but not in other hereditary myopathies or sporadic inclusion body myositis (sIBM). METHODS: Risk factors of osteoporosis, laboratory parameters of bone metabolism, frequency of falls and fractures, walking ability, and pain were surveyed using questionnaires in 89 patients with sIBM and genetically confirmed myopathies facioscapulohumeral muscular dystrophy (FSHD), myotonic dystrophy types 1 and 2 (DM1, DM2), limb girdle muscular dystrophies (LGMD2A, LGMD2B, LGMD2I), MATR3 myopathy, and oculopharyngeal muscular dystrophy (OPMD). Additionally laboratory parameters of bone metabolism were determined. RESULTS: The mean age at examination per disease group ranged from 32 years in LGMD2A to 70 years in sIBM. Myopathies with a higher degree of walking impairment had a higher risk of falls (sIBM, LGMD2A, LGMD2B). At the time of examination 3.4% had a history of osteoporosis. The 25-OH D3 level was decreased in 20% of patients (and in 55% of patients with LGMDs), 57% of them were ambulatory. The 25-OH D3 level was significantly lower in patients with myopathies than in other neurological disorders (p < 0.001). 2.7 falls per year per person occurred. Fractures were reported in 6.8% of patients within the last year. They involved frequently the tibia bone. The pain score didn't correlate with either the walking disability (WGMS) score or the 25-OH D3 level. CONCLUSION: The risk for osteoporosis and reduced 25-OH D3 level seems to be increased in wheelchair-bound patients with myopathy but also in patients with DM1 and autosomal-recessive myopathies.

16.
Klin Monbl Augenheilkd ; 227(11): 864-70, 2010 Nov.
Article in German | MEDLINE | ID: mdl-21077020

ABSTRACT

The amphiphilic surfactant proteins B (SP-B) and C (SP-C) are tightly bound to phospholipids. These proteins play important roles in maintaining the surface tension-lowering properties of pulmonary surfactant. Surfactant protein A (SP-A) and D (SP-D) are hydrophilic and are thought to have a role in recycling surfactant and, especially, in improving host defense in the lung. Moreover, SP-A supports the hydrophobic surfactant proteins B and during surfactant subtype assembly and inhibits the secretion of lamellar bodies into the alveolar space. During recent years surfactant proteins have also been detected at locations outside the lung such as the lacrimal apparatus. In this review, the latest information regarding SP function and regulation in the human lacrimal system, the tear film and the ocular surface is summarised with regard to dry eye, rheological and antimicrobial properties of the tear film, tear outflow, certain disease states and possible therapeutic perspectives.


Subject(s)
Dry Eye Syndromes/physiopathology , Lacrimal Apparatus/physiopathology , Lung/physiopathology , Pulmonary Surfactants/metabolism , Tears/physiology , Humans , Rheology
17.
Thromb Haemost ; 103(2): 450-60, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20024490

ABSTRACT

We investigated the protective effect of ischaemic preconditioning (IP) on the maintenance of coronary patency using on-line measurements of coronary pressures and blood flow in a closed-chest reperfused acute myocardial infarction (MI) model in pigs. Catheter-based 90-min occlusion followed by 60-min reperfusion of the left anterior descending coronary artery (LAD) was performed in anesthetised pigs (MI group). IP was applied (IP group) through two cycles of 5-min occlusion and 5-min reperfusion of the LAD before MI induction. Coronary patency was determined by measurements of coronary wedge pressure, collateral fractional flow reserve (FFRcoll), collateral pressure index (CPI) and absolute coronary blood flow (CBF). Inducible and constitutive nitric oxide synthase (iNOS/cNOS) activities and expressions were determined in the myocardium. Plasma levels of myeloperoxidase (MPO, index of activated leukocytes) and mean platelet volume (MPV, index of activated platelets) were measured. IP resulted in significantly lower levels of MPO (0.52 +/- 0.19 vs. 1.05 +/- 0.24 U/l, p<0.001) and MPV (9.1 +/- 0.6 vs. 9.6 +/- 1.0 fl, p=0.04), higher FFRcoll (0.17 +/- 0.05 vs. 0.04 +/- 0.05, p<0.001), CPI (0.13 +/- 0.05 vs. 0.02 +/- 0.05, p<0.001) and CBF (70.7 +/- 4.2 vs. 50.8 +/- 4.8 m/min, p<0.001) post-reperfusion as compared with the MI group. IP resulted in significantly higher cNOS activity and eNOS expression. Significant negative correlation was found between MPO and measures of coronary patency (FFRcoll, CPI and CBF) and cNOS activity. Moreover, cNOS activity correlated significantly with FFRcoll, CPI and CBF. In conclusion, IP attenuates the release of MPO and platelet activation, thereby contributing to the maintenance of vessel patency at microvascular level after reperfusion of the infarct-related artery.


Subject(s)
Blood Flow Velocity , Blood Pressure , Coronary Circulation/physiology , Ischemic Preconditioning, Myocardial/methods , Animals , Microcirculation , Myocardial Infarction/etiology , Myocardial Infarction/physiopathology , Peroxidase/blood , Platelet Activation , Swine , Vascular Patency
18.
Regen Med ; 4(3): 407-22, 2009 May.
Article in English | MEDLINE | ID: mdl-19438316

ABSTRACT

Cell-based therapy is a promising, novel therapeutic strategy for cardiovascular disease. The rapid transition of this approach from the benchside to clinical trials has left a gap in the understanding of the mechanisms of cell therapy. Monitoring of cell homing and the fate of cardially delivered stem cells is fundamental for clarification of the myocardial regenerative process. Noninvasive imaging techniques allow an in vivo evaluation of the survival, migration and differentiation of implanted stem cells over time, and by this means, can help to answer unresolved questions. The most promising in vivo tracking methods involve the direct, nonspecific labeling of cells including MRI, radionuclide imaging and the use of reporter-gene imaging. This review summarizes the most important results of animal and human studies in which the fate and biodistribution of cardially delivered stem cells are assessed through different in vivo tracking methods.


Subject(s)
Cell Movement , Myocardium/cytology , Stem Cell Transplantation/methods , Stem Cells/cytology , Animals , Genes, Reporter , Humans , Luminescent Measurements , Magnetic Resonance Imaging , Positron-Emission Tomography , Stem Cells/diagnostic imaging
19.
Br J Pharmacol ; 153(5): 983-91, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18157165

ABSTRACT

BACKGROUND AND PURPOSE: Leukotriene B(4) (LTB(4)), formed by the sequential actions of the 5-lipoxygenase (5-LO) and leukotriene A(4) hydrolase (LTA(4)H), is a pro-inflammatory mediator implicated in the pathogenesis of inflammatory bowel disease. However, inhibitors of 5-LO have not proved to be consistent in their therapeutic efficacy in colitis. Another approach to inhibiting LTB(4) synthesis is through the use of inhibitors of LTA(4)H, such as the novel, potent and selective compound, JNJ 26993135. EXPERIMENTAL APPROACH: The effect of oral administration of JNJ 26993135 has been evaluated in a rat model of colitis provoked by colonic instillation of trinitrobenzenesulphonic acid (TNBS). The extent and severity of the macroscopic inflammatory response, the colonic levels of myeloperoxidase (MPO) and LTB(4) and of the pro-inflammatory cytokines, tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were measured. KEY RESULTS: Oral administration of JNJ 26993135 (5, 15 and 30 mg kg(-1), twice a day) dose-dependently reduced both the extent and intensity of the colonic inflammatory damage observed 3 days after TNBS challenge. JNJ 26993135 also dose-dependently reduced the elevated colonic levels of LTB(4), as well as the inflammatory biomarkers, MPO, IL-6 and TNF-alpha. This dosing regimen was supported by the pharmacokinetic profile of JNJ 26993135, along with the demonstration of the inhibition of ex vivo production of LTB(4) in whole blood following oral administration. CONCLUSIONS AND IMPLICATIONS: These results with JNJ 26993135 in the rat TNBS model support the role of LTB(4) in colitis and the potential value of targeting LTA(4)H for the treatment of inflammatory bowel diseases.


Subject(s)
Benzothiazoles/pharmacology , Colitis/drug therapy , Enzyme Inhibitors/pharmacology , Epoxide Hydrolases/antagonists & inhibitors , Inflammation/drug therapy , Piperidines/pharmacology , Administration, Oral , Animals , Benzothiazoles/administration & dosage , Benzothiazoles/pharmacokinetics , Colitis/chemically induced , Colitis/physiopathology , Disease Models, Animal , Dose-Response Relationship, Drug , Drug Delivery Systems , Enzyme Inhibitors/administration & dosage , Enzyme Inhibitors/pharmacokinetics , Inflammation/etiology , Interleukin-6/metabolism , Male , Peroxidase/drug effects , Peroxidase/metabolism , Piperidines/administration & dosage , Piperidines/pharmacokinetics , Rats , Rats, Wistar , Severity of Illness Index , Trinitrobenzenesulfonic Acid , Tumor Necrosis Factor-alpha/drug effects , Tumor Necrosis Factor-alpha/metabolism
20.
Ambio ; 33(1-2): 98-106, 2004 Feb.
Article in English | MEDLINE | ID: mdl-15083655

ABSTRACT

Aspects of transboundary, water shortage, and fisheries issues are discussed in the context of the recently completed Global International Waters Assessment (GIWA) for the Pacific Islands. The region encompasses some 30 million km2 and approximately 12% of the world's ocean space, and features great geographic, demographic and developmental diversity. Global change, especially sea level rise and sea surface temperature increases, is the dominant transboundary concern as it impacts all aspects of life. Water shortage and unsustainable fishing issues are selected for discussion, as they will dominate the region into the foreseeable future, and they are illustrated with examples from Fiji, Kiribati, and Tonga. The environmental impacts are exacerbated by socioeconomic issues such as high population growth rates, urban drift, the breakdown of traditional life styles and the rapid adoption of the cash economy. Policy options that may assist in addressing these issues are proposed.


Subject(s)
Conservation of Natural Resources , Environment , Fisheries , Greenhouse Effect , International Cooperation , Animals , Geography , Pacific Islands , Social Conditions
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