ABSTRACT
Although clinical examination still represents the gold standard for the differential diagnosis of prolonged disorders of consciousness (pDoC), the introduction of innovative markers is essential for diagnosis and prognosis, due to the problem of covert cognition. We evaluated the brain-derived neurotrophic factor protein (BDNF) and the soluble cell adhesion molecules proteins (CAMs) in a cohort of prolonged disorders of consciousness patients to identify a possible application in the clinical context. Furthermore, peripheral blood determinations were correlated with imaging parameters such as white matter hyperintensities (WMH), cranial standardized uptake value (cSUV), electroencephalography (EEG) data and clinical setting. Our results, although preliminary, identify BDNF as a possible blood marker for the diagnosis of pDoC (p value 0.001), the soluble CAMs proteins CD44, Vcam-1, E-selectin (p value < 0.01) and Icam-3 (p value < 0.05) showed a higher peripheral blood value in pDoC compared with control. Finally, soluble Ncam protein could find useful applications in the clinical evolution of the pDoC, showing high levels in the MCS and EMCS subgroups (p value < 0. 001) compared to VS/UWS.
Subject(s)
Brain-Derived Neurotrophic Factor , Consciousness Disorders , Humans , Pilot Projects , Consciousness Disorders/diagnosis , Consciousness , Vascular Cell Adhesion Molecule-1 , Blood ProteinsABSTRACT
BACKGROUND: In our study we used immunohistochemical technique to demonstrate the presence of the cytokines tumour necrosis factor alpha (TNF-α), interleukin 1beta (IL-1ß), transforming growth factor beta1 (TGF-ß1) and intercellular adhesion molecule-1 (ICAM-1) in porcine coronaries even in physiological conditions. MATERIALS AND METHODS: Inflammatory cytokines are polypeptide mediators which act as a communication signal between immune system cells and other types of cellsin different organs and tissues, both in human and pig coronary circulation. RESULTS: Our results show that pro-inflammatory cytokines TNF-α, IL-1ß, TGF-ß1 and ICAM-1 are also present in the medium tunica of the coronary arteries under physiological conditions. These results may be compared with those found in coronary atherosclerosis, where the increase in TNF-α has a dramatic effect on the function of the left ventricle, and the high value of IL-1 correlates directly with the extent of myocardial necrosis. In our study we observe the damage and activation of endothelial cells; this induces endothelial dysfunction by accumulation and oxidation of low density lipoproteins (LDL). The formation of oxidized LDL could play a central role in the amplification of the inflammatory response causing an increased expression of pro-inflammatory cytokines which promotes leukocyte recruitment in the intimal layer. These leukocytes, after the adhesion to the endothelium, penetrate the intimate tunic. CONCLUSIONS: Therefore inflammatory processes promote the onset and evolution of atheroma and the development of thrombotic complications.
Subject(s)
Transforming Growth Factor beta1 , Tumor Necrosis Factor-alpha , Humans , Swine , Animals , Tumor Necrosis Factor-alpha/metabolism , Transforming Growth Factor beta1/metabolism , Transforming Growth Factor beta1/pharmacology , Intercellular Adhesion Molecule-1/metabolism , Intercellular Adhesion Molecule-1/pharmacology , Interleukin-1beta/metabolism , Interleukin-1beta/pharmacology , Endothelial Cells/metabolism , Coronary Vessels , CytokinesABSTRACT
Behavioral assessments during the clinical evaluation in prolonged disorders of consciousness patients could be not sufficient for a correct diagnosis and prognostication. To this aim, we used an innovative approach, involving the ultra-sensitive determination of biological markers, correlating them with imaging parameters to investigate the prolonged disorders of consciousness (pDoC).We assessed the serum concentration of neurofilament light chain(NF-L) and glial fibrillary acidic protein (GFAP) in pDoC (n = 16), and healthy controls (HC, n = 6) as well as several clinical imaging parameters such as Fractional Anisotropy (FA), Whole Brain SUV, and White Matter Hyperintensities volumes (WMH) using PET-MRI acquisition. As for differential diagnosis task, only the imaging WMH volume was able to discriminate between vegetative state/unresponsive wakefulness syndrome (VS/UWS), and minimally conscious state (MCS) patients (p-value < 0.01), while all selected markers (both imaging and in vitro) were able to differentiate between pDoC patients and HC. At subject level, serum NF-L concentrations significantly differ according to clinical progression and consciousness recovery (p-value < 0.01), highlighting a potential play for the longitudinal management of these patients.
Subject(s)
Consciousness , Intermediate Filaments , Humans , Biomarkers , Glial Fibrillary Acidic Protein , Persistent Vegetative State/diagnostic imagingABSTRACT
Physical inactivity represents the fourth leading risk factor with the highest epidemiological impact on population health worldwide, as estimated by the epidemiological measures used in global surveillance systems as the Global Burden of Disease Study. Scientific research has provided compelling evidence to establish and clarify the causal relationships and to devise effective intervention strategies, including the development of both national and international recommendations and the planning of whole-of-system and integrated actions. Over the last few years, new paradigms have been identified, such as the distinction between physical inactivity and sedentary behaviour, the different methods to integrate enough levels of physical activity in daily life, and the relevance of sleep in normal lifestyle activities. The experience in programs planning and in their assessments has led to the definition of a whole-of-system and global approach for the promotion of an active lifestyle, specifically the Global Action Plan on Physical Activity 2018 - 2030 by the World Health Organization, with the definition of overlapping areas with further objectives of public health as established by the 2030 Agenda for Sustainable Development. Thus, the action plan aims to ensure access to inclusive and equitable opportunities for people to be physically active in their daily life (with reference to more socially disadvantaged groups, such as women, people with disabilities, people of low socioeconomic status) and to improve planetary health.
Subject(s)
Exercise/physiology , Global Health , Health Promotion/methods , Humans , Life Style , Risk Factors , Sedentary Behavior , Sleep/physiology , Vulnerable PopulationsABSTRACT
Seventy four Reference Sites of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) have been recognised by the European Commission in 2016 for their commitment to excellence in investing and scaling up innovative solutions for active and healthy ageing. The Reference Site Collaborative Network (RSCN) brings together the EIP on AHA Reference Sites awarded by the European Commission, and Candidate Reference Sites into a single forum. The overarching goals are to promote cooperation, share and transfer good practice and solutions in the development and scaling up of health and care strategies, policies and service delivery models, while at the same time supporting the action groups in their work. The RSCN aspires to be recognized by the EU Commission as the principal forum and authority representing all EIP on AHA Reference Sites. The RSCN will contribute to achieve the goals of the EIP on AHA by improving health and care outcomes for citizens across Europe, and the development of sustainable economic growth and the creation of jobs.
ABSTRACT
Splenitis is uncommonly reported in dogs. Herein, the authors describe its prevalence, clinical findings and outcomes, histologic patterns, and causes. Splenic samples of dogs diagnosed with splenitis between 2005 and 2013 were collected and stained with hematoxylin and eosin, Gram, green-Gram, Giemsa, periodic acid-Schiff, and Ziehl-Neelsen. Samples were processed for polymerase chain reaction (PCR) to detect bacteria, fungi, and protozoa ( Leishmania infantum, Hepatozoon canis). Thirty-three of 660 splenic samples (5%) had splenitis. Clinical findings and outcomes were available in 19 dogs (58%); 49% had weakness, 33% had fever, and 84% survived. The most frequent inflammatory patterns included purulent splenitis (27%), pyogranulomatous splenitis (24%), and neutrophilic perisplenitis (15%). One dog had a putative diagnosis of primary splenitis; in 8 dogs, microorganisms were identified histologically or by PCR in the spleen without obvious comorbidities. Twenty-four dogs (73%) had concurrent diseases; a permissive role in the development of splenitis was suspected in 21 of these cases. Histologic examination identified the cause of splenitis in 10 dogs. Bacteria were identified by PCR in 23 cases, but the bacteria were confirmed histologically in only 6 of these. Leishmania was detected with PCR in 6 dogs. Leishmania was identified in 1 dog and H. canis in another histologically, but both were PCR negative. Fungi were identified in 8 spleens by PCR and in 1 by histology. This study suggests that splenitis is uncommon in dogs and is frequently associated with systemic diseases. Prognosis is favorable in most cases. Identification of bacteria, fungi, and protozoa in the spleens of affected dogs with PCR should be interpreted cautiously, because the findings are not confirmed histologically in many cases.
Subject(s)
Dog Diseases/pathology , Splenic Diseases/veterinary , Animals , Biopsy/veterinary , Dog Diseases/diagnosis , Dog Diseases/etiology , Dogs , Male , Polymerase Chain Reaction/veterinary , Spleen/microbiology , Spleen/parasitology , Spleen/pathology , Splenic Diseases/diagnosis , Splenic Diseases/etiology , Splenic Diseases/pathologyABSTRACT
BACKGROUND: Gastric gastrointestinal stromal tumors (GISTs) represent a subgroup of GISTs with a better prognosis than those located in other areas. In this retrospective study we performed a molecular characterization of a large series of patients with gastric GISTs in relation to clinical-pathological characteristics and prognosis. METHODS: DNA was extracted from paraffin-embedded sections from 221 gastric GIST patients submitted to surgery. Exons 9, 11, 13 and 17 of KIT, exons 12 and 18 of PDGFRA and exons 11 and 15 of BRAF were analyzed by direct sequencing. Cox regression analysis adjusted for clinical-pathological factors was performed to evaluate KIT and PDGFRA mutations in relation to the composite endpoint of relapse or death. RESULTS: KIT and PDGFRA mutations were observed in 119 (53.8%) and 56 (25.3%) patients, respectively, whereas 46 (20.8%) patients had wild type (wt) disease. Univariable analyses showed that a high Miettinen risk category and the presence of ulceration and KIT deletions were associated with increased risk of relapse or death (p < 0.001; p = 0.0389 and p = 0.002, respectively). After adjusting for Miettinen risk score, KIT deletions remained an independent prognostic factor (HRadj = 2.65, 95% CI [1.15-6.13], p = 0.023). Moreover, KIT deletions in exon 11 codons 557, 558 or 559 were associated with a higher risk of relapse or death than wt tumors (HRadj = 3.29 95% CI [1.64-6.64], p = 0.001). CONCLUSIONS: KIT deletions in exon 11, especially those involving codons 557, 558 or 559, were correlated with a more aggressive gastric GIST phenotype and increased risk of relapse or death.
Subject(s)
Gastrointestinal Stromal Tumors/genetics , Mutation , Neoplasm Recurrence, Local/genetics , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins c-kit/genetics , Receptor, Platelet-Derived Growth Factor alpha/genetics , Stomach Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Exons/genetics , Female , Gastrointestinal Stromal Tumors/mortality , Gastrointestinal Stromal Tumors/pathology , Humans , Male , Middle Aged , Prognosis , Proportional Hazards Models , Retrospective Studies , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Tumor Burden , Young AdultABSTRACT
Pancreatic amyloidosis and loss of α and ß cells have been shown to occur in cats with diabetes mellitus, although the number of studies currently available is very limited. Furthermore, it is not known whether pancreatic islet inflammation is a common feature. The aims of the present study were to characterize islet lesions and to investigate whether diabetic cats have inflammation of the pancreatic islets. Samples of pancreas were collected postmortem from 37 diabetic and 20 control cats matched for age, sex, breed, and body weight. Histologic sections were stained with hematoxylin and eosin and Congo red; double labeled for insulin/CD3, insulin/CD20, insulin/myeloperoxidase, insulin/proliferating cell nuclear antigen, and glucagon/Ki67; and single labeled for amylin and Iba1. Mean insulin-positive cross-sectional area was approximately 65% lower in diabetic than control cats (P = .009), while that of amylin and glucagon was similar. Surprisingly, amyloid deposition was similar between groups (P = .408). Proliferation of insulin- and glucagon-positive cells and the number of neutrophils, macrophages, and T (CD3) and B (CD20) lymphocytes in the islets did not differ. The presence of T and B lymphocytes combined tended to be more frequent in diabetic cats (n = 8 of 37; 21.6%) than control cats (n = 1 of 20; 5.0%). The results confirm previous observations that loss of ß cells but not α cells occurs in diabetic cats. Islet amyloidosis was present in diabetic cats but was not greater than in controls. A subset of diabetic cats had lymphocytic infiltration of the islets, which might be associated with ß-cell loss.
Subject(s)
Amyloidosis/veterinary , Cat Diseases/pathology , Diabetes Mellitus/veterinary , Insulin/metabolism , Islets of Langerhans/pathology , Amyloidosis/metabolism , Amyloidosis/pathology , Animals , Cat Diseases/metabolism , Cats , Diabetes Mellitus/metabolism , Diabetes Mellitus/pathology , Female , Glucagon/metabolism , Islet Amyloid Polypeptide/metabolism , Islets of Langerhans/metabolism , Male , Pancreas/metabolism , Pancreas/pathologyABSTRACT
Pancreatitis has been described in cats with diabetes mellitus, although the number of studies currently available is very limited. In addition, ketoacidosis has been hypothesized to be associated with pancreatitis in diabetic cats. The aims of the present study were to investigate whether diabetic cats have pancreatitis and to determine if pancreatitis is more frequent with ketoacidosis. Samples of pancreas were collected postmortem from 37 diabetic cats, including 15 with ketoacidosis, and 20 control cats matched for age, sex, breed, and body weight. Sections were stained with hematoxylin and eosin, double-labeled for insulin/CD3, insulin/CD20, insulin/myeloperoxidase, insulin/PCNA, and glucagon/Ki67, and single-labeled for Iba1. A previously proposed semiquantitative score was used to characterize pancreatitis, along with counts of inflammatory cells. Scores of pancreatitis and the number of neutrophils, macrophages, and lymphocytes in the exocrine pancreas did not differ between diabetic and control cats or between diabetic cats with and without ketoacidosis. Of note, PCNA-positive acinar cells were increased (P = .002) in diabetic cats, particularly near islets (P < .001). Ki67-positive acinar cells were increased only near islets (P = .038). Ketoacidosis was not linked to proliferation. The results suggest that histopathologic evidence of pancreatitis may not be more frequent in diabetic cats and that ketoacidosis may not be associated with it at the time of death. Augmented PCNA-positive acinar cells might indicate increased proliferation due to chronic pancreatitis. The reason behind the prevalent proliferation of acinar cells surrounding pancreatic islets deserves further investigation.
Subject(s)
Cat Diseases/pathology , Diabetes Mellitus/veterinary , Ketosis/veterinary , Pancreas, Exocrine/pathology , Pancreatitis/veterinary , Acinar Cells/pathology , Animals , Cat Diseases/metabolism , Cats , Diabetes Mellitus/metabolism , Diabetes Mellitus/pathology , Female , Glucagon/metabolism , Insulin/metabolism , Ketosis/metabolism , Ketosis/pathology , Male , Pancreas/metabolism , Pancreas/pathology , Pancreas, Exocrine/metabolism , Pancreatitis/metabolism , Pancreatitis/pathologyABSTRACT
Campylobacteriosis is among the most common bacterial causes of human gastroenteritis worldwide and pet ownership has been identified as a risk factor for Campylobacter infection in humans. Since canine and feline prevalence data are scarce in Italy, the present study was carried out to assess the prevalence, species distribution and risk factors for Campylobacter infection in dogs and cats under different husbandry conditions. Rectal swabs were collected from 171 dogs (household pets, n = 100; shelter-housed dogs, n = 50; dogs from breeding kennels, n = 21) and 102 cats (household pets, n = 52; shelter-housed cats, n = 21; free-roaming cats n = 29) in Northern Italy. Campylobacter was isolated from 17% (n = 29) of dogs and 14.7% (n = 15) of cats. C. jejuni was the most common isolate in both species (Campylobacter spp.-positive dogs, 55.2%; Campylobacter spp.-positive cats, 53.3%), followed by C. upsaliensis (Campylobacter spp.-positive dogs, 27.6%; Campylobacter spp.-positive cats, 40%). Other Campylobacter species were rarely detected, but included C. hyointestinalis subsp. hyointestinalis, C. lari and C. coli in dogs and C. coli and C. helveticus in cats. Among considered variables (sex, age, origin, diarrhoea, season of sampling), origin was identified as a risk factor for dogs, with shelter-housed dogs at higher risk than household dogs (odds ratio, 2.84; 95% CI 1.17, 6.92; P = 0.021). The results of this study, particularly the high prevalence of C. jejuni in Campylobacter-positive animals, demonstrated that household and stray dogs and cats in Northern Italy might pose a zoonotic risk for humans. Moreover, biosecurity measures should be improved in dog shelters.
Subject(s)
Campylobacter Infections/veterinary , Campylobacter/isolation & purification , Cat Diseases/microbiology , Dog Diseases/microbiology , Ownership , Animals , Campylobacter Infections/epidemiology , Campylobacter Infections/microbiology , Cat Diseases/epidemiology , Cats , Dog Diseases/epidemiology , Dogs , Female , Italy/epidemiology , Male , Odds Ratio , SeasonsABSTRACT
In humans, diabetes mellitus (DM) is an important cause of renal damage, with glomerular lesions being predominant. In cats, although diabetes is a common endocrinopathy, it is yet unknown whether it leads to renal damage. The aim of the study was to compare renal histologic features and parameters of renal function in diabetic cats against a control population matched for age, gender, breed, and body weight. Thirty-two diabetic and 20 control cats were included. Kidney sections from paraffin-embedded kidney samples were stained and examined with optical microscopy to identify glomerular, tubulointerstitial, and vascular lesions and to assess their frequency and severity. Serum creatinine and urea concentrations were also compared. Glomerular lesions were observed in 29 cats overall, with mesangial matrix increase being more common (19 cats). Tubulointerstitial lesions were observed in 42 cats, including lymphocytic infiltration (29), fibrosis (22), or tubular necrosis (21). Vascular lesions were observed in 5 cases. The frequency and severity of histologic lesions did not differ between diabetic and control cats; however, among diabetics, those that survived longer after diagnosis had more glomerular and vascular lesions. Serum creatinine and urea concentrations were similar between groups; in diabetic cats median creatinine was 109 µmol/l (range, 51-1200) and urea was 12 mmol/l (range, 4-63), and in controls creatinine was 126 µmol/l (range, 50-875) and urea 11 mmol/l (range, 3-80). The results suggest that DM in cats does not lead to microscopically detectable kidney lesions or clinically relevant renal dysfunction. The authors hypothesize that the short life expectancy of diabetic cats may be the main reason for the difference from human diabetics.
Subject(s)
Cat Diseases/pathology , Diabetes Mellitus/veterinary , Kidney Diseases/veterinary , Kidney/pathology , Animals , Case-Control Studies , Cats , Creatinine/blood , Diabetes Mellitus/pathology , Female , Glomerular Mesangium/pathology , Kidney Diseases/pathology , Kidney Glomerulus/pathology , Male , Retrospective Studies , Urea/bloodABSTRACT
BACKGROUND: The present work deals with innervation patterns along collector lymphatic vessels from cervical, mesenteric, and femoral regions, and lymph capillaries in young and elderly subjects. METHODS AND RESULTS: Morphological and morphometric analysis of nerve fibers along lymph vessels was performed by immunohistochemistry for PGP 9.5, NPY, TH, ChAT, VIP, SP, and dopamine. Nerves containing NPY and TH were frequent, whereas immunoreactivity for ChAT and VIP were few. SP-positive fibers were widely distributed in the medial and endothelial layers. Dopamine neurotransmitters were observed in a few short nerve fibers. A more diffuse presence of nerve fibers in mesenteric and femoral lymph vessels, compared to cervical ones, was detected. In lymph capillary vessels, a few nerve fibers positive for neuropeptides and neurotransmitters were detected, whereas no dopamine and VIP immunoreactive fibers were detected. A wide reduction of all specific nerve fibers analyzed was detected in lymph vessels from elderly subjects. CONCLUSIONS: The presence on lymph vessels of sympathetic and parasympathetic nerve systems can be declared. The differences observed in lymphatic vessel innervation patterns may note the involvement in lymph flow regulation, calling attention in aging, when nerve fibers reduction may cause functional default of lymph vessels.
Subject(s)
Biomarkers/metabolism , Lymphatic Vessels/innervation , Nerve Fibers/chemistry , Adult , Age Factors , Aged , Autopsy , Capillaries/innervation , Choline O-Acetyltransferase/metabolism , Femur , Humans , Immunohistochemistry , Lymphatic System/blood supply , Male , Mesentery , Neck , Neuropeptide Y/metabolism , Parasympathetic Nervous System/chemistry , Substance P/metabolism , Sympathetic Nervous System/chemistry , Tyrosine 3-Monooxygenase/metabolism , Ubiquitin Thiolesterase/metabolism , Vasoactive Intestinal Peptide/metabolismABSTRACT
OBJECTIVE: To determine if the circulating nitrotyrosine level significantly correlates with parameters measuring cognitive abilities. MATERIALS AND METHODS: One-hundred and twelve community-living subjects (ranging in age from 27 to 98 years) were evaluated for cognitive abilities [Mini Mental State Examination (MMSE) score] and circulating free nitrotyrosine plasma level, as well as for several variables that might influence cognitive abilities (age, education) and nitrotyrosine level (body mass index, haematological parameters, cardiovascular and inflammatory indices). RESULTS: In the sub-group of cognitively impaired subjects (score at MMSE < 23.9), but not in that of cognitively not impaired subjects, a significant inverse correlation exists between nitrotyrosine level and MMSE score (r = -0.378; P < 0.02). CONCLUSIONS: The finding, if confirmed by longitudinal studies, could play a role in the management of the subjects with Mild Cognitive Impairment, the clinical condition considered as a transitional state between the changes of cognitive ability in normal aging and dementia.
Subject(s)
Cognition Disorders/blood , Tyrosine/analogs & derivatives , Adult , Aged , Aged, 80 and over , Blood Cell Count/methods , Body Weight/physiology , Cognition Disorders/physiopathology , Enzyme-Linked Immunosorbent Assay/methods , Female , Hemoglobins/metabolism , Humans , Male , Mental Status Schedule , Middle Aged , Neuropsychological Tests , Residence Characteristics , Sex Factors , Tyrosine/bloodABSTRACT
Here we report on a study dealing with a self-assembling ethylene oxide-propylene oxide-ethylene oxide triblock copolymer (Pluronic L64) and an anionic surfactant, sodium dodecyl sulfate (SDS), that in water at 25 degrees C form an interesting micellar region (L-phase). We have investigated the sequence of micelle structures in this L-phase across a wide interval of copolymer concentrations using phase diagram determination, steady shear, and NMR self-diffusion (pulsed gradient spin-echo, PGSE) experiments. In solutions which have been prepared at moderately low copolymer concentrations (ca. 20wt.% L64) we report on a transition from discrete micelles to bicontinuous aggregates on the addition of SDS. This change was mainly inferred from self-diffusion coefficient patterns (i.e., the variation of copolymers and surfactant diffusivity vs. SDS content). At midrange and at higher polymer concentrations (i.e., in the interval from 50 to 80wt.% L64) the L-phase occurred with a bicontinuous structure which was not modified by the progressive addition of SDS. Such a bicontinuous structure was identified by the comparison of self-diffusion coefficients of both cosolutes and the bulk viscosity (i.e., the behavior of zero-shear viscosity vs. SDS).
ABSTRACT
OBJECTIVE: In Type 2 diabetes, it is not clear if renal size is constantly related to the glomerular filtration rate. In addition, it is not known if kidney volume (KV) is associated with an increased urinary albumin and IgG excretion. METHODS: The relationship between kidney volume, creatinine clearance (CrCl), urinary albumin and IgG excretion in 95 Type 2 diabetic patients with different stages of nephropathy (1 - 4 Stage sec NKDF-QD) was elevated and compared to 85 non-diabetic subjects with similar degree of kidney function. RESULTS: In Type 2 diabetic patients the KV/CrCl ratio was increased, in comparison with the control subjects, from about 15% in Stage 1 to 53% in Stage 4. In T2D subjects, significant correlations were found between KV and urinary albumin excretion (r = 0.665, p < 0.05), and between KV and urinary IgG excretion (r = 0.800, p < 0.001). CONCLUSION: The present study finds that Type 2 diabetic subjects, are characterized by an increased ratio between KV/CrCl, throughout the different progressive stages of nephropathy. In Type 2 diabetes relationships between KV and urinary albumin and between KV and IgG excretion also were found to be significant, suggesting a role for the impaired size selectivity of proteinuria as a possible determinant of KV.
Subject(s)
Diabetes Mellitus, Type 2/physiopathology , Diabetic Nephropathies/physiopathology , Kidney/physiopathology , Aged , Albuminuria/physiopathology , Biomarkers/urine , Case-Control Studies , Creatinine/urine , Diabetes Mellitus, Type 2/urine , Diabetic Nephropathies/urine , Disease Progression , Female , Humans , Immunoglobulin G/urine , Kidney Function Tests , Male , Middle AgedABSTRACT
OBJECTIVE AND DESIGN: We tested here the effects of acute administration of an oxygen/ozone (O3) mixture on the myocardial tissue damage following an ischemic event. MATERIAL OR SUBJECTS: The study was done in Sprague-Dawley rats subjected to acute myocardial ischemia/reperfusion (I/R). TREATMENT: 100; 150; and 300 microg/kg oxygen/O3 mixture were insufflated intraperitoneally 1 h prior to I/R. METHODS: Myocardial infarct size measurement and immunhistochemistry or ELISA for nitrotyrosine, CD68, CD8,CD4 and caspase-3 were done. RESULTS: I/R produced a marked damage in the rat left ventricle with an infarct size as percentage of the area at risk (IS/ AR) of approximately 45 +/- 4% . Rats insufflated with a oxygen/O3 mixture showed a significant 2-h cardio-protection (e. g. infarct size over area at risk for the dose of 300 microg/kg was approximately 30 +/- 3%,) as compared with control rats (P <0.01). This effect was paralleled by a decrease in tissue levels of immunostaining for biomarkers of nitrosative stress (nitrotyrosine), inflammation (CD68) and immunity response (CD8 and CD4) between heart tissues from infarcted rats and infarcted O3 treated rats. CONCLUSIONS: These data indicate that the tissue and biochemical damages associated with myocardial ischemia/reperfusion can be counteracted by an acute O3 pretreatment.
Subject(s)
Heart/drug effects , Myocardial Infarction/prevention & control , Myocardial Ischemia/drug therapy , Myocardial Reperfusion Injury/prevention & control , Oxygen , Ozone , Animals , Humans , Male , Myocardial Infarction/drug therapy , Myocardial Infarction/pathology , Oxygen/pharmacology , Oxygen/therapeutic use , Ozone/pharmacology , Ozone/therapeutic use , Random Allocation , Rats , Rats, Sprague-DawleyABSTRACT
In this work we report a relatively simple and fast method for analysing oxygen consumption and therefore mitochondrial functionality, in individual human ejaculates. This oxygraphic method requires a low number of cells, is highly reproducible and linearly correlates with sperm concentration. Our results have shown that oxygen uptake by mitochondria of demembranated sperm cells from normozoospermic subjects is significantly stimulated by a large set of respiratory substrates and ADP. The respiratory control ratio (RCR) values indicate a good coupling between respiration and phosphorylation by sperm mitochondria and thus a well preserved integrity of the mitochondria themselves. Interestingly, whereas the rates of oxygen uptake, as expected, changed with different sperm concentrations, the RCR values remained constant, thus demonstrating a linear response of the assay. In asthenozoospermic subjects, however, a significant decrease in the sperm respiratory efficiency was found. The results obtained suggest that this method, besides its potential clinical application, could be useful for a deeper understanding of the biochemical properties of sperm mitochondria and their role in ATP production in human spermatozoa.
Subject(s)
Biological Assay/methods , Energy Metabolism , Mitochondria/metabolism , Oxygen Consumption , Oxygen/metabolism , Spermatozoa/metabolism , Adenosine Diphosphate/metabolism , Adenosine Triphosphate/metabolism , Animals , Asthenozoospermia/metabolism , Cell Respiration , Humans , Hypotonic Solutions , Male , Mitochondria/ultrastructure , Osmotic Pressure , Oxidative Phosphorylation , Rats , Rats, Wistar , Reproducibility of Results , Spermatozoa/ultrastructure , Time FactorsABSTRACT
The safety of low platelet thresholds for prophylactic transfusions was retrospectively evaluated in 673 children with various thrombocytopenic disorders. In patients with idiopathic thrombocytopenic purpura and X linked thrombocytopenia the threshold for the use of platelet transfusion was based on bleeding events rather than platelet count. In children with hypoproliferative thrombocytopenia and Wiskott-Aldrich syndrome, prophylactic platelet transfusions were used when the platelet count was
Subject(s)
Platelet Transfusion , Thrombocytopenia/therapy , Wiskott-Aldrich Syndrome/therapy , Adolescent , Adult , Anemia, Aplastic/complications , Anemia, Aplastic/therapy , Child , Child, Preschool , Fanconi Anemia/complications , Fanconi Anemia/therapy , Female , Follow-Up Studies , Genetic Diseases, X-Linked/complications , Genetic Diseases, X-Linked/therapy , Hemorrhage/etiology , Humans , Male , Platelet Count/statistics & numerical data , Platelet Transfusion/adverse effects , Platelet Transfusion/statistics & numerical data , Purpura, Thrombocytopenic, Idiopathic/therapy , Retrospective Studies , Severity of Illness Index , Thrombocytopenia/etiology , Thrombocytopenia/genetics , Wiskott-Aldrich Syndrome/complicationsABSTRACT
UNLABELLED: Thyroid dysfunction and the presence of thyroid antibodies increase the risk of infertility and miscarriage. The aim of the present study was to assess if patients with autoimmune thyroid disease undergoing assisted reproduction technologies (ART) are afflicted by poor pregnancy and/or delivery rate and if the outcome is conditioned by pre-ART thyroid status. The study was retrospective (from January 2000 to January 2005) and was carried out at the Division of Physiopathology of Human Reproduction. Women who underwent ART were tested for TSH, free T4 (FT4), thyroid peroxidase antibodies (TPOAb) before and during pregnancy. A total of 416 euthyroid women were selected; 42 (10.1%) were TPOAb (+). Women >35 yr were excluded. The endpoints were pregnancy and delivery rates. RESULTS: no differences in pregnancy and delivery rates were observed between women with and without antibodies. In TPOAb (+), women who failed to become pregnant or miscarried displayed higher TSH values before ART (2.8 mIU/l) compared to the ones who delivered (1.6 mIU/l; p=0.032) and compared to TPOAb (-) (1.1 mIU/l; p=0.018). CONCLUSIONS: in euthyroid women undergoing ART the pregnancy and delivery rates are not affected by the presence of TPOAb. In TPOAb (+) high-normal TSH values are associated with increased risk of unsuccessful pregnancy or subsequent miscarriage. Further studies are required to ascertain possible benefits of levo-T4 (L-T4) in such patients.
Subject(s)
Autoimmune Diseases/physiopathology , Autoimmunity/physiology , Pregnancy Complications , Reproductive Techniques, Assisted , Thyroid Diseases/physiopathology , Thyroid Gland/physiology , Adult , Autoantibodies/blood , Autoantigens/immunology , Autoimmune Diseases/blood , Autoimmune Diseases/complications , Female , Humans , Iodide Peroxidase/immunology , Iron-Binding Proteins/immunology , Pregnancy , Pregnancy Outcome , Pregnancy Rate , Retrospective Studies , Thyroid Diseases/blood , Thyroid Diseases/complicationsABSTRACT
BACKGROUND: Oxidative stress and increased inflammation have been reported to be increased in subjects with diabetes and to be involved in the pathogenesis of cardiovascular complications after myocardial infarction (MI). It is well recognized that red wine has antioxidant and anti-inflammatory activities. We examined the effects of moderate red wine intake on echocardiographic parameters of functional cardiac outcome in addition to inflammatory cytokines and nitrotyrosine (oxidative stress marker), in subjects with diabetes after a first uncomplicated MI. METHODS: One hundred and fifteen subjects with diabetes who had sustained a first non-fatal MI were randomized to receive a moderate daily amount of red wine (intervention group) or not (control group). Echocardiographic parameters of ventricular dys-synchrony, circulating levels of nitrotyrosine, tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-18 (IL-18) and C-reactive protein (CRP) were investigated at baseline and 12 months after randomization. RESULTS: After 1 year of diet intervention, concentrations of nitrotyrosine (P < 0.01), CRP (P < 0.01), TNF-alpha (P < 0.01), IL-6 (P < 0.01) and IL-18 (P < 0.01) were increased in the control group compared with the intervention group. In addition, myocardial performance index (P < 0.02) was higher, and transmitral Doppler flow (P < 0.05), pulmonary venous flow analysis (P < 0.02) and ejection fraction (P < 0.05) were lower in the control group, indicating ventricular dys-synchrony. The concentrations of nitrotyrosine, CRP, TNF-alpha and IL-6 were related to echocardiographic parameters of ventricular dys-synchrony. CONCLUSIONS: In subjects with diabetes, red wine consumption, taken with meals, significantly reduces oxidative stress and pro-inflammatory cytokines as well as improving cardiac function after MI. Moderate red wine intake with meals may have a beneficial effect in the prevention of cardiovascular complications after MI in subjects with diabetes.