ABSTRACT
PURPOSE: Mesenchymal stem/stromal cell therapy may reduce radiation-induced xerostomia. We investigated the long-term safety of autologous adipose tissue-derived mesenchymal stem/stromal cell (ASC) injections into the submandibular glands. EXPERIMENTAL DESIGN: An investigator-initiated, randomized, single-center, placebo-controlled trial. Previous patients with oropharyngeal squamous cell carcinoma with radiation-induced xerostomia were randomly (1:1) allocated to receive a 2.8 million ASCs/cm3 injection or placebo in both submandibular glands and followed for a minimum of 2 years. The primary endpoint was number of serious adverse events (SAE). Secondary endpoints included whole saliva flow rates and xerostomia-related symptoms. Data analysis was based on the intention-to-treat population using repeated measures mixed-effects linear models. RESULTS: Thirty-three patients were randomized; 30 patients were treated (ASC group, n = 15; placebo group, n = 15). Long-term safety data were collected from all 30 patients. During follow-up, 6 of 15 (40%) of the ASC-treated patients versus 5 of 15 (33%) of the placebo patients experienced an SAE; no SAEs appeared to be treatment related. Unstimulated whole saliva flow rate increased to 0.20 and 0.16 mL/minute in the ASC and placebo group, respectively, yielding a 0.05 mL/minute (95% confidence interval: 0.00-0.10; P = 0.051) difference between groups. Patient-reported xerostomia symptoms diminished according to a decreased xerostomia questionnaire summary score of 35.0 and 45.1, respectively [-10.1 (-18.1 to -2.2); P = 0.013]. Three of the visual analog scale xerostomia measures indicated clinical benefit following use of ASC. CONCLUSIONS: Our data show that ASC therapy is safe with a clinically relevant effect on xerostomia-related symptoms. Confirmation in larger randomized controlled trials is warranted.
Subject(s)
Head and Neck Neoplasms , Mesenchymal Stem Cells , Radiation Injuries , Xerostomia , Humans , Radiation Injuries/etiology , Radiation Injuries/therapy , Transplantation, Autologous , Xerostomia/etiology , Xerostomia/therapyABSTRACT
Skin ulcerations rank amongst the most prevalent lesions affecting wild common dab (Limanda limanda) with an increase in prevalence of up to 3.5% in the Belgian part of the North Sea. A complex aetiology of these ulcerations is suspected, and many questions remain on the exact factors contributing to these lesions. To construct the aetiological spectrum of skin ulcerations in flatfish, a one-day monitoring campaign was undertaken in the North Sea. Fifteen fish presented with one or more ulcerations on the pigmented and/or non-pigmented side. Pathological features revealed various stages of ulcerations with loss of epidermal and dermal tissue, inflammatory infiltrates and degeneration of the myofibers bordering the ulceration, albeit in varying degrees. Upon bacteriological examination, pure cultures of Vibrio tapetis were retrieved in high numbers from five fish and of Aeromonas salmonicida in one fish. The V. tapetis isolates showed cross-reactivity with the sera against the representative strain of serotype O2 originating form a carpet-shell clam (Ruditapes descussatus). Moreover, the A. salmonicida isolates displayed a previously undescribed vapA gene sequence (A-layer type) with possible specificity towards common dab. Further research is necessary to pinpoint the exact role of these agents in the development of skin ulcerations in common dab.
Subject(s)
Aeromonas salmonicida/isolation & purification , Fish Diseases/pathology , Flounder , Gram-Negative Bacterial Infections/veterinary , Skin Diseases/veterinary , Vibrio Infections/veterinary , Vibrio/isolation & purification , Animals , Belgium , Female , Fish Diseases/microbiology , Gram-Negative Bacterial Infections/microbiology , Gram-Negative Bacterial Infections/pathology , Male , North Sea , Skin Diseases/microbiology , Skin Diseases/pathology , Vibrio Infections/microbiology , Vibrio Infections/pathologyABSTRACT
BACKGROUND: Dermatomyositis (DM) is an autoimmune disease primarily affecting skin and muscle. OBJECTIVES: The purpose of this study was to determine whether an association exists between clinical skin disease activity as measured by the validated Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) and type 1 interferon (IFN) pathway biomarkers in the blood of patients with DM. METHODS: Forty-two patients with DM and 25 healthy volunteers were prospectively enrolled. CDASI scores were obtained, and serum and blood RNA were isolated from all participants. Associations between CDASI activity and type 1 IFN-inducible gene signature were assessed cross-sectionally in all patient samples and longitudinally on 13 paired visits via transcriptional profiling analyses. RESULTS: By RNAseq analysis, type 1 IFN-inducible genes were the most highly differentially regulated. A CDASI activity threshold of 12 was correlated with an elevated type 1 IFN gene signature and with serum IFN-ß, but not with IFN-α protein. Expression analysis showed that all patients with mild disease activity had a low type 1 IFN gene signature, while 93% of patients with moderate-to-high disease activity had elevated gene signature. In longitudinal analysis, changes in CDASI activity showed nonsignificant trends with concordant directional changes in gene signature. CONCLUSIONS: A type 1 IFN pathway signature biomarker in blood is highly correlated with CDASI activity scores in DM, and may be a promising surrogate clinical trial end point. The correlation of serum IFN-ß, but not IFN-α, with both a gene signature and CDASI suggests that IFN-ß drives disease activity in DM.
Subject(s)
Dermatomyositis/genetics , Interferon Type I/genetics , Interferon-beta/genetics , Biomarkers/metabolism , Chemokine CXCL10/metabolism , Cross-Sectional Studies , Dermatomyositis/blood , Female , Healthy Volunteers , Humans , Interferon Type I/metabolism , Interferon-beta/metabolism , Male , Middle Aged , Prospective Studies , RNA, Messenger/metabolism , Severity of Illness IndexSubject(s)
Aeromonas salmonicida/immunology , Fish Diseases/prevention & control , Gram-Negative Bacterial Infections/veterinary , Perciformes , Vibrio Infections/veterinary , Vibrio/immunology , Aeromonas salmonicida/genetics , Animals , Bacterial Vaccines/administration & dosage , Fish Diseases/immunology , Fish Diseases/microbiology , Gram-Negative Bacterial Infections/immunology , Gram-Negative Bacterial Infections/microbiology , Gram-Negative Bacterial Infections/prevention & control , Vibrio/genetics , Vibrio Infections/immunology , Vibrio Infections/microbiology , Vibrio Infections/prevention & controlABSTRACT
Sequence variation in a region of the virulence array protein gene (vapA; A-layer) was assessed in 333 ('typical' and 'atypical') isolates of the fish pathogenic bacterium Aeromonas salmonicida. Resulting similarity dendrograms revealed extensive heterogeneity, with nearly all isolates belonging to either of 14 distinct clusters or A-layer types. All acknowledged A. salmonicida subspecies (except ssp. pectinolytica, from which no vapA sequence could be obtained) were clearly separated, and notably, all isolates phenotypically identified as ssp. salmonicida formed a distinct and exclusive A-layer type. Additionally, an array of un-subspeciated atypical strains formed several equally prominent clusters, demonstrating that the concept of typical/atypical A. salmonicida is inappropriate for describing the high degree of diversity evidently occurring outside ssp. salmonicida. Most representatives assessed in this study were clinical isolates of spatiotemporally diverse origins, and were derived from a variety of hosts. We observed that from several fish species or families, isolates predominantly belonged to certain A-layer types, possibly indicating a need for host-/A-layer type-specific A. salmonicida vaccines. All in all, A-layer typing shows promise as an inexpensive and rapid means of unambiguously distinguishing clinically relevant A. salmonicida subspecies, as well as presently un-subspeciated atypical strains.
Subject(s)
Aeromonas salmonicida/classification , Aeromonas salmonicida/genetics , Bacterial Typing Techniques , Fish Diseases/microbiology , Gram-Negative Bacterial Infections/veterinary , Phylogeny , Virulence Factors/genetics , Animals , Frameshift Mutation/genetics , Genetic Variation , Gram-Negative Bacterial Infections/microbiology , Host-Pathogen Interactions , Molecular Typing , Species SpecificitySubject(s)
Fish Diseases/microbiology , Pasteurella Infections/veterinary , Animals , Fish Diseases/mortality , Fish Diseases/pathology , Fisheries , Host-Pathogen Interactions , Norway , Pasteurella/classification , Pasteurella/genetics , Pasteurella Infections/microbiology , Pasteurella Infections/mortality , Pasteurella Infections/pathology , Perciformes , Phylogeny , RNA, Ribosomal, 16S/geneticsABSTRACT
Due to increasing resistance to chemical therapeutants, the use of 'cleaner fish' (primarily wrasse, Labridae, species) has become popular in European salmon farming for biocontrol of the salmon louse, Lepeophtheirus salmonis (Krøyer). While being efficient de-licers, cleaner fish mortality levels in salmon cages are commonly high, and systemic bacterial infections constitute a major problem. Atypical furunculosis, caused by Aeromonas salmonicida A-layer types V and VI, is among the most common diagnoses reached in clinical investigations. A previously described real-time PCR (qPCR), targeting the A. salmonicida A-layer gene (vapA), was modified and validated for specific and sensitive detection of all presently recognized A-layer types of this bacterium. Before stocking and during episodes of increased mortality in salmon cages, cleaner fish (primarily wild-caught wrasse) were sampled and screened for A. salmonicida by qPCR and culture. Culture indicated that systemic bacterial infections are mainly contracted after salmon farm stocking, and qPCR revealed A. salmonicida prevalences of approximately 4% and 68% in pre- and post-stocked cleaner fish, respectively. This underpins A. salmonicida's relevance as a contributing factor to cleaner fish mortality and emphasizes the need for implementation of preventive measures (e.g. vaccination) if current levels of cleaner fish use are to be continued or expanded.
Subject(s)
Aeromonas salmonicida/isolation & purification , Furunculosis/diagnosis , Gram-Negative Bacterial Infections/veterinary , Perciformes , Real-Time Polymerase Chain Reaction/veterinary , Animals , Colony Count, Microbial/veterinary , Fisheries , Furunculosis/epidemiology , Furunculosis/prevention & control , Furunculosis/transmission , Gram-Negative Bacterial Infections/epidemiology , Gram-Negative Bacterial Infections/prevention & control , Gram-Negative Bacterial Infections/transmission , Norway/epidemiologyABSTRACT
The present study was carried out to develop and evaluate ready to eat extruded snacks incorporated with garlic powder at various levels (5 %, 10 %, 15 %, 20 %). The organoleptic evaluation was conducted for the developed products and the well accepted products were selected for further studies like physical properties and shelf life (stored at room temperature for 2 months). The organoleptic evaluation of the developed snacks revealed that 15 % and 20 % garlic incorporated snacks were not acceptable due to strong garlic flavor, therefore T1 (control), T2 (5 % garlic) and T3 ( 10 % garlic) were selected for further studies. The physical properties showed significant changes with incorporation of garlic powder at 0 %-10 % level. There was an increase in mass flow rate, tap density and bulk density but decrease in the water holding capacity, oil absorption capacity and expansion ratio. The water soluble index and moisture retention of the products showed the same values for all the three selected treatments. The products were packed by ordinary, nitrogen and vacuum packing and stored for 2 months. It was found that there was an increase in moisture content and microbial load, however the increase was within limits. The increase in the moisture content was low in nitrogen packed products where as the microbial load decreased with increase in the percentage of garlic incorporation. The nitrogen and vacuum packed products showed less microbial load than the ordinary packed products. Garlic powder can be incorporated at 5 and 10 % levels in ready-to-eat extruded snacks with well acceptability and can be stored for a period of 2 months with nitrogen packing as an effective packaging.
ABSTRACT
OBJECTIVE: Circulating oestradiol and testosterone, which have been shown to increase in human immunodeficiency virus (HIV)-infected patients following highly active antiretroviral therapy (HAART), may influence fat distribution and insulin sensitivity. Oestradiol increases subcutaneous adipose tissue in humans possibly through binding to oestrogen-receptor-alpha, which in turn activates anti-lipolytic alpha2A-adrenergic-receptor. DESIGN AND METHODS: To address these issues circulating pituitary-gonadal-axis hormones and gene expression of receptors in subcutaneous adipose tissue were determined in 31 nondiabetic HIV-infected male patients receiving HAART (16 with lipodystrophy), in whom measures of fat distribution (CT and DEXA-scans) and insulin sensitivity (hyperinsulinaemic euglycaemic clamp) were available. RESULTS: Total and free oestradiol and testosterone were decreased in lipodystrophic patients compared to nonlipodystrophic patients, whereas luteinizing hormone, follicle-stimulating hormone and prolactin were similar and normal in both study groups. Ratio of subcutaneous to total abdominal fat mass, limb fat, and insulin sensitivity, which were all decreased in lipodystrophic patients, correlated positively with both plasma oestradiol and testosterone (n = 31). Glycerol concentration during clamp (a marker of lipolysis) correlated inversely with expression of alpha2A-adrenergic-receptor, ratio of subcutaneous to total abdominal fat mass, and limb fat, respectively. Expression of alpha2A-adrenergic-receptor correlated positively with expression of oestrogen-receptor-alpha. CONCLUSIONS: The results fit the hypothesis that sex hormones play a role in altered fat distribution and insulin sensitivity of male patients with HIV-lipodystrophy. The effect of oestradiol on the subcutaneous fat depot and lipolysis may be mediated in part through binding to the oestrogen-receptor-alpha, in turn activating anti-lipolytic alpha2A-adrenergic-receptor.
Subject(s)
Gonadal Steroid Hormones/blood , HIV-Associated Lipodystrophy Syndrome/blood , Receptors, Adrenergic, alpha-2/genetics , Subcutaneous Fat/metabolism , Anti-HIV Agents/therapeutic use , Antiretroviral Therapy, Highly Active , Aromatase/genetics , Body Composition , Cross-Sectional Studies , Dehydroepiandrosterone Sulfate/blood , Estradiol/blood , Estradiol/genetics , Estrogen Receptor alpha/genetics , Gene Expression , Glycerol/blood , Gonadal Steroid Hormones/genetics , HIV-1 , HIV-Associated Lipodystrophy Syndrome/drug therapy , Humans , Hydrocortisone/blood , Hypoglycemic Agents , Insulin , Linear Models , Lipolysis , Male , Sex Hormone-Binding Globulin/analysis , Testosterone/bloodABSTRACT
The authors describe a case of left ventricle myocardial infarction who showed right ventricular failure. The patient is been studied by mono and bidimensional echocardiography, myocardial scintigraphy, ecg, chest X ray and right catheterism. Myocardial scintigraphy localized "cold" areas in interventricular septum and in right inferior wall. Echocardiography showed dilatation of the right side but not on the left heart side. The not invasive examinations allowed to assess that right ventricular failure was primary and not secondary left ventricular failure. The authors discuss findings of echocardiographic examination and of other non invasive methods.