ABSTRACT
With excellent energy resolution and ultralow-level radiogenic backgrounds, the high-purity germanium detectors in the Majorana Demonstrator enable searches for several classes of exotic dark matter (DM) models. In this work, we report new experimental limits on keV-scale sterile neutrino DM via the transition magnetic moment from conversion to active neutrinos ν_{s}âν_{a}. We report new limits on fermionic dark matter absorption (χ+Aâν+A) and sub-GeV DM-nucleus 3â2 scattering (χ+χ+AâÏ+A), and new exclusion limits for bosonic dark matter (axionlike particles and dark photons). These searches utilize the (1-100)-keV low-energy region of a 37.5-kg y exposure collected by the Demonstrator between May 2016 and November 2019 using a set of ^{76}Ge-enriched detectors whose surface exposure time was carefully controlled, resulting in extremely low levels of cosmogenic activation.
ABSTRACT
OBJECTIVE: The current study considered assessing the role of miRNA-155 and miRNA-24 in collagen-induced rheumatoid arthritis (RA) in rats' temporomandibular joint (TMJ). Their role in histological aggressiveness of the disease and therapy response to glycogen synthase kinase (GSK) inhibitor 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8) will be studied. MATERIALS AND METHODS: Rats were randomly distributed to four groups (8 rats/group): group I negative control, group II collagen-induced rheumatoid arthritis (CIA), group III Control+TDZD-8 treated group, and group IV CIA+TDZD-8 treated group. Then were euthanized 42 days after the start of the experiment. H&E staining, Masson trichrome staining, and immunohistochemical antibodies against S100 were performed. qRT-PCR of miRNA-155 and miRNA-24 were done for frozen synovial tissues. RESULTS: Histological analysis showed that the most affected structure in induced rheumatoid arthritis of TMJ is the articular disc, condylar head, and subchondral bone. Combined treatment with TDZD-8 improved histological status in the joint. Masson's trichrome (MTC) histochemical staining revealed disarrangement of collagen fibers and adherence between the articular disc and condylar cartilage. Meanwhile, the morphology and collagen composition of the disc and condyle in CIA+ TDZD-8 were similar to those of healthy tissues. Immunohistochemical analysis for S100A4 revealed increased immunoreactivity staining in the CIA group. The immunoreactivity was significantly decreased in CIA+ TDZD-8 treated group. TDZD-8 significantly decreased the levels of miRNA-155 and miRNA-24 in synovial tissue. CONCLUSIONS: Our results reveal for the first-time correlation of miRNA-155 and miRNA-24 that might be implicated in the onset of TMJ RA. Consequently, the treatment of CIA with GSK inhibitor (TDZD-8) yields encouraging results. We predicted the TDZD-8 might protect against CIA by suppressing miRNA-155, miRNA-24, and S100A4 protein levels.
Subject(s)
Arthritis, Rheumatoid , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/immunology , Arthritis, Experimental/drug therapy , Arthritis, Experimental/genetics , Arthritis, Experimental/immunology , Collagen/toxicity , Animals , Rats , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/therapeutic useABSTRACT
This corrects the article DOI: 10.1103/PhysRevLett.129.080401.
ABSTRACT
Coronavirus Disease 2019 (COVID-19) is a current pandemic infection of the human respiratory system, which is caused by which caused by Sever Acute respiratory syndrome virus 2 (SARS-CoV-2). The infection was classified by World Health Organization (WHO) as a universal pandemic in February 2020; there have been 494.587.638 confirmed cases and 6.170.283 deaths. The present study investigated the molecular genetics of the Angiotensin Converting Enzyme 2 (ACE2) gene in correlation to COVID-19 patients in the Kurdish population. Eighty-six individuals were clinically diagnosed with COVID-19 and control groups. After the genomic DNA extraction these participants the target 1, 2 and 8 exons of the ACE2 gene were amplified using the PCR technique, and then the Sanger sequencing technique was performed to analyze genetic variants of the ACE2 gene in 70 DNA samples of COVID-19 hospital patients at Emergency Hospital in Erbil city, Sarchnar Hospital in Sulaymaniyah city, Lalav Hospital in Duhok city and Wafa Hospital in Halabja city from Kurdistan Region of Iraq. The current study was designed into two groups control group and a patient group. The patient group was divided into two subgroups, severe and mild patients of different ages and genders. As a result, there were no mutations at the positions 1, 2 and 8 exons sequences, while single nucleotide polymorphisms (SNPs) were detected and identified three different types of mutation at intron position: twenty-six of c.12405 del T, two of c.12407 T>G, and two of c.12406 G>A in a total 86 participants. This result shows that genetic difference does not impact the COVID-19 infection severity among the Kurdish population regarding ACE2 gene polymorphism.
Subject(s)
Angiotensin-Converting Enzyme 2 , COVID-19 , Female , Humans , Male , Angiotensin-Converting Enzyme 2/genetics , COVID-19/epidemiology , Iraq/epidemiology , Polymorphism, Single Nucleotide , SARS-CoV-2/geneticsABSTRACT
The Majorana Demonstrator searched for neutrinoless double-ß decay (0νßß) of ^{76}Ge using modular arrays of high-purity Ge detectors operated in vacuum cryostats in a low-background shield. The arrays operated with up to 40.4 kg of detectors (27.2 kg enriched to â¼88% in ^{76}Ge). From these measurements, the Demonstrator has accumulated 64.5 kg yr of enriched active exposure. With a world-leading energy resolution of 2.52 keV FWHM at the 2039 keV Q_{ßß} (0.12%), we set a half-life limit of 0νßß in ^{76}Ge at T_{1/2}>8.3×10^{25} yr (90% C.L.). This provides a range of upper limits on m_{ßß} of (113-269) meV (90% C.L.), depending on the choice of nuclear matrix elements.
ABSTRACT
Open testicular biopsy histology and fine needle aspiration cytology (FNAC) are the most popular tests used to diagnose male infertility. This study aimed to assess the cytological characteristics of 186 infertile males aged 24-63 with testicular FNAC. Furthermore, the existing relationship between males with severe oligospermia (sperm count: 5 million/ml) and azoospermia was investigated via both cytological and histological diagnosis methods. With a 1.5-inch and 25-gauge needle, the testis was aspirated from three locations (the upper, middle, and lower poles). Papanicolaou stain or Giemsa stain was used to make smears on albumenized slides, which were then dried in the air and stained. A biopsy of the testicles was performed there, preserved in Bouins solution, processed as usual, and stained with hematoxylin and eosin stain. According to our findings, 66.7% of patients had secondary maturation arrest, whereas 18.3% and 15.1% of them had hypospermatogenesis and Sertoli cell only (SCO). Results of the comparison showed that both procedures were very similar. According to biopsy histological examinations, only 3 (1.6%) of the 28 normal FNAC instances had hypospermatogenesis with lymphocyte infiltration. The majority of SCO patients were over 50 years old. These findings revealed that FNAC is more effective than testicular histology for the assessment of male infertility.
Subject(s)
Azoospermia , Infertility, Male , Oligospermia , Male , Humans , Middle Aged , Testis/pathology , Biopsy, Fine-Needle/veterinary , Biopsy, Fine-Needle/methods , Oligospermia/diagnosis , Oligospermia/pathology , Azoospermia/diagnosis , Azoospermia/veterinary , Azoospermia/pathology , Semen , Infertility, Male/pathologyABSTRACT
The Majorana Demonstrator neutrinoless double-beta decay experiment comprises a 44 kg (30 kg enriched in ^{76}Ge) array of p-type, point-contact germanium detectors. With its unprecedented energy resolution and ultralow backgrounds, Majorana also searches for rare event signatures from beyond standard model physics in the low energy region below 100 keV. In this Letter, we test the continuous spontaneous localization (CSL) model, one of the mathematically well-motivated wave function collapse models aimed at solving the long-standing unresolved quantum mechanical measurement problem. While the CSL predicts the existence of a detectable radiation signature in the x-ray domain, we find no evidence of such radiation in the 19-100 keV range in a 37.5 kg-y enriched germanium exposure collected between December 31, 2015, and November 27, 2019, with the Demonstrator. We explored both the non-mass-proportional (n-m-p) and the mass-proportional (m-p) versions of the CSL with two different assumptions: that only the quasifree electrons can emit the x-ray radiation and that the nucleus can coherently emit an amplified radiation. In all cases, we set the most stringent upper limit to date for the white CSL model on the collapse rate, λ, providing a factor of 40-100 improvement in sensitivity over comparable searches. Our limit is the most stringent for large parts of the allowed parameter space. If the result is interpreted in terms of the Diòsi-Penrose gravitational wave function collapse model, the lower bound with a 95% confidence level is almost an order of magnitude improvement over the previous best limit.
ABSTRACT
Axions were originally proposed to explain the strong-CP problem in QCD. Through axion-photon coupling, the Sun could be a major source of axions, which could be measured in solid state detection experiments with enhancements due to coherent Primakoff-Bragg scattering. The Majorana Demonstrator experiment has searched for solar axions with a set of ^{76}Ge-enriched high purity germanium detectors using a 33 kg-yr exposure collected between January, 2017 and November, 2019. A temporal-energy analysis gives a new limit on the axion-photon coupling as g_{aγ}<1.45×10^{-9} GeV^{-1} (95% confidence level) for axions with mass up to 100 eV/c^{2}. This improves laboratory-based limits between about 1 eV/c^{2} and 100 eV/c^{2}.
ABSTRACT
P-type point contact (PPC) HPGe detectors are a leading technology for rare event searches due to their excellent energy resolution, low thresholds, and multi-site event rejection capabilities. We have characterized a PPC detector's response to α particles incident on the sensitive passivated and p + surfaces, a previously poorly-understood source of background. The detector studied is identical to those in the Majorana Demonstrator experiment, a search for neutrinoless double-beta decay ( 0 ν ß ß ) in 76 Ge. α decays on most of the passivated surface exhibit significant energy loss due to charge trapping, with waveforms exhibiting a delayed charge recovery (DCR) signature caused by the slow collection of a fraction of the trapped charge. The DCR is found to be complementary to existing methods of α identification, reliably identifying α background events on the passivated surface of the detector. We demonstrate effective rejection of all surface α events (to within statistical uncertainty) with a loss of only 0.2% of bulk events by combining the DCR discriminator with previously-used methods. The DCR discriminator has been used to reduce the background rate in the 0 ν ß ß region of interest window by an order of magnitude in the Majorana Demonstrator and will be used in the upcoming LEGEND-200 experiment.
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AIMS: The aim of this study was to isolate and characterize staphylococcal isolates from diabetic foot ulcers (DFU) in Jordanian patients. METHODS AND RESULTS: Selected aerobic pathogens recovered from DFU specimens and patients' nares with a focus on staphylococci were investigated. Antimicrobial susceptibilities and the prevalence of methicillin-resistant staphylococci (MRS) were determined. SCCmec types and toxigenic characteristics were analysed and spa typing was performed for methicillin-resistant Staphylococcus aureus (MRSA) isolates. The relationship between toxigenic characteristics of MRSA and the Wagner ulcer grading system was statistically analysed. A total number of 87 DFU patients were recruited for the study. The DFU cultures were polymicrobial. Members of the genus Staphylococcus were the most common among DFU-associated isolates found in 48·3% (n = 42) of all patients enrolled. Coagulase-negative staphylococci (CoNS) comprised 63·3% of staphylococci isolated from DFUs predominated by Staphylococcus epidermidis in both DFU (7·6%) and nares (39·2%). Staphylococcus aureus was isolated from DFUs and nares in 14·2 and 9·8%, respectively, while 93 and 70% of these isolates were MRSA. Most of MRSA carried SCCmec type IV (76·2%) while SCCmec elements were non-typeable in most methicillin resistant coagulase negative staphylococci (MR-CoNS) (61·9%). The most frequent MRSA spa type was t386 (23·8%). Most MRSA and MR-CoNS exhibited resistance towards aminoglycosides, fluoroquinolones and macrolides and susceptibility towards vancomycin, mupirocin and linezolid. No association was found between the possession of pvl, tst, sea and hlg toxins and Wagner ulcer grading system (P value >0·05). CONCLUSIONS: This analysis of Jordanian DFU culture demonstrated its polymicrobial nature with predominance of Staphylococcus sp. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first of its type to assess the microbiology of DFU among Jordanian patients. The results will help in the appropriate application of antimicrobial chemotherapy in the management of DFU.
Subject(s)
Diabetes Mellitus , Diabetic Foot , Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Anti-Bacterial Agents/pharmacology , Diabetic Foot/epidemiology , Humans , Methicillin Resistance , Methicillin-Resistant Staphylococcus aureus/genetics , Microbial Sensitivity Tests , Staphylococcal Infections/epidemiology , Staphylococcus/geneticsABSTRACT
OBJECTIVES: The practice of dispensing non-prescribed antibiotics aggravates the global burden of antibiotic resistance. The objective of this study is to assess the practice of community pharmacists regarding dispensing antibiotics without a prescription based on simulated clinical scenarios. STUDY DESIGN: Cross-sectional study. METHODS: The study was performed between 15 April to 18 June 2015. Five different clinical scenarios were simulated, involving sore throat, otitis media, cough, diarrhea, and urinary tract infection (UTI). Three different levels of demand were used to convince the pharmacists to dispense antibiotics data was analyzed using SPSS, version 21.0. RESULTS: Two-hundred community pharmacies in Sana'a were visited for each clinical scenario. The majority of pharmacies (73.3%) dispensed antibiotics without medical prescriptions in different levels of demand. Most antibiotics were dispensed for the sore throat simulated scenario (99.5%), followed by cough (92%), diarrhea (75.5%), and otitis media (52%). The lowest percentage of dispensed antibiotics was in the UTI scenario, with 48%. Among the pharmacists who dispensed antibiotics, 74.2% provided an explanation to the simulated patients regarding how to use antibiotics, 77.6% counseled the patient about treatment duration and only 11.9% of the pharmacists asked about the pregnancy status. Regarding the cough scenario, 83% of the pharmacists inquired about the type of cough before dispensing medication. CONCLUSION: Antibiotics in Yemen can be easily obtained without medical prescription or evidence-based indication.
Subject(s)
Anti-Bacterial Agents , Community Pharmacy Services , Drug Prescriptions/statistics & numerical data , Health Services Accessibility/statistics & numerical data , Warfare and Armed Conflicts , Adult , Cross-Sectional Studies , Female , Humans , Male , Pregnancy , YemenSubject(s)
Carcinoma, Hepatocellular/genetics , Hepatitis C, Chronic/genetics , Interleukin-6/genetics , Liver Neoplasms/genetics , Polymorphism, Genetic , Promoter Regions, Genetic , Adult , Alleles , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/pathology , Case-Control Studies , Female , Gene Expression , Gene Frequency , Genotype , Hepacivirus/growth & development , Hepacivirus/pathogenicity , Hepatitis C, Chronic/blood , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/pathology , Humans , Inflammation , Interleukin-6/blood , Liver Neoplasms/blood , Liver Neoplasms/etiology , Liver Neoplasms/pathology , Male , Middle Aged , Models, GeneticABSTRACT
The Majorana Demonstrator is an ultralow-background experiment searching for neutrinoless double-beta decay in ^{76}Ge. The heavily shielded array of germanium detectors, placed nearly a mile underground at the Sanford Underground Research Facility in Lead, South Dakota, also allows searches for new exotic physics. Free, relativistic, lightly ionizing particles with an electrical charge less than e are forbidden by the standard model but predicted by some of its extensions. If such particles exist, they might be detected in the Majorana Demonstrator by searching for multiple-detector events with individual-detector energy depositions down to 1 keV. This search is background-free, and no candidate events have been found in 285 days of data taking. New direct-detection limits are set for the flux of lightly ionizing particles for charges as low as e/1000.
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The prevalence of natural carriage and molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci (MR-CoNS) isolates in a Jordanian community were investigated. The MRSA nasal carriage rate in 227 healthy volunteers was 7·5% and the majority (81%) of MRSA harboured the resistance element SCCmec type IVe and were of a novel spa type t9519 (76%); other significant spa gene types were t223 (14·7%) and t044 (5·9%). All MRSA isolates were susceptible to other classes of antibiotics, and tested positive for at least three virulence factor encoding genes, but only two harboured the pvl gene. MR-CoNS carriage was 54·2% and these isolates were characterized by single, double and untypable SCCmec elements, with Staphylococcus epidermidis SCCmec type IVa predominating. Of eight subjects with nasal co-colonization of MR-CoNS + MRSA, three shared SCCmec type IV in both groups of organisms. This is the first report of methicillin-resistant staphylococci carriage in a Jordanian community and its findings are important for epidemiological study and infection control measures of these organisms.
Subject(s)
Methicillin-Resistant Staphylococcus aureus/isolation & purification , Staphylococcal Infections/microbiology , Anti-Bacterial Agents , Carrier State , DNA, Bacterial , Female , Humans , Jordan/epidemiology , Male , Methicillin Resistance , Methicillin-Resistant Staphylococcus aureus/genetics , Nose/microbiology , Skin/microbiology , Staphylococcal Infections/epidemiologyABSTRACT
This study determined the costs associated with tuberculosis (TB) diagnosis and treatment for the public health services and patients in Sana'a, Yemen. Data were collected prospectively from 320 pulmonary and extrapulmonary TB patients (160 each) who were followed until completion of treatment. Direct medical and nonmedical costs and indirect costs were calculated. The proportionate cost to the patients for pulmonary TB and extrapulmonary TB was 76.1% arid 89.4% respectively of the total for treatment. The mean cost to patients for pulmonary and extrapulmonary TB treatment was US$ 108.4 and US$ 328.0 respectively. The mean cost per patient to the health services for pulmonary and extrapulmonary TB treatment was US$ 34.0 and US$ 38.8 respectively. For pulmonary and extrapulmonary TB, drug treatment represented 59.3% and 77.9% respectively of the total cost to the health services. The greatest proportionate cost to patients for pulmonary TB treatment was time away from work (67.5% of the total cost), and for extrapulmonary TB was laboratory and X-ray costs (55.5%) followed by transportation (28.6%).
Subject(s)
Antitubercular Agents/economics , Health Services Accessibility/economics , Primary Health Care/economics , Tuberculosis/economics , Tuberculosis/epidemiology , Adult , Aged , Antitubercular Agents/therapeutic use , Cost-Benefit Analysis , Female , Hospitalization/economics , Humans , Male , Middle Aged , National Health Programs/economics , Prospective Studies , Regression Analysis , Tuberculosis/diagnosis , Tuberculosis/drug therapy , Tuberculosis, Pulmonary/economics , Tuberculosis, Pulmonary/epidemiology , Yemen/epidemiologyABSTRACT
This study determined the costs associated with tuberculosis [TB] diagnosis and treatment for the public health services and patients in Sana'a, Yemen. Data were collected prospectively from 320 pulmonary and extrapulmonary TB patients [160 each] who were followed until completion of treatment. Direct medical and nonmedical costs and indirect costs were calculated. The proportionate cost to the patients for pulmonary TB and extrapulmonary TB was 76.1% and 89.4% respectively of the total for treatment. The mean cost to patients for pulmonary and extrapulmonary TB treatment was US$ 108.4 and US$ 328.0 respectively. The mean cost per patient to the health services for pulmonary and extrapulmonary TB treatment was US$ 34.0 and US$ 38.8 respectively. For pulmonary and extrapulmonary TB, drug treatment represented 59.3% and 77.9% respectively of the total cost to the health services. The greatest proportionate cost to patients for pulmonary TB treatment was time away from work [67.5% of the total cost], and for extrapulmonary TB was laboratory and X-ray costs [55.5%] followed by transportation [28.6%]
Subject(s)
Tuberculosis , Community Health Services , Costs and Cost Analysis , Prospective StudiesABSTRACT
AIMS: To evaluate the antimicrobial activities of aspirin, EDTA and an aspirin-EDTA (A-EDTA) combination against Pseudomonas aeruginosa, Escherichia coli and Candida albicans in planktonic and biofilm cultures. METHODS AND RESULTS: Minimal inhibitory concentrations (MIC) and minimal biocidal concentrations (MBC) were determined using twofold broth microdilution and viable counting methods, respectively. Aspirin's recorded MIC values ranged from 1.2 to 2.7 mg ml(-1). Checkerboard assay demonstrated a synergism in antimicrobial activity upon combination. Aspirin's minimal biofilm eradication concentration values (MBEC) against the established biofilms ranged between 1.35 and 3.83 mg ml(-1). A complete eradication of bacterial biofilms was achieved after a 4-h treatment with the A-EDTA combination. CONCLUSION: Both aspirin and EDTA possess broad-spectrum antimicrobial activity for both planktonic and biofilm cultures. Aspirin used at the MBEC for 24 h was successful in eradicating P. aeruginosa, E. coli and C. albicans biofilms established on abiotic surfaces. Moreover, the exposure to the A-EDTA combination (4 h) effected complete bacterial biofilm eradication. SIGNIFICANCE AND IMPACT OF THE STUDY: There is a continuous need for the discovery of new antimicrobial agents. Aspirin and EDTA are 'nonantibiotic drugs', the combination of which can be used successfully to treat and eradicate biofilms established on abiotic surfaces.
Subject(s)
Anti-Infective Agents/pharmacology , Aspirin/pharmacology , Biofilms/drug effects , Candida albicans/drug effects , Edetic Acid/pharmacology , Gram-Negative Bacteria/drug effects , Plankton/drug effects , Biofilms/growth & development , Candida albicans/growth & development , Colony Count, Microbial , Disinfectants/pharmacology , Drug Synergism , Drug Therapy, Combination , Escherichia coli/drug effects , Escherichia coli/growth & development , Gram-Negative Bacteria/growth & development , Microbial Sensitivity Tests , Plankton/growth & development , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/growth & developmentABSTRACT
Honey is thought to exhibit a broad spectrum of therapeutic properties including antibacterial, antifungal, cytostatic and anti-inflammatory activity and has been used for the treatment of gastric ulcers, burns, and for storage of skin grafts. The present study investigated the antitumor effect of bee honey against Ehrlich ascites tumor in mice and the possible mode of antitumor action. Peroral administration of mice with honey (10, 100 or 1000 mg/ 100 g BW) every other day for 4 weeks before intraperitoneal inoculation with Ehrlich ascites tumor (EAT, 1 x 10(6) cells) increased the number bone marrow cells as well as peritoneal macrophages, but not peripheral blood leukocytes nor splenocytes. The phagocytic function of macrophages as well as the T- and B-cell functions were also increased. Honey pre-treatment also recovered the total lipids, total proteins, as well as liver and kidney enzyme activities in EAT-bearing mice. In vitro studies on EAT cells demonstrated inhibitory effect of honey on tumor cell proliferation, viability % of tumor cells as well as the size of solid tumor. The present results indicate that the preventive treatment with honey is considerably effective against EAT in mice both in vivo and in vitro. The antitumor activity of honey may occur through the activation of macrophages, T-cells and B-cells.
Subject(s)
Antineoplastic Agents/pharmacology , Bees/chemistry , Carcinoma, Ehrlich Tumor/drug therapy , Honey , Alanine Transaminase/blood , Animals , Antineoplastic Agents/chemistry , Aspartate Aminotransferases/blood , B-Lymphocytes/cytology , B-Lymphocytes/drug effects , B-Lymphocytes/immunology , Blood Proteins/metabolism , Bone Marrow Cells/cytology , Bone Marrow Cells/drug effects , Bone Marrow Cells/immunology , Carcinoma, Ehrlich Tumor/immunology , Carcinoma, Ehrlich Tumor/pathology , Cell Count , Cell Line, Tumor , Cell Survival/drug effects , Dose-Response Relationship, Drug , Female , Lipids/blood , Lymphocyte Count , Macrophages/cytology , Macrophages/drug effects , Macrophages/immunology , Mice , Phagocytosis/drug effects , Phagocytosis/immunology , T-Lymphocytes/cytology , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , Tumor Burden/drug effectsABSTRACT
On the basis that multiple interactions exist between thyroid hormones and immune system, and ageing is accompanied by changes in thyroid hormone secretion, it seems possible that thyroid hormones may be involved in the age-related immune dysfunction. The present study was conducted to evaluate in vivo and in vitro effects of thyroxine (T(4)) treatment on both cell-mediated and humoral immune responses of aged mice. In a trial to improve age-associated immune dysfunction, T(4) (0.2, 1.0 and 5.0 microg) was subcutaneously supplemented to BALB/c mice (over 18 months old) for 30 consecutive days. The present results showed that exogenous treatment of aged mice with T(4) was associated with a marked increase in serum T(4) level, and the total number of peripheral blood leukocytes as well as the total cellularity of thymus, spleen, peripheral lymph nodes (PLNs), mesenteric lymph nodes (MLNs) and bone marrow (BM). T(4) treatment also caused a significant increase in the total and differential numbers of peritoneal exudate cells (PECs), while it caused a slight increase in macrophages' phagocytic activity of PEC. Moreover, T(4) treatment elicited a statistically significant increase in both plaque-forming cell and rosette-forming cell responses. In vitro results showed that the addition of T(4) at concentrations of 0.001, 0.005 and 0.025 microg/well substantially potentiated the ability of splenocytes from aged mice to proliferate in the presence of concanavalin-A mitogen. Histological examination of thymuses from T(4)-treated aged mice revealed that the cortex was preferentially enlarged and repopulated with immature thymocytes. The present study postulates that thyroid hormones may be involved in the observed decrease in the immune responsiveness during ageing, and that T(4) treatment to aged mice is able to restore the age-related decline of the immune efficiency.
Subject(s)
Aging/immunology , Antibody Formation/drug effects , Immunity, Cellular/drug effects , Lymphocytes/immunology , Thyroxine/pharmacology , Aging/blood , Animals , B-Lymphocytes/drug effects , B-Lymphocytes/immunology , Dose-Response Relationship, Drug , Lymphocyte Activation , Lymphocytes/drug effects , Mice , Mice, Inbred BALB C , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , Thyroxine/bloodABSTRACT
An outbreak of encephalitis affecting 265 patients (105 fatally) occurred during 1998-1999 in Malaysia and was linked to a new paramyxovirus, Nipah, that infected pigs, humans, dogs, and cats. Most patients were pig farmers. Clinically undetected Nipah infection was noted in 10 (6%) of 166 community-farm controls (persons from farms without reported encephalitis patients) and 20 (11%) of 178 case-farm controls (persons from farms with encephalitis patients). Case patients (persons with Nipah infection) were more likely than community-farm controls to report increased numbers of sick/dying pigs on the farm (59% vs. 24%, P=.001) and were more likely than case-farm controls to perform activities requiring direct contact with pigs (86% vs. 50%, P=.005). Only 8% of case patients reported no contact with pigs. The outbreak stopped after pigs in the affected areas were slaughtered and buried. Direct, close contact with pigs was the primary source of human Nipah infection, but other sources, such as infected dogs and cats, cannot be excluded.