Pathogens possess the ability to adapt and survive in some host species but not in others-an ecological trait known as host tropism. Transmitted through ticks and carried mainly by mammals and birds, ...the Lyme disease (LD) bacterium is a well-suited model to study such tropism. Three main causative agents of LD, Borrelia burgdorferi, B. afzelii, and B. garinii, vary in host ranges through mechanisms eluding characterization. By feeding ticks infected with different Borrelia species, utilizing feeding chambers and live mice and quail, we found species-level differences in bacterial transmission. These differences localize on the tick blood meal, and specifically complement, a defense in vertebrate blood, and a polymorphic bacterial protein, CspA, which inactivates complement by binding to a host complement inhibitor, Factor H (FH). CspA selectively confers bacterial transmission to vertebrates that produce FH capable of allele-specific recognition. CspA is the only member of the Pfam54 gene family to exhibit host-specific FH-binding. Phylogenetic analyses revealed convergent evolution as the driver of such uniqueness, and that FH-binding likely emerged during the last glacial maximum. Our results identify a determinant of host tropism in Lyme disease infection, thus defining an evolutionary mechanism that shapes host-pathogen associations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine associated with acute and chronic inflammatory disorders and corticosteroid insensitivity. Its expression in the airways of ...patients with chronic obstructive pulmonary disease (COPD), a relatively steroid insensitive inflammatory disease is unclear, however.
Sputum, bronchoalveolar lavage (BAL) macrophages and serum were obtained from non-smokers, smokers and COPD patients. To mimic oxidative stress-induced COPD, mice were exposed to ozone for six-weeks and treated with ISO-1, a MIF inhibitor, and/or dexamethasone before each exposure. BAL fluid and lung tissue were collected after the final exposure. Airway hyperresponsiveness (AHR) and lung function were measured using whole body plethysmography. HIF-1α binding to the Mif promoter was determined by Chromatin Immunoprecipitation assays.
MIF levels in sputum and BAL macrophages from COPD patients were higher than those from non-smokers, with healthy smokers having intermediate levels. MIF expression correlated with that of HIF-1α in all patients groups and in ozone-exposed mice. BAL cell counts, cytokine mRNA and protein expression in lungs and BAL, including MIF, were elevated in ozone-exposed mice and had increased AHR. Dexamethasone had no effect on these parameters in the mouse but ISO-1 attenuated cell recruitment, cytokine release and AHR.
MIF and HIF-1α levels are elevated in COPD BAL macrophages and inhibition of MIF function blocks corticosteroid-insensitive lung inflammation and AHR. Inhibition of MIF may provide a novel anti-inflammatory approach in COPD.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The optimal strategy for treating coronary bifurcation lesions remains a subject of debate. With bare-metal stents, single-stent approaches appear to be superior to systematic 2-stent strategies. ...Drug-eluting stents, however, have low rates of restenosis and might offer improved outcomes with complex stenting techniques.
Patients with significant coronary bifurcation lesions were randomized to either a simple or complex stenting strategy with drug-eluting stents. In the simple strategy, the main vessel was stented, followed by optional kissing balloon dilatation/T-stent. In the complex strategy, both vessels were systematically stented (culotte or crush techniques) with mandatory kissing balloon dilatation. Five hundred patients 64+/-10 years old were randomized; 77% were male. Eighty-two percent of lesions were true bifurcations (>50% narrowing in both vessels). In the simple group (n=250), 66 patients (26%) had kissing balloons in addition to main-vessel stenting, and 7 (3%) had T stenting. In the complex group (n=250), 89% of culotte (n=75) and 72% of crush (n=169) cases were completed successfully with final kissing balloon inflations. The primary end point (a composite at 9 months of death, myocardial infarction, and target-vessel failure) occurred in 8.0% of the simple group versus 15.2% of the complex group (hazard ratio 2.02, 95% confidence interval 1.17 to 3.47, P=0.009). Myocardial infarction occurred in 3.6% versus 11.2%, respectively (P=0.001), and in-hospital major adverse cardiovascular events occurred in 2.0% versus 8.0% (P=0.002), respectively. Procedure duration and x-ray dose favored the simple approach.
When coronary bifurcation lesions are treated, a systematic 2-stent technique results in higher rates of in-hospital and 9-month major adverse cardiovascular events. This difference is largely driven by periprocedural myocardial infarction. Procedure duration is longer, and x-ray dose is higher. The provisional technique should remain the preferred strategy in the majority of cases. Clinical Trial Registration Information- URL: http://www.clinicaltrials.gov. Unique identifier: NCT 00351260.
A 4-year-old castrated male domestic ferret (Mustela putorius furo) was examined because of a 3-week history of intermittent seizures, signs of depression, hypocalcemia, and hyperphosphatemia.
Plasma ...biochemical analysis confirmed hyperphosphatemia (17.7 mg/dL) and low concentrations of total (4.3 mg/dL) and ionized (0.49 mmol/L) calcium. Serum parathyroid hormone concentration (2.30 pmol/L) was low or in the low part of the reference interval.
Calcium gluconate was administered (2.0 mg/kg/h 0.9 mg/lb/h, IV), followed by a transition to administration of calcium carbonate (53 mg/kg 24.1 mg/lb, PO, q 12 h) and dihydrotachysterol (0.02 mg/kg/d 0.009 mg/lb/d, PO). Attitude of the ferret improved and seizures ceased as blood calcium concentrations increased. The ferret was reexamined because of seizures approximately 1 year after oral maintenance administration of dihydrotachysterol and calcium was initiated. The ferret responded well to emergency and long-term treatment but then was lost to follow-up monitoring. The ferret died approximately 2 years after the initial evaluation and treatment. Hypertrophic cardiomyopathy was diagnosed during necropsy, but the parathyroid glands could not be identified.
To the authors' knowledge, primary hypoparathyroidism has not previously been reported in a ferret. The condition should be considered for ferrets with hypocalcemia and hyperphosphatemia without azotemia. Treatment with dihydrotachysterol and oral supplementation of calcium appeared to be a viable option for long-term management.
Hepatic angiosarcoma is a primary sarcoma of the liver, accounting for only 2% of all primary hepatic malignancies. Acute liver failure is an extremely rare presentation of a primary liver tumour.
We ...report a case of a seventy year-old man who presented with a very short period of jaundice leading to fulminant hepatic failure (FHF). On further investigation he was found to have primary angiosarcoma of liver.
The treatment outcomes for hepatic angiosarcoma are poor, we discuss the options available and the need for prompt investigation and establishment of a diagnosis.
6 alpaca crias from a single farm were examined because of diarrhea (n = 4) or decreased fecal production (n = 2).
Cryptosporidium parvum was identified by means of fecal flotation in samples from 5 ...of the 6 crias, and a diagnosis of cryptosporidiosis was made. In the remaining cria, a presumptive diagnosis of cryptosporidiosis was made. Three people involved in caring for the crias from this farm were subsequently confirmed to have cryptosporidiosis, and 3 other people were suspected to have cryptosporidiosis. Sequence analysis of the ssu rDNA gene loci confirmed C parvum as the causative agent in 4 of the 6 crias. Subsequent evaluation of the farm revealed 2 additional crias confirmed to have cryptosporidiosis. Stocking densities on the farm were high, with approximately 20 adults/acre in some pastures.
All 6 hospitalized crias were given supportive treatment consisting of antimicrobials, gastroprotectants, and fluids. All but 1 survived. Farm owners were advised to decrease stocking density on the farm.
Findings suggested that zoonotic transmission of C parvum from alpacas to humans can occur.
A longitudinal study of 2-year duration was conducted to determine the risk, as measured by incidence rate, of
Cryptosporidium parvum infection among dairy cattle in the Catskill/Delaware Watershed ...of New York City (NYC), and the factors that predispose animals to the likelihood of infection. A proportional sampling scheme with follow up at quarterly farm visits was employed for heifers and cows. Additionally, all calves born on the 39 study farms were sampled once during the first four weeks of life and at least once more before weaning. Samples were analyzed for the presence of
C. parvum using a quantitative centrifugation concentration flotation technique and a
C. parvum-specific enzyme-linked immunosorbent assay (ELISA). Of the 9914 fecal samples collected, 747 were found to contain
C. parvum. The average number of oocysts detected was 1.3
×
10
5/g (range: 1.0/g–8.2
×
10
6/g). The average age at time of first detection of the organism was 15.0 days with a standard deviation of 6.59 days. The age range of animals infected with
C. parvum in the study population was 3–60 days (inclusive). The unadjusted (crude) incidence rate of
C. parvum among the entire study population was 2.05 per 1000 animal-days. The unadjusted incidence rate among pre-weaned calves was 15.55 per 1000 animal-days. After controlling for age and prior protozoal risk level, no seasonal impact on the incidence of
C. parvum was detected among animals less than 61 days by negative binomial regression. A seasonal impact was identified among the oocyst counts of infected animals after controlling for age and prior protozoal risk level.
Central diabetes insipidus in an African Grey parrot Starkey, Simon R; Wood, Catherine; de Matos, Ricardo ...
Journal of the American Veterinary Medical Association,
08/2010, Letnik:
237, Številka:
4
Journal Article
Recenzirano
A 5.5-year-old sexually intact female African Grey parrot (Psittacus erithacus) was evaluated for a 1-year history of pronounced polyuria and polydipsia. The bird also had a 1-month history of signs ...of mild depression and mydriasis.
Physical examination revealed a thin body condition and incomplete bilateral mydriasis. Other examination findings as well as CBC and screening radiography results were unremarkable. Plasma biochemical analysis revealed mild hypernatremia. The bird had a 3.3% loss in body weight over 170 minutes during a water deprivation test, and urine osmolality remained low. After IM administration of 0.9 microg of desmopressin, the rate of weight loss decreased substantially and urine osmolality increased 300% over the following 200 minutes.
Initial attempts to treat the bird with orally administered desmopressin failed to correct the polydipsia and polyuria. Ultimately, IM administration of 24 microg of desmopressin/kg (10.9 microg/lb) every 12 hours yielded a noticeable reduction in water consumption and urine production over a 6- to 8-hour period. Eight months later, the bird was returned for a recheck examination, at which time it was in good health and continued to respond to the medication. Despite continued response to the medication, right-sided internal ophthalmoparesis was detected 16 months after the initial diagnosis.
To the authors' knowledge, central diabetes insipidus in birds has not been reported. The condition should be considered in birds with clinical signs of disease similar to those in mammals. Long-term IM administration of desmopressin may be a viable treatment option.
We carried out a study to estimate the public health risk posed by dairy cattle located in New York City's Catskill/Delaware watershed, as measured by daily C. parvum-like oocyst loading. A Monte ...Carlo simulation model that takes into account the nature of the dairy cattle population within the target area, age-specific incidence/prevalence rates, as well as differential fecal production and oocyst-shedding intensity rates was used to address the objectives. Additionally, the model was designed to distinguish between zoonotic and nonzoonotic species/genotypes of Cryptosporidium. Total estimated daily C. parvum-like oocyst shedding across all age/production categories was estimated at 4.15 x 10¹⁰. The zoonotic C. parvum comprised 93.5% of this load. It was estimated that preweaned calves produce 99.5% of the total daily C. parvum ocyst burden. The recently described nonzoonotic C. bovis was estimated to have a daily load of 2.2 x 10⁹ oocysts across all age/production strata. C. parvum deer-like genotype was estimated to have a total daily load of 1.3 x 10⁹ oocysts. The results of this study support earlier assertions that strategies aimed at reducing the cryptosporidial risk posed by dairy cattle to public health will be most efficacious if aimed at preweaned calves.
Our previous studies implicated vitamin E deficiency as a risk factor for equine motor neuron disease, a possible model of human amyotrophic lateral sclerosis, and showed direct effects of this ...deficiency on brain vascular endothelium. To gain better understanding of the pathogenesis of equine motor neuron disease, we determined the effects of dietary antioxidant insufficiency and the resultant brain tissue oxidative stress on blood-brain barrier permeability. Rats (n = 40) were maintained on a diet deficient of vitamin E for 36 to 43 weeks; 40 controls were fed a normal diet. Permeability of the blood-brain barrier in the cerebral cortex was investigated using rhodamine B, and lipid peroxidation was measured as a marker for oxidative stress. Animals on the vitamin E-deficient diet showed less weight gain and had higher brain lipidperoxidation compared with the controls. Fluorometric studies demonstrated greater rhodamine B in the perivascular compartment and central nervous system parenchyma in rats on the deficient diet compared with controls. These results suggest that a deficiency in vitamin E increases brain tissue oxidative stress and impairs the integrity of the blood-brain barrier. These observations may have relevance to the pathogenesis of amyotrophic lateral sclerosis and other neurologic diseases.
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