Therapeutic dosing with anti-interleukin-13 monoclonal antibody inhibits asthma progression in mice

In vivo models have demonstrated that interleukin-13 (IL-13) plays an important role in asthma; however, few studies have evaluated the effect of inhibition of IL-13 on established and persistent disease. In the present study, we have investigated the effect of a therapeutic dosing regimen with an anti-IL-13 monoclonal antibody (mAb) in a chronic mouse model of persistent asthma. BALB/c mice were sensitized to allergen [ovalbumin (OVA); on days 1 and 8] and challenged with OVA weekly from day 22. Anti-IL-13 mAb or vehicle dosing was initiated following two OVA challenges when disease was established. At this time, mice exhibited airway hyperresponsiveness (AHR), increased mucus production, inflammation, and initiation of subepithelial fibrosis compared with saline-challenged mice. Mice received four additional OVA challenges. Treatment with anti-IL-13 mAb inhibited AHR and prevented the further development of subepithelial fibrosis and progression of inflammation. Furthermore, mAb treatment reversed the mucus hyperplasia to basal levels. These effects were associated with an inhibition of cytokines, chemokines, and matrix metalloproteinase-9. These data demonstrate that neutralization of IL-13 can inhibit the progression of established disease in the presence of repeated allergen exposures.     

Resiniferatoxin and Tetrodotoxin Induced NPY and TH Immunoreactivity Changes Within the Paracervical Ganglion Neurons Supplying the Urinary Bladder

Both resiniferatoxin (RTX) and tetrodotoxin (TTX) have been reported to be effective in several urinary bladder dysfunction clinical trials. The aim of this study was to establish the effect of intravesical administration of RTX and TTX on neuropeptides Y (NPY) and tyrosine hydroxylase (TH) relationship in the paracervical ganglion (PCG) neurons supplying the urinary bladder in the pig. TH is an enzyme responsible for catalyzing the conversion of the amino acid L-tyrosine to dihydroxyphenylalanine (DOPA) and is used as a marker of catecholaminergic neurons. NPY augments the vasoconstrictor effects of noradrenergic neurons, and is involved in pathophysiological processes as a neuromodulator. To identify the PCG neurons supplying urinary bladder Fast Blue (FB) was injected into the bladder wall prior to intravesical RTX or TTX administration. Consequent application of immunocytochemical methods revealed that in control group 64.08 % of FB-positive PCG neurons contain NPY and 4.25 % TH. Intravesical infusion of RTX resulted upregulation of the NPY-IR neurons to 82.97 % and TH-IR to 43.78 %. Also administration of TTX induced further increase number of TH-IR neurons to 77.49 % but induced decrease number of NPY-IR neurons to 57.45 %. Both neurotoxins affect chemical coding of the PCG neural somata supplying urinary bladder, but the effects of their action are different. This results shed light on possible involvement of RTX and TTX on curing tissue, and potentially could help us to broaden our neurourological armamentarium.     

Prevalence of Vitamin D insufficiency and low bone mineral density in elderly Thai nursing home residents

ABSTRACT: BACKGROUND: Numerous emerging data from research on osteoporosis among Asians found differences from Caucasians. Therefore, the aim of this study was to determine the prevalence of vitamin D insufficiency and osteoporosis in elderly participants from two nursing homes in Thailand, a country located near the equator. METHODS: The subjects of this cross-sectional study comprised 93 elderly Thai women who were living in institutional long-term nursing homes for the aged. Demographic data, daily food and calcium intake, physical activity, and sunlight exposure were measured. Lumbar spine and femoral neck bone mineral density (BMD) and biochemical levels including serum 25 hydroxyvitamin D [25(OH)D] and bone turnover markers were assessed. Vitamin D insufficiency was defined as 25(OH)D level < 70 nmol/l. RESULTS: The mean age of subjects was 75.2 +/- 6.0 (SD) years. Dietary calcium intake was low (322 +/- 158 mg/day) The mean 25(OH)D level was 64.3 +/- 14.9 nmol/L and the prevalence of vitamin D insufficiency was 38.7 % (95 % CI: 28.8 %, 49.4 %). There was no correlation between serum 25(OH)D concentrations and age (r = -.11, p = 0.3). The mean BMD of lumbar spine and femoral neck were 0.92 +/- 0.19 and 0.65 +/- 0.10 g/cm2, respectively. Nearly a half of the subjects had osteopenia (44.1 %, 95 % CI: 33.8 %, 54.8 %) and osteoporosis (47.3 %, 95 % CI: 36.9 %, 57.9 %). Circulating C-terminal telopeptide of type I collagen (CTx) level correlated significantly with both lumbar spine (r = -0.26, p = 0.01) and femoral neck BMD (r = -0.25, p = 0.02). CONCLUSIONS: More than one-third of Thai elderly women residing in nursing homes had vitamin D insufficiency. Almost all nursing home residents had osteoporosis and/or osteopenia.     

The use of chloride–sodium ratio in the evaluation of metabolic acidosis in critically ill neonates

Acid-base disturbances have been usually evaluated with the traditional Henderson-Hasselbach method and Stewart's physiochemical approach by quantifying anions of tissue acids (TA). It is hypothesized that an increase in tissue acids during metabolic acidosis would cause a compensatory decrease in the plasma chloride (Cl) relative to sodium (Cl-Na ratio) in order to preserve electroneutral balance. Therefore, we aimed to investigate the use of Cl-Na ratio as a bedside tool to evaluate the identifying raised TA in neonates as an alternative to complex calculations of Stewart's physiochemical approach. This retrospective study was conducted between January 2008 and December 2009. Infants were included in the study when blood gas analysis reveals a metabolic acidosis; pH?<7.25 and sHCO(3) concentration was <22?mEq/L. The Cl-Na ratio, sodium-chloride difference (Diff(NaCl)), anion gap (AG), albumin-corrected AG (AG(corr)), strong ion difference (SID), unmeasured anions (UMA), and TA were calculated at each episode of metabolic acidosis. A total of 105 metabolic acidosis episodes occurred in 59 infants during follow-up. Hypochloremic metabolic acidosis occurred in 17 (16%) of samples, and all had increased TA. The dominant component of TA was UMA rather than lactate. There was a negative correlation between the Cl-Na ratio and SID, AG(corr), UMA, and TA. Also, there was a positive correlation between Diff(NaCl) and SID, AG(corr), UMA, and TA. Base deficit and actual bicarbonate performed poorly in identifying the TA. In conclusion, our study suggested that Diff(NaCl) and Cl-Na ratio are simple and fast, and may be an alternative method to complex Stewart's physiochemical approach in identifying raised UMA and TA in critically ill neonates.     

DOUBLE INVASIVE FUNGAL INFECTION AND TYPHLITIS IN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA

Invasive fungal infection is one of the major causes of morbidity and mortality in immunocompromised patients. The occurrence of two invasive fungal infections in one patient at the same time is quite rare. Here the authors report on two adolescent patients with acute lymphoblastic leukemia who developed combined invasive pulmonary aspergillosis and hepatosplenic candidiasis during chemotherapy. They were treated with liposomal amphotericin B, but one of them died due to massive pulmonary hemorrhage during recovery from neutropenia.     

Imaging appearances and endovascular management of uncommon pseudoaneurysms

Pseudoaneurysms are uncommon and their aetiology is varied. They occur in numerous anatomical locations and present with a multitude of clinical presentations sometimes life-threatening. This review describes the causes, sites, and presentations of uncommon pseudoaneurysms, as well as illustrating their diagnostic appearances and endovascular management.