Blocking the human common beta subunit of the GM-CSF, IL-5 and IL-3 receptors markedly reduces hyperinflammation in ARDS models.

Acute respiratory distress syndrome (ARDS) is triggered by various aetiological factors such as trauma, sepsis and respiratory viruses including SARS-CoV-2 and influenza A virus. Immune profiling of severe COVID-19 patients has identified a complex pattern of cytokines including granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-5, which are significant mediators of viral-induced hyperinflammation. This strong response has prompted the development of therapies that block GM-CSF and other cytokines individually to limit inflammation related pathology. The common cytokine binding site of the human common beta (ßc) receptor signals for three inflammatory cytokines: GM-CSF, IL-5 and IL-3. In this study, ßc was targeted with the monoclonal antibody (mAb) CSL311 in engineered mice devoid of mouse ßc and ßIL-3 and expressing human ßc (hßcTg mice). Direct pulmonary administration of lipopolysaccharide (LPS) caused ARDS-like lung injury, and CSL311 markedly reduced lung inflammation and oedema, resulting in improved oxygen saturation levels in hßcTg mice. In a separate model, influenza (HKx31) lung infection caused viral pneumonia associated with a large influx of myeloid cells into the lungs of hßcTg mice. The therapeutic application of CSL311 potently decreased accumulation of monocytes/macrophages, neutrophils, and eosinophils without altering lung viral loads. Furthermore, CSL311 treatment did not limit the viral-induced expansion of NK and NKT cells, or the tissue expression of type I/II/III interferons needed for efficient viral clearance. Simultaneously blocking GM-CSF, IL-5 and IL-3 signalling with CSL311 may represent an improved and clinically applicable strategy to reducing hyperinflammation in the ARDS setting.

Reciprocal modulation of anti-IgE induced histamine release from human mast cells by A1 and A(2B) adenosine receptors.

BACKGROUND AND PURPOSE: Adenosine is believed to participate in the pathological development of asthma through a mast cell-dependent mechanism. Our study aimed to pharmacologically characterize the functions of adenosine receptor (AR) subtypes (A1, A(2A) , A(2B) and A3) in primary human cultured mast cells (HCMC). EXPERIMENTAL APPROACH: HCMC were derived from progenitor stem cells in buffy coat and the effects of adenosine receptor ligands on basal and IgE-dependent histamine release were evaluated. KEY RESULTS: Adenosine and analogues alone did not induce HCMC degranulation. When HCMC were activated by anti-IgE after 10 min pre-incubation with adenosine, a biphasic effect on histamine release was observed with enhancement of HCMC activation at low concentrations of adenosine (10⁻9-10⁻7 mol·L⁻¹) and inhibition at higher concentrations (10⁻6-10⁻4 mol·L⁻¹). The potentiating action was mimicked by A1 AR agonists CCPA and 2'MeCCPA, and inhibited by the A1 AR antagonist PSB36. In contrast, the inhibitory action of adenosine was mimicked by the non-specific A2 AR agonist CV1808 and attenuated by A(2B) AR antagonists PSB1115 and MRS1760. The non-selective AR antagonist CGS15943 attenuated both the potentiating and inhibitory actions. CONCLUSIONS AND IMPLICATIONS: We have defined for the first time the contribution of A1 and A(2B) ARs, respectively, to the potentiating and inhibitory action of adenosine on human mast cell activation. With reference to the current trend of developing novel anti-asthmatic agents from AR ligands, our results suggest that inhibition of human mast cell activation would be a mechanism for A1 AR antagonists, but not A(2B) AR antagonists.

Patterns and forces of occlusal contacts during lateral excursions recorded by the T-Scan II system in young Chinese adults with normal occlusions.

The objective was to characterise the patterns and forces of occlusal contacts during lateral mandibular excursions in a young Chinese adult population. Angle Class I normal occlusions in 85 dental students aged 20-29 were evaluated using the T-Scan II occlusal imaging and analysis system. The frequency of occlusal contacts was recorded for right and left lateral excursions at the position of lateral disclusion, at the canine-to-canine position and at the lateral maximal position. At the canine-to-canine position, the occlusal contact patterns were classified, and the relative forces were compared by multiple regression analysis, with α = 0·05. At the position of lateral disclusion, a high percentage of canine contacts (58·5%) and individual posterior tooth contacts on the working side was observed. At the canine-to-canine position, the canines on the working side contacted most frequently (68·9%), and the occlusal contact patterns could be classified into six groups. At the lateral maximal position, incisors (39·0%) and canines (32·3%) contacted most frequently. At the canine-to-canine position, subjects with occlusal contacts only on canines or on first premolars on the working side had the lowest relative occlusal forces (P < 0·001). Canine protection and group function do not identify all descriptors for lateral occlusal contact patterns in the natural dentition. Six occlusal contact patterns were found at the lateral canine-to-canine position.

A right renal angiomyolipoma with IVC thrombus and pulmonary embolism.

Angiomyolipomas (AML) are benign lesions, commonly found in the kidney, where they may be single or multiple. There is a high association with tuberous sclerosis or lymphangioleiomyomatosis. When found as a solitary lesion, they are usually found in females in the forties to fifties age group. One of the rare complications is that of involvement of the lymph nodes and vascular spread via the inferior vena cava. We review the available literature and present a case of invasive AML with fat embolism.

Inhibition of anti-IgE mediated human mast cell activation by NO donors is dependent on their NO release kinetics.

BACKGROUND AND PURPOSE: Although the mast cell is a source of nitric oxide (NO), the effect of NO on human mast cells has not been defined. This study investigated if exogenous NO could affect human mast cell activation. EXPERIMENTAL APPROACH: Effects of different NO donors on immunoglobulin E (IgE)-dependent activation of human-cultured mast cells (HCMC) derived from precursors in buffy coat were investigated by measuring histamine release. Intracellular NO in HCMC was monitored with confocal microscopy using the fluorescent NO indicator 4-amino-5-methylamino-2', 7'-difluorofluorescein. KEY RESULTS: Diethylamine NONOate (DEA/NO) and MAHMA NONOate (NOC-9), both have rapid NO release rates, only inhibited anti-IgE-induced histamine release when added to HCMC at the time of activation. NO donors with slower NO release kinetics were ineffective even after 30 min incubation. Confocal microscopy revealed that the effectiveness of NO donors was dependent on the availability of adequate NO inside HCMC during activation. The inhibitory action of DEA/NO was diminished by the NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-3-oxide-1-oxyl but potentiated by the anti-oxidant, N-acetylcysteine (NAC). Furthermore, co-incubation with NAC allowed previously ineffective NO donors to suppress HCMC activation and thus suggested that NAC could increase the availability of NO from NO donors. CONCLUSIONS AND IMPLICATIONS: Our results demonstrated that NO was able to modulate human mast cell activation but only when enough NO was present at the time of cell activation. Our findings explain the controversy over the effectiveness of NO on mast cell degranulation and supports the possibility that NO donors could be beneficial for treating allergic inflammation.

Effect of fluoride iontophoresis on the microtensile bond strength between dentin and two adhesive systems.

AIM: To evaluate the effect of fluoride iontophoresis on the microtensile bond strength (MTBS) between coronal dentin and two resin-based adhesive systems, and to measure quantitatively dentinal tubule occlusion. METHODS: Twelve freshly extracted intact human mandibular third molars were divided randomly into four groups. The superficial occlusal dentin of each tooth was exposed and treated. Group A1: One-Step Plus total-etch adhesive system; group A2: One-Step Plus total-etch adhesive system after fluoride iontophoresis; group B1: ACE BOND SE self-etching adhesive system; group B2: ACE BOND SE self-etching adhesive system after fluoride iontophoresis. A resin composite buildup was made for each tooth, which was then sectioned along its long axis to produce 10 beams (1.0 mm x 1.0 mm) for the microtensile bond strength (MTBS) test. Five dentin disks were cut in half and their occlusal surfaces etched with 6% citric acid. The test halves were treated with fluoride iontophoresis. Four SEM photomicrographs were taken from corresponding sites on each test and each non-treated control half-disk. Image-Pro Plus 4 software quantified the percentage of tubule occlusion. Data were analyzed using one-way ANOVA, chi(2)- and t-tests, with the probability level set at alpha=0.05. RESULTS: The mean MTBS (MPa) for each group was, A1: 30.86 (S.D. 6.84); A2: 25.04 (8.49); B1: 19.22 (6.88); B2: 19.40 (6.92). There were significant differences among all groups (P < or = 0.02), except between groups B1 and B2 (P=0.92). Fluoride iontophoresis resulted in significantly increased dentinal tubule occlusion (P<0.001). CONCLUSIONS: Fluoride iontophoresis treatment reduced significantly the dentin bond strength of One-Step Plus total-etch adhesive, but not that of ACE BOND SE self-etching adhesive. However, the bond strength of the former remained significantly higher than that of the latter adhesive system.

Buffy coat preparation is a convenient source of progenitors for culturing mature human mast cells.

Mast cells are unique immune cells that release a spectrum of chemical mediators contributing to the inflammatory symptoms of allergic disorders. Mature mast cells have recently been cultured from CD34(+) progenitors isolated from fresh umbilical cord blood and adult peripheral blood. In the current study, we investigated whether buffy coat preparations, which are readily available from blood banks, could be used as a convenient and more abundant source of progenitors for culturing human mast cells. We were able to culture a homogeneous population of human mast cells from progenitor cells isolated from human buffy coat. Morphologically, our cultured mast cells contained abundant cytoplasmic granules which stained positively using antibodies against human mast cell tryptase and, to a lesser extent, with those against human mast cell chymase. Functionally, these cultured mast cells responded to anti-human-IgE by releasing histamine in a dose-dependent manner after sensitization with human IgE. Taken together, buffy coat preparations can be a convenient source for culturing human mast cells which are predominantly tryptase positive only and express functional high-affinity IgE receptors.

Radiation-induced root surface caries restored with glass-ionomer cement placed in conventional and ART cavity preparations: results at two years.

BACKGROUND: There are no published studies comparing the clinical performances of more-viscous glass-ionomer cement (GIC) restorations when placed using conventional and atraumatic restorative treatment (ART) cavity preparation methods to restore root surface caries. METHODS: One dentist used encapsulated Fuji IX GP and Ketac-Molar to restore 72 conventional and 74 ART cavity preparations for 15 patients who had received cervicofacial radiation therapy. Two assessors evaluated the restorations at six, 12, and 24 months for retention, marginal defects and surface wear, and recurrent caries. RESULTS: After two years, the cumulative restoration successes were 65.2 per cent for the conventional and 66.2 per cent for the ART cavity preparations, without statistical or clinical significance (P > 0.50). Restoration dislodgement accounted for 82.8 per cent and marginal defects for 17.2 per cent of all failures. There were no instances of unsatisfactory restoration wear or recurrent caries observed. Teeth with three or more restored cervical surfaces accounted for 79.3 per cent of all failures (P < 0.0001). CONCLUSIONS: For root surface caries restored with GIC, the use of hand instruments only with the ART method was an equally effective alternative to conventional rotary instrumentation for cavity preparation. Larger restorations had higher failures, usually from dislodgement.

Restoration of teeth with more-viscous glass ionomer cements following radiation-induced caries.

OBJECTIVE: To assess the suitability of more-viscous conventional restorative glass ionomer cements (GICs) in a high-caries risk group of patients. METHODS: Fifteen adult patients with radiation-induced caries were treated at a dental hospital by one dentist. Two encapsulated aesthetic GICs were used in each patient to restore 146 carious lesions in the exposed dentine and cementum of 93 teeth. The restorations were assessed directly over two years for their retention, secondary caries, anatomic form, marginal integrity, marginal discolouration, and surface texture. RESULTS: Both GICs were placed in similar sized cavities (P = 0.63). After two years, although 30.0% of Ketac-Molar Aplicap and 12.5% of Fuji IX GP restorations had been lost (P = 0.01), there were no instances of secondary caries. The remaining GICs showed ongoing marginal deterioration, but there were very few instances where this required the repair or replacement of the restorations. No restorations failed from surface erosion. CONCLUSIONS: In these high-caries risk patients the placement of more-viscous GICs appeared to prevent secondary caries, even when the restorations were subsequently lost.

Ultrasonographic analysis of bladder tumors.

To analyze the ultrasonographic features of bladder tumors during transabdominal ultrasonography. Ultrasonograms of consecutive patients diagnosed to have bladder tumors from August 1992 to May 1999 were reviewed retrospectively and correlated with the final histological diagnoses. Various features, including the location, size, multiplicity, shape, surface and presence of calcification, of the bladder tumors were analyzed. Of 109 patients reviewed, 104 had transitional cell carcinoma, 3 adenocarcinoma, 1 carcinosarcoma and 1 prostatic carcinoma. A total of 130 tumors (including 13 multifocal tumors) were detected with 30 (27.5%) patients having more than one tumor in the bladder. Tumor size ranged from 0.5 to 9.7 cm (mean 2.7 cm). The tumor involved the trigone (63, 48.5%), lateral wall (32, 24.6%), posterior wall (17, 13.1%), anterior wall (5, 3.8%) or was multifocal (13, 10%). Sixty-seven (51.5%) tumors were polypoidal, 47 (36.2%) were sessile and 16 (12.3%) plaque-like. The surface was regular in 50 (38.5%) tumors and irregular in 80 (61.5%) tumors. Calcified foci were noted in 54 (41.5%) tumors. There was no statistically significant correlation between ultrasonographic features. The most common appearance is a polypoid lesion arising from the trigone, but there was much variation in the ultrasonographic features of bladder tumors.

Swine wastewater treatment using attached-growth and suspended-growth two stage sequencing batch reactors with real-time control.

Two two-stage sequencing batch reactors (TSSBR), one attached-growth and one suspended-growth, were operated under three levels of wastewater concentration (approximately 4,000, 2,000 and 500 TOC mg/L), respectively, to compare the pH and ORP (oxidation-reduction potential) patterns and system performance. In both TSSBR systems, the pH and ORP profiles varied with organic loading yet exhibited consistent patterns with distinctive features suitable for real-time control. For all runs at the three levels of influent, both systems achieved similar levels of treatment for BOD5, TOC and TSS of over 97.5, 93.4, and 97.3%, respectively. The attached-growth system out performed the suspended-growth system in achieving the same levels of treatment at much shorter aeration cycle times. The treatment efficiency for NO3(-)-N and PO4(-3) was greatly affected by the carbon content in the wastewater, and the best treatment was achieved during the TOC approximately 4,000 mg/L runs with final effluent at 4.0 and 21.3 mg/L, respectively.

Effects of APF gel on the physical structure of compomers and glass ionomer cements.

This study assessed the effect of an acidulated phosphate fluoride (APF) gel on the surfaces of eight modern esthetic restorative materials. Five specimens each of three high powder: liquid ratio conventional glass ionomer cements (ChemFlex, Fuji IX GP, Ionofil Molar), four polyacid-modified resin composites (compomers) (Compoglass F, Dyract AP, Freedom, F2000) and an alkaline glass filled resin composite (Ariston pHc) were prepared and immersed at 37 degrees C in 2 mL of artificial saliva for six weeks. The aged specimens were then coated with 1.23% APF gel for four minutes, rinsed and again immersed in artificial saliva for another six weeks. The immersed, fresh specimens for each material were then examined with SEM and surface profilometry. After APF gel application, mean surface roughness (Ra) measurements and SEMs showed that roughness increased significantly, generally from the resin composite and compomers to the conventional glass ionomer cements (p < 0.05).

Swine wastewater treatment in a two stage sequencing batch reactor using real-time control.

A laboratory scale two-stage sequencing batch reactor (TSSBR) was used to study the effectiveness of pH as a real-time control parameter in swine wastewater treatment. A Ringlace media was inserted into the A/O (Anoxic/Oxic) reactor for bacteria immobilization. The TSSBR was subjected to three levels of organic loading. The pH and ORP (Oxidation Reduction Potential) patterns obtained were consistent with distinct features, enabling the real-time control strategy to effectively set a flexible aeration time pending on influent concentration, hence resulting in flexible cycle time and HRT (Hydraulic Retention Time) for the system. The real-time process ensured a removal efficiency of over 99% and 95%, respectively, for ammonia and TOC (Total Organic Carbon). For NO3(-)-N and PO4(-3), the run with influent TOC = 4,000 mg/L yielded the most efficient removal of 61% and 95%, respectively. Test results suggest that pH can be a viable tool for on-line real-time control of a biological treatment process.

Splenic vascular lesions: unusual features and a review of the literature.

Hamartoma and peliosis are uncommon splenic lesions. Approximately 120 splenic hamartomas and 40 splenic peliosis have been reported in the English literature. In the present study, a unique case of multiple splenic hamartomas with peliosis was reported. The splenic lesions were incidental findings in a 36-year-old man with ruptured sarcomatoid renal cell carcinoma. They were diagnosed clinically as metastatic renal cell carcinoma. On pathological examination, peliosis was noted in the splenic hamartomas as well as in the splenic parenchyma. In addition, the clinicopathological features of five other splenic hamartomas (including one giant hamartoma) noted in our department were presented. A re-evaluation of the features of the splenic hamartomas documented in the English literature was also done.

Holmium laser lithotripsy for ureteral calculi: an outpatient procedure.

A retrospective review was conducted to evaluate the efficacy of ureteroscopic lithotripsy using the holmium laser with a semirigid endoscope in a newly established day surgery center. In 1996, 69 consecutive patients (40 male and 29 female) with a mean age of 46.7 (range 21-73) years and ASA status I or II underwent ureteroscopic lithotripsy for their ureteral calculi using the holmium laser (365-micron fiber; power setting 0.5-1.4 J/5 Hz) and 8.5F semirigid ureteroscope in a day surgery setting. Stone features, postoperative pain scores, readmissions, and complications were evaluated. Eighteen upper, 17 middle, and 34 lower ureteral stones were treated, with a mean size measuring 12.1 (5-45) mm. The mean operative time was 61 minutes including the anesthetic time (range 15-150 minutes), and the success rate was 91% (63/69). The complication rate was 10% (7/69) including four unscheduled readmissions (6%). Telephone follow-up on postoperative Day 1 and Day 3 revealed mean pain scores of 2 and 1, respectively (on a 0-10 scale) and an analgesic requirement of 1 tablet of Dologesic (containing 32.5 mg of dextropropoxyphene + 320 mg of paracetamol) four times a day on both days. Ureteroscopic lithotripsy using the holmium laser and a semirigid endoscope is highly successful and well tolerated and carries a low complication rate. It is indicated as an ambulatory and minimally invasive treatment modality in low-risk patients with ureteral stones.

Spontaneous rupture of renal tumours: the role of imaging in diagnosis and management.

This study aimed to evaluate whether patients presenting with spontaneous haemorrhage from renal tumours could be accurately diagnosed and initially managed conservatively, and evaluate the role of imaging in guiding the timing and type of subsequent operation. The clinical features, imaging findings and management of seven patients presenting with spontaneous rupture of renal tumour over a 5-year period were reviewed. The information from various imaging studies was evaluated in relation to the subsequent course of intervention. The tumours consisted of six angiomyolipomas and one renal cell carcinoma. In all cases, imaging studies were diagnostic, with computed tomography being the most useful single modality. Emergency surgery was required in one patient for evacuation of suspected infected haematoma and wedge excision of angiomyolipoma. Three elective nephrectomies were performed, while three other patients with ruptured angiomyolipoma were treated conservatively and remained well, without any intervention. In conclusion, patients presenting with spontaneous rupture of renal tumour can be managed conservatively initially. Imaging facilitates accurate pre-operative diagnosis, which was angiomyolipoma in all but one patient in this series. The subsequent intervention can be tailored according to the lesion type and the anticipated risk of re-haemorrhage.

Urolume prostatic stents for urinary retention due to benign prostatic hyperplasia in patients with high medical risks.

A retrospective study was conducted to evaluate the efficacy of using urolume prostatic stents in patients who have developed urinary retention due to benign prostatic hyperplasia but who are medically unfit for conventional transurethral resection of the prostate. From April 1995 through May 1996, 12 patients were studied (mean age, 80 years; range, 72-92 years). Pre-operative assessment pointed to major risk due to an underlying medical condition. Flexible cystoscopy and video-urodynamcis were performed to assess the detrusor function and to ascertain if prostatic obstruction was the cause of retention. After insertion of the prostatic stent, 11 patients managed to void on recovery from the anaesthesia and remained catheter-free during a mean follow up period of seven months (range, 2-18 months). There was no operative morbidity or mortality. Urolume prostatic stents represent a viable option for elderly patients with significant medical risks who have urinary retention. Pre-operative urodynamics are essential to identify appropriate candidates.