A possible role of tryptase in angiogenesis in the brain of mdx mouse, a model of Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is characterized by muscle degeneration and affects the CNS. Dystrophin is absent in muscle and CNS of both DMD patients and mdx mouse, a model of DMD. While the involvement of vascular compartment in DMD was poorly investigated, some studies suggested a role for mast cells (MC). Tryptase, contained in the MC granules, stimulates angiogenesis in vitro and in vivo. We demonstrated for the first time a correlation between the extent of angiogenesis and the number of tryptase-positive neurons and microvessels and suggest that the tryptase contained in the neurons and in the endothelial cells of the mdx mouse brain may be involved in the regulation of angiogenesis taking place in mdx mouse.     

Intravenous treatment with liposome-encapsulated dichloromethylene bisphosphonate (C12MBP)suppresses nitric oxide production and reduces genetic resistance to Marek's disease

In this study the functional effectiveness of in vivo macrophage depletion using liposome-encapsulateddichloromethylene bisphosphonate (C12MBP) was examined in the chicken. The main target organs forsystemic liposome-encapsulated C12MBP treatment are the spleen and the liver. Intravenous treatment withC12MBP of B²¹/B²¹ chickens, genetically resistant to Marek's disease (MD), before challenge with the very virulent strain RB-lB, increased viral load in the blood and spleen after the first week and up to 6 weeks postinfection. In addition, C12MBP treatment dramatically increased tumour incidence and tumour load, especially in the spleens and livers of sick animals, but without affecting MD-specific mortality of B²¹/B²¹ cickens infected with RB-1B at 12 days of age. Nitric oxide (NO) is an important effector of the macrophage and has antiviral and antitumoural properties. NO has been shown to be one of the mechanisms triggered in resistance to Marek's disease. Intravenous treatment with Cl2MBP before infection with RB-1B induced a long-lasting decrease in numbers of macrophages and reduction in splenic inducible NO production associated with an absence of nitrate induction in the serum (up to 6 weeks pi). These results do not identify macrophage and NO production as major effector components in genetic resistance to Marek's disease, but underline their roles in limiting viraemia and tumour development in organs such as the spleen and the liver.     

Chromaffin granules in the rat adrenal medulla release their secretory content in a particulate fashion

Exocytosis is considered the main route of granule discharge in chromaffin cells. We recently provided ultrastructural evidence suggesting that piecemeal degranulation (PMD) occurs in mouse adrenal chromaffin cells. In the present study, we processed rat adrenal glands for transmission electron microscopy (TEM), and examined chromaffin cells for changes characteristic of PMD. Both adrenaline (A)- and noradrenaline (NA)-storing cells express ultrastructural features suggestive of a slow and particulate mode of granule discharge. In adrenaline-containing cells, some granules present enlarged dimensions accompanied by eroded or dissolved matrices. Likewise, a number of granules in NA-releasing cells show content reduction with variably expanded granule chambers. Dilated, empty granule containers are recognizable in the cytoplasm of both cell types. Characteristically, altered granules and empty containers are seen intermingled with normal, resting granules. In addition, chromaffin granules often show irregular profiles, with budding or tail-like projections of their limiting membranes. Thirty 150-nm-diameter membrane-bound vesicles with a moderately electron-dense or -lucent internal structure are observable in the cytoplasm of both cell types. These vesicles are seen among the granules and some of them are fused with the perigranule membranes in the process of attachment to or budding from the granules. These data add further support to the concept that PMD may be an alternative secretory pathway in adrenal chromaffin cells.     

Experimental SARS-CoV-2 Infection of Bank Voles

After experimental inoculation, severe acute respiratory syndrome coronavirus 2 infection was confirmed in bank voles by seroconversion within 8 days and detection of viral RNA in nasal tissue for up to 21 days. However, transmission to contact animals was not detected. Thus, bank voles are unlikely to establish effective transmission cycles in nature.     

Results of uvulopalatopharyngoplasty after diagnostic workup with polysomnography and sleep endoscopy: a report of 136 snoring patients

We subjectively and objectively evaluated 136 patients with socially unacceptable snoring (SUS) or obstructive sleep apnoea syndrome (OSAS) treated with uvulopalatopharyngoplasty (UPPP) after a diagnostic workup by sleep registration (polysomnography, PSG) and sleep endoscopy. Of the 136 patients, there were 88 with OSAS and 48 with SUS. The results of the procedure were considered subjectively to be an improvement in 38 (79%) of the SUS patients and in 74 (84%) of the patients with OSAS. In 36 (40%) of the 88 patients with OSAS, repeating PSG postoperatively was considered unnecessary because of obvious improvement. Of the 52 patients with a measurement after UPPP, a decrease in the apnoea hypopnoea index (AHI) was found in 38 (73%; median decrease: 48%), and AHI dropped below 20 in 32 (62%). The apnoea index (AI) was available in 49 (56%) patients and was reduced in 31 (63%; median decrease: 73%). An overall positive result in the 88 patients with OSAS (combining available data on subjective and objective results) was therefore found in 61 (69%; positive subjective result and AHI <15) or 71 (81%; positive subjective result and decrease in AHI), respectively, depending on the definition. We conclude that after diagnostic workup by sleep registration and sleep endoscopy, the success rate of UPPP increases as compared to historical controls.     

In vivo imaging of apoptosis by 99mTc-Annexin V scintigraphy: visual analysis in relation to treatment response.

BACKGROUND AND PURPOSE: Anticancer therapy induces apoptosis in a dose- and time-dependent fashion. (99m)Tc-Hynic-rh-Annexin V scintigraphy (TAVS) enables non-invasive in vivo imaging of treatment-induced apoptosis. We identified the visual patterns of (99m)Tc-Hynic-rh-Annexin V tumour uptake and related these to treatment response. PATIENTS AND METHODS: Thirty-three patients with malignant lymphoma (n=26), leukaemia (n=1) NSCLC (n=5), H&NSCC (n=1), scheduled for radiotherapy (n=27), platinum-based chemotherapy (n=5) or concurrent chemoradiation (n=1), underwent TAVS before and early after the start of treatment. Planar and SPECT images were visually examined to assess changes in tumour (99m)Tc-Hynic-rh-Annexin V uptake. Twenty-nine patients were eligible for further analysis. Annexin V uptake before (U(baseline)) and early after (U(post)) the start of treatment was graded using a four-step scale: 0, absent; 1, weak; 2, moderate and 3, intense. The difference between these values (Delta U) was calculated and correlated to tumour response after therapy (Spearman rank correlation test). RESULTS: Weak to moderate U(baseline) was detected in 13/15 patients with a complete response and U(post) was markedly increased in all these cases (Delta U range 1-3). Partial response (n=7) was associated with weak to moderate U(baseline) and a moderately increased U(post) (Delta U range 1-2). In patients with stable disease (n=5), U(baseline) was predominantly weak, without considerable changes in uptake after the start of treatment (Delta U range 0-1). Finally, in case of progressive disease (n=2), either no tumour uptake or a decrease in U(post) was detected (Delta U=-1). A statistically significant correlation was found between changes in (99m)Tc-Hynic-rh-Annexin V tumour uptake and clinical response (correlation coefficient=0.62; P<0.001). CONCLUSIONS: Complete or partial tumour response was associated with a marked increase of (99m)Tc Hynic-rh-Annexin V accumulation early during treatment compared to baseline values. In case of stable or progressive disease, pretreatment scans demonstrated predominantly low (99m)Tc Hynic-rh-Annexin V tumour uptake and no significant increase early after treatment. These results indicate that TAVS might be useful as a predictive test for treatment response.     

In vitro and in vivo targeting properties of iodine-123- or iodine-131-labeled monoclonal antibody 14C5 in a non-small cell lung cancer and colon carcinoma model.

PURPOSE: The monoclonal antibody (mAb) 14C5 is a murine IgG1 directed against a yet undefined molecule involved in cell substrate adhesion found on the surface of malignant breast cancer tissue. mAb 14C5 is able to inhibit cell substrate adhesion and invasion of breast cancer cells in vitro. In normal tissues as well as in the stroma surrounding in situ carcinomas of the breast, no expression of the antigen 14C5 occurs. The aim of this study was to investigate the in vitro and in vivo targeting properties of 123I- and 131I-labeled mAb 14C5 as a novel agent for radioimmunodetection and radioimmunotherapy. EXPERIMENTAL DESIGN: Internalization of mAb 14C5 was investigated with 125I-labeled mAb 14C5 and by confocal laser scanning microscopy. Biodistribution studies of 131I-labeled mAb 14C5 and planar gamma imaging were done in nude mice bearing an A549 (non-small cell lung carcinoma) or a LoVo (colon carcinoma) tumor. RESULTS: Internalization studies with both A549 and LoVo cells showed that 125I-labeled mAb 14C5 is slowly internalized with approximately 30% of the initially bound mAb 14C5 internalized after 2 hours at 37 degrees C. Internalization of mAb 14C5 could be visualized with confocal laser scanning microscopy. In vivo, radioisotope uptake peaked at 24 hours for both tumor models (n = 5) with no significant difference in percentage of injected dose/g tissue (A549 10.4 +/- 0.8 and LoVo 9.3 +/- 0.8). Via planar gamma camera imaging, A549 lung tumors as well as LoVo colon tumors could be clearly visualized. CONCLUSIONS: The in vitro and in vivo targeting properties of 123I- and 131I-labeled mAb 14C5 are promising and could provide a new antibody-based agent for radioimmunodetection and radioimmunotherapy of patients bearing antigen 14C5-expressing tumors.     

Effect of a Radiotherapeutic Megavoltage Beam on Ultrasound Contrast Agents

Collateral damage to healthy surrounding tissue during conventional radiotherapy increases when deviations from the treatment plan occur. Ultrasound contrast agents (UCAs) are a possible candidate for radiation dose monitoring. This study investigated the size distribution and acoustic response of two commercial formulations, SonoVue/Lumason and Definity/Luminity, as a function of dose on clinical megavoltage photon beam exposure (24 Gy). SonoVue samples exhibited a decrease in concentration of bubbles smaller than 7 µm, together with an increase in acoustic attenuation and a decrease in acoustic scattering. Definity samples did not exhibit a significant response to radiation, suggesting that the effect of megavoltage photons depends on the UCA formulation. For SonoVue, the influence of the megavoltage photon beam was especially apparent at the second harmonic frequency, and can be captured using pulse inversion and amplitude modulation (3.5-dB decrease for the maximum dose), which could eventually be used for dosimetry in a well-controlled environment.     

Wound ballistic evaluation of the TASER® XREP ammunition

The Taser® eXtended Range Electronic Projectile (XREP®) is a wireless conducted electrical weapon (CEW) designed to incapacitate a person from a larger distance. The aim of this study was to analyze the ballistic injury potential of the XREP. Twenty rounds were fired from the Taser®X12 TM shotgun into ballistic soap covered with artificial skin and clothing at different shooting distances (1–25 m). One shot was fired at pig skin at a shooting distance of 10 m. The average projectile velocity was 67.0 m/s. The kinetic energy levels on impact varied from 28–52 J. Depending on the intermediate target, the projectiles penetrated up to 4.2 cm into the ballistic soap. On impact the nose assembly did not separate from the chassis, and no electrical activation was registered. Upon impact, a skin penetration of the XREP cannot be excluded. However, it is very unlikely at shooting distances of 10 m or more. Clothing and a high elasticity limit of the target body area can significantly reduce the penetration risk on impact.