Long-term thyroid hormone administration reshapes left ventricular chamber and improves cardiac function after myocardial infarction in rats

Thyroid hormone (TH) is critical for tissue differentiation at early stages of development, induces physiological hypertrophy and regulates the expression of important contractile proteins such as myosin heavy chain (MHC) isoform and calcium cycling proteins. Furthermore, TH seems to control the response to stress by regulating important cardioprotective molecules such as heat shock proteins (HSPs). Thus, the present study investigated whether TH administration immediately after acute myocardial infarction can favourably remodel the post-infarcted myocardium. Acute myocardial infarction was induced in rats by coronary artery ligation (AMI, n=10), while SHAM-operated animals served as controls (SHAM, n = 8). TH was administered for 13 weeks (AMI-THYR, n = 9). Cardiac contractile function and left ventricular (LV) chamber remodelling was assessed by serial echocardiography and in Langendorff heart preparations. AMI significantly reduced LV ejection fraction (EF%); 30.0 (s.e.m, 2.3) Vs. 73.8 (1.8) in SHAM, P < 0.05. In addition, +dp/dt and -dp/dt (in mmHg/s) were 4,051 (343) and 2,333 (118) respectively for SHAM Vs. 2,102 (290) and 1,368 (181) for AMI, P < 0.05. With TH treatment, EF% was increased to 49.5 (2.7) in AMI-THYR, P < 0.05, while +dp/dt and -dp/dt (in mmHg/s) were 3,708 (231) and 2,035 (95) for AMI-THYR, P < 0.05 Vs. AMI. A marked elevation of the expression of beta-MHC and a reduced ratio of SERCA/Phospholamban were found in viable myocardium of AMI hearts, which was prevented by TH. Furthermore, heat shock protein 70 myocardial content was decreased in AMI hearts and was significantly increased after TH treatment. An ellipsoidal reshaping of LV chamber was observed with TH; cardiac sphericity index, (ratio of long/short axis, SI), was 1.98 (0.03) for SHAM, 1.52 (0.05) for AMI and 1.72(0.02) for AMI-THYR, P < 0.05. In conclusion, long-term TH administration immediately after AMI results in sustained improvement of cardiac haemodynamics.     

Retronasal testing of olfactory function: an investigation and comparison in seven countries

Flavor perception is to a large extent determined by olfaction, and persons who lost their sense of smell consequently complain about strongly reduced enjoyment of food. The retronasal olfactory function is especially important for flavor appreciation. The aim of this study was to compare retronasal function across different cultures and to develop a test that is applicable across cultures. Identification of 39 retronasal applied odor probes was tested in a total of 518 participants of seven countries; 292 of them were healthy, and 226 exhibited a smell disorder. A retest was performed with 224 of the healthy participants. Furthermore, all participants were tested for orthonasal threshold, identification, and discrimination ability. Significant cultural differences in identification ability were found in 92 % of the probes. The 20 probes that could be identified above chance in healthy participants of all countries and that could differentiate between patients and controls were selected for the final retronasal test. This test was well able to differentiate between controls and patients in different countries and showed a good coherence with the orthonasal test (r = 0.80) and a good retest-reliability (r = 0.76). Furthermore, it is age-independent. The strong cultural differences observed in retronasal identification underline the necessity to develop a culturally independent instrument. This retronasal test is easy to apply and can be used across different countries for diagnostics and clinical research.     

A systematic review and meta-analysis of randomized studies comparing misoprostol versus placebo for cervical ripening prior to hysteroscopy

Objective(s): Hysteroscopy is an effective method for examining the uterine cavity but has some limitations, including the occasional need for cervical dilatation. Misoprostol is routinely used for cervical dilatation in various procedures but has not gained wide acceptance for use before hysteroscopy. Study design: This review includes randomized controlled trials which compare the use of misoprostol versus placebo by different routes and doses before diagnostic or operative hysteroscopy. The MEDLINE database and the Cochrane Central Register of Controlled Trials were searched for articles published from January 1970 to April 2010. The outcome measures studied were related either to the facilitation of the hysteroscopic procedure (need for cervical dilatation, cervical width at the beginning of hysteroscopy, duration of the procedure and complications such as cervical tear and uterine perforation) or to the medication side-effects. With regard to side-effects, we studied the incidence of nausea, diarrhea, abdominal pain, bleeding, and fever. Results: Vaginal misoprostol reduced the need for cervical dilatation in the total population of pre- and post-menopausal women to a statistically significant degree. In the subgroup of operative hysteroscopy the need for dilatation and the duration of the procedure were also significantly reduced. Most other outcomes relating to the facilitation of the procedure did not reach statistical significance. The side effects in the misoprostol group were significantly more frequent than in the placebo group. Conclusion(s): There is insufficient evidence to recommend the routine use of misoprostol before every hysteroscopy. As the lack of serious benefit from misoprostol is unlikely to be due to type II error, its use should be reserved for selected cases.     

Translocator Protein PET Imaging for Glial Activation in Multiple Sclerosis

Glial activation in the setting of central nervous system inflammation is a key feature of the multiple sclerosis (MS) pathology. Monitoring glial activation in subjects with MS, therefore, has the potential to be informative with respect to disease activity. The translocator protein 18?kDa (TSPO) is a promising biomarker of glial activation that can be imaged by positron emission tomography (PET). To characterize the in vivo TSPO expression in MS, we analyzed brain PET scans in subjects with MS and healthy volunteers in an observational study using [¹¹C]PBR28, a newly developed translocator protein-specific radioligand. The [¹¹C]PBR28 PET showed altered compartmental distribution of TSPO in the MS brain compared to healthy volunteers (p?=?0.019). Focal increases in [¹¹C]PBR28 binding corresponded to areas of active inflammation as evidenced by significantly greater binding in regions of gadolinium contrast enhancement compared to contralateral normal-appearing white matter (p?=?0.0039). Furthermore, increase in [¹¹C]PBR28 binding preceded the appearance of contrast enhancement on magnetic resonance imaging in some lesions, suggesting a role for early glial activation in MS lesion formation. Global [¹¹C]PBR28 binding showed correlation with disease duration (p?=?0.041), but not with measures of clinical disability. These results further define TSPO as an informative marker of glial activation in MS.     

Biologic characteristics of mesenchymal stromal cells and their clinical applications in pediatric patients

In the past few years, intensive research in the understanding of the biologic characteristics of the mesenchymal stromal cells has already led to some early clinical applications.The aim of this review is to summarize the latest information from basic science advances and the outcome of their use in clinical practice with a particular focus in pediatric patients. The minimum criteria required to identify mesenchymal stromal cells, their immunosuppressive-nonimmunogenic properties and their attribution in the treatment of graft-versus-host disease, in the acceleration of hematopoietic recovery, in tissue repair/tissue engineering and in the treatment of selected inherited disorders are discussed. Appropriate preclinical models, completion of ongoing and development of new clinical trials will establish the role of these cells in the treatment of both adult and pediatric patients.     

99mTc-depreotide in the evaluation of bone infection and inflammation

BACKGROUND AND AIM: (99m)Tc-depreotide is a (99m)Tc-labelled somatostatin analogue, with high affinity for the 2, 3 and 5 subtypes of somatostatin receptors. These particular receptors are over-expressed on the surface of activated leucocytes, which mediate inflammatory response. Based on this property this study tried to investigate whether (99m)Tc-depreotide scintigraphy could be a useful complementary method in the investigation of bone infection and inflammation. METHODS: Twenty-three patients, who were investigated for probable osteomyelitis, underwent three-phase bone scintigraphy followed by (99m)Tc-depreotide scintigraphy. Clinical and laboratory findings, complementary imaging procedures, clinical follow-up and bone biopsy established the final diagnosis. (99m)Tc-depreotide scintigraphy was performed 3 h after the intravenous administration of 555-740 MBq of the radiopharmaceutical. Scintigraphic images were, at first, blindly interpreted alone and then in comparative assessment with bone scans. RESULTS: (99m)Tc-depreotide was positive in 12/12 cases of active osteomyelitis, one case of recent femoral head osteonecrosis and 6/9 rheumatoid arthritis sites. Negative (99m)Tc-depreotide scans were acquired in five cases of 'no-inflammation' (an uncomplicated fracture, an aseptic loosening of prosthesis, an old osteonecrosis, a healed and a successfully treated osteomyelitis), as well as in 14/14 total sites of degenerative arthritis-osteoarthropathy. In five cases (septic arthritis, periodontal and soft tissue infections) (99m)Tc-depreotide was positive, though spatially discordant with bone scintigraphy, delineating precisely the focus of infection. CONCLUSION: (99m)Tc-depreotide can be a useful complementary imaging method in the evaluation of bone infection and inflammation. Its combination with three-phase bone scintigraphy seems to be accurate in localizing the infection foci and determining the activity of the inflammatory processes.