Znaczenie przedoperacyjnego zastosowania analogów somatostatyny w akromegalii

Different types of treatment, including surgery, medical therapy and radiotherapy, are possible in achieving control of acromegaly. Of the medical therapies available, somatostatin analogues are effective in the majority of patients and can induce pituitary tumour shrinkage. The rationale and outcome of somatostatin analogue treatment before surgery in patients with acromegaly is briefly presented. In summary, the benefits of somatostatin analogues given preoperatively should be considered carefully as optimisation of cardiovascular, respiratory and metabolic functions is clinically relevant for perioperative morbidity. Somatostatin analogues also induce significant shrinkage of GH-secreting pituitary tumours, although this does not seem to be helpful in terms of improved surgical outcome. (Pol J Endocrinol 2007; 58 (4): 356-360)W leczeniu akromegalii możliwe jest zastosowanie różnych form terapii (leczenie operacyjne, farmakoterapia, radioterapia). Analogi somatostatyny wykazują skuteczność u większości pacjentów i mogą powodować zmniejszenie wielkości gruczolaka przysadki. Krótki przegląd przedstawia uzasadnienie i wyniki stosowania analogów somatostatyny przed leczeniem chirurgicznym. W podsumowaniu, korzyści przedoperacyjnego zastosowania analogów somatostatyny powinny być starannie rozważone celem optymalizacji zaburzeń kardiologicznych, oddechowych i metabolicznych ważnych dla chorobowości okołooperacyjnej. Analogi somatostatyny powodują również istotne zmniejszenie guzów przysadki wydzielających GH, chociaż nie udowodniono jego wpływu na poprawę wyników leczenia neurochirurgicznego

Do Changes in the Navy Physical Readiness Test Impact Performance?

The fitness level of our service members is of utmost importance due to the nature of their occupation. This study investigated whether changes to the Navy’s Physical Readiness Test (PRT) impact performance on the fitness test. Participants were college-aged males between the ages of 18 and 29 (n=20; 21.05±2.01 years; BMI 24.85± 2.74). Participants performed both the New PRT and Old PRT at two separate randomized visits. Protocols included push-ups, curl-ups (old version) or a forearm plank hold (new version), and a 1.5-mile run. At the end of each exercise, the participant’s heart rate and rating of perceived exertion (RPE) were recorded. There was a significant difference in points awarded for the plank (54±12.02) protocol compared to the curl-up (32.75±31.30) protocol (p=0.002). A paired samples t-test was run to compare the overall average of points rewarded on the Old PRT versus New PRT was found to be significant with participants scoring higher on the New PRT (37.80±16.01 points; 44.70±14.40 points, p=0.01). Based on the results, the curl-up and forearm plank standards are not equivalent; therefore, the Navy should consider increasing the minimum standard for the forearm plank hold to maintain the same rigor as the Old PRT. The findings of this study provide support for necessary modifications to the Navy PRT, and this could include a separate Navy combat fitness test along with a physical fitness test

Development of a Process Step for the High Purity Recovery of Exosome Material from a Regenerative Cell Product

Exosomes are an emerging sub class of extracellular vesicle which are rapidly gaining momentum as a novel therapeutic platform. Their regenerative and therapeutic potential is reflective of the plethora of cell types from which they can be derived. However, as the technology is in its nascent stage, relatively little exists in terms of defined manufacturing processes. As exosome technologies progress towards pre-clinical and clinical stages, the constraints in manufacturing processes, specifically in downstream processing, will need to be overcome. The current “gold standard” for exosome recovery from conditioned culture medium is ultracentrifugation. This step is time consuming, prone to operator error and difficult to scale and translate. The work presented here shows that monolith chromatography is a scalable, and reproducible purification option which can be used to successfully recover functionally active, and highly pure exosomes. Exosomes derived from the clinically relevant stem cell line, CTX0E03, were shown to present the biomarkers CD 9, CD 63 and CD 81, commonly conserved amongst exosome species throughout the literature. The vesicles were characterised as having a size distribution between 20 to 150 nm, and a flotation density between 1.136 – 1.185 g mL-1, as expected based on literature values. Furthermore, exosomes recovered by tangential flow filtration (TFF), were shown to promote fibroblast migration and wound closure (98% ± 1.5%) in an in vitro potency model, in a dose dependant fashion. In contrast exosomes purified by ultracentrifugation could not achieve wound closure, with no significant difference observed over the 72 hour period. TFF recovered exosomes were purified by the processes developed in this thesis. In the first instance they were purified by use of an anion exchange monolith using the quaternary amine ligand. Exosomes were shown to elute broadly over the elution gradient and overlap with DNA and albumin co-present within the feed material. Samples obtained post purification had purity ratios of 1.5 x 10^9 particles per µg of protein and 9.3 x 10^11 particles per µg of DNA impurity. Based on a hypothetical dose size of 10^9 particles per mL this result indicated purities within the WHO guidelines for injectable therapeutics (100 µg of protein, 10 ng DNA per dose) and benchmarked a potential method for purification of exosomes. A second monolith was also tested, using an orthogonal chemistry: hydrophobic interaction with an OH ligand. The results of this column surpassed those of the AEX process and showed a binding affinity beyond the hypothesized values. Unlike the AEX column, the HIC operation did not co-bind impurities in the form of albumin, DNA or even cell-0derived organelle matter. Resultantly, purities were even higher than those of the AEX column at 3.97 x 10^9 particles per µg of protein, and 3.12 x 10^12 particles per µg of DNA. Finally, combination of the processes showed the potential application of the chromatographic options within a larger process for exosome purification and high performance capillary electrophoresis analysis showed substantial removal of cell culture derived proteins from the recovered material, without substantial loss in particle number. The processes were assessed for potency, both individually and in sequence. No adverse effect in wound closure was noticed with all samples achieving wound closure over 90%. This showed improvement on the current gold-standard method, which could not retain product functionality

Role of the lipid rafts in the life cycle of canine coronavirus

Coronaviruses are enveloped RNA viruses that have evolved complex relationships with their host cells, and modulate their lipid composition, lipid synthesis and signalling. Lipid rafts, enriched in sphingolipids, cholesterol and associated proteins, are special plasma membrane microdomains involved in several processes in viral infections. The extraction of cholesterol leads to disorganization of lipid microdomains and to dissociation of proteins bound to lipid rafts. Because cholesterol-rich microdomains appear to be a general feature of the entry mechanism of non-eneveloped viruses and of several coronaviruses, the purpose of this study was to analyse the contribution of lipids to the infectivity of canine coronavirus (CCoV). The CCoV life cycle is closely connected to plasma membrane cholesterol, from cell entry to viral particle production. The methyl-β-cyclodextrin (MβCD) was employed to remove cholesterol and to disrupt the lipid rafts. Cholesterol depletion from the cell membrane resulted in a dose-dependent reduction, but not abolishment, of virus infectivity, and at a concentration of 15 mM, the reduction in the infection rate was about 68 %. MβCD treatment was used to verify if cholesterol in the envelope was required for CCoV infection. This resulted in a dose-dependent inhibitory effect, and at a concentration of 9 mM MβCD, infectivity was reduced by about 73 %. Since viral entry would constitute a target for antiviral strategies, inhibitory molecules interacting with viral and/or cell membranes, or interfering with lipid metabolism, may have strong antiviral potential. It will be interesting in the future to analyse the membrane microdomains in the CCoV envelope

Solutions to nonlocal evolution equations governed by non-autonomous forms and demicontinuous nonlinearities

We deal with the existence of solutions having L2 regularity for a class of non autonomous evolution equations. Associated with the equation, a general non local condition is studied. The technique we used combines a finite dimensional reduction together with the Leray-Schauder continuation principle. This approach permits to consider a wide class of nonlinear terms by allowing demicontinuity assumptions on the nonlinearity

An approach to the Spanish tax system

This book is an approach to the Spanish tax system, that allows the comprehension and learning of the main structures of the system, both material and formal. Analyses and explains the most important material and formal elements of the system; the coordination among the State, regional and local tax systems, and the nature, structure and functions of the main taxes

Optimization of laser wavelength, power and pulse duration for eye-safe Raman spectroscopy

Abstract Raising the interest in remote chemical analysis, in particular through Raman and fluorescence spectroscopy, the opportunity of increasing the exposure represents an important step for an easier and more reliable spectrum analysis. However, the European directive 2006/25/EC defines the maximum permitted exposure (MPE) to artificial radiations according to exposure duration, wavelength, coherence of the radiation and beam divergence. Though the Raman cross section scales in general according to the fourth power of the excitation wavelength, promoting the use of deep UV radiation, a synergy between wavelength and exposure time can raise the Raman signal in the near UV or in the near IR if compliance to eye-safety directives is requested. In this work we will analyze the possibilities offered by commercially available components for enhancing the Raman scattering under eye-safe conditions

The cardiovascular risk of young women with polycystic ovary syndrome: an observational, analytical, prospective case-control study

To evaluate the cardiovascular risk of polycystic ovary syndrome (PCOS), we investigated lipid profile, metabolic pattern, and echocardiography in 30 young women with PCOS and 30 healthy age- and body mass index (BMI)-matched women. PCOS women had higher fasting glucose and insulin levels, homeostasis model assessment score of insulin sensitivity, total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels, and TC/high density lipoprotein cholesterol (HDL-C) ratio and lower HDL-C levels than controls. Additionally, PCOS women had higher left atrium size (32.0 +/- 4.9 vs. 27.4 +/- 2.1 mm; P < 0.0001) and left ventricular mass index (80.5 +/- 18.1 vs. 56.1 +/- 5.4 g/m(2); P < 0.0001) and lower left ventricular ejection fraction (64.4 +/- 4.1 vs. 67.1 +/- 2.6%; P = 0.003) and early to late mitral flow velocity ratio (1.6 +/- 0.4 vs. 2.1 +/- 0.2; P < 0.0001) than controls. When patients and controls were grouped according to BMI [normal weight (BMI, >18 and <25 kg/m(2)), overweight (BMI, 25.1-30 kg/m(2)), and obese (BMI, >30 kg/m(2))], the differences between PCOS women and controls were maintained in overweight and obese women. In normal weight PCOS women, a significant increase in left ventricular mass index and a decrease in diastolic filling were observed, notwithstanding no change in TC, LDL-C, HDL-C, TC/HDL-C ratio, and TG compared with controls. In conclusion, our data show the detrimental effect of PCOS on the cardiovascular system even in young women asymptomatic for cardiac disease

Time spent with cats is never wasted: Lessons learned from feline acromegalic cardiomyopathy, a naturally occurring animal model of the human disease

<div><p>Background</p><p>In humans, acromegaly due to a pituitary somatotrophic adenoma is a recognized cause of increased left ventricular (LV) mass. Acromegalic cardiomyopathy is incompletely understood, and represents a major cause of morbidity and mortality. We describe the clinical, echocardiographic and histopathologic features of naturally occurring feline acromegalic cardiomyopathy, an emerging disease among domestic cats.</p><p>Methods</p><p>Cats with confirmed hypersomatotropism (IGF-1>1000ng/ml and pituitary mass; n = 67) were prospectively recruited, as were two control groups: diabetics (IGF-1<800ng/ml; n = 24) and healthy cats without known endocrinopathy or cardiovascular disease (n = 16). Echocardiography was performed in all cases, including after hypersomatotropism treatment where applicable. Additionally, tissue samples from deceased cats with hypersomatotropism, hypertrophic cardiomyopathy and age-matched controls (n = 21 each) were collected and systematically histopathologically reviewed and compared.</p><p>Results</p><p>By echocardiography, cats with hypersomatotropism had a greater maximum LV wall thickness (6.5mm, 4.1–10.1mm) than diabetic (5.9mm, 4.2–9.1mm; Mann Whitney, p<0.001) or control cats (5.2mm, 4.1–6.5mm; Mann Whitney, p<0.001). Left atrial diameter was also greater in cats with hypersomatotropism (16.6mm, 13.0–29.5mm) than in diabetic (15.4mm, 11.2–20.3mm; Mann Whitney, p<0.001) and control cats (14.0mm, 12.6–17.4mm; Mann Whitney, p<0.001). After hypophysectomy and normalization of IGF-1 concentration (n = 20), echocardiographic changes proved mostly reversible. As in humans, histopathology of the feline acromegalic heart was dominated by myocyte hypertrophy with interstitial fibrosis and minimal myofiber disarray.</p><p>Conclusions</p><p>These results demonstrate cats could be considered a naturally occurring model of acromegalic cardiomyopathy, and as such help elucidate mechanisms driving cardiovascular remodeling in this disease.</p></div

Complications of Cushing's syndrome: state of the art

Cushing's syndrome is a serious endocrine disease caused by chronic, autonomous, and excessive secretion of cortisol. The syndrome is associated with increased mortality and impaired quality of life because of the occurrence of comorbidities. These clinical complications include metabolic syndrome, consisting of systemic arterial hypertension, visceral obesity, impairment of glucose metabolism, and dyslipidaemia; musculoskeletal disorders, such as myopathy, osteoporosis, and skeletal fractures; neuropsychiatric disorders, such as impairment of cognitive function, depression, or mania; impairment of reproductive and sexual function; and dermatological manifestations, mainly represented by acne, hirsutism, and alopecia. Hypertension in patients with Cushing's syndrome has a multifactorial pathogenesis and contributes to the increased risk for myocardial infarction, cardiac failure, or stroke, which are the most common causes of death; risks of these outcomes are exacerbated by a prothrombotic diathesis and hypokalaemia. Neuropsychiatric disorders can be responsible for suicide. Immune disorders are common; immunosuppression during active disease causes susceptibility to infections, possibly complicated by sepsis, an important cause of death, whereas immune rebound after disease remission can exacerbate underlying autoimmune diseases. Prompt treatment of cortisol excess and specific treatments of comorbidities are crucial to prevent serious clinical complications and reduce the mortality associated with Cushing's syndrome